Identification of chromosomal alpha-proteobacterial small RNAs by comparative genome analysis and detection in Sinorhizobium meliloti strain 1021

<p>Abstract</p> <p>Background</p> <p>Small untranslated RNAs (sRNAs) seem to be far more abundant than previously believed. The number of sRNAs confirmed in <it>E. coli </it>through various approaches is above 70, with several hundred more sRNA candidate genes under biological validation. Although the total number of sRNAs in any one species is still unclear, their importance in cellular processes has been established. However, unlike protein genes, no simple feature enables the prediction of the location of the corresponding sequences in genomes. Several approaches, of variable usefulness, to identify genomic sequences encoding sRNA have been described in recent years.</p> <p>Results</p> <p>We used a combination of <it>in silico </it>comparative genomics and microarray-based transcriptional profiling. This approach to screening identified ~60 intergenic regions conserved between <it>Sinorhizobium meliloti </it>and related members of the alpha-proteobacteria sub-group 2. Of these, 14 appear to correspond to novel non-coding sRNAs and three are putative peptide-coding or 5' UTR RNAs (ORF smaller than 100 aa). The expression of each of these new small RNA genes was confirmed by Northern blot hybridization.</p> <p>Conclusion</p> <p>Small non coding RNA (<it>sra</it>) genes can be found in the intergenic regions of alpha-proteobacteria genomes. Some of these <it>sra </it>genes are only present in <it>S. meliloti</it>, sometimes in genomic islands; homologues of others are present in related genomes including those of the pathogens <it>Brucella </it>and <it>Agrobacterium</it>.</p

How the central domain of dystrophin acts to bridge F-actin to sarcolemmal lipids

Dystrophin is a large intracellular protein that prevents sarcolemmal ruptures by providing a mechanical link between the intracellular actin cytoskeleton and the transmembrane dystroglycan complex. Dystrophin deficiency leads to the severe muscle wasting disease Duchenne Muscular Dystrophy and the milder allelic variant, Becker Muscular Dystrophy (DMD and BMD). Previous work has shown that concomitant interaction of the actin binding domain 2 (ABD2) comprising spectrin like repeats 11 to 15 (R11-15) of the central domain of dystrophin, with both actin and membrane lipids, can greatly increase membrane stiffness. Based on a combination of SAXS and SANS measurements, mass spectrometry analysis of cross-linked complexes and interactive low-resolution simulations, we explored in vitro the molecular properties of dystrophin that allow the formation of ABD2-F-actin and ABD2-membrane model complexes. In dystrophin we identified two subdomains interacting with F-actin, one located in R11 and a neighbouring region in R12 and another one in R15, while a single lipid binding domain was identified at the C-terminal end of R12. Relative orientations of the dystrophin central domain with F-actin and a membrane model were obtained from docking simulation under experimental constraints. SAXS-based models were then built for an extended central subdomain from R4 to R19, including ABD2. Overall results are compatible with a potential F-actin/dystrophin/membrane lipids ternary complex. Our description of this selected part of the dystrophin associated complex bridging muscle cell membrane and cytoskeleton opens the way to a better understanding of how cell muscle scaffolding is maintained through this essential protein

Antifungal activity of amphotericin B conjugated to nanosized magnetite in the treatment of paracoccidioidomycosis

This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications

Artificial intelligence in biological activity prediction

Artificial intelligence has become an indispensable resource in chemoinformatics. Numerous machine learning algorithms for activity prediction recently emerged, becoming an indispensable approach to mine chemical information from large compound datasets. These approaches enable the automation of compound discovery to find biologically active molecules with important properties. Here, we present a review of some of the main machine learning studies in biological activity prediction of compounds, in particular for sweetness prediction. We discuss some of the most used compound featurization techniques and the major databases of chemical compounds relevant to these tasks.This study was supported by the European Commission through project SHIKIFACTORY100 - Modular cell factories for the production of 100 compounds from the shikimate pathway (Reference 814408), and by the Portuguese FCT under the scope of the strategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020.info:eu-repo/semantics/publishedVersio

A united statement of the global chiropractic research community against the pseudoscientific claim that chiropractic care boosts immunity.

BACKGROUND: In the midst of the coronavirus pandemic, the International Chiropractors Association (ICA) posted reports claiming that chiropractic care can impact the immune system. These claims clash with recommendations from the World Health Organization and World Federation of Chiropractic. We discuss the scientific validity of the claims made in these ICA reports. MAIN BODY: We reviewed the two reports posted by the ICA on their website on March 20 and March 28, 2020. We explored the method used to develop the claim that chiropractic adjustments impact the immune system and discuss the scientific merit of that claim. We provide a response to the ICA reports and explain why this claim lacks scientific credibility and is dangerous to the public. More than 150 researchers from 11 countries reviewed and endorsed our response. CONCLUSION: In their reports, the ICA provided no valid clinical scientific evidence that chiropractic care can impact the immune system. We call on regulatory authorities and professional leaders to take robust political and regulatory action against those claiming that chiropractic adjustments have a clinical impact on the immune system

Effects of perceived cost, service quality, and customer satisfaction on health insurance service continuance

This paper aims to contribute to the universal discourse on financial services continuance behavior by examining the impact of service cost on customers\u27 service-quality perception and service continuance intention. It presents the results of an empirical study that has explored the impacts of service cost, service quality, and customer satisfaction on health insurance customers\u27 behavioral intention toward continuing or discontinuing with their service providers. Very few studies had examined the impact of service cost on service-quality perception. Our study attempts to fill that gap. A sample of 820 customers was surveyed, and 624 usable responses were analyzed with ANOVA, standard multiple regression, and logistic regression. Our findings indicate that, although highly satisfied health insurance customers will most likely retain their current service providers, customer dissatisfaction does not necessarily lead to discontinuance. Our results also provide some operational implications for health insurance managers, with strategies for reducing attrition and improving customer retention

Etude de la pression exercée par un champ magnétique sur un conducteur plan. Déformations produites

Les efforts exercés sur une plaque métallique par des impulsions magnétiques sont mesurés au moyen d'un pendule balistique. Le calcul de la pression en fonction de l'épaisseur de la plaque nécessite la connaissance précise des caractéristiques de la décharge : amplitude, fréquence, constante de temps. L'inductance de l'ensemble bobine-plaque est le paramètre déterminant. Les déformations produites varient linéairement selon l'énergie de la décharge

Etude de la pression exercée par un champ magnétique sur un conducteur plan. Déformations produites

Forces on a metallic plate produced by magnetic pulses are measured with a ballistic pendulum. The pressure calculation needs the knowledge of the electric discharge characteristics : amplitude, frequency, time-constant. The effective inductance of the plate-coil system is the most significant parameter. The resulting strains are linear function of the stored energy.Les efforts exercés sur une plaque métallique par des impulsions magnétiques sont mesurés au moyen d'un pendule balistique. Le calcul de la pression en fonction de l'épaisseur de la plaque nécessite la connaissance précise des caractéristiques de la décharge : amplitude, fréquence, constante de temps. L'inductance de l'ensemble bobine-plaque est le paramètre déterminant. Les déformations produites varient linéairement selon l'énergie de la décharge

Étude du groupe de symétrie du pentafluorure de phosphore PF 5

The consequences of a tunnel effect, related to a large amplitude movement, on the determination of the molecular symmetry group have been studied. This study shows that some lines of the vibration-rotation spectrum may be split. During this study, the use of the permutation group S5 has led us to write a program in FORTRAN IV to determine the matrices of its irreducible representations. This program can easily be extended to any group Sn.Nous avons étudié les conséquences d'un effet tunnel, lié à un mouvement de grande amplitude, sur la détermination du groupe de symétrie moléculaire, ce qui a amené à une possibilité de détriplement de certaines raies du spectre de vibration-rotation. Au cours de cette étude, il a fallu utiliser le groupe de permutations S5 dont nous avons déterminé les matrices des représentations irréductibles, ce qui a nécessité l'écriture d'un programme en FORTRAN IV, adaptable au groupe Sn, n quelconque