Magnetic resonance microscopy maps widespread effects of Alzheimer’s disease on brain structures and behavior in mice | Nature Neuroscience Alzheimer’s disease has widespread effects on brain structure, function and behavior, but we lack a systematic dissection of its impact across hundreds of forebrain and brainstem regions. Here, using diffusion tensor MRI at 25 µm, we mapped the global consequences of mutations in APP and PSEN1 across 231 regions of interest (ROIs) in male and female 5×FAD BXD hybrid mice at 14 months. Over half of the ROIs change in volume along rostrocaudal and mediolateral axes of the CNS, with unexpected swelling in the neocortex, hippocampus and amygdala of up to 10%, counterbalanced by shrinkage in the thalamus, brainstem and most white matter tracts. Yet, total brain volume is unaltered. Variation in individual ROI volumes is highest in females. Differences in fear acquisition and contextual memory performance covary with volumes of several regions and can have opposite polarities between cases and controls. These structural benchmarks establish a foundation for testing therapeutic interventions

Alzheimer's mutations in APP/PSEN1 alter over 50% of 231 brain regions in 5×FAD BXD mice. Detailed MRI maps reveal vast changes at 25μm. PMID:41748785, Nat Neurosci 2026, @NatureNeuro https://doi.org/10.1038/s41593-025-02199-4 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1038/s41581-025-01038-w No description available

Chronic kidney disease affects ~10% globally, challenging the single-cause approach. Reassessing kidney capacity-workload balance is key. PMID:41491877, Nat Rev Nephrol 2026, @NatRevNeph https://doi.org/10.1038/s41581-025-01038-w #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

A group of five people in professional attire stand in a well-organized pharmacy setting. They are holding various pharmacy products and smiling at the camera. Shelves with pharmaceutical items are visible in the background.

A team of Badger #pharmacists at @uwhealth.bsky.social spent five years developing and validating a new #IBD monitoring tool, proving that pharmacists can be clinical partners in care. Learn how the tool helps pharmacists improve IBD patient outcomes: https://bit.ly/4cj6jtP #PharmSky #RxSky

https://doi.org/10.1093/nar/gkag172 No description available

CRISPR/Cas9 screening unveils PABPN1 at APA's core. A dBFPR strategy spots APA regulators, boosting detection efficiency. PMID:41755634, Nucleic Acids Res 2026, @NAR_Open @OTSociety @NAR_Open https://doi.org/10.1093/nar/gkag172 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Researchers from Emory University have identified negative allosteric modulators for the GluN1/GluN3A receptor. This could enable a better understanding of those receptors in health and disease. Learn more in Molecular Pharmacology's Editor's Choice: https://ow.ly/zonV50YAUXy
#pharmsky 🧪

https://doi.org/10.1001/jamadermatol.2026.0019 No description available

Woman, 60s, with 3-year pulmonary hypertension, 2-month dyspnea, and abdominal distension. Possible diagnosis? Let's discuss! 🎯 PMID:41879764, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0019 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

In September 2025, CAPC colleague @jscottuob.bsky.social travelled to Jordan for a two-day workshop on the role of pharmacies & pharmacists in substance use disorders in Jordan.

In this @cbrl.bsky.social podcast, Jenny & Shatha Mubaideen reflect on key learning.

Info & link in thread. ⬇️

#pharmsky

https://doi.org/10.1001/jamadermatol.2026.0151 No description available

Reimagine “skin of color” in dermatology—shift to a pigment-focused approach, embracing biological nuances and socio-context sans race. PMID:41848719, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0151 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

An agentic system for rare disease diagnosis with traceable reasoning | Nature Rare diseases affect more than 300 million people worldwide1–3, yet timely and accurate diagnosis remains an urgent challenge1,3–5. Patients often endure a prolonged ‘diagnostic odyssey’ exceeding 5 years, marked by repeated referrals, misdiagnoses and unnecessary interventions, leading to delayed treatment and substantial emotional and economic burden4,5. Here we present DeepRare—a multi-agent system for rare disease differential diagnosis decision support6–8 powered by large language models, integrating more than 40 specialized tools and up-to-date knowledge sources. DeepRare processes heterogeneous clinical inputs, including free-text descriptions, structured human phenotype ontology terms and genetic testing results to generate ranked diagnostic hypotheses with transparent reasoning linked to verifiable medical evidence. Evaluated across nine datasets from literature, case reports and clinical centres across Asia, North America and Europe spanning 14 medical specialties, DeepRare d

DeepRare transforms rare disease diagnosis. It cuts the 5+ year "diagnostic odyssey", reducing emotional and economic costs for 300M affected globally. PMID:41708847, Nature 2026, @Nature https://doi.org/10.1038/s41586-025-10097-9 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Base barrier cells provide compartmentalization of choroid plexus, brain and CSF | Nature Neuroscience The choroid plexus (ChP), located in the brain ventricles, is largely composed of ChP epithelial cells that produce the cerebrospinal fluid (CSF) and form the blood–CSF barrier. At the ChP–brain attachment sites, we have discovered unique fibroblasts referred to as ChP base barrier cells (BBCs). We show that ChP BBCs originate from meningeal mesenchymal precursors, arrive early during development, remain throughout life and are conserved across species. ChP BBCs are transcriptionally similar to meningeal arachnoid barrier cells and are interconnected by both adherens and tight junctions. Notably, we provide evidence that the BBCs function as a barrier, controlling communication between the periphery and central nervous system. Moreover, during inflammatory insult, we observed a loss of barrier integrity and immune cell crossing. Altogether, our research revealed a barrier at the ChP base, crucial in protecting the central nervous system by compartmentalizing the ChP stroma, brain paren

Choroid plexus base barrier cells, derived from meningeal mesenchymal precursors, form blood-CSF barrier, exist lifelong! PMID:41680326, Nat Neurosci 2026, @NatureNeuro https://doi.org/10.1038/s41593-025-02188-7 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1001/jamadermatol.2025.6123 No description available

Man in 90s: granulomatous dermatitis treated with topical delgocitinib. Successful outcome highlighted in JAMA Derm report! PMID:41811334, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2025.6123 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Interested in learning about the development of a drug that could help patients recover after a stroke or TBI? Read the Editor's Choice in the recent issue of The Journal of Pharmacology and Experimental Therapeutics: jpet.aspetjournals.org/article/S0022-3565(26)00... 🧪#pharmsky

https://doi.org/10.1001/jamadermatol.2026.0042 No description available

Preventing HFS in cancer patients: A meta-analysis of 21 RCTs shows promise in pharmacologic strategies against chemotherapy-induced HFS. PMID:41779386, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0042 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Cardiotoxicity of T cell immunotherapies | Nature Reviews Cardiology T cell immunotherapies offer a new approach to cancer therapy. Chimeric antigen receptor (CAR) T cell therapy is the most prolific of these treatments, leveraging genetically engineered T cells to augment the antitumour response. Bispecific antibodies, T cell receptor-engineered T cells and tumour-infiltrating lymphocytes have also emerged as novel T cell therapies with therapeutic benefit. As the variety of T cell therapies and indications for their use expand, a nuanced understanding of potential haemodynamic sequelae and cardiovascular toxicities is required. T cell activation can lead to massive cytokine release and excessive inflammation, termed cytokine release syndrome (CRS). Like other inflammatory syndromes, CRS can lead to cardiovascular complications, including arrhythmias, myocardial infarction and heart failure, with an incidence of cardiovascular events as high as 20% among patients who develop high-grade CRS. In this Review, we summarize the mechanisms, epidemiology and

T cell immunotherapies, like CAR T cells and bispecific antibodies, boost cancer treatment but can risk heart toxicity. PMID:41730987, Nat Rev Cardiol 2026, @NatRevCardiol https://doi.org/10.1038/s41569-026-01265-z #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1001/jamadermatol.2026.0217 No description available

AI's potential in melanoma diagnostics explored: Analysis of dermoscopy, AI, and AI-assisted dermatology shows promising results for future clinical use. PMID:41879756, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0217 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

#medsky #pharmsky

Post-pandemic changes in population immunity have reduced the likelihood of emergence of zoonotic coronaviruses | Nature Communications Infections by endemic viruses, and the vaccines used to control them, often provide cross-protection against related viruses, potentially altering the transmission dynamics and likelihood of emergence of new zoonotic viruses with pandemic potential. Here, we investigate how population immunity after the COVID-19 pandemic has impacted the likelihood of emergence of a novel sarbecovirus, termed SARS-CoV-X. To this end, we combined empirical cross-neutralisation data with mathematical modelling to identify key immunological and epidemiological factors shaping sarbecovirus emergence. We show that sera from individuals with different COVID-19 immunological histories contained cross-neutralising antibodies against the spike (S) protein of multiple zoonotic sarbecoviruses. Simulations parameterised by these data predict that the likelihood of emergence of a novel sarbecovirus has been reduced significantly by population cross-immunity, with outcomes determined by the extent of cross-protectio

Post-COVID population immunity lowers new zoonotic coronavirus risk. Study: Cross-neutralization data + models show reduced SARS-CoV-X threat. PMID:41876522, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-69988-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

NCBP1 stress signaling drives alternative S6K1 splicing inhibiting translation | Nature Chemical Biology Subcellular stress profoundly influences protein synthesis. However, both the nature of spatiotemporally restricted chemical cues and local protein responders to these cues remain elusive. Unlocking these mechanisms requires the ability to functionally map in living systems locale-specific stress responder proteins and interrogate how chemical modification of each responder impacts proteome synthesis. We resolved this problem by integrating precision localized electrophile generation and genetic code expansion tools. Upon examination of four distinct subcellular locales, only nuclear-targeted electrophile stress stalled translation. We discovered that NCBP1—a nuclear-resident protein with multifaceted roles in eukaryotic mRNA biogenesis—propagated this nuclear stress signal through a single cysteine (C436) from among its 19 conserved cysteines. This NCBP1(C436)-specific modification elicited alternative splicing of more than 250 genes. Mechanistically, global protein synthesis stall wa

NCBP₁ stress signaling alters S6K₁ splicing, hindering translation. Researchers integrated localized electrophile methods. PMID:41667655, Nat Chem Biol 2026, @nchembio https://doi.org/10.1038/s41589-025-02135-4 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Cardiomyocyte Cyclin-dependent kinase 9 directly binds to and phosphorylates NF-κB p65 subunit to drive cardiac inflammation and remodeling | Nature Communications Hypertensive heart failure highlights an urgent need for effective therapeutic strategies. Protein kinases regulate multiple pathways in cardiac pathophysiology and may provide promising therapeutic targets. Here, we identified a Cyclin-dependent kinase, CDK9, promoting inflammation and cardiac remodeling in terminally differentiated cardiomyocytes. Firstly, kinase enrichment analysis and experimental evidence revealed CDK9 phosphorylation at Thr-186 in both human and mouse hypertrophic heart tissues. CDK9 loss of function via T186A mutation in cardiomyocytes attenuated Ang II-induced heart remodeling and NF-κB-mediated inflammation, whereas CDK9 overactivation by T186E mutation induces. This regulatory function of CDK9 in cardiac remodeling is cell cycle-independent. Further studies demonstrate that the kinase domain of CDK9 directly binds to NF-κB P65 protein, which leads to the CDK9/P65 complex nuclear translocation, P65 phosphorylation, and transcription of inflammatory and hypertr

CDK9 phosphorylates NF-κB p65 in cardiomyocytes, fueling inflammation and remodeling in hypertensive heart failure. Potential target: Thr-186 site. PMID:41876530, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70410-6 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://www.cell.com/cell/fulltext/S0092-8674(25)01495-3 No description available

EBV alters the transcriptome and immunopeptidome in HLA-DR15+ B cells, enhancing myelin peptide presentation, potentially driving MS pathogenesis. PMID:41534530, Cell 2026, @Cell www.cell.com/cell/fulltext/S0092-8674... #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Proteomic landscape of Ewing sarcoma primary tumors and metastases | Nature Communications Ewing sarcoma (EWS), a rare pediatric bone tumor, poses unique therapeutic challenges due to its distinct microenvironment and limited molecular understanding. To gain a comprehensive molecular and functional view of the tumors in their microenvironment, we perform a deep mass spectrometry-based proteomic analysis of 170 tumor samples from 74 patients from primary, relapsed, and metastatic tumors. Analysis of more than 10,000 proteins across patients reveals insights into cancer prognosis, chemo-resistance, and progression. Our analyses suggest that ferroptosis pathways may be associated with chemotherapy response in EWS, and we delineate molecular subclasses that correlate the tumor immune landscape with DNA damage repair, ubiquitin-related proteins, and patient outcomes. Multiplexed immunofluorescence imaging indicates possible associations between neutrophils and poorer prognosis, and between macrophages/T cells and a more favorable prognosis. Altogether, this investigation provides

Ewing sarcoma proteomics: 10,000+ proteins studied in 170 tumor samples from 74 patients, offering key insights into prognosis and chemoresistance. PMID:41813675, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70449-5 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Mast cell extracellular granules are bioactive condensates assembled by heparin and polyamine | Nature Chemical Biology Biomolecular condensates are membraneless bodies that organize biochemical reactions typically within cells. However, the roles of condensates in extracellular space—where conditions differ substantially from intracellular space—remain poorly understood. Here we report that mast cell extracellular granules (MCEGs), a stable membraneless entity, are condensates assembled through electrostatic interactions between glycosaminoglycans and polyamines. Disrupting polyamine synthesis or trafficking blocks MCEG formation and compromises the storage of proteases and cytokines. Granules reconstituted with heparin and spermine are sufficient to enrich mediators such as carboxypeptidase A3 (CPA3) and tumor necrosis factor (TNF), maintaining an elevated pH and higher concentrations of calcium and zinc compared to the extracellular milieu. This unique environment enhances CPA3 enzymatic activity. Furthermore, the granules increase TNF binding and its bioactivity toward endothelial cells. Together, w

Mast cell extracellular granules (MCEGs) are bioactive condensates formed by heparin and polyamines, crucial for immune responses. PMID:41760814, Nat Chem Biol 2026, @nchembio https://doi.org/10.1038/s41589-026-02165-6 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

A national survey of the infectious diseases and antimicrobial stewardship pharmacist workforce in the US: work settings, characteristics, employment activities, resources and needs

📣Results from a national survey of ID/AMS pharmacists! Grateful to @sidpharm.bsky.social for sponsoring this project and for all the amazing people who contributed! Huge thank you to everyone who participated and to @ashejournal.bsky.social for publishing our work!👏

#IDsky #Pharmsky #Medsky

https://doi.org/10.1126/science.aea1820 No description available

Discover MULTI-evolve: a rapid evolution method efficiently engineering protein multimutants using AI. Transform lengthy, costly trials! PMID:41712694, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.aea1820 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

RNA-specific local translation is patterned by condensates for multinucleate cell growth | Nature Cell Biology Coordination between growth and nuclear division is a common cell feature. In some syncytia, nuclei divide asynchronously throughout the cell but growth occurs only at discrete locations, raising the question how the processes are locally regulated and globally coordinated. In the syncytial fungus Ashbya gossypii, both cell cycle progression and hyphal elongation require condensates formed by the protein Whi3 in complex with distinct mRNA species. Here we show that Whi3 condensates are enriched for translation regulators and are associated with local, spatially patterned translation of specific target RNAs near nuclei and growth sites. Whi3–RNA condensates can both promote and repress mRNA translation in an RNA- and condensate size-dependent manner in vitro. Condensate interfaces are sites of translation, tunable by condensate composition, RNA valency and protein charge state in vitro. Together, these data suggest that Whi3 condensates can generate a continuum of translation states tha

In Ashbya gossypii, Whi3 protein forms RNA condensates to synchronize nuclear division and growth in multinucleate cells. PMID:41772090, Nat Cell Biol 2026, @NatureCellBio https://doi.org/10.1038/s41556-026-01887-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1001/jamadermatol.2026.0181 No description available

Discover the promise: Intralesional interleukin-2 therapy shows potential in treating high-risk or sensitive cSCC cases! 🎯📊 PMID:41848721, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0181 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Heterogeneity in lysosomal dynamics and metabolic functions along the kidney proximal tubule | Nature Communications The kidney proximal tubule is a highly specialized epithelium that transports metabolites and maintains body homeostasis. Cells lining this nephron segment are densely packed with lysosomes, but little is known about the dynamic activity of these organelles in situ. Here, using targeted sensors and live cell and intravital imaging we track acidified lysosomes along the mouse proximal tubule and uncover marked axial heterogeneity in their distribution, characteristics and organellar interactions. In the early part, cathepsin-rich lysosomes frequently contact with apical endosomes to receive and catabolize filtered plasma proteins. Conversely, in the later region, lipase-containing lysosomes traverse cells to mobilize and degrade mitochondria-associated lipid droplets and facilitate their extrusion into the tubular lumen. Acutely de-acidifying lysosomes dramatically alters their movement, causing major changes in tubular protein and lipid processing. Thus, lysosomes in proximal tubules a

Kidney proximal tubule lysosomes show dynamic, axial heterogeneity revealed via live imaging—marked differences in distribution and interactions observed.🚀 PMID:41803103, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70306-5 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1093/nar/gkag226 No description available

Genome-wide CRISPR screens reveal the EXO1-CAF-1 pathway mitigates R-loop DNA damage, critical for repair and cisplatin response. PMID:41841497, Nucleic Acids Res 2026, @NAR_Open @OTSociety @NAR_Open https://doi.org/10.1093/nar/gkag226 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Magnaporthe oryzae MoPh1 perceives ER stress and promotes adaptive responses via a plasma membrane-to-vacuole pathway | Nature Communications During growth and development, cells experience both internal and external stresses, which can exert harmful impacts if they are poorly managed. Endoplasmic reticulum (ER) stress is an internal stress that is induced when protein misfolding or perturbations occur at excess rates, and the conventional response pathways from the ER to the nucleus are activated to address the stress. However, the involvement of the plasma membrane (PM) system in response to this internal stress has been insufficiently investigated. Here, a PM sensor, MoPh1, was observed to perceive stress through ER-PM contact sites and target the autophagosome and vacuole, consequently stimulating the autophagy process and supporting stress relief. The PM-to-vacuole pathway mediated by MoPh1 is independent of the classical ER-to-nucleus pathway and might be highly important in both fungi and plants, as it plays a crucial role in alleviating ER stress and promoting cellular adaptation for cell survival. The unfolded prote

Discovery: Magnaporthe oryzae MoPh1 detects ER stress and boosts adaptive responses via a novel plasma membrane-vacuole route, enhancing stress management! PMID:41839901, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70610-0 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1126/science.adr4661 No description available

Study in Science: Myelin in zebrafish and rodents swells before damage but can recover via remodeling. High neuron activity worsens damage. PMID:41678629, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.adr4661 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪