649 research outputs found
Dynamics of supercoiled DNA with complex knots: Large-scale rearrangements and persistent multi-strand interlocking
Knots and supercoiling are both introduced in bacterial plasmids by catalytic processes involving DNA strand passages. While the effects on plasmid organization has been extensively studied for knotting and supercoiling taken separately, much less is known about their concurrent action. Here, we use molecular dynamics simulations and oxDNA, an accurate mesoscopic DNA model, to study the kinetic and metric changes introduced by complex (five-crossing) knots and supercoiling in 2 kbp-long DNA rings. We find several unexpected results. First, the conformational ensemble is dominated by two distinct states, differing in branchedness and knot size. Secondly, fluctuations between these states are as fast as the metric relaxation of unknotted rings. In spite of this, certain boundaries of knotted and plectonemically-wound regions can persist over much longer timescales. These pinned regions involve multiple strands that are interlocked by the cooperative action of topological and supercoiling constraints. Their long-lived character may be relevant for the simplifying action of topoisomerases
Directional translocation resistance of Zika xrRNA
xrRNAs from flaviviruses survive in host cells because of their exceptional dichotomic response to the unfolding action of different enzymes. They can be unwound, and hence copied, by replicases, and yet can resist degradation by exonucleases. How the same stretch of xrRNA can encode such diverse responses is an open question. Here, by using atomistic models and translocation simulations, we uncover an elaborate and directional mechanism for how stress propagates when the two xrRNA ends, 5 \u2032 and 3 \u2032, are driven through a pore. Pulling the 3 \u2032 end, as done by replicases, elicits a progressive unfolding; pulling the 5 \u2032 end, as done by exonucleases, triggers a counterintuitive molecular tightening. Thus, in what appears to be a remarkable instance of intra-molecular tensegrity, the very pulling of the 5 \u2032 end is what boosts resistance to translocation and consequently to degradation. The uncovered mechanistic principle might be co-opted to design molecular meta-materials
Variable order Mittag-Leffler fractional operators on isolated time scales and application to the calculus of variations
We introduce new fractional operators of variable order on isolated time
scales with Mittag-Leffler kernels. This allows a general formulation of a
class of fractional variational problems involving variable-order difference
operators. Main results give fractional integration by parts formulas and
necessary optimality conditions of Euler-Lagrange type.Comment: This is a preprint of a paper whose final and definite form is with
Springe
Arrhythmia mechanism dependent pulmonary vein ablation in paroxysmal atrial fibrillation
Atrial fibrillation (AF) often requires invasive treatment by ablation to decrease symptom burden. The pulmonary veins (PV) are thought to trigger paroxysms of AF, and ablative PV isolation (PVI) is a cornerstone in AF treatment. However, incomplete PVI, where electrical conduction between the PV and left atrium (LA) is maintained, is curative of AF in a subset of patients. This implies that an antiarrhythmic effect other than electrical isolation between the PV and LA plays a role in AF prevention in these patients. We reason that the PV myocardium constitutes an arrhythmogenic substrate conducive to reentry in the patients with curative incomplete PVI. This PV substrate is amenable to ablation, even when conduction between the LA and PV persists. We propose that PV ablation strategies are differentiated to fit the arrhythmogenic mechanisms in the individual patient. PV substrate modification in patients with PV reentry may constitute a new therapeutic approach that is potentially simpler and more effective, in this subgroup of patients
Stability of biocontrol products carrying Candida sake CPA-1 in starch derivatives as a function of water activity
[EN] The preservation and shelf-life of formulations of the biocontrol
agent Candida sake CPA-1 and starch derivatives as a function of
water activity (aW) were studied in terms of the physical stability
of the products and cell viability. Formulations of biocontrol
products (BCPs), based on combinations of potato starch and pregelatinised
potato starch (F1 and F2) or maltodextrines (MD) (F3)
containing cell protectants, were obtained by fluidised-bed drying.
The carriers and the formulated products were stored at 20°C
under different aW conditions. The water sorption and water
plasticization behaviour of the different products were analysed
through the water sorption isotherms and glass transition
temperatures (Tg). Likewise, the viability of C. sake over time was
determined as a function of the aW. The solubility of the products
was also assessed. Although formulations stored at 20°C and low
aW (≤ 0.33) exhibited a better shelf-life, a significant decrease in
cell survival ratio after 180 storage days was observed. Cold
storage (5°C) was required to better maintain the cell viability,
thus prolonging the shelf-life of BCPs. Formulations containing
MD were the most effective at preserving cell viability and also
exhibited the highest water solubility. All the formulations were
physically stable at ambient temperature; therefore, the cell
stability is the critical point at which to establish both the aW
levels and temperature during storage. Packaging the product
using high water vapour barrier material and under cold storage
would be necessary to ensure a high number of viable cells and
an effective and competitive BCPThe authors are grateful to the Spanish Government for the financial support from the national project RTA2012-00067-C02 (Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria, Spain and FEDER funds) and to the Conselleria d'Educacio of the Generalitat Valenciana, (Spain) for A. Marin's PhD grant.Marín-Gozalbo, A.; Atarés Huerta, LM.; Cháfer Nácher, MT.; Chiralt, A. (2017). Stability of biocontrol products carrying Candida sake CPA-1 in starch derivatives as a function of water activity. Biocontrol Science and Technology. 27(2):268-287. https://doi.org/10.1080/09583157.2017.1279587S26828727
Validation of microscopic observation drug susceptibility testing for rapid, direct rifampicin and isoniazid drug susceptibility testing in patients receiving tuberculosis treatment.
Drug susceptibility testing (DST) is often needed in patients clinically failing tuberculosis (TB) therapy. Most studies of phenotypic direct drug susceptibility tests, such as microscopic observation drug susceptibility (MODS) tests, have been performed in patients not receiving TB treatment. The effect of ongoing TB treatment on the performance of MODS direct DST has not been previously explored, but patients failing such therapy constitute an important target group. The aim of this study was to determine the performance of MODS direct rifampicin and isoniazid DST in patients clinically failing first-line TB treatment, and to compare MODS direct DST with indirect proportion method DST. Sputa from 264 TB patients were cultured in parallel in Lowenstein-Jensen (LJ) and MODS assays; strains were tested for rifampicin and isoniazid susceptibility by the proportion method at the national reference laboratory. Ninety-three samples were culture-positive by LJ and MODS (concordance of 96%; kappa 0.92). With conventional MODS plate DST reading (performed on the same day as the sample is classified as culture-positive), the isoniazid DST concordance was 96.8% (kappa 0.89), and the concordance for rifampicin susceptibility testing was 92.6% (kappa 0.80). Reading of MODS DST plates 1 week after cultures had been determined to be culture-positive improved overall performance marginally-the isoniazid DST concordance was 95.7% (kappa 0.85); and the rifampicin DST concordance was 96.8% (kappa 0.91). Sensitivity for detection of multidrug-resistant TB was 95.8%. MODS testing provided reliable rifampicin and isoniazid DST results for samples obtained from patients receiving TB therapy. A modified DST reading schedule for such samples, with a final reading 1 week after a MODS culture turns positive, marginally improves the concordance with reference DST
Open Data Portal Prototype for the Conservation of Biodiversity of the ‘Universidad Nacional de Loja’
This article describes the possibilities of research and development that exist in the ‘Universidad Nacional de Loja’ (UNL) in the field of biodiversity through the use and exploitation of information and communication technology (ICT) resources. First, the existing methodologies, processes, and initiatives for the publication of open data was explored. Subsequently, a brief description of the biodiversity conservation centers maintained by the UNL was made, highlighting the IT initiatives that have been carried out. Finally, the results of the proposal include the methodology for the release of open data and the creation of the prototype of the biodiversity open data portal of the UNL.
Keywords: programming, open data, biodiversity, botany, artificial intelligenc
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