Mechanisms of DNMT3A–3L-mediated de novo DNA methylation on chromatin - Nature Structural & Molecular Biology Yan et al. use cryo-EM to obtain structures that reveal how DNMT3A2 and DNMT3L cooperate to read histone signals and bind chromatin, illustrating a mechanism that controls DNA methylation and shapes e...

Some hardcore mechanism, for the aficionados (from Peter Jones @vai.org and Ting-Hai Xu @slu-official.bsky.social labs) @natsmb.nature.com www.nature.com/articles/s41...

Congratulations!

On the left - western blot of B16F10 cells wt and KO for CDK8. Our in house produced antibodies give a lot of unspecific bands. On the right same probes with antibodies preincubated with fixed CDK8 KO cells - there is a specific band and faint unspecific bands, which can be probably eliminated with increase of amount of KO cells.

Neat trick if you polycolonal ab's suck. Incubate them with fixed cells with a KO of your protein of interest, then spin. Protocol here: www.med.upenn.edu/markslab/ass...
I was amazed how well it worked on first try (I'm sure that I can completely eliminate unspecific bands)
#WesternBlot #cellsky

The first rule of the Phillies And The World Series is that We. Do. Not. Talk. About. The. Phillies. And. The. World. Series.

Also, 89% of <Phillies> fans are optimistic? 🤔

#RingTheBell but come on, do it responsibly & honestly 😂

I still get chills

Meet Mike
*30+ years severe depression
*first hospitalized @ 13y
*20 meds
*3 rounds of ECT
*2 near-fatal suicide attempts

Mike felt joy for the first time in decades after we turned on his new brain pacemaker or PACE

see videos, read paper, follow thread
doi.org/10.31234/osf...

A postnatal molecular switch drives activity-dependent maturation of parvalbumin interneurons Neuronal activity triggers PGC-1α-mediated transcriptional programs that drive the late maturation of PV+ interneurons, essential for cortical circuit function. PGC-1α partners with ERRγ and Mef2c to ...

Tres cool!
A postnatal molecular switch drives activity-dependent maturation of parvalbumin interneurons: Cell www.cell.com/cell/fulltex...

Neat Elphege. Look forward to seeing the data play out and if there are curious functional differences for any chromatin modification in post-mitotic vs. dividing cell states

My pleasure

LPS-stimulated macrophages
pmc.ncbi.nlm.nih.gov/articles/PMC...

Neural maturation in vivo and pharmacologically stimulated post-mitotic neurons in vitro
elifesciences.org/articles/76539

human post-mitotic neurons
www.biorxiv.org/content/10.1...

as they say: Mo' Loops, Mo' Problems

-Critical developmentally regulated enhancer-promoter loops
-Establishment of new gene expression, not maintenance
-Genes with multiple distant enhancers
-In physiologic or developmentally relevant models
-Strong perturbations and rigorous technology
-Disruption linked to severe disease phenotypes

It has been unambiguously demonstrated that loops are necessary for the establishment of new induced gene expression programs in post-mitotic neurons in vitro and in vivo and in macrophages in vitro. Clean, strong perturbations in physiolgically or developmentally relevant models helped resolve.

It's profound how the OP insight scales to life in science too.
The scientists that find that absolutely most amazing creative unexpected patterns in data that are actually true and stand the test of time tend to obsess about every minor detail and dot every i and cross every t.

Hippocampal ensembles regulate circuit-induced relapse of extinguished fear - Molecular Psychiatry Molecular Psychiatry - Hippocampal ensembles regulate circuit-induced relapse of extinguished fear

Hippocampal ensembles regulate circuit-induced relapse of extinguished fear
www.nature.com/articles/s41...

Molecular Underpinnings of Memory Persistence and Forgetting In this review article, we discuss molecular mechanisms underlying memory durability. We highlight neurotransmitters, receptors, intracellular signaling cascades, gene expression, actin dynamics, and...

Molecular Underpinnings of Memory Persistence and Forgetting
doi.org/10.1111/jnc....

Neural activity in the brain when a #zebrafish recognizes food (paramecium). Credit to Dr. Akira Muto. #ZebrafishZunday 🧪

It's beyond hard right now - profound disappointment in the system. Yet - science and the power of the scientific method to seek truth is timeless. Truth always comes into the light in the end. Your skills and all you've trained to learn will matter more than ever in the coming years.

100% in your corner and in the corner of your very bright future no matter what comes next

A human-specific enhancer fine-tunes radial glia potency and corticogenesis - Nature HARE5, a human accelerated region enhancer, modulates cortical development by influencing neural progenitor cell behaviour, leading to an enlarged neocortex with increased functional independence betw...

Thrilled to share our latest study out in @natureportfolio.nature.com led by the fantastically talented Jing Liu. Our study provides insight into a long standing question in biology: What molecular features make us uniquely human and how do these function? www.nature.com/articles/s41...

🧠 New in Nature from the fabulous Silver Lab @ Duke: A human-specific enhancer, HARE5, boosts radial glia proliferation, expanding neocortical size and connectivity. Knock-in mice showed enlarged cortices and more neurons. This highlights how regulatory DNA changes shaped human brain evolution.

Windows of change: Revisiting temporal and molecular dynamics of memory reconsolidation and persistenc Retrieval can bring memories to a labile state, creating a window to modify its content during reconsolidation. Numerous studies have investigated thi…

➡️ Delighted to contribute to this piece on the mechanisms underlying memory reconsolidation and persistence, together with Hugo Bayer, Cristina Stern and @stevemaren.bsky.social
www.sciencedirect.com/science/arti...

- I want things to be different - *smashes everything* - oh no

I think about this comic at least once a week

aortae

Divergent actions of physiological and pathological amyloid-β on synapses in live human brain slice cultures - Nature Communications Understanding synapse loss in Alzheimer’s disease has been hampered by a lack of human model systems. Here, the authors show that manipulation of physiological or pathological Aβ has differing effects...

Love this. I'm always puzzled by physiological v pathological abeta, tau, & ptau. This is a cool study looking at physiological v pathological abeta on synapses.

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

Over 50 yrs since the discovery of protein kinases, 80% of human kinases still have ≤20 known substrates, and many are “dark.” I'm EXCITED to announce our new work towards solving this- combining (1) deep learning with (2) proximity proteomics in vivo! ➡️
www.biorxiv.org/content/10.1...

awesome family - and Oracle from the inside 🤩

congratulations to Soderling III on carrying the family legacy!

In-depth investigation of proteomic changes in plaque-associated axonal swellings 😮

Empowerment really is as simple as this.

transcriptionally similar cells can be functionally diverse

I am very proud to announce that my PhD paper finally came out in Cell! In this *very* collaborative study, we develop and release a deep-learning approach to predict neuron type identity from their electrical signature. doi.org/10.1016/j.ce... 1/16 🧵

#keepNIHstrong Research brings hope to the hurting. Researchers and Physicians are frontline warriors for some of greatest medical problems of our time.

#keepNIHstrong

Research is a virtuous cycle that brings hope to those hurting.

Researchers and physicians are front line warriors for the greatest medical problems of our time.

Research fuels engines of innovation and drives economic growth.

www.unitedformedicalresearch.org/annual-econo...