Event-triggered hybrid control based on multi-Agent systems for Microgrids

DEFF Research Database (Denmark)

Dou, Chun-xia; Liu, Bin; Guerrero, Josep M.

2014-01-01

This paper is focused on a multi-agent system based event-triggered hybrid control for intelligently restructuring the operating mode of an microgrid (MG) to ensure the energy supply with high security, stability and cost effectiveness. Due to the microgrid is composed of different types...... of distributed energy resources, thus it is typical hybrid dynamic network. Considering the complex hybrid behaviors, a hierarchical decentralized coordinated control scheme is firstly constructed based on multi-agent sys-tem, then, the hybrid model of the microgrid is built by using differential hybrid Petri...

Sea urchin coelomocytes are resistant to a variety of DNA damaging agents

International Nuclear Information System (INIS)

Loram, Jeannette; Raudonis, Renee; Chapman, Jecar; Lortie, Mae; Bodnar, Andrea

2012-01-01

Increasing anthropogenic activities are creating environmental pressures that threaten marine ecosystems. Effective environmental health assessment requires the development of rapid, sensitive, and cost-effective tools to predict negative impacts at the individual and ecosystem levels. To this end, a number of biological assays using a variety of cells and organisms measuring different end points have been developed for biomonitoring programs. The sea urchin fertilization/development test has been useful for evaluating environmental toxicology and it has been proposed that sea urchin coelomocytes represent a novel cellular biosensor of environmental stress. In this study we investigated the sensitivity of coelomocytes from the sea urchin Lytechinus variegatus to a variety of DNA-damaging agents including ultraviolet (UV) radiation, hydrogen peroxide (H 2 O 2 ), methylmethane sulfonate (MMS) and benzo[a]pyrene (BaP). LD 50 values determined for coelomocytes after 24 h of exposure to these DNA damaging agents indicated a high level of resistance to all treatments. Significant increases in the formation of apurinic/apyrimidinic (AP or abasic) sites in DNA were only detected using high doses of H 2 O 2 , MMS and UV radiation. Comparison of sea urchin coelomocytes with hemocytes from the gastropod mollusk Aplysia dactylomela and the decapod crustacean Panulirus argus indicated that sensitivity to different DNA damaging agents varies between species. The high level of resistance to genotoxic agents suggests that DNA damage may not be an informative end point for environmental health assessment using sea urchin coelomocytes however, natural resistance to DNA damaging agents may have implications for the occurrence of neoplastic disease in these animals.

Multi-Agent System based Event-Triggered Hybrid Controls for High-Security Hybrid Energy Generation Systems

DEFF Research Database (Denmark)

Dou, Chun-Xia; Yue, Dong; Guerrero, Josep M.

2017-01-01

This paper proposes multi-agent system based event- triggered hybrid controls for guaranteeing energy supply of a hybrid energy generation system with high security. First, a mul-ti-agent system is constituted by an upper-level central coordi-nated control agent combined with several lower......-level unit agents. Each lower-level unit agent is responsible for dealing with internal switching control and distributed dynamic regula-tion for its unit system. The upper-level agent implements coor-dinated switching control to guarantee the power supply of over-all system with high security. The internal...

Influence of the clay in the stress cracking resistance of PET; Influencia de silicatos em camadas na resistencia ao 'stress cracking' do PET

Energy Technology Data Exchange (ETDEWEB)

Teofilo, Edvania T. [Programa de Pos-Graduacao em Ciencia e Engenharia de Materiais, Universidade Federal de Campina Grande, PB (Brazil); Silva, Emanuela S.; Silva, Suedina M.L.; Rabello, Marcelo S., E-mail: marcelo@dema.ufcg.edu.b [Unidade Academica de Engenharia de Materiais, Universidade Federal de Campina Grande, PB (Brazil)

2011-07-01

The environmental stress cracking resistance in PET and hybrid PET/clay were conducted under stress relaxation test. X-ray diffraction analysis show that was obtained immiscible system. In the absence of aggressive fluids the hybrid exhibited higher relaxation rates than the PET. Already in contact with aggressive fluids showed a similar or lower relaxation rate than the PET, being more resistant. Suggesting that the clay, though not interlayer, interferes with the distribution of the stress cracking agent. Thus, the barrier effect caused by the clay was more significant than the stress concentration caused by it. (author)

Pre-cold stress increases acid stress resistance and induces amino ...

African Journals Online (AJOL)

Pre-cold stress increases acid stress resistance and induces amino acid homeostasis in Lactococcus lactis NZ9000. ... Purpose: To investigate the effects of pre-cold stress treatments on subsequent acid stress resistance ... from 32 Countries:.

Sea urchin coelomocytes are resistant to a variety of DNA damaging agents

Energy Technology Data Exchange (ETDEWEB)

Loram, Jeannette; Raudonis, Renee; Chapman, Jecar; Lortie, Mae [Bermuda Institute of Ocean Sciences, St. George' s, Bermuda, GE 01 (Bermuda); Bodnar, Andrea, E-mail: andrea.bodnar@bios.edu [Bermuda Institute of Ocean Sciences, St. George' s, Bermuda, GE 01 (Bermuda)

2012-11-15

Increasing anthropogenic activities are creating environmental pressures that threaten marine ecosystems. Effective environmental health assessment requires the development of rapid, sensitive, and cost-effective tools to predict negative impacts at the individual and ecosystem levels. To this end, a number of biological assays using a variety of cells and organisms measuring different end points have been developed for biomonitoring programs. The sea urchin fertilization/development test has been useful for evaluating environmental toxicology and it has been proposed that sea urchin coelomocytes represent a novel cellular biosensor of environmental stress. In this study we investigated the sensitivity of coelomocytes from the sea urchin Lytechinus variegatus to a variety of DNA-damaging agents including ultraviolet (UV) radiation, hydrogen peroxide (H{sub 2}O{sub 2}), methylmethane sulfonate (MMS) and benzo[a]pyrene (BaP). LD{sub 50} values determined for coelomocytes after 24 h of exposure to these DNA damaging agents indicated a high level of resistance to all treatments. Significant increases in the formation of apurinic/apyrimidinic (AP or abasic) sites in DNA were only detected using high doses of H{sub 2}O{sub 2}, MMS and UV radiation. Comparison of sea urchin coelomocytes with hemocytes from the gastropod mollusk Aplysia dactylomela and the decapod crustacean Panulirus argus indicated that sensitivity to different DNA damaging agents varies between species. The high level of resistance to genotoxic agents suggests that DNA damage may not be an informative end point for environmental health assessment using sea urchin coelomocytes however, natural resistance to DNA damaging agents may have implications for the occurrence of neoplastic disease in these animals.

Type D personality is associated with the development of stress cardiomyopathy following emotional triggers.

Science.gov (United States)

Compare, Angelo; Bigi, Riccardo; Orrego, Pedro Silva; Proietti, Riccardo; Grossi, Enzo; Steptoe, Andrew

2013-06-01

Stress cardiomyopathy (SCM) can be triggered by emotional events. Recently, type D personality has been established as an independent predictor of acute cardiac adverse events. We sought to examine whether type D personality can be identified in SCM patients. A case-control study with 37 SCM patients, 37 myocardial infarction (AMI) patients, who both experienced emotional triggering, and 37 SCM patients without emotional triggers was performed. The DS14 and Interview for Recent Life Events were administered. Twenty-eight (76 %) SCM emotional trigger patients were categorized as type D compared with 13 (43 %) SCM patients without emotional trigger and 12 (32 %) AMI patients (p emotional triggers had higher scores on the social inhibition subscale than the other patient groups. The present study highlights the possible link between type D, with a specific key role for social inhibition component, and increased biological reactivity to acute emotional stress.

A screen to identify drug resistant variants to target-directed anti-cancer agents

Directory of Open Access Journals (Sweden)

Azam Mohammad

2003-01-01

Full Text Available The discovery of oncogenes and signal transduction pathways important for mitogenesis has triggered the development of target-specific small molecule anti-cancer compounds. As exemplified by imatinib (Gleevec, a specific inhibitor of the Chronic Myeloid Leukemia (CML-associated Bcr-Abl kinase, these agents promise impressive activity in clinical trials, with low levels of clinical toxicity. However, such therapy is susceptible to the emergence of drug resistance due to amino acid substitutions in the target protein. Defining the spectrum of such mutations is important for patient monitoring and the design of next-generation inhibitors. Using imatinib and BCR/ABL as a paradigm for a drug-target pair, we recently reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations. Here we provide a detailed methodology for the screen, which can be generally applied to any drug-target pair.

Arbutin increases Caenorhabditis elegans longevity and stress resistance

Directory of Open Access Journals (Sweden)

Lin Zhou

2017-12-01

Full Text Available Arbutin (p-hydroxyphenyl-β-D-glucopyranoside, a well-known tyrosinase inhibitor, has been widely used as a cosmetic whitening agent. Although its natural role is to scavenge free radicals within cells, it has also exhibited useful activities for the treatment of diuresis, bacterial infections and cancer, as well as anti-inflammatory and anti-tussive activities. Because function of free radical scavenging is also related to antioxidant and the effects of arbutin on longevity and stress resistance in animals have not yet been confirmed, here the effects of arbutin on Caenorhabditis elegans were investigated. The results demonstrated that optimal concentrations of arbutin could extend lifespan and enhance resistance to oxidative stress. The underlying molecular mechanism for these effects involves decreased levels of reactive oxygen species (ROS, improvement of daf-16 nuclear localization, and up-regulated expression of daf-16 and its downstream targets, including sod-3 and hsp16.2. In this work the roles of arbutin in lifespan and health are studied and the results support that arbutin is an antioxidant for maintaining overall health.

Resisting distraction and response inhibition trigger similar enhancements of future performance.

Science.gov (United States)

Bissett, Patrick G; Grant, Lauren D; Weissman, Daniel H

2017-10-01

Resisting distraction and response inhibition are crucial aspects of cognitive control. Interestingly, each of these abilities transiently improves just after it is utilized. Competing views differ, however, as to whether utilizing either of these abilities (e.g., resisting distraction) enhances future performance involving the other ability (e.g., response inhibition). To distinguish between these views, we combined a Stroop-like task that requires resisting distraction with a restraint variant of the stop-signal task that requires response inhibition. We observed similar sequential-trial effects (i.e., performance enhancements) following trials in which participants (a) resisted distraction (i.e., incongruent go trials) and (b) inhibited a response (i.e., congruent stop trials). First, the congruency effect in go trials, which indexes overall distractibility, was smaller after both incongruent go trials and congruent stop trials than it was after congruent go trials. Second, stop failures were less frequent after both incongruent go trials and congruent stop trials than after congruent go trials. A control experiment ruled out the possibility that perceptual conflict or surprise engendered by occasional stop signals triggers sequential-trial effects independent of stopping. Thus, our findings support a novel, integrated view in which resisting distraction and response inhibition trigger similar sequential enhancements of future performance. Copyright © 2017 Elsevier B.V. All rights reserved.

Resistance to cytotoxic and anti-angiogenic anticancer agents: similarities and differences.

NARCIS (Netherlands)

Broxterman, H.J.; Lankelma, J.; Hoekman, K.

2003-01-01

Intrinsic resistance to anticancer drugs, or resistance developed during chemotherapy, remains a major obstacle to successful treatment. This is the case both for resistance to cytotoxic agents, directed at malignant cells, and for resistance to anti-angiogenic agents, directed at non-malignant

Mechanisms of bacterial resistance to antimicrobial agents.

NARCIS (Netherlands)

van Duijkeren, Engeline; Schink, Anne-Kathrin; Roberts, Marilyn C; Wang, Yang; Schwarz, Stefan

During the past decades resistance to virtually all antimicrobial agents has been observed in bacteria of animal origin. This chapter describes in detail the mechanisms so far encountered for the various classes of antimicrobial agents. The main mechanisms include enzymatic inactivation by either

Vrancea slab earthquakes triggered by static stress transfer

Directory of Open Access Journals (Sweden)

A. Ganas

2010-12-01

Full Text Available The purpose of this paper is to study the interaction of the Vrancea seismic activity (Romania in space as result of Coulomb, static stress transfer during M=7+ events. In this area, three large events occurred in 1977, 1986 and 1990 at mid-lower, lithospheric depths and with similar focal mechanisms. Assuming elastic rheology for the deforming rocks it is suggested that frictional sliding on pre-existing fault produced the 1986 M=7.1 event (depth 131 km, that was possibly triggered by the 1977 M=7.4 event (depth 94 km. We calculated a static stress transfer of 0.52–0.78 bar to the hypocentre of the 1986 event. On the contrary, the occurrence of the 1990 event is uncertain: it is located inside the relaxed (shadow zone of the combined 1977 and 1986 static stress field considering an azimuth for maximum compression of N307° E. It follows that, the 1990 earthquake most likely represents an unbroken patch (asperity of the 1977 rupture plane that failed due to loading. However, if a different compression azimuth is assumed (N323° E then the 1990 event was also possibly triggered by static stress transfer of the 1977 and 1986 events (combined. Our modeling is a first-order approximation of the kind of earthquake interaction we might expect at intermediate lithospheric depths (80–90 to 130–140 km. It is also suggested that static stress transfer may explain the clustering of Vrancea earthquakes in space by the rupturing of two (possibly three NW-dipping major zones of weakness (faults which accommodate the extension (vertical elongation of the slab.

An event-triggered control approach for the leader-tracking problem with heterogeneous agents

Science.gov (United States)

Garcia, Eloy; Cao, Yongcan; Casbeer, David W.

2018-05-01

This paper presents an event-triggered control and communication framework for the cooperative leader-tracking problem with communication constraints. Continuous communication among agents is not assumed in this work and decentralised event-based strategies are proposed for agents with heterogeneous linear dynamics. Also, the leader dynamics are unknown and only intermittent measurements of its states are obtained by a subset of the followers. The event-based method not only represents a way to restrict communication among agents, but it also provides a decentralised scheme for scheduling information broadcasts. Notably, each agent is able to determine its own broadcasting instants independently of any other agent in the network. In an extension, the case where transmission of information is affected by time-varying communication delays is addressed. Finally, positive lower-bounds on the inter-event time intervals are obtained in order to show that Zeno behaviour does not exist and, therefore, continuous exchange of information is never needed in this framework.

Stress-Triggered Phase Separation Is an Adaptive, Evolutionarily Tuned Response

Energy Technology Data Exchange (ETDEWEB)

Riback, Joshua A.; Katanski, Christopher D.; Kear-Scott, Jamie L.; Pilipenko, Evgeny V.; Rojek, Alexandra E.; Sosnick, Tobin R.; Drummond, D. Allan

2017-03-01

In eukaryotic cells, diverse stresses trigger coalescence of RNA-binding proteins into stress granules. In vitro, stress-granule-associated proteins can demix to form liquids, hydrogels, and other assemblies lacking fixed stoichiometry. Observing these phenomena has generally required conditions far removed from physiological stresses. We show that poly(A)-binding protein (Pab1 in yeast), a defining marker of stress granules, phase separates and forms hydrogels in vitro upon exposure to physiological stress conditions. Other RNA-binding proteins depend upon low-complexity regions (LCRs) or RNA for phase separation, whereas Pab1’s LCR is not required for demixing, and RNA inhibits it. Based on unique evolutionary patterns, we create LCR mutations, which systematically tune its biophysical properties and Pab1 phase separation in vitro and in vivo. Mutations that impede phase separation reduce organism fitness during prolonged stress. Poly(A)-binding protein thus acts as a physiological stress sensor, exploiting phase separation to precisely mark stress onset, a broadly generalizable mechanism.

Ultrasound-triggered local release of lipophilic drugs from a novel polymeric ultrasound contrast agent

NARCIS (Netherlands)

Kooiman, K.; Böhmer, M.R.; Emmer, M.; Vos, Hendrik J.; Chlon, C.; Foppen-Harteveld, M.; Versluis, Michel; de Jong, N.; van Wamel, A.; Hennink, W.E.; Feijen, J.; Sam, A.P.

2008-01-01

The advantage of ultrasound contrast agents (UCAs) as drug delivery systems is the ability to non-invasively control the local and triggered release of a drug or gene. In this study we designed and characterized a novel UCA-based drug delivery system, based on polymer-shelled microcapsules filled

Beneficial Effect of Jojoba Seed Extracts on Hyperglycemia-Induced Oxidative Stress in RINm5f Beta Cells.

Science.gov (United States)

Belhadj, Sahla; Hentati, Olfa; Hamdaoui, Ghaith; Fakhreddine, Khaskhoussi; Maillard, Elisa; Dal, Stéphanie; Sigrist, Séverine

2018-03-20

Hyperglycemia occurs during diabetes and insulin resistance. It causes oxidative stress by increasing reactive oxygen species (ROS) levels, leading to cellular damage. Polyphenols play a central role in defense against oxidative stress. In our study, we investigated the antioxidant properties of simmondsin, a pure molecule present in jojoba seeds, and of the aqueous extract of jojoba seeds on fructose-induced oxidative stress in RINm5f beta cells. The exposure of RINm5f beta cells to fructose triggered the loss of cell viability (-48%, p jojoba seed extract makes jojoba a powerful agent to prevent the destruction of RINm5f beta cells induced by hyperglycemia.

The role of stress as a trigger for epileptic seizures: a narrative review of evidence from human and animal studies.

Science.gov (United States)

Novakova, Barbora; Harris, Peter R; Ponnusamy, Athi; Reuber, Markus

2013-11-01

Stress is one of the most frequently self-identified seizure triggers in patients with epilepsy; however, most previous publications on stress and epilepsy have focused on the role of stress in the initial development of epilepsy. This narrative review explores the causal role of stress in triggering seizures in patients with existing epilepsy. Findings from human studies of psychological stress, as well as of physiologic stress responses in humans and animals, and evidence from nonpharmacologic interventions for epilepsy are considered. The evidence from human studies for stress as a trigger of epileptic seizures is inconclusive. Although retrospective self-report studies show that stress is the most common patient-perceived seizure precipitant, prospective studies have yielded mixed results and studies of life events suggest that stressful experiences only trigger seizures in certain individuals. There is limited evidence suggesting that autonomic arousal can precede seizures. Interventions designed to improve coping with stress reduce seizures in some individuals. Studies of physiologic stress using animal epilepsy models provide more convincing evidence. Exposure to exogenous and endogenous stress mediators has been found to increase epileptic activity in the brain and trigger overt seizures, especially after repeated exposure. In conclusion, stress is likely to exacerbate the susceptibility to epileptic seizures in a subgroup of individuals with epilepsy and may play a role in triggering "spontaneous" seizures. However, there is currently no strong evidence for a close link between stress and seizures in the majority of people with epilepsy, although animal research suggests that such links are likely. Further research is needed into the relationship between stress and seizures and into interventions designed to reduce perceived stress and improve quality of life with epilepsy. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Stress triggers anhedonia in rats bred for learned helplessness.

Science.gov (United States)

Enkel, Thomas; Spanagel, Rainer; Vollmayr, Barbara; Schneider, Miriam

2010-05-01

Congenitally helpless (cLH) rats, a well-accepted model for depression, show reduced consumption of sweet solutions only under single-housing conditions, indicating anhedonia under stress. We investigated if anhedonic-like behaviour, measured by a reduction of sweetened-condensed milk (SCM) intake and the pleasure-attenuated startle response (PAS), could be induced by an electric foot-shock stress challenge in group-housed rats. After foot-shock stress, reduced SCM intake was observed in cLH rats compared to non-helpless (cNLH) rats. Furthermore, cLH rats also showed a decreased PAS, indicating deficient reward perception. In summary, we demonstrate that a predisposition for learned helplessness interacts with stress to trigger anhedonic-like behaviour in cLH rats. These findings further add to the validity of congenitally learned helplessness as an animal model of depression, since gene-environment interactions are considered to play a role in the etiology of this disorder.

Polypyrrole/silver coaxial nanowire aero-sponges for temperature-independent stress sensing and stress-triggered Joule heating.

Science.gov (United States)

He, Weina; Li, Guangyong; Zhang, Shangquan; Wei, Yong; Wang, Jin; Li, Qingwen; Zhang, Xuetong

2015-04-28

To obtain ideal sensing materials with nearly zero temperature coefficient resistance (TCR) for self-temperature-compensated pressure sensors, we proposed an Incipient Network Conformal Growth (INCG) technology to prepare hybrid and elastic porous materials: the nanoparticles (NPs) are first dispersed in solvent to form an incipient network, another component is then introduced to coat the incipient network conformally via wet chemical route. The conformal coatings not only endow NPs with high stability but also offer them additional structural elasticity, meeting requirements for future generations of portable, compressive and flexible devices. The resultant polypyrrole/silver coaxial nanowire hybrid aero-sponges prepared via INCG technology have been processed into a piezoresistive sensor with highly sensing stability (low TCR 0.86 × 10(-3)/°C), sensitivity (0.33 kPa(-1)), short response time (1 ms), minimum detectable pressure (4.93 Pa) after suffering repeated stimuli, temperature change and electric heating. Moreover, a stress-triggered Joule heater can be also fabricated mainly by the PPy-Ag NW hybrid aero-sponges with nearly zero temperature coefficient.

Leptin and Leptin Resistance in the Pathogenesis of Obstructive Sleep Apnea: A Possible Link to Oxidative Stress and Cardiovascular Complications

Directory of Open Access Journals (Sweden)

Slava Berger

2018-01-01

Full Text Available Obesity-related sleep breathing disorders such as obstructive sleep apnea (OSA and obesity hypoventilation syndrome (OHS cause intermittent hypoxia (IH during sleep, a powerful trigger of oxidative stress. Obesity also leads to dramatic increases in circulating levels of leptin, a hormone produced in adipose tissue. Leptin acts in the hypothalamus to suppress food intake and increase metabolic rate. However, obese individuals are resistant to metabolic effects of leptin. Leptin also activates the sympathetic nervous system without any evidence of resistance, possibly because these effects occur peripherally without a need to penetrate the blood-brain barrier. IH is a potent stimulator of leptin expression and release from adipose tissue. Hyperleptinemia and leptin resistance may upregulate generation of reactive oxygen species, increasing oxidative stress and promoting inflammation. The current review summarizes recent data on a possible link between leptin and oxidative stress in the pathogenesis of sleep breathing disorders.

DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development.

Directory of Open Access Journals (Sweden)

Yosuke Ichijima

Full Text Available During tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration, which induce situations identical to the initial stages of cancer development, trigger tetraploidy/aneuploidy generation in association with mitotic aberration. Although oncogene acceleration primarily induces DNA replication stress and the resulting lesions in the S phase, these lesions are carried over into the M phase and cause cytokinesis failure and genomic instability. Unlike directly induced DNA double-strand breaks, DNA replication stress-associated lesions are cryptogenic and pass through cell-cycle checkpoints due to limited and ineffective activation of checkpoint factors. Furthermore, since damaged M-phase cells still progress in mitotic steps, these cells result in chromosomal mis-segregation, cytokinesis failure and the resulting tetraploidy generation. Thus, our results reveal a process of genomic instability generation triggered by precancerous DNA replication stress.

Stress cracking e ataque químico do PET em diferentes agentes químicos Stress cracking and chemical attack of pet under different chemicals

Directory of Open Access Journals (Sweden)

Edvânia T. Teófilo

2009-01-01

Full Text Available A análise de resistência ao stress cracking (ESCR do PET foi feita em corpos de prova de tração moldados por injeção, utilizando vários agentes químicos (metanol, etanol, propanol, butanol e soluções de hidróxido de sódio em diferentes concentrações. Foram realizados ensaios dinâmicos e estáticos de tração. Durante os testes os corpos de prova foram mantidos em contato com os agentes e as propriedades mecânicas monitoradas. Os resultados evidenciam que todas as soluções de hidróxidos de sódio testadas são agentes agressivos de ESC por diminuírem as propriedades mecânicas do polímero, ocasionando falha catastrófica. Já os demais fluidos, apesar de não terem efeito significativo nas propriedades do PET, afetam drasticamente sua aparência superficial. Observou-se também a ocorrência de ataque químico nos ensaios com NaOH, resultando em redução nas massas molares.The investigation of stress cracking resistance (ESCR of PET was done in injection-moulded tensile test bars using different fluids as active agents. These were methanol, ethanol, propanol, butanol and solutions based on sodium hydroxide. Both dynamic and static tensile experiments were conducted. During the tensile experiments, the samples were kept in contact with the fluids and the mechanical properties were monitored. The results showed that all sodium hydroxide solutions were aggressive stress cracking agents for PET, reducing mechanical properties and causing catastrophic failure. On the other hand, the other fluids did not cause much influence on the mechanical behaviour but changed drastically the surface appearance. Also observed was a chemical attack when NaOH solutions were used, causing a reduction in molar mass of PET molecules.

Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns.

Science.gov (United States)

Williamson, Deborah A; Carter, Glen P; Howden, Benjamin P

2017-07-01

Bacterial skin infections represent some of the most common infectious diseases globally. Prevention and treatment of skin infections can involve application of a topical antimicrobial, which may be an antibiotic (such as mupirocin or fusidic acid) or an antiseptic (such as chlorhexidine or alcohol). However, there is limited evidence to support the widespread prophylactic or therapeutic use of topical agents. Challenges involved in the use of topical antimicrobials include increasing rates of bacterial resistance, local hypersensitivity reactions (particularly to older agents, such as bacitracin), and concerns about the indiscriminate use of antiseptics potentially coselecting for antibiotic resistance. We review the evidence for the major clinical uses of topical antibiotics and antiseptics. In addition, we review the mechanisms of action of common topical agents and define the clinical and molecular epidemiology of antimicrobial resistance in these agents. Moreover, we review the potential use of newer and emerging agents, such as retapamulin and ebselen, and discuss the role of antiseptic agents in preventing bacterial skin infections. A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future. Copyright © 2017 American Society for Microbiology.

Blue light irradiation triggers the antimicrobial potential of ZnO nanoparticles on drug-resistant Acinetobacter baumannii.

Science.gov (United States)

Yang, Ming-Yeh; Chang, Kai-Chih; Chen, Liang-Yu; Wang, Po-Ching; Chou, Chih-Chiang; Wu, Zhong-Bin; Hu, Anren

2018-03-01

Photodynamic inactivation (PDI) is a non-invasive and safe therapeutic method for microbial infections. Bacterial antibiotic resistance is caused by antibiotics abuse. Drug-resistant Acinetobacter spp. is a serious problem in hospitals around the world. These pathogens from nosocomial infections have high mortality rates in frailer people, and Acinetobacter spp. is commonly found in immunocompromised patients. Visible light is safer than ultraviolet light (UV) for PDI of nosocomial pathogens with mammalian cells. Zinc oxide nanoparticles (ZnO-NPs) were used in this study as an antimicrobial agent and a photosensitizer. ZnO is recognized as safe and has extensive usage in food additives, medical and cosmetic products. In this study, we used 0.125 mg/ml ZnO-NPs combined with 10.8 J/cm 2 blue light (BL) on Acinetobacter baumannii (A. baumannii) that could significantly reduce microbial survival. However, individual exposure to ZnO-NPs does not affect the viability of A. baumannii. BL irradiation could trigger the antimicrobial ability of ZnO nanoparticles on A. baumannii. The mechanism of photocatalytic ZnO-NPs treatment for sterilization occurs through bacterial membrane disruptions. Otherwise, the photocatalytic ZnO-NPs treatment showed high microbial eradication in nosocomial pathogens, including colistin-resistant and imipenem-resistant A. baumannii and Klebsiella pneumoniae. Based on our results, the photocatalytic ZnO-NPs treatment could support hygiene control and clinical therapies without antibiotics to nosocomial bacterial infections. Copyright © 2018. Published by Elsevier B.V.

Stress triggering of the Lushan M7. 0 earthquake by the Wenchuan Ms8. 0 earthquake

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Wu Jianchao

2013-08-01

Full Text Available The Wenchuan Ms8. 0 earthquake and the Lushan M7. 0 earthquake occurred in the north and south segments of the Longmenshan nappe tectonic belt, respectively. Based on the focal mechanism and finite fault model of the Wenchuan Ms8. 0 earthquake, we calculated the coulomb failure stress change. The inverted coulomb stress changes based on the Nishimura and Chenji models both show that the Lushan M7. 0 earthquake occurred in the increased area of coulomb failure stress induced by the Wenchuan Ms8. 0 earthquake. The coulomb failure stress increased by approximately 0. 135 – 0. 152 bar in the source of the Lushan M7. 0 earthquake, which is far more than the stress triggering threshold. Therefore, the Lushan M7. 0 earthquake was most likely triggered by the coulomb failure stress change.

The heat shock protein/chaperone network and multiple stress resistance

KAUST Repository

Jacob, Pierre; Hirt, Heribert; Bendahmane, Abdelhafid

2016-01-01

Crop yield has been greatly enhanced during the last century. However, most elite cultivars are adapted to temperate climates and are not well suited to more stressful conditions. In the context of climate change, stress resistance is a major concern. To overcome these difficulties, scientists may help breeders by providing genetic markers associated with stress resistance. However, multi-stress resistance cannot be obtained from the simple addition of single stress resistance traits. In the field, stresses are unpredictable and several may occur at once. Consequently, the use of single stress resistance traits is often inadequate. Although it has been historically linked with the heat stress response, the heat shock protein (HSP)/chaperone network is a major component of multiple stress responses. Among the HSP/chaperone

The heat shock protein/chaperone network and multiple stress resistance

KAUST Repository

Jacob, Pierre

2016-11-15

Crop yield has been greatly enhanced during the last century. However, most elite cultivars are adapted to temperate climates and are not well suited to more stressful conditions. In the context of climate change, stress resistance is a major concern. To overcome these difficulties, scientists may help breeders by providing genetic markers associated with stress resistance. However, multi-stress resistance cannot be obtained from the simple addition of single stress resistance traits. In the field, stresses are unpredictable and several may occur at once. Consequently, the use of single stress resistance traits is often inadequate. Although it has been historically linked with the heat stress response, the heat shock protein (HSP)/chaperone network is a major component of multiple stress responses. Among the HSP/chaperone

Heat-resistant agent used for control sand of steam huff and puff heavy oil well

Science.gov (United States)

Zhang, F. S.; Liu, G. L.; Lu, Y. J.; Xiong, X. C.; Ma, J. H.; Su, H. M.

2018-01-01

Heat-resistant agent containing hydroxymethyl group was synthesized from coal tar, which has similar structure with phenolic resin and could improve the heat resistance of phenolic resin sand control agent. The results showed that the heat resistance of the sand control agent was improved by adding 10% to 30% heat-resistant agent, after 280°C high temperature treatment for 7d, the compressive strength of consolidated core was increased to more than 5MPa. The compressive strength of consolidation core was not decreased after immersion in formation water, crude oil, acid or alkaline medium, which showed good resistance to medium immersion. The sand control agent had small core damage and the core permeability damage ratio of sand control agent consolidation was only 18.7%.

Endoplasmic reticulum stress-induced resistance to doxorubicin is reversed by paeonol treatment in human hepatocellular carcinoma cells.

Directory of Open Access Journals (Sweden)

Lulu Fan

Full Text Available BACKGROUND: Endoplasmic reticulum stress (ER stress is generally activated in solid tumors and results in tumor cell anti-apoptosis and drug resistance. Paeonol (Pae, 2-hydroxy-4-methoxyacetophenone, is a natural product extracted from the root of Paeonia Suffruticosa Andrew. Although Pae displays anti-neoplastic activity and increases the efficacy of chemotherapeutic drugs in various cell lines and in animal models, studies related to the effect of Pae on ER stress-induced resistance to chemotherapeutic agents in hepatocellular carcinoma (HCC are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the effect of the endoplasmic reticulum (ER stress response during resistance of human hepatocellular carcinoma cells to doxorubicin. Treatment with the ER stress-inducer tunicamycin (TM before the addition of doxorubicin reduced the rate of apoptosis induced by doxorubicin. Interestingly, co-pretreatment with tunicamycin and Pae significantly increased apoptosis induced by doxorubicin. Furthermore, induction of ER stress resulted in increasing expression of COX-2 concomitant with inactivation of Akt and up-regulation of the pro-apoptotic transcription factor CHOP (GADD153 in HepG2 cells. These cellular changes in gene expression and Akt activation may be an important resistance mechanism against doxorubicin in hepatocellular carcinoma cells undergoing ER stress. However, co-pretreatment with tunicamycin and Pae decreased the expression of COX-2 and levels of activation of Akt as well as increasing the levels of CHOP in HCC cells. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that Pae reverses ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells by targeting COX-2 mediated inactivation of PI3K/AKT/CHOP.

Inflammation and vascular responses to acute mental stress : implications for the triggering of myocardial infarction

NARCIS (Netherlands)

Paine, N.J.; Bosch, J.A.; Veldhuijzen Van Zanten, J.J.C.S.

2012-01-01

There is evidence that mental stress can trigger myocardial infarction. Even though the underlying mechanisms remain to be determined, both inflammation and vascular responses to mental stress have been implicated as contributing factors. This review explores the effects of inflammation on the

Contrast agents provide a faster learning curve in dipyridamole stress echocardiography.

Science.gov (United States)

Zamorano, Jose; Sánchez, Violeta; Moreno, Raúl; Almería, Carlos; Rodrigo, Jose; Serra, Viviana; Azcona, Luis; Aubele, Adalia; Mataix, Luis; Sánchez-Harguindey, Luis

2002-12-01

Interobserver variability is an important limitation of the stress echocardiography and depends on the echocardiographer training. Our aim was to evaluate if the use of contrast agents during dipyridamole stress echocardiography would improve the agreement between an experienced and a non-experienced observer in stress echo and therefore if contrast would affect the learning period of dypyridamole stress echo. Two independent observers without knowledge of any patient data interpreted all stress studies. One observer was an experienced one and the other had experience in echocardiography but not in stress echo. Two observers analysed 87 non-selected and consecutive studies. Out of the 87 studies, 46 were performed without contrast administration, whereas i.v. contrast (2.5 g Levovist by two bolus at rest and at peak stress) was administered in 41. In all cases, second harmonic imaging and stress digitalisation pack was used. The agreement between observers showed a kappa index of 0.58 and 0.83 without and with contrast administration, respectively. The use of contrast agents provides a better agreement in the evaluation of stress echo between an experienced and a non-experienced observer in stress echo. Adding routinely contrast agents could probably reduce the number of exams required for the necessary learning curve in stress echocardiography.

Promise and problems in using stress triggering models for time-dependent earthquake hazard assessment

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Cocco, M.

2001-12-01

Earthquake stress changes can promote failures on favorably oriented faults and modify the seismicity pattern over broad regions around the causative faults. Because the induced stress perturbations modify the rate of production of earthquakes, they alter the probability of seismic events in a specified time window. Comparing the Coulomb stress changes with the seismicity rate changes and aftershock patterns can statistically test the role of stress transfer in earthquake occurrence. The interaction probability may represent a further tool to test the stress trigger or shadow model. The probability model, which incorporate stress transfer, has the main advantage to include the contributions of the induced stress perturbation (a static step in its present formulation), the loading rate and the fault constitutive properties. Because the mechanical conditions of the secondary faults at the time of application of the induced load are largely unkown, stress triggering can only be tested on fault populations and not on single earthquake pairs with a specified time delay. The interaction probability can represent the most suitable tool to test the interaction between large magnitude earthquakes. Despite these important implications and the stimulating perspectives, there exist problems in understanding earthquake interaction that should motivate future research but at the same time limit its immediate social applications. One major limitation is that we are unable to predict how and if the induced stress perturbations modify the ratio between small versus large magnitude earthquakes. In other words, we cannot distinguish between a change in this ratio in favor of small events or of large magnitude earthquakes, because the interaction probability is independent of magnitude. Another problem concerns the reconstruction of the stressing history. The interaction probability model is based on the response to a static step; however, we know that other processes contribute to

AsrR is an oxidative stress sensing regulator modulating Enterococcus faecium opportunistic traits, antimicrobial resistance, and pathogenicity.

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François Lebreton

Full Text Available Oxidative stress serves as an important host/environmental signal that triggers a wide range of responses in microorganisms. Here, we identified an oxidative stress sensor and response regulator in the important multidrug-resistant nosocomial pathogen Enterococcus faecium belonging to the MarR family and called AsrR (antibiotic and stress response regulator. The AsrR regulator used cysteine oxidation to sense the hydrogen peroxide which results in its dissociation to promoter DNA. Transcriptome analysis showed that the AsrR regulon was composed of 181 genes, including representing functionally diverse groups involved in pathogenesis, antibiotic and antimicrobial peptide resistance, oxidative stress, and adaptive responses. Consistent with the upregulated expression of the pbp5 gene, encoding a low-affinity penicillin-binding protein, the asrR null mutant was found to be more resistant to β-lactam antibiotics. Deletion of asrR markedly decreased the bactericidal activity of ampicillin and vancomycin, which are both commonly used to treat infections due to enterococci, and also led to over-expression of two major adhesins, acm and ecbA, which resulted in enhanced in vitro adhesion to human intestinal cells. Additional pathogenic traits were also reinforced in the asrR null mutant including greater capacity than the parental strain to form biofilm in vitro and greater persistance in Galleria mellonella colonization and mouse systemic infection models. Despite overexpression of oxidative stress-response genes, deletion of asrR was associated with a decreased oxidative stress resistance in vitro, which correlated with a reduced resistance to phagocytic killing by murine macrophages. Interestingly, both strains showed similar amounts of intracellular reactive oxygen species. Finally, we observed a mutator phenotype and enhanced DNA transfer frequencies in the asrR deleted strain. These data indicate that AsrR plays a major role in antimicrobial

Stress coping strategies among agricultural extension agents in Oyo ...

African Journals Online (AJOL)

Stress coping strategies among agricultural extension agents in Oyo State, Nigeria. ... Journal Home > Vol 20, No 1 (2016) >. Log in or ... Employees should have control over work flow to reduce work stress and increase work efficiency.

Mir-34a mimics are potential therapeutic agents for p53-mutated and chemo-resistant brain tumour cells.

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Yuen Ngan Fan

Full Text Available Chemotherapeutic drug resistance and relapse remains a major challenge for paediatric (medulloblastoma and adult (glioblastoma brain tumour treatment. Medulloblastoma tumours and cell lines with mutations in the p53 signalling pathway have been shown to be specifically insensitive to DNA damaging agents. The aim of this study was to investigate the potential of triggering cell death in p53 mutated medulloblastoma cells by a direct activation of pro-death signalling downstream of p53 activation. Since non-coding microRNAs (miRNAs have the ability to fine tune the expression of a variety of target genes, orchestrating multiple downstream effects, we hypothesised that triggering the expression of a p53 target miRNA could induce cell death in chemo-resistant cells. Treatment with etoposide, increased miR-34a levels in a p53-dependent fashion and the level of miR-34a transcription was correlated with the cell sensitivity to etoposide. miR-34a activity was validated by measuring the expression levels of one of its well described target: the NADH dependent sirtuin1 (SIRT1. Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines. Our results show that the need of a functional p53 signaling pathway can be bypassed by direct activation of miR-34a in brain tumour cells.

Thermal stress resistance of ion implanted sapphire crystals

International Nuclear Information System (INIS)

Gurarie, V.N.; Jamieson, D.N.; Szymanski, R.; Orlov, A.V.; Williams, J.S.; Conway, M.

1999-01-01

Monocrystals of sapphire have been subjected to ion implantation with 86 keV Si - and 80 keV Cr - ions to doses in the range of 5x10 14 -5x10 16 cm -2 prior to thermal stress testing in a pulsed plasma. Above a certain critical dose ion implantation is shown to modify the near-surface structure of samples by introducing damage, which makes crack nucleation easier under the applied stress. The effect of ion dose on the stress resistance is investigated and the critical doses which produce a noticeable change in the stress resistance are determined. The critical dose for Si ions is shown to be much lower than that for Cr - ions. However, for doses exceeding 2x10 16 cm -2 the stress resistance parameter decreases to approximately the same value for both implants. The size of the implantation-induced crack nucleating centers and the density of the implantation-induced defects are considered to be the major factors determining the stress resistance of sapphire crystals irradiated with Si - and Cr - ions

Low Temperature-Induced 30 (LTI30 positively regulates drought stress resistance in Arabidopsis: effect on abscisic acid sensitivity and hydrogen peroxide accumulation

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Haitao eShi

2015-10-01

Full Text Available As a dehydrin belonging to group II late embryogenesis abundant protein (LEA family, Arabidopsis Low Temperature-Induced 30 (LTI30/XERO2 has been shown to be involved in plant freezing stress resistance. However, the other roles of AtLTI30 remain unknown. In this study, we found that the expression of AtLTI30 was largely induced by drought stress and abscisic acid (ABA treatments. Thereafter, AtLTI30 knockout mutants and overexpressing plants were isolated to investigate the possible involvement of AtLTI30 in ABA and drought stress responses. AtLTI30 knockout mutants were less sensitive to ABA-mediated seed germination, while AtLTI30 overexpressing plants were more sensitive to ABA compared with wild type (WT. Consistently, the AtLTI30 knockout mutants displayed decreased drought stress resistance, while the AtLTI30 overexpressing plants showed improved drought stress resistance compared with WT, as evidenced by a higher survival rate and lower leaf water loss than WT after drought stress. Moreover, manipulation of AtLTI30 expression positively regulated the activities of catalases (CATs and endogenous proline content, as a result, negatively regulated drought stress-triggered hydrogen peroxide (H2O2 accumulation. All these results indicate that AtLTI30 is a positive regulator of plant drought stress resistance, partially through the modulation of ABA sensitivity, H2O2 and proline accumulation.

Safety of ultrasound contrast agents in stress echocardiography.

Science.gov (United States)

Gabriel, Ruvin S; Smyth, Yvonne M; Menon, Venu; Klein, Allan L; Grimm, Richard A; Thomas, James D; Sabik, Ellen Mayer

2008-11-01

Definity and Optison are perflutren-based ultrasound contrast agents used in echocardiography. United States Food and Drug Administration warnings regarding serious cardiopulmonary reactions and death after Definity administration highlighted the limited safety data in patients who undergo contrast stress echocardiography. From 1998 and 2007, 2,022 patients underwent dobutamine stress echocardiography and 2,764 underwent exercise stress echocardiography with contrast at the Cleveland Clinic. The echocardiographic database, patient records, and the Social Security Death Index were reviewed for the timing and cause of death, severe adverse events, arrhythmias, and symptoms. Complication rates for contrast dobutamine stress echocardiography and exercise stress echocardiography were compared with those in a control group of 5,012 patients matched for test year and type who did not receive contrast. Ninety-five percent of studies were performed in outpatients. There were no differences in the rates of severe adverse events (0.19% vs 0.17%, p = 0.7), death within 24 hours (0% vs 0.04%, p = 0.1), cardiac arrest (0.04% vs 0.04%, p = 0.96), and sustained ventricular tachycardia (0.2% vs 0.1%, p = 0.32) between patients receiving and not receiving intravenous contrast, respectively. In conclusion, severe adverse reactions to intravenous contrast agents during stress echocardiography are uncommon. Contrast use does not add to the baseline risk for severe adverse events in patients who undergo stress echocardiography.

Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

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Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

2016-01-01

In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways.

Science.gov (United States)

Dues, Dylan J; Andrews, Emily K; Schaar, Claire E; Bergsma, Alexis L; Senchuk, Megan M; Van Raamsdonk, Jeremy M

2016-04-01

In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage.

The Cytochrome bd Oxidase of Porphyromonas gingivalis Contributes to Oxidative Stress Resistance and Dioxygen Tolerance.

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Julia Leclerc

Full Text Available Porphyromonas gingivalis is an etiologic agent of periodontal disease in humans. The disease is associated with the formation of a mixed oral biofilm which is exposed to oxygen and environmental stress, such as oxidative stress. To investigate possible roles for cytochrome bd oxidase in the growth and persistence of this anaerobic bacterium inside the oral biofilm, mutant strains deficient in cytochrome bd oxidase activity were characterized. This study demonstrated that the cytochrome bd oxidase of Porphyromonas gingivalis, encoded by cydAB, was able to catalyse O2 consumption and was involved in peroxide and superoxide resistance, and dioxygen tolerance.

Stress, depression, quality of life and salivary cortisol levels in community health agents.

Science.gov (United States)

Knuth, Berenice Scaletzky; Cocco, Rafaela Abreu; Radtke, Vinicius Augusto; Medeiros, João Ricardo Carvalho; Oses, Jean Pierre; Wiener, Carolina David; Jansen, Karen

2016-06-01

To determine the prevalence of and factors associated with depression and stress with perceived quality of life and the salivary cortisol levels in Community Health Agent (CHA). Materials and Methods Cross-sectional descriptive study of CHAs in Pelotas-RS, Brazil. Data collection, including sociodemographic information and factors related to work and health. Beck Depression Inventory (BDI) II was used to assess depressive symptoms, Inventory of Stress Symptoms Lipp (ISSL) was used for the analysis of stress and the WHOQOL-BREF was used to investigate quality of life. Salivary cortisol was quantified via ELISA test. The assessments showed that 71.0% are in a state of stress resistance, 30.5% were in the alert state of stress and 32.8% were in the stress state of exhaustion. Depressive episodes (BDI≥12) were observed in 28.2%. The environmental domain had the lowest score for quality of life. We observed significantly higher salivary cortisol levels in CHAs with less than 1 year of service and with the lowest quality of life scores in the environmental subsection. A high prevalence of stress and depression was observed in this sample of CHAs. In addition, the worst levels of quality of life were identified in the environmental subsection. Cortisol levels corroborate these findings regarding quality of life within the environmental domain and began working less than a year previously.

Loss of Oca2 disrupts the unfolded protein response and increases resistance to endoplasmic reticulum stress in melanocytes.

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Cheng, Tsing; Orlow, Seth J; Manga, Prashiela

2013-11-01

Accumulation of proteins in the endoplasmic reticulum (ER) typically induces stress and initiates the unfolded protein response (UPR) to facilitate recovery. If homeostasis is not restored, apoptosis is induced. However, adaptation to chronic UPR activation can increase resistance to subsequent acute ER stress. We therefore investigated adaptive mechanisms in Oculocutaneous albinism type 2 (Oca2)-null melanocytes where UPR signaling is arrested despite continued tyrosinase accumulation leading to resistance to the chemical ER stressor thapsigargin. Although thapsigargin triggers UPR activation, instead of Perk-mediated phosphorylation of eIF2α, in Oca2-null melanocytes, eIF2α was rapidly dephosphorylated upon treatment. Dephosphorylation was mediated by the Gadd34-PP1α phosphatase complex. Gadd34-complex inhibition blocked eIF2α dephosphorylation and significantly increased Oca2-null melanocyte sensitivity to thapsigargin. Thus, Oca2-null melanocytes adapt to acute ER stress by disruption of pro-apoptotic Perk signaling, which promotes cell survival. This is the first study to demonstrate rapid eIF2α dephosphorylation as an adaptive mechanism to ER stress. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stathmin Mediates Hepatocyte Resistance to Death from Oxidative Stress by down Regulating JNK

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Zhao, Enpeng; Amir, Muhammad; Lin, Yu; Czaja, Mark J.

2014-01-01

Stathmin 1 performs a critical function in cell proliferation by regulating microtubule polymerization. This proliferative function is thought to explain the frequent overexpression of stathmin in human cancer and its correlation with a bad prognosis. Whether stathmin also functions in cell death pathways is unclear. Stathmin regulates microtubules in part by binding free tubulin, a process inhibited by stathmin phosphorylation from kinases including c-Jun N-terminal kinase (JNK). The involvement of JNK activation both in stathmin phosphorylation, and in hepatocellular resistance to oxidative stress, led to an examination of the role of stathmin/JNK crosstalk in oxidant-induced hepatocyte death. Oxidative stress from menadione-generated superoxide induced JNK-dependent stathmin phosphorylation at Ser-16, Ser-25 and Ser-38 in hepatocytes. A stathmin knockdown sensitized hepatocytes to both apoptotic and necrotic cell death from menadione without altering levels of oxidant generation. The absence of stathmin during oxidative stress led to JNK overactivation that was the mechanism of cell death as a concomitant knockdown of JNK1 or JNK2 blocked death. Hepatocyte death from JNK overactivation was mediated by the effects of JNK on mitochondria. Mitochondrial outer membrane permeabilization occurred in stathmin knockdown cells at low concentrations of menadione that triggered apoptosis, whereas mitochondrial β-oxidation and ATP homeostasis were compromised at higher, necrotic menadione concentrations. Stathmin therefore mediates hepatocyte resistance to death from oxidative stress by down regulating JNK and maintaining mitochondrial integrity. These findings demonstrate a new mechanism by which stathmin promotes cell survival and potentially tumor growth. PMID:25285524

Stathmin mediates hepatocyte resistance to death from oxidative stress by down regulating JNK.

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Enpeng Zhao

Full Text Available Stathmin 1 performs a critical function in cell proliferation by regulating microtubule polymerization. This proliferative function is thought to explain the frequent overexpression of stathmin in human cancer and its correlation with a bad prognosis. Whether stathmin also functions in cell death pathways is unclear. Stathmin regulates microtubules in part by binding free tubulin, a process inhibited by stathmin phosphorylation from kinases including c-Jun N-terminal kinase (JNK. The involvement of JNK activation both in stathmin phosphorylation, and in hepatocellular resistance to oxidative stress, led to an examination of the role of stathmin/JNK crosstalk in oxidant-induced hepatocyte death. Oxidative stress from menadione-generated superoxide induced JNK-dependent stathmin phosphorylation at Ser-16, Ser-25 and Ser-38 in hepatocytes. A stathmin knockdown sensitized hepatocytes to both apoptotic and necrotic cell death from menadione without altering levels of oxidant generation. The absence of stathmin during oxidative stress led to JNK overactivation that was the mechanism of cell death as a concomitant knockdown of JNK1 or JNK2 blocked death. Hepatocyte death from JNK overactivation was mediated by the effects of JNK on mitochondria. Mitochondrial outer membrane permeabilization occurred in stathmin knockdown cells at low concentrations of menadione that triggered apoptosis, whereas mitochondrial β-oxidation and ATP homeostasis were compromised at higher, necrotic menadione concentrations. Stathmin therefore mediates hepatocyte resistance to death from oxidative stress by down regulating JNK and maintaining mitochondrial integrity. These findings demonstrate a new mechanism by which stathmin promotes cell survival and potentially tumor growth.

Stress Response and Artemisinin Resistance in Malaria Parasite

Science.gov (United States)

2017-07-01

AWARD NUMBER: W81XWH-16-1-0241 TITLE: Stress Response and Artemisinin Resistance in Malaria Parasite PRINCIPAL INVESTIGATOR: Juan C. Pizarro...SUBTITLE Stress Response and Artemisinin Resistance in Malaria Parasite 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0241 5c. PROGRAM ELEMENT...13. SUPPLEMENTARY NOTES 14. ABSTRACT In malaria , drug resistance is a major treat to disease control efforts. Unfortunately, there is a significant

40 CFR 91.427 - Catalyst thermal stress resistance evaluation.

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2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Catalyst thermal stress resistance... Procedures § 91.427 Catalyst thermal stress resistance evaluation. (a)(1) The purpose of the evaluation procedure specified in this section is to determine the effect of thermal stress on catalyst conversion...

40 CFR 90.427 - Catalyst thermal stress resistance evaluation.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Catalyst thermal stress resistance... Gaseous Exhaust Test Procedures § 90.427 Catalyst thermal stress resistance evaluation. (a) The purpose of... catalyst conversion efficiency for Phase 1 engines. The thermal stress is imposed on the test catalyst by...

Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal Ca2+ release in Leishmania mexicana promastigotes

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Figarella K

2015-12-01

Full Text Available The protozoan parasite Leishmania causes a variety of sicknesses with different clinical manifestations known as leishmaniasis. The chemotherapy currently in use is not adequate because of their side effects, resistance occurrence, and recurrences. Investigations looking for new targets or new active molecules focus mainly on the disruption of parasite specific pathways. In this sense, ergosterol biosynthesis is one of the most attractive because it does not occur in mammals. Here, we report the synthesis of ergosterone coupled molecules and the characterization of their biological activity on Leishmania mexicana promastigotes. Molecule synthesis involved three steps: ergosterone formation using Jones oxidation, synthesis of Girard reagents, and coupling reaction. All compounds were obtained in good yield and high purity. Results show that ergosterone-triazol molecules (Erg-GTr and Erg-GTr2 exhibit an antiproliferative effect in low micromolar range with a selectivity index ~10 when compared to human dermic fibroblasts. Addition of Erg-GTr or Erg-GTr2 to parasites led to a rapid [Ca2+]cyt increase and acidocalcisomes alkalinization, indicating that Ca2+ was released from this organelle. Evaluation of cell death markers revealed some apoptosis-like indicators, as phosphatidylserine exposure, DNA damage, and cytosolic vacuolization and autophagy exacerbation. Furthermore, mitochondrion hyperpolarization and superoxide production increase were detected already 6 hours after drug addition, denoting that oxidative stress is implicated in triggering the observed phenotype. Taken together our results indicate that ergosterone-triazol coupled molecules induce a regulated cell death process in the parasite and may represent starting point molecules in the search of new chemotherapeutic agents to combat leishmaniasis.

Genipin-induced inhibition of uncoupling protein-2 sensitizes drug-resistant cancer cells to cytotoxic agents.

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Ryan J Mailloux

2010-10-01

Full Text Available Uncoupling protein-2 (UCP2 is known to suppress mitochondrial reactive oxygen species (ROS production and is employed by drug-resistant cancer cells to mitigate oxidative stress. Using the drug-sensitive HL-60 cells and the drug-resistant MX2 subline as model systems, we show that genipin, a UCP2 inhibitor, sensitizes drug-resistant cells to cytotoxic agents. Increased MX2 cell death was observed upon co-treatment with genipin and different doses of menadione, doxorubicin, and epirubicin. DCFH-DA fluorimetry revealed that the increase in MX2 cell death was accompanied by enhanced cellular ROS levels. The drug-induced increase in ROS was linked to genipin-mediated inhibition of mitochondrial proton leak. State 4 and resting cellular respiratory rates were higher in the MX2 cells in comparison to the HL-60 cells, and the increased respiration was readily suppressed by genipin in the MX2 cells. UCP2 accounted for a remarkable 37% of the resting cellular oxygen consumption indicating that the MX2 cells are functionally reliant on this protein. Higher amounts of UCP2 protein were detected in the MX2 versus the HL-60 mitochondria. The observed effects of genipin were absent in the HL-60 cells pointing to the selectivity of this natural product for drug-resistant cells. The specificity of genipin for UCP2 was confirmed using CHO cells stably expressing UCP2 in which genipin induced an ∼22% decrease in state 4 respiration. These effects were absent in empty vector CHO cells expressing no UCP2. Thus, the chemical inhibition of UCP2 with genipin sensitizes multidrug-resistant cancer cells to cytotoxic agents.

The heat-shock protein/chaperone network and multiple stress resistance.

Science.gov (United States)

Jacob, Pierre; Hirt, Heribert; Bendahmane, Abdelhafid

2017-04-01

Crop yield has been greatly enhanced during the last century. However, most elite cultivars are adapted to temperate climates and are not well suited to more stressful conditions. In the context of climate change, stress resistance is a major concern. To overcome these difficulties, scientists may help breeders by providing genetic markers associated with stress resistance. However, multistress resistance cannot be obtained from the simple addition of single stress resistance traits. In the field, stresses are unpredictable and several may occur at once. Consequently, the use of single stress resistance traits is often inadequate. Although it has been historically linked with the heat stress response, the heat-shock protein (HSP)/chaperone network is a major component of multiple stress responses. Among the HSP/chaperone 'client proteins', many are primary metabolism enzymes and signal transduction components with essential roles for the proper functioning of a cell. HSPs/chaperones are controlled by the action of diverse heat-shock factors, which are recruited under stress conditions. In this review, we give an overview of the regulation of the HSP/chaperone network with a focus on Arabidopsis thaliana. We illustrate the role of HSPs/chaperones in regulating diverse signalling pathways and discuss several basic principles that should be considered for engineering multiple stress resistance in crops through the HSP/chaperone network. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

OxyR-activated expression of Dps is important for Vibrio cholerae oxidative stress resistance and pathogenesis.

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Xiaoyun Xia

Full Text Available Vibrio cholerae is the causative agent of cholera, a dehydrating diarrheal disease. This Gram-negative pathogen is able to modulate its gene expression in order to combat stresses encountered in both aquatic and host environments, including stress posed by reactive oxygen species (ROS. In order to further the understanding of V. cholerae's transcriptional response to ROS, we performed an RNA sequencing analysis to determine the transcriptional profile of V. cholerae when exposed to hydrogen hydroperoxide. Of 135 differentially expressed genes, VC0139 was amongst the genes with the largest induction. VC0139 encodes a protein homologous to the DPS (DNA-binding protein from starved cells protein family, which are widely conserved and are implicated in ROS resistance in other bacteria. Using a promoter reporter assay, we show that during exponential growth, dps is induced by H2O2 in a manner dependent on the ROS-sensing transcriptional regulator, OxyR. Upon entry into stationary phase, the major stationary phase regulator RpoS is required to transcribe dps. Deletion of dps impaired V. cholerae resistance to both inorganic and organic hydroperoxides. Furthermore, we show that Dps is involved in resistance to multiple environmental stresses. Finally, we found that Dps is important for V. cholerae adult mouse colonization, but becomes dispensable in the presence of antioxidants. Taken together, our results suggest that Dps plays vital roles in both V. cholerae stress resistance and pathogenesis.

[Antibibiotic resistance by nosocomial infections' causal agents].

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Salazar-Holguín, Héctor Daniel; Cisneros-Robledo, María Elena

2016-01-01

The antibibiotic resistance by nosocomial infections (NI) causal agents constitutes a seriously global problematic that involves the Mexican Institute of Social Security's Regional General Hospital 1 in Chihuahua, Mexico; although with special features that required to be specified and evaluated, in order to concrete an effective therapy. Observational, descriptive and prospective study; by means of active vigilance all along 2014 in order to detect the nosocomial infections, for epidemiologic study, culture and antibiogram to identify its causal agents and antibiotics resistance and sensitivity. Among 13527 hospital discharges, 1079 displayed NI (8 %), standed out: the related on vascular lines, of surgical site, pneumonia and urinal track; they added up two thirds of the total. We carried out culture and antibiogram about 300 of them (27.8 %); identifying 31 bacterian species, mainly seven of those (77.9 %): Escherichia coli, Staphylococcus aureus and epidermidis, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Enterobacter cloacae; showing multiresistance to 34 tested antibiotics, except in seven with low or without resistance at all: vancomycin, teicoplanin, linezolid, quinupristin-dalfopristin, piperacilin-tazobactam, amikacin and carbapenems. When we contrasted those results with the recommendations in the clinical practice guides, it aroused several contradictions; so they must be taken with reserves and has to be tested in each hospital, by means of cultures and antibiograms in practically every case of nosocomial infection.

Stress Induced Cardiomyopathy Triggered by Acute Myocardial Infarction: A Case Series Challenging the Mayo Clinic Definition.

Science.gov (United States)

Christodoulidis, Georgios; Kundoor, Vishwa; Kaluski, Edo

2017-08-28

BACKGROUND Various physical and emotional factors have been previously described as triggers for stress induced cardiomyopathy. However, acute myocardial infarction as a trigger has never been reported. CASE REPORT We describe four patients who presented with an acute myocardial infarction, in whom the initial echocardiography revealed wall motion abnormalities extending beyond the coronary distribution of the infarct artery. Of the four patients identified, the mean age was 59 years; three patients were women and two patients had underlying psychiatric history. Electrocardiogram revealed ST elevation in the anterior leads in three patients; QTc was prolonged in all cases. All patients had ≤ moderately elevated troponin. Single culprit lesion was found uniformly in the proximal or mid left anterior descending artery. Initial echocardiography revealed severely reduced ejection fraction with relative sparing of the basal segments, whereas early repeat echocardiography revealed significant improvement in the left ventricular function in all patients. CONCLUSIONS This is the first case series demonstrating that acute myocardial infarction can trigger stress induced cardiomyopathy. Extensive reversible wall motion abnormalities, beyond the ones expected from angiography, accompanied by modest elevation in troponin and marked QTc prolongation, suggest superimposed stress induced cardiomyopathy.

Tsw gene-based resistance is triggered by a functional RNA silencing suppressor protein of the Tomato spotted wilt virus

NARCIS (Netherlands)

Ronde, de D.; Butterbach, P.B.E.; Lohuis, H.; Hedil, M.; Lent, van J.W.M.; Kormelink, R.J.M.

2013-01-01

As a result of contradictory reports, the avirulence (Avr) determinant that triggers Tsw gene-based resistance in Capsicum annuum against the Tomato spotted wilt virus (TSWV) is still unresolved. Here, the N and NSs genes of resistance-inducing (RI) and resistance-breaking (RB) isolates were cloned

Radioresistant Spodoptera frugiperda 9 insect cells display excessive resistance to 'endoplasmic reticulum' stress and calcium disturbances via pre-emptive activation of unfolded protein response pathway

International Nuclear Information System (INIS)

Guleria, Ayushi; Chandna, Sudhir

2016-01-01

Endoplasmic Reticulum (ER) performs multiple cellular functions such as proper folding of newly synthesized proteins and calcium homeostasis. ER stress triggers unfolded protein response (UPR) that attempts to restore normal ER function and resists damage-induced cell death. Lepidopteran Sf9 insect cells (derived from Spodoptera frugiperda) display 100-200 times higher radioresistance than mammalian cells. We have earlier reported that gamma-radiation doses <1000 Gy fail to trigger increase in cytosolic calcium in Sf9 cells, indicating resilience to calcium/ ER disturbances

Alloy SCR-3 resistant to stress corrosion cracking

International Nuclear Information System (INIS)

Kowaka, Masamichi; Fujikawa, Hisao; Kobayashi, Taiki

1977-01-01

Austenitic stainless steel is used widely because the corrosion resistance, workability and weldability are excellent, but the main fault is the occurrence of stress corrosion cracking in the environment containing chlorides. Inconel 600, most resistant to stress corrosion cracking, is not necessarily safe under some severe condition. In the heat-affected zone of SUS 304 tubes for BWRs, the cases of stress corrosion cracking have occurred. The conventional testing method of stress corrosion cracking using boiling magnesium chloride solution has been problematical because it is widely different from actual environment. The effects of alloying elements on stress corrosion cracking are remarkably different according to the environment. These effects were investigated systematically in high temperature, high pressure water, and as the result, Alloy SCR-3 with excellent stress corrosion cracking resistance was found. The physical constants and the mechanical properties of the SCR-3 are shown. The states of stress corrosion cracking in high temperature, high pressure water containing chlorides and pure water, polythionic acid, sodium phosphate solution and caustic soda of the SCR-3, SUS 304, Inconel 600 and Incoloy 800 are compared and reported. (Kako, I.)

Emotions and stress increase respiratory resistance in asthma.

Science.gov (United States)

Ritz, T; Steptoe, A; DeWilde, S; Costa, M

2000-01-01

Clinical reports suggest that various emotions and types of stress can precipitate asthmatic symptoms, but there is little experimental evidence to substantiate this claim. We studied the impact of different emotional states and stress on respiratory resistance in asthmatic and nonasthmatic individuals. Participants (24 asthmatic and 24 nonasthmatic patients) viewed short film sequences selected to induce anxiety, anger, depression, elation, happiness, contentment, or a neutral affective state and completed two stressful tasks, mental arithmetic to induce active coping efforts and viewing of medical slides to induce passive coping efforts. Oscillatory resistance, heart rate, blood pressure, baroreflex sensitivity, skin conductance level, respiration rate and volume, and self-reported affective state were measured throughout the session. Uniform increases in oscillatory resistance were found in all emotional states compared with the neutral state and during mental arithmetic in both groups. Asthmatic patients showed stronger reactions to the medical slides than healthy control subjects, with significant increases in oscillatory resistance, blood pressure, skin conductance level, and minute volume, as well as higher levels of self-reported depression, arousal, and shortness of breath. Changes in oscillatory resistance were inconsistently correlated with other physiological indices. Various emotional states and stress increase oscillatory resistance largely independently of concurrent increases in autonomic or ventilatory activity. The particular sensitivity of asthmatics to passive coping demand requires additional research.

Transgenic crops with an improved resistance to biotic stresses. A review

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Tohidfar, M.

2015-01-01

Full Text Available Introduction. Pests, diseases and weeds (biotic stresses are significant limiting factors for crop yield and production. However, the limitations associated with conventional breeding methods necessitated the development of alternative methods for improving new varieties with higher resistance to biotic stresses. Molecular techniques have developed applicable methods for genetic transformation of a wide range of plants. Genetic engineering approach has been demonstrated to provide enormous options for the selection of the resistance genes from different sources to introduce them into plants to provide resistance against different biotic stresses. Literature. In this review, we focus on strategies to achieve the above mentioned objectives including expression of insecticidal, antifungal, antibacterial, antiviral resistance and herbicide detoxification for herbicide resistance. Conclusion. Regardless of the concerns about commercialization of products from genetically modified (GM crops resistant to biotic stresses, it is observed that the cultivation area of these crops is growing fast each year. Considering this trend, it is expected that production and commercialization of GM crops resistant to biotic stresses will continue to increase but will also extend to production of crops resistant to abiotic stresses (e.g. drought, salinity, etc. in a near future.

Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

KAUST Repository

Yun, Kil-Young; Park, Myoung Ryoul; Mohanty, Bijayalaxmi; Herath, Venura; Xu, Fuyu; Mauleon, Ramil; Wijaya, Edward; Bajic, Vladimir B.; Bruskiewich, Richard; de los Reyes, Benildo G

2010-01-01

-plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress

Early resistance change and stress/electromigrationmodeling in aluminium interconnects

NARCIS (Netherlands)

Petrescu, V.; Mouthaan, A.J.; Schoenmaker, W.

1997-01-01

A complete description for early resistance change and two dimensional simulation of mechanical stress evolution in confined Al interconnects, related to the electromigration, is given in this paper. The model, combines the stress/ vacancy concentration evolution with the early resistance change of

Bmi1 confers resistance to oxidative stress on hematopoietic stem cells.

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Shunsuke Nakamura

Full Text Available The polycomb-group (PcG proteins function as general regulators of stem cells. We previously reported that retrovirus-mediated overexpression of Bmi1, a gene encoding a core component of polycomb repressive complex (PRC 1, maintained self-renewing hematopoietic stem cells (HSCs during long-term culture. However, the effects of overexpression of Bmi1 on HSCs in vivo remained to be precisely addressed.In this study, we generated a mouse line where Bmi1 can be conditionally overexpressed under the control of the endogenous Rosa26 promoter in a hematopoietic cell-specific fashion (Tie2-Cre;R26Stop(FLBmi1. Although overexpression of Bmi1 did not significantly affect steady state hematopoiesis, it promoted expansion of functional HSCs during ex vivo culture and efficiently protected HSCs against loss of self-renewal capacity during serial transplantation. Overexpression of Bmi1 had no effect on DNA damage response triggered by ionizing radiation. In contrast, Tie2-Cre;R26Stop(FLBmi1 HSCs under oxidative stress maintained a multipotent state and generally tolerated oxidative stress better than the control. Unexpectedly, overexpression of Bmi1 had no impact on the level of intracellular reactive oxygen species (ROS.Our findings demonstrate that overexpression of Bmi1 confers resistance to stresses, particularly oxidative stress, onto HSCs. This thereby enhances their regenerative capacity and suggests that Bmi1 is located downstream of ROS signaling and negatively regulated by it.

A new cellular stress response that triggers centriolar satellite reorganization and ciliogenesis

DEFF Research Database (Denmark)

Villumsen, Bine H; Danielsen, Jannie R; Povlsen, Lou

2013-01-01

uncover a new two-pronged signalling response, which by coupling p38-dependent phosphorylation with MIB1-catalysed ubiquitylation of ciliogenesis-promoting factors plays an important role in controlling centriolar satellite status and key centrosomal functions in a cell stress-regulated manner.......Centriolar satellites are small, granular structures that cluster around centrosomes, but whose biological function and regulation are poorly understood. We show that centriolar satellites undergo striking reorganization in response to cellular stresses such as UV radiation, heat shock......, and transcription blocks, invoking acute and selective displacement of the factors AZI1/CEP131, PCM1, and CEP290 from this compartment triggered by activation of the stress-responsive kinase p38/MAPK14. We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts...

Association between the consumption of antimicrobial agents in animal husbandry and the occurrence of resistant bacteria among food animals

DEFF Research Database (Denmark)

Aarestrup, Frank Møller

1999-01-01

Antimicrobial agents are used in food animals for therapy and prophylaxis of bacterial infections and in feed to promote growth. The use of antimicrobial agents for food animals may cause problems in the therapy of infections by selecting for resistance among bacteria pathogenic for animals...... animals, the quantitative impact of the use of different antimicrobial agents on selection for resistance and the most appropriate treatment regimens to limit the development of resistance is incomplete. Surveillance programmes monitoring the occurrence and development of resistance and consumption...... or humans. The emergence of resistant bacteria and resistance genes following the use of antimicrobial agents is relatively well documented and it seems evident that all antimicrobial agents will select for resistance. However, current knowledge regarding the occurrence of antimicrobial resistance in food...

Melatonin Modulates Neuronal Cell Death Induced by Endoplasmic Reticulum Stress under Insulin Resistance Condition.

Science.gov (United States)

Song, Juhyun; Kim, Oh Yoen

2017-06-10

Insulin resistance (IR) is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER) stress under IR condition using SH-SY5Y neuroblastoma cells. Apoptosis cell death signaling markers (cleaved Poly [ADP-ribose] polymerase 1 (PARP), p53, and Bax) and ER stress markers (phosphorylated eIF2α (p-eIF2α), ATF4, CHOP, p-IRE1 , and spliced XBP1 (sXBP1)) were measured using reverse transcription-PCR, quantitative PCR, and western blottings. Immunofluorescence staining was also performed for p-ASK1 and p-IRE1 . The mRNA or protein expressions of cell death signaling markers and ER stress markers were increased under IR condition, but significantly attenuated by melatonin treatment. Insulin-induced activation of ASK1 ( p-ASK1 ) was also dose dependently attenuated by melatonin treatment. The regulatory effect of melatonin on neuronal cells under IR condition was associated with ASK1 signaling. In conclusion, the result suggested that melatonin may alleviate ER stress under IR condition, thereby regulating neuronal cell death signaling.

A set of nutrient limitations trigger yeast cell death in a nitrogen-dependent manner during wine alcoholic fermentation.

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Camille Duc

Full Text Available Yeast cell death can occur during wine alcoholic fermentation. It is generally considered to result from ethanol stress that impacts membrane integrity. This cell death mainly occurs when grape musts processing reduces lipid availability, resulting in weaker membrane resistance to ethanol. However the mechanisms underlying cell death in these conditions remain unclear. We examined cell death occurrence considering yeast cells ability to elicit an appropriate response to a given nutrient limitation and thus survive starvation. We show here that a set of micronutrients (oleic acid, ergosterol, pantothenic acid and nicotinic acid in low, growth-restricting concentrations trigger cell death in alcoholic fermentation when nitrogen level is high. We provide evidence that nitrogen signaling is involved in cell death and that either SCH9 deletion or Tor inhibition prevent cell death in several types of micronutrient limitation. Under such limitations, yeast cells fail to acquire any stress resistance and are unable to store glycogen. Unexpectedly, transcriptome analyses did not reveal any major changes in stress genes expression, suggesting that post-transcriptional events critical for stress response were not triggered by micronutrient starvation. Our data point to the fact that yeast cell death results from yeast inability to trigger an appropriate stress response under some conditions of nutrient limitations most likely not encountered by yeast in the wild. Our conclusions provide a novel frame for considering both cell death and the management of nutrients during alcoholic fermentation.

Hexavalent chromium, a lung carcinogen, confers resistance to thermal stress and interferes with heat shock protein expression in human bronchial epithelial cells.

Science.gov (United States)

Abreu, Patrícia L; Cunha-Oliveira, Teresa; Ferreira, Leonardo M R; Urbano, Ana M

2018-03-16

Exposure to hexavalent chromium [Cr(VI)], a lung carcinogen, triggers several types of cellular stresses, namely oxidative, genotoxic and proteotoxic stresses. Given the evolutionary character of carcinogenesis, it is tempting to speculate that cells that survive the stresses produced by this carcinogen become more resistant to subsequent stresses, namely those encountered during neoplastic transformation. To test this hypothesis, we determined whether pre-incubation with Cr(VI) increased the resistance of human bronchial epithelial cells (BEAS-2B cells) to the antiproliferative action of acute thermal shock, used here as a model for stress. In line with the proposed hypothesis, it was observed that, at mildly cytotoxic concentrations, Cr(VI) attenuated the antiproliferative effects of both cold and heat shock. Mechanistically, Cr(VI) interfered with the expression of two components of the stress response pathway: heat shock proteins Hsp72 and Hsp90α. Specifically, Cr(VI) significantly depleted the mRNA levels of the former and the protein levels of the latter. Significantly, these two proteins are members of heat shock protein (Hsp) families (Hsp70 and Hsp90, respectively) that have been implicated in carcinogenesis. Thus, our results confirm and extend previous studies showing the capacity of Cr(VI) to interfere with the expression of stress response components.

Progranulin causes adipose insulin resistance via increased autophagy resulting from activated oxidative stress and endoplasmic reticulum stress.

Science.gov (United States)

Guo, Qinyue; Xu, Lin; Li, Huixia; Sun, Hongzhi; Liu, Jiali; Wu, Shufang; Zhou, Bo

2017-01-31

Progranulin (PGRN) has recently emerged as an important regulator for insulin resistance. However, the direct effect of progranulin in adipose insulin resistance associated with the autophagy mechanism is not fully understood. In the present study, progranulin was administered to 3T3-L1 adipocytes and C57BL/6 J mice with/without specific inhibitors of oxidative stress and endoplasmic reticulum stress, and metabolic parameters, oxidative stress, endoplasmic reticulum stress and autophagy markers were assessed. Progranulin treatment increased iNOS expression, NO synthesis and ROS generation, and elevated protein expressions of CHOP, GRP78 and the phosphorylation of PERK, and caused a significant increase in Atg7 and LC3-II protein expression and a decreased p62 expression, and decreased insulin-stimulated tyrosine phosphorylation of IRS-1 and glucose uptake, demonstrating that progranulin activated oxidative stress and ER stress, elevated autophagy and induced insulin insensitivity in adipocytes and adipose tissue of mice. Interestingly, inhibition of iNOS and ER stress both reversed progranulin-induced stress response and increased autophagy, protecting against insulin resistance in adipocytes. Furthermore, the administration of the ER stress inhibitor 4-phenyl butyric acid reversed the negative effect of progranulin in vivo. Our findings showed the clinical potential of the novel adipokine progranulin in the regulation of insulin resistance, suggesting that progranulin might mediate adipose insulin resistance, at least in part, by inducing autophagy via activated oxidative stress and ER stress.

Headache triggers in the US military.

Science.gov (United States)

Theeler, Brett J; Kenney, Kimbra; Prokhorenko, Olga A; Fideli, Ulgen S; Campbell, William; Erickson, Jay C

2010-05-01

Headaches can be triggered by a variety of factors. Military service members have a high prevalence of headache but the factors triggering headaches in military troops have not been identified. The objective of this study is to determine headache triggers in soldiers and military beneficiaries seeking specialty care for headaches. A total of 172 consecutive US Army soldiers and military dependents (civilians) evaluated at the headache clinics of 2 US Army Medical Centers completed a standardized questionnaire about their headache triggers. A total of 150 (87%) patients were active-duty military members and 22 (13%) patients were civilians. In total, 77% of subjects had migraine; 89% of patients reported at least one headache trigger with a mean of 8.3 triggers per patient. A wide variety of headache triggers was seen with the most common categories being environmental factors (74%), stress (67%), consumption-related factors (60%), and fatigue-related factors (57%). The types of headache triggers identified in active-duty service members were similar to those seen in civilians. Stress-related triggers were significantly more common in soldiers. There were no significant differences in trigger types between soldiers with and without a history of head trauma. Headaches in military service members are triggered mostly by the same factors as in civilians with stress being the most common trigger. Knowledge of headache triggers may be useful for developing strategies that reduce headache occurrence in the military.

Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

Science.gov (United States)

Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

2011-11-01

The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.

Circumvention of inherent or acquired cytotoxic drug resistance in vitro using combinations of modulating agents.

Science.gov (United States)

Cadagan, David; Merry, Stephen

2013-10-01

Modulating agents are used to circumvent drug resistance in the clinical setting. However achievable serum concentrations are often lower than those which are optimal in vitro. Combination of modulating agents with non-overlapping toxicities may overcome this obstacle. We have investigated combinations of three modulating agents (quinine, verapamil, and cinnarizine) to circumvent inherent or acquired resistance to the cytotoxic drugs doxorubicin, vincristine and paclitaxel. Dose-response curves to cytotoxic drugs in the presence/absence of modulating agents were determined using colony formation and cell proliferation assays. Doxorubicin accumulation into cell monolayers was measured by fluorescence spectrophotometry. Greater (1.9-fold) sensitisation to particular cytotoxic drugs was observed for certain combinations of modulating agents compared to individual effects. The most effective combination was quinine-plus-verapamil with the cytotoxic drug doxorubicin. This increase in sensitivity was associated with increased doxorubicin accumulation. Such enhanced activity was, however, not observed for all combinations of modulating agents or for all studied cytotoxic drugs. The findings of the present study suggest certain combinations of modulating agents to have a clinical role in circumventing drug resistance. Particular combinations of modulating agents must be carefully chosen to suit particular cytotoxic drug treatments.

Psychological stress impairs short-term muscular recovery from resistance exercise.

Science.gov (United States)

Stults-Kolehmainen, Matthew A; Bartholomew, John B

2012-11-01

The primary aim of this study was to determine whether chronic mental stress moderates recovery of muscular function, perceived energy, fatigue, and soreness in the first hour after a bout of strenuous resistance exercise. Thirty-one undergraduate resistance training students (age = 20.26 ± 1.34 yr) completed the Perceived Stress Scale and Undergraduate Stress Questionnaire (USQ; a measure of life event stress) and completed fitness testing. After 5 to 14 d of recovery, they performed an acute heavy-resistance exercise protocol (10-repetition maximum (RM) leg press test plus six sets: 80%-100% of 10 RM). Maximal isometric force (MIF) was assessed before exercise, after exercise, and at 20, 40, and 60 min postexercise. Participants also reported their levels of perceived energy, fatigue, and soreness. Recovery data were analyzed with hierarchical linear modeling growth curve analysis. Life event stress significantly moderated linear (P = 0.013) and squared (P = 0.05) recovery of MIF. This relationship held even when the model was adjusted for fitness, workload, and training experience. Likewise, perceived stress moderated linear recovery of MIF (P = 0.023). Neither USQ nor Perceived Stress Scale significantly moderated changes in energy, fatigue, or soreness. Life event stress and perceived stress both moderated the recovery of muscular function, but not psychological responses, in the first hour after strenuous resistance exercise.

Electric field-triggered metal-insulator transition resistive switching of bilayered multiphasic VOx

Science.gov (United States)

Won, Seokjae; Lee, Sang Yeon; Hwang, Jungyeon; Park, Jucheol; Seo, Hyungtak

2018-01-01

Electric field-triggered Mott transition of VO2 for next-generation memory devices with sharp and fast resistance-switching response is considered to be ideal but the formation of single-phase VO2 by common deposition techniques is very challenging. Here, VOx films with a VO2-dominant phase for a Mott transition-based metal-insulator transition (MIT) switching device were successfully fabricated by the combined process of RF magnetron sputtering of V metal and subsequent O2 annealing to form. By performing various material characterizations, including scanning transmission electron microscopy-electron energy loss spectroscopy, the film is determined to have a bilayer structure consisting of a VO2-rich bottom layer acting as the Mott transition switching layer and a V2O5/V2O3 mixed top layer acting as a control layer that suppresses any stray leakage current and improves cyclic performance. This bilayer structure enables excellent electric field-triggered Mott transition-based resistive switching of Pt-VOx-Pt metal-insulator-metal devices with a set/reset current ratio reaching 200, set/reset voltage of less than 2.5 V, and very stable DC cyclic switching upto 120 cycles with a great set/reset current and voltage distribution less than 5% of standard deviation at room temperature, which are specifications applicable for neuromorphic or memory device applications. [Figure not available: see fulltext.

Characteristics of joint resistance with different kinds of HTS tapes for heater trigger switch

Energy Technology Data Exchange (ETDEWEB)

Lee, Je Yull; Park, Young Gun; Lee, Woo Seung; Jo, Hyun Chul; Ko, Tae Kuk [Yonsei University, Seoul (Korea, Republic of); Yoon, Yong Soo [Shin Ansan University, Ansan (Korea, Republic of)

2014-03-15

Recently, many researches on the system of superconducting power supply and superconducting magnetic energy storage (SMES) using high temperature superconducting (HTS) tapes has been progressed. Those kinds of superconducting devices use the heater trigger switches that have a control delay problem at moments of heating up and cooling down. One way to reduce the time delay is using a different HTS tape at trigger part. For example, HTS tape having lower critical temperature can reduce time delay of heating up and heating down stage for heater trigger operation. This paper deals with resistances joint with different kinds of HTS tapes which have different properties to verify usefulness of the suggested method. Three kinds of commercial HTS tapes with different specifications are selected as samples and two kinds of solders are used for comparison. Joint is performed with temperature and pressure controllable joint machine and the joint characteristics are analyzed under the repeatable conditions.

Early-Life Stress Triggers Juvenile Zebra Finches to Switch Social Learning Strategies.

Science.gov (United States)

Farine, Damien R; Spencer, Karen A; Boogert, Neeltje J

2015-08-17

Stress during early life can cause disease and cognitive impairment in humans and non-humans alike. However, stress and other environmental factors can also program developmental pathways. We investigate whether differential exposure to developmental stress can drive divergent social learning strategies between siblings. In many species, juveniles acquire essential foraging skills by copying others: they can copy peers (horizontal social learning), learn from their parents (vertical social learning), or learn from other adults (oblique social learning). However, whether juveniles' learning strategies are condition dependent largely remains a mystery. We found that juvenile zebra finches living in flocks socially learned novel foraging skills exclusively from adults. By experimentally manipulating developmental stress, we further show that social learning targets are phenotypically plastic. While control juveniles learned foraging skills from their parents, their siblings, exposed as nestlings to experimentally elevated stress hormone levels, learned exclusively from unrelated adults. Thus, early-life conditions triggered individuals to switch strategies from vertical to oblique social learning. This switch could arise from stress-induced differences in developmental rate, cognitive and physical state, or the use of stress as an environmental cue. Acquisition of alternative social learning strategies may impact juveniles' fit to their environment and ultimately change their developmental trajectories. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A shift to organismal stress resistance in programmed cell death mutants.

Directory of Open Access Journals (Sweden)

Meredith E Judy

Full Text Available Animals have many ways of protecting themselves against stress; for example, they can induce animal-wide, stress-protective pathways and they can kill damaged cells via apoptosis. We have discovered an unexpected regulatory relationship between these two types of stress responses. We find that C. elegans mutations blocking the normal course of programmed cell death and clearance confer animal-wide resistance to a specific set of environmental stressors; namely, ER, heat and osmotic stress. Remarkably, this pattern of stress resistance is induced by mutations that affect cell death in different ways, including ced-3 (cell death defective mutations, which block programmed cell death, ced-1 and ced-2 mutations, which prevent the engulfment of dying cells, and progranulin (pgrn-1 mutations, which accelerate the clearance of apoptotic cells. Stress resistance conferred by ced and pgrn-1 mutations is not additive and these mutants share altered patterns of gene expression, suggesting that they may act within the same pathway to achieve stress resistance. Together, our findings demonstrate that programmed cell death effectors influence the degree to which C. elegans tolerates environmental stress. While the mechanism is not entirely clear, it is intriguing that animals lacking the ability to efficiently and correctly remove dying cells should switch to a more global animal-wide system of stress resistance.

Induced resistance in tomato by SAR activators during predisposing salinity stress

Directory of Open Access Journals (Sweden)

Matthew Francis Pye

2013-05-01

Full Text Available Plant activators are chemicals that induce disease resistance. The phytohormone salicylic acid (SA is a crucial signal for systemic acquired resistance (SAR, and SA-mediated resistance is a target of several commercial plant activators, including Actigard (1,2,3-benzothiadiazole-7-thiocarboxylic acid-s-methyl-ester, BTH and Tiadinil (N-(3-chloro-4-methylphenyl-4-methyl-1,2,3-thiadiazole-5-carboxamide, TDL. BTH and TDL were examined for their impact on abscisic acid (ABA-mediated, salt-induced disease predisposition in tomato seedlings. A brief episode of salt stress to roots significantly increased the severity of disease caused by Pseudomonas syringae pv. tomato (Pst and Phytophthora capsici relative to non-stressed plants. Root treatment with TDL induced resistance to Pst in leaves and provided protection in both non-stressed and salt-stressed seedlings in WT and highly susceptible NahG plants. Non-stressed and salt-stressed ABA-deficient sitiens mutants were highly resistant to Pst. Neither TDL nor BTH induced resistance to root infection by P. capsici, nor did they moderate the salt-induced increment in disease severity. Root treatment with these plant activators increased the levels of ABA in roots and shoots similar to levels observed in salt-stressed plants. The results indicate that SAR activators can protect tomato plants from bacterial speck disease under predisposing salt stress, and suggest that some SA-mediated defense responses function sufficiently in plants with elevated levels of ABA.

A Vegetal Biopolymer-Based Biostimulant Promoted Root Growth in Melon While Triggering Brassinosteroids and Stress-Related Compounds

Directory of Open Access Journals (Sweden)

Luigi Lucini

2018-04-01

Full Text Available Plant biostimulants are receiving great interest for boosting root growth during the first phenological stages of vegetable crops. The present study aimed at elucidating the morphological, physiological, and metabolomic changes occurring in greenhouse melon treated with the biopolymer-based biostimulant Quik-link, containing lateral root promoting peptides, and lignosulphonates. The vegetal-based biopolymer was applied at five rates (0, 0.06, 0.12, 0.24, or 0.48 mL plant-1 as substrate drench. The application of biopolymer-based biostimulant at 0.12 and 0.24 mL plant-1 enhanced dry weight of melon leaves and total biomass by 30.5 and 27.7%, respectively, compared to biopolymer applications at 0.06 mL plant-1 and untreated plants. The root dry biomass, total root length, and surface in biostimulant-treated plants were significantly higher at 0.24 mL plant-1 and to a lesser extent at 0.12 and 0.48 mL plant-1, in comparison to 0.06 mL plant-1 and untreated melon plants. A convoluted biochemical response to the biostimulant treatment was highlighted through UHPLC/QTOF-MS metabolomics, in which brassinosteroids and their interaction with other hormones appeared to play a pivotal role. Root metabolic profile was more markedly altered than leaves, following application of the biopolymer-based biostimulant. Brassinosteroids triggered in roots could have been involved in changes of root development observed after biostimulant application. These hormones, once transported to shoots, could have caused an hormonal imbalance. Indeed, the involvement of abscisic acid, cytokinins, and gibberellin related compounds was observed in leaves following root application of the biopolymer-based biostimulant. Nonetheless, the treatment triggered an accumulation of several metabolites involved in defense mechanisms against biotic and abiotic stresses, such as flavonoids, carotenoids, and glucosinolates, thus potentially improving resistance toward plant stresses.

Mutants of Aspergillus nidulans with increased resistance to the alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine.

Science.gov (United States)

Hooley, P; Shawcross, S G; Strike, P

1988-05-01

The isolation and characterisation of mutants of Aspergillus nidulans showing resistance to MNNG is described. Such isolates were stable through prolonged subculture in the absence of the selective agent, and resistance segregated as an allele of a single gene in meiotic and mitotic analysis. MNNG-resistant strains showed an increase in resistance to EMS and UV irradiation but no cross-resistance to MMS was detected. Possible mechanisms of resistance to alkylating agents are discussed.

Proteomics analysis suggests broad functional changes in potato leaves triggered by phosphites and a complex indirect mode of action against Phytophthora infestans.

Science.gov (United States)

Lim, Sanghyun; Borza, Tudor; Peters, Rick D; Coffin, Robert H; Al-Mughrabi, Khalil I; Pinto, Devanand M; Wang-Pruski, Gefu

2013-11-20

Phosphite (salts of phosphorous acid; Phi)-based fungicides are increasingly used in controlling oomycete pathogens, such as the late blight agent Phytophthora infestans. In plants, low amounts of Phi induce pathogen resistance through an indirect mode of action. We used iTRAQ-based quantitative proteomics to investigate the effects of phosphite on potato plants before and after infection with P. infestans. Ninety-three (62 up-regulated and 31 down-regulated) differentially regulated proteins, from a total of 1172 reproducibly identified proteins, were identified in the leaf proteome of Phi-treated potato plants. Four days post-inoculation with P. infestans, 16 of the 31 down-regulated proteins remained down-regulated and 42 of the 62 up-regulated proteins remained up-regulated, including 90% of the defense proteins. This group includes pathogenesis-related, stress-responsive, and detoxification-related proteins. Callose deposition and ultrastructural analyses of leaf tissues after infection were used to complement the proteomics approach. This study represents the first comprehensive proteomics analysis of the indirect mode of action of Phi, demonstrating broad effects on plant defense and plant metabolism. The proteomics data and the microscopy study suggest that Phi triggers a hypersensitive response that is responsible for induced resistance of potato leaves against P. infestans. Phosphie triggers complex functional changes in potato leaves that are responsible for the induced resistance against Phytophthora infestans. This article is part of a Special Issue entitled: Translational Plant Proteomics. Copyright © 2013 Elsevier B.V. All rights reserved.

Resistance of Staphylococcus aureus to antimicrobial agents in Ethiopia: a meta-analysis.

Science.gov (United States)

Deyno, Serawit; Fekadu, Sintayehu; Astatkie, Ayalew

2017-01-01

Emergence of antimicrobial resistance by Staphylococcus aureus has limited treatment options against its infections. The purpose of this study was to determine the pooled prevalence of resistance to different antimicrobial agents by S. aureus in Ethiopia. Web-based search was conducted in the databases of PubMed, Google Scholar, Hinari, Scopus and the Directory of Open Access Journals (DOAJ) to identify potentially eligible published studies. Required data were extracted and entered into Excel spread sheet. Statistical analyses were performed using Stata version 13.0. The metaprop Stata command was used to pool prevalence values. Twenty-one separate meta-analysis were done to estimate the pooled prevalence of the resistance of S. aureus to twenty-one different antimicrobial agents. Heterogeneity among the studies was assessed using the I 2 statistic and chi-square test. Publication bias was assessed using Egger's test. Because of significant heterogeneity amongst the studies, the random effects model was used to pool prevalence values. The electronic database search yielded 1317 studies among which 45 studies met our inclusion criteria. Our analyses demonstrated very high level of resistance to amoxicillin (77% [95% confidence interval (CI): 68%, 0.85%]), penicillin (76% [95% CI: 67%, 84%]), ampicillin (75% [95% CI: 65%, 85%]), tetracycline (62% [95% CI: 55%, 68%]), methicillin (47% [95% CI: 33%, 61%]), cotrimoxaziole (47% [95% CI: 40%, 55%]), doxycycline (43% [95% CI: 26%, 60%]), and erythromycin (41% [95% CI: 29%, 54%]). Relatively low prevalence of resistance was observed with kanamycin (14% [95% CI: 5%, 25%]) and ciprofloxacin (19% [95% CI: 13%, 26%]). The resistance level to vancomycin is 11% 995% CI: (4%, 20%). High heterogeneity was observed for each of the meta-analysis performed (I 2 ranging from 79.36% to 95.93%; all p -values ≤0.01). Eggers' test did not show a significant publication bias for all antimicrobial agents except for erythromycin and

MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant Chronic Myeloid Leukemia Cells.

Directory of Open Access Journals (Sweden)

Shuit-Mun Wong

Full Text Available Chronic myeloid leukemia (CML is a clonal disorder of hematopoietic stem/progenitor cells that is caused by the Bcr-Abl oncoprotein. Clinical resistance to the Bcr-Abl inhibitor imatinib is a critical problem in treating CML. This study investigated the antitumor effect and mechanism of MPT0B169, a new antitubulin agent, in K562 CML cells and their derived imatinib-resistant cells, IMR2 and IMR3. IMR2 and IMR3 cells showed complete resistance to imatinib-induced growth inhibition and apoptosis. Resistance involved ERK1/2 overactivation and MDR1 overexpression. MPT0B169 inhibited the growth of K562, IMR2, and IMR3 cells in a dose- and time-dependent manner. MPT0B169 substantially inhibited the mRNA and protein levels of Bcr-Abl, followed by its downstream pathways including Akt, ERK1/2, and STAT3 in these cells. MPT0B169 treatment resulted in a decrease in the polymer form of tubulin according to Western blot analysis. It triggered cell cycle arrest at the G2/M phase before apoptosis, which was related to the upregulation of the mitotic marker MPM2 and the cyclin B1 level, and a change in the phosphorylation of Cdk1. MPT0B169 induced apoptosis in nonresistant and imatinib-resistant cells via a mitochondrion-mediated caspase pathway. Further study showed that the agent led to a decrease in the antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 and an increase in the apoptotic protein Bax. Taken together, our results suggest that MPT0B169 might be a promising agent for overcoming imatinib resistance in CML cells.

Preparation of Shrinkage Compensating Concrete with HCSA Expansive Agent

Science.gov (United States)

Li, Changcheng; Jia, Fujia

2017-10-01

Shrinkage compensating concrete (SCC) has become one of the best effective methods of preventing and reducing concrete cracking. SCC is prepared by HCSA high performance expansive agent for concrete which restrained expansion rate is optimized by 0.057%. Slump, compressive strength, restrained expansion rate and cracking resistance test were carried out on SCC. The results show that the initial slump of fresh SCC was about 220mm-230mm, while slump after 2 hours was 180mm-200mm. The restrained expansion rate of SCC increased with the mixing amount of expansive agent. After cured in water for 14 days, the restrained expansion rate of C35 and C40 SCC were 0.020%-0.032%. With the dosage of expansive agent increasing, restrained expansion rate of SCC increased, maximum compressive stress and cracking stress improved, cracking temperature fell, thus cracking resistance got effectively improvement.

Evasion of Apoptosis as a Cellular Stress Response in Cancer

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Simone Fulda

2010-01-01

Full Text Available One of the hallmarks of human cancers is the intrinsic or acquired resistance to apoptosis. Evasion of apoptosis can be part of a cellular stress response to ensure the cell's survival upon exposure to stressful stimuli. Apoptosis resistance may contribute to carcinogenesis, tumor progression, and also treatment resistance, since most current anticancer therapies including chemotherapy as well as radio- and immunotherapies primarily act by activating cell death pathways including apoptosis in cancer cells. Hence, a better understanding of the molecular mechanisms regarding how cellular stress stimuli trigger antiapoptotic mechanisms and how this contributes to tumor resistance to apoptotic cell death is expected to provide the basis for a rational approach to overcome apoptosis resistance mechanisms in cancers.

Change Agent – A Force Generating Resistance To Change Within An Organization?

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Mariana Prediscan

2012-12-01

Full Text Available The purpose of this research is to identify if the change agent represents or not a force generating resistance to change within an organization. The employees affected by a change process are usually the ones who oppose to new implementations. Their opposition is bigger or smaller, depending on the extent that they are affected and also by the direction, either positive or negative. However, employee’s opposition can be potentiated or reduced, depending on the manifestation of the following forces within an organization: communications, the type of organizational structure, management style and organizational culture, forces which refer to the organizational climate. To answer our question, we have researched the current literature and discovered that the change agent can represent a force generating resistance to change within an organization in those situations when he or she identifies with a middle or top manager from the organizational pyramid. This information is valuable to researchers and practitioners, as for a long time, employees were considered the only ones manifesting resistance, the possibility that the change agent can oppose new changes being ignored.

Natural thioallyl compounds increase oxidative stress resistance and lifespan in Caenorhabditis elegans by modulating SKN-1/Nrf.

Science.gov (United States)

Ogawa, Takahiro; Kodera, Yukihiro; Hirata, Dai; Blackwell, T Keith; Mizunuma, Masaki

2016-02-22

Identification of biologically active natural compounds that promote health and longevity, and understanding how they act, will provide insights into aging and metabolism, and strategies for developing agents that prevent chronic disease. The garlic-derived thioallyl compounds S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC) have been shown to have multiple biological activities. Here we show that SAC and SAMC increase lifespan and stress resistance in Caenorhabditis elegans and reduce accumulation of reactive oxygen species (ROS). These compounds do not appear to activate DAF-16 (FOXO orthologue) or mimic dietary restriction (DR) effects, but selectively induce SKN-1 (Nrf1/2/3 orthologue) targets involved in oxidative stress defense. Interestingly, their treatments do not facilitate SKN-1 nuclear accumulation, but slightly increased intracellular SKN-1 levels. Our data also indicate that thioallyl structure and the number of sulfur atoms are important for SKN-1 target induction. Our results indicate that SAC and SAMC may serve as potential agents that slow aging.

Trigger factors in migraine with aura

DEFF Research Database (Denmark)

Hauge, A W; Kirchmann, M; Olesen, J

2010-01-01

The aim of the present study was to identify trigger factors in migraine with aura (MA). A total of 629 MA patients representative of the Danish population were sent a questionnaire listing 16 trigger factors thought to be relevant as well as space for free text. Distinction was made between...... attacks with or without aura within each patient. The questionnaire was returned by 522 patients of whom 347 had current MA attacks. In total 80% with current attacks (278/347) indicated that at least one factor triggered their migraine, and 67% (187/278) in this group indicated that they were aware...... of at least one factor often or always giving rise to an attack of MA. Forty-one per cent (113/278) had co-occurring attacks of migraine without aura (MO). Stress (following stress), bright light, intense emotional influences, stress (during stress) and sleeping too much or too little were the trigger factors...

The Role of Tectonic Stress in Triggering Large Silicic Caldera Eruptions

Science.gov (United States)

Cabaniss, Haley E.; Gregg, Patricia M.; Grosfils, Eric B.

2018-05-01

We utilize 3-D temperature-dependent viscoelastic finite element models to investigate the mechanical response of the host rock supporting large caldera-size magma reservoirs (volumes >102 km3) to local tectonic stresses. The mechanical stability of the host rock is used to determine the maximum predicted repose intervals and magma flux rates that systems may experience before successive eruption is triggered. Numerical results indicate that regional extension decreases the stability of the roof rock overlying a magma reservoir, thereby promoting early-onset caldera collapse. Alternatively, moderate amounts of compression (≤10 mm/year) on relatively short timescales (stresses on reservoir stability, our models indicate that the process of rejuvenation and mechanical failure is likely to take place over short time periods of hundreds to thousands of years. These findings support the short preeruption melt accumulation timescales indicated by U series disequilibrium studies.

Stress in Community Health Agents: a Bioethics Protection Perspective

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Ulysses Rodrigues de Castro

2014-09-01

Full Text Available Health care professionals suffer from both regular job stress and caregiver stress that arises from the neglect of their work situation. As principles of bioethics protection, vertical protection ratio, health policies should also target health professionals. So, this paper seeks to understand the issue of stress in relation to mental health professionals, specifically the community health agents of the Federal District in Brazil. Methods: This study is an exploratory study that adopts a quantitative approach. Data were obtained by a questionnaire, that mesure social, work and stress factors, in 97 community health agents, a different class of health professional. The SPSS 19.0 program was used to mesure the results. Results: The sociodemographic data of respondentes revealed that the majority were women, 40,2% of the group members fall in the age range 30‒39 years, 51% of respondents were married and 57.7% were of middle socioeconomic status. All Pearson correlations were significant at the 0.01 level (two-tailed. The results show that all stressors are negatively correlated with the mental health factors. These results showed that mental health deteriorates with increased stress. The mental health indicators are strongly and positively associated, indicating that individuals with better mental health show greater personal, social and workplace support. Conclusions: The results indicate the need for management changes in the public health sector related to Bioethics Protection, which states that populations vulnerable to work exploitation should be protected by guaranteeing minimum working conditions.

Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

OpenAIRE

Dues, Dylan J.; Andrews, Emily K.; Schaar, Claire E.; Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

2016-01-01

In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxi...

Lessons from (triggered) tremor

Science.gov (United States)

Gomberg, Joan

2010-01-01

I test a “clock-advance” model that implies triggered tremor is ambient tremor that occurs at a sped-up rate as a result of loading from passing seismic waves. This proposed model predicts that triggering probability is proportional to the product of the ambient tremor rate and a function describing the efficacy of the triggering wave to initiate a tremor event. Using data mostly from Cascadia, I have compared qualitatively a suite of teleseismic waves that did and did not trigger tremor with ambient tremor rates. Many of the observations are consistent with the model if the efficacy of the triggering wave depends on wave amplitude. One triggered tremor observation clearly violates the clock-advance model. The model prediction that larger triggering waves result in larger triggered tremor signals also appears inconsistent with the measurements. I conclude that the tremor source process is a more complex system than that described by the clock-advance model predictions tested. Results of this and previous studies also demonstrate that (1) conditions suitable for tremor generation exist in many tectonic environments, but, within each, only occur at particular spots whose locations change with time; (2) any fluid flow must be restricted to less than a meter; (3) the degree to which delayed failure and secondary triggering occurs is likely insignificant; and 4) both shear and dilatational deformations may trigger tremor. Triggered and ambient tremor rates correlate more strongly with stress than stressing rate, suggesting tremor sources result from time-dependent weakening processes rather than simple Coulomb failure.

Comparison of checkpoint responses triggered by DNA polymerase inhibition versus DNA damaging agents

International Nuclear Information System (INIS)

Liu, J.-S.; Kuo, S.-R.; Melendy, Thomas

2003-01-01

To better understand the different cellular responses to replication fork pausing versus blockage, early DNA damage response markers were compared after treatment of cultured mammalian cells with agents that either inhibit DNA polymerase activity (hydroxyurea (HU) or aphidicolin) or selectively induce S-phase DNA damage responses (the DNA alkylating agents, methyl methanesulfonate (MMS) and adozelesin). These agents were compared for their relative abilities to induce phosphorylation of Chk1, H2AX, and replication protein A (RPA), and intra-nuclear focalization of γ-H2AX and RPA. Treatment by aphidicolin and HU resulted in phosphorylation of Chk1, while HU, but not aphidicolin, induced focalization of γ-H2AX and RPA. Surprisingly, pre-treatment with aphidicolin to stop replication fork progression, did not abrogate HU-induced γ-H2AX and RPA focalization. This suggests that HU may act on the replication fork machinery directly, such that fork progression is not required to trigger these responses. The DNA-damaging fork-blocking agents, adozelesin and MMS, both induced phosphorylation and focalization of H2AX and RPA. Unlike adozelesin and HU, the pattern of MMS-induced RPA focalization did not match the BUdR incorporation pattern and was not blocked by aphidicolin, suggesting that MMS-induced damage is not replication fork-dependent. In support of this, MMS was the only reagent used that did not induce phosphorylation of Chk1. These results indicate that induction of DNA damage checkpoint responses due to adozelesin is both replication fork and fork progression dependent, induction by HU is replication fork dependent but progression independent, while induction by MMS is independent of both replication forks and fork progression

Comparison of checkpoint responses triggered by DNA polymerase inhibition versus DNA damaging agents

Energy Technology Data Exchange (ETDEWEB)

Liu, J.-S.; Kuo, S.-R.; Melendy, Thomas

2003-11-27

To better understand the different cellular responses to replication fork pausing versus blockage, early DNA damage response markers were compared after treatment of cultured mammalian cells with agents that either inhibit DNA polymerase activity (hydroxyurea (HU) or aphidicolin) or selectively induce S-phase DNA damage responses (the DNA alkylating agents, methyl methanesulfonate (MMS) and adozelesin). These agents were compared for their relative abilities to induce phosphorylation of Chk1, H2AX, and replication protein A (RPA), and intra-nuclear focalization of {gamma}-H2AX and RPA. Treatment by aphidicolin and HU resulted in phosphorylation of Chk1, while HU, but not aphidicolin, induced focalization of {gamma}-H2AX and RPA. Surprisingly, pre-treatment with aphidicolin to stop replication fork progression, did not abrogate HU-induced {gamma}-H2AX and RPA focalization. This suggests that HU may act on the replication fork machinery directly, such that fork progression is not required to trigger these responses. The DNA-damaging fork-blocking agents, adozelesin and MMS, both induced phosphorylation and focalization of H2AX and RPA. Unlike adozelesin and HU, the pattern of MMS-induced RPA focalization did not match the BUdR incorporation pattern and was not blocked by aphidicolin, suggesting that MMS-induced damage is not replication fork-dependent. In support of this, MMS was the only reagent used that did not induce phosphorylation of Chk1. These results indicate that induction of DNA damage checkpoint responses due to adozelesin is both replication fork and fork progression dependent, induction by HU is replication fork dependent but progression independent, while induction by MMS is independent of both replication forks and fork progression.

Triggered creep as a possible mechanism for delayed dynamic triggering of tremor and earthquakes

Science.gov (United States)

Shelly, David R.; Peng, Zhigang; Hill, David P.; Aiken, Chastity

2011-01-01

The passage of radiating seismic waves generates transient stresses in the Earth's crust that can trigger slip on faults far away from the original earthquake source. The triggered fault slip is detectable in the form of earthquakes and seismic tremor. However, the significance of these triggered events remains controversial, in part because they often occur with some delay, long after the triggering stress has passed. Here we scrutinize the location and timing of tremor on the San Andreas fault between 2001 and 2010 in relation to distant earthquakes. We observe tremor on the San Andreas fault that is initiated by passing seismic waves, yet migrates along the fault at a much slower velocity than the radiating seismic waves. We suggest that the migrating tremor records triggered slow slip of the San Andreas fault as a propagating creep event. We find that the triggered tremor and fault creep can be initiated by distant earthquakes as small as magnitude 5.4 and can persist for several days after the seismic waves have passed. Our observations of prolonged tremor activity provide a clear example of the delayed dynamic triggering of seismic events. Fault creep has been shown to trigger earthquakes, and we therefore suggest that the dynamic triggering of prolonged fault creep could provide a mechanism for the delayed triggering of earthquakes. ?? 2011 Macmillan Publishers Limited. All rights reserved.

[Regulating acid stress resistance of lactic acid bacteria--a review].

Science.gov (United States)

Wu, Chongde; Huang, Jun; Zhou, Rongqing

2014-07-04

As cell factories, lactic acid bacteria are widely used in food, agriculture, pharmaceutical and other industries. Acid stress is one the important survival challenges encountered by lactic acid bacteria both in fermentation process and in the gastrointestinal tract. Recently, the development of systems biology and metabolic engineering brings unprecedented opportunity for further elucidating the acid tolerance mechanisms and improving the acid stress resistance of lactic acid bacteria. This review addresses physiological mechanisms of lactic acid bacteria during acid stress. Moreover, strategies to improve the acid stress resistance of lactic acid were proposed.

What Is Better Than Coulomb Failure Stress? A Ranking of Scalar Static Stress Triggering Mechanisms from 105 Mainshock-Aftershock Pairs

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Meade, Brendan J.; DeVries, Phoebe M. R.; Faller, Jeremy; Viegas, Fernanda; Wattenberg, Martin

2017-11-01

Aftershocks may be triggered by the stresses generated by preceding mainshocks. The temporal frequency and maximum size of aftershocks are well described by the empirical Omori and Bath laws, but spatial patterns are more difficult to forecast. Coulomb failure stress is perhaps the most common criterion invoked to explain spatial distributions of aftershocks. Here we consider the spatial relationship between patterns of aftershocks and a comprehensive list of 38 static elastic scalar metrics of stress (including stress tensor invariants, maximum shear stress, and Coulomb failure stress) from 213 coseismic slip distributions worldwide. The rates of true-positive and false-positive classification of regions with and without aftershocks are assessed with receiver operating characteristic analysis. We infer that the stress metrics that are most consistent with observed aftershock locations are maximum shear stress and the magnitude of the second and third invariants of the stress tensor. These metrics are significantly better than random assignment at a significance level of 0.005 in over 80% of the slip distributions. In contrast, the widely used Coulomb failure stress criterion is distinguishable from random assignment in only 51-64% of the slip distributions. These results suggest that a number of alternative scalar metrics are better predictors of aftershock locations than classic Coulomb failure stress change.

Environmental Maternal Effects Mediate the Resistance of Maritime Pine to Biotic Stress

Science.gov (United States)

Vivas, María; Zas, Rafael; Sampedro, Luis; Solla, Alejandro

2013-01-01

The resistance to abiotic stress is increasingly recognised as being impacted by maternal effects, given that environmental conditions experienced by parent (mother) trees affect stress tolerance in offspring. We hypothesised that abiotic environmental maternal effects may also mediate the resistance of trees to biotic stress. The influence of maternal environment and maternal genotype and the interaction of these two factors on early resistance of Pinus pinaster half-sibs to the Fusarium circinatum pathogen was studied using 10 mother genotypes clonally replicated in two contrasting environments. Necrosis length of infected seedlings was 16% shorter in seedlings grown from favourable maternal environment seeds than in seedlings grown from unfavourable maternal environment seeds. Damage caused by F. circinatum was mediated by maternal environment and maternal genotype, but not by seed mass. Mechanisms unrelated to seed provisioning, perhaps of epigenetic nature, were probably involved in the transgenerational plasticity of P. pinaster, mediating its resistance to biotic stress. Our findings suggest that the transgenerational resistance of pines due to an abiotic stress may interact with the defensive response of pines to a biotic stress. PMID:23922944

Environmental maternal effects mediate the resistance of maritime pine to biotic stress.

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María Vivas

Full Text Available The resistance to abiotic stress is increasingly recognised as being impacted by maternal effects, given that environmental conditions experienced by parent (mother trees affect stress tolerance in offspring. We hypothesised that abiotic environmental maternal effects may also mediate the resistance of trees to biotic stress. The influence of maternal environment and maternal genotype and the interaction of these two factors on early resistance of Pinus pinaster half-sibs to the Fusarium circinatum pathogen was studied using 10 mother genotypes clonally replicated in two contrasting environments. Necrosis length of infected seedlings was 16% shorter in seedlings grown from favourable maternal environment seeds than in seedlings grown from unfavourable maternal environment seeds. Damage caused by F. circinatum was mediated by maternal environment and maternal genotype, but not by seed mass. Mechanisms unrelated to seed provisioning, perhaps of epigenetic nature, were probably involved in the transgenerational plasticity of P. pinaster, mediating its resistance to biotic stress. Our findings suggest that the transgenerational resistance of pines due to an abiotic stress may interact with the defensive response of pines to a biotic stress.

Resistance of Staphylococcus aureus to antimicrobial agents in Ethiopia: a meta-analysis

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Serawit Deyno

2017-08-01

Full Text Available Abstract Background Emergence of antimicrobial resistance by Staphylococcus aureus has limited treatment options against its infections. The purpose of this study was to determine the pooled prevalence of resistance to different antimicrobial agents by S. aureus in Ethiopia. Methods Web-based search was conducted in the databases of PubMed, Google Scholar, Hinari, Scopus and the Directory of Open Access Journals (DOAJ to identify potentially eligible published studies. Required data were extracted and entered into Excel spread sheet. Statistical analyses were performed using Stata version 13.0. The metaprop Stata command was used to pool prevalence values. Twenty-one separate meta-analysis were done to estimate the pooled prevalence of the resistance of S. aureus to twenty-one different antimicrobial agents. Heterogeneity among the studies was assessed using the I2 statistic and chi-square test. Publication bias was assessed using Egger’s test. Because of significant heterogeneity amongst the studies, the random effects model was used to pool prevalence values. Results The electronic database search yielded 1317 studies among which 45 studies met our inclusion criteria. Our analyses demonstrated very high level of resistance to amoxicillin (77% [95% confidence interval (CI: 68%, 0.85%], penicillin (76% [95% CI: 67%, 84%], ampicillin (75% [95% CI: 65%, 85%], tetracycline (62% [95% CI: 55%, 68%], methicillin (47% [95% CI: 33%, 61%], cotrimoxaziole (47% [95% CI: 40%, 55%], doxycycline (43% [95% CI: 26%, 60%], and erythromycin (41% [95% CI: 29%, 54%]. Relatively low prevalence of resistance was observed with kanamycin (14% [95% CI: 5%, 25%] and ciprofloxacin (19% [95% CI: 13%, 26%]. The resistance level to vancomycin is 11% 995% CI: (4%, 20%. High heterogeneity was observed for each of the meta-analysis performed (I2 ranging from 79.36% to 95.93%; all p-values ≤0.01. Eggers’ test did not show a significant publication bias for all

Plant-to-plant communication triggered by systemin primes anti-herbivore resistance in tomato.

Science.gov (United States)

Coppola, Mariangela; Cascone, Pasquale; Madonna, Valentina; Di Lelio, Ilaria; Esposito, Francesco; Avitabile, Concetta; Romanelli, Alessandra; Guerrieri, Emilio; Vitiello, Alessia; Pennacchio, Francesco; Rao, Rosa; Corrado, Giandomenico

2017-11-14

Plants actively respond to herbivory by inducing various defense mechanisms in both damaged (locally) and non-damaged tissues (systemically). In addition, it is currently widely accepted that plant-to-plant communication allows specific neighbors to be warned of likely incoming stress (defense priming). Systemin is a plant peptide hormone promoting the systemic response to herbivory in tomato. This 18-aa peptide is also able to induce the release of bioactive Volatile Organic Compounds, thus also promoting the interaction between the tomato and the third trophic level (e.g. predators and parasitoids of insect pests). In this work, using a combination of gene expression (RNA-Seq and qRT-PCR), behavioral and chemical approaches, we demonstrate that systemin triggers metabolic changes of the plant that are capable of inducing a primed state in neighboring unchallenged plants. At the molecular level, the primed state is mainly associated with an elevated transcription of pattern -recognition receptors, signaling enzymes and transcription factors. Compared to naïve plants, systemin-primed plants were significantly more resistant to herbivorous pests, more attractive to parasitoids and showed an increased response to wounding. Small peptides are nowadays considered fundamental signaling molecules in many plant processes and this work extends the range of downstream effects of this class of molecules to intraspecific plant-to-plant communication.

Resistance profiles to antimicrobial agents in bacteria isolated from acute endodontic infections: systematic review and meta-analysis.

Science.gov (United States)

Lang, Pauline M; Jacinto, Rogério C; Dal Pizzol, Tatiane S; Ferreira, Maria Beatriz C; Montagner, Francisco

2016-11-01

Infected root canal or acute apical abscess exudates can harbour several species, including Fusobacterium, Porphyromonas, Prevotella, Parvimonas, Streptococcus, Treponema, Olsenella and not-yet cultivable species. A systematic review and meta-analysis was performed to assess resistance rates to antimicrobial agents in clinical studies that isolated bacteria from acute endodontic infections. Electronic databases and the grey literature were searched up to May 2015. Clinical studies in humans evaluating the antimicrobial resistance of primary acute endodontic infection isolates were included. PRISMA guidelines were followed. A random-effect meta-analysis was employed. The outcome was described as the pooled resistance rates for each antimicrobial agent. Heterogeneity and sensitivity analyses were performed. Subgroup analyses were conducted based upon report or not of the use of antibiotics prior to sampling as an exclusion factor (subgroups A and B, respectively). Data from seven studies were extracted. Resistance rates for 15 different antimicrobial agents were evaluated (range, 3.5-40.0%). Lower resistance rates were observed for amoxicillin/clavulanic acid and amoxicillin; higher resistance rates were detected for tetracycline. Resistance rates varied according to previous use of an antimicrobial agent as demonstrated by the subgroup analyses. Heterogeneity was observed for the resistance profiles of penicillin G in subgroup A and for amoxicillin, clindamycin, metronidazole and tetracycline in subgroup B. Sensitivity analyses demonstrated that resistance rates changed for metronidazole, clindamycin, tetracycline and amoxicillin. These findings suggest that clinical isolates had low resistance to β-lactams. Further well-designed studies are needed to clarify whether the differences in susceptibility among the antimicrobial agents may influence clinical responses to treatment. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights

The effects of anesthetic agents on oxidative stress

Science.gov (United States)

Yakan, Selvinaz; Düzgüner, Vesile

2016-04-01

Oxidative stress can be defined as the instability between antioxidant defense of the body and the production of free radical that causes peroxydation on the lipid layer. Free radicals are reactive oxygen species that are produced in the course of normal metabolisms of aerobe organisms and they may cause disorders in cell structure and organelles by interacting macromolecules, like lipid, protein, nucleic acids. Therefore, they may cause cardiovascular, immune system, liver, kidney illnesses and many other illnesses like cancer, aging, cataract, diabetes. It is known that many drugs used for the purpose of anesthetizing may cause lipid peroxidation in organism. For these reasons, determining the Oxidative stress index of anaesthetic stress chosen in the ones that are exposed to long term anaesthetic agents and anaesthesia appliccations, is so substantial.

Stress Management: Job Stress

Science.gov (United States)

Healthy Lifestyle Stress management Job stress can be all-consuming — but it doesn't have to be. Address your triggers, keep perspective and ... stress triggers, it's often helpful to improve time management skills — especially if you tend to feel overwhelmed ...

The role of endoplasmic reticulum stress in hippocampal insulin resistance.

Science.gov (United States)

Sims-Robinson, Catrina; Bakeman, Anna; Glasser, Rebecca; Boggs, Janet; Pacut, Crystal; Feldman, Eva L

2016-03-01

Metabolic syndrome, which includes hypertension, hyperglycemia, obesity, insulin resistance, and dyslipidemia, has a negative impact on cognitive health. Endoplasmic reticulum (ER) stress is activated during metabolic syndrome, however it is not known which factor associated with metabolic syndrome contributes to this stress. ER stress has been reported to play a role in the development of insulin resistance in peripheral tissues. The role of ER stress in the development of insulin resistance in hippocampal neurons is not known. In the current study, we investigated ER stress in the hippocampus of 3 different mouse models of metabolic syndrome: the C57BL6 mouse on a high fat (HF) diet; apolipoprotein E, leptin, and apolipoprotein B-48 deficient (ApoE 3KO) mice; and the low density lipoprotein receptor, leptin, and apolipoprotein B-48 deficient (LDLR 3KO) mice. We demonstrate that ER stress is activated in the hippocampus of HF mice, and for the first time, in ApoE 3KO mice, but not LDLR 3KO mice. The HF and ApoE 3KO mice are hyperglycemic; however, the LDLR 3KO mice have normal glycemia. This suggests that hyperglycemia may play a role in the activation of ER stress in the hippocampus. Similarly, we also demonstrate that impaired insulin signaling is only present in the HF and ApoE 3KO mice, which suggests that ER stress may play a role in insulin resistance in the hippocampus. To confirm this we pharmacologically induced ER stress with thapsigargin in human hippocampal neurons. We demonstrate for the first time that thapsigargin leads to ER stress and impaired insulin signaling in human hippocampal neurons. Our results may provide a potential mechanism that links metabolic syndrome and cognitive health. Copyright © 2016 Elsevier Inc. All rights reserved.

Targeting the Oxidative Stress Response System of Fungi with Redox-Potent Chemosensitizing Agents

Science.gov (United States)

Kim, Jong H.; Chan, Kathleen L.; Faria, Natália C. G.; Martins, M. de L.; Campbell, Bruce C.

2012-01-01

The cellular antioxidant system is a target in the antifungal action of amphotericin B (AMB) and itraconazole (ITZ), in filamentous fungi. The sakAΔ mutant of Aspergillus fumigatus, a mitogen-activated protein kinase (MAPK) gene deletion mutant in the antioxidant system, was found to be more sensitive to AMB or ITZ than other A. fumigatus strains, a wild type and a mpkCΔ mutant (a MAPK gene deletion mutant in the polyalcohol sugar utilization system). Complete fungal kill (≥99.9%) by ITZ or AMB was also achieved by much lower dosages for the sakAΔ mutant than for the other strains. It appears msnA, an Aspergillus ortholog to Saccharomyces cerevisiae MSN2 (encoding a stress-responsive C2H2-type zinc-finger regulator) and sakA and/or mpkC (upstream MAPKs) are in the same stress response network under tert-butyl hydroperoxide (t-BuOOH)-, hydrogen peroxide (H2O2)- or AMB-triggered toxicity. Of note is that ITZ-sensitive yeast pathogens were also sensitive to t-BuOOH, showing a connection between ITZ sensitivity and antioxidant capacity of fungi. Enhanced antifungal activity of AMB or ITZ was achieved when these drugs were co-applied with redox-potent natural compounds, 2,3-dihydroxybenzaldehyde, thymol or salicylaldehyde, as chemosensitizing agents. We concluded that redox-potent compounds, which target the antioxidant system in fungi, possess a chemosensitizing capacity to enhance efficacy of conventional drugs. PMID:22438852

Early resistance change and stress/electromigration evolution in near bamboo interconnects

NARCIS (Netherlands)

Petrescu, V.; Mouthaan, A.J.; Dima, G.; Govoreanu, B.; Mitrea, O.; Profirescu, M.

1997-01-01

A complete description for early resistance change and mechanical stress evolution in near-bamboo interconnects, related to the electromigration, is given in this paper. The proposed model, for the first time, combines the stress/vacancy concentration evolution with the early resistance change of

Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents.

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Richard C Wang

Full Text Available One of the main reasons for disease recurrence in the curative breast cancer treatment setting is the development of drug resistance. Microtubule targeted agents (MTAs are among the most commonly used drugs for the treatment of breaset cancer and therefore overcoming taxane resistance is of primary clinical importance. Our group has previously demonstrated that the microtubule dynamics of docetaxel-resistant MCF-7TXT cells are insensitivity to docetaxel due to the distinct expression profiles of β-tubulin isotypes in addition to the high expression of p-glycoprotein (ABCB1. In the present investigation we examined whether taxane-resistant breast cancer cells are more sensitive to microtubule destabilizing agents including vinca alkaloids and colchicine-site binding agents (CSBAs than the non-resistant cells.Two isogenic MCF-7 breast cancer cell lines were selected for resistance to docetaxel (MCF-7TXT and the wild type parental cell line (MCF-7CC to examine if taxane-resistant breast cancer cells are sensitive to microtubule-destabilizing agents including vinca alkaloids and CSBAs. Cytotoxicity assays, immunoblotting, indirect immunofluorescence and live imaging were used to study drug resistance, apoptosis, mitotic arrest, microtubule formation, and microtubule dynamics.MCF-7TXT cells were demonstrated to be cross resistant to vinca alkaloids, but were more sensitive to treatment with colchicine compared to parental non-resistant MCF-7CC cells. Cytotoxicity assays indicated that the IC50 of MCF-7TXT cell to vinorelbine and vinblastine was more than 6 and 3 times higher, respectively, than that of MCF-7CC cells. By contrast, the IC50 of MCF-7TXT cell for colchincine was 4 times lower than that of MCF-7CC cells. Indirect immunofluorescence showed that all MTAs induced the disorganization of microtubules and the chromatin morphology and interestingly each with a unique pattern. In terms of microtubule and chromain morphology, MCF-7TXT cells were

Assessment of acute phase proteins and oxidative stress status of Nigerians using bleaching agents

International Nuclear Information System (INIS)

Akibinu, M.O.; Arinola, O.G.; Afolabi, K.A.

2010-01-01

The disruption of primary innate immune function of the epidermal layer of the skin accounts for the susceptibility of individuals using bleaching agents to localized or systemic infections. This subverted innate immunity in these people may lead to other pathological conditions. The resultant effects of skin bleaching and phagocytes activation in response to infections have not been studied in Nigerians using bleaching agents. The present study therefore assessed the levels of C-reactive protein (CRP), albumin, total antioxidant potential (TAP), total plasma peroxides (TPP), oxidative stress index (OSI) and malonaldehyde (MDA) in the users bleaching agents. Thirty (30) people who had used bleaching agents for average of 4.9 + 1.2 years participated in this study. They were recruited from various schools and markets within the city of Ibadan, Oyo State, Nigeria. Thirty apparently healthy staffs of University College Hospital Ibadan, Ibaadan, Nigeria, who had never used bleaching agents served as controls. All the subjects used for this study had no metabolic abnormality and tested negative to both HIV and hepatitis B infections. The mean value of TAP (p 0.20) when compared with the controls. Oxidative stress and chronic inflammation are possible consequences of skin bleaching. The users of skin bleaching agents may need antioxidant therapies to avert the risks of oxidative stress. (author)

Resistance to antimicrobial agents among Salmonella isolates recovered from layer farms and eggs in the Caribbean region.

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Adesiyun, Abiodun; Webb, Lloyd; Musai, Lisa; Louison, Bowen; Joseph, George; Stewart-Johnson, Alva; Samlal, Sannandan; Rodrigo, Shelly

2014-12-01

This investigation determined the frequency of resistance of 84 isolates of Salmonella comprising 14 serotypes recovered from layer farms in three Caribbean countries (Trinidad and Tobago, Grenada, and St. Lucia) to eight antimicrobial agents, using the disc diffusion method. Resistance among isolates of Salmonella was related to the country of recovery, type of sample, size of layer farms, and isolate serotype. Overall, all (100.0%) of the isolates exhibited resistance to one or more of seven antimicrobial agents tested, and all were susceptible to chloramphenicol. The resistance detected ranged from 11.9% to sulphamethoxazole-trimethoprim (SXT) to 100.0% to erythromycin. The difference was, however, not statistically significant (P = 0.23). Across countries, for types of samples that yielded Salmonella, significant differences in frequency of resistance were detected only to SXT (P = 0.002) in Trinidad and Tobago and to gentamycin (P = 0.027) in St. Lucia. For the three countries, the frequency of resistance to antimicrobial agents was significantly different for ampicillin (P = 0.001) and SXT (P = 0.032). A total of 83 (98.8%) of the 84 isolates exhibited 39 multidrug resistance patterns. Farm size significantly (P = 0.032) affected the frequency of resistance to kanamycin across the countries. Overall, among the 14 serotypes of Salmonella tested, significant (P resistance were detected to kanamycin, ampicillin, and SXT. Results suggest that the relatively high frequency of resistance to six of the antimicrobial agents (erythromycin, streptomycin, gentamycin, kanamycin, ampicillin, and tetracycline) tested and the multidrug resistance detected may pose prophylactic and therapeutic concerns for chicken layer farms in the three countries studied.

Biosynthesis of vitamin C by yeast leads to increased stress resistance.

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Paola Branduardi

Full Text Available BACKGROUND: In industrial large scale bio-reactions micro-organisms are generally exposed to a variety of environmental stresses, which might be detrimental for growth and productivity. Reactive oxygen species (ROS play a key role among the common stress factors--directly--through incomplete reduction of O(2 during respiration, or indirectly--caused by other stressing factors. Vitamin C or L-ascorbic acid acts as a scavenger of ROS, thereby potentially protecting cells from harmful oxidative products. While most eukaryotes synthesize ascorbic acid, yeast cells produce erythro-ascorbic acid instead. The actual importance of this antioxidant substance for the yeast is still a subject of scientific debate. METHODOLOGY/PRINCIPAL FINDINGS: We set out to enable Saccharomyces cerevisiae cells to produce ascorbic acid intracellularly to protect the cells from detrimental effects of environmental stresses. We report for the first time the biosynthesis of L-ascorbic acid from D-glucose by metabolically engineered yeast cells. The amount of L-ascorbic acid produced leads to an improved robustness of the recombinant cells when they are subjected to stress conditions as often met during industrial fermentations. Not only resistance against oxidative agents as H(2O(2 is increased, but also the tolerance to low pH and weak organic acids at low pH is increased. CONCLUSIONS/SIGNIFICANCE: This platform provides a new tool whose commercial applications may have a substantial impact on bio-industrial production of Vitamin C. Furthermore, we propose S. cerevisiae cells endogenously producing vitamin C as a cellular model to study the genesis/protection of ROS as well as genotoxicity.

Chronic stress triggers social aversion via glucocorticoid receptor in dopaminoceptive neurons.

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Barik, Jacques; Marti, Fabio; Morel, Carole; Fernandez, Sebastian P; Lanteri, Christophe; Godeheu, Gérard; Tassin, Jean-Pol; Mombereau, Cédric; Faure, Philippe; Tronche, François

2013-01-18

Repeated traumatic events induce long-lasting behavioral changes that are key to organism adaptation and that affect cognitive, emotional, and social behaviors. Rodents subjected to repeated instances of aggression develop enduring social aversion and increased anxiety. Such repeated aggressions trigger a stress response, resulting in glucocorticoid release and activation of the ascending dopamine (DA) system. We bred mice with selective inactivation of the gene encoding the glucocorticoid receptor (GR) along the DA pathway, and exposed them to repeated aggressions. GR in dopaminoceptive but not DA-releasing neurons specifically promoted social aversion as well as dopaminergic neurochemical and electrophysiological neuroadaptations. Anxiety and fear memories remained unaffected. Acute inhibition of the activity of DA-releasing neurons fully restored social interaction in socially defeated wild-type mice. Our data suggest a GR-dependent neuronal dichotomy for the regulation of emotional and social behaviors, and clearly implicate GR as a link between stress resiliency and dopaminergic tone.

Feasibility of prospectively ECG-triggered high-pitch coronary CT angiography with 30 mL iodinated contrast agent at 70 kVp: initial experience

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Zhang, Long Jiang; Qi, Li; Tang, Chun Xiang; Zhou, Chang Sheng; Ji, Xue Man; Lu, Guang Ming [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Wang, Jing [Medical School of Nanjing University, Department of Cardiology, Jinling Hospital, Nanjing, Jiangsu (China); Spearman, James V.; De Cecco, Carlo Nicola; Meinel, Felix G. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Schoepf, U.J. [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States)

2014-07-15

To evaluate the feasibility, image quality and radiation dose of prospectively ECG-triggered high-pitch coronary CT angiography (CCTA) with 30 mL contrast agent at 70 kVp. Fifty-eight patients with suspected coronary artery disease, a body mass index (BMI) of less than 25 kg/m{sup 2}, sinus rhythm and a heart rate (HR) of less than 70 beats per minute (bpm) were prospectively enrolled in this study. Thirty mL of 370 mg I/mL iodinated contrast agent was administrated at a flow rate of 5 mL/s. All patients underwent prospectively ECG-triggered high-pitch CCTA on a second-generation dual-source CT system at 70 kVp using automated tube current modulation. Fifty-six patients (96.6 %) had diagnostic CCTA images and two patients (3.4 %) had one vessel with poor image quality each rated as non-diagnostic. No significant effects of HR, HR variability and BMI on CCTA image quality were observed (all P > 0.05). Effective dose was 0.17 ± 0.02 mSv and the size-specific dose estimate was 1.03 ± 0.13 mGy. Prospectively ECG-triggered high-pitch CCTA at 70 kVp with 30 mL of contrast agent can provide diagnostic image quality at a radiation dose of less than 0.2 mSv in patients with a BMI of less than 25 kg/m{sup 2} and an HR of less than 70 bpm. (orig.)

ATM regulates 3-methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents.

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Agnihotri, Sameer; Burrell, Kelly; Buczkowicz, Pawel; Remke, Marc; Golbourn, Brian; Chornenkyy, Yevgen; Gajadhar, Aaron; Fernandez, Nestor A; Clarke, Ian D; Barszczyk, Mark S; Pajovic, Sanja; Ternamian, Christian; Head, Renee; Sabha, Nesrin; Sobol, Robert W; Taylor, Michael D; Rutka, James T; Jones, Chris; Dirks, Peter B; Zadeh, Gelareh; Hawkins, Cynthia

2014-10-01

Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular, the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM), were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors. Inhibition of ATM and MPG-mediated BER cooperate to sensitize tumor cells to alkylating agents, impairing tumor growth in vitro and in vivo with no toxicity to normal cells, providing an ideal therapeutic window. ©2014 American Association for Cancer Research.

Isoxanthohumol, a constituent of hop (Humulus lupulus L.), increases stress resistance in Caenorhabditis elegans dependent on the transcription factor DAF-16.

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Büchter, Christian; Havermann, Susannah; Koch, Karoline; Wätjen, Wim

2016-02-01

The flavanone isoxanthohumol (IX) has gained attention as antioxidative and chemopreventive agent, but the molecular mechanism of action remains unclear. We investigated effects of this secondary plant compound in vivo using the model organism Caenorhabditis elegans. Adult C. elegans nematodes were incubated with IX, and then, the stress resistance was analysed in the SYTOX assay; lifespan was monitored by touch-provoked movement method, the amount of reactive oxygen species (ROS) was measured in the DCF assay, and the nuclear localisation of the transcription factor DAF-16 was analysed by using a transgenic strain. By the use of a DAF-16 loss-of-function strain, we analysed whether the effects are dependent on DAF-16. IX increases the resistance of the nematode against thermal stress. Additionally, a reduction in ROS in vivo was caused by IX. Since the flavanone only has a marginal radical-scavenging capacity (TEAC assay), we suggest that IX mediates its antioxidative effects indirectly via activation of DAF-16 (homologue to mammalian FOXO proteins). The nuclear translocation of this transcription factor is increased by IX. In the DAF-16-mutated strain, the IX-mediated increase in stress resistance was completely abolished; furthermore, an increased formation of ROS and a reduced lifespan was mediated by IX. IX or a bacterial metabolite of IX causes antioxidative effects as well as an increased stress resistance in C. elegans via activation of DAF-16. The homologous pathway may have implications in the molecular mechanism of IX in mammals.

Streptococcus sanguinis isolate displaying a phenotype with cross-resistance to several rRNA-targeting agents.

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Mendes, Rodrigo E; Deshpande, Lalitagauri M; Kim, Jihye; Myers, Debra S; Ross, James E; Jones, Ronald N

2013-08-01

This study describes a clinical case of a 71-year-old male with a history of ischemic cardiomyopathy after left ventricular assist device (LVAD) endocarditis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) and a rare linezolid-resistant Streptococcus sanguinis strain (MIC, 32 μg/ml). The patient received courses of several antimicrobial agents, including linezolid for 79 days. The S. sanguinis strain had mutations in the 23S rRNA (T2211C, T2406C, G2576T, C2610T) and an amino acid substitution (N56D) in L22 and exhibited cross-resistance to ribosome-targeting agents.

Stress triggering of earthquakes and subsidence in the Louisiana coastal zone due to hydrocarbon production

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Mallman, Ellen P.

This thesis presents contributions towards better understanding of the interaction between earthquakes through elastic stress triggering and the role of hydrocarbon production on subsidence and land loss in southern Louisiana. The first issue addressed in this thesis is that of the role of static stress changes on earthquake triggering. The first study investigated whether observed changes in seismicity rate following the 1992 Landers, California and 1995 Kobe, Japan earthquakes are accurately predicted by elastic Coulomb stress transfer models. The analyses found that for all the tested DeltaCFS models wherever seismicity rate changes could be resolved the rate increased regardless of whether the DeltaCFS theoretically promoted or inhibited failure. The second study the common definition of a stress shadow was extended to independently test the stress shadow hypothesis using a global catalog of seismicity. The analyses indicated that while stress shadows are subtle, they are present in the global catalog. It also explains why "classical" stress shadows, similar to what was observed following the 1906 San Francisco earthquake are rarely observed for individual main shocks. The second issue addressed in this thesis is the role of hydrocarbon production on subsidence and land loss in the Louisiana Coastal Zone. The two studies in this thesis extend previous work by modeling the effect of oil and gas production in the region in two ways. First, multiple producing oil and gas fields and multiple epochs of leveling data are considered to provide constraints on predicted subsidence. Second, the role of compaction of the reservoir bounding shales on the regional subsidence signal is included. The results of the two studies on the role of hydrocarbon production on subsidence in the Louisiana Coastal Zone indicate that regional models of subsidence must include the effects of production-induced subsidence due to both sands and shales, but that this can not account for the

Resistance of functional Lactobacillus plantarum strains against food stress conditions.

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Ferrando, Verónica; Quiberoni, Andrea; Reinhemer, Jorge; Suárez, Viviana

2015-06-01

The survival of three Lactobacillus plantarum strains (Lp 790, Lp 813 and Lp 998) with functional properties was studied taking into account their resistance to thermal, osmotic and oxidative stress factors. Stress treatments applied were: 52 °C-15 min (Phosphate Buffer pH 7, thermal shock), H2O2 0.1% (p/v) - 30 min (oxidative shock) and NaCl aqueous solution at 17, 25 and 30% (p/v) (room temperature - 1 h, osmotic shock). The osmotic stress was also evaluated on cell growth in MRS broth added of 2, 4, 6, 8 and 10% (p/v) of NaCl, during 20 h at 30 °C. The cell thermal adaptation was performed in MRS broth, selecting 45 °C for 30 min as final conditions for all strains. Two strains (Lp 813 and Lp 998) showed, in general, similar behaviour against the three stress factors, being clearly more resistant than Lp 790. An evident difference in growth kinetics in presence of NaCl was observed between Lp 998 and Lp 813, Lp998 showing a higher optical density (OD570nm) than Lp 813 at the end of the assay. Selected thermal adaptation improved by 2 log orders the thermal resistance of both strains, but cell growth in presence of NaCl was enhanced only in Lp 813. Oxidative resistance was not affected with this thermal pre-treatment. These results demonstrate the relevance of cell technological resistance when selecting presumptive "probiotic" cultures, since different stress factors might considerably affect viability or/and performance of the strains. The incidence of stress conditions on functional properties of the strains used in this work are currently under research in our group. Copyright © 2014 Elsevier Ltd. All rights reserved.

Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma.

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Head, R J; Fay, M F; Cosgrove, L; Y C Fung, K; Rundle-Thiele, D; Martin, J H

2017-12-02

Glioblastoma is a lethal form of brain tumour usually treated by surgical resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key to the success of this multimodal approach is maintaining apoptotic sensitivity of tumour cells to the alkylating agent. This initial treatment likely establishes conditions contributing to development of drug resistance as alkylating agents form the O 6 -methylguanine adduct. This activates the mismatch repair (MMR) process inducing apoptosis and mutagenesis. This review describes key juxtaposed drivers in the balance between alkylation induced mutagenesis and apoptosis. Mutations in MMR genes are the probable drivers for alkylation based drug resistance. Critical to this interaction are the dose-response and temporal interactions between adduct formation and MMR mutations. The precision in dose interval, dose-responses and temporal relationships dictate a role for alkylating agents in either promoting experimental tumour formation or inducing tumour cell death with chemotherapy. Importantly, this resultant loss of chemotherapeutic selective pressure provides opportunity to explore novel therapeutics and appropriate combinations to minimise alkylation based drug resistance and tumour relapse.

Exercise-Induced Rhabdomyolysis and Stress-Induced Malignant Hyperthermia Events, Association with Malignant Hyperthermia Susceptibility, and RYR1 Gene Sequence Variations

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Antonella Carsana

2013-01-01

Full Text Available Exertional rhabdomyolysis (ER and stress-induced malignant hyperthermia (MH events are syndromes that primarily afflict military recruits in basic training and athletes. Events similar to those occurring in ER and in stress-induced MH events are triggered after exposure to anesthetic agents in MH-susceptible (MHS patients. MH is an autosomal dominant hypermetabolic condition that occurs in genetically predisposed subjects during general anesthesia, induced by commonly used volatile anesthetics and/or the neuromuscular blocking agent succinylcholine. Triggering agents cause an altered intracellular calcium regulation. Mutations in RYR1 gene have been found in about 70% of MH families. The RYR1 gene encodes the skeletal muscle calcium release channel of the sarcoplasmic reticulum, commonly known as ryanodine receptor type 1 (RYR1. The present work reviews the documented cases of ER or of stress-induced MH events in which RYR1 sequence variations, associated or possibly associated to MHS status, have been identified.

Pull-Based Distributed Event-Triggered Consensus for Multiagent Systems With Directed Topologies.

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Yi, Xinlei; Lu, Wenlian; Chen, Tianping

2017-01-01

This paper mainly investigates consensus problem with a pull-based event-triggered feedback control. For each agent, the diffusion coupling feedbacks are based on the states of its in-neighbors at its latest triggering time, and the next triggering time of this agent is determined by its in-neighbors' information. The general directed topologies, including irreducible and reducible cases, are investigated. The scenario of distributed continuous communication is considered first. It is proved that if the network topology has a spanning tree, then the event-triggered coupling algorithm can realize the consensus for the multiagent system. Then, the results are extended to discontinuous communication, i.e., self-triggered control, where each agent computes its next triggering time in advance without having to observe the system's states continuously. The effectiveness of the theoretical results is illustrated by a numerical example finally.

Abiotic stresses affect Trichoderma harzianum T39-induced resistance to downy mildew in grapevine.

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Roatti, Benedetta; Perazzolli, Michele; Gessler, Cesare; Pertot, Ilaria

2013-12-01

Enhancement of plant defense through the application of resistance inducers seems a promising alternative to chemical fungicides for controlling crop diseases but the efficacy can be affected by abiotic factors in the field. Plants respond to abiotic stresses with hormonal signals that may interfere with the mechanisms of induced systemic resistance (ISR) to pathogens. In this study, we exposed grapevines to heat, drought, or both to investigate the effects of abiotic stresses on grapevine resistance induced by Trichoderma harzianum T39 (T39) to downy mildew. Whereas the efficacy of T39-induced resistance was not affected by exposure to heat or drought, it was significantly reduced by combined abiotic stresses. Decrease of leaf water potential and upregulation of heat-stress markers confirmed that plants reacted to abiotic stresses. Basal expression of defense-related genes and their upregulation during T39-induced resistance were attenuated by abiotic stresses, in agreement with the reduced efficacy of T39. The evidence reported here suggests that exposure of crops to abiotic stress should be carefully considered to optimize the use of resistance inducers, especially in view of future global climate changes. Expression analysis of ISR marker genes could be helpful to identify when plants are responding to abiotic stresses, in order to optimize treatments with resistance inducers in field.

Nonlinear dynamical triggering of slow slip

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Johnson, Paul A [Los Alamos National Laboratory; Knuth, Matthew W [WISCONSIN; Kaproth, Bryan M [PENN STATE; Carpenter, Brett [PENN STATE; Guyer, Robert A [Los Alamos National Laboratory; Le Bas, Pierre - Yves [Los Alamos National Laboratory; Daub, Eric G [Los Alamos National Laboratory; Marone, Chris [PENN STATE

2010-12-10

Among the most fascinating, recent discoveries in seismology have been the phenomena of triggered slip, including triggered earthquakes and triggered-tremor, as well as triggered slow, silent-slip during which no seismic energy is radiated. Because fault nucleation depths cannot be probed directly, the physical regimes in which these phenomena occur are poorly understood. Thus determining physical properties that control diverse types of triggered fault sliding and what frictional constitutive laws govern triggered faulting variability is challenging. We are characterizing the physical controls of triggered faulting with the goal of developing constitutive relations by conducting laboratory and numerical modeling experiments in sheared granular media at varying load conditions. In order to simulate granular fault zone gouge in the laboratory, glass beads are sheared in a double-direct configuration under constant normal stress, while subject to transient perturbation by acoustic waves. We find that triggered, slow, silent-slip occurs at very small confining loads ({approx}1-3 MPa) that are smaller than those where dynamic earthquake triggering takes place (4-7 MPa), and that triggered slow-slip is associated with bursts of LFE-like acoustic emission. Experimental evidence suggests that the nonlinear dynamical response of the gouge material induced by dynamic waves may be responsible for the triggered slip behavior: the slip-duration, stress-drop and along-strike slip displacement are proportional to the triggering wave amplitude. Further, we observe a shear-modulus decrease corresponding to dynamic-wave triggering relative to the shear modulus of stick-slips. Modulus decrease in response to dynamical wave amplitudes of roughly a microstrain and above is a hallmark of elastic nonlinear behavior. We believe that the dynamical waves increase the material non-affine elastic deformation during shearing, simultaneously leading to instability and slow-slip. The inferred

Circumvention of camptothecin-induced resistance during the adaptive cellular stress response.

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Tiligada, Ekaterini; Papamichael, Konstantinos; Vovou, Ioanna; Delitheos, Andreas

2006-01-01

Camptothecin-11 (CPT-11) induces the adaptive stress response in yeast, conferring resistance via not fully characterized mechanisms. This study aimed at exploring, pharmacologically, the mechanisms underlying the CPT-11-induced resistance in yeast. Post-logarithmic yeast cultures were submitted to heat shock following preconditioning with suramin and with CPT-11, either alone or in combination with suramin, cycloheximide, sodium molybdate, okadaic acid, or verapamil. The stress response was evaluated by determining cell viability after heat shock. Preconditioning with CPT-11 or suramin conferred thermotolerance to yeast cells. Co-administration of CPT-11 with suramin, cycloheximide or okadaic acid reversed the CPT-11-induced thermotolerant phenotype, while sodium molybdate and verapamil had no effect on CPT-11-induced resistance. The antagonistic effect of the thermotolerance-inducers and the possible contribution of topoisomerase II activity and post-translational modifications mediated by the phosphatases PP1/2A in CPT-11-induced resistance may have important implications on the acquisition of resistance to stress in eukaryotic cells.

Increase of resistance to cracking on stress relieving of hardened steel

International Nuclear Information System (INIS)

Velichko, V.V.; Zabil'skij, V.V.; Mikheev, G.M.

1995-01-01

Regularities of increase of resistance to cracking during stress relieving of hardened low-alloyed steels were studied, using complex of methods. Effect of carbon, stress concentrator radius, duration and temperature of stress relieving was studies in particular. Results of investigating kinetics of change of physicomechanical properties, hydrogen desorption from hardened specimens showed, that increase of resistance to cracking was caused by desorption from grain boundaries of diffusion-mobile hydrogen, formed during hardening. 18 refs., 8 figs

THE STRESS RESISTANCE OF STUDENTS. THE PARADIGM OF SUBJECT PERSONALITY SELF- ORGANIZATION

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Sergey I. Dyakov

2016-01-01

Full Text Available The aim of the investigation is to consider a problem of stress resistance of students in the context of subject self-organization of the personality. Methods. The following methods of research are used: questioning; psychological and diagnostic tests «Tolerance of Uncertainty» (NTN and «Personal Factors of Decisions» (PFD by T. V. Kornilova; original experimental experiences – «Coding», a technique of a self-assessment (scaling and «A locus control». While data processing the methods of mathematical statistics (SPSS 12 package – the correlation analysis of Pearson and the factorial analysis with rotation use a component by «verimax» method are applied. Results and scientific novelty. Types of subjectivity and strategy of stress resistance are allocated. The nature and a role of the emotional and stressful mechanism having information and semantic properties in its basis are disclosed. Communication of irresponsible mechanisms of mentality with the sphere of consciousness in the context of subjectivity of the personality is shown. Mechanisms of emotional and rational self-control of system of mental self-organization of the person are presented. The statistical and qualitative data opening communications between properties of subjectivity and stress resistance of the personality are empirically obtained. Variation of the relations and also types of subjectivity and stress resistance emphasized based on the results of the presented research. Original (author’s methods of studying of subjectivity and factors of stress resistance are presented. Practical significance. The revealed factors of subject self-organization reveal the stress-producing directions of the environment and the relation of the personality to situations of changes and uncertainty: and also indicate subject properties of resistance to stress which need to be developed to increase the level of health of students, to reduce risk of deviance and delinquency of

A viewpoint on considering physiological principles to study stress resistance and resilience with aging.

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Miller, Benjamin F; Seals, Douglas R; Hamilton, Karyn L

2017-09-01

Adaptation to stress is identified as one of the seven pillars of aging research. Our viewpoint discusses the importance of the distinction between stress resistance and resilience, highlights how integration of physiological principles is critical for further understanding in vivo stress resistance and resilience, and advocates for the use of early warning signs to prevent a tipping point in stress resistance and resilience. Copyright © 2017 Elsevier B.V. All rights reserved.

Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine

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Benitez-Bribiesca Luis

2006-08-01

Full Text Available Abstract Background The development of resistance to cytotoxic chemotherapy continues to be a major obstacle for successful anticancer therapy. It has been shown that cells exposed to toxic concentrations of commonly used cancer chemotherapy agents develop DNA hypermetylation. Hence, demethylating agents could play a role in overcoming drug resistance. Methods MCF-7 cells were rendered adriamycin-resistant by weekly treatment with adriamycin. Wild-type and the resulting MCF-7/Adr cells were analyzed for global DNA methylation. DNA methyltransferase activity and DNA methyltransferase (dnmt gene expression were also determined. MCF-7/Adr cells were then subjected to antisense targeting of dnmt1, -3a, and -b genes and to treatment with the DNA methylation inhibitor hydralazine to investigate whether DNA demethylation restores sensitivity to adriamycin. Results MCF-7/Adr cells exhibited the multi-drug resistant phenotype as demonstrated by adriamycin resistance, mdr1 gene over-expression, decreased intracellular accumulation of adriamycin, and cross-resistance to paclitaxel. The mdr phenotype was accompanied by global DNA hypermetylation, over-expression of dnmt genes, and increased DNA methyltransferase activity as compared with wild-type MCF-7 cells. DNA demethylation through antisense targeting of dnmts or hydralazine restored adriamycin sensitivity of MCF-7/Adr cells to a greater extent than verapamil, a known inhibitor of mdr protein, suggesting that DNA demethylation interferes with the epigenetic reprogramming that participates in the drug-resistant phenotype. Conclusion We provide evidence that DNA hypermethylation is at least partly responsible for development of the multidrug-resistant phenotype in the MCF-7/Adr model and that hydralazine, a known DNA demethylating agent, can revert the resistant phenotype.

Triggering the adaptive immune system with commensal gut bacteria protects against insulin resistance and dysglycemia

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Céline Pomié

2016-06-01

Full Text Available Objective: To demonstrate that glycemia and insulin resistance are controlled by a mechanism involving the adaptive immune system and gut microbiota crosstalk. Methods: We triggered the immune system with microbial extracts specifically from the intestinal ileum contents of HFD-diabetic mice by the process of immunization. 35 days later, immunized mice were fed a HFD for up to two months in order to challenge the development of metabolic features. The immune responses were quantified. Eventually, adoptive transfer of immune cells from the microbiota-immunized mice to naïve mice was performed to demonstrate the causality of the microbiota-stimulated adaptive immune system on the development of metabolic disease. The gut microbiota of the immunized HFD-fed mice was characterized in order to demonstrate whether the manipulation of the microbiota to immune system interaction reverses the causal deleterious effect of gut microbiota dysbiosis on metabolic disease. Results: Subcutaneous injection (immunization procedure of ileum microbial extracts prevented hyperglycemia and insulin resistance in a dose-dependent manner in response to a HFD. The immunization enhanced the proliferation of CD4 and CD8 T cells in lymphoid organs, also increased cytokine production and antibody secretion. As a mechanism explaining the metabolic improvement, the immunization procedure reversed gut microbiota dysbiosis. Finally, adoptive transfer of immune cells from immunized mice improved metabolic features in response to HFD. Conclusions: Glycemia and insulin sensitivity can be regulated by triggering the adaptive immunity to microbiota interaction. This reduces the gut microbiota dysbiosis induced by a fat-enriched diet. Keywords: Gut microbiota and metabolic diseases, Immunity, Insulin resistance

Method of triggering the vacuum arc in source with a resistor

International Nuclear Information System (INIS)

Zheng Le; Lan Zhaohui; Long Jidong; Peng Yufei; Li Jie; Yang Zhen; Dong Pan; Shi Jinshui

2014-01-01

Background: The metal vapor vacuum arc (MEVVA) ion source is a common source which provides strong metal ion flow. To trigger this ion source, a high-voltage trigger pulse generator and a high-voltage isolation pulse transformer are needed, which makes the power supply system complex. Purpose: To simplify the power supply system, a trigger method with a resistor was introduced, and some characteristics of this method were studied. Methods: The ion flow provided by different main arc current was measured, as well as the trigger current. The main arc current and the ion current were recorded with different trigger resistances. Results: Experimental results showed that, within a certain range of resistances, the larger the resistance value, the more difficult it was to success fully trigger the source. Meanwhile, the main arc rising edge became slower on the increasing in the trigger time. However, the resistance value increment had hardly impact on the intensity of ion flow extracted in the end, The ion flow became stronger with the increasing main arc current. Conclusion: The power supply system of ion source is simplified by using the trigger method with a resistor. Only a suitable resistor was needed to complete the conversion process from trigger to arc initiating. (authors)

Most oxidative stress response in water samples comes from unknown chemicals: the need for effect-based water quality trigger values.

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Escher, Beate I; van Daele, Charlotte; Dutt, Mriga; Tang, Janet Y M; Altenburger, Rolf

2013-07-02

The induction of adaptive stress response pathways is an early and sensitive indicator of the presence of chemical and non-chemical stressors in cells. An important stress response is the Nrf-2 mediated oxidative stress response pathway where electrophilic chemicals or chemicals that cause the formation of reactive oxygen species initiate the production of antioxidants and metabolic detoxification enzymes. The AREc32 cell line is sensitive to chemicals inducing oxidative stress and has been previously applied for water quality monitoring of organic micropollutants and disinfection byproducts. Here we propose an algorithm for the derivation of effect-based water quality trigger values for this end point that is based on the combined effects of mixtures of regulated chemicals. Mixture experiments agreed with predictions by the mixture toxicity concept of concentration addition. The responses in the AREc32 and the concentrations of 269 individual chemicals were quantified in nine environmental samples, ranging from treated effluent, recycled water, stormwater to drinking water. The effects of the detected chemicals could explain less than 0.1% of the observed induction of the oxidative stress response in the sample, affirming the need to use effect-based trigger values that account for all chemicals present.

Involvement of Prohibitin Upregulation in Abrin-Triggered Apoptosis

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Yu-Huei Liu

2012-01-01

Full Text Available Abrin (ABR, a protein purified from the seeds of Abrus precatorius, induces apoptosis in various types of cancer cells. However, the detailed mechanism remains largely uncharacterized. By using a cDNA microarray platform, we determined that prohibitin (PHB, a tumor suppressor protein, is significantly upregulated in ABR-triggered apoptosis. ABR-induced upregulation of PHB is mediated by the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK pathway, as demonstrated by chemical inhibitors. In addition, ABR significantly induced the expression of Bax as well as the activation of caspase-3 and poly(ADP-ribose polymerase (PARP in Jurkat T cells, whereas the reduction of PHB by specific RNA interference delayed ABR-triggered apoptosis through the proapoptotic genes examined. Moreover, our results also indicated that nuclear translocation of the PHB-p53 complex may play a role in the transcription of Bax. Collectively, our data show that PHB plays a role in ABR-induced apoptosis, which may be helpful for the development of diagnostic or therapeutic agents.

Stress/strain changes and triggered seismicity at The Geysers, California

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Gomberg, Joan; Davis, Scott

1996-01-01

The principal results of this study of remotely triggered seismicity in The Geysers geothermal field are the demonstration that triggering (initiation of earthquake failure) depends on a critical strain threshold and that the threshold level increases with decreasing frequency, or, equivalently, depends on strain rate. This threshold function derives from (1) analyses of dynamic strains associated with surface waves of the triggering earthquakes, (2) statistically measured aftershock zone dimensions, and (3) analytic functional representations of strains associated with power production and tides. The threshold is also consistent with triggering by static strain changes and implies that both static and dynamic strains may cause aftershocks. The observation that triggered seismicity probably occurs in addition to background activity also provides an important constraint on the triggering process. Assuming the physical processes underlying earthquake nucleation to be the same, Gomberg [this issue] discusses seismicity triggered by the MW 7.3 Landers earthquake, its constraints on the variability of triggering thresholds with site, and the implications of time delays between triggering and triggered earthquakes. Our results enable us to reject the hypothesis that dynamic strains simply nudge prestressed faults over a Coulomb failure threshold sooner than they would have otherwise. We interpret the rate-dependent triggering threshold as evidence of several competing processes with different time constants, the faster one(s) facilitating failure and the other(s) inhibiting it. Such competition is a common feature of theories of slip instability. All these results, not surprisingly, imply that to understand earthquake triggering one must consider not only simple failure criteria requiring exceedence of some constant threshold but also the requirements for generating instabilities.

Stress/strain changes and triggered seismicity at The Geysers, California

Science.gov (United States)

Gomberg, J.; Davis, S.

1996-01-01

The principal results of this study of remotely triggered seismicity in The Geysers geothermal field are the demonstration that triggering (initiation of earthquake failure) depends on a critical strain threshold and that the threshold level increases with decreasing frequency or equivalently, depends on strain rate. This threshold function derives from (1) analyses of dynamic strains associated with surface waves of the triggering earthquakes, (2) statistically measured aftershock zone dimensions, and (3) analytic functional representations of strains associated with power production and tides. The threshold is also consistent with triggering by static strain changes and implies that both static and dynamic strains may cause aftershocks. The observation that triggered seismicity probably occurs in addition to background activity also provides an important constraint on the triggering process. Assuming the physical processes underlying earthquake nucleation to be the same, Gomberg [this issue] discusses seismicity triggered by the MW 7.3 Landers earthquake, its constraints on the variability of triggering thresholds with site, and the implications of time delays between triggering and triggered earthquakes. Our results enable us to reject the hypothesis that dynamic strains simply nudge prestressed faults over a Coulomb failure threshold sooner than they would have otherwise. We interpret the rate-dependent triggering threshold as evidence of several competing processes with different time constants, the faster one(s) facilitating failure and the other(s) inhibiting it. Such competition is a common feature of theories of slip instability. All these results, not surprisingly, imply that to understand earthquake triggering one must consider not only simple failure criteria requiring exceedence of some constant threshold but also the requirements for generating instabilities.

ONC201 activates ER stress to inhibit the growth of triple-negative breast cancer cells.

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Yuan, Xun; Kho, Dhonghyo; Xu, Jing; Gajan, Ambikai; Wu, Kongming; Wu, Gen Sheng

2017-03-28

ONC201 was previously identified as a first-in-class antitumor agent and small-molecule inducer of the TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) gene that induces apoptosis in cancer cells. ONC201 has a safety profile and is currently in phase II clinical trials for the treatment of various malignancies. In the current study, we examine the effect of ONC201 on triple-negative breast cancer cells (TNBC), a subtype of breast cancer that is sensitive to TRAIL. We find that ONC201 inhibits the growth of TNBC cells including TNBC cells that have developed acquired TRAIL resistance. However, TNBC cells that have developed acquired ONC201 resistance are cross-resistant to TRAIL. Mechanistically, ONC201 triggers an integrated stress response (ISR) involving the activation of the transcription factor ATF4. Knockdown of ATF4 impairs ONC201-induced apoptosis of TNBC cells. Importantly, the activation of ATF4 is compromised in ONC201-resistant TNBC cells. Thus, our results indicate that ONC201 induces an ISR to cause TNBC cell death and suggest that TNBC patients may benefit from ONC201-based therapies.

The risk of some veterinary antimicrobial agents on public health associated with antimicrobial resistance and their molecular basis

OpenAIRE

Haihong Hao; Zahid Iqbal; Yulian Wang; Guyue Cheng; Zong-Hui Yuan

2016-01-01

The risk of antimicrobial agents used in food-producing animals on public health associated with antimicrobial resistance continues to be a current topic of discussion as related to animal and human public health. In the present review, resistance monitoring data and risk assessment result of some important antimicrobial agents were cited to elucidate the possible association of antimicrobial use in food animals and antimicrobial resistance in human. From the selected examples, it was obvious...

Central Nervous System (CNS Disease Triggering Takotsubo Syndrome

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Josef Finsterer

2016-01-01

Full Text Available Takotsubo syndrome (TTS is usually triggered by psychological or physical stress. One of the many physical sources of stress are central nervous system (CNS disorders. CNS disorders most frequently triggering TTS include subarachnoid bleeding, epilepsy, ischemic stroke, migraine, and intracerebral bleeding. More rare CNS-triggers of TTS include posterior reversible encephalopathy syndrome (PRES, amyotrophic lateral sclerosis, encephalitis, or traumatic brain or spinal cord injury. TTS triggered by any of the CNS disorders needs to be recognized since adequate treatment of TTS may improve the general outcome from the CNS disorder as well. Neurologists need to be aware of TTS as a complication of specific CNS disorders but TTS may be triggered also by CNS disorders so far not recognised as causes of TTS.

Effect of cold working on the stress corrosion cracking resistance of nickel-chromium-iron alloys

International Nuclear Information System (INIS)

Yonezawa, T.; Onimura, K.

1987-01-01

In order to grasp the stress corrosion cracking resistance of cold worked nickel base alloys in PWR primary water, the effect of cold working on the stress corrosion cracking resistance of alloys 600, X-750 and 690, in high temperature water, have been studied. Stress corrosion cracking tests were conducted at 360 0 C (633K) in a simulated PWR primary water for about 12,000 hours (43.2Ms). From the test results, it is concluded that the stress corrosion cracking resistance in the cold worked Alloy 600 at the same applied stress level increases with an increase in cold working ratio, and the cold worked alloys of thermally treated 690 and X-750 have excellent stress corrosion cracking resistance. (Author)

What Triggers the Establishment of a Works Council?

OpenAIRE

Jens Mohrenweiser; Paul Marginson; Uschi Backes-Gellner

2009-01-01

This paper analyses events that trigger the establishment of a works council and the actor or agent who triggers it. The paper extends previous research in two dimensions. First, we examine specific events that motivate workers to establish a works council, such as a change of owner, founding a spin-off, a firm-acquisition or a radical restructuring. These events express risk protection as workers’ primary motivation for establishing a works council. Second, we analyse the actor or agent who ...

Dynamic Aftershock Triggering Correlated with Cyclic Loading in the Slip Direction

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Hardebeck, J.

2014-12-01

Dynamic stress changes have been shown to contribute to aftershock triggering, but the physical triggering mechanisms are not fully understood. Some proposed mechanisms are based on dynamic stress loading of the target fault in a direction that encourages earthquake slip (e.g. dynamic Coulomb stress triggering), while other mechanisms are based on fault weakening due to shaking. If dynamic stress loading in the fault slip direction plays a role in aftershock triggering, we would expect to see a relationship between the dynamic stress orientations and the aftershock focal mechanisms. Alternatively, if dynamic stress change triggering functions only through a fault weakening mechanism that is independent of the slip direction of the target fault, no such relationship is expected. I study aftershock sequences of 4 M≥6.7 mainshocks in southern California, and find a small but significant relationship between modeled dynamic stress direction and aftershock focal mechanisms. The mainshock dynamic stress changes have two observed impacts: changing the focal mechanisms in a given location to favor those aligned with the dynamic stress change, and changing the spatial distribution of seismicity to favor locations where the dynamic stress change aligns with the background stress. The aftershock focal mechanisms are significantly more aligned with the dynamic stress changes than the preshock mechanisms for only the first 0.5-1 year following most mainshocks, although for at least 10 years following Hector Mine. Dynamic stress effects on focal mechanisms are best observed at long periods (30-60 sec). Dynamic stress effects are only observed when using metrics based on repeated stress cycling in the same direction, for example considering the dominant stress orientation over the full time series, and not for the peak dynamic stress. These results imply that dynamic aftershock triggering operates at least in part through cyclic loading in the direction of fault slip, although

Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?

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Peciña, Susana; Schulkin, Jay; Berridge, Kent C

2006-04-13

Corticotropin-releasing factor (CRF) is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior). Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 microl) or amphetamine (20 microg/0.2 microl). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 microg) selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress, or by persistent attempts to

Stress, “A Proxy Killer” and Role of Adaptogen as Antistress Agent

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T Prakash

2011-02-01

Full Text Available Stress is a non-specific immune response of the body known toalter the physiological homeostasis of the organism resulting invarious neuronal endocrinal and visceral functions. Derailmentof the immune system contributes for the alteration in thehomeostasis and resulting in stress related disturbances.Stress responses are composed of alterations in behavior,autonomic function and the secretion of multiple hormonesincluding adrenocorticotropin hormone (ACTH andcortisol/corticosterone, adrenal catecholamine, oxytocin,prolactin and renin. The concept of “Adaptogen” as a group ofmedicinal substances was first adopted by Lazarev.Adaptogens are the substances that push the organism into “astate of non-specific heightened resistance (SNIR” in order tobetter resist stressors and adapt to extraordinary challenges.They normalize the body functions; strengthen systems andfunctions that are compromised by stress and have aprotective effect against a wide variety of environmental andemotional stress. Till date various substances (natural,synthetic and techniques (yoga, exercise have been used tocontrol the stress and stress related disorder. Among thoseadaptogens are the substances on which less research has beencarried out hence in this article we have made an attempt toreview the history, potential and different plausible mode ofaction of adaptogen along with different experimental animalmodel for the evaluation of an adaptogen.

Taming the Wildness of "Trojan-Horse" Peptides by Charge-Guided Masking and Protease-Triggered Demasking for the Controlled Delivery of Antitumor Agents.

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Shi, Nian-Qiu; Qi, Xian-Rong

2017-03-29

Cell-penetrating peptide (CPP), also called "Trojan Horse" peptide, has become a successful approach to deliver various payloads into cells for achieving the intracellular access. However, the "Trojan Horse" peptide is too wild, not just to "Troy", but rather widely distributed in the body. Thus, there is an urgent need to tame the wildness of "Trojan Horse" peptide for targeted delivery of antineoplastic agents to the tumor site. To achieve this goal, we exploit a masked CPP-doxorubicin conjugate platform for targeted delivery of chemotherapeutic drugs using charge-guided masking and protease-triggered demasking strategies. In this platform, the cell-penetrating function of the positively CPP (d-form nonaarginine) is abrogated by a negatively shielding peptide (masked CPP), and between them is a cleavable substrate peptide by the protease (MMP-2/9). Protease-triggered demasking would occur when the masked CPP reached the MMP-2/9-riched tumor. The CPP-doxorubicin conjugate (CPP-Dox) and the masked CPP-Dox conjugate (mCPP-Dox) were used as models for the evaluation of masking and demasking processes. It was found that exogenous MMP-2/9 could effectively trigger the reversion of CPP-cargo in this conjugate, and this trigger adhered to the Michaelis-Menten kinetics profile. This conjugate was sensitive to the trigger of endogenous MMP-2/9 and could induce enhanced cytotoxicity toward MMP-2/9-rich tumor cells. In vivo antitumor efficacy revealed that this masked conjugate had considerable antitumor activity and could inhibit the tumor growth at a higher level relative to CPP-cargo. Low toxicity in vivo showed the noticeably decreased wildness of this conjugate toward normal tissues and more controllable entry of antitumor agents into "Troy". On the basis of analyses in vitro and in vivo, this mCPP-cargo conjugate delivery system held an improved selectivity toward MMP-2/9-rich tumors and would be a promising strategy for tumor-targeted treatment.

Stress-Induced Premature Senescence or Stress-Induced Senescence-Like Phenotype: One In Vivo Reality, Two Possible Definitions?

OpenAIRE

Toussaint, Olivier; Dumont, Patrick; Remacle, Jose; Dierick, Jean-Francois; Pascal, Thierry; Frippiat, Christophe; Magalhaes, Joao Pedro; Zdanov, Stephanie; Chainiaux, Florence

2002-01-01

No consensus exists so far on the definition of cellular senescence. The narrowest definition of senescence is irreversible growth arrest triggered by telomere shortening counting cell generations (definition 1). Other authors gave an enlarged functional definition encompassing any kind of irreversible arrest of proliferative cell types induced by damaging agents or cell cycle deregulations after overexpression of proto-oncogenes (definition 2). As stress increases, the proportion of cells in...

Vitiligo: How do oxidative stress-induced autoantigens trigger autoimmunity?

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Xie, Heng; Zhou, Fubo; Liu, Ling; Zhu, Guannan; Li, Qiang; Li, Chunying; Gao, Tianwen

2016-01-01

Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes. These factors synergistically contribute to the accumulation of ROS in melanocytes, finally leading to melanocyte damage and the production of autoantigens through the following ways: apoptosis, accumulation of misfolded peptides and cytokines induced by endoplasmic reticulum stress as well as the sustained unfolded protein response, and an 'eat me' signal for phagocytic cells triggered by calreticulin. Subsequently, autoantigens presentation and dendritic cells maturation occurred mediated by the release of antigen-containing exosomes, adenosine triphosphate and melanosomal autophagy. With the involvement of inducible heat shock protein 70, cellular immunity targeting autoantigens takes the essential place in the destruction of melanocytes, which eventually results in vitiligo. Several treatments, such as narrow band ultraviolet, quercetin and α-melanophore-stimulating hormone, are reported to be able to lower ROS thereby achieving repigmentation in vitiligo. In therapies targeting autoimmunity, restore of regulatory T cells is absorbing attention, in which narrow band ultraviolet also plays a role. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Endoplasmic reticulum stress regulates inflammation and insulin resistance in skeletal muscle from pregnant women.

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Liong, Stella; Lappas, Martha

2016-04-15

Sterile inflammation and infection are key mediators of inflammation and peripheral insulin resistance associated with gestational diabetes mellitus (GDM). Studies have shown endoplasmic reticulum (ER) stress to induce inflammation and insulin resistance associated with obesity and type 2 diabetes, however is paucity of studies investigating the effects of ER stress in skeletal muscle on inflammation and insulin resistance associated with GDM. ER stress proteins IRE1α, GRP78 and XBP-1s were upregulated in skeletal muscle of obese pregnant women, whereas IRE1α was increased in GDM women. Suppression of ER stress, using ER stress inhibitor tauroursodeoxycholic acid (TUDCA) or siRNA knockdown of IRE1α and GRP78, significantly downregulated LPS-, poly(I:C)- or IL-1β-induced production of IL-6, IL-8, IL-1β and MCP-1. Furthermore, LPS-, poly(I:C)- or TNF-α-induced insulin resistance was improved following suppression of ER stress, by increasing insulin-stimulated phosphorylation of IR-β, IRS-1, GLUT-4 expression and glucose uptake. In summary, our inducible obesity and GDM-like models suggests that the development of GDM may be involved in activating ER stress-induced inflammation and insulin resistance in human skeletal muscle. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Life without water: cross-resistance of anhydrobiotic cell line to abiotic stresses

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Gusev, Oleg

2016-07-01

Anhydrobiosis is an intriguing phenomenon of natural ability of some organisms to resist water loss. The larvae of Polypedilum vanderplanki, the sleeping chironomid is the largest and most complex anhydrobionts known to date. The larvae showed ability to survive variety of abiotic stresses, including outer space environment. Recently cell line (Pv11) derived from the embryonic mass of the chironomid was established. Initially sensitive to desiccation cells, are capable to "induced" anhydrobiosis, when the resistance to desiccation can be developed by pre-treatment of the cells with trehalose followed by quick desiccation. We have further conducted complex analysis of the whole genome transcription response of Pv11 cells to different abiotic stresses, including oxidative stress and irradiation. Comparative analysis showed that the gene set, responsible for formation of desiccation resistance (ARID regions in the genome) is also activated in response to other types of stresses and likely to contribute to general enhancing of the resistance of the cells to harsh environment. We have further demonstrated that the cells are able to protect recombinant proteins from harmful effect of desiccation

Growth on Alpha-Ketoglutarate Increases Oxidative Stress Resistance in the Yeast Saccharomyces cerevisiae

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Maria Bayliak

2017-01-01

Full Text Available Alpha-ketoglutarate (AKG is an important intermediate in cell metabolism, linking anabolic and catabolic processes. The effect of exogenous AKG on stress resistance in S. cerevisiae cells was studied. The growth on AKG increased resistance of yeast cells to stresses, but the effects depended on AKG concentration and type of stressor. Wild-type yeast cells grown on AKG were more resistant to hydrogen peroxide, menadione, and transition metal ions (Fe2+ and Cu2+ but not to ethanol and heat stress as compared with control ones. Deficiency in SODs or catalases abolished stress-protective effects of AKG. AKG-supplemented growth led to higher values of total metabolic activity, level of low-molecular mass thiols, and activities of catalase and glutathione reductase in wild-type cells compared with the control. The results suggest that exogenous AKG may enhance cell metabolism leading to induction of mild oxidative stress. It turn, it results in activation of antioxidant system that increases resistance of S. cerevisiae cells to H2O2 and other stresses. The presence of genes encoding SODs or catalases is required for the expression of protective effects of AKG.

Emerging Gram negative resistance to last-line antimicrobial agents fosfomycin, colistin and ceftazidime-avibactam - epidemiology, laboratory detection and treatment implications.

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Sherry, Norelle; Howden, Benjamin

2018-04-01

Multidrug-resistant (MDR) and extensively-drug-resistant (XDR) Gram-negative bacteria have emerged as a major threat to human health globally. This has resulted in the 're-discovery' of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas covered: Here we describe recent developments in resistance to three of the most important last-line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime-avibactam. Expert commentary: A key challenge for microbiologists and clinicians using these agents for treating patients with MDR and XDR Gram negative infections is the need to ensure appropriate reference methods are being used to test susceptibility to these agents, especially colistin and fosfomycin. These methods are not available in all laboratories meaning accurate results are either delayed, or potentially inaccurate as non-reference methods are employed. Combination therapy for MDR and XDR Gram negatives is likely to become more common, and future studies should focus on the clinical effects of monotherapy vs combination therapy, as well as validation of synergy testing methods. Effective national and international surveillance systems to detect and respond to resistance to these last line agents are also critical.

Pairing of heterochromatin in response to cellular stress

International Nuclear Information System (INIS)

Abdel-Halim, H.I.; Mullenders, L.H.F.; Boei, J.J.W.A.

2006-01-01

We previously reported that exposure of human cells to DNA-damaging agents (X-rays and mitomycin C (MMC)) induces pairing of the homologous paracentromeric heterochromatin of chromosome 9 (9q12-13). Here, we show that UV irradiation and also heat shock treatment of human cells lead to similar effects. Since the various agents induce very different types and frequencies of damage to cellular constituents, the data suggest a general stress response as the underlying mechanism. Moreover, local UV irradiation experiments revealed that pairing of heterochromatin is an event that can be triggered without induction of DNA damage in the heterochromatic sequences. The repair deficient xeroderma pigmentosum cells (group F) previously shown to fail pairing after MMC displayed elevated pairing after heat shock treatment but not after UV exposure. Taken together, the present results indicate that pairing of heterochromatin following exposure to DNA-damaging agents is initiated by a general stress response and that the sensing of stress or the maintenance of the paired status of the heterochromatin might be dependent on DNA repair

Effects of crystallographic texture on stress-migration resistance in copper thin films

International Nuclear Information System (INIS)

Koike, J.; Wada, M.; Sanada, M.; Maruyama, K.

2002-01-01

The crystallographic texture of heat-treated Cu thin films and its effects on stress-migration resistance were studied as a function of film thickness within a range of 50-900 nm. All as-deposited films had (111) texture. After heat treatment at 723 K, texture transition from (111) to (100) was observed in films of thickness greater than 300 nm. The (111) texture films after heat treatment showed severe stress migration; in contrast, the (100) texture films showed no noticeable stress migration. The observed stress-migration resistance in the (100) texture films can be attributed to the absence of twins and to lower thermal stress as compared with the (111) texture films

What makes you tic? Translational approaches to study the role of stress and contextual triggers in Tourette syndrome.

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Godar, Sean C; Bortolato, Marco

2017-05-01

Tourette syndrome (TS) is a neurodevelopmental condition characterized by multiple, recurring motor and phonic tics. Rich empirical evidence shows that the severity of tics and associated manifestations is increased by several stressors and contextual triggers; however, the neurobiological mechanisms responsible for symptom exacerbation in TS remain poorly understood. This conceptual gap partially reflects the high phenotypic variability in tics, as well as the existing difficulties in operationalizing and standardizing stress and its effects in a clinical setting. Animal models of TS may be highly informative tools to overcome some of these limitations; these experimental preparations have already provided critical insights on key aspects of TS pathophysiology, and may prove useful to identify the neurochemical alterations induced by different stressful contingencies. In particular, emerging knowledge on the role of contextual triggers in animal models of TS may inform the development of novel pharmacological interventions to reduce tic fluctuations in this disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

What makes you tic? Translational approaches to study the role of stress and contextual triggers in Tourette syndrome

Science.gov (United States)

Godar, Sean C; Bortolato, Marco

2016-01-01

Tourette syndrome (TS) is a neurodevelopmental condition characterized by multiple, recurring motor and phonic tics. Rich empirical evidence shows that the severity of tics and associated manifestations is increased by several stressors and contextual triggers; however, the neurobiological mechanisms responsible for symptom exacerbation in TS remain poorly understood. This conceptual gap partially reflects the high phenotypic variability in tics, as well as the existing difficulties in operationalizing and standardizing stress and its effects in a clinical setting. Animal models of TS may be highly informative tools to overcome some of these limitations; these experimental preparations have already provided critical insights on key aspects of TS pathophysiology, and may prove useful to identify the neurochemical alterations induced by different stressful contingencies. In particular, emerging knowledge on the role of contextual triggers in animal models of TS may inform the development of novel pharmacological interventions to reduce tic fluctuations in this disorder. PMID:27939782

Sex differences in oxidative stress resistance in relation to longevity in Drosophila melanogaster.

Science.gov (United States)

Niveditha, S; Deepashree, S; Ramesh, S R; Shivanandappa, T

2017-10-01

Gender differences in lifespan and aging are known across species. Sex differences in longevity within a species can be useful to understand sex-specific aging. Drosophila melanogaster is a good model to study the problem of sex differences in longevity since females are longer lived than males. There is evidence that stress resistance influences longevity. The objective of this study was to investigate if there is a relationship between sex differences in longevity and oxidative stress resistance in D. melanogaster. We observed a progressive age-dependent decrease in the activity of SOD and catalase, major antioxidant enzymes involved in defense mechanisms against oxidative stress in parallel to the increased ROS levels over time. Longer-lived females showed lower ROS levels and higher antioxidant enzymes than males as a function of age. Using ethanol as a stressor, we have shown differential susceptibility of the sexes to ethanol wherein females exhibited higher resistance to ethanol-induced mortality and locomotor behavior compared to males. Our results show strong correlation between sex differences in oxidative stress resistance, antioxidant defenses and longevity. The study suggests that higher antioxidant defenses in females may confer resistance to oxidative stress, which could be a factor that influences sex-specific aging in D. melanogaster.

Yeasts acquire resistance secondary to antifungal drug treatment by adaptive mutagenesis.

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David Quinto-Alemany

Full Text Available Acquisition of resistance secondary to treatment both by microorganisms and by tumor cells is a major public health concern. Several species of bacteria acquire resistance to various antibiotics through stress-induced responses that have an adaptive mutagenesis effect. So far, adaptive mutagenesis in yeast has only been described when the stress is nutrient deprivation. Here, we hypothesized that adaptive mutagenesis in yeast (Saccharomyces cerevisiae and Candida albicans as model organisms would also take place in response to antifungal agents (5-fluorocytosine or flucytosine, 5-FC, and caspofungin, CSP, giving rise to resistance secondary to treatment with these agents. We have developed a clinically relevant model where both yeasts acquire resistance when exposed to these agents. Stressful lifestyle associated mutation (SLAM experiments show that the adaptive mutation frequencies are 20 (S. cerevisiae -5-FC, 600 (C. albicans -5-FC or 1000 (S. cerevisiae--CSP fold higher than the spontaneous mutation frequency, the experimental data for C. albicans -5-FC being in agreement with the clinical data of acquisition of resistance secondary to treatment. The spectrum of mutations in the S. cerevisiae -5-FC model differs between spontaneous and acquired, indicating that the molecular mechanisms that generate them are different. Remarkably, in the acquired mutations, an ectopic intrachromosomal recombination with an 87% homologous gene takes place with a high frequency. In conclusion, we present here a clinically relevant adaptive mutation model that fulfils the conditions reported previously.

Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cells

International Nuclear Information System (INIS)

Tanaka, Mamoru; Kamiya, Takeshi; Joh, Takashi; Kataoka, Hiromi; Yano, Shigenobu; Ohi, Hiromi; Kawamoto, Keisuke; Shibahara, Takashi; Mizoshita, Tsutomu; Mori, Yoshinori; Tanida, Satoshi

2013-01-01

Cisplatin (CDDP) is the most frequently used chemotherapeutic agent for various types of advanced cancer, including gastric cancer. However, almost all cancer cells acquire resistance against CDDP, and this phenomenon adversely affects prognosis. Thus, new chemotherapeutic agents that can overcome the CDDP-resistant cancer cells will improve the survival of advanced cancer patients. We synthesized new glycoconjugated platinum (II) and palladium (II) complexes, [PtCl 2 (L)] and [PdCl 2 (L)]. CDDP-resistant gastric cancer cell lines were established by continuous exposure to CDDP, and gene expression in the CDDP-resistant gastric cancer cells was analyzed. The cytotoxicity and apoptosis induced by [PtCl 2 (L)] and [PdCl 2 (L)] in CDDP-sensitive and CDDP-resistant gastric cancer cells were evaluated. DNA double-strand breaks by drugs were assessed by evaluating phosphorylated histone H2AX. Xenograft tumor mouse models were established and antitumor effects were also examined in vivo. CDDP-resistant gastric cancer cells exhibit ABCB1 and CDKN2A gene up-regulation, as compared with CDDP-sensitive gastric cancer cells. In the analyses of CDDP-resistant gastric cancer cells, [PdCl 2 (L)] overcame cross-resistance to CDDP in vitro and in vivo. [PdCl 2 (L)] induced DNA double-strand breaks. These results indicate that [PdCl 2 (L)] is a potent chemotherapeutic agent for CDDP-resistant gastric cancer and may have clinical applications

Targeting the oxidative stress response system of fungi with safe, redox-potent chemosensitizing agents

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Jong H. eKim

2012-03-01

Full Text Available The cellular antioxidation system is a target in the antifungal action of amphotericin B (AMB and itraconazole (ITZ, in filamentous fungi. The sakAΔ mutant of Aspergillus fumigatus, a mitogen-activated protein kinase (MAPK gene deletion mutant in the antioxidation system, was found to be more sensitive to AMB or ITZ than other A. fumigatus strains, a wild type and a mpkCΔ mutant (MAPK gene deletion mutant in polyalcohol sugar utilization system. The sakAΔ mutant showed no growth at 0.5 μg mL-1 of ITZ or reduced growth at 1.0 to 2.0 μg mL-1 of AMB, while the other strains exhibited robust growth. Complete fungal kill (≥ 99.9% by ITZ or AMB was achieved by much lower dosages for the sakAΔ mutant than for the other strains. SakA and MpkC appear to have overlapping roles in marshalling the oxidative stress response under treatment by an organic peroxide, tert-butyl hydroperoxide (t-BuOOH, or hydrogen peroxide (H2O2. The SakA signalling pathway was found to be responsible for fungal tolerance to AMB or ITZ toxicity. It appears msnA, an Aspergillus ortholog to Saccharomyces cerevisiae MSN2 (encoding a stress-responsive C2H2-type zinc-finger regulator and sakA and/or mpkC (upstream MAPKs are in the same stress response network under t-BuOOH-, H2O2- or AMB-triggered toxicity. Of note is that ITZ-sensitive yeast pathogens (Candida krusei and Cryptococcus neoformans were also sensitive to t-BuOOH, showing a connection between ITZ toxicity and oxidative stress response. This was shown by enhanced antifungal activity of AMB or ITZ when co-applied with redox-potent natural compounds, 2,3-dihydroxybenzaldehyde, thymol or salicylaldehyde, as chemosensitizing agents. Hence, redox compounds, which target the antioxidation system in fungi, possess a potent chemosensitizing capacity to enhance efficacy of conventional drugs inducing oxidative stress. Such chemosensitization can reduce costs and alleviate negative side effects associated with current

Stress proteins and phytohormones: their role in formation of plant resistance

International Nuclear Information System (INIS)

Kosakivska, I.V.

2005-01-01

Full text: Using the disc-electrophoresis methods, we have studied protein biosynthesis of different plants, including 11 species of Orchidaceae, some other tropical and subtropical plants, 9 different fruit plants, and 4 cultivars of Triticum aestivum L. under stresses factors such as high and low temperature, clinostating, radioactive irradiation and osmotic shock. Specific and unspecific reactions of plants protein system on stresses were found. De novo synthesis of 35 and 45 kD polypeptides were observed in total and mitochondrial proteins fractions after heat-shock and radioactive irradiation. This suggests that mitochondries participate in formation of plant resistance. Intensive synthesis of ABA revealed as the universal reaction of all studied plants on action of different kinds of stresses. Specific changes in balance of phytohormones were found under different stresses. We observed the correlation between endogenous ABA, IAA and cytokinin level and plant resistance. We also found the interaction between the process of biosynthesis of proteins and phytohormone balance, as well as their direct participation in formation of plant resistance. (author)

Myocardial Contrast Agents – Safety Considerations and Clinical Efficacy in Stress Echocardiography

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Maier Anca

2016-11-01

Full Text Available Transthoracic echocardiographic examination is known to be a safe, non-invasive and reproducible method, used in every day clinical practice to obtain important information about cardiac structure and function. Unfortunately, a significant proportion of studies have highlighted the considerable technically difficultly in producing diagnostic images due to a poor acoustic window and more than 33% of patients undergoing stress echocardiography have suboptimal echocardiographic images. All these limitations have led to the use of contrast agents to improve the quality of standard ultrasound examination to provide a better delineation of left ventricle endocardial borders or to obtain information that cannot be achieved by using standard echocardiography, such as assessing myocardial microcirculation and therefore perfusion. This paper sought to review the clinical efficacy and safety of ultrasound contrast agents focusing on stress echocardiography.

Change agent's contribution to recipients' resistance to change: A two-sided story

NARCIS (Netherlands)

Vos, Janita F.J.; Rupert, Joyce

2018-01-01

In the change management literature, most studies on recipients’ resistance to change include only the views of agents or of recipients, thereby ignoring that these parties may have different perceptions. In this quantitative study, we include the perceptions of both parties in studying the

[Triggering role of emotional stress and childbirth. Unexpected occurrence of Graves' disease compared to 96 cases of Hashimoto thyroiditis and 97 cases of thyroid nodules].

Science.gov (United States)

Martin-du Pan, R C

1998-07-01

98 patients with Graves' disease have been compared to 95 patients with Hashimoto's thyroiditis and to 97 patients with benign thyroid nodules (control group) in order to evaluate the triggering role of major stressors and pregnancy in the occurrence of autoimmune thyroid diseases. A stress factor has been encountered in 11% cases of Graves' disease and in 6% of Hashimoto's and thyroid nodes (chi 2 test, not different). Graves' disease occurred after a pregnancy in 25% of the women in child bearing age versus 10% of the cases of Hashimoto's (p thyroid nodes. The role of stressors, if any, in triggering Graves' disease seems to be weak and dubious compared to the role of pregnancy and post-partum. It is assumed that the decrease of immunosuppressive hormones occurring after stress or delivery could induce a rebound autoimmune reaction responsible for the thyroid disease. In Hashimoto's thyroiditis, stress and pregnancies do not seem to have any triggering role.

Antitumor agent 25-epi Ritterostatin GN1N induces endoplasmic reticulum stress and autophagy mediated cell death in melanoma cells.

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Riaz Ahmed, Kausar Begam; Kanduluru, Ananda Kumar; Feng, Li; Fuchs, Philip L; Huang, Peng

2017-05-01

Metastatic melanoma is the most aggressive of all skin cancers and is associated with poor prognosis owing to lack of effective treatments. 25-epi Ritterostatin GN1N is a novel antitumor agent with yet undefined mechanisms of action. We sought to delineate the antitumor mechanisms of 25-epi Ritterostatin GN1N in melanoma cells to determine the potential of this compound as a treatment for melanoma. Activation of the endoplasmic reticulum (ER) stress protein glucose-regulated protein 78 (GRP78) has been associated with increased melanoma progression, oncogenic signaling, drug resistance, and suppression of cell death. We found that 25-epi Ritterostatin GN1N induced cell death in melanoma cells at nanomolar concentrations, and this cell death was characterized by inhibition of GRP78 expression, increased expression of the ER stress marker CHOP, loss of mitochondrial membrane potential, and lipidation of the autophagy marker protein LC3B. Importantly, normal melanocytes exhibited limited sensitivity to 25-epi Ritterostatin GN1N. Subsequent in vivo results demonstrated that 25-epi Ritterostatin GN1N reduced melanoma growth in mouse tumor xenografts and did not affect body weight, suggesting minimal toxicity. In summary, our findings indicate that 25-epi Ritterostatin GN1N causes ER stress and massive autophagy, leading to collapse of mitochondrial membrane potential and cell death in melanoma cells, with minimal effects in normal melanocytes. Thus, 25-epi Ritterostatin GN1N is a promising anticancer agent that warrants further investigation.

Stress-triggered synaptic malfunction: a gate along the path from depression to dementia

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Ioannis Sotiropoulos

2014-03-01

Full Text Available Clinical and experimental studies suggest a causal role of chronic stress for brain pathology and diseases e.g. depression and Alzheimer´s disease (AD as stress is strongly associated with neuronal and synaptic atrophy/loss resulting in impaired mood and/or cognition. Indeed, synaptic loss is a key underlying pathomechanism in both disorders while growing clinical evidence supports a pathological link between depression and AD pointing to shared neurobiological underpinnings and pathogenic mechanisms e.g. AD-related mechanisms, such as APP misprocessing, are also found to be affected in depression while depression predisposes individuals to develop AD. Based on the above, our studies have been conceived to contribute towards bridging the current gap monitoring AD-related mechanisms in the CMS (chronic mild stress animal model of depression before and after antidepressant treatment. We found that depressive status in these animals was accompanied by increased APP misprocessing and tau accumulation as well as neuronal atrophy in hippocampus and prefrontal cortex. Interestingly, antidepressant treatment with two different antidepressants reversed both biochemical and synaptic changes. Furthermore, we demonstrate the blockage of stress-triggered depressive behavior and neuronal/synaptic atrophy in animals lacking APP misprocessing and amyloid beta generation, further supporting the involvement of APP misprocessing in depressive pathology and behavior. Thus, this study forms the first in vivo approach to clarify the involvement of AD-related APP misprocessing on stress-driven synaptic pathology underlying depressive pathology.

Tribbles 3 Mediates Endoplasmic Reticulum Stress-Induced Insulin Resistance in Skeletal Muscle

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Koh, Ho-Jin; Toyoda, Taro; Didesch, Michelle M.; Lee, Min-Young; Sleeman, Mark W.; Kulkarni, Rohit N.; Musi, Nicolas; Hirshman, Michael F.; Goodyear, Laurie J.

2013-01-01

Endoplasmic Reticulum (ER) stress has been linked to insulin resistance in multiple tissues but the role of ER stress in skeletal muscle has not been explored. ER stress has also been reported to increase tribbles 3 (TRB3) expression in multiple cell lines. Here, we report that high fat feeding in mice, and obesity and type 2 diabetes in humans significantly increases TRB3 and ER stress markers in skeletal muscle. Overexpression of TRB3 in C2C12 myotubes and mouse tibialis anterior muscles significantly impairs insulin signaling. Incubation of C2C12 cells and mouse skeletal muscle with ER stressors thapsigargin and tunicamycin increases TRB3 and impairs insulin signaling and glucose uptake, effects reversed in cells overexpressing RNAi for TRB3 and in muscles from TRB3 knockout mice. Furthermore, TRB3 knockout mice are protected from high fat diet-induced insulin resistance in skeletal muscle. These data demonstrate that TRB3 mediates ER stress-induced insulin resistance in skeletal muscle. PMID:23695665

Microearthquake Study of the Salton Sea Geothermal Field, California: Evidence of Stress Triggering

International Nuclear Information System (INIS)

Holland, Austin A.

2002-01-01

A digital network of 24 seismograph stations was operated from September 15, 1987 to September 30, 1988, by Lawrence Livermore National Laboratory and Unocal as part of the Salton Sea Scientific Drilling Project to study seismicity related to tectonics and geothermal activity near the drilling site. More than 2001 microearthquakes were relocated in this study in order to image any pervasive structures that may exist within the Salton Sea geothermal field. First, detailed velocity models were obtained through standard 1-D inversion techniques. These velocity models were then used to relocate events using both single event methods and Double-Differencing, a joint hypocenter location method. An anisotropic velocity model was built from anisotropy estimates obtained from well logs within the study area. During the study period, the Superstition Hills sequence occurred with two moderate earthquakes of MS 6.2 and MS 6.6. These moderate earthquakes caused a rotation of the stress field as observed from the inversion of first motion data from microearthquakes at the Salton Sea geothermal field. Coulomb failure analysis also indicates that microearthquakes occurring after the Superstition Hills sequence are located within a region of stress increase suggesting stress triggering caused by the moderate earthquakes

Reef corals bleach to resist stress.

Science.gov (United States)

Obura, David O

2009-02-01

A rationale is presented here for a primary role of bleaching in regulation of the coral-zooxanthellae symbiosis under conditions of stress. Corals and zooxanthellae have fundamentally different metabolic rates, requiring active homeostasis to limit zooxanthellae production and manage translocated products to maintain the symbiosis. The control processes for homeostasis are compromised by environmental stress, resulting in metabolic imbalance between the symbionts. For the coral-zooxanthella symbiosis the most direct way to minimize metabolic imbalance under stress is to reduce photosynthetic production by zooxanthellae. Two mechanisms have been demonstrated that do this: reduction of the chlorophyll concentration in individual zooxanthellae and reduction of the relative biomass of zooxanthellae. Both mechanisms result in visual whitening of the coral, termed bleaching. Arguments are presented here that bleaching provides the final control to minimize physiological damage from stress as an adversity response to metabolic imbalance. As such, bleaching meets the requirements of a stress response syndrome/general adaptive mechanism that is sensitive to internal states rather than external parameters. Variation in bleaching responses among holobionts reflects genotypic and phenotypic differentiation, allowing evolutionary change by natural selection. Thus, reef corals bleach to resist stress, and thereby have some capacity to adapt to and survive change. The extreme thermal anomalies causing mass coral bleaching worldwide lie outside the reaction norms for most coral-zooxanthellae holobionts, revealing the limitations of bleaching as a control mechanism.

Frequency-Dependent Tidal Triggering of Low Frequency Earthquakes Near Parkfield, California

Science.gov (United States)

Xue, L.; Burgmann, R.; Shelly, D. R.

2017-12-01

The effect of small periodic stress perturbations on earthquake generation is not clear, however, the rate of low-frequency earthquakes (LFEs) near Parkfield, California has been found to be strongly correlated with solid earth tides. Laboratory experiments and theoretical analyses show that the period of imposed forcing and source properties affect the sensitivity to triggering and the phase relation of the peak seismicity rate and the periodic stress, but frequency-dependent triggering has not been quantitatively explored in the field. Tidal forcing acts over a wide range of frequencies, therefore the sensitivity to tidal triggering of LFEs provides a good probe to the physical mechanisms affecting earthquake generation. In this study, we consider the tidal triggering of LFEs near Parkfield, California since 2001. We find the LFEs rate is correlated with tidal shear stress, normal stress rate and shear stress rate. The occurrence of LFEs can also be independently modulated by groups of tidal constituents at semi-diurnal, diurnal and fortnightly frequencies. The strength of the response of LFEs to the different tidal constituents varies between LFE families. Each LFE family has an optimal triggering frequency, which does not appear to be depth dependent or systematically related to other known properties. This suggests the period of the applied forcing plays an important role in the triggering process, and the interaction of periods of loading history and source region properties, such as friction, effective normal stress and pore fluid pressure, produces the observed frequency-dependent tidal triggering of LFEs.

Significance and nature of bystander responses induced by various agents.

Science.gov (United States)

Verma, Neha; Tiku, Ashu Bhan

2017-07-01

Bystander effects in a biological system are the responses shown by non-targeted neighbouring cells/tissues/organisms. These responses are triggered by factors released from targeted cells when exposed to a stress inducing agent. The biological response to stress inducing agents is complex, owing to the diversity of mechanisms and pathways activated in directly targeted and bystander cells. These responses are highly variable and can be either beneficial or hazardous depending on the cell lines tested, dose of agent used, experimental end points and time course selected. Recently non-targeted cells have even been reported to rescue the directly exposed cells by releasing protective signals that might be induced by non-targeted bystander responses. The nature of bystander signal/s is not yet clear. However, there are evidences suggesting involvement of ROS, RNS, protein factors and even DNA molecules leading to the activation of a number of signaling pathways. These can act independently or in a cascade, to induce events leading to changes in gene expression patterns that could elicit detrimental or beneficial effects. Many review articles on radiation induced bystander responses have been published. However, to the best of our knowledge, a comprehensive review on bystander responses induced by other genotoxic chemicals and stress inducing agents has not been published so far. Therefore, the aim of the present review is to give an overview of the literature on different aspects of bystander responses: agents that induce these responses, factors that can modulate bystander responses and the mechanisms involved. Copyright © 2017 Elsevier B.V. All rights reserved.

Café Icatu como fonte de resistência a colletotrichum coffeanum Icatu coffee cultivar as source of resistance to the agent of coffe berry disease

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A. Carvalho

1976-07-01

Full Text Available Linhagens e progênies do cultivar icatu, selecionadas em Campinas, foram testadas na Coffee Research Station, Ruiru, Quênia, a fim de avaliar o grau de resistência ao ataque de Colletotrichum coffeanum, agente responsável pela moléstia mais conhecida por CBD. Os dados de infecção obtidos para 11 linhagens e sete progênies foram comparados com os dos cultivares testemunhas Rume Sudan, resistente, e SL 28, suscetível. Considerando apenas a freqüência de resistentes, com grau 1 de infecção, destacaram-se a progênie H 4782-10 M e a linhagem LCH 3851-4 T. As populações com graus de 1 a 4 de resistência ocorreram em menor escala do que no Rume Sudan, porém salientou-se a progênie H 4782-10 M, com elevada resistência. As maiores porcentagens de plantas suscetíveis foram verificadas nas linhagens LCH 3849-7 M e LCH 4782-13 T, as quais se aproximam da linhagem suscetível SL 28. Os dados preliminares indicam que o germoplasma icatu, como o híbrido de timor, oferece perspectivas de constituir razoável fonte de resistência genética ao agente da CBD.Several samples of the coffee cultivar Icatu were evaluated for resistance to the agent of the CBD (Colletotrichum coffeanum. All tests were performed at the Ruiru Coffee Experiment Station, Kenya. Resistant cultivars Rume Sudan and the susceptible SL 28 were used for comparison. Tests were performed using young seedlings innoculation. It was found that seedlings with grade 1 of the resistance scale occurred in several Icatu progenies. Seedlings of the grades 1 to 4, were noticed more frequently in the progenies H 4782-10 M and LCH 3851-4 M. Susceptible plants, in the class with 10-12 grades, occurred in higher proportion in the progenies LCH 3849-7 M and LCH 4782-10 T. All resistant seedlings were transplanted to the field for further tests of resistance. These preliminary data indicated that the Icatu coffee can be considered as a good source of genetic resistance to the agent of the

Exercise and Prebiotics Produce Stress Resistance: Converging Impacts on Stress-Protective and Butyrate-Producing Gut Bacteria.

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Mika, A; Rumian, N; Loughridge, A B; Fleshner, M

2016-01-01

The gut microbial ecosystem can mediate the negative health impacts of stress on the host. Stressor-induced disruptions in microbial ecology (dysbiosis) can lead to maladaptive health effects, while certain probiotic organisms and their metabolites can protect against these negative impacts. Prebiotic diets and exercise are feasible and cost-effective strategies that can increase stress-protective bacteria and produce resistance against the detrimental behavioral and neurobiological impacts of stress. The goal of this review is to describe research demonstrating that both prebiotic diets and exercise produce adaptations in gut ecology and the brain that arm the organism against inescapable stress-induced learned helplessness. The results of this research support the novel hypothesis that some of the stress-protective effects of prebiotics and exercise are due to increases in stress-protective gut microbial species and their metabolites. In addition, new evidence also suggests that prebiotic diet or exercise interventions are most effective if given early in life (juvenile-adolescence) when both the gut microbial ecosystem and the brain are plastic. Based on our new understanding of the mechanistic convergence of these interventions, it is feasible to propose that in adults, both interventions delivered in combination may elevate their efficacy to promote a stress-resistant phenotype. © 2016 Elsevier Inc. All rights reserved.

Glutathione Depletion Induced by c-Myc Downregulation Triggers Apoptosis on Treatment with Alkylating Agents1

Science.gov (United States)

Biroccio, Annamaria; Benassi, Barbara; Fiorentino, Francesco; Zupi, Gabriella

2004-01-01

Abstract Here we investigate the mechanism(s) involved in the c-Myc-dependent drug response of melanoma cells. By using three M14-derived c-Myc low-expressing clones, we demonstrate that alkylating agents, cisplatin and melphalan, trigger apoptosis in the c-Myc antisense transfectants, but not in the parental line. On the contrary, topoisomerase inhibitors, adriamycin and camptothecin, induce apoptosis to the same extent regardless of c-Myc expression. Because we previously demonstrated that c-Myc downregulation decreases glutathione (GSH) content, we evaluated the role of GSH in the apoptosis induced by the different drugs. In control cells treated with one of the alkylating agents or the others, GSH depletion achieved by l-buthionine-sulfoximine preincubation opens the apoptotic pathway. The apoptosis proceeded through early Bax relocalization, cytochrome c release, and concomitant caspase-9 activation, whereas reactive oxygen species production and alteration of mitochondria membrane potential were late events. That GSH was determining in the c-Myc-dependent drug-induced apoptosis was demonstrated by altering the intracellular GSH content of the c-Myc low-expressing cells up to the level of controls. Indeed, GSH ethyl ester-mediated increase of GSH abrogated apoptosis induced by cisplatin and melphalan by inhibition of Bax/cytochrome c redistribution. The relationship among c-Myc, GSH content, and the response to alkylating agent has been also evaluated in the M14 Myc overexpressing clones as well as in the melanoma JR8 c-Myc antisense transfectants. All together, these results demonstrate that GSH plays a key role in governing c-Myc-dependent drug-induced apoptosis. PMID:15153331

Quantitative relationships of the harmful effect of ionizing radiation on natural resistance of the organism to various infectious agents

International Nuclear Information System (INIS)

Mal'tsev, V.N.; Strel'nikov, V.A.

1978-01-01

An analysis of data from the literature and own experimental results shows that there is an inverse linear correlation between the dose of irradiation and natural resistance of the organism to infection with various infectious agents. With increasing doses of irradiation, the irradiated organism is exposed to the greatest risk from the agents of intestinal infections and representatives of normal microflora. These are followed by agents of various diseases of microbial nature. The minimum reduction can be observed in resistance to viruses. (author)

Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?

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Schulkin Jay

2006-04-01

Full Text Available Abstract Background Corticotropin-releasing factor (CRF is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior. Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 μl or amphetamine (20 μg/0.2 μl. Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Results Microinjections of the highest dose of CRF (500 ng or amphetamine (20 μg selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress

Plastic responses to four environmental stresses and cross-resistance in a laboratory population of Drosophila melanogaster

DEFF Research Database (Denmark)

Bubliy, Oleg A; Kristensen, Torsten Nygård; Kellermann, Vanessa

2012-01-01

such as reduction of metabolic rate and accumulation of energy reserves might be involved. 6. The lack of cross-resistance induced by acclimation ⁄ hardening treatments suggests that in an environment with multiple stresses, evolution of shared protective systems associated with plastic responses may be constrained.......1. Acclimation or hardening to one stress in arthropods can lead to a plastic response, which confers increased resistance to other stresses. Such cross-resistance may indicate shared physiological resistance mechanisms and a possibility of joint evolution for resistance traits. 2. In this study...

Dynamic Earthquake Triggering on Seismogenic Faults in Oklahoma

Science.gov (United States)

Qin, Y.; Chen, X.; Peng, Z.; Aiken, C.

2016-12-01

Regions with high pore pressure are generally more susceptible to dynamic triggering from transient stress change caused by surface wave of distant earthquakes. The stress threshold from triggering studies can help understand the stress state of seismogenic faults. The recent dramatic seismicity increase in central US provides a rich database for assessing dynamic triggering phenomena. We begin our study by conducting a systematic analysis of dynamic triggering for the continental U.S using ANSS catalog (with magnitude of completeness Mc=3) from 49 global mainshocks (Ms>6.5, depth1kPa). We calculate β value for each 1° by 1° bins in 30 days before and 10 days after the mainshock. To identify regions that experience triggering from a distant mainshock, we generate a stacked map using β≥2 - which represents significant seismicity rate increase. As expected, the geothermal and volcanic fields in California show clear response to distant earthquakes. We also note areas in Oklahoma and north Texas show enhanced triggering, where wastewater-injection induced seismicity are occurring. Next we focus on Oklahoma and use a local catalog from Oklahoma Geological Survey with lower completeness threshold Mc to calculate the beta map in 0.2° by 0.2° bins for each selected mainshock to obtain finer spatial resolutions of the triggering behavior. For those grids with β larger than 2.0, we use waveforms from nearby stations to search for triggered events. The April 2015 M7.8 Nepal earthquake causes a statistically significant increase of local seismicity (β=3.5) in the Woodward area (west Oklahoma) during an on-going earthquake sequence. By visually examining the surface wave from the nearest station, we identify 3 larger local events, and 10 additional smaller events with weaker but discernable amplitude. Preliminary analysis shows that the triggering is related to Rayleigh wave, which would cause dilatational or shear stress changes along the strike direction of

Novel agents in the management of castration resistant prostate cancer

Directory of Open Access Journals (Sweden)

Shruti Chaturvedi

2014-01-01

Full Text Available Prostate cancer (PCa is a leading cause of cancer mortality in men and despite high cure rates with surgery and/or radiation, 30-40% of patients will eventually develop advanced disease. Androgen deprivation is the first line therapy for standard of care for men with advanced disease. Eventually however all men will progress to castration-resistant prostate cancer (CRPC. Insight into the molecular mechanisms of androgen resistance has led to the development of alternative novel hormonal agents. Newer hormonal agents such as abiraterone, enzalutamide and TOK-001; and the first cancer vaccine, Sipuleucel T have been approved for use in men with CRPC. The recognition of the importance of bone health and morbidity associated with skeletal related events has led to the introduction of the receptor activator of nuclear factor kappa-B-ligand inhibitor denosumab. Other molecularly targeted therapies have shown promise in pre-clinical studies, but this has not consistently translated into clinical efficacy. It is increasingly evident that CRPC is a heterogeneous disease and an individualized approach directed at identifying primary involvement of specific pathways could maximize the benefit from targeted therapies. This review focuses on targeted therapy for PCa with special emphasis on therapies that have been Food and Drug Administration approved for use in men with CRPC.

Carbon-Starvation Induces Cross-Resistance to Thermal, Acid, and Oxidative Stress in Serratia marcescens

Science.gov (United States)

Pittman, Joseph R.; Kline, La’Kesha C.; Kenyon, William J.

2015-01-01

The broad host-range pathogen Serratia marcescens survives in diverse host and non-host environments, often enduring conditions in which the concentration of essential nutrients is growth-limiting. In such environments, carbon and energy source starvation (carbon-starvation) is one of the most common forms of stress encountered by S. marcescens. Related members of the family Enterobacteriaceae are known to undergo substantial changes in gene expression and physiology in response to the specific stress of carbon-starvation, enabling non-spore-forming cells to survive periods of prolonged starvation and exposure to other forms of stress (i.e., starvation-induced cross-resistance). To determine if carbon-starvation also results in elevated levels of cross-resistance in S. marcescens, both log-phase and carbon-starved cultures, depleted of glucose before the onset of high cell-density stationary-phase, were grown in minimal media at either 30 °C or 37 °C and were then challenged for resistance to high temperature (50 °C), low pH (pH 2.8), and oxidative stress (15 mM H2O2). In general, carbon-starved cells exhibited a higher level of resistance to thermal stress, acid stress, and oxidative stress compared to log-phase cells. The extent of carbon-starvation-induced cross-resistance was dependent on incubation temperature and on the particular strain of S. marcescens. In addition, strain- and temperature-dependent variations in long-term starvation survival were also observed. The enhanced stress-resistance of starved S. marcescens cells could be an important factor in their survival and persistence in many non-host environments and within certain host microenvironments where the availability of carbon sources is suboptimal for growth. PMID:27682115

Carbon-Starvation Induces Cross-Resistance to Thermal, Acid, and Oxidative Stress in Serratia marcescens

Directory of Open Access Journals (Sweden)

Joseph R. Pittman

2015-10-01

Full Text Available The broad host-range pathogen Serratia marcescens survives in diverse host and non-host environments, often enduring conditions in which the concentration of essential nutrients is growth-limiting. In such environments, carbon and energy source starvation (carbon-starvation is one of the most common forms of stress encountered by S. marcescens. Related members of the family Enterobacteriaceae are known to undergo substantial changes in gene expression and physiology in response to the specific stress of carbon-starvation, enabling non-spore-forming cells to survive periods of prolonged starvation and exposure to other forms of stress (i.e., starvation-induced cross-resistance. To determine if carbon-starvation also results in elevated levels of cross-resistance in S. marcescens, both log-phase and carbon-starved cultures, depleted of glucose before the onset of high cell-density stationary-phase, were grown in minimal media at either 30 °C or 37 °C and were then challenged for resistance to high temperature (50 °C, low pH (pH 2.8, and oxidative stress (15 mM H2O2. In general, carbon-starved cells exhibited a higher level of resistance to thermal stress, acid stress, and oxidative stress compared to log-phase cells. The extent of carbon-starvation-induced cross-resistance was dependent on incubation temperature and on the particular strain of S. marcescens. In addition, strain- and temperature-dependent variations in long-term starvation survival were also observed. The enhanced stress-resistance of starved S. marcescens cells could be an important factor in their survival and persistence in many non-host environments and within certain host microenvironments where the availability of carbon sources is suboptimal for growth.

Analysis of creep effective stress in austenitic heat resistant steel

International Nuclear Information System (INIS)

Park, In Duck; Nam, Ki Woo

2002-01-01

This paper describes the comparison of calculated effective stress with experimental one in austenitic heat resistant steels, STS310J1TB and STS310S with and without a small amount of Nb and N. Based on a solute atoms diffusion model, contribution from soluble nitrogen to the high-temperature strength was numerically examined for austenitic heat-resisting Fe-Cr-Ni-N(STS310J1TB) and Fe-Cr-Ni(STS310S) alloys. The solute atmosphere dragging stress of dislocation was calculated in optional dislocation velocity of STS310J1TB and STS310S at 650 degree C, 675 degree C and 700 degree C. As a result of the numerical calculation, the solute atmosphere dragging stress of STS310J1TB was about 50 times larger than that of STS310S. When the temperature became high, the maximum value of solute atmosphere dragging stress was small and the velocity of moving dislocation was fast. From the relationship between the dislocation rate and the solute atmosphere dragging stress, the relation of both was proportional and the inclination is about 1 in the level with low velocity of moving dislocation. From above results, the mechanism of dislocation movement in STS310J1TB was the solute atmosphere dragging stress. The solute atmosphere dragging stress, which was calculated from the numerical calculation was close to the effect stress in stress relaxation tests

Pathogen-associated molecular pattern-triggered immunity and resistance to the root pathogen Phytophthora parasitica in Arabidopsis.

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Larroque, Mathieu; Belmas, Elodie; Martinez, Thomas; Vergnes, Sophie; Ladouce, Nathalie; Lafitte, Claude; Gaulin, Elodie; Dumas, Bernard

2013-09-01

The cellulose binding elicitor lectin (CBEL) of the genus Phytophthora induces necrosis and immune responses in several plant species, including Arabidopsis thaliana. However, the role of CBEL-induced responses in the outcome of the interaction is still unclear. This study shows that some of CBEL-induced defence responses, but not necrosis, required the receptor-like kinase BAK1, a general regulator of basal immunity in Arabidopsis, and the production of a reactive oxygen burst mediated by respiratory burst oxidases homologues (RBOH). Screening of a core collection of 48 Arabidopsis ecotypes using CBEL uncovered a large variability in CBEL-induced necrotic responses. Analysis of non-responsive CBEL lines Ws-4, Oy-0, and Bla-1 revealed that Ws-4 and Oy-0 were also impaired in the production of the oxidative burst and expression of defence genes, whereas Bla-1 was partially affected in these responses. Infection tests using two Phytophthora parasitica strains, Pp310 and Ppn0, virulent and avirulent, respectively, on the Col-0 line showed that BAK1 and RBOH mutants were susceptible to Ppn0, suggesting that some immune responses controlled by these genes, but not CBEL-induced cell death, are required for Phytophthora parasitica resistance. However, Ws-4, Oy-0, and Bla-1 lines were not affected in Ppn0 resistance, showing that natural variability in CBEL responsiveness is not correlated to Phytophthora susceptibility. Overall, the results uncover a BAK1- and RBOH-dependent CBEL-triggered immunity essential for Phytophthora resistance and suggest that natural quantitative variation of basal immunity triggered by conserved general elicitors such as CBEL does not correlate to Phytophthora susceptibility.

Increased resistance to a generalist herbivore in a salinity-stressed non-halophytic plant.

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Renault, Sylvie; Wolfe, Scott; Markham, John; Avila-Sakar, Germán

2016-01-01

Plants often grow under the combined stress of several factors. Salinity and herbivory, separately, can severely hinder plant growth and reproduction, but the combined effects of both factors are still not clearly understood. Salinity is known to reduce plant tissue nitrogen content and growth rates. Since herbivores prefer tissues with high N content, and biochemical pathways leading to resistance are commonly elicited by salt-stress, we hypothesized that plants growing in saline conditions would have enhanced resistance against herbivores. The non-halophyte, Brassica juncea, and the generalist herbivore Trichoplusia ni were used to test the prediction that plants subjected to salinity stress would be both more resistant and more tolerant to herbivory than those growing without salt stress. Plants were grown under different NaCl levels, and either exposed to herbivores and followed by removal of half of their leaves, or left intact. Plants were left to grow and reproduce until senescence. Tissue quality was assessed, seeds were counted and biomass of different organs measured. Plants exposed to salinity grew less, had reduced tissue nitrogen, protein and chlorophyll content, although proline levels increased. Specific leaf area, leaf water content, transpiration and root:shoot ratio remained unaffected. Plants growing under saline condition had greater constitutive resistance than unstressed plants. However, induced resistance and tolerance were not affected by salinity. These results support the hypothesis that plants growing under salt-stress are better defended against herbivores, although in B. juncea this may be mostly through resistance, and less through tolerance. Published by Oxford University Press on behalf of the Annals of Botany Company.

The etiology of oxidative stress in insulin resistance

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Samantha Hurrle

2017-10-01

Full Text Available Insulin resistance is a prevalent syndrome in developed as well as developing countries. It is the predisposing factor for type 2 diabetes mellitus, the most common end stage development of metabolic syndrome in the United States. Previously, studies investigating type 2 diabetes have focused on beta cell dysfunction in the pancreas and insulin resistance, and developing ways to correct these dysfunctions. However, in recent years, there has been a profound interest in the role that oxidative stress in the peripheral tissues plays to induce insulin resistance. The objective of this review is to focus on the mechanism of oxidative species generation and its direct correlation to insulin resistance, to discuss the role of obesity in the pathophysiology of this phenomenon, and to explore the potential of antioxidants as treatments for metabolic dysfunction.

The divergence between the virus and cellular oxidative stress as separate environmental agents that trigger autoimmunity originates from their different procedural mechanisms of activating the same molecular entity: the transcription factor NF-kappa B

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Norbert O. Temajo

2017-07-01

Full Text Available To happen, autoimmunity in man requires triggering by environmental factors: the viruses and cellular stress, in genetically primed individuals. The viruses and stress are operatives in this scene as stimuli for the activation of the transcription factor (TF, NF-ΚB. NF-ΚB is unusually activated: the viral activation occurs via serine residues-phosphorylation by IKKβ and IKKε, while the activation by oxidative stress occurs via tyrosine phosphorylation of IΚBα. The phosphorylation of particular amino acid residues of a given protein molecule modulates that protein’s polymorphic conformations, appropriately. For a TF, a given conformation influences its choice of cognate DNA sequence recognition as well as its interactions with neighboring molecules. The TF NF-ΚB performs a battery of regulatory functions. Because it is variously phosphorylated as seen above this implies that NF-ΚB is capable of assuming a multitude of polymorphic conformations that we refer to as “derivative isoforms”. Thus the virus activation of NF-ΚB occurring by phosphorylation at serines S536 and S468 is observed to generate the isoforms with the potential to activate the transcription of viral latency genes, hereby installing a latent infection. But oxidative stress activation of NF-ΚB occurs via phosphorylation of Tyr42 of IΚBα and this yields isoforms that activate the transcription of replication and transcription activator (RTA, the master lytic switch, which thereby abrogates the latency. The steps involved are that the stress-activated NF-ΚB and the viral miRNAs conjoin in a regulatory circuitry identified as feedback and feed-forward network motifs that co-accomplish the switching on of RTA which in turn activates the transcription of the immediate early genes BZLF1 and BRLF1. These two latter genes together mobilize the expression of the set of lytic genes, resulting in a lytic cascade and consequentially set in trend the viral journey to the

Cefepime shows good efficacy and no antibiotic resistance in pneumonia caused by Serratia marcescens and Proteus mirabilis - an observational study.

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Yayan, Josef; Ghebremedhin, Beniam; Rasche, Kurt

2016-03-23

Many antibiotics have no effect on Gram-positive and Gram-negative microbes, which necessitates the prescription of broad-spectrum antimicrobial agents that can lead to increased risk of antibiotic resistance. These pathogens constitute a further threat because they are also resistant to numerous beta-lactam antibiotics, as well as other antibiotic groups. This study retrospectively investigates antimicrobial resistance in hospitalized patients suffering from pneumonia triggered by Gram-negative Serratia marcescens or Proteus mirabilis. The demographic and clinical data analyzed in this study were obtained from the clinical databank of the HELIOS Clinic, Witten/Herdecke University, Wuppertal, Germany, for inpatients presenting with pneumonia triggered by S. marcescens or P. mirabilis from 2004 to 2014. An antibiogram was conducted for the antibiotics utilized as part of the management of patients with pneumonia triggered by these two pathogens. Pneumonia was caused by Gram-negative bacteria in 115 patients during the study period from January 1, 2004, to August 12, 2014. Of these, 43 (37.4 %) hospitalized patients [26 males (60.5 %, 95 % CI 45.9 %-75.1 %) and 17 females (39.5 %, 95 % CI 24.9 %-54.1 %)] with mean age of 66.2 ± 13.4 years had pneumonia triggered by S. marcescens, while 20 (17.4 %) patients [14 males (70 %, 95 % CI 49.9 %-90.1 %) and 6 females (30 %, 95 % CI 9.9 %-50.1 %)] with a mean age of 64.6 ± 12.8 years had pneumonia caused by P. mirabilis. S. marcescens showed an increased antibiotic resistance to ampicillin (100 %), ampicillin-sulbactam (100 %), and cefuroxime (100 %). P. mirabilis had a high resistance to tetracycline (100 %) and ampicillin (55 %). S. marcescens (P < 0.0001) and P. mirabilis (P = 0.0003) demonstrated no resistance to cefepime in these patients with pneumonia. S. marcescens and P. mirabilis were resistant to several commonly used antimicrobial agents, but showed no resistance to

`Special agents' trigger social waves in giant honeybees ( Apis dorsata)

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Schmelzer, Evelyn; Kastberger, Gerald

2009-12-01

Giant honeybees ( Apis dorsata) nest in the open and have therefore evolved a variety of defence strategies. Against predatory wasps, they produce highly coordinated Mexican wavelike cascades termed ‘shimmering’, whereby hundreds of bees flip their abdomens upwards. Although it is well known that shimmering commences at distinct spots on the nest surface, it is still unclear how shimmering is generated. In this study, colonies were exposed to living tethered wasps that were moved in front of the experimental nest. Temporal and spatial patterns of shimmering were investigated in and after the presence of the wasp. The numbers and locations of bees that participated in the shimmering were assessed, and those bees that triggered the waves were identified. The findings reveal that the position of identified trigger cohorts did not reflect the experimental path of the tethered wasp. Instead, the trigger centres were primarily arranged in the close periphery of the mouth zone of the nest, around those parts where the main locomotory activity occurs. This favours the ‘special-agents’ hypothesis that suggest that groups of specialized bees initiate the shimmering.

Pharmaceutical Options for Triggering of Final Oocyte Maturation in ART

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Juan Carlos Castillo

2014-01-01

Full Text Available Since the pioneering days of in vitro fertilization, hCG has been the gold standard to induce final follicular maturation. We herein reviewed different pharmaceutical options for triggering of final oocyte maturation in ART. The new upcoming agent seems to be GnRHa with its potential advantages over hCG trigger. GnRHa triggering elicits a surge of gonadotropins resembling the natural midcycle surge of gonadotropins, without the prolonged action of hCG, resulting in the retrieval of more mature oocytes and a significant reduction in or elimination of OHSS as compared to hCG triggering. The induction of final follicular maturation using GnRHa represents a paradigm shift in the ovulation triggering concept in ART and, thus, a way to develop a safer IVF procedure. Kisspeptins are key central regulators of the neuroendocrine mechanisms of human reproduction, who have been shown to effectively elicit an LH surge and to induce final oocyte maturation in IVF cycles. This new trigger concept may, therefore, offer a completely new, “natural” pharmacological option for ovulation induction. Whether kisspeptins will be the future agent to trigger ovulation remains to be further explored.

Metallurgical and mechanical parameters controlling alloy 718 stress corrosion cracking resistance in PWR primary water

International Nuclear Information System (INIS)

Deleume, J.

2007-11-01

Improving the performance and reliability of the fuel assemblies of the pressurized water reactors requires having a perfect knowledge of the operating margins of both the components and the materials. The choice of alloy 718 as reference material for this study is justified by the industrial will to identify the first order parameters controlling the excellent resistance of this alloy to Stress Corrosion Cracking (SCC). For this purpose, a specific slow strain rate (SSR) crack initiation test using tensile specimen with a V-shaped hump in the middle of the gauge length was developed and modeled. The selectivity of such SSR tests in simulated PWR primary water at 350 C was clearly established by characterizing the SCC resistance of nine alloy 718 thin strip heats. Regardless of their origin and in spite of a similar thermo-mechanical history, they did not exhibit the same susceptibility to SCC crack initiation. All the characterized alloy 718 heats develop oxide scale of similar nature for various exposure times to PWR primary medium in the temperature range [320 C - 360 C]. δ phase precipitation has no impact on alloy 718 SCC initiation behavior when exposed to PWR primary water, contrary to interstitial contents and the triggering of plastic instabilities (PLC phenomenon). (author)

Children as agents of change in combatting antibiotic resistance.

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Molnar, Andreea

2017-01-01

Antibiotic resistance is a worldwide problem and changes are needed in the way antibiotics are used. The value of engaging children as key contributors in health care campaigns to increase the appropriate use of antibiotics has not been fully recognized. Little is known about how to design educational materials for children in order to enable them to be agents of change in their communities. Science education needs to improve the way it engages children so as to give them the tools needed to make responsible decisions on antibiotic use.

Experimental evidence for nutrition regulated stress resistance in Drosophila ananassae.

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Seema Sisodia

Full Text Available The amount and quality of nutrients consumed by organisms have a strong impact on stress resistance, life-history traits and reproduction. The balance between energy acquisition and expenditure is crucial to the survival and reproductive success of animals. The ability of organisms to adjust their development, physiology or behavior in response to environmental conditions, called phenotypic plasticity, is a defining property of life. One of the most familiar and important examples of phenotypic plasticity is the response of stress tolerance and reproduction to changes in developmental nutrition. Larval nutrition may affect a range of different life-history traits as well as responses to environmental stress in adult.Here we investigate the effect of larval nutrition on desiccation, starvation, chill-coma recovery, heat resistance as well as egg to adult viability, egg production and ovariole number in Drosophila ananassae. We raised larvae on either protein rich diet or carbohydrate rich diet. We found that flies consuming protein rich diet have higher desiccation and heat shock resistance whereas flies developed on carbohydrate rich diet have higher starvation and cold resistance. Egg production was higher in females developed on protein rich diet and we also found trade-off between egg production and Egg to adult viability of the flies. Viability was higher in carbohydrate rich diet. However, sex specific viability was found in different nutritional regimes. Higher Egg production might be due to higher ovariole number in females of protein rich diet.Thus, Drosophila ananassae adapts different stress tolerance and life-history strategies according to the quality of the available diet, which are correlated with phenotypic adjustment at anatomical and physiological levels.

Experimental evidence for nutrition regulated stress resistance in Drosophila ananassae.

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Sisodia, Seema; Singh, Bashisth N

2012-01-01

The amount and quality of nutrients consumed by organisms have a strong impact on stress resistance, life-history traits and reproduction. The balance between energy acquisition and expenditure is crucial to the survival and reproductive success of animals. The ability of organisms to adjust their development, physiology or behavior in response to environmental conditions, called phenotypic plasticity, is a defining property of life. One of the most familiar and important examples of phenotypic plasticity is the response of stress tolerance and reproduction to changes in developmental nutrition. Larval nutrition may affect a range of different life-history traits as well as responses to environmental stress in adult. Here we investigate the effect of larval nutrition on desiccation, starvation, chill-coma recovery, heat resistance as well as egg to adult viability, egg production and ovariole number in Drosophila ananassae. We raised larvae on either protein rich diet or carbohydrate rich diet. We found that flies consuming protein rich diet have higher desiccation and heat shock resistance whereas flies developed on carbohydrate rich diet have higher starvation and cold resistance. Egg production was higher in females developed on protein rich diet and we also found trade-off between egg production and Egg to adult viability of the flies. Viability was higher in carbohydrate rich diet. However, sex specific viability was found in different nutritional regimes. Higher Egg production might be due to higher ovariole number in females of protein rich diet. Thus, Drosophila ananassae adapts different stress tolerance and life-history strategies according to the quality of the available diet, which are correlated with phenotypic adjustment at anatomical and physiological levels.

Residual stress effects on the impact resistance and strength of fiber composites

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Chamis, C. C.

1973-01-01

Equations have been derived to predict degradation effects of microresidual stresses on impact resistance of unidirectional fiber composites. Equations also predict lamination residual stresses in multilayered angle ply composites.

Resistencia bacteriana Bacterial resistance to antimicrobial agents

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Jesualdo Fuentes

1993-01-01

Full Text Available

Se presenta un panorama de la resistencia bacteriana incluyendo su fisiopatogenia y formas de presentación y se establecen algunas consideraciones generales de tipo clínico como auxiliares para racionalizar el uso de los antimicrobianos y evitar o retardar el problema de la resistencia; éste plantea la necesidad de un reordenamiento definitivo en la prescripción de antimicrobianos. No será tanto la creación o descubrimiento de nuevos antibióticos sino la racionalización del manejo de los existentes lo que permitirá alcanzar victorias sobre estos microorganismos. Es Importante mantener educación continua sobre el uso adecuado de los antimicrobianos desde los puntos de vista epidemiológico, farmacocinético y fisiopatogénico.

An overview on bacterial resistance to antimicrobial agents is presented. It includes the different genetic mechanisms for Its development and the biochemical phenomena that explain It. Some clinical considerations are proposed in order to rationalize the use of these drugs and to avoid or delay the appearance of resistance.

Simultaneous analysis of residual stress and stress intensity factor in a resist after UV-nanoimprint lithography based on electron moiré fringes

International Nuclear Information System (INIS)

Wang, Qinghua; Kishimoto, Satoshi

2012-01-01

In this study, the residual stress in a resist (PAK01) film and the stress intensity factor (SIF) of an induced crack are simultaneously estimated during ultraviolet nanoimprint lithography (UV-NIL) based on electron moiré fringes. A micro grid in a triangular arrangement on the resist film fabricated by UV-NIL is directly used as the model grid. Electron moiré fringes formed by the interference between the fabricated grid and the electron scan beam are used to measure the displacement distribution around the tip of a crack induced by the residual stress in the resist. The SIF of the crack is estimated using a displacement extrapolation method. The residual strain fields and the corresponding residual stress in the resist film far from the crack are determined and analyzed. This method is effective for evaluating the grid quality fabricated by the UV-NIL technique. (paper)

Daily Stress, Coping, and Negative and Positive Affect in Depression: Complex Trigger and Maintenance Patterns.

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Dunkley, David M; Lewkowski, Maxim; Lee, Ihno A; Preacher, Kristopher J; Zuroff, David C; Berg, Jody-Lynn; Foley, J Elizabeth; Myhr, Gail; Westreich, Ruta

2017-05-01

Major depressive disorder is characterized by emotional dysfunction, but mood states in daily life are not well understood. This study examined complex explanatory models of daily stress and coping mechanisms that trigger and maintain daily negative affect and (lower) positive affect in depression. Sixty-three depressed patients completed perfectionism measures, and then completed daily questionnaires of stress appraisals, coping, and affect for 7 consecutive days. Multilevel structural equation modeling (MSEM) demonstrated that, across many stressors, when the typical individual with depression perceives more criticism than usual, he/she uses more avoidant coping and experiences higher event stress than usual, and this is connected to daily increases in negative affect as well as decreases in positive affect. In parallel, results showed that perceived control, less avoidant coping, and problem-focused coping commonly operate together when daily positive affect increases. MSEM also showed that avoidant coping tendencies and ongoing stress, in combination, explain why people with depression and higher self-critical perfectionism maintain daily negative affect and lower positive affect. These findings advance a richer and more detailed understanding of specific stress and coping patterns to target in order to more effectively accomplish the two predominant therapy goals of decreasing patients' distress and strengthening resilience. Copyright © 2016. Published by Elsevier Ltd.

Selenite exacerbates hepatic insulin resistance in mouse model of type 2 diabetes through oxidative stress-mediated JNK pathway

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Zhou, Jun, E-mail: hustzhj@hust.edu.cn; Xu, Gang; Bai, Zhaoshuai; Li, Kaicheng; Yan, Junyan; Li, Fen; Ma, Shuai; Xu, Huibi; Huang, Kaixun, E-mail: hxxzrf@hust.edu.cn

2015-12-15

Recent evidence suggests a potential pro-diabetic effect of selenite treatment in type 2 diabetics; however, the underlying mechanisms remain elusive. Here we investigated the effects and the underlying mechanisms of selenite treatment in a nongenetic mouse model of type 2 diabetes. High-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice were orally gavaged with selenite at 0.5 or 2.0 mg/kg body weight/day or vehicle for 4 weeks. High-dose selenite treatment significantly elevated fasting plasma insulin levels and insulin resistance index, in parallel with impaired glucose tolerance, insulin tolerance and pyruvate tolerance. High-dose selenite treatment also attenuated hepatic IRS1/Akt/FoxO1 signaling and pyruvate kinase gene expressions, but elevated the gene expressions of phosphoenolpyruvate carboxyl kinase (PEPCK), glucose 6-phosphatase (G6Pase), peroxisomal proliferator-activated receptor-γ coactivator 1α (PGC-1α) and selenoprotein P (SelP) in the liver. Furthermore, high-dose selenite treatment caused significant increases in MDA contents, protein carbonyl contents, and a decrease in GSH/GSSG ratio in the liver, concurrent with enhanced ASK1/MKK4/JNK signaling. Taken together, these findings suggest that high-dose selenite treatment exacerbates hepatic insulin resistance in mouse model of type 2 diabetes, at least in part through oxidative stress-mediated JNK pathway, providing new mechanistic insights into the pro-diabetic effect of selenite in type 2 diabetes. - Highlights: • Selenite exacerbates hepatic insulin resistance in HFD/STZ-induced diabetic mice. • Selenite elevates hepatic gluconeogenesis and reduces glycolysis in diabetic mice. • Selenite exacerbates hepatic oxidative stress and triggers JNK signaling pathway. • Selenite elevates hepatic selenoprotein P expression in diabetic mice.

Selenite exacerbates hepatic insulin resistance in mouse model of type 2 diabetes through oxidative stress-mediated JNK pathway

International Nuclear Information System (INIS)

Zhou, Jun; Xu, Gang; Bai, Zhaoshuai; Li, Kaicheng; Yan, Junyan; Li, Fen; Ma, Shuai; Xu, Huibi; Huang, Kaixun

2015-01-01

Recent evidence suggests a potential pro-diabetic effect of selenite treatment in type 2 diabetics; however, the underlying mechanisms remain elusive. Here we investigated the effects and the underlying mechanisms of selenite treatment in a nongenetic mouse model of type 2 diabetes. High-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice were orally gavaged with selenite at 0.5 or 2.0 mg/kg body weight/day or vehicle for 4 weeks. High-dose selenite treatment significantly elevated fasting plasma insulin levels and insulin resistance index, in parallel with impaired glucose tolerance, insulin tolerance and pyruvate tolerance. High-dose selenite treatment also attenuated hepatic IRS1/Akt/FoxO1 signaling and pyruvate kinase gene expressions, but elevated the gene expressions of phosphoenolpyruvate carboxyl kinase (PEPCK), glucose 6-phosphatase (G6Pase), peroxisomal proliferator-activated receptor-γ coactivator 1α (PGC-1α) and selenoprotein P (SelP) in the liver. Furthermore, high-dose selenite treatment caused significant increases in MDA contents, protein carbonyl contents, and a decrease in GSH/GSSG ratio in the liver, concurrent with enhanced ASK1/MKK4/JNK signaling. Taken together, these findings suggest that high-dose selenite treatment exacerbates hepatic insulin resistance in mouse model of type 2 diabetes, at least in part through oxidative stress-mediated JNK pathway, providing new mechanistic insights into the pro-diabetic effect of selenite in type 2 diabetes. - Highlights: • Selenite exacerbates hepatic insulin resistance in HFD/STZ-induced diabetic mice. • Selenite elevates hepatic gluconeogenesis and reduces glycolysis in diabetic mice. • Selenite exacerbates hepatic oxidative stress and triggers JNK signaling pathway. • Selenite elevates hepatic selenoprotein P expression in diabetic mice.

[Susceptibility and resistence of Pseudomonas aeruginosa to antimicrobial agents].

Science.gov (United States)

Gamero Delgado, M C; García-Mayorgas, A D; Rodríguez, F; Ibarra, A; Casal, M

2007-06-01

Pseudomonas aeruginosa is an opportunistic microorganism that is frequently the cause of nosocomial infections. Multiple mechanisms are involved in its natural and acquired resistance to many of the antimicrobial agents commonly used in clinical practice. The objective of this study was to assess the susceptibility and resistance patterns of P. aeruginosa strains isolated in Hospital Reina Sofia between 2000 and 2005, as well as to analyze the differences between intrahospital and extrahospital isolates in 2005 and to compare the results with those obtained in other studies. A total of 3,019 strains of P. aeruginosa from different hospitals and nonhospital settings were evaluated, taking into consideration their degree of sensitivity to different antibiotics. The MICs were determined by means of the Wider I automated system (Soria Melguizo), taking into consideration the criteria of susceptibility and resistance recommended by MENSURA. Results of the analysis showed that P. aeruginosa maintained similar levels of antimicrobial susceptibility during the period 2000-2005, with increased susceptibility to amikacin, gentamicin and tobramycin. There were also important differences in the degree of susceptibility between intrahospital and extrahospital strains, except for imipenem and fosfomycin. The intrahospital difference in susceptibility was also evaluated, emphasizing the importance of periodically studying susceptibility and resistance patterns of P. aeruginosa in each setting in order to evaluate different therapeutic guidelines, as it is not always advisable to extrapolate data from different regions. These differences can be explained by the different use of antibiotics in each center and the geographic variations of the resistance mechanisms of P. aeruginosa.

Macromolecular agents with antimicrobial potentialities: A drive to combat antimicrobial resistance.

Science.gov (United States)

Bilal, Muhammad; Rasheed, Tahir; Iqbal, Hafiz M N; Hu, Hongbo; Wang, Wei; Zhang, Xuehong

2017-10-01

In recent years, the antimicrobial resistance (AMR) or multidrug resistance (MDR) has become a serious health concern and major challenging issue, worldwide. After decades of negligence, the AMR has now captured global attention. The increasing number of antibiotic-resistant strains has threatened the achievements of science and medicine since it inactivates conventional antimicrobial therapeutics. Scientists are trying to respond to AMR/MDR threat by exploring innovative platforms and new therapeutic strategies to tackle infections from these resistant strains and bypass treatment limitations related to these pathologies. The present review focuses on the utilization of bio-inspired novel constructs and their potential applications as novel antimicrobial agents. The first part of the review describes plant-based biological macromolecules containing an immense variety of secondary metabolites, which could be potentially used as alternative strategies to combat antimicrobial resistance. The second part discusses the potential of metal-based macromolecules as effective antimicrobial platforms for preventing infections from resistant strains. The third part comprehensively elucidates how nanoparticles, in particular, metal-integrated nanoparticles can overcome this AMR or MDR issue. Towards the end, information is given with critical concluding remarks, gaps, and finally envisioned with future considerations. Copyright © 2017 Elsevier B.V. All rights reserved.

High hydrostatic pressure leads to free radicals accumulation in yeast cells triggering oxidative stress.

Science.gov (United States)

Bravim, Fernanda; Mota, Mainã M; Fernandes, A Alberto R; Fernandes, Patricia M B

2016-08-01

Saccharomyces cerevisiae is a unicellular organism that during the fermentative process is exposed to a variable environment; hence, resistance to multiple stress conditions is a desirable trait. The stress caused by high hydrostatic pressure (HHP) in S. cerevisiae resembles the injuries generated by other industrial stresses. In this study, it was confirmed that gene expression pattern in response to HHP displays an oxidative stress response profile which is expanded upon hydrostatic pressure release. Actually, reactive oxygen species (ROS) concentration level increased in yeast cells exposed to HHP treatment and an incubation period at room pressure led to a decrease in intracellular ROS concentration. On the other hand, ethylic, thermic and osmotic stresses did not result in any ROS accumulation in yeast cells. Microarray analysis revealed an upregulation of genes related to methionine metabolism, appearing to be a specific cellular response to HHP, and not related to other stresses, such as heat and osmotic stresses. Next, we investigated whether enhanced oxidative stress tolerance leads to enhanced tolerance to HHP stress. Overexpression of STF2 is known to enhance tolerance to oxidative stress and we show that it also leads to enhanced tolerance to HHP stress. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Endurance- and Resistance-Trained Men Exhibit Lower Cardiovascular Responses to Psychosocial Stress Than Untrained Men.

Science.gov (United States)

Gröpel, Peter; Urner, Maren; Pruessner, Jens C; Quirin, Markus

2018-01-01

Evidence shows that regular physical exercise reduces physiological reactivity to psychosocial stress. However, previous research mainly focused on the effect of endurance exercise, with only a few studies looking at the effect of resistance exercise. The current study tested whether individuals who regularly participate in either endurance or resistance training differ from untrained individuals in adrenal and cardiovascular reactivity to psychosocial stress. Twelve endurance-trained men, 10 resistance-trained men, and 12 healthy but untrained men were exposed to a standardized psychosocial stressor, the Trier Social Stress Test. Measurements of heart rate, free salivary cortisol levels, and mood were obtained throughout the test and compared among the three groups. Overall, both endurance- and resistance-trained men had lower heart rate levels than untrained men, indicating higher cardiac performance of the trained groups. Trained men also exhibited lower heart rate responses to psychosocial stress compared with untrained men. There were no significant group differences in either cortisol responses or mood responses to the stressor. The heart rate results are consistent with previous studies indicating reduced cardiovascular reactivity to psychosocial stress in trained individuals. These findings suggest that long-term endurance and resistance trainings may be related to the same cardiovascular benefits, without exhibiting strong effects on the cortisol reactivity to stress.

Towards a Systematic Search for Triggered Seismic Events in the USA

Science.gov (United States)

Tang, V.; Chao, K.; Van der Lee, S.

2017-12-01

Dynamic triggering of small earthquakes and tectonic tremor by small stress variations associated with passing surface waves from large-magnitude teleseismic earthquakes have been observed in seismically active regions in the western US. Local stress variations as small as 5 10 kPa can suffice to advance slip on local faults. Observations of such triggered events share certain distinct characteristics. With an eye towards an eventual application of machine learning, we began a systematic search for dynamically triggered seismic events in the USA that have these characteristics. Such a systematic survey has the potential to help us to better understand the fundamental process of dynamic triggering and hazards implied by it. Using visual inspection on top of timing and frequency based selection criteria for these seismic phenomena, our search yielded numerous false positives, indicating the challenge posed by moving from ad-hoc observations of dynamic triggering to a systematic search that also includes a catalog of non-triggering, even when sufficient stress variations are supplied. Our search includes a dozen large earthquakes that occurred during the tenure of USArray. One of these earthquakes (11 April 2012 Mw8.6 Sumatra), for example, was observed by USArray-TA stations in the Midwest and other station networks (such as PB and UW), and yielded candidate-triggered events at 413 stations. We kept 79 of these observations after closer visual inspection of the observed events suggested distinct P and S arrivals from a local earthquake, or a tremor modulation with the same period as the surface wave, among other criteria. We confirmed triggered seismic events in 63 stations along the western plate boundary where triggered events have previously been observed. We also newly found triggered tremor sources in eastern Oregon and Yellowstone, and candidate-triggered earthquake sources in New Mexico and Minnesota. Learning whether 14 of remaining candidates are confirmed

Rockfall triggering by cyclic thermal stressing of exfoliation fractures

Science.gov (United States)

Collins, Brian D.; Stock, Greg M.

2016-01-01

Exfoliation of rock deteriorates cliffs through the formation and subsequent opening of fractures, which in turn can lead to potentially hazardous rockfalls. Although a number of mechanisms are known to trigger rockfalls, many rockfalls occur during periods when likely triggers such as precipitation, seismic activity and freezing conditions are absent. It has been suggested that these enigmatic rockfalls may occur due to solar heating of rock surfaces, which can cause outward expansion. Here we use data from 3.5 years of field monitoring of an exfoliating granite cliff in Yosemite National Park in California, USA, to assess the magnitude and temporal pattern of thermally induced rock deformation. From a thermodynamic analysis, we find that daily, seasonal and annual temperature variations are sufficient to drive cyclic and cumulative opening of fractures. Application of fracture theory suggests that these changes can lead to further fracture propagation and the consequent detachment of rock. Our data indicate that the warmest times of the day and year are particularly conducive to triggering rockfalls, and that cyclic thermal forcing may enhance the efficacy of other, more typical rockfall triggers.

Antimicrobial peptides as potential anti-biofilm agents against multidrug-resistant bacteria.

Science.gov (United States)

Chung, Pooi Yin; Khanum, Ramona

2017-08-01

Bacterial resistance to commonly used drugs has become a global health problem, causing increased infection cases and mortality rate. One of the main virulence determinants in many bacterial infections is biofilm formation, which significantly increases bacterial resistance to antibiotics and innate host defence. In the search to address the chronic infections caused by biofilms, antimicrobial peptides (AMP) have been considered as potential alternative agents to conventional antibiotics. Although AMPs are commonly considered as the primitive mechanism of immunity and has been extensively studied in insects and non-vertebrate organisms, there is now increasing evidence that AMPs also play a crucial role in human immunity. AMPs have exhibited broad-spectrum activity against many strains of Gram-positive and Gram-negative bacteria, including drug-resistant strains, and fungi. In addition, AMPs also showed synergy with classical antibiotics, neutralize toxins and are active in animal models. In this review, the important mechanisms of action and potential of AMPs in the eradication of biofilm formation in multidrug-resistant pathogen, with the goal of designing novel antimicrobial therapeutics, are discussed. Copyright © 2017. Published by Elsevier B.V.

Hepatitis C Virus Resistance to Carbohydrate-Binding Agents.

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Laure Izquierdo

Full Text Available Carbohydrate binding agents (CBAs, including natural lectins, are more and more considered as broad-spectrum antivirals. These molecules are able to directly inhibit many viruses such as Human Immunodeficiency Virus (HIV, Hepatitis C Virus (HCV, Dengue Virus, Ebola Virus or Severe Acute Respiratory Syndrome Coronavirus through binding to envelope protein N-glycans. In the case of HIV, it has been shown that CBAs select for mutant viruses with N-glycosylation site deletions which are more sensitive to neutralizing antibodies. In this study we aimed at evaluating the HCV resistance to CBAs in vitro. HCV was cultivated in the presence of increasing Galanthus nivalis agglutinin (GNA, Cyanovirin-N, Concanavalin-A or Griffithsin concentrations, during more than eight weeks. At the end of lectin exposure, the genome of the isolated strains was sequenced and several potential resistance mutations in the E1E2 envelope glycoproteins were identified. The effect of these mutations on viral fitness as well as on sensitivity to inhibition by lectins, soluble CD81 or the 3/11 neutralizing antibody was assessed. Surprisingly, none of these mutations, alone or in combination, conferred resistance to CBAs. In contrast, we observed that some mutants were more sensitive to 3/11 or CD81-LEL inhibition. Additionally, several mutations were identified in the Core and the non-structural proteins. Thus, our results suggest that in contrast to HIV, HCV resistance to CBAs is not directly conferred by mutations in the envelope protein genes but could occur through an indirect mechanism involving mutations in other viral proteins. Further investigations are needed to completely elucidate the underlying mechanisms.

Triggers of oral lichen planus flares and the potential role of trigger avoidance in disease management.

Science.gov (United States)

Chen, Hannah X; Blasiak, Rachel; Kim, Edwin; Padilla, Ricardo; Culton, Donna A

2017-09-01

Many patients with oral lichen planus (OLP) report triggers of flares, some of which overlap with triggers of other oral diseases, including oral allergy syndrome and oral contact dermatitis. The purpose of this study was to evaluate the prevalence of commonly reported triggers of OLP flares, their overlap with triggers of other oral diseases, and the potential role of trigger avoidance as a management strategy. Questionnaire-based survey of 51 patients with biopsy-proven lichen planus with oral involvement seen in an academic dermatology specialty clinic and/or oral pathology clinic between June 2014 and June 2015. Of the participants, 94% identified at least one trigger of their OLP flares. Approximately half of the participants (51%) reported at least one trigger that overlapped with known triggers of oral allergy syndrome, and 63% identified at least one trigger that overlapped with known triggers of oral contact dermatitis. Emotional stress was the most commonly reported trigger (77%). Regarding avoidance, 79% of the study participants reported avoiding their known triggers in daily life. Of those who actively avoided triggers, 89% reported an improvement in symptoms and 70% reported a decrease in the frequency of flares. Trigger identification and avoidance can play a potentially effective role in the management of OLP. Copyright © 2017 Elsevier Inc. All rights reserved.

Low cadmium exposure triggers a biphasic oxidative stress response in mice kidneys

International Nuclear Information System (INIS)

Thijssen, Sandy; Cuypers, Ann; Maringwa, John; Smeets, Karen; Horemans, Nele; Lambrichts, Ivo; Van Kerkhove, Emmy

2007-01-01

Oxidative stress is believed to participate in the early processes of cadmium (Cd)-induced proximal tubular kidney damage. Mice were chronically exposed up to 23 weeks to low Cd concentrations (10 and 100 mg CdCl 2 /l) via the drinking water. Pro- and antioxidant gene expression levels, glutathione, ascorbate and lipid peroxidation levels were measured. Our study provided evidence for an early and a late stress response in the kidney. Metallothioneins were upregulated from 1 week of exposure on and they stayed important during the whole exposure period. After 8 weeks the expression of Bcl2 (anti-apoptotic), Prdx2 and cytosolic superoxide dismutase (Sod1) was reduced in the group exposed to 100 mg CdCl 2 /l, which might indicate a response to Cd-stress. However glutathione, ascorbate and lipid peroxidation levels did not significantly change, and the overall redox balance remained stable. Stable Sod2 transcriptional levels suggested that an increased formation of superoxide anions, which can arise upon Cd-induced mitochondrial free radical generation, was not appearing. A second defence activation was observed after 23 weeks: i.e. an increase of catalase (Cat), glutathione peroxidase 4 (Gpx4) and heme oxygenase 1 (Hmox1), together with NADPH oxidase 4 (Nox4), of which the role has not been studied yet in Cd nephrotoxicity. These findings were in contrast with previous studies, where Cd-induced oxidative stress was detrimental when high Cd concentrations were applied. In conclusion our study provided evidence that a chronic exposure to low Cd concentrations triggered a biphasic defence activation in the kidney that might lead to adaptation and survival

Surface-wave potential for triggering tectonic (nonvolcanic) tremor

Science.gov (United States)

Hill, D.P.

2010-01-01

Source processes commonly posed to explain instances of remote dynamic triggering of tectonic (nonvolcanic) tremor by surface waves include frictional failure and various modes of fluid activation. The relative potential for Love- and Rayleigh-wave dynamic stresses to trigger tectonic tremor through failure on critically stressed thrust and vertical strike-slip faults under the Coulomb-Griffith failure criteria as a function of incidence angle is anticorrelated over the 15- to 30-km-depth range that hosts tectonic tremor. Love-wave potential is high for strike-parallel incidence on low-angle reverse faults and null for strike-normal incidence; the opposite holds for Rayleigh waves. Love-wave potential is high for both strike-parallel and strike-normal incidence on vertical, strike-slip faults and minimal for ~45?? incidence angles. The opposite holds for Rayleigh waves. This pattern is consistent with documented instances of tremor triggered by Love waves incident on the Cascadia mega-thrust and the San Andreas fault (SAF) in central California resulting from shear failure on weak faults (apparent friction, ????? 0.2). However, documented instances of tremor triggered by surface waves with strike-parallel incidence along the Nankai megathrust beneath Shikoku, Japan, is associated primarily with Rayleigh waves. This is consistent with the tremor bursts resulting from mixed-mode failure (crack opening and shear failure) facilitated by near-lithostatic ambient pore pressure, low differential stress, with a moderate friction coefficient (?? ~ 0.6) on the Nankai subduction interface. Rayleigh-wave dilatational stress is relatively weak at tectonic tremor source depths and seems unlikely to contribute significantly to the triggering process, except perhaps for an indirect role on the SAF in sustaining tremor into the Rayleigh-wave coda that was initially triggered by Love waves.

Geometrical Acceptance Analysis for RPC PAC Trigger

CERN Document Server

Seo, Eunsung

2010-01-01

The CMS(Compact Muon Solenoid) is one of the four experiments that will analyze the collision results of the protons accelerated by the Large Hardron Collider(LHC) at CERN(Conseil Europen pour la Recherche Nuclaire). In case of the CMS experiment, the trigger system is divided into two stages : The Level-1 Trigger and High Level Trigger. The RPC(Resistive Plate Chamber) PAC(PAttern Comparator) Trigger system, which is a subject of this thesis, is a part of the Level-1 Muon Trigger System. Main task of the PAC Trigger is to identify muons, measures transverse momenta and select the best muon candidates for each proton bunch collision occurring every 25 ns. To calculate the value of PAC Trigger efficiency for triggerable muon, two terms of different efficiencies are needed ; acceptance efficiency and chamber efficiency. Main goal of the works described in this thesis is obtaining the acceptance efficiency of the PAC Trigger in each logical cone. Acceptance efficiency is a convolution of the chambers geometry an...

Down-regulation of DNA mismatch repair proteins in human and murine tumor spheroids: implications for multicellular resistance to alkylating agents.

Science.gov (United States)

Francia, Giulio; Green, Shane K; Bocci, Guido; Man, Shan; Emmenegger, Urban; Ebos, John M L; Weinerman, Adina; Shaked, Yuval; Kerbel, Robert S

2005-10-01

Similar to other anticancer agents, intrinsic or acquired resistance to DNA-damaging chemotherapeutics is a major obstacle for cancer therapy. Current strategies aimed at overcoming this problem are mostly based on the premise that tumor cells acquire heritable genetic mutations that contribute to drug resistance. Here, we present evidence for an epigenetic, tumor cell adhesion-mediated, and reversible form of drug resistance that is associated with a reduction of DNA mismatch repair proteins PMS2 and/or MLH1 as well as other members of this DNA repair process. Growth of human breast cancer, human melanoma, and murine EMT-6 breast cancer cell lines as multicellular spheroids in vitro, which is associated with increased resistance to many chemotherapeutic drugs, including alkylating agents, is shown to lead to a reproducible down-regulation of PMS2, MLH1, or, in some cases, both as well as MHS6, MSH3, and MSH2. The observed down-regulation is in part reversible by treatment of tumor spheroids with the DNA-demethylating agent, 5-azacytidine. Thus, treatment of EMT-6 mouse mammary carcinoma spheroids with 5-azacytidine resulted in reduced and/or disrupted cell-cell adhesion, which in turn sensitized tumor spheroids to cisplatin-mediated killing in vitro. Our results suggest that antiadhesive agents might sensitize tumor spheroids to alkylating agents in part by reversing or preventing reduced DNA mismatch repair activity and that the chemosensitization properties of 5-azacytidine may conceivably reflect its role as a potential antiadhesive agent as well as reversal agent for MLH1 gene silencing in human tumors.

Oxidative stress in cancer and fibrosis: Opportunity for therapeutic intervention with antioxidant compounds, enzymes, and nanoparticles

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Jingga Morry

2017-04-01

Full Text Available Oxidative stress, mainly contributed by reactive oxygen species (ROS, has been implicated in pathogenesis of several diseases. We review two primary examples; fibrosis and cancer. In fibrosis, ROS promote activation and proliferation of fibroblasts and myofibroblasts, activating TGF-β pathway in an autocrine manner. In cancer, ROS account for its genomic instability, resistance to apoptosis, proliferation, and angiogenesis. Importantly, ROS trigger cancer cell invasion through invadopodia formation as well as extravasation into a distant metastasis site. Use of antioxidant supplements, enzymes, and inhibitors for ROS-generating NADPH oxidases (NOX is a logical therapeutic intervention for fibrosis and cancer. We review such attempts, progress, and challenges. Lastly, we review how nanoparticles with inherent antioxidant activity can also be a promising therapeutic option, considering their additional feature as a delivery platform for drugs, genes, and imaging agents.

Insight into multiple-triggering effect in DTSCRs for ESD protection

Science.gov (United States)

Zhang, Lizhong; Wang, Yuan; Wang, Yize; He, Yandong

2017-07-01

The diode-triggered silicon-controlled rectifier (DTSCR) is widely used for electrostatic discharge (ESD) protection in advanced CMOS process owing to its advantages, such as design simplification, adjustable trigger/holding voltage, low parasitic capacitance. However, the multiple-triggering effect in the typical DTSCR device may cause undesirable larger overall trigger voltage, which results in a reduced ESD safe margin. In previous research, the major cause is attributed to the higher current level required in the intrinsic SCR. The related discussions indicate that it seems to result from the current division rule between the intrinsic and parasitic SCR formed in the triggering process. In this letter, inserting a large space into the trigger diodes is proposed to get a deeper insight into this issue. The triggering current is observed to be regularly reduced along with the increased space, which confirms that the current division is determined by the parasitic resistance distributed between the intrinsic and parasitic SCR paths. The theoretical analysis is well confirmed by device simulation and transmission line pulse (TLP) test results. The reduced overall trigger voltage is achieved in the modified DTSCR structures due to the comprehensive result of the parasitic resistance vs triggering current, which indicates a minimized multiple-triggering effect. Project supported by the Beijing Natural Science Foundation, China (No. 4162030).

Protective effects of Andrographis paniculata extract and pure andrographolide against chronic stress-triggered pathologies in rats.

Science.gov (United States)

Thakur, Ajit Kumar; Soni, Upendra Kumar; Rai, Geeta; Chatterjee, Shyam Sunder; Kumar, Vikas

2014-11-01

This study was designed to experimentally verify the possibility that Andrographis paniculata could be another medicinal herb potentially useful for prevention of diverse spectrums of pathologies commonly associated with chronic unavoidable environmental stress, and whether andrographolide could as well be its quantitatively major bioactive secondary metabolite. Preventive effects of 21 daily oral 50, 100 and 200 mg/kg doses of a therapeutically used extract of the plant (AP) and 30 and 60 mg/kg/day of pure andrographolide were compared in rats subjected to 1-h daily unavoidable foot-shocks. A pharmaceutically well-standardized Withania somnifera (WS) root extract was used as a reference herbal anti-stress agent in all experiments. Effects of the treatments on stress-induced alterations in body weight, gastric ulcer, adrenal and spleen weights, and depressive state and sexual behavior in male rats were quantified. Other parameters quantified were plasma cortisol levels, and expressions of the cytokines TNF-α, IL-10 and IL-1β in blood and brain. All observed stress-induced pathological changes were less pronounced or completely prevented by both AP and pure andrographolide. Even the lowest tested doses of AP (50 mg/kg/day) or of andrographolide (30 mg/kg/day) suppressed almost maximally the blood IL-1β and IL-10 as well as brain TNF-α and IL-10 expressions induced by chronic stress. Qualitatively, the observed activity profiles of both of them were similar to those of WS dose tested. These results reveal that both AP and andrographolide are pharmacologically polyvalent anti-stress agents, and that biological processes regulating corticosterone and cytokine homeostasis are involved in their modes of actions.

Induction of stress responses by polluting agents which dis-regulate cellular homeostasis

International Nuclear Information System (INIS)

Mothersill, Carmel

2001-01-01

There is growing concern both in the scientific community and among the general public about the effects of exposure to low levels of radiation and environmental chemicals. The increased incidence of cancer, reproduction disorders and allergies have been associated with ambient environmental exposure to these pollutants. The pollution burden is generally made up of a mixture of agents, occurring at concentrations of the individual compounds which are not considered harmful and which are below the action level. Individual pollutants can act through a variety of primary toxicity mechanisms. However the resulting secondary and tertiary toxicity mechanisms which affect cellular homeostasis might be more common. These resulting stress responses, including oxidative stress, have been associated with effects that include increased level of death during cell division, increased levels of mutation and increased tolerance of mutations in cell populations, increased levels of cytogenetic abnormalities and many other symptoms. These effects are linked to a persistent increase in (oxidative) stress and are particularly evident in the haematopoietic system (possibly due to the high rate self of renewal in that system). Therefore prolonged exposure to mixtures of chemicals and radiation might result in additive and synergistic stress responses which can induce long-term delayed effects, often in progeny or in cells not directly exposed to the agent/s. The existence of a common (oxidative) stress mechanism means that the effects of individual pollutants may not be considered in isolation. Rather the total pollution burden may need to be measured using a response rather than a dose based scoring or ranking system. Improved understanding of toxicity mechanisms and effects underpins improved risk assessment and identification of biomarkers. The immune system plays a pivotal role in maintaining health status, and disruption of immune functions can lead to increased susceptibility to

Temperature-stress resistance and tolerance along a latitudinal cline in North American Arabidopsis lyrata.

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Guillaume Wos

Full Text Available The study of latitudinal gradients can yield important insights into adaptation to temperature stress. Two strategies are available: resistance by limiting damage, or tolerance by reducing the fitness consequences of damage. Here we studied latitudinal variation in resistance and tolerance to frost and heat and tested the prediction of a trade-off between the two strategies and their costliness. We raised plants of replicate maternal seed families from eight populations of North American Arabidopsis lyrata collected along a latitudinal gradient in climate chambers and exposed them repeatedly to either frost or heat stress, while a set of control plants grew under standard conditions. When control plants reached maximum rosette size, leaf samples were exposed to frost and heat stress, and electrolyte leakage (PEL was measured and treated as an estimate of resistance. Difference in maximum rosette size between stressed and control plants was used as an estimate of tolerance. Northern populations were more frost resistant, and less heat resistant and less heat tolerant, but-unexpectedly-they were also less frost tolerant. Negative genetic correlations between resistance and tolerance to the same and different thermal stress were generally not significant, indicating only weak trade-offs. However, tolerance to frost was consistently accompanied by small size under control conditions, which may explain the non-adaptive latitudinal pattern for frost tolerance. Our results suggest that adaptation to frost and heat is not constrained by trade-offs between them. But the cost of frost tolerance in terms of plant size reduction may be important for the limits of species distributions and climate niches.

Targeting the cell stress response of Plasmodium falciparum to overcome artemisinin resistance.

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Con Dogovski

2015-04-01

Full Text Available Successful control of falciparum malaria depends greatly on treatment with artemisinin combination therapies. Thus, reports that resistance to artemisinins (ARTs has emerged, and that the prevalence of this resistance is increasing, are alarming. ART resistance has recently been linked to mutations in the K13 propeller protein. We undertook a detailed kinetic analysis of the drug responses of K13 wild-type and mutant isolates of Plasmodium falciparum sourced from a region in Cambodia (Pailin. We demonstrate that ART treatment induces growth retardation and an accumulation of ubiquitinated proteins, indicative of a cellular stress response that engages the ubiquitin/proteasome system. We show that resistant parasites exhibit lower levels of ubiquitinated proteins and delayed onset of cell death, indicating an enhanced cell stress response. We found that the stress response can be targeted by inhibiting the proteasome. Accordingly, clinically used proteasome inhibitors strongly synergize ART activity against both sensitive and resistant parasites, including isogenic lines expressing mutant or wild-type K13. Synergy is also observed against Plasmodium berghei in vivo. We developed a detailed model of parasite responses that enables us to infer, for the first time, in vivo parasite clearance profiles from in vitro assessments of ART sensitivity. We provide evidence that the clinical marker of resistance (delayed parasite clearance is an indirect measure of drug efficacy because of the persistence of unviable parasites with unchanged morphology in the circulation, and we suggest alternative approaches for the direct measurement of viability. Our model predicts that extending current three-day ART treatment courses to four days, or splitting the doses, will efficiently clear resistant parasite infections. This work provides a rationale for improving the detection of ART resistance in the field and for treatment strategies that can be employed in areas

Fanconi anemia proteins and endogenous stresses

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Pang Qishen [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States); Andreassen, Paul R., E-mail: Paul.Andreassen@cchmc.org [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States)

2009-07-31

Each of the thirteen identified Fanconi anemia (FA) genes is required for resistance to DNA interstrand crosslinking agents, such as mitomycin C, cisplatin, and melphalan. While these agents are excellent tools for understanding the function of FA proteins in DNA repair, it is uncertain whether a defect in the removal of DNA interstrand crosslinks (ICLs) is the basis for the pathophysiology of FA. For example, DNA interstrand crosslinking agents induce other types of DNA damage, in addition to ICLs. Further, other DNA-damaging agents, such as ionizing or ultraviolet radiation, activate the FA pathway, leading to monoubiquitination of FANCD2 and FANCI. Also, FA patients display congenital abnormalities, hematologic deficiencies, and a predisposition to cancer in the absence of an environmental source of ICLs that is external to cells. Here we consider potential sources of endogenous DNA damage, or endogenous stresses, to which FA proteins may respond. These include ICLs formed by products of lipid peroxidation, and other forms of oxidative DNA damage. FA proteins may also potentially respond to telomere shortening or replication stress. Defining these endogenous sources of DNA damage or stresses is critical for understanding the pathogenesis of deficiencies for FA proteins. We propose that FA proteins are centrally involved in the response to replication stress, including replication stress arising from oxidative DNA damage.

Fanconi anemia proteins and endogenous stresses

International Nuclear Information System (INIS)

Pang Qishen; Andreassen, Paul R.

2009-01-01

Each of the thirteen identified Fanconi anemia (FA) genes is required for resistance to DNA interstrand crosslinking agents, such as mitomycin C, cisplatin, and melphalan. While these agents are excellent tools for understanding the function of FA proteins in DNA repair, it is uncertain whether a defect in the removal of DNA interstrand crosslinks (ICLs) is the basis for the pathophysiology of FA. For example, DNA interstrand crosslinking agents induce other types of DNA damage, in addition to ICLs. Further, other DNA-damaging agents, such as ionizing or ultraviolet radiation, activate the FA pathway, leading to monoubiquitination of FANCD2 and FANCI. Also, FA patients display congenital abnormalities, hematologic deficiencies, and a predisposition to cancer in the absence of an environmental source of ICLs that is external to cells. Here we consider potential sources of endogenous DNA damage, or endogenous stresses, to which FA proteins may respond. These include ICLs formed by products of lipid peroxidation, and other forms of oxidative DNA damage. FA proteins may also potentially respond to telomere shortening or replication stress. Defining these endogenous sources of DNA damage or stresses is critical for understanding the pathogenesis of deficiencies for FA proteins. We propose that FA proteins are centrally involved in the response to replication stress, including replication stress arising from oxidative DNA damage.

Identification of a New Antimicrobial Resistance Gene Provides Fresh Insights Into Pleuromutilin Resistance in Brachyspira hyodysenteriae, Aetiological Agent of Swine Dysentery

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Roderick M. Card

2018-06-01

Full Text Available Brachyspira hyodysenteriae is the aetiological agent of swine dysentery, a globally distributed disease that causes profound economic loss, impedes the free trade and movement of animals, and has significant impact on pig health. Infection is generally treated with antibiotics of which pleuromutilins, such as tiamulin, are widely used for this purpose, but reports of resistance worldwide threaten continued effective control. In Brachyspira hyodysenteriae pleuromutilin resistance has been associated with mutations in chromosomal genes encoding ribosome-associated functions, however the dynamics of resistance acquisition are poorly understood, compromising stewardship efforts to preserve pleuromutilin effectiveness. In this study we undertook whole genome sequencing (WGS and phenotypic susceptibility testing of 34 UK field isolates and 3 control strains to investigate pleuromutilin resistance in Brachyspira hyodysenteriae. Genome-wide association studies identified a new pleuromutilin resistance gene, tva(A (tiamulin valnemulin antibiotic resistance, encoding a predicted ABC-F transporter. In vitro culture of isolates in the presence of inhibitory or sub-inhibitory concentrations of tiamulin showed that tva(A confers reduced pleuromutilin susceptibility that does not lead to clinical resistance but facilitates the development of higher-level resistance via mutations in genes encoding ribosome-associated functions. Genome sequencing of antibiotic-exposed isolates identified both new and previously described mutations in chromosomal genes associated with reduced pleuromutilin susceptibility, including the 23S rRNA gene and rplC, which encodes the L3 ribosomal protein. Interesting three antibiotic-exposed isolates harboured mutations in fusA, encoding Elongation Factor G, a gene not previously associated with pleuromutilin resistance. A longitudinal molecular epidemiological examination of two episodes of swine dysentery at the same farm indicated

HeLa Cells Containing a Truncated Form of DNA Polymerase Beta are More Sensitized to Alkylating Agents than to Agents Inducing Oxidative Stress.

Science.gov (United States)

Khanra, Kalyani; Chakraborty, Anindita; Bhattacharyya, Nandan

2015-01-01

The present study was aimed at determining the effects of alkylating and oxidative stress inducing agents on a newly identified variant of DNA polymerase beta (polβ Δ208-304) specific for ovarian cancer. Pol β Δ208-304 has a deletion of exons 11-13 which lie in the catalytic part of enzyme. We compared the effect of these chemicals on HeLa cells and HeLa cells stably transfected with this variant cloned into in pcDNAI/neo vector by MTT, colony forming and apoptosis assays. Polβ Δ208-304 cells exhibited greater sensitivity to an alkylating agent and less sensitivity towards H2O2 and UV when compared with HeLa cells alone. It has been shown that cell death in Pol β Δ208-304 transfected HeLa cells is mediated by the caspase 9 cascade. Exon 11 has nucleotidyl selection activity, while exons 12 and 13 have dNTP selection activity. Hence deletion of this part may affect polymerizing activity although single strand binding and double strand binding activity may remain same. The lack of this part may adversely affect catalytic activity of DNA polymerase beta so that the variant may act as a dominant negative mutant. This would represent clinical significance if translated into a clinical setting because resistance to radiation or chemotherapy during the relapse of the disease could be potentially overcome by this approach.

P-body proteins regulate transcriptional rewiring to promote DNA replication stress resistance.

Science.gov (United States)

Loll-Krippleber, Raphael; Brown, Grant W

2017-09-15

mRNA-processing (P-) bodies are cytoplasmic granules that form in eukaryotic cells in response to numerous stresses to serve as sites of degradation and storage of mRNAs. Functional P-bodies are critical for the DNA replication stress response in yeast, yet the repertoire of P-body targets and the mechanisms by which P-bodies promote replication stress resistance are unknown. In this study we identify the complete complement of mRNA targets of P-bodies during replication stress induced by hydroxyurea treatment. The key P-body protein Lsm1 controls the abundance of HHT1, ACF4, ARL3, TMA16, RRS1 and YOX1 mRNAs to prevent their toxic accumulation during replication stress. Accumulation of YOX1 mRNA causes aberrant downregulation of a network of genes critical for DNA replication stress resistance and leads to toxic acetaldehyde accumulation. Our data reveal the scope and the targets of regulation by P-body proteins during the DNA replication stress response.P-bodies form in response to stress and act as sites of mRNA storage and degradation. Here the authors identify the mRNA targets of P-bodies during DNA replication stress, and show that P-body proteins act to prevent toxic accumulation of these target transcripts.

Cooperative Robot Localization Using Event-Triggered Estimation

Science.gov (United States)

Iglesias Echevarria, David I.

It is known that multiple robot systems that need to cooperate to perform certain activities or tasks incur in high energy costs that hinder their autonomous functioning and limit the benefits provided to humans by these kinds of platforms. This work presents a communications-based method for cooperative robot localization. Implementing concepts from event-triggered estimation, used with success in the field of wireless sensor networks but rarely to do robot localization, agents are able to only send measurements to their neighbors when the expected novelty in this information is high. Since all agents know the condition that triggers a measurement to be sent or not, the lack of a measurement is therefore informative and fused into state estimates. In the case agents do not receive either direct nor indirect measurements of all others, the agents employ a covariance intersection fusion rule in order to keep the local covariance error metric bounded. A comprehensive analysis of the proposed algorithm and its estimation performance in a variety of scenarios is performed, and the algorithm is compared to similar cooperative localization approaches. Extensive simulations are performed that illustrate the effectiveness of this method.

A novel gene of Kalanchoe daigremontiana confers plant drought resistance.

Science.gov (United States)

Wang, Li; Zhu, Chen; Jin, Lin; Xiao, Aihua; Duan, Jie; Ma, Luyi

2018-02-07

Kalanchoe (K.) daigremontiana is important for studying asexual reproduction under different environmental conditions. Here, we describe a novel KdNOVEL41 (KdN41) gene that may confer drought resistance and could thereby affect K. daigremontiana development. The detected subcellular localization of a KdN41/Yellow Fluorescent Protein (YFP) fusion protein was in the nucleus and cell membrane. Drought, salt, and heat stress treatment in tobacco plants containing the KdN41 gene promoter driving β-glucuronidase (GUS) gene transcription revealed that only drought stress triggered strong GUS staining in the vascular tissues. Overexpression (OE) of the KdN41 gene conferred improved drought resistance in tobacco plants compared to wild-type and transformed with empty vector plants by inducing higher antioxidant enzyme activities, decreasing cell membrane damage, increasing abscisic acid (ABA) content, causing reinforced drought resistance related gene expression profiles. The 3,3'-diaminobenzidine (DAB) and nitroblue tetrazolium (NBT) staining results also showed less relative oxygen species (ROS) content in KdN41-overexpressing tobacco leaf during drought stress. Surprisingly, by re-watering after drought stress, KdN41-overexpressing tobacco showed earlier flowering. Overall, the KdN41 gene plays roles in ROS scavenging and osmotic damage reduction to improve tobacco drought resistance, which may increase our understanding of the molecular network involved in developmental manipulation under drought stress in K. daigremontiana.

Resistance of bacterial biofilms formed on stainless steel surface to disinfecting agent.

Science.gov (United States)

Królasik, Joanna; Zakowska, Zofia; Krepska, Milena; Klimek, Leszek

2010-01-01

The natural ability of microorganisms for adhesion and biofilm formation on various surfaces is one of the factors causing the inefficiency of a disinfection agent, despite its proven activity in vitro. The aim of the study was to determine the effectiveness of disinfecting substances on bacterial biofilms formed on stainless steel surface. A universally applied disinfecting agent was used in the tests. Bacterial strains: Listeria innocua, Pseudomonas putida, Micrococcus luteus, Staphylococcus hominis strains, were isolated from food contact surfaces, after a cleaning and disinfection process. The disinfecting agent was a commercially available acid specimen based on hydrogen peroxide and peroxyacetic acid, the substance that was designed for food industry usage. Model tests were carried out on biofilm formed on stainless steel (type 304, no 4 finish). Biofilms were recorded by electron scanning microscope. The disinfecting agent in usable concentration, 0.5% and during 10 minutes was ineffective for biofilms. The reduction of cells in biofilms was only 1-2 logarithmic cycles. The use of the agent in higher concentration--1% for 30 minutes caused reduction of cell number by around 5 logarithmic cycles only in the case of one microorganism, M. luteus. For other types: L. innocua, P. putida, S. hominis, the requirements placed on disinfecting agents were not fulfilled. The results of experiments proved that bacterial biofilms are resistant to the disinfectant applied in its operational parameters. Disinfecting effectiveness was achieved after twofold increase of the agent's concentration.

Field and polarity dependence of time-to-resistance increase in Fe–O films studied by constant voltage stress method

OpenAIRE

Eriguchi, Koji; Wei, Zhiqiang; Takagi, Takeshi; Ohta, Hiroaki; Ono, Kouichi

2009-01-01

Constant voltage stress (CVS) was applied to Fe–O films prepared by a sputtering process to investigate a stress-induced resistance increase leading to a fundamental mechanism for switching behaviors. Under the CVS, an abrupt resistance increase was found for both stress polarities. A conduction mechanism after the resistance increase exhibited non-Ohmic transport. The time-to-resistance increase (tr) under the CVS was revealed to strongly depend on stress voltage as well as the polarity. Fro...

Oxidative stress and antioxidant responses to progressive resistance exercise intensity in trained and untrained males

OpenAIRE

H Çakır-Atabek; F Özdemir; R Çolak

2015-01-01

The relationship between oxidative stress and some exercise components of resistance exercise (e.g. intensity, exercise volume) has not been clearly defined. Additionally, the oxidative stress markers may respond differently in various conditions. This study aims to determine the effects of progressive intensity of resistance exercise (RE) on oxidative stress and antioxidants in trained and untrained men, and also to investigate the possible threshold intensity required to evoke oxidative str...

Exercise, learned helplessness, and the stress-resistant brain.

Science.gov (United States)

Greenwood, Benjamin N; Fleshner, Monika

2008-01-01

Exercise can prevent the development of stress-related mood disorders, such as depression and anxiety. The underlying neurobiological mechanisms of this effect, however, remain unknown. Recently, researchers have used animal models to begin to elucidate the potential mechanisms underlying the protective effects of physical activity. Using the behavioral consequences of uncontrollable stress or "learned helplessness" as an animal analog of depression- and anxiety-like behaviors in rats, we are investigating factors that could be important for the antidepressant and anxiolytic properties of exercise (i.e., wheel running). The current review focuses on the following: (1) the effect of exercise on the behavioral consequences of uncontrollable stress and the implications of these effects on the specificity of the "learned helplessness" animal model; (2) the neurocircuitry of learned helplessness and the role of serotonin; and (3) exercise-associated neural adaptations and neural plasticity that may contribute to the stress-resistant brain. Identifying the mechanisms by which exercise prevents learned helplessness could shed light on the complex neurobiology of depression and anxiety and potentially lead to novel strategies for the prevention of stress-related mood disorders.

Chronic Stress Triggers Expression of Immediate Early Genes and Differentially Affects the Expression of AMPA and NMDA Subunits in Dorsal and Ventral Hippocampus of Rats

Directory of Open Access Journals (Sweden)

Anibal Pacheco

2017-08-01

Full Text Available Previous studies in rats have demonstrated that chronic restraint stress triggers anhedonia, depressive-like behaviors, anxiety and a reduction in dendritic spine density in hippocampal neurons. In this study, we compared the effect of repeated stress on the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA and N-methyl-D-aspartate (NMDA receptor subunits in dorsal and ventral hippocampus (VH. Adult male Sprague-Dawley rats were randomly divided into control and stressed groups, and were daily restrained in their motion (2.5 h/day during 14 days. We found that chronic stress promotes an increase in c-Fos mRNA levels in both hippocampal areas, although it was observed a reduction in the immunoreactivity at pyramidal cell layer. Furthermore, Arc mRNAs levels were increased in both dorsal and VH, accompanied by an increase in Arc immunoreactivity in dendritic hippocampal layers. Furthermore, stress triggered a reduction in PSD-95 and NR1 protein levels in whole extract of dorsal and VH. Moreover, a reduction in NR2A/NR2B ratio was observed only in dorsal pole. In synaptosomal fractions, we detected a rise in NR1 in dorsal hippocampus (DH. By indirect immunofluorescence we found that NR1 subunits rise, especially in neuropil areas of dorsal, but not VH. In relation to AMPA receptor (AMPAR subunits, chronic stress did not trigger any change, either in dorsal or ventral hippocampal areas. These data suggest that DH is more sensitive than VH to chronic stress exposure, mainly altering the expression of NMDA receptor (NMDAR subunits, and probably favors changes in the configuration of this receptor that may influence the function of this area.

Development of abiotic-stress resistant warm season trufgrasses by proton-beam irradiation

Energy Technology Data Exchange (ETDEWEB)

Seo, Y. W.; Kim, J. Y.; Jeong, S. H. [Korea Univ., Seoul (Korea, Republic of)

2007-04-15

The direct use of mutation is a valuable approach to generate genetic variation in crop species by altering agronomically useful major traits. The proton beam, as a mutagen, was applied to improve resistance traits of Zoysia grass under various abiotic stresses. Proton beam was irradiated to mature dry seeds of Zenith (Zoysia grass), which is well-adapted to Korean climate, using a proton- accelerator with seven different doses (50, 100, 150, 200, 250, 300, 400 Gy). Individual seedling of M1 plant was transplanted from the seed bed and allowed to reach appropriate plant mass. Clones that showed superior growth were chosen and transplanted to pots for further clone propagation and field evaluation. Growth characteristics of turfgrass, such as plant height, leaf length, leaf width, number of tiller were evaluated ninety days after sowing. Although large variation within each dose, noticeable differences were found among different irradiated doses. Most of the mutant clones derived from the irradiation treatment showed more vigorous growth than the control plants. RAPD (Random Amplified Polymorphic DNA) and AFLP (Amplified Fragment Length Polymorphism) methods were conducted to analyze genomic variations associated with proton beam irradiation. In order to establish selection criteria for selection of salt-stress resistance plants, an in vitro method that is able to select salt-stress resistant mutants in liquid media without ambient disturbances. Total 647 predominance clones that were considered as abiotic stress resistant mutants were transplanted to the field for further evaluation.

Shear-Rate-Dependent Behavior of Clayey Bimaterial Interfaces at Landslide Stress Levels

Science.gov (United States)

Scaringi, Gianvito; Hu, Wei; Xu, Qiang; Huang, Runqiu

2018-01-01

The behavior of reactivated and first-failure landslides after large displacements is controlled by the available shear resistance in a shear zone and/or along slip surfaces, such as a soil-bedrock interface. Among the factors influencing the resistance parameter, the dependence on the shear rate can trigger catastrophic evolution (rate-weakening) or exert a slow-down feedback (rate-strengthening) upon stress perturbation. We present ring-shear test results, performed under various normal stresses and shear rates, on clayey soils from a landslide shear zone, on its parent lithology and other lithologies, and on clay-rock interface samples. We find that depending on the materials in contact, the normal stress, and the stress history, the shear-rate-dependent behaviors differ. We discuss possible models and underlying mechanisms for the time-dependent behavior of landslides in clay soils.

Global observation of Omori-law decay in the rate of triggered earthquakes

Science.gov (United States)

Parsons, T.

2001-12-01

Triggered earthquakes can be large, damaging, and lethal as evidenced by the 1999 shocks in Turkey and the 2001 events in El Salvador. In this study, earthquakes with M greater than 7.0 from the Harvard CMT catalog are modeled as dislocations to calculate shear stress changes on subsequent earthquake rupture planes near enough to be affected. About 61% of earthquakes that occurred near the main shocks are associated with calculated shear stress increases, while ~39% are associated with shear stress decreases. If earthquakes associated with calculated shear stress increases are interpreted as triggered, then such events make up at least 8% of the CMT catalog. Globally, triggered earthquakes obey an Omori-law rate decay that lasts between ~7-11 years after the main shock. Earthquakes associated with calculated shear stress increases occur at higher rates than background up to 240 km away from the main-shock centroid. Earthquakes triggered by smaller quakes (foreshocks) also obey Omori's law, which is one of the few time-predictable patterns evident in the global occurrence of earthquakes. These observations indicate that earthquake probability calculations which include interactions from previous shocks should incorporate a transient Omori-law decay with time. In addition, a very simple model using the observed global rate change with time and spatial distribution of triggered earthquakes can be applied to immediately assess the likelihood of triggered earthquakes following large events, and can be in place until more sophisticated analyses are conducted.

Experience of Percutaneous Trigger Finger Release under Local ...

African Journals Online (AJOL)

Background: Trigger finger is a common disorder of upper extremity. Majority of the patients can be treated conservatively but some resistant cases eventually need surgery. Aim: The aim of this study is to evaluate the results of percutaneous trigger finger release under local anesthesia. Subjects and Methods: This is a ...

Alcohol dehydrogenase 1 (ADH1) confers both abiotic and biotic stress resistance in Arabidopsis.

Science.gov (United States)

Shi, Haitao; Liu, Wen; Yao, Yue; Wei, Yunxie; Chan, Zhulong

2017-09-01

Although the transcriptional regulation and upstream transcription factors of AtADH1 in response to abiotic stress are widely revealed, the in vivo roles of AtADH1 remain unknown. In this study, we found that the expression of AtADH1 was largely induced after salt, drought, cold and pathogen infection. Further studies found that AtADH1 overexpressing plants were more sensitive to abscisic acid (ABA) in comparison to wide type (WT), while AtADH1 knockout mutants showed no significant difference compared with WT in ABA sensitivity. Consistently, AtADH1 overexpressing plants showed improved stress resistance to salt, drought, cold and pathogen infection than WT, but the AtADH1 knockout mutants had no significant difference in abiotic and biotic stress resistance. Moreover, overexpression of AtADH1 expression increased the transcript levels of multiple stress-related genes, accumulation of soluble sugars and callose depositions. All these results indicate that AtADH1 confers enhanced resistance to both abiotic and biotic stresses. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasticity in behavioural responses and resistance to temperature stress in Musca domestica

DEFF Research Database (Denmark)

Kjaersgaard, Anders; Blackenhorn, Wolf U.; Pertoldi, Cino

2015-01-01

, at the stressful high temperature Spanish flies flew the furthest and Danish flies the shortest distance. Neither body size nor wing loading affected flight performance, although flies with narrower wings tended to fly further (wing shape effect). Swiss flies were most active in terms of locomotor activity......Organisms can respond to and cope with stressful environments in a number of ways including behavioural, morphological and physiological adjustments. To understand the role of behavioural traits in thermal adaptations we compared heat resistance, locomotor (walking and flying) activity, flight...... performance and morphology of three European populations of Musca domestica (Diptera: Muscidae) originating from different thermal conditions (Spain, Switzerland and Denmark) at benign and stressful high temperatures. Spanish flies showed greater heat resistance than Swiss and Danish flies. Similarly...

State-of-the-Art Materials for Ultrasound-Triggered Drug Delivery

Science.gov (United States)

Sirsi, Shashank; Borden, Mark

2014-01-01

Ultrasound is a unique and exciting theranostic modality that can be used to track drug carriers, trigger drug release and improve drug deposition with high spatial precision. In this review, we briefly describe the mechanisms of interaction between drug carriers and ultrasound waves, including cavitation, streaming and hyperthermia, and how those interactions can promote drug release and tissue uptake. We then discuss the rational design of some state-of-the-art materials for ultrasound-triggered drug delivery and review recent progress for each drug carrier, focusing on the delivery of chemotherapeutic agents such as doxorubicin. These materials include nanocarrier formulations, such as liposomes and micelles, designed specifically for ultrasound-triggered drug release, as well as microbubbles, microbubble-nanocarrier hybrids, microbubble-seeded hydrogels and phase-change agents. PMID:24389162

Chloride stress triggers maturation and negatively affects the postharvest quality of persimmon fruit. Involvement of calyx ethylene production.

Science.gov (United States)

Besada, Cristina; Gil, Rebeca; Bonet, Luis; Quiñones, Ana; Intrigliolo, Diego; Salvador, Alejandra

2016-03-01

In recent years many hectares planted with persimmon trees in E Spain have been diagnosed with chloride toxicity. An effect of this abiotic stress on fruit quality has been reported in different crops. However, the impact of chloride stress on persimmon fruit quality is unknown. The harvest and postharvest quality of persimmons harvested from trees that manifest different intensities of chloride toxicity foliar symptoms was evaluated herein. Our results revealed that fruits from trees under chloride stress conditions underwent chloride accumulation in the calyx, which was more marked the greater the salt stress intensity trees were exposed to. Increased chloride concentrations in the calyx stimulated ethylene production in this tissue. In the fruits affected by slight and moderate chloride stress, calyx ethylene production accelerated the maturity process, as reflected by increased fruit colour and diminished fruit firmness. In the fruits under severe chloride stress, the high ethylene levels in the calyx triggered autocatalytic ethylene production in other fruit tissues, which led fruit maturity to drastically advance. In these fruits effectiveness of CO2 deastringency treatment was not complete and fruit softening enhanced during the postharvest period. Moreover, chloride stress conditions had a marked effect on reducing fruit weight, even in slightly stressed trees. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Coupled stress-strain and electrical resistivity measurements on copper based shape memory single crystals

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Gonzalez Cezar Henrique

2004-01-01

Full Text Available Recently, electrical resistivity (ER measurements have been done during some thermomechanical tests in copper based shape memory alloys (SMA's. In this work, single crystals of Cu-based SMA's have been studied at different temperatures to analyse the relationship between stress (s and ER changes as a function of the strain (e. A good consistency between ER change values is observed in different experiments: thermal martensitic transformation, stress induced martensitic transformation and stress induced reorientation of martensite variants. During stress induced martensitic transformation (superelastic behaviour and stress induced reorientation of martensite variants, a linear relationship is obtained between ER and strain as well as the absence of hys teresis. In conclusion, the present results show a direct evidence of martensite electrical resistivity anisotropy.

Effect of heat treatment conditions on stress corrosion cracking resistance of alloy X-750 in high temperature water

International Nuclear Information System (INIS)

Yonezawa, Toshio; Onimura, Kichiro; Sakamoto, Naruo; Sasaguri, Nobuya; Susukida, Hiroshi; Nakata, Hidenori.

1984-01-01

In order to improve the resistance of the Alloy X-750 in high temperature and high purity water, the authors investigated the influence of heat treatment condition on the stress corrosion cracking resistance of the alloy. This paper describes results of the stress corrosion cracking test and some discussion on the mechanism of the stress corrosion cracking of Alloy X-750 in deaerated high temperature water. The following results were obtained. (1) The stress corrosion cracking resistance of Alloy X-750 in deaerated high temperature water remarkably depended upon the heat treatment condition. The materials solution heat treated and aged within temperature ranges from 1065 to 1100 0 C and from 704 to 732 0 C, respectively, have a good resistance to the stress corrosion cracking in deaerated high temperature water. Especially, water cooling after the solution heat treatment gives an excellent resistance to the stress corrosion cracking in deaerated high temperature water. (2) Any correlations were not observed between the stress corrosion cracking susceptibility of Alloy X-750 in deaerated high temperature water and grain boundary chromium depleted zones, precipitate free zones and the grain boundary segregation of impurity elements and so on. It appears that there are good correlations between the stress corrosion cracking resistance of the alloy in the environment and the kinds, morphology and coherency of precipitates along the grain boundaries. (author)

Combination of Bifunctional Alkylating Agent and Arsenic Trioxide Synergistically Suppresses the Growth of Drug-Resistant Tumor Cells

Directory of Open Access Journals (Sweden)

Pei-Chih Lee

2010-05-01

Full Text Available Drug resistance is a crucial factor in the failure of cancer chemotherapy. In this study, we explored the effect of combining alkylating agents and arsenic trioxide (ATO on the suppression of tumor cells with inherited or acquired resistance to therapeutic agents. Our results showed that combining ATO and a synthetic derivative of 3a-aza-cyclopenta[a]indenes (BO-1012, a bifunctional alkylating agent causing DNA interstrand cross-links, was more effective in killing human cancer cell lines (H460, H1299, and PC3 than combining ATO and melphalan or thiotepa. We further demonstrated that the combination treatment of H460 cells with BO-1012 and ATO resulted in severe G2/M arrest and apoptosis. In a xenograft mouse model, the combination treatment with BO-1012 and ATO synergistically reduced tumor volumes in nude mice inoculated with H460 cells. Similarly, the combination of BO-1012 and ATO effectively reduced the growth of cisplatin-resistant NTUB1/P human bladder carcinoma cells. Furthermore, the repair of BO-1012-induced DNA interstrand cross-links was significantly inhibited by ATO, and consequently, γH2AX was remarkably increased and formed nuclear foci in H460 cells treated with this drug combination. In addition, Rad51 was activated by translocating and forming foci in nuclei on treatment with BO-1012, whereas its activation was significantly suppressed by ATO. We further revealed that ATO might mediate through the suppression of AKT activity to inactivate Rad51. Taken together, the present study reveals that a combination of bifunctional alkylating agents and ATO may be a rational strategy for treating cancers with inherited or acquired drug resistance.

Effect of Myricetin, Pyrogallol, and Phloroglucinol on Yeast Resistance to Oxidative Stress

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Vanda Mendes

2015-01-01

Full Text Available The health beneficial effects of dietary polyphenols have been attributed to their intrinsic antioxidant activity, which depends on the structure of the compound and number of hydroxyl groups. In this study, the protective effects of pyrogallol, phloroglucinol, and myricetin on the yeast Saccharomyces cerevisiae were investigated. Pyrogallol and myricetin, which have a pyrogallol structure in the B ring, increased H2O2 resistance associated with a reduction in intracellular oxidation and protein carbonylation, whereas phloroglucinol did not exert protective effects. The acquisition of oxidative stress resistance in cells pretreated with pyrogallol and myricetin was not associated with an induction of endogenous antioxidant defences as assessed by the analysis of superoxide dismutase and catalase activities. However, myricetin, which provided greater stress resistance, prevented H2O2-induced glutathione oxidation. Moreover, myricetin increased the chronological lifespan of yeast lacking the mitochondrial superoxide dismutase (Sod2p, which exhibited a premature aging phenotype and oxidative stress sensitivity. These findings show that the presence of hydroxyl groups in the ortho position of the B ring in pyrogallol and myricetin contributes to the antioxidant protection afforded by these compounds. In addition, myricetin may alleviate aging-induced oxidative stress, particularly when redox homeostasis is compromised due to downregulation of endogenous defences present in mitochondria.

Testing for the 'predictability' of dynamically triggered earthquakes in The Geysers geothermal field

Science.gov (United States)

Aiken, Chastity; Meng, Xiaofeng; Hardebeck, Jeanne

2018-03-01

The Geysers geothermal field is well known for being susceptible to dynamic triggering of earthquakes by large distant earthquakes, owing to the introduction of fluids for energy production. Yet, it is unknown if dynamic triggering of earthquakes is 'predictable' or whether dynamic triggering could lead to a potential hazard for energy production. In this paper, our goal is to investigate the characteristics of triggering and the physical conditions that promote triggering to determine whether or not triggering is in anyway foreseeable. We find that, at present, triggering in The Geysers is not easily 'predictable' in terms of when and where based on observable physical conditions. However, triggered earthquake magnitude positively correlates with peak imparted dynamic stress, and larger dynamic stresses tend to trigger sequences similar to mainshock-aftershock sequences. Thus, we may be able to 'predict' what size earthquakes to expect at The Geysers following a large distant earthquake.

Field and polarity dependence of time-to-resistance increase in Fe-O films studied by constant voltage stress method

International Nuclear Information System (INIS)

Eriguchi, Koji; Ohta, Hiroaki; Ono, Kouichi; Wei Zhiqiang; Takagi, Takeshi

2009-01-01

Constant voltage stress (CVS) was applied to Fe-O films prepared by a sputtering process to investigate a stress-induced resistance increase leading to a fundamental mechanism for switching behaviors. Under the CVS, an abrupt resistance increase was found for both stress polarities. A conduction mechanism after the resistance increase exhibited non-Ohmic transport. The time-to-resistance increase (t r ) under the CVS was revealed to strongly depend on stress voltage as well as the polarity. From a polarity-dependent resistance increase determined by a time-zero measurement, the voltage and polarity-dependent t r were discussed on the basis of field- and structure-enhanced thermochemical reaction mechanisms

[Physiological responses of mycorrhizal Pinus massoniana seedlings to drought stress and drought resistance evaluation].

Science.gov (United States)

Wang, Yi; Ding, Gui-jie

2013-03-01

A greenhouse pot experiment was conducted to study the effects of inoculating Pisolithus tinctorius, Cenococcum geophilum, Cantharellus cibarius, and Suillus luteus on the physiological characteristics of Pinus massoniana seedlings under the conditions of drought stress and re-watering, with the drought resistance of the mycorrhizal seedlings evaluated. Under drought stress, the MDA content and membrane' s relative permeability of P. massoniana seedlings increased, but these two indices in the inoculated (mycorrhizal) seedlings were significantly lower than these in the un-inoculated (control) seedlings. After re-watering, the MDA content and membrane's relative permeability of mycorrhizal seedlings had a rapid decrease, as compared with the control. In the first 21 days of drought stress, the production rate of superoxide radical of the seedlings increased, and the SOD, POD and NR activities of mycorrhizal seedlings increased significantly. With the extending of drought stress, the seedlings after re-watering had different recovery ability. Under the re-watering after 14 days drought stress, the SOD, POD and NR activities recovered. The drought resistance of the mycorrhizal seedlings was in the order of Suillus luteus 1 > Suillus luteus 7 > Cantharellus cibarius > Cenococcum geophilum > Pisolithus tinctorius. The SOD and MDA activities had a greater correlation with the mycorrhizal seedlings drought resistance, being able to be used as the indicators to evaluate the drought resistance of mycorrhizal seedlings.

A vanillin derivative causes mitochondrial dysfunction and triggers oxidative stress in Cryptococcus neoformans.

Science.gov (United States)

Kim, Jin Hyo; Lee, Han-Ok; Cho, Yong-Joon; Kim, Jeongmi; Chun, Jongsik; Choi, Jaehyuk; Lee, Younghoon; Jung, Won Hee

2014-01-01

Vanillin is a well-known food and cosmetic additive and has antioxidant and antimutagenic properties. It has also been suggested to have antifungal activity against major human pathogenic fungi, although it is not very effective. In this study, the antifungal activities of vanillin and 33 vanillin derivatives against the human fungal pathogen Cryptococcus neoformans, the main pathogen of cryptococcal meningitis in immunocompromised patients, were investigated. We found a structural correlation between the vanillin derivatives and antifungal activity, showing that the hydroxyl or alkoxy group is more advantageous than the halogenated or nitrated group in benzaldehyde. Among the vanillin derivatives with a hydroxyl or alkoxy group, o-vanillin and o-ethyl vanillin showed the highest antifungal activity against C. neoformans. o-Vanillin was further studied to understand the mechanism of antifungal action. We compared the transcriptome of C. neoformans cells untreated or treated with o-vanillin by using RNA sequencing and found that the compound caused mitochondrial dysfunction and triggered oxidative stress. These antifungal mechanisms of o-vanillin were experimentally confirmed by the significantly reduced growth of the mutants lacking the genes involved in mitochondrial functions and oxidative stress response.

Shear flow generation by Reynolds stress and suppression of resistive g-modes

International Nuclear Information System (INIS)

Sugama, H.; Horton, W.

1993-08-01

Suppression of resistive g-mode turbulence by background shear flow generated from a small external flow source and amplified by the fluctuation-induced Reynolds stress is demonstrated and analyzed. The model leads to a paradigm for the low-to-high (L-H) confinement mode transition. To demonstrate the L-H transition model, single-helicity nonlinear fluid simulations using the vorticity equation for the electrostatic potential, the pressure fluctuation equation and the background poloidal flow equation are used in the sheared slab configuration. The relative efficiency of the external flow and the Reynolds stress for producing shear flow depends on the poloidal flow damping parameter ν which is given by neoclassical theory. For large ν, the external flow is a dominant contribution to the total background poloidal shear flow and its strength predicted by the neoclassical theory is not enough to suppress the turbulence significantly. In contrast, for small ν, we show that the fluctuations drive a Reynolds stress that becomes large and suddenly, at some critical point in time, shear flow much larger than the external flow is generated and leads to an abrupt, order unity reduction of the turbulent transport just like that of the L-H transition in tokamak experiments. It is also found that, even in the case of no external flow, the shear flow generation due to the Reynolds stress occurs through the nonlinear interaction of the resistive g-modes and reduces the transport. To supplement the numerical solutions we derive the Landau equation for the mode amplitude of the resistive g-mode taking into account the fluctuation-induced shear flow and analyze the opposite action of the Reynolds stress in the resistive g turbulence compared with the classical shear flow Kelvin-Helmholtz (K-H) driven turbulence

The CMS Barrel Muon trigger upgrade

International Nuclear Information System (INIS)

Triossi, A.; Sphicas, P.; Bellato, M.; Montecassiano, F.; Ventura, S.; Ruiz, J.M. Cela; Bedoya, C. Fernandez; Tobar, A. Navarro; Fernandez, I. Redondo; Ferrero, D. Redondo; Sastre, J.; Ero, J.; Wulz, C.; Flouris, G.; Foudas, C.; Loukas, N.; Mallios, S.; Paradas, E.; Guiducci, L.; Masetti, G.

2017-01-01

The increase of luminosity expected by LHC during Phase1 will impose tighter constraints for rate reduction in order to maintain high efficiency in the CMS Level1 trigger system. The TwinMux system is the early layer of the muon barrel region that concentrates the information from different subdetectors: Drift Tubes, Resistive Plate Chambers and Outer Hadron Calorimeter. It arranges the slow optical trigger links from the detector chambers into faster links (10 Gbps) that are sent in multiple copies to the track finders. Results from collision runs, that confirm the satisfactory operation of the trigger system up to the output of the barrel track finder, will be shown.

Crif1 Deficiency Reduces Adipose OXPHOS Capacity and Triggers Inflammation and Insulin Resistance in Mice

Science.gov (United States)

Ryu, Min Jeong; Kim, Soung Jung; Kim, Yong Kyung; Choi, Min Jeong; Tadi, Surendar; Lee, Min Hee; Lee, Seong Eun; Chung, Hyo Kyun; Jung, Saet Byel; Kim, Hyun-Jin; Jo, Young Suk; Kim, Koon Soon; Lee, Sang-Hee; Kim, Jin Man; Kweon, Gi Ryang; Park, Ki Cheol; Lee, Jung Uee; Kong, Young Yun; Lee, Chul-Ho; Chung, Jongkyeong; Shong, Minho

2013-01-01

Impaired mitochondrial oxidative phosphorylation (OXPHOS) has been proposed as an etiological mechanism underlying insulin resistance. However, the initiating organ of OXPHOS dysfunction during the development of systemic insulin resistance has yet to be identified. To determine whether adipose OXPHOS deficiency plays an etiological role in systemic insulin resistance, the metabolic phenotype of mice with OXPHOS–deficient adipose tissue was examined. Crif1 is a protein required for the intramitochondrial production of mtDNA–encoded OXPHOS subunits; therefore, Crif1 haploinsufficient deficiency in mice results in a mild, but specific, failure of OXPHOS capacity in vivo. Although adipose-specific Crif1-haploinsufficient mice showed normal growth and development, they became insulin-resistant. Crif1-silenced adipocytes showed higher expression of chemokines, the expression of which is dependent upon stress kinases and antioxidant. Accordingly, examination of adipose tissue from Crif1-haploinsufficient mice revealed increased secretion of MCP1 and TNFα, as well as marked infiltration by macrophages. These findings indicate that the OXPHOS status of adipose tissue determines its metabolic and inflammatory responses, and may cause systemic inflammation and insulin resistance. PMID:23516375

Modeling and Validation of the Ecological Behavior of Wild-Type Listeria monocytogenes and Stress-Resistant Variants.

Science.gov (United States)

Metselaar, Karin I; Abee, Tjakko; Zwietering, Marcel H; den Besten, Heidy M W

2016-09-01

Listeria monocytogenes exhibits a heterogeneous response upon stress exposure which can be partially attributed to the presence of stable stress-resistant variants. This study aimed to evaluate the impact of the presence of stress-resistant variants of Listeria monocytogenes and their corresponding trade-offs on population composition under different environmental conditions. A set of stress robustness and growth parameters of the wild type (WT) and an rpsU deletion variant was obtained and used to model their growth behavior under combined mild stress conditions and to model their kinetics under single- and mixed-strain conditions in a simulated food chain. Growth predictions for the WT and the rpsU deletion variant matched the experimental data generally well, although some deviations from the predictions were observed. The data highlighted the influence of the environmental conditions on the ratio between the WT and variant. Prediction of performance in the simulated food chain proved to be challenging. The trend of faster growth and lower stress robustness for the WT than for the rpsU variant in the different steps of the chain was confirmed, but especially for the inactivation steps and the time needed to resume growth after an inactivation step, the experimental data deviated from the model predictions. This report provides insights into the conditions which can select for stress-resistant variants in industrial settings and discusses their potential persistence in food processing environments. Listeria monocytogenes exhibits a heterogeneous stress response which can partially be attributed to the presence of genetic variants. These stress-resistant variants survive better under severe conditions but have, on the other hand, a reduced growth rate. To date, the ecological behavior and potential impact of the presence of stress-resistant variants is not fully understood. In this study, we quantitatively assessed growth and inactivation behavior of wild-type L

Experimental Study of Laser - enhanced 5A03 Aluminum Alloy and Its Stress Corrosion Resistance

Science.gov (United States)

Wang, Guicheng; Chen, Jing; Pang, Tao

2018-02-01

Based on the study of improving the stress corrosion resistance of 5A03 aluminum alloy for ship, this paper mainly studied the tensile test, surface morphology and residual stress under laser shock, high temperature and stress corrosion. It is found that the residual compressive stress and the grain refinement on the surface of the material during the heat strengthening process increase the breaking strength of the sample in the stress corrosion environment. Appropriate high temperature maintenance helps to enhance the effect of deformation strengthening. In the 300°C environment insulation, due to recrystallization of the material, the performance decreased significantly. This study provides an experimental basis for effectively improving the stress corrosion resistance of 5A03 aluminum alloy.

Evaluation of stress corrosion cracking as a function of its resistance to eddy currents

International Nuclear Information System (INIS)

Yusa, Noritaka; Hashizume, Hidetoshi

2009-01-01

This study discusses the equivalent conductivity, the equivalent width, and the equivalent resistance of stress corrosion cracks from the viewpoint of eddy current testing. Four artificial stress corrosion cracks were prepared for this study, and their eddy current signals were gathered using two absolute pancake probes and two differential type plus point probes. Then their numerical models were evaluated using finite element simulations on the basis of the measured eddy current signals and their profiles revealed by destructive tests. The results of this study revealed that whereas the equivalent conductivity and the equivalent width depend on the exciting frequency utilized, the equivalent resistance of a crack has much less dependency, which agrees well with an earlier report. This study also revealed that the resistance of a crack depends on probe utilized. Larger probes tend to lead to smaller crack resistance. Pancake type probes tend to lead to larger crack resistance than plus point probes. Analyzing the results together with earlier reports indicates that cracks with a large equivalent conductivity tend to have large equivalent width, and supports the validity of assuming the minimum resistance of a stress corrosion crack whereas considering the conductivity and the width individually would not be viable.

Importance of SigB for Listeria monocytogenes static and continuous flow biofilm formation and disinfectant resistance

NARCIS (Netherlands)

Veen, van der S.; Abee, T.

2010-01-01

Listeria monocytogenes is a food-borne pathogen that is able to form biofilms in food processing facilities. Biofilms are generally more resistant to antimicrobial agents, making it difficult to eradicate them during cleanup procedures. So far, little is known about the function of stress resistance

Exogenous Salicylic Acid Enhances the Resistance of Wheat Seedlings to Hessian Fly (Diptera: Cecidomyiidae) Infestation Under Heat Stress.

Science.gov (United States)

Underwood, Joshua; Moch, John; Chen, Ming-Shun; Zhu, Lieceng

2014-10-01

Heat stress exerts significant impact on plant-parasite interactions. Phytohormones, such as salicylic acid (SA), play important roles in plant defense against parasite attacks. Here, we studied the impact of a combination of heat stress and exogenous SA on the resistance of wheat (Triticum aestivum L.) plants to the Hessian fly [Mayetiola destructor (Say)]. We found that the wheat cultivar 'Molly', which contains the resistance gene H13, lost resistance to Hessian fly under heat stress (40°C for 3 and 6 h), and that exogenous application of SA on Molly seedlings right before heat stress can partially prevent the loss of resistance of Molly plants under heat conditions. Our findings have significant implications for understanding the dynamics of plant-insect interactions in the context of heat stress. © 2014 Entomological Society of America.

Distinct Functional Domains of Ubc9 Dictate Cell Survival and Resistance to Genotoxic Stress

Science.gov (United States)

van Waardenburg, Robert C. A. M.; Duda, David M.; Lancaster, Cynthia S.; Schulman, Brenda A.; Bjornsti, Mary-Ann

2006-01-01

Covalent modification with SUMO alters protein function, intracellular localization, or protein-protein interactions. Target recognition is determined, in part, by the SUMO E2 enzyme, Ubc9, while Siz/Pias E3 ligases may facilitate select interactions by acting as substrate adaptors. A yeast conditional Ubc9P123L mutant was viable at 36°C yet exhibited enhanced sensitivity to DNA damage. To define functional domains in Ubc9 that dictate cellular responses to genotoxic stress versus those necessary for cell viability, a 1.75-Å structure of yeast Ubc9 that demonstrated considerable conservation of backbone architecture with human Ubc9 was solved. Nevertheless, differences in side chain geometry/charge guided the design of human/yeast chimeras, where swapping domains implicated in (i) binding residues within substrates that flank canonical SUMOylation sites, (ii) interactions with the RanBP2 E3 ligase, and (iii) binding of the heterodimeric E1 and SUMO had distinct effects on cell growth and resistance to DNA-damaging agents. Our findings establish a functional interaction between N-terminal and substrate-binding domains of Ubc9 and distinguish the activities of E3 ligases Siz1 and Siz2 in regulating cellular responses to genotoxic stress. PMID:16782883

Uncoupling of oxidative stress resistance and lifespan in long-lived isp-1 mitochondrial mutants in Caenorhabditis elegans.

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Dues, Dylan J; Schaar, Claire E; Johnson, Benjamin K; Bowman, Megan J; Winn, Mary E; Senchuk, Megan M; Van Raamsdonk, Jeremy M

2017-07-01

Mutations affecting components of the mitochondrial electron transport chain have been shown to increase lifespan in multiple species including the worm Caenorhabditis elegans. While it was originally proposed that decreased generation of reactive oxygen species (ROS) resulting from lower rates of electron transport could account for the observed increase in lifespan, recent evidence indicates that ROS levels are increased in at least some of these long-lived mitochondrial mutants. Here, we show that the long-lived mitochondrial mutant isp-1 worms have increased resistance to oxidative stress. Our results suggest that elevated ROS levels in isp-1 worms cause the activation of multiple stress-response pathways including the mitochondrial unfolded protein response, the SKN-1-mediated stress response, and the hypoxia response. In addition, these worms have increased expression of specific antioxidant enzymes, including a marked upregulation of the inducible superoxide dismutase genes sod-3 and sod-5. Examining the contribution of sod-3 and sod-5 to the oxidative stress resistance in isp-1 worms revealed that loss of either of these genes increased resistance to oxidative stress, but not other forms of stress. Deletion of sod-3 or sod-5 decreased the lifespan of isp-1 worms and further exacerbated their slow physiologic rates. Thus, while deletion of sod-3 and sod-5 genes has little impact on stress resistance, physiologic rates or lifespan in wild-type worms, these genes are required for the longevity of isp-1 worms. Overall, this work shows that the increased resistance to oxidative stress in isp-1 worms does not account for their longevity, and that resistance to oxidative stress can be experimentally dissociated from lifespan. Copyright © 2017 Elsevier Inc. All rights reserved.

HDAC Inhibitors Disrupt Programmed Resistance to Apoptosis During Drosophila Development

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Yunsik Kang

2017-06-01

Full Text Available We have previously shown that the ability to respond to apoptotic triggers is regulated during Drosophila development, effectively dividing the fly life cycle into stages that are either sensitive or resistant to apoptosis. Here, we show that the developmentally programmed resistance to apoptosis involves transcriptional repression of critical proapoptotic genes by histone deacetylases (HDACs. Administration of HDAC inhibitors (HDACi, like trichostatin A or suberoylanilide hydroxamic acid, increases expression of proapoptotic genes and is sufficient to sensitize otherwise resistant stages. Conversely, reducing levels of proapoptotic genes confers resistance to otherwise sensitive stages. Given that resistance to apoptosis is a hallmark of cancer cells, and that HDACi have been recently added to the repertoire of FDA-approved agents for cancer therapy, our results provide new insights for how HDACi help kill malignant cells and also raise concerns for their potential unintended effects on healthy cells.

Dermatófitos: interação patógeno-hospedeiro e resistência a antifúngicos Dermatophytes: host-pathogen interaction and antifungal resistance

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Nalu Teixera de Aguiar Peres

2010-10-01

Full Text Available As micoses cutâneas estão entre as infecções mais comuns em humanos e se tornaram um importante problema de saúde pública, principalmente por causarem infecções invasivas em pacientes imunodeprimidos. Durante a infecção, a interação dermatófito-hospedeiro desencadeia adaptações metabólicas específicas que permitem aos patógenos aderirem e penetrarem no tecido, remodelando seu metabolismo para captar nutrientes e superar os mecanismos de defesa do hospedeiro. Esse remodelamento metabólico e a inter-relação entre metabolismo, morfogênese e resposta ao estresse são importantes fatores que estão sendo intensamente avaliados em diversos patógenos. As células do hospedeiro também respondem aos estímulos do patógeno, ativando vias de sinalização intracelular que culminam no desencadeamento de uma resposta imune contra o agente infeccioso. O entendimento molecular dessas respostas metabólicas pode ajudar no estabelecimento de novas estratégias terapêuticas. Nesta revisão, são abordados diferentes aspectos da biologia dos dermatófitos, com ênfase na interação dermatófito-hospedeiro e nos mecanismos de resistência a antifúngicos.Cutaneous mycoses are among the most common infections in humans and have become an important public health issue because they cause invasive infections in immunocompromised patients. During the infectious process, dermatophyte-host interactions trigger specific metabolic adaptations that allow the pathogen to adhere to and penetrate the host tissue, scavenge nutrients, and overcome the host defense mechanisms. This metabolic shift and the interplay between metabolism, morphogenesis and stress response are important factors that have been extensively studied in several pathogens. Host cells also respond to the pathogen stimuli by activating intracellular signaling pathways that trigger the immune response against the infectious agent. The comprehension of the molecular aspects of these

Testing for the ‘predictability’ of dynamically triggered earthquakes in Geysers Geothermal Field

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Aiken, Chastity; Meng, Xiaofeng; Hardebeck, Jeanne L.

2018-01-01

The Geysers geothermal field is well known for being susceptible to dynamic triggering of earthquakes by large distant earthquakes, owing to the introduction of fluids for energy production. Yet, it is unknown if dynamic triggering of earthquakes is ‘predictable’ or whether dynamic triggering could lead to a potential hazard for energy production. In this paper, our goal is to investigate the characteristics of triggering and the physical conditions that promote triggering to determine whether or not triggering is in anyway foreseeable. We find that, at present, triggering in The Geysers is not easily ‘predictable’ in terms of when and where based on observable physical conditions. However, triggered earthquake magnitude positively correlates with peak imparted dynamic stress, and larger dynamic stresses tend to trigger sequences similar to mainshock–aftershock sequences. Thus, we may be able to ‘predict’ what size earthquakes to expect at The Geysers following a large distant earthquake.

OxyR of Haemophilus parasuis is a global transcriptional regulator important in oxidative stress resistance and growth.

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Wen, Yongping; Wen, Yiping; Wen, Xintian; Cao, Sanjie; Huang, Xiaobo; Wu, Rui; Zhao, Qin; Liu, Mafeng; Huang, Yong; Yan, Qigui; Han, Xinfeng; Ma, Xiaoping; Dai, Ke; Ding, Lingqiang; Liu, Sitong; Yang, Jian

2018-02-15

Haemophilus parasuis is an opportunistic pathogen and the causative agent of Glässer's disease in swine. This disease has high morbidity and mortality rates in swine populations, and is responsible for major economic losses worldwide. Survival of H. parasuis within the host requires mechanisms for coping with oxidative stress conditions. In many bacteria, OxyR is known to mediate protection against oxidative stress; however, little is known about the role of OxyR in H. parasuis. In the current study, an oxyR mutant strain was constructed in H. parasuis strain SC1401 and designated H. parasuis SC1401∆oxyR. The oxyR mutant strain had a slower growth rate and impaired biofilm formation compared to the wild type strain. Complementation restored the growth-associated phenotypes to wild type levels. Oxidative stress susceptibility testing, using a range of concentrations of H 2 O 2 , indicated that H. parasuis SC1401∆oxyR was more sensitive to oxidative stress than the wild type strain. RNA sequencing transcriptome analysis comparing H. parasuis SC1401 with H. parasuis SC1401∆oxyR identified 466 differentially expressed genes. These genes were involved in a wide range of biological processes, including: oxidative stress, transcriptional regulation, and DNA replication, recombination, and repair. These findings provide a foundation for future research to examine the role of OxyR as a global transcriptional regulator and to better define its role in oxidative stress resistance in H. parasuis. Copyright © 2017 Elsevier B.V. All rights reserved.

Transient heat stress compromises the resistance of wheat (Poales: Poaceae) seedlings to Hessian fly (Diptera: Cecidomyiidae) infestation.

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Currie, Yaleaka; Moch, John; Underwood, Joshua; Kharabsheh, Hamzah; Quesenberry, Amy; Miyagi, Risa; Thomas, Carolyn; Boney, Melanie; Woods, Samantha; Chen, Ming-Shun; Zhu, Lieceng

2014-02-01

Heat stress exerts a profound impact on the resistance of plants to parasites. In this research, we investigated the impact of an acute transient heat stress on the resistance of the wheat line 'Molly,' which contains the R gene H13, to an avirulent Hessian fly (Mayetiola destructor (Say)) population. We found that a significant portion of Molly seedlings stressed at 40 degrees C for 6 h during or after the initial Hessian fly larval attack became susceptible to otherwise avirulent insects, whereas unstressed control plants remained 100% resistant. Specifically, 77.8, 73.3, 83.3, and 46.7% of plants heat stressed at 0, 6,12, and 24 h, respectively, after the initial larval attack became susceptible. Biochemical analysis revealed that heat stress caused a transient decrease in 12-oxo-phytodienoic acid, but an increase in salicylic acid accumulation in Molly plants. The change in phytohormones after heat stress and Hessian fly infestation was not observed in 'Newton,' a near-isogenic but Hessian fly susceptible wheat line. Instead, heat stress caused a relatively prolonged reduction in palmitoleic acid. The role of phytohormones in heat-induced loss of wheat resistance was discussed.

Note: Triggering behavior of a vacuum arc plasma source

Energy Technology Data Exchange (ETDEWEB)

Lan, C. H., E-mail: lanchaohui@163.com; Long, J. D.; Zheng, L.; Dong, P.; Yang, Z.; Li, J.; Wang, T.; He, J. L. [Institute of Fluid Physics, China Academy of Engineering Physics, Mianyang 621900 (China)

2016-08-15

Axial symmetry of discharge is very important for application of vacuum arc plasma. It is discovered that the triggering method is a significant factor that would influence the symmetry of arc discharge at the final stable stage. Using high-speed multiframe photography, the transition processes from cathode-trigger discharge to cathode-anode discharge were observed. It is shown that the performances of the two triggering methods investigated are quite different. Arc discharge triggered by independent electric source can be stabilized at the center of anode grid, but it is difficult to achieve such good symmetry through resistance triggering. It is also found that the triggering process is highly correlated to the behavior of emitted electrons.

FLCN and AMPK Confer Resistance to Hyperosmotic Stress via Remodeling of Glycogen Stores.

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Elite Possik

2015-10-01

Full Text Available Mechanisms of adaptation to environmental changes in osmolarity are fundamental for cellular and organismal survival. Here we identify a novel osmotic stress resistance pathway in Caenorhabditis elegans (C. elegans, which is dependent on the metabolic master regulator 5'-AMP-activated protein kinase (AMPK and its negative regulator Folliculin (FLCN. FLCN-1 is the nematode ortholog of the tumor suppressor FLCN, responsible for the Birt-Hogg-Dubé (BHD tumor syndrome. We show that flcn-1 mutants exhibit increased resistance to hyperosmotic stress via constitutive AMPK-dependent accumulation of glycogen reserves. Upon hyperosmotic stress exposure, glycogen stores are rapidly degraded, leading to a significant accumulation of the organic osmolyte glycerol through transcriptional upregulation of glycerol-3-phosphate dehydrogenase enzymes (gpdh-1 and gpdh-2. Importantly, the hyperosmotic stress resistance in flcn-1 mutant and wild-type animals is strongly suppressed by loss of AMPK, glycogen synthase, glycogen phosphorylase, or simultaneous loss of gpdh-1 and gpdh-2 enzymes. Our studies show for the first time that animals normally exhibit AMPK-dependent glycogen stores, which can be utilized for rapid adaptation to either energy stress or hyperosmotic stress. Importantly, we show that glycogen accumulates in kidneys from mice lacking FLCN and in renal tumors from a BHD patient. Our findings suggest a dual role for glycogen, acting as a reservoir for energy supply and osmolyte production, and both processes might be supporting tumorigenesis.

Where do we stand after twenty years of dynamic triggering studies? (Invited)

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Prejean, S. G.; Hill, D. P.

2013-12-01

In the past two decades, remote dynamic triggering of earthquakes by other earthquakes has been explored in a variety of physical environments with a wide array of observation and modeling techniques. These studies have significantly refined our understanding of the state of the crust and the physical conditions controlling earthquake nucleation. Despite an ever growing database of dynamic triggering observations, significant uncertainties remain and vigorous debate in almost all aspects of the science continues. For example, although dynamic earthquake triggering can occur with peak dynamic stresses as small as 1 kPa, triggering thresholds and their dependence on local stress state, hydrological environment, and frictional properties of faults are not well understood. Some studies find a simple threshold based on the peak amplitude of shaking while others find dependencies on frequency, recharge time, and other parameters. Considerable debate remains over the range of physical processes responsible for dynamic triggering, and the wide variation in dynamic triggering responses and time scales suggests triggering by multiple physical processes. Although Coulomb shear failure with various friction laws can often explain dynamic triggering, particularly instantaneous triggering, delayed dynamic triggering may be dependent on fluid transport and other slowly evolving aseismic processes. Although our understanding of the global distribution of dynamic triggering has improved, it is far from complete due to spatially uneven monitoring. A major challenge involves establishing statistical significance of potentially triggered earthquakes, particularly if they are isolated events or time-delayed with respect to triggering stresses. Here we highlight these challenges and opportunities with existing data. We focus on environmental dependence of dynamic triggering by large remote earthquakes particularly in volcanic and geothermal systems, as these systems often have high

Analysis of Trigger Factors in Episodic Migraineurs Using a Smartphone Headache Diary Applications.

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Jeong-Wook Park

Full Text Available Various stimuli can trigger migraines in susceptible individuals. We examined migraine trigger factors by using a smartphone headache diary application.Episodic migraineurs who agreed to participate in our study downloaded smartphone headache diary application, which was designed to capture the details regarding headache trigger factors and characteristics for 3 months. The participants were asked to access the smartphone headache diary application daily and to confirm the presence of a headache and input the types of trigger factors.Sixty-two participants kept diary entries until the end of the study. The diary data for 4,579 days were analyzed. In this data set, 1,099 headache days (336 migraines, 763 non-migraine headaches were recorded; of these, 772 headache events had with trigger factors, and 327 events did not have trigger factors. The common trigger factors that were present on headache days included stress, fatigue, sleep deprivation, hormonal changes, and weather changes. The likelihood of a headache trigger was 57.7% for stress, 55.1% for sleep deprivation, 48.5% for fatigue, and 46.5% for any trigger. The headaches with trigger factors were associated with greater pain intensity (p<0.001, headache-related disability (p<0.001, abortive medication use (p = 0.02, and the proportion of migraine (p < 0.001, relative to those without trigger factors. Traveling (odd ratios [OR]: 6.4, hormonal changes (OR: 3.5, noise (OR: 2.8, alcohol (OR: 2.5, overeating (OR: 2.4, and stress (OR:1.8 were significantly associated with migraines compared to non-migraine headaches. The headaches that were associated with hormonal changes or noise were more often migraines, regardless of the preventive medication. The headaches due to stress, overeating, alcohol, and traveling were more often migraines without preventive medication, but it was not evident with preventive medication.Smartphone headache diary application is an effective tool to assess migraine

Systems modeling of anti-apoptotic pathways in prostate cancer: psychological stress triggers a synergism pattern switch in drug combination therapy.

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Xiaoqiang Sun

Full Text Available Prostate cancer patients often have increased levels of psychological stress or anxiety, but the molecular mechanisms underlying the interaction between psychological stress and prostate cancer as well as therapy resistance have been rarely studied and remain poorly understood. Recent reports show that stress inhibits apoptosis in prostate cancer cells via epinephrine/beta2 adrenergic receptor/PKA/BAD pathway. In this study, we used experimental data on the signaling pathways that control BAD phosphorylation to build a dynamic network model of apoptosis regulation in prostate cancer cells. We then compared the predictive power of two different models with or without the role of Mcl-1, which justified the role of Mcl-1 stabilization in anti-apoptotic effects of emotional stress. Based on the selected model, we examined and quantitatively evaluated the induction of apoptosis by drug combination therapies. We predicted that the combination of PI3K inhibitor LY294002 and inhibition of BAD phosphorylation at S112 would produce the best synergistic effect among 8 interventions examined. Experimental validation confirmed the effectiveness of our predictive model. Moreover, we found that epinephrine signaling changes the synergism pattern and decreases efficacy of combination therapy. The molecular mechanisms responsible for therapeutic resistance and the switch in synergism were explored by analyzing a network model of signaling pathways affected by psychological stress. These results provide insights into the mechanisms of psychological stress signaling in therapy-resistant cancer, and indicate the potential benefit of reducing psychological stress in designing more effective therapies for prostate cancer patients.

Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (II

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Rongshi Li

2013-08-01

Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA continues to be a major problem, causing severe and intractable infections worldwide. MRSA is resistant to all beta-lactam antibiotics, and alternative treatments are limited. A very limited number of new antibiotics have been discovered over the last half-century, novel agents for the treatment of MRSA infections are urgently needed. Marinopyrrole A was reported to show antibiotic activity against MRSA in 2008. After we reported the first total synthesis of (±-marinopyrrole A, we designed and synthesized a series of marinopyrrole derivatives. Our structure activity relationship (SAR studies of these novel derivatives against a panel of Gram-positive pathogens in antibacterial assays have revealed that a para-trifluoromethyl analog (33 of marinopyrrole A is ≥63-, 8-, and 4-fold more potent than vancomycin against methicillin-resistant Staphylococcus epidermidis (MRSE, methicillin-susceptible Staphylococcus aureus (MSSA and MRSA, respectively. The results provide valuable information in the search for new-generation antibiotics.

Skin Resistivity Value of Upper Trapezius Latent Trigger Points

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Elżbieta Skorupska

2015-01-01

Full Text Available Introduction. The skin resistivity (SkR measurement is commonly recommended for acupoints measurement, but for trigger points (TrPs only one study is available. The purpose of the study was to evaluate SkR for latent TrPs compared to non-TrPs and the surrounding tissue. Material and Methods. Forty-two healthy volunteers with unilateral latent upper trapezius TrPs (12 men, 30 women aged 21–23 (mean age: 22.1 ± 0.6 y participated in the study. Keithley electrometer 610B was used for measuring SkR (Ag/AgCl self-adhesive, disposable ground electrode: 30 mm diameter. SkR was measured for latent TrPs and compared to opposite non-TrPs sites and the surrounding tissue. Results. The SkR decrease of TrPs-positive sites as compared to TrPs-negative sites and the surrounding tissue was confirmed. However, no statistically significant difference in the SkR value occurred when all data were analyzed. The same was confirmed after gender division and for TrPs-positive subjects examined for referred pain and twitch response presence. Conclusion. SkR reactive changes at latent TrPs are possible but the results were not consistent with the previous study. Thus, caution in applying SkR to latent TrPs isolation is recommended and its clinical use should not be encouraged yet. Further studies, especially on active TrPs, are yet required.

Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents

International Nuclear Information System (INIS)

Wan, X. Steven; Ware, Jeffrey H.; Zhou, Zhaozong; Donahue, Jeremiah J.; Guan, Jun; Kennedy, Ann R.

2006-01-01

Purpose: To evaluate the protective effects of antioxidant agents against space radiation-induced oxidative stress in cultured human epithelial cells. Methods and Materials: The effects of selected concentrations of N-acetylcysteine, ascorbic acid, sodium ascorbate, co-enzyme Q10, α-lipoic acid, L-selenomethionine, and vitamin E succinate on radiation-induced oxidative stress were evaluated in MCF10 human breast epithelial cells exposed to radiation with X-rays, γ-rays, protons, or high mass, high atomic number, and high energy particles using a dichlorofluorescein assay. Results: The results demonstrated that these antioxidants are effective in protecting against radiation-induced oxidative stress and complete or nearly complete protection was achieved by treating the cells with a combination of these agents before and during the radiation exposure. Conclusion: The combination of antioxidants evaluated in this study is likely be a promising countermeasure for protection against space radiation-induced adverse biologic effects

Staphylococcus aureus Adapts to Oxidative Stress by Producing H2O2-Resistant Small-Colony Variants via the SOS Response

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Painter, Kimberley L.; Strange, Elizabeth; Bamford, Kathleen B.; Armstrong-James, Darius

2015-01-01

The development of chronic and recurrent Staphylococcus aureus infections is associated with the emergence of slow-growing mutants known as small-colony variants (SCVs), which are highly tolerant of antibiotics and can survive inside host cells. However, the host and bacterial factors which underpin SCV emergence during infection are poorly understood. Here, we demonstrate that exposure of S. aureus to sublethal concentrations of H2O2 leads to a specific, dose-dependent increase in the population frequency of gentamicin-resistant SCVs. Time course analyses revealed that H2O2 exposure caused bacteriostasis in wild-type cells during which time SCVs appeared spontaneously within the S. aureus population. This occurred via a mutagenic DNA repair pathway that included DNA double-strand break repair proteins RexAB, recombinase A, and polymerase V. In addition to triggering SCV emergence by increasing the mutation rate, H2O2 also selected for the SCV phenotype, leading to increased phenotypic stability and further enhancing the size of the SCV subpopulation by reducing the rate of SCV reversion to the wild type. Subsequent analyses revealed that SCVs were significantly more resistant to the toxic effects of H2O2 than wild-type bacteria. With the exception of heme auxotrophs, gentamicin-resistant SCVs displayed greater catalase activity than wild-type bacteria, which contributed to their resistance to H2O2. Taken together, these data reveal a mechanism by which S. aureus adapts to oxidative stress via the production of a subpopulation of H2O2-resistant SCVs with enhanced catalase production. PMID:25690100

Autonomous stimulus triggered self-healing in smart structural composites

International Nuclear Information System (INIS)

Norris, C J; White, J A P; McCombe, G; Chatterjee, P; Bond, I P; Trask, R S

2012-01-01

Inspired by the ability of biological systems to sense and autonomously heal damage, this research has successfully demonstrated the first autonomous, stimulus triggered, self-healing system in a structural composite material. Both the sensing and healing mechanisms are reliant on microvascular channels incorporated within a laminated composite material. For the triggering mechanism, a single air filled vessel was pressurized, sealed and monitored. Upon drop weight impact (10 J), delamination and microcrack connectivity between the pressurized vessel and those open to ambient led to a pressure loss which, with the use of a suitable sensor, triggered a pump to deliver a healing agent to the damage zone. Using this autonomous healing approach, near full recovery of post-impact compression strength was achieved (94% on average). A simplified alternative system with healing agent continuously flowing through the vessels, akin to blood flow, was found to offer 100% recovery of the material’s virgin strength. Optical microscopy and ultrasonic C-scanning provided further evidence of large-scale infusion of matrix damage with the healing agent. The successful implementation of this bioinspired technology could substantially enhance the integrity and reliability of aerospace structures, whilst offering benefits through improved performance/weight ratios and extended lifetimes. (paper)

Association of Oxidative Stress and Obesity with Insulin Resistance in Type 2 Diabetes Mellitus.

Science.gov (United States)

Das, P; Biswas, S; Mukherjee, S; Bandyopadhyay, S K

2016-01-01

Oxidative stress occurs due to delicate imbalance between pro-oxidant and anti oxidant forces in our system. It has been found to be associated with many morbidities but its association with obesity and insulin resistance is still controversial. Here in our study we examined 167 patients of recent onset type 2 diabetes mellitus and 60 age sex matched non-diabetic control. Body Mass Index (BMI), abdominal circumference, fasting blood glucose, serum insulin and plasma Malondealdehyde (MDA, marker for oxidative stress) were measured in them. On the basis of BMI, subjects were divided into obese (BMI≥25) and non obese (BMIobese and non-obese sub groups. Insulin resistance score showed positive correlation with BMI, abdominal circumference, and plasma MDA, strength of association being highest with abdominal circumference. Plasma MDA was found to have positive correlation with physical parameters. Study concludes that, obesity mainly central type may predispose to insulin resistance and oxidative stress may be a crucial factor in its pathogenesis. Thus, oxidative stress may be the connecting link between obesity and type 2 diabetes mellitus, two on going global epidemics.

The General Adaptation Syndrome: Potential misapplications to resistance exercise.

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Buckner, Samuel L; Mouser, J Grant; Dankel, Scott J; Jessee, Matthew B; Mattocks, Kevin T; Loenneke, Jeremy P

2017-11-01

Within the resistance training literature, one of the most commonly cited tenets with respect to exercise programming is the "General Adaptation Syndrome" (GAS). The GAS is cited as a central theory behind the periodization of resistance exercise. However, after examining the original stress research by Hans Selye, the applications of GAS to resistance exercise may not be appropriate. To examine the original work of Hans Selye, as well as the original papers through which the GAS was established as a central theory for periodized resistance exercise. We conducted a review of Selye's work on the GAS, as well as the foundational papers through which this concept was applied to resistance exercise. The work of Hans Selye focused on the universal physiological stress responses noted upon exposure to toxic levels of a variety of pharmacological agents and stimuli. The extrapolations that have been made to resistance exercise appear loosely based on this concept and may not be an appropriate basis for application of the GAS to resistance exercise. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Survival of Listeria monocytogenes with different antibiotic resistance patterns to food-associated stresses.

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Komora, Norton; Bruschi, Carolina; Magalhães, Rui; Ferreira, Vânia; Teixeira, Paula

2017-03-20

The ongoing rise of antibiotic resistant microbial pathogens has become one of the major public health threats worldwide. Despite all the effort and actions taken so far, a proliferation of antibiotic resistant (AR) and multi-antibiotic resistant (MAR) strains is still observed, including in foodborne pathogens. This trend has been also noted recently for isolates of Listeria monocytogenes, a species that, although remaining largely sensitive to clinically relevant antimicrobials, has been reported to develop increased tolerance to antibiotics, particularly in isolates recovered from the food-chain. In this study we compared the ability of MAR (n=8), AR (n=18) and antibiotic susceptible (AS, n=11) L. monocytogenes strains from food and clinical origin to survive to different environmental stress conditions, including temperature (58°C), acidic stress (1% v/v lactic acid, pH3.5), and osmotic stress (37% w/v NaCl). The presence of antibiotic active efflux among MAR and AR strains, and its role on L. monocytogenes tolerance to different antimicrobial compounds was also investigated, namely; hydrogen peroxide; organic acids (acetic, citric and lactic); nisin; benzalkonium chloride (BC); and, sodium nitrite. While no significant differences were observed in the survival of the 37 strains exposed to high temperature (58°C), overall the mean logarithmic reduction of clinical strains was statistically lower after acid and salt exposure than that observed for strains of food origin; but both food and clinical strains resistant to two or three antibiotics were significantly less susceptible to acid (lactic acid 1% v/v) and osmotic stresses (37% w/v NaCl) when compared to AS strains. Using the EtBr-agar Cartwheel method, it was possible to detect efflux pumps in three of the 26 MAR and AR isolates, including one control strain; the active efflux in theses isolates was proven to be associated with fluoroquinolone resistance, and possible extrusion of BC and hydrogen peroxide

Resistance and resilience: the final frontier in traumatic stress management.

Science.gov (United States)

Everly, George S; Welzant, Victor; Jacobson, Jodi M

2008-01-01

This paper asserts that the constructs of resistance and resilience represent a domain rich in potential for a wide variety of applications in the field of traumatic stress. Resilience holds great potential for those working in applied settings such as public health planning and preparedness, Employee Assistance Programs (EAPs) and business continuity, as well as transportation, law enforcement, fire suppression, emergency medical services, pre-deployment training for military and other high risk professional groups. Additionally, its application to "the war on terrorism" cannot be denied. Finally, the construct of resilience may have direct applicability to businesses and organizations wherein there is perceived value in preparing a workforce to effectively function under adverse or high stress conditions. The putative value of resistance and resiliency in such applied settings resides in their ability to protect against stress-related behavioral morbidity, as well as counterproductive behavioral reactions. Given its importance, the question arises as to whether resilience is an innate trait or an acquired skill. This paper will report on preliminary data suggesting resiliency may be an attribute that can be acquired through participation in a relatively brief training program.

Antibody-Based Agents in the Management of Antibiotic-Resistant Staphylococcus aureus Diseases

Science.gov (United States)

Speziale, Pietro; Rindi, Simonetta

2018-01-01

Staphylococcus aureus is a human pathogen that can cause a wide spectrum of diseases, including sepsis, pneumonia, arthritis, and endocarditis. Ineffective treatment of a number of staphylococcal infections with antibiotics is due to the development and spread of antibiotic-resistant strains following decades of antibiotic usage. This has generated renewed interest within the scientific community in alternative therapeutic agents, such as anti-S. aureus antibodies. Although the role of antibodies in the management of S. aureus diseases is controversial, the success of this pathogen in neutralizing humoral immunity clearly indicates that antibodies offer the host extensive protection. In this review, we report an update on efforts to develop antibody-based agents, particularly monoclonal antibodies, and their therapeutic potential in the passive immunization approach to the treatment and prevention of S. aureus infections. PMID:29533985

Geographic variation for climatic stress resistance traits in the sprintail Orchesella cincta

DEFF Research Database (Denmark)

Bahrndorff, Simon; Holmstrup, Martin; Petersen, H.

2006-01-01

Multiple traits of stress resistance were investigated in the epedaphic springtail Orchesella cincta. Second generation adults from five laboratory populations were compared with respect to resistance to extreme temperatures and desiccation, and traits relevant to climatic adaptation. Populations...... were collected along a 2000-km latitudinal gradient ranging from Denmark to southern Italy and reared under the same standard laboratory conditions. Traits investigated were resistance to high and low temperature, desiccation resistance, body size and water loss rate (WLR). Results showed genetically...... based differences in resistance to high and low temperature, desiccation, WLR, water pool and body size between populations. Individuals from the most northern population had the highest desiccation-and cold shock resistance, and the lowest heat shock resistance. Females were significantly more...

Insulin resistance in H pylori infection and its association with oxidative stress.

Science.gov (United States)

Aslan, Mehmet; Horoz, Mehmet; Nazligul, Yasar; Bolukbas, Cengiz; Bolukbas, F Fusun; Selek, Sahbettin; Celik, Hakim; Erel, Ozcan

2006-11-14

To determine the insulin resistance (IR) and oxidative status in H pylori infection and to find out if there is any relationship between these parameters and insulin resistance. Fifty-five H pylori positive and 48 H pylori negative patients were enrolled. The homeostasis model assessment (HOMA) was used to assess insulin resistance. Serum total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined in all subjects. The total antioxidant capacity was significantly lower in H pylori positive group than in H pylori negative group (1.36 +/- 0.33 and 1.70 +/- 0.50, respectively; P total oxidant status and oxidative stress index were significantly higher in H pylori positive group than in H pylori negative group (6.79 +/- 3.40 and 5.08 +/- 0.95, and 5.42 +/- 3.40 and 3.10 +/- 0.92, respectively; P total antioxidant capacity (r = -0.251, P total oxidant status (r = 0.365, P antioxidant vitamins to H pylori eradication therapy on insulin resistance during H pylori infection.

Temperature and Oxidative Stress as Triggers for Virulence Gene Expression in Pathogenic Leptospira spp.

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Tricia Fraser

2017-05-01

Full Text Available Leptospirosis is a zooanthroponosis aetiologically caused by pathogenic bacteria belonging to the genus, Leptospira. Environmental signals such as increases in temperatures or oxidative stress can trigger response regulatory modes of virulence genes during infection. This study sought to determine the effect of temperature and oxidative stress on virulence associated genes in highly passaged Leptospira borgpeterseneii Jules and L. interrogans Portlandvere. Bacteria were grown in EMJH at 30°C, 37°C, or at 30°C before being transferred to 37°C. A total of 14 virulence-associated genes (fliY, invA, lenA, ligB, lipL32, lipL36, lipL41, lipL45, loa22, lsa21, mce, ompL1, sph2, and tlyC were assessed using endpoint PCR. Transcriptional analyses of lenA, lipL32, lipL41, loa22, sph2 were assessed by quantitative real-time RT-PCR at the temperature conditions. To assess oxidative stress, bacteria were exposed to H2O2 for 30 and 60 min with or without the temperature stress. All genes except ligB (for Portlandvere and ligB and mce (for Jules were detectable in the strains. Quantitatively, temperature stress resulted in significant changes in gene expression within species or between species. Temperature changes were more influential in gene expression for Jules, particularly at 30°C and upshift conditions; at 37°C, expression levels were higher for Portlandvere. However, compared to Jules, where temperature was influential in two of five genes, temperature was an essential element in four of five genes in Portlandvere exposed to oxidative stress. At both low and high oxidative stress levels, the interplay between genetic predisposition (larger genome size and temperature was biased towards Portlandvere particularly at 30°C and upshift conditions. While it is clear that expression of many virulence genes in highly passaged strains of Leptospira are attenuated or lost, genetic predisposition, changes in growth temperature and/or oxidative intensity and

Impact of Oxidative Stress on Hemorheological Parameters in Patients with Acute Poisonings by Psychopharmacological Agents

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M. V. Belova

2010-01-01

Full Text Available Objective: to evaluate the impact of oxidative stress intensity on hemorheological parameters in acute poisonings by psychopharmacological agents. Subjects and methods. The blood values of lipid peroxidation (LPO and the antioxidant system (AOS, and hemorheological parameters were determined in 196 patients with acute poisoning by psychopharmacological agents. Results. Mild poisoning was accompanied by a moderate rise in peroxidation processes, by compensated antioxidant activity, and by a decrease in hemorheological parameters. In moderate poisoning, and severe one in particular, there was an increase in the LPO/AOS imbalance attended by increases in the viscosity characteristics of blood and plasma and in the aggregation activity of platelets and red blood cells. Conclusion. As the intensity of oxidative stress increases, there are more severe impairments in blood viscosity and aggregation properties, the leading mechanism of which is damage to blood cells due to higher stiffness of their membranes and to plasma release of large-disperse molecules under the action of an excess of LPO products. Key words: oxidative stress, acute poisonings, hemorheology.

Non-linear impact of glutathione depletion on C. elegans life span and stress resistance

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Nadine Urban

2017-04-01

Full Text Available The redox environment in cells and organisms is set by low-molecular mass and protein-bound thiols, with glutathione (GSH representing a major intracellular redox buffer. Subtle thiol oxidation elicits signal transduction processes and adaptive responses to cope with stressors, whereas highly oxidizing conditions may provoke cell death. We here tested how thiol depletion affects life span, stress resistance and stress signaling in the model organism Caenorhabditis elegans. Diethyl maleate (DEM, an α,β-unsaturated carbonyl compound that conjugates to GSH and other thiols, decreased C. elegans life span at a concentration of 1 mM. In contrast, low and moderate doses of DEM (10–100 µM increased mean and maximum life span and improved resistance against oxidative stress. DEM-induced life span extension was not detectable in worms deficient in either the FoxO orthologue, DAF-16, or the Nrf2 orthologue, SKN-1, pointing to a collaborative role of the two transcription factors in life span extension induced by thiol depletion. Cytoprotective target genes of DAF-16 and SKN-1 were upregulated after at least 3 days of exposure to 100 µM DEM, but not 1 mM DEM, whereas only 1 mM DEM caused upregulation of egl-1, a gene controlled by a p53-orthologue, CEP-1. In order to test whether depletion of GSH may elicit effects similar to DEM, we suppressed GSH biosynthesis in worms by attenuating γ-glutamylcysteine synthetase (gcs-1 expression through RNAi. The decline in GSH levels elicited by gcs-1 knockdown starting at young adult stage did not impair viability, but increased both stress resistance and life expectancy of the worms. In contrast, gcs-1 knockdown commencing right after hatching impaired nematode stress resistance and rendered young adult worms prone to vulval ruptures during egg-laying. Thus, modest decrease in GSH levels in young adult worms may promote stress resistance and life span, whereas depletion of GSH is detrimental to freshly

Non-linear impact of glutathione depletion on C. elegans life span and stress resistance.

Science.gov (United States)

Urban, Nadine; Tsitsipatis, Dimitrios; Hausig, Franziska; Kreuzer, Katrin; Erler, Katrin; Stein, Vanessa; Ristow, Michael; Steinbrenner, Holger; Klotz, Lars-Oliver

2017-04-01

The redox environment in cells and organisms is set by low-molecular mass and protein-bound thiols, with glutathione (GSH) representing a major intracellular redox buffer. Subtle thiol oxidation elicits signal transduction processes and adaptive responses to cope with stressors, whereas highly oxidizing conditions may provoke cell death. We here tested how thiol depletion affects life span, stress resistance and stress signaling in the model organism Caenorhabditis elegans. Diethyl maleate (DEM), an α,β-unsaturated carbonyl compound that conjugates to GSH and other thiols, decreased C. elegans life span at a concentration of 1mM. In contrast, low and moderate doses of DEM (10-100µM) increased mean and maximum life span and improved resistance against oxidative stress. DEM-induced life span extension was not detectable in worms deficient in either the FoxO orthologue, DAF-16, or the Nrf2 orthologue, SKN-1, pointing to a collaborative role of the two transcription factors in life span extension induced by thiol depletion. Cytoprotective target genes of DAF-16 and SKN-1 were upregulated after at least 3 days of exposure to 100µM DEM, but not 1mM DEM, whereas only 1mM DEM caused upregulation of egl-1, a gene controlled by a p53-orthologue, CEP-1. In order to test whether depletion of GSH may elicit effects similar to DEM, we suppressed GSH biosynthesis in worms by attenuating γ-glutamylcysteine synthetase (gcs-1) expression through RNAi. The decline in GSH levels elicited by gcs-1 knockdown starting at young adult stage did not impair viability, but increased both stress resistance and life expectancy of the worms. In contrast, gcs-1 knockdown commencing right after hatching impaired nematode stress resistance and rendered young adult worms prone to vulval ruptures during egg-laying. Thus, modest decrease in GSH levels in young adult worms may promote stress resistance and life span, whereas depletion of GSH is detrimental to freshly hatched and developing worms

Aerobic exercise increases resistance to oxidative stress in sedentary older middle-aged adults. A pilot study.

Science.gov (United States)

Done, Aaron J; Traustadóttir, Tinna

2016-12-01

Older individuals who exercise regularly exhibit greater resistance to oxidative stress than their sedentary peers, suggesting that exercise can modify age-associated loss of resistance to oxidative stress. However, we recently demonstrated that a single bout of exercise confers protection against a subsequent oxidative challenge in young, but not older adults. We therefore hypothesized that repeated bouts of exercise would be needed to increase resistance to an oxidative challenge in sedentary older middle-aged adults. Sedentary older middle-aged men and women (50-63 years, n = 11) participated in an 8-week exercise intervention. Maximal oxygen consumption was measured before and after the intervention. The exercise intervention consisted of three sessions per week, for 45 min at an intensity corresponding to 70-85 % maximal heart rate (HR max ). Resistance to oxidative stress was measured by F 2 -isoprostane response to a forearm ischemia/reperfusion (I/R) trial. Each participant underwent the I/R trial before and after the exercise intervention. The intervention elicited a significant increase in maximal oxygen consumption (VO 2max ) (P exercise intervention (time-by-trial interaction, P = 0.043). Individual improvements in aerobic fitness were associated with greater improvements in the F 2 -isoprostane response (r = -0.761, P = 0.011), further supporting the role of aerobic fitness in resistance to oxidative stress. These data demonstrate that regular exercise with improved fitness leads to increased resistance to oxidative stress in older middle-aged adults and that this measure is modifiable in previously sedentary individuals.

Comparative effectiveness of fourth-line anti-hypertensive agents in resistant hypertension: A systematic review and meta-analysis.

Science.gov (United States)

Sinnott, Sarah-Jo; Tomlinson, Laurie A; Root, Adrian A; Mathur, Rohini; Mansfield, Kathryn E; Smeeth, Liam; Douglas, Ian J

2017-02-01

Aim We assessed the effectiveness of fourth-line mineralocorticoid receptor antagonists in comparison with other fourth-line anti-hypertensive agents in resistant hypertension. Methods and results We systematically searched Medline, EMBASE and the Cochrane library from database inception until January 2016. We included randomised and non-randomised studies that compared mineralocorticoid receptor antagonists with other fourth-line anti-hypertensive agents in patients with resistant hypertension. The outcome was change in systolic blood pressure, measured in the office, at home or by ambulatory blood pressure monitoring. Secondary outcomes were changes in serum potassium and occurrence of hyperkalaemia. We used random effects models and assessed statistical heterogeneity using the I 2 test and corresponding 95% confidence intervals. From 2,506 records, 5 studies met our inclusion criteria with 755 included patients. Two studies were randomised and three were non-randomised. Comparative fourth-line agents included bisoprolol, doxazosin, furosemide and additional blockade of the renin angiotensin-aldosterone system. Using data from randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 7.4 mmHg (95%CI 3.2 - 11.6) more than the active comparator. When limited to non-randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 11.9 mmHg (95% CI 9.3 - 14.4) more than the active comparator. Conclusion On the basis of this meta-analysis, mineralocorticoid receptor antagonists reduce blood pressure more effectively than other fourth-line agents in resistant hypertension. Effectiveness stratified by ethnicity and comorbidities, in addition to information on clinical outcomes such as myocardial infarction and stroke, now needs to be determined.

Observing earthquakes triggered in the near field by dynamic deformations

Science.gov (United States)

Gomberg, J.; Bodin, P.; Reasenberg, P.A.

2003-01-01

We examine the hypothesis that dynamic deformations associated with seismic waves trigger earthquakes in many tectonic environments. Our analysis focuses on seismicity at close range (within the aftershock zone), complementing published studies of long-range triggering. Our results suggest that dynamic triggering is not confined to remote distances or to geothermal and volcanic regions. Long unilaterally propagating ruptures may focus radiated dynamic deformations in the propagation direction. Therefore, we expect seismicity triggered dynamically by a directive rupture to occur asymmetrically, with a majority of triggered earthquakes in the direction of rupture propagation. Bilaterally propagating ruptures also may be directive, and we propose simple criteria for assessing their directivity. We compare the inferred rupture direction and observed seismicity rate change following 15 earthquakes (M 5.7 to M 8.1) that occured in California and Idaho in the United States, the Gulf of Aqaba, Syria, Guatemala, China, New Guinea, Turkey, Japan, Mexico, and Antarctica. Nine of these mainshocks had clearly directive, unilateral ruptures. Of these nine, seven apparently induced an asymmetric increase in seismicity rate that correlates with the rupture direction. The two exceptions include an earthquake preceded by a comparable-magnitude event on a conjugate fault and another for which data limitations prohibited conclusive results. Similar (but weaker) correlations were found for the bilaterally rupturing earthquakes we studied. Although the static stress change also may trigger seismicity, it and the seismicity it triggers are expected to be similarly asymmetric only if the final slip is skewed toward the rupture terminus. For several of the directive earthquakes, we suggest that the seismicity rate change correlates better with the dynamic stress field than the static stress change.

RPCs as trigger detector for the ATLAS experiment performances, simulation and application to the level-1 di-muon trigger

CERN Document Server

Di Simone, A; Di Ciaccio, A

2005-01-01

In the muon spectrometer different detectors are used to provide trigger functionality and precision momentum measurements. In the pseudorapidity range |eta|<1 the first level muon trigger is based on Resistive Plate Chambers, gas ionization detectors which are characterized by a fast response and an excellent time resolution (<1.5ns). The working principles of the Resistive Plate Chambers will be illustrated in chapter 3. Given the long time of operation expected for the ATLAS experiment (~10 years), ageing phenomena have been carefully studied, in order to ensure stable long-term operation of all the subdetectors. Concerning Resistive Plate Chambers, a very extensive ageing test has been performed at CERN's Gamma Irradiation Facility on three production chambers. The results of this test are presented in chapter 4. One of the most commonly used gases in RPCs operation is C2H2F4, which during the gas discharge can produce fluorine ions. Being F one of the most aggressive elements in nature, the presenc...

Antarctic icequakes triggered by the 2010 Maule earthquake in Chile

Science.gov (United States)

Peng, Zhigang; Walter, Jacob I.; Aster, Richard C.; Nyblade, Andrew; Wiens, Douglas A.; Anandakrishnan, Sridhar

2014-09-01

Seismic waves from distant, large earthquakes can almost instantaneously trigger shallow micro-earthquakes and deep tectonic tremor as they pass through Earth's crust. Such remotely triggered seismic activity mostly occurs in tectonically active regions. Triggered seismicity is generally considered to reflect shear failure on critically stressed fault planes and is thought to be driven by dynamic stress perturbations from both Love and Rayleigh types of surface seismic wave. Here we analyse seismic data from Antarctica in the six hours leading up to and following the 2010 Mw 8.8 Maule earthquake in Chile. We identify many high-frequency seismic signals during the passage of the Rayleigh waves generated by the Maule earthquake, and interpret them as small icequakes triggered by the Rayleigh waves. The source locations of these triggered icequakes are difficult to determine owing to sparse seismic network coverage, but the triggered events generate surface waves, so are probably formed by near-surface sources. Our observations are consistent with tensile fracturing of near-surface ice or other brittle fracture events caused by changes in volumetric strain as the high-amplitude Rayleigh waves passed through. We conclude that cryospheric systems can be sensitive to large distant earthquakes.

Robust Self-Triggered Coordination With Ternary Controllers

NARCIS (Netherlands)

De Persis, Claudio; Frasca, Paolo; Nair, G.N.

2013-01-01

This paper regards the coordination of networked systems, studied in the framework of hybrid dynamical systems. We design a coordination scheme which combines the use of ternary controllers with a self-triggered communication policy. The communication policy requires the agents to measure, at each

Robust self-triggered coordination with ternary controllers

NARCIS (Netherlands)

De Persis, Claudio; Frasca, Paolo

2013-01-01

This paper regards the coordination of networked systems, studied in the framework of hybrid dynamical systems. We design a coordination scheme which combines the use of ternary controllers with a self-triggered communication policy. The communication policy requires the agents to measure, at each

Overview of mechanisms of cancer chemopreventive agents

International Nuclear Information System (INIS)

De Flora, Silvio; Ferguson, Lynnette R.

2005-01-01

Epidemiological data provide evidence that it is possible to prevent cancer and other chronic diseases, some of which share common pathogenetic mechanisms, such as DNA damage, oxidative stress, and chronic inflammation. An obvious approach is avoidance of exposure to recognized risk factors. As complementary strategies, it is possible to render the organism more resistant to mutagens/carcinogens and/or to inhibit progression of the disease by administering chemopreventive agents. In a primary prevention setting, addressed to apparently healthy individuals, it is possible to inhibit mutation and cancer initiation by triggering protective mechanisms either in the extracellular environment or inside cells, e.g., by modifying transmembrane transport, modulating metabolism, blocking reactive species, inhibiting cell replication, maintaining DNA structure, modulating DNA metabolism and repair, and controlling gene expression. Tumor promotion can be counteracted by inhibiting genotoxic effects, favoring antioxidant and anti-inflammatory activity, inhibiting proteases and cell proliferation, inducing cell differentiation, modulating apoptosis and signal transduction pathways, and protecting intercellular communications. In a secondary prevention setting, when a premalignant lesion has been detected, it is possible to inhibit tumor progression via the same mechanisms, and in addition by affecting the hormonal status and the immune system in various ways, and by inhibiting tumor angiogenesis. Although tertiary prevention, addressed to cancer patients after therapy, is outside the classical definition of chemoprevention, it exploits similar mechanisms. It is also possible to affect cell-adhesion molecules, to activate antimetastasis genes, and to inhibit proteases involved in basement membrane degradation

Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance.

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Motoharu Hayashi

Full Text Available A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory cytokines [Monocyte Chemoattractant Protein-1 (MCP-1, tumor necrosis factor-α, and interleukin-6] were assessed with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT was observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose tolerance tests (GTTs and insulin tolerance tests, and mRNA expression of insulin receptor substrate-1 (IRS-1 and glucose transporter 4 (GLUT4 in WAT. Restraint stress increased monocyte accumulation, plasma free fatty acids, expression of angiotensinogen and proinflammatory cytokines including MCP-1, and reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and reversed changes in adiponectin expression. Notably, irbesartan suppressed stress-induced reduction in adipose tissue weight and free fatty acid release, and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA expressions in WAT. The results

Trends and Sources of Zoonoses, Zoonotic Agents and Antimicrobial resistance in the European Union in 2004

DEFF Research Database (Denmark)

Helwigh, Birgitte

EFSA's Community Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Antimicrobial resistance in the European Union in 2004 was published in December 2005. The zoonoses, meaning infectious diseases transmissible from animals to humans, affected over 380,000 EU citizens in 2004....... Often the human form of the disease is acquired through contaminated food. According to the report, the two most frequently reported zoonotic diseases in humans were Salmonella and Campylobacter infections. These bacteria were also commonly found in food and animals. The report includes information...... of 11 zoonoses, antimicrobial resistance in zoonotic agents as well as foodborne outbreaks. The national zoonoses country reports which have been used as a basis for this Summary report are below. The utmost effort was made to keep the information in the Summary Report and the national reports identical...

Resistência à Mudança Organizacional e stress no trabalho

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Antônio Luiz Marques

2016-03-01

Full Text Available O objetivo deste trabalho é entender como a mudança organizacional, especificamente a implantação da Avaliação de Desempenho Individual (ADI pelo governo de Minas Gerais, afeta o nível de stress dos servidores. Portanto, neste estudo descritivo e explicativo, um survey foi desenvolvido e questionários padronizados foram aplicados em 679 respondentes, sendo 247 da Secretaria de Estado da Saúde (SES, 248 na Secretaria de Estado da Educação (SEE e 184 da Secretaria de Estado do Planejamento e Gestão (SEPLAG. A análise dos dados indica que a resistência à mudança influencia o stress no trabalho. Ou seja, indivíduos que apresentam níveis mais elevados de aceitação à mudança tendem ter um nível mais baixo de stress global representado pelo desgaste físico e mental. Assim como altos níveis de resistência individual à mudança geram maiores níveis de stress. Os resultados oferecem implicações relevantes para a teoria e para a prática da Gestão de Recursos Humanos.

Reduction in perceived stress as a migraine trigger

Science.gov (United States)

Lipton, Richard B.; Hall, Charles B.; Tennen, Howard; DeFreitas, Tiffani A.; Borkowski, Thomas M.; Grosberg, Brian M.; Haut, Sheryl R.

2014-01-01

Objective: To test whether level of perceived stress and reductions in levels of perceived stress (i.e., “let-down”) are associated with the onset of migraine attacks in persons with migraine. Methods: Patients with migraine from a tertiary headache center were invited to participate in a 3-month electronic diary study. Participants entered data daily regarding migraine attack experience, subjective stress ratings, and other data. Stress was assessed using 2 measures: the Perceived Stress Scale and the Self-Reported Stress Scale. Logit-normal, random-effects models were used to estimate the odds ratio for migraine occurrence as a function of level of stress over several time frames. Results: Of 22 enrolled participants, 17 (median age 43.8 years) completed >30 days of diaries, yielding 2,011 diary entries including 110 eligible migraine attacks (median 5 attacks per person). Level of stress was not generally associated with migraine occurrence. However, decline in stress from one evening diary to the next was associated with increased migraine onset over the subsequent 6, 12, and 18 hours, with odds ratios ranging from 1.5 to 1.9 (all p values < 0.05) for the Perceived Stress Scale. Decline in stress was associated with migraine onset after controlling for level of stress for all time points. Findings were similar using the Self-Reported Stress Scale. Conclusions: Reduction in stress from one day to the next is associated with migraine onset the next day. Decline in stress may be a marker for an impending migraine attack and may create opportunities for preemptive pharmacologic or behavioral interventions. PMID:24670889

Influence of quenching agent on microstructure, properties and thermal stress of SiC{sub p}/2009 composites

Energy Technology Data Exchange (ETDEWEB)

He, Tianbing, E-mail: tianbing_1988@sina.com [Beijing Institute of Aeronautic Materials, Beijing 100095 (China); Beijing Engineering Research Center of Advanced Aluminum Alloys and Application, Beijing 100095 (China); Li, Huiqu; Tang, Pengjun; He, Xiaolei; Li, Peiyong [Beijing Institute of Aeronautic Materials, Beijing 100095 (China); Beijing Engineering Research Center of Advanced Aluminum Alloys and Application, Beijing 100095 (China)

2016-08-15

15% vol. SiC{sub p}/2009 composites prepared by powder metallurgy were quenched in room temperature water and 20% polyethylene glycol (PEG) solution respectively, then aged naturally. The influence of quenching agent on microstructure, properties and thermal stress of SiC{sub p}/2009 composites were investigated by means of scanning/transmission electron microscope, hardness and tensile test. The results showed that the number of precipitated phase in water quenched composites increased, with much finer in size and more homogeneous in distribution compared with 20% PEG quenched one. Meanwhile, the density of dislocation in composites by water quenching was also much higher. Intergranular corrosion did not occur with the two quenching agents. The 20% PEG quenched composites exhibited slight lower hardness and higher electrical conductivity than that of water quenched one. The two quenched composites showed same level in tensile strength, but the yield strength of water-quenched composites was higher (8 MPa, 3%). The usage of 20% PEG reduced thermal stress and minimized warping deformation of the parts, it is a more suitable quenching agent for SiC{sub p}/2009 composites in engineering application fields. - Highlights: •SiC{sub p}/2009 composites quenched by water and 20% PEG solution were investigated. •Aging precipitation behavior of SiC{sub p}/2009 composites is sensitive to quenchant. •Influence of quenching agent on properties of SiC{sub p}/2009 composites are minimal. •Quenching with 20% PEG reduces thermal stress of SiC{sub p}/2009 composites remarkably. •20% PEG is a more suitable quenching agent for SiC{sub p}/2009 composites than water.

Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells.

Science.gov (United States)

Tanimoto, Azusa; Yamada, Tadaaki; Nanjo, Shigeki; Takeuchi, Shinji; Ebi, Hiromichi; Kita, Kenji; Matsumoto, Kunio; Yano, Seiji

2014-07-15

Alectinib is a new generation ALK inhibitor with activity against the gatekeeper L1196M mutation that showed remarkable activity in a phase I/II study with echinoderm microtubule associated protein-like 4 (EML4)--anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) patients. However, alectinib resistance may eventually develop. Here, we found that EGFR ligands and HGF, a ligand of the MET receptor, activate EGFR and MET, respectively, as alternative pathways, and thereby induce resistance to alectinib. Additionally, the heat shock protein 90 (Hsp90) inhibitor suppressed protein expression of ALK, MET, EGFR, and AKT, and thereby induced apoptosis in EML4-ALK NSCLC cells, even in the presence of EGFR ligands or HGF. These results suggest that Hsp90 inhibitors may overcome ligand-triggered resistance to new generation ALK inhibitors and may result in more successful treatment of NSCLC patients with EML4-ALK.

Rhein triggers apoptosis via induction of endoplasmic reticulum stress, caspase-4 and intracellular calcium in primary human hepatic HL-7702 cells

Energy Technology Data Exchange (ETDEWEB)

KoraMagazi, Arouna [Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu (China); Wang, Dandan [Department of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu (China); Yousef, Bashir; Guerram, Mounia [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu (China); Yu, Feng, E-mail: yufengcpu14@yahoo.com [Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu (China); Department of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu (China); Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing, Jiangsu (China)

2016-04-22

Rhein is an active component of rhubarb; a traditional Chinese medicine reported to induce apoptosis and cause liver toxicity. However, rhein's apoptotic-inducing effects, as well as its molecular mechanisms of action on hepatic cells need to be further explored. In the present study, rhein was found to trigger apoptosis in primary human hepatic HL-7702 cells as showed by annexin V/PI double staining assay and nuclear morphological changes demonstrated by Hoechst 33258 staining. Moreover, it was observed that the mechanism implicated in rhein-induced apoptosis was caspase-dependent, presumably via ER-stress associated pathways, as illustrated by up-regulation of glucose-regulated protein 78 (GRP 78), PKR-like ER kinase (PERK), C-Jun N-terminal kinase (JNK) and CCAAT/enhancer-binding protein homologous protein (CHOP). Meanwhile, caspase-4 as a hallmark of ER-stress, was also showed to be activated following by caspase-3 activation. Furthermore, rhein also promoted intracellular elevation of calcium that contributed in apoptosis induction. Interestingly, pre-treatment with calpain inhibitor I reduced the effects of rhein on apoptosis induction and JNK activation. These data suggested that rhein-induced apoptosis through ER-stress and elevated intracellular calcium level in HL-7702 cells. - Highlights: • Rhein triggers apoptotic cell death on primary human hepatic HL-7702 cells. • Rhein leads to caspase-4 activation in HL-7702 cells. • Rhein induces endoplasmic reticulum stress pathways in HL-7702 cells. • Rhein causes elevation of intracellular calcium concentrations in HL-7702 cells.

The first-level muon trigger system advances

CERN Multimedia

Ellis, N.

2006-01-01

Important advances have been made in the last few months in the first-level muon trigger, both for the barrel system and for the endcap system, in a close collaboration between the detector and trigger-electronics groups for the RPCs (Resistive-Plate Chambers) and TGCs (Thin-Gap Chambers). These trigger systems are crucial for the success of the muon-related physics programme of the experiment; events that are not triggered will be lost forever, and the trigger chambers also provide the second coordinate for the reconstruction of muons that are only measured in the bending plane by the MDT detectors. Integration and installation of the barrel muon trigger electronics on the RPC detectors is in full swing. The on-detector electronics consists of more than 800 units each of "Splitter" and "Pad" boxes which have been tested and integrated by a team of physicists, engineers and technicians from Italy and Romania. This work will continue for a further few months until the complete system has been installed and so...

[Clinical significance of drug resistance-associated mutations in treatment of hepatitis C with direct-acting antiviral agents].

Science.gov (United States)

Li, Z; Chen, Z W; Ren, H; Hu, P

2017-03-20

Direct-acting antiviral agents (DAAs) achieve a high sustained virologic response rate in the treatment of chronic hepatitis C virus infection. However, drug resistance-associated mutations play an important role in treatment failure and have attracted more and more attention. This article elaborates on the clinical significance of drug resistance-associated mutations from the aspects of their definition, association with genotype, known drug resistance-associated mutations and their prevalence rates, the impact of drug resistance-associated mutations on treatment naive and treatment-experienced patients, and the role of clinical detection, in order to provide a reference for clinical regimens with DAAs and help to achieve higher sustained virologic response rates.

Variation in adult stress resistance does not explain vulnerability to climate change in copper butterflies.

Science.gov (United States)

Klockmann, Michael; Wallmeyer, Leonard; Fischer, Klaus

2017-03-15

Ongoing climate change is a major threat to biodiversity. However, although many species clearly suffer from ongoing climate change, others benefit from it, for example, by showing range expansions. However, which specific features determine a species' vulnerability to climate change? Phenotypic plasticity, which has been described as the first line of defence against environmental change, may be of utmost importance here. Against this background, we here compare plasticity in stress tolerance in 3 copper butterfly species, which differ arguably in their vulnerability to climate change. Specifically, we investigated heat, cold and desiccation resistance after acclimatization to different temperatures in the adult stage. We demonstrate that acclimation at a higher temperature increased heat but decreased cold tolerance and desiccation resistance. Contrary to our predictions, species did not show pronounced variation in stress resistance, though plastic capacities in temperature stress resistance did vary across species. Overall, our results seemed to reflect population-rather than species-specific patterns. We conclude that the geographical origin of the populations used should be considered even in comparative studies. However, our results suggest that, in the 3 species studied here, vulnerability to climate change is not in the first place determined by stress resistance in the adult stage. As entomological studies focus all too often on adults only, we argue that more research effort should be dedicated to other developmental stages when trying to understand insect responses to environmental change. © 2017 Institute of Zoology, Chinese Academy of Sciences.

The role of autophagy in THP-1 macrophages resistance to HIV- vpr-induced apoptosis

Energy Technology Data Exchange (ETDEWEB)

Zhou, Hua-ying, E-mail: zhouhuaying_2004@126.com; Zheng, Yu-huang; He, Yan; Chen, Zi; He, Bo

2017-02-01

Macrophages are resistant to cell death and are one of HIV reservoirs. HIV viral protein Vpr has the potential to promote infection of and survival of macrophages, which could be a highly significant factor in the development and/or maintenance of macrophage viral reservoirs. However, the impact of vpr on macrophages resistance to apoptosis is yet to be comprehended. Autophagy is a cell survival mechanism under stress state. In this study, we investigated whether autophagy is involved in macrophages resistant to vpr-induced apoptosis. Using the THP1 macrophages, we studied the interconnection between macrophages resistance to apoptosis and autophagy. We found that vpr is able to trigger autophagy in transfected THP-1 macrophages confirmed by electron microscopy (EM) and western blot analysis, and inhibition of autophagy with 3MA increased vpr-induced apoptosis. The results indicate that autophagy may be responsible for maintenance of macrophage HIV reservoirs. - Highlights: • HIV Vpr is able to trigger autophagy in transfected THP-1 macrophages. • Autophagy inhibition increases vpr-transfected THP1-macrophages apoptosis. • Autophagy is involved in THP-1 macrophages resistant to vpr-induced apoptosis.

Impact of Pathogen Population Heterogeneity and Stress-Resistant Variants on Food Safety.

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Abee, T; Koomen, J; Metselaar, K I; Zwietering, M H; den Besten, H M W

2016-01-01

This review elucidates the state-of-the-art knowledge about pathogen population heterogeneity and describes the genotypic and phenotypic analyses of persister subpopulations and stress-resistant variants. The molecular mechanisms underlying the generation of persister phenotypes and genetic variants are identified. Zooming in on Listeria monocytogenes, a comparative whole-genome sequence analysis of wild types and variants that enabled the identification of mutations in variants obtained after a single exposure to lethal food-relevant stresses is described. Genotypic and phenotypic features are compared to those for persistent strains isolated from food processing environments. Inactivation kinetics, models used for fitting, and the concept of kinetic modeling-based schemes for detection of variants are presented. Furthermore, robustness and fitness parameters of L. monocytogenes wild type and variants are used to model their performance in food chains. Finally, the impact of stress-resistant variants and persistence in food processing environments on food safety is discussed.

Comparative proteomic responses of two bermudagrass (Cynodon dactylon (L). Pers.) varieties contrasting in drought stress resistance.

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Shi, Haitao; Ye, Tiantian; Chan, Zhulong

2014-09-01

Drought (water-deficit) stress is a serious environmental problem in plant growth and cultivation. As one of widely cultivated warm-season turfgrass, bermudagrass (Cynodon dactylon (L). Pers.) exhibits drastic natural variation in the drought stress resistance in leaves and stems of different varieties. In this study, proteomic analysis was performed to identify drought-responsive proteins in both leaves and stems of two bermudagrass varieties contrasting in drought stress resistance, including drought sensitive variety (Yukon) and drought tolerant variety (Tifgreen). Through comparative proteomic analysis, 39 proteins with significantly changed abundance were identified, including 3 commonly increased and 2 decreased proteins by drought stress in leaves and stems of Yukon and Tifgreen varieties, 2 differentially regulated proteins in leaves and stems of two varieties after drought treatment, 23 proteins increased by drought stress in Yukon variety and constitutively expressed in Tifgreen variety, and other 3 differentially expressed proteins under control and drought stress conditions. Among them, proteins involved in photosynthesis (PS), glycolysis, N-metabolism, tricarboxylicacid (TCA) and redox pathways were largely enriched, which might be contributed to the natural variation of drought resistance between Yukon and Tifgreen varieties. These studies provide new insights to understand the molecular mechanism underlying bermudagrass response to drought stress. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The ER stress inducer DMC enhances TRAIL-induced apoptosis in glioblastoma

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van Roosmalen, Ingrid A. M.; Dos Reis, Carlos R; Setroikromo, Rita; Yuvaraj, Saravanan; Joseph, Justin V.; Tepper, Pieter G.; Kruyt, Frank A. E.; Quax, Wim J.

2014-01-01

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour in humans and is highly resistant to current treatment modalities. We have explored the combined treatment of the endoplasmic reticulum (ER) stress-inducing agent 2,5-dimethyl-celecoxib (DMC) and TNF-related

The CMS Barrel Muon Trigger Upgrade

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Triossi, Andrea

2017-01-01

ABSTRACT: The increase of luminosity expected by LHC during Phase 1 will impose several constrains for rate reduction while maintaining high efficiency in the CMS Level 1 trigger system. The TwinMux system is the early layer of the muon barrel region that concentrates the information from different subdetectors DT, RPC and HO. It arranges and fan-out the slow optical trigger links from the detector chambers into faster links (10 Gbps) that are sent to the track finders. Results, from collision runs, that confirm the satisfactory operation of the trigger system up to the output of the barrel track finder, will be shown. SUMMARY: In view of the increase of luminosity during phase 1 upgrade of LHC, the muon trigger chain of the Compact Muon Solenoid (CMS) experiment underwent considerable improvements. The muon detector was designed for preserving the complementarity and redundancy of three separate muon detection systems, Cathode Strip Chambers (CSC), Drift Tubes (DT) and Resistive Plate Chambers (RPC), until ...

Relaxation of stresses in polystyrene–carbon microcomposite resistive layers

International Nuclear Information System (INIS)

Łukasik, Andrzej; Sibiński, Maciej; Walczak, Sylwia

2012-01-01

This paper presents the investigation results on thermoresistive elements made with a styrene–butadiene–styrene (SBS) modified polystyrene binder and carbon filler. Resistive layers were deposited by screen-printing method onto a polyethylene terephthalate (PET) foil. The temperature–resistance dependence of the examined layers was observed. The carbon filler content was precisely selected to obtain high values of TCR, such as 70,000 ppm/°C, for resistive layers with a SBS-modified polystyrene binder in the temperature range from 24 to 100 °C. Because of high TCR the influence of mechanical stresses, which is unfavorable feature of the examined layers, may be omitted. The highest TCR value and stability of electrical parameters during operation were observed for layers containing 42.9% of carbon filler by mass content. The measurements were carried out with the aid of an infrared camera and an oscilloscope because of very fast changes of resistive elements parameters. The analysis of the obtained results allows to draw conclusions about the carbon layer properties and to determine the stress–relaxation rate of the polymer structures.

Distributed Event-Triggered Control of Multiagent Systems with Time-Varying Topology

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Jingwei Ma

2014-01-01

Full Text Available This paper studies the consensus of first-order discrete-time multiagent systems, where the interaction topology is time-varying. The event-triggered control is used to update the control input of each agent, and the event-triggering condition is designed based on the combination of the relative states of each agent to its neighbors. By applying the common Lyapunov function method, a sufficient condition for consensus, which is expressed as a group of linear matrix inequalities, is obtained and the feasibility of these linear matrix inequalities is further analyzed. Simulation examples are provided to explain the effectiveness of the theoretical results.

Patterns of infections, aetiological agents and antimicrobial resistance at a tertiary care hospital in northern Tanzania.

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Kumburu, Happiness Houka; Sonda, Tolbert; Mmbaga, Blandina Theophil; Alifrangis, Michael; Lund, Ole; Kibiki, Gibson; Aarestrup, Frank M

2017-04-01

To determine the causative agents of infections and their antimicrobial susceptibility at a tertiary care hospital in Moshi, Tanzania, to guide optimal treatment. A total of 590 specimens (stool (56), sputum (122), blood (126) and wound swabs (286)) were collected from 575 patients admitted in the medical and surgical departments. The bacterial species were determined by conventional methods, and disc diffusion was used to determine the antimicrobial susceptibility pattern of the bacterial isolates. A total of 249 (42.2%) specimens were culture-positive yielding a total of 377 isolates. A wide range of bacteria was isolated, the most predominant being Gram-negative bacteria: Proteus spp. (n = 48, 12.7%), Escherichia coli (n = 44, 11.7%), Pseudomonas spp. (n = 40, 10.6%) and Klebsiella spp (n = 38, 10.1%). Wound infections were characterised by multiple isolates (n = 293, 77.7%), with the most frequent being Proteus spp. (n = 44, 15%), Pseudomonas (n = 37, 12.6%), Staphylococcus (n = 29, 9.9%) and Klebsiella spp. (n = 28, 9.6%). All Staphylococcus aureus tested were resistant to penicillin (n = 22, 100%) and susceptible to vancomycin. Significant resistance to cephalosporins such as cefazolin (n = 62, 72.9%), ceftriaxone (n = 44, 51.8%) and ceftazidime (n = 40, 37.4%) was observed in Gram-negative bacteria, as well as resistance to cefoxitin (n = 6, 27.3%) in S. aureus. The study has revealed a wide range of causative agents, with an alarming rate of resistance to the commonly used antimicrobial agents. Furthermore, the bacterial spectrum differs from those often observed in high-income countries. This highlights the imperative of regular generation of data on aetiological agents and their antimicrobial susceptibility patterns especially in infectious disease endemic settings. The key steps would be to ensure the diagnostic capacity at a sufficient number of sites and implement structures to routinely exchange, compare, analyse and report data. Sentinel sites

ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases.

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Kline, C Leah B; Van den Heuvel, A Pieter J; Allen, Joshua E; Prabhu, Varun V; Dicker, David T; El-Deiry, Wafik S

2016-02-16

ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation- and cell survival-promoting kinases Akt and ERK and induces cell death through the proapoptotic protein TRAIL. ONC201 is currently in early-phase clinical testing for various malignancies. We found through gene expression and protein analyses that ONC201 triggered an increase in TRAIL abundance and cell death through an integrated stress response (ISR) involving the transcription factor ATF4, the transactivator CHOP, and the TRAIL receptor DR5. ATF4 was not activated in ONC201-resistant cancer cells, and in ONC201-sensitive cells, knockdown of ATF4 or CHOP partially abrogated ONC201-induced cytotoxicity and diminished the ONC201-stimulated increase in DR5 abundance. The activation of ATF4 in response to ONC201 required the kinases HRI and PKR, which phosphorylate and activate the translation initiation factor eIF2α. ONC201 rapidly triggered cell cycle arrest, which was associated with decreased abundance of cyclin D1, decreased activity of the kinase complex mTORC1, and dephosphorylation of the retinoblastoma (Rb) protein. The abundance of X-linked inhibitor of apoptosis protein (XIAP) negatively correlated with the extent of apoptosis in response to ONC201. These effects of ONC201 were independent of whether cancer cells had normal or mutant p53. Thus, ONC201 induces cell death through the coordinated induction of TRAIL by an ISR pathway. Copyright © 2016, American Association for the Advancement of Science.

Relationship among Periodontal Disease, Insulin Resistance, Salivary Cortisol, and Stress Levels during Pregnancy.

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Seraphim, Ana Paula Castilho Garcia; Chiba, Fernando Yamamoto; Pereira, Renato Felipe; Mattera, Maria Sara de Lima Coutinho; Moimaz, Suzely Adas Saliba; Sumida, Doris Hissako

2016-01-01

Pregnancy is a period involving important metabolic changes that enable the maintenance of the mother's health and development of the fetus. This study aimed to assess the relationship among periodontal disease, insulin resistance, salivary cortisol concentration and level of perceived stress in pregnant women. This was a cross-sectional study. The sample comprised 96 pregnant women between the fifth and seventh month of pregnancy registered at the Basic Health Units of the Unified Health System (SUS). The periodontal condition was assessed after obtainment free and informed consent from the participants. Participants were divided into three groups: control subjects with a healthy periodontal condition (CN; n=46), patients with gingivitis (GI; n=26), and patients with periodontitis (PI; n=24). Saliva and blood samples were collected for evaluation of salivary cortisol concentration, glycemia, insulinemia and Homeostasis Model Assessment-Insulin Resistance index. A validated survey for the assessment of perceived stress levels was also performed. PI group showed significantly higher (pperiodontal disease during pregnancy. This study emphasizes the importance of preventing periodontitis in order to avoid insulin resistance and stress during pregnancy since these can cause systemic complications for the mother and the fetus.

The Ablation of Mitochondrial Protein Phosphatase Pgam5 Confers Resistance Against Metabolic Stress.

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Sekine, Shiori; Yao, Akari; Hattori, Kazuki; Sugawara, Sho; Naguro, Isao; Koike, Masato; Uchiyama, Yasuo; Takeda, Kohsuke; Ichijo, Hidenori

2016-03-01

Phosphoglycerate mutase family member 5 (PGAM5) is a mitochondrial protein phosphatase that has been reported to be involved in various stress responses from mitochondrial quality control to cell death. However, its roles in vivo are largely unknown. Here, we show that Pgam5-deficient mice are resistant to several metabolic insults. Under cold stress combined with fasting, Pgam5-deficient mice better maintained body temperature than wild-type mice and showed an extended survival rate. Serum triglycerides and lipid content in brown adipose tissue (BAT), a center of adaptive thermogenesis, were severely reduced in Pgam5-deficient mice. Moreover, although Pgam5 deficiency failed to maintain proper mitochondrial integrity in BAT, it reciprocally resulted in the dramatic induction of fibroblast growth factor 21 (FGF21) that activates various functions of BAT including thermogenesis. Thus, the enhancement of lipid metabolism and FGF21 may contribute to the cold resistance of Pgam5-deficient mice under fasting condition. Finally, we also found that Pgam5-deficient mice are resistant to high-fat-diet-induced obesity. Our study uncovered that PGAM5 is involved in the whole-body metabolism in response to stresses that impose metabolic challenges on mitochondria.

Multilayered control of peroxisomal activity upon salt stress in Saccharomyces cerevisiae.

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Manzanares-Estreder, Sara; Espí-Bardisa, Joan; Alarcón, Benito; Pascual-Ahuir, Amparo; Proft, Markus

2017-06-01

Peroxisomes are dynamic organelles and the sole location for fatty acid β-oxidation in yeast cells. Here, we report that peroxisomal function is crucial for the adaptation to salt stress, especially upon sugar limitation. Upon stress, multiple layers of control regulate the activity and the number of peroxisomes. Activated Hog1 MAP kinase triggers the induction of genes encoding enzymes for fatty acid activation, peroxisomal import and β-oxidation through the Adr1 transcriptional activator, which transiently associates with genes encoding fatty acid metabolic enzymes in a stress- and Hog1-dependent manner. Moreover, Na + and Li + stress increases the number of peroxisomes per cell in a Hog1-independent manner, which depends instead of the retrograde pathway and the dynamin related GTPases Dnm1 and Vps1. The strong activation of the Faa1 fatty acyl-CoA synthetase, which specifically localizes to lipid particles and peroxisomes, indicates that adaptation to salt stress requires the enhanced mobilization of fatty acids from internal lipid stores. Furthermore, the activation of mitochondrial respiration during stress depends on peroxisomes, mitochondrial acetyl-carnitine uptake is essential for salt resistance and the number of peroxisomes attached to the mitochondrial network increases during salt adaptation, which altogether indicates that stress-induced peroxisomal β-oxidation triggers enhanced respiration upon salt shock. © 2017 John Wiley & Sons Ltd.

Analysis of Trigger Factors in Episodic Migraineurs Using a Smartphone Headache Diary Applications

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Park, Jeong-Wook; Chu, Min Kyung; Kim, Jae-Moon; Park, Sang-Gue; Cho, Soo-Jin

2016-01-01

Background Various stimuli can trigger migraines in susceptible individuals. We examined migraine trigger factors by using a smartphone headache diary application. Method Episodic migraineurs who agreed to participate in our study downloaded smartphone headache diary application, which was designed to capture the details regarding headache trigger factors and characteristics for 3 months. The participants were asked to access the smartphone headache diary application daily and to confirm the presence of a headache and input the types of trigger factors. Results Sixty-two participants kept diary entries until the end of the study. The diary data for 4,579 days were analyzed. In this data set, 1,099 headache days (336 migraines, 763 non-migraine headaches) were recorded; of these, 772 headache events had with trigger factors, and 327 events did not have trigger factors. The common trigger factors that were present on headache days included stress, fatigue, sleep deprivation, hormonal changes, and weather changes. The likelihood of a headache trigger was 57.7% for stress, 55.1% for sleep deprivation, 48.5% for fatigue, and 46.5% for any trigger. The headaches with trigger factors were associated with greater pain intensity (pSmartphone headache diary application is an effective tool to assess migraine trigger factors. The headaches with trigger factors had greater severity or migraine features. The type of triggers and the presence of preventive medication influenced the headache characteristics; hence, an investigation of trigger factors would be helpful in understanding migraine occurrences. PMID:26901341

Analysis of Trigger Factors in Episodic Migraineurs Using a Smartphone Headache Diary Applications.

Science.gov (United States)

Park, Jeong-Wook; Chu, Min Kyung; Kim, Jae-Moon; Park, Sang-Gue; Cho, Soo-Jin

2016-01-01

Various stimuli can trigger migraines in susceptible individuals. We examined migraine trigger factors by using a smartphone headache diary application. Episodic migraineurs who agreed to participate in our study downloaded smartphone headache diary application, which was designed to capture the details regarding headache trigger factors and characteristics for 3 months. The participants were asked to access the smartphone headache diary application daily and to confirm the presence of a headache and input the types of trigger factors. Sixty-two participants kept diary entries until the end of the study. The diary data for 4,579 days were analyzed. In this data set, 1,099 headache days (336 migraines, 763 non-migraine headaches) were recorded; of these, 772 headache events had with trigger factors, and 327 events did not have trigger factors. The common trigger factors that were present on headache days included stress, fatigue, sleep deprivation, hormonal changes, and weather changes. The likelihood of a headache trigger was 57.7% for stress, 55.1% for sleep deprivation, 48.5% for fatigue, and 46.5% for any trigger. The headaches with trigger factors were associated with greater pain intensity (pSmartphone headache diary application is an effective tool to assess migraine trigger factors. The headaches with trigger factors had greater severity or migraine features. The type of triggers and the presence of preventive medication influenced the headache characteristics; hence, an investigation of trigger factors would be helpful in understanding migraine occurrences.

A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress-Resistant Mutants in Campylobacter jejuni.

Science.gov (United States)

Dai, Lei; Sahin, Orhan; Tang, Yizhi; Zhang, Qijing

2017-12-15

Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. As a microaerophilic organism, C. jejuni must be able to defend against oxidative stress encountered both in the host and in the environment. How Campylobacter utilizes a mutation-based mechanism for adaptation to oxidative stress is still unknown. Here we present a previously undescribed phenotypic and genetic mechanism that promotes the emergence of oxidative stress-resistant mutants. Specifically, we showed that a naturally occurring mutator phenotype, resulting from a loss of function mutation in the DNA repair enzyme MutY, increased oxidative stress resistance (OX R ) in C. jejuni We further demonstrated that MutY malfunction did not directly contribute to the OX R phenotype but increased the spontaneous mutation rate in the peroxide regulator gene perR , which functions as a repressor for multiple genes involved in oxidative stress resistance. Mutations in PerR resulted in loss of its DNA binding function and derepression of PerR-controlled oxidative stress defense genes, thereby conferring an OX R phenotype and facilitating Campylobacter survival under oxidative stress. These findings reveal a new mechanism that promotes the emergence of spontaneous OX R mutants in bacterial organisms. IMPORTANCE Although a mutator phenotype has been shown to promote antibiotic resistance in many bacterial species, little is known about its contribution to the emergence of OX R mutants. This work describes the link between a mutator phenotype and the enhanced emergence of OX R mutants as well as its underlying mechanism involving DNA repair and mutations in PerR. Since DNA repair systems and PerR are well conserved in many bacterial species, especially in Gram positives, the same mechanism may operate in multiple bacterial species. Additionally, we developed a novel method that allows for rapid quantification of spontaneous OX R mutants in a bacterial population. This method represents a technical

Global Omori law decay of triggered earthquakes: Large aftershocks outside the classical aftershock zone

Science.gov (United States)

Parsons, Tom

2002-09-01

Triggered earthquakes can be large, damaging, and lethal as evidenced by the1999 shocks in Turkey and the 2001 earthquakes in El Salvador. In this study, earthquakes with Ms ≥ 7.0 from the Harvard centroid moment tensor (CMT) catalog are modeled as dislocations to calculate shear stress changes on subsequent earthquake rupture planes near enough to be affected. About 61% of earthquakes that occurred near (defined as having shear stress change ∣Δτ∣ ≥ 0.01 MPa) the Ms ≥ 7.0 shocks are associated with calculated shear stress increases, while ˜39% are associated with shear stress decreases. If earthquakes associated with calculated shear stress increases are interpreted as triggered, then such events make up at least 8% of the CMT catalog. Globally, these triggered earthquakes obey an Omori law rate decay that lasts between ˜7-11 years after the main shock. Earthquakes associated with calculated shear stress increases occur at higher rates than background up to 240 km away from the main shock centroid. Omori's law is one of the few time-predictable patterns evident in the global occurrence of earthquakes. If large triggered earthquakes habitually obey Omori's law, then their hazard can be more readily assessed. The characteristic rate change with time and spatial distribution can be used to rapidly assess the likelihood of triggered earthquakes following events of Ms ≥ 7.0. I show an example application to the M = 7.7 13 January 2001 El Salvador earthquake where use of global statistics appears to provide a better rapid hazard estimate than Coulomb stress change calculations.

Herbal supplement extends life span under some environmental conditions and boosts stress resistance.

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Bryant Villeponteau

Full Text Available Genetic studies indicate that aging is modulated by a great number of genetic pathways. We have used Drosophila longevity and stress assays to test a multipath intervention strategy. To carry out this strategy, we supplemented the flies with herbal extracts (SC100 that are predicted to modulate the expression of many genes involved in aging and stress resistance, such as mTOR, NOS, NF-KappaB, and VEGF. When flies were housed in large cages with SC100 added, daily mortality rates of both male and female flies were greatly diminished in mid to late life. Surprisingly, SC100 also stabilized midlife mortality rate increases so as to extend the maximum life span substantially beyond the limits previously reported for D. melanogaster. Under these conditions, SC100 also promoted robust resistance to partial starvation stress and to heat stress. Fertility was the same initially in both treated and control flies, but it became significantly higher in treated flies at older ages as the fertility of control flies declined. Mean and maximum life spans of flies in vials at the same test site were also extended by SC100, but the life spans were short in absolute terms. In contrast, at an independent test site where stress was minimized, the flies exhibited much longer mean life spans, but the survival curves became highly rectangular and the effects of SC100 on both mean and maximum life spans declined greatly or were abolished. The data indicate that SC100 is a novel herbal mix with striking effects on enhancing Drosophila stress resistance and life span in some environments, while minimizing mid to late life mortality rates. They also show that the environment and other factors can have transformative effects on both the length and distribution of survivorship, and on the ability of SC100 to extend the life span.

Plant growth-promoting rhizobacteria (PGPR: their potential as antagonists and biocontrol agents

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Anelise Beneduzi

2012-01-01

Full Text Available Bacteria that colonize plant roots and promote plant growth are referred to as plant growth-promoting rhizobacteria (PGPR. PGPR are highly diverse and in this review we focus on rhizobacteria as biocontrol agents. Their effects can occur via local antagonism to soil-borne pathogens or by induction of systemic resistance against pathogens throughout the entire plant. Several substances produced by antagonistic rhizobacteria have been related to pathogen control and indirect promotion of growth in many plants, such as siderophores and antibiotics. Induced systemic resistance (ISR in plants resembles pathogen-induced systemic acquired resistance (SAR under conditions where the inducing bacteria and the challenging pathogen remain spatially separated. Both types of induced resistance render uninfected plant parts more resistant to pathogens in several plant species. Rhizobacteria induce resistance through the salicylic acid-dependent SAR pathway, or require jasmonic acid and ethylene perception from the plant for ISR. Rhizobacteria belonging to the genera Pseudomonas and Bacillus are well known for their antagonistic effects and their ability to trigger ISR. Resistance-inducing and antagonistic rhizobacteria might be useful in formulating new inoculants with combinations of different mechanisms of action, leading to a more efficient use for biocontrol strategies to improve cropping systems.

Non-linear actions of physiological agents: Finite disarrangements elicit fitness benefits.

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Sedlic, Filip; Kovac, Zdenko

2017-10-01

Finite disarrangements of important (vital) physiological agents and nutrients can induce plethora of beneficial effects, exceeding mere attenuation of the specific stress. Such response to disrupted homeostasis appears to be universally conserved among species. The underlying mechanism of improved fitness and longevity, when physiological agents act outside their normal range is similar to hormesis, a phenomenon whereby toxins elicit beneficial effects at low doses. Due to similarity with such non-linear response to toxins described with J-shaped curve, we have coined a new term "mirror J-shaped curves" for non-linear response to finite disarrangement of physiological agents. Examples from the clinical trials and basic research are provided, along with the unifying mechanisms that tie classical non-linear response to toxins with the non-linear response to physiological agents (glucose, oxygen, osmolarity, thermal energy, calcium, body mass, calorie intake and exercise). Reactive oxygen species and cytosolic calcium seem to be common triggers of signaling pathways that result in these beneficial effects. Awareness of such phenomena and exploring underlying mechanisms can help physicians in their everyday practice. It can also benefit researchers when designing studies and interpreting growing number of scientific data showing non-linear responses to physiological agents. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Non-linear actions of physiological agents: Finite disarrangements elicit fitness benefits

Directory of Open Access Journals (Sweden)

Filip Sedlic

2017-10-01

Full Text Available Finite disarrangements of important (vital physiological agents and nutrients can induce plethora of beneficial effects, exceeding mere attenuation of the specific stress. Such response to disrupted homeostasis appears to be universally conserved among species. The underlying mechanism of improved fitness and longevity, when physiological agents act outside their normal range is similar to hormesis, a phenomenon whereby toxins elicit beneficial effects at low doses. Due to similarity with such non-linear response to toxins described with J-shaped curve, we have coined a new term “mirror J-shaped curves” for non-linear response to finite disarrangement of physiological agents. Examples from the clinical trials and basic research are provided, along with the unifying mechanisms that tie classical non-linear response to toxins with the non-linear response to physiological agents (glucose, oxygen, osmolarity, thermal energy, calcium, body mass, calorie intake and exercise. Reactive oxygen species and cytosolic calcium seem to be common triggers of signaling pathways that result in these beneficial effects. Awareness of such phenomena and exploring underlying mechanisms can help physicians in their everyday practice. It can also benefit researchers when designing studies and interpreting growing number of scientific data showing non-linear responses to physiological agents.

Fracture resistance improvement of polypropylene by joint action of core-shell particles and nucleating agent

International Nuclear Information System (INIS)

Yang Gang; Han Liang; Ding Haifeng; Wu Haiyan; Huang Ting; Li Xiaoxi; Wang Yong

2011-01-01

Research highlights: →The core-shell particles, which were prepared from melt blending of POE and nano-CaCO 3 , and different nucleating agents (α-form NA or β-form NA) were first introduced into PP to prepare the super toughened PP materials. →NAs control the crystalline structures of PP matrix including the spherulites diameter and the crystal form. →NAs and core-shell particles exhibit apparent joint effect in improving the fracture resistance of PP. - Abstract: As a serial work about the fracture resistance improvement of polypropylene (PP), this work reports the joint effect of core-shell particles and nucleating agent (NA) on the microstructure and fracture resistance of PP. Core-shell particles were prepared through melt blending of ethylene-octene copolymer (POE) and calcium carbonate (CaCO 3 ). Different NA, i.e. α-form NA (P-tert-butylbenzoic acid-Al, MD-NA-28) and β-form NA (aryl amides compound, TMB-5) were introduced into PP matrix to control the crystalline structure. The phase morphology of POE and the distribution of CaCO 3 were characterized by using scanning electron microscope (SEM), and the crystallization behavior of PP matrix were investigated by using differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and polarization optical microscope (POM). The mechanical properties were obtained through universal tensile measurement and notched Izod impact measurement. Surprisingly, the results show that through addition of so-called core-shell particles and NA simultaneously, the fracture resistance of PP can be dramatically improved.

Water stress as a trigger of demand change: exploring the implications for drought planning

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Garcia, M. E.; Islam, S.; Portney, K. E.

2015-12-01

Drought in the Anthropocene is a function of both supply and demand. Despite its importance, demand is typically incorporated into planning models exogenously using a single scenario of demand change over time. Alternatively, demand is incorporated endogenously in hydro-economic models based on the assumption of rationality. However, actors are constrained by limited information and information processing capabilities, casting doubt on the rationality assumption. Though the risk of water shortage changes incrementally with demand growth and hydrologic change, significant shifts in management are punctuated and often linked to periods of stress. The observation of lasting decreases in per capita demands in a number of cities during periods of water stress prompts an alternate hypothesis: the occurrence of water stress increases the tendency of cities to promote and enforce efficient technologies and behaviors and the tendency of users to adopt them. We show the relevance of this hypothesis by building a model of a hypothetical surface water system to answer the following question: what is the impact of reservoir operation policy on the reliability of water supply for a growing city? The model links the rate of demand decreases to the past reliability to compare standard operating policy (SOP) with hedging policy (HP). Under SOP, demand is fulfilled unless available supply drops below demand; under HP, water releases are reduced in anticipation of a deficit to decrease the risk of a large shortfall. The model shows that reservoir storage acts both as a buffer for variability and as a delay triggering oscillations around a sustainable level of demand. HP reduces the threshold for action thereby decreasing the delay and the oscillation effect. As a result per capita demand decrease during periods of water stress are more frequent but less drastic and the additive effect of small adjustments decreases the tendency of the system to overshoot available supplies.

Enterobacter and Klebsiella species isolated from fresh vegetables marketed in Valencia (Spain) and their clinically relevant resistances to chemotherapeutic agents.

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Falomir, María Pilar; Rico, Hortensia; Gozalbo, Daniel

2013-12-01

Occurrence of antibiotic-resistant pathogenic or commensal enterobacteria in marketed agricultural foodstuffs may contribute to their incorporation into the food chain and constitutes an additional food safety concern. In this work, we have determined the clinically relevant resistances to 11 common chemotherapeutic agents in Enterobacter and Klebsiella isolates from fresh vegetables from various sources (supermarkets and greengrocers' shops in Valencia, Spain). A total of 96 isolates were obtained from 160 vegetables analyzed (50% positive samples): 68 Enterobacter isolates (59 E. cloacae, two E. aerogenes, two E. cancerogenus, one E. gergoviae, and four E. sakazakii, currently Cronobacter spp.), and 28 Klebsiella isolates (19 K. oxytoca and 9 K. pneumoniae). Only seven isolates were susceptible to all agents tested, and no resistances to ceftazidime, ciprofloxacin, gentamicin, and chloramphenicol were detected. Most isolates were resistant to amoxicillin/clavulanic acid (74 [58 Enterobacter and 16 Klebsiella]) or to ampicillin (80 [55/25]). Other resistances were less frequent: nitrofurantoin (13 isolates [12/1]), tetracycline (6 [5/1]), co-trimoxazole (3 [3/0]), cefotaxime (1 [1/0]), and streptomycin (2 [1/1]). Multiresistant isolates to two (56 [41/15]), three (10 E. cloacae isolates), four (one E. cloacae and one K. pneumoniae isolate), and five (two E. cloacae isolates) chemotherapeutic agents were also detected. The presence of potential pathogens points to marketed fresh produce, which often is eaten raw, as a risk factor for consumer health. In addition, these results support the usefulness of these bacterial species as indicators of the spreading of antibiotic resistances into the environment, particularly in the food chain, and suggest their role as carriers of resistance determinants from farms to consumers, which may constitute an additional "silent" food safety concern. Therefore, there is a need to improve the hygienic quality of marketed fresh

Evaluation of the onset of failure under mechanical and thermal stresses on luting agent for metal-ceramic and metal crowns by finite element analysis

Directory of Open Access Journals (Sweden)

Hema Agnihotri

2010-01-01

Full Text Available Long-term clinical failures of cemented prosthesis depend, to a large extent, on the integrity of the luting agent. The causative factors that lead to microfracture and, hence, failure of the luting agents are the stresses acting inside the oral cavity. Therefore, the present study was designed to develop an understanding of the relationship between stresses in the tooth and the failure potential of the luting agent. Two-dimensional finite element stress analysis was performed on the mandibular second premolar. The behavior of zinc-phosphate and glass-ionomer were studied under different crowns (metal-ceramic and metal crown and loading conditions (mechanical force of 450 N acting vertically over the occlusal surface, thermal loads of 60° and 0°C. It was observed from the study that failure threshold of the luting agent was influenced both by the elastic modulus of the luting agent and by the type of the crown.

In vitro and in vivo analysis of antimicrobial agents alone and in combination against multi-drug resistant Acinetobacter baumannii

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Songzhe eHE

2015-05-01

Full Text Available Objective To investigate the in vitro and in vivo antibacterial activities of tigecycline and other 13 common antimicrobial agents, alone or in combination, against multi-drug resistant Acinetobacter baumannii.MethodsAn in vitro susceptibility test of 101 Acinetobacter baumannii was used to detect minimal inhibitory concentrations (MICs. A mouse lung infection model of multi-drug resistant Acinetobacter baumannii,established by the ultrasonic atomization method, was used to define in vivo antimicrobial activities.Results Multi-drug resistant Acinetobacter baumannii showed high sensitivity to tigecycline (98% inhibition, polymyxin B (78.2% inhibition, and minocycline (74.2% inhibition. However, the use of these antimicrobial agents in combination with other antimicrobial agents produced synergistic or additive effects. In vivo data showed that white blood cell (WBC counts in drug combination groups C (minocycline + amikacin and D (minocycline + rifampicin were significantly higher than in groups A (tigecycline and B (polymyxin B (P < 0.05, after administration of the drugs 24h post-infection. Lung tissue inflammation gradually increased in the model group during the first 24h after ultrasonic atomization infection; vasodilation, congestion with hemorrhage were observed 48h post infection. After three days of anti-infective therapy in groups A, B, C and D, lung tissue inflammation in each group gradually recovered with clear structures. The mortality rates in drug combination groups (groups C and D were much lower than in groups A and B.ConclusionThe combination of minocycline with either rifampicin or amikacin is more effective against multidrug-resistant Acinetobacter baumannii than single-agent tigecycline or polymyxin B. In addition, the mouse lung infection by ultrasonic atomization is a suitable model for drug screening and analysis of infection mechanism.

Pharmacological Correction of Stress-Induced Gastric Ulceration by Novel Small-Molecule Agents with Antioxidant Profile

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Konstantin V. Kudryavtsev

2014-01-01

Full Text Available This study was designed to determine novel small-molecule agents influencing the pathogenesis of gastric lesions induced by stress. To achieve this goal, four novel organic compounds containing structural fragments with known antioxidant activity were synthesized, characterized by physicochemical methods, and evaluated in vivo at water immersion restraint conditions. The levels of lipid peroxidation products and activities of antioxidative system enzymes were measured in gastric mucosa and correlated with the observed gastroprotective activity of the active compounds. Prophylactic single-dose 1 mg/kg treatment with (2-hydroxyphenylthioacetyl derivatives of L-lysine and L-proline efficiently decreases up to 86% stress-induced stomach ulceration in rats. Discovered small-molecule antiulcer agents modulate activities of gastric mucosa tissue superoxide dismutase, catalase, and xanthine oxidase in concerted directions. Gastroprotective effect of (2-hydroxyphenylthioacetyl derivatives of L-lysine and L-proline at least partially depends on the correction of gastric mucosa oxidative balance.

Selection for increased desiccation resistance in Drosophila melanogaster: Additive genetic control and correlated responses for other stresses

International Nuclear Information System (INIS)

Hoffmann, A.A.; Parsons, P.A.

1989-01-01

Previously we found that Drosophila melanogaster lines selected for increased desiccation resistance have lowered metabolic rate and behavioral activity levels, and show correlated responses for resistance to starvation and a toxic ethanol level. These results were consistent with a prediction that increased resistance to many environmental stresses may be genetically correlated because of a reduction in metabolic energy expenditure. Here we present experiments on the genetic basis of the selection response and extend the study of correlated responses to other stresses. The response to selection was not sex-specific and involved X-linked and autosomal genes acting additively. Activity differences contributed little to differences in desiccation resistance between selected and control lines. Selected lines had lower metabolic rates than controls in darkness when activity was inhibited. Adults from selected lines showed increased resistance to a heat shock, 60 Co-gamma-radiation, and acute ethanol and acetic acid stress. The desiccation, ethanol and starvation resistance of isofemale lines set up from the F2s of a cross between one of the selected and one of the control lines were correlated. Selected and control lines did not differ in ether-extractable lipid content or in resistance to acetone, ether or a cold shock

Novel quinazolinone MJ-29 triggers endoplasmic reticulum stress and intrinsic apoptosis in murine leukemia WEHI-3 cells and inhibits leukemic mice.

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Chi-Cheng Lu

Full Text Available The present study was to explore the biological responses of the newly compound, MJ-29 in murine myelomonocytic leukemia WEHI-3 cells in vitro and in vivo fates. We focused on the in vitro effects of MJ-29 on ER stress and mitochondria-dependent apoptotic death in WEHI-3 cells, and to hypothesize that MJ-29 might fully impair the orthotopic leukemic mice. Our results indicated that a concentration-dependent decrease of cell viability was shown in MJ-29-treated cells. DNA content was examined utilizing flow cytometry, whereas apoptotic populations were determined using annexin V/PI, DAPI staining and TUNEL assay. Increasing vital factors of mitochondrial dysfunction by MJ-29 were further investigated. Thus, MJ-29-provaked apoptosis of WEHI-3 cells is mediated through the intrinsic pathway. Importantly, intracellular Ca(2+ release and ER stress-associated signaling also contributed to MJ-29-triggered cell apoptosis. We found that MJ-29 stimulated the protein levels of calpain 1, CHOP and p-eIF2α pathways in WEHI-3 cells. In in vivo experiments, intraperitoneal administration of MJ-29 significantly improved the total survival rate, enhanced body weight and attenuated enlarged spleen and liver tissues in leukemic mice. The infiltration of immature myeloblastic cells into splenic red pulp was reduced in MJ-29-treated leukemic mice. Moreover, MJ-29 increased the differentiations of T and B cells but decreased that of macrophages and monocytes. Additionally, MJ-29-stimulated immune responses might be involved in anti-leukemic activity in vivo. Based on these observations, MJ-29 suppresses WEHI-3 cells in vitro and in vivo, and it is proposed that this potent and selective agent could be a new chemotherapeutic candidate for anti-leukemia in the future.

Development of bacterial resistance to biocides and antimicrobial agents as a consequence of biocide usage

DEFF Research Database (Denmark)

Seier-Petersen, Maria Amalie

to antimicrobial agents. So far, only few studies have investigated the susceptibility of livestock-associated isolates to biocides used in their environment. Pigs are increasingly recognised as a potential reservoir of community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA), especially clones...... be of potential risk for human health, since these disinfectants are widely used at hospitals and in the food industry. Mobile genetic elements such as conjugative transposons are important vectors in the dissemination of antibiotic resistance determinants. Tn916 including the tetracycline resistance gene tet......Biocides are chemical compounds with antimicrobial properties and they are widely used for disinfection, antiseptic and preservation purposes. Biocides have been applied for centuries due to early empirical approaches, such as cleansing of wounds with wine, vinegar and honey and salting of fish...

The Ablation of Mitochondrial Protein Phosphatase Pgam5 Confers Resistance Against Metabolic Stress

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Shiori Sekine

2016-03-01

Full Text Available Phosphoglycerate mutase family member 5 (PGAM5 is a mitochondrial protein phosphatase that has been reported to be involved in various stress responses from mitochondrial quality control to cell death. However, its roles in vivo are largely unknown. Here, we show that Pgam5-deficient mice are resistant to several metabolic insults. Under cold stress combined with fasting, Pgam5-deficient mice better maintained body temperature than wild-type mice and showed an extended survival rate. Serum triglycerides and lipid content in brown adipose tissue (BAT, a center of adaptive thermogenesis, were severely reduced in Pgam5-deficient mice. Moreover, although Pgam5 deficiency failed to maintain proper mitochondrial integrity in BAT, it reciprocally resulted in the dramatic induction of fibroblast growth factor 21 (FGF21 that activates various functions of BAT including thermogenesis. Thus, the enhancement of lipid metabolism and FGF21 may contribute to the cold resistance of Pgam5-deficient mice under fasting condition. Finally, we also found that Pgam5-deficient mice are resistant to high-fat-diet-induced obesity. Our study uncovered that PGAM5 is involved in the whole-body metabolism in response to stresses that impose metabolic challenges on mitochondria.

Stress corrosion cracking resistance of aluminum alloy 7000 series after two-step aging

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Jegdić Bore V.

2015-01-01

Full Text Available The effect of one step-and a new (short two-step aging on the resistance to stress corrosion cracking of an aluminum alloy 7000 series was investigated, using slow strain rate test and fracture mechanics method. Aging level in the tested alloy was evaluated by means of scanning electron microscopy and measurements of electrical resistivity. It was shown that the alloy after the new two-step aging is significantly more resistant to stress corrosion cracking. Values of tensile properties and fracture toughness are similar for both thermal states. Processes that take place at the crack tip have been considered. The effect of the testing solution temperature on the crack growth rate on the plateau was determined. Two values of the apparent activation energy were obtained. These values correspond to different processes that control crack growth rate on the plateau at higher and lower temperatures. [Projekat Ministarstva nauke Republike Srbije, br. TR 34028 i br. TR 34016

Antimicrobial Agent of Susceptibilities and Antiseptic Resistance Gene Distribution among Methicillin-Resistant Staphylococcus aureus Isolates from Patients with Impetigo and Staphylococcal Scalded Skin Syndrome

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Noguchi, Norihisa; Nakaminami, Hidemasa; Nishijima, Setsuko; Kurokawa, Ichiro; So, Hiromu; Sasatsu, Masanori

2006-01-01

The susceptibilities to antimicrobial agents of and distributions of antiseptic resistance genes in methicillin-resistant Staphylococcus aureus (MRSA) strains isolated between 1999 and 2004 in Japan were examined. The data of MRSA strains that are causative agents of impetigo and staphylococcal scalded skin syndrome (SSSS) were compared with those of MRSA strains isolated from patients with other diseases. The susceptibilities to antiseptic agents in MRSA isolates from patients with impetigo and SSSS were higher than those in MRSA isolates from patients with other diseases. The distribution of the qacA/B genes in MRSA strains isolated from patients with impetigo and SSSS (1.3%, 1/76) was remarkably lower than that in MRSA strains isolated from patients with other diseases (45.9%, 95/207). Epidemiologic typings of staphylococcal cassette chromosome mec (SCCmec) and pulsed-field gel electrophoresis (PFGE) showed that MRSA strains isolated from patients with impetigo and SSSS had type IV SCCmec (75/76), except for one strain, and 64.5% (49/76) of the strains had different PFGE types. In addition, the patterns of restriction digestion of all tested qacA/B plasmid in MRSA isolates having different PFGE types were identical. The results showed that a specific MRSA clone carrying qacA/B was not prevalent, but qacA/B was spread among health care-associated MRSA strains. Therefore, it was concluded that the lower distribution rate of qacA/B resulted in higher susceptibilities to cationic antiseptic agents in MRSA isolated from patients with impetigo and SSSS. PMID:16757607

TRIGGER

CERN Multimedia

Wesley Smith

Level-1 Trigger Hardware and Software The hardware of the trigger components has been mostly finished. The ECAL Endcap Trigger Concentrator Cards (TCC) are in production while Barrel TCC firmware has been upgraded, and the Trigger Primitives can now be stored by the Data Concentrator Card for readout by the DAQ. The Regional Calorimeter Trigger (RCT) system is complete, and the timing is being finalized. All 502 HCAL trigger links to RCT run without error. The HCAL muon trigger timing has been equalized with DT, RPC, CSC and ECAL. The hardware and firmware for the Global Calorimeter Trigger (GCT) jet triggers are being commissioned and data from these triggers is available for readout. The GCT energy sums from rings of trigger towers around the beam pipe beam have been changed to include two rings from both sides. The firmware for Drift Tube Track Finder, Barrel Sorter and Wedge Sorter has been upgraded, and the synchronization of the DT trigger is satisfactory. The CSC local trigger has operated flawlessly u...

Event-Triggered Distributed Average Consensus Over Directed Digital Networks With Limited Communication Bandwidth.

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Li, Huaqing; Chen, Guo; Huang, Tingwen; Dong, Zhaoyang; Zhu, Wei; Gao, Lan

2016-12-01

In this paper, we consider the event-triggered distributed average-consensus of discrete-time first-order multiagent systems with limited communication data rate and general directed network topology. In the framework of digital communication network, each agent has a real-valued state but can only exchange finite-bit binary symbolic data sequence with its neighborhood agents at each time step due to the digital communication channels with energy constraints. Novel event-triggered dynamic encoder and decoder for each agent are designed, based on which a distributed control algorithm is proposed. A scheme that selects the number of channel quantization level (number of bits) at each time step is developed, under which all the quantizers in the network are never saturated. The convergence rate of consensus is explicitly characterized, which is related to the scale of network, the maximum degree of nodes, the network structure, the scaling function, the quantization interval, the initial states of agents, the control gain and the event gain. It is also found that under the designed event-triggered protocol, by selecting suitable parameters, for any directed digital network containing a spanning tree, the distributed average consensus can be always achieved with an exponential convergence rate based on merely one bit information exchange between each pair of adjacent agents at each time step. Two simulation examples are provided to illustrate the feasibility of presented protocol and the correctness of the theoretical results.

Comparison of white spot syndrome virus infection resistance between Exopalaemon carinicauda and Litopenaeus vannamei under different salinity stresses

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Ge, Qianqian; Yu, Ge; Sun, Ming; Li, Jitao; Li, Jian

2017-12-01

Exopalaemon carinicauda is one of the important economic shrimp species in China, and can tolerate a wide range of salinities. However, its disease resistance remains to be unclear in comparison with other shrimp species under salinity stress. In this study, the resistance to white spot syndrome virus (WSSV) of E. carinicauda and Litopenaeus vannamei was determined by comparing their hemocyanin (Hc) and phenoloxidase (PO) activities under different salinity stresses. In E. carinicauda, the PO activity and Hc gene transcript abundance showed a coherent pattern of increase and decrease while Hc content showed a slightly decrease with Vibrio anguillarum and WSSV infections. For both E. carinicauda and L. vannamei under salinity stress, the PO activity showed a positive correlation with the salinity while the Hc content and expression level of its gene increased significantly in salinities of 5, 15 and 25 g L-1. The survival rate of E. carinicauda with WSSV infection was higher than that of L. vannamei in the first 24 h under different salinity stresses. Drastic mortality of E.carinicauda and L. vannamei appeared at 48 h and 3 h post-injection, respectively. Furthermore, compared with L. vannamei, E. carinicauda displayed higher PO activity, Hc content and abundance of Hc gene mRNA. The results collectively indicated that Hc and PO have obviously functional connection in resisting pathogens and tolerating salinity stress, and PO activity and Hc gene mRNA abundance may reflect the resistance of shrimp to disease. E. carinicauda has higher level of immune potential than L. vannamei, suggesting its greater capacity in resisting pathogens under salinity stresses.

Rest-Stress Limb Perfusion Imaging in Humans with Contrast Ultrasound Using Intermediate-Power Imaging and Microbubbles Resistant to Inertial Cavitation.

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Davidson, Brian P; Hodovan, James; Belcik, J Todd; Moccetti, Federico; Xie, Aris; Ammi, Azzdine Y; Lindner, Jonathan R

2017-05-01

Contrast-enhanced ultrasound (CEU) limb perfusion imaging is a promising approach for evaluating peripheral artery disease (PAD). However, low signal enhancement in skeletal muscle has necessitated high-power intermittent imaging algorithms, which are not clinically feasible. We hypothesized that CEU using a combination of intermediate power and a contrast agent resistant to inertial cavitation would allow real-time limb stress perfusion imaging. In normal volunteers, CEU of the calf skeletal muscle was performed on separate days with Sonazoid, Optison, or Definity. Progressive reduction in the ultrasound pulsing interval was used to assess the balance between signal enhancement and agent destruction at escalating mechanical indices (MI, 0.1-0.4). Real-time perfusion imaging at MI 0.1-0.4 using postdestructive replenishment kinetics was performed at rest and during 25 W plantar flexion contractile exercise. For Optison, limb perfusion imaging was unreliable at rest due to very low signal enhancement generated at all MIs and was possible during exercise-induced hyperemia only at MI 0.1 due to agent destruction at higher MIs. For Definity, signal intensity progressively increased with MI but was offset by microbubble destruction, which resulted in modest signal enhancement during CEU perfusion imaging and distortion of replenishment curves at MI ≥ 0.2. For Sonazoid, there strong signal enhancement at MI ≥ 0.2, with little destruction detected only at MI 0.4. Accordingly, high signal intensity and nondistorted perfusion imaging was possible at MI 0.2-0.3 and detected an 8.0- ± 5.7-fold flow reserve. Rest-stress limb perfusion imaging in humans with real-time CEU, which requires only seconds to perform, is possible using microbubbles with viscoelastic properties that produce strong nonlinear signal generation without destruction at intermediate acoustic pressures. Copyright © 2016 American Society of Echocardiography. All rights reserved.

Correlation of oxidative stress in patients with HBV-induced liver disease with HBV genotypes and drug resistance mutations.

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Xianyu, Jianbo; Feng, Jiafu; Yang, Yuwei; Tang, Jie; Xie, Gang; Fan, Lingying

2018-05-01

This study aims to explore the correlation of oxidative stress (OxS) in patients with chronic hepatitis B (CHB) and the disease severity with HBV genotypes and drug resistance mutations. A total of 296 patients with CHB were enrolled into the study. PCR-reverse dot-blot hybridization was used to detect the HBV genotypes (B, C, and D) and the drug resistance-causing HBV mutant genes. In addition, the total oxidative stress (TOS) and total antioxidant status (TAS) were determined, and oxidative stress index (OSI) was calculated and compared. Serum levels of TOS and OSI, the B/C ratio, and drug resistance mutation rate were increased along with the elevated disease severity degree (CHBHBV mutation had higher serum TOS and OSI levels, while lower serum TAS levels (P HBV-induced liver disease, and the damage degree is correlated with the HBV genotype and drug resistance mutation. Oxidative stress might be a useful indicator of the progression of HBV-induced liver disease in patients. Copyright © 2018. Published by Elsevier Inc.

The Herb Medicine Formula “Chong Lou Fu Fang” Increases the Cytotoxicity of Chemotherapeutic Agents and Down-Regulates the Expression of Chemotherapeutic Agent Resistance-Related Genes in Human Gastric Cancer Cells In Vitro

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Yongping Liu

2011-01-01

Full Text Available The herb medicine formula “Chong Lou Fu Fang” (CLFF has efficacy in inhibiting the proliferation of human gastric cancer in vitro and in vivo. To explore the potentially useful combination of CLFF with chemotherapeutic agents commonly used in gastric cancer therapy, we assess the interaction between CLFF and these chemotherapeutic agents in both SGC-7901 cell lines and BGC-823 cell lines using a median effect analysis and apoptosis analysis, and we also investigate the influence of CLFF on chemotherapeutic agent-associated gene expression. The synergistic analysis indicated that CLFF had a synergistic effect on the cytotoxicity of 5-fluorouracil (5-FU in a relative broad dose inhibition range (20–95% fraction affected in SGC-7901cell lines and 5–65% fraction affected in BGC-823 cell lines, while the synergistic interaction between CLFF and oxaliplatin or docetaxel only existed in a low dose inhibition range (≤50% fraction affected in both cell lines. Combination of CLFF and chemotherapeutic agents could also induce apoptosis in a synergistic manner. After 24 h, CLFF alone or CLFF combination with chemotherapeutic agents could significantly suppress the levels of expression of chemotherapeutic agent resistance related genes in gastric cancer cells. Our findings indicate that there are useful synergistic interactions between CLFF and chemotherapeutic agents in gastric cancer cells, and the possible mechanisms might be partially due to the down-regulation of chemotherapeutic agent resistance related genes and the synergistic apoptotic effect.

Insulin resistance in non-obese women with polycystic ovary syndrome: relation to byproducts of oxidative stress.

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Macut, D; Simic, T; Lissounov, A; Pljesa-Ercegovac, M; Bozic, I; Djukic, T; Bjekic-Macut, J; Matic, M; Petakov, M; Suvakov, S; Damjanovic, S; Savic-Radojevic, A

2011-07-01

To get more insight into molecular mechanisms underlying oxidative stress and its link with insulin resistance, oxidative stress parameters, as well as, antioxidant enzyme activities were studied in young, non-obese women with polycystic ovary syndrome (PCOS). Study was performed in 34 PCOS women and 23 age and body mass index (BMI)-matched healthy controls. Plasma nitrotyrosine and malondialdehyde (MDA), representative byproducts of protein and lipid oxidative damage, were determined by enzyme immunoassay. Antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Insulin resistance was calculated using homeostasis assessment model (HOMA-IR). Plasma nitrotyrosine and MDA were increased, but only nitrotyrosine was significantly higher (p PCOS women compared to controls. Uric acid (surrogate marker of × antine oxidase) was also significantly elevated in PCOS (p PCOS and controls. Indices of insulin resistance (insulin and HOMAIR) were significantly higher in PCOS group and positively correlated with level of MDA (r = 0.397 and r = 0.523, respectively; p insulin resistance could be responsible for the existence of subtle form of oxidative stress in young, nonobese PCOS women. Hence, presence of insulin resistance, hyperinsulinemia and oxidative damage are likely to accelerate slow development of cardiovascular disease in PCOS. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

[Cellular composition of lymphoid nodules in the trachea wall in rats with different resistance to emotional stress in a model of hemorrhagic stroke].

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Klyueva, L A

2017-01-01

To reveal regularities of changes in cellular composition of lymphoid nodules in the tracheal wall in male Wistar rats resistant and not resistant to emotional stress in a model of hemorrhagic stroke. Lymphoid formations of the tracheal wall (an area near the bifurcation of the organ) were investigated in 98 male Wistar rats using histological methods. Significant changes in the cellular composition of lymphoid nodules were found. The pattern of changes depends on the stress resistance of rats and the period of the experiment. The active cell destruction in lymphoid nodules was noted both in stress resistant and stress susceptible animals. The changes in the structure of lymphoid nodules found in the experimental hemorrhagic stroke suggest a decrease in the local immune resistance, which is most pronounced in rats not resistant to stress, that may contribute to the development of severe inflammatory complications of stroke such as pneumonia.

Multi-agent chemotherapy overcomes glucocorticoid resistance conferred by a BIM deletion polymorphism in pediatric acute lymphoblastic leukemia.

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Sheila Xinxuan Soh

Full Text Available A broad range of anti-cancer agents, including glucocorticoids (GCs and tyrosine kinase inhibitors (TKIs, kill cells by upregulating the pro-apoptotic BCL2 family member, BIM. A common germline deletion in the BIM gene was recently shown to favor the production of non-apoptotic BIM isoforms, and to predict inferior responses in TKI-treated chronic myeloid leukemia (CML and EGFR-driven lung cancer patients. Given that both in vitro and in vivo GC resistance are predictive of adverse outcomes in acute lymphoblastic leukemia (ALL, we hypothesized that this polymorphism would mediate GC resistance, and serve as a biomarker of poor response in ALL. Accordingly, we used zinc finger nucleases to generate ALL cell lines with the BIM deletion, and confirmed the ability of the deletion to mediate GC resistance in vitro. In contrast to CML and lung cancer, the BIM deletion did not predict for poorer clinical outcome in a retrospective analysis of 411 pediatric ALL patients who were uniformly treated with GCs and chemotherapy. Underlying the lack of prognostic significance, we found that the chemotherapy agents used in our cohort (vincristine, L-asparaginase, and methotrexate were each able to induce ALL cell death in a BIM-independent fashion, and resensitize BIM deletion-containing cells to GCs. Together, our work demonstrates how effective therapy can overcome intrinsic resistance in ALL patients, and suggests the potential of using combinations of drugs that work via divergent mechanisms of cell killing to surmount BIM deletion-mediated drug resistance in other cancers.

Alkylating Agent-Induced NRF2 Blocks Endoplasmic Reticulum Stress-Mediated Apoptosis via Control of Glutathione Pools and Protein Thiol Homeostasis.

Science.gov (United States)

Zanotto-Filho, Alfeu; Masamsetti, V Pragathi; Loranc, Eva; Tonapi, Sonal S; Gorthi, Aparna; Bernard, Xavier; Gonçalves, Rosângela Mayer; Moreira, José C F; Chen, Yidong; Bishop, Alexander J R

2016-12-01

Alkylating agents are a commonly used cytotoxic class of anticancer drugs. Understanding the mechanisms whereby cells respond to these drugs is key to identify means to improve therapy while reducing toxicity. By integrating genome-wide gene expression profiling, protein analysis, and functional cell validation, we herein demonstrated a direct relationship between NRF2 and Endoplasmic Reticulum (ER) stress pathways in response to alkylating agents, which is coordinated by the availability of glutathione (GSH) pools. GSH is essential for both drug detoxification and protein thiol homeostasis within the ER, thus inhibiting ER stress induction and promoting survival, an effect independent of its antioxidant role. NRF2 accumulation induced by alkylating agents resulted in increased GSH synthesis via GCLC/GCLM enzyme, and interfering with this NRF2 response by either NRF2 knockdown or GCLC/GCLM inhibition with buthionine sulfoximine caused accumulation of damaged proteins within the ER, leading to PERK-dependent apoptosis. Conversely, upregulation of NRF2, through KEAP1 depletion or NRF2-myc overexpression, or increasing GSH levels with N-acetylcysteine or glutathione-ethyl-ester, decreased ER stress and abrogated alkylating agents-induced cell death. Based on these results, we identified a subset of lung and head-and-neck carcinomas with mutations in either KEAP1 or NRF2/NFE2L2 genes that correlate with NRF2 target overexpression and poor survival. In KEAP1-mutant cancer cells, NRF2 knockdown and GSH depletion increased cell sensitivity via ER stress induction in a mechanism specific to alkylating drugs. Overall, we show that the NRF2-GSH influence on ER homeostasis implicates defects in NRF2-GSH or ER stress machineries as affecting alkylating therapy toxicity. Mol Cancer Ther; 15(12); 3000-14. ©2016 AACR. ©2016 American Association for Cancer Research.

Alkylating agent induced NRF2 blocks endoplasmic reticulum stress-mediated apoptosis via control of glutathione pools and protein thiol homeostasis

Science.gov (United States)

Zanotto-Filho, Alfeu; Masamsetti, V. Pragathi; Loranc, Eva; Tonapi, Sonal S.; Gorthi, Aparna; Bernard, Xavier; Gonçalves, Rosângela Mayer; Moreira, José C. F.; Chen, Yidong; Bishop, Alexander J. R.

2016-01-01

Alkylating agents are a commonly used cytotoxic class of anticancer drugs. Understanding the mechanisms whereby cells respond to these drugs is key to identify means to improve therapy while reducing toxicity. By integrating genome-wide gene expression profiling, protein analysis and functional cell validation, we herein demonstrated a direct relationship between NRF2 and Endoplasmic Reticulum (ER) stress pathways in response to alkylating agents, which is coordinated by the availability of glutathione (GSH) pools. GSH is essential for both drug detoxification and protein thiol homeostasis within the ER, thus inhibiting ER stress induction and promoting survival; an effect independent of its antioxidant role. NRF2 accumulation induced by alkylating agents resulted in increased GSH synthesis via GCLC/GCLM enzyme, and interfering with this NRF2 response by either NRF2 knockdown or GCLC/GCLM inhibition with buthionine sulfoximine (BSO) caused accumulation of damaged proteins within the ER, leading to PERK-dependent apoptosis. Conversely, upregulation of NRF2, through KEAP1 depletion or NRF2-myc overexpression, or increasing GSH levels with N-acetylcysteine (NAC) or glutathione-ethyl-ester (GSH-E), decreased ER stress and abrogated alkylating agents-induced cell death. Based on these results, we identified a subset of lung and head-and-neck carcinomas with mutations in either KEAP1 or NRF2/NFE2L2 genes that correlate with NRF2 targets overexpression and poor survival. In KEAP1 mutant cancer cells, NRF2 knockdown and GSH depletion increased cell sensitivity via ER stress induction in a mechanism specific to alkylating drugs. Overall, we show that the NRF2-GSH influence on ER homeostasis implicates defects in NRF2-GSH or ER stress machineries as affecting alkylating therapy toxicity. PMID:27638861

Transgenic plants: resistance to abiotic and biotic stresses

Directory of Open Access Journals (Sweden)

Akila Wijerathna-Yapa

2017-06-01

Full Text Available Today’s crop breeding combined with improved agricultural management has brought substantial increases in food production. But irrigation, fertilizers pest management requires a high energy input that creates a drain on the already scare fossil fuels. It is thus clear that different strategy has to be adopted to increase crop productivity further to meet the needs of rapidly increasing world population. Crop breeders are endeavoring to meet this challenge by developing crops with higher yield, better resistance to pest, disease and weedicides, tolerance to various stress conditions.

Impact of thermal stress on evolutionary trajectories of pathogen resistance in three-spined stickleback (Gasterosteus aculeatus).

Science.gov (United States)

Schade, Franziska M; Shama, Lisa N S; Wegner, K Mathias

2014-07-26

Pathogens are a major regulatory force for host populations, especially under stressful conditions. Elevated temperatures may enhance the development of pathogens, increase the number of transmission stages, and can negatively influence host susceptibility depending on host thermal tolerance. As a net result, this can lead to a higher prevalence of epidemics during summer months. These conditions also apply to marine ecosystems, where possible ecological impacts and the population-specific potential for evolutionary responses to changing environments and increasing disease prevalence are, however, less known. Therefore, we investigated the influence of thermal stress on the evolutionary trajectories of disease resistance in three marine populations of three-spined sticklebacks Gasterosteus aculeatus by combining the effects of elevated temperature and infection with a bacterial strain of Vibrio sp. using a common garden experiment. We found that thermal stress had an impact on fish weight and especially on survival after infection after only short periods of thermal acclimation. Environmental stress reduced genetic differentiation (QST) between populations by releasing cryptic within-population variation. While life history traits displayed positive genetic correlations across environments with relatively weak genotype by environment interactions (GxE), environmental stress led to negative genetic correlations across environments in pathogen resistance. This reversal of genetic effects governing resistance is probably attributable to changing environment-dependent virulence mechanisms of the pathogen interacting differently with host genotypes, i.e. GPathogenxGHostxE or (GPathogenxE)x(GHostxE) interactions, rather than to pure host genetic effects, i.e. GHostxE interactions. To cope with climatic changes and the associated increase in pathogen virulence, host species require wide thermal tolerances and pathogen-resistant genotypes. The higher resistance we found

Observations of static Coulomb stress triggering of the November 2011 M5.7 Oklahoma earthquake sequence

Science.gov (United States)

Sumy, Danielle F.; Cochran, Elizabeth S.; Keranen, Katie M.; Wei, Maya; Abers, Geoffrey A.

2014-01-01

In November 2011, a M5.0 earthquake occurred less than a day before a M5.7 earthquake near Prague, Oklahoma, which may have promoted failure of the mainshock and thousands of aftershocks along the Wilzetta fault, including a M5.0 aftershock. The M5.0 foreshock occurred in close proximity to active fluid injection wells; fluid injection can cause a buildup of pore fluid pressure, decrease the fault strength, and may induce earthquakes. Keranen et al. [2013] links the M5.0 foreshock with fluid injection, but the relationship between the foreshock and successive events has not been investigated. Here we examine the role of coseismic Coulomb stress transfer on earthquakes that follow the M5.0 foreshock, including the M5.7 mainshock. We resolve the static Coulomb stress change onto the focal mechanism nodal plane that is most consistent with the rupture geometry of the three M ≥ 5.0 earthquakes, as well as specified receiver fault planes that reflect the regional stress orientation. We find that Coulomb stress is increased, e.g., fault failure is promoted, on the nodal planes of ~60% of the events that have focal mechanism solutions, and more specifically, that the M5.0 foreshock promoted failure on the rupture plane of the M5.7 mainshock. We test our results over a range of effective coefficient of friction values. Hence, we argue that the M5.0 foreshock, induced by fluid injection, potentially triggered a cascading failure of earthquakes along the complex Wilzetta fault system.

Not changes in membrane fluidity but proteotoxic stress triggers heat shock protein expression in Chlamydomonas reinhardtii.

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Rütgers, Mark; Muranaka, Ligia Segatto; Schulz-Raffelt, Miriam; Thoms, Sylvia; Schurig, Juliane; Willmund, Felix; Schroda, Michael

2017-12-01

A conserved reaction of all organisms exposed to heat stress is an increased expression of heat shock proteins (HSPs). Several studies have proposed that HSP expression in heat-stressed plant cells is triggered by an increased fluidity of the plasma membrane. Among the main lines of evidence in support of this model are as follows: (a) the degree of membrane lipid saturation was higher in cells grown at elevated temperatures and correlated with a lower amplitude of HSP expression upon a temperature upshift, (b) membrane fluidizers induce HSP expression at physiological temperatures, and (c) membrane rigidifier dimethylsulfoxide dampens heat-induced HSP expression. Here, we tested whether this holds also for Chlamydomonas reinhardtii. We show that heat-induced HSP expression in cells grown at elevated temperatures was reduced because they already contained elevated levels of cytosolic HSP70A/90A that apparently act as negative regulators of heat shock factor 1. We find that membrane rigidifier dimethylsulfoxide impaired translation under heat stress conditions and that membrane fluidizer benzyl alcohol not only induced HSP expression but also caused protein aggregation. These findings support the classical model for the cytosolic unfolded protein response, according to which HSP expression is induced by the accumulation of unfolded proteins. Hence, the membrane fluidity model should be reconsidered. © 2017 John Wiley & Sons Ltd.

Shear flow generation by Reynolds stress and suppression of resistive g modes

International Nuclear Information System (INIS)

Sugama, H.; Horton, W.

1993-01-01

The authors have investigated suppression of the resistive g mode turbulence by background shear flow produced by the external source and by the fluctuation-induced Reynolds stress. For that purpose, the authors used the model consisting of the equations describing the electrostatic potential φ≡(φ 0 +φ) and the pressure fluctuation p of the resistive g mode, and the equation for the background poloidal flow. They have done the single-helicity nonlinear simulations using the model equations in the sheared slab configuration. They find that, in the nonlinear turbulent regime, significant suppression of the turbulent transport is realized only when the shear flow v' E exceeds that which makes the fastest-growing linear modes marginally stable. With the shear flow which decreases the fastest linear growth rates by about a half, the turbulent transport in the saturated state is about the same as in the case of no shear flow. As seen from the equation for the background flow v E , the relative efficiency of the external flow and the Reynolds stress for producing shear flow depends on the parameter ν. For large ν, the external flow is a dominant contribution to the total background poloidal shear flow although its strength predicted by the neoclassical theory is not enough to suppress the turbulence significantly. On the other hand, for small ν, they observe that, as the fluctuations grow, the Reynolds stress becomes large and suddenly at some critical point in time shear flow much larger than the external one is generated and leads to the significant reduction of the turbulent transport just like that of the L-H transition in tokamak experiments. It is remarkable that the Reynolds stress due to the resistive g mode fluctuations works not as a conventional viscosity term weakening the shear flow but as a negative viscosity term enhancing it

A resistance locus in the American heirloom rice variety Carolina Gold Select is triggered by TAL effectors with diverse predicted targets and is effective against African strains of Xanthomonas oryzae pv. oryzicola.

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Triplett, Lindsay R; Cohen, Stephen P; Heffelfinger, Christopher; Schmidt, Clarice L; Huerta, Alejandra I; Tekete, Cheick; Verdier, Valerie; Bogdanove, Adam J; Leach, Jan E

2016-09-01

The rice pathogens Xanthomonas oryzae pathovar (pv.) oryzae and pv. oryzicola produce numerous transcription activator-like (TAL) effectors that increase bacterial virulence by activating expression of host susceptibility genes. Rice resistance mechanisms against TAL effectors include polymorphisms that prevent effector binding to susceptibility gene promoters, or that allow effector activation of resistance genes. This study identifies, in the heirloom variety Carolina Gold Select, a third mechanism of rice resistance involving TAL effectors. This resistance manifests through strong suppression of disease development in response to diverse TAL effectors from both X. oryzae pathovars. The resistance can be triggered by an effector with only 3.5 central repeats, is independent of the composition of the repeat variable di-residues that determine TAL effector binding specificity, and is independent of the transcriptional activation domain. We determined that the resistance is conferred by a single dominant locus, designated Xo1, that maps to a 1.09 Mbp fragment on chromosome 4. The Xo1 interval also confers complete resistance to the strains in the African clade of X. oryzae pv. oryzicola, representing the first dominant resistance locus against bacterial leaf streak in rice. The strong phenotypic similarity between the TAL effector-triggered resistance conferred by Xo1 and that conferred by the tomato resistance gene Bs4 suggests that monocots and dicots share an ancient or convergently evolved mechanism to recognize analogous TAL effector epitopes. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells

DEFF Research Database (Denmark)

Zub, Kamila Anna; Sousa, Mirta Mittelstedt Leal de; Sarno, Antonio

2015-01-01

of the AKR1C family involved in prostaglandin synthesis contribute to the resistant phenotype. Finally, selected metabolic and oxidative stress response enzymes were targeted by inhibitors, several of which displayed a selective cytotoxicity against the melphalan-resistant cells and should be further...... and pathways not previously associated with melphalan resistance in multiple myeloma cells, including a metabolic switch conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo-keto reductase levels...

Susceptibility patterns and the role of extracellular DNA in Staphylococcus epidermidis biofilm resistance to physico-chemical stress exposure.

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Olwal, Charles Ochieng'; Ang'ienda, Paul Oyieng'; Onyango, David Miruka; Ochiel, Daniel Otieno

2018-05-02

Over 65% of human infections are ascribed to bacterial biofilms that are often highly resistant to antibiotics and host immunity. Staphylococcus epidermidis is the predominant cause of recurrent nosocomial and biofilm-related infections. However, the susceptibility patterns of S. epidermidis biofilms to physico-chemical stress induced by commonly recommended disinfectants [(heat, sodium chloride (NaCl), sodium hypochlorite (NaOCl) and hydrogen peroxide (H 2 O 2 )] in domestic and human healthcare settings remains largely unknown. Further, the molecular mechanisms of bacterial biofilms resistance to the physico-chemical stresses remain unclear. Growing evidence demonstrates that extracellular DNA (eDNA) protects bacterial biofilms against antibiotics. However, the role of eDNA as a potential mechanism underlying S. epidermidis biofilms resistance to physico-chemical stress exposure is yet to be understood. Therefore, this study aimed to evaluate the susceptibility patterns of and eDNA release by S. epidermidis biofilm and planktonic cells to physico-chemical stress exposure. S. epidermidis biofilms exposed to physico-chemical stress conditions commonly recommended for disinfection [heat (60 °C), 1.72 M NaCl, solution containing 150 μL of waterguard (0.178 M NaOCl) in 1 L of water or 1.77 M H 2 O 2 ] for 30 and 60 min exhibited lower log reductions of CFU/mL than the corresponding planktonic cells (p chemical stress induced by the four commonly recommended disinfectants than the analogous planktonic cells. Further, S. epidermidis biofilms enhanced eDNA release in response to the sub-lethal heat and oxidative stress exposure than the corresponding planktonic cells suggesting a role of eDNA in biofilms resistance to the physico-chemical stresses.

Insights on antimicrobial resistance, biofilms and the use of phytochemicals as new antimicrobial agents.

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Borges, Anabela; Saavedra, Maria J; Simões, Manuel

2015-01-01

Antimicrobial resistance is one of the most serious public health problems. This is of particular concern when bacteria become resistant to various antimicrobial agents simultaneously and when they form biofilms. Consequently, therapeutic options for the treatment of infections have become limited, leading frequently to recurrent infections, treatment failure and increase of morbidity and mortality. Both, persistence and spread of antibiotic resistance, in combination with decreased effectiveness and increased toxicity of current antibiotics have emphasized the urgent need to search alternative sources of antimicrobial substances. Plants are recognized as a source of unexplored chemical structures with high therapeutic potential, including antimicrobial activity against clinically important microorganisms. Additionally, phytochemicals (plant secondary metabolites) present several advantages over synthetic molecules, including green status and different mechanisms of action from antibiotics which could help to overcome the resistance problem. In this study, an overview of the main classes of phytochemicals with antimicrobial properties and their mode of action is presented. A revision about the application of phytochemicals for biofilm prevention and control is also done. Moreover, the use of phytochemicals as scaffolds of new functional molecules to expand the antibiotics pipeline is reviewed.

Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress

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Klingelhoeffer Christoph

2012-05-01

Full Text Available Abstract Background Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L. The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress. Methods Effective concentration (EC50 values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay. Results The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC50 > 20 mmol/L and fifty-five percent had an EC50 50 of 2.6–5.5 mmol/L, glioblastoma cells were the most susceptible cancer cell lines analysed in this study. A correlation between catalase activity and the susceptibility to ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC50: 94,9 mmol/L, was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L. Conclusions Fifty-five percent of the human cancer cell lines tested were unable to protect themselves

Haemophilus parasuis CpxRA two-component system confers bacterial tolerance to environmental stresses and macrolide resistance.

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Cao, Qi; Feng, Fenfen; Wang, Huan; Xu, Xiaojuan; Chen, Huanchun; Cai, Xuwang; Wang, Xiangru

2018-01-01

Haemophilus parasuis is an opportunistic pathogen localized in the upper respiratory tracts of pigs, its infection begins from bacterial survival under complex conditions, like hyperosmosis, oxidative stress, phagocytosis, and sometimes antibiotics as well. The two-component signal transduction (TCST) system serves as a common stimulus-response mechanism that allows microbes to sense and respond to diverse environmental conditions via a series of phosphorylation reactions. In this study, we investigated the role of TCST system CpxRA in H. parasuis in response to different environmental stimuli by constructing the ΔcpxA and ΔcpxR single deletion mutants as well as the ΔcpxRA double deletion mutant from H. parasuis serotype 4 isolate JS0135. We demonstrated that H. parasuis TCST system CpxRA confers bacterial tolerance to stresses and bactericidal antibiotics. The CpxR was found to play essential roles in mediating oxidative stress, osmotic stresses and alkaline pH stress tolerance, as well as macrolide resistance (i.e. erythromycin), but the CpxA deletion did not decrease bacterial resistance to abovementioned stresses. Moreover, we found via RT-qPCR approach that HAPS_RS00160 and HAPS_RS09425, both encoding multidrug efflux pumps, were significantly decreased in erythromycin challenged ΔcpxR and ΔcpxRA mutants compared with wild-type strain JS0135. These findings characterize the role of the TCST system CpxRA in H. parasuis conferring stress response tolerance and bactericidal resistance, which will deepen our understanding of the pathogenic mechanism in H. parasuis. Copyright © 2017 Elsevier GmbH. All rights reserved.

Utilizing Genetic Resources and Precision Agriculture to Enhance Resistance to Biotic and Abiotic Stress in Watermelon

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Mihail KANTOR

2018-03-01

Full Text Available Originally from Africa, watermelon is a staple crop in South Carolina and rich source of important phytochemicals that promote human health. As a result of many years of domestication and selection for desired fruit quality, modern watermelon cultivars are susceptible to biotic and abiotic stress. The present review discusses how genetic selection and breeding combined with geospatial technologies (precision agriculture may help enhance watermelon varieties for resistance to biotic and abiotic stress. Gene loci identified and selected in undomesticated watermelon accessions are responsible for resistance to diseases, pests and abiotic stress. Vegetable breeding programs use traditional breeding methodologies and genomic tools to introduce gene loci conferring biotic or abiotic resistance into the genome background of elite watermelon cultivars. This continuous approach of collecting, evaluating and identifying useful genetic material is valuable for enhancing genetic diversity and tolerance and combined with precision agriculture could increase food security in the Southeast.

TRIGGER

CERN Multimedia

Wesley Smith

Level-1 Trigger Hardware and Software The trigger synchronization procedures for running with cosmic muons and operating with the LHC were reviewed during the May electronics week. Firmware maintenance issues were also reviewed. Link tests between the new ECAL endcap trigger concentrator cards (TCC48) and the Regional Calorimeter Trigger have been performed. Firmware for the energy sum triggers and an upgraded tau trigger of the Global Calorimeter Triggers has been developed and is under test. The optical fiber receiver boards for the Track-Finder trigger theta links of the DT chambers are now all installed. The RPC trigger is being made more robust by additional chamber and cable shielding and also by firmware upgrades. For the CSC’s the front-end and trigger motherboard firmware have been updated. New RPC patterns and DT/CSC lookup tables taking into account phi asymmetries in the magnetic field configuration are under study. The motherboard for the new pipeline synchronizer of the Global Trigg...

2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

Science.gov (United States)

Miller, E. S.; Bates, R. A.; Koebel, D. A.; Fuchs, B. B.; Sonnenfeld, G.

1998-01-01

Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

Analysis of cytotoxic effects of chlorhexidine gluconate as antiseptic agent on human blood lymphocytes.

Science.gov (United States)

Salimi, Ahmad; Alami, Bahare; Pourahmad, Jalal

2017-08-01

The aim of this study was to assess the cytotoxicity of chlorhexidine gluconate (CHG) on human blood lymphocytes as a useful ex vivo model for accelerated human toxicity studies. Using biochemical and flow cytometry assessments, we demonstrated that addition of CHG at 1 μM concentration to human blood lymphocytes induced cytotoxicity following 6 h. The CHG-induced cytotoxicity on human blood lymphocytes was associated with intracellular reactive oxygen species generation, mitochondrial membrane potential collapse, lysosomal membrane injury, lipid peroxidation, and depletion of glutathione. According to our results, CHG triggers oxidative stress and organelles damages in lymphocytes which are important cells in defense against foreign agents. Finally our findings suggest that using of antioxidants and mitochondrial/lysosomal protective agents could be of benefit for the people in the exposure with CHG. © 2017 Wiley Periodicals, Inc.

The Role of Oxidative Stress in the Longevity and Insecticide Resistance Phenotype of the Major Malaria Vectors Anopheles arabiensis and Anopheles funestus.

Science.gov (United States)

Oliver, Shüné V; Brooke, Basil D

2016-01-01

Oxidative stress plays numerous biological roles, both functional and pathological. The role of oxidative stress in various epidemiologically relevant biological traits in Anopheles mosquitoes is not well established. In this study, the effects of oxidative stress on the longevity and insecticide resistance phenotype in the major malaria vector species An. arabiensis and An. funestus were examined. Responses to dietary copper sulphate and hydrogen peroxide were used as proxies for the oxidative stress phenotype by determining the effect of copper on longevity and hydrogen peroxide lethal dose. Glutathione peroxidase and catalase activities were determined colorimetrically. Oxidative burden was quantified as protein carbonyl content. Changes in insecticide resistance phenotype were monitored by WHO bioassay. Insecticide resistant individuals showed an increased capacity for coping with oxidative stress, mediated by increased glutathione peroxidase and catalase activity. This effect was observed in both species, as well as in laboratory strains and F1 individuals derived from wild-caught An. funestus mothers. Phenotypic capacity for coping with oxidative stress was greatest in strains with elevated Cytochrome P450 activity. Synergism of oxidative stress defence enzymes by dietary supplementation with haematin, 3-Amino-1, 2, 4-triazole and Sodium diethyldithiocarbamate significantly increased pyrethroid-induced mortality in An. arabiensis and An. funestus. It is therefore concluded that defence against oxidative stress underlies the augmentation of the insecticide resistance phenotype associated with multiple blood-feeding. This is because multiple blood-feeding ultimately leads to a reduction of oxidative stress in insecticide resistant females, and also reduces the oxidative burden induced by DDT and pyrethroids, by inducing increased glutathione peroxidase activity. This study highlights the importance of oxidative stress in the longevity and insecticide resistance

Inclusion of copepod Acartia tonsa nauplii in the feeding of Centropomus undecimalis larvae increases stress resistance

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Wanessa de Melo-Costa

2015-09-01

Full Text Available This research represents the first result of studies of the common snook Centropomus undecimalis larvae from broodstock matured in captivity in Brazil. The aim of this study was to evaluate if the inclusion of Acartia tonsa nauplii improves stress resistance of common snook larvae. The larvae were fed with: rotifers Brachionus plicatilis (10 to 15 mL-1; A. tonsa nauplii (0.25 to 0.5 mL-1 and rotifers (5 to 7.5 mL-1, and A. tonsa nauplii (0.12 to 0.25 mL-1. The average percentage of survival of the treatments was 11.9%. At 20 days of age, larvae were subjected to thermal stress. Subsequently, the stress resistance was evaluated. Common snook larvae fed B. plicatilis+A. tonsa reached a higher weight and length (7.5 ± 0.00 mg and 9.1 ± 0.23 mm, respectively and resisted more heat stress (87.4% than larvae fed other foods, indicating that the feed mixture is satisfactory as a starter diet for larvae of common snook. However, more research is needed to confirm these results.

Associations between the use of antimicrobial agents for growth promotion and the occurrence of resistance among Enterococcus faecium from broilers and pigs in Denmark, Finland, and Norway

DEFF Research Database (Denmark)

Aarestrup, Frank Møller; Kruse, H.; Tast, E.

2000-01-01

This study compares the susceptibility of Enterococcus faecium isolated from pigs and poultry in Denmark, Finland, and Norway to antimicrobial agents used for growth promotion. E. faecium was isolated from 211 broilers and 55 pigs in Denmark in 1997, from Norwegian 55 poultry farms (turkey and br......%) of the virginiamycin-resistant isolates from pigs in Denmark. This study indicates that the use of antimicrobial agents for growth promotion in Denmark, Finland, and Norway have selected for resistance to most of these drugs among E. faecium in food animals....... as resistant to monensin or salinomycin. In general, an association between the usage of antimicrobial agents in the respective countries and the occurrence of associated resistance was observed. Resistance to avilamycin was frequently observed among isolates from broilers in Denmark, where avilamycin has been...... used, whereas all isolates from Finland and Norway, where these drugs have not been used, were susceptible. The same phenomenon could be observed for avoparcin, bacitracin, tylosin, and virginiamycin; resistance was frequently observed among isolates from where these antimicrobials have been widely...

Tidal triggering of earthquakes suggests poroelastic behavior on the San Andreas Fault

International Nuclear Information System (INIS)

Delorey, Andrew A.; Elst, Nicholas J. van der; Johnson, Paul Allan

2016-01-01

Tidal triggering of earthquakes is hypothesized to provide quantitative information regarding the fault's stress state, poroelastic properties, and may be significant for our understanding of seismic hazard. To date, studies of regional or global earthquake catalogs have had only modest successes in identifying tidal triggering. We posit that the smallest events that may provide additional evidence of triggering go unidentified and thus we developed a technique to improve the identification of very small magnitude events. We identify events applying a method known as inter-station seismic coherence where we prioritize detection and discrimination over characterization. Here we show tidal triggering of earthquakes on the San Andreas Fault. We find the complex interaction of semi-diurnal and fortnightly tidal periods exposes both stress threshold and critical state behavior. Lastly, our findings reveal earthquake nucleation processes and pore pressure conditions – properties of faults that are difficult to measure, yet extremely important for characterizing earthquake physics and seismic hazards.

Tidal triggering of earthquakes suggests poroelastic behavior on the San Andreas Fault

Science.gov (United States)

Delorey, Andrew; Van Der Elst, Nicholas; Johnson, Paul

2017-01-01

Tidal triggering of earthquakes is hypothesized to provide quantitative information regarding the fault's stress state, poroelastic properties, and may be significant for our understanding of seismic hazard. To date, studies of regional or global earthquake catalogs have had only modest successes in identifying tidal triggering. We posit that the smallest events that may provide additional evidence of triggering go unidentified and thus we developed a technique to improve the identification of very small magnitude events. We identify events applying a method known as inter-station seismic coherence where we prioritize detection and discrimination over characterization. Here we show tidal triggering of earthquakes on the San Andreas Fault. We find the complex interaction of semi-diurnal and fortnightly tidal periods exposes both stress threshold and critical state behavior. Our findings reveal earthquake nucleation processes and pore pressure conditions – properties of faults that are difficult to measure, yet extremely important for characterizing earthquake physics and seismic hazards.

Insulin resistance and its possible personal stress moderators

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Oleg G. Motovilin

2017-08-01

Full Text Available Background. Recently, insulin resistance (IR has been actively investigated by experts in various fields. Here we aim to study the effect of stress on the development of IR. Objective. To study the associations between IR and personal stress moderators (self-attitude, locus of control and coping strategies as well as the related performance lifestyles. Methods. The study included 63 patients (16 men; mean age, 48.2 ± 11.7 years. Of these participants, 26 were diagnosed with type 2 diabetes mellitus, 10 with impaired glucose tolerance, 6 with impaired fasting glucose and 21 with normal glucose tolerance. The levels of HbA1c and IR ratio were determined using HOMA. Well-known psychological assessment questionnaires were used to assess the effect of personal stress moderators. Results. There was a significant relationship between IR and personal stress moderators. A positive self-attitude was associated with a lower risk of IR (p < 0.05, which can be explained by a decrease in the risk of developing stress. Assertive coping strategies were most pronounced in subjects with a low level of IR (p < 0.05. Personal characteristics also determined an individual’s lifestyle, which may have an impact on the increase in IR. There was an association between high levels of IR and unhealthy alimentary preferences (p < 0.05. Such preferences were also associated with personal characteristics, such as external locus of control, less positive self-attitude and passive coping strategies (p < 0.05. People with high IR rarely engage in a regular physical activity; there was a direct correlation between the frequency of physical activity and assertive coping strategies (p < 0.01. Married participants had high levels of IR (p < 0.05. Conclusion. There were significant relationships between IR and personal stress moderators, such as self-attitude and coping strategies. Besides the direct effects on stress levels, personality traits may also indirectly increase the

Effect of aspartic acid and glutamate on metabolism and acid stress resistance of Acetobacter pasteurianus.

Science.gov (United States)

Yin, Haisong; Zhang, Renkuan; Xia, Menglei; Bai, Xiaolei; Mou, Jun; Zheng, Yu; Wang, Min

2017-06-15

Acetic acid bacteria (AAB) are widely applied in food, bioengineering and medicine fields. However, the acid stress at low pH conditions limits acetic acid fermentation efficiency and high concentration of vinegar production with AAB. Therefore, how to enhance resistance ability of the AAB remains as the major challenge. Amino acids play an important role in cell growth and cell survival under severe environment. However, until now the effects of amino acids on acetic fermentation and acid stress resistance of AAB have not been fully studied. In the present work the effects of amino acids on metabolism and acid stress resistance of Acetobacter pasteurianus were investigated. Cell growth, culturable cell counts, acetic acid production, acetic acid production rate and specific production rate of acetic acid of A. pasteurianus revealed an increase of 1.04, 5.43, 1.45, 3.30 and 0.79-folds by adding aspartic acid (Asp), and cell growth, culturable cell counts, acetic acid production and acetic acid production rate revealed an increase of 0.51, 0.72, 0.60 and 0.94-folds by adding glutamate (Glu), respectively. For a fully understanding of the biological mechanism, proteomic technology was carried out. The results showed that the strengthening mechanism mainly came from the following four aspects: (1) Enhancing the generation of pentose phosphates and NADPH for the synthesis of nucleic acid, fatty acids and glutathione (GSH) throughout pentose phosphate pathway. And GSH could protect bacteria from low pH, halide, oxidative stress and osmotic stress by maintaining the viability of cells through intracellular redox equilibrium; (2) Reinforcing deamination of amino acids to increase intracellular ammonia concentration to maintain stability of intracellular pH; (3) Enhancing nucleic acid synthesis and reparation of impaired DNA caused by acid stress damage; (4) Promoting unsaturated fatty acids synthesis and lipid transport, which resulted in the improvement of cytomembrane

Agentes bacterianos enteropatogênicos em suínos de diferentes faixas etárias e perfil de resistência a antimicrobianos de cepas de Escherichia coli e Salmonella spp Enteropathogenic bacterial agents in pigs of different age groups and profile of resistance in strains of Escherichia coli and Salmonella spp. to antimicrobial agents

Directory of Open Access Journals (Sweden)

Álvaro Menin

2008-09-01

Full Text Available As enterites infecciosas bacterianas provocam severas perdas para a indústria suína em todo o mundo. Os objetivos deste trabalho foram determinar os agentes bacterianos, associados com a ocorrência de diarréia em suínos, em diferentes faixas etárias, no Estado de Santa Catarina, Brasil, e verificar o perfil de resistência das cepas de Escherichia coli e Salmonella spp, frente aos principais antimicrobianos utilizados em granjas de suínos. Os principais gêneros/espécies bacterianos diagnosticados foram Escherichia coli, Clostridium spp, Salmonella spp Brachyspira hyodysenteriae, Brachyspira pilosicoli e Lawsonia intracellularis. Os fatores de virulência de E. coli mais prevalentes na fase de maternidade foram F5 / (K99 20%, F6 / (987P 16,3%, F42 6,8% e F41 5,7%, já nas fases de creche e terminação, predominaram cepas com fimbrias F4 (K88 11,2% e 5,4%, respectivamente. Para E. coli os maiores índices de resistência foram encontrados para oxitetraciclina (94% e tetraciclina (89,5% e os menores índices de resistência para neomicina (55%, ceftiofur (57,4%. Quanto às amostras de Salmonella spp, estas apresentaram maior resistência à oxitetraciclina (77%, e à tetraciclina (42,1% e menor à gentamicina (3,5% e amoxicilina (4,8%.Infectious bacterial enteritis causes severe losses to the swine industry worldwide. The objective of this study was to determine the epidemiology of bacterial agents that are associated with the occurrence of diarrhea in pigs at different age groups, and to verify the profile of resistance of strains of Escherichia coli and Salmonella spp to the main antimicrobial agents. The main bacterial species diagnosed were Escherichia coli, Clostridium spp, Salmonella spp, Brachyspira hyodysenteriae, Brachyspira pilosicoli and Lawsonia intracellularis. The E. coli virulence factors of higher prevalence in preweaning piglets were F5 / (K99 20%, F6 / (987P 16.3%, F42 6.8% and F41 5.7%, whereas at the nursery and with