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Biology subjects

Hesse, C.

Publications and source records attributed to Hesse, C..

6 recordsLinked to original sources

Roughness or sliminess: What makes a haptic material unpleasant

The current study aims to identify materials that most people experience as being unpleasant to touch and to uncover the perceptual attributes that link to unpleasantness. We sampled 79 everyday materials covering a wide range of sensory properties such as fluidity, granularity, roughness, and softness, e.g., cooking oil, sand, coconut, and silk. We asked participants to freely explore these materials with their dominant hand and subsequently rate their unpleasantness and 23 sensory attributes (e.g., elasticity, stickiness) in the absence of visual and auditory feedback. We collected data on material unpleasantness from two populations: Germany and the UK. Our wide array of materials showed different unpleasantness levels that correlated with specific perceptual material attributes. In general, viscous and deformable materials (e.g., hair gel, play-doh) felt more unpleasant to touch than surface-soft and smooth materials. Results were comparable for the German and UK samples. Overall, our results revealed a relationship between specific sensory attributes of materials and their unpleasantness, which seems to be consistent across German and UK samples. Our findings contribute to the understanding of how various sensory attributes are related to haptic unpleasantness. These insights advance our understanding of haptic perception with various implications, such as product design and affective computing systems, as both seek to integrate touch for detecting and modulating human affective states.

neuroscience↗

MRI-Compatible Rigid Head Holders for Artifact-Free Multimodal Imaging in Mice

PurposeHigh-resolution intravital microscopy allows cellular-scale analysis of the brain in vivo but is greatly sensitive to physiological motion. Combining optical microscopy with magnetic resonance imaging (MRI) in the same animal could relate cellular and mesoscale functional readout to whole-brain structural information, but this requires head holders that are both mechanically rigid and MRI compatible. Conventional metallic head holders introduce MRI artifacts, whereas many nonmetallic alternatives lack sufficient stability for chronic microscopy. Thus, we developed rigid, MRI-compatible head holders engineered from 3D-printed zirconia ceramics to reduce motion during microscopy while preserving MRI image quality. MethodsHead holders were designed for mouse cranial fixation and fabricated from zirconia ceramics using additive manufacturing. We quantified motion artifacts during two-photon and multimodal widefield imaging of the mouse cortex and assessed their impact on neuronal calcium activity, functional connectivity, and hemodynamic readouts. MRI compatibility was evaluated by measuring image quality in the presence of the head holder. ResultsThe ceramic head holders provided mechanical stability to reduce motion artifacts to micrometer levels during intravital imaging. The head holders produced no detectable susceptibility artifacts in MRI, and image contrast was comparable to control acquisitions performed without head holder. Sequential optical and MRI imaging of the same brain regions established artifact-minimized multimodal data acquisition within the same animal. ConclusionsNon-metallic ceramic head holders support longitudinal multimodal studies that combine high-resolution optical microscopy with whole-brain MRI measurements in the same animal.

neuroscience↗

Tankyrase inhibition demonstrates anti-fibrotic effects in preclinical pulmonary fibrosis models

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited treatment options. Although transforming growth factor beta 1 (TGFB1, TGF{beta}) is a key driver of fibrosis, additional signaling pathways, including wingless-type mammary tumor virus integration site (WNT)/{beta}-catenin and yes-associated protein 1 (YAP), contribute to IPF pathogenesis. Clinical data indicate that inhibition of TGF{beta} alone provides limited efficacy or is associated with toxicity, underscoring the need for alternative therapeutic approaches. Tankyrase (TNKS) 1 and 2 are post-translational regulators of WNT/{beta}-catenin and YAP signaling and therefore represent promising antifibrotic targets. OM-153, a potent and selective TNKS inhibitor, exhibits pharmacological properties suitable for preclinical development in IPF. MethodsPrimary normal human lung fibroblasts (NHLF), Scar-in-a-Jar assays, lung-on-a-chip models, and precision-cut lung slices (PCLS) from non-pulmonary fibrosis (non-PF) tissue were stimulated with an IPF-relevant cytokine cocktail (IPF-RC) designed to accurately recapitulate the pro-fibrotic environment and compared to TGF{beta}. These models, with bleomycin-challenged mice and PCLS from end-stage pulmonary fibrosis (PF) patients, were treated with OM-153. Fibrosis markers, extracellular matrix (ECM) components, and signaling pathway-specific gene expression or protein markers were assessed by real-time qRT-PCR, RNA sequencing, immunoblotting, ELISA, and immunofluorescence. ResultsOM-153 stabilized the direct TNKS targets axin 1 (AXIN1) and angiomotin-like 1 (AMOTL1), suppressed WNT/{beta}-catenin and YAP signaling. In parallel, it reduced profibrotic ECM expression across in vitro, in vivo, and ex vivo IPF models. ConclusionsSelective TNKS inhibition by OM-153 demonstrates broad antifibrotic activity in multiple preclinical models, supporting further development as a potential disease-modifying strategy for IPF. Shareable abstractOur findings show that the potent and selective TNKS inhibitor OM-153 suppresses WNT/{beta}-catenin and YAP signaling, reducing pro-fibrotic ECM expression in preclinical IPF models, supporting TNKS inhibition as a novel antifibrotic strategy.

cell biology↗

Telomerase modRNA offers a novel RNA-based approach to treat human pulmonary fibrosis

Pulmonary Fibrosis (PF) is a life-threatening illness that is characterized by progressive scarring in the lung interstitium. There is an urgent need for new PF therapies because current treatments only slow down the progression of fibrosis and the median life expectancy post-diagnosis is only 4 to 6 years. Since PF patients frequently exhibit telomere attrition, overexpressing telomerase, the enzyme responsible for synthesizing telomeres represents a compelling therapeutic option. In this study, we in vitro transcribed human telomerase reverse transcriptase (hTERT) mRNA using modified nucleosides (modRNA). ModRNA hTERT treatment led to transient activation of telomerase activity in a dose-dependent manner in MRC-5 cells and, importantly, in primary human alveolar type II pneumocytes (ATII cells). Consequently, the proliferative capacity was increased, concomitant with reduced DNA damage and elongated telomere length. Notably, induction of cellular immune response was only detectable at the highest modRNA concentration, and returned to normal levels within 48 hours. Next, we demonstrated that circularized, exonuclease-resistant modRNA hTERT extended the transient expression profile which may be clinically advantageous. Finally, we provided therapeutic proof of concept in organotypic 3D ex vivo human precision-cut lung slices derived from end-stage PF patients. Intriguingly, a single modRNA hTERT treatment inhibited senescence as indicated by significantly lower levels of senescence-associated {beta}-galactosidase, and pro-inflammatory IL6 and IL8. Concurrently, the key fibrosis mediators TGF{beta} and COL1A1 were markedly reduced. In conclusion, the data presented herein provide initial evidence for the potential of RNA-based hTERT therapy for treating human lung fibrosis.

molecular biology↗

Visuo-tactile integration in texture perception: A replication and extension study

Employing a sensory conflict paradigm, previous research has found that vision and touch contribute, on average, equally to the visuo-tactile perception of surface texture. Our study aimed to, firstly, replicate the original findings using a comparable setup and stimulus set; secondly, examine whether equal modality contributions can also be observed on an individual basis (using a within-subject design); and thirdly, explore how visuo-tactile integration is affected by illumination angle (top vs. oblique). Participants explored a discrepant standard consisting of different abrasive papers by vision, touch, and using both modalities simultaneously, and subsequently had to find the closest visual, tactile, and visuo-tactile match from a set of matching stimuli. We replicated equal contribution from vision and touch across the whole sample in both illumination conditions. We also found considerable inter-individual variations in the modality contributions when the stimuli were illuminated from the top. Interestingly, this variation decreased under oblique illumination, with most participants showing an about-equal contribution from both modalities to the combined texture percept. These findings are consistent with the assumption that the perceived discrepancy between vision and touch was reduced under oblique illumination suggesting overall that visual and tactile information are only weighted equally within a certain range of experienced discrepancy. Outside this individual range, one of the modalities is weighted higher with no clear preference for either modality.

neuroscience↗

Ribosome-targeting antibiotics impair T cell effector function and ameliorate autoimmunity by blocking mitochondrial protein synthesis

While antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive, for reasons that remain unclear. Here we show that linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell-mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of Th17 effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondrial translation in differentiating T cells, either with RAbos or through the inhibition of mitochondrial elongation factor G1 (mEF-G1) progressively compromises the integrity of the electron transport chain (ETC). Ultimately, this leads to loss of mitochondrial metabolism and cytokine production in differentiating Th cells. In accordance, mice lacking Gfm1 in T cells are protected from EAE, demonstrating that this pathway plays a key role in maintaining T cell function and pathogenicity.

immunology↗