The CCL2-CCR2 axis drives neuromuscular denervation in amyotrophic lateral sclerosis - Nature Communications Neuromuscular junctions (NMJs) are denervated in amyotrophic lateral sclerosis (ALS) through unknown mechanisms. Here, the authors show immune cells infiltrating muscle of ALS patients and mouse model...

The CCL2-CCR2 axis drives neuromuscular denervation in amyotrophic lateral sclerosis | Nature Communications www.nature.com/articles/s41... important and consequential work, finally provides a solid mechanistic rationale for immunological interventions in ALS

Sympathetic innervation maintains the murine quiescent skeletal muscle stem cell pool via perivascular-derived Angpt1 Muscle stem cells rely on their niche for maintenance, yet how β-adrenergic innervation regulates these cells remains elusive. Here, we show that symp…

Sympathetic innervation maintains the murine quiescent skeletal muscle stem cell pool via perivascular-derived Angpt1 - ScienceDirect www.sciencedirect.com/science/arti... @myoblue.bsky.social

Removal of promoter CpG methylation by epigenome editing reverses HBG silencing - Nature Communications DNA methylation is a critical component for repression of fetal haemoglobin in adult blood cells. Removing DNA methylation from the fetal haemoglobin promoter effectively upregulates the gene, opening...

Removal of promoter CpG methylation by epigenome editing reverses HBG silencing | Nature Communications www.nature.com/articles/s41... elegant and effective esample of epigenetic therapy at its best!

few outcomes, except for 99% of FDA-approved drugs, 174 recipients of 104 Nobel Prizes, training ~30K MDs and ~10K PhDs per year to enter the workforce, and a 34% reduction in age-adjusted cancer deaths since 1990 -- the largest decrease in history

B0092 tumor-bearing mice are a new model for the study of cachexia in head and neck cancer | American Journal of Physiology-Cell Physiology | American Physiological Society Introduction: Head and neck cancer (HNC) accounts for ~4% of all cancers but causes ~15,000 deaths annually in the U.S. Over 40% of HNC patients present with cachexia, a severe comorbidity associated with skeletal muscle defects, worsened treatment response, and poor outcomes. The mechanisms behind HNC cachexia remain unclear, partly due to limited small animal models. This study characterizes functional and molecular features of cachexia in a novel preclinical model using tobacco-induced B0092 oral squamous cell carcinoma in C57BL/6J mice. Methods: C2C12 myotubes were exposed to various concentrations of B0092 conditioned media (CM) to assess effects on myotube diameter and expression of muscle-specific ubiquitin ligases (MuRF−1, Atrogin−1). C57BL/6J male and female mice were implanted with B0092 cells (5x105 cells) to investigate musculoskeletal effects of HNC. RNA sequencing of muscle identified gene signatures associated with cachexia. Results: Myotubes treated with B0092 CM showed atrophy already at 25% CM (−21%, p<0.01), along with elevated MuRF-1 (+81%, p<0.05) and Atrogin-1 (+27%, p<0.05). B0092 tumor growth in male mice led to muscle atrophy, reduced strength (−36%, p<0.001), and lower bone mineral density (−8%, p<0.01). Muscle atrophy correlated with increased MuRF-1 (+1.96-fold, p<0.05) and Atrogin-1 (+1.97-fold, p<0.05). Female mice exhibited moderate cachexia despite similar tumor size. RNA sequencing of muscle in male B0092 hosts revealed mitochondrial dysfunction and upregulation of proteasome- and translation-related pathways, supporting a shift toward protein degradation and impaired energy metabolism. Conclusion: These findings suggest that B0092-bearing mice are valuable to uncover novel molecular pathways and potential therapeutic targets for HNC cachexia.

B0092 tumor-bearing mice are a new model for the study of cachexia in head and neck cancer | American Journal of Physiology-Cell Physiology | American Physiological Society journals.physiology.org/doi/abs/10.1... @myoblue.bsky.social new work in cachexia from the Bonetto lab

JCI - Iron supplementation alleviates pathologies in a mouse model of facioscapulohumeral muscular dystrophy www.jci.org/articles/vie... @jclinical-invest.bsky.social @myoblue.bsky.social

Protect the integrity of the US National Institutes of Health Letter to the Editor

Protect the integrity of the US National Institutes of Health www.nature.com/articles/d41... sobering editorial by three appointed members of the NIH Council of Councils Drs. Kent Lloyd, Johnston and Kelley against the planned 40% cut to the NIH budget and the Institutes restructuring

‘Science Fair’ of Lost Research Protests Trump Cuts A protest at a congressional office building highlighted future research findings that vast cuts to science will erase

Thousands of research projects—some years in, with taxpayer money already spent—were wiped out by Trump’s budget cuts.

At the Science Fair of Lost Research, scientists showed what was lost: cancer breakthroughs, climate solutions, public health progress.

zurl.co/1KB6I

#standupforscience

Delving into LLM-assisted writing in biomedical publications through excess vocabulary Excess words track LLM usage in biomedical publications.

The appearance of large language models caused a drastic shift in the vocabulary of academic writing, according to an analysis in #ScienceAdvances of more than 15 million biomedical abstracts published from 2010 to 2024. scim.ag/3IhpoQF

Two-Faced Gene Variant Appears Good for Men, Bad for Women - Research Horizons

3) finally, if you want to have a comprehensive view on the significance of these data, here you can find a great in-depth commentary by @timbonfield.bsky.social from the @cincyresearch.bsky.social on the CCHMC science blog Research Horizons

scienceblog.cincinnatichildrens.org/two-faced-ge...

2) in @jclinical-invest.bsky.social , we report the rs6190 mechanism promoting a sex-specific increase of circulating cholesterol and atherosclerosis risk
www.jci.org/articles/vie...

The human genetic variant rs6190 unveils Foxc1 and Arid5a as novel prometabolic targets of the glucocorticoid receptor in muscle While discovering a metabolic SNP mechanism, myocyte-autonomous mechanisms of metabolic health are unveiled.

new from the lab (this is a thread): we discovered that the human variant rs6190 has a double-edged effect on metabolic health:

1) in Science Advances, we report the rs6190 mechanism promoting insulin sensitivity, unveiling two muscle-specific pro-metabolic genes www.science.org/doi/10.1126/...

At last: the mitochondrial pyruvate carrier structure revealed! Mitochondrial pyruvate carrier (MPC) inhibitors have shown promise as therapeutics for treating several chronic diseases. However, the structure of MP…

At last: the mitochondrial pyruvate carrier structure revealed! www.sciencedirect.com/science/arti... great editorial by Brian Finck (WUSTL) and co-Authors

An American research crisis with real human consequences Ivy League universities have dominated recent news headlines, having become popular targets for critics of higher education. But the threats they face—cuts to federal research funding, assaults on aca...

“Undermining them [research universities] doesn’t just jeopardize higher education, it threatens national and global strength. … economic, technological, and intellectual collapse is inevitable if US research institutions fall to federal and state disinvestment.”
🧪

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

Patent applications per year past 2 decades are flat in USA while China has surged far above

A bad time to crush American science funding and universities

The good doctor digging in to the #DumpRFKjr story with some serious bullets here...

#StandUpForScience

I’ve signed. Join us #AcademicSky 🧪

NIH staff and biomedical community sound alarm about agency politicization, funding slowdown In test of NIH director’s support of dissent, NIH staff sign Bethesda Declaration urging reversal of grant cuts and freezes

NIH staff and biomedical community sound alarm about agency politicization, funding slowdown. NIH staff sign Bethesda Declaration urging reversal of grant cuts and freezes. NIH director to testify in front of Senate spending committee. www.science.org/content/arti...

The State of the #Science Address 2025 at the National Academy of Science by Dr. Marcia McNutt was courageous and identified the mistakes the government is making against the US leadership in science. Thank you @nasonline.org for this inspiring yet sobering moment! @science.bsky.social

@myoblue.bsky.social

Not all atrophic roads lead to GR: cool new study shows that GR genetic or pharmacologic activation is dispensable for muscle atrophy in ARDS @myoblue.bsky.social journals.physiology.org/doi/pdf/10.1...

Perspectives on the interpretation of mitochondrial responses during skeletal muscle disuse‐induced atrophy Abstract figure legend Common human and rodent muscle disuse models and associated changes in skeletal muscle mitochondrial function; respiration, redox stress and apoptotic cell death. I–V, complexe...

important perspective from @chrisperrymito.bsky.social and co-Authors on complexity and context for mitochondrial readouts in muscle atrophy physoc.onlinelibrary.wiley.com/doi/pdf/10.1... @myoblue.bsky.social

Cancer-induced FOXP1 disrupts and reprograms skeletal-muscle circadian transcription in cachexia Cancer cachexia is a debilitating metabolic disorder characterized by involuntary loss of body and muscle mass, leading to increased morbidity and mor…

from the @andyjudge24.bsky.social lab www.sciencedirect.com/science/arti... Skeletal-muscle FoxP1 is required for cancer to induce circadian disruptions in muscle. Also,direct targeting of core clock components by cancer-induced FoxP1 may contribute to cachexia. @myoblue.bsky.social

Why I’m Resigning from the NSF and Library of Congress I cannot participate in systems that require dishonesty as the price of belonging.

"For me, the answer now lies in refusal, the withdrawal of participation from systems that require dishonesty as the price of belonging."

Today I am resigning from the National Science Board and the Library of Congress Scholars Council.

I wrote about my decision in TIME.

time.com/7285045/resi...

The Heart Has Intrinsic Ketogenic Capacity that Mediates NAD+ Therapy in HFpEF | Circulation Research BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has overtaken heart failure with reduced ejection fraction as the leading type of heart failure globally and is marked by high morbid...

new paper on the therapeutic link between NAD+ - cardiomyocyte ketogenesis (yup, that's right, ketone production by the cardiomyocytes) and restored lipid oxidation in HFpEF www.ahajournals.org/doi/10.1161/... #cardiosky

Pervasive glycative stress links metabolic imbalance and muscle atrophy in early-onset Parkinson’s disease Parkinson’s disease (PD) is recognized as a systemic condition, with clinical features potentially modifiable by dietary intervention. Diets high in s…

great new work in muscle atrophy and Parkinson's disease by @dyarken.bsky.social lab, intriguing new ideas on glycative stress (yup, it's a thing!) www.sciencedirect.com/science/arti...

thought-provoking and paradigm-challenging results, we will have to (re)think quite a bit after this one

looking forward to the AGE 2025 conference in Anchorage, AK in ten days or so!

BMAL1–HIF2A heterodimer modulates circadian variations of myocardial injury - Nature The core circadian transcription factor BMAL1 regulates circadian-dependent myocardial injury.

amphiregulin (AREG) is a rhythmic target of the BMAL1–HIF2A complex and is critical for regulating daytime variations of myocardial injury www.nature.com/articles/s41... @myoblue.bsky.social @cardiosky11.bsky.social #circadian #clock

Vaccine experts band together to counter U.S. government misinformation Vaccine Integrity Project intends to provide scientific responses to ill-founded vaccine moves

Vaccine scientists and medical leaders have announced they are launching an unprecedented initiative to react to vaccine misinformation and scientifically unfounded vaccine decisions by the U.S. government. scim.ag/3ES9r1Q