Sterol and fatty acid profile in negrinha and santulhana varietal olive oils from Trás-os-Montes region

info:eu-repo/semantics/publishedVersio

Neuronal deletion of GSK3beta increases microtubule speed in the growth cone and enhances axon regeneration via CRMP-2 and independently of MAP1B and CLASP2

BACKGROUND: In the adult central nervous system, axonal regeneration is abortive. Regulators of microtubule dynamics have emerged as attractive targets to promote axonal growth following injury as microtubule organization is pivotal for growth cone formation. In this study, we used conditioned neurons with high regenerative capacity to further dissect cytoskeletal mechanisms that might be involved in the gain of intrinsic axon growth capacity. RESULTS: Following a phospho-site broad signaling pathway screen, we found that in conditioned neurons with high regenerative capacity, decreased glycogen synthase kinase 3β (GSK3β) activity and increased microtubule growth speed in the growth cone were present. To investigate the importance of GSK3β regulation during axonal regeneration in vivo, we used three genetic mouse models with high, intermediate or no GSK3β activity in neurons. Following spinal cord injury, reduced GSK3β levels or complete neuronal deletion of GSK3β led to increased growth cone microtubule growth speed and promoted axon regeneration. While several microtubule-interacting proteins are GSK3β substrates, phospho-mimetic collapsin response mediator protein 2 (T/D-CRMP-2) was sufficient to decrease microtubule growth speed and neurite outgrowth of conditioned neurons and of GSK3β-depleted neurons, prevailing over the effect of decreased levels of phosphorylated microtubule-associated protein 1B (MAP1B) and through a mechanism unrelated to decreased levels of phosphorylated cytoplasmic linker associated protein 2 (CLASP2). In addition, phospho-resistant T/A-CRMP-2 counteracted the inhibitory myelin effect on neurite growth, further supporting the GSK3β-CRMP-2 relevance during axon regeneration. CONCLUSIONS: Our work shows that increased microtubule growth speed in the growth cone is present in conditions of increased axonal growth, and is achieved following inactivation of the GSK3β-CRMP-2 pathway, enhancing axon regeneration through the glial scar. In this context, our results support that a precise control of microtubule dynamics, specifically in the growth cone, is required to optimize axon regrowth

Pedestrian exposure to air pollution in cities: modeling the effect of roadside trees

The exposure of students to traffic-emitted carbon monoxide (CO) in their daily walk to school is evaluated, with a particular emphasis on the effect of trees and route choice. The study is focused on the city centre of Aveiro, in central Portugal. Time evolution of the georeferenced location of an individual is tracked with a GPS for different alternative walking routes to a school. Spatial distribution of CO concentration is simulated with a computational fluid dynamics (CFD) model. An exposure model is developed that associates the georeferenced location of the student with the computed air quality levels (at an average breathing height) for that specific grid cell. For each individual, the model calculates the instantaneous exposure at each time frame and the mean value for a given period. Results show a general benefit induced by the trees over the mean exposure of the student in each route. However, in the case of instantaneous exposure values, this is not consistent along the entire period. Also, the variability of the estimated exposure values indicates the potential error that can be committed when using a single value of air quality as a surrogate of air pollution exposure., The exposure of students to traffic-emitted carbon monoxide (CO) in their daily walk to school is evaluated, with a particular emphasis on the effect of trees and route choice. The study is focused on the city centre of Aveiro, in central Portugal. Time evolution of the georeferenced location of an individual is tracked with a GPS for different alternative walking routes to a school. Spatial distribution of CO concentration is simulated with a computational fluid dynamics (CFD) model. An exposure model is developed that associates the georeferenced location of the student with the computed air quality levels (at an average breathing height) for that specific grid cell. For each individual, the model calculates the instantaneous exposure at each time frame and the mean value for a given period. Results show a general benefit induced by the trees over the mean exposure of the student in each route. However, in the case of instantaneous exposure values, this is not consistent along the entire period. Also, the variability of the estimated exposure values indicates the potential error that can be committed when using a single value of air quality as a surrogate of air pollution exposure.The authors would like to acknowledge the financial support of the 3rd European Framework Program and the Portuguese Ministry of Science, Technology and Higher Education, through the Foundation for Science and Technology (FCT), for the Postdoc grants of Jorge Humberto Amorim (SFRH/BPD/48121/2008) and Joana Valente (SFRH/BPD/78933/2011) and for the funding of research project INSPIRAR (PTDC/AAC-AMB/103895/2008), supported in the scope of the Competitiveness Factors Thematic Operational Programme (COMPETE) of the Community Support Framework III and by the European Community Fund FEDER. This work was also partly supported by COST Action FP1204 “Green Infrastructure approach: linking environmental with social aspects in studying and managing urban forests.”publishe

Plasmodium chabaudi chabaudi malaria parasites can develop stable resistance to atovaquone with a mutation in the cytochrome b gene

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum</it>, has developed resistance to many of the drugs in use. The recommended treatment policy is now to use drug combinations. The atovaquone-proguanil (AP) drug combination, is one of the treatment and prophylaxis options. Atovaquone (ATQ) exerts its action by inhibiting plasmodial mitochondria electron transport at the level of the cytochrome bc1 complex. <it>Plasmodium falciparum in vitro </it>resistance to ATQ has been associated with specific point mutations in the region spanning codons 271-284 of the <it>cytochrome b </it>gene. ATQ -resistant <it>Plasmodium yoelii </it>and <it>Plasmodium berghei </it>lines have been obtained and resistant lines have amino acid mutations in their CYT <it>b </it>protein sequences. <it>Plasmodium chabaudi </it>model for studying drug-responses and drug-resistance selection is a very useful rodent malaria model but no ATQ resistant parasites have been reported so far. The aim of this study was to determine the ATQ sensitivity of the <it>P. chabaudi </it>clones, to select a resistant parasite line and to perform genotypic characterization of the <it>cytb </it>gene of these clones.</p> <p>Methods</p> <p>To select for ATQ resistance, <it>Plasmodium. chabaudi chabaudi </it>clones were exposed to gradually increasing concentrations of ATQ during several consecutive passages in mice. <it>Plasmodium chabaudi cytb </it>gene was amplified and sequenced.</p> <p>Results</p> <p>ATQ resistance was selected from the clone AS-3CQ. In order to confirm whether an heritable genetic mutation underlies the response of AS-ATQ to ATQ, the stability of the drug resistance phenotype in this clone was evaluated by measuring drug responses after (i) multiple blood passages in the absence of the drug, (ii) freeze/thawing of parasites in liquid nitrogen and (iii) transmission through a mosquito host, <it>Anopheles stephensi</it>. ATQ resistance phenotype of the drug-selected parasite clone kept unaltered. Therefore, ATQ resistance in clone AS-ATQ is genetically encoded. The Minimum Curative Dose of AS-ATQ showed a six-fold increase in MCD to ATQ relative to AS-3CQ.</p> <p>Conclusions</p> <p>A mutation was found on the <it>P. chabaudi cytb </it>gene from the AS-ATQ sample a substitution at the residue Tyr268 for an Asn, this mutation is homologous to the one found in <it>P. falciparum </it>isolates resistant to ATQ.</p

The Portuguese Society of Rheumatology position paper on the use of biosimilars

Biotechnological drugs have become a fundamental resource for the treatment of rheumatic patients. Patent expiry of some of these drugs created the opportunity for biopharmaceutical manufacturers to develop biosimilar drugs intended to be as efficacious as the originator product but with a lower cost to healthcare systems. Due to the complex manufacturing process and highly intricate structure of biologicals, a biosimilar can never be an exact copy of its reference product. Consequently, regulatory authorities issued strict preclinical and clinical guidelines to ensure safety and efficacy equivalence and, in September 2013, the biosimilar of infliximab was the first biosimilar monoclonal antibody to be authorized for use in the European Union. The current document is a position statement of the "Sociedade Portuguesa de Reumatologia" (Portuguese Society of Rheumatology) on the use of biosimilar drugs in rheumatic diseases. Two systematic literature reviews were performed, one concerning clinical trials and the other one concerning international position papers on biosimilars. The results were presented and discussed in a national meeting and a final position document was discussed, written and approved by Portuguese rheumatologists. Briefly, this position statement is contrary to automatic substitution of the originator by the biosimilar, defends either a different INN or the prescription by brand name, supports that switching between biosimilars and the originator molecule should be done after at least 6 months of treatment and based on the attending physician decision and after adequate patient information, recommends the registration of all biosimilar treated patients in Reuma.pt for efficacy, safety and immunogenicity surveillance, following the strategy already ongoing for originators, and opposes to extrapolation of indications approved to the originator to completely different diseases and/or age groups without adequate pre-clinical, safety or efficacy data.info:eu-repo/semantics/publishedVersio

Risk factors and outcome of COVID-19 in patients with hematological malignancies

Background: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defned. Patients and methods: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confrmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. Results: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n=58) or allogeneic stem cell transplantation (allo-SCT) (n=65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p=0.02). Prognostic factors identifed for day 45 overall mortality (OM) by logistic regression multivariate analysis included age>70 years [odds ratio (OR) 2.1, 95% con‑ fdence interval (CI) 1.2-3.8, p=0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p<0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p=0.02) whereas the use of hidroxycloroquine did not show signifcant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P=0.1). Conclusions: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of infammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19

Epistatic interaction of ERAP1 and HLA-B in Behçet disease: a replication study in the Spanish population

Behçet's disease (BD) is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078) and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987) associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population

Does public awareness increase support for invasive species management?:Promising evidence across taxa and landscape types

Management of invasive species often raises substantial conflicts of interest. Since such conflicts can hamper proposed management actions, managers, decision makers and researchers increasingly recognize the need to consider the social dimensions of invasive species management. In this exploratory study, we aimed (1) to explore whether species’ taxonomic position (i.e. animals vs. plants) and type of invaded landscape (i.e. urban vs. nonurban) might influence public perception about the management of invasive species, and (2) to assess the potential of public awareness to increase public support for invasive species management. We reviewed the scientific literature on the conflicts of interest around the management of alien species and administered two-phased questionnaires (before and after providing information on the target species and its management) to members of the public in South Africa and the UK (n = 240). Our review suggests that lack of public support for the management of invasive animals in both urban and non-urban areas derives mainly from moralistic value disagreements, while the management of invasive plants in non-urban areas mostly causes conflicts based on utilitarian value disagreements. Despite these general trends, conflicts are context dependent and can originate from a wide variety of different views. Notably, informing the public about the invasive status and negative impacts of the species targeted for management appeared to increase public support for the management actions. Therefore, our results align with the view that increased public awareness might increase the public support for the management of invasive species, independent of taxonomic position and type of landscape