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Fuehrer, D.

Publications and source records attributed to Fuehrer, D..

3 recordsLinked to original sources

msiFlow: Automated Workflows for Reproducible and Scalable Multimodal Mass Spectrometry Imaging and Immunofluorescence Microscopy Data Processing and Analysis

Multimodal imaging by matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI MSI) and immunofluorescence microscopy holds great potential for understanding pathological mechanisms by mapping molecular signatures from the tissue microenvironment to specific cell populations. However, existing open-source software solutions for analysis of MALDI MSI data are incomplete, require programming skills and contain laborious manual steps, hindering broadly applicable, reproducible, and high-throughput analysis to generate impactful biological discoveries across interdisciplinary research fields. Here we present msiFlow, an accessible open-source, platform-independent and vendor-neutral software for end-to-end, high-throughput, transparent and reproducible analysis of multimodal imaging data. msiFlow integrates all necessary steps from import and pre-processing of raw MALDI MSI data to visual analysis output, as well as registration, along with state-of-the-art and newly developed algorithms, into automated workflows. Using msiFlow, we unravel the molecular heterogeneity of leukocytes in infected tissues by spatial regulation of ether-linked phospholipids containing arachidonic acid. We anticipate that msiFlow will facilitate the broad applicability of MSI in the emerging field of multimodal imaging to uncover context-dependent cellular regulations in disease states.

bioinformatics↗

Partial resistance to thyroid hormone-induced tachycardia and cardiac hypertrophy in mice lacking thyroid hormone receptor beta

BackgroundThyroid hormones regulate cardiac functions mainly via direct actions in the heart and binding to the thyroid hormone receptor (TR) isoforms 1 and {beta}. While the role of the most abundantly expressed isoform, TR1, is widely studied and well characterized, the role of TR{beta} in regulating heart functions is still poorly understood, primarily due to the accompanying elevation of circulating thyroid hormone in mice lacking TR{beta} (TR{beta}-KO). However, their hyperthyroidism is ameliorated at thermoneutrality, which allows studying the role of TR{beta} without this confounding factor. MethodsHere we non-invasively monitored heart rate in TR{beta}-KO mice over several days using radiotelemetry at different housing temperatures (22{degrees}C and 30{degrees}C), and upon T3 administration in comparison to wildtype animals. ResultsTR{beta}-KO mice displayed normal average heart rate at both 22{degrees}C and 30{degrees}C with only minor changes in heart rate frequency distribution, which was confirmed by independent electrocardiogram recordings in freely-moving conscious mice. Parasympathetic nerve activity was, however, impaired in TR{beta}-KO mice at 22{degrees}C, and only partly rescued at 30{degrees}C. As expected, oral treatment with pharmacological doses of T3 at 30{degrees}C led to tachycardia in wildtypes, accompanied by broader heart rate frequency distribution and increased heart weight, while TR{beta}-KO mice showed blunted tachycardia, as well as resistance to changes in heart rate frequency distribution and heart weight. At the molecular level, these observations were paralleled by a blunted cardiac mRNA induction of several important genes, including the pacemaker channels Hcn2 and Hcn4, as well as Kcna7. ConclusionsThe phenotyping of TR{beta}-KO mice conducted at thermoneutrality allows novel insights on the role of TR{beta} in cardiac functions in absence of the usual confounding hyperthyroidism. Even though TR{beta} is expressed at lower levels than TR1 in the heart, our findings demonstrate an important role for this isoform in the cardiac response to thyroid hormones.

physiology↗

The highly and perpetually upregulated thyroglobulin gene is a hallmark of functional thyrocytes

Abnormalities are indispensable for studying normal biological processes and mechanisms. In the present work, we draw attention to the remarkable phenomenon of a perpetually and robustly upregulated gene, the thyroglobulin gene (Tg). The gene is expressed in the thyroid gland and, as it has been recently demonstrated, forms so-called transcription loops, easily observable by light microscopy. Using this feature, we show that Tg is expressed at a high level from the moment a thyroid cell acquires its identity and both alleles remain highly active over the entire life of the cell, i.e. for months or years depending on the species. We demonstrate that this high upregulation is characteristic of thyroglobulin genes in all major vertebrate groups. We provide evidence that Tg is not influenced by the thyroid hormone status, does not oscillate round the clock and is expressed during both the exocrine and endocrine phases of thyrocyte activity. We conclude that the thyroglobulin gene represents a valuable model to study the maintenance of a high transcriptional upregulation. SUMMARY STATEMENTThe thyroglobulin gene is highly and permanently expressed in thyrocytes of all vertebrates, at any condition and round the clock, offering a unique model to study mechanisms of high upregulation maintenance and chromatin dynamics

cell biology↗