Biology subjects

Betz, J.

Publications and source records attributed to Betz, J..

3 recordsLinked to original sources

bioRxiv2022

The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm

The novel coronavirus pandemic, whose first outbreak was reported in December 2019 in Wuhan, China (COVID-19), is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Tissue damage caused by the virus leads to a strong immune response and activation of antigen-presenting cells, which can elicit acute respiratory distress syndrome (ARDS) characterized by the rapid onset of widespread inflammation, the so-called cytokine storm. In many viral infections the recruitment of monocytes into the lung and their differentiation to dendritic cells (DCs) are seen as a response to the viral infection. DCs are critical players in the development of the acute lung inflammation that causes ARDS. Here we focus on the interaction of the ORF8 protein, a specific SARS-CoV-2 open reading frame protein, with dendritic cells (DCs). We show that ORF8 binds to dendritic cells, causes a pre-maturation of differentiating DCs, and induces the secretion of multiple pro-inflammatory cytokines by these cells. In addition, we identified dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) as a possible interaction partner of ORF8 on dendritic cells. Blockade of ORF8 signaling leads to reduced production of IL-1{beta}, IL-6, IL-12p70, TNF-, MCP-1 (CCL2), and IL-10 by dendritic cells. Analysis of patient sera with high anti-ORF8 antibody titers showed that there was nearly no neutralization of the ORF8 protein and its function. Therefore, a neutralizing antibody that has the capacity of blocking the cytokine and chemokine response mediated by ORF8 protein might be an essential and novel additional step in the therapy of severe SARS-CoV-2 cases.

immunology↗

bioRxiv2022

Radioactive Contamination in Feral Dogs in the Chernobyl Exclusion Zone: Population Body-Burden Survey and Implications for Human Radiation Exposure

This report describes a two-year effort to survey the internal 137Cs and external {beta}-emitter contamination present in the feral dog population near the Chernobyl nuclear power plant (ChNPP) site, and to quantify the potential for human radiation exposure from this contamination. This work was performed as an integral part of the radiation safety and control procedures of an animal welfare oriented trap-neuter-release (TNR) program. The measurement program employed handheld {beta}-sensitive probes, and a simple whole-body counter to measure internal 137Cs burden during post-surgical observation and recovery. External {beta} contamination surveys performed during intake showed that 21/288 animals had significant, removable external contamination. Measurements with the whole-body counter indicated internal 137Cs body burdens ranging from undetectable (minimum detection level [~]100 Bq/kg in 2017, [~] 30 Bq/kg in 2018) to approximately 30,000 Bq/kg. A total of 33 animals had 137Cs body-burdens above 1 kBq/kg. We observe that internal contamination levels are positively correlated with capture locations within ChNPP boundaries. The large variation in the 137Cs concentration in these animals is not well-understood, could be due to prey selection, access to human food scraps, or extended residence in highly contaminated areas. These internally-contaminated animals are unlikely to pose an exposure hazard despite their large body-burdens due to their limited exposure to humans. However, the small minority of animals with external contamination may pose a contamination hazard to workers, tourists, and others interacting with the dogs, as evidenced by total quantity of removable activity and incidents of transfer to materials used in animal capture.

zoology↗

bioRxiv2021

Ablation of the FACIT collagen XII disturbs musculoskeletal ECM organization and causes patella dislocation and myopathy

Collagen XII, belonging to the fibril-associated collagens with interrupted triple helix (FACIT) family, assembles from three identical -chains encoded by the COL12A1 gene. The trimeric molecule consists of three N-terminal noncollagenous NC3 domains joined by disulfide bonds followed by a short interrupted collagen triple helix at the C-terminus. Collagen XII is expressed widely in the musculoskeletal system and mutations in the COL12A1 gene cause an Ehlers-Danlos/myopathy overlap syndrome, which is associated with skeletal abnormalities and muscle weakness. Our study defines the role of collagen XII in patella development using the Col12a1-/- mouse model. Deficiency in Col12a1 expression causes malformed facies patellaris femoris grooves at an early stage, which leads to patella subluxation and growth retardation. Due to the patella subluxation, more muscle fibers with centralized nuclei occur in the quadriceps than in the gastrocnemius muscles indicating a local effect. To further understand the role of collagen XII in the skeletal tissues single cell RNAseq (scRNA-seq) was performed. Comparison of the gene expression in the tenocyte cell sub-population of wild type and Col12a1-/- mice showed that several matrix genes are altered. Finally, we reinvestigated collagen XII deficient patients and observed a patella instability.

genetics↗