Podcasts about proteomic

Large-scale study of proteins

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Best podcasts about proteomic

Latest podcast episodes about proteomic

Proteomics in Proximity
Decoding Aging and the Environment with Cornelia van Duijn

Proteomics in Proximity

Play Episode Listen Later Nov 12, 2024 56:58


Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode:  Olink tools and softwareOlink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/  UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies  Research articlesThe support of human genetic evidence for approved drug indicationsMatthew R Nelson et al,  Nature Genetics 2015https://www.nature.com/articles/ng.3314 Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populationsM. Austin Argentieri et al,  Nature Medicine 2024https://www.nature.com/articles/s41591-024-03164-7 Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systemsLudger J.E. Goeminne et al, Cell Metabolism 2024, in presshttps://www.sciencedirect.com/science/article/abs/pii/S1550413124004017?via%3Dihub Plasma proteomic associations with genetics and health in the UK BiobankBenjamin B. Sun et, Nature 2023https://www.nature.com/articles/s41586-023-06592-6 Rare variant associations with plasma protein levels in the UK BiobankRyan S. Dhindsa; Nature 2023https://www.nature.com/articles/s41586-023-06547-x Disease prediction with multi-omics and biomarkers empowers case–control genetic discoveries in the UK BiobankManik Garg, Nature Genetics, 2024https://www.nature.com/articles/s41588-024-01898-1 China Kadoorie Biobank: https://www.ckbiobank.org/publicationsPublications: https://www.ckbiobank.org/publications Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm  Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO...  Google Podcasts: https://podcasts.google.com/feed/aHR0...   Amazon Music: https://music.amazon.com/podcasts/d97...   Podcast Addict:

JACC Podcast
Comprehensive Proteomic Profiling of Human Myocardium Reveals Signaling Pathways Dysregulated in Hypertrophic Cardiomyopathy

JACC Podcast

Play Episode Listen Later Nov 4, 2024 12:16


In this episode, Dr. Valentin Fuster discusses groundbreaking research on hypertrophic cardiomyopathy (HCM), revealing dysregulated signaling pathways through comprehensive proteomic profiling of human myocardial tissue. The study identifies novel therapeutic targets, including the Ras MAPK pathway and the ubiquitin-proteasome system, while emphasizing the need for further exploration beyond obstructive cases to better understand the disease's molecular mechanisms.

JACC Podcast
Reaffirmation of Mechanistic Proteomic Signatures Accompanying SGLT2 Inhibition in Heart Failure: a EMPEROR Validation Cohort

JACC Podcast

Play Episode Listen Later Nov 4, 2024 11:30


In this episode, Dr. Valentin Fuster discusses groundbreaking research on SGLT2 inhibitors and their impact on heart failure, highlighting the validation of mechanistic proteomic signatures from a major clinical trial. The study reveals how empagliflozin influences over 2,000 proteins, promoting autophagy, enhancing mitochondrial health, and normalizing kidney function, offering new insights into therapeutic strategies for heart failure management.

Aging-US
Novel Deep Proteomic Approach Unveils Molecular Signatures Affected by Aging and Resistance Training

Aging-US

Play Episode Listen Later May 1, 2024 5:00


BUFFALO, NY- May 1, 2024 – A new #researchpaper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 8, entitled, “A novel deep proteomic approach in human skeletal muscle unveils distinct molecular signatures affected by aging and resistance training.” The skeletal muscle proteome alterations to aging and resistance training have been reported in prior studies. However, conventional proteomics in skeletal muscle typically yields wide protein abundance ranges that mask the detection of lowly expressed proteins. In this new study, researchers Michael D. Roberts, Bradley A. Ruple, Joshua S. Godwin, Mason C. McIntosh, Shao-Yung Chen, Nicholas J. Kontos, Anthony Agyin-Birikorang, Max Michel, Daniel L. Plotkin, Madison L. Mattingly, Brooks Mobley, Tim N. Ziegenfuss, Andrew D. Fruge, and Andreas N. Kavazis from Auburn University, Seer, Inc., and The Center for Applied Health Sciences adopted a novel deep proteomics approach whereby myofibril (MyoF) and non-MyoF fractions were separately subjected to protein corona nanoparticle complex formation prior to digestion and Liquid Chromatography Mass Spectrometry (LC-MS). “Specifically, we investigated MyoF and non-MyoF proteomic profiles of the vastus lateralis muscle of younger (Y, 22±2 years old; n=5) and middle-aged participants (MA, 56±8 years old; n=6). Additionally, MA muscle was analyzed following eight weeks of resistance training (RT, 2d/week).” Across all participants, the number of non-MyoF proteins detected averaged to be 5,645±266 (range: 4,888–5,987) and the number of MyoF proteins detected averaged to be 2,611±326 (range: 1,944–3,101). Differences in the non-MyoF (8.4%) and MyoF (2.5%) proteomes were evident between age cohorts, and most differentially expressed non-MyoF proteins (447/543) were more enriched in MA versus Y. Biological processes in the non-MyoF fraction were predicted to be operative in MA versus Y including increased cellular stress, mRNA splicing, translation elongation, and ubiquitin-mediated proteolysis. RT in MA participants only altered ~0.3% of MyoF and ~1.0% of non-MyoF proteomes. “In summary, aging and RT predominantly affect non-contractile proteins in skeletal muscle. Additionally, marginal proteome adaptations with RT suggest more rigorous training may stimulate more robust effects or that RT, regardless of age, subtly alters basal state skeletal muscle protein abundances.” DOI - https://doi.org/10.18632/aging.205751 Corresponding author - Michael D. Roberts - mdr0024@auburn.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205751 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer's diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases. Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

GovCast
Cancer HealthCast: NCI Program Unlocks Emerging Proteomic Data to Advance Precision Medicine

GovCast

Play Episode Listen Later Apr 29, 2024 32:25


Proteomics is an emerging field in cancer care and research. The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) aims to get to the heart of cancer by studying its molecular basis across different cancers. The group believes expanding open-source resources and other data can lead to new treatments in cancer and expand precision medicine. Dr. Henry Rodriguez, the founding director of the Office of Cancer Clinical Proteomics Research at NCI, discusses the program and how the related International Cancer Proteogenome Consortium (ICPC) is helping researchers pull together resources necessary to innovate cancer care.

The Lens Pod
Newsletter: March 27, 2024

The Lens Pod

Play Episode Listen Later Mar 27, 2024 8:22


In this week's issue: Learn about the geographic distribution of oculofacial plastic surgeons and its correlation to socioeconomic demographics in the United States. A case series of patients with Pseudomonas aeruginosa keratitis shows increasing resistance and virulence and suggests a novel new therapeutic approach. A new model predicts axial length in children after bilateral cataract surgery to customize intraocular lens selection for the best visual outcomes. Proteomic profiles of aqueous fluid in those with diabetic retinal disease show signs of inflammation and neuronal dysfunction prior to clinical findings of retinopathy.

Authentic Biochemistry
Biochemical Mosaic II. c.5 Peroxisomal plasmalogen biosynthesis may regulate transcriptomic and proteomic sequalae to plasmamembrane mediated signal transduction. DJGPhD.4March24.

Authentic Biochemistry

Play Episode Listen Later Mar 4, 2024 30:00


References Front Physiol. 2021; 12: 730829. Non-coding RNA Investig 2017. 1:5. Genome Biology 2011. volume 12, Article number: 236 RNA Biol . 2021 Nov 12;18(sup2):574-585. Hunter. R. 1975. "Cruel White Water" https://youtu.be/T-oBD3F74Nk?si=zsrEBN0JKan_FXdH --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Authentic Biochemistry
Biochemical Mosaic Event Ontologies I. Phosphatidic Acid Phosphatase. c.3 Indirect consequences of mitochondrial proteomic variation potentially obtains GLN-linked Warburg glycolysis preventing ROS.

Authentic Biochemistry

Play Episode Listen Later Feb 9, 2024 29:48


References Cell Metabolism 2019. 30, 720–734 Redox Biology2013. Volume 1, Issue 1: 427-432 Nature 2019. volume 575. 361–365 Mozart, WA, 1779.Sinfonia Concertante Es-Dur, KV 364 https://youtu.be/iGDfj5uM_qA?si=bKNmj1r1o9zSMaA7 Lennon-McCartney. 1966. "Im Only Sleeping" https://youtu.be/sAG3m3p9UeI?si=oT6Luxnc6eFS_pEq --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Authentic Biochemistry
Dyslipiaemia Coda III. The proposed use of apolipoprotein serum concentration and hyperTAG may require a deeper analysis at the transcriptomic and proteomic levels. DJGPhD.20.12.23 Authentic Biochem.

Authentic Biochemistry

Play Episode Listen Later Dec 21, 2023 30:00


References Biomolecules 2021, 11(7), 1016 Journal of Clinical LipidologyVolume 16, Issue 4, July–August Pages 472-482 Lennon-McCartney 1964. If I Fell https://youtu.be/F_80s6S_7Vw?si=PmlyAATePHfqmzqv Lennon-McCartney. 1963. Misery.https://youtu.be/qhbcN3ew9z0?si=DvePBioaAgZ7_dRW Alexander. A. 1962. Anna. Cover by the Beatles. https://youtu.be/b3zNKWyLfus?si=kEaNqNy_JF_HZNji --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

The Incubator
#164 - Journal Club -

The Incubator

Play Episode Listen Later Nov 19, 2023 75:04 Transcription Available


In this engaging episode of the Incubator Podcast's Journal Club series, hosts Ben and Daphna take listeners through a journey of groundbreaking research in neonatal care. The episode kicks off with an in-depth analysis of a study on Gastroesophageal Reflux Disease (GERD) in infants, delving into the challenges of diagnosing reflux through symptoms like arching and irritability. This sets the stage for a nuanced discussion on the complexities of identifying acid and bolus reflux in newborns.The conversation then shifts to a compelling study from India, which compares 90 versus 60 minutes of early skin-to-skin contact and its impact on exclusive breastfeeding rates in newborns. This segment not only underscores the benefits of extended maternal-infant contact but also offers a cultural contrast in breastfeeding practices.Diving into the realm of pediatric cardiology, the hosts discuss a study from the Children's Hospital of Philadelphia on the efficacy of exome sequencing in diagnosing various subtypes of cardiomyopathy. This part of the episode highlights the significant advancements in genetic diagnostics in pediatric care.In a poignant and sensitive part of the episode, the focus turns to neonatal autopsies and organ donation. The hosts discuss a study centered on parents' experiences and decision-making processes, emphasizing the vital importance of compassionate communication and offering informed choices to grieving families. As always, feel free to send us questions, comments, or suggestions to our email: nicupodcast@gmail.com. You can also contact the show through Instagram or Twitter, @nicupodcast. Or contact Ben and Daphna directly via their Twitter profiles: @drnicu and @doctordaphnamd. The papers discussed in today's episode are listed and timestamped on the webpage linked below. Enjoy!

Proteomics in Proximity
How proteomics is shaping pharma strategies

Proteomics in Proximity

Play Episode Listen Later Nov 16, 2023 43:54


Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode: Olink tools and software• Olink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/• Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/ UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies Research articles• Dhindsa, R.S., Burren, O.S., Sun, B.B. et al. Rare variant associations with plasma protein levels in the UK Biobank. 2023 Nature, DOI: 10.1038/s41586-023-06547-xhttps://www.nature.com/articles/s41586-023-06547-x• Sun, B.B., Chiou, J., Traylor, M. et al.  Plasma proteomic associations with genetics and health in the UK Biobank. 2023 Nature, DOI: 10.1038/s41586-023-06592-6 https://www.nature.com/articles/s41586-023-06592-6• Ticau S, Sridharan G, Tsour S, et al. Neurofilament Light Chain as a Biomarker of Hereditary Transthyretin-Mediated Amyloidosis 2021 Neurology, DOI: 10.1212/WNL.0000000000011090https://n.neurology.org/content/96/3/e412.long• Zannad F, Ferreira JP, Butler J, et al.  Effect of Empagliflozin on Circulating Proteomics in Heart Failure: Mechanistic Insights from the EMPEROR Program. 2022 European Heart Journal, DOI: 10.1093/eurheartj/ehac495                https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac495/6676779• Eldjarn GH, et al. Large-scale plasma proteomics comparisons through genetics and disease associations. Nature. 2023 Oct;622(7982):348-358. doi: 10.1038/s41586-023-06563-xhttps://www.nature.com/articles/s41586-023-06563-x#Sec44• [PREPRINT] Carrasco-Zanini et al 2023 Proteomic prediction of common and rare diseases MedRxiv https://www.medrxiv.org/content/10.1101/2023.07.18.23292811v1• Michaëlsson E, Lund LH, Hage C, et al. Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF. 2023 JACC. Heart Failure, DOI: 10.1016/j.jchf.2023.03.002https://www.sciencedirect.com/science/article/pii/S2213177923001257• Girerd N, Levy D, Duarte K, et al.  Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study. 2023 Circulation Heart Failure, DOI: 10.1161/CIRCHEARTFAILURE.122.009694https://www.ahajournals.org/doi/abs/10.1161/CIRCHEARTFAILURE.122.009694Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO... Google Podcasts: https://podcasts.google.com/feed/aHR0... Amazon Music: https://music.amazon.com/podcasts/d97... Podcast Addict: https://podcastaddict.com/podcast/409... Deezer: https://www.deezer.com/show/5178787 Player FM: https://player.fm/series/series-3396598 In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink technology called the Proximity Extension Assay (PEA). More information about the assay and how it works can be found here: https://bit.ly/3Rt7YiY For any questions regarding information about Olink Proteomics, please email us at info@olink.com or visit our website: https://www.olink.com/Interested in a specific podcast topic or guest? Reach out to us at PIP@olink.comWHAT IS PROTEOMICS IN PROXIMITY?Proteomics in Proximity discusses the intersection of proteomics with genomics for drug target discovery, the application of proteomics to reveal disease biomarkers, and current trends in using proteomics to unlock biological mechanisms. Co-hosted by Olink's Cindy Lawley and Sarantis Chlamydas.

Aging-US
Deciphering Reproductive Aging in Women Using a NOD/SCID Mouse Model

Aging-US

Play Episode Listen Later Nov 7, 2023 4:18


BUFFALO, NY- November 7, 2023 – A new #researchpaper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 20, entitled, “Deciphering reproductive aging in women using a NOD/SCID mouse model for distinct physiological ovarian phenotypes.” Female fertility is negatively correlated with age, with noticeable declines in oocyte quantity and quality until menopause. To understand this physiological process and evaluate human approaches for treating age-related infertility, preclinical studies in appropriate animal models are needed. In this new study, researchers María Marchante, Noelia Ramirez-Martin, Anna Buigues, Jessica Martinez, Nuria Pellicer, Antonio Pellicer, and Sonia Herraiz from IVIRMA, University of Valencia and Instituto Investigación Sanitaria La Fe aimed to characterize an immunodeficient physiological aging mouse model displaying ovarian characteristics of different stages during women's reproductive life. “The main purpose of our study was to establish a physiological ovarian aging mouse model that could be employed to evaluate potential therapeutic interventions derived from human origin.” NOD/SCID mice of different ages (8-, 28-, and 36–40-week-old) were employed to mimic ovarian phenotypes of young, Advanced Maternal Age (AMA), and old women (~18–20-, ~36–38-, and >45-years-old, respectively). Mice were stimulated, mated, and sacrificed to recover oocytes and embryos. Then, ovarian reserve, follicular growth, ovarian stroma, mitochondrial dysfunction, and proteomic profiles were assessed. Age-matched C57BL/6 mice were employed to cross-validate the reproductive outcomes. The quantity and quality of oocytes were decreased in AMA and Old mice. These age-related effects associated spindle and chromosome abnormalities, along with decreased developmental competence to blastocyst stage. Old mice had less follicles, impaired follicle activation and growth, an ovarian stroma inconducive to growth, and increased mitochondrial dysfunctions. Proteomic analysis corroborated these histological findings. Based on that, NOD/SCID mice can be used to model different ovarian aging phenotypes and potentially test human anti-aging treatments. “In summary, in this study we characterized the quality of the ovarian microenvironment and reproductive outcomes of an immunodeficient murine model of physiological ovarian aging by evaluating fertility outcomes, ovarian reserve and stroma, mitochondrial dysfunctions, and the ovarian proteome at different stages. This model adequately mimicked the characteristics of the reproductive stages in women, without external agents compromising folliculogenesis, or disrupting molecular mechanisms and ovarian function, which could mask the processes of physiological aging.” DOI - https://doi.org/10.18632/aging.205086 Corresponding author - Sonia Herraiz - sonia_herraiz@iislafe.es About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Aging-US
Aging-Related Fibro-Inflammatory Signature in Mouse Ovaries

Aging-US

Play Episode Listen Later Oct 31, 2023 4:28


BUFFALO, NY- October 31, 2023 – A new priority research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 20, entitled, “Proteomic quantification of native and ECM-enriched mouse ovaries reveals an age-dependent fibro-inflammatory signature.” The ovarian microenvironment becomes fibrotic and stiff with age, in part due to increased collagen and decreased hyaluronan. However, the extracellular matrix (ECM) is a complex network of hundreds of proteins, glycoproteins, and glycans which are highly tissue specific and undergo pronounced changes with age. In this new study, researchers Shweta S. Dipali, Christina D. King, Jacob P. Rose, Joanna E. Burdette, Judith Campisi, Birgit Schilling, and Francesca E. Duncan from Northwestern University's Feinberg School of Medicine, the Buck Institute for Research on Aging and the University of Illinois at Chicago used label-free quantitative proteomic methods to define comprehensive, age-dependent changes in the murine ovarian proteome and ECM in an unbiased manner. “To obtain an unbiased and comprehensive profile of age-associated alterations to the murine ovarian proteome and ECM, we used a label-free quantitative proteomic methodology.” The researchers validated conditions to enrich for the ECM prior to proteomic analysis. Following analysis by data-independent acquisition (DIA) and quantitative data processing, they observed that both native and ECM-enriched ovaries clustered separately based on age, indicating distinct age-dependent proteomic signatures. The team identified a total of 4,721 proteins from both native and ECM-enriched ovaries, of which 383 proteins were significantly altered with advanced age, including 58 ECM proteins. Several ECM proteins upregulated with age have been associated with fibrosis in other organs, but to date their roles in ovarian fibrosis are unknown. Pathways regulating DNA metabolism and translation were downregulated with age, whereas pathways involved in ECM remodeling and immune response were upregulated. Interestingly, immune-related pathways were upregulated with age even in ECM-enriched ovaries, suggesting a novel interplay between the ECM and the immune system. Moreover, the researchers identified putative markers of unique immune cell populations present in the ovary with age. These findings provide evidence from a proteomic perspective that the aging ovary provides a fibroinflammatory milieu, and their study suggests target proteins which may drive these age-associated phenotypes for future investigation.” “To our knowledge, this is the first study to utilize unbiased proteomic approaches to investigate the effect of reproductive aging on the murine ovarian proteome and matrisome. DOI - https://doi.org/10.18632/aging.205190 Corresponding authors - Francesca E. Duncan - f-duncan@northwestern.edu, and Birgit Schilling - bschilling@buckinstitute.org About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ MEDIA@IMPACTJOURNALS.COM

PaperPlayer biorxiv neuroscience
Identification of state-specific proteomic and transcriptomic signatures of microglia-derived extracellular vesicles

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Jul 29, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.28.551012v1?rss=1 Authors: Santiago, J. V., Natu, A., Ramelow, C. C., Rayaprolu, S., Xiao, H., Kumar, V., Seyfried, N., Rangaraju, S. Abstract: Microglia are resident immune cells of the brain that play important roles in mediating inflammatory responses in several neurological diseases via direct and indirect mechanisms. One indirect mechanism may involve extracellular vesicle (EV) release, so that the molecular cargo transported by microglia-derived EVs can have functional effects by facilitating intercellular communication. The molecular composition of microglia-derived EVs, and how microglial activation states impacts EV composition and EV-mediated effects in neuroinflammation, remain poorly understood. We hypothesize that microglia-derived EVs have unique molecular profiles that are determined by microglial activation state. Using size-exclusion chromatography to purify EVs from BV2 microglia, combined with proteomic (label-free quantitative mass spectrometry or LFQ-MS) and transcriptomic (mRNA and non-coding RNA seq) methods, we obtained comprehensive molecular profiles of microglia-derived EVs. LFQ-MS identified several classic EV proteins (tetraspanins, ESCRT machinery, and heat shock proteins), in addition to over 200 proteins not previously reported in the literature. Unique mRNA and microRNA signatures of microglia-derived EVs were also identified. After treating BV2 microglia with lipopolysaccharide (LPS), interleukin-10, or transforming growth factor beta, to mimic pro-inflammatory, anti-inflammatory, or homeostatic states, respectively, LFQ-MS and RNA seq revealed novel state-specific proteomic and transcriptomic signatures of microglia-derived EVs. Particularly, LPS treatment had the most profound impact on proteomic and transcriptomic compositions of microglia-derived EVs. Furthermore, we found that EVs derived from LPS-activated microglia were able to induce pro-inflammatory transcriptomic changes in resting responder microglia, confirming the ability of microglia-derived EVs to relay functionally-relevant inflammatory signals. These comprehensive microglia-EV molecular datasets represent important resources for the neuroscience and glial communities, and provide novel insights into the role of microglia-derived EVs in neuroinflammation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Proteomic analysis reveals APOE isoform-specific regulation of ribosomes in neural precursor cells

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Jul 18, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.15.549177v1?rss=1 Authors: M, S., Paul, P., Ramakrishna, S., Ghose, V., Dey, G., Muddashetty, R., Jain, S., Purushottam, M., Viswanath, B., Sud, R. Abstract: ApoE4 isoform contributes to increased risk for Alzheimers Disease (AD) over the life course of individuals. Much remains unknown about the biological pathways that connect APOE4 genotype with the development of pathology that eventually leads to AD, nor do we know how early in life these cellular alterations begin. To answer these questions, we derived neural precursor cells (NPCs) from induced pluripotent stem cells (IPSCs) that were CRISPR-edited at the APOE locus. We intended to characterize the protein expression landscape in the NPCs subsequent to targeted deletion of E4 from a parent IPSC line of APOE3/4 genotype. Differentially expressed proteins (DEPs) following mass spectrometric analysis were determined from the protein abundance fold change values obtained for each protein. Proteins which showed greater than 1.5-fold difference with FDR adjusted P-value less than 0.05 were considered differentially expressed. DEPs were mapped to the STRING database (v11.5) for retrieval of interacting proteins and functional enrichment. CRISPR-editing of E4 from the parent line revealed 98 differential expressed proteins. Of these, 54 were upregulated, and 44 were downregulated. Further analysis of the DEPs via STRING database showed that these changes primarily affect pathways linked to RNA processing, plasma membrane repair, and cytoskeleton organization. Indeed, we find the effects of E4 extend beyond proteins considered central to AD pathology. Knowing more about the protein interactions regulated by ApoE, in an isoform-specific manner, can reveal new mechanistic insights into development of AD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

AAD's Dialogues in Dermatology
May JAAD: Proteomic Characterization of Atopic Dermatitis Blood from Infancy to Adulthood

AAD's Dialogues in Dermatology

Play Episode Listen Later Jul 6, 2023


Ester Del Duca, MD interviewed by Jules Lipoff, MD, FAAD

Aging-US
Age Prediction From Human Blood Plasma Using Proteomic and Small RNA Data: A Comparative Analysis

Aging-US

Play Episode Listen Later Jun 30, 2023 3:17


A new research paper was published on the cover of Aging (Aging-US) Volume 15, Issue 12, entitled, “Age prediction from human blood plasma using proteomic and small RNA data: a comparative analysis.” Aging clocks, built from comprehensive molecular data, have emerged as promising tools in medicine, forensics, and ecological research. However, few studies have compared the suitability of different molecular data types to predict age in the same cohort and whether combining them would improve predictions. In this new study, researchers Jérôme Salignon, Omid R. Faridani, Tasso Miliotis, Georges E. Janssens, Ping Chen, Bader Zarrouki, Rickard Sandberg, Pia Davidsson, and Christian G. Riedel from Karolinska Institutet, University of New South Wales, Garvan Institute of Medical Research, and AstraZeneca explored this at the level of proteins and small RNAs in 103 human blood plasma samples. “Here we expand the limited portfolio of comparisons between aging clocks built from different types of molecular data from the same cohort.” First, the researchers used a two-step mass spectrometry approach measuring 612 proteins to select and quantify 21 proteins that changed in abundance with age. Notably, proteins increasing with age were enriched for components of the complement system. Next, they used small RNA sequencing to select and quantify a set of 315 small RNAs that changed in abundance with age. Most of these were microRNAs (miRNAs), downregulated with age, and predicted to target genes related to growth, cancer, and senescence. Finally, the team used the collected data to build age-predictive models. Among the different types of molecules, proteins yielded the most accurate model (R² = 0.59 ± 0.02), followed by miRNAs as the best-performing class of small RNAs (R² = 0.54 ± 0.02). Interestingly, the use of protein and miRNA data together improved predictions (R2 = 0.70 ± 0.01). Future work using larger sample sizes and a validation dataset will be necessary to confirm these results. “Nevertheless, our study suggests that combining proteomic and miRNA data yields superior age predictions, possibly by capturing a broader range of age-related physiological changes. It will be interesting to determine if combining different molecular data types works as a general strategy to improve future aging clocks.” DOI - https://doi.org/10.18632/aging.204787 Corresponding author - Christian G. Riedel - christian.riedel@ki.se Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204787 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, human blood plasma, small RNAs, proteomics, age prediction About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Discover CircRes
June 2023 Discover CircRes

Discover CircRes

Play Episode Listen Later Jun 15, 2023 26:41


This month on Episode 49 of Discover CircRes, host Cynthia St. Hilaire highlights two original research articles featured in the May 26th issue and provides an overview of the June 9th Compendium on Early Cardiovascular Disease of Circulation Research. This Episode also includes a discussion with Dr Tejasvi Dudiki and Dr Tatiana Byzova about their study, Mechanism of Tumor Platelet Communications in Cancer. Article highlights: Nichtová, et al. Mitochondria-SR Tethering and Cardiac Remodeling Ferrucci, et al. Muscle Transcriptomic and Proteomic in PAD Compendium on Early Cardiovascular Disease.

Tom Nikkola Audio Articles
What You Need to Know About Gluten-Free Beer

Tom Nikkola Audio Articles

Play Episode Listen Later May 30, 2023 14:47


On average, adults aged 21 and older drink almost 30 gallons of beer per year in the United States. If I had to guess, I maybe drink a gallon or two, so others drink way more than 30 gallons per year to even out people like me. Since it's such a popular beverage, and more and more people avoid gluten, many people wonder, "Can you drink beer on a gluten-free diet?" In this article, I'll briefly address what gluten is and how it shows up in beer. I'll also review how you can follow a strict, gluten-free diet and still drink it now and then. Finally, I'll wrap it up with some of the best gluten-free beers to try. Of course, I'm not advocating drinking alcohol. It can lead to numerous health problems, even if you don't drink to get drunk. But I want to help people who drink responsibly and do so occasionally as part of an overall healthy diet and lifestyle. What is gluten? Gluten is a group of proteins found in certain grains, including wheat, barley, and rye.Shewry, P. R., & Halford, N. G. (2002). Cereal seed storage proteins: structures, properties and role in grain utilization. Journal of Experimental Botany, 53(370), 947-958. It's the "glue" that gives bread its chewy texture and helps it rise. In beer production, barley is a common ingredient, and hence, so is gluten. Some people react negatively to gluten. Reactions range from mild sensitivity to severe intolerance, known as Celiac Disease.Ludvigsson, J. F., Leffler, D. A., Bai, J. C., Biagi, F., Fasano, A., Green, P. H., ... & Ciacci, C. (2013). The Oslo definitions for coeliac disease and related terms. Gut, 62(1), 43-52. These reactions can lead to many problems, including digestive issues, fatigue, and even damage to the intestines, in the case of Celiac. Gluten consumption can also lead to cognitive problems. Symptoms of gluten sensitivity or allergy include: Headache Joint pain Muscle pain or twitches Numbness in limbs Chronic fatigue Foggy headedness Anemia Difficulty breathing Depression Abdominal pain Nausea Bloating and gas Diarrhea or constipation Irritable bowel syndrome Muscle wasting Weight loss Hypoglycemia Type I diabetes Psoriasis Autism Schizophrenia Gastroesophageal reflux disease (GERD) Skin rash Rhinitis / asthma Ingrown hairs Oligo- or polymenorrhea Hallucinations Beyond the issues above, gluten may cause mental problems, including: Ataxia Appetite stimulation Brain-active exorphins Peripheral neuropathy Epilepsy General cognitive impairment Dementia Psychiatric disorders If you want to read more about these gluten-related health problems, check out my article Gluten: Health Concerns for Your Brain and Body. Gluten and Beer Most beers are brewed from barley, which is malted and fermented along with water, hops, and yeast.Bamforth, C. (2009). Beer: Tap into the Art and Science of Brewing. Oxford University Press, USA. Gluten in the barley makes its way into the final product. Some beers can contain significant amounts of gluten, especially those brewed with wheat or other high-gluten grains. While it can be challenging to quantify the exact amount of gluten in a serving of beer due to variations in brewing processes, some sources estimate it to range anywhere between 15-60 milligrams per liter.Colgrave, M. L., Goswami, H., Howitt, C. A., & Tanner, G. J. (2012). What is in a beer? Proteomic characterization and relative quantification of hordein (gluten) in beer. Journal of proteome research, 11(1), 386-396. A 12-ounce (354ml) beer serving could contain approximately 5-20 milligrams of gluten. Comparatively, a slice of wheat bread contains approximately 4.8 grams of gluten, far higher than the content in beer.Gallagher, E., Gormley, T. R., & Arendt, E. K. (2004). Recent advances in the formulation of gluten-free cereal-based products. Trends in Food Science & Technology, 15(3-4), 143-152. However,

Oncotarget
Using Cancer Proteomics Data to Identify Gene Candidates for Therapeutic Targeting

Oncotarget

Play Episode Listen Later May 10, 2023 2:50


A new research perspective was published in Oncotarget's Volume 14 on May 4, 2023, entitled, “Using cancer proteomics data to identify gene candidates for therapeutic targeting.” Gene-level associations obtained from mass-spectrometry-based cancer proteomics datasets represent a resource for identifying gene candidates for functional studies. In their new research perspective, researchers Diana Monsivais, Sydney E. Parks, Darshan S. Chandrashekar, Sooryanarayana Varambally, and Chad J. Creighton from Baylor College of Medicine and University of Alabama at Birmingham discuss their recent study where they surveyed proteomic correlates of tumor grade across multiple cancer types and identified specific protein kinases having a functional impact on uterine endometrial cancer cells. “This previously published study provides just one template for utilizing public molecular datasets to discover potential novel therapeutic targets and approaches for cancer patients.” Proteomic profiling data combined with corresponding multi-omics data on human tumors and cell lines can be analyzed in various ways to prioritize genes of interest for interrogating biology. Across hundreds of cancer cell lines, CRISPR loss of function and drug sensitivity scoring can be readily integrated with protein data to predict any gene's functional impact before bench experiments are carried out. Public data portals make cancer proteomics data more accessible to the research community. Drug discovery platforms can screen hundreds of millions of small molecule inhibitors for those that target a gene or pathway of interest. “Here, we discuss some of the available public genomic and proteomic resources while considering approaches to how these could be leveraged for molecular biology insights or drug discovery. We also demonstrate the inhibitory effect of BAY1217389, a TTK inhibitor recently tested in a Phase I clinical trial for the treatment of solid tumors, on uterine cancer cell line viability.” DOI: https://doi.org/10.18632/oncotarget.28420 Correspondence to: Chad J. Creighton - creighto@bcm.edu Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28402 Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/ Keywords: proteomics, proteogenomics, multi-omics, cancer, TTK protein kinase About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

PaperPlayer biorxiv neuroscience
Microglia-mediated synaptic pruning in the nucleus accumbens during adolescence: A preliminary study of the proteomic consequences and putative female-specific pruning target

PaperPlayer biorxiv neuroscience

Play Episode Listen Later May 3, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.02.539121v1?rss=1 Authors: Kirkland, J. M., Patel, I., Kopec, A. M. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Proteomic analysis of peripheral nerve myelin during murine aging

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Apr 28, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.26.538413v1?rss=1 Authors: Helbing, D. L., Kirkpatrick, J. M., Reuter, M., Bischoff, J., Stockdale, A. C., Carlstedt, A., Cirri, E., Bauer, R., Morrison, H. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Proteomic Investigation of Neural Stem Cell to Oligodendrocyte Precursor Cell Differentiation Reveals Phosphorylation-Dependent Dclk1 Processing

PaperPlayer biorxiv cell biology

Play Episode Listen Later Apr 17, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.17.537129v1?rss=1 Authors: Hardt, R., Dehghani, A., Schoor, C., Goedderz, M., Cengiz Winter, N., Ahmadi, S., Sharma, R., Schork, K., Eisenacher, M., Gieselmann, V., Winter, D. Abstract: Oligodendrocytes are generated via a two-step mechanism from pluripotent neural stem cells (NSCs): after differentiation of NSCs to oligodendrocyte precursor/NG2 cells (OPCs), they further develop into mature oligodendrocytes. The first step of this differentiation process is only incompletely understood. In this study, we utilized the neurosphere assay to investigate NSC to OPC differentiation in a time course-dependent manner by mass spectrometry-based (phospho-) proteomics. We identify double cortin like kinase 1 (Dclk1) as one of the most prominently regulated proteins in both datasets, and show that it undergoes a gradual transition between its short/long isoform during NSC to OPC differentiation. This is regulated by phosphorylation of its SP-rich region, resulting in inhibition of proteolytic Dclk1 long cleavage, and therefore Dclk1 short generation. Through interactome analyses of different Dclk1 isoforms by proximity biotinylation, we characterize their individual putative interaction partners and substrates. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
SEL1L-HRD1 ER-associated degradation is a new ataxia gene

PaperPlayer biorxiv cell biology

Play Episode Listen Later Apr 14, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.13.536796v1?rss=1 Authors: Lin, L. L., Torres, M., Pederson, B., Wang, H. H., Wei, X., Li, Z. J., Liu, X., Mao, H., Hanzel, M., Govek, E. E., Lu, Y., Wang, H., Zhao, Z., Hatten, M. E., Sun, S. E., Qi, L. Abstract: Despite recent advances in our understanding of the physiological importance of SEL1L-HRD1 endoplasmic reticulum (ER)-associated protein degradation (ERAD) using cell type-specific knockout (KO) mouse models, its relevance and importance in ataxia pathogenesis remain unknown. Here we show that loss of SEL1L-HRD1 ERAD complex interaction or function in Purkinje cells leads to cerebellar ataxia. Both homozygous knock-in (KI) mice carrying SEL1L variant p.Ser658Pro (S658P) and mice with Purkinje cell-specific deletion of SEL1L exhibit early-onset cerebellar ataxia, although disease severity and progression differ between the models. Structure-function analyses reveal that SEL1L S658P variant impairs, not abolishes, ERAD function by attenuating the interaction between SEL1L and HRD1. Proteomic screen of potential endogenous substrates leads to the identification of Astrotactin 1 and 2, two integral membrane proteins involved in neuronal function and development, whose maturation and biogenesis in the ER depend on SEL1L-HRD1 ERAD activity. These data demonstrate the pathophysiological importance of SEL1L-HRD1 interaction and function in the pathogenesis of cerebellar ataxia. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Compilation of all known protein changes in the human Alzheimer's disease brain

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Apr 14, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.13.536828v1?rss=1 Authors: Askenazi, M., Kavanagh, T., Pires, G., Ueberheide, B., Wisniewski, T., Drummond, E. Abstract: Proteomic studies of human Alzheimer's disease brain tissue have exceptional potential to identify protein changes that drive disease and to identify new drug targets. Here, we detail a combined analysis of 38 published Alzheimer's disease proteomic studies, generating a comprehensive map of protein changes in human brain tissue across thirteen brain regions, three disease stages (preclinical Alzheimer's disease, mild cognitive impairment, advanced Alzheimer's disease), and proteins enriched in amyloid plaques, neurofibrillary tangles, and cerebral amyloid angiopathy. Our dataset is compiled into a user-friendly, searchable database called NeuroPro. Our combined analysis included 18,119 reported protein differences in human Alzheimer's disease brain tissue, which mapped to 5,311 total altered proteins. Proteomic studies were remarkably consistent. 848 proteins were consistently altered in greater than or equal to 5 studies, many of which are understudied in the Alzheimer's field. Comparison of protein changes in early-stage and advanced Alzheimer's disease revealed significant synapse, vesicle, and lysosomal changes early in disease, but widespread mitochondrial changes only in advanced Alzheimer's disease. Comparison of vulnerable and resistant brain regions suggested that protein changes in resistant regions in advanced Alzheimer's disease are similar to those in vulnerable regions in early-stage Alzheimer's disease, indicating a temporal progression of protein dysfunction during Alzheimer's disease advancement. We conclude that NeuroPro is a powerful new resource that provides new insights into human Alzheimer's disease brain protein changes and highlights novel proteins of particular interest that may mechanistically drive Alzheimer's disease. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Unique proteomic signature of JCPyV-infected human astrocytes: from cells to extracellular vesicles

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Apr 13, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.11.536379v1?rss=1 Authors: Oberholster, L., Mathias, A., Perriot, S., Blaser, E., Canales, M., Jones, S., Culebras, L., Gimenez, M., Kaynor, G. C., Sapozhnik, A., Richetin, K., Goelz, S., Du Pasquier, R. Abstract: JC polyomavirus (JCPyV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a severe, and often fatal, demyelinating disease of the central nervous system. While PML has traditionally been characterized as a lytic infection of oligodendrocytes, more recent findings suggest an important role for astrocytes during the initial stages of disease. Here, using human induced pluripotent stem cell-derived astrocytes coupled with a multiparametric approach, we show that astrocytes are readily infected with JCPyV that strongly impacts their biology, inducing a unique proteomic signature. Furthermore, the changes observed mirror elements of ex vivo findings in PML brain lesions, including dysregulation of the cell cycle and activation of the DNA damage response. We also demonstrate that this signature is extended to extracellular vesicles (EVs) while being strikingly different from that of inflammatory conditions. Thus, our results support the relevance of using brain-derived EVs as a means to gain mechanistic insights into JCPyV pathophysiology in the brain and pave the way towards the identification of new biomarkers for the early stratification of patients at risk of developing PML. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
The human acetylcholinesterase c-terminal T30 peptide activates neural growth through an alpha 7 nicotinic acetylcholine receptor mTOR pathway

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Apr 7, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.07.536081v1?rss=1 Authors: Graur, A., Kabbani, N. Abstract: Acetylcholinesterase (AChE) is a highly conserved enzyme responsible for the regulation of acetylcholine signaling within the brain and periphery. AChE has also been shown to participate in non-enzymatic activity and contributing to development and aging. In particular, enzymatic cleavage of the carboxy terminal region of the synaptic AChE isoform, AChE-T, is shown to generate a bioactive T30 peptide that binds to the 7 nicotinic acetylcholine receptor (nAChR) at synapses. Here, we explore intracellular mechanisms of T30 signaling within the human cholinergic neural cell line SH-SY5Y using high performance liquid chromatography (HPLC) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). Proteomic analysis of cells exposed to (100nM) T30 for 3-days reveals significant changes within proteins important for cell growth. Specifically, bioinformatic analysis identifies proteins that converge onto the mammalian target of rapamycin (mTOR) pathway signaling. Functional experiments confirm that T30 regulates neural cell growth via mTOR signaling and 7 nAChR activation. In addition, T30 was found promote mTORC1 pro-growth signaling through an increase in phosphorylated elF4E, and a decrease in autophagy LC3B-II level. Taken together, our findings define mTOR as a novel pathway activated by the T30 cleavage peptide of AChE and suggest a role for mTOR signaling in cholinergic aspects of brain development, as well as disease. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
An integrated RNA-proteomic landscape of drug induced senescence in a cancer cell line

PaperPlayer biorxiv cell biology

Play Episode Listen Later Mar 21, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.21.533605v1?rss=1 Authors: Görtler, F., Al-Roshdi, M., Grellscheid, S. N., Stevenson, T. Abstract: Senescent cells are characterized by an arrest in proliferation. In addition to replicative senescence resulting from telomere exhaustion, sub-lethal genotoxic stress resulting from DNA damage, oncogene activation, mitochondrial dysfunction or reactive metabolites also elicits a senescence phenotype. Senescence is a controlled programme affecting a wide variety of biological processes with some core hallmarks of senescence as well as tissue specific changes. This study presents an integrative multi-omic analysis of proteomic and RNA-seq from proliferating and senescent osteosarcoma cells. This study demonstrates senescence induction in a widely used cell line which can be used as a model system for characterising cancer cell responses to sub-lethal doses of chemotherapeutic agents, and makes available both RNA-seq and proteomic data from proliferating and senescent cells in open access repositories to aid reuse by the community. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Spatially Resolved Proteomic Profiling Uncovers Structural and Functional Regulators of the Axon Initial Segment

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Mar 8, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.06.531334v1?rss=1 Authors: Zhang, W., Fu, Y., Peng, L., Ogawa, Y., Zhou, X., Rasband, M. N., Zou, P. Abstract: Axon initial segments (AISs) are specialized neuronal compartments crucial for action potential generation and neuronal polarity. However, a detailed understanding of the mechanisms regulating AIS structure and function has been hindered by an incomplete knowledge of its molecular composition. Here, we profile the AIS proteome and its dynamic changes in-depth during neuronal maturation. Our method capitalizes on antibody targeted proximity labeling with subcellular spatial specificity in fixed primary neurons. Among the AIS proteins labeled, we identified novel AIS components, including PHGDH and SCRIB. PHGDH and SCRIB are highly enriched in the AIS both in vitro and in vivo, and exhibit a periodic architecture like the axonal spectrin-based cytoskeleton. Furthermore, we show that neuronal PHGDH activity is necessary for AIS integrity and action potential initiation. This powerful and flexible approach defines the AIS proteome and provides a rich resource to elucidate the mechanisms regulating AIS structure and function. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Comparative Proteomic Analysis of Paired Human Milk Fat Globules and Membranes and Mouse Milk Fat Globules Identifies Core Cellular Systems Contributing to Mammary Lipid Trafficking and Secretion

PaperPlayer biorxiv cell biology

Play Episode Listen Later Mar 1, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.28.530322v1?rss=1 Authors: Carli, J. M., Monks, J., McManaman, J. L. Abstract: Human milk delivers critical nutritional and immunological support to the infant. The milk fat globule and its membrane contain many bioactive components, yet the mechanism of milk fat secretion and how milk fat globule (MFG) components are regulated are poorly defined. In this study, we perform quantitative proteomic profiling of milk fat globules from human and mouse milk, as well as from isolated membranes physically disrupted from human milk fat globules. Using paired analyses of the human samples we report membrane enrichment of the proteins involved in docking/tethering the lipid droplet to the membrane as well as minor components involved in the signaling pathway for secretion. Comparing abundance between human and mouse milk fat globules we find that 8 of 12 major milk fat globule proteins are shared between the two species. Comparative pathway enrichment analyses between human and mouse samples reveal similarities in shared membrane trafficking and signaling pathways involved in milk fat secretion. Our results advance knowledge of the composition and relative quantities of proteins in human and mouse milk fat globules in greater detail, provide a quantitative profile of specifically enriched human milk fat globule membrane proteins, and identify core cellular systems involved in milk lipid secretion. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Mitochondrial translocation of TFEB regulates complex I and inflammation

PaperPlayer biorxiv cell biology

Play Episode Listen Later Feb 28, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.27.530219v1?rss=1 Authors: Calabrese, C., Nolte, H., Pitman, M. R., Ganesan, R., Lampe, P., Laboy, R., Ripa, R., Fischer, J., Chipurupalli, S., Gutierrez, S., Polara, R., Thomas, D., Pitson, S. M., Antebi, A., Robinson, N. Abstract: TFEB is a master regulator of autophagy, lysosome biogenesis and mitochondrial metabolism that works, and immunity, primarily through transcription controlled by cytosol-to-nuclear translocation. Emerging data indicate additional regulatory interactions at the surface of organelles such as lysosomes. Here we show that TFEB has a non-transcriptional role in mitochondria, regulating the electron transport chain complex I to down-modulate inflammation. Proteomic analysis revealed extensive TFEB co-precipitation with several mitochondrial proteins, whose interactions are disrupted upon infection with S. Typhimurium. Localization of TFEB in the mitochondrial matrix was confirmed by high resolution confocal microscopy and biochemistry with translocation dependent on a conserved N-terminal TOMM20-binding motif enhanced by mTOR inhibition. Within the mitochondria, TFEB and protease LONP1 antagonistically co-regulate complex I, reactive oxygen species and the inflammatory response. Consequently, during infection, lack of TFEB specifically in the mitochondria exacerbates the expression of pro-inflammatory cytokines, contributing to innate immune pathogenesis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Multi-modal Proteomic Characterization of Lysosomal Function and Proteostasis in Progranulin-Deficient Neurons

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Feb 24, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.24.529955v1?rss=1 Authors: Hasan, S., Fernandopulle, M. S., Humble, S. W., Frankenfield, A. M., Li, H., Prestil, R., Johnson, K. R., Ryan, B. J., Wade-Martins, R., Ward, M. E., Hao, L. Abstract: Progranulin (PGRN) is a lysosomal protein implicated in various neurodegenerative diseases. Over 70 mutations discovered in the GRN gene all result in reduced expression of PGRN protein. However, the detailed molecular function of PGRN within lysosomes and the impact of PGRN deficiency on lysosomal biology remain unclear. Here we leveraged multifaceted proteomic techniques to comprehensively characterize how PGRN deficiency changes the molecular and functional landscape of neuronal lysosomes. Using lysosome proximity labeling and immuno-purification of intact lysosomes, we characterized lysosome compositions and interactomes in both human induced pluripotent stem cell (iPSC)-derived glutamatergic neurons (i3Neurons) and mouse brains. Using dynamic stable isotope labeling by amino acids in cell culture (dSILAC) proteomics, we measured global protein half-lives in i3Neurons for the first time and characterized the impact of progranulin deficiency on neuronal proteostasis. Together, this study indicated that PGRN loss impairs the lysosome degradative capacity with increased levels of v-ATPase subunits on the lysosome membrane, increased catabolic enzymes within the lysosome, elevated lysosomal pH, and pronounced alterations in neuron protein turnover. Collectively, these results suggested PGRN as a critical regulator of lysosomal pH and degradative capacity, which in turn influences global proteostasis in neurons. The multi-modal techniques developed here also provided useful data resources and tools to study the highly dynamic lysosome biology in neurons. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Luminescence-based screening for extracellular vesicle release modulators reveals a role for PI4KIIIβ in exosome biogenesis upon lysosome inhibition

PaperPlayer biorxiv cell biology

Play Episode Listen Later Feb 23, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.23.529257v1?rss=1 Authors: Bebelman, M. P., Crudden, C., Snieder, B., Thanou, E., Langedijk, C. J. M., Viola, M., Eleonora, S., Baginska, U., Cotugno, O., Bebelman, J. P. M., van Eijndhoven, M. A. J., Bosch, L., Li, K. W., Smit, M. J., van Niel, G., Smit, A. B., Verweij, F. J., Pegtel, D. M. Abstract: Dysregulated extracellular vesicle (EV) release has been implicated in various pathologies, including cancer, neurodegenerative disease and osteoarthritis. Despite clear therapeutic potential, drug screening for EV release modulators has yielded limited success due to the lack of a sensitive and scalable EV read-out system. Here, we employed CRISPR-Cas9 to engineer HEK293 cells expressing HA-NanoLuciferase-(NL)-tagged endogenous CD63. We found that under basal culture conditions, CD63-containing EVs are released via a mechanism that is independent of the exocytic SNARE protein SNAP23, presumably by direct budding from the plasma membrane. Endo-lysosome inhibition by chemical or genetic perturbation of vATPase strongly increased SNAP23 and nSmase2-dependent exosome secretion from intracellular compartments. Proteomic analysis revealed these exosomes are enriched for early- and late endosomal markers, but also for autophagosomal proteins. This suggests that a proportion of these exosomes originate from amphisomes, although chemical inhibition of canonical autophagy did not affect exosome secretion upon lysosome inhibition. Using a broad-spectrum kinase inhibitor screen, we identified and subsequently validated the lipid kinase PI4KIII{beta} as a critical mediator of exosome secretion and amphisome-mediated secretory autophagy, upon lysosome inhibition. We conclude that tagging of endogenous CD63 with NanoLuciferase represents a sensitive, scalable reporter strategy that enables identification of (druggable) modulators of EV biogenesis and release under physiological and pathological conditions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
The Zinc-BED transcription factor Bedwarfed promotes proportional dendritic growth and branching through transcriptional and translational regulation in Drosophila

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Feb 15, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.15.528686v1?rss=1 Authors: Bhattacharjee, S., Iyer, E. P. R., Iyer, S. C., Nanda, S., Rubaharan, M., Ascoli, G. A., Cox, D. N. Abstract: Dendrites are the primary points of sensory or synaptic inputs to a neuron and play an essential role in synaptic integration and neural function. Despite the functional importance of dendrites, relatively less is known about the underlying mechanisms regulating cell-type specific dendritic patterning. Herein, we have dissected functional roles of a previously uncharacterized gene, CG3995, in cell-type specific dendritic development in Drosophila melanogaster. CG3995, which we have named bedwarfed (bdwf), encodes a zinc-finger BED-type protein which is required for proportional growth and branching of dendritic arbors, exhibits nucleocytoplasmic expression, and functions in both transcriptional and translational cellular pathways. At the transcriptional level, we demonstrate a reciprocal regulatory relationship between Bdwf and the homeodomain transcription factor (TF) Cut. We show that Cut positively regulates Bdwf expression and that Bdwf acts as a downstream effector of Cut-mediated dendritic development, whereas overexpression of Bdwf negatively regulates Cut expression in multidendritic sensory neurons. Proteomic analyses revealed that Bdwf interacts with ribosomal proteins and disruption of these proteins produced phenotypically similar dendritic hypotrophy defects as observed in bdwf mutant neurons. We further demonstrate that Bdwf and its ribosomal protein interactors are required for normal microtubule and F-actin cytoskeletal architecture. Finally, our findings reveal that Bdwf is required to promote protein translation and ribosome trafficking along the dendritic arbor. Taken together, these results provide new insights into the complex, combinatorial and multi-functional roles of transcription factors (TFs) in directing diversification of cell-type specific dendritic development. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction, progression, and prion-like spread of Alzheimer s disease pathogenesis

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Feb 12, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.10.527926v1?rss=1 Authors: Pomeshchik, Y., Velasquez, E., Gil, J., Klementieva, O., Gidlof, R., Sydoff, M., Bagnoli, S., Nacmias, B., Sorbi, S., Westergren-Thorsson, G., Gouras, G. K., Rezeli, M., roybon, l. Abstract: The hippocampus is a primary region affected in Alzheimer s disease (AD). Because AD postmortem brain tissue is not available prior to symptomatic stage, we lack understanding of early cellular pathogenic mechanisms. To address this issue, we examined the cellular origin and progression of AD pathogenesis in patient-based model systems including iPSC-derived brain cells transplanted into the mouse brain hippocampus. Proteomic analysis of the graft enabled the identification of proteomic alterations in AD patient brain cells, associated with increased levels of beta-sheet structures and Ab42 peptides. Interestingly, the host cells surrounding the AD graft also presented alterations in cellular biological pathways. Furthermore, proteomic analysis across human iPSC-based models and human post-mortem hippocampal tissue projected coherent longitudinal cellular changes indicative of disease progression from early to end stage AD. Our data showcase patient-based models to study the cellular origin, progression, and prion-like spread of AD pathogenesis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
The proteomic landscape of synaptic diversity across brain regions and cell types

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Jan 27, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.27.525780v1?rss=1 Authors: van Oostrum, M., Blok, T., Giandomenico, S. L., tom Dieck, S., Tushev, G., Fuerst, N., Langer, J. D., Schuman, E. M. Abstract: Brain function relies on communication via neuronal synapses. Neurons build and diversify synaptic contacts using different protein combinations that define the specificity, function and plasticity potential of synapses. More than a thousand proteins have been globally identified in both pre- and postsynaptic compartments, providing substantial potential for synaptic diversity. While there is ample evidence of diverse synaptic structures, states or functional properties, the diversity of the underlying individual synaptic proteomes remains largely unexplored. Here we used 7 different Cre-driver mouse lines crossed with a floxed mouse line in which the presynaptic terminals were fluorescently labeled (SypTOM) to identify the proteomes that underlie synaptic diversity. We combined microdissection of 5 different brain regions with fluorescent-activated synaptosome sorting to isolate and analyze using quantitative mass spectrometry 18 types of synapses and their underlying synaptic proteomes. We discovered ~1800 unique synapse-enriched proteins and allocated thousands of proteins to different types of synapses. We identify commonly shared synaptic protein modules and highlight the hotspots for proteome specialization. A protein-protein correlation network classifies proteins into modules and their association with synaptic traits reveals synaptic protein communities that correlate with either neurotransmitter glutamate or GABA. Finally, we reveal specializations and commonalities of the striatal dopaminergic proteome and outline the proteome diversity of synapses formed by parvalbumin, somatostatin and vasoactive intestinal peptide-expressing cortical interneuron subtypes, highlighting proteome signatures that relate to their functional properties. This study opens the door for molecular systems biology analysis of synapses and provides a framework to integrate proteomic information for synapse subtypes of interest with cellular or circuit-level experiments. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
The effect of Dnaaf5 gene dosage on primary ciliary dyskinesia phenotypes

PaperPlayer biorxiv cell biology

Play Episode Listen Later Jan 14, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.13.523966v1?rss=1 Authors: Horani, A., Gupta, D. K., Xu, J., Xu, H., Puga-Molina, L. D. C., Santi, C., Ramagiri, S., Brennen, S. K., Pan, J., Huang, T., Hyland, R. M., Gunsten, S., Tzeng, S.-C., Strahle, J. M., Mill, P., Mahjoub, M. R., Dutcher, S. K., Brody, S. L. Abstract: DNAAF5 is a dynein motor assembly factor associated with the autosomal heterogenic recessive condition of motile cilia, primary ciliary dyskinesia (PCD). The effects of allele heterozygosity on motile cilia function are unknown. We used CRISPR-Cas9 genome editing in mice to recreate a human missense variant identified in patients with mild PCD and a second, frameshift null deletion in Dnaaf5. Litters with Dnaaf5 heteroallelic variants showed distinct missense and null gene dosage effects. Homozygosity for the null Dnaaf5 alleles was embryonic lethal. Compound heterozygous animals with the missense and null alleles showed severe disease manifesting as hydrocephalus and early lethality. However, animals homozygous for the missense mutation had improved survival, with partial preserved cilia function and motor assembly observed by ultrastructure analysis. Notably, the same variant alleles exhibited divergent cilia function across different multiciliated tissues. Proteomic analysis of isolated airway cilia from mutant mice revealed reduction in some axonemal regulatory and structural proteins not previously reported in DNAAF5 variants. While transcriptional analysis of mouse and human mutant cells showed increased expression of genes coding for axonemal proteins. Together, these findings suggest allele-specific and tissue-specific molecular requirements for cilia motor assembly that may affect disease phenotypes and clinical trajectory in motile ciliopathies. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Atheroprone shear stress stimulates noxious endothelial extracellular vesicle uptake by MCAM and PECAM-1 cell adhesion molecules

PaperPlayer biorxiv cell biology

Play Episode Listen Later Jan 2, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.31.522373v1?rss=1 Authors: Coly, P.-M., Chatterjee, S., Mezine, F., El Jekmek, C., Devue, C., Nipoti, T., Lara Corona, M., Dingli, F., Loew, D., van Niel, G., Boulanger, C. M. Abstract: Atherosclerotic lesions mainly form in arterial areas exposed to low shear stress (LSS), where endothelial cells express a senescent and inflammatory phenotype. Conversely, high shear stress (HSS) has atheroprotective effects on the endothelium. Endothelial cell-derived extracellular vesicles have been shown to regulate inflammation, senescence and angiogenesis and therefore play a crucial role in vascular homeostasis and disease. While previous studies have shown links between hemodynamic forces and extracellular vesicle release, the exact consequences of shear stress on the release and uptake of endothelial EVs remains elusive. Our aim is therefore to decipher the interplay between these processes in endothelial cells exposed to atheroprone or atheroprotective shear stress. Confluent human umbilical vein endothelial cells (HUVEC) were exposed to either LSS or HSS for 24 hours. Large and small EVs were isolated from conditioned medium by sequential centrifugation and size exclusion chromatography. They were characterized by TEM, Western blot analysis of EV markers, tunable resistive pulse sensing, flow cytometry and proteomics. Uptake experiments were performed using fluorescently-labeled EVs and differences between groups were assessed by flow cytometry and confocal microscopy. We found that levels of large and small EVs in HUVEC conditioned media were fifty and five times higher in HSS than in LSS conditions, respectively. In vivo and in vitro uptake experiments revealed greater EV incorporation by cells exposed to LSS conditions compared to HSS. Additionally, endothelial LSS-EVs appeared to have a greater affinity for HUVECs than HSS-EVs or EVs derived from platelets, red blood cells, granulocytes and peripheral blood mononuclear cells. Proteomic analysis revealed that LSS-EVs were enriched in adhesion proteins such as PECAM1, MCAM, which were involved in EV uptake by endothelial cells. LSS-EVs also carried mitochondrial material, which may be involved in elevating reactive oxygen species levels in recipient cells. These findings suggest that endothelial shear stress has a significant impact during EV biogenesis and uptake. Given the major role of EVs and shear stress in vascular health, deciphering the relation between these processes may yield innovative strategies for the early detection and treatment of endothelial dysfunction. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Proteomic landscape of tunneling nanotubes reveals CD9 and CD81 tetraspanins as key regulators

PaperPlayer biorxiv cell biology

Play Episode Listen Later Dec 22, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.21.521537v1?rss=1 Authors: Notario Manzano, R., Chaze, T., Rubinstein, E., Matondo, M., Zurzolo, C., Brou, C. Abstract: Tunneling nanotubes (TNTs) are open actin- and membrane-based channels, connecting remote cells and allowing direct transfer of cellular material (e.g. vesicles, mRNAs, protein aggregates) from cytoplasm to cytoplasm. Although they are important especially in pathological conditions (e.g., cancers, neurodegenerative diseases), their precise composition and their regulation were still poorly described. Here, using a biochemical approach allowing to separate TNTs from cell bodies and from extracellular vesicles and particles (EVPs), we obtained the full composition of TNTs compared to EVPs. We then focused to two major components of our proteomic data, the CD9 and CD81 tetraspanins, and further investigated their specific roles in TNT formation and function. We show that these two tetraspanins have distinct functions: CD9 participates in the initiation of TNTs, whereas CD81 expression is required to allow the functional transfer of vesicle in the newly formed TNTs, possibly by regulating fusion with the opposing cell. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Changes in gut microbiome composition drive fentanyl intake and striatal proteomic changes

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Dec 1, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.30.518531v1?rss=1 Authors: Hofford, R. S., Meckel, K. R., Wang, W., Kim, M., Godino, A., Lam, T. T., Kiraly, D. Abstract: Opioid use disorder (OUD) is a public health crisis currently being exacerbated by increased rates of use and overdose of synthetic opioids, primarily fentanyl. Therefore, the identification of novel biomarkers and treatment strategies to reduce problematic fentanyl use and relapse to fentanyl taking is critical. In recent years, there has been a growing body of work demonstrating that the gut microbiome can serve as a potent modulator of the behavioral and transcriptional responses to both stimulants and opioids. Here, we advance this work to define how manipulations of the microbiome drive fentanyl intake and fentanyl seeking in a translationally relevant drug self-administration model. Additionally, we utilize global proteomic analysis of the nucleus accumbens following microbiome manipulation and fentanyl administration to define how microbiome status alters the functional proteomic landscape in this key limbic substructure. These findings establish clear relevance for gut-brain signaling in OUD, and lay foundations for further translational work in this space. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
METTL17 is an Fe-S cluster checkpoint for mitochondrial translation

PaperPlayer biorxiv cell biology

Play Episode Listen Later Nov 24, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.24.517765v1?rss=1 Authors: Ast, T., Itoh, Y., Sadre, S., McCoy, J. G., Namkoong, G., Chicherin, I., Joshi, P. R., Kamenski, P., Suess, D. L. M., Amunts, A., Mootha, V. K. Abstract: Friedreich's ataxia (FA) is the most common monogenic mitochondrial disease. FA is caused by a depletion of the mitochondrial protein frataxin (FXN), an iron-sulfur (Fe-S) cluster biogenesis factor. To better understand the cellular consequences of FA, we performed quantitative proteome profiling of human cells depleted for FXN. Nearly every known Fe-S cluster-containing protein was depleted in the absence of FXN, indicating that as a rule, cluster binding confers stability to Fe-S proteins. Proteomic and genetic interaction mapping identified impaired mitochondrial translation downstream of FXN loss, and specifically highlighted the methyltransferase-like protein METTL17 as a candidate effector. Using comparative sequence analysis, mutagenesis, biochemistry and cryogenic electron microscopy we show that METTL17 binds to the mitoribosomal small subunit during late assembly and harbors a previously unrecognized [Fe4S4]2+ cluster required for its stability on the mitoribosome. Notably, METTL17 overexpression rescued the mitochondrial translation and bioenergetic defects, but not the cellular growth, of FXN null cells. Our data suggest that METTL17 serves as an Fe-S cluster checkpoint: promoting the translation and assembly of Fe-S cluster rich OXPHOS proteins only when Fe-S cluster levels are replete. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
IGF2BP2 is Induced by Stress in the Heart and Mediates Dilated Cardiomyopathy

PaperPlayer biorxiv cell biology

Play Episode Listen Later Nov 4, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.03.515033v1?rss=1 Authors: Krumbein, M., Oberman, F., Cinnamon, Y., Golomb, M., May, D., Vainer, G., Belzer, V., Meir, K., Fridman, I., Haybaeck, J., Poelzl, G., Kehat, I., Beeri, R., Kessler, S., Yisraeli, J. K. Abstract: The IGF2BP family of RNA binding proteins consists of three paralogs that regulate intracellular RNA localization, RNA stability, and translational control. Although IGF2BP1 and 3 are oncofetal proteins, IGF2BP2 expression is maintained in many tissues, including the heart, into adulthood. Previous studies indicated that IGF2BP2 is upregulated in cardiomyocytes during cardiac stress and remodelling and returns to normal levels in recovering hearts. These results suggested that IGF2BP2 might play an adaptive role during cardiac stress and recovery. Using a conditional, inducible transgenic mouse line, we found that enhanced expression of the IGF2BP2 transgene in newborn or adult hearts leads to dilated cardiomyopathy (DCM), with remodelling, fibrosis, and death within 3-4 weeks. Downregulation of the transgene after 2 weeks, however, rescues these mice, with complete recovery by 12 weeks. Proteomic analysis identified a downregulation of sarcomeric and mitochondrial proteins in hearts overexpressing IGF2BP2, and electron microscopy revealed fragmented mitochondria and elongated, thinner sarcomeres. Consistent with these results, IGF2BP2 is upregulated in patients with DCM or after myocardial infarction. These results show that cardiac stress upregulates IGF2BP2, leading to remodelling and compensation of the heart. Prolonged expression, however, leads to heart failure and death, making it an attractive target for therapeutic intervention. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Proteomics in Proximity
Proteomic Profiling Platforms

Proteomics in Proximity

Play Episode Listen Later Oct 25, 2022 32:24


The 2022 Science Advances paper, “Proteomic profiling platforms head to head: Leveraging genetics and clinical traits to compare aptamer- and antibody-based methods” by Daniel H Katz and Rob Gerszten et al. is available online here.A highly informative Twitter thread by the first author Dr. Daniel Katz reviewing the figures of the paper is available here.If you are interested in learning more about the use of proteomics in multiomic strategies, here's link to the Olink website where examples of combinations of omics methods are combined.If you would like to contact Dale, Cindy or Sarantis feel free to email us at info@olink.com.In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink Proteomics assay technology called the Proximity Extension Assay (PEA), and more information about the assay and how it works can be found here.Would you like to subscribe to the podcast on your favorite player or app? You can do so here: Apple Podcasts: https://apple.co/3T0YbSm Spotify Podcasts: https://open.spotify.com/show/2sZ2wxOqI4b4vSngkajLs8?si=d957d55c8db046f7 Google Podcasts: https://podcasts.google.com/feed/aHR0cHM6Ly9mZWVkcy50cmFuc2lzdG9yLmZtL3Byb3Rlb21pY3MtaW4tcHJveGltaXR5 Amazon Music: https://music.amazon.com/podcasts/d97ace94-f02b-4b37-9532-799548ef2840 Podcast Addict: https://podcastaddict.com/podcast/4098296 Deezer: https://www.deezer.com/show/5178787 Player FM: https://player.fm/series/series-3396598

PaperPlayer biorxiv neuroscience
A cross-species proteomic map of synapse development reveals neoteny during human postsynaptic density maturation

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Oct 25, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.24.513541v1?rss=1 Authors: Wang, L., Pang, K., Zhou, L., Cebrian-Silla, A., Gonzalez-Granero, S., Wang, S., Bi, Q., White, M. L., Ho, B., Li, J., Li, T., Perez, Y., Huang, E. J., Winkler, E. A., Paredes, M. F., Kovner, R., Sestan, N., Pollen, A. A., Liu, P., Li, J., Piao, X., Garcia-Verdugo, J. M., Alvarez-Buylla, A., Liu, Z., Kriegstein, A. R. Abstract: The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood. Here, we generated a cross-species proteomic map of synapse development in the human, macaque, and mouse neocortex. By tracking the changes of greater than 1,000 postsynaptic density (PSD) proteins from midgestation to adolescence, we found that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that the human PSD matures about three times slower than other species and contains higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the perinatal period. Enhancement of the RhoGEF signaling in human neurons delays the morphological maturation of dendritic spines and functional maturation of synapses, potentially contributing to the neotenic traits of human brain development. In addition, PSD proteins can be divided into four modules that exert stage- and cell type-specific functions, possibly explaining their differential associations with cognitive functions and diseases. Together, our proteomic map of synapse development provides a blueprint for studying the molecular basis and evolutionary changes of synapse maturation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Proteomic profiling reveals lysosomal heterogeneity in association with longevity

PaperPlayer biorxiv cell biology

Play Episode Listen Later Oct 17, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.16.512400v1?rss=1 Authors: Yu, Y., Gao, S. M., Guan, Y., Hu, P., Zhang, Q., Liu, J., Jing, B., Zhao, Q., Sabatini, D. M., Abu-Remaileh, M., Jung, S. Y., Wang, M. C. Abstract: Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins enriched at lysosomes mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked with longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using large-scale proteomic profiling, we systemically profiled lysosome-enriched proteomes in association with different longevity mechanisms. We further discovered the lysosomal recruitment of AMPK and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with different markers, we discovered lysosomal heterogeneity across tissues as well as the specific enrichment of the Ragulator complex on Cystinonsin positive lysosomes. Together, this work uncovers lysosomal proteome heterogeneity at different levels and provides resources for understanding the contribution of lysosomal proteome dynamics in modulating signal transduction, organelle crosstalk and organism longevity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Alterations in platelet proteome signature and impaired platelet integrin αIIbβ3 activation in patients with COVID-19

PaperPlayer biorxiv cell biology

Play Episode Listen Later Oct 12, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.12.511145v1?rss=1 Authors: Goudswaard, L. J., Williams, C. M., Khalil, J., Burley, K. L., Hamilton, F., Arnold, D., Milne, A., Lewis, P. A., Heesom, K. J., Mundell, S. J., Davidson, A. D., Poole, A. W., Hers, I. Abstract: BackgroundPatients with coronavirus disease-19 (COVID-19) are at increased risk of thrombosis, which is associated with altered platelet function and coagulopathy, contributing to excess mortality. ObjectivesWe aimed to characterise the mechanism of altered platelet function in COVID-19 patients. MethodsThe platelet proteome, platelet functional responses and platelet-neutrophil aggregates were compared between patients hospitalised with COVID-19 and healthy control subjects using Tandem Mass Tag (TMT) proteomic analysis, Western blotting and flow cytometry. ResultsCOVID-19 patients showed a different profile of platelet protein expression (858 altered out of 5773 quantified). Levels of COVID-19 plasma markers were enhanced in COVID-19 platelets. Gene ontology (GO) pathway analysis demonstrated that levels of granule secretory proteins were raised, whereas some platelet activation proteins, such as the thrombopoietin receptor and PKC, were lowered. Basally, COVID-19 platelets showed enhanced phosphatidylserine (PS) exposure, with unaltered integrin IIb{beta}3 activation and P-selectin expression. Agonist-stimulated integrin IIb{beta}3 activation and PS exposure, but not P-selectin expression, were significantly decreased in COVID-19 patients. COVID-19 patients had high levels of platelet-neutrophil aggregates, even under basal conditions, compared to controls. This interaction was disrupted by blocking P-selectin, demonstrating that platelet P-selectin is critical for the interaction. ConclusionsOverall, our data suggests the presence of two platelet populations in patients with COVID-19: one with circulating platelets with an altered proteome and reduced functional responses and another with P-selectin expressing neutrophil-associated platelets. Platelet driven thromboinflammation may therefore be one of the key factors enhancing the risk of thrombosis in COVID-19 patients. Essentials- COVID-19 patient platelet function and platelet proteins were compared with healthy controls - Proteomic analysis of platelets indicated that COVID-19 decreased platelet activation proteins - Agonist induced PS exposure and integrin IIb{beta}3 activation were impaired in COVID-19 - COVID-19 led to maximal levels of P-selectin dependent platelet-neutrophil aggregates Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Oct 10, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.10.511434v1?rss=1 Authors: Lopez-Tobon, A., Shyti, R., Villa, C. E., Cheroni, C., Fuentes-Bravo, P., Trattaro, S., Caporale, N., Troglio, F., Tenderini, E., Mihailovich, M., Skaros, A., Gibson, W. T., Cuomo, A., Bonaldi, T., Mercurio, C., Varasi, M., Osborne, L. R., Testa, G. Abstract: Copy number variations at 7q11.23 cause neurodevelopmental disorders with shared and opposite manifestations. Deletion causes Williams-Beuren syndrome (WBS), while duplication causes 7q11.23 microduplication syndrome (7Dup). Converging evidence indicates GTF2I, from the 7q11.23 locus, is a key mediator of the cognitive-behavioral phenotypes associated with WBS and 7Dup. Here we integrate molecular profiling of patient-derived cortical organoids (COs) and transgenic mouse models to dissect 7q11.23 disease mechanisms. Proteomic and transcriptomic profiling of COs revealed opposite dynamics of neural progenitor proliferation and transcriptional imbalances, leading to precocious excitatory neuron production in 7Dup. The accelerated excitatory neuron production in 7Dup COs could be rescued by GTF2I knockdown. Transgenic mice with Gtf2i duplication recapitulated early neuronal differentiation defects and ASD-like behaviors. Remarkably, inhibition of LSD1, a downstream effector of GTF2I, was sufficient to rescue ASD-like phenotypes. We propose that the GTF2I-LSD1 axis constitutes a molecular pathway amenable to therapeutic intervention. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Simulation
#803 Dr. Tiannan Guo — Proteomic Big Data

Simulation

Play Episode Listen Later Jun 29, 2022 84:40


Dr. Tiannan Guo is a PI at Westlake University and Founder of Westlake Omics boosting precision medicine and drug research and development by integrating technological innovations in proteomics and multimodal big data. https://guomics.com https://westlakeomics.com/en https://twitter.com/guomics https://twitter.com/OmicsWestlake What is I? ► https://bit.ly/WhatisI High Level Perception ► https://highlevelperception.com No Limits Society ► https://bentinhomassaro.com/nls

Oncotarget
Trending With Impact: Dual Requirement in Stem Cell Leukemia/Lymphoma

Oncotarget

Play Episode Listen Later May 18, 2022 7:20


Listen to a blog summary of a trending research paper published by Oncotarget, entitled, "Proteomic analysis reveals dual requirement for Grb2 and PLCγ1 interactions for BCR-FGFR1-Driven 8p11 cell proliferation." ___________________________________________ Chromosomes are found in the nucleus of cells and consist of proteins and tightly coiled strands of DNA. During cell division, chromosomal translocations can occur while the chromosomes are being copied. This type of mutation can mean that an entire chromosome has moved to another location, or that a chromosome has broken, usually into two pieces, and moved to another site. Some translocations are harmless, but others can lead to aberrant cell proliferation and cancer. “Over the last half century, chromosomal translocations encoding functional oncogenic proteins have been identified as drivers of multiple cancers, and account for 20% of all malignant neoplasms [1, 2].” For example, the t(8;22)(p11;q11) chromosomal translocation leads to the initiation of an oncogenic fusion protein called the Breakpoint Cluster Region Fibroblast Growth Factor Receptor 1 (BCR-FGFR1). BCR-FGFR1 is a single driver of 8p11 myeloproliferative syndrome, which is also known as stem cell leukemia/lymphoma (SCLL). “Stem cell leukemia/lymphoma (SCLL) exhibits distinct clinical and pathological features characterized by chromosomal translocations involving the FGFR1 gene at chromosome 8p11.” In a trending new study, researchers from the University of California San Diego and Sanford Burnham Prebys Medical Discovery Institute examined mutations in PLCγ1 and Grb2 binding sites individually and when combined together in a double mutant within BCR-FGFR1. On May 11, 2022, the research paper was published in Oncotarget and entitled, “Proteomic analysis reveals dual requirement for Grb2 and PLCγ1 interactions for BCR-FGFR1-Driven 8p11 cell proliferation.” Full blog - https://www.oncotarget.org/2022/05/12/trending-with-impact-dual-requirement-in-stem-cell-leukemia-lymphoma/ DOI - https://doi.org/10.18632/oncotarget.28228 Correspondence to - Daniel J. Donoghue - ddonoghue@ucsd.edu Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28228 Keywords - oncogenic fusion protein, chromosomal translocation, protein interactome, phosphoproteome, stem cell leukemia/lymphoma About Oncotarget Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

The MM+M Podcast
Using AI and proteomic technology to change the way disease is detected

The MM+M Podcast

Play Episode Listen Later Nov 19, 2021 17:56


Steve Williams, chief medical officer of SomaLogic, joined Steve Madden at HLTH, where they discussed the power of proteomics and its potential impact on health.