Jonathan Ling

Seeded aggregation of TDP-43 induces its loss of function and reveals early pathological signatures TDP-43 pathology characterizes neurodegenerative diseases. Scialò et al. use in vitro-generated and patient-derived TDP-43 aggregates as seeds to show that seed-induced TDP-43 cytoplasmic aggregation ...

Happy to share our new study that was just published in Neuron! www.cell.com/neuron/fullt...

Friends, I’m excited to release OpenSpliceAI, an open‐source, efficient, and modular framework for splice site prediction. It reimplements and extends SpliceAI (Jaganathan et al., 2019) using the modern PyTorch framework. 1/

Mihaela Pertea, @stevensalzberg.bsky.social, Anqi Liu, Alan Mao

a cartoon of homer simpson holding a card ALT: a cartoon of homer simpson holding a card

Bluetorial:

The announcement to move scientific review out of the institutes and centers into the Center for Scientific Review (CSR) and its potential consequences

Long-read RNA sequencing atlas of human microglia isoforms elucidates disease-associated genetic regulation of splicing - Nature Genetics This isoform-centric microglia genomic atlas includes 35,879 novel human microglia isoforms identified by long-read RNA sequencing. A multi-ancestry quantitative trait locus meta-analysis of known and...

Ecstatic to see our paper "Long-read RNA sequencing atlas of human microglia isoforms elucidates disease-associated genetic regulation of splicing" now published in @naturegenet.bsky.social with @trajnp.bsky.social and @panosroussos.bsky.social @sinaibrain.bsky.social www.nature.com/articles/s41...

Roche's SBX sequencing by expansion - preprint out!
www.biorxiv.org/content/10.1...

Indirect Costs at NIH . . . I wasn’t planning on spending part of a Saturday writing about cost accounting principles and the like, but NIH-world was hit with a doozy of a policy announcement on Friday night:

New essay on NIH and indirect costs:
goodscience.substack.com/p/indirect-c...

On changes to #NIH indirect rates, there is a law in place that prohibits NIH from making such changes without the approval of Congress. See Division D, Title II Section 224 of The Further Consolidated Appropriations Act, 2024 (Public Law No: 118-47) grants.nih.gov/grants/guide...

Oh. My. God.

grants.nih.gov/grants/guide...

What's Happening Inside the NIH and NSF

A long post about what’s happening to the science funding agencies in the US and why. As mentioned, this one just kept getting longer even as I kept stripping curse words from it.

www.science.org/content/blog...

Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor Prion disease is caused by misfolding of the prion protein (PrP) into pathogenic self-propagating conformations, leading to rapid-onset dementia and death. However, elimination of endogenous PrP halts...

Insanely good news if this holds up.

Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor

www.science.org/doi/10.1126/...

a man with glasses and a black shirt says " it 's a small step that really goes a long way " ALT: a man with glasses and a black shirt says " it 's a small step that really goes a long way "

SOME GOOD NEWS ABOUT NIH FUNDING

Closed sessions of institute and center Advisory Counsel meetings are now permitted. This is where grant applications are discussed and approved for potential funding.

Open sessions where there are public presentations and discussions are still not allowed.

Just coincidentally found GenBank Release 84.0 from 1994 in the neighboring lab. Anyone out there with an even older version?

Ai2 ScholarQA logo

Can AI really help with literature reviews? 🧐
Meet Ai2 ScholarQA, an experimental solution that allows you to ask questions that require multiple scientific papers to answer. It gives more in-depth and contextual answers with table comparisons and expandable sections 💡
Try it now: scholarqa.allen.ai

1/5

So, how did DeepSeek develop DeepSeek R1?

They used both DeepSeek-V3-Base and a simple prompt:

1. They asked the same question multiple times to DeepSeek-V3-Base as a group.
2. They then graded the answers, assigning an accuracy score and a format score (e.g., <think></think>).

Meta AI creates speech-to-speech translator that works in dozens of languages Machine-learning system can process words spoken in 101 languages, spitting out voice-synthesized translations in 36 target languages.

Researchers at tech giant Meta have created a machine-learning system that almost instantaneously translates speech in 101 languages into words spoken by a voice synthesizer in any of 36 target languages.

https://go.nature.com/3WiibUA

Ultima Genomics Announces UG 100™ Sequencing Platform Selected for UK Biobank's Groundbreaking Human Proteome Study /PRNewswire/ -- Ultima Genomics, Inc., a developer of an ultra-high throughput next-generation sequencing (NGS) platform, today announced that its UG 100™ was...

www.prnewswire.com/news-release...

UK Biobank to run 5.4K protein Olink assay on 600K samples using Ultima UG100

Aberrant splicing in Huntington’s disease accompanies disrupted TDP-43 activity and altered m6A RNA modification - Nature Neuroscience Nguyen et al. identify TDP-43 and METTL3 as key regulators of disrupted RNA splicing in Huntington’s disease, offering insight into how TDP-43 mislocalization and aberrant m6A RNA modification and loc...

#Splicing #Huntingtons #Disease #TDP43 #m6A
www.nature.com/articles/s41...

A foundation model of transcription across human cell types - Nature A foundation model learns transcriptional regulatory syntax from chromatin accessibility and sequence data across a range of cell types to predict gene expression and transcription factor interactions...

A new large language of life model (LLLM) for the transcriptome that predicts gene expression within and across human cell types www.nature.com/articles/s41... @nature.com
For more on the remarkable surge of LLLMs see erictopol.substack.com/p/learning-t...

The recombinant shingles vaccine is associated with lower risk of dementia - Nature Medicine A natural experiment including more than 200,000 people who received a shingles vaccine reveals that, within 6 years of vaccination, the recombinant vaccine is associated with lower risk of dementia t...

So here's an interesting development...

It's been observed that shingles vaccination with the live attenuated vaccine Zostavax:
www.medrxiv.org/content/10.1...
and also with the (much more effective) recombinant vaccine:
www.nature.com/articles/s41...

But, though the study designs are strong...

A timeline titled "Antibiotics: time from discovery to introduction" shows when each antibiotic drug class was first discovered versus first available for medical use. Data: Hutchings, Truman, Wilkinson (2019). Created by Saloni Dattani for Our World in Data.

You may have heard that it took a long time for penicillin to be scaled up.

What about other antibiotics? How long did it take for them to be mass produced and introduced clinically, after they were discovered?

I created a visualization of this here:

Research scholar program Overview

Google research scholar programme applications open until 27th Jan. support early-career professors (received PhD within seven years of submission).
research.google/programs-and...

Synaptic basis of feature selectivity in hippocampal neurons - Nature A temporally asymmetric synaptic plasticity kernel results from bidirectional modifications of synaptic weights around the induction of a place field.

Delighted to highlight our new paper in
@natureportfolio.bsky.social entitled 'Synaptic basis of feature selectivity in hippocampal neurons' (thread below 👇): www.nature.com/articles/s41...

What are recurrent networks doing in the brain? The cortex is filled with excitatory local synapses, but we know little about their role in brain function. New experimental tools, along with ideas from artificial intelligence, are poised to change…

@markhisted.org lays down some knowledge.
What are recurrent networks doing in the brain?
www.thetransmitter.org/neural-netwo...
#neuroscience

Last update of our databases for the year.

Download them here:

493 early-career funding opportunities: research.jhu.edu/rdt/funding-...

313 postdoc fellowships: research.jhu.edu/rdt/funding-...

189 PhD fellowships: research.jhu.edu/rdt/funding-...

The mechanism of mRNA cap recognition - Nature Allosteric communication between the eIF4F subunits drives mRNA cap-recognition and subsequent activation of the message.

#RNA, #RNAbiology. #RNASky
www.nature.com/articles/s41...

how do you all remember every UUID? I find it really hard. so I wrote them all down on every uuid dot com

the list has fast search across all 2^122 values (so you can find your favorites) - hoping to add some social features like "trending UUIDs" soon!

Synthetic GPCRs for programmable sensing and control of cell behaviour - Nature Modular synthetic G-protein-coupled receptors with nanobody-based ligand-recognition domains can be designed and used to programme transgene expression, real-time fluorescence or endogenous G-protein ...

Amazing new work from the lab of @aliceyting.bsky.social @stanfordmedicine.bsky.social @stanfordbiosci.bsky.social, engineered GPCRs for ligand-activated cell responses

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

Crosslinks can sometimes improve AlphaFold3 models. Crosslinking is an experimental method often used as a source of distance restraints in modeling. In AlphaFold3, instead of using restraints, crosslinks can be included as covalent ligands. Thanks to Agnieszka Obarska-Kosinska for the idea.

@bookmarkit.bsky.social is a temporary solution