327 research outputs found

    SWI/SNF senses carbon starvation with a pH-sensitive low complexity sequence [preprint]

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    It is increasingly appreciated that intracellular pH changes are important biological signals. This motivates the elucidation of molecular mechanisms of pH-sensing. We determined that a nucleocytoplasmic pH oscillation was required for the transcriptional response to carbon starvation in S. cerevisiae. The SWI/SNF chromatin remodeling complex is a key mediator of this transcriptional response. We found that a glutamine-rich low complexity sequence (QLC) in the SNF5 subunit of this complex, and histidines within this sequence, were required for efficient transcriptional reprogramming during carbon starvation. Furthermore, the SNF5 QLC mediated pH-dependent recruitment of SWI/SNF to a model promoter in vitro. Simulations showed that protonation of histidines within the SNF5 QLC lead to conformational expansion, providing a potential biophysical mechanism for regulation of these interactions. Together, our results indicate that that pH changes are a second messenger for transcriptional reprogramming during carbon starvation, and that the SNF5 QLC acts as a pH-sensor

    New tetracyclic heteroaromatic compounds based on dehydroamino acids : photophysical and electrochemical studies of interaction with DNA

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    A benzothienoindole (BTIN) and a benzofuroindole (BFIN) were synthesized in high yields, as potential new target DNA compounds, using a metal-assisted intramolecular C-N cyclization, developed by us, of the methyl esters of N-(t-butoxycarbonyl)-b,b-bis(dibenzothien-4-yl or dibenzofuro-4-yl)dehydroalanines. The latter were obtained by a bis-Suzuki coupling of a b,b-dibromodehydroalanine with the corresponding heteroarylboronic acids. The absorption and fluorescence properties of the novel tetracyclic heteroaromatic compounds were studied in different solvents and in the presence of natural double-stranded (ds) salmon sperm DNA. The results in several solvents show that either BTIN or BFIN can be used as fluorescence solvent sensitive probes. Spectroscopic studies of the interaction of both compounds with dsDNA allowed to determine binding constant (Ki) values and binding site sizes (n). Fluorescence quenching experiments using iodide ion allowed the determination of the accessibilities to the quencher, showing that intercalation is the preferred mode of binding of these molecules to DNA. From the results obtained BTIN is the more intercalative compound and has a higher affinity to DNA. The interaction of this more promising compound with DNA was also studied electrochemically, by using differential pulse voltammetry (DPV) in connection with disposable pencil graphite electrode (PGE). These studies are based on the differences in the BTIN and adenine oxidation signals. After the interaction of BTIN with DNA, the oxidation signals of BTIN and adenine strongly decreased. The latter was attributed to the binding of the BTIN to DNA and the former points to a possible damage of the oxidizable groups of the compound after intercalation into DNA. Several concentrations of BTIN were tested and 50 μg/mL was found to be the optimum concentration in order to detect its interaction with DNA. In addition, the detection limit and the reproducibility were determined by using a disposable electrochemical transducer. The results of spectroscopic and electrochemical detection of BTIN interaction with DNA are in good agreement.Academy of Pharmacists and Turkish Pharmacists Association (TEB)Turkish Academy of Sciences - Young Scientist Award Program (KAE/TUBA-GEBIP/2001-2-8)FEDERFundação para a Ciência e a Tecnologia (FCT) - Projecto POCI/QUI/59407/2004. A.S.A. acknowledges a post-doc. grant SFRH/BPD/24548/2005, Bolsa SFRH/BPD/24548/2005.Scientific and Technical Research Council of Turkey (TUBITAK)

    Screening of antioxidant properties of the apple juice using the front-face synchronous fluorescence and chemometrics

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    Fluorescence spectroscopy is gaining increasing attention in food analysis due to its higher sensitivity and selectivity as compared to other spectroscopic techniques. Synchronous scanning fluorescence technique is particularly useful in studies of multi-fluorophoric food samples, providing a further improvement of selectivity by reduction in the spectral overlapping and suppressing light-scattering interferences. Presently, we study the feasibility of the prediction of the total phenolics, flavonoids, and antioxidant capacity using front-face synchronous fluorescence spectra of apple juices. Commercial apple juices from different product ranges were studied. Principal component analysis (PCA) applied to the unfolded synchronous fluorescence spectra was used to compare the fluorescence of the entire sample set. The regression analysis was performed using partial least squares (PLS1 and PLS2) methods on the unfolded total synchronous and on the single-offset synchronous fluorescence spectra. The best calibration models for all of the studied parameters were obtained using the PLS1 method for the single-offset synchronous spectra. The models for the prediction of the total flavonoid content had the best performance; the optimal model was obtained for the analysis of the synchronous fluorescence spectra at Delta lambda = 110 nm (R (2) = 0.870, residual predictive deviation (RPD) = 2.7). The optimal calibration models for the prediction of the total phenolic content (Delta lambda = 80 nm, R (2) = 0.766, RPD = 2.0) and the total antioxidant capacity (Delta lambda = 70 nm, R (2) = 0.787, RPD = 2.1) had only an approximate predictive ability. These results demonstrate that synchronous fluorescence could be a useful tool in fast semi-quantitative screening for the antioxidant properties of the apple juices.info:eu-repo/semantics/publishedVersio

    A Large Hadron Electron Collider at CERN

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    This document provides a brief overview of the recently published report on the design of the Large Hadron Electron Collider (LHeC), which comprises its physics programme, accelerator physics, technology and main detector concepts. The LHeC exploits and develops challenging, though principally existing, accelerator and detector technologies. This summary is complemented by brief illustrations of some of the highlights of the physics programme, which relies on a vastly extended kinematic range, luminosity and unprecedented precision in deep inelastic scattering. Illustrations are provided regarding high precision QCD, new physics (Higgs, SUSY) and electron-ion physics. The LHeC is designed to run synchronously with the LHC in the twenties and to achieve an integrated luminosity of O(100) fb1^{-1}. It will become the cleanest high resolution microscope of mankind and will substantially extend as well as complement the investigation of the physics of the TeV energy scale, which has been enabled by the LHC

    ERS International Congress 2022: highlights from the Respiratory Clinical Care and Physiology Assembly

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    It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of the laboratory-based science, clinical trials and qualitative research that were presented during the 2022 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, mobile/electronic health (m-health/e-health), clinical respiratory physiology, exercise and functional imaging

    Investigation of the Performance of the New Orleans Flood Protection System in Hurricane Katrina on August 29, 2005: Volume 1

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    This report presents the results of an investigation of the performance of the New Orleans regional flood protection system during and after Hurricane Katrina, which struck the New Orleans region on August 29, 2005. This event resulted in the single most costly catastrophic failure of an engineered system in history. Current damage estimates at the time of this writing are on the order of 100to100 to 200 billion in the greater New Orleans area, and the official death count in New Orleans and southern Louisiana at the time of this writing stands at 1,293, with an additional 306 deaths in nearby southern Mississippi. An additional approximately 300 people are currently still listed as “missing”; it is expected that some of these missing were temporarily lost in the shuffle of the regional evacuation, but some of these are expected to have been carried out into the swamps and the Gulf of Mexico by the storm’s floodwaters, and some are expected to be recovered in the ongoing sifting through the debris of wrecked homes and businesses, so the current overall regional death count of 1,599 is expected to continue to rise a bit further. More than 450,000 people were initially displaced by this catastrophe, and at the time of this writing more than 200,000 residents of the greater New Orleans metropolitan area continue to be displaced from their homes by the floodwater damages from this storm event. This investigation has targeted three main questions as follow: (1) What happened?, (2) Why?, and (3) What types of changes are necessary to prevent recurrence of a disaster of this scale again in the future? To address these questions, this investigation has involved: (1) an initial field reconnaissance, forensic study and data gathering effort performed quickly after the arrival of Hurricanes Katrina (August 29, 2005) and Rita (September 24, 2005), (2) a review of the history of the regional flood protection system and its development, (3) a review of the challenging regional geology, (4) detailed studies of the events during Hurricanes Katrina and Rita, as well as the causes and mechanisms of the principal failures, (4) studies of the organizational and institutional issues affecting the performance of the flood protection system, (5) observations regarding the emergency repair and ongoing interim levee reconstruction efforts, and (6) development of findings and preliminary recommendations regarding changes that appear warranted in order to prevent recurrence of this type of catastrophe in the future. In the end, it is concluded that many things went wrong with the New Orleans flood protection system during Hurricane Katrina, and that the resulting catastrophe had it roots in three main causes: (1) a major natural disaster (the Hurricane itself), (2) the poor performance of the flood protection system, due to localized engineering failures, questionable judgments, errors, etc. involved in the detailed design, construction, operation and maintenance of the system, and (3) more global “organizational” and institutional problems associated with the governmental and local organizations responsible for the design, construction, operation, maintenance and funding of the overall flood protection system

    European Respiratory Society International Congress, Barcelona, 2022: Highlights from the Respiratory clinical care and physiology assembly

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    It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of laboratory-based science, clinical trials and qualitative research that were presented during the 2022 European Respiratory Society International Congress within the sessions from the five groups of the Assembly 1 – Respiratory clinical care and physiology. Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, electronic/mobile health (e-health/m-health), clinical respiratory physiology, exercise and functional imaging
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