While many interactions between proteins and their binding targets are as specific as a lock and key, chromatin proteins — like transcription factors (TFs) and coregulators — contain intrinsically disordered regions (IDRs) that allow some leeway in the partners they bind with. In Molecular Cell, Amanda Waterbury, Ph.D., Hui Si Kwok, and Ceejay Lee in Brian Liau 's lab; Malvina Papanastasiou, Shaunak Raval, and Steven Carr in the Proteomics Platform; and colleagues describe how the IDR of one coregulator, LSD1, has the opposite effect: It imparts specificity by insulating LSD1's structured domain from indiscriminate TF association. Mutations in LSD1's IDR break this insulation, leading to aberrant LSD1-TF association, enhancer dysregulation, and drug resistance in leukemia. https://lnkd.in/d8-JR-Zk #BroadInstitute #Science #ScienceNews #Research #ScientificResearch
Broad Institute of MIT and Harvard’s Post
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Evaluating the impact of 3D and 2D cell culture systems on the potency of trophoblast extracellular vesicles: in this study, Alireza Fazeli at The University of Sheffield at collaborators cultivated the trophoblast analogue human chorionic carcinoma cell line in both conventional monolayer culture (2D) and spheroids in suspension culture (3D) to study how the cell growth environment affects the physical, biochemical, and cellular signaling properties of the EVs they produce https://lnkd.in/eE8HGng4 They observed that the 3D system was secreting more EVs compared to the 2D system, and although no significant differences were observed in morphology, size, and classical EV protein marker expression, 2D EVs were more effective in eliciting a cellular response in endometrial epithelial cells compared to 3D EVs. An article also authored by Norhayati Liaqat Ali Khan, Subhashini Muhandiram, Keerthie Dissanayake, Kasun godakumara, Getnet Balcha, Aneta Andronowska, Paul Heath, Suranga Kodithuwakku and Amber Rose Hart #extracellularvesicles #exosomes #cellculture #proteomics #translationalmedicine #Vesiculab
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Extracellular vesicles show tremendous potential as sources of biomarkers for clinical diagnostics. They contain markers of cellular/tissue origin as well as a snapshot of the metabolic state of same. There are of course challenges to overcome in this process that are neatly summarized by David Walt's group at Harvard in the recent special issue of Molecular & Cellular Proteomics on Clinical Proteomics. The article is Open Access and found here: https://lnkd.in/gjaRrwrV #clinicalproteomics #LCMS4BetterCare
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Happy to share the most recent publication from my lab employing RNA-seq to compare the transcriptomes of bone marrow derived Lin-LEPR SSPCs isolated by FACS, Lin-SCA1+ MSCs enriched by immunodepletion and culture expanded for 7d. K-means cluster analysis of these data resolved isolation status-dependent changes in transcription in pseudotime thereby revealing how culture adaptation endows MSCs with unique traits. https://lnkd.in/eyrMbPNf
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Our collaborative paper with Gaurav Sahay and Milan Gautam is now out in Molecular Therapy! This work delivered nucleic acids to the brain by lipid nanoparticles, focusing on miR137 and the regulation of synaptic proteins related to schizophrenia. https://lnkd.in/gqDeaUd6
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Exploring how extracellular vesicle-depleted serum affects endothelial cell traits across time: Luiz Fernando Garcia, Pryscilla Wowk and Letusa Albrecht at FIOCRUZ - Fundação Oswaldo Cruz presented the first study comparing EV characteristics from human endothelial cells collected at two different culture times https://lnkd.in/gdJGp6Df Their findings revealed that human brain microvascular endothelial cells cultured with EV-depleted serum produce extracellular vesicles with evolving physical properties and varying protein levels over time #extracellularvesicles #exosomes #cellculture #proteomics #Vesiculab
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Therapeutic RNAs (aptamers, antisense nucleotides, siRNA, miRNA, mRNA, and CRISPR-Cas9) can modulate or induce protein expression, inhibit molecular interactions, and achieve genome editing, as well as exon-skipping. The authors show how these RNAs can be studied by biophysical techniques (liquid-state #NMR, scattering, reactivity, and computational simulations), with a focus on dynamics, flexibility, and binding properties. Read the article: https://lnkd.in/eqXx_rUF Frontiers #RNA #mRNA #StructuralBiology #BioTechnology
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The lag in protein sequencing vs. nucleic acid sequencing. Solving this puzzle demands a collaborative effort from a multidisciplinary team, harnessing the power of mass spectrometry-based proteomics, fluorescence and nanopore technologies. The challenge primarily lies in the sensitivity (low abundance proteins) and throughput (encompassing splicing and post-translational modifications). Overcoming these obstacles would hold the potential to revolutionize early disease diagnostics, elucidate disease mechanisms, and propel drug discovery and development, among other significant advancements. sources: PMID (PMC9809159, PMC8223677, and 36899163). #proteomics #sequencing #proteoforms #singlecellproteomics #singlemoleculesequencing #nanopore #fluorescence #multidisciplinary #precisionmedicine #personalizedmedicine #diagnostics #earlydiagnosis
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Therapeutic RNAs (aptamers, antisense nucleotides, siRNA, miRNA, mRNA, and CRISPR-Cas9) can modulate or induce protein expression, inhibit molecular interactions, and achieve genome editing, as well as exon-skipping. The authors show how these RNAs can be studied by biophysical techniques (liquid-state #NMR, scattering, reactivity, and computational simulations), with a focus on dynamics, flexibility, and binding properties. Read the article: https://lnkd.in/eTTtCcjm Frontiers #RNA #mRNA #StructuralBiology #BioTechnology
An overview of structural approaches to study therapeutic RNAs
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Multiparametric MRI-based fusion radiomics for predicting telomerase reverse transcriptase (TERT) promoter mutations and progression-free survival in glioblastoma: a multicentre study, by H Zhang et al on #Neuroradiology January Issue https://lnkd.in/djeWZqMs #Neurorad
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💦The hydrogen molecule is TEENY TINY (molecular weight 2 Da), electrically neutral, and nonpolar. These properties allow for its easy entrance into cells and rapid diffusion across all biological cell membranes. 💥In this way, molecular hydrogen can reach the subcellular compartments, such as mitochondria and endo/sarcoplasmic reticulum, and nuclei, which are the primary sites of reactive oxygen species (ROS) generation and DNA damage. Moreover, it can easily penetrate several barriers, such as the blood-brain barrier, the placental barrier, and the testis barrier. 💥Molecular hydrogen is recognized as an emerging therapeutic, and its positive effects in the treatment of pathologies (the cause of diseases) have been documented in both experimental and clinical studies. Hundreds. 💥The therapeutic potential of hydrogen is attributed to several major molecular mechanisms. The positive effects of hydrogen on the cardiovascular and central nervous systems, and the regulation of redox and intracellular signaling, alterations in gene expressions, and modulation of cellular responses (e.g., autophagy, apoptosis, and tissue remodeling). 🔗Are you a health clinic or therapeutic healing center? DM me, let’s chat about getting you an Axiom H2 generator to support your clients💌 (Source: MDPI) #healthclinic #healingjourney #molecularhydrogen #h2 #cellularhealth #detoxyourbody #healthandwellness #biohacking
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