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Vogel, E.

Publications and source records attributed to Vogel, E..

4 recordsLinked to original sources

Mechanosensitive Piezo Channels Contribute to Airway Changes in Chronic Obstructive Pulmonary Disease

As an intrinsically mechanosensitive organ, the lung experiences a range of mechanical forces. Chronic obstructive pulmonary disease (COPD) involves abnormal macroscopic cellular and extracellular matrix (ECM) changes that impact mechanical properties of the lung. Mechanosensitive Piezo1/2 channels are expressed in the lung including on airway smooth muscle cells (ASM) that mediate cellular responses to stretch and ECM biomechanics. The expression and roles of Piezos in COPD lung ASM are not known. We hypothesized that Piezo expression and activation are altered in COPD lung ASM influencing ECM regulation. Distribution of Piezo proteins in ASM and epithelium of small airways of COPD stage II and IV vs. non-COPD controls was assessed using immunohistochemistry and ImageJ (n=10-17/group). Isolated ASM cells from control (n=6) vs. COPD stage II and IV patients (n=3 each stage) were exposed to stretch or the Piezo1 agonist Yoda1 followed by measurement of ECM gene and protein expression. Less Piezo2 staining was observed in COPD IV patients compared to controls, with lesser area and intensity of staining in the epithelial layer, and lower intensity of staining in ASM and small airways as a whole. Fura-2-based imaging of ASM Ca2+ showed lower influx after Yoda1 exposure in COPD II compared to control and COPD IV. Gene expression of Piezo1 increased upon stretching in controls but not in COPD ASM, while Piezo2 protein expression decreased with stretching in all groups. Yoda1 treatment resulted in decreased collagen1, fibulin1 and periostin gene and collagen 1 and periostin protein expression in ASM. Overall, these results support a role for Piezo activation in abnormal ECM-ASM cell crosstalk in COPD.

physiology↗

Identification of a novel myosin antigen activating CD8+ T cells in C57BL/6 mice

Heart-specific T cells play important roles in myocardial diseases, including myocarditis, myocardial infarction, and heart failure. However, only few cardiac antigens and their respective specific T cell receptors (TCRs) have been validated so far. Therefore, we sought to identify new cardiac T cell epitopes in C57BL/6 mice and to characterize the specific TCRs. Antigen mapping of myosin heavy chain alpha (MYHCA) led to the identification of a 9-mer epitope (MYHCA724-732) recognized by CD8+ T cells. Single-cell TCR sequencing (scTCR-seq) analysis of MYHCA-stimulated CD8+ T cells enabled the identification of distinct TCRs enriched on specific T cells. Selected TCRs inferred from scTCR-seq data were then expressed on reporter cell lines and functionally validated. Our study expands the toolkit required to study heart-directed immune responses by revealing a new cardiac antigen and specific TCRs. These tools will enable in vivo characterization of myosin-specific CD8+ T cells in murine models of myocardial diseases.

immunology↗

Detection of tomato brown rugose fruit virus in environmental residues: the importance of contextualizing test results

Tomato brown rugose fruit virus (ToBRFV) is regulated as a quarantine pest in many countries worldwide. To assess whether ToBRFV is present in cultivations, plants or seed lots, testing is required. The interpretation of test results, however, can be challenging. Real-time RT-PCR results, even though considered "positive", may not always signify plant infection or indicate the presence of infectious virus, but could be due to the presence of viral residues in the environment. Here, case studies from the Netherlands, Belgium, and the United Kingdom address questions regarding the detection of ToBRFV in various settings, and the infectiousness of ToBRFV positive samples. These exploratory analyses demonstrate widespread detection of ToBRFV in diverse samples and environments. ToBRFV was detected inside and around greenhouses with no prior history of ToBRFV infection, on different materials and surfaces including those that were untouched by individuals, plants, or objects. This suggested the dispersal of viral residues through aerosols. ToBRFV or its residues were more often detected in areas with nearby tomato production yet were also found in a wider environment extending beyond infected crops. Given that ToBRFV originating from environmental contamination may or may not be infectious, adds complexity to decision-making in response to positive test results. Contextual information, such as the origin of the sample and the likelihood of residues from prior cultivations and/or the broader environment, is important for interpreting test results. A nuanced approach is crucial to correctly interpret ToBRFV test results, necessitating further research to support risk assessment.

microbiology↗

Perturbing neural representations of working memory with task-irrelevant interruption

Working memory maintains information so that it can be used in complex cognitive tasks. A key challenge for this system is to maintain relevant information in the face of task-irrelevant perturbations. In this series of experiments, we investigated the impact of task-irrelevant interruptions on neural representations of working memory. We recorded electroencephalogram (EEG) activity in humans while they performed a working memory task. On a subset of trials, we interrupted participants with salient, but task-irrelevant objects. To track the impact of these task-irrelevant interruptions on neural representations of working memory, we measured two well-characterized, temporally sensitive EEG markers that reflect active, prioritized working memory representations: the contralateral delay activity (CDA) and lateralized alpha power (8-12hz). Following interruption, we found that CDA momentarily sustained, but was gone by the end of the trial. Lateralized alpha power was immediately influenced by the interrupters, but recovered by the end of the trial. This suggests that dissociable neural processes contribute to the maintenance of working memory information. Additionally, we found that task expectancy modulated the timing and magnitude of how these two neural signals responded to task-irrelevant interruptions, suggesting that the brains response to task-irrelevant interruption is shaped by task context. The distinct time courses of and influence of task context on these two neural signatures of working memory have many interesting theoretical implications about how information is actively maintained in working memory.\n\nSignificance statementWorking memory plays a central role in intelligent behaviors because it actively maintains relevant information that is easily accessible and manipulatable. In everyday life, we are often interrupted while performing such complex cognitive tasks. Therefore, understanding how working memory responds to and overcomes momentary task-irrelevant interruptions is critical for us to understand how complex cognition works. Here, we unveil how two distinct neural signatures of working memory respond to task-irrelevant interruptions by recording electroencephalogram activity in humans. Our findings raise long-standing theoretical questions about how different neural and cognitive processes contribute to the maintenance of information in working memory.

neuroscience↗