Biology subjects

Wadsak, W.

Publications and source records attributed to Wadsak, W..

5 recordsLinked to original sources

bioRxiv2024

Detection of Unlabeled Micro- and Nanoplastics in Unstained Tissue with Optical Photothermal Infrared Spectroscopy

In this study, we investigate the efficacy of Optical Photothermal Infrared (O-PTIR) spectroscopy, also known as mid-infrared photothermal (MIP) microscopy, for the detection of micro- and nano plastics (MNPs) down to diameters of 250 nm in mammalian tissues. Experiments with both in vitro 3D cell cultures derived from HTC116 colorectal cancer cell line and in vivo mouse tissue models were conducted to evaluate the spatial resolution limits and quality of spectra that formed the basis for label-free and non- destructive identification of MNPs. Our findings demonstrate the superior resolution of O-PTIR in imaging individual particles of 250 nm in mouse kidney tissues, surpassing the capabilities of traditional FTIR spectroscopy, which was applied as a reference technique. Furthermore, we introduce a semi-automated image analysis that incorporates machine learning algorithms to accelerate the detection process, thus improving throughput and minimizing the potential for human error. The results confirm that O-PTIR produces high-quality, artefact-free spectral images in a contact-less manner and significantly outperforms FTIR in terms of spatial resolution and signal-to-noise ratio in complex biological matrices.

biophysics↗

bioRxiv2022

Metabolic demands of the posteromedial default mode network are shaped by dorsal attention and frontoparietal control networks

Although BOLD signal decreases in the default mode network (DMN) are commonly observed during attention-demanding tasks, their neurobiological underpinnings are not fully understood. Previous work has shown decreases but also increases in glucose metabolism that match with or dissociate from these BOLD signal decreases, respectively. To resolve this discrepancy, we analyzed functional PET/MRI data from 50 healthy subjects during the performance of the visuo-spatial processing game Tetris(R) and combined this with previously published data sets of working memory as well as visual and motor stimulation. Our findings show that the glucose metabolism of the posteromedial DMN is dependent on the metabolic demands of the correspondingly engaged task-positive brain networks. Specifically, the dorsal attention (involved in Tetris(R)) and frontoparietal networks (engaged during working memory) shape the glucose metabolism of the posteromedial DMN in opposing directions. External attention-demanding tasks lead to a downregulation of the posteromedial DMN with consistent decreases in the BOLD signal and glucose metabolism, whereas working memory is subject to metabolically expensive mechanisms of BOLD signal suppression. We suggest that the former finding is mediated by decreased glutamate signaling, while the latter results from active GABAergic inhibition, regulating the competition between self-generated and task-driven internal demands. The results demonstrate that the DMN relates to cognitive processing in a flexible manner and does not always act as a cohesive task-negative network in isolation.

neuroscience↗

bioRxiv2021

Learning induces coordinated neuronal plasticity of metabolic demands and functional brain networks

The neurobiological basis of learning is reflected in adaptations of brain structure, network organization and energy metabolism. However, it is still unknown how different neuroplastic mechanisms act together and if cognitive advancements relate to general or task-specific changes. To address these questions, we tested how hierarchical network interactions contribute to improvements in the performance of a visuo-spatial processing task by employing simultaneous PET/MR neuroimaging before and after a 4-week learning period. We combined functional PET with metabolic connectivity mapping (MCM) to infer directional interactions across brain regions and subsequently performed simulations to disentangle the role of functional network dynamics and glucose metabolism. As a result, learning altered the top-down regulation of the salience network onto the occipital cortex, with increases in MCM at resting-state and decreases during task execution. Accordingly, a higher divergence between resting-state and task-specific effects was associated with better cognitive performance, indicating that these adaptations are complementary and both required for successful skill learning. Simulations further showed that changes at resting-state were dependent on glucose metabolism, whereas those during task performance were driven by functional connectivity between salience and visual networks. Referring to previous work, we suggest that learning establishes a metabolically expensive skill engram at rest, whose retrieval serves for efficient task execution by minimizing prediction errors between neuronal representations of brain regions on different hierarchical levels.

neuroscience↗

bioRxiv2019

Sex differences in monetary reward and punishment processing are associated with fast dynamics of dopamine synthesis

PurposeIn the human brain endogenous dopamine release is commonly assessed by the PET competition model. Although thoroughly validated, cognitive processing yields low signal changes and the assessment of several task conditions requires repeated scanning. Using the framework of functional PET imaging we introduce a novel approach which leverages the incorporation of the radioligand 6-[18F]FDOPA into the dynamic fast-acting regulation of the corresponding enzyme activities by neuronal firing and neurotransmitter release. We demonstrate the feasibility of the approach by the assessment of widely described sex differences in dopamine neurotransmission. MethodsReward and punishment processing was behaviorally investigated in 36 healthy participants, where 16 underwent fPET and fMRI while performing the monetary incentive delay task. 6-[18F]FDOPA was applied as bolus+infusion during a single 50 min PET acquisition. Task-specific changes in dopamine synthesis were identified with the general linear model and quantified with the Gjedde-Patlak plot. ResultsMonetary gain induced 78% increase in nucleus accumbens dopamine synthesis vs. 49% for loss in men. Interestingly, the opposite was discovered in women (gain: 51%, loss: 78%). Behavioral modeling revealed direct associations of task-specific dopamine synthesis with reward sensitivity in men (rho = -0.7) and with punishment sensitivity in women (rho = 0.89). As expected, fMRI showed robust task-specific neuronal activation but no sex difference. ConclusionsOur findings provide a dopaminergic basis for well-known behavioral differences in reward and punishment processing between women and men. This has important implications in psychiatric conditions showing sex-specific prevalence rates, altered reward processing and dopamine signaling. The high temporal resolution and pronounced magnitude of task-specific changes make fPET a promising tool to investigate functional neurotransmitter dynamics during cognitive or emotional processing in various brain disorders.

neuroscience↗

bioRxiv2019

STAT3-dependent systems-level analysis reveals PDK4 as an independent predictor of biochemical recurrence in prostate cancer

Prostate cancer (PCa) has a broad spectrum of clinical behaviour, hence biomarkers are urgently needed for risk stratification. We previously described the protective effect of STAT3 in a prostate cancer mouse model. By utilizing a gene co-expression network in addition to laser microdissected proteomics from human and murine prostate FFPE samples, we describe STAT3-induced downregulation of the TCA cycle/OXPHOS in PCa on transcriptomic and proteomic level. We identify pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging and PSA level. Furthermore, PDK4 expression is causally linked to type 2 diabetes mellitus, which is known to have a protective effect on PCa. We conclude that this effect is related to PDK4 expression and that PDK4 loss could serve as a biomarker for PCa with dismal prognosis.

cancer biology↗