GJB2: Frequency of the less common variants in a sample of the Portuguese population

Introduction: Sequence variants in the GJB2 gene account for up to 50% of cases of non-syndromic sensorineural hearing loss in the Caucasian population. In this study, we report the frequency of the less common variants of the GJB2 gene in a Portuguese sample and compare these frequencies with those of a group of hearing-impaired patients. Material and Methods: In order to select the less common GJB2 variants, 147 hearing-impaired patients followed in Centro Hospitalar Universitário de São João were evaluated. Afterwards, the presence of those variants was tested in 360 individuals from Generation 21. Results: The patient assessment enabled the selection of 11 GJB2 variants. Of those, 10 were investigated in Generation 21 participants, with only four being detected, in heterozygosity: p.Phe83Leu, p.Arg127His, p.Val153Ile and p.Asn206Ser, with the allelic frequencies (95% confidence interval) of 0.14% (0.01% - 0.87%), 0.28% (0.01% - 1.08%), 0.97% (0.43% - 2.04%) and 0.14% (0.01% - 0.88%), respectively. Two variants, p.Val37Ile and p.Val95Met, were more frequent in the patients’ group with statistical significance. Discussion: Our results allow for the p.Arg127His and p.Val153Ile variants to comply with polymorphism criteria and support the pathogenicity of p.Val37Ile and p.Val95Met variants. Moreover, two cases of moderate hearing loss were explained by the p.Val37Ile/p. Asn206Ser genotype, substantiating both the pathogenicity of such variants and the hypothesis that compound heterozygosity with p.Ans206Ser is associated with mild-moderate genotypes. Conclusion: Understanding the role of the variants is essential in order to provide genetic counselling to patients and their families. We explored a set of uncommon GJB2 variants that comprised 12% of the hearing-impaired patients in this study, supporting the relevance of their description.Generation XXI was funded by Programa Operacional de Saúde – Saúde XXI, Quadro Comunitário de Apoio III and Administração Regional de Saúde Norte (Regional Department of Ministry of Health). This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) by the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FED-ER-006862; Ref. UID/DTP/ 04750/2013), and the Calouste Gulbenkian Foundation. Ana Cristina Santos holds an FCT Investigator contract IF/ 01060/2015. (POCI-01-0145-FEDER-016837)

Optimized Herschel/PACS photometer observing and data reduction strategies for moving solar system targets

The "TNOs are Cool!: A survey of the trans-Neptunian region" is a Herschel Open Time Key Program that aims to characterize planetary bodies at the outskirts of the Solar System using PACS and SPIRE data, mostly taken as scan-maps. In this paper we summarize our PACS data reduction scheme that uses a modified version of the standard pipeline for basic data reduction, optimized for faint, moving targets. Due to the low flux density of our targets the observations are confusion noise limited or at least often affected by bright nearby background sources at 100 and 160\,$\mu$m. To overcome these problems we developed techniques to characterize and eliminate the background at the positions of our targets and a background matching technique to compensate for pointing errors. We derive a variety of maps as science data products that are used depending on the source flux and background levels and the scientific purpose. Our techniques are also applicable to a wealth of other Herschel solar system photometric observations, e.g. comets and near-Earth asteroids. The principles of our observing strategies and reduction techniques for moving targets will also be applicable for similar surveys of future infrared space projects.Comment: Accepted for publication in Experimental Astronom

Controlling competing interactions at oxide interfaces: Enhanced anisotropy in La0.7Sr0.3MnO3 films via interface engineering

We investigated thin La0.7Sr0.3MnO3-SrTiO3 heterostructures, where the band alignment is engineered by a variation of La/Sr stoichiometry only at the interface. In thin films, the engineered interface leads to an enhancement of the reversed spin configuration that mimics bulk behavior. Microscopically, this enhancement is closely connected with an increased magnetic anisotropy as well as intercoupling between an e(g) orbital reconstruction and a corresponding anisotropic lattice fluctuation. Furthermore, a reentrant-type behavior, triggered by this intercoupling, is observed in the remanent spin state. This microscopic perspective leads to insights on developing new strategies for maintaining bulk-like properties even in very thin La0.7Sr0.3MnO3 heterostructures.open11910Ysciescopu

Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'

We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts.

Towards an in-depth understanding of physical activity and eating behaviours during COVID-19 social confinement: A combined approach from a Portuguese National Survey

Rapid worldwide decreases in physical activity (PA), an increase in sedentary behaviour (SB) and poorer dietary patterns have been reported during COVID-19 confinement periods. However, as national variability has been observed, this study sought to describe PA, SB and eating patterns, and to explore their gender as well as other socio-demographic correlates and how they interrelate in a representative sample of Portuguese adults during the COVID-19 first mandatory social confinement. The survey was applied online and by telephone to 5856 adults (mean age = 45.8 years; 42.6% women). The majority reported high (46.0%) or moderate (20.5%) PA levels. Men, younger participants, those with higher education levels and a favourable perception of their financial situation reported higher PA levels, with the opposite pattern for SB. Physical fitness activities and household chores were more reported by women, with more strength training and running activities reported by men. Regarding eating behaviours, 45.1% reported changes, positive (58%) and negative (42%), with 18.2% reporting increases in consumption of fruit, vegetables, and fish and other seafood consumption, while 10.8% (most with lower educational level and less comfortable with their income) reported an increase in consumption of ready-to-eat meals, soft drinks, savoury snacks, and take-away and delivered meals. Two clustersa health-enhancing vs. risky patternemerged through multiple correspondence analysis characterized by co-occurrence of high vs. low PA levels, positive vs. negative eating changes, awareness or not of the COVID-19 PA and dietary recommendations, perceived financial situation, higher vs. lower educational level and time in social confinement. In conclusion, while in social confinement, both positive and negative PA and eating behaviours and trends were displayed, highlighting the role of key sociodemographic correlates contributing to healthy vs. risky patterns. Results may inform future health interventions and policies to be more targeted to those at risk, and also advocate the promotion of PA and healthy eating in an integrated fashion.</jats:p

Highly Dynamic Host Actin Reorganization around Developing Plasmodium Inside Hepatocytes

Plasmodium sporozoites are transmitted by Anopheles mosquitoes and infect hepatocytes, where a single sporozoite replicates into thousands of merozoites inside a parasitophorous vacuole. The nature of the Plasmodium-host cell interface, as well as the interactions occurring between these two organisms, remains largely unknown. Here we show that highly dynamic hepatocyte actin reorganization events occur around developing Plasmodium berghei parasites inside human hepatoma cells. Actin reorganization is most prominent between 10 to 16 hours post infection and depends on the actin severing and capping protein, gelsolin. Live cell imaging studies also suggest that the hepatocyte cytoskeleton may contribute to parasite elimination during Plasmodium development in the liver