02.11.2020

Patrolling Alveolar Macrophages Conceal Bacteria from the Immune Syste... Cell, 2020

Abstract During respiration, humans breathe in more than 10,000 liters of non-sterile air daily, allowing some pathogens access to alveoli. Interestingly, alveoli outnumber alveolar macrophages (AMs), which favors alveoli devoid of AMs. If AMs, like most tissue macrophages, are sessile, then this numerical advantage would be exploited by pathogens unless neutrophils from the blood stream intervened. However, this would translate to omnipresent persistent inflammation. Developing in vivo real-time intravital imaging of alveoli...

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08.11.2020

Neuropathology of patients with COVID-19 in Germany: a post-mortem cas... The Lancet, 2020

Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. Here, Matschke et al. investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS. The group detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in a...

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27.10.2020

Coupling of bone resorption and formation by RANKL reverse signalling Nature, 2018

Abstract Receptor activator of nuclear factor-kappa B (RANK) ligand (RANKL) binds RANK on the surface of osteoclast precursors to trigger osteoclastogenesis. Recent studies have indicated that osteocytic RANKL has an important role in osteoclastogenesis during bone remodelling; however, the role of osteoblastic RANKL remains unclear. Here we show that vesicular RANK, which is secreted from the maturing osteoclasts, binds osteoblastic RANKL and promotes bone formation by triggering RANKL reverse signalling, which activates Runt-related tran...

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12.10.2020

Transcorneal Electrical Stimulation Reduces Neurodegenerative Processi... Annals of Biomedical Engineering, 2020

Abstract Glaucoma is a neurodegenerative disease in which the retinal ganglion cell axons of the optic nerve degenerate concomitant with synaptic changes in the retina, leading finally to death of the retinal ganglion cells (RGCs). Electrical stimulation has been used to improve neural regeneration in a variety of systems, including in diseases of the retina. Therefore, the focus of this study was to investigate whether transcorneal electrical stimulation (TES) in the DBA2/J mouse model of glaucoma could improve retinal or optic nerve path...

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05.10.2020

Generation of a Broadly Useful Modelfor COVID-19 Pathogenesis,Vaccinat... Cell, 2020

Summary COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and hi...

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30.09.2020

IL26 modulates cytokine response and anti-TNF consumption in Crohn's d... J Mol Med (Berl), 2017

Abstract Interleukin IL26 supports killing of microbes and the innate sensing of bacterial-derived DNA (bactDNA). We evaluated the relationship between IL26 serum levels and bactDNA translocation in Crohn's disease (CD). We ran a prospective study on CD patients in remission. IL26 common polymorphisms, serum cytokines and complement protein, amplified-bactDNA, and anti-TNF-α were evaluated. In vitro PBMC analysis was performed. Three hundred and thirteen patients were included (mean CDAI: 83.6 ± 32.8; mean fecal calprotect...

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11.09.2020

Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Pri... The New England Journal of Medicine, 2020

Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. In this study, nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication...

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28.08.2020

Plasma cell survival in the absence of B cellmemory Nature Communications, 2017

Abstract Pre-existing serum antibodies play an important role in vaccine-mediated protection againstinfection but the underlying mechanisms of immune memory are unclear. Clinical studiesindicate that antigen-specific antibody responses can be maintained for many years, leadingto theories that reactivation/differentiation of memory B cells into plasma cells is required tosustain long-term antibody production. Here, we present a decade-long study in which wedemonstrate site-specific survival of bone marrow-derived plasma cells and durable an...

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21.08.2020

Mechanical regulation of glycolysis via cytoskeleton architecture Nature, 2020

Recently, Park et al. identified an actin-TRIM21-PFK mechanistic pathway utilized by cells to adapt their metabolic activity in response to mechanical cues; this is the first report to identify a direct link between mechanical inputs from the cell environment and metabolic responses.  Human bronchial epithelial cells (HBECs) were exposed to stiff or soft substrates to mimic environmental mechanical stimuli.  Analysis of HBECs exposed to these different stimuli, using an array of metabolic, biological, and molecular tools, identified a signif...

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14.08.2020

Histopathology and ultrastructural findings of fatal COVID-19 infectio... The Lancet, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. Bradley at al. aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism. The primary pathology observed in this cohort...

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