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Sample records for markedly increased resistance

  1. A radioattenuated Leishmania major vaccine markedly increases the resistance of CBA mice to subsequent infection with Leishmania mexicana mexicana

    International Nuclear Information System (INIS)

    Alexander, J.

    1982-01-01

    Vaccinating CBA mice with radioattenuated Leishmania major amastigotes but not with radioattenuated L. mexicana amastigotes rendered them highly resistant to subsequent infection with L. m. mexicana. Unvaccinated CBA mice were highly susceptible to infection with L. m. mexicana producing rapidly growing non-ulcerating cutaneous lesions. Two manifestations of resistance were induced in vaccinated animals depending on the timing of the challenge infection: no lesions appeared at the site of subcutaneous challenge in animals vaccinated four or more weeks previously, while lesions grew rapidly but ulcerated and healed in animals vaccinated less than 3 weeks beforehand. L. major amastigotes were found to be markedly more resistant to γ irradiation than L. m.mexicana amastigotes both as measured by their ability to infect susceptible strains of mice and to transform and multiply as promastigotes in NNN medium. (author)

  2. Electromigration early resistance increase measurements

    NARCIS (Netherlands)

    Niehof, J.; Flinn, P.A.; Maloney, T.J.

    1993-01-01

    An early resistance change measurement set-up, using an AC bridge technique, has been developed, and measurements have been performed. Large sample-to-sample variations occur. The characteristic time for the resistance change curve is shorter for resistance increase (under current stress) than for

  3. Cold thyroid nodules show a marked increase in proliferation markers.

    Science.gov (United States)

    Krohn, Knut; Stricker, Ingo; Emmrich, Peter; Paschke, Ralf

    2003-06-01

    Thyroid follicular adenomas and adenomatous thyroid nodules are a frequent finding in geographical areas with iodine deficiency. They occur as hypofunctioning (scintigraphically cold) or hyperfunctioning (scintigraphically hot) nodules. Their predominant clonal origin suggests that they result from clonal expansion of a single cell, which is very likely the result of a prolonged increase in proliferation compared with non-affected surrounding cells. To test whether increased cell proliferation is detectable in cold thyroid nodules, we studied paraffin-embedded tissue from 40 cold thyroid nodules and their surrounding normal thyroid tissue for the occurrence of the proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1 antibody) epitopes as markers for cell proliferation. All 40 thyroid nodules were histologically well characterized and have been studied for molecular characteristics before. The labeling index (number of labeled cells versus total cell number) for nodular and surrounding tissue was calculated. In 33 cold thyroid nodules a significant (p thyroid nodules a significant (p thyroid epithelial cell proliferation is a uniform feature common to most cold nodules. However, the increase of proliferation markers shows a heterogeneity that is not correlated with histopathologic, molecular, or clinical characteristics.

  4. EXPERIMENTAL VERIFICATION OF THE MECHANICAL RESISTANCE OF FORENSIC MARKING BY MEANS SYNTHETIC DNA

    Directory of Open Access Journals (Sweden)

    Marek HÜTTER

    2017-06-01

    Full Text Available This article deals with experimental verification of resistance of forensic identification marks (microdots in combination with artificial DNA to property. It is considered mechanical abrasion from potential offender to remove or damage readability of marking and following identification. The aim of this work is to test the hypothesis that forensic marking can be completely removed by the process of mechanical abrasion without causing damages to a protected object. To fulfill this purpose it was designed and built a test equipment, where experiments were carried out to confirm or refute the above mentioned hypothesis.

  5. Antibiotic resistance increases with local temperature

    Science.gov (United States)

    MacFadden, Derek R.; McGough, Sarah F.; Fisman, David; Santillana, Mauricio; Brownstein, John S.

    2018-06-01

    Bacteria that cause infections in humans can develop or acquire resistance to antibiotics commonly used against them1,2. Antimicrobial resistance (in bacteria and other microbes) causes significant morbidity worldwide, and some estimates indicate the attributable mortality could reach up to 10 million by 20502-4. Antibiotic resistance in bacteria is believed to develop largely under the selective pressure of antibiotic use; however, other factors may contribute to population level increases in antibiotic resistance1,2. We explored the role of climate (temperature) and additional factors on the distribution of antibiotic resistance across the United States, and here we show that increasing local temperature as well as population density are associated with increasing antibiotic resistance (percent resistant) in common pathogens. We found that an increase in temperature of 10 °C across regions was associated with an increases in antibiotic resistance of 4.2%, 2.2%, and 2.7% for the common pathogens Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The associations between temperature and antibiotic resistance in this ecological study are consistent across most classes of antibiotics and pathogens and may be strengthening over time. These findings suggest that current forecasts of the burden of antibiotic resistance could be significant underestimates in the face of a growing population and climate change4.

  6. Ethanologenic bacteria with increased resistance to furfural

    Science.gov (United States)

    Miller, Elliot Norman; Jarboe, Laura R.; Yomano, Lorraine P.; York, Sean W.; Shanmugam, Keelnatham; Ingram, Lonnie O'Neal

    2015-10-06

    The invention relates to bacterium that have increased resistance to furfural and methods of preparation. The invention also relates to methods of producing ethanol using the bacterium and corresponding kits.

  7. Marked increase in leptospirosis infections in humans and dogs in the Netherlands, 2014

    NARCIS (Netherlands)

    Pijnacker, Roan; Goris, M.G.; Wierik, te M.J.; Broens, E.M.; Giessen, van der J.W.; Rosa, de M.; Wagenaar, J.A.; Hartskeerl, R.A.; Notermans, D.W.; Maassen, K.; Schimmer, B.

    2016-01-01

    In the Netherlands, 97 human leptospirosis cases were notified in 2014. This represents a 4.6-fold increase in autochthonous cases (n = 60) compared with the annual average between 2010 and 2013. Most cases had symptom onset between June and November. This marked increase in humans coincided with

  8. Marked increase in leptospirosis infections in humans and dogs in the Netherlands, 2014

    NARCIS (Netherlands)

    Pijnacker, Roan; Goris, Marga G. A.; te Wierik, Margreet J. M.; Broens, Els M.; van der Giessen, Joke W. B.; de Rosa, Mauro; Wagenaar, Jaap A.; Hartskeerl, Rudy A.; Notermans, Daan W.; Maassen, Kitty; Schimmer, Barbara

    2016-01-01

    In the Netherlands, 97 human leptospirosis cases were notified in 2014. This represents a 4.6-fold increase in autochthonous cases (n = 60) compared with the annual average between 2010 and 2013. Most cases had symptom onset between June and November. This marked increase in humans coincided with an

  9. Meal ingestion markedly increases liver stiffness suggesting the need for liver stiffness determination in fasting conditions.

    Science.gov (United States)

    Alvarez, Daniel; Orozco, Federico; Mella, José María; Anders, Maria; Antinucci, Florencia; Mastai, Ricardo

    2015-01-01

    The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. We evaluated the effect of food intake on LS in patients with different degrees of liver disease. We evaluated 24 patients (F≤1, n=11 and F> 1, n=13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30min after ingestion of a standard liquid meal. Food intake increased PBF (51±10%, p1). Hemodynamic and LS values returned to baseline pre-meal levels within 2hours. LS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  10. Skin markings in external radiotherapy by temporary tattooing with henna: Improvement of accuracy and increased patient comfort

    International Nuclear Information System (INIS)

    Wurstbauer, Karl; Sedlmayer, Felix; Kogelnik, H. Dieter

    2001-01-01

    Purpose: To guarantee invariable skin markings in patients undergoing a course of external radiotherapy, especially using conformal techniques. Cutaneous markings with henna also increase patient comfort, because washing and showering are allowed. Methods and Materials: Henna, a completely natural product, is a skin colorant with a history of 5,000 years. It is applied to the skin in the form of a paste. While drying, henna stains the superficial skin layers for several weeks, and the marked area can be exposed to water arbitrarily. In case of fading of the stain before the end of radiotherapy, the marking procedure can be repeated. From November 1998 until March 2000, we performed skin markings with henna in 158 patients with different tumor sites. The majority of patients received conformal radiotherapy techniques. All patients have been evaluated concerning durability of the markings, the required number of marking procedures per treatment course, and possible related side effects. Results: The median durability of henna staining is 23 days (range 12-48 days). On average, two marking procedures (range 1-4) are necessary for a patient treated with curative intent. Although washing and showering are freely permitted, no adverse cutaneous side effects (e.g., erythema, allergic reactions) have been observed. Conclusions: Skin marking by temporary tattooing with henna increases the accuracy of external radiotherapy. It yields stable and invariable markings for the entire course of radiotherapy and also increases the comfort of patients

  11. Age-associated increase in heterochromatic marks in murine and primate tissues.

    Science.gov (United States)

    Kreiling, Jill A; Tamamori-Adachi, Mimi; Sexton, Alec N; Jeyapalan, Jessie C; Munoz-Najar, Ursula; Peterson, Abigail L; Manivannan, Jayameenakshi; Rogers, Elizabeth S; Pchelintsev, Nikolay A; Adams, Peter D; Sedivy, John M

    2011-04-01

    Chromatin is highly dynamic and subject to extensive remodeling under many physiologic conditions. Changes in chromatin that occur during the aging process are poorly documented and understood in higher organisms, such as mammals. We developed an immunofluorescence assay to quantitatively detect, at the single cell level, changes in the nuclear content of chromatin-associated proteins. We found increased levels of the heterochromatin-associated proteins histone macro H2A (mH2A) and heterochromatin protein 1 beta (HP1β) in human fibroblasts during replicative senescence in culture, and for the first time, an age-associated increase in these heterochromatin marks in several tissues of mice and primates. Mouse lung was characterized by monophasic mH2A expression histograms at both ages, and an increase in mean staining intensity at old age. In the mouse liver, we observed increased age-associated localization of mH2A to regions of pericentromeric heterochromatin. In the skeletal muscle, we found two populations of cells with either low or high mH2A levels. This pattern of expression was similar in mouse and baboon, and showed a clear increase in the proportion of nuclei with high mH2A levels in older animals. The frequencies of cells displaying evidence of increased heterochromatinization are too high to be readily accounted for by replicative or oncogene-induced cellular senescence, and are prominently found in terminally differentiated, postmitotic tissues that are not conventionally thought to be susceptible to senescence. Our findings distinguish specific chromatin states in individual cells of mammalian tissues, and provide a foundation to investigate further the progressive epigenetic changes that occur during aging. © 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

  12. Knee joint passive stiffness and moment in sagittal and frontal planes markedly increase with compression.

    Science.gov (United States)

    Marouane, H; Shirazi-Adl, A; Adouni, M

    2015-01-01

    Knee joints are subject to large compression forces in daily activities. Due to artefact moments and instability under large compression loads, biomechanical studies impose additional constraints to circumvent the compression position-dependency in response. To quantify the effect of compression on passive knee moment resistance and stiffness, two validated finite element models of the tibiofemoral (TF) joint, one refined with depth-dependent fibril-reinforced cartilage and the other less refined with homogeneous isotropic cartilage, are used. The unconstrained TF joint response in sagittal and frontal planes is investigated at different flexion angles (0°, 15°, 30° and 45°) up to 1800 N compression preloads. The compression is applied at a novel joint mechanical balance point (MBP) identified as a point at which the compression does not cause any coupled rotations in sagittal and frontal planes. The MBP of the unconstrained joint is located at the lateral plateau in small compressions and shifts medially towards the inter-compartmental area at larger compression forces. The compression force substantially increases the joint moment-bearing capacities and instantaneous angular rigidities in both frontal and sagittal planes. The varus-valgus laxities diminish with compression preloads despite concomitant substantial reductions in collateral ligament forces. While the angular rigidity would enhance the joint stability, the augmented passive moment resistance under compression preloads plays a role in supporting external moments and should as such be considered in the knee joint musculoskeletal models.

  13. Evolution of methicillin-resistant Staphylococcus aureus towards increasing resistance

    DEFF Research Database (Denmark)

    Strommenger, Birgit; Bartels, Mette Damkjær; Kurt, Kevin

    2014-01-01

    To elucidate the evolutionary history of Staphylococcus aureus clonal complex (CC) 8, which encompasses several globally distributed epidemic lineages, including hospital-associated methicillin-resistant S. aureus (MRSA) and the highly prevalent community-associated MRSA clone USA300.......To elucidate the evolutionary history of Staphylococcus aureus clonal complex (CC) 8, which encompasses several globally distributed epidemic lineages, including hospital-associated methicillin-resistant S. aureus (MRSA) and the highly prevalent community-associated MRSA clone USA300....

  14. Increasing Incidence of Linezolid-Intermediate or -Resistant, Vancomycin-Resistant Enterococcus faecium Strains Parallels Increasing Linezolid Consumption▿

    OpenAIRE

    Scheetz, Marc H.; Knechtel, Stephanie A.; Malczynski, Michael; Postelnick, Michael J.; Qi, Chao

    2008-01-01

    Clinical enterococcal resistance to linezolid is defined by the presence of the G2576T mutation. We evaluated the incidence of genetically proven linezolid resistance among vancomycin-resistant Enterococcus faecium strains and linezolid consumption for a possible association. A relationship was found (r2 = 0.73, P = 0.03) and predicts increasing resistance with current trends of linezolid use.

  15. IAEA and WANO Mark Anniversary of Fukushima Accident, Increase Cooperation, 5 March 2012, Vienna/London

    International Nuclear Information System (INIS)

    2012-01-01

    Full text: Next Sunday, 11 March 2012, marks the first anniversary of the devastating earthquake and tsunami that struck the east coast of Japan. One year on, the International Atomic Energy Agency (IAEA) and the World Association of Nuclear Operators (WANO) are increasing their mutual cooperation to maximise nuclear safety efforts around the globe. The two organisations are revising their Memorandum of Understanding in light of the lessons learned from the Fukushima accident, and will be stepping up their efforts to share expertise and knowledge between operators and governments. There will be greater coordination between WANO peer reviews and IAEA OSART missions, in which international experts assess the safety of individual nuclear power plants, and discussions are under way to examine further areas to improve information sharing. This is in addition to the other work each organisation is doing to reinforce nuclear safety worldwide. IAEA Director General, Yukiya Amano said: 'The IAEA is delighted to strengthen its coordination and cooperation with WANO. One of the lessons of Fukushima is the need for strong and effective communication between governments, regulators and nuclear operators. The IAEA's Action Plan on Nuclear Safety underlines the need for all stakeholders to work together to put these lessons into practice as tangibly and swiftly as possible, to deliver concrete results. By working more closely together, we can help to ensure that practical experience is properly shared to reinforce nuclear safety everywhere'. Laurent Stricker, Chairman of WANO, commented: 'While the terrible events of last year had a major lasting impact on the industry, they have also served as the catalyst for huge change. WANO has shifted from primarily focusing on accident prevention, to an emphasis on both prevention and mitigation, and has redoubled its efforts to promote excellence in nuclear safety in each and every plant across the world. All nuclear plants have carefully

  16. Influence of femtosecond laser marking on the corrosion resistance of stainless steels

    International Nuclear Information System (INIS)

    Valette, S.; Steyer, P.; Richard, L.; Forest, B.; Donnet, C.; Audouard, E.

    2006-01-01

    Marking is of prime importance in the field of biomaterials to allow the identification of surgical tools as well as prostheses. Nowadays, marking is often achieved by means of laser beam, which may modify the characteristics of the treated surfaces. The use of laser devices delivering nanosecond pulses is known to induce dramatic corrosion degradations during sterilization or decontamination processes of the biomaterials. The aim of the present study is to investigate the ability of femtosecond (pulse duration in the 10 -15 s range) laser treatments to avoid preferential corrosion processes of the marked areas, in order to extend the durability and the reliability of biomaterials. Experiments have been performed on martensitic Z30C13 and austenitic 316L stainless steels. Electrochemical measurements (cyclic polarization curves) were carried out to determine the passive state of samples before and after engraving, their corrosion rate and their susceptibility to localized corrosion. Further protracted immersion tests were also carried out to evaluate the natural long-term degradation of engraved parts. The electrochemical behavior is then explained on the basis of surface characterizations. Femtosecond laser marking is shown to provide an electrochemical ennoblement. Moreover, the chemical composition is not affected so that the passive character of both stainless steels is maintained, even improved if we consider the susceptibility to localized corrosion

  17. Total and cause-specific mortality by moderately and markedly increased ferritin concentrations

    DEFF Research Database (Denmark)

    Ellervik, Christina; Marott, Jacob Louis; Tybjærg-Hansen, Anne

    2014-01-01

    . Stepwise increasing concentrations of ferritin were associated with a stepwise increased risk of premature death overall (log rank, P = 2 × 10(-22)), with median survival of 55 years at ferritin concentrations ≥600 μg/L, 72 years at 400-599 μg/L, 76 years at 200-399 μg/L, and 79 years at ferritin

  18. Increasing quinolone resistance in Salmonella enterica serotype enteritidis

    DEFF Research Database (Denmark)

    Mølbak, K.; Gerner-Smidt, P.; Wegener, Henrik Caspar

    2002-01-01

    Until recently, Salmonella enterica serotype Enteritidis has remained sensitive to most antibiotics. However, national surveillance data from Denmark show that quinolone resistance in S. Enteritidis has increased from 0.8% in 1995 to 8.5% in 2000. These data support concerns that the current use...... of quinolone in food animals leads to increasing resistance in S. Enteritidis and that action should be taken to limit such use....

  19. Increased radiation resistance in lithium-counterdoped silicon solar cells

    Science.gov (United States)

    Weinberg, I.; Swartz, C. K.; Mehta, S.

    1984-01-01

    Lithium-counterdoped n(+)p silicon solar cells are found to exhibit significantly increased radiation resistance to 1-MeV electron irradiation when compared to boron-doped n(+)p silicon solar cells. In addition to improved radiation resistance, considerable damage recovery by annealing is observed in the counterdoped cells at T less than or equal to 100 C. Deep level transient spectroscopy measurements are used to identify the defect whose removal results in the low-temperature aneal. It is suggested that the increased radiation resistance of the counterdoped cells is primarily due to interaction of the lithium with interstitial oxygen.

  20. Steam drying compared to drum drying markedly increases early phase rumen fermentability of sugar beet pulp

    DEFF Research Database (Denmark)

    Nielsen, Mette Olaf; Larsen, Kasper; Jensen, Arne Sloth

    2017-01-01

    Freshly pressed and dried sugar beet pulp was sampled from 2 different factories located within a distance of 30 km and on 4 different dates. One factory was equipped with a steam dryer and the other with a drum dryer. A recognized in vitro technique was used to establish, how the drying process...... affected rumen fermentability of the pulp, since fibrous feeds (such as sugar beet pulp) rely on microbial fermentation in the rumen to be digestible to the cow. Steam dried pulp had a remarkable >60% higher fermentability compared to drum dried pulp during the first 12(-15) hours of fermentation...... (such as pectin) and small particles as low as 6.7-13.3 hours. Future feeding trials are needed to establish exactly how much the feeding value is increased in steam dried sugar beet pulp....

  1. Elastic Resistance Effectiveness on Increasing Strength of Shoulders and Hips.

    Science.gov (United States)

    Picha, Kelsey J; Almaddah, Muataz R; Barker, Jordan; Ciochetty, Tavis; Black, W Scott; Uhl, Tim L

    2017-09-12

    Elastic resistance is a common training method used to gain strength. Currently, progression with elastic resistance is based on the perceived exertion of the exercise or completion of targeted repetitions; exact resistance is typically unknown. This study's objective is to determine if knowledge of load during elastic resistance exercise will increase strength gains during exercises. Participants were randomized into two strength training groups, elastic resistance only and elastic resistance using a load cell (LC) that displays force during exercise. The LC group used a Smart Handle (Patterson Medical Supply, Chicago, IL) to complete all exercises. Each participant completed the same exercises three times weekly for 8 weeks. The LC group was provided with a set load for exercises whereas the elastic resistance only group was not. Participant's strength was tested at baseline and program completion, measuring isometric strength for shoulder abduction (SAb), shoulder external rotation (SER), hip abduction (HAb), and hip extension (HEx). Independent t-tests were used to compare the normalized torques between groups. No significant differences were found between groups. Shoulder strength gains did not differ between groups (SAb p>0.05; SER p>0.05). Hip strength gains did not differ between groups (HAb p>0.05; HEx p>0.05). Both groups increased strength due to individual supervision, constantly evaluating degree of difficulty associated with exercise and providing feedback while using elastic resistance. Using a LC is as effective as supervised training and could provide value in a clinic setting when patients are working unsupervised.

  2. Increased complement C1q level marks active disease in human tuberculosis.

    Directory of Open Access Journals (Sweden)

    Yi Cai

    Full Text Available BACKGROUND: Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis. METHODS: Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy. RESULTS: C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α. CONCLUSIONS: C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy.

  3. Approaches to a markedly increased sensitivity of the radioimmunoassay for thyrotropin-releasing hormone by derivatization

    Energy Technology Data Exchange (ETDEWEB)

    Visser, T J; Klootwijk, W [Erasmus Universiteit, Rotterdam (Netherlands). Dept. of Internal Medicine 3 and Clinical Endocrinology

    1981-04-03

    Studies on the specificity of the antisera obtained suggested that the sensitivity of the radioimmunoassay for TRH may be increased substantially by prior conversion of the hormone into dinitrophenylene derivatives. To test this possibility, several TRH-Dnp derivatives were prepared by reaction of TRH with equimolar amounts of 1,5-difluoro-2,4-dinitrobenzene yielding N/sup im/-(5-fluoro-2,4-dinitrophenyl)TRH. This intermediate was reacted with ammonia, histamine, tyramine or N/sup ..cap alpha../-acetyl-lysine methyl ester (N/sup ..cap alpha../Ac-LysOMe) to yield the respective unsubstituted and N-substituted N/sup im/-(5-amino-2,4-dinitrophenyl)TRH derivatives: TRH-Dnp-NH/sub 2/, TRH-Dnp-histamine, TRH-Dnp-tyramine and TRH-Dnp-N/sup ..cap alpha../Ac-Lys-OMe. N/sup im/-(2,4-Dinitrophenyl)TRH was prepared similarly by reaction of TRH with 1-fluoro-2,4-dinitrobenzene. The products were isolated by means of high-performance liquid chromatography (HPLC) and were found to be pure by HPLC and thin-layer chromatography using several solvent systems. TRH-Dnp-histamine and TRH-Dnp-tyramine were labelled with /sup 125/I using the chloramine-T method. The labelled products were purified to homogeneity by ion-exchange chromography on SP-Sephadex and adsorption chromatography on Sephadex LH-20, respectively, and were found by HPLC to be pure.

  4. 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.

  5. Biodiversity increases the resistance of ecosystem productivity to climate extremes.

    Science.gov (United States)

    Isbell, Forest; Craven, Dylan; Connolly, John; Loreau, Michel; Schmid, Bernhard; Beierkuhnlein, Carl; Bezemer, T Martijn; Bonin, Catherine; Bruelheide, Helge; de Luca, Enrica; Ebeling, Anne; Griffin, John N; Guo, Qinfeng; Hautier, Yann; Hector, Andy; Jentsch, Anke; Kreyling, Jürgen; Lanta, Vojtěch; Manning, Pete; Meyer, Sebastian T; Mori, Akira S; Naeem, Shahid; Niklaus, Pascal A; Polley, H Wayne; Reich, Peter B; Roscher, Christiane; Seabloom, Eric W; Smith, Melinda D; Thakur, Madhav P; Tilman, David; Tracy, Benjamin F; van der Putten, Wim H; van Ruijven, Jasper; Weigelt, Alexandra; Weisser, Wolfgang W; Wilsey, Brian; Eisenhauer, Nico

    2015-10-22

    It remains unclear whether biodiversity buffers ecosystems against climate extremes, which are becoming increasingly frequent worldwide. Early results suggested that the ecosystem productivity of diverse grassland plant communities was more resistant, changing less during drought, and more resilient, recovering more quickly after drought, than that of depauperate communities. However, subsequent experimental tests produced mixed results. Here we use data from 46 experiments that manipulated grassland plant diversity to test whether biodiversity provides resistance during and resilience after climate events. We show that biodiversity increased ecosystem resistance for a broad range of climate events, including wet or dry, moderate or extreme, and brief or prolonged events. Across all studies and climate events, the productivity of low-diversity communities with one or two species changed by approximately 50% during climate events, whereas that of high-diversity communities with 16-32 species was more resistant, changing by only approximately 25%. By a year after each climate event, ecosystem productivity had often fully recovered, or overshot, normal levels of productivity in both high- and low-diversity communities, leading to no detectable dependence of ecosystem resilience on biodiversity. Our results suggest that biodiversity mainly stabilizes ecosystem productivity, and productivity-dependent ecosystem services, by increasing resistance to climate events. Anthropogenic environmental changes that drive biodiversity loss thus seem likely to decrease ecosystem stability, and restoration of biodiversity to increase it, mainly by changing the resistance of ecosystem productivity to climate events.

  6. Increased corrosion resistance of basalt reinforced cement compositions with nanosilica

    Directory of Open Access Journals (Sweden)

    URKHANOVA Larisa Alekseevna

    2014-08-01

    Full Text Available Disperse fiber reinforcement is used to improve deformation and shrinkage characteristics, flexural strength of concrete. Basalt roving and thin staple fiber are often used as mineral fibers. The paper considers the problems of using thin basalt fiber produced by centrifugal-blow method. Evaluation of the corrosion resistance of basalt fiber as part of the cement matrix was performed. Nanodispersed silica produced by electron beam accelerator was used to increase corrosion resistance of basalt fiber.

  7. Increased corrosion resistance of basalt reinforced cement compositions with nanosilica

    OpenAIRE

    URKHANOVA Larisa Alekseevna; LKHASARANOV Solbon Aleksandrovich; ROZINA Victoria Yevgenievna; BUYANTUEV Sergey Lubsanovich; BARDAKHANOV Sergey Prokopievich

    2014-01-01

    Disperse fiber reinforcement is used to improve deformation and shrinkage characteristics, flexural strength of concrete. Basalt roving and thin staple fiber are often used as mineral fibers. The paper considers the problems of using thin basalt fiber produced by centrifugal-blow method. Evaluation of the corrosion resistance of basalt fiber as part of the cement matrix was performed. Nanodispersed silica produced by electron beam accelerator was used to increase corrosion resistance of ba...

  8. The Nuclear Receptor, Nor-1, Markedly Increases Type II Oxidative Muscle Fibers and Resistance to Fatigue

    OpenAIRE

    Pearen, Michael A.; Eriksson, Natalie A.; Fitzsimmons, Rebecca L.; Goode, Joel M.; Martel, Nick; Andrikopoulos, Sofianos; Muscat, George E. O.

    2012-01-01

    Nuclear hormone receptors (NR) have been implicated as regulators of lipid and carbohydrate metabolism. The orphan NR4A subgroup has emerged as regulators of metabolic function. Targeted silencing of neuron-derived orphan receptor 1 (Nor-1)/NR4A3 in skeletal muscle cells suggested that this NR was necessary for oxidative metabolism in vitro. To investigate the in vivo role of Nor-1, we have developed a mouse model with preferential expression of activated Nor-1 in skeletal muscle. In skeletal...

  9. Marked Increase in Flow Velocities During Deep Expiration: A Duplex Doppler Sign of Celiac Artery Compression Syndrome

    International Nuclear Information System (INIS)

    Erden, Ayse; Yurdakul, Mehmet; Cumhur, Turhan

    1999-01-01

    Symptoms of chronic mesenteric ischemia develop when the celiac artery is constricted by the median arcuate ligament of the diaphragm. Lateral aortography is the primary modality for diagnosing ligamentous compression of the celiac artery. However, duplex Doppler sonography performed during deep expiration can cause a marked increase in flow velocities at the compressed region of the celiac artery and suggest the diagnosis of celiac arterial constriction due to the diaphragmatic ligament. RID='''' ID='''' Correspondence to: A. Erden, M.D., Hafta sokak. 23/6, Gaziosmanpasa, 06700 Ankara, Turkey

  10. Marked increase in rat red blood cell membrane protein glycosylation by one-month treatment with a cafeteria diet

    Directory of Open Access Journals (Sweden)

    Laia Oliva

    2015-07-01

    Full Text Available Background and Objectives. Glucose, an aldose, spontaneously reacts with protein amino acids yielding glycosylated proteins. The compounds may reorganize to produce advanced glycosylation products, which regulatory importance is increasingly being recognized. Protein glycosylation is produced without the direct intervention of enzymes and results in the loss of function. Glycosylated plasma albumin, and glycosylated haemoglobin are currently used as index of mean plasma glucose levels, since higher glucose availability results in higher glycosylation rates. In this study we intended to detect the early changes in blood protein glycosylation elicited by an obesogenic diet.Experimental Design. Since albumin is in constant direct contact with plasma glucose, as are the red blood cell (RBC membranes, we analyzed their degree or glycosylation in female and male rats, either fed a standard diet or subjected to a hyper-energetic self-selected cafeteria diet for 30 days. This model produces a small increase in basal glycaemia and a significant increase in body fat, leaving the animals in the initial stages of development of metabolic syndrome. We also measured the degree of glycosylation of hemoglobin, and the concentration of glucose in contact with this protein, that within the RBC. Glycosylation was measured by colorimetric estimation of the hydroxymethylfurfural liberated from glycosyl residues by incubation with oxalate.Results. Plasma glucose was higher in cafeteria diet and in male rats, both independent effects. However, there were no significant differences induced by sex or diet in either hemoglobin or plasma proteins. Purified RBC membranes showed a marked effect of diet: higher glycosylation in cafeteria rats, which was more marked in females (not in controls. In any case, the number of glycosyl residues per molecule were higher in hemoglobin than in plasma proteins (after correction for molecular weight. The detected levels of glucose in

  11. Clarithromycin increases linezolid exposure in multidrug-resistant tuberculosis patients

    NARCIS (Netherlands)

    Bolhuis, Mathieu S.; van Altena, Richard; van Soolingen, Dick; de Lange, Wiel C. M.; Uges, Donald R. A.; van der Werf, Tjip S.; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.

    2013-01-01

    The use of linezolid for the treatment of multidrug-resistant tuberculosis is limited by dose-and time-dependent toxicity. Recently, we reported a case of pharmacokinetic drug drug interaction between linezolid and clarithromycin that resulted in increased linezolid exposure. The aim of this

  12. Increasing trend of metronidazole resistance in the treatment of ...

    African Journals Online (AJOL)

    Helicobacter pylori are gram negative spiral bacteria that colonize the human stomach. Infection with H. pylori is associated with chronic gastritis, peptic ulcer, gastric adenocarcinoma and gastric mucosaassociated lymphoid tissue (MALT) lymphoma. Antibiotic resistance is an ever increasing problem with the treatment of ...

  13. Irradiated aromatic polysulphones of increased flow resistance and molecular weight

    International Nuclear Information System (INIS)

    Staniland, P.A.; Jarrett, W.G.

    1976-01-01

    Aromatic polymers of increased resistance to flow and molecular weight are obtained by irradiation using β-rays or γ-rays at temperatures up to 400 0 C of an aromatic polymer whose molecular chains comprise benzenoid groups and bivalent linking groups, and where irradiation is γ-rays by heating subsequent to irradiation at 200 to 400 0 C

  14. Increase in cellular concrete resistance to brittle fracture

    International Nuclear Information System (INIS)

    Chernyshov, E.M.; Krokhin, A.M.

    1979-01-01

    Considered are theoretical premises of decrease in cellular concrete resistance to brittle fracture at the expense of dispersed reinforcement. It is stated experimentally that the introduction of 3% asbestos fibers permits to increase the ultimate extensibility and strength during cellular concrete tension by 15-30% and to increase in unit rupture work 1.4-1.6 time more and therefore to decrease its brittleness

  15. In Utero Estrogen Exposure Increases Antiestrogen Resistance by Inducing EMT

    Science.gov (United States)

    2015-02-01

    currently unclear. Our recent preclinical study found that maternal exposure to excess estrogens during pregnancy increases the risk that AE resistance in...References: 1. Hilakivi-Clarke L, Clarke R, Onojafe I, Raygada M, Cho E, Lippman M. A maternal diet high in n-6-polyunsaturated fats alters mammary...the rate of obesity in this country (high fat diets resulting in elevated circulating estrogen levels), the prevelance of bisphenol A in our drinking

  16. Epidemic Increase in Methicillin-resistant Staphylococcus aureus in Copenhagen

    DEFF Research Database (Denmark)

    Westh, Henrik; Boye, Kit; Bartels, Mette Damkjær

    2006-01-01

    INTRODUCTION: We have found an epidemic increase in methicillin-resistant Staphylococcus aureus (MRSA) in Copenhagen. The increase has a complex background and involves hospitals, nursing homes and persons nursed in their own home. MATERIAL AND METHODS: We found 33 MRSA patients in 2003 and 121...... in 2004. All isolates have been spa-typed and epidemiologic information collected. RESULTS: The number of MRSA cases has a doubling time of about six months. The epidemic has been caused by many different MRSA types and 31 staphylococcus protein A genotypes (spa types). MRSA has caused several hospital...

  17. Immobilisation increases yeast cells' resistance to dehydration-rehydration treatment.

    Science.gov (United States)

    Borovikova, Diana; Rozenfelde, Linda; Pavlovska, Ilona; Rapoport, Alexander

    2014-08-20

    This study was performed with the goal of revealing if the dehydration procedure used in our new immobilisation method noticeably decreases the viability of yeast cells in immobilised preparations. Various yeasts were used in this research: Saccharomyces cerevisiae cells that were rather sensitive to dehydration and had been aerobically grown in an ethanol-containing medium, a recombinant strain of S. cerevisiae grown in aerobic conditions which were completely non-resistant to dehydration and an anaerobically grown bakers' yeast strain S. cerevisiae, as well as a fairly resistant Pichia pastoris strain. Experiments performed showed that immobilisation of all these strains essentially increased their resistance to a dehydration-rehydration treatment. The increase of cells' viability (compared with control cells dehydrated in similar conditions) was from 30 to 60%. It is concluded that a new immobilisation method, which includes a dehydration stage, does not lead to an essential loss of yeast cell viability. Correspondingly, there is no risk of losing the biotechnological activities of immobilised preparations. The possibility of producing dry, active yeast preparations is shown, for those strains that are very sensitive to dehydration and which can be used in biotechnology in an immobilised form. Finally, the immobilisation approach can be used for the development of efficient methods for the storage of recombinant yeast strains. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. INCREASED PROLIFERATION RESISTANCE FOR 21ST CENTURY NUCLEAR POWER

    International Nuclear Information System (INIS)

    Demuth, Scott F.; Thomas, Ken E.; Wallace, Richard K.

    2007-01-01

    World energy demand and greenhouse gases are expected to significantly increase in the near future. Key developing countries have identified nuclear power as a major contributor to their future energy sources. Consequently, the US and others are currently exploring the concept of a Global Nuclear Energy Partnership (GNEP) to address the concerns of nuclear proliferation. This effort is also being encouraged by the International Atomic Energy Agency (IAEA). While the IAEA currently provides the framework for monitoring of state sponsored nuclear proliferation by way of international treaties, a complimentary action is to promote more proliferation resistant fuel cycles and advanced safeguards technology. As such, it is the responsibility of current technology owners to increase their nuclear fuel cycle proliferation resistance. For those countries that have an active and well-developed fuel cycle, it will require future enhancements. For those countries with extensive nuclear energy experience, yet less active programs, it requires re-engagement for technology development and deployment. The following paper discusses potential fuel cycle and technology changes that affect proliferation resistance; and consequently, may form the basis of future technology development efforts.

  19. Trophic assimilation efficiency markedly increases at higher trophic levels in four-level host-parasitoid food chain.

    Science.gov (United States)

    Sanders, Dirk; Moser, Andrea; Newton, Jason; van Veen, F J Frank

    2016-03-16

    Trophic assimilation efficiency (conversion of resource biomass into consumer biomass) is thought to be a limiting factor for food chain length in natural communities. In host-parasitoid systems, which account for the majority of terrestrial consumer interactions, a high trophic assimilation efficiency may be expected at higher trophic levels because of the close match of resource composition of host tissue and the consumer's resource requirements, which would allow for longer food chains. We measured efficiency of biomass transfer along an aphid-primary-secondary-tertiary parasitoid food chain and used stable isotope analysis to confirm trophic levels. We show high efficiency in biomass transfer along the food chain. From the third to the fourth trophic level, the proportion of host biomass transferred was 45%, 65% and 73%, respectively, for three secondary parasitoid species. For two parasitoid species that can act at the fourth and fifth trophic levels, we show markedly increased trophic assimilation efficiencies at the higher trophic level, which increased from 45 to 63% and 73 to 93%, respectively. In common with other food chains, δ(15)N increased with trophic level, with trophic discrimination factors (Δ(15)N) 1.34 and 1.49‰ from primary parasitoids to endoparasitic and ectoparasitic secondary parasitoids, respectively, and 0.78‰ from secondary to tertiary parasitoids. Owing to the extraordinarily high efficiency of hyperparasitoids, cryptic higher trophic levels may exist in host-parasitoid communities, which could alter our understanding of the dynamics and drivers of community structure of these important systems. © 2016 The Authors.

  20. Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Manuela Sailer

    Full Text Available In humans, plasma amino acid concentrations of branched-chain amino acids (BCAA and aromatic amino acids (AAA increase in states of obesity, insulin resistance and diabetes. We here assessed whether these putative biomarkers can also be identified in two different obesity and diabetic mouse models. C57BL/6 mice with diet-induced obesity (DIO mimic the metabolic impairments of obesity in humans characterized by hyperglycemia, hyperinsulinemia and hepatic triglyceride accumulation. Mice treated with streptozotocin (STZ to induce insulin deficiency were used as a type 1 diabetes model. Plasma amino acid profiling of two high fat (HF feeding trials revealed that citrulline and ornithine concentrations are elevated in obese mice, while systemic arginine bioavailability (ratio of plasma arginine to ornithine + citrulline is reduced. In skeletal muscle, HF feeding induced a reduction of arginine levels while citrulline levels were elevated. However, arginine or citrulline remained unchanged in their key metabolic organs, intestine and kidney. Moreover, the intestinal conversion of labeled arginine to ornithine and citrulline in vitro remained unaffected by HF feeding excluding the intestine as prime site of these alterations. In liver, citrulline is mainly derived from ornithine in the urea cycle and DIO mice displayed reduced hepatic ornithine levels. Since both amino acids share an antiport mechanism for mitochondrial import and export, elevated plasma citrulline may indicate impaired hepatic amino acid handling in DIO mice. In the insulin deficient mice, plasma citrulline and ornithine levels also increased and additionally these animals displayed elevated BCAA and AAA levels like insulin resistant and diabetic patients. Therefore, type 1 diabetic mice but not DIO mice show the "diabetic fingerprint" of plasma amino acid changes observed in humans. Additionally, citrulline may serve as an early indicator of the obesity-dependent metabolic

  1. Advanced Wear-resistant Nanocomposites for Increased Energy Efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Cook, B. A.; Harringa, J. L.; Russel, A. M.

    2012-12-01

    This report summarizes the work performed by an Ames-led project team under a 4-year DOE-ITP sponsored project titled, 'Advanced Wear-resistant Nanocomposites for Increased Energy Efficiency.' The Report serves as the project deliverable for the CPS agreement number 15015. The purpose of this project was to develop and commercialize a family of lightweight, bulk composite materials that are highly resistant to degradation by erosive and abrasive wear. These materials, based on AlMgB{sub 14}, are projected to save over 30 TBtu of energy per year when fully implemented in industrial applications, with the associated environmental benefits of eliminating the burning of 1.5 M tons/yr of coal and averting the release of 4.2 M tons/yr of CO{sub 2} into the air. This program targeted applications in the mining, drilling, machining, and dry erosion applications as key platforms for initial commercialization, which includes some of the most severe wear conditions in industry. Production-scale manufacturing of this technology has begun through a start-up company, NewTech Ceramics (NTC). This project included providing technical support to NTC in order to facilitate cost-effective mass production of the wear-resistant boride components. Resolution of issues related to processing scale-up, reduction in energy intensity during processing, and improving the quality and performance of the composites, without adding to the cost of processing were among the primary technical focus areas of this program. Compositional refinements were also investigated in order to achieve the maximum wear resistance. In addition, synthesis of large-scale, single-phase AlMgB{sub 14} powder was conducted for use as PVD sputtering targets for nanocoating applications.

  2. Intermittent hypoxia increases insulin resistance in genetically obese mice.

    Science.gov (United States)

    Polotsky, Vsevolod Y; Li, Jianguo; Punjabi, Naresh M; Rubin, Arnon E; Smith, Philip L; Schwartz, Alan R; O'Donnell, Christopher P

    2003-10-01

    Obstructive sleep apnoea, a syndrome that leads to recurrent intermittent hypoxia, is associated with insulin resistance in obese individuals, but the mechanisms underlying this association remain unknown. We utilized a mouse model to examine the effects of intermittent hypoxia on insulin resistance in lean C57BL/6J mice and leptin-deficient obese (C57BL/6J-Lepob) mice. In lean mice, exposure to intermittent hypoxia for 5 days (short term) resulted in a decrease in fasting blood glucose levels (from 173 +/- 11 mg dl-1 on day 0 to 138 +/- 10 mg dl-1 on day 5, P obese mice, short-term intermittent hypoxia led to a decrease in blood glucose levels accompanied by a 607 +/- 136 % (P intermittent hypoxia was completely abolished by prior leptin infusion. Obese mice exposed to intermittent hypoxia for 12 weeks (long term) developed a time-dependent increase in fasting serum insulin levels (from 3.6 +/- 1.1 ng ml-1 at baseline to 9.8 +/- 1.8 ng ml-1 at week 12, P intermittent hypoxia is dependent on the disruption of leptin pathways.

  3. Concentric resistance training increases muscle strength without affecting microcirculation

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Marc-Andre [Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg (Germany)], E-mail: MarcAndre.Weber@med.uni-heidelberg.de; Hildebrandt, Wulf [Immunochemistry, German Cancer Research Center (dkfz), Heidelberg (Germany); Schroeder, Leif [Medical Physics in Radiology, German Cancer Research Center (dkfz), Heidelberg (Germany); Kinscherf, Ralf [Department of Anatomy and Developmental Biology, University of Heidelberg, Heidelberg (Germany); Krix, Martin [Radiology, German Cancer Research Center (dkfz), Heidelberg (Germany); Bachert, Peter [Medical Physics in Radiology, German Cancer Research Center (dkfz), Heidelberg (Germany); Delorme, Stefan; Essig, Marco [Radiology, German Cancer Research Center (dkfz), Heidelberg (Germany); Kauczor, Hans-Ulrich [Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg (Germany); Krakowski-Roosen, Holger [National Center for Tumor Diseases (NCT), Heidelberg (Germany)

    2010-03-15

    Purpose: While the evidence is conclusive regarding the positive effects of endurance training, there is still some controversy regarding the effects of resistance training on muscular capillarity. Thus, the purpose was to assess whether resistance strength training influences resting skeletal muscle microcirculation in vivo. Materials and methods: Thirty-nine middle-aged subjects (15 female, 24 male; mean age, 54 {+-} 9 years) were trained twice a week on an isokinetic system (altogether 16 sessions lasting 50 min, intensity 75% of maximum isokinetic and isometric force of knee flexors and extensors). To evaluate success of training, cross-sectional area (CSA) of the quadriceps femoris muscle and its isokinetic and isometric force were quantified. Muscular capillarization was measured in biopsies of the vastus lateralis muscle. In vivo, muscular energy and lipid metabolites were quantified by magnetic resonance spectroscopy and parameters of muscular microcirculation, such as local blood volume, blood flow and velocity, by contrast-enhanced ultrasound analyzing replenishment kinetics. Results: The significant (P < 0.001) increase in CSA (60 {+-} 16 before vs. 64 {+-} 15 cm{sup 2} after training) and in absolute muscle strength (isometric, 146 {+-} 44 vs. 174 {+-} 50 Nm; isokinetic, 151 {+-} 53 vs. 174 {+-} 62 Nm) demonstrated successful training. Neither capillary density ex vivo (351 {+-} 75 vs. 326 {+-} 62) nor ultrasonographic parameters of resting muscle perfusion were significantly different (blood flow, 1.2 {+-} 1.2 vs. 1.1 {+-} 1.1 ml/min/100 g; blood flow velocity, 0.49 {+-} 0.44 vs. 0.52 {+-} 0.74 mm s{sup -1}). Also, the intensities of high-energy phosphates phosphocreatine and {beta}-adenosintriphosphate were not different after training within the skeletal muscle at rest ({beta}-ATP/phosphocreatine, 0.29 {+-} 0.06 vs. 0.28 {+-} 0.04). Conclusion: The significant increase in muscle size and strength in response to concentric isokinetic and isometric

  4. Concentric resistance training increases muscle strength without affecting microcirculation

    International Nuclear Information System (INIS)

    Weber, Marc-Andre; Hildebrandt, Wulf; Schroeder, Leif; Kinscherf, Ralf; Krix, Martin; Bachert, Peter; Delorme, Stefan; Essig, Marco; Kauczor, Hans-Ulrich; Krakowski-Roosen, Holger

    2010-01-01

    Purpose: While the evidence is conclusive regarding the positive effects of endurance training, there is still some controversy regarding the effects of resistance training on muscular capillarity. Thus, the purpose was to assess whether resistance strength training influences resting skeletal muscle microcirculation in vivo. Materials and methods: Thirty-nine middle-aged subjects (15 female, 24 male; mean age, 54 ± 9 years) were trained twice a week on an isokinetic system (altogether 16 sessions lasting 50 min, intensity 75% of maximum isokinetic and isometric force of knee flexors and extensors). To evaluate success of training, cross-sectional area (CSA) of the quadriceps femoris muscle and its isokinetic and isometric force were quantified. Muscular capillarization was measured in biopsies of the vastus lateralis muscle. In vivo, muscular energy and lipid metabolites were quantified by magnetic resonance spectroscopy and parameters of muscular microcirculation, such as local blood volume, blood flow and velocity, by contrast-enhanced ultrasound analyzing replenishment kinetics. Results: The significant (P 2 after training) and in absolute muscle strength (isometric, 146 ± 44 vs. 174 ± 50 Nm; isokinetic, 151 ± 53 vs. 174 ± 62 Nm) demonstrated successful training. Neither capillary density ex vivo (351 ± 75 vs. 326 ± 62) nor ultrasonographic parameters of resting muscle perfusion were significantly different (blood flow, 1.2 ± 1.2 vs. 1.1 ± 1.1 ml/min/100 g; blood flow velocity, 0.49 ± 0.44 vs. 0.52 ± 0.74 mm s -1 ). Also, the intensities of high-energy phosphates phosphocreatine and β-adenosintriphosphate were not different after training within the skeletal muscle at rest (β-ATP/phosphocreatine, 0.29 ± 0.06 vs. 0.28 ± 0.04). Conclusion: The significant increase in muscle size and strength in response to concentric isokinetic and isometric resistance training occurs without an increase in the in vivo microcirculation of the skeletal muscles at

  5. Increased platelet expression of glycoprotein IIIa following aspirin treatment in aspirin-resistant but not aspirin-sensitive subjects

    Science.gov (United States)

    Floyd, Christopher N; Goodman, Timothy; Becker, Silke; Chen, Nan; Mustafa, Agnesa; Schofield, Emma; Campbell, James; Ward, Malcolm; Sharma, Pankaj; Ferro, Albert

    2014-01-01

    Aims Aspirin is widely used as an anti-platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin-resistant subjects. Methods Ninety-three healthy subjects received aspirin 300 mg daily for 28 days. Before and at the end of treatment, urine was taken to determine 11-dehydrothromboxane B2, and blood was taken to measure arachidonic acid (AA)-induced aggregation of platelet-rich plasma and to interrogate the platelet proteome by mass spectrometric analysis with further confirmation of findings using Western blotting. Results In two of the 93 subjects, neither AA-induced aggregation nor urinary 11-dehydrothromboxane B2 was effectively suppressed by aspirin, despite measurable plasma salicylate concentrations, suggesting the presence of true aspirin resistance. Despite no detectable differences in the platelet proteome at baseline, following aspirin a marked increase was seen in platelet glycoprotein IIIa expression in the aspirin-resistant but not aspirin-sensitive subjects. An increase in platelet glycoprotein IIIa expression with aspirin resistance was confirmed in a separate cohort of 17 patients with stable coronary artery disease on long term aspirin treatment, four of whom exhibited aspirin resistance. Conclusions In a healthy population, true aspirin resistance is uncommon but exists. Resistance is associated with an increase in platelet glycoprotein IIIa expression in response to aspirin. These data shed new light on the mechanism of aspirin resistance, and provide the potential to identify aspirin-resistant subjects using a novel biomarker. PMID:25099258

  6. Carboxylesterase-mediated insecticide resistance: Quantitative increase induces broader metabolic resistance than qualitative change.

    Science.gov (United States)

    Cui, Feng; Li, Mei-Xia; Chang, Hai-Jing; Mao, Yun; Zhang, Han-Ying; Lu, Li-Xia; Yan, Shuai-Guo; Lang, Ming-Lin; Liu, Li; Qiao, Chuan-Ling

    2015-06-01

    Carboxylesterases are mainly involved in the mediation of metabolic resistance of many insects to organophosphate (OP) insecticides. Carboxylesterases underwent two divergent evolutionary events: (1) quantitative mechanism characterized by the overproduction of carboxylesterase protein; and (2) qualitative mechanism caused by changes in enzymatic properties because of mutation from glycine/alanine to aspartate at the 151 site (G/A151D) or from tryptophan to leucine at the 271 site (W271L), following the numbering of Drosophila melanogaster AChE. Qualitative mechanism has been observed in few species. However, whether this carboxylesterase mutation mechanism is prevalent in insects remains unclear. In this study, wild-type, G/A151D and W271L mutant carboxylesterases from Culex pipiens and Aphis gossypii were subjected to germline transformation and then transferred to D. melanogaster. These germlines were ubiquitously expressed as induced by tub-Gal4. In carboxylesterase activity assay, the introduced mutant carboxylesterase did not enhance the overall carboxylesterase activity of flies. This result indicated that G/A151D or W271L mutation disrupted the original activities of the enzyme. Less than 1.5-fold OP resistance was only observed in flies expressing A. gossypii mutant carboxylesterases compared with those expressing A. gossypii wild-type carboxylesterase. However, transgenic flies universally showed low resistance to OP insecticides compared with non-transgenic flies. The flies expressing A. gossypii W271L mutant esterase exhibited 1.5-fold resistance to deltamethrin, a pyrethroid insecticide compared with non-transgenic flies. The present transgenic Drosophila system potentially showed that a quantitative increase in carboxylesterases induced broader resistance of insects to insecticides than a qualitative change. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Suppression in growth hormone during overeating ameliorates the increase in insulin resistance and cardiovascular disease risk.

    Science.gov (United States)

    Cornford, Andrea S; Barkan, Ariel L; Hinko, Alexander; Horowitz, Jeffrey F

    2012-11-15

    Previously, we reported that overeating for only a few days markedly suppressed the secretion of growth hormone (GH). The purpose of the present study was to determine the role of this reduction in GH concentration on key metabolic adaptations that occur during 2 wk of overeating. Nine nonobese, healthy adults were admitted to the hospital for 2 wk, during which time they ate ∼4,000 kcal/day (70 kcal·kg fat-free mass(-1)·day(-1); 50% carbohydrate, 35% fat, and 15% protein), and their plasma GH concentration was allowed to decline naturally (control). An additional eight subjects underwent the same overeating intervention and received exogenous GH treatment (GHT) administered in four daily injections to mimic physiological GH secretion throughout the 2-wk overeating period. We measured plasma insulin and glucose concentrations in the fasting and postprandial state as well as fasting lipolytic rate, proteolytic rate, and fractional synthetic rate (FSR) using stable-isotope tracer methods. GHT prevented the fall in plasma GH concentration, maintaining plasma GH concentration at baseline levels (1.2 ± 0.2 ng/ml), which increased fasting and postprandial assessments of insulin resistance (P overeating also blunted the increase in systemic proteolysis (P overeating. In conclusion, our main findings suggest that the suppression in GH secretion that naturally occurs during the early stages of overeating may help attenuate the insulin resistance and hyperlipidemia that typically accompany overeating.

  8. Increased systemic vascular resistance in neonates with pulmonary hypertension.

    Science.gov (United States)

    Milstein, J M; Goetzman, B W; Riemenschneider, T A; Wennberg, R P

    1979-11-01

    The time necessary for aortic diastolic pressure to decrease to 50 percent of an initially selected value after dissipation of the dicrotic notch (T 1/2) was determined in newborn infants with and without pulmonary hypertension. The mean T 1/2 was 671 +/- 167 msec in seven infants with clinical evidence of pulmonary hypertension and documented right to left ductus arteriosus shunting; 849 +/- 243 msec in nine infants with clinical evidence of pulmonary hypertension but no documented right to left ductus arteriosus shunting; and 457 +/- 66 msec in eight infants with hyaline membrane disease and no clinical evidence of pulmonary hypertension or a patent ductus arteriosus. The mean T 1/2 values in the former two groups were significantly different from that in the group with no pulmonary hypertension (P less than 0.01). An evaluation of factors affecting T 1/2 leads to the conclusion that the patients with pulmonary hypertension had increased systemic vascular resistance as well. This finding has important diagnostic, etiologic and therapeutic implications.

  9. Increased Prevalence of Activated Protein C Resistance During ...

    African Journals Online (AJOL)

    Background: Acquired resistance to protein C in pregnancy has been established as one of the factors associated with ..... diabetes, sickle cell disease, smoking, anti-phospholipid syndrome inherited thrombophilia, and previous history of.

  10. Analysis on the evaluation of dose of the team reader TLD SOLARO, post-adjustment of the heating resistance marks

    International Nuclear Information System (INIS)

    Morales C, M.

    2000-09-01

    This report describes the process carried out in the area of personal dosimetry as for different evaluations carried out in the team reader TLD SOLARO it marks, which evaluates chips of LiF and cards containing two pellets of LiF-700, to determine if after having carried out an adjustment in the heating system the dose evaluations they continue being acceptable, that is to say, the evaluated doses stay inside the error margin allowed for the case of external individual monitoring

  11. Increasing transmission of antibiotic resistance from animals to humans

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Frimodt-Møller, Niels

    2011-01-01

    The importance of the animal reservoir for emergence of antimicrobial resistance in bacteria in humans is difficult to estimate. In this article we give our estimate of the importance and also highlight on which points we have become wiser during recent years. We conclude that it still is the human...... usage of antibiotics which contributes most to resistance observed in humans, but also that the contribution from animals is large and larger than estimated just a few years ago. This indicates the need to implement restriction on antimicrobial usage for both humans and animals....

  12. Increasing transmission of antibiotic resistance from animals to humans

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Frimodt-Møller, Niels

    2011-01-01

    usage of antibiotics which contributes most to resistance observed in humans, but also that the contribution from animals is large and larger than estimated just a few years ago. This indicates the need to implement restriction on antimicrobial usage for both humans and animals.......The importance of the animal reservoir for emergence of antimicrobial resistance in bacteria in humans is difficult to estimate. In this article we give our estimate of the importance and also highlight on which points we have become wiser during recent years. We conclude that it still is the human...

  13. Increased multi-drug resistant Escherichia coli from hospitals in ...

    African Journals Online (AJOL)

    Background: Multidrug-resistant Escherichia coli (MDR E. coli) has become a major public health concern in Sudan and many countries, causing failure in treatment with consequent huge health burden. Objectives: To determine the prevalence and susceptibility of MDR E. coli isolated from patients in hospitals at Khartoum ...

  14. Mining the Genus Solanum for Increasing Disease Resistance

    NARCIS (Netherlands)

    Vossen, J.H.; Kwang-Ryong Jo,; Vosman, B.J.

    2014-01-01

    Plant Breeding is the art of selecting and discarding genetic material to achieve crop improvement. Favourable alleles resulting in quality improvement or disease resistance must be added, while unfavourable alleles must be removed. The source for novel alleles can be other varieties, landraces or

  15. Increased resistance of environmental anaerobic spores to inactivation by UV

    NARCIS (Netherlands)

    Hijnen, W.A.M.; Veer, A.J. van der; Beerendonk, E.F.; Medema, Gerriet Jan

    2004-01-01

    Water Company Europoort started a pilot plant (MP)UV study to determine the UV-fluence to meet the Dutch drinking water standards. The results of large volume sampling of this pilot plant demonstrated that environmental spores of sulphite-reducing clostridia (SSRC) were highly resistant against UV.

  16. Increasing resistant coagulase negative staphylococci in bovine clinical mastitis.

    Science.gov (United States)

    Moniri, R; Dastehgoli, K; Akramian, A

    2007-08-01

    The aim of this study was to determine Coagulase Negative Staphylococci (CNS) and other bacteria for their resistance to antimicrobial agents approved for the control of pathogens involved in clinical bovine mastitis. This descriptive study was done on 106 milk samples obtained from clinical mastitis in dairy cattle husbandry from April 2006 through August 2006 in Kashan, Iran. From the total of 106 milk samples collected from clinical mastitis, 96 (90.6%) lead to positive culture. Coagulase negative Staphylococci isolated in 51 out of 96 samples (53.1%), Staphylococcus aureus isolated in 21 out of 96 (21.9%), gram negative bacilli isolated in 14 out of 96 (14.6%) and Enterococci isolated in 4 (4.2%). The highest rate of resistant CNS observed to penicillin (56.6%) and the highest rate of sensitivity to enrofloxacin 100%, followed by kanamycin, streptomycin and neomycin, 92.2, 82.3 and 82.3%, respectively. The highest rate of resistance S. aureus exhibited to penicillin (66.6%); while the highest rate of sensitivity showed to trimethoprim-sulphamethoxasole (81%), followed by kanamycin and enrofloxacin both at 76.2%. The highest rate of resistance gram negative bacilli exhibited to ampicillin and erythromycin at 71.4%. Their highest rate of sensitivity observed to enrofloxacin (78.6%), followed by kanamycin, (71.4%). In recent years, CNS is emerging as important minor mastitis pathogens and can be the cause of substantial economic losses. The high resistance rate to penicillin and other antibiotics found in this study emphasize the importance of identification of CNS when a bovine clinical mastitis is present.

  17. Interleukin-6 markedly decreases skeletal muscle protein turnover and increases nonmuscle amino acid utilization in healthy individuals

    DEFF Research Database (Denmark)

    van Hall, Gerrit; Steensberg, Adam; Fischer, Christian

    2008-01-01

    CONTEXT: IL-6 is a key modulator of immune function and suggested to be involved in skeletal muscle wasting as seen in sepsis. OBJECTIVE: Our objective was to determine the role of IL-6 in human in vivo systemic and skeletal muscle amino acid metabolism and protein turnover. SUBJECTS AND METHODS...... synthesis was more suppressed than breakdown, causing a small increase in net muscle protein breakdown. Furthermore, rhIL-6 decreased arterial amino acid concentration with 20-40%, despite the increase net release from muscle. CONCLUSIONS: We demonstrated that IL-6 profoundly alters amino acid turnover....... A substantial decrease in plasma amino acids was observed with a concomitant 50% decrease in muscle protein turnover, however, modest increase in net muscle degradation. We hypothesize that the profound reduction in muscle protein turnover and modest increase in net degradation are primarily caused...

  18. Increased STAT1 signaling in endocrine-resistant breast cancer.

    Directory of Open Access Journals (Sweden)

    Rui Huang

    Full Text Available Proteomic profiling of the estrogen/tamoxifen-sensitive MCF-7 cell line and its partially sensitive (MCF-7/LCC1 and fully resistant (MCF-7/LCC9 variants was performed to identify modifiers of endocrine sensitivity in breast cancer. Analysis of the expression of 120 paired phosphorylated and non-phosphorylated epitopes in key oncogenic and tumor suppressor pathways revealed that STAT1 and several phosphorylated epitopes (phospho-STAT1(Tyr701 and phospho-STAT3(Ser727 were differentially expressed between endocrine resistant and parental controls, confirmed by qRT-PCR and western blotting. The STAT1 inhibitor EGCG was a more effective inhibitor of the endocrine resistant MCF-7/LCC1 and MCF-7/LCC9 lines than parental MCF-7 cells, while STAT3 inhibitors Stattic and WP1066 were equally effective in endocrine-resistant and parental lines. The effects of the STAT inhibitors were additive, rather than synergistic, when tested in combination with tamoxifen in vitro. Expression of STAT1 and STAT3 were measured by quantitative immunofluorescence in invasive breast cancers and matched lymph nodes. When lymph node expression was compared to its paired primary breast cancer expression, there was greater expression of cytoplasmic STAT1 (∼3.1 fold, phospho-STAT3(Ser727 (∼1.8 fold, and STAT5 (∼1.5 fold and nuclear phospho-STAT3(Ser727 (∼1.5 fold in the nodes. Expression levels of STAT1 and STAT3 transcript were analysed in 550 breast cancers from publicly available gene expression datasets (GSE2990, GSE12093, GSE6532. When treatment with tamoxifen was considered, STAT1 gene expression was nearly predictive of distant metastasis-free survival (DMFS, log-rank p = 0.067, while STAT3 gene expression was predictive of DMFS (log-rank p<0.0001. Analysis of STAT1 and STAT3 protein expression in a series of 546 breast cancers also indicated that high expression of STAT3 protein was associated with improved survival (DMFS, p = 0.006. These results suggest

  19. Insulin-mediated increases in renal plasma flow are impaired in insulin-resistant normal subjects

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; Moshage, HJ; Gans, ROB

    2000-01-01

    Background Impaired vasodilatation in skeletal muscle is a possible mechanism linking insulin resistance to blood pressure regulation. Increased renal vascular resistance has been demonstrated in the offspring of essential hypertensives. We assessed whether insulin-mediated renal vasodilatation is

  20. 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:.

  1. Dietary alleviation of maternal obesity and diabetes: increased resistance to diet-induced obesity transcriptional and epigenetic signatures.

    Science.gov (United States)

    Attig, Linda; Vigé, Alexandre; Gabory, Anne; Karimi, Moshen; Beauger, Aurore; Gross, Marie-Sylvie; Athias, Anne; Gallou-Kabani, Catherine; Gambert, Philippe; Ekstrom, Tomas J; Jais, Jean-Philippe; Junien, Claudine

    2013-01-01

    According to the developmental origins of health and diseases (DOHaD), and in line with the findings of many studies, obesity during pregnancy is clearly a threat to the health and well-being of the offspring, later in adulthood. We previously showed that 20% of male and female inbred mice can cope with the obesogenic effects of a high-fat diet (HFD) for 20 weeks after weaning, remaining lean. However the feeding of a control diet (CD) to DIO mice during the periconceptional/gestation/lactation period led to a pronounced sex-specific shift (17% to 43%) from susceptibility to resistance to HFD, in the female offspring only. Our aim in this study was to determine how, in the context of maternal obesity and T2D, a CD could increase resistance on female fetuses. Transcriptional analyses were carried out with a custom-built mouse liver microarray and by quantitative RT-PCR for muscle and adipose tissue. Both global DNA methylation and levels of pertinent histone marks were assessed by LUMA and western blotting, and the expression of 15 relevant genes encoding chromatin-modifying enzymes was analyzed in tissues presenting global epigenetic changes. Resistance was associated with an enhancement of hepatic pathways protecting against steatosis, the unexpected upregulation of neurotransmission-related genes and the modulation of a vast imprinted gene network. Adipose tissue displayed a pronounced dysregulation of gene expression, with an upregulation of genes involved in lipid storage and adipocyte hypertrophy or hyperplasia in obese mice born to lean and obese mothers, respectively. Global DNA methylation, several histone marks and key epigenetic regulators were also altered. Whether they were themselves lean (resistant) or obese (sensitive), the offspring of lean and obese mice clearly differed in terms of several metabolic features and epigenetic marks suggesting that the effects of a HFD depend on the leanness or obesity of the mother.

  2. Increased androgenic sensitivity in the hind limb muscular system marks the evolution of a derived gestural display.

    Science.gov (United States)

    Mangiamele, Lisa A; Fuxjager, Matthew J; Schuppe, Eric R; Taylor, Rebecca S; Hödl, Walter; Preininger, Doris

    2016-05-17

    Physical gestures are prominent features of many species' multimodal displays, yet how evolution incorporates body and leg movements into animal signaling repertoires is unclear. Androgenic hormones modulate the production of reproductive signals and sexual motor skills in many vertebrates; therefore, one possibility is that selection for physical signals drives the evolution of androgenic sensitivity in select neuromotor pathways. We examined this issue in the Bornean rock frog (Staurois parvus, family: Ranidae). Males court females and compete with rivals by performing both vocalizations and hind limb gestural signals, called "foot flags." Foot flagging is a derived display that emerged in the ranids after vocal signaling. Here, we show that administration of testosterone (T) increases foot flagging behavior under seminatural conditions. Moreover, using quantitative PCR, we also find that adult male S. parvus maintain a unique androgenic phenotype, in which androgen receptor (AR) in the hind limb musculature is expressed at levels ∼10× greater than in two other anuran species, which do not produce foot flags (Rana pipiens and Xenopus laevis). Finally, because males of all three of these species solicit mates with calls, we accordingly detect no differences in AR expression in the vocal apparatus (larynx) among taxa. The results show that foot flagging is an androgen-dependent gestural signal, and its emergence is associated with increased androgenic sensitivity within the hind limb musculature. Selection for this novel gestural signal may therefore drive the evolution of increased AR expression in key muscles that control signal production to support adaptive motor performance.

  3. Military training elicits marked increases in plasma metabolomic signatures of energy metabolism, lipolysis, fatty acid oxidation, and ketogenesis.

    Science.gov (United States)

    Karl, J Philip; Margolis, Lee M; Murphy, Nancy E; Carrigan, Christopher T; Castellani, John W; Madslien, Elisabeth H; Teien, Hilde-Kristin; Martini, Svein; Montain, Scott J; Pasiakos, Stefan M

    2017-09-01

    Military training studies provide unique insight into metabolic responses to extreme physiologic stress induced by multiple stressor environments, and the impacts of nutrition in mediating these responses. Advances in metabolomics have provided new approaches for extending current understanding of factors modulating dynamic metabolic responses in these environments. In this study, whole-body metabolic responses to strenuous military training were explored in relation to energy balance and macronutrient intake by performing nontargeted global metabolite profiling on plasma collected from 25 male soldiers before and after completing a 4-day, 51-km cross-country ski march that produced high total daily energy expenditures (25.4 MJ/day [SD 2.3]) and severe energy deficits (13.6 MJ/day [SD 2.5]). Of 737 identified metabolites, 478 changed during the training. Increases in 88% of the free fatty acids and 91% of the acylcarnitines, and decreases in 88% of the mono- and diacylglycerols detected within lipid metabolism pathways were observed. Smaller increases in 75% of the tricarboxylic acid cycle intermediates, and 50% of the branched-chain amino acid metabolites detected were also observed. Changes in multiple metabolites related to lipid metabolism were correlated with body mass loss and energy balance, but not with energy and macronutrient intakes or energy expenditure. These findings are consistent with an increase in energy metabolism, lipolysis, fatty acid oxidation, ketogenesis, and branched-chain amino acid catabolism during strenuous military training. The magnitude of the energy deficit induced by undereating relative to high energy expenditure, rather than macronutrient intake, appeared to drive these changes, particularly within lipid metabolism pathways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  4. SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity.

    Science.gov (United States)

    Yilmaz, Omer H; Kiel, Mark J; Morrison, Sean J

    2006-02-01

    Recent advances have increased the purity of hematopoietic stem cells (HSCs) isolated from young mouse bone marrow. However, little attention has been paid to the purity of HSCs from other contexts. Although Thy-1 low Sca-1+ Lineage- c-kit+ cells from young bone marrow are highly enriched for HSCs (1 in 5 cells gives long-term multilineage reconstitution after transplantation into irradiated mice), the same population from old, reconstituted, or cytokine-mobilized mice engrafts much less efficiently (1 in 78 to 1 in 185 cells gives long-term multilineage reconstitution). To test whether we could increase the purity of HSCs isolated from these contexts, we examined the SLAM family markers CD150 and CD48. All detectable HSCs from old, reconstituted, and cyclophosphamide/G-CSF-mobilized mice were CD150+ CD48-, just as in normal young bone marrow. Thy-1 low Sca-1+ Lineage- c-kit+ cells from old, reconstituted, or mobilized mice included mainly CD48+ and/or CD150- cells that lacked reconstituting ability. CD150+ CD48- Sca-1+ Lineage- c-kit+ cells from old, reconstituted, or mobilized mice were much more highly enriched for HSCs, with 1 in 3 to 1 in 7 cells giving long-term multilineage reconstitution. SLAM family receptor expression is conserved among HSCs from diverse contexts, and HSCs from old, reconstituted, and mobilized mice engraft relatively efficiently after transplantation when contaminating cells are eliminated.

  5. 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.

  6. Engineering of Bacillus subtilis 168 for increased nisin resistance

    DEFF Research Database (Denmark)

    Hansen, Mette; Wangari, Romilda; Hansen, Egon Bech

    2009-01-01

    . Bacillus subtilis had been suggested as a potential host for the biosynthesis of nisin but was discarded due to its sensitivity to the lethal action of nisin. In this study, we have reevaluated the potential of B. subtilis as a host organism for the heterologous production of nisin. We applied...... transcriptome and proteome analyses of B. subtilis and identified eight genes upregulated in the presence of nisin. We demonstrated that the overexpression of some of these genes boosts the natural defenses of B. subtilis, which allows it to sustain higher levels of nisin in the medium. We also attempted...... to overcome the nisin sensitivity of B. subtilis by introducing the nisin resistance genes nisFEG and nisI from L. lactis under the control of a synthetic promoter library....

  7. Stretch Marks

    Science.gov (United States)

    ... completely without the help of a dermatologist or plastic surgeon. These doctors may use one of many types of treatments — from actual surgery to techniques like microdermabrasion and laser treatment — to reduce the appearance of stretch marks. These techniques are ...

  8. Negatively-marked MCQ assessments that reward partial knowledge do not introduce gender bias yet increase student performance and satisfaction and reduce anxiety.

    Directory of Open Access Journals (Sweden)

    A Elizabeth Bond

    Full Text Available Multiple-choice question (MCQ examinations are increasingly used as the assessment method of theoretical knowledge in large class-size modules in many life science degrees. MCQ-tests can be used to objectively measure factual knowledge, ability and high-level learning outcomes, but may also introduce gender bias in performance dependent on topic, instruction, scoring and difficulty. The 'Single Answer' (SA test is often used in which students choose one correct answer, in which they are unable to demonstrate partial knowledge. Negatively marking eliminates the chance element of guessing but may be considered unfair. Elimination testing (ET is an alternative form of MCQ, which discriminates between all levels of knowledge, while rewarding demonstration of partial knowledge. Comparisons of performance and gender bias in negatively marked SA and ET tests have not yet been performed in the life sciences. Our results show that life science students were significantly advantaged by answering the MCQ test in elimination format compared to single answer format under negative marking conditions by rewarding partial knowledge of topics. Importantly, we found no significant difference in performance between genders in either cohort for either MCQ test under negative marking conditions. Surveys showed that students generally preferred ET-style MCQ testing over SA-style testing. Students reported feeling more relaxed taking ET MCQ and more stressed when sitting SA tests, while disagreeing with being distracted by thinking about best tactics for scoring high. Students agreed ET testing improved their critical thinking skills. We conclude that appropriately-designed MCQ tests do not systematically discriminate between genders. We recommend careful consideration in choosing the type of MCQ test, and propose to apply negative scoring conditions to each test type to avoid the introduction of gender bias. The student experience could be improved through the

  9. Negatively-marked MCQ assessments that reward partial knowledge do not introduce gender bias yet increase student performance and satisfaction and reduce anxiety.

    Science.gov (United States)

    Bond, A Elizabeth; Bodger, Owen; Skibinski, David O F; Jones, D Hugh; Restall, Colin J; Dudley, Edward; van Keulen, Geertje

    2013-01-01

    Multiple-choice question (MCQ) examinations are increasingly used as the assessment method of theoretical knowledge in large class-size modules in many life science degrees. MCQ-tests can be used to objectively measure factual knowledge, ability and high-level learning outcomes, but may also introduce gender bias in performance dependent on topic, instruction, scoring and difficulty. The 'Single Answer' (SA) test is often used in which students choose one correct answer, in which they are unable to demonstrate partial knowledge. Negatively marking eliminates the chance element of guessing but may be considered unfair. Elimination testing (ET) is an alternative form of MCQ, which discriminates between all levels of knowledge, while rewarding demonstration of partial knowledge. Comparisons of performance and gender bias in negatively marked SA and ET tests have not yet been performed in the life sciences. Our results show that life science students were significantly advantaged by answering the MCQ test in elimination format compared to single answer format under negative marking conditions by rewarding partial knowledge of topics. Importantly, we found no significant difference in performance between genders in either cohort for either MCQ test under negative marking conditions. Surveys showed that students generally preferred ET-style MCQ testing over SA-style testing. Students reported feeling more relaxed taking ET MCQ and more stressed when sitting SA tests, while disagreeing with being distracted by thinking about best tactics for scoring high. Students agreed ET testing improved their critical thinking skills. We conclude that appropriately-designed MCQ tests do not systematically discriminate between genders. We recommend careful consideration in choosing the type of MCQ test, and propose to apply negative scoring conditions to each test type to avoid the introduction of gender bias. The student experience could be improved through the incorporation of the

  10. Fitness cost of resistance to Bt cotton linked with increased gossypol content in pink bollworm larvae.

    Directory of Open Access Journals (Sweden)

    Jennifer L Williams

    Full Text Available Fitness costs of resistance to Bacillus thuringiensis (Bt crops occur in the absence of Bt toxins, when individuals with resistance alleles are less fit than individuals without resistance alleles. As costs of Bt resistance are common, refuges of non-Bt host plants can delay resistance not only by providing susceptible individuals to mate with resistant individuals, but also by selecting against resistance. Because costs typically vary across host plants, refuges with host plants that magnify costs or make them less recessive could enhance resistance management. Limited understanding of the physiological mechanisms causing fitness costs, however, hampers attempts to increase costs. In several major cotton pests including pink bollworm (Pectinophora gossypiella, resistance to Cry1Ac cotton is associated with mutations altering cadherin proteins that bind this toxin in susceptible larvae. Here we report that the concentration of gossypol, a cotton defensive chemical, was higher in pink bollworm larvae with cadherin resistance alleles than in larvae lacking such alleles. Adding gossypol to the larval diet decreased larval weight and survival, and increased the fitness cost affecting larval growth, but not survival. Across cadherin genotypes, the cost affecting larval growth increased as the gossypol concentration of larvae increased. These results suggest that increased accumulation of plant defensive chemicals may contribute to fitness costs associated with resistance to Bt toxins.

  11. Oxidized fish oil in rat pregnancy causes high newborn mortality and increases maternal insulin resistance.

    Science.gov (United States)

    Albert, Benjamin B; Vickers, Mark H; Gray, Clint; Reynolds, Clare M; Segovia, Stephanie A; Derraik, José G B; Lewandowski, Paul A; Garg, Manohar L; Cameron-Smith, David; Hofman, Paul L; Cutfield, Wayne S

    2016-09-01

    Fish oil is commonly taken by pregnant women, and supplements sold at retail are often oxidized. Using a rat model, we aimed to assess the effects of supplementation with oxidized fish oil during pregnancy in mothers and offspring, focusing on newborn viability and maternal insulin sensitivity. Female rats were allocated to a control or high-fat diet and then mated. These rats were subsequently randomized to receive a daily gavage treatment of 1 ml of unoxidized fish oil, a highly oxidized fish oil, or control (water) throughout pregnancy. At birth, the gavage treatment was stopped, but the same maternal diets were fed ad libitum throughout lactation. Supplementation with oxidized fish oil during pregnancy had a marked adverse effect on newborn survival at day 2, leading to much greater odds of mortality than in the control (odds ratio 8.26) and unoxidized fish oil (odds ratio 13.70) groups. In addition, maternal intake of oxidized fish oil during pregnancy led to increased insulin resistance at the time of weaning (3 wks after exposure) compared with control dams (HOMA-IR 2.64 vs. 1.42; P = 0.044). These data show that the consumption of oxidized fish oil is harmful in rat pregnancy, with deleterious effects in both mothers and offspring. Copyright © 2016 the American Physiological Society.

  12. HIV drug resistance in infants increases with changing prevention of mother-to-child transmission regimens.

    Science.gov (United States)

    Poppe, Lisa K; Chunda-Liyoka, Catherine; Kwon, Eun H; Gondwe, Clement; West, John T; Kankasa, Chipepo; Ndongmo, Clement B; Wood, Charles

    2017-08-24

    The objectives of this study were to determine HIV drug resistance (HIVDR) prevalence in Zambian infants upon diagnosis, and to determine how changing prevention of mother-to-child transmission (PMTCT) drug regimens affect drug resistance. Dried blood spot (DBS) samples from infants in the Lusaka District of Zambia, obtained during routine diagnostic screening, were collected during four different years representing three different PMTCT drug treatment regimens. DNA extracted from dried blood spot samples was used to sequence a 1493 bp region of the reverse transcriptase gene. Sequences were analyzed via the Stanford HIVDRdatabase (http://hivdb.standford.edu) to screen for resistance mutations. HIVDR in infants increased from 21.5 in 2007/2009 to 40.2% in 2014. Nonnucleoside reverse transcriptase inhibitor resistance increased steadily over the sampling period, whereas nucleoside reverse transcriptase inhibitor resistance and dual class resistance both increased more than threefold in 2014. Analysis of drug resistance scores in each group revealed increasing strength of resistance over time. In 2014, children with reported PMTCT exposure, defined as infant prophylaxis and/or maternal treatment, showed a higher prevalence and strength of resistance compared to those with no reported exposure. HIVDR is on the rise in Zambia and presents a serious problem for the successful lifelong treatment of HIV-infected children. PMTCT affects both the prevalence and strength of resistance and further research is needed to determine how to mitigate its role leading to resistance.

  13. Increased Resistance to osmotic lysis of sickled erythrocytes ...

    African Journals Online (AJOL)

    treated with CNw had significantly reduced osmotic lysis when compared with the untreated set (P<0.05, respectively) at various hypotonic NaCl concentrations. Various Hb genotypes exhibited a graded increase in osmotic pressure lysis in ...

  14. Does employee resistance during a robbery increase the risk of customer injury?

    Science.gov (United States)

    Yau, Rebecca K; Casteel, Carri; Nocera, Maryalice; Bishop, Stephanie F; Peek-Asa, Corinne

    2015-04-01

    Retail business robberies can lead to employee and customer injury. Previous work demonstrates that employee resistance increases employee injury risk; limited research has investigated customer injuries. This study examines associations between employee resistance against perpetrators and the risk of customer injury. Retail and service robbery reports were obtained from a metropolitan police department. Generalized estimating equations estimated risk ratios and 95% confidence intervals (CIs). Customers were injured in 75 out of 697 robberies. Employees resisted the perpetrator in 32 out of 697 robberies. Customers had higher injury risk when employees resisted the perpetrator, compared with robberies where employees did not resist (adjusted risk ratio [95% CI], 2.6 [1.5 to 4.5]). Employee resistance against a perpetrator during a robbery increased customer injury risk. Businesses can train employees to not resist during a robbery, providing benefits for both customers and the business itself.

  15. Subinhibitory concentrations of imipenem induce increased resistance to methicillin and imipenem in vitro in methicillin-resistant Staphylococcus aureus.

    OpenAIRE

    Forbes, B A; McClatchey, K D; Schaberg, D R

    1984-01-01

    Methicillin-resistant (MR) Staphylococcus aureus that was susceptible to less than 0.75 micrograms of imipenem per ml demonstrated inducible resistance. MR S. aureus preincubated with 0.05 microgram of imipenem per ml grew in medium with an imipenem concentration of 32 micrograms/ml, and methicillin MICs increased 20-fold. Non-MR S. aureus exhibited no induction. Preincubation with methicillin produced no effect. Induction appeared to be a unique interaction of imipenem with MR S. aureus.

  16. Ampicillin-Resistant Non-β-Lactamase-Producing Haemophilus influenzae in Spain: Recent Emergence of Clonal Isolates with Increased Resistance to Cefotaxime and Cefixime▿

    Science.gov (United States)

    García-Cobos, Silvia; Campos, José; Lázaro, Edurne; Román, Federico; Cercenado, Emilia; García-Rey, César; Pérez-Vázquez, María; Oteo, Jesús; de Abajo, Francisco

    2007-01-01

    The sequence of the ftsI gene encoding the transpeptidase domain of penicillin-binding protein 3 (PBP 3) was determined for 354 nonconsecutive Haemophilus influenzae isolates from Spain; 17.8% of them were ampicillin susceptible, 56% were β-lactamase nonproducing ampicillin resistant (BLNAR), 15.8% were β-lactamase producers and ampicillin resistant, and 10.4% displayed both resistance mechanisms. The ftsI gene sequences had 28 different mutation patterns and amino acid substitutions at 23 positions. Some 93.2% of the BLNAR strains had amino acid substitutions at the Lys-Thr-Gly (KTG) motif, the two most common being Asn526 to Lys (83.9%) and Arg517 to His (9.3%). Amino acid substitutions at positions 377, 385, and 389, which conferred cefotaxime and cefixime MICs 10 to 60 times higher than those of susceptible strains, were found for the first time in Europe. In 72 isolates for which the repressor acrR gene of the AcrAB efflux pump was sequenced, numerous amino acid substitutions were found. Eight isolates with ampicillin MICs of 0.25 to 2 μg/ml showed changes that predicted the early termination of the acrR reading frame. Pulsed-field gel electrophoresis analysis demonstrated that most BLNAR strains were genetically diverse, although clonal dissemination was detected in a group of isolates presenting with increased resistance to cefotaxime and cefixime. Background antibiotic use at the community level revealed a marked trend toward increased amoxicillin-clavulanic acid consumption. BLNAR H. influenzae strains have arisen by vertical and horizontal spread and have evolved to adapt rapidly to the increased selective pressures posed by the use of oral penicillins and cephalosporins. PMID:17470649

  17. Standardized deceased donor kidney donation rates in the UK reveal marked regional variation and highlight the potential for increasing kidney donation: a prospective cohort study†

    Science.gov (United States)

    Summers, D. M.; Johnson, R. J.; Hudson, A. J.; Collett, D.; Murphy, P.; Watson, C. J. E.; Neuberger, J. M.; Bradley, J. A.

    2014-01-01

    Background The UK has implemented a national strategy for organ donation that includes a centrally coordinated network of specialist nurses in organ donation embedded in all intensive care units and a national organ retrieval service for deceased organ donors. We aimed to determine whether despite the national approach to donation there is significant regional variation in deceased donor kidney donation rates. Methods The UK prospective audit of deaths in critical care was analysed for a cohort of patients who died in critical care between April 2010 and December 2011. Multivariate logistic regression was used to identify the factors associated with kidney donation. The logistic regression model was then used to produce risk-adjusted funnel plots describing the regional variation in donation rates. Results Of the 27 482 patients who died in a critical care setting, 1528 (5.5%) became kidney donors. Factors found to influence donation rates significantly were: type of critical care [e.g. neurointensive vs general intensive care: OR 1.53, 95% confidence interval (CI) 1.34–1.75, P69 vs age 18–39 yr: OR 0.2, 0.15–0.25, Pdonation rates for the 20 UK kidney donor regions showed marked variation. The overall standardized donation rate ranged from 3.2 to 7.5%. Four regions had donation rates of >2 standard deviations (sd) from the mean (two below and two above). Regional variation was most marked for donation after circulatory death (DCD) kidney donors with 9 of the 20 regions demonstrating donation rates of >2 sd from the mean (5 below and 4 above). Conclusions The marked regional variation in kidney donation rates observed in this cohort after adjustment for factors strongly associated with donation rates suggests that there is considerable scope for further increasing kidney donation rates in the UK, particularly DCD. PMID:24335581

  18. Increased resistance during jump exercise does not enhance cortical bone formation.

    Science.gov (United States)

    Boudreaux, Ramon D; Swift, Joshua M; Gasier, Heath G; Wiggs, Michael P; Hogan, Harry A; Fluckey, James D; Bloomfield, Susan A

    2014-01-01

    This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cortical bone of the tibia and femur mid-diaphyses. Sprague-Dawley rats (male, 6 months old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15), or cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE for 5 wk. Load in the HRE group was progressively increased from 80 g added to a weighted vest (50 repetitions) to 410 g (16 repetitions). The LRE rats completed the same protocol as the HRE group (same number of repetitions), with only a 30-g vest applied. Low- and high-load jump RE resulted in 6%-11% higher cortical bone mineral content and cortical bone area compared with controls, as determined by in vivo peripheral quantitative computed tomography measurements. In the femur, however, only LRE demonstrated improvements in cortical volumetric bone mineral density (+11%) and cross-sectional moment of inertia (+20%) versus the CC group. The three-point bending to failure revealed a marked increase in tibial maximum force (25%-29%), stiffness (19%-22%), and energy to maximum force (35%-55%) and a reduction in elastic modulus (-11% to 14%) in both LRE and HRE compared with controls. Dynamic histomorphometry assessed at the tibia mid-diaphysis determined that both LRE and HRE resulted in 20%-30% higher periosteal mineralizing surface versus the CC group. Mineral apposition rate and bone formation rate were significantly greater in animals in the LRE group (27%, 39%) than those in the HRE group. These data demonstrate that jump training with minimal loading is equally, and sometimes more, effective at augmenting cortical bone integrity compared with overload training in skeletally mature rats.

  19. The contribution of agricultural insecticide use to increasing insecticide resistance in African malaria vectors

    OpenAIRE

    Reid, Molly C.; McKenzie, F. Ellis

    2016-01-01

    The fight against malaria is increasingly threatened by failures in vector control due to growing insecticide resistance. This review examines the recent primary research that addresses the putative relationship between agricultural insecticide use and trends in insecticide resistance. To do so, descriptive evidence offered by the new research was categorized, and additional factors that impact the relationship between agricultural insecticide use and observed insecticide resistance in malari...

  20. Increasing incidence of fluoroquinolone-resistant Mycobacterium tuberculosis in Mumbai, India.

    Science.gov (United States)

    Agrawal, D; Udwadia, Z F; Rodriguez, C; Mehta, A

    2009-01-01

    Tertiary referral centre, private hospital, Mumbai, India. To analyse the incidence of fluoroquinolone (FQ) resistant Mycobacterium tuberculosis (TB) in our laboratory from 1995 to 2004. Retrospective review and analysis of the drug susceptibility test records of all M. tuberculosis culture-positive samples from our Microbiology Department from 1995 to 2004. FQ resistance has increased exponentially in our laboratory, from 3% in 1996 to 35% in 2004. The incidence of multidrug-resistant tuberculosis has also increased during the same period, from 33% in 1995 to 56% in 2004. The incidence of FQ-resistant M. tuberculosis is gradually increasing to alarming levels. This may be due to widespread use of this vital group of drugs in the treatment of community-acquired infections. We urge that these broad spectrum antibiotics be used judiciously, and ideally be reserved for treatment of resistant TB in TB-endemic areas.

  1. Mixed-Methods Resistance Training Increases Power and Strength of Young and Older Men.

    Science.gov (United States)

    Newton, Robert U.; Hakkinen, Keijo; Hakkinen, Arja; McCormick, Matt; Volek, Jeff; Kraemer, William J.

    2002-01-01

    Examined the effects of a 10-week, mixed-methods resistance training program on young and older men. Although results confirmed some age-related reductions in muscle strength and power, the older men demonstrated similar capacity to the younger men for increases in muscle strength and power via an appropriate, periodized resistance training…

  2. The contribution of agricultural insecticide use to increasing insecticide resistance in African malaria vectors.

    Science.gov (United States)

    Reid, Molly C; McKenzie, F Ellis

    2016-02-19

    The fight against malaria is increasingly threatened by failures in vector control due to growing insecticide resistance. This review examines the recent primary research that addresses the putative relationship between agricultural insecticide use and trends in insecticide resistance. To do so, descriptive evidence offered by the new research was categorized, and additional factors that impact the relationship between agricultural insecticide use and observed insecticide resistance in malaria vectors were identified. In 23 of the 25 relevant recent publications from across Africa, higher resistance in mosquito populations was associated with agricultural insecticide use. This association appears to be affected by crop type, farm pest management strategy and urban development.

  3. Prayer marks.

    Science.gov (United States)

    Abanmi, Abdullah A; Al Zouman, Abdulrahman Y; Al Hussaini, Husa; Al-Asmari, Abdulrahman

    2002-07-01

    Prayer marks (PMs) are asymptomatic, chronic skin changes that consist mainly of thickening, lichenification, and hyperpigmentation, and develop over a long period of time as a consequence of repeated, extended pressure on bony prominences during prayer. Three hundred and forty-nine Muslims and 24 non-Muslims were examined for the appearance of PMs at different body sites. The prospective study of 349 Muslims (both males and females) with regular praying habits showed the occurrence of PMs on specific locations, such as the forehead, knees, ankles, and dorsa of the feet, leading to dermatologic changes consisting of lichenification and hyperpigmentation. The incidence of PMs was significantly higher in males than in females. Older subjects (over 50 years of age) demonstrated a significantly higher frequency of lichenification and hyperpigmentation, suggesting that repeated pressure and friction for prolonged periods are the causative factors for the development of PMs. Histologic examination of skin biopsies from the affected sites showed compact orthokeratosis, hypergranulosis, dermal papillary fibrosis, and dermal vascularization. PMs were not associated with any risk of secondary complications, such as erythema, bullous formation, and infections. PMs are commonly occurring dermatologic changes in Muslims who pray for prolonged periods.

  4. Sucralose Increases Antimicrobial Resistance and Stimulates Recovery of Escherichia coli Mutants.

    Science.gov (United States)

    Qu, Yilin; Li, Rongyan; Jiang, Mingshan; Wang, Xiuhong

    2017-07-01

    Because of heavy use of antimicrobials, antimicrobial resistance in bacteria has become of great concern. The effect of some widely used food additives such as sucralose on bacteria in the gut and the environment has also drawn increasing attention. In this study, we investigated the interaction between antimicrobials and sucralose impacting antimicrobial resistance and mutation of Escherichia coli (E. coli). To examine antimicrobial resistance and mutation frequency, different subinhibitory concentrations of sucralose were added to cultures of E.coli BW25113 that were then treated with antimicrobials, oxolinic acid, or moxifloxacin. Then the E.coli were assayed for bacterial survival and recovery of mutants resistant to an unrelated antimicrobial, rifampicin. Pre-treatment of E.coli BW25113 with 1/2 minimal inhibitory concentration (MIC) of sucralose increased the survival rate in oxolinic acid or moxifloxacin. A 1/3 MIC of sucralose increased rifampicin-resistant mutation rate of E.coli BW25113 after 72 h, while rifampicin-resistant mutation rate was increased when co-treated with 1/8 MIC, 1/4 MIC, 1/3 MIC sucralose, and oxolinic acid after 24 h. Sucralose can increase the antimicrobial resistance and mutation frequency of E.coli to some antimicrobials.

  5. Liraglutide increases FGF-21 activity and insulin sensitivity in high fat diet and adiponectin knockdown induced insulin resistance.

    Directory of Open Access Journals (Sweden)

    Mengliu Yang

    Full Text Available BACKGROUND: Liraglutide is a glucagon-like peptide-1 analogue that stimulates insulin secretion and improves β-cell function. However, it is not clear whether liraglutide achieves its glucose lowering effect only by its known effects or whether other as yet unknown mechanisms are involved. The aim of this study was to examine the effects of liraglutide on Fibroblast growth factor-21 (FGF-21 activity in High-fat diet (HFD fed ApoE(-/- mice with adiponectin (Acrp30 knockdown. METHOD: HFD-fed ApoE(-/- mice were treated with adenovirus vectors expressing shAcrp30 to produce insulin resistance. Hyperinsulinemic-euglycemic clamp studies were performed to evaluate insulin sensitivity of the mouse model. QRT-PCR and Western blot were used to measure the mRNA and protein expression of the target genes. RESULTS: The combination of HFD, ApoE deficiency, and hypoadiponectinemia resulted in an additive effect on insulin resistance. FGF-21 mRNA expressions in both liver and adipose tissues were significantly increased while FGF-21 receptor 1 (FGFR-1 and β-Klotho mRNA levels in adipose tissue, as well as FGFR-1-3 and β-Klotho mRNA levels in liver were significantly decreased in this model. Liraglutide treatment markedly improved insulin resistance and increased FGF-21 expression in liver and FGFR-3 in adipose tissue, restored β-Klotho mRNA expression in adipose tissue as well as FGFR-1-3, β-Klotho levels and phosphorylation of FGFR1 up to the levels observed in control mice in liver. Liraglutide treatment also further increased FGF-21 proteins in liver and plasma. In addition, as shown by hyperinsulinemic-euglycemic clamp, liraglutide treatment also markedly improved glucose metabolism and insulin sensitivity in these animals. CONCLUSION: These findings demonstrate an additive effect of HFD, ApoE deficiency, and adiponectin knockdown on insulin resistance and unveil that the regulation of glucose metabolism and insulin sensitivity by liraglutide may be

  6. 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

  7. Gemfibrozil markedly increases the plasma concentrations of montelukast: a previously unrecognized role for CYP2C8 in the metabolism of montelukast.

    Science.gov (United States)

    Karonen, T; Filppula, A; Laitila, J; Niemi, M; Neuvonen, P J; Backman, J T

    2010-08-01

    According to available information, montelukast is metabolized by cytochrome P450 (CYP) 3A4 and 2C9. In order to study the significance of CYP2C8 in the pharmacokinetics of montelukast, 10 healthy subjects were administered gemfibrozil 600 mg or placebo twice daily for 3 days, and 10 mg montelukast on day 3, in a randomized, crossover study. Gemfibrozil increased the mean area under the plasma concentration-time curve (AUC)(0-infinity), peak plasma concentration (C(max)), and elimination half-life (t(1/2)) of montelukast 4.5-fold, 1.5-fold, and 3.0-fold, respectively (P gemfibrozil, the time to reach C(max) (t(max)) of the montelukast metabolite M6 was prolonged threefold (P = 0.005), its AUC(0-7) was reduced by 40% (P = 0.027), and the AUC(0-24) of the secondary metabolite M4 was reduced by >90% (P gemfibrozil 1-O-beta glucuronide inhibited the formation of M6 (but not of M5) from montelukast 35-fold more potently than did gemfibrozil (half-maximal inhibitory concentration (IC(50)) 3.0 and 107 micromol/l, respectively). In conclusion, gemfibrozil markedly increases the plasma concentrations of montelukast, indicating that CYP2C8 is crucial in the elimination of montelukast.

  8. Curcumin increases the sensitivity of Paclitaxel-resistant NSCLC cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction.

    Science.gov (United States)

    Lu, Yimin; Wang, Jun; Liu, Lei; Yu, Lequn; Zhao, Nian; Zhou, Xingju; Lu, Xudong

    2017-04-01

    Non-small-cell lung cancer is one of the most lethal cancers in the worldwide. Although Paclitaxel-based combinational therapies have long been used as a standard treatment in aggressive non-small-cell lung cancers, Paclitaxel resistance emerges as a major clinical problem. It has been demonstrated that Curcumin from Curcuma longa as a traditional Chinese medicine can inhibit cancer cell proliferation. However, the role of Curcumin in Paclitaxel-resistant non-small-cell lung cancer cells is not clear. In this study, we investigated the effect of Curcumin on the Paclitaxel-resistant non-small-cell lung cancer cells and found that Curcumin treatment markedly increased the sensitivity of Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel. Mechanically, the study revealed that Curcumin could reduce the expression of metastasis-associated gene 1 (MTA1) gene through upregulation of microRNA-30c in Paclitaxel-resistant non-small-cell lung cancer cells. During the course, MTA1 reduction sensitized Paclitaxel-resistant non-small-cell lung cancer cells and enhanced the effect of Paclitaxel. Taken together, our studies indicate that Curcumin increases the sensitivity of Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction. Curcumin might be a potential adjuvant for non-small-cell lung cancer patients during Paclitaxel treatment.

  9. Profiling of barrier capacitance and spreading resistance using a transient linearly increasing voltage technique.

    Science.gov (United States)

    Gaubas, E; Ceponis, T; Kusakovskij, J

    2011-08-01

    A technique for the combined measurement of barrier capacitance and spreading resistance profiles using a linearly increasing voltage pulse is presented. The technique is based on the measurement and analysis of current transients, due to the barrier and diffusion capacitance, and the spreading resistance, between a needle probe and sample. To control the impact of deep traps in the barrier capacitance, a steady state bias illumination with infrared light was employed. Measurements of the spreading resistance and barrier capacitance profiles using a stepwise positioned probe on cross sectioned silicon pin diodes and pnp structures are presented.

  10. 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.

  11. Genetic variation associated with increased insecticide resistance in the malaria mosquito, Anopheles coluzzii.

    Science.gov (United States)

    Main, Bradley J; Everitt, Amanda; Cornel, Anthony J; Hormozdiari, Fereydoun; Lanzaro, Gregory C

    2018-04-04

    Malaria mortality rates in sub-Saharan Africa have declined significantly in recent years as a result of increased insecticide-treated bed net (ITN) usage. A major challenge to further progress is the emergence and spread of insecticide resistance alleles in the Anopheles mosquito vectors, like An. coluzzii. A non-synonymous mutation in the para voltage-gated sodium channel gene reduces pyrethroid-binding affinity, resulting in knockdown resistance (kdr). Metabolic mechanisms of insecticide resistance involving detoxification genes like cytochrome P450 genes, carboxylesterases, and glutathione S-transferases are also important. As some gene activity is tissue-specific and/or environmentally induced, gene regulatory variation may be overlooked when comparing expression from whole mosquito bodies under standard rearing conditions. We detected complex insecticide resistance in a 2014 An. coluzzii colony from southern Mali using bottle bioassays. Additional bioassays involving recombinant genotypes from a cross with a relatively susceptible 1995 An. coluzzii colony from Mali confirmed the importance of kdr and associated increased permethrin resistance to the CYP9K1 locus on the X chromosome. Significant differential expression of CYP9K1 was not observed among these colonies in Malpighian tubules. However, the P450 gene CYP6Z1 was overexpressed in resistant individuals following sublethal permethrin exposure and the carboxylesterase gene COEAE5G was constitutively overexpressed. The significant P450-related insecticide resistance observed in the 2014 An. coluzzii colony indicates that ITNs treated with the P450 inhibitor piperonyl butoxide (PBO) would be more effective in this region. The known insecticide resistance gene CYP6Z1 was differentially expressed exclusively in the context of sublethal permethrin exposure, highlighting the importance of tissue-specificity and environmental conditions in gene expression studies. The increased activity of the carboxylesterase

  12. Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells

    International Nuclear Information System (INIS)

    Guo, Xianling; Zhang, Baihe; Wu, Mengchao; Wei, Lixin; Ma, Nannan; Wang, Jin; Song, Jianrui; Bu, Xinxin; Cheng, Yue; Sun, Kai; Xiong, Haiyan; Jiang, Guocheng

    2008-01-01

    Chemoresistance is one of the main obstacles to successful cancer therapy and is frequently associated with Multidrug resistance (MDR). Many different mechanisms have been suggested to explain the development of an MDR phenotype in cancer cells. One of the most studied mechanisms is the overexpression of P-glycoprotein (P-gp), which is a product of the MDR1 gene. Tumor cells often acquire the drug-resistance phenotype due to upregulation of the MDR1 gene. Overexpression of MDR1 gene has often been reported in primary gastric adenocarcinoma. This study investigated the role of p38-MAPK signal pathway in vincristine-resistant SGC7901/VCR cells. P-gp and MDR1 RNA were detected by Western blot analysis and RT-PCR amplification. Mitgen-activated protein kinases and function of P-gp were demonstrated by Western blot and FACS Aria cytometer analysis. Ap-1 activity and cell apoptosis were detected by Dual-Luciferase Reporter Assay and annexin V-PI dual staining. The vincristine-resistant SGC7901/VCR cells with increased expression of the multidrug-resistance 1 (MDR1) gene were resistant to P-gp-related drug and P-gp-unrelated drugs. Constitutive increases of phosphorylated p38-MAPK and AP-1 activities were also found in the drug-resistant cells. Inhibition of p38-MAPK by SB202190 reduced activator protein-1 (AP-1) activity and MDR1 expression levels and increased the sensitivity of SGC7901/VCR cells to chemotherapy. Activation of the p38-MAPK pathway might be responsible for the modulation of P-glycoprotein-mediated and P-glycoprotein-unmediated multidrug resistance in the SGC7901/VCR cell line

  13. HIF-2α mediates a marked increase in migration and stemness characteristics in a subset of glioma cells under hypoxia by activating an Oct-4/Sox-2-Mena (INV) axis.

    Science.gov (United States)

    Bhagat, Mohita; Palanichamy, Jayanth Kumar; Ramalingam, Pradeep; Mudassir, Madeeha; Irshad, Khushboo; Chosdol, Kunzang; Sarkar, Chitra; Seth, Pankaj; Goswami, Sumanta; Sinha, Subrata; Chattopadhyay, Parthaprasad

    2016-05-01

    Hypoxia is a salient feature of most solid tumors and plays a central role in tumor progression owing to its multiple contributions to therapeutic resistance, metastasis, angiogenesis and stemness properties. Reports exist in literature about hypoxia increasing stemness characteristics and invasiveness potential of malignant cells. In order to delineate molecular crosstalk among factors driving glioma progression, we used knockdown and overexpression strategies. We have demonstrated that U87MG and A172 glioma cells inherently have a subset of cells with high migratory potential due to migration-inducing Mena transcripts. These cells also have elevated stemness markers (Sox-2 and Oct-4). There was a significant increase of number in this subset of migratory cells on exposure to hypoxia with corresponding elevation (over 1000 fold) in migration-inducing Mena transcripts. We were able to demonstrate that a HIF-2α-Sox-2/Oct-4-Mena (INV) axis that is strongly activated in hypoxia and markedly increases the migratory potential of the cells. Such cells also formed tumor spheres with greater efficiency. We have correlated our in-vitro results with human glioblastoma samples and found that hypoxia, invasiveness and stemness markers correlated well in native tumor samples. This study identifies a novel signaling mechanism mediated by HIF-2α in regulating invasiveness and stemness characteristics, suggesting that under hypoxic conditions, some tumor cells acquire more migratory potential by increased Pan Mena and Mena INV expression as a consequence of this HIF-2α mediated increase in Oct-4 and Sox-2. These properties would help the cells to form a new nidus after local invasion or metastasis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number.

    Science.gov (United States)

    Price, Ric N; Uhlemann, Anne-Catrin; Brockman, Alan; McGready, Rose; Ashley, Elizabeth; Phaipun, Lucy; Patel, Rina; Laing, Kenneth; Looareesuwan, Sornchai; White, Nicholas J; Nosten, François; Krishna, Sanjeev

    The borders of Thailand harbour the world's most multidrug resistant Plasmodium falciparum parasites. In 1984 mefloquine was introduced as treatment for uncomplicated falciparum malaria, but substantial resistance developed within 6 years. A combination of artesunate with mefloquine now cures more than 95% of acute infections. For both treatment regimens, the underlying mechanisms of resistance are not known. The relation between polymorphisms in the P falciparum multidrug resistant gene 1 (pfmdr1) and the in-vitro and in-vivo responses to mefloquine were assessed in 618 samples from patients with falciparum malaria studied prospectively over 12 years. pfmdr1 copy number was assessed by a robust real-time PCR assay. Single nucleotide polymorphisms of pfmdr1, P falciparum chloroquine resistance transporter gene (pfcrt) and P falciparum Ca2+ ATPase gene (pfATP6) were assessed by PCR-restriction fragment length polymorphism. Increased copy number of pfmdr1 was the most important determinant of in-vitro and in-vivo resistance to mefloquine, and also to reduced artesunate sensitivity in vitro. In a Cox regression model with control for known confounders, increased pfmdr1 copy number was associated with an attributable hazard ratio (AHR) for treatment failure of 6.3 (95% CI 2.9-13.8, p<0.001) after mefloquine monotherapy and 5.4 (2.0-14.6, p=0.001) after artesunate-mefloquine therapy. Single nucleotide polymorphisms in pfmdr1 were associated with increased mefloquine susceptibility in vitro, but not in vivo. Amplification in pfmdr1 is the main cause of resistance to mefloquine in falciparum malaria. Multidrug resistant P falciparum malaria is common in southeast Asia, but difficult to identify and treat. Genes that encode parasite transport proteins maybe involved in export of drugs and so cause resistance. In this study we show that increase in copy number of pfmdr1, a gene encoding a parasite transport protein, is the best overall predictor of treatment failure with

  15. A Lipid Transfer Protein Increases the Glutathione Content and Enhances Arabidopsis Resistance to a Trichothecene Mycotoxin.

    Directory of Open Access Journals (Sweden)

    John E McLaughlin

    Full Text Available Fusarium head blight (FHB or scab is one of the most important plant diseases worldwide, affecting wheat, barley and other small grains. Trichothecene mycotoxins such as deoxynivalenol (DON accumulate in the grain, presenting a food safety risk and health hazard to humans and animals. Despite considerable breeding efforts, highly resistant wheat or barley cultivars are not available. We screened an activation tagged Arabidopsis thaliana population for resistance to trichothecin (Tcin, a type B trichothecene in the same class as DON. Here we show that one of the resistant lines identified, trichothecene resistant 1 (trr1 contains a T-DNA insertion upstream of two nonspecific lipid transfer protein (nsLTP genes, AtLTP4.4 and AtLTP4.5. Expression of both nsLTP genes was induced in trr1 over 10-fold relative to wild type. Overexpression of AtLTP4.4 provided greater resistance to Tcin than AtLTP4.5 in Arabidopsis thaliana and in Saccharomyces cerevisiae relative to wild type or vector transformed lines, suggesting a conserved protection mechanism. Tcin treatment increased reactive oxygen species (ROS production in Arabidopsis and ROS stain was associated with the chloroplast, the cell wall and the apoplast. ROS levels were attenuated in Arabidopsis and in yeast overexpressing AtLTP4.4 relative to the controls. Exogenous addition of glutathione and other antioxidants enhanced resistance of Arabidopsis to Tcin while the addition of buthionine sulfoximine, an inhibitor of glutathione synthesis, increased sensitivity, suggesting that resistance was mediated by glutathione. Total glutathione content was significantly higher in Arabidopsis and in yeast overexpressing AtLTP4.4 relative to the controls, highlighting the importance of AtLTP4.4 in maintaining the redox state. These results demonstrate that trichothecenes cause ROS accumulation and overexpression of AtLTP4.4 protects against trichothecene-induced oxidative stress by increasing the glutathione

  16. Aromatic polymers of increased resistance to flow and molecular weight obtained by irradiation

    International Nuclear Information System (INIS)

    Staniland, P.A.; Jarrett, G.

    1976-01-01

    Aromatic polymers of increased resistance to flow and increased molecular weight are obtained by irradiation using β rays or gamma rays at temperatures up to 400 0 C of an aromatic polymer whose molecular chains comprise benzenoid groups and bivalent linking groups, and where irradiation is gamma rays by heating subsequent to irradiation at 200 0 C to 400 0 C. The polymeric materials having increased molecular weight are useful for coating non-cooking surfaces of cookware

  17. NotaMark industrial laser marking system: a new security marking technology

    Science.gov (United States)

    Moreau, Vincent G.

    2004-06-01

    Up until now, the only variable alphanumeric data which could be added to banknotes was the number, applied by means of impact typographical numbering boxes. As an additional process or an alternative to this mechanical method, a non-contact laser marking process can be used offering high quality and greater levels of flexibility. For this purpose KBA-GIORI propose an exclusive laser marking solution called NotaMark. The laser marking process NotaMark is the ideal solution for applying variable data and personalizing banknotes (or any other security documents) with a very high resolution, for extremely large production volumes. A completely integrated solution has been developed comprised of laser light sources, marking head units, and covers and extraction systems. NotaMark allows the marking of variable data by removing locally and selectively, specific printed materials leaving the substrate itself untouched. A wide range of materials has already been tested extensively. NotaMark is a new security feature which is easy to identify and difficult to counterfeit, and which complies with the standard mechanical and chemical resistance tests in the security printing industry as well as with other major soiling tests. The laser marking process opens up a whole new range of design possibilities and can be used to create a primary security feature such as numbering, or to enhance the value of existing features.

  18. Development and evaluation of a HEPA filter for increased strength and resistance to elevated temperature

    International Nuclear Information System (INIS)

    Gilbert, H.; Bergman, W.; Fretthold, J.K.

    1992-01-01

    We have developed an improved HEPA filter for increased strength and resistance to elevated temperature to improve the reliability of HEPA filters under accident conditions. The improvements to the HEPA filter consist of a silicone rubber sealant and a new HEPA medium reinforced with a glass cloth. Several prototype filters were built and evaluated for temperature and pressure resistance and resistance to rough handling. The temperature resistance test consisted of exposing the HEPA filter to 1,000 scan at 700 degrees F for five minutes. The pressure resistance test consisted of exposing the HEPA filter to a differential pressure of 10 in. w.g. using a water saturated air flow at 95 degrees F. For the rough handling test, we used a vibrating machine designated the Q110. DOP filter efficiency tests were performed before and after each of the environmental tests. In addition to following the standard practice of using a separate new filter for each environmental test, we also subjected the same filter to the elevated temperature test followed by the pressure resistance test. The efficiency test results show that the improved HEPA filter is significantly better than the standard HEPA filter

  19. Development and evaluation of a HEPA filter for increased strength and resistance to elevated temperature

    International Nuclear Information System (INIS)

    Gilbert, H.; Bergman, W.; Fretthold, J.K.

    1993-01-01

    We have completed a preliminary study of an improved HEPA filter for increased strength and resistance to elevated temperature to improve the reliability of the standard deep pleated HEPA filter under accident conditions. The improvements to the HEPA filter consist of a silicone rubber sealant and a new HEPA medium reinforced with a glass cloth. Three prototype filters were built and evaluated for temperature and pressure resistance and resistance to rough handling. The temperature resistance test consisted of exposing the HEPA filter to 1,000 scan (1,700 m 3 /hr) at 700 degrees F (371 degrees C) for five minutes.The pressure resistance test consisted of exposing the HEPA filter to a differential pressure of 10 in. w.g. (2.5 kPa) using a water saturated air flow at 95 degrees F (35 degrees C). For the rough handling test, we used a vibrating machine designated the Q110. DOP filter efficiency tests were performed before and after each of the environmental tests. In addition to following the standard practice of using a separate new filter for each environmental test, we also subjected the same filter to the elevated temperature test followed by the pressure resistance test. The efficiency test results show that the improved HEPA filter is significantly better than the standard HEPA filter. Further studies are recommended to evaluate the improved HEPA filter and to assess its performance under more severe accident conditions

  20. Diabetes and hypertension markedly increased the risk of ischemic stroke associated with high serum resistin concentration in a general Japanese population: the Hisayama Study

    Directory of Open Access Journals (Sweden)

    Kawamura Ryoichi

    2009-11-01

    Full Text Available Abstract Background Resistin, secreted from adipocytes, causes insulin resistance in mice. The relationship between resistin and coronary artery disease is highly controversial, and the information regarding resistin and ischemic stroke is limited. In the present study, the association between serum resistin concentration and cardiovascular disease (CVD was investigated in a general Japanese population. Methods A total of 3,201 community-dwelling individuals aged 40 years or older (1,382 men and 1,819 women were divided into quintiles of serum resistin, and the association between resistin and CVD was examined cross-sectionally. The combined effect of either diabetes or hypertension and high serum resistin was also assessed. Serum resistin was measured using ELISA. Results Compared to those without CVD, age- and sex-adjusted mean serum resistin concentrations were greater in subjects with CVD (p = 0.002 or ischemic stroke (p Conclusion Elevated serum resistin concentration appears to be an independent risk factor for ischemic stroke, especially lacunar and atherothrombotic infarction in the general Japanese population. The combination of high resistin and the presence of either diabetes or hypertension increased the risk of ischemic stroke.

  1. GCKR variants increase triglycerides while protecting from insulin resistance in Chinese children.

    Science.gov (United States)

    Shen, Yue; Wu, Lijun; Xi, Bo; Liu, Xin; Zhao, Xiaoyuan; Cheng, Hong; Hou, Dongqing; Wang, Xingyu; Mi, Jie

    2013-01-01

    Variants in gene encoding glucokinase regulator protein (GCKR) were found to have converse effects on triglycerides and glucose metabolic traits. We aimed to investigate the influence of GCKR variants for triglycerides and glucose metabolic traits in Chinese children and adults. We genotyped two GCKR variants rs1260326 and rs1260333 in children and adults, and analyzed the association between two variants and triglycerides, glucose, insulin and HOMA-IR using linear regression model, and estimated the effect on insulin resistance using logistic regression model. Rs1260326 and rs1260333 associated with increased triglycerides in children and adults (ptriglycerides in Chinese children and adults. Triglycerides-increasing alleles of GCKR variants reduce insulin and HOMA-IR index, and protect from insulin resistance in children. Our results suggested GCKR has an effect on development of insulin resistance in Chinese children.

  2. Coaxial Tubing Systems Increase Artificial Airway Resistance and Work of Breathing.

    Science.gov (United States)

    Wenzel, Christin; Schumann, Stefan; Spaeth, Johannes

    2017-09-01

    Tubing systems are an essential component of the ventilation circuit, connecting the ventilator to the patient's airways. Coaxial tubing systems incorporate the inspiratory tube within the lumen of the expiratory one. We hypothesized that by design, these tubing systems increase resistance to air flow compared with conventional ones. We investigated the flow-dependent pressure gradient across coaxial, conventional disposable, and conventional reusable tubing systems from 3 different manufacturers. Additionally, the additional work of breathing and perception of resistance during breathing through the different devices were determined in 18 healthy volunteers. The pressure gradient across coaxial tubing systems was up to 6 times higher compared with conventional ones (1.90 ± 0.03 cm H 2 O vs 0.34 ± 0.01 cm H 2 O, P tubing systems, accordingly. Our findings suggest that the use of coaxial tubing systems should be carefully considered with respect to their increased resistance. Copyright © 2017 by Daedalus Enterprises.

  3. Impetigo: A need for new therapies in a world of increasing antimicrobial resistance.

    Science.gov (United States)

    D'Cunha, N M; Peterson, G M; Baby, K E; Thomas, J

    2018-02-01

    Impetigo is a highly contagious bacterial skin infection and is one of the most common skin infections in children. Antibiotics are the first-line treatment when multiple lesions exist, but with an increasing prevalence of antibiotic-resistant bacteria the successful management of impetigo in the future is an area of concern. Current treatment options that favour the use of oral antibiotic therapy are increasingly problematic. Widespread use of these agents contributes to antimicrobial resistance and has adverse consequences for individuals and communities. There is a need for new topical antimicrobials and antiseptics as an alternative treatment strategy. To successfully treat impetigo into the future and ensure that therapy does not contribute to bacterial resistance, additional research is required to ascertain the usefulness of alternative agents, including new topical antimicrobials and antiseptics. © 2017 John Wiley & Sons Ltd.

  4. Cisplatin-resistant cells express increased levels of a factor that recognizes damaged DNA

    International Nuclear Information System (INIS)

    Chu, G.; Chang, E.

    1990-01-01

    Cancer treatment with the drug cisplatin is often thwarted by the emergence of drug-resistant cells. To study this phenomenon, the authors identified two independent cellular factors that recognize cisplatin-damaged DNA. One of the two factors, designated XPE binding factor, is deficient in complementation group E of xeroderma pigmentosum, an inherited disease characterized by defective repair of DNA damaged by ultraviolet radiation, cisplatin, and other agents. Human tumor cell lines selected for resistance to cisplatin showed more efficient DNA repair and increased expression of XPE binding factor. These results suggest that XPE binding factor may be responsible, at least in part, for the development of cisplatin resistance in human tumors and that the mechanism may be increased DNA repair

  5. Transgenic Pm3 multilines of wheat show increased powdery mildew resistance in the field.

    Science.gov (United States)

    Brunner, Susanne; Stirnweis, Daniel; Diaz Quijano, Carolina; Buesing, Gabriele; Herren, Gerhard; Parlange, Francis; Barret, Pierre; Tassy, Caroline; Sautter, Christof; Winzeler, Michael; Keller, Beat

    2012-05-01

    Resistance (R) genes protect plants very effectively from disease, but many of them are rapidly overcome when present in widely grown cultivars. To overcome this lack of durability, strategies that increase host resistance diversity have been proposed. Among them is the use of multilines composed of near-isogenic lines (NILs) containing different disease resistance genes. In contrast to classical R-gene introgression by recurrent backcrossing, a transgenic approach allows the development of lines with identical genetic background, differing only in a single R gene. We have used alleles of the resistance locus Pm3 in wheat, conferring race-specific resistance to wheat powdery mildew (Blumeria graminis f. sp. tritici), to develop transgenic wheat lines overexpressing Pm3a, Pm3c, Pm3d, Pm3f or Pm3g. In field experiments, all tested transgenic lines were significantly more resistant than their respective nontransformed sister lines. The resistance level of the transgenic Pm3 lines was determined mainly by the frequency of virulence to the particular Pm3 allele in the powdery mildew population, Pm3 expression levels and most likely also allele-specific properties. We created six two-way multilines by mixing seeds of the parental line Bobwhite and transgenic Pm3a, Pm3b and Pm3d lines. The Pm3 multilines were more resistant than their components when tested in the field. This demonstrates that the difference in a single R gene is sufficient to cause host-diversity effects and that multilines of transgenic Pm3 wheat lines represent a promising strategy for an effective and sustainable use of Pm3 alleles. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  6. Increased bioactive lipids content in human subcutaneous and epicardial fat tissue correlates with insulin resistance.

    Science.gov (United States)

    Błachnio-Zabielska, Agnieszka U; Baranowski, Marcin; Hirnle, Tomasz; Zabielski, Piotr; Lewczuk, Anna; Dmitruk, Iwona; Górski, Jan

    2012-12-01

    Obesity is a risk factor for metabolic diseases. Intramuscular lipid accumulation of ceramides, diacylglycerols, and long chain acyl-CoA is responsible for the induction of insulin resistance. These lipids are probably implicated in obesity-associated insulin resistance not only in skeletal muscle but also in fat tissue. Only few data are available about ceramide content in human subcutaneous adipose tissue. However, there are no data on DAG and LCACoA content in adipose tissue. The aim of our study was to measure the lipids content in human SAT and epicardial adipose tissue we sought to determine the bioactive lipids content by LC/MS/MS in fat tissue from lean non-diabetic, obese non-diabetic, and obese diabetic subjects and test whether the lipids correlate with HOMA-IR. We found, that total content of measured lipids was markedly higher in OND and OD subjects in both types of fat tissue (for all p lipids content is greater in subcutaneous and epicardial fat tissue and the particular lipids content positively correlates with HOMA-IR.

  7. Increased Resistance of Skin Flora to Antimicrobial Prophylaxis in Patients Undergoing Hip Revision Arthroplasty.

    Science.gov (United States)

    Mühlhofer, Heinrich M L; Deiss, Lukas; Mayer-Kuckuk, Philipp; Pohlig, Florian; Harrasser, Norbert; Lenze, Ulrich; Gollwitzer, Hans; Suren, Christian; Prodinger, Peter; VON Eisenhart-Rothe, Rüdiger; Schauwecker, Johannes

    2017-01-01

    Prosthetic joint infection (PJI) remains a major complication after total joint replacement and is the primary indication for revision arthroplasty. Specifically, coagulase-negative Staphylococci (CNS) can cause low-grade infections. Despite the use of cephalosporin-based antimicrobial prophylaxis (AMP) and antiseptic treatment at the surgical site, evidence suggests that a significant number of cases of dermal CNS results in low-grade PJI. Thus, this study examined the bacterial colonization and resistance patterns at the surgical site. We hypothesized that the bacteria developed resistance to antibiotics that are frequently used in primary and revision total hip arthroplasty (THA) procedures. Ninety patients, including 63 primary and 27 revision THA patients, were enrolled in this study. For each patient, a single swab of the skin at the surgical site was subjected to clinical microbiology to assess bacterial colonization. Furthermore, resistance to a sentinel panel of antibiotics (benzylpenicillin, erythromycin, tetracycline, oxacillin, fusidic acid, clindamycin, gentamicin, levofloxacin/moxifloxacin, rifampicin, linezolid and vancomycin) was tested. In 96.7% of the patients, at least one bacterial strain was identified at the surgical site, with CNS strains comprising 93.1% of the total. The sentinel panel showed that 30.7% of the CNS strains exhibited maximal resistance to oxacillin, a commonly used cephalosporin. Additionally, oxacillin resistance increased 1.9-fold (p=0.042) between primary and revision THA. Notably, 8.1% of the CNS stains found on patients undergoing primary THA were resistant to gentamicin, an aminoglycoside, and this rate increased 4.7-fold (p=0.001) for patients undergoing revision THA. CNS strains have significant resistance to standard AMP, particularly in individuals undergoing revision THA. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. Overexpression of a citrus NDR1 ortholog increases disease resistance in Arabidopsis

    Science.gov (United States)

    Emerging devastating diseases, such as Huanglongbing (HLB) and citrus canker, have caused tremendous losses to the citrus industry worldwide. Genetic engineering is a powerful approach that could allow us to increase citrus resistance against these diseases. The key to the success of this approach r...

  9. Production of mutants of Candida utilis with increased resistence against furfural

    International Nuclear Information System (INIS)

    Stehlik, G.; Baron, M.; Turanitz, K.; Schneider, F.

    1978-01-01

    By repeated γ-irradiation treatments and following selections a mutant of Candida utilis weissenbachii was isolated showing increased resistance against furfural as compared to its wild type. Growing and radiation survival behavior of these yeasts are compared. Analysis of furfural was done by gaschromatography on Porapak Q. (author)

  10. METHODS OF INCREASING THE RESISTANCE OF A HEAVILY HOT TOOL LANDING BOLT HEADS

    Directory of Open Access Journals (Sweden)

    V. N. Fedoulov

    2016-01-01

    Full Text Available The present study focuses on increasing resistance of highly-loaded instrument (in particular, punches for stud driving head diameter of 8 mm and 10 mm countersunk hex through the optimization of heat hardening process using a forged-rolled steel billet DI23 in its production.

  11. Increased incidences of multidrug-resistant gonorrhea in Taiwanese men: Experiences from a single institute

    Directory of Open Access Journals (Sweden)

    Yu-Hua Lin

    2016-06-01

    Conclusion: Genital discharge swab culture is a more effective method than urine culture to detect gonorrhea in patients with dysuria and urethral discharge. The increasing numbers of antibiotic-resistant N. gonorrhoeae strains is a major problem in treating gonococcal urethritis.

  12. METHODS OF INCREASING THE RESISTANCE OF A HEAVILY HOT TOOL LANDING BOLT HEADS

    OpenAIRE

    V. N. Fedoulov

    2016-01-01

    The present study focuses on increasing resistance of highly-loaded instrument (in particular, punches) for stud driving head diameter of 8 mm and 10 mm countersunk hex through the optimization of heat hardening process using a forged-rolled steel billet DI23 in its production.

  13. Crack resistance increasing in epoxide-rubber coatings of NPP room floors

    International Nuclear Information System (INIS)

    Khorenzhenko, V.I.

    1986-01-01

    Problems of crack resistance increasing in epoxide-rubber coatings for the floors are considered. Exploitation experience of the floors in the special rooms of NPP is given. Perspectivity of application of the compositions described as the building materials for nuclear power stations is pointed out

  14. Studying titanium-molybdenum-zirconium alloys of increased corrosion resistance in acid solutions

    International Nuclear Information System (INIS)

    Tomashov, N.D.; Kazarin, V.I.; Mikheev, V.S.; Goncharenko, B.A.; Sigalovskaya, T.M.; Kalyanova, M.P.

    1977-01-01

    New promising Ti-Mo-Nb-Zr system alloys, possessing good workability and a high corrosion resistance in non-oxidizing solutions of acids, have been developed. The alloys may be recommended as structural materials for equipment operating in severely agressive acid media, such as hydrochloric, sulphuric and phosphoric acids. The corrosion resistance of alloys of the above system in solutions of H 2 SO 4 , HCl and H 3 PO 4 acids may be maximized by increasing the overall alloying to 42% (keeping the ratio of the alloying components Mo/Nb/Zr=4/1/1 unchanged), while retaining sufficiently good plasticity and workability

  15. Wear resistance increase of the modified coatings, deposited in the beam of relativistic electrons

    International Nuclear Information System (INIS)

    Poletika, I.M.; Perovskaya, M.V.; Balushkina, M.A.

    2015-01-01

    The 1.5-3 mm thickness coatings have been obtained by vacuum - free electron beam cladding of tungsten carbide on low - carbon steel sub state. The coatings have an increased hardness but low wear resistance. Adding both nickel and titanium carbide to the tungsten carbide results in essentially improving the wear resistance of the coatings due to austenite-promoting effect of nickel and precipitation of fine Tic particles resulting in the formation of the final and nano grain structure. In the layer of weld one can find 30-100 nm grain - size structures. (authors)

  16. Combined whole-body vibration, resistance exercise, and sustained vascular occlusion increases PGC-1α and VEGF mRNA abundances.

    Science.gov (United States)

    Item, Flurin; Nocito, Antonio; Thöny, Sandra; Bächler, Thomas; Boutellier, Urs; Wenger, Roland H; Toigo, Marco

    2013-04-01

    We previously reported that high load resistance exercise with superimposed whole-body vibration and sustained vascular occlusion (vibroX) markedly improves cycling endurance capacity, increases capillary-to-fibre ratio and skeletal muscle oxidative enzyme activity in untrained young women. These findings are intriguing, since increases in oxidative muscle phenotype and endurance capacity are typically induced by endurance but not heavy resistance exercise. Here, we tested the hypothesis that vibroX activates genes associated with mitochondrial biogenesis and angiogenesis. Eight healthy, recreationally resistance-trained young men performed either vibroX or resistance exercise (RES) in a randomised, cross-over design. Needle biopsies (M. vastus lateralis) were obtained at rest and 3 h post-exercise. Changes in relative gene expression levels were assessed by real-time quantitative PCR. After vibroX, vascular endothelial growth factor and peroxisome proliferator-activated receptor-γ coactivator 1α mRNA abundances increased to 2- and 4.4-fold, respectively, but did not significantly change above resting values after RES. Other genes involved in mitochondrial biogenesis were not affected by either exercise modality. While vibroX increased the expression of hexokinase II, xanthine dehydrogenase, and manganese superoxide dismutase mRNA, there were no changes in these transcripts after RES. This study demonstrates that high load resistance exercise with superimposed whole-body vibration and sustained vascular occlusion activates metabolic and angiogenic gene programs, which are usually activated after endurance but not resistance exercise. Thus, targeted modification of high load resistance exercise by vibration and vascular occlusion might represent a novel strategy to induce endurance-type muscle adaptations.

  17. TIMP-1 increases expression and phosphorylation of proteins associated with drug resistance in breast cancer cells

    DEFF Research Database (Denmark)

    Hekmat, Omid; Munk, Stephanie; Fogh, Louise

    2013-01-01

    may explain the resistance phenotype to topoisomerase inhibitors that was observed in cells with high TIMP-1 levels. Pathway analysis showed an enrichment of proteins from functional categories such as apoptosis, cell cycle, DNA repair, transcription factors, drug targets and proteins associated......Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a protein with a potential biological role in drug resistance. To elucidate the unknown molecular mechanisms underlying the association between high TIMP-1 levels and increased chemotherapy resistance, we employed SILAC-based quantitative mass...... spectrometry to analyze global proteome and phosphoproteome differences of MCF-7 breast cancer cells expressing high or low levels of TIMP-1. In TIMP-1 high expressing cells, 312 proteins and 452 phosphorylation sites were up-regulated. Among these were the cancer drug targets topoisomerase 1, 2A and 2B, which...

  18. Relationship between increased serum tumor necrosis factor levels and insulin resistance in patients with essential hypertension

    International Nuclear Information System (INIS)

    Wang Weimin; Li Jinliang; Huang Yongqiang

    2010-01-01

    Objective: To investigate the relationship between serum tumor necrosis factor-α (TNF-α) levels and insulin resistance (IR) in patients with essential by pertension. Methods: Serum TNF-α and free insulin (fINS)levels were measured with RIA in 41 patients with essential hypertension and 38 controls. Insulin resistance was calculated with insulin resistance index (HOMA-IR). Results: The serum TNF-α levels were significantly higher in patients with essential hypertension than those in the controls (P<0.001). The HOMA-IR was also significantly higher in hypertension group than that in controls (P<0.001). Serum TNF-α levels was positively correlated with BMI, HOMA-IR and SBP both in hypertension group and control group (P<0.05). Conclusion: Serum TNF-α level was increased in hypertensive patients and positively correlated with obesity and IR. (authors)

  19. Mice fed a high-fat diet supplemented with resistant starch display marked shifts in the liver metabolome concurrent with altered gut bacteria

    Science.gov (United States)

    High-amylose maize resistant starch type 2 (HAMRS2) is a fermentable dietary fiber known to alter the gut milieu, including the gut microbiota, which may explain reported effects of resistant starch to ameliorate obesity-associated metabolic dysfunction. Our working hypothesis is that HAMRS2-induced...

  20. Increased fitness and realized heritability in emamectin benzoate-resistant Chrysoperla carnea (Neuroptera: Chrysopidae).

    Science.gov (United States)

    Mansoor, Muhammad Mudassir; Abbas, Naeem; Shad, Sarfraz Ali; Pathan, Attaullah Khan; Razaq, Muhammad

    2013-10-01

    The common green lacewing Chrysoperla carnea is a key biological control agent employed in integrated pest management (IPM) programs for managing various insect pests. A field collected population of C. carnea was selected for emamectin benzoate resistance in the laboratory and fitness costs and realized heritability were investigated. After five generations of selection with emamectin benzoate, C. carnea developed a 318-fold resistance to the insecticide. The resistant population had a relative fitness of 1.49, with substantially higher emergence rate of healthy adults, fecundity and hatchability and shorter larval duration, pupal duration, and development time compared to the susceptible population. Mean population growth rates; such as the intrinsic rate of natural population increase and biotic potential were higher for the emamectin benzoate selected population compared to the susceptible population. The realized heritability (h(2)) value of emamectin benzoate resistance was 0.34 in emamectin benzoate selected population of C. carnea. Chrysoperla species which show resistance to insecticides makes them compatible with those IPM systems where emamectin benzoate is employed.

  1. Increasing resistance to quinolones: A four-year prospective study of urinary tract infection pathogens

    Directory of Open Access Journals (Sweden)

    Orhiosefe Omigie

    2009-08-01

    Full Text Available Orhiosefe Omigie, Lawrence Okoror, Patience Umolu, Gladys IkuuhDepartment of Microbiology, Ambrose Alli University, Ekpoma, NigeriaAbstract: A four-year prospective study was carried out to determine the incidence and rate of development of resistance by common urinary tract infection (UTI pathogens to quinolone antimicrobial agents. Results show that there is high intrinsic resistance to the quinolones among strains of Pseudomonas aeruginosa (43.4%, Escherichia coli (26.3%, and Proteus spp. (17.1%. Over four years, rising rates of resistance were observed in P. aeruginosa (14.6% increase, Staphylococcus aureus (9.8%, and E. coli (9.7%. The highest potency was exhibited by ciprofloxacin (91.2%, levofloxacin (89.2%, and moxifloxacin (85.1%, while there were high rates of resistance to nalidixic acid (51.7% and pefloxacin (29.0%. Coliforms, particularly E. coli (>45%, remain the most prevalent causative agents of UTI while females within the age range of 20–50 years were most vulnerable to UTI.Keywords: UTI, microorganisms, antibiotics, resistance

  2. Increasing antibiotic resistance in preservative-tolerant bacterial strains isolated from cosmetic products.

    Science.gov (United States)

    Orús, Pilar; Gomez-Perez, Laura; Leranoz, Sonia; Berlanga, Mercedes

    2015-03-01

    To ensure the microbiological quality, consumer safety and organoleptic properties of cosmetic products, manufacturers need to comply with defined standards using several preservatives and disinfectants. A drawback regarding the use of these preservatives is the possibility of generating cross-insusceptibility to other disinfectants or preservatives, as well as cross resistance to antibiotics. Therefore, the objective of this study was to understand the adaptive mechanisms of Enterobacter gergoviae, Pseudomonas putida and Burkholderia cepacia that are involved in recurrent contamination in cosmetic products containing preservatives. Diminished susceptibility to formaldehyde-donors was detected in isolates but not to other preservatives commonly used in the cosmetics industry, although increasing resistance to different antibiotics (β-lactams, quinolones, rifampicin, and tetracycline) was demonstrated in these strains when compared with the wild-type strain. The outer membrane protein modifications and efflux mechanism activities responsible for the resistance trait were evaluated. The development of antibiotic-resistant microorganisms due to the selective pressure from preservatives included in cosmetic products could be a risk for the emergence and spread of bacterial resistance in the environment. Nevertheless, the large contribution of disinfection and preservation cannot be denied in cosmetic products. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

  3. Progressive increase in point mutations associates chloroquine resistance: Even after withdrawal of chloroquine use in India

    Directory of Open Access Journals (Sweden)

    Sabyasachi Das

    2017-12-01

    Full Text Available Chloroquine (CQ is highly effective against P. vivax, due to the rapid spread of CQ resistance in P. falciparum parasites; it is no longer the drug of choice against P. falciparum. This study elucidates the scenario of chloroquine efficacy at times that coincided with a new drug policy and especially assessed the chloroquine resistant molecular markers after withdrawal of chloroquine in Kolkata and Purulia, two malaria endemic zones of West Bengal, India. In vitro CQ susceptibility was tested in 781 patients with P. falciparum mono infections between 2008 and 2013, of which 338 patients had received CQ in 2008–2009. Genotyping of the pfcrt and the pfmdr1 gene was carried out in all isolates. Early treatment failure was detected in 114 patients {43 (31·39% from Kolkata and 71 (35·32% from Purulia} while recrudescence was identified in 13 (9.49% and 17 (8.46% patients from Kolkata and Purulia respectively. In vivo chloroquine resistance was strongly associated with CVMNT-YYSNY (p < 0.01 and SVMNT-YYSNY (p < 0.05 allele in Kolkata. In Purulia chloroquine resistance was associated with CVMNK-YYSNY (P < 0.005, SVMNT-YYSNY (P < 0.01 allele. The proportion of in vitro chloroquine resistance increased in subsequent years to 87.23% and 93·10% in 2013, in Kolkata and Purulia, respectively. Isolates with SVMNT-YFSND, SVMNT-YFSNY, CVIET-YFSND and CVIET-YYSNY haplotypes increased gradually (p < 0.05 from 2010 to 2013, leading to a rise in IC50 (p < 0.05 of chloroquine. An increase in in vitro chloroquine resistance and candidate gene mutations even after five years of chloroquine withdrawal against P. falciparum calls for synchronized research surveillance and proper containment strategies. Keywords: Plasmodium falciparum, ChloroQuine resistance in India, pfcrt polymorphism, pfmdr1 mutation, In vitro chloroquine resistance

  4. Increasing awareness about antibiotic use and resistance: a hands-on project for high school students.

    Science.gov (United States)

    Fonseca, Maria João; Santos, Catarina L; Costa, Patrício; Lencastre, Leonor; Tavares, Fernando

    2012-01-01

    Health-promoting education is essential to foster an informed society able to make decisions about socio-scientific issues based on scientifically sustained criteria. Antibiotic resistance is currently a major public health issue. Considering that irrational antibiotic use has been associated with the development and widespread of antibiotic resistant bacteria, educational interventions to promote prudent antibiotic consumption are required. This study focuses on the outcomes of an interventional program implemented at the University of Porto, Portugal, to promote awareness about antibiotic resistance at high school levels (15-17 year old). The project Microbiology recipes: antibiotics à la carte articulates a set of wet and dry lab activities designed to promote the participants' understanding of concepts and processes underlying antibiotics' production and activity, such as the notion of mechanisms of action of antibiotics. Following a mix-method approach based on a pre-/post design, the effectiveness of this project was assessed by gathering data from surveys, direct observation and analysis of artifacts of 42 high school students (aged 15 and 16 years). The results indicate that the participants developed a more comprehensive picture of antibiotic resistance. The project was shown to promote more sophisticated conceptualizations of bacteria and antibiotics, increased awareness about the perils of antibiotic resistance, and enhanced consciousness towards measures that can be undertaken to mitigate the problem. The participants regarded their experiences as enjoyable and useful, and believed that the project contributed to improve their understanding and raise their interest about the issues discussed. Furthermore, there were also improvements in their procedural skills concerning the laboratory techniques performed. This study evidences the possibility of increasing high school students' awareness about the consequences of antibiotic resistance and the

  5. Neratinib resistance and cross-resistance to other HER2-targeted drugs due to increased activity of metabolism enzyme cytochrome P4503A4.

    Science.gov (United States)

    Breslin, Susan; Lowry, Michelle C; O'Driscoll, Lorraine

    2017-02-28

    Neratinib is in Phase 3 clinical trials but, unfortunately, the development of resistance is inevitable. Here, we investigated the effects of acquired neratinib resistance on cellular phenotype and the potential mechanism of this resistance. Neratinib-resistant variants of HER2-positive breast cancer cells were developed and their cross-resistance investigated using cytotoxicity assays. Similarly, sensitivity of trastuzumab-resistant and lapatinib-resistant cells to neratinib was assessed. Cellular phenotype changes were evaluated using migration, invasion and anoikis assays. Immunoblotting for HER family members and drug efflux pumps, as well as enzyme activity assays were performed. Neratinib resistance conferred cross-resistance to trastuzumab, lapatinib and afatinib. Furthermore, the efficacy of neratinib was reduced in trastuzumab- and lapatinib-resistant cells. Neratinib-resistant cells were more aggressive than their drug-sensitive counterparts, with increased CYP3A4 activity identified as a novel mechanism of neratinib resistance. The potential of increased CYP3A4 activity as a biomarker and/or target to add value to neratinib warrants investigation.

  6. Trophic compensation reinforces resistance: herbivory absorbs the increasing effects of multiple disturbances.

    Science.gov (United States)

    Ghedini, Giulia; Russell, Bayden D; Connell, Sean D

    2015-02-01

    Disturbance often results in small changes in community structure, but the probability of transitioning to contrasting states increases when multiple disturbances combine. Nevertheless, we have limited insights into the mechanisms that stabilise communities, particularly how perturbations can be absorbed without restructuring (i.e. resistance). Here, we expand the concept of compensatory dynamics to include countervailing mechanisms that absorb disturbances through trophic interactions. By definition, 'compensation' occurs if a specific disturbance stimulates a proportional countervailing response that eliminates its otherwise unchecked effect. We show that the compounding effects of disturbances from local to global scales (i.e. local canopy-loss, eutrophication, ocean acidification) increasingly promote the expansion of weedy species, but that this response is countered by a proportional increase in grazing. Finally, we explore the relatively unrecognised role of compensatory effects, which are likely to maintain the resistance of communities to disturbance more deeply than current thinking allows. © 2015 John Wiley & Sons Ltd/CNRS.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  9. Decolonization of Staphylococcus aureus in patients with atopic dermatitis: a reason for increasing resistance to antibiotics?

    Directory of Open Access Journals (Sweden)

    Izabela Błażewicz

    2017-12-01

    Full Text Available Introduction : Exacerbation of atopic dermatitis can be associated with bacterial infection. The skin of patients is colonized with Staphylococcus aureus in 90% of cases. An attempt has been made to demonstrate that eradication significantly reduces the severity of the disease. Studies indicate the efficacy of topical antibiotics, topical corticosteroids and calcineurin inhibitors. Due to increasing resistance to drugs and the defective antimicrobial peptide profile, decolonization is virtually impossible. Aim : To determine the prevalence of S. aureus colonization among patients with atopic dermatitis and to assess antimicrobial susceptibility of isolated strains to antibiotics, especially fusidic acid and mupirocin. Material and methods : One hundred patients with atopic dermatitis and 50 healthy subjects were microbiologically assessed for the carriage of S. aureus . Antimicrobial susceptibility tests were performed using the broth-microdilution method for antibiotics: ampicillin, ciprofloxacin, daptomycin, erythromycin, fusidic acid, linezolid, lincomycin, mupirocin, tetracycline and vancomycin. Results : Staphylococcus aureus strains were isolated from the majority of our patients, either from the skin (71% or the anterior nares (67%. In the present study, 10% of isolations represented methicillin-resistant S. aureus (MRSA. Antibiotics exhibited diverse activities against clinical isolates of S. aureus . Among those tested, the highest rates of resistance were shown for ampicillin – 58.5%, lincomycin – 37.5% and erythromycin – 31.0%. Enhanced resistance levels were expressed to mupirocin (17.5% and fusidic acid (15.5%. Conclusions : According to the increasing rate of resistance and quick recolonization after discontinuation of the treatment, chronic use of topical antibiotics is not recommended and should be limited to exacerbation of atopic dermatitis with clinical signs of bacterial infection.

  10. Enzalutamide inhibits proliferation of gemcitabine-resistant bladder cancer cells with increased androgen receptor expression.

    Science.gov (United States)

    Kameyama, Koji; Horie, Kengo; Mizutani, Kosuke; Kato, Taku; Fujita, Yasunori; Kawakami, Kyojiro; Kojima, Toshio; Miyazaki, Tatsuhiko; Deguchi, Takashi; Ito, Masafumi

    2017-01-01

    Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder cancer cells and also the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling. Microarray analysis revealed upregulation of AR expression in T24GR cells compared with T24 cells. AR mRNA and protein expression was confirmed to be increased in T24GR cells, respectively, by quantitative RT-PCR and western blot analysis, which was associated with more potent AR transcriptional activity as measured by luciferase reporter assay. The copy number of AR gene in T24GR cells determined by PCR was twice as many as that of T24 cells. AR silencing by siRNA transfection resulted in inhibition of proliferation of T24GR cells. Cell culture in charcoal-stripped serum and treatment with enzalutamide inhibited growth of T24GR cells, which was accompanied by cell cycle arrest. AR transcriptional activity was found to be reduced in T24GR cells by enzalutamide treatment. Lastly, enzalutamide also inhibited cell proliferation of HTB5 bladder cancer cells that express AR and possess intrinsic resistance to gemcitabine. Our results suggest that enzalutamide may have the potential to treat patients with advanced gemcitabine-resistant bladder cancer with increased AR expression.

  11. Rapid Increase of Genetically Diverse Methicillin-Resistant Staphylococcus aureus, Copenhagen, Denmark

    DEFF Research Database (Denmark)

    Bartels, Mette Damkjær; Boye, Kit; Larsen, Anders Rhod

    2007-01-01

    In Copenhagen, methicillin-resistant Staphylococcus aureus (MRSA) accounted for <15 isolates per year during 1980-2002. However, since 2003 an epidemic increase has been observed, with 33 MRSA cases in 2003 and 110 in 2004. We analyzed these 143 cases epidemiologically and characterized isolates ...... and soft tissue infections dominated. CO-MRSA with diverse genetic backgrounds is rapidly emerging in a low MRSA prevalence area. Udgivelsesdato: October...

  12. Deletion of Lytic Transglycosylases Increases Beta-Lactam Resistance in Shewanella oneidensis

    Science.gov (United States)

    Yin, Jianhua; Sun, Yiyang; Sun, Yijuan; Yu, Zhiliang; Qiu, Juanping; Gao, Haichun

    2018-01-01

    Production of chromosome-encoded β-lactamases confers resistance to β-lactams in many Gram-negative bacteria. Some inducible β-lactamases, especially the class C β-lactamase AmpC in Enterobacteriaceae, share a common regulatory mechanism, the ampR-ampC paradigm. Induction of ampC is intimately linked to peptidoglycan recycling, and the LysR-type transcriptional regulator AmpR plays a central role in the process. However, our previous studies have demonstrated that the expression of class D β-lactamase gene blaA in Shewanella oneidensis is distinct from the established paradigm since an AmpR homolog is absent and major peptidoglycan recycling enzymes play opposite roles in β-lactamase expression. Given that lytic transglycosylases (LTs), a class of peptidoglycan hydrolases cleaving the β-1,4 glycosidic linkage in glycan strands of peptidoglycan, can disturb peptidoglycan recycling, and thus may affect induction of blaA. In this study, we investigated impacts of such enzymes on susceptibility to β-lactams. Deletion of three LTs (SltY, MltB and MltB2) increased β-lactam resistance, while four other LTs (MltD, MltD2, MltF, and Slt2) seemed dispensable to β-lactam resistance. The double LT mutants ΔmltBΔmltB2 and ΔsltYΔmltB2 had β-lactam resistance stronger than any of the single mutants. Deletion of ampG (encoding permease AmpG) and mrcA (encoding penicillin binding protein 1a, PBP1a) from both double LT mutants further increased the resistance to β-lactams. Notably, all increased β-lactam resistance phenotypes were in accordance with enhanced blaA expression. Although significant, the increase in β-lactamase activity after inactivating LTs is much lower than that produced by PBP1a inactivation. Our data implicate that LTs play important roles in blaA expression in S. oneidensis. PMID:29403465

  13. Novel Functional Changes during Podocyte Differentiation: Increase of Oxidative Resistance and H-Ferritin Expression

    Directory of Open Access Journals (Sweden)

    Emese Bányai

    2014-01-01

    Full Text Available Podocytes are highly specialized, arborized epithelial cells covering the outer surface of the glomerular tuft in the kidney. Terminally differentiated podocytes are unable to go through cell division and hereby they are lacking a key property for regeneration after a toxic injury. Podocytes are long-lived cells but, to date, little is known about the mechanisms that support their stress resistance. Our aim was to investigate whether the well-known morphological changes during podocyte differentiation are accompanied by changes in oxidative resistance in a manner that could support their long-term survival. We used a conditionally immortalized human podocyte cell line to study the morphological and functional changes during differentiation. We followed the differentiation process for 14 days by time-lapse microscopy. During this period nondifferentiated podocytes gradually transformed into large, nonproliferating, frequently multinucleated cells, with enlarged nuclei and opened chromatin structure. We observed that differentiated podocytes were highly resistant to oxidants such as H2O2 and heme when applied separately or in combination, whereas undifferentiated cells were prone to such challenges. Elevated oxidative resistance of differentiated podocytes was associated with increased activities of antioxidant enzymes and H-ferritin expression. Immunohistochemical analysis of normal human kidney specimens revealed that podocytes highly express H-ferritin in vivo as well.

  14. Salivary testosterone and immunoglobulin A were increased by resistance training in adults with Down syndrome

    Directory of Open Access Journals (Sweden)

    G. Fornieles

    2014-04-01

    Full Text Available This study was designed to assess the influence of resistance training on salivary immunoglobulin A (IgA levels and hormone profile in sedentary adults with Down syndrome (DS. A total of 40 male adults with DS were recruited for the trial through different community support groups for people with intellectual disabilities. All participants had medical approval for participation in physical activity. Twenty-four adults were randomly assigned to perform resistance training in a circuit with six stations, 3 days per week for 12 weeks. Training intensity was based on functioning in the eight-repetition maximum (8RM test for each exercise. The control group included 16 age-, gender-, and BMI-matched adults with DS. Salivary IgA, testosterone, and cortisol levels were measured by ELISA. Work task performance was assessed using the repetitive weighted-box-stacking test. Resistance training significantly increased salivary IgA concentration (P=0.0120; d=0.94 and testosterone levels (P=0.0088; d=1.57 in the exercising group. Furthermore, it also improved work task performance. No changes were seen in the controls who had not exercised. In conclusion, a short-term resistance training protocol improved mucosal immunity response as well as salivary testosterone levels in sedentary adults with DS.

  15. Increased corrosion resistance of the AZ80 magnesium alloy by rapid solidification.

    Science.gov (United States)

    Aghion, E; Jan, L; Meshi, L; Goldman, J

    2015-11-01

    Magnesium (Mg) and Mg-alloys are being considered as implantable biometals. Despite their excellent biocompatibility and good mechanical properties, their rapid corrosion is a major impediment precluding their widespread acceptance as implantable biomaterials. Here, we investigate the potential for rapid solidification to increase the corrosion resistance of Mg alloys. To this end, the effect of rapid solidification on the environmental and stress corrosion behavior of the AZ80 Mg alloy vs. its conventionally cast counterpart was evaluated in simulated physiological electrolytes. The microstructural characteristics were examined by optical microscopy, SEM, TEM, and X-ray diffraction analysis. The corrosion behavior was evaluated by immersion, salt spraying, and potentiodynamic polarization. Stress corrosion resistance was assessed by Slow Strain Rate Testing. The results indicate that the corrosion resistance of rapidly solidified ribbons is significantly improved relative to the conventional cast alloy due to the increased Al content dissolved in the α-Mg matrix and the correspondingly reduced presence of the β-phase (Mg17 Al12 ). Unfortunately, extrusion consolidated solidified ribbons exhibited a substantial reduction in the environmental performance and stress corrosion resistance. This was mainly attributed to the detrimental effect of the extrusion process, which enriched the iron impurities and increased the internal stresses by imposing a higher dislocation density. In terms of immersion tests, the average corrosion rate of the rapidly solidified ribbons was <0.4 mm/year compared with ∼2 mm/year for the conventionally cast alloy and 26 mm/year for the rapidly solidified extruded ribbons. © 2014 Wiley Periodicals, Inc.

  16. Increased frequency of pink bollworm resistance to Bt toxin Cry1Ac in China.

    Directory of Open Access Journals (Sweden)

    Peng Wan

    Full Text Available Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt kill some key insect pests, but evolution of resistance by pests can reduce their efficacy. The main approach for delaying pest adaptation to Bt crops uses non-Bt host plants as "refuges" to increase survival of susceptible pests. To delay evolution of pest resistance to transgenic cotton producing Bt toxin Cry1Ac, the United States and some other countries have required refuges of non-Bt cotton, while farmers in China have relied on "natural" refuges of non-Bt host plants other than cotton. The "natural" refuge strategy focuses on cotton bollworm (Helicoverpa armigera, the primary target of Bt cotton in China that attacks many crops, but it does not apply to another major pest, pink bollworm (Pectinophora gossypiella, which feeds almost entirely on cotton in China. Here we report data showing field-evolved resistance to Cry1Ac by pink bollworm in the Yangtze River Valley of China. Laboratory bioassay data from 51 field-derived strains show that the susceptibility to Cry1Ac was significantly lower during 2008 to 2010 than 2005 to 2007. The percentage of field populations yielding one or more survivors at a diagnostic concentration of Cry1Ac increased from 0% in 2005-2007 to 56% in 2008-2010. However, the median survival at the diagnostic concentration was only 1.6% from 2008 to 2010 and failure of Bt cotton to control pink bollworm has not been reported in China. The early detection of resistance reported here may promote proactive countermeasures, such as a switch to transgenic cotton producing toxins distinct from Cry1A toxins, increased planting of non-Bt cotton, and integration of other management tactics together with Bt cotton.

  17. Overexpression of copper/zinc-superoxide dismutase in transgenic mice markedly impairs regeneration and increases development of neuropathic pain after sciatic nerve injury.

    Science.gov (United States)

    Kotulska, Katarzyna; LePecheur, Marie; Marcol, Wiesław; Lewin-Kowalik, Joanna; Larysz-Brysz, Magdalena; Paly, Evelyn; Matuszek, Iwona; London, Jacqueline

    2006-10-01

    Despite the general capacity of peripheral nervous system to regenerate, peripheral nerve injury is often followed by incomplete recovery of function, sometimes with the burden of neuropathic pain. The mechanisms of both regeneration and nociception have not been clarified, but it is known that inflammatory reactions are involved. Cu/Zn-superoxide dismutase (SOD1) is an important scavenger protein that acts against oxidative stress. It has been shown to play an important role in apoptosis and inflammation. The aim of this study was to examine the role of SOD1 overexpression in peripheral nerve regeneration and neuropathic pain-related behavior in mice. Sciatic nerves of SOD1-overexpressing and FVB/N wild type-mice were transected and immediately resutured. Evaluation of motor and sensory function and autotomy was carried out during 4 weeks of followup. We found markedly worse sciatic function index outcome as well as more significant atrophy of denervated muscles in SOD1-overexpressing animals compared with wild type. Autotomy was markedly worse in SOD1 transgenic mice than in wild-type animals. Histological evaluation revealed that the intensity of regeneration features, including numbers of GAP-43-positive growth cones, Schwann cells, and macrophages in the distal stump of the transected nerve, was also decreased in transgenic mice. Neuroma formation at the injury site was significantly more prominent in this group. Taken together, our findings suggest that SOD1 overexpression is deleterious for nerve regeneration processes and aggravates neuropathic pain-like state in mice. This can be at least partially ascribed to disturbed inflammatory reactions at the injury site. Copyright 2006 Wiley-Liss, Inc.

  18. Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance

    Directory of Open Access Journals (Sweden)

    Yi Hu

    2017-05-01

    Full Text Available Helicobacter pylori (H. pylori is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori.

  19. Muscle Volume Increases Following 16 Weeks of Resistive Exercise Training with the Advanced Resistive Exercise Device (ARED) and Free Weights

    Science.gov (United States)

    Nash, R. E.; Loehr, J. A.; Lee, S. M. C.; English, K. L.; Evans, H.; Smith, S. A.; Hagan, R. D.

    2009-01-01

    Space flight-induced muscle atrophy, particularly in the postural and locomotorymuscles, may impair task performance during long-duration space missions and planetary exploration. High intensity free weight (FW) resistive exercise training has been shown to prevent atrophy during bed rest, a space flight analog. NASA developed the Advanced Resistive Exercise Device (ARED) to simulate the characteristics of FW exercise (i.e. constant mass, inertial force) and to be used as a countermeasure during International Space Station (ISS) missions. PURPOSE: To compare the efficacy of ARED and FW training to induce hypertrophy in specific muscle groups in ambulatory subjects prior to deploying ARED on the ISS. METHODS: Twenty untrained subjects were assigned to either the ARED (8 males, 3 females) or FW (6 males, 3 females) group and participated in a periodizedtraining protocol consisting of squat (SQ), heel raise (HR), and deadlift(DL) exercises 3 d wk-1 for 16 wks. SQ, HR, and DL muscle strength (1RM) was measured before, after 8 wks, and after 16 wks of training to prescribe exercise and measure strength changes. Muscle volume of the vastigroup (V), hamstring group (H), hip adductor group (ADD), medial gastrocnemius(MG), lateral gastrocnemius(LG), and deep posterior muscles including soleus(DP) was measured using MRI pre-and post-training. Consecutive cross-sectional images (8 mm slices with a 2 mm gap) were analyzed and summed. Anatomical references insured that the same muscle sections were analyzed pre-and post-training. Two-way repeated measures ANOVAs (ptraining devices. RESULTS: SQ, HR, and DL 1RM increased in both FW (SQ: 49+/-6%, HR: 12+/-2%, DL: 23+/-4%) and ARED (SQ: 31+/-4%, HR: 18+/-2%, DL: 23+/-3%) groups. Both groups increased muscle volume in the V (FW: 13+/-2%, ARED: 10+/-2%), H (FW: 3+/-1%, ARED: 3+/-1 %), ADD (FW: 15=/-2%, ARED: 10+/-1%), LG (FW: 7+/-2%, ARED: 4+/-1%), MG (FW: 7+/-2%, ARED: 5+/-2%), and DP (FW: 2+/-1%; ARED: 2+/-1%) after training. There

  20. Increasing antibiotic resistance among uropathogens isolated during years 2006-2009: impact on the empirical management

    Directory of Open Access Journals (Sweden)

    Hamid Mohammad-Jafari

    2012-02-01

    Full Text Available Urinary tract infections (UTI are one of the most common infections with an increasing resistance to antimicrobial agents. PURPOSE: Empirical initial antibiotic treatment of UTI must rely on susceptible data from local studies. MATERIALS AND METHODS: Retrospective analysis of isolated bacteria from children with UTIs was performed at the university hospital during years 2006-2009. The findings were compared with data collected in a similar study carried out in 2002- 2003. RESULTS: A total of 1439 uropathogens were isolated. Escherichia coli (E.coli was the leading cause, followed by Enterobacter, and other gram negative bacilli. It was observed resistance of E.coli to ceftriaxone, cefexime, amikacin, gentamycin, and nalidixic acid; Enterobacter to cefexime; and the resistance of gram negative bacilli to gentamicin and cefexime increased significantly. The highest effective antibiotic was Imipenem, ciprofloxacin, and amikacin with 96.7%, 95% and 91% sensitivity rates , respectively, followed by ceftriaxone 77.2%, gentamicin 77%, nitrofurantoin 76.4%, nalidixic acid 74.3% and cefexime with 70%. CONCLUSION: The use of nitrofurantoin or nalidixic acid as initial empirical antibacterial therapy for cystitis seems appropriate. For cases of simple febrile UTI, the use of initial parenteral therapies with amikacin or ceftriaxone followed by an oral third generation cephalosporin also seemed appropriated, and in cases of severely ill patients or complicated UTI, imipenem as monotherapy or, a combination of Ceftriaxone with an aminoglycoside, are recommended.

  1. Management of urinary tract infections in children in an era of increasing antimicrobial resistance.

    Science.gov (United States)

    Robinson, Joan L; Le Saux, Nicole

    2016-09-01

    Accurate diagnosis and appropriate use of antimicrobials for treatment and prevention of urinary tract infections (UTIs) is vital in an era of increasing antibiotic resistance. The article reviews indications for and interpretation of urinalysis and urine culture results for diagnosis of UTI, choice of antibiotics for empiric and definitive UTI therapy, the rationale behind and indications for radiographic investigations, and prevention of UTIs including the complex decision as to whether antibiotic prophylaxis will benefit a child. Expert commentary: Over-diagnosis of UTI is a prevalent problem due to the lack of specificity of both urinalysis and urine culture. The most major recent advance in the field has been the recognition that antibiotic prophylaxis for UTI is rarely indicated as in most situations, the number needed to treat to prevent one UTI is too high to justify the risk of adverse events and development of antimicrobial resistance.

  2. Increasing Prevalence of Pediatric Drug-Resistant Tuberculosis in Mumbai, India and its Outcome.

    Science.gov (United States)

    Shah, Miti A; Shah, Ira

    2018-03-24

    B.J.Wadia Hospital,Mumbai OBJECTIVE:: The prevalence and type of DR-TB was evaluated pre and post-2013 and outcome was studied. Descriptive retrospective study. Children were defined as having DR-TB on the basis of GeneXpert or LPA and/or drug susceptibility testing(DST) of MTB grown on culture or from contact's DST. The prevalence of DR-TB was 110 out of 1145 cases (9.6%) which showed an increase, compared to 5.6% pre-2010 and 7% in 2010-2013(p=0.014408). Twenty-two (20%) children had pulmonary-TB(PTB) and 88(80%) had extra-pulmonary-TB(EPTB) with disseminated-TB being the most common presentation in 31 children (28.18%). Ninety-six (87.3%) children were bacteriologically confirmed TB cases and 14 (12.7%) were clinically diagnosed-TB and treated as per contact DST. Eight (7.2%) cases were monoresistant, 7 (6.3%) polyresistant, MDR-TB seen in 28 (25.45%) patients, 32 (29.09%) had pre-XDR-TB, 9 (8.18%) had XDR-TB and 12 (10.9%) were rifampicin resistant. Ethionamide resistance increased from 26.1% pre-2013 to 60.8% post-2013(p=0.014408) and ofloxacin resistance rose from 30.4% pre-2010, to 47.6% in 2010-2013 and 56.9% post-2013(p=0.080863). Moxifloxacin resistance showed an acute rise from 8.7% pre-2010, to 46% in 2010-2013 and 57% post-2013(p=0.000275). Thirty-three (30%) patients had completed their treatment, 21(19.09%) were lost to follow up and 56(50.09%) patients are still on treatment.

  3. Treatment Resistant Epilepsy in Autism Spectrum Disorder: Increased Risk for Females.

    Science.gov (United States)

    Blackmon, Karen; Bluvstein, Judith; MacAllister, William S; Avallone, Jennifer; Misajon, Jade; Hedlund, Julie; Goldberg, Rina; Bojko, Aviva; Mitra, Nirmala; Giridharan, Radha; Sultan, Richard; Keller, Seth; Devinsky, Orrin

    2016-02-01

    The male:female ratio in autism spectrum disorder (ASD) averages greater than 4:1 while the male:female ratio of ASD with epilepsy averages less than 3:1. This indicates an elevated risk of epilepsy in females with ASD; yet, it is unknown whether phenotypic features of epilepsy and ASD differ between males and females with this comorbidity. The goal of this study is to investigate sex differences in phenotypic features of epilepsy and ASD in a prospective sample of 130 children and young adults with an initial ASD diagnosis and subsequent epilepsy diagnosis. All participants were characterized by standardized diagnostic inventories, parent/caregiver completed questionnaires, and medical/academic record review. Diagnostic classifications of epilepsy, ASD, and intellectual disability were performed by board certified neurologists and a pediatric neuropsychologist. Results demonstrated a lower male:female ratio (1.8:1) in individuals with ASD and treatment-resistant epilepsy relative to those with ASD and treatment-responsive epilepsy (4.9:1), indicating a higher risk of treatment-resistant epilepsy in females. Mild neuroimaging abnormalities were more common in females than males and this was associated with increased risk of treatment-resistance. In contrast, ASD symptom severity was lower in females compared with males. Findings distinguish females with ASD and epilepsy as a distinct subgroup at higher risk for a more severe epilepsy phenotype in the context of a less severe ASD phenotype. Increased risk of anti-epileptic treatment resistance in females with ASD and epilepsy suggests that comprehensive genetic, imaging, and neurologic screening and enhanced treatment monitoring may be indicated for this subgroup. Autism Res 2016, 9: 311-320. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  4. Prolonged exposure of methicillin-resistant Staphylococcus aureus (MRSA) COL strain to increasing concentrations of oxacillin results in a multidrug-resistant phenotype

    DEFF Research Database (Denmark)

    Martins, Ana; Couto, Isabel; Aagaard, Lone

    2007-01-01

    Our previous studies demonstrated that exposure of a bacterium to increasing concentrations of an antibiotic would increase resistance to that antibiotic as a consequence of activating efflux pumps. This study utilises the same approach; however, it employs the methicillin-resistant Staphylococcus...... aureus (MRSA) COL strain, which is highly resistant to oxacillin (OXA). MRSA COL was adapted to 3200 mg/L of OXA. Changes in resistance to other antibiotics were evaluated and efflux pump activity during the adaptation process was determined. MRSA COL was exposed to stepwise two-fold increases of OXA....... At the end of each step, minimum inhibitory concentration determination for erythromycin (ERY) and other antibiotics was conducted. Reserpine (RES) was employed to evaluate whether resistance to ERY was dependent on efflux pump activity. Efflux pump activity was also evaluated using the ethidium bromide (EB...

  5. Species interactions can maintain resistance of subtidal algal habitats to an increasingly modified world

    Directory of Open Access Journals (Sweden)

    Laura J. Falkenberg

    2015-07-01

    Full Text Available Current trends in habitat loss have been forecast to accelerate under anticipated global change, thereby focusing conservation attention on identifying the circumstances under which key species interactions retard habitat loss. Urbanised coastlines are associated with broad-scale loss of kelp canopies and their replacement by less productive mats of algal turf, a trend predicted to accelerate under ocean acidification and warming (i.e. enhanced CO2 and temperature. Here we use kelp forests as a model system to test whether efforts to maintain key species interactions can maintain habitat integrity under forecasted conditions. First, we assessed whether increasing intensity of local human activity is associated with more extensive turf mats and sparser canopies via structured field observations. Second, we experimentally tested the hypothesis that intact canopies can resist turf expansion under enhanced CO2 and temperature in large mesocosms. In the field, there was a greater proportion of turf patches on urbanised coasts of South Australia than in agricultural and urban catchments in which there was a greater proportion of canopy-forming algae. Mesocosm experiments revealed this expansion of turfs is likely to accelerate under increases in CO2 and temperature, but may be limited by the presence of intact canopies. We note that even in the presence of canopy, increases in CO2 and temperature facilitate greater turf covers than occurs under contemporary conditions. The influence of canopy would likely be due to shading of the understorey turfs which, in turn, can modify their photosynthetic activity. These results suggest that resistance of habitat to change under human-dominated conditions may be managed via the retention of key species and their interactions. Management that directly reduces the disturbance of habitat-forming organisms (e.g. harvesting or reverses loss through restoration may, therefore, reinforce habitat resistance in an

  6. APPLICATIONS OF POTASSIUM FERTILIZER AND Bacillus sp. BIOPESTICIDE FOR INCREASING TOMATO RESISTANCE TO BACTERIAL WILT DISEASE

    Directory of Open Access Journals (Sweden)

    Nur Prihatiningsih

    2011-02-01

    Full Text Available Bacterial wilt on tomato caused by Ralstonia solanacearum is a crucial disease, because it can reduce yield until 50%. The aims of this research were: 1 to find out biopesticide formula for Bacillus sp.growth, 2 to test Bacillus sp. against R. solanacearum in vitro, 3 to test potassium fertilizer combined with Bacillus sp. for enhancing tomato resistance to the bacterial wilt disease. The research was conducted in 2 steps i.e to test the persistence of Bacillus sp. in biopesticide formula, and to test the best combination of both potassium and the Bacillus sp. biopesticide. The results showed that Bacillus B298 was the best isolate in its persistence on the biopesticide formula of organic growth medium+CaCO3+CMC 1%+mannitol 1%, and in inhibiting R. solanacearum. The best biopesticide formula for the Bacillus sp. persistence was growth organic media+ CaCO3+CMC 1%+mannitol 1%. Bacillus sp. was able to increase tomato resistance to the bacterial wilt disease from the category of susceptible to be tolerant and becoming resistant.

  7. Inventions in the nanotechnological area considerably increase wear- and chemical resistance of construction products

    Directory of Open Access Journals (Sweden)

    VLASOV Vladimir Alexeevich

    2014-08-01

    Full Text Available The invention «Reinforced flaked element made of natural or conglomerate stone and its multilayer protective coating (RU 2520193» is referred to construction materials. Reinforced flaked element made of natural or conglomerate stone consists of: natural or conglomerate materials as the basis; multilayer coating which protects the mentioned basis from chemical substances and wearing mechanical factors influencing on this element where the multilayer coating includes at least three layers formed by one or many film-forming compositions which comprise top layer with scratch-resistant nanoparticles and encircled with polyester, melamine, phenolic, acryl or epoxy resin (or any combination of them which provides protection against scratches; damper intermediate layer made of epoxy and/or acryl resin which provides impact resistant; lower layer adjoining to the basis and containing particles of Al2O3 or silicon carbide plus acryl polymer and providing resistance to abrasive wear. Technical result is increased wear- and chemical resistance of flaked elements from natural or conglomerate materials. The invention «Fine organic suspension of carbon metal-containing nanostructures and the method to produce it (RU 2515858» is referred to the area of physical and colloid chemistry and can be used to obtain polymer compositions. Fine organic suspension of carbon metal-containing nanostructures is produced by interaction between nanostructures and polyethylenepolyamine. At first the powder of carbon metalcontaining nanostructures (which are nanoparticles of 3d-metal such as copper, cobalt, nickel stabilized in carbon nanostructures is mechanically milled, then it is mechanically ground with polyethylenepolyamine introduced portionally unless and until the content of nanostructures is less 1 g/ml. The invention results in decreased power inputs as the obtained fine organic suspension of carbon and metal-containing nanostructures is able to recover due to

  8. Oral antimicrobials increase antimicrobial resistance in porcine E. coli--a systematic review.

    Science.gov (United States)

    Burow, E; Simoneit, C; Tenhagen, B-A; Käsbohrer, A

    2014-03-01

    Administration of antimicrobials to livestock increases the risk of antimicrobial resistance (AMR) in commensal bacteria. Antimicrobials in pig production are usually administered per pen via feed which implies treatment of sick alongside with healthy animals. The objective of this systematic literature review was to investigate the effect of orally administered antimicrobials on AMR in Escherichia coli of swine. Studies published in peer reviewed journals were retrieved from the international online databases ISI Web of Knowledge, PubMed, Scopus and the national electronic literature data base of Deutsches Institut für Medizinische Dokumentation und Information. The studies were assessed using the eligibility criteria English or German language, access to full paper version, defined treatment and control group (initial value or non-treatment) as well as administration and resistance testing of the same antimicrobial class. In the qualitative synthesis, only studies were included presenting the summary measures odds ratio or prevalence of resistance, the category of the applied antimicrobial and the dosage. An effect of the antimicrobial on AMR in E. coli was evaluated as an "increase", "no effect" or "decrease" if the odds or alternatively the prevalence ratio were >1.0, 1.0 or antimicrobial substance and dosage was missing in 4 and 5 of the 11 finally selected studies. The 36 identified trials were inhomogenous in usage and provision of information on sample size. Oral administration of antimicrobials increases the risk of AMR in E. coli from swine. There is however a lack of studies on the impact of dosage and longitudinal effects of treatment. The published studies have a number of issues concerning their scientific quality. More high quality research is needed to better address and quantifiy the effect of orally administered antimicrobials on AMR in swine. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Application of Functionalized SWCNTs for Increase of Degradation Resistance of Acrylic Paint for Cars

    Directory of Open Access Journals (Sweden)

    Osiel Lucas Flores

    2013-01-01

    Full Text Available Physical properties of automotive acrylic paint are improved by incorporation of three different types of carbon nanotubes: single-wall carbon nanotubes (SWCNTs, OH-functionalized single-wall carbon nanotubes (OH-SWCNTs, and aniline-functionalized single-wall carbon nanotubes (aniline-SWCNTs. The formed composites are studied by electron miscroscopy methods and Raman spectrometry. It is found that the acrylic paints with addition of OH-SWCNTs and aniline-SWCNTs show better quality for their applications. In particular, the resistance against degradation by electron beam increased in ~500%.

  10. TOR signaling downregulation increases resistance to the cereal killer Fusarium graminearum.

    Science.gov (United States)

    Aznar, Néstor R; Consolo, V Fabiana; Salerno, Graciela L; Martínez-Noël, Giselle M A

    2018-02-01

    TOR is the master regulator of growth and development that senses energy availability. Biotic stress perturbs metabolic and energy homeostasis, making TOR a good candidate to participate in the plant response. Fusarium graminearum (Fusarium) produces important losses in many crops all over the world. To date, the role of TOR in Fusarium infection has remained unexplored. Here, we show that the resistance to the pathogen increases in different Arabidopsis mutants impaired in TOR complex or in wild-type plants treated with a TOR inhibitor. We conclude that TOR signaling is involved in plant defense against Fusarium.

  11. Copper Pollution Increases the Resistance of Soil Archaeal Community to Changes in Water Regime.

    Science.gov (United States)

    Li, Jing; Liu, Yu-Rong; Cui, Li-Juan; Hu, Hang-Wei; Wang, Jun-Tao; He, Ji-Zheng

    2017-11-01

    Increasing efforts have been devoted to exploring the impact of environmental stresses on soil bacterial communities, but the work on the archaeal community is seldom. Here, we constructed microcosm experiments to investigate the responses of archaeal communities to the subsequent dry-rewetting (DW) disturbance in two contrasting soils (fluvo-aquic and red soil) after 6 years of copper pollution. Ten DW cycles were exerted on the two soils with different copper levels, followed by a 6-week recovery period. In both soils, archaeal diversity (Shannon index) in the high copper-level treatments increased over the incubation period, and archaeal community structure changed remarkably as revealed by the non-metric multidimensional scaling ordinations. In both soils, copper pollution altered the response of dominant operational taxonomic units (OTUs) to the DW disturbance. Throughout the incubation and recovery period, the resistance of archaeal abundance to the DW disturbance was higher in the copper-polluted soils than soils without pollution. Taken together, copper pollution altered the response of soil archaeal diversity and community composition to the DW disturbance and increased the resistance of the archaeal abundance. These findings have important implications for understanding soil microbial responses to ongoing environmental change.

  12. Increasing the radiation resistance of single-crystal silicon epitaxial layers

    Directory of Open Access Journals (Sweden)

    Kurmashev Sh. D.

    2014-12-01

    Full Text Available The authors investigate the possibility of increasing the radiation resistance of silicon epitaxial layers by creating radiation defects sinks in the form of dislocation networks of the density of 109—1012 m–2. Such networks are created before the epitaxial layer is applied on the front surface of the silicon substrate by its preliminary oxidation and subsequent etching of the oxide layer. The substrates were silicon wafers KEF-4.5 and KDB-10 with a diameter of about 40 mm, grown by the Czochralski method. Irradiation of the samples was carried out using electron linear accelerator "Electronics" (ЭЛУ-4. Energy of the particles was 2,3—3,0 MeV, radiation dose 1015—1020 m–2, electron beam current 2 mA/m2. It is shown that in structures containing dislocation networks, irradiation results in reduction of the reverse currents by 5—8 times and of the density of defects by 5—10 times, while the mobility of the charge carriers is increased by 1,2 times. Wafer yield for operation under radiation exposure, when the semiconductor structures are formed in the optimal mode, is increased by 7—10% compared to the structures without dislocation networks. The results obtained can be used in manufacturing technology for radiation-resistant integrated circuits (bipolar, CMOS, BiCMOS, etc..

  13. Beta-lactam resistance in the gram negatives: increasing complexity of conditional, composite and multiply resistant phenotypes.

    Science.gov (United States)

    Iredell, Jon; Thomas, Lee; Espedido, Björn

    2006-12-01

    The greatest impact of microbiology data on clinical care is in the critically ill. Unfortunately, this is also the area in which microbiology laboratories are most often non-contributive. Attempts to move to rapid, culture-independent diagnostics are driven by the need to expedite urgent results. This is difficult in Gram-negative infection because of the complexity of the antibiotic resistance phenotype. Here, we discuss resistance to modern beta-lactams as a case in point. Recent outbreaks of transmissible carbapenem resistance among Gram-negative enteric pathogens in Sydney and Melbourne serve to illustrate the pitfalls of traditional phenotypical approaches. A better understanding of the epidemiology and mosaic nature of antibiotic resistance elements in the microflora is needed for us to move forward.

  14. Increased retinol-free RBP4 contributes to insulin resistance in gestational diabetes mellitus.

    Science.gov (United States)

    Chen, Yanmin; Lv, Ping; Du, Mengkai; Liang, Zhaoxia; Zhou, Menglin; Chen, Danqing

    2017-07-01

    Retinol-binding protein 4 (RBP4) is a circulating retinol transporter that is strongly associated with insulin resistance. The aim of this study was to evaluate the RBP4 and retinol level in rat model of gestational diabetes mellitus and the relationship between retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) and insulin resistance. Pregnant rats were administered streptozotocin to induce diabetes. The RBP4 and retinol levels were evaluated in GDM and normal pregnant rats. After then, normal pregnant rats were divided into two groups to receive either apo-RBP4 or vehicle injection. The metabolic parameters and insulin signaling in adipose tissue, skeletal muscle and liver were determined in apo-RBP4 and control groups. Primary human adipocytes were cultured in vitro with different proportions of apo-RBP4 and holo-RBP4 for 24 h. The interaction between RBP4 and STRA6 was assessed by co-immunoprecipitation, and the expression of JAK-STAT pathway and insulin signaling were detected by Western blotting and immunofluorescence. We found increases in serum RBP4 levels and the RBP4:retinol ratio but not in the retinol levels in GDM rats. Exogenous apo-RBP4 injection attenuated insulin sensitivity in pregnant rats. In vitro, a prolonged interaction between RBP4 and STRA6 was observed when apo-RBP4 was present. In response to increased apo-RBP4 levels, cells showed elevated activation of the JAK2/STAT5 cascade and SOCS3 expression, decreased phosphorylation of IR and IRS1, and attenuated GLUT4 translocation and glucose uptake upon insulin stimulation. Apo-RBP4 is a ligand that activates the STRA6 signaling cascade, inducing insulin resistance in GDM.

  15. Kaempferol increases apoptosis in human acute promyelocytic leukemia cells and inhibits multidrug resistance genes.

    Science.gov (United States)

    Moradzadeh, Maliheh; Tabarraei, Alijan; Sadeghnia, Hamid Reza; Ghorbani, Ahmad; Mohamadkhani, Ashraf; Erfanian, Saiedeh; Sahebkar, Amirhossein

    2018-02-01

    Acute promyelocytic leukemia (APL) is one of the most life-threatening hematological malignancies. Defects in the cell growth and apoptotic pathways are responsible for both disease pathogenesis and treatment resistance. Therefore, pro-apoptotic agents are potential candidates for APL treatment. Kaempferol is a flavonoid with antioxidant and anti-tumor properties. This study was designed to investigate the cytotoxic, pro-apoptotic, and differentiation-inducing effects of kaempferol on HL-60 and NB4 leukemia cells. Resazurin assay was used to determine cell viability following treatment with kaempferol (12.5-100 μM) and all-trans retinoic acid (ATRA; 10 μM; used as a positive control). Apoptosis and differentiation were also detected using propidium iodide and NBT staining techniques, respectively. Furthermore, the expression levels of genes involved in apoptosis (PI3 K, AKT, BCL2, BAX, p53, p21, PTEN, CASP3, CASP8, and CASP9), differentiation (PML-RAR and HDAC1), and multi-drug resistance (ABCB1 and ABCC1) were determined using quantitative real-time PCR. The protein expressions of Bax/Bcl2 and casp3 were confirmed using Western blot. The results showed that kaempferol decreased cell viability and increased subG1 population in the tested leukemic cells. This effect was associated with decreased expression of Akt, BCL2, ABCB1, and ABCC1 genes, while the expression of CASP3 and BAX/BCL-2 ratio were significantly increased at both gene and protein levels. Kaempferol promoted apoptosis and inhibited multidrug resistance in a concentration-dependent manner, without any differential effect on leukemic cells. In conclusion, this study suggested that kaempferol may be utilized as an appropriate alternative for ATRA in APL patients. © 2017 Wiley Periodicals, Inc.

  16. Pediatric neck abscesses: No increase in methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Fellner, Avital; Marom, Tal; Muallem-Kalmovich, Limor; Shlamkovitch, Nathan; Eviatar, Ephraim; Lazarovitch, Tzilia; Pitaro, Jacob

    2017-10-01

    Recent studies from Western countries showed an increased incidence rate of methicillin-resistant Staphylococcus aureus (MRSA) isolated from pediatric neck abscesses cultures. We sought to examine the microbiology and antibiotic susceptibility of such samples over a 10-year period, and particularly of Staphylococcus aureus (SA), in order to determine whether a similar trend exists in our institution. A retrospective chart review of children ≤18 years that underwent needle aspiration or surgical drainage of neck abscesses, including suppurative lymphadenitis, retropharyngeal abscesses, and parapharyngeal abscesses was conducted between 1/1/06-31/12/15. Sixty-two children were identified with a male predominance (34, 55%). The median age was 2 years. There were 37 (60%) suppurative lymphadenitis, 15 (24%) parapharyngeal abscess, and 10 (16%) retropharyngeal abscess cases. Twenty-nine (47%) children received antibiotic treatment prior to admission, most commonly β-lactam agents. Of them, 15 (52%) had positive cultures, including 7 (47%) with SA. On admission, 45 (73%) children had already received amoxicillin-clavulanate. Of those who did not improve, 16 (26%) received ceftriaxone and clindamycin. Twenty-one (38%) cultures were negative. The most common isolated bacteria were SA in 13 (24%), Streptococcus pyogenes in 7 (13%), and Streptococcus viridians group in 9 (16%). Of the SA isolates, there was only 1 (8%) case of MRSA; however, there were 4 (31%) clindamycin-resistant SA isolates. Unlike previously published data, there was no increase in MRSA incidence at our institution. However, the high prevalence of clindamycin-resistant SA was in line with previous reports. These findings should be considered when starting empirical therapy in pediatric neck abscesses. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Voluntary resistance running induces increased hippocampal neurogenesis in rats comparable to load-free running.

    Science.gov (United States)

    Lee, Min Chul; Inoue, Koshiro; Okamoto, Masahiro; Liu, Yu Fan; Matsui, Takashi; Yook, Jang Soo; Soya, Hideaki

    2013-03-14

    Recently, we reported that voluntary resistance wheel running with a resistance of 30% of body weight (RWR), which produces shorter distances but higher work levels, enhances spatial memory associated with hippocampal brain-derived neurotrophic factor (BDNF) signaling compared to wheel running without a load (WR) [17]. We thus hypothesized that RWR promotes adult hippocampal neurogenesis (AHN) as a neuronal substrate underlying this memory improvement. Here we used 10-week-old male Wistar rats divided randomly into sedentary (Sed), WR, and RWR groups. All rats were injected intraperitoneally with the thymidine analogue 5-Bromo-2'-deoxuridine (BrdU) for 3 consecutive days before wheel running. We found that even when the average running distance decreased by about half, the average work levels significantly increased in the RWR group, which caused muscular adaptation (oxidative capacity) for fast-twitch plantaris muscle without causing any negative stress effects. Additionally, immunohistochemistry revealed that the total BrdU-positive cells and newborn mature cells (BrdU/NeuN double-positive) in the dentate gyrus increased in both the WR and RWR groups. These results provide new evidence that RWR has beneficial effects on AHN comparable to WR, even with short running distances. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. At-home resistance tubing strength training increases shoulder strength in the trained and untrained limb.

    Science.gov (United States)

    Magnus, C R A; Boychuk, K; Kim, S Y; Farthing, J P

    2014-06-01

    The purpose was to determine if an at-home resistance tubing strength training program on one shoulder (that is commonly used in rehabilitation settings) would produce increases in strength in the trained and untrained shoulders via cross-education. Twenty-three participants were randomized to TRAIN (strength-trained one shoulder; n = 13) or CONTROL (no intervention; n = 10). Strength training was completed at home using resistance tubing and consisted of maximal shoulder external rotation, internal rotation, scaption, retraction, and flexion 3 days/week for 4 weeks. Strength was measured via handheld dynamometry and muscle size measured via ultrasound. For external rotation strength, the trained (10.9 ± 10.9%) and untrained (12.7 ± 9.6%) arm of TRAIN was significantly different than CONTROL (1.6 ± 13.2%; -2.7 ± 12.3%; pooled across arm; P tubing training program on one limb can produce increases in strength in both limbs, and has implications for rehabilitation after unilateral shoulder injuries. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Coral resistance to ocean acidification linked to increased calcium at the site of calcification.

    Science.gov (United States)

    DeCarlo, T M; Comeau, S; Cornwall, C E; McCulloch, M T

    2018-05-16

    Ocean acidification threatens the persistence of biogenic calcium carbonate (CaCO 3 ) production on coral reefs. However, some coral genera show resistance to declines in seawater pH, potentially achieved by modulating the chemistry of the fluid where calcification occurs. We use two novel geochemical techniques based on boron systematics and Raman spectroscopy, which together provide the first constraints on the sensitivity of coral calcifying fluid calcium concentrations ([Formula: see text]) to changing seawater pH. In response to simulated end-of-century pH conditions, Pocillopora damicornis increased [Formula: see text] to as much as 25% above that of seawater and maintained constant calcification rates. Conversely, Acropora youngei displayed less control over [Formula: see text], and its calcification rates strongly declined at lower seawater pH. Although the role of [Formula: see text] in driving calcification has often been neglected, increasing [Formula: see text] may be a key mechanism enabling more resistant corals to cope with ocean acidification and continue to build CaCO 3 skeletons in a high-CO 2 world. © 2018 The Author(s).

  20. Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy

    Science.gov (United States)

    Wong, Michael; Daly, Seth M.; Greenberg, David E.; Toprak, Erdal

    2016-01-01

    The lack of effective and well-tolerated therapies against antibiotic-resistant bacteria is a global public health problem leading to prolonged treatment and increased mortality. To improve the efficacy of existing antibiotic compounds, we introduce a new method for strategically inducing antibiotic hypersensitivity in pathogenic bacteria. Following the systematic verification that the AcrAB-TolC efflux system is one of the major determinants of the intrinsic antibiotic resistance levels in Escherichia coli, we have developed a short antisense oligomer designed to inhibit the expression of acrA and increase antibiotic susceptibility in E. coli. By employing this strategy, we can inhibit E. coli growth using 2- to 40-fold lower antibiotic doses, depending on the antibiotic compound utilized. The sensitizing effect of the antisense oligomer is highly specific to the targeted gene’s sequence, which is conserved in several bacterial genera, and the oligomer does not have any detectable toxicity against human cells. Finally, we demonstrate that antisense oligomers improve the efficacy of antibiotic combinations, allowing the combined use of even antagonistic antibiotic pairs that are typically not favored due to their reduced activities. PMID:27631336

  1. Damage to the microbial cell membrane during pyrolytic sugar utilization and strategies for increasing resistance.

    Science.gov (United States)

    Jin, Tao; Rover, Marjorie R; Petersen, Elspeth M; Chi, Zhanyou; Smith, Ryan G; Brown, Robert C; Wen, Zhiyou; Jarboe, Laura R

    2017-09-01

    Lignocellulosic biomass is an appealing feedstock for the production of biorenewable fuels and chemicals, and thermochemical processing is a promising method for depolymerizing it into sugars. However, trace compounds in this pyrolytic sugar syrup are inhibitory to microbial biocatalysts. This study demonstrates that hydrophobic inhibitors damage the cell membrane of ethanologenic Escherichia coli KO11+lgk. Adaptive evolution was employed to identify design strategies for improving pyrolytic sugar tolerance and utilization. Characterization of the resulting evolved strain indicates that increased resistance to the membrane-damaging effects of the pyrolytic sugars can be attributed to a glutamine to leucine mutation at position 29 of carbon storage regulator CsrA. This single amino acid change is sufficient for decreasing EPS protein production and increasing membrane integrity when exposed to pyrolytic sugars.

  2. A combination of resistance and endurance training increases leg muscle strength in COPD

    DEFF Research Database (Denmark)

    Iepsen, Ulrik Winning; Jørgensen, Karsten Juhl; Ringbæk, Thomas

    2015-01-01

    Resistance training (RT) is thought to be effective in preventing muscle depletion, whereas endurance training (ET) is known to improve exercise capacity and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD). Our objectives were to assess the efficiency...... improvements in HRQoL, walking distance and exercise capacity. However, we found moderate quality evidence of a significant increase in leg muscle strength favouring a combination of RT and ET (standardized mean difference of 0.69 (95% confidence interval: 0.39-0.98). In conclusion, we found significantly...... increased leg muscle strength favouring a combination of RT with ET compared with ET alone. Therefore, we recommend that RT should be incorporated in rehabilitation of COPD together with ET....

  3. Exposure to dairy manure leads to greater antibiotic resistance and increased mass-specific respiration in soil microbial communities

    Science.gov (United States)

    Avera, Bethany; Badgley, Brian; Barrett, John E.; Franklin, Josh; Knowlton, Katharine F.; Ray, Partha P.; Smitherman, Crystal

    2017-01-01

    Intensifying livestock production to meet the demands of a growing global population coincides with increases in both the administration of veterinary antibiotics and manure inputs to soils. These trends have the potential to increase antibiotic resistance in soil microbial communities. The effect of maintaining increased antibiotic resistance on soil microbial communities and the ecosystem processes they regulate is unknown. We compare soil microbial communities from paired reference and dairy manure-exposed sites across the USA. Given that manure exposure has been shown to elicit increased antibiotic resistance in soil microbial communities, we expect that manure-exposed sites will exhibit (i) compositionally different soil microbial communities, with shifts toward taxa known to exhibit resistance; (ii) greater abundance of antibiotic resistance genes; and (iii) corresponding maintenance of antibiotic resistance would lead to decreased microbial efficiency. We found that bacterial and fungal communities differed between reference and manure-exposed sites. Additionally, the β-lactam resistance gene ampC was 5.2-fold greater under manure exposure, potentially due to the use of cephalosporin antibiotics in dairy herds. Finally, ampC abundance was positively correlated with indicators of microbial stress, and microbial mass-specific respiration, which increased 2.1-fold under manure exposure. These findings demonstrate that the maintenance of antibiotic resistance associated with manure inputs alters soil microbial communities and ecosystem function. PMID:28356447

  4. Exposure to dairy manure leads to greater antibiotic resistance and increased mass-specific respiration in soil microbial communities.

    Science.gov (United States)

    Wepking, Carl; Avera, Bethany; Badgley, Brian; Barrett, John E; Franklin, Josh; Knowlton, Katharine F; Ray, Partha P; Smitherman, Crystal; Strickland, Michael S

    2017-03-29

    Intensifying livestock production to meet the demands of a growing global population coincides with increases in both the administration of veterinary antibiotics and manure inputs to soils. These trends have the potential to increase antibiotic resistance in soil microbial communities. The effect of maintaining increased antibiotic resistance on soil microbial communities and the ecosystem processes they regulate is unknown. We compare soil microbial communities from paired reference and dairy manure-exposed sites across the USA. Given that manure exposure has been shown to elicit increased antibiotic resistance in soil microbial communities, we expect that manure-exposed sites will exhibit (i) compositionally different soil microbial communities, with shifts toward taxa known to exhibit resistance; (ii) greater abundance of antibiotic resistance genes; and (iii) corresponding maintenance of antibiotic resistance would lead to decreased microbial efficiency. We found that bacterial and fungal communities differed between reference and manure-exposed sites. Additionally, the β-lactam resistance gene ampC was 5.2-fold greater under manure exposure, potentially due to the use of cephalosporin antibiotics in dairy herds. Finally, ampC abundance was positively correlated with indicators of microbial stress, and microbial mass-specific respiration, which increased 2.1-fold under manure exposure. These findings demonstrate that the maintenance of antibiotic resistance associated with manure inputs alters soil microbial communities and ecosystem function. © 2017 The Author(s).

  5. Overexpression of NtWRKY50 Increases Resistance to Ralstonia solanacearum and Alters Salicylic Acid and Jasmonic Acid Production in Tobacco.

    Science.gov (United States)

    Liu, Qiuping; Liu, Ying; Tang, Yuanman; Chen, Juanni; Ding, Wei

    2017-01-01

    WRKY transcription factors (TFs) modulate plant responses to biotic and abiotic stresses. Here, we characterized a WRKY IIc TF, NtWRKY50, isolated from tobacco ( Nicotiana tabacum ) plants. The results showed that NtWRKY50 is a nuclear-localized protein and that its gene transcript is induced in tobacco when inoculated with the pathogenic bacterium Ralstonia solanacearum . Overexpression of NtWRKY50 enhanced bacterial resistance, which correlated with enhanced SA and JA/ET signaling genes. However, silencing of the NtWRKY50 gene had no obvious effects on plant disease resistance, implying functional redundancy of NtWRKY50 with other TFs. In addition, it was found that NtWRKY50 can be induced by various biotic or abiotic stresses, such as Potato virus Y, Rhizoctonia solani, Phytophthora parasitica , hydrogen peroxide, heat, cold, and wounding as well as the hormones salicylic acid (SA), jasmonic acid (JA), and ethylene (ET). Importantly, additional analysis suggests that NtWRKY50 overexpression markedly promotes SA levels but prevents pathogen-induced JA production. These data indicate that NtWRKY50 overexpression leads to altered SA and JA content, increased expression of defense-related genes and enhanced plant resistance to R. solanacearum. These probably due to increased activity of endogenous NtWRKY50 gene or could be gain-of-function phenotypes by altering the profile of genes affected by NtWRKY50 .

  6. Resistance exercise-induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men.

    Science.gov (United States)

    West, Daniel W D; Kujbida, Gregory W; Moore, Daniel R; Atherton, Philip; Burd, Nicholas A; Padzik, Jan P; De Lisio, Michael; Tang, Jason E; Parise, Gianni; Rennie, Michael J; Baker, Steven K; Phillips, Stuart M

    2009-11-01

    We aimed to determine whether exercise-induced elevations in systemic concentration of testosterone, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) enhanced post-exercise myofibrillar protein synthesis (MPS) and phosphorylation of signalling proteins important in regulating mRNA translation. Eight young men (20 +/- 1.1 years, BMI = 26 +/- 3.5 kg m(-2)) completed two exercise protocols designed to maintain basal hormone concentrations (low hormone, LH) or elicit increases in endogenous hormones (high hormone, HH). In the LH protocol, participants performed a bout of unilateral resistance exercise with the elbow flexors. The HH protocol consisted of the same elbow flexor exercise with the contralateral arm followed immediately by high-volume leg resistance exercise. Participants consumed 25 g of protein after arm exercise to maximize MPS. Muscle biopsies and blood samples were taken as appropriate. There were no changes in serum testosterone, GH or IGF-1 after the LH protocol, whereas there were marked elevations after HH (testosterone, P anabolic hormones do not enhance fed-state anabolic signalling or MPS following resistance exercise. Local mechanisms are likely to be of predominant importance for the post-exercise increase in MPS.

  7. Loss of BRCA1 or BRCA2 markedly increases the rate of base substitution mutagenesis and has distinct effects on genomic deletions

    DEFF Research Database (Denmark)

    Zamborszky, J.; Szikriszt, B.; Gervai, J. Z.

    2017-01-01

    -genome sequencing of multiple isogenic chicken DT40 cell clones to precisely determine the consequences of BRCA1/2 loss on all types of genomic mutagenesis. Spontaneous base substitution mutation rates increased sevenfold upon the disruption of either BRCA1 or BRCA2, and the arising mutation spectra showed strong...... of stalled replication forks as the cause of increased mutagenesis. The high rate of base substitution mutagenesis demonstrated by our experiments is likely to significantly contribute to the oncogenic effect of the inactivation of BRCA1 or BRCA2....

  8. Temporary reversal by topotecan of marked insulin resistance in a patient with myelodysplastic syndrome: case report and possible mechanism for tumor necrosis factor alpha (TNF-alpha)-induced insulin resistance.

    Science.gov (United States)

    Huntington, M O; Krell, K E; Armour , W E; Liljenquist, J E

    2001-06-01

    Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor. We report here a remarkable degree of insulin resistance in a patient with adult respiratory distress syndrome and myelodysplasia.

  9. Laser marking method and device

    International Nuclear Information System (INIS)

    Okazaki, Yuki; Aoki, Nobutada; Mukai, Narihiko; Sano, Yuji; Yamamoto, Seiji.

    1997-01-01

    An object is disposed in laser beam permeating liquid or gaseous medium. Laser beams such as CW laser or pulse laser oscillated from a laser device are emitted to the object to apply laser markings with less degradation of identification and excellent corrosion resistance on the surface of the object simply and easily. Upon applying the laser markings, a liquid or gas as a laser beam permeating medium is blown onto the surface of the object, or the liquid or gas in the vicinity of the object is sucked, the laser beam-irradiated portion on the surface can be cooled positively. Accordingly, the laser marking can be formed on the surface of the object with less heat affection to the object. In addition, if the content of a nitrogen gas in the laser beam permeating liquid medium is reduced by degassing to lower than a predetermined value, or the laser beam permeating gaseous medium is formed by an inert gas, a laser marking having high corrosion resistance and reliability can be formed on the surface of the objective member. (N.H.)

  10. Rapid Increase in Prevalence of Carbapenem-Resistant Enterobacteriaceae (CRE) and Emergence of Colistin Resistance Gene mcr-1 in CRE in a Hospital in Henan, China.

    Science.gov (United States)

    Li, Yi; Sun, Qiao-Ling; Shen, Yingbo; Zhang, Yangjunna; Yang, Jun-Wen; Shu, Ling-Bin; Zhou, Hong-Wei; Wang, Yang; Wang, Bing; Zhang, Rong; Wang, Shaolin; Shen, Zhangqi

    2018-04-01

    The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is one of the most severe threats to human health in a clinical setting. The recent emergence of plasmid-mediated colistin resistance gene mcr-1 among CRE strains greatly compromises the use of colistin as a last resort for the treatment of infections caused by CRE. This study aimed to understand the current epidemiological trends and characteristics of CRE from a large hospital in Henan, the most populous province in China. From 2014 to 2016, a total of 7,249 Enterobacteriaceae isolates were collected from clinical samples, among which 18.1% (1,311/7,249) were carbapenem resistant. Carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli were the two most common CRE species, with Klebsiella pneumoniae carbapenemases (KPC) and New Delhi metallo-β-lactamases (NDM), respectively, responsible for the carbapenem resistance of the two species. Notably, >57.0% ( n = 589) of the K. pneumoniae isolates from the intensive care unit were carbapenem resistant. Furthermore, bla NDM-5 and mcr-1 were found to coexist in one E. coli isolate, which exhibited resistance to almost all tested antibiotics. Overall, we observed a significant increase in the prevalence of CRE isolates during the study period and suggest that carbapenems may no longer be considered to be an effective treatment for infections caused by K. pneumoniae in the studied hospital. Copyright © 2018 American Society for Microbiology.

  11. Normobaric hypoxia increases the growth hormone response to maximal resistance exercise in trained men.

    Science.gov (United States)

    Filopoulos, Dean; Cormack, Stuart J; Whyte, Douglas G

    2017-08-01

    This study examined the effect of hypoxia on growth hormone (GH) release during an acute bout of high-intensity, low-volume resistance exercise. Using a single-blinded, randomised crossover design, 16 resistance-trained males completed two resistance exercise sessions in normobaric hypoxia (HYP; inspiratory oxygen fraction, (FiO 2 ) 0.12, arterial oxygen saturation (SpO 2 ) 82 ± 2%) and normoxia (NOR; FiO 2 0.21, SpO 2 98 ± 0%). Each session consisted of five sets of three repetitions of 45° leg press and bench press at 85% of one repetition maximum. Heart rate, SpO 2 , and electromyographic activity (EMG) of the vastus lateralis muscle were measured throughout the protocol. Serum lactate and GH levels were determined pre-exposure, and at 5, 15, 30 and 60 min post-exercise. Differences in mean and integrated EMG between HYP and NOR treatments were unclear. However, there was an important increase in the peak levels and area under the curve of both lactate (HYP 5.8 ± 1.8 v NOR 3.9 ± 1.1 mmol.L -1 and HYP 138.7 ± 33.1 v NOR 105.8 ± 20.8 min.mmol.L -1 ) and GH (HYP 4.4 ± 3.1 v NOR 2.1 ± 2.5 ng.mL -1 and HYP 117.7 ± 86.9 v NOR 72.9 ± 85.3 min.ng.mL -1 ) in response to HYP. These results suggest that performing high-intensity resistance exercise in a hypoxic environment may provide a beneficial endocrine response without compromising the neuromuscular activation required for maximal strength development.

  12. FZD4 Marks Lateral Plate Mesoderm and Signals with NORRIN to Increase Cardiomyocyte Induction from Pluripotent Stem Cell-Derived Cardiac Progenitors

    Directory of Open Access Journals (Sweden)

    Charles Yoon

    2018-01-01

    Full Text Available The identification of cell surface proteins on stem cells or stem cell derivatives is a key strategy for the functional characterization, isolation, and understanding of stem cell population dynamics. Here, using an integrated mass spectrometry- and microarray-based approach, we analyzed the surface proteome and transcriptome of cardiac progenitor cells (CPCs generated from the stage-specific differentiation of mouse and human pluripotent stem cells. Through bioinformatics analysis, we have identified and characterized FZD4 as a marker for lateral plate mesoderm. Additionally, we utilized FZD4, in conjunction with FLK1 and PDGFRA, to further purify CPCs and increase cardiomyocyte (CM enrichment in both mouse and human systems. Moreover, we have shown that NORRIN presented to FZD4 further increases CM output via proliferation through the canonical WNT pathway. Taken together, these findings demonstrate a role for FZD4 in mammalian cardiac development.

  13. Neisseria gonorrhoeae: testing, typing and treatment in an era of increased antimicrobial resistance

    NARCIS (Netherlands)

    Wind, C.M.

    2017-01-01

    This thesis discusses the management of Neisseria gonorrhoeae infections while under threat of emerging antimicrobial resistance. It focuses on improved diagnostics, and antimicrobial resistance to current and future therapies. We describe a new method of targeted deferred culture, using nucleic

  14. Antibiotic resistance in Pseudomonas aeruginosa strains with increased mutation frequency due to inactivation of the DNA oxidative repair system

    DEFF Research Database (Denmark)

    Mandsberg, Lotte F; Ciofu, Oana; Kirkby, N

    2009-01-01

    ,8-dihydro-8-oxodeoxyguanosine) than PAO1 after exposure to PMNs, and they developed resistance to antibiotics more frequently. The mechanisms of resistance were increased β-lactamase production and overexpression of the MexCD-OprJ efflux-pump. Mutations in either the mutT or the mutY gene were found...... in resistant HP clinical isolates from patients with CF, and complementation with wild-type genes reverted the phenotype. In conclusion, oxidative stress might be involved in the development of resistance to antibiotics. We therefore suggest the possible use of antioxidants for CF patients to prevent...

  15. NVENTIONS IN THE NANOTECHNOLOGICAL AREA PROVIDE INCREASED RESISTANCE OF CONSTRUCTION MATERIALS AND PRODUCTS TO OPERATIONAL LOAD

    Directory of Open Access Journals (Sweden)

    VLASOV Vladimir Alexeevich

    2013-12-01

    Full Text Available The invention «Dispersion of Carbon Nanotubes (RU 2494961» can be used in production of modifying additives for construction materials. Dispersion of carbon nanotubes contains, mass %: carbon nanotubes 1–20; surface active agent – sodium chloride of sulfonated derived naphthalene 1–20; fumed silica 5–15; water – the rest. Dispersion can additionally contain ethylene glycol as antifreeze. Dispersion is steady in storage, it is soluble in water, provides increased strength of construction materials. Invention «Building Structures Reinforcement Composition (RU 2493337» can beused in construction to reinforce concrete, brick and masonry structures. Composition contains glass or basalt roving taken in quantity 90÷100 parts by weight, soaked in polymer binder based on epoxy taken in quantity 0,001÷1,5 parts by weight. This invention provides high resistance to operational load.

  16. Blood lipid peroxides and muscle damage increased following intensive resistance training of female weightlifters.

    Science.gov (United States)

    Liu, Jen-Fang; Chang, Wei-Yin; Chan, Kuei-Hui; Tsai, Wen-Yee; Lin, Chen-Li; Hsu, Mei-Chieh

    2005-05-01

    The aim of this study was to examine changes in muscle cell injury and antioxidant capacity of weightlifters following a 1-week intensive resistance-training regimen. Thirty-six female subjects participated in this study, and their ages ranged from 18 to 25 years. The sample group included 19 elite weightlifters with more than 3 years of weightlifting training experience, while the control group comprised 17 non-athletic individuals. Compared with non-athletes, weightlifters had significantly lower glutathione peroxidase activity and plasma vitamin C concentrations. Weightlifters also had significantly higher malondialdehyde + 4-hydroxy 2-(E)-nonenal (MDA+4-HNE) and thiobarbituric acid-reactive substance (TBARS) levels and creatine kinase (CK) activity. For weightlifters, the plasma vitamin E level and the activity of superoxide dismutase (SOD) decreased, and CK activity increased significantly (P weightlifters (P injury in female weightlifters. Furthermore, proper rest after intensive training was found to be important for recovery.

  17. Methods for Increasing the Material Resistance of the Mulching Tool Body Against its Deformation in Operation

    Science.gov (United States)

    Ľuptáčiková, Veronika; Ťavodová, Miroslava

    2017-12-01

    Instruments working in the cultivation of forest areas, for example under the guidance of high stress, are exposed to factors of heterogeneous environment which are soil, wood, various types of rocks, sometimes waste - metal, plastics or glass as well. The mulching tool body, the forging, deforms and worsens rapidly after loss of the WC toe-caps. Currently used tools have a non-heat-treated body material with a ferritic-pearlitic structure that has low abrasion resistance. One of the possibilities is to heat the tool body. Another possibility is to apply suitable welds to exposed areas. By correctly selecting the thermal mode of the tool material or by applying the welded material to the exposed body part of the tool, we can ensure that the tool's operating time is increased.

  18. Engineering works for increasing earthquake resistance of Hamaoka nuclear power plant

    International Nuclear Information System (INIS)

    Oonishi, Yoshihiro; Kondou, Makoto; Hattori, Kazushi

    2007-01-01

    The improvement works of the ground of outdoor piping and duct system of Hamaoka-3, one of engineering works for increasing earthquake resistance of the plant, are reported. The movable outdoor piping systems were moved. SJ method, one of the high-pressure jet mixing method, improved the ground between the duct and the unmoved light oil tank on the western side, and the environmental ground. The other places were improved by the concrete replacement works. The results of ground treated by SJ method showed the high quality of stiffness and continuity. Outline of engineering works, execution of concrete replacement works, the high-pressure jet mixing method, SJ method, the quality control and treatment of the generated mud by SJ method are reported. A seismic response analysis, execution facilities, construction planning, working diagram, improvement work conditions of three methods, and steps of SJ method are illustrated. (S.Y.)

  19. Oral administration of antimicrobials increase antimicrobial resistance in E. coli from chicken--a systematic review.

    Science.gov (United States)

    Simoneit, C; Burow, E; Tenhagen, B-A; Käsbohrer, A

    2015-01-01

    Antimicrobials play an important role in animal and human health care. It was the aim of this systematic review to assess the effects of oral administration of antimicrobials on the development of antimicrobial resistance (AMR) in Escherichia coli (E. coli) from chickens. Moreover, the effects of the administration of more than one antimicrobial and of different dosages were studied. Literature was searched in November 2012 from the electronic databases ISI Web of Science, PubMed, Scopus and a national literature database (DIMDI) as well as the database ProQuest LLC. The search was updated in March 2014. Original studies describing a treatment (A) and a control group of either non-treatment (C) or initial value (0) and determining AMR in E. coli at different sample points (SP) were included. The literature search resulted in 35 full text articles on the topic, seven (20%) of which contained sufficient information on the administered antimicrobial and the impact of treatment on AMR. Most papers described the use of more than one antimicrobial, several dosages, controls (non-treatment or pre-treatment) and measured AMR at different SPs leading to a total of 227 SPs on the impact of the use of antimicrobials on AMR in chickens. 74% of the SPs (168/227) described a higher AMR-rate in E. coli from treated animals than from controls. After the administration of a single antimicrobial, AMR increased at 72% of the SPs. Administration of more than one antimicrobial increased AMR at 82% of the SPs. Higher dosages were associated with similar or higher AMR rates. The limited number of studies for each antimicrobial agent and the high variability in the resistance effect call for more well designed studies on the impact of oral administration on AMR development and spread. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma.

    Science.gov (United States)

    Dhabhar, Firdaus S; Saul, Alison N; Daugherty, Christine; Holmes, Tyson H; Bouley, Donna M; Oberyszyn, Tatiana M

    2010-01-01

    In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposure would enhance protective immunity and increase resistance to SCC. Control and short-term stress groups were treated identically except that the short-term stress group was restrained (2.5h) before each of nine UV-exposure sessions (minimum erythemal dose, 3-times/week) during weeks 4-6 of the 10-week UV exposure protocol. Tumors were measured weekly, and tissue collected at weeks 7, 20, and 32. Chemokine and cytokine gene expression was quantified by real-time PCR, and CD4+ and CD8+ T cells by flow cytometry and immunohistochemistry. Compared to controls, the short-term stress group showed greater cutaneous T-cell attracting chemokine (CTACK)/CCL27, RANTES, IL-12, and IFN-gamma gene expression at weeks 7, 20, and 32, higher skin infiltrating T cell numbers (weeks 7 and 20), lower tumor incidence (weeks 11-20) and fewer tumors (weeks 11-26). These results suggest that activation of short-term stress physiology increased chemokine expression and T cell trafficking and/or function during/following UV exposure, and enhanced Type 1 cytokine-driven cell-mediated immunity that is crucial for resistance to SCC. Therefore, the physiological fight-or-flight stress response and its adjuvant-like immuno-enhancing effects, may provide a novel and important mechanism for enhancing immune system mediated tumor-detection/elimination that merits further investigation.

  1. A Shotgun Proteomic Approach Reveals That Fe Deficiency Causes Marked Changes in the Protein Profiles of Plasma Membrane and Detergent-Resistant Microdomain Preparations from Beta vulgaris Roots.

    Science.gov (United States)

    Gutierrez-Carbonell, Elain; Takahashi, Daisuke; Lüthje, Sabine; González-Reyes, José Antonio; Mongrand, Sébastien; Contreras-Moreira, Bruno; Abadía, Anunciación; Uemura, Matsuo; Abadía, Javier; López-Millán, Ana Flor

    2016-08-05

    In the present study we have used label-free shotgun proteomic analysis to examine the effects of Fe deficiency on the protein profiles of highly pure sugar beet root plasma membrane (PM) preparations and detergent-resistant membranes (DRMs), the latter as an approach to study microdomains. Altogether, 545 proteins were detected, with 52 and 68 of them changing significantly with Fe deficiency in PM and DRM, respectively. Functional categorization of these proteins showed that signaling and general and vesicle-related transport accounted for approximately 50% of the differences in both PM and DRM, indicating that from a qualitative point of view changes induced by Fe deficiency are similar in both preparations. Results indicate that Fe deficiency has an impact in phosphorylation processes at the PM level and highlight the involvement of signaling proteins, especially those from the 14-3-3 family. Lipid profiling revealed Fe-deficiency-induced decreases in phosphatidic acid derivatives, which may impair vesicle formation, in agreement with the decreases measured in proteins related to intracellular trafficking and secretion. The modifications induced by Fe deficiency in the relative enrichment of proteins in DRMs revealed the existence of a group of cytoplasmic proteins that appears to be more attached to the PM in conditions of Fe deficiency.

  2. Effect of Trinexapac-ethyl on Increased Resistance to Drought Stress in Wheatgrass (Agropyron desertorum L.

    Directory of Open Access Journals (Sweden)

    mohamad hossein sheikh mohamadi

    2017-10-01

    Full Text Available Introduction: Drought is one of the most detrimental abiotic stresses for turfgrass growth across a wide range of geographic locations. Most cool-season grass species are not well adapted to extended periods of drought, particularly during summer months. Decline in turf quality caused by drought stress is a major concern in turfgrass culture. Therefore, developing management practices for improving drought resistance of turfgrasses has become essential in arid and semi-arid regions, especially during water use restriction. One strategy to improve plant drought resistance is to promote drought avoidance by reducing water loss during drought, which may be achieved by slowing growth rate of shoots and lowering leaf area canopy to reduce demand for water. Application of growth regulators is one of the methods for increasing resistance of plants to biotic and abiotic stresses. Trinexapac-ethyl (TE is one of the most widely used PGRs in the management of cool-season and warm-season turfgrass species. TE absorbed quickly by foliage and slow cell elongation through inhibiting of converting one form of gibberellic acid (GA20 to another (GA1. Most studies conducted under non-stressed conditions found that TE application increased chlorophyll content, turf quality, turf density and reduced shoot extension rate. We hypothesized that TE may influence plant tolerance to drought stress. Limited available data─ as reported in the above referred studies─ suggest that TE application may be beneficial for plant tolerance to stresses, but the effectiveness varies with turfgrass species, dose and duration of TE treatment, and type of stress. The main aim of this research is to evaluate the effect of Trinexapac-ethyl on increased resistance to drought stress in wheatgrass. Materials and Methods: Wheatgrass (Agropyron desertorum L. was used in this study. This study was conducted in field conditions at Isfahan University of Technology, Isfahan, Iran.. Wheatgrass

  3. Reconfiguring trade mark law

    DEFF Research Database (Denmark)

    Elsmore, Matthew James

    2013-01-01

    -border setting, with a particular focus on small business and consumers. The article's overall message is to call for a rethink of received wisdom suggesting that trade marks are effective trade-enabling devices. The case is made for reassessing how we think about European trade mark law.......First, this article argues that trade mark law should be approached in a supplementary way, called reconfiguration. Second, the article investigates such a reconfiguration of trade mark law by exploring the interplay of trade marks and service transactions in the Single Market, in the cross...

  4. Multiple mechanisms increase levels of resistance in Rapistrum rugosum to ALS herbicides

    Directory of Open Access Journals (Sweden)

    Zhara M Hatami

    2016-02-01

    Full Text Available Rapistrum rugosum (turnip weed is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM, a sulfonylurea (SU belonging to the acetolactate synthase (ALS inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose–response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF for resistant (R populations was 2.5 to 6.6 fold higher than susceptible (S plant. Neither foliar retention, nor 14C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1, in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (resistance factors were from 28 to 38 and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT, pyrimidinyl-thiobenzoate (PTB and triazolopyrimidine (TP, with no cross-resistance to imidazolinone (IMI. Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM.

  5. Strengthening of oxidation resistant materials for gas turbine applications. [treatment of silicon ceramics for increased flexural strength and impact resistance

    Science.gov (United States)

    Kirchner, H. P.

    1974-01-01

    Silicon nitride and silicon carbide ceramics were treated to form compressive surface layers. On the silicon carbide, quenching and thermal exposure treatments were used, and on the silicon nitride, quenching, carburizing, and a combination of quenching and carburizing were used. In some cases substantial improvements in impact resistance and/or flexural strength were observed. The presence of compressive surface stresses was demonstrated by slotted rod tests.

  6. Increase of the electrical resistance of thin aluminium film due to 14 MeV neutron irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Agrawal, S K; Kumar, U; Singh, S P; Bhattacharya, S; Nigam, A K [Banaras Hindu Univ. (India). Dept. of Physics

    1978-01-01

    The effect of 14 MeV neutron bombardment on the electrical resistance of 500 A thick vacuum-coated Al film is investigated. In the beginning, a slow, then sharp and finally again slow increase is observed in the electrical resistance of the film. Transmission electron micrographs of the film after the same dose of neutron irradiation show a large number of defects produced in the film due to neutron irradiation, which seems to be the cause of this increase.

  7. Regulation of glucose homeostasis by KSR1 and MARK2.

    Directory of Open Access Journals (Sweden)

    Paula J Klutho

    Full Text Available Protein scaffolds control the intensity and duration of signaling and dictate the specificity of signaling through MAP kinase pathways. KSR1 is a molecular scaffold of the Raf/MEK/ERK MAP kinase cascade that regulates the intensity and duration of ERK activation. Relative to wild-type mice, ksr1⁻/⁻ mice are modestly glucose intolerant, but show a normal response to exogenous insulin. However, ksr1⁻/⁻ mice also demonstrate a three-fold increase in serum insulin levels in response to a glucose challenge, suggesting a role for KSR1 in insulin secretion. The kinase MARK2 is closely related to C-TAK1, a known regulator of KSR1. Mice lacking MARK2 have an increased rate of glucose disposal in response to exogenous insulin, increased glucose tolerance, and are resistant to diet-induced obesity. mark2⁻/⁻ksr1⁻/⁻ (DKO mice were compared to wild type, mark2⁻/⁻, and ksr1⁻/⁻ mice for their ability to regulate glucose homeostasis. Here we show that disruption of KSR1 in mark2⁻/⁻ mice reverses the increased sensitivity to exogenous insulin resulting from MARK2 deletion. DKO mice respond to exogenous insulin similarly to wild type and ksr1⁻/⁻ mice. These data suggest a model whereby MARK2 negatively regulates insulin sensitivity in peripheral tissue through inhibition of KSR1. Consistent with this model, we found that MARK2 binds and phosphorylates KSR1 on Ser392. Phosphorylation of Ser392 is a critical regulator of KSR1 stability, subcellular location, and ERK activation. These data reveal an unexpected role for the molecular scaffold KSR1 in insulin-regulated glucose metabolism.

  8. Is Shift Work Associated with Lipid Disturbances and Increased Insulin Resistance?

    Science.gov (United States)

    Alefishat, Eman; Abu Farha, Rana

    2015-11-01

    Shift work is associated with higher risk of metabolic disturbances and cardiovascular diseases. There are contradictory reports on the effect of shift work on lipid parameters in the literature. No studies have investigated any possible association between shift work and the ratio of serum triglyceride to high density lipoprotein cholesterol (TG/HDL-C ratio). This ratio can be used as a predictor for insulin resistance. The main aim of the present cross-sectional study was to investigate the association between shift work and serum TG/HDL-C ratio, TG level, and HDL-C level. One hundred and forty adult Jordanian employees were recruited. Demographic data, lifestyle habits, clinical parameters, and working patterns data were documented through a well-structured questionnaire. Serum TG and HDL-C levels were measured after at least 9 hours fasting using enzymatic assay procedure. Compared with daytime workers (58 subjects), shift workers (82 subjects) displayed higher TG/HDL-C ratio (r = 0.217, P = 0.013), higher serum TG levels (r = 0.220, P = 0.012), and lower HDL-C levels (r = -0.200, P = 0.016). Among shift workers, 30.5% were found to have a TG/HDL-C ratio >3.5 compared with 8.6% of daytime workers (P = 0.002). In the present study, shift work was shown to be associated with higher TG/HDL-C ratio, higher serum TG, and lower HDL-C levels. These findings might indicate that shift work is associated with increased insulin resistance and consequently higher risk of metabolic syndrome and cardiovascular diseases.

  9. Progesterone increases resistance of ophthalmic and central retinal arteries in climacteric women.

    Science.gov (United States)

    Souza, M A M De; Souza, B M De; Geber, S

    2013-04-01

    To evaluate the effect of a synthetic progestin on the vascular resistance of the ophthalmic and central retinal arteries in climacteric women, compared to placebo, using transorbital ultrasound with Doppler velocimetry. We performed a prospective, randomized, double-blinded, placebo-controlled study with 216 climacteric women. Subjects were randomly allocated to one of two groups: either the group receiving placebo (one pill/day for 30 days) (n = 108) or the group receiving progestin (5 mg medroxyprogesterone acetate/day for 30 days) (n = 108). Transorbital Doppler velocimetric ultrasound was performed, before and after treatment; we measured the pulsatility index, resistance index and systole/diastole ratio. The mean ages of the participants in the study group and the control group were 54 ± 6.2 years (range 48-59 years) and 55 ± 6.8 years (range 46-60 years), respectively. When we compared the effect of the progestin on the central retinal artery before and after treatment, we observed a significant increase after the treatment in all Doppler indices. The same was observed when we compared the effect of the progestin on the ophthalmic artery. In the group of women receiving placebo, the Doppler indices were similar before and after treatment. Our results demonstrate the existence of a progestogenic vasoconstrictive effect in the ophthalmic and central retinal arteries. As this study provides new data, the observed effect needs further investigations to better elucidate its extent. Moreover, our findings may be particularly useful to others interested in understanding the vascular dynamics of the cerebral vessels and to researchers running clinical trials related to hormone replacement therapy.

  10. Using glass-graded zirconia to increase delamination growth resistance in porcelain/zirconia dental structures.

    Science.gov (United States)

    Chai, Herzl; Mieleszko, Adam J; Chu, Stephen J; Zhang, Yu

    2018-01-01

    Porcelain fused to zirconia (PFZ) restorations are widely used in prosthetic dentistry. However, their tendency to delaminate along the P/Z interface remains a practical problem so that assessing and improving the interfacial strength are important design aspects. This work examines the effect of modifying the zirconia veneering surface with an in-house felspathic glass on the interfacial fracture resistance of fused P/Z. Three material systems are studied: porcelain fused to zirconia (control) and porcelain fused to glass-graded zirconia with and without the presence of a glass interlayer. The specimens were loaded in a four-point-bend fixture with the porcelain veneer in tension. The evolution of damage is followed with the aid of a video camera. The interfacial fracture energy G C was determined with the aid of a FEA, taking into account the stress shielding effects due to the presence of adjacent channel cracks. Similarly to a previous study on PFZ specimens, the fracture sequence consisted of unstable growth of channel cracks in the veneer followed by stable cracking along the P/Z interface. However, the value of GC for the graded zirconia was approximately 3 times that of the control zirconia, which is due to the good adhesion between porcelain and the glass network structure on the zirconia surface. Combined with its improved bonding to resin-based cements, increased resistance to surface damage and good esthetic quality, graded zirconia emerges as a viable material concept for dental restorations. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  11. Longer repetition duration increases muscle activation and blood lactate response in matched resistance training protocols

    Directory of Open Access Journals (Sweden)

    Hugo Cesar Martins-Costa

    2016-03-01

    Full Text Available Abstract This study analyzed the effect of different repetition durations on electromyographic and blood lactate responses of the bench press exercise. Fifteen recreationally trained male volunteers completed two training protocols, matched for intensity (% one-repetition maximum; 1RM, number of sets, number of repetitions, and rest intervals. One of the protocols was performed with a repetition duration of 4 s (2 s concentric: 2 s eccentric; 2:2 protocol, whereas the second protocol had a repetition duration of 6 s (2 s concentric: 4 s eccentric; 2:4 protocol. The results showed higher normalized integrated electromyography (pectoralis major and triceps brachii for the 2:4 protocol. Blood lactate concentration was also higher in the 2:4 protocol across all sets. These results show that adding 2 s to the eccentric action in matched training protocols increases muscle activation and blood lactate response, which reinforces the notion that increasing repetition duration is an alternative load progression in resistance training.

  12. Acute resistance exercise reduces increased gene expression in muscle atrophy of ovariectomised arthritic rats

    Directory of Open Access Journals (Sweden)

    Roberto Furlanetto Jr

    2017-02-01

    Full Text Available Objective: We studied the effect of resistance exercise (RE on mRNA levels of atrogin-1, MuRF-1, and myostatin in the gastrocnemius muscle of arthritic rats after loss of ovarian function (LOF. Material and methods : Thirty female Wistar rats (nine weeks old, 195.3 ±17.4 grams were randomly allocated into five groups: control group (CT-Sham; n = 6; group with rheumatoid arthritis (RA; n = 6; group with rheumatoid arthritis subjected to RE (RAEX; n = 6; ovariectomy group with rheumatoid arthritis (RAOV; n = 6; and an ovariectomy group with rheumatoid arthritis subjected to RE (RAOVEX; n = 6. After 15 days of intra-articular injections with Met-BSA the animals were subjected to RE and six hours after workout were euthanised. Results : The rheumatoid arthritis provoked reduction in the cross-sectional area (CSA of muscle fibres, but the CSA was lower in the RAOV when compared to the RA groups. Skeletal muscle atrogin-1 mRNA level was increased in arthritic rats (RA and RAOV, but the atrogin-1 level was higher in RAOV group when compared to other arthritic groups. The Muscle MuRF-1 mRNA level was also increased in the RAOV group. The increased atrogin-1 and MuRF-1 mRNA levels were lower in the RAOVEX group than in the RAOV group. The myostatin mRNA level was similar in all groups, except for the RAOVEX group, in which it was lower than the other groups. Conclusions : LOF results in increased loss of skeletal muscle-related ubiquitin ligases (atrogin-1 and MuRF-1. However, the RE reduces the atrogin-1, MuRF-1, and myostatin mRNA levels in muscle of arthritic rats affected by LOF.

  13. New approach to increasing rice lodging resistance and biomass yield through the use of high gibberellin producing varieties.

    Directory of Open Access Journals (Sweden)

    Ayako Okuno

    Full Text Available Traditional breeding for high-yielding rice has been dependent on the widespread use of fertilizers and the cultivation of gibberellin (GA-deficient semi-dwarf varieties. The use of semi-dwarf plants facilitates high grain yield since these varieties possess high levels of lodging resistance, and thus could support the high grain weight. Although this approach has been successful in increasing grain yield, it is desirable to further improve grain production and also to breed for high biomass. In this study, we re-examined the effect of GA on rice lodging resistance and biomass yield using several GA-deficient mutants (e.g. having defects in the biosynthesis or perception of GA, and high-GA producing line or mutant. GA-deficient mutants displayed improved bending-type lodging resistance due to their short stature; however they showed reduced breaking-type lodging resistance and reduced total biomass. In plants producing high amounts of GA, the bending-type lodging resistance was inferior to the original cultivars. The breaking-type lodging resistance was improved due to increased lignin accumulation and/or larger culm diameters. Further, these lines had an increase in total biomass weight. These results show that the use of rice cultivars producing high levels of GA would be a novel approach to create higher lodging resistance and biomass.

  14. New approach to increasing rice lodging resistance and biomass yield through the use of high gibberellin producing varieties.

    Science.gov (United States)

    Okuno, Ayako; Hirano, Ko; Asano, Kenji; Takase, Wakana; Masuda, Reiko; Morinaka, Yoichi; Ueguchi-Tanaka, Miyako; Kitano, Hidemi; Matsuoka, Makoto

    2014-01-01

    Traditional breeding for high-yielding rice has been dependent on the widespread use of fertilizers and the cultivation of gibberellin (GA)-deficient semi-dwarf varieties. The use of semi-dwarf plants facilitates high grain yield since these varieties possess high levels of lodging resistance, and thus could support the high grain weight. Although this approach has been successful in increasing grain yield, it is desirable to further improve grain production and also to breed for high biomass. In this study, we re-examined the effect of GA on rice lodging resistance and biomass yield using several GA-deficient mutants (e.g. having defects in the biosynthesis or perception of GA), and high-GA producing line or mutant. GA-deficient mutants displayed improved bending-type lodging resistance due to their short stature; however they showed reduced breaking-type lodging resistance and reduced total biomass. In plants producing high amounts of GA, the bending-type lodging resistance was inferior to the original cultivars. The breaking-type lodging resistance was improved due to increased lignin accumulation and/or larger culm diameters. Further, these lines had an increase in total biomass weight. These results show that the use of rice cultivars producing high levels of GA would be a novel approach to create higher lodging resistance and biomass.

  15. 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

  16. Mark Tompkins Canaccord

    OpenAIRE

    Mark Tompkins Canaccord

    2018-01-01

    Mark Tompkins Canaccord is a senior technologist for ecosystem and water resources management in SEC SAID Oakland, California office. In his career which lasts over fifteen years Mark has worked on project involving lake restorations, clean water engineering, ecological engineering and management, hydrology, hydraulics, sediment transport and other projects for environmental planning all over the country. Mark Tompkins Canaccord tries to blend his skills of planning and engineering with s...

  17. Wear Resistance Increase by Friction Stir Processing for Partial Magnesium Replacement in Aluminium Alloys

    Science.gov (United States)

    Balos, Sebastian; Labus Zlatanovic, Danka; Janjatovic, Petar; Dramicanin, Miroslav; Rajnovic, Dragan; Sidjanin, Leposava

    2018-03-01

    In this paper, the influence of friction stir processing (FSP) was evaluated as a way of increasing mechanical properties and a way of replacing the magnesium content in aluminium alloys. FSP was done on AA5754 H111 aluminium alloy, containing 3 % Mg, by using various types of tools and different welding speeds, rotational speeds and tilt angles. Wear test was done against SiC abrasive papers. SiC was used to simulate extreme abrasive wear conditions. The wear test was done on untreated AA5754 specimens, processed AA5754 specimens and untreated AA5083 H111 specimens, the latter containing 4.5 % Mg. AA5083 was chosen as an alternative to AA5754, but with a significantly higher Mg content. Base material microhardness was 60 HV1 and 80 HV1 for AA5754 and AA5083 alloys respectively. To find the effect of FSP on AA5754 alloy, microstructures were studied, mainly grain size in the stir zone. It was found, that an elevated processing and rotational speed, without tilt angle and the tool without a reservoir resulted in an increase in hardness of the AA5754 to 70 HV1, but with the occurrence of tunneling defect and the wear rate of 79.3 mg. Lower FSP parameters and a tilted tool with a reservoir resulted in microhardness of 68 HV1 and wear rate of 68.2 mg without tunneling. These wear values are lower than those obtained with unmodified Al-alloys: AA5754 97.2 mg and AA5083 86.3 mg. An increased wear resistance can be attributed to the combined effect of grain boundary strengthening mechanism and solid solution strengthening, versus only the latter in untreated alloys.

  18. Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression.

    Science.gov (United States)

    Roseman, Leor; Demetriou, Lysia; Wall, Matthew B; Nutt, David J; Carhart-Harris, Robin L

    2017-12-27

    Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments' therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions. ISRCTN, number ISRCTN14426797. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Importance of sigma factor mutations in increased triclosan resistance in Salmonella Typhimurium

    DEFF Research Database (Denmark)

    Gantzhorn, Mette Rørbæk; Olsen, John Elmerdahl; Thomsen, Line Elnif

    2015-01-01

    towards the antibiotics enrofloxacin and sulphamethoxazole/trimethoprim. CONCLUSIONS: Medium level triclosan resistance could be obtained by fabI mutations in S. Typhimurium, however, high level resistance was found to require sigma factor mutations in addition to a fabI mutation. Reduced antibiotic...

  20. Collateral damage: rapid exposure-induced evolution of pesticide resistance leads to increased susceptibility to parasites.

    Science.gov (United States)

    Jansen, Mieke; Stoks, Robby; Coors, Anja; van Doorslaer, Wendy; de Meester, Luc

    2011-09-01

    Although natural populations may evolve resistance to anthropogenic stressors such as pollutants, this evolved resistance may carry costs. Using an experimental evolution approach, we exposed different Daphnia magna populations in outdoor containers to the carbamate pesticide carbaryl and control conditions, and assessed the resulting populations for both their resistance to carbaryl as well as their susceptibility to infection by the widespread bacterial microparasite Pasteuria ramosa. Our results show that carbaryl selection led to rapid evolution of carbaryl resistance with seemingly no cost when assessed in a benign environment. However, carbaryl-resistant populations were more susceptible to parasite infection than control populations. Exposure to both stressors reveals a synergistic effect on sterilization rate by P. ramosa, but this synergism did not evolve under pesticide selection. Assessing costs of rapid adaptive evolution to anthropogenic stress in a semi-natural context may be crucial to avoid too optimistic predictions for the fitness of the evolving populations. © 2011 The Author(s).

  1. Increasing antimicrobial resistance in clinical isolates of Staphylococcus intermedius group bacteria and emergence of MRSP in the UK.

    Science.gov (United States)

    Beever, L; Bond, R; Graham, P A; Jackson, B; Lloyd, D H; Loeffler, A

    2015-02-14

    Frequencies of antimicrobial resistance were determined amongst 14,555 clinical Staphylococcus intermedius group (SIG) isolates from UK dogs and cats to estimate resistance trends and quantify the occurrence of meticillin-resistant Staphylococcus pseudintermedius (MRSP). Reports from two diagnostic laboratories (13,313 general submissions, 1242 referral centre only submissions) were analysed retrospectively (2003/2006-2012). MRSP were defined by phenotypic resistance to meticillin and concurrent broad β-lactam resistance; a subset was confirmed genetically (SIG-specific nuc and mecA). Trends were analysed by Cochran-Armitage test. Resistance remained below 10 per cent for cefalexin, amoxicillin-clavulanic acid and the fluoroquinolones. Increasing resistance trends were seen in both laboratories for ampicillin/amoxicillin (both PResistance to cefalexin increased over time in referral hospital isolates (Presistance to important antimicrobials was identified overtime and the emergence of MRSP from UK clinical cases was confirmed. Attention to responsible use of antibacterial therapy in small animal practice is urgently needed. British Veterinary Association.

  2. Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells.

    Science.gov (United States)

    Xia, Yin; Babitt, Jodie L; Bouley, Richard; Zhang, Ying; Da Silva, Nicolas; Chen, Shanzhuo; Zhuang, Zhenjie; Samad, Tarek A; Brenner, Gary J; Anderson, Jennifer L; Hong, Charles C; Schneyer, Alan L; Brown, Dennis; Lin, Herbert Y

    2010-04-01

    The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.

  3. Activated STAT5 Confers Resistance to Intestinal Injury by Increasing Intestinal Stem Cell Proliferation and Regeneration

    Directory of Open Access Journals (Sweden)

    Shila Gilbert

    2015-02-01

    Full Text Available Intestinal epithelial stem cells (IESCs control the intestinal homeostatic response to inflammation and regeneration. The underlying mechanisms are unclear. Cytokine-STAT5 signaling regulates intestinal epithelial homeostasis and responses to injury. We link STAT5 signaling to IESC replenishment upon injury by depletion or activation of Stat5 transcription factor. We found that depletion of Stat5 led to deregulation of IESC marker expression and decreased LGR5+ IESC proliferation. STAT5-deficient mice exhibited worse intestinal histology and impaired crypt regeneration after γ-irradiation. We generated a transgenic mouse model with inducible expression of constitutively active Stat5. In contrast to Stat5 depletion, activation of STAT5 increased IESC proliferation, accelerated crypt regeneration, and conferred resistance to intestinal injury. Furthermore, ectopic activation of STAT5 in mouse or human stem cells promoted LGR5+ IESC self-renewal. Accordingly, STAT5 promotes IESC proliferation and regeneration to mitigate intestinal inflammation. STAT5 is a functional therapeutic target to improve the IESC regenerative response to gut injury.

  4. Degradation Behavior of Lithium-Ion Batteries during Calendar Ageing – The Case of the Internal Resistance Increase

    DEFF Research Database (Denmark)

    Stroe, Daniel-Ioan; Swierczynski, Maciej Jozef; Kær, Søren Knudsen

    2018-01-01

    Lithium-ion batteries are regarded as the key energy storage technology for both e-mobility and stationary renewable energy storage applications. Nevertheless, the Lithium-ion batteries are complex energy storage devices, which are characterized by a complex degradation behavior, which affects both...... their capacity and internal resistance. This paper investigates, based on extended laboratory calendar ageing tests, the degradation of the internal resistance of a Lithium-ion battery. The dependence of the internal resistance increase on the temperature and state-of-charge level have been extensive studied...... and quantified. Based on the obtained laboratory results, an accurate semi-empirical lifetime model, which is able to predict with high accuracy the internal resistance increase of the Lithium-ion battery over a wide temperature range and for all state-of-charge levels was proposed and validated....

  5. Ultrafast lasers for precise and corrosion free marking on chirurgical steels

    Science.gov (United States)

    Neugebauer, Christoph; Aalderink, Dennis; Maurer, Erich; Faisst, Birgit; Budnicki, Aleksander

    2017-02-01

    The unique properties of ultrashort laser pulses and the decrease of invest pave the way to numerous novel applications. Even in the very price sensitive field of laser marking, ultrashort laser can compete due to a new cost structure and remarkable properties of the marking results. In this study we concentrated on industrial marking of medical equipment by using IR ultrashort lasers and compared the results with common marking laser systems. We demonstrate the benefits of ultrashort lasers marking on chirurgical devices, observing the influence of pulse energy, pulse duration, scanning velocity in respect to the visibility, corrosion resistance and long term durability under clinical conditions. Nowadays many parts and products are marked for the purpose of identification and traceability. One kind of laser marking is the well known annealing of stainless steel by nanosecond marking lasers. When annealing occurs a colored oxide layer grows due to the local heating of the material surface. Compared to the raw material, the annealed marking shows increased corrosion sensitivity. Regarding the traceability, the poor durability of the ns marking resulting in contrast reduction and the corrosion susceptibility are a huge problem. Therefore three different laser sources with ns-psfs pulse duration were observed. The focus rests on the realization of parameter studies (various lasers) and their effect on the corrosion and passivation behavior. Furthermore analysis of the oxide layers by use of EDX and XRD were performed to obtain further information on the composition and structure of the markings.

  6. Effects of Increased Respiratory Resistance on Maximal O2 Uptake and Anaerobic Threshold during Incremental Exercise Tests

    OpenAIRE

    ÖZÇELİK, Oğuz

    2014-01-01

    This study was undertaken to assess whether maximal O2 uptake (VO2max) can be used as an index of measuring aerobic capacity under the condition of increased respiratory resistance. Seven male subjects performed two incremental exercise tests on a cycle ergometer on different days: one control (C) and one breathing through an 8 mm bore diameter respiratory resistance (R). Ventilatory and gas exchange responses were measured with a turbine volume transducer and mass spectrometry, and processed...

  7. High dietary zinc supplementation increases the occurrence of tetracycline and sulfonamide resistance genes in the intestine of weaned pigs

    OpenAIRE

    Vahjen, Wilfried; Pietruszy?ska, Dominika; Starke, Ingo C.; Zentek, J?rgen

    2015-01-01

    Background Dietary zinc oxide is used in pig nutrition to combat post weaning diarrhoea. Recent data suggests that high doses (2.5?g/kg feed) increase the bacterial antibiotic resistance development in weaned pigs. Therefore, the aim of this study was to investigate the development of enterobacterial antibiotic resistance genes in the intestinal tract of weaned pigs. Findings Weaned pigs were fed diets for 4?weeks containing 57 (low), 164 (intermediate) or 2425 (high) mg?kg?1 analytical grade...

  8. Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression.

    Science.gov (United States)

    Lyons, Taylor; Carhart-Harris, Robin L

    2018-01-01

    Previous research suggests that classical psychedelic compounds can induce lasting changes in personality traits, attitudes and beliefs in both healthy subjects and patient populations. Here we sought to investigate the effects of psilocybin on nature relatedness and libertarian-authoritarian political perspective in patients with treatment-resistant depression (TRD). This open-label pilot study with a mixed-model design studied the effects of psilocybin on measures of nature relatedness and libertarian-authoritarian political perspective in patients with moderate to severe TRD ( n=7) versus age-matched non-treated healthy control subjects ( n=7). Psilocybin was administered in two oral dosing sessions (10 mg and 25 mg) 1 week apart. Main outcome measures were collected 1 week and 7-12 months after the second dosing session. Nature relatedness and libertarian-authoritarian political perspective were assessed using the Nature Relatedness Scale (NR-6) and Political Perspective Questionnaire (PPQ-5), respectively. Nature relatedness significantly increased ( t(6)=-4.242, p=0.003) and authoritarianism significantly decreased ( t(6)=2.120, p=0.039) for the patients 1 week after the dosing sessions. At 7-12 months post-dosing, nature relatedness remained significantly increased ( t(5)=-2.707, p=0.021) and authoritarianism remained decreased at trend level ( t(5)=-1.811, p=0.065). No differences were found on either measure for the non-treated healthy control subjects. This pilot study suggests that psilocybin with psychological support might produce lasting changes in attitudes and beliefs. Although it would be premature to infer causality from this small study, the possibility of drug-induced changes in belief systems seems sufficiently intriguing and timely to deserve further investigation.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Increasing the resistance of common bean to white mold through recurrent selection

    Directory of Open Access Journals (Sweden)

    Monik Evelin Leite

    2016-02-01

    Full Text Available ABSTRACT White mold, caused by Sclerotinea sclerotiorum (Lib. de Bary is one of the most important diseases of the common bean (Phaseolus vulgaris L. worldwide. Physiological resistance and traits related to disease avoidance such as architecture contribute to field resistance. The aim of this study was to verify the efficiency of recurrent selection in physiological resistance to white mold, “Carioca” grain type and upright habit in common bean. Thirteen common bean lines with partial resistance to white mold were intercrossed by means of a circulant diallel table, and seven recurrent selection cycles were obtained. Of these cycles, progenies of the S0:1, S0:2 and S0:3 generations of cycles III, IV, V and VI were evaluated. The best (8 to 10 progenies of the seven cycles were also evaluated, in two experiments, one in the greenhouse and one in the field. Lattice and/or randomized block experimental designs were used. The traits evaluated were: resistance to white mold by the straw test method, growth habit and grain type. The most resistant progenies were selected based on the average score of resistance to white mold. Subsequently, they were evaluated with regard to grain type and growth habit. Recurrent selection allowed for genetic progress of about 11 % per year for white mold resistance and about 15 % per year for the plant architecture. There was no gain among cycles for grain type. Progeny selection and recurrent selection were efficient for obtaining progenies with a high level of resistance to white mold with “Carioca” grain type and upright habit.

  11. Increased prevalence of antibiotic-resistant E. coli in gulls sampled in southcentral Alaska is associated with urban environments

    Science.gov (United States)

    Atterby, Clara; Ramey, Andrew M.; Gustafsson Hall, Gabriel; Jarhult, Josef; Borjesson, Stefan; Bonnedahl, Jonas

    2016-01-01

    BackgroundAntibiotic-resistant bacteria pose challenges to healthcare delivery systems globally; however, limited information is available regarding the prevalence and spread of such bacteria in the environment. The aim of this study was to compare the prevalence of antibiotic-resistant bacteria in large-bodied gulls (Larus spp.) at urban and remote locations in Southcentral Alaska to gain inference into the association between antibiotic resistance in wildlife and anthropogenically influenced habitats.MethodsEscherichia coli was cultured (n=115 isolates) from fecal samples of gulls (n=160) collected from a remote location, Middleton Island, and a more urban setting on the Kenai Peninsula.ResultsScreening of E. coli from fecal samples collected from glaucous-winged gulls (Larus glaucescens) at Middleton Island revealed 8% of isolates were resistant to one or more antibiotics and 2% of the isolates were resistant to three or more antibiotics. In contrast, 55% of E. coli isolates derived from fecal samples collected from large-bodied gulls (i.e. glaucous, herring [Larus argentatus], and potentially hybrid gulls) on the Kenai Peninsula were resistant to one or more antibiotics and 22% were resistant to three or more antibiotics. In addition, total of 16% of the gull samples from locations on the Kenai Peninsula harbored extended-spectrum cephalosporin-resistant E. coli isolates (extended-spectrum beta-lactamases [ESBL] and plasmid-encoded AmpC [pAmpC]), in contrast to Middleton Island where no ESBL- or pAmpC-producing isolates were detected.ConclusionOur findings indicate that increased prevalence of antibiotic resistance is associated with urban environments in Southcentral Alaska and presumably influenced by anthropogenic impacts. Further investigation is warranted to assess how migratory birds may maintain and spread antimicrobial-resistant bacteria of relevance to human and animal health.

  12. Blunted angiogenesis and hypertrophy are associated with increased fatigue resistance and unchanged aerobic capacity in old overloaded mouse muscle.

    Science.gov (United States)

    Ballak, Sam B; Busé-Pot, Tinelies; Harding, Peter J; Yap, Moi H; Deldicque, Louise; de Haan, Arnold; Jaspers, Richard T; Degens, Hans

    2016-04-01

    We hypothesize that the attenuated hypertrophic response in old mouse muscle is (1) partly due to a reduced capillarization and angiogenesis, which is (2) accompanied by a reduced oxidative capacity and fatigue resistance in old control and overloaded muscles, that (3) can be rescued by the antioxidant resveratrol. To investigate this, the hypertrophic response, capillarization, oxidative capacity, and fatigue resistance of m. plantaris were compared in 9- and 25-month-old non-treated and 25-month-old resveratrol-treated mice. Overload increased the local capillary-to-fiber ratio less in old (15 %) than in adult (59 %) muscle (P muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity.

  13. Lujan Mark-4

    Energy Technology Data Exchange (ETDEWEB)

    Mocko, Michael Jeffrey [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Zavorka, Lukas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Koehler, Paul E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-11-13

    This is a review of Mark-IV target neutronics design. It involved the major redesign of the upper tier, offering harder neutron spectra for upper-tier FPs; a redesign of the high-resolution (HR) moderator; and a preservation of the rest of Mark-III features.

  14. Mark Stock | NREL

    Science.gov (United States)

    Stock Mark Stock Scientific Visualization Specialist Mark.Stock@nrel.gov | 303-275-4174 Dr. Stock , virtual reality, parallel computing, and manipulation of large spatial data sets. As an artist, he creates . Stock built the SUNLIGHT artwork that is installed on the Webb Building in downtown Denver. In addition

  15. Differential Reinforcement of Alternative Behavior Increases Resistance to Extinction: Clinical Demonstration, Animal Modeling, and Clinical Test of One Solution

    Science.gov (United States)

    Mace, F. Charles; McComas, Jennifer J.; Mauro, Benjamin C.; Progar, Patrick R.; Taylor, Bridget; Ervin, Ruth; Zangrillo, Amanda N.

    2010-01-01

    Basic research with pigeons on behavioral momentum suggests that differential reinforcement of alternative behavior (DRA) can increase the resistance of target behavior to change. This finding suggests that clinical applications of DRA may inadvertently increase the persistence of target behavior even as it decreases its frequency. We conducted…

  16. Progressive resistance training increases strength after stroke but this may not carry over to activity: a systematic review.

    Science.gov (United States)

    Dorsch, Simone; Ada, Louise; Alloggia, Daniella

    2018-04-01

    Does progressive resistance training improve strength and activity after stroke? Does any increase in strength carry over to activity? Systematic review of randomised trials with meta-analysis. Adults who have had a stroke. Progressive resistance training compared with no intervention or placebo. The primary outcome was change in strength. This measurement had to be of maximum voluntary force production and performed in muscles congruent with the muscles trained in the intervention. The secondary outcome was change in activity. This measurement had to be a direct measure of performance that produced continuous or ordinal data, or with scales that produced ordinal data. Eleven studies involving 370 participants were included in this systematic review. The overall effect of progressive resistance training on strength was examined by pooling change scores from six studies with a mean PEDro score of 5.8, representing medium quality. The effect size of progressive resistance training on strength was 0.98 (95% CI 0.67 to 1.29, I 2 =0%). The overall effect of progressive resistance training on activity was examined by pooling change scores from the same six studies. The effect size of progressive resistance training on activity was 0.42 (95% CI -0.08 to 0.91, I 2 =54%). After stroke, progressive resistance training has a large effect on strength compared with no intervention or placebo. There is uncertainty about whether these large increases in strength carry over to improvements in activity. PROSPERO CRD42015025401. [Dorsch S, Ada L, Alloggia D (2018) Progressive resistance training increases strength after stroke but this may not carry over to activity: a systematic review. Journal of Physiotherapy 64: 84-90]. Copyright © 2018 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

  17. Increase in stenotic resistance following a brief coronary occlusion in the anesthetized open-chest dog.

    OpenAIRE

    Saito, Daiji; Yasuhara, Koichiro; Takeda, Hikaru; Hyodo, Tatuo; Yamada, Nobuyuki; Uchida, Toshiaki; Haraoka, Shoichi; Nagashima, Hideo

    1982-01-01

    Changes in the stenotic resistance of a coronary artery following brief coronary occlusion were studied in the anesthetized open-chest dog. A critical coronary stenosis was constructed by tying a thick string around the circumflex coronary artery (LCx) near its origin. The LCx was occluded for 5, 10, 15, 20 and 30 seconds with and without coronary stenosis then the reactive hyperemia was observed. In the absence of the stenosis, resistance of the segment of the large coronary artery remained ...

  18. Increasing trend of community-acquired methicillin-resistant: Staphylococcal carriers: An alarming bell for urgent measures

    Directory of Open Access Journals (Sweden)

    Poongodi Lakshmi Santhana Kumarasamy

    2015-01-01

    Full Text Available Background: An increase in the incidence of infections caused by community-associated-methicillin resistant Staphylococcus aureus (MRSA has been reported. Hence, the knowledge of resistance pattern of these isolates is a precondition for alleviating emerging antibiotic resistance and devising better treatment strategies Aim: To find out the prevalence of community-acquired methicillin-resistant staphylococcal strains from nasal carriers. Materials and Methods: A total of 352 nasal swabs collected during routine health checkup were analyzed. Results: Of the 58 (16% staphylococci isolated, 32 (55% were S. aureus and 26 (45% were coagulase-negative staphylococci (CoNS. Methicillin resistance was observed in 7 (22% of staphylococci aureus and 11 (42% of CoNS. "D test" was positive in 1 (14% MRSA, 2 (8% methicillin-susceptible S. aureus and 2 (8% methicillin resistant-CoNS. Conclusion: Effective implementation of the antibiotic policy along with measures like hand wash, isolation of patients will reduce the incidence of resistance.

  19. Increasing penicillin resistance in pneumococci isolated from cerebrospinal fluid samples: Fifteen-year experience from a teaching hospital

    Directory of Open Access Journals (Sweden)

    Filiz Pehlivanoğlu

    2014-12-01

    Full Text Available Objective: There have been prominent changes in evaluation of resistance patterns of pneumococci and breakpoint values in recent years. We aimed to investigate the penicillin sensitivity of pneumococcal strains isolated from the ce­rebrospinal fluid specimens between the years 1997-2011 in our hospital and determine the MIC values under the light of these changes. Methods: Identification of pneumococci was made with conventional methods in patients with meningitis. MIC values for penicillin G were investigated by E test method in all strains. MIC values of pneumococci strains were evaluated ac­cording to values determined by CLSI for meningitis isolates in 2008. Results: A total of 57 strains were investigated in this study. The MIC range for penicillin was 0.016 - 0.75 μg/ml in S. pneumoniae strains. Seventy five percent of the strains were sensitive and eight strains (14% had resistance. MIC50 value was sensitive, and a MIC90 value was resistant. The first resistant strain was detected in 2000, and three strains were resistant in the last year. When examined over the years increased resistance was 5.3% in the first five-year period seems to be 28.6% in the last five-year period. Conclusions: Knowledge on penicillin resistance patterns and surveillance is very important in the empirical treatment in pneumococcal meningitis. J Microbiol Infect Dis 2014; 4(4: 136-140

  20. Natural resistance to experimental feline infectious peritonitis virus infection is decreased rather than increased by positive genetic selection.

    Science.gov (United States)

    Pedersen, Niels C; Liu, Hongwei; Durden, Monica; Lyons, Leslie A

    2016-03-01

    A previous study demonstrated the existence of a natural resistance to feline infectious peritonitis virus (FIPV) among 36% of randomly bred laboratory cats. A genome wide association study (GWAS) on this population suggested that resistance was polygenic but failed to identify any strong specific associations. In order to enhance the power of GWAS or whole genome sequencing to identify strong genetic associations, a decision was made to positively select for resistance over three generations. The inbreeding experiment began with a genetically related parental (P) population consisting of three toms and four queens identified from among the survivors of the earlier study and belonging to a closely related subgroup (B). The subsequent effects of inbreeding were measured using 42 genome-wide STR markers. P generation cats produced 57 first filial (F1) kittens, only five of which (9.0%) demonstrated a natural resistance to FIPV infection. One of these five F1 survivors was then used to produce six F1/P-backcrosses kittens, only one of which proved resistant to FIP. Six of eight of the F1 and F1/P survivors succumbed to a secondary exposure 4-12 months later. Therefore, survival after both primary and secondary infection was decreased rather than increased by positive selection for resistance. The common genetic factor associated with this diminished resistance was a loss of heterozygosity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Increases of Antibiotic Resistance in Excessive Use of Antibiotics in Smallholder Dairy Farms in Northern Thailand

    Directory of Open Access Journals (Sweden)

    W. Suriyasathaporn

    2012-09-01

    Full Text Available Antibiotic resistance patterns of bacterial isolates from both quarter teat-tip swabs and their quarter milk samples were evaluated in smallholder dairy farms in northern Thailand with excessive use of antibiotics (HIGH compared with normal use (NORM. Results from teat-tip swab samples showed that the percentage of Bacillus spp. resistance to overall antibiotics was significantly lower in the NORM group than that of the HIGH group, whereas, the resistance percentage of coagulase-negative staphylococci in the NORM group was higher than that of the HIGH one. The overall mastitis-causing bacteria isolated from milk samples were environmental streptococci (13.8%, coagulase-negative staphylococci (9.9%, Staphylococcus aureus (5.4%, and Corynebacterium bovis (4.5%. Both staphylococci and streptococci had significantly higher percentages of resistance to cloxacillin and oxacillin in the HIGH group when compared to the NORM one. An occurrence of vancomycin-resistant bacteria was also observed in the HIGH group. In conclusion, the smallholder dairy farms with excessive use of antibiotics had a higher probability of antibiotic-resistant pattern than the farms with normal use.

  2. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    International Nuclear Information System (INIS)

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V.

    1990-01-01

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3

  3. 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...

  4. HF diets increase hypothalamic PTP1B and induce leptin resistance through both leptin-dependent and -independent mechanisms

    Science.gov (United States)

    White, Christy L.; Whittington, Amy; Barnes, Maria J.; Wang, Zhong; Bray, George A.; Morrison, Christopher D.

    2009-01-01

    Protein tyrosine phosphatase 1B (PTP1B) contributes to leptin resistance by inhibiting intracellular leptin receptor signaling. Mice with whole body or neuron-specific deletion of PTP1B are hypersensitive to leptin and resistant to diet-induced obesity. Here we report a significant increase in PTP1B protein levels in the mediobasal hypothalamus (P = 0.003) and a concomitant reduction in leptin sensitivity following 28 days of high-fat (HF) feeding in rats. A significant increase in PTP1B mRNA levels was also observed in rats chronically infused with leptin (3 μg/day icv) for 14 days (P = 0.01) and in leptin-deficient ob/ob mice infused with leptin (5 μg/day sc for 14 days; P = 0.003). When saline-infused ob/ob mice were placed on a HF diet for 14 days, an increase in hypothalamic PTP1B mRNA expression was detected (P = 0.001) despite the absence of circulating leptin. In addition, although ob/ob mice were much more sensitive to leptin on a low-fat (LF) diet, a reduction in this sensitivity was still observed following exposure to a HF diet. Taken together, these data indicate that hypothalamic PTP1B is specifically increased during HF diet-induced leptin resistance. This increase in PTP1B is due in part to chronic hyperleptinemia, suggesting that hyperleptinemia is one mechanism contributing to the development of leptin resistance. However, these data also indicate that leptin is not required for the increase in hypothalamic PTP1B or the development of leptin resistance. Therefore, additional, leptin-independent mechanisms must exist that increase hypothalamic PTP1B and contribute to leptin resistance. PMID:19017730

  5. Increased tolerance and resistance to virus infections: a possible factor in the survival of Varroa destructor-resistant honey bees (Apis mellifera.

    Directory of Open Access Journals (Sweden)

    Barbara Locke

    Full Text Available The honey bee ectoparasitic mite, Varroa destructor, has a world-wide distribution and inflicts more damage than all other known apicultural diseases. However, Varroa-induced colony mortality is more accurately a result of secondary virus infections vectored by the mite. This means that honey bee resistance to Varroa may include resistance or tolerance to virus infections. The aim of this study was to see if this is the case for a unique population of mite-resistant (MR European honey bees on the island of Gotland, Sweden. This population has survived uncontrolled mite infestation for over a decade, developing specific mite-related resistance traits to do so. Using RT-qPCR techniques, we monitored late season virus infections, Varroa mite infestation and honey bee colony population dynamics in the Gotland MR population and compared this to mite-susceptible (MS colonies in a close by apiary. From summer to autumn the deformed wing virus (DWV titres increased similarly between the MR and MS populations, while the black queen cell virus (BQCV and sacbrood virus (SBV titres decreased substantially in the MR population compared to the MS population by several orders of magnitude. The MR colonies all survived the following winter with high mite infestation, high DWV infection, small colony size and low proportions of autumn brood, while the MS colonies all perished. Possible explanations for these changes in virus titres and their relevance to Varroa resistance and colony winter survival are discussed.

  6. Acute extracellular fluid volume changes increase ileocolonic resistance to saline flow in anesthetized dogs

    Directory of Open Access Journals (Sweden)

    Santiago Jr. A.T.

    1997-01-01

    Full Text Available We determined the effect of acute extracellular fluid volume changes on saline flow through 4 gut segments (ileocolonic, ileal, ileocolonic sphincter and proximal colon, perfused at constant pressure in anesthetized dogs. Two different experimental protocols were used: hypervolemia (iv saline infusion, 0.9% NaCl, 20 ml/min, volume up to 5% body weight and controlled hemorrhage (up to a 50% drop in mean arterial pressure. Mean ileocolonic flow (N = 6 was gradually and significantly decreased during the expansion (17.1%, P<0.05 and expanded (44.9%, P<0.05 periods while mean ileal flow (N = 7 was significantly decreased only during the expanded period (38%, P<0.05. Mean colonic flow (N = 7 was decreased during expansion (12%, P<0.05 but returned to control levels during the expanded period. Mean ileocolonic sphincter flow (N = 6 was not significantly modified. Mean ileocolonic flow (N = 10 was also decreased after hemorrhage (retracted period by 17% (P<0.05, but saline flow was not modified in the other separate circuits (N = 6, 5 and 4 for ileal, ileocolonic sphincter and colonic groups, respectively. The expansion effect was blocked by atropine (0.5 mg/kg, iv both on the ileocolonic (N = 6 and ileal (N = 5 circuits. Acute extracellular fluid volume retraction and expansion increased the lower gastrointestinal resistances to saline flow. These effects, which could physiologically decrease the liquid volume being supplied to the colon, are possible mechanisms activated to acutely balance liquid volume deficit and excess.

  7. Baculovirus p35 increases pancreatic β-cell resistance to apoptosis

    International Nuclear Information System (INIS)

    Hollander, Kenneth; Bar-Chen, Michal; Efrat, Shimon

    2005-01-01

    β-cells die by apoptosis in type 1 diabetes as a result of autoimmune attack mediated by cytokines, and in type 2 diabetes by various perpetrators including human islet amyloid polypeptide (hIAPP). The cascade of apoptotic events induced by cytokines and hIAPP is mediated through caspases and reactive oxygen species. The baculovirus p35 protein is a potent anti-apoptotic agent shown to be effective in a variety of species and able to inhibit a number of apoptotic pathways. Here, we aimed at determining the protective potential of p35 in β-cells exposed to cytokines and hIAPP, as well as the effects of p35 on β-cell function. The p35 gene was introduced into βTC-tet cells, a differentiated murine β-cell line capable of undergoing inducible growth-arrest. Both proliferating and growth-arrested cells expressing p35 manifested increased resistance to cytokines and hIAPP, compared with control cells, as judged by cell viability, DNA fragmentation, and caspase-3 activity assays. p35 was significantly more protective in growth-arrested, compared with proliferating, cells. No significant differences were observed in proliferation and insulin content between cells expressing p35 and control cells. In contrast, p35 manifested a perturbing effect on glucose-induced insulin secretion. These findings suggest that p35 could be incorporated as part of a multi-pronged approach of immunoprotective strategies to provide protection from recurring autoimmunity for transplanted β-cells, as well as in preventive gene therapy in type 1 diabetes. p35 may also be protective from β-cell damage caused by hIAPP in type 2 diabetes

  8. Double mutation in eleusine indica alpha-tubulin increases the resistance of transgenic maize calli to dinitroaniline and phosphorothioamidate herbicides

    Science.gov (United States)

    Anthony; Hussey

    1999-06-01

    The repeated use of dinitroaniline herbicides on the cotton and soybean fields of the southern United States has resulted in the appearance of resistant biotypes of one of the world's worst weeds, Eleusine indica. Two biotypes have been characterized, a highly resistant (R) biotype and an intermediate resistant (I) biotype. In both cases the resistance has been attributed to a mutation in alpha-tubulin, a component of the alpha/beta tubulin dimer that is the major constituent of microtubules. We show here that the I-biotype mutation, like the R-biotype mutation shown in earlier work, can confer dinitroaniline resistance on transgenic maize calli. The level of resistance obtained is the same as that for E. indica I- or R-biotype seedlings. The combined I- and R-biotype mutations increase the herbicide tolerance of transgenic maize calli by a value close to the summation of the maximum herbicide tolerances of calli harbouring the single mutations. These data, taken together with the position of the two different mutations within the atomic structure of the alpha/beta tubulin dimer, imply that each mutation is likely to exert its effect by a different mechanism. These mechanisms may involve increasing the stability of microtubules against the depolymerizing effects of the herbicide or changing the conformation of the alpha/beta dimer so that herbicide binding is less effective, or a combination of both possibilities.

  9. Long-term exposure to benzalkonium chloride disinfectants results in change of microbial community structure and increased antimicrobial resistance.

    Science.gov (United States)

    Tandukar, Madan; Oh, Seungdae; Tezel, Ulas; Konstantinidis, Konstantinos T; Pavlostathis, Spyros G

    2013-09-03

    The effect of benzalkonium chlorides (BACs), a widely used class of quaternary ammonium disinfectants, on microbial community structure and antimicrobial resistance was investigated using three aerobic microbial communities: BACs-unexposed (DP, fed a mixture of dextrin/peptone), BACs-exposed (DPB, fed a mixture of dextrin/peptone and BACs), and BACs-enriched (B, fed only BACs). Long-term exposure to BACs reduced community diversity and resulted in the enrichment of BAC-resistant species, predominantly Pseudomonas species. Exposure of the two microbial communities to BACs significantly decreased their susceptibility to BACs as well as three clinically relevant antibiotics (penicillin G, tetracycline, ciprofloxacin). Increased resistance to BACs and penicillin G of the two BACs-exposed communities is predominantly attributed to degradation or transformation of these compounds, whereas resistance to tetracycline and ciprofloxacin is largely due to the activity of efflux pumps. Quantification of several key multidrug resistance genes showed a much higher number of copies of these genes in the DPB and B microbial communities compared to the DP community. Collectively, our findings indicate that exposure of a microbial community to BACs results in increased antibiotic resistance, which has important implications for both human and environmental health.

  10. Mutation of the Glucosinolate Biosynthesis Enzyme Cytochrome P450 83A1 Monooxygenase Increases Camalexin Accumulation and Powdery Mildew Resistance.

    Science.gov (United States)

    Liu, Simu; Bartnikas, Lisa M; Volko, Sigrid M; Ausubel, Frederick M; Tang, Dingzhong

    2016-01-01

    Small secondary metabolites, including glucosinolates and the major phytoalexin camalexin, play important roles in immunity in Arabidopsis thaliana. We isolated an Arabidopsis mutant with increased resistance to the powdery mildew fungus Golovinomyces cichoracearum and identified a mutation in the gene encoding cytochrome P450 83A1 monooxygenase (CYP83A1), which functions in glucosinolate biosynthesis. The cyp83a1-3 mutant exhibited enhanced defense responses to G. cichoracearum and double mutant analysis showed that this enhanced resistance requires NPR1, EDS1, and PAD4, but not SID2 or EDS5. In cyp83a1-3 mutants, the expression of genes related to camalexin synthesis increased upon G. cichoracearum infection. Significantly, the cyp83a1-3 mutant also accumulated higher levels of camalexin. Decreasing camalexin levels by mutation of the camalexin synthetase gene PAD3 or the camalexin synthesis regulator AtWRKY33 compromised the powdery mildew resistance in these mutants. Consistent with these observations, overexpression of PAD3 increased camalexin levels and enhanced resistance to G. cichoracearum. Taken together, our data indicate that accumulation of higher levels of camalexin contributes to increased resistance to powdery mildew.

  11. Mutation of the glucosinolate biosynthesis enzyme cytochrome P450 83A1 monooxygenase increases camalexin accumulation and powdery mildew resistance

    Directory of Open Access Journals (Sweden)

    Simu eLiu

    2016-03-01

    Full Text Available Small secondary metabolites, including glucosinolates and the major phytoalexin camalexin, play important roles in immunity in Arabidopsis thaliana. We isolated an Arabidopsis mutant with increased resistance to the powdery mildew fungus Golovinomyces cichoracearum and identified a mutation in the gene encoding cytochrome P450 83A1 monooxygenase (CYP83A1, which functions in glucosinolate biosynthesis. The cyp83a1-3 mutant exhibited enhanced defense responses to G. cichoracearum and double mutant analysis showed that this enhanced resistance requires NPR1, EDS1, and PAD4, but not SID2 or EDS5. In cyp83a1-3 mutants, the expression of genes related to camalexin synthesis increased upon G. cichoracearum infection. Significantly, the cyp83a1-3 mutant also accumulated higher levels of camalexin. Decreasing camalexin levels by mutation of the camalexin synthetase gene PAD3 or the camalexin synthesis regulator AtWRKY33 compromised the powdery mildew resistance in these mutants. Consistent with these observations, overexpression of PAD3 increased camalexin levels and enhanced resistance to G. cichoracearum. Taken together, our data indicate that accumulation of higher levels of camalexin contributes to increased resistance to powdery mildew.

  12. Failure to increase insulin secretory capacity during pregnancy-induced insulin resistance is associated with ethnicity and gestational diabetes.

    Science.gov (United States)

    Mørkrid, Kjersti; Jenum, Anne K; Sletner, Line; Vårdal, Mari H; Waage, Christin W; Nakstad, Britt; Vangen, Siri; Birkeland, Kåre I

    2012-10-01

    To assess changes in insulin resistance and β-cell function in a multiethnic cohort of women in Oslo, Norway, from early to 28 weeks' gestation and 3 months post partum and relate the findings to gestational diabetes mellitus (GDM). Population-based cohort study of 695 healthy pregnant women from Western Europe (41%), South Asia (25%), Middle East (15%), East Asia (6%) and elsewhere (13%). Blood samples and demographics were recorded at mean 15 (V1) and 28 (V2) weeks' gestation and 3 months post partum (V3). Universal screening was by 75 g oral glucose tolerance test at V2, GDM with modified IADPSG criteria (no 1-h measurement): fasting plasma glucose (PG) ≥5.1 or 2-h PG ≥8.5 mmol/l. Homeostatic model assessment (HOMA)-β (β-cell function) and HOMA-IR (insulin resistance) were calculated from fasting glucose and C-peptide. Characteristics were comparable across ethnic groups, except age (South Asians: younger, Pinsulin resistant than Western Europeans at V1. From V1 to V2, the increase in insulin resistance was similar across the ethnic groups, but the increase in β-cell function was significantly lower for the East and South Asians compared with Western Europeans. GDM women compared with non-GDM women were more insulin resistant at V1; from V1 to V2, their β-cell function increased significantly less and the percentage increase in β-cell function did not match the change in insulin resistance. Pregnant women from East Asia and South Asia were more insulin resistant and showed poorer HOMA-β-cell function than Western Europeans.

  13. THE IMPACT OF FERTILIZATION AND FOLIAR STIMULATION PRODUCTS BOTH ON INCREASING THE RESISTANCE TO MAJOR PHYTOPATHOGENS ATTACKS, AND ON INCREASING THE QUANTITY AND QUALITY OF WINE GRAPES HARVEST

    Directory of Open Access Journals (Sweden)

    Cristina BUNESCU

    2014-12-01

    Full Text Available The paper aimed to demonstrate the impact of fertilization and foliar stimulation products both on increasing the resistance to major phytopathogens attacks, and on increasing the quantity and quality of wine grapes harvest. Applying the foliar fertilizer products Plonvit Kali (c1, Tytanit (c2 and Optysil (c3 to vines, for a period of three years (2011/2013, in phenophases of intensive growth of shoots and grapes at approved dosages, simultaneously with pesticide treatment, not only a reduction of pathogenic fungi attack was obtained, but also and an increase of harvest without diminishing the quality of the grapes.

  14. Parity and increased risk of insulin resistance in postmenopausal women: the 2010 Korean National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Kim, Jin Hwi; Lee, Sung Jong

    2017-07-01

    The objective of this study was to assess the association between parity and insulin resistance in nondiabetic, postmenopausal women. This cross-sectional study was conducted using data from the 2010 Korean National Health and Nutrition Examination Survey administered by the Korean Ministry of Health and Welfare. A total of 1,243 nondiabetic postmenopausal women were included in this study and subdivided into three groups according to parity (1-2, 3-4, and ≥5 live births). Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR) index. The relationship between parity and insulin resistance was investigated using analysis of covariance. HOMA-IR showed a positive relationship with parity. Mean HOMA-IR (geometric mean and 95% CI) increased according to increasing parity group (1-2, 3-4, and ≥5 live births) after adjustment for age, smoking, alcohol consumption, exercise, education, income, and body mass index as follows: 2.1 (2.0-2.2) insulin resistance was accompanied by obesity. The mean parity of the obese and insulin-resistant group was significantly higher than that of the nonobese insulin-sensitive group (3.6 ± 0.1 vs 3.2 ± 0.1, P = 0.047). Our study provides the first evidence that parity is significantly associated with insulin resistance in nondiabetic postmenopausal women. Further prospective longitudinal studies are needed to confirm the impact of parity on insulin resistance.

  15. The increasing importance of community-acquired methicillin-resistant Staphylococcus aureus infections.

    Science.gov (United States)

    Agostino, Jason W; Ferguson, John K; Eastwood, Keith; Kirk, Martyn D

    2017-11-06

    To identify groups at risk of methicillin-resistant Staphylococcus aureus (MRSA) infection, patterns of antimicrobial resistance, and the proportion of patients with MRSA infections but no history of recent hospitalisation. Case series of 39 231 patients with S. aureus isolates from specimens processed by the Hunter New England Local Health District (HNELHD) public pathology provider during 2008-2014. Proportion of MRSA infections among people with S. aureus isolates; antimicrobial susceptibility of MRSA isolates; origin of MRSA infections (community- or health care-associated); demographic factors associated with community-associated MRSA infections. There were 71 736 S. aureus-positive specimens during the study period and MRSA was isolated from 19.3% of first positive specimens. Most patients (56.9%) from whom MRSA was isolated had not been admitted to a public hospital in the past year. Multiple regression identified that patients with community-associated MRSA were more likely to be younger (under 40), Indigenous Australians (odds ratio [OR], 2.6; 95% CI, 2.3-2.8), or a resident of an aged care facility (OR, 4.7; 95% CI, 3.8-5.8). The proportion of MRSA isolates that included the dominant multi-resistant strain (AUS-2/3-like) declined from 29.6% to 3.4% during the study period (P resistant strain decreased, new strategies for controlling infections in the community are needed to reduce the prevalence of non-multi-resistant strains.

  16. Prosodic Focus Marking in Bai.

    NARCIS (Netherlands)

    Liu, Zenghui; Chen, A.; Van de Velde, Hans

    2014-01-01

    This study investigates prosodic marking of focus in Bai, a Sino-Tibetan language spoken in the Southwest of China, by adopting a semi-spontaneous experimental approach. Our data show that Bai speakers increase the duration of the focused constituent and reduce the duration of the post-focus

  17. Enhanced mechanical properties and increased corrosion resistance of a biodegradable magnesium alloy by plasma electrolytic oxidation (PEO).

    Science.gov (United States)

    White, Leon; Koo, Youngmi; Neralla, Sudheer; Sankar, Jagannathan; Yun, Yeoheung

    2016-06-01

    We report the enhanced mechanical properties of AZ31 magnesium alloys by plasma electrolytic oxidation (PEO) coating in NaOH, Na 2 SiO 3 , KF and NaH 2 PO 4 ·2H 2 O containing electrolytes. Mechanical properties including wear resistance, surface hardness and elastic modulus were increased for PEO-coated AZ31 Mg alloys (PEO-AZ31). DC polarization in Hank's solution indicating that the corrosion resistance significantly increased for PEO-coating in KF-contained electrolyte. Based on these results, the PEO coating method shows promising potential for use in biodegradable implant applications where tunable corrosion and mechanical properties are needed.

  18. Successive increases in the resistance of Drosophila to viral infection through a transposon insertion followed by a Duplication.

    Directory of Open Access Journals (Sweden)

    Michael M Magwire

    2011-10-01

    Full Text Available To understand the molecular basis of how hosts evolve resistance to their parasites, we have investigated the genes that cause variation in the susceptibility of Drosophila melanogaster to viral infection. Using a host-specific pathogen of D. melanogaster called the sigma virus (Rhabdoviridae, we mapped a major-effect polymorphism to a region containing two paralogous genes called CHKov1 and CHKov2. In a panel of inbred fly lines, we found that a transposable element insertion in the protein coding sequence of CHKov1 is associated with increased resistance to infection. Previous research has shown that this insertion results in a truncated messenger RNA that encodes a far shorter protein than the susceptible allele. This resistant allele has rapidly increased in frequency under directional selection and is now the commonest form of the gene in natural populations. Using genetic mapping and site-specific recombination, we identified a third genotype with considerably greater resistance that is currently rare in the wild. In these flies there have been two duplications, resulting in three copies of both the truncated allele of CHKov1 and CHKov2 (one of which is also truncated. Remarkably, the truncated allele of CHKov1 has previously been found to confer resistance to organophosphate insecticides. As estimates of the age of this allele predate the use of insecticides, it is likely that this allele initially functioned as a defence against viruses and fortuitously "pre-adapted" flies to insecticides. These results demonstrate that strong selection by parasites for increased host resistance can result in major genetic changes and rapid shifts in allele frequencies; and, contrary to the prevailing view that resistance to pathogens can be a costly trait to evolve, the pleiotropic effects of these changes can have unexpected benefits.

  19. Intrahepatic upregulation of MRTF-A signaling contributes to increased hepatic vascular resistance in cirrhotic rats with portal hypertension.

    Science.gov (United States)

    Zheng, Lei; Qin, Jun; Sun, Longci; Gui, Liang; Zhang, Chihao; Huang, Yijun; Deng, Wensheng; Huang, An; Sun, Dong; Luo, Meng

    2017-06-01

    Portal hypertension in cirrhosis is mediated, in part, by increased intrahepatic resistance, reflecting massive structural changes associated with fibrosis and intrahepatic vasoconstriction. Activation of the Rho/MRTF/SRF signaling pathway is essential for the cellular regulatory network of fibrogenesis. The aim of this study was to investigate MRTF-A-mediated regulation of intrahepatic fibrogenesis in cirrhotic rats. Portal hypertension was induced in rats via an injection of CCl 4 oil. Hemodynamic measurements were obtained using a polyethylene PE-50 catheter and pressure transducers. Expression of hepatic fibrogenesis was measured using histological staining. Expression of protein was measured using western blotting. Upregulation of MRTF-A protein expression in the livers of rats with CCl 4 -induced cirrhosis was relevant to intrahepatic resistance and hepatic fibrogenesis in portal hypertensive rats with increased modeling time. Inhibition of MRTF-A by CCG-1423 decelerated hepatic fibrosis, decreased intrahepatic resistance and portal pressure, and alleviated portal hypertension. Increased intrahepatic resistance in rats with CCl 4 -induced portal hypertension is associated with an upregulation of MRTF-A signaling. Inhibition of this pathway in the liver can decrease hepatic fibrosis and intrahepatic resistance, as well as reduce portal pressure in cirrhotic rats with CCl 4 -induced portal hypertension. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. 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.

  1. Poor zinc status is associated with increased risk of insulin resistance in Spanish children.

    Science.gov (United States)

    Ortega, R M; Rodríguez-Rodríguez, E; Aparicio, A; Jiménez, A I; López-Sobaler, A M; González-Rodríguez, L G; Andrés, P

    2012-02-01

    Zn plays a key role in the synthesis and action of insulin. The aim of the present work was to determine whether a poorer Zn status was associated with insulin resistance in a group of 357 Spanish schoolchildren. Zn intake was determined by using a 3 d food record (i.e. Sunday to Tuesday). The body weight, height and waist and hip circumferences of all subjects were recorded and fasting plasma glucose, insulin and Zn concentrations were determined. Insulin resistance was determined using the homoeostasis model assessment (HOMA) marker. Children (11·5 %) with Zn deficiency (serum Zn concentration 3·16 made a significantly smaller contribution to the coverage of those recommended (59·7 (sd 14·7) %) than observed in children with lower HOMA values (73·6 (sd 18·2) %; P health and nutritional status of these children, and thus contribute to diminish problems of insulin resistance.

  2. Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men

    Directory of Open Access Journals (Sweden)

    Schilling Brian K

    2009-01-01

    Full Text Available Abstract Background Dietary supplements targeting fat loss and increased thermogenesis are prevalent within the sport nutrition/weight loss market. While some isolated ingredients have been reported to be efficacious when used at high dosages, in particular in animal models and/or via intravenous delivery, little objective evidence is available pertaining to the efficacy of a finished product taken by human subjects in oral form. Moreover, many ingredients function as stimulants, leading to increased hemodynamic responses. The purpose of this investigation was to determine the effects of a finished dietary supplement on plasma catecholamine concentration, markers of lipolysis, metabolic rate, and hemodynamics. Methods Ten resistance trained men (age = 27 ± 4 yrs; BMI = 25 ± 3 kg· m-2; body fat = 9 ± 3%; mean ± SD ingested a dietary supplement (Meltdown®, Vital Pharmaceuticals or a placebo, in a random order, double blind cross-over design, with one week separating conditions. Fasting blood samples were collected before, and at 30, 60, and 90 minutes post ingestion and were assayed for epinephrine (EPI, norepinephrine (NE, glycerol, and free fatty acids (FFA. Area under the curve (AUC was calculated for all variables. Gas samples were collected from 30–60 minutes post ingestion for measurement of metabolic rate. Heart rate and blood pressure were recorded at all blood collection times. Results AUC was greater for the dietary supplement compared to the placebo for NE (1332 ± 128 pg·mL-1·90 min-1 vs. 1003 ± 133 pg·mL-1·90 min-1; p = 0.03, glycerol (44 ± 3 μg·mL-1·90 min-1 vs. 26 ± 2 μg·mL-1·90 min-1; p -1·90 min-1 vs. 0.88 ± 0.12 mmol·L-1·90 min-1; p = 0.0003. No difference between conditions was noted for EPI AUC (p > 0.05. For all variables, values were highest at 90 minutes post ingestion. Total kilocalorie expenditure during the 30 minute collection period was 29.6% greater (p = 0.02 for the dietary supplement (35 ± 3

  3. Mark 1 Test Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Mark I Test Facility is a state-of-the-art space environment simulation test chamber for full-scale space systems testing. A $1.5M dollar upgrade in fiscal year...

  4. Mark Raidpere portreefotod Kielis

    Index Scriptorium Estoniae

    1999-01-01

    Kieli Linnagaleriis avatud 2. Ars Baltica fototriennaalil 'Can You Hear Me?' esindab Eestit Mark Raidpere seeriaga 'Portreed 1998'. Näituse Eesti-poolne kuraator Anu Liivak, kataloogiteksti kirjutas Anders Härm. Tuntumaid osalejaid triennaalil Wolfgang Tillmans

  5. Microbial radio-resistance of Salmonella Typhimurium in egg increases due to repetitive irradiation with electron beam

    International Nuclear Information System (INIS)

    Tesfai, Adiam T.; Beamer, Sarah K.; Matak, Kristen E.; Jaczynski, Jacek

    2011-01-01

    Ionizing radiation improves food safety. However, foodborne pathogens develop increased resistance in response to sub-lethal stresses such as heat, pH, antibiotics, etc. Therefore, it is hypothesized that foodborne pathogens may develop increased radio-resistance to electron beam (e-beam) radiation. The objective was to determine if D 10 -value for Salmonella Typhimurium in de-shelled raw egg (egg white and yolk mixed together) increases due to repetitive processing with e-beam at sub-lethal doses. Survivors were enumerated on non-selective (TSA) and selective (XLD) media. Survivors from the highest dose were isolated and used in subsequent e-beam cycle. This process was repeated four times for a total of five e-beam cycles. D 10 -values for S. Typhimurium enumerated on TSA and XLD following each e-beam cycle were calculated as inverse reciprocal of the slope of survivor curves. D 10 -values for the ATCC strain were 0.59±0.031 and 0.46±0.022 kGy on TSA and XLD, respectively. However, following the fifth e-beam cycle, the respective D 10 -values increased (P 0.05) to develop radio-resistance faster on selective media, likely due to facilitated selection of radio-resistant cells within microbial population following each e-beam cycle. For all five e-beam cycles, S. Typhimurium had higher (P 10 -values on non-selective media, indicating that sub-lethal injury followed by cellular repair and recovery are important for radio-resistance and inactivation of this microorganism. This study demonstrated that e-beam efficiently inactivates S. Typhimurium in raw egg; however, similar to other inactivation techniques and factors affecting microbial growth, S. Typhimurium develops increased radio-resistance if repetitively processed with e-beam at sub-lethal doses.

  6. Marks of Metal Copenhell

    DEFF Research Database (Denmark)

    2015-01-01

    Planchebaseret udendørs udstilling på musikfestivalen Copenhell 18-20/6 2015. En mindre udgave af udstillingen Marks of Metal - Logodesign og visualitet i heavy metal. Udarbejdet i samarbejde med Mediemuseet.......Planchebaseret udendørs udstilling på musikfestivalen Copenhell 18-20/6 2015. En mindre udgave af udstillingen Marks of Metal - Logodesign og visualitet i heavy metal. Udarbejdet i samarbejde med Mediemuseet....

  7. Minnesota Local Agency Pavement Marking : Mining Existing Data

    Science.gov (United States)

    2017-11-01

    Pavement marking is important for safety. Maximizing pavement marking performance in terms of increased retroreflectivity, within limited budget constraints, allows agencies to make better decisions toward providing more effective pavement marking pe...

  8. COMPUTER HARDWARE MARKING

    CERN Multimedia

    Groupe de protection des biens

    2000-01-01

    As part of the campaign to protect CERN property and for insurance reasons, all computer hardware belonging to the Organization must be marked with the words 'PROPRIETE CERN'.IT Division has recently introduced a new marking system that is both economical and easy to use. From now on all desktop hardware (PCs, Macintoshes, printers) issued by IT Division with a value equal to or exceeding 500 CHF will be marked using this new system.For equipment that is already installed but not yet marked, including UNIX workstations and X terminals, IT Division's Desktop Support Service offers the following services free of charge:Equipment-marking wherever the Service is called out to perform other work (please submit all work requests to the IT Helpdesk on 78888 or helpdesk@cern.ch; for unavoidable operational reasons, the Desktop Support Service will only respond to marking requests when these coincide with requests for other work such as repairs, system upgrades, etc.);Training of personnel designated by Division Leade...

  9. Increase of the electrical resistance of thin copper film due to 14 MeV neutron irradiation

    International Nuclear Information System (INIS)

    Agrawal, S.K.; Kumar, U.; Nigam, A.K.; Singh, S.P.

    1981-01-01

    The variation in the electrical resistance of thin copper film (500 A 0 thick), grown on the glass slide has been measured with increasing 14 MeV neutron irradiation time. The electrical resistance vs irradiation time curve shows an interesting behaviour after an irradiation of 40 minutes. However, there is a net increase in the electrical resistance with increasing neutron dose. The maximum increase in the observed electrical resistance after an irradiation of 115 mins, is 4.45%. The microstructural studies of irradiated film were made using TEM and TED techniques. The TEM patterns up to an irradiation time of 1.00 hr do not show any appreciable change in the microstructure. The TED patterns also do not show any appreciable change in the diffraction pattern up to an irradiation time of 1.0 hr. But after an irradiation time of 1.5 hrs, two extra rings appear in the TED pattern which disappear with increasing neutron irradiation time

  10. Enhanced mechanical properties and increased corrosion resistance of a biodegradable magnesium alloy by plasma electrolytic oxidation (PEO)

    International Nuclear Information System (INIS)

    White, Leon; Koo, Youngmi; Neralla, Sudheer; Sankar, Jagannathan; Yun, Yeoheung

    2016-01-01

    Highlights: • Plasma electrolytic oxidation (PEO) method was developed to control corrosion, porosity, and mechanical property. • Mechanical properties of PEO-coated AZ31 alloys were affected by the different electrolyte. • Mechanical properties and corrosion resistance of PEO-coated AZ31 alloys were compared with uncoated one. - Abstract: We report the enhanced mechanical properties of AZ31 magnesium alloys by plasma electrolytic oxidation (PEO) coating in NaOH, Na_2SiO_3, KF and NaH_2PO_4·2H_2O containing electrolytes. Mechanical properties including wear resistance, surface hardness and elastic modulus were increased for PEO-coated AZ31 Mg alloys (PEO-AZ31). DC polarization in Hank's solution indicating that the corrosion resistance significantly increased for PEO-coating in KF-contained electrolyte. Based on these results, the PEO coating method shows promising potential for use in biodegradable implant applications where tunable corrosion and mechanical properties are needed.

  11. Interview with Professor Mark Wilcox.

    Science.gov (United States)

    Wilcox, Mark

    2016-08-01

    Mark Wilcox speaks to Georgia Patey, Commissioning Editor: Professor Mark Wilcox is a Consultant Microbiologist and Head of Microbiology at the Leeds Teaching Hospitals (Leeds, UK), the Professor of Medical Microbiology at the University of Leeds (Leeds, UK), and is the Lead on Clostridium difficile and the Head of the UK C. difficile Reference Laboratory for Public Health England (PHE). He was the Director of Infection Prevention (4 years), Infection Control Doctor (8 years) and Clinical Director of Pathology (6 years) at the Leeds Teaching Hospitals. He is Chair of PHE's Rapid Review Panel (reviews utility of infection prevention and control products for National Health Service), Deputy Chair of the UK Department of Health's Antimicrobial Resistance and Healthcare Associated Infection Committee and a member of PHE's HCAI/AR Programme Board. He is a member of UK/European/US working groups on C. difficile infection. He has provided clinical advice as part of the FDA/EMA submissions for the approval of multiple novel antimicrobial agents. He heads a healthcare-associated infection research team at University of Leeds, comprising approximately 30 doctors, scientists and nurses; projects include multiple aspects of C. difficile infection, diagnostics, antimicrobial resistance and the clinical development of new antimicrobial agents. He has authored more than 400 publications, and is the coeditor of Antimicrobial Chemotherapy (5th/6th/7th Editions, 15 December 2007).

  12. Ablation of the mitochondrial complex IV assembly protein Surf1 leads to increased expression of the UPRMT and increased resistance to oxidative stress in primary cultures of fibroblasts

    Directory of Open Access Journals (Sweden)

    Gavin Pharaoh

    2016-08-01

    Full Text Available Mice deficient in the electron transport chain (ETC complex IV assembly protein SURF1 have reduced assembly and activity of cytochrome c oxidase that is associated with an upregulation of components of the mitochondrial unfolded protein response (UPRMT and increased mitochondrial number. We hypothesized that the upregulation of proteins associated with the UPRMT in response to reduced cytochrome c oxidase activity in Surf1−/− mice might contribute to increased stress resistance. To test this hypothesis we asked whether primary cultures of fibroblasts from Surf1−/− mice exhibit enhanced resistance to stressors compared to wild-type fibroblasts. Here we show that primary dermal fibroblasts isolated from Surf1−/− mice have increased expression of UPRMT components ClpP and Hsp60, and increased expression of Lon protease. Fibroblasts from Surf1−/− mice are significantly more resistant to cell death caused by oxidative stress induced by paraquat or tert-Butyl hydroperoxide compared to cells from wild-type mice. In contrast, Surf1−/− fibroblasts show no difference in sensitivity to hydrogen peroxide stress. The enhanced cell survival in response to paraquat or tert-Butyl hydroperoxide in Surf1−/− fibroblasts compared to wild-type fibroblasts is associated with induced expression of Lon, ClpP, and Hsp60, increased maximal respiration, and increased reserve capacity as measured using the Seahorse Extracellular Flux Analyzer. Overall these data support a protective role for the activation of the UPRMT in cell survival.

  13. Concrete surface with nano-particle additives for improved wearing resistance to increasing truck traffic.

    Science.gov (United States)

    2012-07-01

    This study focused on the use of nanotechnology in concrete to improve the wearing resistance of concrete. The nano : materials used were polymer cross-linked aerogels, carbon nanotubes, and nano-SiO2, nano-CaCO3, and nano-Al2O3 : particles. As an in...

  14. Intracellular, genetic or congenital immunisation--transgenic approaches to increase disease resistance of farm animals.

    Science.gov (United States)

    Müller, M; Brem, G

    1996-01-26

    Novel approaches to modify disease resistance or susceptibility in livestock are justified not only by economical reasons and with respect to animal welfare but also by recent advancements in molecular genetics. The control or elimination of infectious pathogens in farm animals is historically achieved by the use of vaccines and drugs and by quarantine safeguards and eradication. Currently, research on the improvement of disease resistance based on nucleic acid technology focuses on two main issues: additive gene transfer and the development of nucleic acid vaccines. The strategies aim at the stable or transient expression of components known to influence non-specific or specific host defence mechanisms against infectious pathogens. Thus, candidates for gene transfer experiments include all genes inducing or conferring innate and acquired immunity as well as specific disease resistance genes. Referring to the site and mode of action and the source of the effective agent the strategies are termed 'intracellular', 'genetic' and 'congenital' immunisation. The targeted disruption (deletive gene transfer) of disease susceptibility genes awaits the establishment of totipotential embryonic cell lineages in farm animals. The cytokine network regulates cellular viability, growth and differentiation in physiological and pathophysiological states. The identification of the JAK-STAT pathway used by many cytokines for their intracellular signal propagation has provided not only new target molecules for modulating the immune response but will also permit the further elucidation of host-pathogen interactions and resistance mechanisms.

  15. Increasing Antibiotic Resistance in Shigella spp. from Infected New York City Residents, New York, USA.

    Science.gov (United States)

    Murray, Kenya; Reddy, Vasudha; Kornblum, John S; Waechter, HaeNa; Chicaiza, Ludwin F; Rubinstein, Inessa; Balter, Sharon; Greene, Sharon K; Braunstein, Sarah L; Rakeman, Jennifer L; Dentinger, Catherine M

    2017-02-01

    Approximately 20% of Shigella isolates tested in New York City, New York, USA, during 2013-2015 displayed decreased azithromycin susceptibility. Case-patients were older and more frequently male and HIV infected than those with azithromycin-susceptible Shigella infection; 90% identified as men who have sex with men. Clinical interpretation guidelines for azithromycin resistance and outcome studies are needed.

  16. Variations of electric resistance and H2 and Rn emissions of concrete blocks under increasing uniaxial compression

    Science.gov (United States)

    King, C.-Y.; Luo, G.

    1990-01-01

    Electric resistance and emissions of hydrogen and radon isotopes of concrete (which is somewhat similar to fault-zone materials) under increasing uniaxial compression were continuously monitored to check whether they show any pre- and post-failure changes that may correspond to similar changes reported for earthquakes. The results show that all these parameters generally begin to increase when the applied stresses reach 20% to 90% of the corresponding failure stresses, probably due to the occurrence and growth of dilatant microcracks in the specimens. The prefailure changes have different patterns for different specimens, probably because of differences in spatial and temporal distributions of the microcracks. The resistance shows large co-failure increases, and the gas emissions show large post-failure increases. The post-failure increase of radon persists longer and stays at a higher level than that of hydrogen, suggesting a difference in the emission mechanisms for these two kinds of gases. The H2 increase may be mainly due to chemical reaction at the crack surfaces while they are fresh, whereas the Rn increases may be mainly the result of the increased emanation area of such surfaces. The results suggest that monitoring of resistivity and gas emissions may be useful for predicting earthquakes and failures of concrete structures. ?? 1990 Birkha??user Verlag.

  17. Mutants with increased resistance to herbicide in Guinea corn Sorghum bicolor (L.) Moench

    International Nuclear Information System (INIS)

    Odeigah, P.G.C.; Adewoyin, A.F.; Obatayo, O.O.

    1990-01-01

    Sorghum is an important staple food in many tropical countries. In Nigeria, it is extensively cultivated for food and, in recent times, as raw material for the brewing, baking and starch-making industries. We have investigated the possibilities of breeding crop cultivars of Sorghum with improved seed protein, amylase activities and resistance to herbicide by means of induced mutation. Seeds were treated by soaking them in an aqueous solution of ethyl methane sulphonate (EMS) 8 or 64 mM at room temperature 3, 6, 9, 12, 15 or 24 hours. After the treatment, the seeds were briefly rinsed in water and transferred to petri dishes containing moist filter paper for germination. The seedlings were later transplanted to loamy sand soil in plastic trays. M, seedlings were grown to maturity in the greenhouse. The M 1 contained plants with variegated leaves and other morphological abnormalities. Only the progenies of normal plants were grown for further generations. Resistance to Igran 500 E.G. (2-tert-butylamino-4-ethylamino-6-methylthio-striazine; from Ciba Geigy) was tested in M 2 seedlings by mixing 1 part per 100 (by volume) of the herbicide with the soil a day before sowing the seeds. Preliminary screening of 2,500 M 2 plants revealed a number of morphological and leaf colour mutations. 50 seedlings were more resistant to the herbicide but no seedling resistance was observed in the parent cultivar. There was a 23.43% reduction in seedling weight of the M 2 lines grown in soil treated with Igran 500, whereas the reduction in seedling weight of the original cultivar was 42.46%. The resistant M 2 seedlings had longer and better roots

  18. Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity

    International Nuclear Information System (INIS)

    Powell, Ashley A; Akare, Sandeep; Qi, Wenqing; Herzer, Pascal; Jean-Louis, Samira; Feldman, Rebecca A; Martinez, Jesse D

    2006-01-01

    There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA. To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis. We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype

  19. Effects of drop sets with resistance training on increases in muscle CSA, strength, and endurance: a pilot study.

    Science.gov (United States)

    Ozaki, Hayao; Kubota, Atsushi; Natsume, Toshiharu; Loenneke, Jeremy P; Abe, Takashi; Machida, Shuichi; Naito, Hisashi

    2018-03-01

    To investigate the effects of a single high-load (80% of one repetition maximum [1RM]) set with additional drop sets descending to a low-load (30% 1RM) without recovery intervals on muscle strength, endurance, and size in untrained young men. Nine untrained young men performed dumbbell curls to concentric failure 2-3 days per week for 8 weeks. Each arm was randomly assigned to one of the following three conditions: 3 sets of high-load (HL, 80% 1RM) resistance exercise, 3 sets of low-load [LL, 30% 1RM] resistance exercise, and a single high-load (SDS) set with additional drop sets descending to a low-load. The mean training time per session, including recovery intervals, was lowest in the SDS condition. Elbow flexor muscle cross-sectional area (CSA) increased similarly in all three conditions. Maximum isometric and 1RM strength of the elbow flexors increased from pre to post only in the HL and SDS conditions. Muscular endurance measured by maximum repetitions at 30% 1RM increased only in the LL and SDS conditions. A SDS resistance training program can simultaneously increase muscle CSA, strength, and endurance in untrained young men, even with lower training time compared to typical resistance exercise protocols using only high- or low-loads.

  20. Lifelong Physical Activity Prevents Aging-Associated Insulin Resistance in Human Skeletal Muscle Myotubes via Increased Glucose Transporter Expression

    DEFF Research Database (Denmark)

    Bunprajun, Tipwadee; Henriksen, Tora Ida; Scheele, Camilla

    2013-01-01

    , and significantly higher GLUT4 protein. It is likely that physical activity induces a number of stable adaptations, including increased GLUT4 expression that are retained in cells ex vivo and protect, or delay the onset of middle-aged-associated insulin resistance. Additionally, a sedentary lifestyle has an impact...

  1. Pre-exposure to drought increases the resistance of tropical forest soil bacterial communities to extended drought

    Science.gov (United States)

    Nicholas J. Bouskill; Hsiao Chien Lim; Sharon Borglin; Rohit Salve; Tana Wood; Whendee L. Silver; Eoin L. Brodie

    2013-01-01

    Global climate models project a decrease in the magnitude of precipitation in tropical regions. Changes in rainfall patterns have important implications for the moisture content and redox status of tropical soils, yet little is known about how these changes may affect microbial community structure. Specifically, does exposure to prior stress confer increased resistance...

  2. Testing dependence of anomalous Hall effect on resistivity in SrRuO3 by its increase with electron irradiation

    NARCIS (Netherlands)

    Haham, N.; Konczykowski, M.; Kuiper, Bouwe; Koster, Gertjan; Klein, L.

    2013-01-01

    We measure the anomalous Hall effect (AHE) in several patterns of the itinerant ferromagnet SrRuO 3 before and after the patterns are irradiated with electrons. The irradiation increases the resistivity of the patterns due to the introduction of point defects and we find that the AHE coefficient R s

  3. Resistance to oxidative stress induced by paraquat correlates well with both decreased and increased lifespan in Drosophila melanogaster

    NARCIS (Netherlands)

    Vermeulen, CJ; Van De Zande, L; Bijlsma, R

    2005-01-01

    There is increasing support for the notion that genetic variation for lifespan, both within and between species, is correlated with variation in the efficiency of the free radical scavenging system and the ability to withstand oxidative stress. In Drosophila, resistance to dietary paraquat, a free

  4. Increase in resistance to extended-spectrum cephalosporins in Salmonella isolated from retail chicken products in Japan.

    Science.gov (United States)

    Noda, Tamie; Murakami, Koichi; Etoh, Yoshiki; Okamoto, Fuyuki; Yatsuyanagi, Jun; Sera, Nobuyuki; Furuta, Munenori; Onozuka, Daisuke; Oda, Takahiro; Asai, Tetsuo; Fujimoto, Shuji

    2015-01-01

    Extended-spectrum β-lactamase (ESBL)-producing Salmonella are one of the most important public health problems in developed countries. ESBL-producing Salmonella strains have been isolated from humans in Asian countries neighboring Japan, along with strains harboring the plasmid-mediated extended-spectrum cephalosporin (ESC)-resistance gene, ampC (pAmpC). However, only a few studies have investigated the prevalence of ESC-resistant Salmonella in chicken products in Japan, which are the main vehicle of Salmonella transmission. The aim of this study was to investigate the prevalence of ESBL-producing, pAmpC-harboring, or carbapenem-resistant Salmonella in chicken products in Japan. In total, 355 out of 779 (45.6%) chicken product samples collected from 1996-2010 contained Salmonella, resulting in 378 distinct isolates. Of these isolates, 373 were tested for resistance to ESCs, cephamycins, or carbapenems. Isolates that showed resistance to one or more of these antimicrobials were then examined by PCR and DNA sequence analysis for the presence of the bla(CMY), bla(CTX-M), bla(TEM), and bla(SHV) resistance genes. Thirty-five resistant isolates were detected, including 26 isolates that contained pAmpC (bla(CMY-2)), and nine ESBL-producing isolates harboring bla(CTX-M) (n = 4, consisting of two bla(CTX-M-2) and two bla(CTX-M-15 genes)), bla(TEM) (n = 4, consisting of one bla(TEM-20) and three bla(TEM-52) genes), and bla(SHV) (n = 1, bla(SHV-12)). All pAmpC-harboring and ESBL-producing Salmonella isolates were obtained from samples collected after 2005, and the percentage of resistant isolates increased significantly from 0% in 2004 to 27.9% in 2010 (P for trend = 0.006). This increase was caused in part by an increase in the number of Salmonella enterica subsp. enterica serovar Infantis strains harboring an approximately 280-kb plasmid containing bla(CMY-2) in proximity to ISEcp1. The dissemination of ESC-resistant Salmonella containing plasmid-mediated bla(CMY-2) in

  5. Increase in resistance to extended-spectrum cephalosporins in Salmonella isolated from retail chicken products in Japan.

    Directory of Open Access Journals (Sweden)

    Tamie Noda

    Full Text Available Extended-spectrum β-lactamase (ESBL-producing Salmonella are one of the most important public health problems in developed countries. ESBL-producing Salmonella strains have been isolated from humans in Asian countries neighboring Japan, along with strains harboring the plasmid-mediated extended-spectrum cephalosporin (ESC-resistance gene, ampC (pAmpC. However, only a few studies have investigated the prevalence of ESC-resistant Salmonella in chicken products in Japan, which are the main vehicle of Salmonella transmission. The aim of this study was to investigate the prevalence of ESBL-producing, pAmpC-harboring, or carbapenem-resistant Salmonella in chicken products in Japan. In total, 355 out of 779 (45.6% chicken product samples collected from 1996-2010 contained Salmonella, resulting in 378 distinct isolates. Of these isolates, 373 were tested for resistance to ESCs, cephamycins, or carbapenems. Isolates that showed resistance to one or more of these antimicrobials were then examined by PCR and DNA sequence analysis for the presence of the bla(CMY, bla(CTX-M, bla(TEM, and bla(SHV resistance genes. Thirty-five resistant isolates were detected, including 26 isolates that contained pAmpC (bla(CMY-2, and nine ESBL-producing isolates harboring bla(CTX-M (n = 4, consisting of two bla(CTX-M-2 and two bla(CTX-M-15 genes, bla(TEM (n = 4, consisting of one bla(TEM-20 and three bla(TEM-52 genes, and bla(SHV (n = 1, bla(SHV-12. All pAmpC-harboring and ESBL-producing Salmonella isolates were obtained from samples collected after 2005, and the percentage of resistant isolates increased significantly from 0% in 2004 to 27.9% in 2010 (P for trend = 0.006. This increase was caused in part by an increase in the number of Salmonella enterica subsp. enterica serovar Infantis strains harboring an approximately 280-kb plasmid containing bla(CMY-2 in proximity to ISEcp1. The dissemination of ESC-resistant Salmonella containing plasmid-mediated bla(CMY-2 in chicken

  6. Increased expression of the yeast multidrug resistance ABC transporter Pdr18 leads to increased ethanol tolerance and ethanol production in high gravity alcoholic fermentation

    Directory of Open Access Journals (Sweden)

    Teixeira Miguel C

    2012-07-01

    Full Text Available Abstract Background The understanding of the molecular basis of yeast tolerance to ethanol may guide the design of rational strategies to increase process performance in industrial alcoholic fermentations. A set of 21 genes encoding multidrug transporters from the ATP-Binding Cassette (ABC Superfamily and Major Facilitator Superfamily (MFS in S. cerevisiae were scrutinized for a role in ethanol stress resistance. Results A yeast multidrug resistance ABC transporter encoded by the PDR18 gene, proposed to play a role in the incorporation of ergosterol in the yeast plasma membrane, was found to confer resistance to growth inhibitory concentrations of ethanol. PDR18 expression was seen to contribute to decreased 3 H-ethanol intracellular concentrations and decreased plasma membrane permeabilization of yeast cells challenged with inhibitory ethanol concentrations. Given the increased tolerance to ethanol of cells expressing PDR18, the final concentration of ethanol produced during high gravity alcoholic fermentation by yeast cells devoid of PDR18 was lower than the final ethanol concentration produced by the corresponding parental strain. Moreover, an engineered yeast strain in which the PDR18 promoter was replaced in the genome by the stronger PDR5 promoter, leading to increased PDR18 mRNA levels during alcoholic fermentation, was able to attain a 6 % higher ethanol concentration and a 17 % higher ethanol production yield than the parental strain. The improved fermentative performance of yeast cells over-expressing PDR18 was found to correlate with their increased ethanol tolerance and ability to restrain plasma membrane permeabilization induced throughout high gravity fermentation. Conclusions PDR18 gene over-expression increases yeast ethanol tolerance and fermentation performance leading to the production of highly inhibitory concentrations of ethanol. PDR18 overexpression in industrial yeast strains appears to be a promising approach to

  7. Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats

    International Nuclear Information System (INIS)

    Ribeiro Júnior, Rogério Faustino; Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa; Araújo, Julia F.P. de; Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim; Graceli, Jones B.; Stefanon, Ivanita

    2016-01-01

    Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration–response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT 1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O 2 − production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. - Highlights: • Tributyltin chloride reduces estrogen levels in female rats. • Treatment with TBT

  8. Increased US emergency department visits for skin and soft tissue infections, and changes in antibiotic choices, during the emergence of community-associated methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Pallin, Daniel J; Egan, Daniel J; Pelletier, Andrea J; Espinola, Janice A; Hooper, David C; Camargo, Carlos A

    2008-03-01

    Test the hypotheses that emergency department (ED) visits for skin and soft tissue infections became more frequent during the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA), and that antibiotics typically active against community-associated MRSA were chosen increasingly. From merged National Hospital Ambulatory Medical Care Survey data for 1993-2005, we identified ED visits with diagnosis of cellulitis, abscess, felon, impetigo, hidradenitis, folliculitis, infective mastitis, nonpurulent mastitis, breast abscess, or carbuncle and furuncle. Main outcomes were change over time in rate of ED visits with such a diagnosis and proportion of antibiotic regimens including an agent typically active against community-associated MRSA. We report national estimates derived from sample weights. We tested trends with least squares linear regression. In 1993, infections of interest were diagnosed at 1.2 million visits (95% confidence interval [CI] 0.96 to 1.5 million) versus 3.4 million in 2005 (95% CI 2.8 to 4.1 million; P for trend trend trend skin and soft tissue infections increased markedly from 1993 to 2005, contemporaneously with the emergence of community-associated MRSA. ED clinicians prescribed more antibiotics typically active against community-associated MRSA, especially trimethoprim-sulfamethoxazole. Possible confounders are discussed, such as increasing diabetes or shifts in locus of care.

  9. Radiation resistance in mice increased following chronic application of Li/sub 2/CO/sub 3/

    Energy Technology Data Exchange (ETDEWEB)

    Vacek, A.; Sikulova, J.; Bartonickova, A. (Ceskoslovenska Akademie Ved, Brno. Biofysikalni Ustav)

    1982-01-01

    In experiments on strain H mice the increased radiation resistance of mice was analysed after three weeks' feeding with a diet including Li given as lithium carbonicum. The concentration of Li in the serum during the first three days of feeding was increased to 0.5 mmol/l and remained at that level to the end of feeding. The application of Li increased the overall number of stem cells in the spleen by 80 per cent compared with the control group. D/sub 0/ of the line of dependence of the number of endogenous colonies on radiation dose increased following Li application by 1.2 Gy compared with controls. The proliferation activity of haemopoietic stem cells observed 90 min after injection of hydroxyurea was, after 21 days feeding with a mixture containing Li, increased by 200 per cent. The results support the idea that the increased radiation resistance of mice following feeding with Li salts before irradiation may be due to the increased content and resistance of the haemopoietic stem cells, as well as activation of granulopoiesis.

  10. Increasing incidence of penicillin- and cefotaxime-resistant Streptococcus pneumoniae causing meningitis in India: Time for revision of treatment guidelines?

    Science.gov (United States)

    Verghese, Valsan Philip; Veeraraghavan, Balaji; Jayaraman, Ranjith; Varghese, Rosemol; Neeravi, Ayyanraj; Jayaraman, Yuvaraj; Thomas, Kurien; Mehendale, Sanjay M

    2017-01-01

    Pneumococcal meningitis is a life-threatening infection, requiring prompt diagnosis and effective treatment. Penicillin resistance in pneumococcal infections is a concern. Here, we present the antibiotic susceptibility profile of pneumococcal meningeal isolates from January 2008 to August 2016 to elucidate treatment guidelines for pneumococcal meningitis. Invasive pneumococcal isolates from all age groups, were included in this study. Minimum inhibitory concentrations for the isolates were identified by agar dilution technique and VITEK System 2. Serotyping of isolates was done by co-agglutination technique. Out of 830 invasive pneumococcal isolates, 167 (20.1%) isolates were from meningeal infections. Cumulative penicillin resistance in pneumococcal meningitis was 43.7% and cefotaxime non-susceptibility was 14.9%. Penicillin resistance amongst meningeal isolates in those younger than 5 years, 5-16 years of age and those aged 16 years and older was 59.7%, 50% and 27.3%, respectively, with non-susceptibility to cefotaxime in the same age groups being 18%, 22.2% and 10.4%. Penicillin resistance amongst pneumococcal meningeal isolates increased from 9.5% in 2008 to 42.8% in 2016, whereas cefotaxime non-susceptibility increased from 4.7% in 2008 to 28.5% in 2016. Serotypes 14, 19F, 6B, 6A, 23F, 9V and 5 were the most common serotypes causing meningitis, with the first five accounting for over 75% of resistant isolates. The present study reports increasing penicillin resistance and cefotaxime non-susceptibility to pneumococcal meningitis in our setting. This highlights the need for empiric therapy with third-generation cephalosporins and vancomycin for all patients with meningitis while awaiting results of culture and susceptibility testing.

  11. 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.

  12. Neratinib resistance and cross-resistance to other HER2-targeted drugs due to increased activity of metabolism enzyme cytochrome P4503A4

    OpenAIRE

    Breslin, Susan; Lowry, Michelle C; O'Driscoll, Lorraine

    2017-01-01

    Background: Neratinib is in Phase 3 clinical trials but, unfortunately, the development of resistance is inevitable. Here, we investigated the effects of acquired neratinib resistance on cellular phenotype and the potential mechanism of this resistance. Methods: Neratinib-resistant variants of HER2-positive breast cancer cells were developed and their cross-resistance investigated using cytotoxicity assays. Similarly, sensitivity of trastuzumab-resistant and lapatinib-resistant cells to nerat...

  13. Benomyl-resistant mutant strain of Trichoderma sp. with increased mycoparasitic activity.

    Science.gov (United States)

    Olejníková, P; Ondrusová, Z; Krystofová, S; Hudecová, D

    2010-01-01

    Application of UV radiation to the strain Trichoderma sp. T-bt (isolated from lignite) resulted in the T-brm mutant which was resistant to the systemic fungicide benomyl. The tub2 gene sequence in the T-brm mutant differed from the parent as well as the collection strain (replacing tyrosine with histidine in the TUB2 protein). Under in vitro conditions this mutant exhibited a higher mycoparasitic activity toward phytopathogenic fungi.

  14. Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats.

    Science.gov (United States)

    Ribeiro Júnior, Rogério Faustino; Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa; de Araújo, Julia F P; Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim; Graceli, Jones B; Stefanon, Ivanita

    2016-03-15

    Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration-response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O2(-) production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. A method for increase abrasive wear resistance parts by obtaining on methods casting on gasifying models

    Science.gov (United States)

    Sedukhin, V. V.; Anikeev, A. N.; Chumanov, I. V.

    2017-11-01

    Method optimizes hardening working layer parts’, working in high-abrasive conditions looks in this work: bland refractory particles WC and TiC in respect of 70/30 wt. % prepared by beforehand is applied on polystyrene model in casting’ mould. After metal poured in mould, withstand for crystallization, and then a study is carried out. Study macro- and microstructure received samples allows to say that thickness and structure received hardened layer depends on duration interactions blend harder carbides and liquid metal. Different character interactions various dispersed particles and matrix metal observed under the same conditions. Tests abrasive wear resistance received materials of method calculating residual masses was conducted in laboratory’ conditions. Results research wear resistance showed about that method obtaining harder coating of blend carbide tungsten and carbide titanium by means of drawing on surface foam polystyrene model before moulding, allows receive details with surface has wear resistance in 2.5 times higher, than details of analogy steel uncoated. Wherein energy costs necessary for transformation units mass’ substances in powder at obtained harder layer in 2.06 times higher, than materials uncoated.

  16. Increased incidence of resistance to antimicrobials by urinary pathogens isolated at Tikur Anbessa Hospital.

    Science.gov (United States)

    Wolday, D; Erge, W

    1997-04-01

    A retrospective analysis of 2209 urine samples submitted for culture to the Microbiology Laboratory of the Tikur Anbessa Hospital (TAH), Addis Ababa, between January 1992 and December 1994 was made. Significant bacteriuria (colony count > 10(5) colony forming units/ml urine) was detected in 672 (30%). Pure culture was obtained in 510 (23%) of all samples and polymicrobial growth was detected in the remaining 162 (7%). Gram-negative bacteria comprised 95% of all isolates. The commonest organisms being Escherichia coli (39%) and Klebsiella species (26%). Among the gram-positives, Staphylococcus aureus (57%) was the most common pathogen isolated. Most of the organisms were resistant to multiple drugs. Ampicillin, carbenicillin, chloramphenicol, tetracycline and trimethoprim-sulphamethoxazole were effective in less than 30% of all cases. There was also a significant resistance to cephalothin, gentamicin and kanamycin. Only nalidixic acid and nitrofurantoin were effective for most of the organisms. Compared to previous studies, there is an indication of reduced effectiveness of the commonly prescribed antibiotics. The rational use of drugs should be practiced in order to prevent the emergence of multi-drug resistant microorganisms.

  17. Alkaloids and phenolics biosynthesis increases mango resistance to infection by Ceratocystis fimbriata

    Directory of Open Access Journals (Sweden)

    Leonardo Araujo

    2016-01-01

    Full Text Available ABSTRACT Mango wilt, caused by Ceratocystis fimbriata, is one of the most important diseases affecting mango yields in Brazil. Information regarding the biochemical mechanisms involved in mango resistance against C. fimbriata is absent in the literature. Thus, the present study determined and quantified alkaloids and phenolics in the stem tissue of mango plants from Palmer (susceptible and Ubá (resistant cultivars. Furthermore, it was examined the effect of these secondary metabolites against C. fimbriata growth in vitro. The high-performance liquid chromatography revealed that the concentration of two alkaloids (theobromine and 7-methylxanthine and six phenolic compounds (caffeic acid, p-coumaric acid, gallic acid, protocatechuic acid, catechin and epicatechin in the inoculated plants from cv. Ubá was higher in comparison with inoculated plants from cv. Palmer. The concentration of the secondary metabolites was higher in the non-inoculated plants from cv. Palmer than in the inoculated ones, while the opposite was observed for plants of cv. Ubá. Peaks in the concentrations of secondary metabolites in the inoculated plants from both cultivars occurred at 7 and 14 days after inoculation. The different concentrations (10 to 30 mg∙mL−1 of secondary metabolites added to the Petri dishes greatly inhibited C. fimbriata growth over time. These results suggest that secondary metabolites played an important role in the resistance of mango plants against C. fimbriata infection.

  18. Inclusion of copepod Acartia tonsa nauplii in the feeding of Centropomus undecimalis larvae increases stress resistance

    Directory of Open Access Journals (Sweden)

    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.

  19. Severe asthma with markedly increased asbestos of 2 types & TXB2, and markedly reduced acetylcholine, DHEA & drug uptake in parts of upper lungs, & similar abnormalities at respiratory & cardiac center of medulla oblongata: complete elimination of this asthma within 15 days using one optimal dose of astragalus & application of strong red light & EMF neutralizer on respiratory centers of abnormal medulla oblongata.

    Science.gov (United States)

    Omura, Yoshiaki; Henoch, Avraham; Shimotsuura, Yasuhira; Duvvi, Harsha; Kawashima, Hiroshi; Ohki, Motomu

    2009-01-01

    When the window of an Asbestos-contaminated room from a broken ceiling was opened wide, A 73 year-old male physician of Oriental origin, who was sitting in the next room, suddenly developed a severe asthma attack, which did not stop by the use of a hand-held Albuterol inhaler. Temporary relief was obtained only by using a Compressor-Nebulizer (Inspiration 626 with Albuterol Sulfate Inhalation Solution 0.083%). During the attack, abnormal areas were discovered at the upper lobes of both lungs, where Thromboxane B2 (TXB2) was markedly increased to 500 ng (BDORT units) (the rest of the lung had about 2.5 ng), 2 types of Asbestos (Chrysotile and Crocidolite) were abnormally increased to 0.120-0.135 mg, (BDORT units) Acetylcholine was markedly reduced to 0.5 ng (the rest of the lung was low, about 100 ng), DHEA was extremely reduced to 1 ng (the rest of the lung had about 52 ng), and telomere was less than 1 yg (= 10(-24) g). Bacterial & viral infections were also present in these abnormal areas, but no antibiotics entered the abnormal parts of the lungs. Therefore, one optimal dose of Astragalus was given once, which resulted in a rapid continuous excretion of large amounts of the above 2 types of Asbestos & TXB2 in urine & sputum, and Asthma symptoms reduced slightly in severity. Additional acupuncture & shiatsu given on all the known acupuncture points for lung disease only created slight, temporary improvement. Then, the respiratory & cardiac center of the Medulla Oblongata was found to have similar abnormalities as the lungs. Therefore, 100 mW output of Light Emitting Diode of red spectra (650 nm center spectrum) was projected on the abnormal area of the medulla oblongata on the back of the head. This resulted drug uptake of on and off and significantly reduced difficulty of breathing. Additional application of the EMF Neutralizer on the abnormal area of the Medulla Oblongata for 3 hours resulted in continuous drug uptake and complete disappearance of asthma. As a

  20. Has the emergence of community-associated methicillin-resistant Staphylococcus aureus increased trimethoprim-sulfamethoxazole use and resistance?: a 10-year time series analysis.

    Science.gov (United States)

    Wood, Jameson B; Smith, Donald B; Baker, Errol H; Brecher, Stephen M; Gupta, Kalpana

    2012-11-01

    There are an increasing number of indications for trimethoprim-sulfamethoxazole use, including skin and soft tissue infections due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Assessing the relationship between rates of use and antibiotic resistance is important for maintaining the expected efficacy of this drug for guideline-recommended conditions. Using interrupted time series analysis, we aimed to determine whether the 2005 emergence of CA-MRSA and recommendations of trimethoprim-sulfamethoxazole as the preferred therapy were associated with changes in trimethoprim-sulfamethoxazole use and susceptibility rates. The data from all VA Boston Health Care System facilities, including 118,863 inpatient admissions, 6,272,661 outpatient clinic visits, and 10,138 isolates were collected over a 10-year period. There was a significant (P = 0.02) increase in trimethoprim-sulfamethoxazole prescriptions in the post-CA-MRSA period (1,605/year) compared to the pre-CA-MRSA period (1,538/year). Although the overall susceptibility of Escherichia coli and Proteus spp. to trimethoprim-sulfamethoxazole decreased over the study period, the rate of change in the pre- versus the post-CA-MRSA period was not significantly different. The changes in susceptibility rates of S. aureus to trimethoprim-sulfamethoxazole and to methicillin were also not significantly different. The CA-MRSA period is associated with a significant increase in use of trimethoprim-sulfamethoxazole but not with significant changes in the rates of susceptibilities among clinical isolates. There is also no evidence for selection of organisms with increased resistance to other antimicrobials in relation to increased trimethoprim-sulfamethoxazole use.

  1. Augmented marked graphs

    CERN Document Server

    Cheung, King Sing

    2014-01-01

    Petri nets are a formal and theoretically rich model for the modelling and analysis of systems. A subclass of Petri nets, augmented marked graphs possess a structure that is especially desirable for the modelling and analysis of systems with concurrent processes and shared resources.This monograph consists of three parts: Part I provides the conceptual background for readers who have no prior knowledge on Petri nets; Part II elaborates the theory of augmented marked graphs; finally, Part III discusses the application to system integration. The book is suitable as a first self-contained volume

  2. Increased Abundance and Transferability of Resistance Genes after Field Application of Manure from Sulfadiazine-Treated Pigs

    Science.gov (United States)

    Jechalke, Sven; Kopmann, Christoph; Rosendahl, Ingrid; Groeneweg, Joost; Weichelt, Viola; Krögerrecklenfort, Ellen; Brandes, Nikola; Nordwig, Mathias; Ding, Guo-Chun; Siemens, Jan; Heuer, Holger

    2013-01-01

    Spreading manure containing antibiotics in agriculture is assumed to stimulate the dissemination of antibiotic resistance in soil bacterial populations. Plant roots influencing the soil environment and its microflora by exudation of growth substrates might considerably increase this effect. In this study, the effects of manure from pigs treated with sulfadiazine (SDZ), here called SDZ manure, on the abundance and transferability of sulfonamide resistance genes sul1 and sul2 in the rhizosphere of maize and grass were compared to the effects in bulk soil in a field experiment. In plots that repeatedly received SDZ manure, a significantly higher abundance of both sul genes was detected compared to that in plots where manure from untreated pigs was applied. Significantly lower abundances of sul genes relative to bacterial ribosomal genes were encountered in the rhizosphere than in bulk soil. However, in contrast to results for bulk soil, the sul gene abundance in the SDZ manure-treated rhizosphere constantly deviated from control treatments over a period of 6 weeks after manuring, suggesting ongoing antibiotic selection over this period. Transferability of sulfonamide resistance was analyzed by capturing resistance plasmids from soil communities into Escherichia coli. Increased rates of plasmid capture were observed in samples from SDZ manure-treated bulk soil and the rhizosphere of maize and grass. More than 97% of the captured plasmids belonged to the LowGC type (having low G+C content), giving further evidence for their important contribution to the environmental spread of antibiotic resistance. In conclusion, differences between bulk soil and rhizosphere need to be considered when assessing the risks associated with the spreading of antibiotic resistance. PMID:23315733

  3. Identification markings for gemstones

    International Nuclear Information System (INIS)

    Dreschhoff, G.A.M.; Zeller, E.J.

    1980-01-01

    A method is described of providing permanent identification markings to gemstones such as diamond crystals by irradiating the cooled gemstone with protons in the desired pattern. The proton bombardment results in a reaction limited to a defined plane and converting the bombarded area of the plane into a different crystal lattice from that of the preirradiated stone. (author)

  4. The small molecule triclabendazole decreases the intracellular level of cyclic AMP and increases resistance to stress in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Yong Joo Lee

    Full Text Available The Ras-adenylyl cyclase-protein kinase A nutrient-sensing pathway controls metabolism, proliferation and resistance to stress in Saccharomyces cerevisiae. The genetic disruption of this pathway increases resistance to a variety of stresses. We show here that the pharmacological inhibition of this pathway by the drug triclabendazole increases resistance to oxidants, heat stress and extends the chronological life. Evidence is presented that triclabendazole decreases the intracellular level of cyclic AMP by inhibiting adenylyl cyclase and triggers the parallel rapid translocation of the stress-resistance transcription factor Msn2 from the cytosol into the nucleus, as deduced from experiments employing a strain in which MSN2 is replaced with MSN2-GFP (GFP, green fluorescent protein. Msn2 and Msn4 are responsible for activating the transcription of numerous genes that encode proteins that protect cells from stress. The results are consistent with triclabendazole either inhibiting the association of Ras with adenylyl cyclase or directly inhibiting adenylyl cyclase, which in turn triggers Msn2/4 to enter the nucleus and activate stress-responsible element gene expression.

  5. Acceptance and stress effects of aircraft obstruction markings of wind turbines

    International Nuclear Information System (INIS)

    Pohl, Johannes; Hübner, Gundula; Mohs, Anja

    2012-01-01

    A dominant resistance factor against wind power projects seems to be their visual impact on the landscape. In addition stress effects from aircraft obstruction markings are an emerging topic related to acceptance. As the height of wind turbines increases, so does the number of mandatory obstruction markings. Recently, obstruction markings have caused a growing number of complaints from residents. Whether obstruction markings indeed cause stress or even substantial annoyance remains an open question. To analyse the stress impact of obstruction markings, we used environmental and stress psychology methodologies. Residents (N=420) with direct sight of turbines at 13 wind farms participated in a questionnaire survey. Evidence of substantial annoyance caused by obstruction markings was not found. However, residents exposed to xenon lights reported more intense and multifaceted stress responses than exposed to LED or colour markings on blades. Moreover, xenon lights negatively affected the general acceptance of wind energy. Additionally, synchronised navigation lights were found to be less annoying than non-synchronised lights under certain weather conditions. Markings with light intensity adjustment proved to be advantageous. To reduce stress and increase social acceptance of wind power, xenon lights should be abandoned, navigation lights synchronised, and light intensity adjustment applied. - Research highlights: ► Wind turbine obstruction markings influence the social acceptance of wind energy. ► Residents exposed to xenon lights reported more intense stress responses than exposed to LED or colour markings. ► Synchronised lights were found to be less annoying under certain weather conditions. ► Markings with light intensity adjustment proved to be advantageous. ► Evidence of substantial annoyance caused by obstruction markings was not found.

  6. Insulin resistance induced by hydrocortisone is increased in patients with abdominal obesity.

    Science.gov (United States)

    Darmon, Patrice; Dadoun, Frédéric; Boullu-Ciocca, Sandrine; Grino, Michel; Alessi, Marie-Christine; Dutour, Anne

    2006-11-01

    Glucocorticoids hypersensitivity may be involved in the development of abdominal obesity and insulin resistance. Eight normal weight and eight obese women received on two occasions a 3-h intravenous infusion of saline or hydrocortisone (HC) (1.5 microg x kg(-1) x min(-1)). Plasma cortisol, insulin, and glucose levels were measured every 30 min from time(-30) (min) (time(-30)) to time(240). Free fatty acids, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were measured at time(-30), time(180), and time(240). At time(240), subjects underwent an insulin tolerance test to obtain an index of insulin sensitivity (K(ITT)). Mean(30-240) cortisol level was similar in control and obese women after saline (74 +/- 16 vs. 75 +/- 20 microg/l) and HC (235 +/- 17 vs. 245 +/- 47 microg/l). The effect of HC on mean(180-240) insulin, mean(180-240) insulin resistance obtained by homeostasis model assessment (HOMA-IR), and K(ITT) was significant in obese (11.4 +/- 2.0 vs. 8.2 +/- 1.3 mU/l, P obese women (+25%) than in controls (+12%) (P obese women than in controls. These deleterious effects are correlated with the amount of visceral fat.

  7. AJUBA increases the cisplatin resistance through hippo pathway in cervical cancer.

    Science.gov (United States)

    Bi, Lihong; Ma, Feng; Tian, Rui; Zhou, Yanli; Lan, Weiguang; Song, Quanmao; Cheng, Xiankui

    2018-02-20

    Though LIM-domain protein AJUBA was identified as a putative oncogene, the function and underlying mechanisms of AJUBA in cervical cancer remain largely unknown. Firstly, AJUBA expression was detected via real-time quantitative PCR in patients' samples. Furthermore, Hela and Siha cells were transfected with AJUBA-overexpressing plasmids, and then exposed to cisplatin, the apoptosis was measured by cytometry assay. In addition, the expression of YAP and TAZ was disclosed through western blot assay. Our results revealed that AJUBA expression was significantly higher in the cervical cancer patients resistant to cisplatin treatment compared with cervical cancer patients sensitive to cisplatin treatment. In addition, overall survival time was significantly shorter in the cervical cancer patients with high AJUBA expression compare with those with low AJUBA expression using kaplan-meier analysis. Hela and Siha cells transfected with AJUBA-expressing plasmids exposed to cisplatin treatment had higher survival rate compared with the cells transfected with empty vector control. Mechanistic studies revealed the AJUBA upregulated the downstream targets YAP and TAZ. These results suggest that high AJUBA level enhances cervical cancer cells drug resistance to cisplatin, also associates with decreased patient survival times. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Simultaneous targeting of ATM and Mcl-1 increases cisplatin sensitivity of cisplatin-resistant non-small cell lung cancer.

    Science.gov (United States)

    Zhang, Fuquan; Shen, Mingjing; Yang, Li; Yang, Xiaodong; Tsai, Ying; Keng, Peter C; Chen, Yongbing; Lee, Soo Ok; Chen, Yuhchyau

    2017-08-03

    Development of cisplatin-resistance is an obstacle in non-small cell lung cancer (NSCLC) therapeutics. To investigate which molecules are associated with cisplatin-resistance, we analyzed expression profiles of several DNA repair and anti-apoptosis associated molecules in parental (A549P and H157P) and cisplatin-resistant (A549CisR and H157CisR) NSCLC cells. We detected constitutively upregulated nuclear ATM and cytosolic Mcl-1 molcules in cisplatin-resistant cells compared with parental cells. Increased levels of phosphorylated ATM (p-ATM) and its downstream molecules, CHK2, p-CHK2, p-53, and p-p53 were also detected in cisplatin-resistant cells, suggesting an activation of ATM signaling in these cells. Upon inhibition of ATM and Mcl-1 expression/activity using specific inhibitors of ATM and/or Mcl-1, we found significantly enhanced cisplatin-cytotoxicity and increased apoptosis of A549CisR cells after cisplatin treatment. Several A549CisR-derived cell lines, including ATM knocked down (A549CisR-siATM), Mcl-1 knocked down (A549CisR-shMcl1), ATM/Mcl-1 double knocked down (A549CisR-siATM/shMcl1) as well as scramble control (A549CisR-sc), were then developed. Higher cisplatin-cytotoxicity and increased apoptosis were observed in A549CisR-siATM, A549CisR-shMcl1, and A549CisR-siATM/shMcl1 cells compared with A549CisR-sc cells, and the most significant effect was shown in A549CisR-siATM/shMcl1 cells. In in vivo mice studies using subcutaneous xenograft mouse models developed with A549CisR-sc and A549CisR-siATM/shMcl1 cells, significant tumor regression in A549CisR-siATM/shMcl1 cells-derived xenografts was observed after cisplatin injection, but not in A549CisR-sc cells-derived xenografts. Finally, inhibitor studies revealed activation of Erk signaling pathway was most important in upregulation of ATM and Mcl-1 molcules in cisplatin-resistant cells. These studies suggest that simultaneous blocking of ATM/Mcl-1 molcules or downstream Erk signaling may recover the

  9. Microbial radio-resistance of Salmonella Typhimurium in egg increases due to repetitive irradiation with electron beam

    Energy Technology Data Exchange (ETDEWEB)

    Tesfai, Adiam T.; Beamer, Sarah K.; Matak, Kristen E. [West Virginia University, Division of Animal and Nutritional Sciences, PO Box 6108, Morgantown, WV 26508 (United States); Jaczynski, Jacek, E-mail: Jacek.Jaczynski@mail.wvu.ed [West Virginia University, Division of Animal and Nutritional Sciences, PO Box 6108, Morgantown, WV 26508 (United States)

    2011-04-15

    Ionizing radiation improves food safety. However, foodborne pathogens develop increased resistance in response to sub-lethal stresses such as heat, pH, antibiotics, etc. Therefore, it is hypothesized that foodborne pathogens may develop increased radio-resistance to electron beam (e-beam) radiation. The objective was to determine if D{sub 10}-value for Salmonella Typhimurium in de-shelled raw egg (egg white and yolk mixed together) increases due to repetitive processing with e-beam at sub-lethal doses. Survivors were enumerated on non-selective (TSA) and selective (XLD) media. Survivors from the highest dose were isolated and used in subsequent e-beam cycle. This process was repeated four times for a total of five e-beam cycles. D{sub 10}-values for S. Typhimurium enumerated on TSA and XLD following each e-beam cycle were calculated as inverse reciprocal of the slope of survivor curves. D{sub 10}-values for the ATCC strain were 0.59{+-}0.031 and 0.46{+-}0.022 kGy on TSA and XLD, respectively. However, following the fifth e-beam cycle, the respective D{sub 10}-values increased (P<0.05) to 0.69{+-}0.026 and 0.61{+-}0.029 kGy, respectively. S. Typhimurium showed a trend (P>0.05) to develop radio-resistance faster on selective media, likely due to facilitated selection of radio-resistant cells within microbial population following each e-beam cycle. For all five e-beam cycles, S. Typhimurium had higher (P<0.05) D{sub 10}-values on non-selective media, indicating that sub-lethal injury followed by cellular repair and recovery are important for radio-resistance and inactivation of this microorganism. This study demonstrated that e-beam efficiently inactivates S. Typhimurium in raw egg; however, similar to other inactivation techniques and factors affecting microbial growth, S. Typhimurium develops increased radio-resistance if repetitively processed with e-beam at sub-lethal doses.

  10. A randomized trial of protein supplementation compared with extra fast food on the effects of resistance training to increase metabolism.

    Science.gov (United States)

    Hambre, David; Vergara, Marta; Lood, Yvonne; Bachrach-Lindström, Margareta; Lindström, Torbjörn; Nystrom, Fredrik H

    2012-10-01

    To prospectively evaluate the effects of resistance training combined with increased energy intake or protein-supplementation on lean body-mass, resting metabolic-rate (RMR) and cardiovascular risk factors. Twenty-four healthy males (aged 19-32 years) performed resistance exercise for 12 weeks aiming for at least 1 hour training-sessions 3 times a week. The participants were randomized to consume extra protein (33 g whey protein/day) or a meal of fast-food/day (1350 kcal, 41 g protein). Body-composition was measured with Dual-Energy X-ray Absorptiometry (DEXA) and RMR by indirect calorimetry. Fasting blood samples were drawn before and after the 3-month training period and after 12 months. The body weight increased from 75.1 ± 6.9 kg to 78.7 ± 7.2 kg (p < 0.0001), without differences between the groups. RMR increased from 1787 ± 143 kcal/24 h to 1954 ± 187 kcal/24 h (p < 0.0001, N = 24), which was more than expected from the increase in lean body-mass (increase from 59.7 ± 4.3 kg to 61.8 ± 4.1 kg p = 0.004). Fasting serum-insulin levels increased in the fast-food group compared with the extra-protein group (p = 0.03). ApoB increased from 0.691 ± 0.14 g/L to 0.768 ± 0.17 g/L, p = 0.004, in the fast-food group only. Long-term follow up after 12 months showed that RMR, body weight, total fat and lean body-masses did not differ from baseline (n = 19). Resistance training for 12 weeks increased RMR and lean body-mass similarly when based on either an increased energy-intake or protein supplement. However, the increase in RMR was higher than expected from the increase in lean body-mass. Thus resistance training could potentially decrease the risk of obesity by induction of increased RMR.

  11. Pollen contamination in seed mixture increases the dominance of resistance to Bt maize in Spodoptera frugiperda (Lepidoptera: Noctuidae).

    Science.gov (United States)

    Yang, Fei; Kerns, David L; Brown, Sebe; Head, Graham P; Huang, Fangneng

    2017-11-01

    Seed mixture, also called 'RIB', has been used to provide refuge populations for delaying insect resistance. Pollen contamination in RIB could result in refuge kernels of non-Bt maize expressing variable Bt proteins. Data are lacking regarding the impact of pollen contamination on evolution of resistance for ear-feeding insects. Here, we used Spodoptera frugiperda and Cry1F-maize as a model to examine if pollen contamination in RIB increases the dominance of insect resistance. Pollen contamination caused >66% refuge kernels in 5:95% (non-Bt:Bt) and 20:80% RIBs to express Cry1F protein. Survival at adult stage on pure non-Bt ears was similar (54.4-63.3%) among Cry1F-susceptible (SS), Cry1F-resistant (RR) and Cry1F-heterozygous (RS) S. frugiperda. On Bt ears, survival was similar between SS and RS (0.0-1.7%), but it was significantly less than that of RR (59.2%). On the two RIB refuge ears, survival at adult stage for RS (42.3% in 5:95% RIB; 50.0% in 20:80% RIB) was significantly higher than for SS (8.7% in 5:95% RIB; 10.0% in 20:80% RIB). The results suggest that pollen contamination in RIB could increase the dominance of resistance for ear-feeding insects by significantly reducing susceptible refuge populations and supporting higher survival of heterozygotes relative to homozygous susceptible insects. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  12. Insulin Resistance and Increased Muscle Cytokine Levels in Patients With Mitochondrial Myopathy

    DEFF Research Database (Denmark)

    Rue, Nana; Vissing, John; Galbo, Henrik

    2014-01-01

    CONTEXT: Mitochondrial dysfunction has been proposed to cause insulin resistance and that might stimulate cytokine production. OBJECTIVE: The objective of the study was to elucidate the association between mitochondrial myopathy, insulin sensitivity, and cytokine levels in muscle. DESIGN......: The intervention included a 120-minute hyperinsulinemic, euglycemic clamp. Another morning, microdialysis of both vastus lateralis muscles for 4 hours, including one-legged, knee extension exercise for 30 minutes, was performed. MAIN OUTCOME MEASURES: Glucose infusion rate during 90-120 minutes of insulin infusion...... was measured. Cytokine concentrations in dialysate were also measured. RESULTS: Muscle strength, percentage fat mass, and creatine kinase in plasma did not differ between groups. The maximal oxygen uptake was 21 ± 3 (SE) (P) and 36 ± 3(C) mL/kg·min (2P insulin, C-peptide, and glucagon were higher...

  13. Increasing leaf longevity and disease resistance by altering salicylic acid catabolism

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Susheng; Zhang, Kewei

    2018-01-23

    The present invention relates to a transgenic plant having an altered level of salicylic acid 3-hydroxylase ("S3H") protein, compared to that of a non-transgenic plant, where the transgenic plant displays an altered leaf senescence phenotype, relative to a non-transgenic plant. The present invention relates to a mutant plant comprising an inactivated gene encoding S3H protein, where the mutant plant displays a premature or precocious leaf senescence phenotype, relative to a non-mutant plant. The present invention also relates to methods for promoting premature or precocious leaf senescence in a plant, delaying leaf senescence in a plant, and making a mutant plant having a decreased level of S3H protein compared to that of a non-mutant plant, where the mutant plant displays a premature or precocious leaf senescence phenotype relative to a non-mutant plant. The present invention also relates to inducing or promoting pathogen resistance in plants.

  14. Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity.

    Science.gov (United States)

    Paramsothy, Pathmaja; Knopp, Robert H; Kahn, Steven E; Retzlaff, Barbara M; Fish, Brian; Ma, Lina; Ostlund, Richard E

    2011-11-01

    The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively. We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis. Plasma sterols were measured by gas chromatography-mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (S(I)) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis. The mean (±SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS, 3.25 ± 1.06 in LIR, and 2.82 ± 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol-cholesterol ratios were as follows: LIS > OIR (P LIR (P OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants, 0.95 ± 0.47 in the LIR participants, and 1.29 ± 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS sterol concentrations were positively associated with S(I) and negatively associated with obesity, whereas lathosterol correlations were the opposite. Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve S(I) and to decrease cholesterol overproduction in LIR and OIR persons.

  15. Resistance training and hormone replacement increase MMP-2 activity, quality and quantity of bone in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Markus V.C Souza

    2017-12-01

    Full Text Available Abstract AIMS The aim of the present study was to investigate the influence of resistance training (RT and hormone replacement (HR on MMP-2 activity, biomechanical and physical properties bone of ovariectomized (OVX rats. METHODS Sprague-Dawley female rats were grouped into six experimental groups (n = 11 per group: sham-operated sedentary (SHAM Sed, ovariectomized sedentary (OVX Sed, sham-operated resistance training (SHAM RT, ovariectomized resistance training (OVX RT, ovariectomized sedentary hormone replacement (OVX Sed-HR, and ovariectomized resistance training hormone replacement (OVX RT-HR. HR groups received implanted silastic capsules with a 5% solution of 17β-estradiol (50 mg 17β-estradiol/ml of sunflower oil. In a 12-week RT period (27 sessions; 4-9 climbs the animals climbed a 1.1 m vertical ladder with weights attached to their tails. Biomechanical and physical bone analyses were performed using a universal testing machine, and MMP-2 activity analysis was done by zymography. RESULTS Bone density and bone mineral content was higher in the RT and HR groups. The MMP-2 activity was higher in the RT and HR groups. The biomechanical analysis (stiffness, fracture load and maximum load demonstrated better bone tissue quality in the RT associated with HR. CONCLUSION The RT alone as well as when it is associated with HR was efficient in increasing MMP-2 activity, biomechanical and biophysical properties bone of ovariectomized rats.

  16. Expression of a radish defensin in transgenic wheat confers increased resistance to Fusarium graminearum and Rhizoctonia cerealis.

    Science.gov (United States)

    Li, Zhao; Zhou, Miaoping; Zhang, Zengyan; Ren, Lijuan; Du, Lipu; Zhang, Boqiao; Xu, Huijun; Xin, Zhiyong

    2011-03-01

    Fusarium head blight (scab), primarily caused by Fusarium graminearum, is a devastating disease of wheat (Triticum aestivum L.) worldwide. Wheat sharp eyespot, mainly caused by Rhizoctonia cerealis, is one of the major diseases of wheat in China. The defensin RsAFP2, a small cyteine-rich antifungal protein from radish (Raphanus sativus), was shown to inhibit growth in vitro of agronomically important fungal pathogens, such as F. graminearum and R. cerealis. The RsAFP2 gene was transformed into Chinese wheat variety Yangmai 12 via biolistic bombardment to assess the effectiveness of the defensin in protecting wheat from the fungal pathogens in multiple locations and years. The genomic PCR and Southern blot analyses indicated that RsAFP2 was integrated into the genomes of the transgenic wheat lines and heritable. RT-PCR and Western blot proved that the RsAFP2 was expressed in these transgenic wheat lines. Disease tests showed that four RsAFP2 transgenic lines (RA1-RA4) displayed enhanced resistance to F. graminearum compared to the untransformed Yangmai 12 and the null-segregated plants. Assays on Q-RT-PCR and disease severity showed that the express level of RsAFP2 was associated with the enhanced resistance degree. Two of these transgenic lines (RA1 and RA2) also exhibited enhanced resistance to R. cerealis. These results indicated that the expression of RsAFP2 conferred increased resistance to F. graminearum and R. cerealis in transgenic wheat.

  17. Complementation of a pKM101 derivative that decreases resistance to UV killing but increases susceptibility to mutagenesis

    International Nuclear Information System (INIS)

    Langer, P.J.; Perry, K.L.; Walker, G.C.

    1985-01-01

    The drug resistance plasmid pKM101 makes Escherichia coli resistant to the lethal effects of ultraviolet (UV) irradiation and more susceptible to mutagenesis by a variety of agents. The plasmid operon responsible for increasing mutagenesis has been termed mucAB (Mutagenesis, UV and chemical). The authors have isolated a derivative of pKM101 called pGW1975 which makes cells more sensitive to killing by UV but which retains the ability of pKM101 to increase susceptibility to methyl methanesulfonate (MMS) mutagenesis. pGW1975 increases UV mutagenesis less than pKM101 in a uvrA + strain but more than pKM101 in a uvrA - strain. muc - point and insertion mutants of pKM101 and pGW1975 complement to restore the plasmid-mediated: (i) ability to reactivate UV-irradiated phage, (ii) resistance to killing by UV, and (iii) level of susceptibility to UV mutagenesis. They have identified a 2.0 kb region of pKM101 which is responsible for the complementation and which maps counterclockwise of mucAB. (Auth)

  18. Interview with Mark Watson

    Directory of Open Access Journals (Sweden)

    Katy Shaw

    2016-04-01

    Full Text Available Mark Watson is a British comedian and novelist. His five novels to date – 'Bullet Points' (2004, 'A Light-Hearted Look At Murder' (2007, 'Eleven' (2010, 'The Knot' (2012 and 'Hotel Alpha' (2014 – explore human relationships and communities in contemporary society. His latest novel Hotel Alpha tells the story of an extraordinary hotel in London and two mysterious disappearances that raise questions no one seems willing to answer. External to the novel, readers can also discover more about the hotel and its inhabitants in one hundred extra stories that expand the world of the novel and can be found at http://www.hotelalphastories.com. In conversation here with Dr Katy Shaw, Mark offers some reflections on his writing process, the field of contemporary literature, and the vitality of the novel form in the twenty-first century.

  19. Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro Júnior, Rogério Faustino, E-mail: rogeriofaustinoribeiro@hotmail.com [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Araújo, Julia F.P. de [Department of Morphology, Federal University of Espírito Santo (Brazil); Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Graceli, Jones B. [Department of Morphology, Federal University of Espírito Santo (Brazil); Stefanon, Ivanita [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil)

    2016-03-15

    Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration–response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT{sub 1} receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O{sub 2}{sup −} production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. - Highlights: • Tributyltin chloride reduces estrogen levels in female rats.

  20. Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance

    International Nuclear Information System (INIS)

    Beckman, J.S.; Minor, R.L. Jr.; White, C.W.; Repine, J.E.; Rosen, G.M.; Freeman, B.A.

    1988-01-01

    Covalent conjugation of superoxide dismutase and catalase with polyethylene glycol (PEG) increases the circulatory half-lives of these enzymes from 125 I-PEG-catalase or 125 I-PEG-superoxide dismutase produced a linear, concentration-dependent increase in cellular enzyme activity and radioactivity. Fluorescently labeled PEG-superoxide dismutase incubated with endothelial cells showed a vesicular localization. Mechanical injury to cell monolayers, which is known to stimulate endocytosis, further increased the uptake of fluorescent PEG-superoxide dismutase. Addition of PEG and PEG-conjugated enzymes perturbed the spin-label binding environment, indicative of producing an increase in plasma membrane fluidity. Thus, PEG conjugation to superoxide dismutase and catalase enhances cell association of these enzymes in a manner which increases cellular enzyme activities and provides prolonged protection from partially reduced oxygen species

  1. Insulin resistance and increased muscle cytokine levels in patients with mitochondrial myopathy.

    Science.gov (United States)

    Rue, Nana; Vissing, John; Galbo, Henrik

    2014-10-01

    Mitochondrial dysfunction has been proposed to cause insulin resistance and that might stimulate cytokine production. The objective of the study was to elucidate the association between mitochondrial myopathy, insulin sensitivity, and cytokine levels in muscle. This was an experimental, controlled study in outpatients. Eight overnight-fasted patients (P) with various inherited mitochondrial myopathies and eight healthy subjects (C) matched for sex, age, weight, height, and physical activity participated in the study. The intervention included a 120-minute hyperinsulinemic, euglycemic clamp. Another morning, microdialysis of both vastus lateralis muscles for 4 hours, including one-legged, knee extension exercise for 30 minutes, was performed. Glucose infusion rate during 90-120 minutes of insulin infusion was measured. Cytokine concentrations in dialysate were also measured. Muscle strength, percentage fat mass, and creatine kinase in plasma did not differ between groups. The maximal oxygen uptake was 21 ± 3 (SE) (P) and 36 ± 3(C) mL/kg·min (2P fatty acids and glycerol at 120 minutes were higher in P vs C (2P myopathies, insulin sensitivity of muscle, adipose tissue, and pancreatic A cells is reduced, supporting that mitochondrial function influences insulin action. Furthermore, a local, low-grade inflammation of potential clinical importance exists in the muscle of these patients.

  2. Past, Present, and Future of Antibacterial Economics: Increasing Bacterial Resistance, Limited Antibiotic Pipeline, and Societal Implications.

    Science.gov (United States)

    Luepke, Katherine H; Suda, Katie J; Boucher, Helen; Russo, Rene L; Bonney, Michael W; Hunt, Timothy D; Mohr, John F

    2017-01-01

    Growing antimicrobial resistance and a dwindling antibiotic pipeline have resulted in an emerging postantibiotic era, as patients are now dying from bacterial infections that were once treatable. The fast-paced "Golden Age" of antibiotic development that started in the 1940s has lost momentum; from the 1980s to the early 2000s, there was a 90% decline in the approval of new antibiotics as well as the discovery of few new novel classes. Many companies have shifted away from development due to scientific, regulatory, and economic hurdles that proved antibiotic development to be less attractive compared with more lucrative therapeutic areas. National and global efforts are focusing attention toward potential solutions for reinvigorating the antibiotic pipeline and include "push" incentives such as public-private partnerships and "pull" incentives such as reimbursement reform and market exclusivity. Hybrid models of incentives, global coordination among stakeholders, and the appropriate balance of antibiotic pricing, volume of drug used, and proper antimicrobial stewardship are key to maximizing efforts toward drug development to ensure access to patients in need of these therapies. © 2016 Pharmacotherapy Publications, Inc.

  3. Increased pulse pressure is associated with left atrial enlargement in resistant hypertensive patients.

    Science.gov (United States)

    Armario, Pedro; Oliveras, Anna; Hernández-Del-Rey, Raquel; Suárez, Carmen; Martell, Nieves; Ruilope, Luis M; De La Sierra, Alejandro

    2013-02-01

    Resistant hypertension (RH) is frequently associated with a high prevalence of target organ damage, which impairs the prognosis of these patients. Considering cardiac alterations in RH, most attention has been devoted to left ventricular hypertrophy (LVH), but data concerning left atrial enlargement (LAE) is less known. This cross-sectional study assessed the factors associated with LAE, with special focus on blood pressure (BP) estimates obtained by ambulatory blood pressure monitoring (ABPM), in 250 patients with RH, aged 64 ± 11 years. LAE and LVH were observed in 10.0% (95% CI 6.3-13.7) and 57.1% (95% CI 50.8-63.5) of patients, respectively. Compared with patients with normal atrium size, those exhibiting LAE were older, more frequently women, had elevated pulse pressure (PP) measured both at the office and by ABPM, and showed higher prevalence of LVH (83% vs 54%; p = 0.016). In a logistic regression analysis, adjusting for age, gender, body mass index, left ventricular mass index and BP pressure estimates, night-time PP was independently associated with LAE (OR for 5 mmHg = 1.28, 95% CI 1.24-1.32; p = 0.001). In conclusion, besides classical determinants of LAE, such as age and LVH, an elevated night-time PP was independently associated with LAE in patients with RH.

  4. Increased circulating interleukin-8 in patients with resistance to thyroid hormone receptor α

    Directory of Open Access Journals (Sweden)

    Anne H van der Spek

    2017-11-01

    Full Text Available Innate immune cells have recently been identified as novel thyroid hormone (TH target cells in which intracellular TH levels appear to play an important functional role. The possible involvement of TH receptor alpha (TRα, which is the predominant TR in these cells, has not been studied to date. Studies in TRα0/0 mice suggest a role for this receptor in innate immune function. The aim of this study was to determine whether TRα affects the human innate immune response. We assessed circulating interleukin-8 concentrations in a cohort of 8 patients with resistance to TH due to a mutation of TRα (RTHα and compared these results to healthy controls. In addition, we measured neutrophil and macrophage function in one of these RTHα patients (mutation D211G. Circulating interleukin-8 levels were elevated in 7 out of 8 RTHα patients compared to controls. These patients harbor different mutations, suggesting that this is a general feature of the syndrome of RTHα. Neutrophil spontaneous apoptosis, bacterial killing, NAPDH oxidase activity and chemotaxis were unaltered in cells derived from the RTHαD211G patient. RTHα macrophage phagocytosis and cytokine induction after LPS treatment were similar to results from control cells. The D211G mutation did not result in clinically relevant impairment of neutrophil or pro-inflammatory macrophage function. As elevated circulating IL-8 is also observed in hyperthyroidism, this observation could be due to the high-normal to high levels of circulating T3 found in patients with RTHα.

  5. Rhizobacteria induces resistance against Fusarium wilt of tomato by increasing the activity of defense enzymes

    Directory of Open Access Journals (Sweden)

    Hélvio Gledson Maciel Ferraz

    2014-09-01

    Full Text Available Fusarium wilt, caused by Fusarium oxysporum f.sp. lycopersici (Fol, is one of the most important diseases that affect tomato yield worldwide. This study investigated the potential of three antagonists, Streptomyces setonii (UFV 618, Bacillus cereus (UFV 592 and Serratia marcescens (UFV 252, and as positive control the hormone jasmonic acid (JA, to reduce Fusarium wilt symptoms and to potentiate the defense enzymes in the stem tissues of tomato plants infected by Fol. The seeds were microbiolized with each antagonist, and the soil was also drenched with them. The plants were sprayed with JA 48 h before Fol inoculation. The area under the Fusarium wilt index progress curve was reduced by 54, 48, 47 and 45% for the UFV 618, JA, UFV 592 and UFV 252 treatments, respectively. The three antagonists, and even the JA spray, efficiently reduced the Fusarium wilt symptoms on the tomato plant stems, which can be explained by the lower malondialdehyde concentration (an indication of oxidative damage to lipids in the plasma membranes and the greater activities of peroxidases, polyphenoloxidases, glucanases, chitinases, phenylalanine ammonia-lyases and lipoxygenases, which are commonly involved in host resistance against fungal diseases. These results present a novel alternative that can be used in the integrated management of Fusarium wilt on tomatoes.

  6. Enhanced mechanical properties and increased corrosion resistance of a biodegradable magnesium alloy by plasma electrolytic oxidation (PEO)

    Energy Technology Data Exchange (ETDEWEB)

    White, Leon; Koo, Youngmi [FIT BEST Laboratory, Engineering Research Center, Department of Chemical, Biological, and Bio Engineering, North Carolina A& T State University, Greensboro, NC 27411 (United States); Neralla, Sudheer [Jet-Hot LLC, Burlington, NC 27215 (United States); Sankar, Jagannathan [FIT BEST Laboratory, Engineering Research Center, Department of Chemical, Biological, and Bio Engineering, North Carolina A& T State University, Greensboro, NC 27411 (United States); Yun, Yeoheung, E-mail: yyun@ncat.edu [FIT BEST Laboratory, Engineering Research Center, Department of Chemical, Biological, and Bio Engineering, North Carolina A& T State University, Greensboro, NC 27411 (United States)

    2016-06-15

    Highlights: • Plasma electrolytic oxidation (PEO) method was developed to control corrosion, porosity, and mechanical property. • Mechanical properties of PEO-coated AZ31 alloys were affected by the different electrolyte. • Mechanical properties and corrosion resistance of PEO-coated AZ31 alloys were compared with uncoated one. - Abstract: We report the enhanced mechanical properties of AZ31 magnesium alloys by plasma electrolytic oxidation (PEO) coating in NaOH, Na{sub 2}SiO{sub 3}, KF and NaH{sub 2}PO{sub 4}·2H{sub 2}O containing electrolytes. Mechanical properties including wear resistance, surface hardness and elastic modulus were increased for PEO-coated AZ31 Mg alloys (PEO-AZ31). DC polarization in Hank's solution indicating that the corrosion resistance significantly increased for PEO-coating in KF-contained electrolyte. Based on these results, the PEO coating method shows promising potential for use in biodegradable implant applications where tunable corrosion and mechanical properties are needed.

  7. Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats.

    Science.gov (United States)

    Foletto, Kelly Carraro; Melo Batista, Bruna Aparecida; Neves, Alice Magagnin; de Matos Feijó, Fernanda; Ballard, Cíntia Reis; Marques Ribeiro, Maria Flávia; Bertoluci, Marcello Casaccia

    2016-01-01

    In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Maternal Western diet increases adiposity even in male offspring of obesity-resistant rat dams: early endocrine risk markers.

    Science.gov (United States)

    Frihauf, Jennifer B; Fekete, Éva M; Nagy, Tim R; Levin, Barry E; Zorrilla, Eric P

    2016-12-01

    Maternal overnutrition or associated complications putatively mediate the obesogenic effects of perinatal high-fat diet on developing offspring. Here, we tested the hypothesis that a Western diet developmental environment increases adiposity not only in male offspring from obesity-prone (DIO) mothers, but also in those from obesity-resistant (DR) dams, implicating a deleterious role for the Western diet per se. Selectively bred DIO and DR female rats were fed chow (17% kcal fat) or Western diet (32%) for 54 days before mating and, thereafter, through weaning. As intended, despite chow-like caloric intake, Western diet increased prepregnancy weight gain and circulating leptin levels in DIO, but not DR, dams. Yet, in both genotypes, maternal Western diet increased the weight and adiposity of preweanlings, as early as in DR offspring, and increased plasma leptin, insulin, and adiponectin of weanlings. Although body weight normalized with chow feeding during adolescence, young adult Western diet offspring subsequently showed decreased energy expenditure and, in DR offspring, decreased lipid utilization as a fuel substrate. By mid-adulthood, maternal Western diet DR offspring ate more chow, weighed more, and were fatter than controls. Thus, maternal Western diet covertly programmed increased adiposity in childhood and adulthood, disrupted relations of energy regulatory hormones with body fat, and decreased energy expenditure in offspring of lean, genetically obesity-resistant mothers. Maternal Western diet exposure alone, without maternal obesity or overnutrition, can promote offspring weight gain. Copyright © 2016 Frihauf et al.

  9. Increasing Resistance to Extended-Spectrum Cephalosporins, Fluoroquinolone, and Carbapenem in Gram-Negative Bacilli and the Emergence of Carbapenem Non-Susceptibility in Klebsiella pneumoniae: Analysis of Korean Antimicrobial Resistance Monitoring System (KARMS) Data From 2013 to 2015.

    Science.gov (United States)

    Kim, Dokyun; Ahn, Ji Young; Lee, Chae Hoon; Jang, Sook Jin; Lee, Hyukmin; Yong, Dongeun; Jeong, Seok Hoon; Lee, Kyungwon

    2017-05-01

    National surveillance of antimicrobial resistance becomes more important for the control of antimicrobial resistance and determination of treatment guidelines. We analyzed Korean Antimicrobial Resistance Monitoring System (KARMS) data collected from 2013 to 2015. Of the KARMS participants, 16 secondary or tertiary hospitals consecutively reported antimicrobial resistance rates from 2013 to 2015. Data from duplicate isolates and institutions with fewer than 20 isolates were excluded. To determine the long-term trends, previous KARMS data from 2004 to 2012 were also considered. The prevalence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium from 2013 to 2015 was 66-72% and 29-31%, respectively. The resistance rates of Escherichia coli to cefotaxime and cefepime gradually increased to 35% and 31%, respectively, and fluoroquinolone resistance reached 48% in 2015. The resistance rates of Klebsiella pneumoniae to cefotaxime, cefepime, and carbapenem were 38-41%, 33-41%, and carbapenem susceptibility rates of E. coli and K. pneumoniae decreased from 100% and 99.3% in 2011 to 99.0% and 97.0% in 2015, respectively. The resistance rate of Pseudomonas aeruginosa to carbapenem increased to 35% and the prevalence of carbapenem-resistant Acinetobacter baumannii increased from 77% in 2013 to 85% in 2015. Between 2013 and 2015, the resistance rates of E. coli to third- and fourth-generation cephalosporins increased continuously, while carbapenem-susceptibility gradually decreased, particularly in K. pneumoniae. The prevalence of carbapenem-resistant P. aeruginosa and A. baumannii increased significantly; therefore, few treatment options remain for these resistant strains. © The Korean Society for Laboratory Medicine

  10. Isotopic marking and tracers

    International Nuclear Information System (INIS)

    Morel, F.

    1997-01-01

    The use of radioactive isotopes as tracers in biology has been developed thanks to the economic generation of the required isotopes in accelerators and nuclear reactors, and to the multiple applications of tracers in the life domain; the most usual isotopes employed in biology are carbon, hydrogen, phosphorus and sulfur isotopes, because these elements are present in most of organic molecules. Most of the life science knowledge appears to be dependent to the extensive use of nuclear tools and radioactive tracers; the example of the utilization of radioactive phosphorus marked ATP to study the multiple reactions with proteins, nucleic acids, etc., is given

  11. Ceremony marking Einstein Year

    CERN Multimedia

    2005-01-01

    Sunday 13th November at 10:00amat Geneva's St. Peter's Cathedral To mark Einstein Year and the importance of the intercultural dialogue of which it forms a part, a religious service will take place on Sunday 13 November at 10 a.m. in St. Peter's Cathedral, to which CERN members and colleagues are warmly welcomed. Pastor Henry Babel, senior minister at the Cathedral, will speak on the theme: 'God in Einstein's Universe'. Diether Blechschmidt will convey a message on behalf of the scientific community.

  12. Minimal Marking: A Success Story

    Science.gov (United States)

    McNeilly, Anne

    2014-01-01

    The minimal-marking project conducted in Ryerson's School of Journalism throughout 2012 and early 2013 resulted in significantly higher grammar scores in two first-year classes of minimally marked university students when compared to two traditionally marked classes. The "minimal-marking" concept (Haswell, 1983), which requires…

  13. Including dietary fiber and resistant starch to increase satiety and reduce aggression in gestating sows

    Science.gov (United States)

    The swine industry is under a great deal of pressure to return sows to group housing. However, aggression during mixing of pregnant sows impacts sow welfare and productivity. The aim of this study was to increase satiety and reduce aggression by including dietary fiber and fermentable carbohydrate. ...

  14. Cecal ligation and puncture followed by methicillin-resistant Staphylococcus aureus pneumonia increases mortality in mice and blunts production of local and systemic cytokines.

    Science.gov (United States)

    Jung, Enjae; Perrone, Erin E; Liang, Zhe; Breed, Elise R; Dominguez, Jessica A; Clark, Andrew T; Fox, Amy C; Dunne, W Michael; Burd, Eileen M; Farris, Alton B; Hotchkiss, Richard S; Coopersmith, Craig M

    2012-01-01

    Mortality in the intensive care unit frequently results from the synergistic effect of two temporally distinct infections. This study examined the pathophysiology of a new model of intra-abdominal sepsis followed by methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Mice underwent cecal ligation and puncture (CLP) or sham laparotomy followed 3 days later by an intratracheal injection of MRSA or saline. Both CLP/saline and sham/MRSA mice had 100% survival, whereas animals with CLP followed by MRSA pneumonia had 67% 7-day survival. Animals subjected to CLP/MRSA had increased bronchoalveolar lavage concentrations of MRSA compared with sham/MRSA animals. Animals subjected to sham/MRSA pneumonia had increased bronchoalveolar lavage levels of interleukin 6 (IL-6), tumor necrosis factor α, and granulocyte colony-stimulating factor compared with those given intratracheal saline, whereas CLP/MRSA mice had a blunted local inflammatory response with markedly decreased cytokine levels. Similarly, animals subjected to CLP/saline had increased peritoneal lavage levels of IL-6 and IL-1β compared with those subjected to sham laparotomy, whereas this response was blunted in CLP/MRSA mice. Systemic cytokines were upregulated in both CLP/saline and sham/MRSA mice, and this was blunted by the combination of CLP/MRSA. In contrast, no synergistic effect on pneumonia severity, white blood cell count, or lymphocyte apoptosis was identified in CLP/MRSA mice compared with animals with either insult in isolation. These results indicate that a clinically relevant model of CLP followed by MRSA pneumonia causes higher mortality than could have been predicted from studying either infection in isolation, and this was associated with a blunted local (pulmonary and peritoneal) and systemic inflammatory response and decreased ability to clear infection.

  15. In the eye of the beholder: eye contact increases resistance to persuasion.

    Science.gov (United States)

    Chen, Frances S; Minson, Julia A; Schöne, Maren; Heinrichs, Markus

    2013-11-01

    Popular belief holds that eye contact increases the success of persuasive communication, and prior research suggests that speakers who direct their gaze more toward their listeners are perceived as more persuasive. In contrast, we demonstrate that more eye contact between the listener and speaker during persuasive communication predicts less attitude change in the direction advocated. In Study 1, participants freely watched videos of speakers expressing various views on controversial sociopolitical issues. Greater direct gaze at the speaker's eyes was associated with less attitude change in the direction advocated by the speaker. In Study 2, we instructed participants to look at either the eyes or the mouths of speakers presenting arguments counter to participants' own attitudes. Intentionally maintaining direct eye contact led to less persuasion than did gazing at the mouth. These findings suggest that efforts at increasing eye contact may be counterproductive across a variety of persuasion contexts.

  16. Increases in muscle strength and balance using a resistance training program administered via a telecommunications system in older adults.

    Science.gov (United States)

    Sparrow, David; Gottlieb, Daniel J; Demolles, Deborah; Fielding, Roger A

    2011-11-01

    Resistance training programs have been found to improve muscle strength, physical function, and depressive symptoms in middle-aged and older adults. These programs have typically been provided in clinical facilities, health clubs, and senior centers, which may be inconvenient and/or cost prohibitive for some older adults. The purpose of this study was to investigate the effectiveness of an automated telemedicine intervention that provides real-time guidance and monitoring of resistance training in the home. A randomized clinical trial in 103 middle-aged or older participants. Participants were assigned to use of a theory-driven interactive voice response system designed to promote resistance training (Telephone-Linked Computer-based Long-term Interactive Fitness Trainer; n = 52) or to an attention control (n = 51) for a period of 12 months. Measurements of muscle strength, balance, walk distance, and mood were obtained at baseline, 3, 6, and 12 months. We observed increased strength, improved balance, and fewer depressive symptoms in the intervention group than in the control group. Using generalized estimating equations modeling, group differences were statistically significant for knee flexion strength (p = .035), single-leg stance time (p = .029), and Beck Depression Inventory (p = .030). This computer-based telecommunications exercise intervention led to improvements in participants' strength, balance, and depressive symptoms. Because of their low cost and easy accessibility, computer-based interventions may be a cost-effective way of promoting exercise in the home.

  17. Mutations in durum wheat SBEII genes conferring increased amylose and resistant starch affect grain yield components, semolina and pasta quality and fermentation responses in rats

    Science.gov (United States)

    Increased amylose in wheat (Triticum spp.) starch is associated with increased resistant starch, a fermentable dietary fiber. Fermentation of resistant starch in the large intestine produces short-chain fatty acids that provide human health benefits. Since wheat foods are an important component of t...

  18. Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance

    DEFF Research Database (Denmark)

    Vernochet, Cecile; Mourier, Arnaud; Bezy, Olivier

    2012-01-01

    Obesity and type 2 diabetes are associated with mitochondrial dysfunction in adipose tissue, but the role for adipose tissue mitochondria in the development of these disorders is currently unknown. To understand the impact of adipose tissue mitochondria on whole-body metabolism, we have generated...... oxygen consumption and uncoupling. As a result, F-TFKO mice exhibit higher energy expenditure and are protected from age- and diet-induced obesity, insulin resistance, and hepatosteatosis, despite a greater food intake. Thus, TFAM deletion in the adipose tissue increases mitochondrial oxidation that has...... positive metabolic effects, suggesting that regulation of adipose tissue mitochondria may be a potential therapeutic target for the treatment of obesity....

  19. Resistance Training Does Not Protect Against Increases in Plasma Cytokine Levels Among Germ Cell Cancer Patients During and After Chemotherapy

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Tolver, Anders; Andersen, J.L.

    2014-01-01

    Abstract Context: Testicular germ cell cancer (GCC) patients treated with cisplatin-etoposide-bleomycin chemotherapy (BEP) have excellent prognosis but have an increased risk of late-occurring morbidities, which may be associated with changes in the inflammatory profile. Objective: The objective...... of the study was to explore plasma cytokine concentrations in GCC patients randomized to resistance training or usual care during BEP, in comparison with healthy controls. Design/Setting: This was a randomized controlled trial in GCC patients enrolled from an oncology clinic, including a healthy reference......). Changes in TNF-α correlated with pulmonary toxicity (P BEP display consistently elevated levels of systemic inflammatory markers compared with healthy...

  20. Increased serum chemerin concentrations in patients with polycystic ovary syndrome: Relationship between insulin resistance and ovarian volume.

    Science.gov (United States)

    Huang, Rong; Yue, Jiang; Sun, Yun; Zheng, Jun; Tao, Tao; Li, Shengxian; Liu, Wei

    2015-10-23

    Chemerin has been linked to adiposity, and insulin resistance (IR) which are the common characteristics of polycystic ovary syndrome (PCOS). Chemerin also shows inhibitory action on follicular steroidogenesis. We investigated the associations between chemerin and IR or polycystic ovary morphology in patients with PCOS. A total of 148 women with newly diagnosed PCOS using Rotterdam criteria and 88 healthy individuals were enrolled. The recruited patients with PCOS were further stratified by tertiles of serum chemerin concentrations as follows: Group 1 ( 30.27 ng/ml). Compared to controls, women with PCOS in each tertile had higher serum chemerin concentrations. By linear regression analysis, homeostasis model assessment-insulin resistance and ovarian volume showed significant associations with chemerin after adjusting for confounding factors (β = 0.257, P = 0.028; β = 0.276, P = 0.005, respectively). The odds ratios (ORs) for ovarian volume excess gradually increased across increasing tertiles of chemerin in the adjusted model [Group 1: reference; Group 2: OR 1.602; 95% confidence interval (CI): 1.170–2.194; Group 3: OR 1.857; 95% CI: 1.335-2.583]. Patients with PCOS showed increased serum chemerin concentrations as compared to healthy women. Individuals with higher chemerin tended to have higher risk for ovarian volume excess in patients with PCOS, regardless of adiposity.

  1. Walnut consumption increases satiation but has no effect on insulin resistance or the metabolic profile over a 4-day period.

    Science.gov (United States)

    Brennan, Aoife M; Sweeney, Laura L; Liu, Xiaowen; Mantzoros, Christos S

    2010-06-01

    Obesity and diabetes have been associated with increased consumption of highly processed foods, and reduced consumption of whole grains and nuts. It has been proposed, mainly on the basis of observational studies, that nuts may provide superior satiation, may lead to reduced calorie consumption, and may decrease the risk of type 2 diabetes; but evidence from randomized, interventional studies is lacking. A total of 20 men and women with the metabolic syndrome participated in a randomized, double-blind, crossover study of walnut consumption. Subjects had two 4-day admissions to the clinical research center where they were fed an isocaloric diet. In addition, they consumed shakes for breakfast containing either walnuts or placebo (shakes were standardized for calories, carbohydrate, and fat content). Appetite, insulin resistance, and metabolic parameters were measured. We found an increased level of satiety (overall P value = 0.0079) and sense of fullness (P = 0.05) in prelunch questionnaires following the walnut breakfast as compared to the placebo breakfast, with the walnut effect achieving significance on day 3 and 4 (P = 0.02 and P = 0.03). We did not find any change in resting energy expenditure, hormones known to mediate satiety, or insulin resistance when comparing the walnut vs. placebo diet. Walnut consumption over 4 days increased satiety by day 3. Long-term studies are needed to confirm the physiologic role of walnuts, the duration of time needed for these effects to occur, and to elucidate the underlying mechanisms.

  2. Endurance and Resistance Training Affect High Fat Diet-Induced Increase of Ceramides, Inflammasome Expression, and Systemic Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Cornelia Mardare

    2016-01-01

    Full Text Available The study aimed to investigate the effects of differentiated exercise regimes on high fat-induced metabolic and inflammatory pathways. Mice were fed a standard diet (ST or a high fat diet (HFD and subjected to regular endurance training (ET or resistance training (RT. After 10 weeks body weight, glucose tolerance, fatty acids (FAs, circulating ceramides, cytokines, and immunological mediators were determined. The HFD induced a significant increase in body weight and a disturbed glucose tolerance (p<0.05. An increase of plasma FA, ceramides, and inflammatory mediators in adipose tissue and serum was found (p<0.05. Both endurance and resistance training decreased body weight (p<0.05 and reduced serum ceramides (p<0.005. While RT attenuated the increase of NLRP-3 (RT expression in adipose tissue, ET was effective in reducing TNF-α and IL-18 expression. Furthermore, ET reduced levels of MIP-1γ, while RT decreased levels of IL-18, MIP-1γ, Timp-1, and CD40 in serum (p<0.001, respectively. Although both exercise regimes improved glucose tolerance (p<0.001, ET was more effective than RT. These results suggest that exercise improves HFD-induced complications possibly through a reduction of ceramides, the reduction of inflammasome activation in adipose tissues, and a systemic downregulation of inflammatory cytokines.

  3. Intense resistance exercise induces early and transient increases in ryanodine receptor 1 phosphorylation in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Sebastian Gehlert

    Full Text Available BACKGROUND: While ryanodine receptor 1 (RyR1 critically contributes to skeletal muscle contraction abilities by mediating Ca²⁺ion oscillation between sarcoplasmatic and myofibrillar compartments, AMP-activated protein kinase (AMPK senses contraction-induced energetic stress by phosphorylation at Thr¹⁷². Phosphorylation of RyR1 at serine²⁸⁴³ (pRyR1Ser²⁸⁴³ results in leaky RyR1 channels and impaired Ca²⁺homeostasis. Because acute resistance exercise exerts decreased contraction performance in skeletal muscle, preceded by high rates of Ca²⁺-oscillation and energetic stress, intense myofiber contractions may induce increased RyR1 and AMPK phosphorylation. However, no data are available regarding the time-course and magnitude of early RyR1 and AMPK phosphorylation in human myofibers in response to acute resistance exercise. PURPOSE: Determine the effects and early time-course of resistance exercise on pRyR1Ser²⁸⁴³ and pAMPKThr¹⁷² in type I and II myofibers. METHODS: 7 male subjects (age 23±2 years, height: 185±7 cm, weight: 82±5 kg performed 3 sets of 8 repetitions of maximum eccentric knee extensions. Muscle biopsies were taken at rest, 15, 30 and 60 min post exercise. pRyR1Ser²⁸⁴³ and pAMPKThr¹⁷² levels were determined by western blot and semi-quantitative immunohistochemistry techniques. RESULTS: While total RyR1 and total AMPK levels remained unchanged, RyR1 was significantly more abundant in type II than type I myofibers. pRyR1Ser²⁸⁴³ increased 15 min and peaked 30 min (p<0.01 post exercise in both myofiber types. Type I fibers showed relatively higher increases in pRyR1Ser²⁸⁴³ levels than type II myofibers and remained elevated up to 60 min post resistance exercise (p<0.05. pAMPKThr¹⁷² also increased 15 to 30 min post exercise (p<0.01 in type I and II myofibers and in whole skeletal muscle. CONCLUSION: Resistance exercise induces acutely increased pRyR1Ser²⁸⁴³ and

  4. Cancer Stem-Like Cells Enriched in Panc-1 Spheres Possess Increased Migration Ability and Resistance to Gemcitabine

    Science.gov (United States)

    Yin, Tao; Wei, Hongji; Gou, Shanmiao; Shi, Pengfei; Yang, Zhiyong; Zhao, Gang; Wang, Chunyou

    2011-01-01

    Pancreatic cancer is one of the most lethal malignancies with poor prognosis. Previously, we found that a subpopulation of cancer stem cells (CSCs) in the Panc-1 pancreatic cancer cell line could propagate to form spheres. Here we characterized the malignant phenotypes of the pancreatic cancer stem CD44+/CD24+ cells, which were enriched under sphere forming conditions as analyzed by flow cytometry. These cells demonstrated increased resistance to gemcitabine and increased migration ability. Moreover, these cells exhibited epithelial to mesenchymal transition characterized by a decreased level of the epithelial marker E-cadherin and an increased level of the mesenchymal marker vimentin. Notably, abnormal expression of Bmi-1, ABCG2, Cyclin D1 and p16 were found in Panc-1 CSCs. Our results suggest that targeted inhibition of CSCs represents a novel therapeutic approach to overcome chemoresistance and metastasis of pancreatic cancer. PMID:21673909

  5. Fluconazole Resistance Associated with Drug Efflux and Increased Transcription of a Drug Transporter Gene, PDH1, in Candida glabrata

    Science.gov (United States)

    Miyazaki, Haruko; Miyazaki, Yoshitsugu; Geber, Antonia; Parkinson, Tanya; Hitchcock, Christopher; Falconer, Derek J.; Ward, Douglas J.; Marsden, Katherine; Bennett, John E.

    1998-01-01

    Sequential Candida glabrata isolates were obtained from the mouth of a patient infected with human immunodeficiency virus type 1 who was receiving high doses of fluconazole for oropharyngeal thrush. Fluconazole-susceptible colonies were replaced by resistant colonies that exhibited both increased fluconazole efflux and increased transcripts of a gene which codes for a protein with 72.5% identity to Pdr5p, an ABC multidrug transporter in Saccharomyces cerevisiae. The deduced protein had a molecular mass of 175 kDa and was composed of two homologous halves, each with six putative transmembrane domains and highly conserved sequences of ATP-binding domains. When the earliest and most azole-susceptible isolate of C. glabrata from this patient was exposed to fluconazole, increased transcripts of the PDR5 homolog appeared, linking azole exposure to regulation of this gene. PMID:9661006

  6. IS ENHANCED-ECCENTRIC RESISTANCE TRAINING SUPERIOR TO TRADITIONAL TRAINING FOR INCREASING ELBOW FLEXOR STRENGTH?

    Directory of Open Access Journals (Sweden)

    Thomas W. Kaminski

    2003-06-01

    Full Text Available Protocols for strengthening muscle are important for fitness, rehabilitation, and the prevention of myotendinous injuries. In trained individuals, the optimal method of increasing strength remains unclear. The purpose of this study was to compare the effects of a traditional method of strengthening with a method that allowed for enhanced-eccentric training, on changes in elbow flexor strength in trained subjects. Thirty-nine (8 male, 31 female trained subjects with normal elbow function participated in this study. Subjects were rank-ordered according to isometric force production and randomly assigned to one of three training groups: control (CONT, traditional concentric/eccentric (TRAD, and concentric/enhanced-eccentric (NEG. The training groups completed 24 training sessions. An evaluator blinded to training group performed all testing. Mixed model ANOVA techniques were used to determine if differences existed in concentric one repetition maximum strength, and isometric force production among groups. Changes in peak and average isokinetic force production were also compared. Type 1 error was maintained at 5%. While both groups improved concentric one repetition maximum (NEG = 15.5%, TRAD = 13.8% neither training group statistically differed from changes demonstrated by the CONT group. Nor did either training group show significant improvements in isometric or isokinetic force production over the CONT group. These results do not support the superiority of enhanced-eccentric training for increasing force production in trained subjects.

  7. 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

  8. Increase in operation safety of high-current pulsed accelerators by means of nonlinear resistances

    International Nuclear Information System (INIS)

    Demidov, B.A.; Ivkin, M.V.; Petrov, V.A.; Fanchenko, S.D.

    1975-01-01

    A circuit for connecting a shaping line through a nonlinear resistor in a high-current pulsed accelerator is proposed and investigated experimentally. For experimental purposes standard resistors are used as nonlinear resistors, they are made in the form of cylinders 100 mm in dia and 60 mm long. The results obtained show that if two resistors are connected in series, the reduction in an initial potential is less than 5% at the logarithmic damping coefficient equal to 1.3. It is also shown that such a method allows elimination of the reverse pumpover of energy to the storage device for untimely actuation of a spark gap that results in the prolongation of the time of potential applying thereby it permits a substantial increase in the reliability of a high-voltage insulation [ru

  9. Fluoroquinolone resistance mechanisms in urinary tract pathogenic Escherichia coli isolated during rapidly increasing fluoroquinolone consumption in a low-use country

    DEFF Research Database (Denmark)

    Christiansen, Nina; Nielsen, Lene; Jakobsen, Lotte

    2011-01-01

    Resistance to ciprofloxacin in Escherichia coli from urinary tract infections (UTI) in Denmark is increasing parallel to increased use of fluoroquinolones both in Denmark and in other European countries. The objective was to investigate the occurrence of ciprofloxacin resistance mechanisms......, phenotypic coresistance, and if ciprofloxacin resistance was caused by clonal spread or to individual mutational events in a collection of consecutively obtained E. coli submitted to a clinical microbiology department at a Danish hospital. One hundred four UTI-related E. coli resistant toward nalidixic acid...

  10. A single amino acid substitution in the core protein of West Nile virus increases resistance to acidotropic compounds.

    Directory of Open Access Journals (Sweden)

    Miguel A Martín-Acebes

    Full Text Available West Nile virus (WNV is a worldwide distributed mosquito-borne flavivirus that naturally cycles between birds and mosquitoes, although it can infect multiple vertebrate hosts including horses and humans. This virus is responsible for recurrent epidemics of febrile illness and encephalitis, and has recently become a global concern. WNV requires to transit through intracellular acidic compartments at two different steps to complete its infectious cycle. These include fusion between the viral envelope and the membrane of endosomes during viral entry, and virus maturation in the trans-Golgi network. In this study, we followed a genetic approach to study the connections between viral components and acidic pH. A WNV mutant with increased resistance to the acidotropic compound NH4Cl, which blocks organelle acidification and inhibits WNV infection, was selected. Nucleotide sequencing revealed that this mutant displayed a single amino acid substitution (Lys 3 to Glu on the highly basic internal capsid or core (C protein. The functional role of this replacement was confirmed by its introduction into a WNV infectious clone. This single amino acid substitution also increased resistance to other acidification inhibitor (concanamycin A and induced a reduction of the neurovirulence in mice. Interestingly, a naturally occurring accompanying mutation found on prM protein abolished the resistant phenotype, supporting the idea of a genetic crosstalk between the internal C protein and the external glycoproteins of the virion. The findings here reported unveil a non-previously assessed connection between the C viral protein and the acidic pH necessary for entry and proper exit of flaviviruses.

  11. A single amino acid substitution in the core protein of West Nile virus increases resistance to acidotropic compounds.

    Science.gov (United States)

    Martín-Acebes, Miguel A; Blázquez, Ana-Belén; de Oya, Nereida Jiménez; Escribano-Romero, Estela; Shi, Pei-Yong; Saiz, Juan-Carlos

    2013-01-01

    West Nile virus (WNV) is a worldwide distributed mosquito-borne flavivirus that naturally cycles between birds and mosquitoes, although it can infect multiple vertebrate hosts including horses and humans. This virus is responsible for recurrent epidemics of febrile illness and encephalitis, and has recently become a global concern. WNV requires to transit through intracellular acidic compartments at two different steps to complete its infectious cycle. These include fusion between the viral envelope and the membrane of endosomes during viral entry, and virus maturation in the trans-Golgi network. In this study, we followed a genetic approach to study the connections between viral components and acidic pH. A WNV mutant with increased resistance to the acidotropic compound NH4Cl, which blocks organelle acidification and inhibits WNV infection, was selected. Nucleotide sequencing revealed that this mutant displayed a single amino acid substitution (Lys 3 to Glu) on the highly basic internal capsid or core (C) protein. The functional role of this replacement was confirmed by its introduction into a WNV infectious clone. This single amino acid substitution also increased resistance to other acidification inhibitor (concanamycin A) and induced a reduction of the neurovirulence in mice. Interestingly, a naturally occurring accompanying mutation found on prM protein abolished the resistant phenotype, supporting the idea of a genetic crosstalk between the internal C protein and the external glycoproteins of the virion. The findings here reported unveil a non-previously assessed connection between the C viral protein and the acidic pH necessary for entry and proper exit of flaviviruses.

  12. A silver ion-doped calcium phosphate-based ceramic nanopowder-coated prosthesis increased infection resistance.

    Science.gov (United States)

    Kose, Nusret; Otuzbir, Ali; Pekşen, Ceren; Kiremitçi, Abdurrahman; Doğan, Aydin

    2013-08-01

    Despite progress in surgical techniques, 1% to 2% of joint arthroplasties become complicated by infection. Coating implant surfaces with antimicrobial agents have been attempted to prevent initial bacterial adhesion to implants with varying success rates. We developed a silver ion-containing calcium phosphate-based ceramic nanopowder coating to provide antibacterial activity for orthopaedic implants. We asked whether titanium prostheses coated with this nanopowder would show resistance to bacterial colonization as compared with uncoated prostheses. We inserted titanium implants (uncoated [n = 9], hydroxyapatite-coated [n = 9], silver-coated [n = 9]) simulating knee prostheses into 27 rabbits' knees. Before implantation, 5 × 10(2) colony-forming units of Staphylococcus aureus were inoculated into the femoral canal. Radiology, microbiology, and histology findings were quantified at Week 6 to define the infection, microbiologically by increased rate of implant colonization/positive cultures, histologically by leukocyte infiltration, necrosis, foreign-body granuloma, and devitalized bone, and radiographically by periosteal reaction, osteolysis, or sequestrum formation. Swab samples taken from medullary canals and implants revealed a lower proportion of positive culture in silver-coated implants (one of nine) than in uncoated (eight of nine) or hydroxyapatite-coated (five of nine) implants. Silver-coated implants also had a lower rate of colonization. No cellular inflammation or foreign-body granuloma was observed around the silver-coated prostheses. Silver ion-doped ceramic nanopowder coating of titanium implants led to an increase in resistance to bacterial colonization compared to uncoated implants. Silver-coated orthopaedic implants may be useful for resistance to local infection but will require in vivo confirmation.

  13. Light-load resistance exercise increases muscle protein synthesis and hypertrophy signaling in elderly men

    DEFF Research Database (Denmark)

    Agergaard, Jakob; Bülow, Jacob; Jensen, Jacob K

    2017-01-01

    to 13 h of supine rest. After 2.5 h of rest, unilateral LL-RE, consisting of leg extensions (10 sets, 36 repetitions) at 16% of 1 repetition maximum (RM), was conducted. Subsequently, the subjects were randomized to oral intake of 4 g of whey protein per hour (PULSE, n = 10), 28 g of whey protein at 0 h...... and 12 g of whey protein at 7 h postexercise (BOLUS, n = 10), or 4 g of maltodextrin per hour (placebo, n = 10). Quadriceps muscle biopsies were taken at 0, 3, 7, and 10 h postexercise from the resting and the exercised leg of each subject. Myofibrillar FSR and activity of select targets from...... persisted in the placebo group only. Levels of phosphorylated (T37/46) eukaryotic translation initiation factor 4E-binding protein 1 increased throughout the postexercise period in the exercised leg in the placebo and BOLUS groups and peaked at 7 h. In all three groups, phosphorylated (T56) eukaryotic...

  14. Lifespan extension and increased resistance to environmental stressors by N-Acetyl-L-Cysteine in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Seung-Il Oh

    2015-05-01

    Full Text Available OBJECTIVE: This study was performed to determine the effect of N-acetyl-L-cysteine, a modified sulfur-containing amino acid that acts as a strong cellular antioxidant, on the response to environmental stressors and on aging in C. elegans. METHOD: The survival of worms under oxidative stress conditions induced by paraquat was evaluated with and without in vivo N-acetyl-L-cysteine treatment. The effect of N-acetyl-L-cysteine on the response to other environmental stressors, including heat stress and ultraviolet irradiation (UV, was also monitored. To investigate the effect on aging, we examined changes in lifespan, fertility, and expression of age-related biomarkers in C. elegans after N-acetyl-L-cysteine treatment. RESULTS: Dietary N-acetyl-L-cysteine supplementation significantly increased resistance to oxidative stress, heat stress, and UV irradiation in C. elegans. In addition, N-acetyl-L-cysteine supplementation significantly extended both the mean and maximum lifespan of C. elegans. The mean lifespan was extended by up to 30.5% with 5 mM N-acetyl-L-cysteine treatment, and the maximum lifespan was increased by 8 days. N-acetyl-L-cysteine supplementation also increased the total number of progeny produced and extended the gravid period of C. elegans. The green fluorescent protein reporter assay revealed that expression of the stress-responsive genes, sod-3 and hsp-16.2, increased significantly following N-acetyl-L-cysteine treatment. CONCLUSION: N-acetyl-L-cysteine supplementation confers a longevity phenotype in C. elegans, possibly through increased resistance to environmental stressors.

  15. Methamphetamine increases Prion Protein and induces dopamine-dependent expression of protease resistant PrPsc.

    Science.gov (United States)

    Ferrucci, M; Ryskalin, L; Biagioni, F; Gambardella, S; Busceti, C L; Falleni, A; Lazzeri, G; Fornai, F

    2017-07-01

    The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions.Methamphetamine (METH) is a widely abused drug which produces oxidative stress in various brain areas causing mitochondrial alterations and protein misfolding. These effects produce a compensatory increase of chaperones while clogging cell clearing pathways. In the present study, we explored whether METH administration modifies the amount of PrPc. Since high levels of PrPc when the clearing systems are clogged may lead to its misfolding into PrPsc, we further tested whether METH exposure triggers the appearance of PrPsc. We analysed the effects of METH and dopamine administration in PC12 and striatal cells by using SDS-PAGE Coomassie blue, immune- histochemistry and immune-gold electron microscopy. To analyze whether METH administration produces PrPsc aggregates we used antibodies directed against PrP following exposure to proteinase K or sarkosyl which digest folded PrPc but misfolded PrPsc. We fond that METH triggers PrPsc aggregates in DA-containing cells while METH is not effective in primary striatal neurons which do not produce DA. In the latter cells exogenous DA is needed to trigger PrPsc accumulation similarly to what happens in DA containing cells under the effects of METH. The present findings, while fostering novel molecular mechanisms involving prion proteins, indicate that, cell pathology similar to prion disorders can be mimicked via a DA-dependent mechanism by a drug of abuse.

  16. Increasing Wear Resistance of Titanium Alloys by Anode Plasma Electrolytic Saturation with Interstitial Elements

    Science.gov (United States)

    Belkin, P. N.; Kusmanov, S. A.; Dyakov, I. G.; Silkin, S. A.; Smirnov, A. A.

    2017-05-01

    In our previous studies, we have shown that anode plasma electrolytic saturation of titanium alloys with nitrogen and carbon can improve their tribological properties. Obtained structure containing oxide layer and solid solution of diffused element in titanium promotes the enhancement of running-in ability and the decrease in the wear rate in some special cases. In this paper, further investigations are reported regarding the tribological properties of alpha- and beta-titanium alloys in wear test against hardened steel (50 HRC) disk using pin-on-disk geometry and balls of Al2O3 (6.25 mm in diameter) or bearing steel (9.6 mm in diameter) with ball-on-plate one and normal load from 5 to 209 N. Reproducible results were obtained under testing samples treated by means of the plasma electrolytic nitriding (PEN) with the mechanical removal of the oxide layer. Friction coefficient of nitrided samples is 0.5-0.9 which is somewhat higher than that for untreated one (0.48-0.75) during dry sliding against Al2O3 ball. An increase in the sliding speed results in the polishing of nitrided samples and reduction of their wear rate by 60 times. This result is obtained for 5 min at 850 °C using PEN in electrolyte containing 5 wt.% ammonia and 10 wt.% ammonium chloride followed by quenching in solution. Optical microscope was employed to assist in the evaluation of the wear behavior. Sizes of wear tracks were measured by profilometer TR200.

  17. Dietary flavonoid fisetin increases abundance of high-molecular-mass hyaluronan conferring resistance to prostate oncogenesis.

    Science.gov (United States)

    Lall, Rahul K; Syed, Deeba N; Khan, Mohammad Imran; Adhami, Vaqar M; Gong, Yuansheng; Lucey, John A; Mukhtar, Hasan

    2016-09-01

    We and others have shown previously that fisetin, a plant flavonoid, has therapeutic potential against many cancer types. Here, we examined the probable mechanism of its action in prostate cancer (PCa) using a global metabolomics approach. HPLC-ESI-MS analysis of tumor xenografts from fisetin-treated animals identified several metabolic targets with hyaluronan (HA) as the most affected. Efficacy of fisetin on HA was then evaluated in vitro and also in vivo in the transgenic TRAMP mouse model of PCa. Size exclusion chromatography-multiangle laser light scattering (SEC-MALS) was performed to analyze the molar mass (Mw) distribution of HA. Fisetin treatment downregulated intracellular and secreted HA levels both in vitro and in vivo Fisetin inhibited HA synthesis and degradation enzymes, which led to cessation of HA synthesis and also repressed the degradation of the available high-molecular-mass (HMM)-HA. SEC-MALS analysis of intact HA fragment size revealed that cells and animals have more abundance of HMM-HA and less of low-molecular-mass (LMM)-HA upon fisetin treatment. Elevated HA levels have been shown to be associated with disease progression in certain cancer types. Biological responses triggered by HA mainly depend on the HA polymer length where HMM-HA represses mitogenic signaling and has anti-inflammatory properties whereas LMM-HA promotes proliferation and inflammation. Similarly, Mw analysis of secreted HA fragment size revealed less HMM-HA is secreted that allowed more HMM-HA to be retained within the cells and tissues. Our findings establish that fisetin is an effective, non-toxic, potent HA synthesis inhibitor, which increases abundance of antiangiogenic HMM-HA and could be used for the management of PCa. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Highly loaded behavior of kinesins increases the robustness of transport under high resisting loads.

    Directory of Open Access Journals (Sweden)

    Woochul Nam

    2015-03-01

    Full Text Available Kinesins are nano-sized biological motors which walk by repeating a mechanochemical cycle. A single kinesin molecule is able to transport its cargo about 1 μm in the absence of external loads. However, kinesins perform much longer range transport in cells by working collectively. This long range of transport by a team of kinesins is surprising because the motion of the cargo in cells can be hindered by other particles. To reveal how the kinesins are able to accomplish their tasks of transport in harsh intracellular circumstances, stochastic studies on the kinesin motion are performed by considering the binding and unbinding of kinesins to microtubules and their dependence on the force acting on kinesin molecules. The unbinding probabilities corresponding to each mechanochemical state of kinesin are modeled. The statistical characterization of the instants and locations of binding are captured by computing the probability of unbound kinesin being at given locations. It is predicted that a group of kinesins has a more efficient transport than a single kinesin from the perspective of velocity and run length. Particularly, when large loads are applied, the leading kinesin remains bound to the microtubule for long time which increases the chances of the other kinesins to bind to the microtubule. To predict effects of this behavior of the leading kinesin under large loads on the collective transport, the motion of the cargo is studied when the cargo confronts obstacles. The result suggests that the behavior of kinesins under large loads prevents the early termination of the transport which can be caused by the interference with the static or moving obstacles.

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

    Science.gov (United States)

    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.

  20. Gas Plasma Pre-treatment Increases Antibiotic Sensitivity and Persister Eradication in Methicillin-Resistant Staphylococcus aureus

    Science.gov (United States)

    Guo, Li; Xu, Ruobing; Zhao, Yiming; Liu, Dingxin; Liu, Zhijie; Wang, Xiaohua; Chen, Hailan; Kong, Michael G.

    2018-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of serious nosocomial infections, and recurrent MRSA infections primarily result from the survival of persister cells after antibiotic treatment. Gas plasma, a novel source of ROS (reactive oxygen species) and RNS (reactive nitrogen species) generation, not only inactivates pathogenic microbes but also restore the sensitivity of MRSA to antibiotics. This study further found that sublethal treatment of MRSA with both plasma and plasma-activated saline increased the antibiotic sensitivity and promoted the eradication of persister cells by tetracycline, gentamycin, clindamycin, chloramphenicol, ciprofloxacin, rifampicin, and vancomycin. The short-lived ROS and RNS generated by plasma played a primary role in the process and induced the increase of many species of ROS and RNS in MRSA cells. Thus, our data indicated that the plasma treatment could promote the effects of many different classes of antibiotics and act as an antibiotic sensitizer for the treatment of antibiotic-resistant bacteria involved in infectious diseases. PMID:29628915

  1. Ectopic expression of a horseradish peroxidase enhances growth rate and increases oxidative stress resistance in hybrid aspen.

    Science.gov (United States)

    Kawaoka, Akiyoshi; Matsunaga, Etsuko; Endo, Saori; Kondo, Shinkichi; Yoshida, Kazuya; Shinmyo, Atsuhiko; Ebinuma, Hiroyasu

    2003-07-01

    We previously demonstrated that overexpression of the horseradish (Armoracia rusticana) peroxidase prxC1a gene stimulated the growth rate of tobacco (Nicotiana tabacum) plants. Here, the cauliflower mosaic virus 35S::prxC1a construct was introduced into hybrid aspen (Populus sieboldii x Populus grandidentata). The growth rate of these transformed hybrid aspen plants was substantially increased under greenhouse conditions. The average stem length of transformed plants was 25% greater than that of control plants. There was no other obvious phenotypic difference between the transformed and control plants. Fast-growing transformed hybrid aspen showed high levels of expression of prxC1a and had elevated peroxidase activities toward guaiacol and ascorbate. However, there was no increase of the endogenous class I ascorbate peroxidase activities in the transformed plants by separate assay and activity staining of native polyacrylamide gel electrophoresis. Furthermore, calli derived from the transformed hybrid aspen grew faster than those from control plants and were resistant to the oxidative stress imposed by hydrogen peroxide. Therefore, enhanced peroxidase activity affects plant growth rate and oxidative stress resistance.

  2. Hepatocyte DACH1 Is Increased in Obesity via Nuclear Exclusion of HDAC4 and Promotes Hepatic Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Lale Ozcan

    2016-06-01

    Full Text Available Defective insulin signaling in hepatocytes is a key factor in type 2 diabetes. In obesity, activation of calcium/calmodulin-dependent protein kinase II (CaMKII in hepatocytes suppresses ATF6, which triggers a PERK-ATF4-TRB3 pathway that disrupts insulin signaling. Elucidating how CaMKII suppresses ATF6 is therefore essential to understanding this insulin resistance pathway. We show that CaMKII phosphorylates and blocks nuclear translocation of histone deacetylase 4 (HDAC4. As a result, HDAC4-mediated SUMOylation of the corepressor DACH1 is decreased, which protects DACH1 from proteasomal degradation. DACH1, together with nuclear receptor corepressor (NCOR, represses Atf6 transcription, leading to activation of the PERK-TRB3 pathway and defective insulin signaling. DACH1 is increased in the livers of obese mice and humans, and treatment of obese mice with liver-targeted constitutively nuclear HDAC4 or DACH1 small hairpin RNA (shRNA increases ATF6, improves hepatocyte insulin signaling, and protects against hyperglycemia and hyperinsulinemia. Thus, DACH1-mediated corepression in hepatocytes emerges as an important link between obesity and insulin resistance.

  3. Increasing the brittle fracture resistance in manual arc welding and heat treatment of type 12KhM steels

    International Nuclear Information System (INIS)

    Tikhonov, V.P.; Bychenkova, G.A.; Gordeev, Y.V.; Ilyuhov, C.V.

    1984-01-01

    The extensive application of heat-resisting steels is delayed by their poor weldability. Optimum technology has been developed for manual arc welding and heat treatment of structures of type 12KhM steels resulting in high cracking resistance. Trials were conducted to evaluate the efficiency of removing the structural stresses in tempering the structures. On the basis of the experimental results, it may be assumed that the toughness properties of the welded joints produced by manual arc welding can be improved by optimizing the alloying system of the weld metal, with the parent metal treated in the optimum heat treatment conditions. The aim of subsequent investigations was to assess the properties of the weld metal made with vanadium-free electrodes. It was found that the impact toughness increased two to three times; the mean hardness and the maximum hardness were both less than 220. The reduction in hardness and increase of the toughness properties of the metal are caused by the lower degree of hardening of the bulk of the grain and, consequently, by the lower concentration of plastic strain at the grain boundaries

  4. Increased heat resistance in mycelia from wood fungi prevalent in forests characterized by fire: a possible adaptation to forest fire.

    Science.gov (United States)

    Carlsson, Fredrik; Edman, Mattias; Holm, Svante; Eriksson, Anna-Maria; Jonsson, Bengt Gunnar

    2012-10-01

    Forest fires have been the major stand-replacing/modifying disturbance in boreal forests. To adapt to fire disturbance, different strategies have evolved. This study focuses on wood fungi, and a specific adaptation to forest fire: increased heat resistance in their mycelia. Fifteen species of wood fungi were selected and a priori sorted in two groups according to their prevalence in fire-affected environments. The fungi were cultivated on fresh wood and exposed to 100, 140, 180, 220 °C for 5, 10, 15, 20 and 25 min. under laboratory conditions. A clear difference was found among the two groups. Species prevalent in fire-affected habitats had a much higher survival rate over all combinations of time and temperature compared to species associated with other environments. Thus, the results indicate that fire adaptation in terms of increased heat resistance in mycelia occurs in some species of wood fungi. Such adaptation will influence the ecology and population dynamics of wood fungi, as well as having implications for best practices during restoration fires. Copyright © 2012 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  5. Root jasmonic acid synthesis and perception regulate folivore-induced shoot metabolites and increase Nicotiana attenuata resistance.

    Science.gov (United States)

    Fragoso, Variluska; Rothe, Eva; Baldwin, Ian T; Kim, Sang-Gyu

    2014-06-01

    While jasmonic acid (JA) signaling is widely accepted as mediating plant resistance to herbivores, and the importance of the roots in plant defenses is recently being recognized, the role of root JA in the defense of above-ground parts remains unstudied. To restrict JA impairment to the roots, we micrografted wildtype Nicotiana attenuata shoots to the roots of transgenic plants impaired in JA signaling and evaluated ecologically relevant traits in the glasshouse and in nature. Root JA synthesis and perception are involved in regulating nicotine production in roots. Strikingly, systemic root JA regulated local leaf JA and abscisic acid (ABA) concentrations, which were associated with differences in nicotine transport from roots to leaves via the transpiration stream. Root JA signaling also regulated the accumulation of other shoot metabolites; together these account for differences in resistance against a generalist, Spodoptera littoralis, and a specialist herbivore, Manduca sexta. In N. attenuata's native habitat, silencing root JA synthesis increased the shoot damage inflicted by Empoasca leafhoppers, which are able to select natural jasmonate mutants. Silencing JA perception in roots also increased damage by Tupiocoris notatus. We conclude that attack from above-ground herbivores recruits root JA signaling to launch the full complement of plant defense responses. © 2014 Max Planck Society. New Phytologist © 2014 New Phytologist Trust.

  6. Values, inter-attitudinal structure, and attitude change: value accessibility can increase a related attitude's resistance to change.

    Science.gov (United States)

    Blankenship, Kevin L; Wegener, Duane T; Murray, Renee A

    2015-12-01

    Accessibility is one of the most basic structural properties of an attitude and an important factor to consider in attitude strength. Despite its importance, relatively little work has examined the role of attitude accessibility in an inter-attitudinal context, particularly as it relates to the strength of related attitudes in the network. The present research examines accessibility as a property of one attitude (toward an abstract goal or end-state, that is, a value) that might influence the strength of a different but related attitude (toward a social policy conceptually related to the value). In Study 1, a highly accessible evaluative component of a value increased resistance to change of attitudes and behavioral intentions toward a social policy related to that value. Similarly, a manipulation of value accessibility (Studies 2 and 3) led to increased resistance of attitudes and behavioral intentions toward a social policy related to that value. Implications for the role of accessibility in inter-attitudinal strength are discussed. © 2015 by the Society for Personality and Social Psychology, Inc.

  7. Association of dyslipidemia, increased insulin resistance, and serum CA 15-3 with increased risk of breast cancer in urban areas of North and Central India

    Directory of Open Access Journals (Sweden)

    Poonam Kachhawa

    2018-01-01

    Full Text Available Objective: This study aims to determine the association of dyslipidemia and increased insulin resistance (IR with increased breast cancer (BC risk. Materials and Methods: The study group comprised 110 premenopausal and 143 postmenopausal, untreated female BC patients in the age range of 29–72 years. Control group consisted of 117 premenopausal and 141 postmenopausal healthy females in the age range of 23–75. Approximately 8-ml blood samples were drawn to measure various biochemical parameters. Serum glucose, total cholesterol, triglyceride (TG, and high-density lipoprotein-cholesterol were measured. Very low-density lipoprotein-cholesterol (VLDL-C and LDL-C were calculated using Friedewald's formula. Serum insulin and serum CA 15-3 were estimated by immune enzymatic assay. IR was assessed using homeostasis model assessment IR index (HOMA-IR. Results: Clinical variables in the case and control groups were compared using the unpaired Student's t-test. The crude and adjusted odds ratios (ORs and 95% confidence intervals (CIs were calculated by binary logistic regression analysis. Pearson's correlation analysis was used to determine the association between CA 15-3 and variables of interest. Total cholesterol, TG, LDL, VLDL, serum glucose, serum insulin, HOMA-IR, and serum CA 15-3 were significantly higher (P < 0.001 in BC patients compared to those in controls. Significant adjusted ORs with 95% CI were found to be fasting glucose, total cholesterol, and TGs. We also found a significant positive correlation between total cholesterol, TG, LDL, serum glucose, serum insulin, HOMA-IR, and serum CA 15-3. Conclusion: This study confirms the association between dyslipidemia, IR, and increased BC risk.

  8. SLARette Mark 2 system

    International Nuclear Information System (INIS)

    Burnett, D.J.

    1992-01-01

    The SLAR (Spacer Location and Repositioning) program has developed the technology and tooling necessary to locate and reposition the fuel channel spacers that separate the pressure tube from the calandria tube in a CANDU reactor. The in-channel SLAR tool contains all the inspection probes, and is capable of moving spacers under remote control. The SLAR inspection computer system translates all eddy currents and ultrasonic signals from the in-channel tool into various graphic displays. The in-channel SLAR tool can be delivered and manipulated in a fuel channel by either a SLAR delivery machine or a SLARette delivery machine. The SLAR delivery machine consists of a modified fuelling machine, and is capable of operating under totally remote control in automatic or semi-automatic mode. The SLARette delivery machine is a smaller less automated version, which was designed to be quickly installed, operated, and removed from a limited number of fuel channels during regular annual maintenance outages. This paper describes the design and operation of the SLARette Mark 2 system. 5 figs

  9. Enriching the drinking water of rats with extracts of Salvia officinalis and Thymus vulgaris increases their resistance to oxidative stress.

    Science.gov (United States)

    Horváthová, Eva; Srančíková, Annamária; Regendová-Sedláčková, Eva; Melušová, Martina; Meluš, Vladimír; Netriová, Jana; Krajčovičová, Zdenka; Slameňová, Darina; Pastorek, Michal; Kozics, Katarína

    2016-01-01

    Nature is an attractive source of therapeutic compounds. In comparison to the artificial drugs, natural compounds cause less adverse side effects and are suitable for current molecularly oriented approaches to drug development and their mutual combining. Medicinal plants represent one of the most available remedy against various diseases. Proper examples are Salvia officinalis L. and Thymus vulgaris L. which are known aromatic medicinal plants. They are very popular and frequently used in many countries. The molecular mechanism of their biological activity has not yet been fully understood. The aim of this study was to ascertain if liver cells of experimental animals drinking extracts of sage or thyme will manifest increased resistance against oxidative stress. Adult Sprague-Dawley rats were divided into seven groups. They drank sage or thyme extracts for 2 weeks. At the end of the drinking period, blood samples were collected for determination of liver biochemical parameters and hepatocytes were isolated to analyze (i) oxidatively generated DNA damage (conventional and modified comet assay), (ii) activities of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx)] and (iii) content of glutathione. Intake of sage and thyme had no effect either on the basal level of DNA damage or on the activity of SOD in rat hepatocytes and did not change the biochemical parameters of blood plasma. Simultaneously, the activity of GPx was significantly increased and the level of DNA damage induced by oxidants was decreased. Moreover, sage extract was able to start up the antioxidant protection expressed by increased content of glutathione. Our results indicate that the consumption of S.officinalis and T.vulgaris extracts positively affects resistency of rat liver cells against oxidative stress and may have hepatoprotective potential. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved

  10. Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome.

    Science.gov (United States)

    Tosi, Flavia; Dorizzi, Romolo; Castello, Roberto; Maffeis, Claudio; Spiazzi, Giovanna; Zoppini, Giacomo; Muggeo, Michele; Moghetti, Paolo

    2009-11-01

    Increased serum C-reactive protein (CRP), an independent predictor of coronary heart disease, was reported in women with polycystic ovary syndrome (PCOS). It remains unclear whether this finding is due to the association between PCOS and either insulin resistance, obesity, or androgen excess, which are all common features of this condition. The aims of this study were to assess whether increased serum CRP is a specific feature of PCOS and to investigate the mechanisms underlying this association. Serum high-sensitivity CRP (hs-CRP) was measured in 86 hyperandrogenic women (age 21.6+/-4.2 years, body mass index (BMI) 23.6+/-3.5 kg/m2), 50 with PCOS and 36 with idiopathic hyperandrogenism (HA). Thirty-five BMI-matched healthy women were also studied as controls. In these subjects, endocrine and metabolic profiles were assessed. In all hyperandrogenic subjects and 14 controls, insulin sensitivity was measured by the glucose clamp technique. Body fat was measured by bioelectrical impedance. Hs-CRP concentrations were higher in PCOS women (3.43+/-2.01 mg/l) than in HA subjects and healthy women (2.43+/-1.04, PPCOS). In multiple regression analyses, increased serum hs-CRP was independently predicted by higher body fat and lower insulin sensitivity. However, in lean women, serum-free testosterone was an additional, negative, predictive variable. PCOS is accompanied by a low-grade chronic inflammation. Body fat appears the main determining factor of this finding, which is only partly explained by insulin resistance. At least in lean women, androgen excess per se seems to play an additional, possibly protective, role in this association.

  11. Mutations in the NOT Genes or in the Translation Machinery Similarly Display Increased Resistance to Histidine Starvation

    Directory of Open Access Journals (Sweden)

    Martine A. Collart

    2017-05-01

    Full Text Available The NOT genes encode subunits of the conserved Ccr4-Not complex, a global regulator of gene expression, and in particular of mRNA metabolism. They were originally identified in a selection for increased resistance to histidine starvation in the yeast S. cerevisiae. Recent work indicated that the Not5 subunit, ortholog of mammalian CNOT3, determines global translation levels by defining binding of the Ccr4-Not scaffold protein Not1 to ribosomal mRNAs during transcription. This is needed for optimal translation of ribosomal proteins. In this work we searched for mutations in budding yeast that were resistant to histidine starvation using the same selection that originally led to the isolation of the NOT genes. We thereby isolated mutations in ribosome-related genes. This common phenotype of ribosome mutants and not mutants is in good agreement with the positive role of the Not proteins for translation. In this regard, it is interesting that frequent mutations in RPL5 and RPL10 or in CNOT3 have been observed to accumulate in adult T-cell acute lymphoblastic leukemia (T-ALL. This suggests that in metazoans a common function implicating ribosome subunits and CNOT3 plays a role in the development of cancer. In this perspective we suggest that the Ccr4-Not complex, according to translation levels and fidelity, could itself be involved in the regulation of amino acid biosynthesis levels. We discuss how this could explain why mutations have been identified in many cancers.

  12. Pyrethroid resistance in Anopheles gambiae leads to increased susceptibility to the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana

    NARCIS (Netherlands)

    Howard, A.F.V.; Koenraadt, C.J.M.; Farenhorst, M.; Knols, B.G.J.; Takken, W.

    2010-01-01

    Background: Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have

  13. Pyrethroid resistance in Anopheles gambiae leads to increased susceptibility to the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana

    NARCIS (Netherlands)

    Howard, Annabel F. V.; Koenraadt, Constantianus J. M.; Farenhorst, Marit; Knols, Bart G. J.; Takken, Willem

    2010-01-01

    Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have previously

  14. SIRT1/PGC1α-Dependent Increase in Oxidative Phosphorylation Supports Chemotherapy Resistance of Colon Cancer

    NARCIS (Netherlands)

    Vellinga, Thomas T.; Borovski, Tijana; de Boer, Vincent C. J.; Fatrai, Szabolcs; van Schelven, Susanne; Trumpi, Kari; Verheem, Andre; Snoeren, Nikol; Emmink, Benjamin L.; Koster, Jan; Rinkes, Inne H. M. Borel; Kranenburg, Onno

    2015-01-01

    Chemotherapy treatment of metastatic colon cancer ultimately fails due to development of drug resistance. Identification of chemotherapy-induced changes in tumor biology may provide insight into drug resistance mechanisms. We studied gene expression differences between groups of liver metastases

  15. Recent urbanization in China is correlated with a Westernized microbiome encoding increased virulence and antibiotic resistance genes.

    Science.gov (United States)

    Winglee, Kathryn; Howard, Annie Green; Sha, Wei; Gharaibeh, Raad Z; Liu, Jiawu; Jin, Donghui; Fodor, Anthony A; Gordon-Larsen, Penny

    2017-09-15

    Urbanization is associated with an increased risk for a number of diseases, including obesity, diabetes, and cancer, which all also show associations with the microbiome. While microbial community composition has been shown to vary across continents and in traditional versus Westernized societies, few studies have examined urban-rural differences in neighboring communities within a single country undergoing rapid urbanization. In this study, we compared the gut microbiome, plasma metabolome, dietary habits, and health biomarkers of rural and urban people from a single Chinese province. We identified significant differences in the microbiota and microbiota-related plasma metabolites in rural versus recently urban subjects from the Hunan province of China. Microbes with higher relative abundance in Chinese urban samples have been associated with disease in other studies and were substantially more prevalent in the Human Microbiome Project cohort of American subjects. Furthermore, using whole metagenome sequencing, we found that urbanization was associated with a loss of microbial diversity and changes in the relative abundances of Viruses, Archaea, and Bacteria. Gene diversity, however, increased with urbanization, along with the proportion of reads associated with antibiotic resistance and virulence, which were strongly correlated with the presence of Escherichia and Shigella. Our data suggest that urbanization has produced convergent evolution of the gut microbial composition in American and urban Chinese populations, resulting in similar compositional patterns of abundant microbes through similar lifestyles on different continents, including a loss of potentially beneficial bacteria and an increase in potentially harmful genes via increased relative abundance of Escherichia and Shigella.

  16. Gender differences in the progression of target organ damage in patients with increased insulin resistance: the LOD-DIABETES study.

    Science.gov (United States)

    Gómez-Marcos, Manuel Ángel; Recio-Rodríguez, José Ignacio; Gómez-Sánchez, Leticia; Agudo-Conde, Cristina; Rodríguez-Sanchez, Emiliano; Maderuelo-Fernandez, JoseAngel; Gomez-Sanchez, Marta; García-Ortiz, Luís

    2015-10-01

    The purpose of this study was to analyze the evolution of vascular, cardiac and renal target organ damage (TOD) in patients with increased insulin resistance over a 3.5 year follow-up and to investigate gender difference and factors that influence its progression. We performed a prospective observational study involving 112 patients (71 men, 41 women) who were followed for 3.5 years. Measurements included blood pressure, blood glucose, lipids, smoking, body mass index (BMI) and HOMA-Ir Vascular TOD included carotid intima-media thickness (IMT), pulse wave velocity (PWV) and ankle/brachial index (ABI). Cardiac TOD included Cornell voltage-duration product and Sokolow. Renal TOD included creatinine, glomerular filtration and albumin/creatinine ratio. The IMT increased in both genders. Each year, the IMT increased 0.005 mm in men and 0.011 in women and the PWV 0.024 and 0.020 m/sec, respectively. The highest increase was in women with type 2 diabetes mellitus, who had an increase in TOD carotid (40%), PWV (24%) and renal TOD (20 %). Multiple regression analysis, after adjusting for age and gender, showed a negative association between duration since diabetes diagnosis and ABI (β = -0.006; p = 0.017) and between BMI and glomerular filtration (β = -0.813; p = 0.014). HbA1c was positively associated with PWV (β = 0.501; p = 0.014). This study showed that the progression of vascular and renal TOD differs by gender. The increase in vascular and renal TOD was higher in women, especially in diabetic women. The PWV increase showed a positive association with mean HbA1c levels during the follow-up. Glomerular filtration was associated with BMI and the ABI was associated with duration since type 2 diabetes mellitus diagnosis. Clinical Trials.gov Identifier NCT01065155.

  17. Use of non-quarter-wave designs to increase the damage resistance of reflectors at 532 and 1064 nanometers

    International Nuclear Information System (INIS)

    Gill, D.H.; Newnam, B.E.; McLeod, J.

    1977-01-01

    The damage resistance of multilayer dielectric laser reflectors has been increased by using non-quarter-wave thicknesses for the top few layers. These designs minimize the standing-wave electric field in the high-index layers, which are generally the weaker layers. Algebraic equations have been derived for optimum film thicknesses and for the resulting peak electric fields. Five sets of reflectors for 532 and 1064 nm were fabricated according to these designs by two vendors using two different material combinations. Each set contained one reflector of standard all-quarter-wave design and three reflectors each with a different number of modified layers. The damage thresholds of the modified designs were found to be higher than the all-quarter-wave designs, in some cases by a factor greater than 2. The damage thresholds have been analyzed and explained in terms of standing-wave electric field patterns

  18. Increasing insulin resistance accentuates the effect of triglyceride-associated loci on serum triglycerides during 5 years

    DEFF Research Database (Denmark)

    Justesen, Johanne M; Andersson, Ehm Astrid; Allin, Kristine H

    2016-01-01

    Blood concentrations of triglycerides are influenced by genetic factors as well as a number of environmental factors, including adiposity and glucose homeostasis. The aim was to investigate the association between a serum triglyceride weighted genetic risk score (wGRS) and changes in fasting serum...... triglyceride level over 5 years and to test whether the effect of the wGRS was modified by 5 year changes of adiposity, insulin resistance, and lifestyle factors. A total of 3,474 nondiabetic individuals from the Danish Inter99 cohort participated in both the baseline and 5 year follow-up physical examinations...... and had information on the wGRS comprising 39 genetic variants. In a linear regression model adjusted for age, sex, and baseline serum triglyceride, the wGRS was associated with increased serum triglyceride levels over 5 years [per allele effect = 1.3% (1.0-1.6%); P = 1.0 × 10(-17)]. This triglyceride...

  19. p-Glycoprotein ABCB5 and YB-1 expression plays a role in increased heterogeneity of breast cancer cells: correlations with cell fusion and doxorubicin resistance

    International Nuclear Information System (INIS)

    Yang, Ji Yeon; Ha, Seon-Ah; Yang, Yun-Sik; Kim, Jin Woo

    2010-01-01

    Cancer cells recurrently develop into acquired resistance to the administered drugs. The iatrogenic mechanisms of induced chemotherapy-resistance remain elusive and the degree of drug resistance did not exclusively correlate with reductions of drug accumulation, suggesting that drug resistance may involve additional mechanisms. Our aim is to define the potential targets, that makes drug-sensitive MCF-7 breast cancer cells turn to drug-resistant, for the anti-cancer drug development against drug resistant breast cancer cells. Doxorubicin resistant human breast MCF-7 clones were generated. The doxorubicin-induced cell fusion events were examined. Heterokaryons were identified and sorted by FACS. In the development of doxorubicin resistance, cell-fusion associated genes, from the previous results of microarray, were verified using dot blot array and quantitative RT-PCR. The doxorubicin-induced expression patterns of pro-survival and pro-apoptotic genes were validated. YB-1 and ABCB5 were up regulated in the doxorubicin treated MCF-7 cells that resulted in certain degree of genomic instability that accompanied by the drug resistance phenotype. Cell fusion increased diversity within the cell population and doxorubicin resistant MCF-7 cells emerged probably through clonal selection. Most of the drug resistant hybrid cells were anchorage independent. But some of the anchorage dependent MCF-7 cells exhibited several unique morphological appearances suggesting minor population of the fused cells maybe de-differentiated and have progenitor cell like characteristics. Our work provides valuable insight into the drug induced cell fusion event and outcome, and suggests YB-1, GST, ABCB5 and ERK3 could be potential targets for the anti-cancer drug development against drug resistant breast cancer cells. Especially, the ERK-3 serine/threonine kinase is specifically up-regulated in the resistant cells and known to be susceptible to synthetic antagonists

  20. Increased minimal vascular resistance and arteriolar hyalinosis in skin on the leg in insulin-dependent diabetic patients

    DEFF Research Database (Denmark)

    Kastrup, J; Nørgaard, T; Parving, H H

    1987-01-01

    Minimal vascular resistance (MVR) was determined in a paralysed cutaneous vascular bed at the dorsum of the foot in diabetic patients. Twelve long-term insulin-dependent diabetic (IDDM) patients with and nine short-term IDDM patients without nephropathy and retinopathy and eight control subjects......-wise increases of external counter pressure. The MVR was calculated from the reciprocal of the slope of the relationship between blood flow and applied pressure. The MVR was significantly increased in diabetic patients with (mean: 9.3 mmHg ml-1.100 g.min) and without nephropathy and retinopathy (8.5 mmHg ml-1.......100 g.min) compared with non-diabetic subjects (5.2 mmHg ml-1.100 g.min) (p less than 0.001 and p less than 0.005, respectively). Diabetic microangiopathy (increased hyalinosis of the basement membranes in the terminal arterioles) was found in skin biopsies in nine of the 12 long-term IDDM patients...

  1. SCIENTIFIC-METHODICAL PREREQUISITES FOR DEVELOPMENT OF THE STEEL COMPOSITIONS FOR INCREASE OF RESISTANCE OF HIGH-LOADED STAMPS OF COLD DEFORMATION

    Directory of Open Access Journals (Sweden)

    V. N. Fedulov

    2005-01-01

    Full Text Available The basis of perfecting of the known steels composition with the purpose of using for solving of concrete production problem, in particular increase of instrument resistance, are examined in the article.

  2. Mark Kostabi soovib muuta inimesi õnnelikumaks / Kalev Mark Kostabi

    Index Scriptorium Estoniae

    Kostabi, Kalev Mark, 1960-

    2008-01-01

    Kalev Mark Kostabi oma sisekujunduslikest eelistustest, ameeriklaste ja itaallaste kodude sisekujunduse erinevustest, kunstist kui ruumikujunduse ühest osast, oma New Yorgi ja Rooma korterite kujundusest

  3. Increased Muscular 5α-Dihydrotestosterone in Response to Resistance Training Relates to Skeletal Muscle Mass and Glucose Metabolism in Type 2 Diabetic Rats

    OpenAIRE

    Horii, Naoki; Sato, Koji; Mesaki, Noboru; Iemitsu, Motoyuki

    2016-01-01

    Regular resistance exercise induces skeletal muscle hypertrophy and improvement of glycemic control in type 2 diabetes patients. Administration of dehydroepiandrosterone (DHEA), a sex steroid hormone precursor, increases 5?-dihydrotestosterone (DHT) synthesis and is associated with improvements in fasting blood glucose level and skeletal muscle hypertrophy. Therefore, the aim of this study was to investigate whether increase in muscle DHT levels, induced by chronic resistance exercise, can co...

  4. Increased CD19+CD24+CD27+ B regulatory cells are associated with insulin resistance in patients with type I Hashimoto's thyroiditis.

    Science.gov (United States)

    Yang, Min; Du, Changji; Wang, Yinping; Liu, Jun

    2017-06-01

    Hashimoto's thyroiditis (HT) is characterized by dysregulated immune responses and is commonly associated with insulin resistance. However, the mechanism of insulin resistance in HT remains to be fully elucidated. The aim of the present study was to investigate the correlation between the percentage of B regulatory lymphocytes (Bregs) and insulin resistance in patients with HT but with normal thyroid function (type I). A total of 59 patients with type I HT and 38 healthy volunteers were enrolled in the study. An oral glucose tolerance test was performed to measure insulin secretion and assess β‑cell functions. Flow cytometry was performed to examine the percentages of lymphocyte populations. The patients with HT exhibited normal fasting and postprandial glucose and fasting insulin secretion, but increased secretion of early‑phase and total insulin. The patients with HT also had insufficient β‑cell compensation for insulin resistance, indicated by a reduced disposition index, in the fasting state. An elevation in the percentage of CD19+CD24+CD27+ Bregs was also observed, which correlated positively with insulin secretion and insulin resistance in the fasting state. The patients with type I HT had postprandial insulin resistance and insufficient β‑cell compensation for fasting insulin resistance. Therefore, the increase in CD19+CD24+CD27+ Bregs was closely associated with fasting insulin secretion. These results provide novel insight into the mechanism of insulin resistance in HT.

  5. Sulfamethoxazole and COD increase abundance of sulfonamide resistance genes and change bacterial community structures within sequencing batch reactors.

    Science.gov (United States)

    Guo, Xueping; Pang, Weihai; Dou, Chunling; Yin, Daqiang

    2017-05-01

    The abundant microbial community in biological treatment processes in wastewater treatment plants (WWTPs) may potentially enhance the horizontal gene transfer of antibiotic resistance genes with the presence of antibiotics. A lab-scale sequencing batch reactor was designed to investigate response of sulfonamide resistance genes (sulI, sulII) and bacterial communities to various concentrations of sulfamethoxazole (SMX) and chemical oxygen demand (COD) of wastewater. The SMX concentrations (0.001 mg/L, 0.1 mg/L and 10 mg/L) decreased with treatment time and higher SMX level was more difficult to remove. The presence of SMX also significantly reduced the removal efficiency of ammonia nitrogen, affecting the normal function of WWTPs. All three concentrations of SMX raised both sulI and sulII genes with higher concentrations exhibiting greater increases. The abundance of sul genes was positive correlated with treatment time and followed the second-order reaction kinetic model. Interestingly, these two genes have rather similar activity. SulI and sulII gene abundance also performed similar response to COD. Simpson index and Shannon-Weiner index did not show changes in the microbial community diversity. However, the 16S rRNA gene cloning and sequencing results showed the bacterial community structures varied during different stages. The results demonstrated that influent antibiotics into WWTPs may facilitate selection of ARGs and affect the wastewater conventional treatment as well as the bacteria community structures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Cisplatin-resistant lung cancer cell-derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100-5p-dependent manner.

    Science.gov (United States)

    Qin, Xiaobing; Yu, Shaorong; Zhou, Leilei; Shi, Meiqi; Hu, Yong; Xu, Xiaoyue; Shen, Bo; Liu, Siwen; Yan, Dali; Feng, Jifeng

    2017-01-01

    Exosomes derived from lung cancer cells confer cisplatin (DDP) resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP) was established. Microarray was used to analyze microRNA (miRNA) expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100-5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100-5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR) expression was reverse regulated by miR-100-5p. Exosomes confer recipient cells' resistance to DDP in an exosomal miR-100-5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells' sensitivity to DDP in exosomal miR-100-5p-dependent manner. Our study provides new insights into the molecular mechanism of DDP resistance in lung cancer.

  7. 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.

  8. Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Nathan L. Price

    2018-02-01

    Full Text Available While therapeutic modulation of miRNAs provides a promising approach for numerous diseases, the promiscuous nature of miRNAs raises concern over detrimental off-target effects. miR-33 has emerged as a likely target for treatment of cardiovascular diseases. However, the deleterious effects of long-term anti-miR-33 therapies and predisposition of miR-33−/− mice to obesity and metabolic dysfunction exemplify the possible pitfalls of miRNA-based therapies. Our work provides an in-depth characterization of miR-33−/− mice and explores the mechanisms by which loss of miR-33 promotes insulin resistance in key metabolic tissues. Contrary to previous reports, our data do not support a direct role for SREBP-1-mediated lipid synthesis in promoting these effects. Alternatively, in adipose tissue of miR-33−/− mice, we observe increased pre-adipocyte proliferation, enhanced lipid uptake, and impaired lipolysis. Moreover, we demonstrate that the driving force behind these abnormalities is increased food intake, which can be prevented by pair feeding with wild-type animals.

  9. Ultrafine Ceramic Grains Embedded in Metallic Glass Matrix: Achieving Superior Wear Resistance via Increase in Both Hardness and Toughness.

    Science.gov (United States)

    Yang, Lina; Wen, Mao; Dai, Xuan; Cheng, Gang; Zhang, Kan

    2018-05-09

    As structural materials, crystalline or metallic glass materials have attracted scientific and practical interests. However, some mechanisms involving critical size and shear bands have adverse effects on their mechanical properties. Here, we counter these two effects by introducing a special structure with ultrafine ceramic grains (with a diameter of ∼2.0 nm) embedded into a metallic glass matrix, wherein the grains are mainly composed of a Ta-W-N solid solution structure in nature, surrounded by a W-based amorphous matrix that contains Ta and N atoms. Such a structure is in situ formed during preparation, which combines the merits of both phases to achieve simultaneous increase in hardness and toughness relative to references (pure TaN and W) and thus superior wear resistance. Even more remarkable, a favorable variation of increased hardness but reduced elasticity modulus can be induced by this structure. Intrinsically, ultrafine ceramic grains (free of dislocations), embedded in the metallic glass matrix, could prevent shear band propagation within the glass matrix and further improve the hardness of the matrix material. In return, such glass matrix allows for stiffness neutralization and structural relaxation to reduce the elasticity modulus of ceramic grains. This study will offer a new guidance to fabricate ultrahigh-performance metal-based composites.

  10. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance.

    Directory of Open Access Journals (Sweden)

    José María Moreno-Navarrete

    Full Text Available Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity. Circulating zonulin increased with body mass index (BMI, waist to hip ratio (WHR, fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002 contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01 contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase.

  11. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance.

    Science.gov (United States)

    Moreno-Navarrete, José María; Sabater, Mònica; Ortega, Francisco; Ricart, Wifredo; Fernández-Real, José Manuel

    2012-01-01

    Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity). Circulating zonulin increased with body mass index (BMI), waist to hip ratio (WHR), fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002) contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01) contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase.

  12. Exposure to high hydrostatic pressure rapidly selects for increased RpoS activity and general stress-resistance in Escherichia coli O157:H7.

    Science.gov (United States)

    Vanlint, Dietrich; Rutten, Nele; Govers, Sander K; Michiels, Chris W; Aertsen, Abram

    2013-04-15

    Exposure to high hydrostatic pressure (HHP) is increasingly being used in food preservation as a non-thermal pasteurization process, and its further implementation necessitates a more thorough understanding of bacterial resistance development and intraspecies variability with regard to inactivation by HHP. In this report, we discovered that exposure to high hydrostatic pressure stress can rapidly select for strongly increased RpoS activity in a hypersensitive Escherichia coli O157:H7 strain (ATCC 43888), leading to a simultaneous increase in HHP and heat resistance. Moreover, the level of RpoS activity correlated well with the original hypersensitivity and the extent of acquired HHP resistance, and extremely HHP-resistant mutants of ATCC 43888 clearly incurred a number of additional RpoS-dependent phenotypes. These findings suggest that implementation of novel processing techniques in the food production chain can readily affect the physiology of food-borne pathogens. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Cavernous hemangioma presenting marked hyperostosis

    International Nuclear Information System (INIS)

    Kobata, Hitoshi; Miyake, Hiroji; Kitamura, Junji; Kajikawa, Hiroshi; Ohta, Tomio

    1988-01-01

    The authors report here a case of hemangioma of the left parietal bone which presented headache and papilledema. This patient is a 37-year-old female who had, prior to admission, complained of increasing headache for one year and blurred vision for three months. She had no history of head injury. Local physical examinations revealed a slight bulging in her left parietal region which was insensitive to palpation and not adherent to the overlying scalp. Neurological examinations revealed bilateral papilledema and an incongruous bitemporal upper quadrant defect in the visual field. All the other neurological and laboratory data were normal. A plain skull roentogenogram showed a 9 x 9 cm osteolytic and characteristic honeycomb lesion in the parietal region. Systemic bone survey revealed a similar lesion in the right tibia which was not histologically examined. A marked accumulation of isotopes was detected on the bone scintigrams at both lesions. Selective external carotid angiograms demonstrated a tumor stain fed by the superficial temporal, occipital, and middle meningial arteries. CT scans of the brain and skull clearly showed a local thickening of and structural changes in the skull bone and also a mass effect on the brain and lateral ventricle. The lesioned bone was removed en bloc and replaced by an artificial bone. It was highly vascular, but not adherent to the overlying dura. The post-operative course was uneventful, and the headache and papilledema disappeared. Hemangioma of the skull presenting marked hyperostosis, as reported above, seems to be rare. In addition, in this case, skeletal angioma without any clinical manifestation was detected. Clinical and radiological pictures of the hemangioma of the skull and other bones were briefly discussed. (author)

  14. Long-term field application of sewage sludge increases the abundance of antibiotic resistance genes in soil.

    Science.gov (United States)

    Chen, Qinglin; An, Xinli; Li, Hu; Su, Jianqiang; Ma, Yibing; Zhu, Yong-Guan

    2016-01-01

    Sewage sludge and manure are common soil amendments in crop production; however, their impact on the abundance and diversity of the antibiotic resistome in soil remains elusive. In this study, by using high-throughput sequencing and high-throughput quantitative PCR, the patterns of bacterial community and antibiotic resistance genes (ARGs) in a long-term field experiment were investigated to gain insights into these impacts. A total of 130 unique ARGs and 5 mobile genetic elements (MGEs) were detected and the long-term application of sewage sludge and chicken manure significantly increased the abundance and diversity of ARGs in the soil. Genes conferring resistance to beta-lactams, tetracyclines, and multiple drugs were dominant in the samples. Sewage sludge or chicken manure applications caused significant enrichment of 108 unique ARGs and MGEs with a maximum enrichment of up to 3845 folds for mexF. The enrichment of MGEs suggested that the application of sewage sludge or manure may accelerate the dissemination of ARGs in soil through horizontal gene transfer (HGT). Based on the co-occurrence pattern of ARGs subtypes revealed by network analysis, aacC, oprD and mphA-02, were proposed to be potential indicators for quantitative estimation of the co-occurring ARGs subtypes abundance by power functions. The application of sewage sludge and manure resulted in significant increase of bacterial diversity in soil, Proteobacteria, Acidobacteria, Actinobacteria and Chloroflexi were the dominant phyla (>10% in each sample). Five bacterial phyla (Chloroflexi, Planctomycetes, Firmicutes, Gemmatimonadetes and Bacteroidetes) were found to be significantly correlated with the ARGs in soil. Mantel test and variation partitioning analysis (VPA) suggested that bacterial community shifts, rather than MGEs, is the major driver shaping the antibiotic resistome. Additionally, the co-occurrence pattern between ARGs and microbial taxa revealed by network analysis indicated that four

  15. Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner

    Directory of Open Access Journals (Sweden)

    Qin X

    2017-05-01

    Full Text Available Xiaobing Qin,1,2,* Shaorong Yu,1,3,* Leilei Zhou,1,4 Meiqi Shi,3 Yong Hu,1 Xiaoyue Xu,1 Bo Shen,1 Siwen Liu,1 Dali Yan,1 Jifeng Feng1,3 1Research Center for Clinical Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 2Department of Oncology, Xuzhou First People’s Hospital, Xuzhou, 3Department of Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 4Department of Oncology, Affiliated Huai’an Hospital of Nanjing Medical University, Huai’an, Jiangsu, China *These authors have contributed equally to this work Abstract: Exosomes derived from lung cancer cells confer cisplatin (DDP resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP was established. Microarray was used to analyze microRNA (miRNA expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100–5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100–5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR expression was reverse regulated by miR-100–5p. Exosomes confer recipient cells’ resistance to DDP in an exosomal miR-100–5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells’ sensitivity to DDP in exosomal miR-100–5p

  16. Acquired resistance to HSP90 inhibitor 17-AAG and increased metastatic potential are associated with MUC1 expression in colon carcinoma cells.

    Science.gov (United States)

    Liu, Xin; Ban, Li-Li; Luo, Gang; Li, Zhi-Yao; Li, Yun-Feng; Zhou, Yong-Chun; Wang, Xi-Cai; Jin, Cong-Guo; Ye, Jia-Gui; Ma, Ding-Ding; Xie, Qing; Huang, You-Guang

    2016-06-01

    Heat shock protein 90 (HSP90) is a molecular chaperone required for the stability and function of many proteins. The chaperoning of oncoproteins by HSP90 enhances the survival, growth, and invasive potential of cancer cells. HSP90 inhibitors are promising new anticancer agents, in which the benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in clinical evaluation. However, the implications of acquired resistance to this class of drug remain largely unexplored. In the present study, we have generated isogenic human colon cancer cell lines that are resistant to 17-AAG by continued culturing in the compound. Cross-resistance was found with another HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin. The resistant cells showed obvious morphology changes with a metastatic phenotype and significant increases in migration and adhesion to collagens. Western blotting analysis of epithelial-mesenchymal transition molecular markers found that expression of E-cadherin downregulated, whereas expression of N-cadherin and β-catenin upregulated in the resistant cells. Mucin 1 (MUC1) has been reported to mediate metastasis as well as chemical resistance in many cancers. Here, we found that MUC1 expression was significantly elevated in the acquired drug resistance cells. 17-AAG treatment could decrease MUC1 more in parental cells than in acquired 17-AAG-resistant cells. Further study found that knockdown of MUC1 expression by small interfering RNA could obviously re-sensitize the resistant cells to 17-AAG treatment, and decrease the cell migration and adhesion. These were coupled with a downregulation in N-cadherin and β-catenin. The results indicate that HSP90 inhibitor therapies in colon carcinomas could generate resistance and increase metastatic potential that might mediated by upregulation of MUC1 expression. Findings from this study further our understanding of the potential clinical effects of HSP90-directed therapies in

  17. Natural dissolved humic substances increase the lifespan and promote transgenerational resistance to salt stress in the cladoceran Moina macrocopa.

    Science.gov (United States)

    Suhett, Albert L; Steinberg, Christian E W; Santangelo, Jayme M; Bozelli, Reinaldo L; Farjalla, Vinicius F

    2011-07-01

    Evidence has accumulated that humic substances (HS) are not inert biogeochemicals. Rather, they cause stress symptoms and may modulate the life history of aquatic organisms. Nevertheless, it is still not clear how HS interact with additional stressors and if their effects are transgenerational. We tested the interactive effects of HS and salt to cladocerans, discussing their consequences for the persistence in fluctuating environments, such as coastal lagoons. We used life-table experiments to test the effects of natural HS from a polyhumic coastal lagoon (0, 5, 10, 20, 50, and 100 mg dissolved organic carbon (DOC) L(-1)) on the life-history of the cladoceran Moina macrocopa. We further tested the effects of HS (10 mg DOC L(-1)), within and across generations, on the resistance of M. macrocopa to salt stress (5.5 g L(-1)). HS at 5-20 mg DOC L(-1) extended the mean lifespan of M. macrocopa by ~30%. HS also increased body length at maturity by ~4% at 5-50 mg DOC L(-1) and stimulated male offspring production at all tested concentrations. Exposure to HS (even maternal only) alleviated the salt-induced reduction of somatic growth. Co-exposure to HS increased body volume by 12-22% relative to salt-only treatments, while pre-exposure to HS increased body volume by 40-56% in treatments with salt presence, when compared to non-pre-exposed animals. HS at environmentally realistic concentrations, by acting as mild chemical stressors, modify crucial life-history traits of M. macrocopa, favoring its persistence in fluctuating environments. Some of the effects of HS are even transgenerational.

  18. Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil.

    Science.gov (United States)

    Magalhães, Lucas S; Bomfim, Lays Gs; Mota, Sthefanne G; Cruz, Geydson S; Corrêa, Cristiane B; Tanajura, Diego M; Lipscomb, Michael W; Borges, Valéria M; Jesus, Amélia R de; Almeida, Roque P de; Moura, Tatiana R de

    2018-02-01

    BACKGROUND Treatment-refractory visceral leishmaniasis (VL) has become an important problem in many countries. OBJECTIVES We evaluated the antimony-resistance mechanisms of Leishmania infantum isolated from VL patients refractory or responsive to treatment with pentavalent antimony. METHODS Strains isolated from antimony-refractory patients (in vitro antimony-resistant isolates) and antimony-responsive patients (in vitro antimony-sensitive isolates) were examined. Morphological changes were evaluated by transmission electron microscopy after trivalent antimony exposure. P-glycoprotein (P-gp) efflux pump activity was evaluated using the pump-specific inhibitor verapamil hydrochloride, and the role of thiol in trivalent antimony resistance was investigated using the enzymatic inhibitor L-buthionine sulfoximine. FINDINGS Antimony treatment induced fewer alterations in the cellular structure of L. infantum resistant isolates than in that of sensitive isolates. P-gp efflux activity was not involved in antimony resistance in these isolates. Importantly, the resistant isolates contained higher levels of thiol compared to the sensitive isolates, and inhibition of thiol synthesis in the resistant isolates recovered their sensitivity to trivalent antimony treatment, and enhanced the production of reactive oxygen species in promastigotes exposed to the drug. MAIN CONCLUSIONS Our results demonstrate that isolates from patients with antimony-refractory VL exhibited higher thiol levels than antimony-sensitive isolates. This indicates that redox metabolism plays an important role in the antimony-resistance of New World VL isolates.

  19. Enhanced pest resistance and increased phenolic production in maize callus transgenically expressing a maize chalcone isomerase -3 like gene

    Science.gov (United States)

    Significant losses in maize production are due to damage by insects and ear rot fungi. A gene designated as chalcone-isomerase-like, located in a quantitative trait locus for resistance to Fusarium ear rot fungi, was cloned from a Fusarium ear rot resistant inbred and transgenically expressed in mai...

  20. Increased autophagy in CD4(+) T cells of rheumatoid arthritis patients results in T-cell hyperactivation and apoptosis resistance

    NARCIS (Netherlands)

    van Loosdregt, Jorg; Rossetti, Maura; Spreafico, Roberto; Moshref, Maryam; Olmer, Merissa; Williams, Gary W; Kumar, Pavanish; Copeland, Dana; Pischel, Ken; Lotz, Martin; Albani, Salvatore

    2016-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease hallmarked by aberrant cellular homeostasis, resulting in hyperactive CD4(+) T cells that are more resistant to apoptosis. Both hyperactivation and resistance to apoptosis may contribute to the pathogenicity of CD4(+) T cells in the autoimmune

  1. SIRT1/PGC1a-dependent increase in oxidative phosphorylation supports chemotherapy resistance of colon cancer

    NARCIS (Netherlands)

    Vellinga, T.T.; Borovski, T.; Boer, de V.C.J.; Kranenburg, O.

    2015-01-01

    PURPOSE:
    Chemotherapy treatment of metastatic colon cancer ultimately fails due to development of drug resistance. Identification of chemotherapy-induced changes in tumor biology may provide insight into drug resistance mechanisms.
    EXPERIMENTAL DESIGN:
    We studied gene expression

  2. Identification marking by means of laser peening

    Science.gov (United States)

    Hackel, Lloyd A.; Dane, C. Brent; Harris, Fritz

    2002-01-01

    The invention is a method and apparatus for marking components by inducing a shock wave on the surface that results in an indented (strained) layer and a residual compressive stress in the surface layer. One embodiment of the laser peenmarking system rapidly imprints, with single laser pulses, a complete identification code or three-dimensional pattern and leaves the surface in a state of deep residual compressive stress. A state of compressive stress in parts made of metal or other materials is highly desirable to make them resistant to fatigue failure and stress corrosion cracking. This process employs a laser peening system and beam spatial modulation hardware or imaging technology that can be setup to impress full three dimensional patterns into metal surfaces at the pulse rate of the laser, a rate that is at least an order of magnitude faster than competing marking technologies.

  3. Coexistence of insulin resistance and increased glucose tolerance in pregnant rats: a physiological mechanism for glucose maintenance.

    Science.gov (United States)

    Carrara, Marcia Aparecida; Batista, Márcia Regina; Saruhashi, Tiago Ribeiro; Felisberto, Antonio Machado; Guilhermetti, Marcio; Bazotte, Roberto Barbosa

    2012-06-06

    The contribution of insulin resistance (IR) and glucose tolerance to the maintenance of blood glucose levels in non diabetic pregnant Wistar rats (PWR) was investigated. PWR were submitted to conventional insulin tolerance test (ITT) and glucose tolerance test (GTT) using blood sample collected 0, 10 and 60 min after intraperitoneal insulin (1 U/kg) or oral (gavage) glucose (1g/kg) administration. Moreover, ITT, GTT and the kinetics of glucose concentration changes in the fed and fasted states were evaluated with a real-time continuous glucose monitoring system (RT-CGMS) technique. Furthermore, the contribution of the liver glucose production was investigated. Conventional ITT and GTT at 0, 7, 14 and 20 days of pregnancy revealed increased IR and glucose tolerance after 20 days of pregnancy. Thus, this period of pregnancy was used to investigate the kinetics of glucose changes with the RT-CGMS technique. PWR (day 20) exhibited a lower (pinsulin sensitivity and/or glucose tolerance during late pregnancy. In contrast to the general view that IR is a pathological process associated with gestational diabetes, a certain degree of IR may represent an important physiological mechanism for blood glucose maintenance during fasting. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Overexpressing the Sedum alfredii Cu/Zn Superoxide Dismutase Increased Resistance to Oxidative Stress in Transgenic Arabidopsis

    Directory of Open Access Journals (Sweden)

    Zhen Li

    2017-06-01

    Full Text Available Superoxide dismutase (SOD is a very important reactive oxygen species (ROS-scavenging enzyme. In this study, the functions of a Cu/Zn SOD gene (SaCu/Zn SOD, from Sedum alfredii, a cadmium (Cd/zinc/lead co-hyperaccumulator of the Crassulaceae, was characterized. The expression of SaCu/Zn SOD was induced by Cd stress. Compared with wild-type (WT plants, overexpression of SaCu/Zn SOD gene in transgenic Arabidopsis plants enhanced the antioxidative defense capacity, including SOD and peroxidase activities. Additionally, it reduced the damage associated with the overproduction of hydrogen peroxide (H2O2 and superoxide radicals (O2•-. The influence of Cd stress on ion flux across the root surface showed that overexpressing SaCu/Zn SOD in transgenic Arabidopsis plants has greater Cd uptake capacity existed in roots. A co-expression network based on microarray data showed possible oxidative regulation in Arabidopsis after Cd-induced oxidative stress, suggesting that SaCu/Zn SOD may participate in this network and enhance ROS-scavenging capability under Cd stress. Taken together, these results suggest that overexpressing SaCu/Zn SOD increased oxidative stress resistance in transgenic Arabidopsis and provide useful information for understanding the role of SaCu/Zn SOD in response to abiotic stress.

  5. Soil Hydrological Attributes of an Integrated Crop-Livestock Agroecosystem: Increased Adaptation through Resistance to Soil Change

    International Nuclear Information System (INIS)

    Liebig, M.A; Tanaka, D.L; Kronberg, S.L; Karn, J.F; Scholljegerdes, E.J

    2011-01-01

    Integrated crop-livestock systems have been purported to have significant agronomic and environmental benefits compared to specialized, single-enterprise production systems. However, concerns exist regarding the effect of livestock in integrated systems to cause soil compaction, thereby decreasing infiltration of water into soil. Such concerns are compounded by projections of more frequent high-intensity rainfall events from anticipated climate change, which would act to increase surface runoff and soil erosion. A study was conducted to evaluate the effects of residue management, frequency of hoof traffic, season, and production system (e.g., integrated annual cropping versus perennial grass) on infiltration rates from 2001 through 2008 in central North Dakota, USA. Imposed treatments had no effect on infiltration rate at three, six, and nine years after study establishment, implying that agricultural producers should not be concerned with inhibited infiltration in integrated annual cropping systems, where winter grazing is used. The use of no-till management, coupled with annual freeze/thaw and wet/dry cycles, likely conferred an inherent resistance to change in near-surface soil properties affecting soil hydrological attributes. Accordingly, caution should be exercised in applying these results to other regions or management systems.

  6. A multicopy phr-plasmid increases the ultraviolet resistance of a recA strain of Escherichia coli

    International Nuclear Information System (INIS)

    Yamamoto, K.; Satake, M.; Shinagawa, H.

    1984-01-01

    It has been previously reported that the ultraviolet sensitivity of recA strains of Escherichia coli in the dark is suppressed by a plasmid pKY1 which carries the phr gene, suggesting that this is due to a novel effect of photoreactivating enzyme (PRE) of E. coli in the dark. In this work, it is observed that an increase of UV-resistance by pKY1 in the dark is not apparent in strains with a mutation in either uvrA, uvrB, uvrC, lexA, recBC or recF. The sensitivity of recA lexA and recA recBC multiple mutants to UV is suppressed by the plasmid but that of recA uvrA, recA uvrB and recA uvrC is not. Host-cell reactivation of UV-irradiated lambda phage is slightly more efficient in the recA/pKY1 strain compared with the parental recA strain. On the other hand, the recA and recA/pKY1 strains do not differ significantly in the following properties: Hfr recombination, induction of lambda by UV, and mutagenesis. It is suggested that dark repair of PRE is correlated with its capacity of excision repair. (Auth.)

  7. Paclitaxel-resistant HeLa cells have up-regulated levels of reactive oxygen species and increased expression of taxol resistance gene 1.

    Science.gov (United States)

    Bi, Wenxiang; Wang, Yuxia; Sun, Gaoying; Zhang, Xiaojin; Wei, Yongqing; Li, Lu; Wang, Xiaoyuan

    2014-07-01

    This study is to establish a paclitaxel (PTX)-resistant human cervical carcinoma HeLa cell line (HeLa/PTX) and to investigate its redox characteristics and the expression of taxol resistance gene 1 (Txr1). HeLa cells were treated with PTX and effects of PTX on cell proliferation were detected through cell counting and the MTT assay. Levels of cellular reactive oxygen species (ROS), reduced glutathione (GSH), and oxidized glutathione (GSSG) as well as the ratio of GSH to GSSG were measured by the 2,7-difluorescein diacetate (DCFH-DA) method and the 5,5'dithiobis(2-nitrobenzoic acid) (DTNB) method. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined by the nitrite formation method, the molybdate colorimetric method, and the DTNB colorimetric method, respectively. The level of Txr1 mRNA was determined by real-time PCR. Compared with the regular HeLa cells, HeLa/PTX cells were larger in size and had more cytoplasmic granules. The population doubling time for HeLa/PTX cells was 1.32 times of that of HeLa cells (PHeLa/PTX cells showed stronger resistance to PTX than HeLa cells with a resistance index of 122.69. HeLa/PTX cells had higher levels of ROS (PHeLa cells. HeLa/PTX cells, with higher levels of ROS and Txr1 mRNA expression, are more resistant to PTX than HeLa cells.

  8. Evidence of Increased Antibiotic Resistance in Phylogenetically-Diverse Aeromonas Isolates from Semi-Intensive Fish Ponds Treated with Antibiotics.

    Science.gov (United States)

    Patil, Hemant J; Benet-Perelberg, Ayana; Naor, Alon; Smirnov, Margarita; Ofek, Tamir; Nasser, Ahmed; Minz, Dror; Cytryn, Eddie

    2016-01-01

    The genus Aeromonas is ubiquitous in aquatic environments encompassing a broad range of fish and human pathogens. Aeromonas strains are known for their enhanced capacity to acquire and exchange antibiotic resistance genes and therefore, are frequently targeted as indicator bacteria for monitoring antimicrobial resistance in aquatic environments. This study evaluated temporal trends in Aeromonas diversity and antibiotic resistance in two adjacent semi-intensive aquaculture facilities to ascertain the effects of antibiotic treatment on antimicrobial resistance. In the first facility, sulfadiazine-trimethoprim was added prophylactically to fingerling stocks and water column-associated Aeromonas were monitored periodically over an 11-month fish fattening cycle to assess temporal dynamics in taxonomy and antibiotic resistance. In the second facility, Aeromonas were isolated from fish skin ulcers sampled over a 3-year period and from pond water samples to assess associations between pathogenic strains to those in the water column. A total of 1200 Aeromonas isolates were initially screened for sulfadiazine resistance and further screened against five additional antimicrobials. In both facilities, strong correlations were observed between sulfadiazine resistance and trimethoprim and tetracycline resistances, whereas correlations between sulfadiazine resistance and ceftriaxone, gentamicin, and chloramphenicol resistances were low. Multidrug resistant strains as well as sul1, tetA , and intI1 gene-harboring strains were significantly higher in profiles sampled during the fish cycle than those isolated prior to stocking and these genes were extremely abundant in the pathogenic strains. Five phylogenetically distinct Aeromonas clusters were identified using partial rpoD gene sequence analysis. Interestingly, prior to fingerling stocking the diversity of water column strains was high, and representatives from all five clusters were identified, including an A. salmonicida

  9. Evidence of increased antibiotic resistance in phylogenetically-diverse Aeromonas isolates from semi-intensive fish ponds treated with antibiotics

    Directory of Open Access Journals (Sweden)

    Hemant J Patil

    2016-11-01

    Full Text Available The genus Aeromonas is ubiquitous in aquatic environments encompassing a broad range of fish and human pathogens. Aeromonas strains are known for their enhanced capacity to acquire and exchange antibiotic resistance genes and therefore, are frequently targeted as indicator bacteria for monitoring antimicrobial resistance in aquatic environments. This study evaluated temporal trends in Aeromonas diversity and antibiotic resistance in two adjacent semi-intensive aquaculture facilities to ascertain effects of antibiotic treatment on antimicrobial resistance. In the first facility, sulfadiazine-trimethoprim was added prophylactically upon fingerling stocking and water column-associated Aeromonas were monitored periodically over an eleven-month fish-fattening cycle to assess temporal dynamics in taxonomy and antibiotic resistance. In the second facility, Aeromonas were isolated from fish skin ulcers sampled over a three-year period and from pond water samples to assess associations between pathogenic strains to those in the water column. A total of 1200 Aeromonas spp. were isolated, initially screened for sulfadiazine resistance and further screened against five additional antibiotics. In both facilities, strong correlations were observed between sulfadiazine resistance and trimethoprim and tetracycline resistances, whereas correlations between sulfadiazine resistance and ceftriaxone, gentamycin and chloramphenicol resistances were low. Abundance of multi-drug resistant strains as well as sul1, tetA and intI1 gene-harboring strains was significantly higher in profiles sampled during the fish cycle than those isolated prior to stocking and these genes were extremely abundant in the pathogenic strains. Five phylogenetically-distinct Aeromonas clusters were revealed using partial rpoD gene sequence analysis. Interestingly, prior to fingerling stocking the diversity of water column strains was high, and representatives from all five clusters were

  10. Increased Muscular 5α-Dihydrotestosterone in Response to Resistance Training Relates to Skeletal Muscle Mass and Glucose Metabolism in Type 2 Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Naoki Horii

    Full Text Available Regular resistance exercise induces skeletal muscle hypertrophy and improvement of glycemic control in type 2 diabetes patients. Administration of dehydroepiandrosterone (DHEA, a sex steroid hormone precursor, increases 5α-dihydrotestosterone (DHT synthesis and is associated with improvements in fasting blood glucose level and skeletal muscle hypertrophy. Therefore, the aim of this study was to investigate whether increase in muscle DHT levels, induced by chronic resistance exercise, can contribute to skeletal muscle hypertrophy and concomitant improvement of muscular glucose metabolism in type 2 diabetic rats. Male 20-week-old type 2 diabetic rats (OLETF were randomly divided into 3 groups: sedentary control, resistance training (3 times a week on alternate days for 8 weeks, or resistance training with continuous infusion of a 5α-reductase inhibitor (n = 8 each group. Age-matched, healthy nondiabetic Long-Evans Tokushima Otsuka (LETO rats (n = 8 were used as controls. The results indicated that OLETF rats showed significant decrease in muscular DHEA, free testosterone, DHT levels, and protein expression of steroidogenic enzymes, with loss of skeletal muscle mass and hyperglycemia, compared to that of LETO rats. However, 8-week resistance training in OLETF rats significantly increased the levels of muscle sex steroid hormones and protein expression of steroidogenic enzymes with a concomitant increase in skeletal muscle mass, improved fasting glucose level, and insulin sensitivity index. Moreover, resistance training accelerated glucose transporter-4 (GLUT-4 translocation and protein kinase B and C-ζ/λ phosphorylation. Administering the 5α-reductase inhibitor in resistance-trained OLETF rats resulted in suppression of the exercise-induced effects on skeletal muscle mass, fasting glucose level, insulin sensitivity index, and GLUT-4 signaling, with a decline in muscular DHT levels. These findings suggest that resistance training

  11. TMPRSS2- driven ERG expression in vivo increases self-renewal and maintains expression in a castration resistant subpopulation.

    Directory of Open Access Journals (Sweden)

    Orla M Casey

    Full Text Available Genomic rearrangements commonly occur in many types of cancers and often initiate or alter the progression of disease. Here we describe an in vivo mouse model that recapitulates the most frequent rearrangement in prostate cancer, the fusion of the promoter region of TMPRSS2 with the coding region of the transcription factor, ERG. A recombinant bacterial artificial chromosome including an extended TMPRSS2 promoter driving genomic ERG was constructed and used for transgenesis in mice. TMPRSS2-ERG expression was evaluated in tissue sections and FACS-fractionated prostate cell populations. In addition to the anticipated expression in luminal cells, TMPRSS2-ERG was similarly expressed in the Sca-1(hi/EpCAM(+ basal/progenitor fraction, where expanded numbers of clonogenic self-renewing progenitors were found, as assayed by in vitro sphere formation. These clonogenic cells increased intrinsic self renewal in subsequent generations. In addition, ERG dependent self-renewal and invasion in vitro was demonstrated in prostate cell lines derived from the model. Clinical studies have suggested that the TMPRSS2-ERG translocation occurs early in prostate cancer development. In the model described here, the presence of the TMPRSS2-ERG fusion alone was not transforming but synergized with heterozygous Pten deletion to promote PIN. Taken together, these data suggest that one function of TMPRSS2-ERG is the expansion of self-renewing cells, which may serve as targets for subsequent mutations. Primary prostate epithelial cells demonstrated increased post transcriptional turnover of ERG compared to the TMPRSS2-ERG positive VCaP cell line, originally isolated from a prostate cancer metastasis. Finally, we determined that TMPRSS2-ERG expression occurred in both castration-sensitive and resistant prostate epithelial subpopulations, suggesting the existence of androgen-independent mechanisms of TMPRSS2 expression in prostate epithelium.

  12. Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Wang, G.; Thanos, P.K.; Cho, J. Kim, R.; Michaelides, M.; Primeaux, S.; Bray, G.; Wang, G.-J.; Volkow, N.D.

    2010-10-27

    Dopamine (DA) and DAD{sub 2} receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.

  13. Induction of resistance to gray mold with benzothiadiazole modifies amino acid profile and increases proanthocyanidins in grape: primary versus secondary metabolism.

    Science.gov (United States)

    Iriti, Marcello; Rossoni, Mara; Borgo, Michele; Ferrara, Luigia; Faoro, Franco

    2005-11-16

    Field treatments of grapevine (cv. Merlot) with the plant activator benzothiadiazole (BTH, 0.3 mM) induced resistance against gray mold caused by Botrytis cinerea. Both incidence and severity of the disease were reduced. The resistance was associated with an increase of total polyphenols in berry skins, in particular, the proanthocyanidin fraction, that increased up to 36%. The amino acid profile of leaves was also modified by treatments, particularly lysine, that augmented 4-fold. Other amino acids involved in resistance mechanisms to either biotic or abiotic stress increased as well. These results indicate that BTH treatments can be used to control gray mold, thereby limiting an excessive use of fungicides, and could be exploited to increase the content of micronutrients of high nutritional value, arising from both primary and secondary metabolisms.

  14. Differentiation-Associated Downregulation of Poly(ADP-Ribose Polymerase-1 Expression in Myoblasts Serves to Increase Their Resistance to Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Gábor Oláh

    Full Text Available Poly(ADP-ribose polymerase 1 (PARP-1, the major isoform of the poly (ADP-ribose polymerase family, is a constitutive nuclear and mitochondrial protein with well-recognized roles in various essential cellular functions such as DNA repair, signal transduction, apoptosis, as well as in a variety of pathophysiological conditions including sepsis, diabetes and cancer. Activation of PARP-1 in response to oxidative stress catalyzes the covalent attachment of the poly (ADP-ribose (PAR groups on itself and other acceptor proteins, utilizing NAD+ as a substrate. Overactivation of PARP-1 depletes intracellular NAD+ influencing mitochondrial electron transport, cellular ATP generation and, if persistent, can result in necrotic cell death. Due to their high metabolic activity, skeletal muscle cells are particularly exposed to constant oxidative stress insults. In this study, we investigated the role of PARP-1 in a well-defined model of murine skeletal muscle differentiation (C2C12 and compare the responses to oxidative stress of undifferentiated myoblasts and differentiated myotubes. We observed a marked reduction of PARP-1 expression as myoblasts differentiated into myotubes. This alteration correlated with an increased resistance to oxidative stress of the myotubes, as measured by MTT and LDH assays. Mitochondrial function, assessed by measuring mitochondrial membrane potential, was preserved under oxidative stress in myotubes compared to myoblasts. Moreover, basal respiration, ATP synthesis, and the maximal respiratory capacity of mitochondria were higher in myotubes than in myoblasts. Inhibition of the catalytic activity of PARP-1 by PJ34 (a phenanthridinone PARP inhibitor exerted greater protective effects in undifferentiated myoblasts than in differentiated myotubes. The above observations in C2C12 cells were also confirmed in a rat-derived skeletal muscle cell line (L6. Forced overexpression of PARP1 in C2C12 myotubes sensitized the cells to oxidant

  15. The impact of the increased use of piperacillin/tazobactam on the selection of antibiotic resistance among invasive Escherichia coli and Klebsiella pneumoniae isolates.

    Science.gov (United States)

    Lee, Jina; Oh, Chi Eun; Choi, Eun Hwa; Lee, Hoan Jong

    2013-08-01

    Increasing antimicrobial resistance is related to the selective pressure exerted by antibiotic usage. This study evaluated the impact of the increased use of piperacillin/tazobactam (TZP) on the selection of antibiotic resistance. From 1999 to 2010, Escherichia coli and Klebsiella pneumoniae invasive isolates obtained from hospitalized Korean children were analyzed in antibiotic susceptibility tests and subjected to characterization of the β-lactamase types. Antibiotic consumption data were also analyzed. Between January 1999 and December 2010, 409 invasive isolates of E. coli (n=170) and K. pneumoniae (n=239) were obtained. A rebound of extended-spectrum β-lactamase (ESBL) prevalence with an increase in total antibiotics was noted. Non-susceptibility to TZP was determined in 7.6% of E. coli isolates and 20.9% of K. pneumoniae isolates. Despite the increase in TZP usage, the overall prevalence of TZP resistance did not significantly increase over time, especially in E. coli. The mechanisms for TZP resistance included the presence of AmpC producers, possible TEM-1 hyperproducers, and multiple β-lactamases in individual organisms of a given isolate. Replacement of only the antibiotic class appears to be insufficient to control antibiotic resistance, and continued efforts to decrease overall antibiotic pressure are needed, especially in highly endemic situations. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  16. Selective breeding can increase resistance of Atlantic salmon to furunculosis, infectious salmon anaemia and infectious pancreatic necrosis

    DEFF Research Database (Denmark)

    Kjøglum, Sissel; Henryon, Mark; Aasmundstad, Torunn

    2008-01-01

    We reasoned that by challenging large numbers of Atlantic salmon families with the causative agents of furunculosis, infectious salmon anaemia (ISA) and infectious pancreatic necrosis (IPN), we could show unequivocally that resistance to these diseases expresses moderate-to-high levels of additive...... genetic variation, and that the resistances are weakly correlated genetically. We tested this reasoning by challenging Atlantic salmon from 920 (approximately) full-sib families with the causative agents of furunculosis and ISA, and fish from 265 of these families with the causative agent of IPN. Additive...... indicate that it should be relatively easy to improve resistance to the diseases simultaneously. We believe that there is now strong evidence that selectively breeding Atlantic salmon for resistance can be highly successful...

  17. Correlation between apramycin and gentamicin use in pigs and an increasing reservoir of gentamicin-resistant Escherichia coli

    DEFF Research Database (Denmark)

    Jensen, Vibeke Frøkjær; Jakobsen, Lotte; Emborg, Hanne-Dorthe

    2006-01-01

    Objectives: Resistance towards the veterinary drug apramycin can be caused by the aac(3)-IV gene, which also confers resistance towards the important human antibiotic gentamicin. The objectives of this study were to investigate the temporal occurrence and the genetic background of apramycin...... and gentamicin resistance in Escherichia coli strains from pork, healthy pigs and diagnostic submissions from pigs and to investigate potential relationships to the use of apramycin and gentamicin at farm and national levels. Methods: Data on Danish E. coli isolates from healthy pigs (indicator bacteria......), diagnostic submissions from pigs (clinical isolates) and pork were obtained from the national surveillance of antimicrobial resistance and from routine diagnostic laboratories. Antimicrobial consumption data were obtained from the Danish Medicines Agency (1997-2000) and from the VetStat database (2001...

  18. Increased plasma levels of FABP4 and PTEN is associated with more severe insulin resistance in women with gestational diabetes mellitus.

    Science.gov (United States)

    Li, Yuan-yuan; Xiao, Rui; Li, Cai-ping; Huangfu, Jian; Mao, Jiang-feng

    2015-02-08

    The aim of this study was to investigate the relationship between plasma fatty acid binding protein 4 (FABP4), phosphatase and tensin homolog (PTEN), and insulin resistance in patients with gestational diabetes mellitus (GDM). Plasma FABP4 and PTEN were determined by ELISA in GDM patients (GDM group, n=30) and in euglycemic pregnant women (control group, n=30). The clinical features, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles were compared between the 2 groups. The influence of risk factors on insulin resistance, including BMI, lipid profiles, FABP4, and PTEN, were further investigated by multiple-factor stepwise regression analysis. Higher levels of BMI, ΔBMI, triglyceride (TG), fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), fasting insulin, HOMA-IR, FABP4, PTEN, and lower level of high-density lipoprotein cholesterol (HDL-C) were found in the GDM patients than in the controls (all Pinsulin resistance. GDM patients have more severe insulin resistance compared to euglycemic pregnant women. Higher levels of plasma FABP4 and PTEN are associated with increased insulin resistance and may participate in the pathogenesis of insulin resistance during gestation.

  19. Rapid increase in resistance to third generation cephalosporins, imipenem and co-resistance in Klebsiella pneumoniae from isolated from 7,140 blood-cultures (2010-2014) using EARS-Net data in Spain.

    Science.gov (United States)

    Aracil-García, Belén; Oteo-Iglesias, Jesús; Cuevas-Lobato, Óscar; Lara-Fuella, Noelia; Pérez-Grajera, Isabel; Fernández-Romero, Sara; Pérez-Vázquez, María; Campos, José

    2017-10-01

    An analysis was made about the evolution of resistance to 3rd generation cephalosporins, imipenem, and other antibiotics in invasive isolates of Klebsiella pneumoniae (K. pneumoniae) according to the Spanish EARS-Net database (2010-2014). Forty-two hospitals from 16 Autonomous Communities with an approximate population coverage of 33% participated. A total 7,140 pneumoniae corresponding to the same number of patients were studied. Overall resistance percentages (I+R) were: cefotaxime 15.8%, ceftazidime 13.7%, imipenem 1.7%, ciprofloxacin 20.1%, tobramycin 14.1%, gentamicin 10.4%, and amikacin 1.9%. Resistance to 3rd generation cephalosporins increased from 9.8% (2010) to 19% (2014); to ciprofloxacin from 15.4% (2010) to 19.6% (2014); to gentamicin from 6.2% (2010) to 10.3% (2014) and to tobramycin from 7.1% (2010) to 14.2% (2014) (presistance to 3rd generation cephalosporins, ciprofloxacin, and aminoglycosides increased from 3.3% (2010) to 9.7% (2014) (pResistance to imipenem also increased from 0.27% (2010) to 3.46% (2014) (presistant to imipenem, of which 104 (86%) produced carbapenemases: 74 OXA-48, 14 VIM, 9 KPC (6 KPC-2 and 3 KPC-3), 6 IMP, and 1 GES. Over the 5 year period (2010-2014), resistance to 3rd generation cephalosporins in invasive K. pneumoniae in Spain has doubled. The combined resistance to 3rd generation cephalosporins, ciprofloxacin, and aminoglycosides has tripled, and imipenem resistance has increased almost 13 times, mostly due to the spread of carbapenemase-producing isolates. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. Increased anaerobic metabolism is a distinctive signature in a colorectal cancer cellular model of resistance to antiepidermal growth factor receptor antibody.

    Science.gov (United States)

    Monteleone, Francesca; Rosa, Roberta; Vitale, Monica; D'Ambrosio, Chiara; Succoio, Mariangela; Formisano, Luigi; Nappi, Lucia; Romano, Maria Fiammetta; Scaloni, Andrea; Tortora, Giampaolo; Bianco, Roberto; Zambrano, Nicola

    2013-03-01

    Cetuximab is a chimeric antibody approved for the treatment of metastatic colorectal cancer that selectively targets epidermal growth factor receptor (EGFR) signaling. Treatment efficacy with this drug is often impaired by acquired resistance and poor information has been accumulated on the mechanisms underlying such a phenomenon. By taking advantage of a syngenic cellular system of sensitivity and acquired resistance to anti-EGFR therapy in the colorectal carcinoma GEO cell line, we profiled protein expression differences between Cetuximab-sensitive and -resistant cells. Combined 2D DIGE and MS analyses revealed a main proteomic signature resulting from selective deregulation of various metabolic enzymes, including glucose-6-phosphate dehydrogenase, transketolase, lactate dehydrogenase B, and pyruvate dehydrogenase E1, which was also confirmed by Western blotting experiments. Lactate dehydrogenase B downregulation has been already related to an increased anaerobic utilization of glucose by tumor cells; accordingly, we verified that Cetuximab-resistant cells have a significantly higher production of lactate. Resistant cells also showed decreased nicotinamide adenine dinucleotide phosphate (NADPH) levels. Observed protein deregulations were not related to functional alterations of the hypoxia-inducible factor 1-associated pathways. Our data demonstrate that increased anaerobic metabolism is a prominent feature observed in the GEO syngenic model of acquired resistance to anti-EGFR therapy in colorectal cancer. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Civilsamfundets ABC: M for Marked

    DEFF Research Database (Denmark)

    Lund, Anker Brink; Meyer, Gitte

    2016-01-01

    Bogstaveligt talt: Hvad er civilsamfundet? Anker Brink Lund og Gitte Meyer fra CBS Center for Civil Society Studies gennemgår civilsamfundet bogstav for bogstav. Vi er nået til M for Marked.......Bogstaveligt talt: Hvad er civilsamfundet? Anker Brink Lund og Gitte Meyer fra CBS Center for Civil Society Studies gennemgår civilsamfundet bogstav for bogstav. Vi er nået til M for Marked....

  2. Marks on the petroleum fiscality

    International Nuclear Information System (INIS)

    2007-02-01

    This document offers some marks on the petroleum fiscality in France: the taxes as the 'accises' and the 'TVA', the part of the taxes in the sale price at the service station, the comparison with other countries of Europe, the tax revenues and the Government budget. It provides also marks on the fuels prices formation (margins), the world petroleum markets (supply and demand) and the part of the petroleum companies on the petroleum market. (A.L.B.)

  3. TRANSGENIC PLANTS OF RAPE (BRASSICA NAPUS L. WITH GENE OSMYB4 HAVE INCREASED RESISTANCE TO SALTS OF HEAVY METALS

    Directory of Open Access Journals (Sweden)

    Raldugina G.N.

    2012-08-01

    fact that at very high concentrations of salts non-transformed plants died after 12-13 days, whereas the transgenic oilseed rape remained alive long enough time. Thus, the incorporation of the plant gene transcription factor OSMYB4 increased the resistance of transgenic plants to the stress effect of HM.

  4. Pyrethroid resistance in Anopheles gambiae leads to increased susceptibility to the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana

    Directory of Open Access Journals (Sweden)

    Knols Bart GJ

    2010-06-01

    Full Text Available Abstract Background Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have previously examined the effects of entomopathogenic fungi against adult mosquitoes, most application methods used cannot be readily deployed in the field. Because the fungi are biological organisms it is important to test potential field application methods that will not adversely affect them. The two objectives of this study were to investigate any differences in fungal susceptibility between an insecticide-resistant and insecticide-susceptible strain of Anopheles gambiae sensu stricto, and to test a potential field application method with respect to the viability and virulence of two fungal species Methods Pieces of white polyester netting were dipped in Metarhizium anisopliae ICIPE-30 or Beauveria bassiana IMI391510 mineral oil suspensions. These were kept at 27 ± 1°C, 80 ± 10% RH and the viability of the fungal conidia was recorded at different time points. Tube bioassays were used to infect insecticide-resistant (VKPER and insecticide-susceptible (SKK strains of An. gambiae s.s., and survival analysis was used to determine effects of mosquito strain, fungus species or time since fungal treatment of the net. Results The resistant VKPER strain was significantly more susceptible to fungal infection than the insecticide-susceptible SKK strain. Furthermore, B. bassiana was significantly more virulent than M. anisopliae for both mosquito strains, although this may be linked to the different viabilities of these fungal species. The viability of both fungal species decreased significantly one day after application onto polyester netting when compared to the viability of conidia remaining in suspension. Conclusions The insecticide-resistant

  5. Pyrethroid resistance in Anopheles gambiae leads to increased susceptibility to the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana

    Science.gov (United States)

    2010-01-01

    Background Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have previously examined the effects of entomopathogenic fungi against adult mosquitoes, most application methods used cannot be readily deployed in the field. Because the fungi are biological organisms it is important to test potential field application methods that will not adversely affect them. The two objectives of this study were to investigate any differences in fungal susceptibility between an insecticide-resistant and insecticide-susceptible strain of Anopheles gambiae sensu stricto, and to test a potential field application method with respect to the viability and virulence of two fungal species Methods Pieces of white polyester netting were dipped in Metarhizium anisopliae ICIPE-30 or Beauveria bassiana IMI391510 mineral oil suspensions. These were kept at 27 ± 1°C, 80 ± 10% RH and the viability of the fungal conidia was recorded at different time points. Tube bioassays were used to infect insecticide-resistant (VKPER) and insecticide-susceptible (SKK) strains of An. gambiae s.s., and survival analysis was used to determine effects of mosquito strain, fungus species or time since fungal treatment of the net. Results The resistant VKPER strain was significantly more susceptible to fungal infection than the insecticide-susceptible SKK strain. Furthermore, B. bassiana was significantly more virulent than M. anisopliae for both mosquito strains, although this may be linked to the different viabilities of these fungal species. The viability of both fungal species decreased significantly one day after application onto polyester netting when compared to the viability of conidia remaining in suspension. Conclusions The insecticide-resistant mosquito strain was susceptible

  6. Increased Levels of Antinutritional and/or Defense Proteins Reduced the Protein Quality of a Disease-Resistant Soybean Cultivar.

    Science.gov (United States)

    Sousa, Daniele O B; Carvalho, Ana F U; Oliveira, José Tadeu A; Farias, Davi F; Castelar, Ivan; Oliveira, Henrique P; Vasconcelos, Ilka M

    2015-07-22

    The biochemical and nutritional attributes of two soybean (Glycine max (L.) Merr.) cultivars, one susceptible (Seridó) and the other resistant (Seridó-RCH) to stem canker, were examined to assess whether the resistance to pathogens was related to levels of antinutritional and/or defense proteins in the plant and subsequently affected the nutritional quality. Lectin, urease, trypsin inhibitor, peroxidase and chitinase activities were higher in the resistant cultivar. Growing rats were fed with isocaloric and isoproteic diets prepared with defatted raw soybean meals. Those on the Seridó-RCH diet showed the worst performance in terms of protein quality indicators. Based on regression analysis, lectin, trypsin inhibitor, peroxidase and chitinase appear to be involved in the resistance trait but also in the poorer nutritional quality of Seridó-RCH. Thus, the development of cultivars for disease resistance may lead to higher concentrations of antinutritional compounds, affecting the quality of soybean seeds. Further research that includes the assessment of more cultivars/genotypes is needed.

  7. [Transgenic wheat (Triticum aestivum L.) with increased resistance to the storage pest obtained by Agrobacterium tumefaciens--mediated].

    Science.gov (United States)

    Bi, Rui-Ming; Jia, Hai-Yan; Feng, De-Shun; Wang, Hong-Gang

    2006-05-01

    The transgenic wheat of improved resistance to the storage pest was production. We have introduced the cowpea trypsin inhibitor gene (CpTI) into cultured embryonic callus cells of immature embryos of wheat elite line by Agrobacterium-mediated method. Independent plantlets were obtained from the kanamycin-resistant calli after screening. PCR and real time PCR analysis, PCR-Southern and Southern blot hybridization indicated that there were 3 transgenic plants viz. transformed- I, II and III (T- I, T-II and T-III). The transformation frequencies were obviously affected by Agrobacterium concentration, the infection duration and transformation treatment. The segregations of CpTI in the transgenic wheat progenies were not easily to be elucidated, and some transgenic wheat lines (T- I and T-III) showed Mendelian segregations. The determinations of insect resistance to the stored grain insect of wheat viz. the grain moth (Sitotroga cerealella Olivier) indicated that the 3 transgenic wheat progeny seeds moth-resistance was improved significantly. The seed moth-eaten ratio of T- I, T-II, T-III and nontransformed control was 19.8%, 21.9%, 32.9% and 58.3% respectively. 3 transgenic wheat T1 PCR-positive plants revealed that the 3 transgenic lines had excellent agronomic traits. They supplied good germplasm resource of insect-resistance for wheat genetic improvement.

  8. Usage of the Heterologous Expression of the Antimicrobial Gene afp From Aspergillus giganteus for Increasing Fungal Resistance in Olive

    Science.gov (United States)

    Narvaez, Isabel; Khayreddine, Titouh; Pliego, Clara; Cerezo, Sergio; Jiménez-Díaz, Rafael M.; Trapero-Casas, José L.; López-Herrera, Carlos; Arjona-Girona, Isabel; Martín, Carmen; Mercado, José A.; Pliego-Alfaro, Fernando

    2018-01-01

    The antifungal protein (AFP) produced by Aspergillus giganteus, encoded by the afp gene, has been used to confer resistance against a broad range of fungal pathogens in several crops. In this research, transgenic olive plants expressing the afp gene under the control of the constitutive promoter CaMV35S were generated and their disease response against two root infecting fungal pathogens, Verticillium dahliae and Rosellinia necatrix, was evaluated. Embryogenic cultures derived from a mature zygotic embryo of cv. ‘Picual’ were used for A. tumefaciens transformation. Five independent transgenic lines were obtained, showing a variable level of afp expression in leaves and roots. None of these transgenic lines showed enhanced resistance to Verticillium wilt. However, some of the lines displayed a degree of incomplete resistance to white root rot caused by R. necatrix compared with disease reaction of non-transformed plants or transgenic plants expressing only the GUS gene. The level of resistance to this pathogen correlated with that of the afp expression in root and leaves. Our results indicate that the afp gene can be useful for enhanced partial resistance to R. necatrix in olive, but this gene does not protect against V. dahliae. PMID:29875785

  9. Preoperative Site Marking: Are We Adhering to Good Surgical Practice?

    Science.gov (United States)

    Bathla, Sonia; Chadwick, Michael; Nevins, Edward J; Seward, Joanna

    2017-06-29

    Wrong-site surgery is a never event and a serious, preventable patient safety incident. Within the United Kingdom, national guidance has been issued to minimize the risk of such events. The mandate includes preoperative marking of all surgical patients. This study aimed to quantify regional variation in practice within general surgery and opinions of the surgeons, to help guide the formulation and implementation of a regional general surgery preoperative marking protocol. A SurveyMonkey questionnaire was designed and distributed to 120 surgeons within the Mersey region, United Kingdom. This included all surgical trainees in Mersey (47 registrars, 56 core trainees), 15 consultants, and 2 surgical care practitioners. This sought to ascertain their routine practice and how they would choose to mark for 12 index procedures in general surgery, if mandated to do so. A total of 72 responses (60%) were obtained to the SurveyMonkey questionnaire. Only 26 (36.1%) said that they routinely marked all of their patients preoperatively. The operating surgeon marked the patient in 69% of responses, with the remainder delegating this task. Markings were visible after draping in only 55.6% of marked cases. Based on our findings, surgeons may not be adhering to "Good Surgical Practice"; practice is widely variable and surgeons are largely opposed and resistant to marking patients unless laterality is involved. We suggest that all surgeons need to be actively engaged in the design of local marking protocols to gain support, change practice, and reduce errors.

  10. Fractionated irradiation of H69 small-cell lung cancer cells causes stable radiation and drug resistance with increased MRP1, MRP2, and topoisomerase IIα expression

    International Nuclear Information System (INIS)

    Henness, Sheridan; Davey, Mary W.; Harvie, Rozelle M.; Davey, Ross A.

    2002-01-01

    Purpose: After standard treatment with chemotherapy and radiotherapy, small-cell lung cancer (SCLC) often develops resistance to both treatments. Our aims were to establish if fractionated radiation treatment alone would induce radiation and drug resistance in the H69 SCLC cell line, and to determine the mechanisms of resistance. Methods and Materials: H69 SCLC cells were treated with fractionated X-rays to an accumulated dose of 37.5 Gy over 8 months to produce the H69/R38 subline. Drug and radiation resistance was determined using the MTT (3,-4,5 dimethylthiazol-2,5 diphenyltetrazolium bromide) cell viability assay. Protein expression was analyzed by Western blot. Results: The H69/R38 subline was resistant to radiation (2.0 ± 0.2-fold, p<0.0001), cisplatin (14 ± 7-fold, p < 0.001), daunorubicin (6 ± 3-fold, p<0.05), and navelbine (1.7 ± 0.15-fold, p<0.02). This was associated with increased expression of the multidrug resistance-associated proteins, MRP1 and MRP2, and topoisomerase IIα and decreased expression of glutathione-S-transferase π (GSTπ) and bcl-2 and decreased cisplatin accumulation. Treatment with 4 Gy of X-rays produced a 66% decrease in MRP2 in the H69 cells with no change in the H69/R38 cells. This treatment also caused a 5-fold increase in topoisomerase IIα in the H69/R38 cells compared with a 1.5-fold increase in the H69 cells. Conclusions: Fractionated radiation alone can lead to the development of stable radiation and drug resistance and an altered response to radiation in SCLC cells

  11. Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability

    Directory of Open Access Journals (Sweden)

    Xiaolin Zhang

    2016-10-01

    Full Text Available Metronidazole (MNZ is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori. The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC, plays an important role in selecting or enriching resistant mutants and regulating therapeutic effects. A strategy to reduce the MPC that can not only effectively treat H. pylori but also prevent resistance mutations is needed. H. pylori is highly resistant to lysozyme. Lysozyme possesses a hydrolytic bacterial cell wall peptidoglycan and a cationic dependent mode. These effects can increase the permeability of bacterial cells and promote antibiotic absorption into bacterial cells. In this study, human lysozyme (hLYS was used to probe its effects on the integrity of the H. pylori outer and inner membranes using as fluorescent probe hydrophobic 1-N-phenyl-naphthylamine (NPN and the release of aspartate aminotransferase. Further studies using a propidium iodide staining method assessed whether hLYS could increase cell permeability and promote cell absorption. Finally, we determined the effects of hLYS on the bactericidal dynamics and MPC of MNZ in H. pylori. Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ for H. pylori, and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations.

  12. Elevated CO2 increases R gene-dependent resistance of Medicago truncatula against the pea aphid by up-regulating a heat shock gene.

    Science.gov (United States)

    Sun, Yucheng; Guo, Huijuan; Yuan, Erliang; Ge, Feng

    2018-03-01

    Resistance against pathogens and herbivorous insects in many plant results from the expression of resistance (R) genes. Few reports, however, have considered the effects of elevated CO 2 on R gene-based resistance in plants. The current study determined the responses of two near isogenic Medicago truncatula genotypes (Jester has an R gene and A17 does not) to the pea aphid and elevated CO 2 in open-top chambers in the field. Aphid abundance, mean relative growth rate and feeding efficiency were increased by elevated CO 2 on A17 plants but were reduced on Jester plants. According to proteomic and gene expression data, elevated CO 2 enhanced pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) but decreased the effector-triggered immunity (ETI) in aphid-infested A17 plants. For aphid-infested Jester plants, by contrast, elevated CO 2 enhanced the ETI-related heat shock protein (HSP) 90 and its co-chaperones, the jasmonic acid (JA) signaling pathway, and ubiquitin-mediated proteolysis. In a loss-of-function experiment, silencing of the HSP90 gene in Jester plants impaired the JA signaling pathway and ubiquitin-mediated proteolysis against the aphid under ambient CO 2 , and negated the increased resistance against the aphid under elevated CO 2 . Our results suggest that increases in expression of HSP90 are responsible for the enhanced resistance against the aphid under elevated CO 2 . © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  13. High serum resistin is associated with an increase in adiposity but not a worsening of insulin resistance in Pima Indians

    DEFF Research Database (Denmark)

    de Courten, Barbora; Degawa-Yamauchi, Mikako; Considine, Robert V

    2004-01-01

    Resistin is an adipokine with putative prodiabetogenic properties. Like other hormones secreted by adipose tissue, resistin is being investigated as a possible etiologic link between excessive adiposity and insulin resistance. Although there is growing evidence that circulating levels...... of this adipokine are proportional to the degree of adiposity, an effect on insulin resistance in humans remains unproven. To evaluate the relations among resistin, obesity, and insulin resistance, we measured fasting serum resistin levels in 113 nondiabetic (75-g oral glucose tolerance test) Pima Indians (ages 29...... +/- 7 years, body fat 31 +/- 8%, resistin 3.7 +/- 1.1 ng/ml [means +/- SD]), who were characterized for body composition (assessed by hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M; assessed by hyperinsulinemic clamp), basal hepatic glucose output (BHGO...

  14. Increased interaction with insulin receptor substrate 1, a novel abnormality in insulin resistance and type 2 diabetes

    DEFF Research Database (Denmark)

    Caruso, Michael; Ma, Danjun; Msallaty, Zaher

    2014-01-01

    Insulin receptor substrate 1 (IRS1) is a key mediator of insulin signal transduction. Perturbations involving IRS1 complexes may lead to the development of insulin resistance and type 2 diabetes (T2D). Surprisingly little is known about the proteins that interact with IRS1 in humans under health...... in obesity and T2D in humans, provides new insights into the molecular mechanism of insulin resistance and identifies new targets for T2D drug development....... and disease conditions. We used a proteomic approach to assess IRS1 interaction partners in skeletal muscle from lean healthy control subjects (LCs), obese insulin-resistant nondiabetic control subjects (OCs), and participants with T2D before and after insulin infusion. We identified 113 novel endogenous IRS1...

  15. Cost-Effectiveness of Antibiotic Prophylaxis Strategies for Transrectal Prostate Biopsy in an Era of Increasing Antimicrobial Resistance.

    Science.gov (United States)

    Lee, Kyueun; Drekonja, Dimitri M; Enns, Eva A

    2018-03-01

    To determine the optimal antibiotic prophylaxis strategy for transrectal prostate biopsy (TRPB) as a function of the local antibiotic resistance profile. We developed a decision-analytic model to assess the cost-effectiveness of four antibiotic prophylaxis strategies: ciprofloxacin alone, ceftriaxone alone, ciprofloxacin and ceftriaxone in combination, and directed prophylaxis selection based on susceptibility testing. We used a payer's perspective and estimated the health care costs and quality-adjusted life-years (QALYs) associated with each strategy for a cohort of 66-year-old men undergoing TRPB. Costs and benefits were discounted at 3% annually. Base-case resistance prevalence was 29% to ciprofloxacin and 7% to ceftriaxone, reflecting susceptibility patterns observed at the Minneapolis Veterans Affairs Health Care System. Resistance levels were varied in sensitivity analysis. In the base case, single-agent prophylaxis strategies were dominated. Directed prophylaxis strategy was the optimal strategy at a willingness-to-pay threshold of $50,000/QALY gained. Relative to the directed prophylaxis strategy, the incremental cost-effectiveness ratio of the combination strategy was $123,333/QALY gained over the lifetime time horizon. In sensitivity analysis, single-agent prophylaxis strategies were preferred only at extreme levels of resistance. Directed or combination prophylaxis strategies were optimal for a wide range of resistance levels. Facilities using single-agent antibiotic prophylaxis strategies before TRPB should re-evaluate their strategies unless extremely low levels of antimicrobial resistance are documented. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  16. Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1-40/42 and Phospho-Tau May Abet Alzheimer Development.

    Science.gov (United States)

    Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret; Farese, Robert V

    2016-07-01

    Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat-fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1-40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1-40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1–40/42 and Phospho-Tau May Abet Alzheimer Development

    Science.gov (United States)

    Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret

    2016-01-01

    Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat–fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1–40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1–40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. PMID:26895791

  18. BWR Mark I pressure suppression study: bench mark experiments

    International Nuclear Information System (INIS)

    Lai, W.; McCauley, E.W.

    1977-01-01

    Computer simulations representative of the wetwell of Mark I BWR's have predicted pressures and related phenomena. However, calculational predictions for purposes of engineering decision will be possible only if the code can be verified, i.e., shown to compute in accord with measured values. Described in the report is a set of single downcomer spherical flask bench mark experiments designed to produce quantitative data to validate various air-water dynamic computations; the experiments were performed since relevant bench mark data were not available from outside sources. Secondary purposes of the study were to provide a test bed for the instrumentation and post-experiment data processing techniques to be used in the Laboratory's reactor safety research program and to provide additional masurements for the air-water scaling study

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

    Science.gov (United States)

    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.

  20. Consumption of a liquid high-fat meal increases triglycerides but decreases high-density lipoprotein cholesterol in abdominally obese subjects with high postprandial insulin resistance.

    Science.gov (United States)

    Wang, Feng; Lu, Huixia; Liu, Fukang; Cai, Huizhen; Xia, Hui; Guo, Fei; Xie, Yulan; Huang, Guiling; Miao, Miao; Shu, Guofang; Sun, Guiju

    2017-07-01

    Abdominal obesity is associated with an increased risk of insulin resistance, which may be a potential contributor to dyslipidemia. However, the relationship between postprandial insulin resistance and lipid metabolism in abdominally obese subjects remains unknown. We hypothesized that postprandial dyslipidemia would be exaggerated in abdominally obese subjects with high postprandial insulin resistance. To test this hypothesis, serum glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B were measured at baseline and postprandial state at 0.5, 1, 2, 4, 6, and 8 hours after a liquid high-fat meal in non-abdominally obese controls (n=44) and abdominally obese subjects with low (AO-LPIR, n=40), middle (n=40), and high postprandial insulin resistance (AO-HPIR, n=40) based on the tertiles ratio of the insulin to glucose areas under the curve (AUC). Their serum adipokines were tested at baseline only. Fasting serum leptin was higher (Pinsulin resistance and controls. The present study indicated that the higher degree of postprandial insulin resistance, the more adverse lipid profiles in abdominally obese subjects, which provides insight into opportunity for screening in health. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Levels of betatrophin decrease during pregnancy despite increased insulin resistance, beta-cell function and triglyceride levels.

    Science.gov (United States)

    Zielińska, A; Maciulewski, R; Siewko, K; Popławska-Kita, A; Lipińska, D; Kozłowska, G; Górska, M; Szelachowska, M

    2016-12-01

    Evidence in support of an association between betatrophin and insulin resistance (IR) is mounting, with studies demonstrating that betatrophin is elevated in patients with type 2 diabetes, obesity and gestational diabetes. The aim of this study was to evaluate the role of betatrophin in IR and physiological proliferation of beta cells during pregnancy in healthy women. Eighty healthy pregnant women were examined at each trimester [T1 (first), T2 (second), T3 (third)], with a subgroup (n=45) that was also examined at 3 months postpartum (3MPP). The controls comprised 30 non-pregnant healthy women (HW) of reproductive age. Also measured were levels of betatrophin (ELISA), glucose (enzymatic method with hexokinase), insulin (IRMA), C-peptide (EASIA) and HbA 1c (HPLC), while HOMA-IR and HOMA-β scores were calculated. Betatrophin concentration was highest at T1, and differed significantly from T2 and T3 (1.84 [Q 1 =1.16, Q 3 =2.67]ng/mL vs 1.46 [Q 1 =0.96, Q 3 =2.21]ng/mL; Pindex scores increased during gestation, peaking at T3 (2.3 [Q 1 =1.66, Q 3 =2.72] and 227.7 [Q 1 =185.49, Q 3 =326.31], respectively) and returning to levels similar to those of HW at 3MPP (1.53 [Q 1 =1.12, Q 3 =2.41] and 88.86 [Q 1 =62.73, Q 3 =130.45] vs 1.35 [Q 1 =1.02, Q 3 =1.62] and 92.5 [Q 1 =74.20, Q 3 =111.47], respectively). Concentrations of betatrophin decrease during pregnancy, suggesting that the hormone does not play a significant role in the expansion of beta-cell mass and IR during pregnancy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Development of a three component complex to increase isoniazid efficacy against isoniazid resistant and nonresistant Mycobacterium tuberculosis.

    Science.gov (United States)

    Manning, Thomas; Plummer, Sydney; Baker, Tess; Wylie, Greg; Clingenpeel, Amy C; Phillips, Dennis

    2015-10-15

    The bacterium responsible for causing tuberculosis has evolved resistance to antibiotics used to treat the disease, resulting in new multidrug resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug resistant M. tuberculosis (XDR-TB) strains. Analytical techniques (1)H and (13)C Nuclear Magnetic Resonance (NMR), Fourier Transform-Ion Cyclotron Resonance with Electrospray Ionization (FT-ICR/ESI), and Matrix Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-TOF-MS) were used to study different aspects of the Cu(II)-polyethylene glycol (PEG-3350)-sucrose-isoniazid and Cu(II)-polyethylene glycol (PEG3350)-glucose-isoniazid complexes. The Cu(II) cation, sucrose or glucose, and the aggregate formed by PEG primarily serve as a composite drug delivery agent for the frontline antibiotic, however the improvement in MIC values produced with the CU-PEG-SUC-INH complex suggest an additional effect. Several Cu-PEG-SUC-INH complex variations were tested against INH resistant and nonresistant strains of M. tuberculosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. The Tribological Performance of Hardfaced/ Thermal Sprayed Coatings for Increasing the Wear Resistance of Ventilation Mill Working Parts

    Directory of Open Access Journals (Sweden)

    A. Vencl

    2015-09-01

    Full Text Available During the coal pulverizing, the working parts of the ventilation mill are being worn by the sand particles. For this reason, the working parts are usually protected with materials resistant to wear (hardfaced/thermal sprayed coatings. The aim of this study was to evaluate the tribological performance of four different types of coatings as candidates for wear protection of the mill’s working parts. The coatings were produced by using the filler materials with the following nominal chemical composition: NiFeBSi-WC, NiCrBSiC, FeCrCTiSi, and FeCrNiCSiBMn, and by using the plasma arc welding and flame and electric arc spraying processes. The results showed that Ni-based coatings exhibited higher wear resistance than Fe-based coatings. The highest wear resistance showed coating produced by using the NiFeBSi-WC filler material and plasma transferred arc welding deposition process. The hardness was not the only characteristic that affected the wear resistance. In this context, the wear rate of NiFeBSi-WC coating was not in correlation with its hardness, in contrast to other coatings. The different wear performance of NiFeBSi-WC coating was attributed to the different type and morphological features of the reinforcing particles (WC.

  4. The proteomic signature of insulin-resistant human skeletal muscle reveals increased glycolytic and decreased mitochondrial enzymes

    DEFF Research Database (Denmark)

    Giebelstein, J; Poschmann, G; Højlund, K

    2012-01-01

    The molecular mechanisms underlying insulin resistance in skeletal muscle are incompletely understood. Here, we aimed to obtain a global picture of changes in protein abundance in skeletal muscle in obesity and type 2 diabetes, and those associated with whole-body measures of insulin action....

  5. Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa.

    Science.gov (United States)

    Manasa, Justen; Danaviah, Siva; Lessells, Richard; Elshareef, Muna; Tanser, Frank; Wilkinson, Eduan; Pillay, Sureshnee; Mthiyane, Hloniphile; Mwambi, Henry; Pillay, Deenan; de Oliveira, Tulio

    2016-08-01

    As more human immunodeficiency virus (HIV)-infected patients access combination antiretroviral therapy (cART), higher proportions of newly infected patients may be infected with drug-resistant viruses. Regular surveillance of transmitted drug resistance (TDR) is required in southern Africa where high rates of transmission persist despite rapid expansion of ART. Dried blood spot samples from cART-naive participants from two rounds of an annual population-based HIV surveillance program in rural KwaZulu-Natal were tested for HIV RNA, and samples with HIV RNA >10,000 copies/ml were genotyped for drug resistance. The 2009 surveillance of drug resistance mutation (SDRM) list was used for drug resistance interpretation. The data were added to previously published data from the same program, and the χ(2) test for trend was used to test for trend in estimated prevalence of any TDR. Seven hundred and one participants' data were analyzed: 67 (2010), 381 (2011), and 253 (2012). No TDR was detected in 2010. Years 2011 and 2012 had 18 participants with SDRMs 4.7% and 7.1%, respectively (p = .02, χ(2) test for trend). The nonnucleoside reverse transcriptase inhibitor mutation, K103N, was the most common mutation, occurring in 27 (3.8%) of the participants, while nucleoside reverse transcriptase inhibitor (NRTI) SDRMs were detected in 10 (1.4%) of the participants, of whom eight had only a single NRTI SDRM. The increase in levels of drug resistance observed in this population could be a signal of increasing transmission of drug-resistant HIV. Thus, continued surveillance is critical to inform public health policies around HIV treatment and prevention.

  6. Increase in Docetaxel-Resistance of Ovarian Carcinoma-Derived RMG-1 Cells with Enhanced Expression of Lewis Y Antigen

    Directory of Open Access Journals (Sweden)

    Bei Lin

    2011-10-01

    Full Text Available Epithelial carcinomas of the ovary exhibit the highest mortality rate among gynecologic malignancies. Studies found that the metabolism of glycolipids or carbohydrates is associated with acquirement of anticancer drug-resistance by cancer cells. This study was to characterize possible involvement of Lewis Y (LeY antigen in the drug-resistance of cancer cells. We transfected the α1,2-fucosyltransferase gene into human ovarian carcinoma-derived RMG-1 cells and established RMG-1-hFUT cells with enhanced expression of LeY. We determined the effects of docetaxel on the survival of cells by MTT assaying and observed the apoptosis of cells in the presence of docetaxel by flow cytometric analysis and by transmission electron microscopy. Plasma membranes and intracellular granules in RMG-1-hFUT cells were stained with anti-LeY antibody, the intensity of the staining was higher than that in control cells. The RMG-1-hFUT cells exhibited higher resistance to docetaxel than the control cells with regard to the docetaxel concentration and time course. After treatment with 10 μg/mL docetaxel for 72 h, the control cells, but not RMG-1-hFUT, contained abundant positively stained cell debris due to disintegration of the cytoskeleton. On transmission electron microscopy, although the control cells treated with docetaxel as above showed the following morphology, i.e., absence of villi, cells shrunken in size, pyknosis, agglutinated chromatin and cell buds containing nuclei in the process of apoptosis, the RMG-1-hFUT cells showed only agglutinated chromatin and vacuoles in the cytoplasm. In summary, cells with enhanced expression of LeY were shown to acquire docetaxel-resistance, indicating the possible involvement of glycoconjugates in the drug-resistance.

  7. Dynamics of resistance development to imatinib under increasing selection pressure: a combination of mathematical models and in vitro data.

    Directory of Open Access Journals (Sweden)

    Benjamin Werner

    Full Text Available In the last decade, cancer research has been a highly active and rapidly evolving scientific area. The ultimate goal of all efforts is a better understanding of the mechanisms that discriminate malignant from normal cell biology in order to allow the design of molecular targeted treatment strategies. In individual cases of malignant model diseases addicted to a specific, ideally single oncogene, e.g. Chronic myeloid leukemia (CML, specific tyrosine kinase inhibitors (TKI have indeed been able to convert the disease from a ultimately life-threatening into a chronic disease with individual patients staying in remission even without treatment suggestive of operational cure. These developments have been raising hopes to transfer this concept to other cancer types. Unfortunately, cancer cells tend to develop both primary and secondary resistance to targeted drugs in a substantially higher frequency often leading to a failure of treatment clinically. Therefore, a detailed understanding of how cells can bypass targeted inhibition of signaling cascades crucial for malignant growths is necessary. Here, we have performed an in vitro experiment that investigates kinetics and mechanisms underlying resistance development in former drug sensitive cancer cells over time in vitro. We show that the dynamics observed in these experiments can be described by a simple mathematical model. By comparing these experimental data with the mathematical model, important parameters such as mutation rates, cellular fitness and the impact of individual drugs on these processes can be assessed. Excitingly, the experiment and the model suggest two fundamentally different ways of resistance evolution, i.e. acquisition of mutations and phenotype switching, each subject to different parameters. Most importantly, this complementary approach allows to assess the risk of resistance development in the different phases of treatment and thus helps to identify the critical periods where

  8. The Physiological and Biochemical Mechanisms Providing the Increased Constitutive Cold Resistance in the Potato Plants, Expressing the Yeast SUC2 Gene Encoding Apoplastic Invertase

    Directory of Open Access Journals (Sweden)

    A.N. Deryabin

    2016-05-01

    Full Text Available The expression of heterologous genes in plants is an effective method to improve our understanding of plant resistance mechanisms. The purpose of this work was to investigate the involvement of cell-wall invertase and apoplastic sugars into constitutive cold resistance of potato (Solanum tuberosum L., cv. Dйsirйe plants, which expressed the yeast SUC2 gene encoding apoplastic invertase. WT-plants of a potato served as the control. The increase in the essential cell-wall invertase activity in the leaves of transformed plants indicates significant changes in the cellular carbohydrate metabolism and regulatory function of this enzyme. The activity of yeast invertase changed the composition of intracellular sugars in the leaves of the transformed potato plant. The total content of sugars (sucrose, glucose, fructose in the leaves and apoplast was higher in the transformants, in comparison by WT-plants. Our data indicate higher constitutive resistance of transformants to severe hypothermia conditions compared to WT-plants. This fact allows us to consider cell-wall invertase as a enzyme of carbohydrate metabolism playing an important regulatory role in the metabolic signaling upon forming increased plant resistance to low temperature. Thus, the potato line with the integrated SUC2 gene is a convenient tool to study the role of the apoplastic invertase and the products of its activity during growth, development and formation constitutive resistance to hypothermia.

  9. Possible increase in insulin resistance and concealed glucose-coupled potassium-lowering mechanisms during acute coronary syndrome documented by covariance structure analysis.

    Science.gov (United States)

    Ito, Satoshi; Nagoshi, Tomohisa; Minai, Kosuke; Kashiwagi, Yusuke; Sekiyama, Hiroshi; Yoshii, Akira; Kimura, Haruka; Inoue, Yasunori; Ogawa, Kazuo; Tanaka, Toshikazu D; Ogawa, Takayuki; Kawai, Makoto; Yoshimura, Michihiro

    2017-01-01

    Although glucose-insulin-potassium (GIK) therapy ought to be beneficial for ischemic heart disease in general, variable outcomes in many clinical trials of GIK in acute coronary syndrome (ACS) had a controversial impact. This study was designed to examine whether "insulin resistance" is involved in ACS and to clarify other potential intrinsic compensatory mechanisms for GIK tolerance through highly statistical procedure. We compared the degree of insulin resistance during ACS attack and remission phase after treatment in individual patients (n = 104). During ACS, homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly increased (Pcovariance structure analysis with a strong impact (β: 0.398, P = 0.015). Intriguingly, a higher incidence of myocardial infarction relative to unstable angina pectoris, as well as a longer hospitalization period were observed in patients with larger ΔK, indicating that ΔK also reflects disease severity of ACS. Insulin resistance most likely increases during ACS; however, ΔK was positively correlated with plasma glucose level, which overwhelmed insulin resistance condition. The present study with covariance structure analysis suggests that there are potential endogenous glucose-coupled potassium lowering mechanisms, other than insulin, regulating glucose metabolism during ACS.

  10. Method for increasing the resistance of a plant or a part thereof to a pathogen, method for screening the resistance of a plant or part thereof to a pathogen, and use thereof

    NARCIS (Netherlands)

    Wit, de P.; Stergiopoulos, I.; Kema, G.H.J.

    2011-01-01

    (EN)The present invention relates to the field of plant biotechnology. More in particular, the present invention relates to methods for increasing the resistance of a plant or part thereof that is susceptible to infection with a pathogen comprising an ortholog of the Avr4 protein of Cladosporium

  11. Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss

    Directory of Open Access Journals (Sweden)

    J. Schmitz

    2016-05-01

    Conclusions: These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as well as in a significant subpopulation of obese patients.

  12. Increasing the use of second-line therapy is a cost-effective approach to prevent the spread of drug-resistant HIV: a mathematical modelling study

    NARCIS (Netherlands)

    Nichols, Brooke E.; Sigaloff, Kim C. E.; Kityo, Cissy; Hamers, Raph L.; Baltussen, Rob; Bertagnolio, Silvia; Jordan, Michael R.; Hallett, Timothy B.; Boucher, Charles A. B.; de Wit, Tobias F. Rinke; van de Vijver, David A. M. C.

    2014-01-01

    Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR. We develop a

  13. Mark Napier / Mark Napier ; interv. Tilman Baumgärtel

    Index Scriptorium Estoniae

    Napier, Mark

    2006-01-01

    Ameerika kunstnikust Mark Napierist (sünd. 1961) ja tema loomingust, 2001. a. tehtud meiliintervjuu kunstnikuga. Võrguteosest "The Digital Landfill" (1998), koos Andy Deckiga loodud tööst "GrafficJam" (1999), töödest "Shredder" (1998), "Feed", "Riot", "P-Soup" (2000), võrgukunstist ja muust

  14. Minimal Marking: A Success Story

    Directory of Open Access Journals (Sweden)

    Anne McNeilly

    2014-11-01

    Full Text Available The minimal-marking project conducted in Ryerson’s School of Journalism throughout 2012 and early 2013 resulted in significantly higher grammar scores in two first-year classes of minimally marked university students when compared to two traditionally marked classes. The “minimal-marking” concept (Haswell, 1983, which requires dramatically more student engagement, resulted in more successful learning outcomes for surface-level knowledge acquisition than the more traditional approach of “teacher-corrects-all.” Results suggest it would be effective, not just for grammar, punctuation, and word usage, the objective here, but for any material that requires rote-memory learning, such as the Associated Press or Canadian Press style rules used by news publications across North America.

  15. Method for increasing the resistance of a plant or a part thereof to a pathogen, method for screening the resistance of a plant or part thereof to a pathogen, and use thereof

    OpenAIRE

    Wit, de, P.; Stergiopoulos, I.; Kema, G.H.J.

    2011-01-01

    (EN)The present invention relates to the field of plant biotechnology. More in particular, the present invention relates to methods for increasing the resistance of a plant or part thereof that is susceptible to infection with a pathogen comprising an ortholog of the Avr4 protein of Cladosporium fulvum, wherein said plant is not a tomato or tobacco plant. The invention also relates to methods for screening the resistance of a plant or a part thereof to at least one pathogen, wherein said path...

  16. Percentage Retail Mark-Ups

    OpenAIRE

    Thomas von Ungern-Sternberg

    1999-01-01

    A common assumption in the literature on the double marginalization problem is that the retailer can set his mark-up only in the second stage of the game after the producer has moved. To the extent that the sequence of moves is designed to reflect the relative bargaining power of the two parties it is just as plausible to let the retailer move first. Furthermore, retailers frequently calculate their selling prices by adding a percentage mark-up to their wholesale prices. This allows a retaile...

  17. High-frequency resistance training is not more effective than low-frequency resistance training in increasing muscle mass and strength in well-trained men.

    Science.gov (United States)

    Gomes, Gederson K; Franco, Cristiane M; Nunes, Paulo Ricardo P; Orsatti, Fábio L

    2018-02-27

    We studied the effects of two different weekly frequency resistance training (RT) protocols over eight weeks on muscle strength and muscle hypertrophy in well-trained men. Twenty-three subjects (age: 26.2±4.2 years; RT experience: 6.9±3.1 years) were randomly allocated into the two groups: low frequency (LFRT, n = 12) or high frequency (HFRT, n = 11). The LFRT performed a split-body routine, training each specific muscle group once a week. The HFRT performed a total-body routine, training all muscle groups every session. Both groups performed the same number of sets (10-15 sets) and exercises (1-2 exercise) per week, 8-12 repetitions maximum (70-80% of 1RM), five times per week. Muscle strength (bench press and squat 1RM) and lean tissue mass (dual-energy x-ray absorptiometry) were assessed prior to and at the end of the study. Results showed that both groups improved (ptrained subjects when the sets and intensity are equated per week.

  18. Increasing penicillin resistance in pneumococci isolated from cerebrospinal fluid samples: Fifteen-year experience from a teaching hospital

    OpenAIRE

    Pehlivanoglu, Filiz; Sengoz, Gonul; Şengöz, Gönül; Gursoy, Sevtap

    2015-01-01

    Objective: There have been prominent changes in evaluation of resistance patterns of pneumococci and breakpoint values in recent years. We aimed to investigate the penicillin sensitivity of pneumococcal strains isolated from the ce­rebrospinal fluid specimens between the years 1997-2011 in our hospital and determine the MIC values under the light of these changes. Methods: Identification of pneumococci was made with conventional methods in patients with meningitis. MIC values for penicilli...

  19. Study of new heat treatment parameters for increasing mechanical strength and stress corrosion cracking resistance of 7075 Aluminium alloy

    OpenAIRE

    Silva, G.; Rivolta, B.; Gerosa, R.; Derudi, U.

    2013-01-01

    For many years 7075 Aluminum alloys have been widely used especially in those applications for which highmechanical performances are required. It is well known that the alloy in the T6 condition is characterized bythe highest ultimate and yield strengths, but, at the same time, by poor stress corrosion cracking (SCC)resistance. For this reason, in the aeronautic applications, new heat treatments have been introduced toproduce T7X conditions, which are characterized by lower mechanical strengt...

  20. Circulating Zonulin, a Marker of Intestinal Permeability, Is Increased in Association with Obesity-Associated Insulin Resistance

    OpenAIRE

    Moreno-Navarrete, José María; Sabater, Mònica; Ortega, Francisco; Ricart, Wifredo; Fernández-Real, José Manuel

    2012-01-01

    Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measure...

  1. Increased Frequency of ColV Plasmids and Mannose-Resistant Hemagglutinating Activity in an Escherichia coli K1 Population

    OpenAIRE

    1984-01-01

    The expression of traits linked to pathogenicity was studied in a population of Escherichia coli K1 strains. It was found that E. coli K1 strains isolated from extraintestinal infection harbor the ColV plasmid and express mannose-resistant hemagglutinating activity type VI with a high frequency. The presence of these properties may play a role in the ability of some E. coli K1 serogroups to invade.

  2. Increased resistance of contact lens related bacterial biofilms to antimicrobial activity of soft contact lens care solutions

    Science.gov (United States)

    Szczotka-Flynn, Loretta B.; Imamura, Yoshifumi; Chandra, Jyotsna; Yu, Changping; Mukherjee, Pranab K.; Pearlman, Eric; Ghannoum, Mahmoud A.

    2014-01-01

    PURPOSE To determine if clinical and reference strains of Pseudomonas aeruginosa, Serratia marcescens, and Staphylococcus aureus form biofilms on silicone hydrogel contact lenses, and ascertain antimicrobial activities of contact lens care solutions. METHODS Clinical and American Type Culture Collection (ATCC) reference strains of Pseudomonas aeruginosa, Serratia marcescens, and Staphylococcus aureus were incubated with lotrafilcon A lenses under conditions that facilitate biofilm formation. Biofilms were quantified by quantitative culturing (colony forming units, CFUs), and gross morphology and architecture were evaluated using scanning electron microscopy (SEM) and confocal microscopy. Susceptibilities of the planktonic and biofilm growth phases of the bacteria to five common multipurpose contact lens care solutions and one hydrogen peroxide care solution were assessed. RESULTS P. aeruginosa, S. marcescens, and S. aureus reference and clinical strains formed biofilms on lotrafilcon A silicone hydrogel contact lenses, as dense networks of cells arranged in multiple layers with visible extracellular matrix. The biofilms were resistant to commonly used biguanide preserved multipurpose care solutions. P. aeruginosa and S. aureus biofilms were susceptible to a hydrogen peroxide and a polyquaternium preserved care solution, whereas S. marcescens biofilm was resistant to a polyquaternium preserved care solution but susceptible to hydrogen peroxide disinfection. In contrast, the planktonic forms were always susceptible. CONCLUSIONS P. aeruginosa, S. marcescens, and S. aureus form biofilms on lotrafilcon A contact lenses, which in contrast to planktonic cells, are resistant to the antimicrobial activity of several soft contact lens care products. PMID:19654521

  3. Opening the mind to close it: considering a message in light of important values increases message processing and later resistance to change.

    Science.gov (United States)

    Blankenship, Kevin L; Wegener, Duane T

    2008-02-01

    Past research showed that considering a persuasive message in light of important rather than unimportant values creates attitudes that resist later attack. The traditional explanation is that the attitudes come to express the value or that a cognitive link between the value and attitude enhances resistance. However, the current research showed that another explanation is plausible. Similar to other sources of involvement, considering important rather than unimportant values increases processing of the message considered in light of those values. This occurs when the values are identified as normatively high or low in importance and when the perceived importance differs across participants for the same values. The increase in processing creates resistance to later attacks, and unlike past research, individual-level measures of initial amount of processing mediate value importance effects on later resistance to change. Important values motivate processing because they increase personal involvement with the issue, rather than creating attitudes that represent or express core values. (c) 2008 APA, all rights reserved

  4. Neuroendocrine prostate cancer (NEPCa) increased the neighboring PCa chemo-resistance via altering the PTHrP/p38/Hsp27/androgen receptor (AR)/p21 signals

    Science.gov (United States)

    Cui, Yun; Sun, Yin; Hu, Shuai; Luo, Jie; Li, Lei; Li, Xin; Yeh, Shuyuan; Jin, Jie; Chang, Chawnshang

    2016-01-01

    Prostatic neuroendocrine cells (NE) are an integral part of prostate cancer (PCa) that are associated with PCa progression. As the current androgen-deprivation therapy (ADT) with anti-androgens may promote the neuroendocrine PCa (NEPCa) development, and few therapies can effectively suppress NEPCa, understanding the impact of NEPCa on PCa progression may help us to develop better therapies to battle PCa. Here we found NEPCa cells could increase the docetaxel-resistance of their neighboring PCa cells. Mechanism dissection revealed that through secretion of PTHrP, NEPCa cells could alter the p38/MAPK/Hsp27 signals in their neighboring PCa cells that resulted in increased androgen receptor (AR) activity via promoting AR nuclear translocation. The consequences of increased AR function might then increase docetaxel-resistance via increasing p21 expression. In vivo xenograft mice experiments also confirmed NEPCa could increase the docetaxel-resistance of neighboring PCa, and targeting this newly identified PTHrP/p38/Hsp27/AR/p21 signaling pathway with either p38 inhibitor (SB203580) or sh-PTHrP may result in improving/restoring the docetaxel sensitivity to better suppress PCa. PMID:27375022

  5. Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Euphemia Yee Leung

    2014-09-01

    Full Text Available The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment.

  6. The Transcriptional Heat Shock Response of Salmonella Typhimurium Shows Hysteresis and Heated Cells Show Increased Resistance to Heat and Acid Stress

    DEFF Research Database (Denmark)

    Pin, C.; Hansen, Trine; Munoz-Cuevas, M.

    2012-01-01

    We investigated if the transcriptional response of Salmonella Typhimurium to temperature and acid variations was hysteretic, i.e. whether the transcriptional regulation caused by environmental stimuli showed memory and remained after the stimuli ceased. The transcriptional activity of non......, implying that down-regulation was significantly less synchronized than upregulation. The hysteretic transcriptional response to heat shock was accompanied by higher resistance to inactivation at 50uC as well as cross-resistance to inactivation at pH 3; however, growth rates and lag times at 43uC and at p......H 4.5 were not affected. The exposure to pH 5 only caused up-regulation of 12 genes and this response was neither hysteretic nor accompanied of increased resistance to inactivation conditions. Cellular memory at the transcriptional level may represent a mechanism of adaptation to the environment...

  7. High-speed resistance training is more effective than low-speed resistance training to increase functional capacity and muscle performance in older women.

    Science.gov (United States)

    Ramírez-Campillo, Rodrigo; Castillo, Angélica; de la Fuente, Carlos I; Campos-Jara, Christian; Andrade, David C; Álvarez, Cristian; Martínez, Cristian; Castro-Sepúlveda, Mauricio; Pereira, Ana; Marques, Mário C; Izquierdo, Mikel

    2014-10-01

    To examine the effects of 12 weeks of high-speed resistance training (RT) versus low-speed RT on muscle strength [one repetition of maximum leg-press (1RMLP) and bench-press (1RMBP), plus dominant (HGd) and non-dominant maximum isometric handgrip], power [counter-movement jump (CMJ), ball throwing (BT) and 10-m walking sprint (S10)], functional performance [8-foot up-and-go test (UG) and sit-to-stand test (STS)], and perceived quality of life in older women. 45 older women were divided into a high-speed RT group [EG, n=15, age=66.3±3.7y], a low-speed RT group [SG, n=15, age=68.7±6.4y] and a control group [CG, n=15, age=66.7±4.9y]. The SG and EG were submitted to a similar 12-week RT program [3 sets of 8 reps at 40-75% of the one-repetition maximum (1work per exercise without CMJ and BT). Over the 12-week training period, both RT groups showed small to large clinically significant improvements in the dependent variables; however, a significant difference was found between the EG and SG for the performance changes in BT, S10 and UG (20% vs. 11%, pperformance and quality of life in older women, although a high-speed RT program induces greater improvements in muscle power and functional capacity. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Better marking means cheaper pruning.

    Science.gov (United States)

    Kenneth R. Eversole

    1953-01-01

    Careful selection of trees to be pruned can make the difference between profit and loss on the pruning investment, especially in stands where no thinning is contemplated. Expert marking is required to make sure that the pruned trees will grow rapidly. The most important variable influencing the cost of clear wood produced by pruning is growth rate. For example, at 3...

  9. Increased fluoroquinolone resistance with time in Escherichia coli from >17,000 patients at a large county hospital as a function of culture site, age, sex, and location

    Directory of Open Access Journals (Sweden)

    Hamill Richard J

    2008-01-01

    Full Text Available Abstract Background Escherichia coli infections are common and often treated with fluoroquinolones. Fluoroquinolone resistance is of worldwide importance and is monitored by national and international surveillance networks. In this study, we analyzed the effects of time, culture site, and patient age, sex, and location on fluoroquinolone resistance in E. coli clinical isolates. Methods To understand how patient factors and time influenced fluoroquinolone resistance and to determine how well data from surveillance networks predict trends at Ben Taub General Hospital in Houston, TX, we used Perl to parse and MySQL to house data from antibiograms (n ≅ 21,000 for E. coli isolated between 1999 to 2004 using Chi Square, Bonferroni, and Multiple Linear Regression methods. Results Fluoroquinolone resistance (i increased with time; (ii exceeded national averages by 2- to 4-fold; (iii was higher in males than females, largely because of urinary isolates from male outpatients; (iv increased with patient age; (v was 3% in pediatric patients; (vi was higher in hospitalized patients than outpatients; (vii was higher in sputum samples, particularly from inpatients, than all other culture sites, including blood and urine, regardless of patient location; and (viii was lowest in genital isolates than all other culture sites. Additionally, the data suggest that, with regard to susceptibility or resistance by the Dade Behring MicroScan system, a single fluoroquinolone suffices as a "surrogate marker" for all of the fluoroquinolone tested. Conclusion Large surveillance programs often did not predict E. coli fluoroquinolone resistance trends at a large, urban hospital with a largely indigent, ethnically diverse patient population or its affiliated community clinics.

  10. Experimental evolution of defense against a competitive mold confers reduced sensitivity to fungal toxins but no increased resistance in Drosophila larvae

    Directory of Open Access Journals (Sweden)

    Trienens Monika

    2011-07-01

    Full Text Available Abstract Background Fungal secondary metabolites have been suggested to function as chemical defenses against insect antagonists, i.e. predators and competitors. Because insects and fungi often compete for dead organic material, insects may achieve protection against fungi by reducing sensitivity to fungal chemicals. This, in turn, may lead to increased resistance allowing insects better to suppress the spread of antagonistic but non-pathogenic microbes in their habitat. However, it remains controversial whether fungal toxins serve as a chemical shield that selects for insects that are less sensitive to toxins, and hence favors the evolution of insect resistance against microbial competitors. Results To examine the relationship between the ability to survive competition with toxic fungi, sensitivity to fungal toxins and resistance, we created fungal-selected (FS replicated insect lines by exposing Drosophila melanogaster larvae to the fungal competitor Aspergillus nidulans over 26 insect generations. Compared to unselected control lines (UC, larvae from the FS lines had higher survival rates in the presence of A. nidulans indicating selection for increased protection against the fungal antagonist. In line with our expectation, FS lines were less susceptible to the A. nidulans mycotoxin Sterigmatocystin. Of particular interest is that evolved protection against A. nidulans and Sterigmatocytin was not correlated with increased insect survival in the presence of other fungi and mycotoxins. We found no evidence that FS lines were better at suppressing the expansion of fungal colonies but observed a trend towards a less detrimental effect of FS larvae on fungal growth. Conclusion Antagonistic but non-pathogenic fungi favor insect variants better protected against the fungal chemical arsenal. This highlights the often proposed but experimentally underexplored importance of secondary metabolites in driving animal-fungus interactions. Instead of

  11. Arterial Retention of Remnant Lipoproteins Ex Vivo Is Increased in Insulin Resistance Because of Increased Arterial Biglycan and Production of Cholesterol-Rich Atherogenic Particles That Can Be Improved by Ezetimibe in the JCR:LA-cp Rat

    Science.gov (United States)

    Mangat, Rabban; Warnakula, Samantha; Borthwick, Faye; Hassanali, Zahra; Uwiera, Richard R.E.; Russell, James C.; Cheeseman, Christopher I.; Vine, Donna F.; Proctor, Spencer D

    2012-01-01

    Background Literature supports the “response-to-retention” hypothesis—that during insulin resistance, impaired metabolism of remnant lipoproteins can contribute to accelerated cardiovascular disease progression. We used the JCR:LA-cp rat model of metabolic syndrome (MetS) to determine the extent of arterial accumulation of intestinal-derived remnants ex vivo and potential mechanisms that contribute to exacerbated cholesterol deposition in insulin resistance. Methods and Results Arteries from control and MetS (insulin-resistant) JCR:LA-cp rats were perfused ex vivo with Cy5-labeled remnant lipoproteins, and their arterial retention was quantified by confocal microscopy. Arterial proteoglycans were isolated from control and MetS rats at 6, 12, and 32 weeks of age. There was a significant increase in the arterial retention of remnants and in associated cholesterol accumulation in MetS rats as compared to control rats. Mechanistic studies reveal that increased cholesterol deposition is a result of greater arterial biglycan content; longer glycosaminoglycans and increased production of cholesterol-rich intestinal-derived remnants, as compared to controls. Additionally, perfusion of vessels treated with ezetimibe, alone or in combination with simvastatin, with remnants isolated from the respective treatment group reduced ex vivo arterial retention of remnant-derived cholesterol ex vivo as compared to untreated controls. Conclusions Increased progression of atherosclerotic cardiovascular disease in MetS and type 2 diabetes mellitus might be explained in part by an increase in the arterial retention of cholesterol-rich remnants. Furthermore, ezetimibe alone or in combination treatment with simvastatin could be beneficial in ameliorating atherosclerotic cardiovascular disease in insulin resistance and MetS. PMID:23316299

  12. 30 CFR 14.7 - Approval marking and distribution records.

    Science.gov (United States)

    2010-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS REQUIREMENTS FOR THE APPROVAL OF FLAME-RESISTANT CONVEYOR BELTS General Provisions § 14.7 Approval marking and distribution records. (a) An approved conveyor belt must be marketed only under the name specified in the approval. (b) Approved conveyor belt must be legibly and...

  13. INSIG2 gene polymorphism is associated with increased subcutaneous fat in women and poor response to resistance training in men

    Directory of Open Access Journals (Sweden)

    Zoeller Robert F

    2008-12-01

    Full Text Available Abstract Background A common SNP upstream of the INSIG2 gene, rs7566605 (g.-10,1025G>C, Chr2:118,552,255, NT_022135.15, was reported to be associated with obesity (Body Mass Index, [BMI] in a genome-wide association scan using the Framingham Heart Study but has not been reproduced in other cohorts. As BMI is a relatively insensitive measure of adiposity that is subject to many confounding variables, we sought to determine the relationship between the INSIG2 SNP and subcutaneous fat volumes measured by MRI in a young adult population. Methods We genotyped the INSIG2 SNP rs7566605 in college-aged population enrolled in a controlled resistance-training program, (the Functional Polymorphism Associated with Human Muscle Size and Strength, FAMuSS cohort, n = 752 volunteers 18–40 yrs. In this longitudinal study, we examined the effect of the INSIG2 polymorphism on subcutaneous fat and muscle volumes of the upper arm measured by magnetic resonance imaging (MRI before and after 12 wks of resistance training. Gene/phenotype associations were tested using an analysis of covariance model with age and weight as covariates. Further, the % variation in each phenotype attributable to genotype was determined using hierarchical models and tested with a likelihood ratio test. Results Women with a copy of the C allele had higher levels of baseline subcutaneous fat (GG: n = 139; 243473 ± 5713 mm3 vs. GC/CC: n = 181; 268521 ± 5003 mm3; p = 0.0011; but men did not show any such association. Men homozygous for the G ancestral allele showed a loss of subcutaneous fat, while those with one or two copies of the C allele gained a greater percentage of subcutaneous fat with resistance training (GG: n = 103; 1.02% ± 1.74% vs. GC/CC: n = 93; 6.39% ± 1.82%; p = 0.035. Conclusion Our results show that the INSIG2 rs7566605 polymorphism underlies variation in subcutaneous adiposity in young adult women and suppresses the positive effects of resistance training on men. This

  14. Increased proximal reflux in a hypersensitive esophagus might explain symptoms resistant to proton pump inhibitors in patients with gastroesophageal reflux disease.

    Science.gov (United States)

    Rohof, Wout O; Bennink, Roelof J; de Jonge, Hugo; Boeckxstaens, Guy E

    2014-10-01

    Approximately 30% of patients with gastroesophageal reflux disease have symptoms resistant to treatment with proton pump inhibitors (PPIs). Several mechanisms such as esophageal hypersensitivity, increased mucosal permeability, and possibly the position of the gastric acid pocket might underlie a partial response to PPIs. To what extent these mechanisms interact and contribute to PPI-resistant symptoms, however, has not been investigated previously. In 18 gastroesophageal reflux disease patients (9 PPI responders and 9 PPI partial responders), esophageal sensitivity, mucosal permeability, and postprandial reflux parameters were determined during PPI use. Esophageal sensitivity for distension was measured by gradual balloon inflation at 5 and 15 cm above the lower esophageal sphincter. The mucosal permeability of 4 esophageal biopsy specimens per patient was determined in Ussing chambers by measuring the transepithelial electrical resistance and transmucosal flux of fluorescein. Postprandial reflux parameters were determined using concurrent high-resolution manometry/pH impedance after a standardized meal. In addition, the acid pocket was visualized using scintigraphy. No difference in the rate of postprandial acid reflux, in the pH of the acid pocket (PPI responders 3.7 ± 0.7 vs PPI partial responders 4.2 ± 0.4; P = .54), or in the position of the acid pocket was observed in PPI partial responders compared with PPI responders. In addition, the permeability of the esophageal mucosa was similar in both groups, as shown by a similar transepithelial electrical resistance and flux of fluorescein. PPI partial responders had more reflux episodes with a higher mean proximal extent, compared with PPI responders, and were more sensitive to balloon distension, both in the upper and lower esophagus. PPI-resistant symptoms most likely are explained by increased proximal reflux in a hypersensitive esophagus and less likely by increased mucosal permeability or the position of

  15. Evaluation of copper for divider subassembly in MCO Mark IA and Mark IV scrap fuel baskets

    International Nuclear Information System (INIS)

    Graves, C.E.

    1997-01-01

    The K Basin Spent Nuclear Fuel (SNF) Project Multi-Canister Overpack (MCO) subprojection eludes the design and fabrication of a canister that will be used to confine, contain, and maintain fuel in a critically safe array to enable its removal from the K Basins, vacuum drying, transport, staging, hot conditioning, and interim storage (Goldinann 1997). Each MCO consists of a shell, shield plug, fuel baskets (Mark IA or Mark IV), and other incidental equipment. The Mark IA intact and scrap fuel baskets are a safety class item for criticality control and components necessary for criticality control will be constructed from 304L stainless steel. It is proposed that a copper divider subassembly be used in both Mark IA and Mark IV scrap baskets to increase the safety basis margin during cold vacuum drying. The use of copper would increase the heat conducted away from hot areas in the baskets out to the wall of the MCO by both radiative and conductive heat transfer means. Thus copper subassembly will likely be a safety significant component of the scrap fuel baskets. This report examines the structural, cost and corrosion consequences associated with using a copper subassembly in the stainless steel MCO scrap fuel baskets

  16. Design of a CRISPR-Cas system to increase resistance of Bacillus subtilis to bacteriophage SPP1.

    Science.gov (United States)

    Jakutyte-Giraitiene, Lina; Gasiunas, Giedrius

    2016-08-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) together with CRISPR-associated (cas) genes form an adaptive prokaryotic immune system which provides acquired resistance against viruses and plasmids. Bacillus subtilis presently is the best-characterized laboratory model for Gram-positive bacteria and also widely used for industrial production of enzymes, vitamins and antibiotics. In this study, we show that type II-A CRISPR-Cas system from Streptococcus thermophilus can be transferred into B. subtilis and provides heterologous protection against phage infection. We engineered a heterologous host by cloning S. thermophilus Cas9 and a spacer targeting bacteriophage SPP1 into the chromosome of B. subtilis, which does not harbor its own CRISPR-Cas systems. We found that the heterologous CRISPR-Cas system is functionally active in B. subtilis and provides resistance against bacteriophage SPP1 infection. The high efficiency of the acquired immunity against phage could be useful in generation of biotechnologically important B. subtilis strains with engineered chromosomes.

  17. Decision and cost analysis of empirical antibiotic therapy of acute sinusitis in the era of increasing antimicrobial resistance: do we have an additional tool for antibiotic policy decisions?

    Science.gov (United States)

    Babela, Robert; Jarcuska, Pavol; Uraz, Vladimir; Krčméry, Vladimír; Jadud, Branislav; Stevlik, Jan; Gould, Ian M

    2017-11-01

    No previous analyses have attempted to determine optimal therapy for upper respiratory tract infections on the basis of cost-minimization models and the prevalence of antimicrobial resistance among respiratory pathogens in Slovakia. This investigation compares macrolides and cephalosporines for empirical therapy and look at this new tool from the aspect of potential antibiotic policy decision-making process. We employed a decision tree model to determine the threshold level of macrolides and cephalosporines resistance among community respiratory pathogens that would make cephalosporines or macrolides cost-minimising. To obtain information on clinical outcomes and cost of URTIs, a systematic review of the literature was performed. The cost-minimization model of upper respiratory tract infections (URTIs) treatment was derived from the review of literature and published models. We found that the mean cost of empirical treatment with macrolides for an URTIs was €93.27 when the percentage of resistant Streptococcus pneumoniae in the community was 0%; at 5%, the mean cost was €96.45; at 10%, €99.63; at 20%, €105.99, and at 30%, €112.36. Our model demonstrated that when the percentage of macrolide resistant Streptococcus pneumoniae exceeds 13.8%, use of empirical cephalosporines rather than macrolides minimizes the treatment cost of URTIs. Empirical macrolide therapy is less expensive than cephalosporines therapy for URTIs unless macrolide resistance exceeds 13.8% in the community. Results have important antibiotic policy implications, since presented model can be use as an additional decision-making tool for new guidelines and reimbursement processes by local authorities in the era of continual increase in antibiotic resistance.

  18. Effective Use of Water and Increased Dry Matter Partitioned to Grain Contribute to Yield of Common Bean Improved for Drought Resistance

    Directory of Open Access Journals (Sweden)

    Jose A. Polania

    2016-05-01

    Full Text Available Common bean (Phaseolus vulgaris L. is the most important food legume in the diet of poor people in the tropics. Drought causes severe yield loss in this crop. Identification of traits associated with drought resistance contributes to improving the process of generating bean genotypes adapted to these conditions. Field studies were conducted at the International Center for Tropical Agriculture (CIAT, Palmira, Colombia, to determine the relationship between grain yield and different parameters such as effective use of water (EUW, canopy biomass and dry partitioning indices (pod partitioning index, harvest index and pod harvest index in elite lines selected for drought resistance over the past decade. Carbon isotope discrimination (CID was used for estimation of water use efficiency (WUE. The main objectives were: (i to identify specific morpho-physiological traits that contribute to improved resistance to drought in lines developed over several cycles of breeding and that could be useful as selection criteria in breeding; and (ii to identify genotypes with desirable traits that could serve as parents in the corresponding breeding programs. A set of 36 bean genotypes belonging to the Middle American gene pool were evaluated under field conditions with two levels of water supply (irrigated and drought over two seasons. Eight bean lines (NCB 280, NCB 226, SEN 56, SCR 2, SCR 16, SMC 141, RCB 593 and BFS 67 were identified as resistant to drought stress. Resistance to terminal drought stress was positively associated with EUW combined with increased dry matter partitioned to pod and seed production and negatively associated with days to flowering and days to physiological maturity. Differences in genotypic response were observed between grain CID and grain yield under irrigated and drought stress. Based on phenotypic differences in CID, leaf stomatal conductance, canopy biomass and grain yield under drought stress, the lines tested were classified into

  19. Automated road marking recognition system

    Science.gov (United States)

    Ziyatdinov, R. R.; Shigabiev, R. R.; Talipov, D. N.

    2017-09-01

    Development of the automated road marking recognition systems in existing and future vehicles control systems is an urgent task. One way to implement such systems is the use of neural networks. To test the possibility of using neural network software has been developed with the use of a single-layer perceptron. The resulting system based on neural network has successfully coped with the task both when driving in the daytime and at night.

  20. Insulin Resistance of Puberty.

    Science.gov (United States)

    Kelsey, Megan M; Zeitler, Philip S

    2016-07-01

    Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity.

  1. High-Intensity Progressive Resistance Training Increases Strength With No Change in Cardiovascular Function and Autonomic Neural Regulation in Older Adults.

    Science.gov (United States)

    Kanegusuku, Hélcio; Queiroz, Andréia C; Silva, Valdo J; de Mello, Marco T; Ugrinowitsch, Carlos; Forjaz, Cláudia L

    2015-07-01

    The effects of high-intensity progressive resistance training (HIPRT) on cardiovascular function and autonomic neural regulation in older adults are unclear. To investigate this issue, 25 older adults were randomly divided into two groups: control (CON, N = 13, 63 ± 4 years; no training) and HIPRT (N = 12, 64 ± 4 years; 2 sessions/week, 7 exercises, 2–4 sets, 10–4 RM). Before and after four months, maximal strength, quadriceps cross-sectional area (QCSA), clinic and ambulatory blood pressures (BP), systemic hemodynamics, and cardiovascular autonomic modulation were measured. Maximal strength and QCSA increased in the HIPRT group and did not change in the CON group. Clinic and ambulatory BP, cardiac output, systemic vascular resistance, stroke volume, heart rate, and cardiac sympathovagal balance did not change in the HIPRT group or the CON group. In conclusion, HIPRT was effective at increasing muscle mass and strength without promoting changes in cardiovascular function or autonomic neural regulation.

  2. Heat, hydrogen peroxide, and UV resistance of Bacillus subtilis spores with increased core water content and with or without major DNA-binding proteins

    International Nuclear Information System (INIS)

    Popham, D.L.; Sengupta, S.; Setlow, P.

    1995-01-01

    Spores of a Bacillus subtilis strain with an insertion mutation in the dacB gene, which codes for an enzyme involved in spore cortex biosynthesis, have a higher core water content than wild-type spores. Spores lacking the two major α/β-type small, acid-soluble proteins (SASP) (termed a α - β - spores) have the same core water content as do wild-type spores, but α - β - dacB spores had more core water than did dacB spores. The resistance of α - β - , α - β - dacB, dacB, and wild-type spores to dry and moist heat, hydrogen peroxide, and UV radiation has been determined, as has the role of DNA damage in spore killing by moist heat and hydrogen peroxide. These data (1) suggest that core water content has little if any role in spore UV resistance and are consistent with binding of α/β-type SASP to DNA being the major mechanism providing protection to spores from UV radiation; (2) suggest that binding of αβ-type SASP to DNA is the major mechanism unique to spores providing protection from dry heat; (3) suggest that spore resistance to moist heat and hydrogen peroxide is affected to a large degree by the core water content, as increased core water resulted in large decreases in spore resistance to these agents; and (4) indicate that since this decreased resistance (i.e., in dacB spores) is not associated with increased spore killing by DNA damage, spore DNA must normally be extremely well protected against such damage, presumably by the saturation of spore DNA by α/β-type SASP. 19 refs., 2 figs., 5 tabs

  3. Novel strategy in increasing stability and corrosion resistance for super-hydrophobic coating on aluminum alloy surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Yin Bo [Department of Applied Physics, Chongqing University, Chongqing, 400044 (China); Fang Liang, E-mail: fangliangcqu@yahoo.com.cn [Department of Applied Physics, Chongqing University, Chongqing, 400044 (China); National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing, 400044 (China); Tang Anqiong; Huang Qiuliu; Hu Jia; Mao Jianhui [Department of Applied Physics, Chongqing University, Chongqing, 400044 (China); Bai, Ge; Bai, Huan [State Key Laboratory of Power Transmission Equipment and System Security and New Technology, Chongqing University, Chongqing, 400044 (China)

    2011-10-15

    A novel super-hydrophobic coating was prepared by chemical modification on the anodized aluminum alloy surface. The surface structure was characterized by water contact angle measurement, scanning electron microscopy (SEM), and the composition was measured by X-ray photoelectron spectroscopy (XPS). The corrosion behavior of the super-hydrophobic coating was evaluated by the polarization curve and the electrochemical impedance spectroscopy (EIS). It was found that the static water contact angle on the surface of super-hydrophobic coating was as high as 167.7 {+-} 1.2 deg., and the sliding angle was 5 deg. The super-hydrophobic coating resulted in excellent corrosion resistance property and the super-hydrophobic coating showed a good stability.

  4. First feeding of Eugerres brasilianus (Carapeva larvae with Acartia tonsa (Copepod nauplii increases survival and resistance to acute stress

    Directory of Open Access Journals (Sweden)

    Wanessa de Melo Costa

    2016-01-01

    Full Text Available The rotifer Brachionus sp. is commonly used for larval feeding in marine fish hatcheries. The aim of this study was to evaluate whether the inclusion of Acartia tonsa nauplii in the initial diet of carapeva larvae improves their survival, growth and resistance to stress when compared to the regimen containing only rotifers. Adult copepods were collected in the wild and cultured with the microalgae Chaetoceros muelleri, Isochrysis galbana and Nannochloropsis oculata to obtain nauplii. Carapeva larvae were grown for 15 days using four treatments and three replicates: 1 Brachionus plicatilis rotifers (10 to 15/mL; 2 A. tonsa nauplii (0.25 to 0.5/mL; 3 Brachionus plicatilis rotifers (5 to 7.5/mL + A. tonsa nauplii (0.12 to 0.25/mL, and 4 no supply of live feed. After 15 days, the carapeva larvae were subjected to stress by exposure to air for 10 seconds and then returned to the source tank to evaluate survival after 24 h. Survival and stress resistance were higher in carapeva larvae fed B. plicatilis + A. tonsa nauplii (P<0.05, 20.9 ± 11.2% and 88.9%, respectively. These results confirm the positive effect of the inclusion of copepod nauplii in the diet of fish larvae. However, more research is needed to validate these results.

  5. Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity1234

    Science.gov (United States)

    Knopp, Robert H; Kahn, Steven E; Retzlaff, Barbara M; Fish, Brian; Ma, Lina; Ostlund, Richard E

    2011-01-01

    Background: The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively. Objective: We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis. Design: Plasma sterols were measured by gas chromatography–mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (SI) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis. Results: The mean (±SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS, 3.25 ± 1.06 in LIR, and 2.82 ± 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol–cholesterol ratios were as follows: LIS > OIR (P LIR (P OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants, 0.95 ± 0.47 in the LIR participants, and 1.29 ± 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS sterol concentrations were positively associated with SI and negatively associated with obesity, whereas lathosterol correlations were the opposite. Conclusions: Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve SI and to decrease cholesterol overproduction in LIR and OIR persons. PMID:21940599

  6. Molecular epidemiology of carbapenem resistant gram-negative bacilli from infected pediatric population in tertiary - care hospitals in Medellín, Colombia: an increasing problem.

    Science.gov (United States)

    Vanegas, Johanna M; Parra, O Lorena; Jiménez, J Natalia

    2016-09-01

    Gram-negative bacilli are a cause of serious infections in the pediatric population. Carbapenem are the treatment of choice for infections caused by multidrug-resistant Gram-negative bacilli, but the emergence of carbapenem resistance has substantially reduced access to effective antimicrobial regimens. Children are a population vulnerable to bacterial infections and the emergence of resistance can worsen prognosis. The aim of this study is to describe the clinical and molecular characteristics of infections caused by carbapenem-resistant Gram-negative bacilli in pediatric patients from five tertiary-care hospitals in Medellín, Colombia. A cross-sectional study was conducted in five tertiary-care hospitals from June 2012 to June 2014. All pediatric patients infected by carbapenem-resistant Gram-negative bacilli were included. Clinical information for each patient was obtained from medical records. Molecular analyses included PCR for detection of bla VIM, bla IMP bla NDM, bla OXA-48 and bla KPC genes and PFGE and MLST for molecular typing. A total of 59 patients were enrolled, most of them less than 1 year old (40.7 % n = 24), with a previous history of antibiotic use (94.9 %; n = 56) and healthcare-associated infections - predominately urinary tract infections (31.0 %; n = 18). Klebsiella pneumoniae was the most frequent bacteria (47.4 %), followed by Enterobacter cloacae (40.7 %) and Pseudomonas aeruginosa (11.9 %). For K. pneumoniae, KPC was the predominant resistance mechanism (85.7 %; n = 24) and ST14 was the most common clone (39.3 % n = 11), which included strains closely related by PFGE. In contrast, E. cloacae and P. aeruginosa were prevailing non-carbapenemase-producing isolates (only KPC and VIM were detected in 1 and 3 isolates, respectively) and high genetic diversity according to PFGE and MLST was found in the majority of the cases. In recent years, increasing carbapenem-resistant bacilli in children has become in a matter

  7. Mark Twain: inocente ou pecador? = Mark Twain: innocent or sinner?

    Directory of Open Access Journals (Sweden)

    Heloisa Helou Doca

    2009-01-01

    Full Text Available A leitura cuidadosa do texto do “Tratado de Paris”, em 1900, leva Mark Twain a concluir que a intenção política norte-americana era, claramente, a de subjugação. Declara-se, abertamente, antiimperialista, nesse momento, apesar das inúmeras críticasrecebidas por antagonistas políticos que defendiam o establishment dos Estados Unidos. Após viajar para a Europa e Oriente, em 1867, como correspondente do jornal Daily Alta Califórnia, Mark Twain publica, em 1869, seu relato de viagem, The Innocents Abroad or TheNew Pilgrim’s Progress. Nosso estudo demonstra que o autor, apesar das diversas máscaras usadas em seus relatos, narra histórias, culturas e tradições, tanto da Europa quanto do Oriente, já com os olhos bem abertos pelo viés antiimperialista. Faz uso da paródia, sátira, ironia e humor para dessacralizar impérios, monarcas e a Igreja que subjugavam os mais fracos, iluminando, desde então, os estudos sobre culturas. Nosso estudo, outrossim, faz uma reflexão sobre cultura, tradição e o olhar do viajante, justificando o “olhar inocente” do narrador em seu relato.After carefully reading the Treaty of Paris in 1900, Mark Twain concluded that the goal of U.S. policy was clearly one ofsubjugation. He openly declared himself an anti-imperialist at that time, in spite of the numerous criticisms he received from political opponents who supported the United States status quo. After traveling to Europe and the East in 1867 as a correspondent for The DailyAlta California newspaper, Mark Twain published his travel report, The Innocents Abroad or The New Pilgrim’s Progress in 1869. Our study demonstrates that the author, in spite of using different guises in his reports, narrated histories, cultures and traditions – from both Europe and the East – with a viewpoint already imbued by his anti-imperialistic ideals. Twain made use of parody, satire, irony and humor within his texts in order to desecrate empires,monarchs and

  8. Telithromycin resistance in Streptococcus pneumoniae is conferred by a deletion in the leader sequence of erm(B) that increases rRNA methylation

    DEFF Research Database (Denmark)

    Wolter, Nicole; Smith, Anthony M; Farrell, David J

    2008-01-01

    A telithromycin-resistant clinical isolate of Streptococcus pneumoniae (strain P1501016) has been found to contain a version of erm(B) that is altered by a 136-bp deletion in the leader sequence. By allele replacement mutagenesis, a second strain of S. pneumoniae (PC13) with a wild-type erm(B) gene...... was transformed to the telithromycin-resistant phenotype by introduction of the mutant erm(B) gene. Whereas the wild-type PC13 strain showed slight telithromycin resistance only after induction by erythromycin (telithromycin MIC increased from 0.06 to 0.5 microg/ml), the transformed PC13 strain is constitutively...... resistant (MIC of 16 mug/ml). Expression of erm(B) was quantified by real-time reverse transcription-PCR in the presence of erythromycin or telithromycin; erm(B) expression was significantly higher in the transformed PC13 strain than the wild-type strain. Furthermore, the transformed strain had...

  9. Expression of Brain-Derived Neurotrophic Factor (BDNF Increases the Resistance of Neurons to Death in the Postresuscitation Period

    Directory of Open Access Journals (Sweden)

    I. V. Ostrova

    2015-01-01

    Full Text Available A search for substances that are able to protect brain cells from the damaging effect of hypoxia remains one of the most relevant issues in modern neurobiology and medicine. Whether neurotrophic factors, brain-derived neurotrophic factor (BDNF protein in particular, can be used to treat neurological diseases is the subject of wide speculation in the literature now. However, how the expression of this protein in the brain neurons changes after systemic circulatory arrest in the postresuscitation period remains uncertain.Objective: to estimate the level of BDNF expression in the highly ischemia-sensitive neuronal population of cerebellar Purkinje cells and the value of BDNF in the resistance of neurons to ischemia-reperfusion.Materials and methods. In mature outbred male albino rats (n=11, the heart was stopped under ether anesthesia at 12 minutes via intrathoracic ligation of the vascular fascicle, followed by revivification. A control group included pseudo-operated animals (n=11. On days 7 after revivification, a morphometric analysis of Nissl-stained paraffin sections 5—6 μm thick was used to determine the total number of Purkinje cells per 1 mm of their layer length. The expression of BDNF protein in the Purkinje cells was immunohistochemically examined by an indirect peroxidase-antiperoxidase test using primary polyclonal antibodies against BDNF. The count of Purkinje cells with different immune responses to BDNF protein was calculated. The intensity of BDNF expression was estimated from the mean optical density. Results. 12-minute systemic circulatory arrest in the rats resulted in a 12.5% reduction in the number of Purkinje cells. The immunohistochemical examination revealed a lower numbers of BDNF– neurons in the resuscitated rats. In this case, the count of BDNF+ and BDNF++ neurons corresponded to their reference level. Consequently, only BDNF-negative neurons, i.e. those that failed to express BDNF protein, died. Analysis of the

  10. Alleviation of insulin resistance and liver damage by oral administration of Imm124-E is mediated by increased Tregs and associated with increased serum GLP-1 and adiponectin: results of a phase I/II clinical trial in NASH

    Directory of Open Access Journals (Sweden)

    Mizrahi M

    2012-12-01

    Full Text Available Meir Mizrahi,1 Yehudit Shabat,1 Ami Ben Ya'acov,1 Gadi Lalazar,1 Tomer Adar,1 Victor Wong,2 Brian Muller,2 Grant Rawlin,2 Yaron Ilan11Liver Unit, Hebrew University-Hadassah Medical Center, Jerusalem, Israel; 2Immuron Limited, North Melbourne, AustraliaBackground: Nonalcoholic steatohepatitis (NASH is considered to be part of the nonalcoholic fatty liver disorders and its incidence is increasing. Imm124-E (Immuron Ltd, Melbourne, Australia, containing hyperimmune bovine colostrum, has been shown to exert an immunomodulatory effect and to alleviate target organ damage in animal models of NASH. The aim of our study was to determine the safety and efficacy of oral administration of Imm124-E to patients with insulin resistance and NASH.Methods: In an open-label trial, ten patients with biopsy-proven NASH and insulin resistance were orally treated with Imm124-E for 30 days.Results: Oral administration of Imm124-E was safe, and no side effects were noted. Alleviation of insulin resistance was reflected by significantly improved hemoglobin A1c (HbA1c values in all ten treated patients. For between five and eight responders, the following effects were noted: a decrease in fasting glucose levels; improved oral glucose tolerance test (OGGT and homeostatic model assessment insulin resistance (HOMA scores; and alleviation in lipid profile. These effects were accompanied by increased serum levels of glucagon-like peptide 1 (GLP-1, adiponectin and T regulatory cells.Conclusion: Hyperimmune colostrum alleviates NASH.Keywords: NASH, anti-LPS, diabetes, adipokines, regulatory T cells

  11. Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses*

    Science.gov (United States)

    Huo, Yuqing; Guo, Xin; Li, Honggui; Xu, Hang; Halim, Vera; Zhang, Weiyu; Wang, Huan; Fan, Yang-Yi; Ong, Kuok Teong; Woo, Shih-Lung; Chapkin, Robert S.; Mashek, Douglas G.; Chen, Yanming; Dong, Hui; Lu, Fuer; Wei, Lai; Wu, Chaodong

    2012-01-01

    Increasing evidence demonstrates the dissociation of fat deposition, the inflammatory response, and insulin resistance in the development of obesity-related metabolic diseases. As a regulatory enzyme of glycolysis, inducible 6-phosphofructo-2-kinase (iPFK2, encoded by PFKFB3) protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance independently of adiposity. Using aP2-PFKFB3 transgenic (Tg) mice, we explored the ability of targeted adipocyte PFKFB3/iPFK2 overexpression to modulate diet-induced inflammatory responses and insulin resistance arising from fat deposition in both adipose and liver tissues. Compared with wild-type littermates (controls) on a high fat diet (HFD), Tg mice exhibited increased adiposity, decreased adipose inflammatory response, and improved insulin sensitivity. In a parallel pattern, HFD-fed Tg mice showed increased hepatic steatosis, decreased liver inflammatory response, and improved liver insulin sensitivity compared with controls. In both adipose and liver tissues, increased fat deposition was associated with lipid profile alterations characterized by an increase in palmitoleate. Additionally, plasma lipid profiles also displayed an increase in palmitoleate in HFD-Tg mice compared with controls. In cultured 3T3-L1 adipocytes, overexpression of PFKFB3/iPFK2 recapitulated metabolic and inflammatory changes observed in adipose tissue of Tg mice. Upon treatment with conditioned medium from iPFK2-overexpressing adipocytes, mouse primary hepatocytes displayed metabolic and inflammatory responses that were similar to those observed in livers of Tg mice. Together, these data demonstrate a unique role for PFKFB3/iPFK2 in adipocytes with regard to diet-induced inflammatory responses in both adipose and liver tissues. PMID:22556414

  12. Spread of ISCR1 Elements Containing blaDHA-1 and Multiple Antimicrobial Resistance Genes Leading to Increase of Flomoxef Resistance in Extended-Spectrum-β-Lactamase-Producing Klebsiella pneumoniae▿

    Science.gov (United States)

    Lee, Chen-Hsiang; Liu, Jien-Wei; Li, Chia-Chin; Chien, Chun-Chih; Tang, Ya-Fen; Su, Lin-Hui

    2011-01-01

    Increasing resistance to quinolones, aminoglycosides, and/or cephamycins in extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae exacerbates the already limited antibiotic treatment options for infections due to these microbes. In this study, the presence of resistance determinants for these antimicrobial agents was examined by PCR among ESBL-producing Klebsiella pneumoniae (ESBL-KP) isolates that caused bacteremia. Pulsed-field gel electrophoresis was used to differentiate the clonal relationship among the isolates studied. Transferability and the location of the resistance genes were analyzed by conjugation experiments, followed by DNA-DNA hybridization. Among the 94 ESBL-KP isolates studied, 20 isolates of flomoxef-resistant ESBL-KP were identified. They all carried a DHA-1 gene and were genetically diverse. CTX-M genes were found in 18 of the isolates. Among these DHA-1/CTX-M-producing K. pneumoniae isolates, ISCR1 was detected in 13 (72%) isolates, qnr genes (1 qnrA and 17 qnrB genes) were detected in 18 (100%), aac(6′)-Ib-cr was detected in 11 (61%), and 16S rRNA methylase (all armA genes) was detected in 14 (78%). Four transconjugants were available for further analysis, and qnrB4, aac(6′)-Ib-cr, armA, and blaDHA-1 were all identified on these self-transferable blaCTX-M-carrying plasmids. The genetic environments of ISCR1 associated with armA, blaDHA-1, and qnrB4 genes in the four transconjugants were identical. Replicon-type analysis revealed a FIIA plasmid among the four self-transferable plasmids, although the other three were nontypeable. The cotransfer of multiple resistance genes with the ISCR1 element-carrying plasmids has a clinical impact and warrants close monitoring and further study. PMID:21746945

  13. Spread of ISCR1 elements containing blaDHA-₁ and multiple antimicrobial resistance genes leading to increase of flomoxef resistance in extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae.

    Science.gov (United States)

    Lee, Chen-Hsiang; Liu, Jien-Wei; Li, Chia-Chin; Chien, Chun-Chih; Tang, Ya-Fen; Su, Lin-Hui

    2011-09-01

    Increasing resistance to quinolones, aminoglycosides, and/or cephamycins in extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae exacerbates the already limited antibiotic treatment options for infections due to these microbes. In this study, the presence of resistance determinants for these antimicrobial agents was examined by PCR among ESBL-producing Klebsiella pneumoniae (ESBL-KP) isolates that caused bacteremia. Pulsed-field gel electrophoresis was used to differentiate the clonal relationship among the isolates studied. Transferability and the location of the resistance genes were analyzed by conjugation experiments, followed by DNA-DNA hybridization. Among the 94 ESBL-KP isolates studied, 20 isolates of flomoxef-resistant ESBL-KP were identified. They all carried a DHA-1 gene and were genetically diverse. CTX-M genes were found in 18 of the isolates. Among these DHA-1/CTX-M-producing K. pneumoniae isolates, ISCR1 was detected in 13 (72%) isolates, qnr genes (1 qnrA and 17 qnrB genes) were detected in 18 (100%), aac(6')-Ib-cr was detected in 11 (61%), and 16S rRNA methylase (all armA genes) was detected in 14 (78%). Four transconjugants were available for further analysis, and qnrB4, aac(6')-Ib-cr, armA, and bla(DHA-1) were all identified on these self-transferable bla(CTX-M)-carrying plasmids. The genetic environments of ISCR1 associated with armA, bla(DHA-1), and qnrB4 genes in the four transconjugants were identical. Replicon-type analysis revealed a FIIA plasmid among the four self-transferable plasmids, although the other three were nontypeable. The cotransfer of multiple resistance genes with the ISCR1 element-carrying plasmids has a clinical impact and warrants close monitoring and further study.

  14. Plasma Progranulin Concentrations Are Increased in Patients with Type 2 Diabetes and Obesity and Correlated with Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Hua Qu

    2013-01-01

    Full Text Available Insulin resistance (IR is considered to be one of the most important pathogenesis of glycolipid metabolism disorders. However, the molecular mechanism responsible for IR is not fully understood. Recently, the chronic inflammation has been proposed to be involved in the pathogenesis of IR. In this study, we aim to investigate the concentrations of plasma progranulin in Chinese patients with obesity (OB and type 2 diabetes mellitus (T2DM, and its relationship to IR. Plasma progranulin concentrations were significantly higher in the T2DM patients than in the normal glucose tolerant (NGT subjects (. Within the T2DM and the NGT patients, the concentrations of progranulin were significantly higher in obese subjects than that in the normal weight subjects (225.22 ± 34.39 ng/mL versus 195.59 ± 50.47 ng/mL and 183.79 ± 61.63 ng/mL versus 148.69 ± 55.27 ng/mL, . Plasma progranulin concentrations correlated positively with weight, waist circumferences, BMI, HbA1c, TG, IL-6, FINS and HOMA-IR (, while correlated negatively with HOMA-β (. Multiple linear regression analysis showed that BMI, HbA1c, IL-6 and TG correlated independently with circulating progranulin concentrations (. These results suggested that Plasma progranulin concentrations were higher in Chinese patients with type 2 diabetes and obesity and correlated closely with glycolipid metabolism, chronic inflammation and IR.

  15. Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice

    Directory of Open Access Journals (Sweden)

    Shih-Yin Tsai

    2016-08-01

    Full Text Available Obesity is a major risk factor driving the global type II diabetes pandemic. However, the molecular factors linking obesity to disease remain to be elucidated. Gender differences are apparent in humans and are also observed in murine models. Here, we link these differences to expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1, which, upon HFD feeding, becomes significantly reduced in the skeletal muscle and adipose tissue of male but not female mice. Strikingly, restoring 4E-BP1 expression in male mice protects them against HFD-induced obesity and insulin resistance. Male 4E-BP1 transgenic mice also exhibit reduced white adipose tissue accumulation accompanied by decreased circulating levels of leptin and triglycerides. Importantly, transgenic 4E-BP1 male mice are also protected from aging-induced obesity and metabolic decline on a normal diet. These results demonstrate that 4E-BP1 is a gender-specific suppressor of obesity that regulates insulin sensitivity and energy metabolism.

  16. Increased resistance to first-line agents among bacterial pathogens isolated from urinary tract infections in Latin America: time for local guidelines?

    Directory of Open Access Journals (Sweden)

    Soraya S Andrade

    2006-11-01

    Full Text Available Emerging resistance phenotypes and antimicrobial resistance rates among pathogens recovered from community-acquired urinary tract infections (CA-UTI is an increasing problem in specific regions, limiting therapeutic options. As part of the SENTRY Antimicrobial Surveillance Program, a total of 611 isolates were collected in 2003 from patients with CA-UTI presenting at Latin American medical centers. Each strain was tested in a central laboratory using Clinical Laboratory Standard Institute (CLSI broth microdilution methods with appropriate controls. Escherichia coli was the leading pathogen (66%, followed by Klebsiella spp. (7%, Proteus mirabilis (6.4%, Enterococcus spp. (5.6%, and Pseudomonas aeruginosa (4.6%. Surprisingly high resistance rates were recorded for E. coli against first-line orally administered agents for CA-UTI, such as ampicillin (53.6%, TMP/SMX (40.4%, ciprofloxacin (21.6%, and gatifloxacin (17.1%. Decreased susceptibility rates to TMP/SMX and ciprofloxacin were also documented for Klebsiella spp. (79.1 and 81.4%, respectively, and P. mirabilis (71.8 and 84.6%, respectively. For Enterococcus spp., susceptibility rates to ampicillin, chloramphenicol, ciprofloxacin, and vancomycin were 88.2, 85.3, 55.9, and 97.1%, respectively. High-level resistance to gentamicin was detected in 24% of Enterococcus spp. Bacteria isolated from patients with CA-UTI in Latin America showed limited susceptibility to orally administered antimicrobials, especially for TMP/SMX and fluoroquinolones. Our results highlight the need for developing specific CA-UTI guidelines in geographic regions where elevated resistance to new and old compounds may influence prescribing decisions.

  17. Recent results for Mark III

    International Nuclear Information System (INIS)

    Brient, J.C.

    1987-12-01

    This paper presents recent results from the Mark III detector at SPEAR, in the open charm sector. The first topic discussed is the reanalysis of the direct measurement of the D hadronic branching fractions, where a detailed study has been made of the Cabibbo suppressed and multi-π 0 's D decays backgrounds in the double tag sample. Next, the Dalitz plot analysis of the D decays to Kππ is presented, leading to the relative fractions of three-body versus pseudoscalarvector decays. 7 refs., 5 figs

  18. The Mark III vertex chamber

    International Nuclear Information System (INIS)

    Adler, J.; Bolton, T.; Bunnell, K.

    1987-07-01

    The design and construction of the new Mark III vertex chamber is described. Initial tests with cosmic rays prove the ability of track reconstruction and yield triplet resolutions below 50 μm at 3 atm using argon/ethane (50:50). Also performed are studies using a prototype of a pressurized wire vertex chamber with 8 mm diameter straw geometry. Spatial resolution of 35mm was obtained using dimethyl ether (DME) at 1 atm and 30 μm using argon/ethane (50/50 mixture) at 4 atm. Preliminary studies indicate the DME to adversely affect such materials as aluminized Mylar and Delrin

  19. Transgenic plants expressing the AaIT/GNA fusion protein show increased resistance and toxicity to both chewing and sucking pests.

    Science.gov (United States)

    Liu, Shu-Min; Li, Jie; Zhu, Jin-Qi; Wang, Xiao-Wei; Wang, Cheng-Shu; Liu, Shu-Sheng; Chen, Xue-Xin; Li, Sheng

    2016-04-01

    The adoption of pest-resistant transgenic plants to reduce yield losses and decrease pesticide use has been successful. To achieve the goal of controlling both chewing and sucking pests in a given transgenic plant, we generated transgenic tobacco, Arabidopsis, and rice plants expressing the fusion protein, AaIT/GNA, in which an insecticidal scorpion venom neurotoxin (Androctonus australis toxin, AaIT) is fused to snowdrop lectin (Galanthus nivalis agglutinin, GNA). Compared with transgenic tobacco and Arabidopsis plants expressing AaIT or GNA, transgenic plants expressing AaIT/GNA exhibited increased resistance and toxicity to one chewing pest, the cotton bollworm, Helicoverpa armigera. Transgenic tobacco and rice plants expressing AaIT/GNA showed increased resistance and toxicity to two sucking pests, the whitefly, Bemisia tabaci, and the rice brown planthopper, Nilaparvata lugens, respectively. Moreover, in the field, transgenic rice plants expressing AaIT/GNA exhibited a significant improvement in grain yield when infested with N. lugens. This study shows that expressing the AaIT/GNA fusion protein in transgenic plants can be a useful approach for controlling pests, particularly sucking pests which are not susceptible to the toxin in Bt crops. © 2015 Institute of Zoology, Chinese Academy of Sciences.

  20. A UV-resistant mutant without an increased repair synthesis activity, established from a UV-sensitive human clonal cell line

    International Nuclear Information System (INIS)

    Suzuki, N.

    1984-01-01

    When cells of a human clonal cell line, RSa, with high sensitivity to UV lethality, were treated with the mutagen, ethyl methanesulfonate, a variant cell strain, UVr-1, was established as a mutant resistant to 254-nm far-ultraviolet radiation