Biology subjects

Vogt, S.

Publications and source records attributed to Vogt, S..

8 recordsLinked to original sources

bioRxiv2026

Lysosomal Expansion Compartments Mediate Zinc and Copper Homeostasis in Caenorhabditis elegans

Zinc is an essential transition metal that participates in many biological processes. In C. elegans, excess zinc is stored in lysosomes in intestinal cells; this process involves increasing the expression of the zinc transporter CDF-2 and remodeling of lysosomes characterized by an increase in the volume of the expansion compartment. To determine if this is a more general property, we investigated other metals. Here we report that lysosomes are remodeled in response to excess copper, manganese, and cadmium, with each metal causing an increase in the volume of the expansion compartment. Mutants with a reduced number of lysosomes were hypersensitive to growth retardation caused by excess copper and manganese, suggesting metal toxicity is prevented by metal sequestration in lysosomes. Using a novel method to analyze isolated lysosomes by X-ray Fluorescence Microscopy we demonstrated that zinc, copper and manganese are detectable in the lumen of lysosomes. To further analyze copper, we examined localization of CUA-1.1, a copper transporter that moves copper into the lumen of lysosomes. Like the zinc transporter CDF-2, CUA-1.1 localizes to both the acidified and expansion compartments in excess copper. These results indicate that the same intestinal lysosomes store zinc, copper and manganese. Lysosome remodeling characterized by an increase in volume of the expansion compartment is not specific to zinc but is a more general phenomenon during metal storage in lysosomes.

molecular biology↗

bioRxiv2025

Endothelial Cu Uptake Transporter CTR1 Senses Disturbed Flow to Promote Atherosclerosis through Cuproptosis

Endothelial cells (ECs) lining blood vessels sense disturbed blood flow (D-flow), which drives mitochondrial dysfunction and atherosclerosis. Copper (Cu) is an essential micronutrient, and its disruption of homeostasis has been implicated in atherosclerosis. Cellular Cu levels are tightly controlled by Cu transport proteins including the Cu importer CTR1. Cuproptosis is a recently discovered form of regulated cell death triggered by mitochondrial Cu accumulation, but its endogenous stimulants and role in atherosclerosis remain unknown. Using EC-specific CTR1-deficient mice and cultured ECs, we show that endothelial CTR1 responds to D-flow by increasing mitochondrial Cu levels through its interaction with the mitochondrial Cu transporter SLC25A3 at caveolae/lipid rafts. This leads to the aggregation of lipoylated mitochondrial proteins, mitochondrial dysfunction, and cuproptosis, thereby exacerbating atherosclerosis. Importantly, mitochondria-targeted Cu-chelating nanoparticles effectively mitigate D-flow-induced cuproptosis and atherosclerosis, highlighting the endothelial CTR1-SLC25A3-mitochondrial Cu axis as a potential therapeutic target.

cell biology↗

bioRxiv2024

Snorkel-tag Based Affinity Chromatography for Recombinant Extracellular Vesicle Purification

Extracellular vesicles (EVs) are lipid nanoparticles and play an important role in cell-cell communications, making them potential therapeutic agents and allowing to engineer for targeted drug delivery. The expanding applications of EVs in next generation medicine are still limited by existing tools for scaling standardized EV production, single EV tracing and analytics, and thus provide only a snapshot of tissue-specific EV cargo information. Here, we present CD81, an EV surface marker protein, genetically fused to series of tags with additional transmembrane domain to be displayed on the EV surface, which we term Snorkel-tag. This system enables to affinity purify EVs from complex matrices in a non-destructive form. In future applications, this strategy will allow generating transgenic animals to enable tracing and analyzing EVs, and their cargo in physiological and pathophysiological set-ups, and facilitate the development of EV based diagnostic tools in murine models which can be translated to humans.

bioengineering↗

bioRxiv2021

The superior salinity tolerance of wheat cultivar Shanrong No. 3 cannot be attributed to elevated Ta-sro1 poly(ADP-ribose) polymerase activity

Saline soils limit the production of important staple crops such as wheat, particularly in arid and semiarid regions. Salt tolerance is a multi-gene trait and this complicates breeding of wheat varieties that deliver high yields under saline soil conditions. Notably, the elevated salinity tolerance of wheat cultivar Shanrong No. 3 (SR3) has been linked to a specific proteoform of the wheat SIMILAR TO RCD1 ONE (SRO1) protein that was created in an asymmetric genome hybridization with tall wheat grass. The two amino acid polymorphisms of the Ta-sro1 proteoform enhance the poly(ADP-ribose) polymerase (PARP) activity of the protein suggesting that altered poly-ADP-ribosylation of unknown substrate proteins or nucleic acids underlie the elevated salinity tolerance of cultivar SR3. To elucidate the molecular basis for the elevated PARP activity of the Ta-sro1 proteoform we solved a crystal structure of the catalytic PARP domain. Surprisingly, the structure revealed that the postulated binding site for the co-substrate NAD+ substantially differs from the structurally conserved NAD+ binding sites of canonical PARP enzymes. Consistently, we find that Ta-sro1 does not bind NAD+ and lacks ADP-ribosyltransferase activity. Therefore, although the structure revealed that one of the polymorphic amino acids is located close to the proposed active site, the elevated salinity tolerance of cultivar SR3 cannot be explained by altered ADP-ribosyltransferase activity of Ta-sro1.

plant biology↗

bioRxiv2020

Action Imagery and Observation in Neurorehabilitation for Parkinson's Disease (ACTION-PD): development and pilot randomised controlled trial of a user-informed home training intervention to improve everyday functional actions

BackgroundParkinsons disease (PD) causes difficulties with everyday manual activities, but few studies have addressed these therapeutically. Training with action observation (AO) and motor imagery (MI) can significantly improve performance in healthy individuals, particularly when these techniques are applied simultaneously (AO+MI). Both AO and MI have shown promising effects in PD, but previous studies have used these separately. This article describes the development and pilot testing of an intervention combining AO+MI and physical practice to improve functional manual actions in PD. MethodsThe home-based intervention, delivered using a tablet computer app, was iteratively designed by an interdisciplinary team including people with PD, and further developed through focus groups and initial testing. The intervention was then tested in a six-week randomised controlled trial (ISRCTN 11184024) of 10 participants with mild to moderate PD (6 intervention; 4 treatment as usual). Results and ConclusionsUsage and qualitative data provided preliminary evidence of acceptability and usability, indicating that a feasibility RCT is warranted. Exploratory analyses suggested potential improvements in manual actions. The importance of personalisation, choice, and motivation was highlighted, as well as the need to facilitate engagement in motor imagery. The findings also have broader relevance for AO+MI interventions in PD and other populations.

neuroscience↗

bioRxiv2018

A new universal pore measurement and clustering approach for surgical meshes

The pore structure and pore size is a crucial characteristic of surgical meshes. A huge amount of different approaches for mesh classification based on pore size or materials are available. It is difficult to use these classification methods because of the large variety in knitting structures and pore shapes. No agreement on an established method to measure the pore size is available despite the fact that the surgical community agrees that pore size and geometry are crucial factors for the result of a hernia repair. In this publication a new approach to characterize meshes based on their pore shape and pore size is presented. The pore size is defined by the largest inscribed circle within a mesh pore and the smallest circumscribed circle outside the pore, in addition to hence calculated values. This allows a characterization with regards to tissue ingrowth and bridging behavior. The measurements are made using the scientific image processing software ImageJ and additional customized software plug-in. Since the program ImageJ is public domain and the plug-ins are available, the measurements can be reproduced. Furthermore, the presented pore descriptions can also be used for manual pore size verification.

bioengineering↗

bioRxiv2017

Optogenetic silencing of primary afferents reduces evoked and ongoing bladder pain

Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) suffer from chronic pain that severely affects quality of life. Although the underlying pathophysiology is not well understood, inhibition of bladder sensory afferents temporarily relieves pain. Here, we explored the possibility that optogenetic inhibition of bladder sensory afferents could be used to modulate bladder pain. Specifically, we chose to study the role of Nav1.8+ sensory afferents before and after induction of a mouse model of bladder pain. The light-activated inhibitory proton pump Archaerhodopsin (Arch) was expressed under control of the Nav1.8+ promoter to selectively silence these neurons. Optically silencing Nav1.8+ afferents significantly blunted the evoked visceromotor response to bladder distension and led to small but significant changes in bladder function. To study of the role of these fibers in freely behaving mice, we developed a fully implantable, flexible, wirelessly powered optoelectronic system for the long-term manipulation of bladder afferent expressed opsins. We found that optogenetic inhibition of Nav1.8+ fibers reduced both ongoing pain and evoked cutaneous hypersensitivity in the context of cystitis, but had no effect in uninjured, naive mice. These results suggest that selective optogenetic silencing of bladder afferents may represent a potential future therapeutic strategy for the treatment of bladder pain.

neuroscience↗

bioRxiv2016

Cobalt enrichment in anaerobic microbial cocultures revealed by synchrotron X-ray fluorescence imaging

Metal cofactors are required for many enzymes in anaerobic microbial respiration. This study examined iron, cobalt, nickel, copper, and zinc in cellular and abiotic phases at the single-cell scale for a sulfate-reducing bacterium (Desulfococcus multivorans) and a methanogenic archaeon (Methanosarcina acetivorans) using synchrotron x-ray fluorescence microscopy. Relative abundances of cellular metals were also measured by inductively coupled plasma mass spectrometry. For both species, zinc and iron were consistently the most abundant cellular metals. M. acetivorans contained higher nickel and cobalt content than D. multivorans, likely due to elevated metal requirements for methylotrophic methanogenesis. Cocultures contained spheroid zinc sulfides and cobalt/copper-sulfides.

microbiology↗