Reduced triacylglycerols and lipid droplets are associated with resilience to Alzheimer’s disease Introduction While it has become clear that alterations in lipid metabolism are associated with AD, it is unclear how they contribute to both cognitive decline and the pathophysiology of AD. Methods ...

Happy to share our new preprint! We analyzed lipid metabolism in a unique cohort of controls, AD patients, and individuals resilient to AD. We found reduced lipid droplets in resilience compared to AD. Interesting finding as more literature converges on an important role for lipid droplets in AD!

Depletion-dependent activity-based protein profiling using SWATH/DIA-MS detects serine hydrolase lipid remodeling in lung adenocarcinoma progression - Nature Communications Functional profiling of enzyme family classes is essential for clinical tissue phenotyping. Here, the authors develop and apply an alternative approach in activity-based protein profiling of serine hy...

#chembio #massspec #proteomics

www.nature.com/articles/s41...

Due to donor shortages, #liver #transplantation may require use of fatty livers. This #proteomic and #lipoprotein profiling study reports on machine # perfusion under #hyperthermia (40 C) as a potential strategy to improve functionality and use of #fattyliver grafts.

Direct sensing of dietary ω-6 linoleic acid through FABP5-mTORC1 signaling Diet influences macronutrient availability to cells, and although mechanisms of sensing dietary glucose and amino acids are well characterized, less is known about sensing lipids. We defined a nutrien...

Direct sensing of dietary ω-6 linoleic acid through FABP5-mTORC1 signaling | Science www.science.org/doi/10.1126/...

Finally solved: how the body's own marijuana spreads through the brain Since its discovery thirty years ago, it remained a mystery: how does the body’s own marijuana move between nerve cells in the brain? Mario van der Stelt and his research group have now uncovered the ...

🧠🔬 Researchers at Leiden University have uncovered how the brain's own marijuana travels between nerve cells. 2-AG is transported in fatty vesicles, revealing a novel form of neural communication. This breakthrough could pave the way for new treatments for pain and neurological disorders.

Our paper is now out in PNAS, a journal that has a history of publishing seminal papers on endocannabinoid transport and therefore is the perfect home for this story:
www.pnas.org/doi/10.1073/...

Thank you to everyone that has contributed!

It’s incredibly hard to study lipids in biological membranes on the nanoscale. You need near-perfect information on both membrane ultrastructure and lipid density, which usually isn’t attainable. Lipid-CLEM brought to you by @mathilda95.bsky.social changes that.
www.biorxiv.org/content/10.1...

Could one envision a synthetic receptor technology that is fully programmable, able to detect diverse extracellular antigens – both soluble and cell-attached – and convert that recognition into a wide range of intracellular responses, from gene expression and real-time fluorescence to modulation..

Fantastic work and a masterclass in multi-omics data integration and visualization 🎨

A Scientist’s Final Quest Is to Find New Schizophrenia Drugs. Will He Live to See Them? Edward Scolnick led the development of dozens of medicines while at Merck. His current mission pits him against time and the mental illness of millions, including his son.

Since leaving his perch in Big Pharma, drug developer extraordinaire Ed Scolnick has sought to find effective treatments for mental-health conditions like bipolar disorder. One reason: He’s trying to help his son.

homer simpson from the simpsons is holding a cup in front of a picture ALT: homer simpson from the simpsons is holding a cup in front of a picture

A bluetorial about some challenges for our two-career family and some flaws in the culture of biomedical research.

☺️

Bluesky Starter Packs - Bluesky Directory Browse a list of Bluesky Starter Packs. Discover and connect with your community on Bluesky

This?
blueskydirectory.com/starter-pack...

Need more starter packs for haters.

“We refuse to propose doing AI in our grants” starter pack
“What does the Golgi even do” starter pack

Preprint on lipid changes in postmortem AD patient brains and the 5xFAD mouse model. Increased BMP, LPC and LPE levels in amyloidosis. Microglia depletion reduces AA-containing BMP but not LPC and LPE. LPC accumulation is associated with astroglial activation, LPE with oxidative stress

Endocannabinoid biology in Cell this week!
Anandamide is involved in memory generalization induced by stress. Find the paper here and a nice write-up below
www.cell.com/cell/abstrac...

So much chemistry history in Heidelberg. I can’t believe I never visited the Bergfriedhof during my time in Heidelberg even though I lived closeby. I guess I was too busy studying in rooms named after the chemists buried there 😅

Leiden is absolutely beautiful and great to explore on a run. So many hidden corners

Check out CellEKT, an effort from Joel Rüegger and Berend Gagestein to expand the ligandable kinome for cellular target engagement using chemical proteomics 🎯
Including new broad-spectrum kinase probes
www.biorxiv.org/content/10.1...

CellEKT: A robust chemical proteomics workflow to profile cellular target engagement of kinase inhibitors https://www.biorxiv.org/content/10.1101/2024.10.01.616061v1 The human genome encodes 518 protein kinases that are pivotal for drug discovery in various therapeu

CellEKT: A robust chemical proteomics workflow to profile cellular target engagement of kinase inhibitors www.biorxiv.org/content/10.1101/2024.10....

Effect of chronic upregulation of endocannabinoid signaling in vivo with JZL184 on striatal synaptic plasticity and motor learning in YAC128 Huntington disease mice https://www.biorxiv.org/content/10.1101/2024.09.25.614804v1 Synaptic dysfunction underlies early sensorimotor and cognitive deficits, and precedes neurodegenera

Effect of chronic upregulation of endocannabinoid signaling in vivo with JZL184 on striatal synaptic plasticity and motor learning in YAC128 Huntington disease mice www.biorxiv.org/content/10.1101/2024.09....

There’s a desperate need for new and better therapies for schizophrenia and other psychiatric disorders so the approval of Cobenfy is great news. Nice thread on its discovery:

Charged Molecular Glue Discovery Enabled by Targeted Degron Display https://www.biorxiv.org/content/10.1101/2024.09.24.614843v1 Small molecules that induce protein interactions hold tremendous potential as new medicines, as prob

Charged Molecular Glue Discovery Enabled by Targeted Degron Display www.biorxiv.org/content/10.1101/2024.09....

Thank you to all co-authors for this fantastic collaboration: @mvdstelt.bsky.social, Benjamin Barti, Sebastian Tandar, Floor Stevens, Tom van der Wel, Na Zhu, Joel Rüegger, Cas van der Horst, Laura Heitman, Yulong Li, Nephi Stella, @cvhasselt.bsky.social and István Katona
5/5

The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution

We hope that this will provide a framework to better understand endocannabinoid signalling.
Check out the manuscript for the full story:
www.biorxiv.org/content/10.1...
4/5

We combined this with biochemical isolation and characterisation of EVs, electrophysiology recordings and mathematical modelling to arrive at an ‘on-demand release’ model
3/5

How endocannabinoids are released and traverse the synapse is still poorly understood. We made use of the fantastic endocannabinoid GRAB sensor in a co-culture system to study the underlying mechanisms
2/5

The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution

I’m happy to share that my PhD work is now out on #biorxiv. We propose an ‘on-demand release’ model for the release of the endocannabinoid 2-arachidonoylglycerol in extravellular vesicles (EVs) #lipidtime #neuroskyence #biosky
🔗 www.biorxiv.org/content/10.1...
1/5

Register for the Virtual @chembiotalks.bsky.social next Tuesday (Sep 24th) to hear Joel talk about his amazing PhD work. Registration is free!
web.cvent.com/event/7b3b6c...