On the equivariant 2-type of a G-space

A classical theorem of Mac Lane and Whitehead states that the homotopy type of a topological space with trivial homotopy at dimensions 3 and greater can be reconstructed from its π1 and π2, and a cohomology class k3 /gE H3(π1, π2). More recently, Moerdijk and Svensson suggested the possibility of using Bredon cohomology to extend this result to the equivariant case, that is, for spaces X equipped with an action by a fixed group G. In this paper we carry out this suggestion and prove an analogue of the classical result in the equivariant case

Gene Therapy in Cancer Treatment: Why Go Nano?

The proposal of gene therapy to tackle cancer development has been instrumental for the development of novel approaches and strategies to fight this disease, but the efficacy of the proposed strategies has still fallen short of delivering the full potential of gene therapy in the clinic. Despite the plethora of gene modulation approaches, e.g., gene silencing, antisense therapy, RNA interference, gene and genome editing, finding a way to efficiently deliver these effectors to the desired cell and tissue has been a challenge. Nanomedicine has put forward several innovative platforms to overcome this obstacle. Most of these platforms rely on the application of nanoscale structures, with particular focus on nanoparticles. Herein, we review the current trends on the use of nanoparticles designed for cancer gene therapy, including inorganic, organic, or biological (e.g., exosomes) variants, in clinical development and their progress towards clinical applications.This work was supported by the Applied Molecular Biosciences Unit - UCIBIO which is financed by national funds from FCT (UIDB/04378/2020), CRR (SFRH/BPD/124612/2016) and LRG (Inn-Indigo 00002/2015 RA Detect)

Tackling Multidrug Resistance in Streptococci: From Novel Biotherapeutic Strategies to Nanomedicines

UID/Multi/04378/2020 SFRH/BD/118350/2016 Inn-Indigo 0002/2015 RA DetectThe pyogenic streptococci group includes pathogenic species for humans and other animals and has been associated with enduring morbidity and high mortality. The main reason for the treatment failure of streptococcal infections is the increased resistance to antibiotics. In recent years, infectious diseases caused by pyogenic streptococci resistant to multiple antibiotics have been raising with a significant impact to public health and veterinary industry. The rise of antibiotic-resistant streptococci has been associated to diverse mechanisms, such as efflux pumps and modifications of the antimicrobial target. Among streptococci, antibiotic resistance emerges from previously sensitive populations as result of horizontal gene transfer or chromosomal point mutations due to excessive use of antimicrobials. Streptococci strains are also recognized as biofilm producers. The increased resistance of biofilms to antibiotics among streptococci promote persistent infection, which comprise circa 80% of microbial infections in humans. Therefore, to overcome drug resistance, new strategies, including new antibacterial and antibiofilm agents, have been studied. Interestingly, the use of systems based on nanoparticles have been applied to tackle infection and reduce the emergence of drug resistance. Herein, we present a synopsis of mechanisms associated to drug resistance in (pyogenic) streptococci and discuss some innovative strategies as alternative to conventional antibiotics, such as bacteriocins, bacteriophage, and phage lysins, and metal nanoparticles. We shall provide focused discussion on the advantages and limitations of agents considering application, efficacy and safety in the context of impact to the host and evolution of bacterial resistance.publishersversionpublishe

Light Triggered Enhancement of Antibiotic Efficacy in Biofilm Elimination Mediated by Gold-Silver Alloy Nanoparticles

This work was financed by national funds from FCT-Funda??o para a Ci?ncia e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences - UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy-i4HB. FCT?MEC have also acknowledged for SFRH/BD/118350/2016 to CA-B, and Inn-Indigo 00002/2015 RA Detect to LR-G. Publisher Copyright: Copyright © 2022 Alves-Barroco, Rivas-García, Fernandes and Baptista.Bacterial biofilm is a tri-dimensional complex community of cells at different metabolic stages involved in a matrix of self-produced extracellular polymeric substances. Biofilm formation is part of a defense mechanism that allows the bacteria to survive in hostile environments, such as increasing resistance or tolerance to antimicrobial agents, causing persistent infections hard to treat and impair disease eradication. One such example is bovine mastitis associated with Streptococcus dysgalactiae subsp. dysgalactiae (SDSD), whose worldwide health and economic impact is on the surge. As such, non-conventional nanobased approaches have been proposed as an alternative to tackle biofilm formation and to which pathogenic bacteria fail to adapt. Among these, metallic nanoparticles have gained significant attention, particularly gold and silver nanoparticles, due to their ease of synthesis and impact against microorganism growth. This study provides a proof-of-concept investigation into the use of gold-silver alloy nanoparticles (AuAgNPs) toward eradication of bacterial biofilms. Upon visible light irradiation of AuAgNPs there was considerable disturbance of the biofilms' matrix. The hindering of structural integrity of the biofilm matrix resulted in an increased permeability for entry of antibiotics, which then cause the eradication of biofilm and inhibit subsequent biofilm formation. Additionally, our results that AuAgNPs inhibited the formation of SDSD biofilms via distinct stress pathways that lead to the downregulation of two genes critical for biofilm production, namely, brpA-like encoding biofilm regulatory protein and fbpA fibronectin-binding protein A. This study provides useful information to assist the development of nanoparticle-based strategies for the active treatment of biofilm-related infections triggered by photoirradiation in the visible.publishersversionpublishe

Single and Combined Associations of Plasma and Urine Essential Trace Elements (Zn, Cu, Se, and Mn) with Cardiovascular Risk Factors in a Mediterranean Population

Trace elements are micronutrients that are required in very small quantities through diet but are crucial for the prevention of acute and chronic diseases. Despite the fact that initial studies demonstrated inverse associations between some of the most important essential trace elements (Zn, Cu, Se, and Mn) and cardiovascular disease, several recent studies have reported a direct association with cardiovascular risk factors due to the fact that these elements can act as both antioxidants and pro-oxidants, depending on several factors. This study aims to investigate the association between plasma and urine concentrations of trace elements and cardiovascular risk factors in a general population from the Mediterranean region, including 484 men and women aged 18–80 years and considering trace elements individually and as joint exposure. Zn, Cu, Se, and Mn were determined in plasma and urine using an inductively coupled plasma mass spectrometer (ICP-MS). Single and combined analysis of trace elements with plasma lipid, blood pressure, diabetes, and anthropometric variables was undertaken. Principal component analysis, quantile-based g-computation, and calculation of trace element risk scores (TERS) were used for the combined analyses. Models were adjusted for covariates. In single trace element models, we found statistically significant associations between plasma Se and increased total cholesterol and systolic blood pressure; plasma Cu and increased triglycerides and body mass index; and urine Zn and increased glucose. Moreover, in the joint exposure analysis using quantile g-computation and TERS, the combined plasma levels of Zn, Cu, Se (directly), and Mn (inversely) were strongly associated with hypercholesterolemia (OR: 2.03; 95%CI: 1.37–2.99; p < 0.001 per quartile increase in the g-computation approach). The analysis of urine mixtures revealed a significant relationship with both fasting glucose and diabetes (OR: 1.91; 95%CI: 1.01–3.04; p = 0.046). In conclusion, in this Mediterranean population, the combined effect of higher plasma trace element levels (primarily Se, Cu, and Zn) was directly associated with elevated plasma lipids, whereas the mixture effect in urine was primarily associated with plasma glucose. Both parameters are relevant cardiovascular risk factors, and increased trace element exposures should be considered with caution.Instituto de Salud Carlos IIISpanish Government Spanish Government CIBER 06/03 SAF2016-80532-RJunta de Andalucia AGR145Center for Forestry Research & Experimentation (CIEF)European Commission PROMETEO2017/017 APOSTD/2019/136 PROMETEO/2021/021ERDF A way of making EuropeAEI PID2019-108858RB-I0

Identification of Prognosis Associated microRNAs in HNSCC Subtypes Based on TCGA Dataset

We calculate the effects of doping nanostructuration and the patterning of thin films of high-temperature superconductors (HTS) with the aim of optimizing their functionality as sensing materials for resistive transition-edge bolometer devices (TES). We focus, in particular, on spatial variations of the carrier doping into the CuO 2 layers due to oxygen off-stoichiometry, (that induce, in turn, critical temperature variations) and explore following two major cases of such structurations: First, the random nanoscale disorder intrinsically associated to doping levels that do not maximize the superconducting critical temperature; our studies suggest that this first simple structuration already improves some of the bolometric operational parameters with respect to the conventional, nonstructured HTS materials used until now. Secondly, we consider the imposition of regular arrangements of zones with different nominal doping levels (patterning); we find that such regular patterns may improve the bolometer performance even further. We find one design that improves, with respect to nonstructured HTS materials, both the saturation power and the operating temperature width by more than one order of magnitude. It also almost doubles the response of the sensor to radiationThis work was supported by projects FIS2016-79109-P (AEI/FEDER, UE) and AYA2016-78773-C2-2-P(AEI/FEDER, UE), by the Xunta de Galicia under grants ED431D 2017/06 and ED431C 2018/11, the Consellería de Educación Program for Development of a Strategic Grouping in Materials AeMAT under Grant No. ED431 2018/08, Xunta de Galicia, and by the CA16218 nanocohybri COST Action. JCV thanks the Spanish Ministry of Education for grant FPU14/00838S

La gota fría del 6 de enero de 1989: evolución y actividad

Ponencia presentada en: I Simposio Nacional de Predictores, celebrado en 1989 en Madrid

Estudio de una situación atmosférica con intensa circulación zonal en la Sierra de Grazalema (Cádiz)

Ponencia presentada en: I Simposio Nacional de Predictores, celebrado en 1989 en Madrid

Contribución al estudio y predicción de los vientos en el Estrecho de Gibraltar

Ponencia presentada en: I Simposio Nacional de Predictores, celebrado en 1989 en Madri

Ultra-Small Iron Nanoparticles Target Mitochondria Inducing Autophagy, Acting on Mitochondrial DNA and Reducing Respiration

The application of metallic nanoparticles (materials with size at least in one dimension ranging from 1 to 100 nm) as a new therapeutic tool will improve the diagnosis and treatment of diseases. The mitochondria could be a therapeutic target to treat pathologies whose origin lies in mitochondrial dysfunctions or whose progression is dependent on mitochondrial function. We aimed to study the subcellular distribution of 2–4 nm iron nanoparticles and its effect on mitochondrial DNA (mtDNA), mitochondrial function, and autophagy in colorectal cell lines (HT-29). Results showed that when cells were exposed to ultra-small iron nanoparticles, their subcellular fate was mainly mitochondria, affecting its respiratory and glycolytic parameters, inducing the migration of the cellular state towards quiescence, and promoting and triggering the autophagic process. These effects support the potential use of nanoparticles as therapeutic agents using mitochondria as a target for cancer and other treatments for mitochondria-dependent pathologies.Government of Asturias through the Science, Technology and Innovation Plan (PCTI) - FEDER funds FC-GRUPIN-IDI/2018/000242Spanish Ministry of Economy, Industry and Competitiveness (MINECO) CTQ2016-80069-C 2-1R RTI2018-094605-B-I0