Mechanism of co-transcriptional cap snatching by influenza polymerase | Nature Influenza virus mRNAs are stable and competent for nuclear export and translation because they receive a 5′ cap(1) structure in a process called cap snatching1. During cap snatching, the viral RNA-dependent RNA polymerase (FluPol) binds to host RNA polymerase II (Pol II) and the emerging transcript2,3. The FluPol endonuclease then cleaves a capped RNA fragment that subsequently acts as a primer for the transcription of viral genes4,5. Here we present the cryogenic electron microscopy structure of FluPol bound to a transcribing Pol II in complex with the elongation factor DSIF in the pre-cleavage state. The structure shows that FluPol directly interacts with both Pol II and DSIF, positioning the FluPol endonuclease domain near the RNA exit channel of Pol II. These interactions are important for the endonuclease activity of FluPol and FluPol activity in cells. A second structure, trapped after cap snatching, shows that the cleaved capped RNA rearranges within FluPol, directing the c

Discover the co-transcriptional cap snatching by influenza virus polymerase: Cryo-EM reveals how FluPol hijacks Pol II to prime viral gene transcription. PMID:41781612, Nature 2026, @Nature https://doi.org/10.1038/s41586-026-10189-0 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1126/science.adz5344 No description available

Discover the budding yeast telomerase structure via cryo-EM: RNA TLC1, Est1, Est2, Est3, and Pop1/6/7 form its unique core. Fascinating! PMID:41886584, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.adz5344 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Oh boy, what do we think #PharmSky #MedSky #PublicHealth 🧪

#Kratom's active component #mitragynine is a partial #opioid agonist that has been effective in reducing pain and withdrawal symptoms without the 'high' of traditional opioids, and thus should likely be regulated differently than 7-OH and other opioids due to decreased risk. 🧪 #science 💊 #pharmsky

Pills from work 💊
Yes. We have a tray dedicated to the counting of the residuey and yellow sulfasalazine tablets 🙃

#retailpharmacy #pharmacy #pharmsky #pharmlife

https://doi.org/10.1093/nar/gkag118 No description available

Explore the distinct roles of alternative promoters in drug response using CRISPRi screens, revealing functions in 60% of genes. PMID:41728950, Nucleic Acids Res 2026, @NAR_Open @OTSociety @NAR_Open https://doi.org/10.1093/nar/gkag118 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Each month, JPET selects a featured article that is free-to-read. This month we're proud to present "Pharmacogenetic influence on bupropion bioactivation and clinical outcomes in major depressive disorder." Read and share this important research: https://ow.ly/Clij50YFK64
#pharmsky 🧪

Each month, JPET selects a featured article that is free-to-read. This month we're proud to present "Pharmacogenetic influence on bupropion bioactivation and clinical outcomes in major depressive disorder." Read and share this important research: https://ow.ly/Clij50YFK64
#pharmsky 🧪

Personalized brain decoding of spontaneous pain in individuals with chronic pain | Nature Neuroscience Spontaneous pain is a hallmark of chronic pain disorders, but its assessment remains limited by the lack of objective biomarkers. Here we used precision functional magnetic resonance imaging data, collected over more than half a year from two individuals with chronic pain, to develop personalized brain-decoding models of spontaneous pain. The personalized decoding models accurately tracked fluctuations in spontaneous pain intensity across sessions, runs and minutes (Participant 1: prediction–outcome correlation, r = 0.40–0.61; Participant 2: r = 0.51–0.65) and effectively discriminated between median-dichotomized high- versus low-pain states (Participant 1: area under the curve = 0.71–0.87; Participant 2: area under the curve = 0.76–0.93). Model performance improved with increased training data, with conventional data quantities failing to achieve significant predictive accuracy. Furthermore, each model relied on individually unique brain features and did not generalize across particip

Study uses fMRI data from 2 chronic pain patients over 6+ months to develop personalized brain models that reliably predict pain intensity variations. PMID:41748786, Nat Neurosci 2026, @NatureNeuro https://doi.org/10.1038/s41593-026-02221-3 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

CD177⁺ neutrophil-platelet aggregates contribute to thromboinflammation via NETs in necrotizing enterocolitis | Nature Communications Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease affecting premature infants, yet its precise pathogenic mechanisms remain unclear. While immunothrombosis, an interplay between inflammation and coagulation, is well recognized in systemic inflammatory diseases, its role in NEC pathogenesis and local intestinal regulation has been incompletely characterized. Here, we combine multi-omics profiling, histopathological analyses, and functional studies using clinical NEC samples and neonatal mouse models. We demonstrate prominent intestinal thromboinflammation in NEC, histologically characterized by immunothrombosis with infiltrating CD177⁺ neutrophils, activated platelets, and fibrin deposition. We show that extensive formation of CD177⁺ neutrophil–platelet aggregates (NPAs) amplifies intestinal injury through neutrophil extracellular trap (NET)-mediated thromboinflammation. Blocking CD177⁺ NPAs or inhibiting NET formation significantly alleviates NEC severity in mouse mo

CD177⁺ neutrophil-platelet aggregates heighten thromboinflammation in NEC via NETs; shedding light on critical pathways in disease. PMID:41857007, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70717-4 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1126/science.aeg1547 No description available

A polymer forms inside animals using a blood protein catalyst, paving the way for innovative therapies. Novel use of bio-catalysis! 🌟 PMID:41926603, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.aeg1547 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://www.cell.com/cell/fulltext/S0092-8674(26)00224-2 No description available

Mitochondria regulate glycerolipid synthesis via SLC25A35, which orchestrates the efflux of PEP—crucial for lipogenesis—transforming pyruvate into PEP. PMID:41850288, Cell 2026, @Cell www.cell.com/cell/fulltext/S0092-8674... #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Self-powered in-stent restenosis diagnosis via magnetoelastic stents | Nature Cardiovascular Research Widely used in millions of atherosclerosis treatments, conventional metal stents, although pervasive, only provide mechanical support to narrowed arteries. However, many patients experience in-stent restenosis after implantation. Here we developed smart magnetoelastic stents that preserve mechanical functionality while enabling self-powered hemodynamic monitoring for continuous and timely diagnosis of in-stent restenosis. Using a clinical catheter, the smart stent is deployed in the swine carotid artery for in vivo hemodynamic sensing, enabling effective detection of induced stenosis through artificial intelligence-assisted signal interpretation. In vivo and in vitro studies demonstrate the biosafety of the smart stent through immune profiling, human cytokine analysis and single-cell RNA sequencing. These results underscore the smart stent’s potential for seamless integration into biological systems as a reliable diagnostic tool. This platform technology could potentially revolutionize

Smart magnetoelastic stents in swine carotids enable self-powered monitoring, ensuring timely in-stent restenosis diagnosis post-implantation. PMID:41699202, Nat Cardiovasc Res 2026 https://doi.org/10.1038/s44161-025-00773-4 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Precancerous niche remodelling dictates nascent tumour persistence | Nature Interactions between mutant cells and their environment have a key role in determining cancer susceptibility1–3. However, understanding of how the precancerous microenvironment contributes to early tumorigenesis remains limited. Here we show that newly emerging tumours at their most incipient stages shape their microenvironment in a critical process that determines their survival. Analysis of nascent squamous tumours in the upper gastrointestinal tract of the mouse reveals that the stress response of early tumour cells instructs the underlying mesenchyme to form a supportive ‘precancerous niche’, which dictates the long-term outcome of epithelial lesions. Stimulated fibroblasts beneath emerging tumours activate a wound-healing response that triggers a marked remodelling of the underlying extracellular matrix, resulting in the formation of a fibronectin-rich stromal scaffold that promotes tumour growth. Functional heterotypic 3D culture assays and in vivo grafting experiments, combining

Newly emerging tumors in mice's upper GI tract reshape their microenvironment to survive, highlighting a critical role in early cancer persistence. PMID:41781610, Nature 2026, @Nature https://doi.org/10.1038/s41586-026-10157-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

#MedSky #PharmSky

In vivo site-specific engineering to reprogram T cells | Nature Engineered T cells, reprogrammed to express chimeric antigen receptors (CAR) or T cell receptors (TCR), have transformed cancer treatment and are being explored as therapeutics for autoimmune and infectious diseases. Enhancing T cell function through genome editing, either by disrupting endogenous genes or precisely inserting DNA payloads, has shown considerable promise1. However, the ex vivo manufacturing process is lengthy and costly, limiting accessibility of these therapies. In vivo generation of CAR T cells could overcome these barriers, but current methods rely either on transient expression with limited durability, or on random integration of DNA payloads that lack specificity. Here we demonstrate that stable and cell-specific transgene expression can be achieved through in vivo site-specific integration of large DNA payloads. We developed a two-vector system to deliver CRISPR–Cas9 ribonucleoproteins and a DNA donor template, using enveloped delivery vehicles and

In vivo T cell engineering for cancer, autoimmune, and infectious therapies cuts costs and time. Precision matters! PMID:41851456, Nature 2026, @Nature @OTSociety @NAR_Open https://doi.org/10.1038/s41586-026-10235-x #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://www.cell.com/ajhg/fulltext/S0002-9297(26)00075-3 No description available

Inclusion bias in EHR-linked biobanks can skew genetic variant discovery & replication, affecting ~70% of studies. #GeneticBias PMID:41812654, Am J Hum Genet 2026, @AJHGNews www.cell.com/ajhg/fulltext/S0002-9297... #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Fibroblasts as regulators of lung immunity, repair and fibrosis | Nature Reviews Immunology Fibrosis is a complex disorder characterized by the excessive deposition of extracellular matrix, which disrupts normal tissue architecture and compromises organ function. Fibrosis can affect any organ, with pulmonary fibrosis being one of the most common and life-threatening forms. Despite marked research efforts, effective antifibrotic therapies remain limited, largely due to an incomplete understanding of the underlying disease mechanisms. At the centre of fibrotic processes are fibroblasts, which are tissue-resident mesenchymal cells responsible for extracellular matrix production, tissue remodelling, wound healing and fibrosis. For decades, the biology of fibroblasts remained poorly understood, but advances in single-cell sequencing have recently provided deeper insights into their heterogeneity, plasticity and functional diversity. These insights have prompted renewed efforts to identify the core regulatory programmes that govern fibroblast states in health and disease. In this R

Fibrosis disrupts organs; fibroblasts drive it. Pulmonary fibrosis is deadly. Research ongoing, therapies limited. PMID:41680464, Nat Rev Immunol 2026, @NatRevImmunol https://doi.org/10.1038/s41577-026-01268-4 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Generation of marmoset monkeys with a non-mosaic disruption of the OTOF gene as a model of human deafness | Nature Communications Disabling hearing impairment is a common human sensory deficit. OTOF is a major deafness gene. It codes for the synaptic protein otoferlin and is essential for transmitter release by inner hair cells (IHCs). Upon genetic loss of otoferlin, cochlear structure and function remain intact up to the IHC synapses, which fail to encode sound. Building on preclinical hearing restoration by AAV-mediated cochlear gene transfer in mice, clinical OTOF-gene-therapy trials are now targeting the pediatric population. However, preclinical optimization and characterization remain urgent needs for the development of OTOF-gene-therapy. Here, we report on the generation and characterization of a marmoset KO that models OTOF-related auditory synaptopathy and can thus address these needs. Following ovary stimulation, harvesting, in vitro maturation and fertilization of oocytes, we injected the zygotes with Cas9 and guide RNAs to disrupt OTOF. Mutant embryos were transferred into the uterus of foster mothers

The study creates marmoset monkeys with non-mosaic OTOF gene disruption, modeling human deafness. It supports upcoming OTOF-gene-therapy trials in kids. PMID:41904122, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-71047-1 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1093/nar/gkag131 No description available

Revolutionizing DNA tech: Ouroborosyn-ssDNA uses NEAR to synthesize pure ssDNA via phi29 DNA polymerase and Nb.BbvCI. High-precision. PMID:41674382, Nucleic Acids Res 2026, @NAR_Open @OTSociety @NAR_Open https://doi.org/10.1093/nar/gkag131 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Using the linear references from the pangenome to discover missing autism variants | Nature Communications To better understand large-effect pathogenic variation associated with autism, we generated long-read sequencing (LRS) data to construct phased and near-complete genome assemblies (average contig N50 = 43 Mbp, QV = 56) for 189 individuals from 51 families with unsolved cases. We applied read- and assembly-based strategies to facilitate comprehensive characterization of de novo mutations, structural variants (SVs), and DNA methylation. Using LRS pangenome controls, we efficiently filtered >97% of common SVs exclusive to 87 offspring. We find no evidence of increased autosomal SV burden for probands when compared to unaffected siblings yet observe a suggestive trend toward an increased SV burden on the X chromosome among affected females. We establish a workflow to prioritize potential pathogenic variants by integrating autism risk genes and putative noncoding regulatory elements defined from ATAC-seq and CUT&Tag data from the developing cortex. In total, we identified three

Discover missing autism variants: Analyzed 189 individuals from 51 families using long-read sequencing to find de novo mutations, SVs, and methylation! PMID:41577710, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-68378-4 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1001/jamaneurol.2026.0548 No description available

Exciting insights! 6 cases of interstitial lung disease noted in patients after long-term ocrelizumab treatment for multiple sclerosis. 🤔 PMID:41941213, JAMA Neurol 2026, @JAMANeuro https://doi.org/10.1001/jamaneurol.2026.0548 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

A cancer patient enrolled in this trial died because of duloxetine. Adding insult to injury it was already known that duloxetine doesn't work (and why should it?) in the prevention or treatment of chemotherapy induced neuropathy spcare.bmj.com/content/13/1... #MedSky #Oncosky #Pharmsky

https://doi.org/10.1126/science.adw0288 No description available

Human DHX29 is crucial for regulating mRNA stability by detecting nonoptimal codons, revealed by CRISPR and cryo-EM studies. PMID:41855277, Science 2026, @ScienceMagazine @OTSociety @NAR_Open https://doi.org/10.1126/science.adw0288 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1126/science.adv5974 No description available

Study reveals Pdyn+ sympathetic neurons in mice drive stress-worsened dermatitis via eosinophils. Targeting these pathways may help! PMID:41855337, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.adv5974 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Bullet With Butterfly Wings - Remastered 2012

I wish other people’s prescribing didn’t feel so personal…

#IDSky #AMSSky #PharmSky
#FridayFeelings

open.spotify.com/track/6GtX0j...

You have until August 31 to submit your work to Molecular Pharmacology's upcoming special collection, which celebrates the world-leading research showcased by attendees of the 5th Transatlantic ECI GPCR Symposium. Learn more: https://ow.ly/CGTm50YGvB9
#pharmsky 🧪

The NPR1 agonist antibody XXB750 in heart failure: a phase 2 randomized trial | Nature Medicine Therapies targeting the natriuretic peptide system have the potential to reduce death or heart failure events in heart failure with reduced ejection fraction. Here we assess XXB750, a human monoclonal antibody activating natriuretic peptide receptor 1, in patients with heart failure. Patients with heart failure and a left ventricular ejection fraction <50% were enrolled. Those patients who were on background angiotensin-converting enzyme inhibitor or angiotensin receptor blocker treatment were randomized to receive 60 mg XXB750, 120 mg XXB750 or placebo in a blinded fashion or sacubitril/valsartan treatment in an open-label fashion. Those patients on background sacubitril/valsartan treatment were randomized to either 60 mg XXB750, 120 mg XXB750 or placebo treatment in a blinded fashion. The primary endpoint was the change in NT-proBNP levels at 16 weeks after treatment initiation, and safety was also assessed. We randomized 136 participants (70% male, 30% female) to 60 mg XXB750 (n 

"Phase 2 trial finds XXB750, an NPR1 agonist antibody, improves outcomes in heart failure patients with LVEF<50%. Promising step!" PMID:41912806, Nat Med 2026, @NatureMedicine https://doi.org/10.1038/s41591-026-04313-w #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1093/nar/gkag248 No description available

YAP, regulated by nuclear G-actin binding, is key in Hippo pathway, affecting processes like cell proliferation, cancer and more. PMID:41854080, Nucleic Acids Res 2026, @NAR_Open https://doi.org/10.1093/nar/gkag248 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

A group of people in lab coats sitting in a lecture hall, attentively listening. They appear engaged and interested, suggesting an academic or professional setting.

PharmD student Joey Jimenez completed a Residency Track APPE & an Antimicrobial Stewardship PharmD specialization, to be residency-ready. He's one of a record number of Badgers personalizing their #PharmD through the School's specialized tracks. https://bit.ly/3Pu4a5E #PharmEd #PharmSky #RxSky