UPENN_ITMAT

Individuals w/ #BMAL1 variants share #DevelopmentalDelay, #AutismSpectrumDisorder, #SleepDisturbances, #Seizure, #MarfanoidHabitus as clinical symptomatology w/ mechanistic links to disrupted BMAL1 function doi.org/10.1073/pnas... @amitaseh #TranslationalScience

Cardiotropic #DrugDelivery system: Proof-of-concept for #LipidNanoparticles targeting cardiomyocyte-specific SERCA2A to modulate contractility & relaxation www.pnas.org/doi/10.1073/... #siRNA #Myocardium #TranslationalScience

#Neuropeptides essential for complex social behavior with phenotypic plasticity in social insect model doi.org/10.1016/j.ce... #SocialAnalysis #SocialHierarchy #TranslationalScience

Join us via Zoom!
Register Here: tinyurl.com/virtualTRIPICA

Examining mechanisms relevant for restoring #Erythropoiesis & mitigation of pro-inflammatory IFNγ action in #MouseModel #Anemia of #Inflammation (AI) doi.org/10.1182/bloo... #TranslationalScience

Early Vascular Aging Determined by 3-Dimensional Aortic Geometry: Genetic Determinants and Clinical Consequences | Circulation BACKGROUND: Vascular aging is an important phenotype characterized by structural and geometric remodeling. Some individuals exhibit supernormal vascular aging, associated with improved cardiovascular ...

Penn Medicine #BioBank growing its impact: Discerning early aortic #aging from imaging data with links to adverse #CardiacRemodeling and poor #CardiovascularOutcomes www.ahajournals.org/doi/10.1161/... @ThePMBioBank #PMBB #TranslationalScience

You’re Invited: Where Science Meets Art: ITMAT Artist-in-Residence Ceramic Showcase on 7/24 from 5-7 PM at the Institute for Contemporary Art in Philadelphia, PA!
RSVP at www.instagram.com/upenn_itmat/

Blood α‐Synuclein Separates Parkinson's Disease from Dementia with Lewy Bodies Objective Aggregation of misfolded α-synuclein (aSyn) within the brain is the pathologic hallmark of Lewy body diseases (LBDs), including Parkinson's disease (PD), and dementia with Lewy bodies (DLB.....

Developing biomarkers to differentiate between #Parkinsons disease (PD) and dementia with #LewyBodyDisease: Implications for #α-synuclein (aSyn) misfolding & aggregation doi.org/10.1002/ana.... @alicechenplotkin.bsky.social‬ #NeuroDegeneration #Neurology #TranslationalScience

Loss of DOT1L disrupts neuronal transcription and leads to a neurodevelopmental disorder Maroni et al. examine the effects of partial loss of the histone lysine methyltransferase DOT1L on neuronal development and function. Using zebrafish and m

Discerning underlying mechanisms linking loss in the methyltransferase DOT1L activity to #NeurodevelopmentalDisorders (#NDDs) doi.org/10.1093/brai... #MentalHealth #Neurology #TranslationalScience

#AdolescentBrain: #SexDifferences in the spatial organization of functional #Brain networks accentuated in association networks especially in frontoparietal & ventral attention networks doi.org/10.1192/bjp.... #MentalHealth #TranslationalScience

In vivo CAR T cell generation to treat cancer and autoimmune disease Chimeric antigen receptor (CAR) T cell therapies have transformed treatment of B cell malignancies. However, their broader application is limited by complex manufacturing processes and the necessity f...

Broadening clinical utility of #CARTcelltherapy through in vivo engineering targeted lipid nanoparticles (tLNPs) for messenger RNA delivery to specific T cell subsets doi.org/10.1126/scie... @carlhjune @Haig_Ag #CellTherapy #CARTCell #TranslationalScience

Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes | NEJM Zimislecel is an allogeneic stem cell–derived islet-cell therapy. Data on the safety and efficacy of zimislecel in persons with type 1 diabetes are needed. We conducted a phase 1–2 study of zimisle...

Exploring the potential to restore physiologic islet function through fully differ¬entiated, allogeneic pluripotent stem cell–derived islet-cell therapy for #Type1Diabetes www.nejm.org/doi/10.1056/... #StemCell #CellTherapy #TranslationalScience

How do biological systems interact with foreign materials? How is decision-making reflected in biological signaling networks? Using complement activation as a model system doi.org/10.1016/j.ce... dives into these questions @jakebrenner #TranslationalScience

Unraveling the often undefined pathogenesis of #MyxomatousValveDisease (MVD) doi.org/10.1172/JCI1... #SignalingMechanism #ValveDisease #HeartValve #CardiacHealth #TranslationalScience

Building the foundation to address the mechanistic gap between two hallmarks of #Neurodegeneration: excitotoxicity and RNA regulation by #RNA #BindingProteins (RBPs). doi.org/10.1016/j.is... @KJSsci #NeuroSci #MolecularBiology #TranslationalScience

Engineering genetic approaches to develop a CAR-T cell therapy efficaciously targeting #SolidTumor doi.org/10.1016/j.cc... @DJPowellLab #NeoCARs #CellTherapy #CARTCell #GeneTherapy #ImmunoTherapy #Oncology #TranslationalScience

Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo–electron microscopy single-particle analysis and cryo–electro...

Pairing high-resolution cryo–electron microscopy & tomography to design the next-generation broad-spectrum anti-influenza therapeutics www.science.org/doi/10.1126/... @yiweichang.bsky.social‬ #Flu #FluVirus #CryoEM #CryoET #TranslationalScience

Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles - Nature Neuroscience Rogers et al. show that psilocybin enhances fear extinction, suppresses fear neurons and recruits extinction neurons in the retrosplenial cortex in mice, providing evidence that its effects are linked...

Dissecting effects of #psychedelics at the cellular level to understand their therapeutic potential in #NeuropsychiatricDisorders www.nature.com/articles/s41... #MentalHealth #PTSD #Depression #SubstanceUseDisorder #TranslationalScience

Electroconvulsive therapy generates a postictal wave of spreading depolarization in mice and humans - Nature Communications The underlying mechanism of electroconvulsive therapy remains not fully understood. Here, the authors use optical neuroimaging in mice and humans to show that electroconvulsive therapy elicits a secon...

Cortical spreading depolarization (CSD) discovered as second brain event following controlled seizure induction during #ElectroconvulsiveTherapy (ECT) for #TreatmentResistantDepression doi.org/10.1038/s414... #MentalHealth #TranslationalScience

An AAV variant selected through NHP screens robustly transduces the brain and drives secreted protein expression in NHPs and mice AAV capsid variants enriched for transduction of ventricular lining cells and brain parenchyma reduce the dose required for gene therapy to the CNS.

Hope for children with #CLN2disease: #GeneTherapy enables steady-state protein delivery to the CSF in preclinical models doi.org/10.1126/scit... #LysosomalStorageDisorders #RareDisease #OrphanDrugs #TranslationalScience

Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset - Nature Communications The status of immune cells within human pancreatic lymphatic tissues during the onset and progression of type 1 diabetes (T1D) is underexplored. Here, by flow cytometry and CITEseq, the authors profil...

Tissue-specific loss of #Tregs and rise of stem-like CD8+ T cells prior to the onset of #TypeIDiabetes may offer promising window for early intervention doi.org/10.1038/s414... @BettsLab #Diabetes #T1D #ImmunePhenotype #Autoimmunity #TranslationalScience

Ppp1r3b is a metabolic switch that shifts hepatic energy storage from lipid to glycogen PPP1R3B expression determines how hepatic energy is stored and changes contribute to liver damage and metabolic disease.

Discovering molecular lever that controls whether liver stores energy as fat or glycogen. Tuning this switch could open new paths to tackle #MetabolicDisorders. doi.org/10.1126/scia... #Ppp1r3b #HepaticMetabolism #TranslationalScience

Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease | NEJM Base editors can correct disease-causing genetic variants. After a neonate had received a diagnosis of severe carbamoyl-phosphate synthetase 1 deficiency, a disease with an estimated 50% mortality ...

World’s first: Gene editing clinically deployed for breakthrough treatment of rare genetic disease led by @kiranmusunuru & Rebecca Ahrens-Nicklas www.nejm.org/doi/full/10.... #GeneEditing #CRIPR #OrphanDisease #CPS1deficiency #TranslationalScience

Multiscale simulations that incorporate patient-specific neural network models of platelet calcium signaling predict diverse thrombotic outcomes under flow Author summary Blood clots play a key role in serious conditions such as heart attacks and strokes. In this work, we utilized a computer model to understand how platelets, the key cellular components ...

Elucidating donor-specific #Thrombus growth through #Computational #3Dmodelling of #Platelet calcium mobilization, motion & bonding, agonist release & blood velocity field doi.org/10.1371/jour... #Atherosclerosis #TranslationalScience

Expanding the toolbox for #GeneTagging: Higher antitumor efficacy & lower #GenoToxicity of Cas9 nickase–based adenine-base editing vs to nuclease-active Cas9 opens avenues to improve #CARTcelltherapy doi.org/10.1073/pnas... @carlhjune #TranslationalScience

Intracellular protein editing enables incorporation of noncanonical residues in endogenous proteins The ability to study proteins in their native cellular context is crucial to our understanding of biology. In this work, we report a technology for intracellular protein editing, drawing from split intein–mediated protein splicing, genetic code expansion,...

Expanding the toolbox for #ProteinTagging: #Posttranslational #ProteinEditing in living #MammalianCells allows classic cell biology experiments while retaining #ProteinFunction www.science.org/doi/10.1126/... @BurslemLab #TranslationalScience

Waking up after #Anesthesia: Neuronal dynamics model predicts both population- and individual-level features of emergence doi.org/10.1016/j.bj... #Anaesthesia #Anesthesiology #Anaesthesiology #TranslationalScience

Lipid Nanoparticles for In Vivo Lung Delivery of CRISPR-Cas9 Ribonucleoproteins Allow Gene Editing of Clinical Targets In the past 10 years, CRISPR-Cas9 has revolutionized the gene-editing field due to its modularity, simplicity, and efficacy. It has been applied for the creation of in vivo models, to further understa...

Targeting #Lung #EndothelialCells & #EpithelialCells through #LNPtechnology without off-target editing in the liver offers #DrugDevelopment pubs.acs.org/doi/10.1021/... @MJMitchell_Lab #LipidNanoparticles #Nanomedicine #TranslationalScience

Glutathione-specific gamma–glutamylcyclotransferase 1 (CHAC1) increases kidney disease risk by modulating ferroptosis CHAC1 is a kidney disease risk gene, and removal of one copy of Chac1 protects mice from kidney disease by controlling glutathione and ferroptosis.

CHAC1 emerging as #KidneyDisease #RiskGene with a central role of modulating tubule cell glutathione and #Ferroptosis doi.org/10.1126/scit... @ksusztak.bsky.social‬ #DrugDevelopmentOption #TranslationalScience

Red blood cell aggregation within a blood clot causes platelet-independent clot shrinkage Key Points. RBCs suspended in platelet-depleted plasma undergo aggregation within a thrombin-induced clot and cause platelet-independent clot shrinkage.RBC

#RedBloodCells (RBCs) display mechanically active role in contraction of #BloodClots: Platelet-depleted clots formed in the presence of RBCs exhibited >20% volume shrinkage 10.1182/bloodadvances.2024015533 #Thrombosis #Hemostasis #TranslationalScience