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cytokine release syndrome (CRS) may not be limited to CAR-T cells themselves, but rather due to downstream effects of pyroptosis: cleavage & activation of gasdermin E (GSDME) in B cells -> downstream activation & cytokine release from macrophages -> CRShttps://immunology.sciencemag.org/content/5/43/eaax7969 …
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another major contribution from the Broad's cancer cell line encyclopedia (CCLE) effort: quantitative proteomics data on 375 cancer cell lines, open-source as always, to aid researchers in their quest to understand this disease https://gygi.med.harvard.edu/publications/ccle …https://www.cell.com/cell/fulltext/S0092-8674(19)31385-6#%20 …
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encouraging data at 12 mo follow-up from 9 patients with chronic granulomatous disease who received phagocyte NADPH oxidase subunit gp91phox via autologous CD34+ HSC lentiviral delivery 6/9 patients showed no new infections & remain off prophylactic abx https://www.nature.com/articles/s41591-019-0735-5.epdf?shared_access_token=fckMdWKyynKiEyguIK1ZD9RgN0jAjWel9jnR3ZoTv0OFoELIHEEWRS_63bYPCSx2zaAvHFqXMrceMPK2sZcm2yaEHG9dbgz0gNmdqWHJNhXJ69p6nlWprC9WpRHw3-YzGEcT_mW9SJRtOoZyWQ9fpw%3D%3D …
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highlights from a great NYT piece on the 2019-nCoV: 1) transmission rate of ~1.5-3.5 people/infected individual (~1.3 for seasonal flu) 2) <3% fatality rate (10% for Spanish flu & SARS) 3) 2-14d asymptomatic incubation period 4) vaccination efforts underway but far away (~1 yr)https://twitter.com/DrEricDing/status/1223262730506964992 …
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a really clever way to fluorescently & covalently label proteins of interest (incl. nuclear hormone receptors) inside cells with a small molecule cyclization (lactonization) results in coumarin moiety & subsequent "turn-on" fluorescence of POI!https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(20)30006-4?sf229096198=1 …
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a really impressive body of work dissecting out biochemical requirements for E3 ligase ternary complex efficiency; highly recommend those in the TPD field look at figs. 5 & 6 PIKES analysis can help tease out nuances of cell line differences, DC50s, etc.https://www.cell.com/molecular-cell/pdfExtended/S1097-2765(19)30926-8 …
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turns out NAFLD & NASH might actually be alcoholic after all high-alcohol-producing strains of Klebsiella pneumoniae in the gut microbiome leads to NAFLD in mice given FMT from patient-derived strains https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30447-4?utm_campaign=Cell%20Reports%20Medicine&utm_source=hs_email&utm_medium=email&utm_content=82177456&_hsenc=p2ANqtz-9tgtqBniONsgGNFFi6qVFqDeZmH0aKIwMT42V7saG77jI1XjP58knAl_zNpefORVI6yG2ZABrj2pnbjk6-ARkcx757pcVEv_RM2cBWJs-LeEg1iXs&_hsmi=82248076 …
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nice demonstration of in vivo clonal dynamics of infused CD8+ CD19-targeting CAR-T cells: these cell-based therapeutics respond to environmental cues (i.e. infusion into a patient), resulting in oligoclonal expansion & shifted transcriptional signatureshttps://www.nature.com/articles/s41467-019-13880-1 …
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flu season meets a new enemy: an emerging coronavirus (same +ssRNA viral family as SARS, MERS) in Wuhan, China there have now been >200 cases reported and the number is expected to rise with imminent Lunar New Year travelhttp://nytimes.com/2020/01/20/world/asia/coronavirus-china-symptoms.html …
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really wonderful piece from a chemist on his daughter's cancer diagnosis & the place that an unfettered childhood imagination can have for future treatment of disease thanks to
@NatureChemistry for publishing; surely will motivate more fun structures!https://www.nature.com/articles/s41557-019-0390-y …Hvala. Twitter će to iskoristiti za poboljšanje vaše vremenske crte. PoništiPoništi -
big day for TPD: initial demonstrations of PCSK9 and KRAS-G12C degradation, using Arg(Boc)3 and CRBN, respectively https://www.cell.com/cell-chemical-biology/pdfExtended/S2451-9456(19)30322-8 …https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(19)30402-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2451945619304027%3Fshowall%3Dtrue …
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Regeneron's tumor-specific antigen (TSA)xCD3 bispecifics (signal 1) + TSAxCD28 costimulatory bispecifics (signal 2) show profound activity in an ovarian tumor model while sparing the non-specific superagonist activity of prior CD28 bivalent antibodieshttps://stm.sciencemag.org/content/12/525/eaaw7888 …
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the rare patient-scientist can play an essential role in advancing treatment for their own disease: "Perhaps there is something peculiarly clarifying about defining success by honestly answering the question 'What would you want for your own brain?'"https://www.nejm.org/doi/full/10.1056/NEJMp1909471 …
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humbled to be at a pioneering institution and amazed by pioneering patients like Helen Obando whose bravery will pave the way for so many individuals (and younger children) who have sickle cell diseasehttps://www.nytimes.com/2020/01/11/health/sickle-cell-disease-cure.html?te=1&nl=morning-briefing&emc=edit_nn_20200112?campaign_id=9&instance_id=15136&segment_id=20262&user_id=1a199d22ca10ee4924ffe43e31cce664®i_id=10315982920200112 …
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even though my eyes are closed here, this was quite the eye-opening talk from
@NeenaNizar on her rare disease (Jansen's metaphyseal chondrodysplasia) and the essential role that patients play as advocates in advancing science, legislation, and biomedical translation to the clinichttps://twitter.com/NeenaNizar/status/1215433812223676416 …
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note-to-self as a trainee: "I suddenly understood that I was like some myopic thespian acting out a wartime drama on a real battlefield — posturing to impress with elegant soliloquies, impeccable costume, and false bravado, while real patients suffered."https://www.nejm.org/doi/full/10.1056/NEJMp1909660 …
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this is an incredible thread for anyone interested in drug dev/med chem be sure to check out post #3 for some really wacky protein-ligand molecular interactions, sourced from this JMC paper that Roche published using data from the PDB: https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.9b01545 …https://twitter.com/DennisWhom/status/1213534864407855104 …
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vaccine nanoparticle containing antigen-encoding RNA to optimally stimulate CAR-T cells targeting this oncofetal tight junction protein (claudin 6) method provides a way for tunable expansion of CAR-T cells, especially in the context of solid tumors https://science.sciencemag.org/content/early/2019/12/30/science.aay5967 …pic.twitter.com/L3CtWS1ADB
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placing a bet that this form of chirality will haunt organic chemistry students by 2050https://twitter.com/BaranLabReads/status/1212809146401095680 …
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