Immunoglobulin genes implicated in glioma risk

Both genetic and environmental factors are thought to be causal in gliomagenesis. Several genes have been implicated in glioma development, but the putative role of a major immunity-related gene complex member, immunoglobulin heavy chain γ (IGHG) has not been evaluated. Prior observations that IGHG-encoded γ marker (GM) allotypes exhibit differential sensitivity to an immunoevasion strategy of cytomegalovirus, a pathogen implicated as a promoter of gliomagenesis, has lead us to hypothesize that these determinants are risk factors for glioma. To test this hypothesis, we genotyped the IGHG locus comprising the GM alleles, specifically GM alleles 3 and 17, of 120 glioma patients and 133 controls via TaqMan® genotyping assay. To assess the associations between GM genotypes and the risk of glioma, we applied an unconditional multivariate logistic regression analysis adjusted for potential confounding variables. In comparison to subjects who were homozygous for the GM 17 allele, the GM 3 homozygotes were over twice as likely, and the GM 3/17 heterozygotes were over three times as likely, to develop glioma. Similar results were achieved when analyzed by combining the data corresponding to alleles GM 3 and GM 3/17 in a dominant model. The GM 3/17 genotype and the combination of GM 3 and GM 3/17 were found to be further associated with over 3 times increased risk for high-grade astrocytoma (grades III-IV). Allele frequency analyses also showed an increased risk for gliomas and high-grade astrocytoma in association with GM 3. Our findings support the premise that the GM 3 allele may present risk for the development of glioma, possibly by modulating immunity to cytomegalovirus

Unveiling the Toxicity of Fine and Nano-Sized Airborne Particles Generated from Industrial Thermal Spraying Processes in Human Alveolar Epithelial Cells

High-energy industrial processes have been associated with particle release into workplace air that can adversely affect workers' health. The present study assessed the toxicity of incidental fine (PGFP) and nanoparticles (PGNP) emitted from atmospheric plasma (APS) and high-velocity oxy-fuel (HVOF) thermal spraying. Lactate dehydrogenase (LDH) release, 2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) metabolisation, intracellular reactive oxygen species (ROS) levels, cell cycle changes, histone H2AX phosphorylation (γ-H2AX) and DNA damage were evaluated in human alveolar epithelial cells at 24 h after exposure. Overall, HVOF particles were the most cytotoxic to human alveolar cells, with cell viability half-maximal inhibitory concentration (IC50) values of 20.18 μg/cm2 and 1.79 μg/cm2 for PGFP and PGNP, respectively. Only the highest tested concentration of APS-PGFP caused a slight decrease in cell viability. Particle uptake, cell cycle arrest at S + G2/M and γ-H2AX augmentation were observed after exposure to all tested particles. However, higher levels of γ-H2AX were found in cells exposed to APS-derived particles (~16%), while cells exposed to HVOF particles exhibited increased levels of oxidative damage (~17% tail intensity) and ROS (~184%). Accordingly, APS and HVOF particles seem to exert their genotoxic effects by different mechanisms, highlighting that the health risks of these process-generated particles at industrial settings should not be underestimated. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding text 1: transitória (Ref. DL-57/INSA-06/2018). Thanks are also due to FCT/MCTES for the financial support to EPIUnit and ITR (UIDB/04750/2020 and LA/P/0064/2020). Informed Consent Statement: Not applicable. Institutional Review Board Statement: Not applicable.; Funding text 2: Funding: This research was funded by the project CERASAFE with the support of ERA-NET SIINN (project id:16) and the Portuguese Foundation for Science and Technology (FCT; SIINN/0004/2014). This work was also supported by the project NanoBioBarriers (PTDC/MED-TOX/31162/2017), cofinanced by the Operational Program for Competitiveness and Internationalization (POCI) through European Regional Development Funds (FEDER/FNR) and FCT and the Spanish Ministry of Sci- ence and Innovation (projects PCIN-2015-173-C02-01 and CEX2018-000794-S-Severo Ochoa). M.J. Bessa (SFRH/BD/120646/2016) and F. Brandão (SFRH/BD/101060/2014) are recipients of FCT PhD scholarships under the framework of the Human Capital Operating Program (POCH) and European Union funding. The Doctoral Program in Biomedical Sciences of the ICBAS—University of Porto Int.J.Mol. Sci. 2022,of23fer, x FOR PEER REVIEWed additional funds. S. Fraga thanks FCT for funding through program DL 57/2016—Norm

In Vitro Toxicity of Industrially Relevant Engineered Nanoparticles in Human Alveolar Epithelial Cells: Air-Liquid Interface versus Submerged Cultures

Diverse industries have already incorporated within their production processes engineered nanoparticles (ENP), increasing the potential risk of worker inhalation exposure. In vitro models have been widely used to investigate ENP toxicity. Air–liquid interface (ALI) cell cultures have been emerging as a valuable alternative to submerged cultures as they are more representative of the inhalation exposure to airborne nano-sized particles. We compared the in vitro toxicity of four ENP used as raw materials in the advanced ceramics sector in human alveolar epithelial-like cells cultured under submerged or ALI conditions. Submerged cultures were exposed to ENP liquid suspensions or to aerosolised ENP at ALI. Toxicity was assessed by determining LDH release, WST-1 metabolisation and DNA damage. Overall, cells were more sensitive to ENP cytotoxic effects when cultured and exposed under ALI. No significant cytotoxicity was observed after 24 h exposure to ENP liquid suspensions, although aerosolised ENP clearly affected cell viability and LDH release. In general, all ENP increased primary DNA damage regardless of the exposure mode, where an increase in DNA strand-breaks was only detected under submerged conditions. Our data show that at relevant occupational concentrations, the selected ENP exert mild toxicity to alveolar epithelial cells and exposure at ALI might be the most suitable choice when assessing ENP toxicity in respiratory models under realistic exposure conditions.This research was funded by CERASAFE (www.cerasafe.eu; accessed on 26 October 2021), with the support of ERA-NET SIINN (project id:16) and the Portuguese Foundation for Science and Technology (FCT; SIINN/0004/2014). This work was also supported by the NanoBioBarriers project (PTDC/MED-TOX/31162/2017), co-financed by the Operational Program for Competitiveness and Internationalization (POCI) through European Regional Development Funds (FEDER/FNR) and FCT; Spanish Ministry of Science and Innovation (projects PCIN-2015-173-C02-01 and CEX2018-000794-S-Severo Ochoa), and by the Romanian National Authority for Scientific Research and Innovation (CCCDI-UEFISCDI, project number 29/2016 within PNCDI III). M.J. Bessa (SFRH/BD/120646/2016) and F. Brandão (SFRH/BD/101060/2014) are recipients of FCT PhD scholarships under the framework of Human Capital Operating Program (POCH) and European Union funding. The Doctoral Program in Biomedical Sciences, of the ICBAS—University of Porto, offered additional funds. S. Fraga thanks FCT for funding through program DL 57/2016–Norma transitória (Ref. DL-57/INSA-06/2018). Thanks are also due to FCT/MCTES for the financial support to EPIUnit (info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04750/2020/PT)

Interpolating the Sherrington-Kirkpatrick replica trick

The interpolation techniques have become, in the past decades, a powerful approach to lighten several properties of spin glasses within a simple mathematical framework. Intrinsically, for their construction, these schemes were naturally implemented into the cavity field technique, or its variants as the stochastic stability or the random overlap structures. However the first and most famous approach to mean field statistical mechanics with quenched disorder is the replica trick. Among the models where these methods have been used (namely, dealing with frustration and complexity), probably the best known is the Sherrington-Kirkpatrick spin glass: In this paper we are pleased to apply the interpolation scheme to the replica trick framework and test it directly to the cited paradigmatic model: interestingly this allows to obtain easily the replica-symmetric control and, synergically with the broken replica bounds, a description of the full RSB scenario, both coupled with several minor theorems. Furthermore, by treating the amount of replicas $n\in(0,1]$ as an interpolating parameter (far from its original interpretation) this can be though of as a quenching temperature close to the one introduce in off-equilibrium approaches and, within this viewpoint, the proof of the attended commutativity of the zero replica and the infinite volume limits can be obtained.Comment: This article is dedicated to David Sherrington on the occasion of his seventieth birthda

Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patient

BACKGROUND: The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk. METHODS: We genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk. RESULTS: Haplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45-0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41-7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13-7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect. CONCLUSION: Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample

Kalirin: a novel genetic risk factor for ischemic stroke

Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispose to ischemic stroke (IS) in a cohort of Portuguese patients and controls. We genotyped 34 tagging SNPs in the KALRN and ROPN1 chromosomal region on 565 IS patients and 517 unrelated controls, and performed genotype imputation for 405 markers on chromosome 3. We tested the single-marker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1-KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed significant (P < 0.05) allelic and genotypic (unadjusted and adjusted for hypertension, diabetes, and ever smoking) association with IS risk. Thirty-two imputed SNPs also showed an association at P < 0.05, and actual genotyping of three of these polymorphisms (rs7620580, rs6438833, and rs11712039) validated their association. Furthermore, rs11712039 was associated with IS (0.001 < P < 0.01) in a recent well-powered genomewide association study (Ikram et al. 2009). These studies suggest that variants in the KALRN gene region constitute risk factors for stroke and that KALRN may represent a common risk factor for vascular diseases

The XMM cluster survey: Testing chameleon gravity using the profiles of clusters

The chameleon gravity model postulates the existence of a scalar field that couples with matter to mediate a fifth force. If it exists, this fifth force would influence the hot X-ray emitting gas filling the potential wells of galaxy clusters. However, it would not influence the clusters weak lensing signal. Therefore, by comparing X-ray and weak lensing profiles, one can place upper limits on the strength of a fifth force. This technique has been attempted before using a single, nearby cluster (Coma, z = 0.02). Here we apply the technique to the stacked profiles of 58 clusters at higher redshifts (0.1 R0| R0| on cosmological scales. We hope to improve this constraint in future by extending the study to hundreds of clusters using data from the Dark Energy Survey

Consórcio couve-coentro em cultivo orgânico e sua influência nas populações de joaninhas.

O consórcio de culturas é comumente praticado na produção de hortaliças devido a diversos benefícios econômicos. Em alguns casos, podem reduzir infestações de pragas por favorecer a conservação dos inimigos naturais nos agroecossistemas. Avaliou-se a viabilidade agronômica do consórcio de couve e coentro, sob manejo orgânico, com base em parâmetros fitotécnicos, além de sua influência sobre populações de joaninhas (Coleoptera: Coccinellidae), na comparação com os respectivos cultivos solteiros. O coentro, representando a cultura secundária, foi utilizado com a finalidade de fornecer recursos para as joaninhas. O estudo foi realizado em área do Sistema Integrado de Produção Agroecológica em Seropédica-RJ. O experimento consistiu dos consórcios: 1) couve consorciada com coentro, cujas quatro linhas de plantas foram colhidas na fase vegetativa (consórcio I), e 2) couve consorciada com coentro, cujas plantas das duas linhas internas (próximas à linha da couve) foram colhidas na fase vegetativa e as duas linhas externas foram cortadas após floração (consórcio II). Em ambos consórcios foram avaliados os parâmetros fitotécnicos da couve e do coentro na fase vegetativa (padrão comercial), enquanto que no consórcio II, também se avaliou as populações de joaninhas, por meio de coletas semanais de adultos, em comparação com a couve em cultivo solteiro. O delineamento experimental foi em blocos ao acaso com quatro repetições. O coentro não interferiu na produtividade da couve consorciada e sua introdução contribuiu positivamente para a abundância e diversidade de espécies de joaninhas. O índice de equivalência de área para o consórcio I, com referência aos rendimentos de biomassa aérea fresca, foi superior em 92% em relação ao cultivo solteiro. Este resultado demonstra a viabilidade do consórcio I, no manejo orgânico adotado, para plantios de outono nas condições edafoclimáticas da Baixada Fluminense

The XMM Cluster Survey: An independent demonstration of the fidelity of the eFEDS galaxy cluster data products and implications for future studies

We present the first comparison between properties of clusters of galaxies detected by the eROSITA Final Equatorial-Depth Survey (eFEDS) and the XMM Cluster Survey (XCS). We have compared, in an ensemble fashion, properties from the eFEDS X-ray cluster catalogue with those from the Ultimate XMM eXtragaLactic (XXL) survey project (XXL-100-GC). We find the redshift and temperature (TX) distributions to be similar, with a larger proportion of clusters above 4 keV in the XXL-100-GC sample; fractional temperature uncertainties are significantly larger in eFEDS compared to XXL. We find 62 eFEDS cluster candidates with XMM data (eFEDS-XMM sample); 10 do not have good enough XMM data to confirm or deny, 11 are classed as sample contaminants, and 4 have their X-ray flux contaminated by another source. The majority of eFEDS-XMM sources have longer XMM exposures than eFEDS, and most eFEDS positions are within 100 kpc of XCS positions. Our eFEDS-XCS sample of 37 clusters is used to calculate minimum sample contamination fractions of ∼18 and ∼9 per cent in the eFEDS X-ray and optically confirmed samples, respectively, in general agreement with eFEDS findings. We directly compare 29 X-ray luminosities (LX) measured by eFEDS and XCS, finding excellent agreement. Eight clusters have a TX measured by XCS and eFEDS, and we find that XMM temperatures are 25 ± 9 per cent larger than their eROSITA counterparts. Finally, we construct LX-TX scaling relations based on eFEDS and XCS measurements, which are in tension; the tension is decreased when we measure a third scaling relation with calibrated XCS temperatures