Biology subjects

Zielinski, C.

Publications and source records attributed to Zielinski, C..

5 recordsLinked to original sources

bioRxiv2026

MEX3B is a positive pan-inflammasome regulator

Inflammasomes lead to activation of inflammatory caspases, which induce pyroptosis and an inflammatory immune response to control microbial infections. Inflammasomes are tightly regulated to avoid lethal sepsis and chronic autoimmune conditions. However, posttranslational regulation of inflammatory caspases remains poorly defined. We constructed 375 individual ubiquitin ligase knockout lines by CRISPR-Cas9, performed an unbiased screening, and identified Muscle Excess 3B (MEX3B), an RNA-binding protein and ubiquitin ligase, as a positive regulator of the caspase-4 inflammasome. Genetic depletion of MEX3B inhibited not only the caspase-4 but also NLRP3 and NLRC4 inflammasomes, regarding caspase activation, pyroptosis, and secretion of inflammasome-dependent cytokines, in human cells and murine primary macrophages. This MEX3B function required its RNA-binding, but not ubiquitin ligase activity. These results suggest that MEX3B is a pan-inflammasome regulator and a potential therapeutic target for inflammation.

immunology↗

bioRxiv2023

Single-cell RNA sequencing reveals HIF1A as a severity-sensitive immunological scar in circulating monocytes of convalescent comorbidity-free COVID-19 patients

COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is characterized by a wide range of clinical symptoms and a poorly predictable disease course. Although in-depth transcriptomic investigations of peripheral blood samples from COVID-19 patients have been performed, the detailed molecular mechanisms underlying an asymptomatic, mild or severe disease course, particularly in patients without relevant comorbidities, remain poorly understood. While previous studies have mainly focused on the cellular and molecular dissection of ongoing COVID-19, we set out to characterize transcriptomic immune cell dysregulation at the single-cell level at different time points in patients without comorbidities after disease resolution to identify signatures of different disease severities in convalescence. With single-cell RNA sequencing we reveal a role for hypoxia-inducible factor 1-alpha (HIF1A) as a severity-sensitive long-term immunological scar in circulating monocytes of convalescent COVID-19 patients. Additionally, circulating complexes formed by monocytes with either T cells or NK cells represent a characteristic cellular marker in convalescent COVID-19 patients irrespective of their preceding symptom severity. Together, these results provide cellular and molecular correlates of recovery from COVID-19 and could help in immune monitoring and in the design of new treatment strategies.

immunology↗

bioRxiv2023

Perception of Speech Turn Dynamics is preserved in Congenitally Deaf children with Cochlear Implants

Perceptual and speech production abilities of children with cochlear implants (CI) are usually tested by word and sentence repetition or naming tests. However, in their daily life they show very heterogeneous language skills. Here, we describe a way of increasing the ecological validity of language assessment, promoting the use of close to real-life listening situations. The setup consists in watching the audio-visual conversation of two individuals. Childrens gaze-switches from one speaker to the other serve as a proxy of their prediction abilities. Moreover, to better understand the basis and the impact of anticipatory behaviour, we also measured childrens ability to understand the dialogue content, their speech perception and memory skills as well as their rhythmic skills. Importantly, we compared children with CI performances with those of an age-matched group of children with NH. While children with CI revealed poorer speech perception and verbal working memory abilities than NH children, there was no difference in gaze anticipatory behaviour. Interestingly, in children with CI only, we found a significant correlation between dialogue comprehension, perceptive skills and gaze anticipatory behaviour. Our results confirm and extend to a conversational context previous findings showing an absence of predictive deficits in children with CI. The current design seems an interesting avenue to provide an accurate and objective estimate of anticipatory language behaviour in a rather ecological conversational context also with young children.

neuroscience↗

bioRxiv2020

The specificity of sperm-mediated paternal effects in threespined sticklebacks

Parental effects can help offspring cope with challenging environments, but whether these effects are unique to specific environmental conditions is largely unknown. Parental effects may evolve via a core pathway that generally prepares offspring for risky environments or could be stimuli-specific, with offspring developing phenotypes that are tailored to specific environmental challenges. We exposed threespined sticklebacks (Gasterosteus aculeatus) fathers to a potentially threatening stimulus (net) versus native predator (sculpin). Offspring of sculpin-exposed fathers were more responsive (greater change in activity) to a simulated predator attack, while offspring of net-exposed fathers were less responsive (lower plasma cortisol and fewer antipredator behaviors). To evaluate offspring response to native and non-native stimuli, we sequentially exposed offspring of net-exposed, sculpin-exposed or control fathers to a net, native sculpin model, or non-native trout model. Paternal treatment did not influence offspring response to stimuli; instead, offspring were more responsive to the native sculpin predator compared to nets or non-native trout predator. Collectively, we demonstrate that sperm-mediated paternal effects in response to different, potentially stressful stimuli result in distinct offspring phenotypes. This specificity may be key to understanding the evolution of adaptive parental effects and how parents prime offspring for encountering both evolved and novel environmental stimuli.Competing Interest StatementThe authors have declared no competing interest.View Full Text

animal behavior and cognition↗

bioRxiv2018

Meeting the challenges of high-dimensional data analysis in immunology

Recent advances in cytometry have radically altered the fate of single-cell proteomics by allowing a more accurate understanding of complex biological systems. Mass cytometry (CyTOF) provides simultaneous single-cell measurements that are crucial to understand cellular heterogeneity and identify novel cellular subsets. High-dimensional CyTOF data were traditionally analyzed by gating on bivariate dot plots, which are not only laborious given the quadratic increase of complexity with dimension but are also biased through manual gating. This review aims to discuss the impact of new analysis techniques for in-depths insights into the dynamics of immune regulation obtained from static snapshot data and to provide tools to immunologists to address the high dimensionality of their single-cell data.

immunology↗