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Biology subjects

Sander, J.

Publications and source records attributed to Sander, J..

3 recordsLinked to original sources

Individual versus fixed parametrization of an electrocutaneous warning signal during manual work tasks

Electrocutaneous stimulation provides a means to warn workers of potential hazards. Our previous parameter studies were conducted at rest or under controlled external influences such as vibration, temperature, and humidity, whereas actual work tasks have not yet been addressed. As a step towards greater practical applicability, we conducted two studies in which a circumferential electrocutaneous warning signal was applied to the upper right arm while participants performed a reading task, screw-driving, and polishing. In study 1 (n = 32), the pulse interval was adjusted individually to evoke a vibrating sensation, and the intolerance threshold was determined. In study 2 (n = 29), a fixed pulse interval of 36 ms was applied to all participants, the warning threshold was determined in addition to the intolerance threshold, and muscle twitches were documented both by participant report and by an independent observer. Study 1 demonstrated that electrocutaneous warning during work tasks is feasible, with a median intolerance threshold higher during polishing (16.5 mA) than during reading or screw-driving (14 mA each). In study 2, the fixed parameter setting elicited the intended pulsating or vibrating sensation at rest in 89 % of the participants in both presentations. The median warning threshold was 8 mA and did not differ between the three work tasks, whereas the intolerance threshold was lower during reading (18 mA) than during screw-driving and polishing (20 mA each). Muscle twitches were largely absent at the warning threshold and became frequent towards the intolerance threshold, with a ventral dominance of their location in both studies. An individual parametrization is therefore not required for the majority of users when a binary warning is to be conveyed, and operating the system slightly above the warning threshold provides a usable amplitude range while minimizing muscle twitches. Future work will focus on electrode optimization and on the objective measurement of motor responses.

neuroscience↗

From Brown to White: Brown Adipose Tissue Endothelial Cells whiten in Culture Conditions

Endothelial cells (ECs) are central regulators of vascular and metabolic homeostasis, yet their organ- and depot-specific diversity remains underexplored. Two major types of adipose tissue (AT) can be distinguished that differ substantially in their physiological function and vascularization: white AT (WAT), which is the major energy storage and brown AT (BAT), which is highly vascularized and dissipates energy [1-5]. While ECs from these depots likely contribute to adipose function, their characterization has been hindered by technical limitations in isolation and culture. Here, we establish a protocol for isolating and expanding ECs from murine BAT and WAT, enabling transcriptomic and functional analyses across depots. We demonstrate that freshly isolated BAT-ECs express depot-specific gene signatures, including Rgcc, Cdkn1c, Tcf15, Meox2, and Efnb1, several of which are dynamically regulated during cold-induced BAT activation. These findings reveal novel BAT-EC markers and highlight specialized endothelial programs that may support thermogenesis. However, we also uncover that culturing BAT-ECs profoundly remodels EC identity. Transcriptomic profiling shows that BAT-ECs rapidly downregulate BAT-specific markers and acquire features resembling WAT- and lymphatic ECs. This dedifferentiation is accompanied by signatures of proliferation, adhesion remodeling, and endothelial-to-mesenchymal transition. While these changes present challenges for maintaining depot-specific identity in culture, they also provide a framework to better interpret experimental outcomes and to investigate EC plasticity. Taken together, our study delivers a novel isolation and culture protocol for adipose ECs, defines BAT-EC markers, and demonstrates how culture conditions reshape their identity. These insights build the foundation for future research of AT vasculature. HighlightsO_LIFast method to purify endothelial cells (ECs) for direct RNA or protein extraction. C_LIO_LIEasy method to isolate and culture ECs specifically from thermogenic adipose tissue. C_LIO_LINovel signature of BAT-ECs regulated upon browning and lost in culture. C_LIO_LIRGC-32, p57kip2, TCF15/MEOX2 and EFNB1 as novel BAT-EC-specific markers. C_LI

cell biology↗

Cellular reprogramming of human monocytes is regulated by time-dependent IL4 signalling and NCOR2

The clinical and therapeutic value of human in vitro generated monocyte-derived dendritic cell (moDC) and macrophages is well established. However, in line with recent findings regarding myeloid cell ontogeny and due to our limited understanding of their physiological counterparts, transcriptional regulation and heterogeneity, the full potential of these important cellular systems is still underestimated.\n\nIn this study, we use cutting edge high-dimensional analysis methods to better understand the transcriptional organization, phenotypic heterogeneity and functional differences between human ex vivo isolated and in vitro generated mononuclear phagocytes with the aim to better realize their full potential in the clinic.\n\nWe demonstrate that human monocytes activated by MCSF or GMCSF most closely resemble inflammatory macrophages identified in vivo, while IL4 signalling in the presence of GMCSF generates moDCs resembling inflammatory DCs in vivo, but not steady state cDC1 or cDC2. Moreover, these reprogramming regimes lead to activated monocytes that present with profoundly different transcriptomic, metabolic, phenotypic and functional profiles. Furthermore, we demonstrate that CD14+ monocytes are integrating multiple exogenous activation signals such as GMCSF and IL4 in a combinatorial and temporal fashion, resulting in a high-dimensional cellular continuum of reprogrammed monocytes dependent on the mode and timing of cytokine exposure. Utilizing nanostraw-based knockdown technology, we demonstrate that the IL4-dependent generation of moDCs relies on the induction, nuclear localization and function of the transcriptional regulator NCOR2.\n\nFinally, we unravel unappreciated heterogeneity within the clinically moDCs population and propose a novel high-dimensional phenotyping strategy to better tailor clinical quality control strategies for patient need and culture conditions to enhance therapeutic outcome.

immunology↗