Simon McArthur

New month, new paper! Very happy to have this review published in Life

mdpi.com/2075-1729/13/2/396

I put together an overview of what we know about how microbes affect the physiology of cell-cell junctions in the gut (we know a bit), the blood-brain barrier (we know a little bit) and the epidermis (we know very little at all...). Hopefully it'll be useful/interesting, but the main conclusion is that there is still so much more to learn!

Regulation of Physiological Barrier Function by the Commensal Microbiota

A fundamental characteristic of living organisms is their ability to separate the internal and external environments, a function achieved in large part through the different physiological barrier systems and their component junctional molecules. Barrier integrity is subject to multiple influences, but one that has received comparatively little attention to date is the role of the commensal microbiota. These microbes, which represent approximately 50% of the cells in the human body, are increasingly recognized as powerful physiological modulators in other systems, but their role in regulating barrier function is only beginning to be addressed. Through comparison of the impact commensal microbes have on cell–cell junctions in three exemplar physiological barriers—the gut epithelium, the epidermis and the blood–brain barrier—this review will emphasize the important contribution microbes and microbe-derived mediators play in governing barrier function. By extension, this will highlight the critical homeostatic role of commensal microbes, as well as identifying the puzzles and opportunities arising from our steadily increasing knowledge of this aspect of physiology.

www.mdpi.com
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Professor Lesley Hoyles

Professor in Neuroscience position open at Nottingham Trent University in the School of Science and Technology. Closing date for applications is 16 February 2023.

vacancies.ntu.ac.uk/Job/JobDet

#jobs #neuroscience

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Simon McArthur boosted
Sky "Bunny" Stanton 🌈♾️🧠

I needed to read this today. My New Years revolution is to live life vibrantly, like a benevolent alien.

I think it might help. 🧡

tweet by @boywaif that reads "I had a french professor who once said if you just did something like going to the supermarket and experienced it fully without the goggles of habit and catégories you would go crazy with pure sense and joy. I think about it allthe time. In a way this is all for him."
tweet by @thanatosinfurs that reads "yet another sentiment that makes me think about kurt vonnegut telling his wife he's going out to buy envelopes". Below a quote from Vonnegut reads: "Oh, she says well, you're not a poor man. You know, why don't you go online and buy a hundred envelopes and put them in the closet? And so I pretend not to hear her. And go out to get an envelope because I'm going to have a hell of a good time in the process of buying one envelope. I meet a lot of people. And, see some great looking babes. And a fire engine goes by. And I give them the thumbs up. And, and ask a woman what kind of dog that is. And, and I don't know...And, of course, the computers will do us out of that. And, what the computer people don't realize, or they don't care, is we're dancing animals. You know, we love to move around. And, we're not supposed to dance at all anymore."
Quote tweet by @volkuri that reads "Genuinely genuinely the best thing I ever did for myself was start treating the world like I’m a benevolent alien. everything is so beautiful and people are so cool and food is so delicious and helping other people is fun. You can live so vibrantly". Tweet is a quote tweet of the first of these photos.
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Simon McArthur boosted
TeelaResists

A statue honoring Henrietta Lacks whose whose cells resulted in countless medical breakthroughs will be built in her birthplace Roanoke #Virginia

The statue replaces Gen Robert E Lee

#BlackMastodon
#tuesdayvibe 😻

abcnews.go.com/US/henrietta-la

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Simon McArthur boosted
Matthew Fuchter

RT @ImperialLifeSci
FIVE new Faculty posts now available in Life Sciences, Imperial College London
@imperialcollege
- Pls apply, tell friends, RT

imperial.ac.uk/jobs/descriptio
imperial.ac.uk/jobs/descriptio
imperial.ac.uk/jobs/descriptio
imperial.ac.uk/jobs/descriptio
imperial.ac.uk/jobs/descriptio
imperial.ac.uk/life-sciences/

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Hwamee Oh

#Neuroinflammation is independently associated with brain #network dysfunction in #Alzheimer’s disease.

rdcu.be/c09vc

#PET #DTI #rsfMRI #graphmetrics

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audreykist

Reaching out to the #brain #science community out there! Let's say we are planning a #Wikipedia raid to improve pages of women scientists in fields related to the brain (#psychology #neuroscience #psychiatry etc). Can you think of women scientists who deserve improving or creating a Wikipedia page?

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Simon McArthur boosted
Rebecca Hirst

Resharing everything I ever found useful on 🐦🐤 part 3

Connected Papers!

Makes a graph of papers connected to the article you search!🔎🤓💻

connectedpapers.com/

Absolute time saver #AcademicMastodon 🐘 #lifehacks #research #academia

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Simon McArthur boosted
Michael Hendricks

RT @SteveStuWill@twitter.com

Wow! Scientists have observed a single-cell alga evolve in real time into a multicellular organism. The transition took around a year and was caused by the introduction of a predator into the environment. nature.com/articles/s41598-019

🐦🔗: twitter.com/SteveStuWill/statu

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Dave nλ=2dsinθ

The dear leader, light of a thousand suns has had some thoughts and committed them to paper. And being who he is, Nature have published those thoughts.

nature.com/articles/d41586-021

These thoughts aren't as awful as some of the thoughts he has previously had, and in fact are in opposition to what he was saying before he became president of the Royal Society.

#Research #StructuralBiology #Alphafold #DubiousCareerChoices

🧵⬇️

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Simon McArthur boosted
Jess Wade

“The disproportionate scientific productivity of elite researchers can be largely explained by their substantial labor advantage rather than inherent differences in talent.” #AcademicMastodon #ScienceMastodon science.org/doi/10.1126/sciadv

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Sam

16/ Takeaway: adding research labor, eg, via targeted funding, is likely a strong policy lever for mitigating prestige-driven inequalities 📈; and, it raises an uncomfortable question: What discoveries aren't being made because non-elite faculty lack sufficient labor? 🤔

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Dr Shaun O’Boyle

Happy LGBTQIA+ STEM Day from my nerdy gay heart to yours 💖
#LGBTSTEMDay #LGBTQSTEMDay #LGBTQIASTEMDay

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Professor Lesley Hoyles

Hello, and an #introduction.

I use and integrate omics data to understand how the gut microbiota influences mammalian intestinal and systemic health. I'm particularly interested in how microbially produced metabolites interact with host metabolic pathways.

My team is looking at functional and genomic aspects of gut bacteria, especially Klebsiella and Collinsella spp.

I have a soft spot for phages.

#microbiome #NAFLD #cancer #gutbrainaxis

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Professor Lesley Hoyles

In vitro, brain endothelial cells exposed to haemodialysis patient serum (high in pCS) were affected in the same way as treatment with pCS: i.e. blood-brain barrier integrity was impaired. Erlotinib protected against effects seen in cells treated with patient serum.

Targeting the EGFR-mediated pathway may be useful in reducing cerebrovascular damage in chronic kidney disease.

4/4

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Professor Lesley Hoyles

pCS binds to the epidermal growth factor receptor (EGFR), leading via annexin A1 and STAT3 signalling to mobilisation of matrix metalloproteinase (MMP)-2/9.

Pre-treatment with the EGFR antagonist erlotinib or the MMP2/9 inhibitor SB-3CT prevents the damaging effects of pCS.

/3

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Professor Lesley Hoyles

Patients with #chronickidneydisease have high levels of the microbiome-associated metabolite p-cresol sulfate (pCS) in their blood.

We hypothesized this metabolite could impair the functioning of the blood-brain barrier in these patients.

Using mouse work, we were able to show suppression of neuronal activity, transcription and mitochondrial respiration pathways by pCS.

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Professor Lesley Hoyles

Very pleased to see this out. Another huge effort from @SimonMcArthur and his research team.

Cerebrovascular damage caused by the gut microbe-derived uraemic toxin p-cresol sulfate is prevented by blockade of the epidermal growth factor receptor biorxiv.org/content/10.1101/20

#gutbrainaxis #microbiome #metabolome #chronickidneydisease

Cerebrovascular damage caused by the gut microbe-derived uraemic toxin p-cresol sulfate is prevented by blockade of the epidermal growth factor receptor

Chronic kidney disease is linked to impaired cognitive function and increased neurovascular disease risk even after correction for classical risk factors. The mechanism(s) underlying these links are unclear but may involve interactions of uraemic toxins with the blood-brain barrier (BBB). Here, we studied how the major uraemic toxin p-cresol sulfate (pCS) could affect BBB integrity. Exposure of human hCMEC/D3 endothelial cells to pCS dose-dependently increased paracellular permeability and disrupted intercellular tight junctions, a permeabilising effect mirrored in mice. Whole brain RNAseq analysis identified pCS-mediated suppression of neuronal activity, transcription and mitochondrial respiration pathways. In vitro studies identified pCS binding to the epidermal growth factor receptor (EGFR), leading via annexin A1 and STAT3 signalling to mobilisation of matrix metalloproteinase (MMP)-2/9. Confirming this pathway in vivo, the BBB damaging effects of pCS were prevented by pre-treatment with the EGFR antagonist erlotinib or the MMP2/9 inhibitor SB-3CT. Finally, hCMEC/D3 cells exposed to haemodialysis patient serum, but not to that of healthy donors, showed an erlotinib-sensitive increase in paracellular permeability that closely correlated in size to the total serum pCS content. Overall, we define a pathway linking the uraemic toxin pCS with BBB damage suggesting that targeting the EGFR may be useful in mitigating against cerebrovascular damage in chronic kidney disease. ### Competing Interest Statement The authors have declared no competing interest.

www.biorxiv.org
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Simon McArthur

Presenting our new preprint on the gut-brain axis in chronic kidney disease 

Very pleased to present our latest work on the mechanisms of the gut-brain axis (doi.org/10.1101/2022.11.12.516) and how the blood-brain barrier is affected in chronic kidney disease

Work was led by Sita Shah and co-authors Tobias Knausenberger, Emily Connell, Gwen Le Gall, Tom Hardy, David Randall, Kieran McCafferty, Magdi Yaqoob, Egle Solito, Michael Muller, Andrew Stachulski, Bobby Glen, David Vauzour and @BugsInYourGuts

People with CKD are at increased risk of stroke and brain blood vessel disease, but we don’t really know why. We looked at the role of the gut microbe-derived toxin p-cresol sulfate (pCS)

Using cell and mouse models we show that pCS activates the EGF receptor to cause metalloprotease release, damaging and weakening the blood-brain barrier

Importantly, we also showed that serum from patients undergoing haemodialysis for CKD damaged blood-brain barrier integrity in vitro, an effect we could block by treating with an EGF receptor inhibitor

We think this further highlights the importance of gut microbes in disease, and shows just how interlinked different organ systems are

And maybe EGF receptor inhibitors might be useful in modifying CKD stroke risk?

All of this was made possible by Alzheimer's Research UK awarding us a pilot project grant six years ago. Think we might have got a bit carried away with the amount of work we did with it, but we are incredibly grateful!

'sResearchUK

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Dr. Lucky Tran :verified:

Timeline cleanse: This baby elephant messing around with an on air reporter is totally adorbs 🥰

(h/t Sheldrick Wildlife Trust)

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