SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Com o diabo no corpo: os terríveis papagaios do Brasil colônia

Desde a Antiguidade, papagaios, periquitos e afins (Psittacidae) fascinaram os europeus por seu vivo colorido e uma notável capacidade de interação com seres humanos. A descoberta do Novo Mundo nada faria além de acrescentar novos elementos ao tráfico de animais exóticos há muito estabelecido pelos europeus com a África e o Oriente. Sem possuir grandes mamíferos, a América tropical participaria desse comércio com o que tinha de mais atrativo, essencialmente felinos, primatas e aves - em particular os papagaios, os quais eram embarcados em bom número. Contudo, a julgar pelos documentos do Brasil colônia, esses voláteis podiam inspirar muito pouca simpatia, pois nenhum outro animal - exceto as formigas - foi tantas vezes mencionado como praga para a agricultura. Além disso, alguns psitácidas mostravam-se tão loquazes que inspiravam a séria desconfiança de serem animais demoníacos ou possessos, pois só três classes de entidades - anjos, homens e demônios - possuíam o dom da palavra. Nos dias de hoje, vários representantes dos Psittacidae ainda constituem uma ameaça para a agricultura, enquanto os indivíduos muito faladores continuam despertando a suspeita de estarem possuídos pelo demônio. Transcendendo a mera curiosidade, essa crença exemplifica o quão intrincadas podem ser as relações do homem com o chamado “mundo natural”, revelando um universo mais amplo e multifacetado do que se poderia supor a princípio. Nesse sentido, a existência de aves capazes de falar torna essa relação ainda mais complexa e evidencia que as dificuldades de estabelecer o limite entre o animal e o humano se estendem além dos primatas e envolvem as mais inusitadas espécies zoológicas.Since ancient times, parrots and their allies (Psittacidae) have fascinated Europeans by their striking colors and notable ability to interact with human beings. The discovery of the New World added new species to the international exotic animal trade, which for many centuries had brought beasts to Europe from Africa and the Orient. Lacking large mammals, tropical America participated in this trade with its most appealing species, essentially felines, primates and birds - especially parrots - which were shipped in large numbers. It should be noted, however, that at times these birds were not well liked. In fact, according to documents from colonial Brazil, only the ants rank higher than parrots as the animals most often mentioned as agricultural pests. On the other hand, some of these birds were so chatty that people suspected them to be demonic or possessed animals, since only three classes of beings - angels, men and demons - have the ability to speak. Nowadays, several Psittacidae still constitute a threat to agriculture, and the suspicion that extremely talkative birds were demon possessed has also survived. More than a joke or a mere curiosity, this belief exemplifies how intricate man’s relationships with the “natural world” may be. In this sense, the existence of birds that are able to speak adds a further twist to these relationships, demonstrating that the problem of establishing a boundary between the animal and the human does not only involve primates, but also includes some unusual zoological species

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

De docent als onderzoeksbegeleider: ontwerprichtlijnen voor professionalisering

Praktijkgericht onderzoek behoort sinds 2001 tot het takenpakket van de Nederlandse hogescholen. Maar bij de invoering ervan is nauwelijks stilgestaan bij docentprofessionalisering. ‘De behoefte wordt vaak pas gevoeld en onderkend bij tegenvallende studieresultaten of accreditatiebeoordelingen’, aldus Ann Van der Auweraert en Erik Blokland. Dat kan anders, vinden zij

Housing conditions.

<p>Pictures of the 3 different housing conditions; solitary housed animals (A), socially housed animals (B), and the animals housed in an enriched environment (C). Of note, the enriched environment picture only represents the object arrangement during one particular week, the constellation and number of items was changed weekly.</p

PDE5 Inhibition Improves Object Memory in Standard Housed Rats but Not in Rats Housed in an Enriched Environment: Implications for Memory Models?

<div><p>Drug effects are usually evaluated in animals housed under maximally standardized conditions. However, it is assumed that an enriched environment (EE) more closely resembles human conditions as compared to maximally standardized laboratory conditions. In the present study, we examined the acute cognition enhancing effects of vardenafil, a PDE5 inhibitor, which stimulates protein kinase G/CREB signaling in cells, in three different groups of male Wistar rats tested in an object recognition task (ORT). Rats were either housed solitarily (SOL) or socially (SOC) under standard conditions, or socially in an EE. Although EE animals remembered object information longer in the vehicle condition, vardenafil only improved object memory in SOL and SOC animals. While EE animals had a heavier dorsal hippocampus, we found no differences between experimental groups in total cell numbers in the dentate gyrus, CA2–3 or CA1. Neither were there any differences in markers for pre- and postsynaptic density. No changes in PDE5 mRNA- and protein expression levels were observed. Basal pCREB levels were increased in EE rats only, whereas β-catenin was not affected, suggesting specific activation of the MAP kinase signaling pathway and not the AKT pathway. A possible explanation for the inefficacy of vardenafil could be that CREB signaling is already optimally stimulated in the hippocampus of EE rats. Since previous data has shown that acute PDE5 inhibition does not improve memory performance in humans, the use of EE animals could be considered as a more valid model for testing cognition enhancing drugs.</p></div

ORT 24 h intervals.

<p>Discrimination performance (d2, mean + SEM) of SOL (A), SOC (B) and EE (C) rats after administration of different doses of vardenafil in the object recognition task. All housing conditions were tested in a 24 h retention interval in combination with 0, 0.1, 0.3 and 1 mg/kg vardenafil (x-axis). A difference from zero is indicated with hash symbols (one-sample <i>t</i>-test; #: <i>p</i><0.05; ##: <i>p</i><0.01; ###: <i>p</i><0.001), differences from the vehicle condition (0 mg/kg) within the same retention interval are indicated with an asterisk (Tukey HSD; *: <i>p</i><0.05). Of note, the 0 mg/kg vardenafil conditions are identical to those used in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111692#pone-0111692-g002" target="_blank">Figure 2</a>.</p

ORT 48 h intervals.

<p>Discrimination performance (d2, mean + SEM) of SOL (A), SOC (B) and EE (C) rats after administration of different doses of vardenafil in the object recognition task. All housing conditions were tested in a 48 h retention interval in combination with 0, 0.1, 0.3 and 1 mg/kg vardenafil (x-axis), EE animals also received 0.03 mg/kg vardenafil. A difference from zero is indicated with hash symbols (one-sample <i>t</i>-test; ###: <i>p</i><0.001), differences from the vehicle condition (0 mg/kg) within the same retention interval are indicated with asterisks (Tukey HSD; **: <i>p</i><0.01; ***: p<0.001). Of note, the 0 mg/kg vardenafil conditions are identical to those used in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111692#pone-0111692-g002" target="_blank">Figure 2</a>.</p