UPENN_ITMAT

Sleep-dependent clearance of brain lipids by peripheral blood cells - Nature Peripheral macrophage-like haemocytes in Drosophila promote sleep by clearing lipid buildup in the brain, helping to maintain metabolic homeostasis and brain function and fitness.

#Drosophila model updates our understanding of brain–periphery interactions: www.nature.com/articles/s41... @amitaseh #BrainHealth #Neurobiology #SleepResearch #Neuroscience #TranslationalScience

Revising the model for #SurfactantProteinC maturation: doi.org/10.1016/j.jb... #PulmonaryFibrosis #CellBiology #ProteinTrafficking #AT2Cells #LungDisease #TranslationalScience

#Epigenetic factor #BRD4: Discerning its role as central regulator of #LungDevelopment with implications to understand its function in adult #LungBiology and disease insight.jci.org/articles/vie... #BromodomainContainingProtein4 #TranslationalScience

#1 in Medical Breakthroughs: Seven of the top 20 papers honored by the Clinical Research Forum (CRF) are from Penn @CRForumUS #TranslationalScience

#NSAID induced #Enteropathy: #Prostaglandin suppression plays only trivial role while enteropathic response to #NSAIDs might be amplified through #Dysbiosis of the #GutMicrobiome www.jci.org/articles/vie... @FitzGerald__Lab #TranslationalScience

Can #BrownAdipose tissue be activated for therapeutic benefit in #MetabolicDisease? Possibly by harnessing cell-autonomous pathways: doi.org/10.1016/j.mo... @BaurLab #TranslationalScience

Social Determinants of Health and Clinical Outcomes in Hypertrophic Cardiomyopathy This cohort study using data from the Sarcomeric Human Cardiomyopathy Registry determines the association of area-based social determinants of health with clinical outcomes in patients with hypertroph...

How your neighborhood modulates genetically determined disease risk jamanetwork.com/journals/jam... #HypertrophicCardiomyopathy #HCM #TranslationalScience

Regulating acetyl-CoA levels through Acetyl-CoA Synthetase 2 emerges as potential safeguard for #CognitiveFunction www.pnas.org/doi/10.1073/... #ACSS2 #Neurodegeneration #Tauopathy #TranslationalScience

Need to consider pharmacokinetic & -dynamic properties & patient-specific risk factors when comparing the cardiovascular risk associated with specific #NSAIDs www.ahajournals.org/doi/epub/10.... @ktheken @TiloGrosser #TranslationalScience

Happy New Year from ITMAT!

Characterizing individual contributions of the different components of #mRNA #vaccine to mount #ImmuneResponse doi.org/10.1016/j.ce... #mRNAvaccine @Loccilab #TranslationalScience

#TargetedGeneTherapy for partial restoration of #MitochondrialFunction and protection against #DilatedCardiomyopathy www.nature.com/articles/s41... #MitochondrialCardiomyopathy #CardiacFunction #PGC1α #TranslationalScience

Cell-Specific Inducible Human APOL1 Risk Variant Expression in Mice Causes Hypertension and Renal Damage | Circulation BACKGROUND: Black people bear a disproportionate burden of hypertension and hypertension-attributed chronic kidney disease. A role of apolipoprotein L1 (APOL1) risk variants (RVs; G1 and G2) in these ...

Defining the role of #ApolipoproteinL1 (#APOL1) #RiskVariants on #BloodPressure www.ahajournals.org/doi/10.1161/... @ksusztak.bsky.social‬ #HealthEquity #KidneyHealth #TranslationalScience

Scaling personalized gene-editing therapy into a future of “interventional genetics” through “umbrella of umbrellas” master protocol clinical trial approaches doi.org/10.1016/j.aj... @ahrensnicklas.bsky.social @kiranmusunuru.bsky.social #CRISPR #TranslationalScience

Hepatocyte mitochondrial NAD+ content is limiting for liver regeneration - Nature Metabolism Modulating mitochondrial NAD+ levels by changing the expression of the mitochondrial NAD+ transporter, SLC25A51, Mukherjee et al. demonstrate that mitochondrial, rather than cytosolic or nuclear, NAD+...

Honing in on characterizing biological implications of the #hepatic #Mitochondria NAD+ pool www.nature.com/articles/s42... #OrganRegeneration #MembraneTransporter #TranslationalScience

#CARTCell based hyperlocalized targeting of #InflammatoryPathways involved in development of #AtheroscleroticPlaque doi.org/10.1161/CIRC... @IAmDrDex @PoseyLab #CellTherapy #ImmunoTherapy #Atherosclerosis #TranslationalScience

Wishing you a joyful and restful Thanksgiving!

Ilucidating the critical interplay between environmental timing cues and endogenous #CircadianRhythms for #Influenza outcomes www.jci.org/articles/vie... @sengupta_shaon #ImmuneResponse #Chronobiology #CircadianMedicine #TranslationalScience

Critically ill patients with a reverse blood pressure dipping phenotype at increased risk for delirium and death - Scientific Reports Scientific Reports - Critically ill patients with a reverse blood pressure dipping phenotype at increased risk for delirium and death

#ICU patients w/ reverse #BloodPressure dipping at 40% higher risk to be diagnosed w/ #Delirium & 13% increased #RiskOfDeath www.nature.com/articles/s41... @Nadimeljamal @carstenskarke.bsky.social #CriticalCare #BiologicalRhythm #Cognition #TranslationalScience

How Patients With Amyotrophic Lateral Sclerosis Perceive Respiratory Interventions | Neurology Clinical Practice Background and ObjectivesAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that commonly leads to respiratory failure. Early respiratory interventions that may improve symptoms and ou...

Determinants of receptiveness to respiratory care in patients w/ diagnosis of #AmyotrophicLateralSclerosis www.neurology.org/doi/10.1212/... #ALS #ALSResearch #LouGehrigDisease #ImplementationScience #TranslationalScience

Remote, Automated Gamification and Community-Based Physical Activity in Parkinson Disease This nonrandomized clinical trial tests the efficacy of a remote, automated gamification intervention for increasing daily steps in people with Parkinson disease.

Remote incentivized trialing raises #PhysicalActivity levels by ≈30% in #ParkinsonsDisease jamanetwork.com/journals/jam... #Parkinsons #TranslationalScience

Circumventing #CancerTherapyResistance: #NanoMedicine to engage #Tcells with CD19+tumor cells for #Tumor #CellLysis www.pnas.org/doi/10.1073/pnas.2409564122 @MJMitchell_Lab #TranslationalScience

Depleting #ChromatinRegulators, #DNAmodifyingEnzymes & #TranscriptionFactors linked to #AutismSpectrumDisorder as experimental approaches to decipher mechanisms genome.cshlp.org/content/earl... #TranslationalScience

Visualization of lysosomal membrane proteins by cryo electron tomography - Nature Communications Lysosomes are vital for cellular health and linked to many diseases. Here, authors use cryo-ET to image intact lysosomes and resolve lysosomal protein structures, providing a platform to advance the s...

Integrating #Proteomics & #StructuralBiology to study lysosomal membrane protein function at scale doi.org/10.1038/s414... @bridget_mcveigh #CryoEM #TranslationalScience

A tumor-on-a-chip for in vitro study of CAR-T cell immunotherapy in solid tumors - Nature Biotechnology The interactions of CAR-T cells and solid tumors are modeled on a chip.

Advancing chimeric antigen receptor #CARTcellTherapy for #SolidMalignancies through tumor-on-a-chip technology www.nature.com/articles/s41... #OrganTumorOnAChip #Cancer #CellTherapy #CARTCell #ImmunoTherapy #Oncology #TranslationalScience

PRDM16 regulates smooth muscle cell identity and atherosclerotic plaque composition - Nature Cardiovascular Research Tan et al. identify PRDM16 as a key repressor of fibrotic switching in smooth muscle cells and show that its downregulation in atherosclerosis drives smooth muscle cells toward a synthetic fate, promo...

#PRDM16 identified as gatekeeper for #proatherogenic phenotype switching of #VascularSmoothMuscleCells (SMCs) with potential interest as #DrugTarget www.nature.com/articles/s44... @PatrickSeale11 #SingleCell #AtheroscleroticPlaque #TranslationalScience

A ternary-code DNA methylome atlas of mouse tissues - Genome Biology Background DNA cytosine modifications, including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), are key epigenetic regulators with distinct functions. Dissecting the ternary code (C, 5mC, 5hmC) across tissues and cell types remains a critical priority due to the limitations of traditional profiling methods based on bisulfite conversion. Results Here, we leverage the combined bisulfite and enzymatic (bACE) conversion with the Mouse Methylation BeadChip to generate 265 base-resolution ternary-code modification maps of 5mC and 5hmC across 29 mouse tissue types spanning 8–76 weeks of age and both sexes. Our atlas reveals a complex grammar of 5hmC distribution, jointly shaped by cell mitotic activity, chromatin states, and interplay with 5mC at the same and neighboring CpG sites. Of note, we demonstrate that 5hmC significantly complements 5mC-based biomarkers in delineating cell identity in both brain and non-brain tissues. Each modification state, including 5hmC alone, accurately discriminates tissue types, enabling high-precision machine learning classification of epigenetic identity. Furthermore, the ternary methylome variations extensively implicate gene transcriptional variation, with age-related changes correlated with gene expression in a tissue-dependent manner. Conclusions Our work reveals how tissue, sex, and age jointly govern the dynamics of the two cytosine modifications, augments the scope of DNA modification biomarker discovery, and provides a reference atlas to explore epigenetic dynamics in development and disease.

#Epigenetics profiling of C57BL/6 J mice across 29 tissues, both sexes, age range of 8–76 weeks for population-scale analysis doi.org/10.1186/s130... @SolmoeLee @KohliLab @zhouwanding.bsky.social #Methylome #Aging #TranslationalScience

Single-dose psilocybin rapidly and sustainably relieves allodynia and anxiodepressive-like behaviors in mouse models of chronic pain - Nature Neuroscience Hammo et al. show that a single dose of psilocybin rapidly and sustainably relieves both chronic pain and anxiodepressive-like behaviors in mice by restoring prefrontal activity through partial agonism at 5-HT2A and 5-HT1A receptors.

Two needs one deed: #MoodDisorders & #ChronicPain alleviated by single-agent therapeutic approach. More in doi.org/10.1038/s415... #Psilocybin @jmcichon #MentalHealth #Anxiety #Depression #TranslationalScience