Are Virulence and Antibiotic Resistance Genes Linked? A Comprehensive Analysis of Bacterial Chromosomes and Plasmids

Although pathogenic bacteria are the targets of antibiotics, these drugs also affect hundreds of commensal or mutualistic species. Moreover, the use of antibiotics is not only restricted to the treatment of infections but is also largely applied in agriculture and in prophylaxis. During this work, we tested the hypothesis that there is a correlation between the number and the genomic location of antibiotic resistance (AR) genes and virulence factor (VF) genes. We performed a comprehensive study of 16,632 reference bacterial genomes in which we identified and counted all orthologues of AR and VF genes in each of the locations: chromosomes, plasmids, or in both locations of the same genome. We found that, on a global scale, no correlation emerges. However, some categories of AR and VF genes co-occur preferentially, and in the mobilome, which supports the hypothesis that some bacterial pathogens are under selective pressure to be resistant to specific antibiotics, a fact that can jeopardize antimicrobial therapy for some human-threatening diseasesinfo:eu-repo/semantics/publishedVersio

Sustainable lithium-ion battery separators based on cellulose and soy protein membranes

The food industry produces millions of tons of natural by-products. Through this study, we followed an environmentally friendly strategy using discards, such as soy protein isolate (SPI) from soya oil production and marine cellulose (Cell) from the agar industry, in order to achieve added-value applications. In particular, this work focuses on the development of membranes based on soy protein and cellulose, and their validation as battery separator membranes toward sustainable energy storage systems. SPI membranes with Cell show excellent compatibility with the electrolyte based on physical interactions. These physical interactions favor the swelling of the membranes, reaching swelling values of 1000% after three days in the liquid electrolyte. The membranes are thermally stable up to 180 °C. After being subjected to the liquid electrolyte, it is observed that the microstructure of the membranes change, but the porous structure is maintained, while the materials remain easy to handle. The ionic conductivity value, lithium transference number and battery performance in cathodic half-cells are ∼ 5.8 mS.cm−1, 0.77, and 112 mAh.g−1 at 1C-rate, respectively. Overall, considering environmental issues and circular economy, it is proven that it is possible to obtain more sustainable high-performance lithium-ion batteries based on waste materials.The authors thank the Fundação para a Ciência e Tecnologia (FCT) for financial support under the framework of Strategic Funding UIDB/04650/2020, UID/FIS/04650/2020, UID/EEA/04436/2020, and UID/QUI/00686/2020 and under projects MIT-EXPL/TDI/0033/2021, POCI-01-0247-FEDER-046985 and 2022.03931.PTDC funded by national funds through FCT and by the ERDF through the COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI). The authors also thank the FCT for financial support under Grant 2021.08158.BD (J.P.S.) and FCT investigator contracts CEECIND/00833/2017 (RG) and 2020.04028.CEECIND (C.M.C.). This study forms part of the Advanced Materials program and was supported by MCIN with funding from European Union NextGenerationEU (PRTR-C17.I1) and by The Basque Government under the IKUR program. The authors also thank the project BIDEKO, funded by MCIN/AEI, NextGenerationEU, PRTR. This work was also supported by the (IT1658-22) and Grant PID2021-124294OB-C22 funded by MCI/AEI10.13039/501100011033 and by “ERDF A way of making Europe”. J.U. thanks the University of the Basque Country for her fellowship (ESPDOC21/74)

Environmentally friendly carrageenan-based ionic-liquid driven soft actuators

UID/FIS/04650/2020 UID/QUI/0686/2020 LA/P/0008/2020 PID2019-106099RB-C43/AEI/10.13039/501100011033A naturally derived polymer based on iota carrageenan and different ammonium and imidazolium based ionic liquids (ILs) are used for the development of environmentally friendly soft actuators. The influence of IL content and type and solvent evaporation temperature on the morphological and physico-chemical properties of the materials was evaluated, together with the effect on actuator functional response. Independently of the IL content and type, and the solvent evaporation temperature, a non-porous structure is obtained. The incorporation of the IL within the polymer matrix does not affect the thermal stability but leads to a decrease in the Young modulus for the different IL/carrageenan samples. The highest influence was observed by using the [Ch][DHP] IL at a filler content of 40% w/w with a decrease in the Young modulus from 748 MPa for the neat polymer to 145 MPa for the [Ch][DHP]/carrageenan sample. Furthermore, the ionic conductivity of the samples increases with increasing IL content, with the highest values being 2.9 × 10-6 S cm-1 and 1.2 × 10-6 S cm-1 for the samples with 40% w/w of [Bmim][FeCl4] and [Ch][DHP], respectively. Regarding the soft actuator performance, the maximum displacement was obtained for the [Ch][DHP]/carrageenan sample with an IL content of 40% w/w, showing a maximum displacement of 5.8 mm at a DC applied voltage of 9 V.publishersversionpublishe

iFloW: an integrated logistics software system for inbound supply chain traceability

Visibility plays an important role in supply chain management. Such visibility is not only important for better planning, but especially for real-time execution related with the traceability of goods. In inbound supply chain management, logistics planners need to trace raw materials from their requests in order to properly plan a plant’s production. The iFloW (Inbound Logistics Tracking System) integrates logistics providers IT applications and Global Positioning System (GPS) technology to track and trace incoming freights. The Estimated Time of Arrival (ETA) is updated in real-time allowing an improved materials planning process. This paper presents the iFloW project and describes how these issues are addressed and validated in a real pilot project.This research is sponsored by the Portugal Incentive System for Research and technological Development PEst-UID/CEC/00319/2013 and by project in co-promotion no 36265/2013 (Project HMIExcel—2013–2015)

Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation

Background. The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta. Methods. Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression. Results. Men within the first quartile had a mean eGFR slope of -0.1 mL/min/1.73m2/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of -6.7 mL/min/1.73m2/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr) ≥1 g/g (odds ratio 112, 95% confidence interval (95% CI) 4-3109, P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19, 95% CI 2-184, P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope -4.4 mL/min/1.73m2/year). Conclusions. Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy, particularly if proteinuria is ≥1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcome

Dominant negative effect of polyglutamine expansion perturbs normal function of ataxin-3 in neuronal cells

The physiological function of Ataxin-3 (ATXN3), a deubiquitylase (DUB) involved in Machado–Joseph Disease (MJD), remains elusive. In this study, we demonstrate that ATXN3 is required for neuronal differentiation and for normal cell morphology, cytoskeletal organization, proliferation and survival of SH-SY5Y and PC12 cells. This cellular phenotype is associated with increased proteasomal degradation of a5 integrin subunit (ITGA5) and reduced activation of integrin signalling and is rescued by ITGA5 overexpression. Interestingly, silencing of ATXN3, overexpression of mutant versions of ATXN3 lacking catalytic activity or bearing an expanded polyglutamine (polyQ) tract led to partially overlapping phenotypes. In vivo analysis showed that both Atxn3 knockout and MJD transgenic mice had decreased levels of ITGA5 in the brain. Furthermore, abnormal morphology and reduced branching were observed both in cultured neurons expressing shRNA for ATXN3 and in those obtained from MJD mice. Our results show that ATXN3 rescues ITGA5 from proteasomal degradation in neurons and that polyQ expansion causes a partial loss of this cellular function, resulting in reduced integrin signalling and neuronal cytoskeleton modifications, which may be contributing to neurodegeneration.National Institutes of Health (NIH) ‘(R01NS038712)Fundação para a Ciência e a Tecnologia (FCT) and COMPETE through the project ‘(PTDC/SAU-GMG/ 101572/2008)Fundação para a Ciência e a Tecnologia (FCT) - fellowships SFRH/BD/51059/2010, SFRH/BD/ 78388/2011 and SFRH/BPD/91562/201

Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242839/Anthrax is an infectious disease caused by Bacillus anthracis, a bioterrorism agent that develops resistance to clinically used antibiotics. Therefore, alternative mechanisms of action remain a challenge. Herein, we disclose deoxy glycosides responsible for specific carbohydrate-phospholipid interactions, causing phosphatidylethanolamine lamellar-to-inverted hexagonal phase transition and acting over B. anthracis and Bacillus cereus as potent and selective bactericides. Biological studies of the synthesized compound series differing in the anomeric atom, glycone configuration and deoxygenation pattern show that the latter is indeed a key modulator of efficacy and selectivity. Biomolecular simulations show no tendency to pore formation, whereas differential metabolomics and genomics rule out proteins as targets. Complete bacteria cell death in 10 min and cellular envelope disruption corroborate an effect over lipid polymorphism. Biophysical approaches show monolayer and bilayer reorganization with fast and high permeabilizing activity toward phosphatidylethanolamine membranes. Absence of bacterial resistance further supports this mechanism, triggering innovation on membrane-targeting antimicrobials.The European Union is gratefully acknowledged for the support of the project “Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease” (D3i4AD), FP7-PEOPLE-2013-IAPP, GA 612347. We thank the Management Authorities of the European Regional Development Fund and the National Strategic Reference Framework for the support of the Incentive System - Research and Technological Development Co-Promotion FACIB Project number 21457. Fundação para a Ciência e a Tecnologia is also acknowledged for the support of projects UID/Multi/00612/2013, FCT/UID/ Multi/04046/2013, IF/00808/2013/CP1159/CT0003, PTDC/BBBBQB/6071/2014, as well as for the post-doc grant SFRH/BPD/42567/2007 (A.M.), the Ph.D. grants SFRH/BDE/51998/2012 (C.D.), and SFRH/BDE/51957/2012 (J.P.P.), both co-sponsored by CIPAN, and also for the Ph.D. grant SFRH/BD/116614/2016 (R.N.).info:eu-repo/semantics/publishedVersio

Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD.A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with ≥75% agreement and no disagreement.For classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of ≥16 years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD. Consensus was achieved that treatment should not be withheld from patients with severe renal insufficiency (GFR < 45 ml/min/1.73 m(2)) and from those on dialysis or with cognitive decline, but carefully considered on an individual basis. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1 year. In those with cognitive decline of any cause, or lack of response for 1 year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered. ERT in patients who are non-compliant or fail to attend regularly at visits should be stopped.The recommendations can be used as a benchmark for initiation and cessation of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations.Ministry of Health (ZonMw

The international entrepreneurial firm's social networks

This paper investigates theoretically the importance and impact of the international entrepreneurial firms’ (IEFs) social networks on selected firms’ strategies. We focus specifically on some core attributes of IEFs and the impact of social networks on such strategies as the choice of the foreign markets to operate and the foreign entry modes. The social networks are a major driver of the internationalization from inception and help in overcoming a variety of physical and social resource limitations as well as transactional hazards. We conclude that it is likely that both some fundamental characteristics of the IEFs and those of the foreign markets entered account for these firms reliance on their social networks