117 research outputs found

    Interaction of the tetracyclines with double-stranded RNAs of random base sequence: new perspectives on the target and mechanism of action

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    The 16S rRNA binding mechanism proposed for the antibacterial action of the tetracyclines does not explain their mechanism of action against non-bacterial pathogens. In addition, several contradictory base pairs have been proposed as their binding sites on the 16S rRNA. This study investigated the binding of minocycline and doxycycline to short double-stranded RNAs (dsRNAs) of random base sequences. These tetracyclines caused a dose-dependent decrease in the fluorescence intensities of 6-carboxyfluorescein (FAM)-labelled dsRNA and ethidium bromide (EtBr)-stained dsRNA, indicating that both drugs bind to dsRNA of random base sequence in a manner that is competitive with the binding of EtBr and other nucleic acid ligands often used as stains. This effect was observable in the presence of Mg2+. The binding of the tetracyclines to dsRNA changed features of the fluorescence emission spectra of the drugs and the CD spectra of the RNA, and inhibited RNase III cleavage of the dsRNA. These results indicate that the double-stranded structures of RNAs may have a more important role in their interaction with the tetracyclines than the specific base pairs, which had hitherto been the subject of much investigation. Given the diverse functions of cellular RNAs, the binding of the tetracyclines to their double-stranded helixes may alter the normal processing and functioning of the various biological processes they regulate. This could help to explain the wide range of action of the tetracyclines against various pathogens and disease condition

    Sense and Antisense Transcripts of Convergent Gene Pairs in Arabidopsis thaliana Can Share a Common Polyadenylation Region

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    The Arabidopsis genome contains a large number of gene pairs that encode sense and antisense transcripts with overlapping 3′ regions, indicative for a potential role of natural antisense transcription in regulating sense gene expression or transcript processing. When we mapped poly(A) transcripts of three plant gene pairs with long overlapping antisense transcripts, we identified an unusual transcript composition for two of the three gene pairs. Both genes pairs encoded a class of long sense transcripts and a class of short sense transcripts that terminate within the same polyadenylation region as the antisense transcripts encoded by the opposite strand. We find that the presence of the short sense transcript was not dependent on the expression of an antisense transcript. This argues against the assumption that the common termination region for sense and antisense poly(A) transcripts is the result of antisense-specific regulation. We speculate that for some genes evolution may have especially favoured alternative polyadenylation events that shorten transcript length for gene pairs with overlapping sense/antisense transcription, if this reduces the likelihood for dsRNA formation and transcript degradation

    Management of chronic obstructive pulmonary disease in India: a systematic review.

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    OBJECTIVES: Chronic diseases are fast becoming the largest health burden in India. Despite this, their management in India has not been well studied. We aimed to systematically review the nature and efficacy of current management strategies for chronic obstructive pulmonary disease (COPD) in India. METHODS: We used database searches (MEDLINE, EMBASE, IndMED, CENTRAL and CINAHL), journal hand-searches, scanning of reference lists and contact with experts to identify studies for systematic review. We did not review management strategies aimed at chronic diseases more generally, nor management of acute exacerbations. Due to the heterogeneity of reviewed studies, meta-analysis was not appropriate. Thus, narrative methods were used. SETTING: India. PARTICIPANTS: All adult populations resident in India. MAIN OUTCOME MEASURES: 1. Trialled interventions and outcomes 2. Extent and efficacy of current management strategies 3. Above outcomes by subgroup. RESULTS: We found information regarding current management - particularly regarding the implementation of national guidelines and primary prevention - to be minimal. This led to difficulty in interpreting studies of management strategies, which were varied and generally of positive effect. Data regarding current management outcomes were very few. CONCLUSIONS: The current understanding of management strategies for COPD in India is limited due to a lack of published data. Determination of the extent of current use of management guidelines, availability and use of treatment, and current primary prevention strategies would be useful. This would also provide evidence on which to interpret existing and future studies of management outcomes and novel interventions

    Predictors of persistently positive Mycobacterium-tuberculosis-specific interferon-gamma responses in the serial testing of health care workers

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    <p>Abstract</p> <p>Background</p> <p>Data on the performance of Mycobacterium-tuberculosis-specific interferon-(IFN)-γ release assays (IGRAs) in the serial testing of health care workers (HCWs) is limited. The objective of the present study was to determine the frequency of IGRA conversions and reversions and to identify predictors of persistent IGRA positivity among serially tested German HCWs in the absence of recent extensive tuberculosis (TB) exposure.</p> <p>Methods</p> <p>In this observational cohort-study HCWs were prospectively recruited within occupational safety and health measures and underwent a tuberculin skin test (TST) and the IGRA QuantiFERON<sup>®</sup>-TB Gold In-Tube (QFT-GIT) at baseline. The QFT-GIT was repeated 18 weeks later in the median. QFT-GIT conversions (and reversions) were defined as baseline IFN-γ < 0.35 IU/ml and follow-up IFN-γ ≥ 0.35 IU/ml (and vice versa). Predictors of persistently positive QFT-GIT results were calculated by logistic regression analysis.</p> <p>Results</p> <p>In total, 18 (9.9%) and 15 (8.2%) of 182 analyzed HCWs were QFT-GIT-positive at baseline and at follow-up, respectively. We observed a strong overall agreement between baseline and follow-up QFT-GIT results (κ = 0.70). Reversions (6/18, 33.3%) occurred more frequently than conversions (3/162, 1.9%). Age and positive prior and recent TST results independently predicted persistent QFT-GIT positivity. Furthermore, the chance of having persistently positive QFT-GIT results raised about 3% with each additional 0.1 IU/ml increase in the baseline IFN-γ response (adjusted odds ratio 1.03, 95% confidence interval 1.01-1.04). No active TB cases were detected within an observational period of more than two years.</p> <p>Conclusions</p> <p>The QFT-GIT's utility for the application in serial testing was limited by a substantial proportion of reversions. This shortcoming could be overcome by the implementation of a borderline zone for the interpretation of QFT-GIT results. However, further studies are needed to clearly define the within-subject variability of the QFT-GIT and to confirm that increasing age, concordantly positive TST results, and the extend of baseline IFN-γ responses may predict the persistence of QFT-GIT positivity over time in serially tested HCWs with only a low or medium TB screening risk in a TB low-incidence setting.</p

    Elastic and anelastic relaxation behaviour of perovskite multiferroics I: PbZr0.53Ti0.47O3 (PZT)–PbFe0.5Nb0.5O3 (PFN)

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    Brazilian Consensus on Photoprotection

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    Not AvailableHYDROLOGICAL MONITORING OF WATERSHEDS FORMS AS ESSENTIAL COMPONENT OF WATERSHED MANAGEMENT. IN THIS PAPER, THE STRUCTURAL DEVICES AND TECHNIQUES FOR MEASUREMENTS OF RUNOFF AND SEDIMENT FROM SMALL WATERSHEDS AT NATURAL AND ARTIFICIAL CONTROLS HAVE BEEN DISCUSSED.Not Availabl

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    Not AvailableTHE AUTHORS HAVE ATTEMPTED TO CALCULATE RAINFALL- EXCESS , PERTAINING TO KOTA REGION OF RAJASTHAN STATE, USING DIFFERENT INFILTRATION MODELS, TO ESTABLISH A SIMPLE FLOW ROUTING PROCEDURE WHICH COULD BE APPLIED TO OVERLAND FLOW AND TO DEVELOP AN EVENT BASED RAINFALL- RUNOFF SIMULATION MODEL USING THE PHYSICAL PROCESSES INVOLVED. THE STUDY REVEALED THAT THE VARIABLE RAINFALL INFILTRATION MODEL PRODUCED BETTER RESULTS THAN HORTON'S OR PHILIP'S INFILTRATION MODEL. THE SIMULATION MODEL EFFICIENCY RANGED BETWEEN 80 AND 95% FOR VARIOUS RAINFALL EVENTS. RUNOFF VARIED BETWEEN 11.5 AND 66.6 % AND IT WAS WELL- RELATED TO THE RAINFALL INTENSITY.Not Availabl
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