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Sci Rep ; 11(1): 17595, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475457


Pandemics such as the Covid-19 pandemic have shown to impact our physical and mental well-being, with particular challenges for children and families. We describe data from 43 adults (31♀, ages = 22-51; 21 mothers) and 26 children (10♀, ages = 7-17 years) including pre-pandemic brain function and seven assessment points during the first months of the pandemic. We investigated (1) changes in child and adult well-being, (2) mother-child associations of mental well-being, and (3) associations between pre-pandemic brain activation during mentalizing and later fears or burden. In adults the prevalence of clinically significant anxiety-levels was 34.88% and subthreshold depression 32.56%. Caregiver burden in parents was moderately elevated. Overall, scores of depression, anxiety, and caregiver burden decreased across the 11 weeks after Covid-19-onset. Children's behavioral and emotional problems during Covid-19 did not significantly differ from pre-pandemic levels and decreased during restrictions. Mothers' subjective burden of care was associated with children's emotional and behavioral problems, while depression levels in mothers were related to children's mood. Furthermore, meeting friends was a significant predictor of children's mood during early restrictions. Pre-pandemic neural correlates of mentalizing in prefrontal regions preceded later development of fear of illnesses and viruses in all participants, while temporoparietal activation preceded higher subjective burden in mothers.

Ansiedade , COVID-19 , Depressão , Imageamento por Ressonância Magnética , Saúde Mental , Pandemias , SARS-CoV-2 , Estresse Psicológico , Adolescente , Adulto , Ansiedade/diagnóstico por imagem , Ansiedade/epidemiologia , Ansiedade/psicologia , COVID-19/diagnóstico por imagem , COVID-19/epidemiologia , COVID-19/psicologia , Criança , Depressão/diagnóstico por imagem , Depressão/epidemiologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estresse Psicológico/diagnóstico por imagem , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia
Artigo em Inglês | MEDLINE | ID: mdl-33014890


An important component in host resistance to malaria infection are inherited mutations that give rise to abnormalities and deficiencies in erythrocyte proteins and enzymes. Understanding how such mutations confer protection against the disease may be useful for developing new treatment strategies. A mouse ENU-induced mutagenesis screen for novel malaria resistance-conferring mutations identified a novel non-sense mutation in the gene encoding porphobilinogen deaminase (PBGD) in mice, denoted here as Pbgd MRI58155. Heterozygote Pbgd MRI58155 mice exhibited ~50% reduction in cellular PBGD activity in both mature erythrocytes and reticulocytes, although enzyme activity was ~10 times higher in reticulocytes than erythrocytes. When challenged with blood-stage P. chabaudi, which preferentially infects erythrocytes, heterozygote mice showed a modest but significant resistance to infection, including reduced parasite growth. A series of assays conducted to investigate the mechanism of resistance indicated that mutant erythrocyte invasion by P. chabaudi was normal, but that following intraerythrocytic establishment a significantly greater proportions of parasites died and therefore, affected their ability to propagate. The Plasmodium resistance phenotype was not recapitulated in Pbgd-deficient mice infected with P. berghei, which prefers reticulocytes, or when P. falciparum was cultured in erythrocytes from patients with acute intermittent porphyria (AIP), which had modest (20-50%) reduced levels of PBGD. Furthermore, the growth of Pbgd-null P. falciparum and Pbgd-null P. berghei parasites, which grew at the same rate as their wild-type counterparts in normal cells, were not affected by the PBGD-deficient background of the AIP erythrocytes or Pbgd-deficient mice. Our results confirm the dispensability of parasite PBGD for P. berghei infection and intraerythrocytic growth of P. falciparum, but for the first time identify a requirement for host erythrocyte PBGD by P. chabaudi during in vivo blood stage infection.

Malária , Plasmodium chabaudi , Porfiria Aguda Intermitente , Animais , Eritrócitos , Humanos , Camundongos , Plasmodium berghei/genética , Plasmodium falciparum
mSphere ; 3(1)2018.
Artigo em Inglês | MEDLINE | ID: mdl-29404413


During their development within the vertebrate host, Plasmodium parasites infect hepatocytes and red blood cells. Within these cells, parasites are surrounded by a parasitophorous vacuole membrane (PVM). The PVM plays an essential role for the interaction of parasites with their host cells; however, only a limited number of proteins of this membrane have been identified so far. This is partially because systematic proteomic analysis of the protein content of the PVM has been difficult in the past, due to difficulties encountered in attempts to separate the PVM from other membranes such as the parasite plasma membrane. In this study, we adapted the BioID technique to in vitro-cultivated Plasmodium berghei blood stage parasites and utilized the promiscuous biotin ligase BirA* fused to PVM-resident exported protein 1 to biotinylate proteins of the PVM. These we further processed by affinity purification, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and label-free quantitation, leading to a list of 61 known and candidate PVM proteins. Seven proteins were analyzed further during blood and liver stage development. This resulted in the identification of three novel PVM proteins, which were the serine/threonine protein phosphatase UIS2 (PlasmoDB accession no. PBANKA_1328000) and two conserved Plasmodium proteins with unknown functions (PBANKA_0519300 and PBANKA_0509000). In conclusion, our report expands the number of known PVM proteins and experimentally validates BioID as a powerful method to screen for novel constituents of specific cellular compartments in P. berghei. IMPORTANCE Intracellular pathogens are often surrounded by a host-cell derived membrane. This membrane is modified by the pathogens to their own needs and is crucial for their intracellular lifestyle. In Plasmodium parasites, this membrane is referred to as the PVM and only a limited number of its proteins are known so far. Here, we applied in rodent P. berghei parasites a method called BioID, which is based on biotinylation of proximal and interacting proteins by the promiscuous biotin ligase BirA*, and demonstrated its usefulness in identification of novel PVM proteins.