Biology subjects

Jung, T.

Publications and source records attributed to Jung, T..

7 recordsLinked to original sources

bioRxiv2026

A single-stranded DNA virus replicates in the mitochondria of a marine oomycete

A virus with a circular single-stranded DNA genome, HthCRESSV1, was discovered in an oomycete, Halophytophthora thermoambigua, isolated from brackish waters off the Algarve coast in southern Portugal. Phylogenetic analyses place this virus outside of all currently classified families within the phylum Cressdnaviricota, suggesting it represents a distinct lineage. Cellular fractionation, mitochondrial marker co-enrichment, and Southern blot analyses indicate that HthCRESSV1 is associated with mitochondria and replicates episomally. The virus is stably transmitted through zoospores and, notably, infected host isolates are associated with reduced growth and changes in temperature-dependent performance. Homologous sequences corresponding to both the replication-associated protein and a membrane-associated hypothetical protein were identified in the mitochondrial genomes of several oomycete species, suggesting recurrent endogenization of HthCRESSV1-like viruses in oomycete mitochondria. Together, these findings expand the known diversity of oomycete-associated DNA viruses, identify mitochondria as an unexpected niche for DNA virus replication, and highlight marine environments as underexplored reservoirs of DNA viruses in stramenopiles.

evolutionary biology↗

bioRxiv2024

Stable, chronic in-vivo recordings from a fully wireless subdural-contained 65,536-electrode brain-computer interface device

Minimally invasive, high-bandwidth brain-computer-interface (BCI) devices can revolutionize human applications. With orders-of-magnitude improvements in volumetric efficiency over other BCI technologies, we developed a 50-m-thick, mechanically flexible micro-electrocorticography (ECoG) BCI, integrating a 256x256 array of electrodes, signal processing, data telemetry, and wireless powering on a single complementary metal-oxide-semiconductor (CMOS) substrate containing 65,536 recording channels, from which we can simultaneously record a selectable subset of up to 1024 channels at a given time. Fully implanted below the dura, our chip is wirelessly powered, communicating bi-directionally with an external relay station outside the body. We demonstrated chronic, reliable recordings for up to two weeks in pigs and up to two months in behaving non-human primates from somatosensory, motor, and visual cortices, decoding brain signals at high spatiotemporal resolution.

neuroscience↗

bioRxiv2024

Age pigment lipofuscin causes oxidative stress, lysosomal dysfunction, and pyroptotic cell death

Accumulation of the age pigment lipofuscin represents a ubiquitous hallmark of the aging process. However, our knowledge about cellular effects of lipofuscin accumulation is potentially flawed, because previous research mainly utilized highly artificial methods of lipofuscin generation. In order to address this tremendous problem, we developed a convenient protocol for isolation of authentic lipofuscin from human and equine cardiac tissue in high purity and quantity. Isolated lipofuscin aggregates contained elevated concentrations of proline and metals such as calcium or iron. The material was readily incorporated by fibroblasts and caused cell death at low concentrations (LC50 = 5.0 {micro}g/mL) via a pyroptosis-like pathway. Lipofuscin boosted mitochondrial ROS production and caused lysosomal dysfunction by lysosomal membrane permeabilization leading to reduced lysosome quantity and impaired cathepsin D activity. In conclusion, this is the first study utilizing authentic lipofuscin to experimentally validate the concept of the lysosomal-mitochondrial axis theory of aging and cell death.

cell biology↗

bioRxiv2023

Oxic microbial electrosynthesis can be more energy efficient for biomass production than knallgas or photosynthesis based processes

Data on the efficiency and development of continuous processes are scarce in the emerging field of oxic microbial electrosynthesis (OMES). Therefore, the recently isolated knallgas bacterium Kyrpidia spormannii was observed in a bioelectrochemical flow cell setup to study biomass formation and energy efficiency of cathode dependent growth. The study revealed that a potential of -500 mV vs. the standard hydrogen electrode (SHE) caused differences in the structure of the biofilm developing on the cathode, but had almost no impact on biomass growth behavior compared to -375 mV vs. SHE. No growth was observed at 0 mV vs SHE. Coulombic efficiency (CE) was calculated for the cultivation at -500 mV vs. SHE. The process can be conducted with the same electron efficiency as traditional gas fermentation. The solar energy demand with 67.89 kWh kg-1 dry biomass is highly competitive to alternative and already established processes for converting (solar) energy to biomass. Additionally, with suggestions for a biomass harvesting method and subsequent recultivation, proof of principle for a continuously operable process was provided. The results pave the way for a new concept in carbon dioxide-based biotechnology. Significance statementTo mitigate global climate change, it is imperative to transition the human economy to a different resource foundation, moving away from fossil fuels and reducing atmospheric carbon dioxide levels. Biotechnological production based on CO2 necessitates a supply of energy and electrons. This study reveals that an oxic process, wherein bacteria are directly cultivated as a biofilm on the cathode surface of a bioelectrochemical system, can exhibit higher energy efficiency than plant-based systems or systems reliant on hydrogen generated through water electrolysis. This technology could be instrumental in establishing carbon dioxide and renewable energy as the foundation for feed, food, and platform chemical production.

bioengineering↗

bioRxiv2023

Endogenous inflammatory mediators produced by injury activate TRPV1 and TRPA1 nociceptors to induce sexually dimorphic cold pain that is dependent on TRPM8 and GFRalpha3

The detection of environmental temperatures is critical for survival, yet inappropriate responses to thermal stimuli can have a negative impact on overall health. The physiological effect of cold is distinct among somatosensory modalities in that it is soothing and analgesic, but also agonizing in the context of tissue damage. Inflammatory mediators produced during injury activate nociceptors to release neuropeptides, such as CGRP and substance P, inducing neurogenic inflammation which further exasperates pain. Many inflammatory mediators induce sensitization to heat and mechanical stimuli but, conversely, inhibit cold responsiveness, and the identity of molecules inducing cold pain peripherally is enigmatic, as are the cellular and molecular mechanisms altering cold sensitivity. Here, we asked if inflammatory mediators that induce neurogenic inflammation via the nociceptive ion channels TRPV1 and TRPA1 lead to cold pain in mice. Specifically, we tested cold sensitivity in mice after intraplantar injection of lysophosphatidic acid (LPA) or 4-hydroxy-2-nonenal (4HNE), finding each induces cold pain that is dependent on the cold-gated channel TRPM8. Inhibition of either CGRP, substance P, or toll-like receptor 4 (TLR4) signaling attenuates this phenotype, and each neuropeptide produces TRPM8-dependent cold pain directly. Further, the inhibition of CGRP or TLR4 signaling alleviates cold allodynia differentially by sex. Lastly, we find that cold pain induced by inflammatory mediators and neuropeptides requires the neurotrophin artemin and its receptor GFR3. These results demonstrate that tissue damage alters cold sensitivity via neurogenic inflammation, likely leading to localized artemin release that induces cold pain via GFR3 and TRPM8. Significance StatementThe cellular and molecular mechanisms that generate pain are complex with a diverse array of pain-producing molecules generated during injury that act to sensitize peripheral sensory neurons, thereby inducing pain. Here we identify a specific neuroinflammatory pathway involving the ion channel TRPM8 and the neurotrophin receptor GFR3 that leads to cold pain, providing select targets for potential therapies for this pain modality.

neuroscience↗

bioRxiv2018

Structural basis of recognition and destabilization of histone H2B ubiquitinated nucleosome by DOT1L histone H3 Lys79 methyltransferase

DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B-ubiquitination. Here, we present cryo-EM structures of DOT1L complex with unmodified and H2B-ubiquitinated nucleosomes, showing that DOT1L recognizes H2B-ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L respectively. Furthermore, the structures combined with single-molecule FRET experiment show that H2B-ubiquitination enhances a non-catalytic function of DOT1L destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L.

biophysics↗

bioRxiv2017

Structural insights into the architecture of human Importin4_histone H3/H4_Asf1a complex and its histone H3 tail binding

Importin4 transports histone H3/H4 in complex with Asf1a to the nucleus for chromatin assembly. Importin4 recognizes the nuclear localization sequence located at the N-terminal tail of histones. Here, we analyzed the structures and interactions of human Importin4, histones and Asf1a by cross-linking mass spectrometry, X-ray crystallography, negative-stain electron microscopy, small-angle X-ray scattering and integrative modeling. The XL-MS data showed that the C-terminal region of Importin4 interacts extensively with the histone H3 tail. We determined the crystal structure of the C-terminal region of Importin4 bound to the histone H3 peptide, thus revealing that the acidic path in Importin4 accommodates the histone H3 tail and that histone H3 Lys14 is the primary residue interacting with Importin4. Furthermore, the molecular architecture of the Importin4_histone H3/H4_Asf1a complex was produced through an integrative modeling approach. Overall, this work provides structural insights into how Importin4 recognizes histones and their chaperone complex.

biochemistry↗