Oxidative stress dependent microRNA-34a activation via PI3Kα reduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells

Sirtuin-1 (SIRT1) and SIRT6, NAD(+)-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress. Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD. Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins. Induction of miR-34a expression with H2O2 was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction. Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible. Other sirtuin isoforms were not affected by miR-34a. Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases

Thermal oxidative degradation reactions of linear perfluoroalky lethers

Thermal and thermal oxidative stability studies were performed on linear perfluoro alkyl ether fluids. The effect on degradation by metal catalysts and degradation inhibitors are reported. The liner perfluoro alkylethers are inherently unstable at 316 C in an oxidizing atmosphere. The metal catalysts greatly increased the rate of degradation in oxidizing atmospheres. In the presence of these metals in an oxidizing atmosphere, the degradation inhibitors were highly effective in arresting degradation at 288 C. However, the inhibitors had only limited effectiveness at 316 C. The metals promote degradation by chain scission. Based on elemental analysis and oxygen consumption data, the linear perfluoro alkylether fluids have a structural arrangement based on difluoroformyl and tetrafluoroethylene oxide units, with the former predominating

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

Memory consolidation in the cerebellar cortex

Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABA(A) agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage

Seroprevalence of Toxoplasma gondii IgG antibody in HIV/AIDS-infected individuals in Maputo, Mozambique

OBJETIVO Avaliar a prevalência de anticorpos IgG anti- Toxoplasma gondii em pessoas infectadas pelo HIV/Aids e a associação de variáveis demográficas e sociais. MÉTODOS Estudo transversal que incluiu a análise de dados sociodemográficos e laboratoriais de 200 pessoas infectadas por HIV/Aids, atendidas em unidade laboratorial em 2010 na Província de Maputo, Moçambique. Os dados foram coletados por meio de questionário autopreenchido por todos os participantes. Para a análise de anticorpos, amostras de plasma coletadas foram confirmadas para testagem de IgG anti- T. gondii por hemaglutinação. RESULTADOS A soroprevalência de IgG anti- T. gondii foi de 46,0% (IC95% 39,2;52,9), 39,3% (IC95% 29,5;50,0) em homens e de 50,9% (IC95% 41,9;59,8) em mulheres, sem diferença entre sexo (OR 1.30; IC95% 0.95;1.77; p = 0.12). A idade variou de 10 a 60 anos, com maior prevalência de infecção em grupos etários mais idosos, mas sem haver diferença significativa entre eles. Ter consumo regular de carne de gado bovino (OR 1,74; IC95% 1,04;2,89, p = 0,05), possuir criação de gatos/cães (OR 6,18; IC95% 3,60;10,62, p < 0,000) e ter contato regular com a terra (OR 3,38; IC95% 2,19;5,21, p < 0,000) estiveram significativamente associados ao risco de infecção latente. CONCLUSÕES A infecção por toxoplasmose apresenta alta prevalência na população de Moçambique, cujo risco amplia-se pelos aspectos culturais e comportamentais. A toxoplasmose pode ser responsável pela grande carga de morbimortalidade associada a lesões meningoencefálicas em pessoas com HIV/Aids no país.OBJETIVO Evaluar la prevalencia de anticuerpos IgG anti- Toxoplasma gondii en personas infectadas por VIH/SIDA y la asociación de variables demográficas y sociales. MÉTODOS Estudio transversal que incluyó el análisis de datos sociodemográficos y de laboratorio de 200 personas infectadas por VIH/SIDA, atendidas en unidad de laboratorio en 2010 en la Provincia de Maputo, Mozambique. Los datos fueron colectados por medio de cuestionario auto llenado por todos los participantes. Para el análisis de anticuerpos, las muestras de plasma colectadas fueron confirmadas para evaluación anti- T. gondii por hemaglutinación. RESULTADOS La seroprevalencia de IgG anti- T. gondii fue de 46% (IC95% 39,2;52,9), 39,3% (IC95% 29,5;50,0) en hombres y de 50,9% (41,9-59,8%) en mujeres, sin diferencia entre sexo (OR 1.30; IC95% 0.95;1.77; p = 0.12). La edad varió de 10 a 60 años, con mayor prevalencia de infección en grupos etarios más ancianos, pero sin haber diferencia significativa entre ellos. Consumir carne de ganado bovino regularmente (OR 1,74; IC95% 1,04;2,89, p = 0,05), poseer cria de gatos/perros (OR 6,18; IC95% 3,60;10,62, p < 0,000) y tener contacto regular con la tierra (OR 3,38; IC95% 2,19;5,21, p < 0,000) estuvieron significativamente asociados al riesgo de infección latente. CONCLUSIONES La infección por toxoplasmosis presenta alta prevalencia en la población de Mozambique, cuyo riesgo se amplía por los aspectos culturales y de comportamiento. La toxoplasmosis puede ser responsable por la gran carga de morbi-mortalidad asociada a lesiones meningoencefálicas en personas con VIH/SIDA en el país.OBJECTIVE To analyze the prevalence of IgG antibodies to Toxoplasma gondii in patients infected with HIV/AIDS and the association of demographic and social variables. METHODS Descriptive cross-sectional study that included the analysis of sociodemographic data and laboratory findings of 200 patients infected with HIV/AIDS treated in a laboratory unit in Maputo, Mozambique, in 2010. Individual data for all participants were collected with a self-administered questionnaire. Plasma samples were tested for IgG testing of anti- T. gondii using hemagglutination for the analysis of antibodies. RESULTS The seroprevalence of IgG anti- T. gondii was 46.0% (95%CI 39.2;52.9), 39.3% (95%CI 29.5;50.0) in men and 50.9% (95%CI 41.9;59.8) in women, with no difference between sex (OR 1.30; 95%CI 0.95;1.77; p = 0.12). Ages ranged from 10 to 60 years, with a higher prevalence of infection in older age groups, but with no significant difference between them. Regularly consuming cattle meat (OR 1.74; 95%CI 1.04;2.89, p = 0.05), breeding cats/dogs (OR 6.18; 95%CI 3.60;10.62, p < 0.000) and having regular contact with soil (OR 3.38; 95%CI 2.19;5.21; p < 0.000) were significantly associated with risk of latent infection. CONCLUSIONS Toxoplasmosis is an infection with high prevalence in Mozambique. Cultural and behavioral aspects increase the risk. Toxoplasmosis can be responsible in our environment by the great burden of morbidity and mortality associated with meningoencephalic injuries in patients with HIV/AIDS

Measurement of the Superparticle Mass Spectrum in the Long-Lived Stau Scenario at the LHC

In supersymmetric scenarios with a long-lived stau, the LHC experiments provide us with a great environment for precise mass measurements of superparticles. We study a case in which the mass differences between the lightest stau and other sleptons are about 10 GeV or larger, so that the decay products of heavier sleptons are hard enough to be detected. We demonstrate that the masses of neutralinos, sleptons, and squarks can be measured with a good accuracy.Comment: 20 pages, 6 figure

Ac transport studies in polymers by a resistor network and transfer matrix approaches: application to polyaniline

A statistical model of resistor network is proposed to describe a polymer structure and to simulate the real and imaginary components of its ac resistivity. It takes into account the polydispersiveness of the material as well as intrachain and interchain charge transport processes. By the application of a transfer matrix technique, it reproduces ac resistivity measurements carried out with polyaniline films in different doping degrees and at different temperatures. Our results indicate that interchain processes govern the resistivity behavior in the low frequency region while, for higher frequencies, intrachain mechanisms are dominant.Comment: LaTeX file, 15 pages, 5 ps figures, to appear in Phys. Rev.

The application of a VUV Fourier transform spectrometer and synchrotron radiation source to measurements of: II. The δ(1,0) band of NO

Line-by-line photoabsorption cross-sections of the NO δ(1,0) band were measured with the VUV Fourier transform spectrometer from Imperial College, London, using synchrotron radiation at Photon Factory, KEK, Japan, as a continuum light source. The analysis of the NO δ(1,0) band provides accurate rotational line positions and term values as well as the photoabsorption cross-sections. The molecular constants of the C(1)2 II level are found to be T0 = 54 690.155±0.03 cm–1, Bv = 1.944 06±0.000 62 cm–1, Dv = (5.91±0.42)×10–5 cm–1, AD = –0.0187±0.0050 cm–1, p = –0.0189±0.0037 cm–1, and q = –0.015 21±0.000 20 cm–1. The sum of the line strengths for all rotational transitions of the NO δ(1,0) band is determined as 4.80×10–15 cm2 cm–1, corresponding to a band oscillator strength of 0.0054±0.0003.published_or_final_versio