294 research outputs found

    Prospecting and informed dispersal : Understanding and predicting their joint eco-evolutionary dynamics

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    ACKNOWLEDGMENTS AP was funded by a European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 753420 (EcoEvoProspectS project). JMJT and AS were funded by the Biotechnology and Biological Sciences Research Council, project grant BB/S507349/1.Peer reviewedPublisher PD

    Evaluation of the performances of a single-use duodenoscope: Prospective multi-center national study

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    Objectives: A single-use duodenoscope (SUD) has been recently developed to overcome issues with endoscopic retrograde cholangiopancreatography (ERCP)-related cross-infections. The aim was to evaluate SUD safety and performance in a prospective multi-centre study. Methods: All consecutive patients undergoing ERCP in six French centers were prospectively enrolled. All procedures were performed with the SUD; in case of ERCP failure, operators switched to a reusable duodenoscope. Study outcomes were the successful completion of the procedure with SUD, safety and operators’ satisfaction based on a VAS 0–10 and on 22 qualitative items. The study protocol was approved by French authorities and registered (ID-RCB: 2020-A00346-33). External companies collected the database and performed statistical analysis. Results: Sixty patients (34 females, median age 65.5 years old) were enrolled. Main indications were bile duct stones (41.7%) and malignant biliary obstruction (26.7%). Most ERCP were considered ASGE grade 2 (58.3%) or 3 (35.0%). Fifty-seven (95.0%) procedures were completed using the SUD. Failures were unrelated to SUD (one duodenal stricture, one ampullary infiltration, and one tight biliary stricture) and could not be completed with reusable duodenoscopes. Median operators’ satisfaction was 9 (7–9). Qualitative assessments were considered clinically satisfactory in a median of 100% of items and comparable to a reusable duodenoscope in 97.9% of items. Three patients (5%) reported an adverse event. None was SUD-related. Conclusions: The use of a SUD allows ERCP to be performed with an optimal successful rate. Our data show that SUD could be used for several ERCP indications and levels of complexity

    Treatment of post-cholecystectomy biliary strictures with fully-covered self-expanding metal stents - results after 5 years of follow-up

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    BACKGROUND: Endoscopic treatment of post-cholecystectomy biliary strictures (PCBS) with multiple plastic biliary stents placed sequentially is a minimally invasive alternative to surgery but requires multiple interventions. Temporary placement of a single fully-covered self-expanding metal stent (FCSEMS) may offer safe and effective treatment with fewer re-interventions. Long-term effectiveness of treatment with FCSEMS to obtain PCBS resolution has not yet been studied. METHODS: In this prospective multi-national study in patients with symptomatic benign biliary strictures (N = 187) due to various etiologies received a FCSEMS with scheduled removal at 6-12 months and were followed for 5 years. We report here long-term outcomes of the subgroup of patients with PCBS (N = 18). Kaplan Meier analyses assessed long-term freedom from re-stenting. Adverse events were documented. RESULTS: Endoscopic removal of the FCSEMS was achieved in 83.3% (15/18) of patients after median indwell of 10.9 (range 0.9-13.8) months. In the remaining 3 patients (16.7%), the FCSEMS spontaneously migrated and passed without complications. At the end of FCSEMS indwell, 72% (13/18) of patients had stricture resolution. At 5 years after FCSEMS removal, 84.6% (95% CI 65.0-100.0%) of patients who had stricture resolution at FCSEMS removal remained stent-free. In addition, at 75 months after FCSEMS placement, the probability of remaining stent-free was 61.1% (95% CI 38.6-83.6%) for all patients. Stent or removal related serious adverse events occurred in 38.9% (7/18) all resolved without sequalae. CONCLUSIONS: In patients with symptomatic PCBS, temporary placement of a single FCSEMS intended for 10-12 months indwell is associated with long-term stricture resolution up to 5 years. Temporary placement of a single FCSEMS may be considered for patients with PCBS not involving the main hepatic confluence. TRIAL REGISTRATION NUMBERS: NCT01014390; CTRI/2012/12/003166; Registered 17 November 2009

    Frequency components of systolic blood pressure variability reflect vasomotor and cardiac sympathetic functions in conscious rats

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    In this study, after confirming the suppression of autonomic nervous function by isoflurane anesthesia using autonomic antagonists, we pharmacologically investigated the involvement of vasomotor and cardiac sympathetic functions in systolic blood pressure variability (SBPV) frequency components in conscious rats at rest and during exposure to low-ambient temperature (LT-exposure, 9°C for 90 min). Under unanesthesia, phentolamine administration (α-adrenoceptor antagonist, 10 mg/kg) decreased the mid-frequency component (MF 0.33–0.73 Hz) and inversely increased the high-frequency component (HF 1.3–2.5 Hz). The increased HF was suppressed by subsequent treatment with atenolol (β-adrenoceptor antagonist, 10 mg/kg), but not with atropine (muscarinic receptor antagonist, 10 mg/kg). Moreover, phentolamine administration after atenolol decreased MF, but did not increase HF. LT-exposure increased MF and HF; however, phentolamine pretreatment suppressed the increased MF during LT-exposure, and atenolol pretreatment dose-dependently decreased the increased HF. These results suggest that MF and HF of SBPV may reflect α-adrenoceptor-mediated vasomotor function and β-adrenoceptor-mediated cardiac sympathetic function, respectively, in the conscious state

    Site-specific labeling of nucleotides for making RNA for high resolution NMR studies using an E. coli strain disabled in the oxidative pentose phosphate pathway

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    Escherichia coli (E. coli) is a versatile organism for making nucleotides labeled with stable isotopes (13C, 15N, and/or 2H) for structural and molecular dynamics characterizations. Growth of a mutant E. coli strain deficient in the pentose phosphate pathway enzyme glucose-6-phosphate dehydrogenase (K10-1516) on 2-13C-glycerol and 15N-ammonium sulfate in Studier minimal medium enables labeling at sites useful for NMR spectroscopy. However, 13C-sodium formate combined with 13C-2-glycerol in the growth media adds labels to new positions. In the absence of labeled formate, both C5 and C6 positions of the pyrimidine rings are labeled with minimal multiplet splitting due to 1JC5C6 scalar coupling. However, the C2/C8 sites within purine rings and the C1′/C3′/C5′ positions within the ribose rings have reduced labeling. Addition of 13C-labeled formate leads to increased labeling at the base C2/C8 and the ribose C1′/C3′/C5′ positions; these new specific labels result in two- to three-fold increase in the number of resolved resonances. This use of formate and 15N-ammonium sulfate promises to extend further the utility of these alternate site specific labels to make labeled RNA for downstream biophysical applications such as structural, dynamics and functional studies of interesting biologically relevant RNAs

    Preparation of selective and segmentally labeled single-stranded DNA for NMR by self-primed PCR and asymmetrical endonuclease double digestion

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    We demonstrate a new, efficient and easy-to-use method for enzymatic synthesis of (stereo-)specific and segmental 13C/15N/2H isotope-labeled single-stranded DNA in amounts sufficient for NMR, based on the highly efficient self-primed PCR. To achieve this, new approaches are introduced and combined. (i) Asymmetric endonuclease double digestion of tandem-repeated PCR product. (ii) T4 DNA ligase mediated ligation of two ssDNA segments. (iii) In vitro dNTP synthesis, consisting of in vitro rNTP synthesis followed by enzymatic stereo-selective reduction of the C2′ of the rNTP, and a one-pot add-up synthesis of dTTP from dUTP. The method is demonstrated on two ssDNAs: (i) a 36-nt three-way junction, selectively 13C9/15N3/2H(1′,2″,3′,4′,5′,5″)-dC labeled and (ii) a 39-nt triple-repeat three-way junction, selectively 13C9/15N3/2H(1′,2″,3′,4′,5′,5″)-dC and 13C9/15N2/2H(1′,2″,3′,4′,5′,5″)-dT labeled in segment C20-C39. Their NMR spectra show the spectral simplification, while the stereo-selective 2H-labeling in the deoxyribose of the dC-residues, straightforwardly provided assignment of their C1′–H2′ and C2′–H2′ resonances. The labeling protocols can be extended to larger ssDNA molecules and to more than two segments

    Foraging Fidelity as a Recipe for a Long Life: Foraging Strategy and Longevity in Male Southern Elephant Seals

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    Identifying individual factors affecting life-span has long been of interest for biologists and demographers: how do some individuals manage to dodge the forces of mortality when the vast majority does not? Answering this question is not straightforward, partly because of the arduous task of accurately estimating longevity in wild animals, and of the statistical difficulties in correlating time-varying ecological covariables with a single number (time-to-event). Here we investigated the relationship between foraging strategy and life-span in an elusive and large marine predator: the Southern Elephant Seal (Mirounga leonina). Using teeth recovered from dead males on îles Kerguelen, Southern Ocean, we first aged specimens. Then we used stable isotopic measurements of carbon () in dentin to study the effect of foraging location on individual life-span. Using a joint change-point/survival modelling approach which enabled us to describe the ontogenetic trajectory of foraging, we unveiled how a stable foraging strategy developed early in life positively covaried with longevity in male Southern Elephant Seals. Coupled with an appropriate statistical analysis, stable isotopes have the potential to tackle ecological questions of long standing interest but whose answer has been hampered by logistic constraints

    Viral capsids: Mechanical characteristics, genome packaging and delivery mechanisms

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    The main functions of viral capsids are to protect, transport and deliver their genome. The mechanical properties of capsids are supposed to be adapted to these tasks. Bacteriophage capsids also need to withstand the high pressures the DNA is exerting onto it as a result of the DNA packaging and its consequent confinement within the capsid. It is proposed that this pressure helps driving the genome into the host, but other mechanisms also seem to play an important role in ejection. DNA packaging and ejection strategies are obviously dependent on the mechanical properties of the capsid. This review focuses on the mechanical properties of viral capsids in general and the elucidation of the biophysical aspects of genome packaging mechanisms and genome delivery processes of double-stranded DNA bacteriophages in particular
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