The Journal of Clinical Investigation’s Post

New work with Andrés Palencia (INSERM) and Malene Jensen (Institut de Biologie Structurale (IBS)) out on Structure! In this work, we present the structural bases of the homodimerization of human JIP2 and the heterodimerization of human JIP1 and JIP2, two scaffold proteins involved in the JNK pathway, a eukaryotic signal transduction system fundamental to the cell’s response to various stress sources. To achieve this, we employed an integrative structural biology approach, combining Nuclear Magnetic Resonance (NMR) and X-ray crystallography, with the valuable support of EMBL and ESRF - The European Synchrotron. https://lnkd.in/e-iMXMgi

The D84G mutation in STIM1 causes nuclear envelope dysfunction and myopathy in mice: https://buff.ly/4cS3tdN Authors: Victoria Bryson, Chaojian Wang, Zirui Zhou, Kavisha Singh, Noah M. Volin, Eda Yildirim, Paul Rosenberg #CellBiology #MuscleBiology

Glad to see my collaborative research is published in Nature Communications. https://lnkd.in/eJ2DnWJK. We found a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin- 1, and a SUMO-interacting motif on FOXO1. These findings will aid cold survival and tissue storage, also provide potential therapeutic targets at FOXO1 SIM or SUMOylation sites on IPO7 or XPO1. 

Nuclear RNA regulation impacts genome organization, transcription and isoform selection, but remains puzzling because these processes are so rapid, multi-factorial and interconnected. Anastasakis et. al delved into the dense nucleus and discovered that precursor-mRNA G4 structures significantly impact the ongoing processing. So much, that pre-mRNA G4s evolved to shape entire cellular programs, and that the nuclear entry of a single RNA-binding protein may drive epithelial-mesenchymal transition (EMT) and #cancer. As a colleague and friend of the authors, I can attest to the immense brainpower, expertise and dedication invested, in accordance with the great challenge of nuclear RNA regulation. #PKM2 #rG4ome Dimitrios Anastasakis Markus Hafner Astrid Haase Ahsan Polash Mubarak Umar Ishaq Jeremy Scutenaire

📢 Review paper Sharing-Vol. 29 No. 6 💕 Title: Role of the Nrf2/ARE Pathway in the mtDNA Reparation 🤵 Authors: Artem P. Gureev,*, Ekaterina V. Chernyshova, Ekaterina P. Krutskikh, Irina S. Sadovnikova, Elena E. Tekutskaya, Anna A. Dorohova 🔔 Full Text: https://lnkd.in/g7A3Rydj 🔑 Keywords: Nrf2/ARE pathway mtDNA base excision repair BRCA1 p53 😎Welcome to your reading! #Bioscience #biomedicalscience #biochem #medicalscience #ScienceCommunication #Biochemistry #StemCell #Virology #CancerResearch #immunology #Genetics #MolecularBiology #Microbiology #medicine #health #CellularHealth #CellCancer

New very interesting paper in Nature: https://lnkd.in/eMdcfGTx Circular RNAs (circRNAs) are generated due to backsplicing of precursor RNAs but are mostly found in cytoplasm meaning that they are being transported from nucleus. The authors determine that the transport mechanism is akin to nucleocytosolic protein transport (rather than nucleocytosolic mRNA transport) involving exportin-2 and driven by Ran-GTP gradient. IGF2BP1 plays a role of an adapter in the process bindng to circRNA and then recruiting exportin and Ran-GTP.

Blink and you’ll miss these wonderful retinal organoids! Retinal organoids are three dimensional structures induced from stem cells, and are a heterologous mixture of all major retinal cell types, glia, and rod and cone photoreceptors. Retinal organoids can be defined into 3 stages of development. Below is an image of fully formed retinal organoid at Day 220 in stage 3 from a Proteintech customer. You can clearly see ARR3 expressed, a marker for cone photoreceptors. Figure legend: Retinal organoids (day 220) generated from human induced pluripotent stem cells (iPSCs) and fixed with 4% PFA, Stained for ARR3 with 11100-2-AP at 1:400. Nuclear stain DAPI (blue). Scale bar = 20 µm. Data generated by Alessandro Bellapianta at Johannes Kepler Universität Linz, Austria.

Source: Journal of nuclear medicine : official publication, Society of Nuclear Medicine The study describes the synthesis of a radiotracer called [¹⁸F]4-fluoro-4-deoxyfructose ([¹⁸F]4-FDF) that can be used to trace fructose metabolism in various diseases. Through experiments, it was shown that the radiotracer effectively trapped fructose metabolites in vitro and in vivo, unlike other analogs. [¹⁸F]4-FDF also showed low uptake in healthy brain and heart tissues, making it a promising tool for imaging fructose metabolism. The study concludes that aldolase-guided C₄ radiodeoxyfluorination of fructose can overcome limitations of other radioanalogs and enable effective imaging of fructolysis in highly glycolytic tissues.

Source: Talanta A metabolomic analysis using nuclear magnetic resonance (NMR) spectroscopy was conducted in tears to identify biomarkers for the diagnosis of primary open-angle glaucoma (POAG). A classification model based on the metabolomic fingerprint in tears was generated, showing high accuracy in distinguishing between the POAG group and control group. The study identified specific metabolites that were decreased or increased in tear concentration in the POAG group, suggesting the potential of tear metabolomics as a non-invasive approach for early diagnosis and prevention of visual loss in POAG.

#Annexin A11 is widely expressed in our tissues. Phosphorylation results in its nuclear translocation. In this preprint the authors report that AnxA11 and especially its N-terminal fragment is associated with TAR DNA-binding protein (TDP-43) and form ordered filaments. TDP-43 is a highly conserved and ubiquitously expressed RNA/DNA-binding protein belonging to the heterogeneous nuclear ribonucleoprotein (hnRNP) family. TDP-43 is pivotal in multiple cellular functions including regulation of RNA metabolism, mRNA transport, microRNA maturation and stress granule formation. In line with its nuclear and cytoplasmic functions, TDP-43 (like Annexin A11 !) can shuttle between the nucleus and the cytoplasm, but under normal physiological conditions, localisation is predominantly nuclear. The ordered filament fold is formed by TDP-43 residues G282/284-N345 and ANXA11 residues L39-L74 Regions of TDP-43 and ANXA11 previously implicated in protein-protein interactions form an extensive hydrophobic interface at the centre of the filament fold. Immunoblots of the filaments revealed that the majority of ANXA11 exists as a ~22 kDa N-terminal fragment (NTF) lacking the annexin core domain. https://lnkd.in/erNTeJWN More on annexins at: Annexins - an overview (Open access Website) https://lnkd.in/db_NER2K #annexin #AnxA11 #amyloid #fibrils #filament #amyotrophic #lateral #sclerosis #neurodegeneration #dementia #Alzheimers