Biology subjects

Rohr, J.

Publications and source records attributed to Rohr, J..

5 recordsLinked to original sources

bioRxiv2026

Treatment with saturating dose of conventional anti-CD28 monoclonal antibody well tolerated in pig acute myocardial infarction model

CD4+ Foxp3+ regulatory T cells (Treg) efficiently foster wound healing after myocardial infarction (MI). Therapeutically shifting the balance between CD4+ Foxp3- conventional T cells (Tconv) and Treg towards Tregs enhanced survival in a mouse model of MI. Due to species-specific differences in cardiac wound healing and remodelling, it remains, however, unclear whether these findings can be translated into novel immunotherapies for human patients after MI. Therefore, we studied pigs whose cardiac wound healing after MI and the composition of the immune system are very close to humans. This includes the relevant complication of developing a cytokine release syndrome (CRS) after infusion of saturating amounts of a superagonistic anti-CD28 monoclonal antibody (mAb). To achieve the intended shift in the Treg/Tconv balance, we treated pigs three days after interventional MI induction with a non-superagonistic, i.e. conventional, anti-CD28 mAb, clone 3D11. Infusion of a saturating dose (1 mg/kg body weight) of mAb 3D11 was clinically well tolerated without signs of CRS induction or any other complications. Molecularly, mAb 3D11 infusion led to a downmodulation of CD28 expression on porcine T cells in vivo with the remaining CD28 molecules blocked from binding natural ligand proteins CD80 and CD86, as we show in this publication. Apart from modulating CD28 expression, treatment with mAb 3D11 did not induce any overt changes in the peripheral T cell compartment. However, after mAb 3D11 treatment, we observed Treg accumulation in the infarcted heart, particularly the border zone, on day 7 post-MI using immunofluorescence histology. Our findings thus suggest that even saturating doses of conventional anti-CD28 monoclonal antibodies could potentially be safely administered in patients to therapeutically shift the Treg/Tconv balance in the infarcted myocardium. This might be sufficient to enhance cardiac wound healing in patients short-term and prevent adverse remodelling long-term.

immunology↗

bioRxiv2020

Pesticide-induced Alterations to Phytoplankton Abundance and Community Structure Alter Ecosystem Respiration: Implications for the Carbon Cycle?

AO_SCPLOWBSTRACTC_SCPLOWCurrent predictions of the effects of synthetic chemicals on freshwater ecosystems are hampered by the sheer number of chemical contaminants entering aquatic systems, the diversity of organisms inhabiting these systems, and uncertainties about how contaminants alter ecosystem metabolism. We conducted a mesocosm experiment that elucidated the responses of ponds composed of phytoplankton and zooplankton to standardized concentrations of 12 pesticides, nested within four pesticide classes and two pesticide types. We show that the effects of the pesticides on algae were consistent within herbicides and insecticides and responses of over 70 phytoplankton species and genera were consistent within broad taxonomic groups. Insecticides generated top-down effects on phytoplankton community composition and abundance, which were associated with persistent increases in ecosystem respiration. Herbicides reduced phytoplankton abundance, which was associated with decreases in primary productivity and ecosystem respiration. These results suggest that widespread pesticide use could have underexplored implications for the global carbon cycle. While these effects on ecosystem respiration were mediated through complex effects on communities, taxonomic groups of organisms responded similarly to pesticide types, suggesting opportunities to simplify ecological risk assessment.

ecology↗

bioRxiv2020

Consistent Effects of Pesticides on Community Structure and Ecosystem Function in Freshwater Systems

AO_SCPLOWBSTRACTC_SCPLOWPredicting ecological effects of contaminants remains challenging because of the sheer number of chemicals and their ambiguous role in biodiversity-ecosystem function relationships. We evaluated responses of pond ecosystems to standardized concentrations of 12 pesticides, nested in four pesticide classes and two pesticide types. We show consistent effects of herbicides and insecticides on ecosystem function, but slightly less consistent effects on community composition. Effects of pesticides on ecosystem functions were often mediated by changes to biodiversity, and our analyses show that consistency in effects of pesticide types on functions was driven by functional redundancy among species. These results suggest that risk assessment of the thousands of registered chemicals on ecosystem responses could be simplified to a smaller number of chemical groups and to groups of functionally redundant taxa.

ecology↗

bioRxiv2018

Impacts of thermal mismatches on chytrid fungus Batrachochytrium dendrobatidis prevalence are moderated by life stage, body size, elevation and latitude

Global climate change is increasing the frequency of unpredictable weather conditions; however, it remains unclear how species-level and geographic factors, including body size and latitude, moderate impacts of unusually warm or cool temperatures on disease. Because larger hosts and lower-latitude hosts generally have slower acclimation times, we hypothesized that their disease susceptibility increases under \"thermal mismatches\", or differences between baseline climate and the temperature during surveying. Here, we examined how thermal mismatches interact with body size, life stage, habitat, latitude, elevation, phylogeny, and IUCN conservation status to predict infection prevalence of the chytrid fungus Batrachochytrium dendrobatidis (Bd) in a global analysis of 38,967 amphibian hosts. As hypothesized, we found that the susceptibility of larger hosts and hosts from lower latitudes was strongly influenced by thermal mismatches. Furthermore, hosts of conservation concern are more susceptible than others following thermal mismatches, suggesting that thermal mismatches might have contributed to recent amphibian declines.\n\nData Accessibility StatementShould the manuscript be accepted, the data supporting the results will be archived in an appropriate public repository such as Dryad or Figshare and the data DOI will be included at the end of the article.

ecology↗

bioRxiv2017

Structural basis for EarP-mediated arginine glycosylation of translation elongation factor EF-P

Glycosylation is a universal strategy to post-translationally modify proteins. The recently discovered arginine rhamnosylation activates the polyproline specific bacterial translation elongation factor EF-P. EF-P is rhamnosylated on arginine 32 by the glycosyltransferase EarP. However, the enzymatic mechanism remains elusive. In the present study, we solved the crystal structure of EarP from Pseudomonas putida. The enzyme is composed of two opposing domains with Rossmann-folds, thus constituting a GT-B glycosyltransferase. While TDP-rhamnose is located within a highly conserved pocket of the C-domain, EarP recognizes the EF-P via its KOW-like N-domain. Based on our structural data combined with an in vitro /in vivo enzyme characterization, we propose a mechanism of inverting arginine glycosylation. As EarP is essential for pathogenicity in P. aeruginosa our study provides the basis for targeted inhibitor design.

biochemistry↗