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Concluding, we characterized two in tandem BRCA1 and BRCA2 duplications that likely occurred by Alu-mediated homologous recombination, allowing identification of the underlying cause of the HBOC syndrome in these families.

Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors.

We systematically examined the human upper and lower respiratory tract using single-cell RNA sequencing and immunohistochemistry to determine receptor expression and evaluated its association with risk factors for severe COVID-19.

Our results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. ACE2 protein was not increased by pulmonary risk factors for severe COVID-19. Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19.

These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.

These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.Five subsets of ILCs are extensively described, Lymphoid Tissue inducer (LTi) cells, cytotoxic NK cells and non-cytotoxic helper ILC1s, ILC2s and ILC3s. So far, the main focus has been on the potent cytokine production by helper ILCs and their plastic nature that allows them to switch function and phenotype upon environmental changes. Recent advances in the field indicate the presence of cytotoxic helper ILCs that are distinct from conventional NK cells. In humans, these cytotoxic ILCs can develop from conventional helper ILCs whereas in mice this remains to be elucidated. STAT3-IN-1 in vitro In this review we discuss the identification, development and function of cytotoxic helper ILCs subsets in humans and mice.Attention-deficit/hyperactivity disorder (ADHD) is a prevalent childhood disorder marked by inattention and/or hyperactivity symptoms. ADHD may also relate to impaired executive function (EF), but is often studied in a single EF task per sample. The current study addresses the question of unique vs. overlapping relations in brain activity across multiple EF tasks and ADHD symptom burden. Three in-scanner tasks drawn from distinct EF domains (cognitive flexibility, working memory, and inhibition) were collected from children with and without an ADHD diagnosis (N = 63). Whole-brain activity and 11 regions of interest were correlated with parent reports of inattention and hyperactivity symptoms. Across the three EF domains, brain activity related to ADHD symptom burden, but the direction and location of these associations differed across tasks. Overall, activity in sensory and default mode network regions related to ADHD, and these relations did not consistently overlap across EF domains. We observed both distinct and overlapping patterns for inattention and hyperactivity symptoms. By studying multiple EF tasks in the same sample, we identified a heterogenous neural profile related to attention symptom burden in children. Our results inform ADHD characterization and treatment and explain some of the variable brain results related to EF and ADHD reported in the literature.Studying older adults with excellent cognitive capacities (Supernormals) provides a unique opportunity for identifying factors related to cognitive success – a critical topic across lifespan. There is a limited understanding of Supernormals’ neural substrates, especially whether any of them attends shaping and supporting superior cognitive function or confer resistance to age-related neurodegeneration such as Alzheimer’s disease (AD). Here, applying a state-of-the-art diffusion imaging processing pipeline and finite mixture modelling, we longitudinally examine the structural connectome of Supernormals. We find a unique structural connectome, containing the connections between frontal, cingulate, parietal, temporal, and subcortical regions in the same hemisphere that remains stable over time in Supernormals, relatively to typical agers. The connectome significantly classifies positive vs. negative AD pathology at 72% accuracy in a new sample mixing Supernormals, typical agers, and AD risk [amnestic mild cognitive impairment (aMCI)] subjects. Among this connectome, the mean diffusivity of the connection between right isthmus cingulate cortex and right precuneus most robustly contributes to predicting AD pathology across samples. The mean diffusivity of this connection links negatively to global cognition in those Supernormals with positive AD pathology. But this relationship does not exist in typical agers or aMCI. Our data suggest the presence of a structural connectome supporting cognitive success. Cingulate to precuneus white matter integrity may be useful as a structural marker for monitoring neurodegeneration and may provide critical information for understanding how some older adults maintain or excel cognitively in light of significant AD pathology.

Many brain tumor patients suffer from fatigue which severely affects their quality of life. There is a lack of objective measurements for fatigue in brain tumor patients. We aimed to find a neurophysiological correlate for fatigue in brain tumor patients. For this purpose, we correlated brain activity associated with phasic alertness with self-reported ratings of fatigue.

Patients with a meningioma, a low-grade glioma or a high-grade glioma (N=63) participated in this fMRI study. Brain activity in the central executive network (CEN) and default mode network (DMN) associated with phasic alertness was correlated with self-reported fatigue measured with the multidimensional fatigue inventory (MFI-20). Follow-up analyses were performed for MFI-20 domain scores, individual regions within CEN and DMN, and the tumor sub-groups separately.

MFI-20 scores correlated significantly with DMN activity associated with phasic alertness, but not with CEN activity. These results were consistent for each tumor sub-group. Within the DMN, the correlations were strongest in left and right lingual cortex, left and right cuneus, and right precuneus.