Biology subjects

Coates, A.

Publications and source records attributed to Coates, A..

4 recordsLinked to original sources

bioRxiv2024

Broad diversity of human gut bacteria accessible via a traceable strain deposition system

Numerous bacteria in the human gut microbiome remain unknown and/or have yet to be cultured. While collections of human gut bacteria have been published, few strains have been made publicly available. A major hurdle in making strains publicly available is their deposition to public culture collections. We propose a framework for the bulk-deposition of strains to culture collections, which removes many of the barriers previously identified (www.dsmz.de/bulk-deposit). Using this bulk-deposition system we have created a publicly available collection of human gut isolates. The Human intestinal Bacteria Collection (HiBC) (www.hibc.rwth-aachen.de) contains 340 strains representing 198 species within 29 families and 7 phyla, of which 29 previously unknown species are taxonomically described and named. These included two butyrate-producing species of Faecalibacterium and new dominant species associated with health and inflammatory bowel disease, Ruminococcoides intestinale and Blautia intestinihominis, respectively. Plasmids were prolific within the HiBC isolates, with almost half (46%) of strains containing plasmids, with a maximum of six within a strain. This included a broadly occurring plasmid (pBAC) that exists in three diverse forms across Bacteroidales species. Megaplasmids were identified within two strains, the pMMCAT megaplasmid is globally present within multiple Bacteroidales species. This collection of easily searchable and publicly available gut bacterial isolates will facilitate functional studies of the gut microbiome.

microbiology↗

bioRxiv2023

ALDH1A3-acetaldehyde re-wires neural crest stem cell and high metabolism states to potentiate melanoma heterogeneity

Cancer cellular heterogeneity and therapy resistance arise substantially from metabolic and transcriptional adaptations, but how these are interconnected is poorly understood. Here, we show that in melanoma, the cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) forms an enzymatic partnership with acetyl-CoA synthetase 2 (ACSS2) in the nucleus to couple high glucose metabolic flux with acetyl-histone H3 modification of neural crest lineage and glucose metabolism genes. Importantly, we show acetaldehyde is a metabolite source for acetyl-histone H3 modification in an ALDH1A3, dependent manner providing a physiologic function for this highly volatile and toxic metabolite. In a zebrafish model of melanoma residual disease, a subpopulation of ALDH1-high cells emerges following BRAF inhibitor treatment and targeting these with an ALDH1 suicide inhibitor, nifuroxazide, delays or prevents BRAF inhibitor drug-resistant relapse. Our work reveals that the ALDH1A3-ACSS2 couple directly coordinates nuclear acetaldehyde-acetyl-CoA metabolism with specific chromatin-based gene regulation and represents a potential therapeutic vulnerability in melanoma. HighlightsO_LIALDH1A3-high melanomas are in a high glucose metabolic flux and neural crest stem cell dual state. C_LIO_LINuclear ALDH1A3 partners with ACSS2 to promote selective acetyl-histone H3. C_LIO_LIAcetaldehyde is an acetyl source for ALDH1A3 dependent histone H3 acetylation. C_LIO_LIALDH1A3 is a master regulator and pharmaceutical target for melanoma heterogeneity. C_LI

cancer biology↗

bioRxiv2023

Effects of intensified training with insufficient recovery on joint level and single muscle fibre mechanical function: The role of myofibrillar Ca2+ sensitivity

Intense exercise training with insufficient recovery is associated with reductions in neuromuscular performance. However, it is unclear how single muscle fibre mechanical function and myofibrillar Ca2+ sensitivity contribute to these impairments. We investigated the effects of overload training on joint-level neuromuscular performance and cellular-level mechanical function. Fourteen athletes (4 female, 10 male) underwent a 3-week intensified training protocol consisting of [~]140% of their regular training hours with three additional high-intensity training sessions per week. Neuromuscular performance of the knee extensors was assessed via maximum voluntary contraction (MVC) force, electrically evoked twitch contractions, and a force-frequency relationship. Muscle biopsies were taken from the vastus lateralis to assess single fibre mechanical function. Neither MVC force nor twitch parameters were altered following intensified training (all p>0.05), but a rightward shift in the force-frequency curve was observed with a 6-27% reduction in force at low-frequencies (5-20Hz, all p<0.05). In single fibres, maximal force output was not reduced following intensified training, but there was a rightward shift in the force-pCa curve driven by a 6% reduction in Ca2+ sensitivity as indicated by a lower pCa50 value (i.e., higher [Ca2+]) across fibre types (Pre=6.477{+/-}0.157, Post=6.088{+/-}0.480, p<0.05). These data indicate intensified training leads to impaired Ca2+ sensitivity at the single fibre level, which in part explains impaired neuromuscular function at the joint level during lower frequencies of activation. This is an important consideration for athletes, as performance is often assessed at maximal levels of activation, and these underlying impairments in force generation may be less obvious. New & NoteworthyIntense exercise training with insufficient recovery leads to impaired muscle contractile performance. These impairments often manifest at lower frequencies of muscle stimulation, termed prolonged low-frequency force depression. Impaired myofibrillar calcium sensitivity has been suggested as a potential mechanism of prolonged low-frequency force depression. Our work shows that impaired calcium sensitivity of single muscle fibres coincided with joint level prolonged low-frequency force depression after intense exercise training with insufficient recovery.

physiology↗

bioRxiv2023

High-resolution 7T fMRI reveals the visual sensory zone of the human claustrum

The claustrum is a thin subcortical gray matter structure located between the insula and the putamen. It has numerous bilateral connections with the cortex and is thought to play an important role in higher-level aspects of perception and cognition, with hypotheses including multisensory integration, attention and consciousness. The claustrums thin shape makes it difficult to investigate, leaving the hypothesis regarding its function largely untested. In the current study, we used high-resolution ultra-high field (7 Tesla) functional magnetic resonance imaging (fMRI) to measure claustrum activity in human participants, while they were presented with visual, auditory or audiovisual naturalistic stimuli. We found distinct visual responses in the claustrum at a spatial location that was consistent across participants, hemispheres and scanning sessions. This is the first study to demonstrate evoked sensory responses within the human claustrum. It opens the possibility for future noninvasive investigation of the claustrums role in sensory processing.

neuroscience↗