Podcasts about mirnas

Play Episode Listen Later Jul 11, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.10.548401v1?rss=1 Authors: Chen, X., Sokirniy, I., Wang, X., Jiang, M., Mseis-Jackson, N., Williams, C., Mayes, K., Jiang, N., Puls, B., Du, Q., Shi, Y., Li, H. Abstract: While astrocyte-to-neuron (AtN) reprogramming holds great promise in regenerative medicine, the molecular mechanisms that govern this unique biological process remain elusive. MicroRNAs (miRNAs), as post-transcriptional regulators of gene expression, play crucial roles during development and under various pathological conditions. To understand the function of miRNAs during AtN reprogramming process, we performed RNA-seq of both mRNAs and miRNAs on human astrocyte (HA) cultures upon NeuroD1 overexpression. Bioinformatics analyses showed that NeuroD1 not only activates essential neuronal genes to initiate reprogramming process but also induces miRNA changes in HA. Among the upregulated miRNAs, we identified miR-375 and its targets, neuronal ELAVL genes (nELAVLs), which encode a family of RNA-binding proteins and are also upregulated by NeuroD1. We further showed that manipulating miR-375 level regulates nELAVLs expression during NeuroD1-mediated reprogramming. Interestingly, miR-375/nELAVLs are also induced by reprogramming factors Neurog2 and ASCL1 in HA suggesting a conserved function to neuronal reprogramming, and by NeuroD1 in the mouse astrocyte culture and spinal cord. Functionally, we showed that miR-375 overexpression improves NeuroD1-mediated reprogramming efficiency by promoting cell survival at early stages in HA even in cultures treated with the chemotherapy drug Cisplatin. Moreover, miR-375 overexpression does not appear to compromise maturation of the reprogrammed neurons in long term HA cultures. Lastly, overexpression of miR-375-refractory ELAVL4 induces apoptosis and reverses the cell survival-promoting effect of miR-375 during AtN reprogramming. Together, we demonstrate a neuro-protective role of miR-375 during NeuroD1-mediated AtN reprogramming and suggest a strategy of combinatory overexpression of NeuroD1 and miR-375 for improving neuronal reprogramming efficiency. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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

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

IRE1-mediated degradation of pre-miR-301a promotes apoptosis through upregulation of GADD45A

Play Episode Listen Later Jun 22, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.21.545854v1?rss=1 Authors: Gebert, M., Bartoszewska, S., Opalinski, L., Collawn, J., Bartoszewski, R. Abstract: The unfolded protein response is a survival signaling pathway that is induced during various types of ER stress. Here we focus on the IRE1 pathway to determine IRE1 role in miRNA regulation during ER stress. During induction of ER stress in human bronchial epithelial cells, we utilized next generation sequencing to demonstrate that pre-miR-301a and pre-miR-106b, were significantly increased in the presence of an IRE1 inhibitor. Conversely, using nuclear-cytosolic fractionation on ER stressed cells, we found that these three pre-miRNAs were decreased in the nuclear fractions without the IRE1 inhibitor. We also found that miR-301a-3p targets the proapoptotic UPR factor, growth arrest and DNA-damage-inducible alpha (GADD45A). Inhibiting miR-301a-3p levels or blocking its predicted miRNA binding site in GADD45A 3 UTR with a target protector increased GADD45A mRNA expression. An elevation of XBP1s expression had no effect on GADD45A mRNA expression. We also demonstrated that the introduction of a target protector for the miR-301a-3p binding site in GADD45A mRNA during ER stress promoted cell death in the airway epithelial cells. These results indicated that IRE1 endonuclease activity is a two-edged sword that splices XBP1 mRNA for survival and degrades pre-miR-301a to elevate the mRNA expression of a pro-apoptotic gene, GADD45A. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Small RNA Sequencing Reveals a Distinct MicroRNA Signature between Glucocorticoid Responder and Glucocorticoid Non-responder Primary Human Trabecular Meshwork Cells after Dexamethasone Treatment

Play Episode Listen Later Jun 19, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.19.545545v1?rss=1 Authors: Kandasamy, K., Fan, X., Haribalaganesh, R., Bharanidharan, D., Sharmila, R., Krishnadas, R., Muthukkaruppan, V., Willoughby, C. E., Srinivasan, S. Abstract: The present study aimed to understand the role of miRNAs in differential glucocorticoid (GC) responsiveness in human trabecular meshwork (HTM) cells using small RNA sequencing. For this, total RNA was extracted from cultured HTM cells with known GC responsiveness using Human organ-cultured anterior segment (HOCAS) (GC-responder GC-R; n=4) and GC-non-responder (GC-NR; n=4) after treatment with either 100nM dexamethasone (DEX) or ethanol (ETH) for 7 days. Differentially expressed miRNAs (DEMIRs) were compared among 5 groups and validated by RT-PCR. There were 13 and 21 DEMIRs identified in Group #1 (ETH vs DEX-treated GC-R) and Group #2 (ETH vs DEX-treated GC-NR) respectively. Seven miRNAs were found as common miRNAs dysregulated in both GC-R and GC-NR (Group #3). There were 6 and 14 unique DEMIRs were identified in GC-R (Gropu#4) and GC-NR (Group#5) HTM cells respectively. Ingenuity Pathway Analysis identified enriched pathways and biological processes associated with differential GC responsiveness in HTM cells. Integrative analysis of miRNA-mRNA of the same set of HTM cells revealed several molecular regulators for GC non-responsiveness. This is the first study revealed a unique miRNA signature between GC-R and GC-NR HTM cells which raises the possibility of developing new molecular targets for the management of steroid-OHT/glaucoma. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Spinal Cord Injury regulates circular RNA expression in axons

Play Episode Listen Later Apr 27, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.26.538466v1?rss=1 Authors: Siddiq, M. M., Toro, C. A., Johnson, N. P., Hansen, J., Xiong, Y., Mellado, W., Tolentino, R. E., Johnson, K., Jayaraman, G., Suhail, Z., Harlow, L., Beaumont, K. G., Sebra, R. G., Willis, D. E., Cardozo, C. P., Iyengar, R. Abstract: Introduction- Neurons transport mRNA and translational machinery to axons for local translation. After spinal cord injury (SCI), de novo translation is assumed to enable neurorepair. Knowledge of the identity of axonal mRNAs that participate in neurorepair after SCI is limited. We sought to identify and understand how axonal RNAs play a role in axonal regeneration. Methods- We obtained preparations enriched in axonal mRNAs from control and SCI rats by digesting spinal cord tissue with cold-active protease (CAP). The digested samples were then centrifuged to obtain a supernatant that were then sequenced. We used bioinformatics analyses to identify DEGS and map them to various biological processes. We validated the DEGs by RT-qPCR and RNA-scope. Results- The supernatant fraction was highly enriched for axonal mRNA. Using Gene Ontology, the second most significant pathway for all differentially expressed genes (DEGs) was axonogenesis. Among the DEGs was Rims2, which is predominately a circular RNA (circRNA) in the CNS. We show that Rims2 RNA within spinal cord axons is circular. We found an additional 200 putative circRNAs in the axonal-enriched fraction. Knockdown in primary rat cortical neurons of the RNA editing enzyme ADAR1, which inhibits formation of circRNAs, significantly increased axonal outgrowth. Focusing on Rims2 we used Circular RNA Interactome to predict that several of the miRNAs that bind to circRims2 also bind to the 3 prime UTR of GAP-43, PTEN or CREB1, all known regulators of axonal outgrowth. Axonally-translated GAP-43 supports axonal elongation and we detect GAP-43 mRNA in the rat axons by RNAscope. Discussion- By using our method for enrichment of axonal RNA, we detect SCI induced DEGs, including circRNA such as Rims2. Ablation of ADAR1, the enzyme that regulates circRNA formation, promotes axonal outgrowth of cortical neurons. We developed a pathway model using Circular RNA Interactome that indicates that Rims2 through miRNAs can regulate the axonal translation GAP-43 a known regulator of axonal regeneration indicating that axonal mRNA contribute to regeneration. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

RNA landscapes of brain tissue and brain tissue-derived extracellular vesicles in simian immunodeficiency virus (SIV) infection and SIV-related central nervous system pathology

Play Episode Listen Later Apr 2, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.01.535193v1?rss=1 Authors: Huang, Y., Abdelgawad, A. G. A., Turchinovich, A., Queen, S., Abreu, C. M., Zhu, X., Batish, M., Zheng, L., Witwer, K. W. Abstract: Introduction: Antiretroviral treatment regimens can effectively control HIV replication and some aspects of disease progression. However, molecular events in end-organ diseases such as central nervous system (CNS) disease are not yet fully understood, and routine eradication of latent reservoirs is not yet in reach. Extracellular vesicle (EV) RNAs have emerged as important participants in HIV disease pathogenesis. Brain tissue-derived EVs (bdEVs) act locally in the source tissue and may indicate molecular mechanisms in HIV CNS pathology. Using brain tissue and bdEVs from the simian immunodeficiency virus (SIV) model of HIV disease, we profiled messenger RNAs (mRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), seeking to identify possible networks of RNA interaction in SIV infection and neuroinflammation. Methods: Postmortem occipital cortex tissues were obtained from pigtailed macaques either not infected or dual-inoculated with SIV swarm B670 and clone SIV/17E-Fr. SIV-inoculated groups included samples collected at different time points during acute infection or chronic infection without or with CNS pathology (CP- or CP+). bdEVs were separated and characterized in accordance with international consensus standards. RNAs from bdEVs and source tissue were used for sequencing and qPCR to detect mRNA, miRNA, and circRNA levels. Results: Multiple dysregulated bdEV RNAs, including mRNAs, miRNAs, and circRNAs, were identified in acute and CP+. Most dysregulated mRNAs in bdEVs reflected dysregulation in their source tissues. These mRNAs are disproportionately involved in inflammation and immune responses, especially interferon pathways. For miRNAs, qPCR assays confirmed the differential abundance of miR-19a-3p, let-7a-5p, and miR-29a-3p (acute phase), and miR-146a-5p and miR-449a-5p (CP+) in bdEVs. In addition, target prediction suggested that several circRNAs that were differentially abundant in source tissue might be responsible for specific differences in small RNA levels in bdEVs during SIV infection. Conclusions: RNA profiling of bdEVs and source tissues reveals potential regulatory networks in SIV infection and SIV-related CNS pathology. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Senescence-Associated Exosomes Transfer Fibrosis to Neighboring Cells

Play Episode Listen Later Mar 17, 2023 4:22

A new research paper was published in Aging (Aging-US) Volume 15, Issue 5, entitled, “Senescence-associated exosomes transfer miRNA-induced fibrosis to neighboring cells.” Radiation-induced fibrosis is a common side effect of radiotherapy, which is the most common treatment for cancer. However, radiation also causes p53-mediated cell cycle arrest, prolonged expression of p21, and the development of senescence in normal cells that reside in irradiated tissues. Bone marrow-derived mesenchymal stem cells (MSCs) accumulate in primary tumor sites because of their natural tropism for inflammatory and fibrotic tissues. MSCs are extremely sensitive to low doses of ionizing radiation and acquire senescence as a result of bystander radiation effects. Senescent cells remain metabolically active but develop a potent senescence-associated secretory phenotype (SASP) that correlates to hyperactive secretion of cytokines, pro-fibrotic growth factors, and exosomes (EXOs). Integrative pathway analysis has highlighted that radiation-induced senescence significantly enriched cell-cycle, extracellular matrix, transforming growth factor-β (TGF-β) signaling, and vesicle-mediated transport genes in MSCs. EXOs are cell-secreted nanovesicles (a subclass of small extracellular vesicles) that contain biomaterials—proteins, RNAs, microRNAs (miRNAs)—that are critical in cell-cell communication. miRNA content analysis of secreted EXOs further revealed that radiation-induced senescence uniquely altered miRNA profiles. “In fact, several of the standout miRNAs directly targeted TGF-β or downstream genes.” In this new study, researchers Amy H. Lee, Deepraj Ghosh, Ivy L. Koh, and Michelle R. Dawson from Brown University further treated normal MSCs with senescence-associated EXOs (SA-EXOs) to examine bystander effects of radiation-induced senescence. The researchers found that these modulated genes were related to TGF-β pathway and elevated both alpha smooth muscle actin (protein increased in senescent, activated cells) and Ki-67 (proliferative marker) expression in SA-EXO treated MSCs compared to untreated MSCs. They revealed that SA-EXOs possess unique miRNA content that influence myofibroblast phenotypes via TGF-β pathway activation. This highlights that SA-EXOs are potent SASP factors that play a large role in cancer-related fibrosis. “Our integrated omics and EXO microarray analyses show that senescent MSCs possess differential transcriptional genes and secrete vesicles that contain unique post-transcriptional cargo. We subsequently demonstrated that these EXO miRNAs can play important roles in cell-cell communication during disease progression.” Paper: DOI: https://doi.org/10.18632/aging.204539 Corresponding Author: Michelle R. Dawson - michelle_dawson@brown.edu Keywords: radiation-induced senescence, exosomes (EXOs), microRNA (miRNA), transforming growth factor-β (TGF-β), mesenchymal stem cells (MSCs) 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

Light-Responsive MicroRNAs in Human Retinal Tissue are Differentially Regulated by Distinct Wavelengths of Light

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Play Episode Listen Later Feb 12, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.10.528054v1?rss=1 Authors: Celiker, C., Weissova, K., Cerna, K. A., Oppelt, J., Sebestikova, J., Liskova, P., Barta, T. Abstract: Retinal microRNA (miRNA) molecules play critical roles in a wide range of processes including cell proliferation, cell death, and synaptic plasticity. Recently they have been shown to regulate crucial processes that are associated with perception of light including visual function, light adaptation, and control of genes regulating circadian light entrainment. Despite extensive work on retinal miRNAs in different model organisms, light-regulated miRNAs in human retina are not known. Here, we aim to characterize these miRNAs. We generated light responsive human retinal organoids that express miRNA families and clusters typically found in the retina. Using in-house-developed photostimulation device, we found that 51 miRNAs are up- or downregulated upon brief photostimulation periods. Clustering analysis revealed that only two miRNA families and three clusters are upregulated, while eight families and ten cluster are downregulated upon photostimulation. Additionally, we found that the light-regulated miRNAs have rapid turnover, and their expression is differentially regulated by distinct wavelengths of light. This study demonstrates that only a small subset of miRNAs is light-responsive in human retinal tissue and the generated human retinal organoids are a valuable model for studying the molecular mechanisms of light perception in the retina. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

SVF-Secreted miRNAs in Lipedema

Living Well with Lipedema

Play Episode Listen Later Jan 19, 2023 6:24

In this episode, we talk about a paper in Austria titled, SVF-derived extracellular vesicles carry characteristic miRNAs in lipedema.

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Two RNA-binding proteins mediate the sorting of miR223 from mitochondria into exosomes

Play Episode Listen Later Jan 11, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.11.523558v1?rss=1 Authors: Ma, L., Singh, J., Schekman, R. Abstract: Fusion of multivesicular bodies (MVBs) with the plasma membrane results in the secretion of intraluminal vesicles (ILVs), or exosomes. The sorting of one exosomal cargo RNA, miR223, is facilitated by the RNA-binding protein, YBX1 (Shurtleff et al., 2016). We found that miR223 specifically binds a "cold shock" domain (CSD) of YBX1 through a 5' proximal sorting motif UCAGU. Prior to sorting into exosomes, most of the cytoplasmic miR223 resides in mitochondria. An RNA-binding protein localized to the mitochondrial matrix, YBAP1, appears to serve as a negative regulator of miR223 enrichment into exosomes. miR223 levels decreased in the mitochondria and increased in exosomes after loss of YBAP1. We observed YBX1 shuttle between mitochondria and endosomes in live cells. YBX1 also partitions into P body granules in the cytoplasm (Liu et al., 2021). We propose a model in which miR223 and likely other miRNAs are stored in mitochondria and are then mobilized by YBX1 to cytoplasmic phase condensate granules for capture into invaginations in the endosome that give rise to exosomes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Serum microRNAs as New Criteria for Referral to Early Palliative Care Services

Play Episode Listen Later Jan 3, 2023 3:47

A new research paper was published in Oncotarget's Volume 13 on December 17, 2022, entitled, “Serum microRNAs as new criteria for referral to early palliative care services in treatment-naïve advanced cancer patients.” A major obstacle to the implementation of early palliative care (EPC) is the lack of objective criteria for referral to EPC. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers. In the current study, researchers Tomofumi Miura, Shuichi Mitsunaga, Juntaro Matsuzaki, Satoko Takizawa, Ken Kato, Atsushi Ochiai, and Takahiro Ochiya from National Cancer Center Research Institute, National Cancer Center Hospital, Keio University, Toray Industries, Inc., and Tokyo Medical University investigated objective definitions for referral to EPC using microRNA. A total of 178 serum samples were obtained from patients with lung, gastrointestinal, colorectal, bile duct, pancreas, and bladder cancers who were treatment-naïve and received chemotherapy between January 2011 and December 2013 at National Cancer Center Hospital East. “The aim of the present study was to develop predictive models using serum miRNAs for patients who [were] admitted to a PCU [palliative care unit] ≤6 months after starting anti-tumor treatment.” The team investigated expression levels of miRNAs using microarrays. The primary outcome was prediction of admission to a palliative care unit ≤6 months after first visit. Diagnostic models using clinical characteristics, miRNAs and combinations of both were constructed. The miRNA models were constructed using 6 miRNA levels. The best areas under the receiver operating characteristic curve (AUCs) of the clinical model was 0.741, while the average AUCs of miRNA-based models and combination models were 0.769 and 0.806, respectively. Combination models showed higher AUCs than the clinical model (p < 0.023). The researchers assert that the present combination models might offer new objective definitions for referral to EPC and thus contribute to real-world implementation of EPC. “The present study developed a predictive model using miRNA for patients admitted to a PCU ≤6 months after starting anti-tumor treatment. The present models might offer objective criteria for oncologists to facilitate the referral of patients to the EPC.” DOI: https://doi.org/10.18632/oncotarget.28327 Correspondence to: Shuichi Mitsunaga - smitsuna@east.ncc.go.jp Keywords: microRNA, early palliative care, integration, cancer, referral About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.

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SARS-CoV-2 protein NSP2 enhances microRNA-mediated translational repression

Play Episode Listen Later Jan 3, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.01.522328v1?rss=1 Authors: Naeli, P., Zhang, X., Harris Snell, P., Chatterjee, S., Kamran, M., Ladak, R. J., Orr, N., Duchaine, T., Sonenberg, N., Jafarnejad, S. M. Abstract: microRNAs (miRNAs) inhibit mRNA translation initiation by recruiting the GIGYF2/4EHP translation repressor complex to the mRNA 5' cap structure. Viruses utilise miRNAs to impair the host antiviral immune system and facilitate viral infection by expressing their own miRNAs or co-opting cellular miRNAs. We recently reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encoded non-structural protein 2 (NSP2) interacts with GIGYF2. This interaction is critical for blocking translation of the Ifn1-b mRNA that encodes the cytokine Interferon-beta, and thereby impairs the host antiviral immune response. However, it is not known whether NSP2 also affects miRNA-mediated silencing. Here, we demonstrate the pervasive augmentation of the miRNA-mediated translational repression of cellular mRNAs by NSP2. We show that NSP2 interacts with Argonaute 2, the core component of the miRNA-Induced Silencing Complex (miRISC) and enhances the translational repression mediated by natural miRNA binding sites in the 3' UTR of cellular mRNAs. Our data reveal an additional layer of the complex mechanism by which SARS-CoV-2 and likely other coronaviruses manipulate the host gene expression program through co-opting the host miRNA-mediated silencing machinery. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Extracellular vesicles improve GABAergic transmission in Huntington's disease iPSC-derived neurons

Play Episode Listen Later Dec 18, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.18.520919v1?rss=1 Authors: Beatriz, M., Rodrigues, R., Vilaca, R., Egas, C., Pinheiro, P., Daley, G. Q., Schlaeger, T. M., Rego, A. C., Lopes, C. Abstract: Extracellular vesicles (EVs) carry bioactive molecules associated with various biological processes, including miRNAs. In both Huntingtons disease (HD) models and human samples, altered expression of miRNAs involved in synapse regulation were reported. Recently, the use of EV cargo to reverse phenotypic alterations in disease models with synaptopathy as the end-result of the pathophysiological cascade has become an interesting possibility. Here, we assessed the contribution of EVs to GABAergic synaptic alterations using a human HD model and studied the miRNA content of isolated EVs. After differentiating HD human induced-pluripotent stem cells into electrophysiologically active striatal-like GABAergic neurons, we found that HD-derived neurons displayed reduced density of inhibitory synapse markers and of GABA receptor-mediated ionotropic signaling. Treatment with EVs secreted by control (CTR) fibroblasts reversed the deficits in GABAergic synaptic transmission and increased the density of inhibitory synapses on HD-neuron cultures, while EVs from HD-derived fibroblasts had the opposite effects on CTR-neurons. Moreover, analysis of miRNAs from purified EVs identified a set of differentially expressed miRNAs between manifest HD, premanifest and CTR lines with predicted synaptic targets. The EVs-mediated reversal of the abnormal GABAergic phenotype in HD-derived neurons reinforces the potential role of EVs-miRNAs on synapse regulation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Extracellular vesicles improve GABAergic transmission in Huntington's disease iPSC-derived neurons

Play Episode Listen Later Dec 18, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.18.520919v1?rss=1 Authors: Beatriz, M., Rodrigues, R., Vilaca, R., Egas, C., Pinheiro, P., Daley, G. Q., Schlaeger, T. M., Rego, A. C., Lopes, C. Abstract: Extracellular vesicles (EVs) carry bioactive molecules associated with various biological processes, including miRNAs. In both Huntington's disease (HD) models and human samples, altered expression of miRNAs involved in synapse regulation were reported. Recently, the use of EV cargo to reverse phenotypic alterations in disease models with synaptopathy as the end-result of the pathophysiological cascade has become an interesting possibility. Here, we assessed the contribution of EVs to GABAergic synaptic alterations using a human HD model and studied the miRNA content of isolated EVs. After differentiating HD human induced-pluripotent stem cells into electrophysiologically active striatal-like GABAergic neurons, we found that HD-derived neurons displayed reduced density of inhibitory synapse markers and of GABA receptor-mediated ionotropic signaling. Treatment with EVs secreted by control (CTR) fibroblasts reversed the deficits in GABAergic synaptic transmission and increased the density of inhibitory synapses in HD-neuron cultures, while EVs from HD-derived fibroblasts had the opposite effects on CTR-neurons. Moreover, analysis of miRNAs from purified EVs identified a set of differentially expressed miRNAs between manifest HD, premanifest and CTR lines with predicted synaptic targets. The EVs-mediated reversal of the abnormal GABAergic phenotype in HD-derived neurons reinforces the potential role of EVs-miRNAs on synapse regulation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Aortic valve disease augments vesicular microRNA-145-5p to regulate the calcification of valvular interstitial cells via cellular crosstalk

Play Episode Listen Later Nov 29, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.29.518326v1?rss=1 Authors: Goody, P. R., Christmann, D., Goody, D., Nehl, D., Backer, K., Wilhelm-Juengling, K., Uchida, S., Moore, J. B., Zimmer, S., Bakhtiary, F., Pfeifer, A., Latz, E., Nickenig, G., Jansen, F., Hosen, M. R. Abstract: Rationale: Aortic valve stenosis (AVS) is a major contributor to cardiovascular death in the elderly population worldwide. MicroRNAs (miRNAs) are highly dysregulated in patients with AVS undergoing surgical aortic valve replacement (SAVR). However, miRNA-dependent mechanisms regulating inflammation and calcification or miRNA-mediated cell-cell crossstalk during the pathogenesis of AVS are still poorly understood. Here, we explored the role of extracellular vesicles (EV)-associated miR-145-5p, which we showed to be highly upregulated upon valvular calcification in AVS in mice and humans. Methods: Human TaqMan miRNA arrays identified dysregulated miRNAs in aortic valve tissue explants from AVS patients compared to non-calcified valvular tissue explants of patients undergoing SAVR. Echocardiographic parameters were measured in association with the quantification of dysregulated miRNAs in a murine AVS model. In vitro calcification experiments were performed to explore the effects of EV-miR-145-5p on calcification and crosstalk in valvular cells. To dissect molecular miRNA signatures and their effect on signaling pathways, integrated OMICS analyses were performed. RNA sequencing (RNA-seq), high-throughput transcription factor (TF) and proteome arrays showed that a number of genes, miRNAs, TFs, and proteins are crucial for calcification and apoptosis, which are involved in the pathogenesis of AVS. Results: Among several miRNAs dysregulated in valve explants of AVS patients, miR-145-5p was the most highly gender-independently dysregulated miRNA (AUC, 0.780, p-value, 0.01). MiRNA arrays utilizing patient-derived- and murine aortic-stenosis samples demonstrated that the expression of miR-145-5p is significantly upregulated and correlates positively with cardiac function based on echocardiography. In vitro experiments confirmed that miR-145-5p is encapsulated into EVs and shuttled into valvular interstitial cells. Based on the integrated OMICs results, miR-145-5p interrelates with markers of inflammation, calcification, and apoptosis. In vitro calcification experiments demonstrated that miR-145-5p regulates the ALPL gene, a hallmark of calcification in vascular and valvular cells. EV-mediated shuttling of miR-145-5p suppressed the expression of ZEB2, a negative regulator of the ALPL gene, by binding to its 3' untranslated region to inhibit its translation, thereby diminishing the calcification of target valvular interstitial cells. Conclusion: Elevated levels of pro-calcific and pro-apoptotic EV-associated miR-145-5p contribute to the progression of AVS via the ZEB2-ALPL axis, which could potentially be therapeutically targeted to minimize the burden of AVS. Keywords: aortic valve stenosis, microRNA, extracellular vesicles, cellular crosstalk, valvular calcification Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

llc disease ev mir valve cells evs zimmer regulate rna cellular jansen avs hosen tf goody backer pfeifer crosstalk interstitial aortic tfs microrna latz omics augments biorxiv calcification uchida savr mirnas micrornas mirnas results among

A novel pathway of functional microRNA uptake and mitochondria delivery

Play Episode Listen Later Nov 7, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.07.515397v1?rss=1 Authors: Liu, J., Li, W., Li, J., Song, E., Liang, H., Rong, W., Jiang, X., Xu, N., Wang, W., Qu, S., Zhang, Y., Zhang, C.-Y., Zen, K. Abstract: Extracellular miRNAs serve as signal molecules in the recipient cells. Uptake of extracellular miRNAs by the recipient cells and their intracellular transport, however, remains elusive. Here we show RNA phase separation as a novel pathway of miRNA uptake. In the presence of serum, synthetic miRNAs rapidly self-assembly into ~110nm discrete nanoparticles which enable miRNAs' entry into different cells. Depleting serum cationic proteins prevents the formation of such nanoparticles and thus blocks miRNA uptake. Different from lipofectamine-mediated miRNA transfection in which the majority of miRNAs are in lysosomes of transfected cells, nanoparticles-mediated miRNA uptake predominantly delivers miRNAs into mitochondria in a polyribonucleotide nucleotidyltransferase 1-dependent manner. Functional assays further show that the internalized miR-21 via miRNA phase separation enhances mitochondrial translation of Cytochrome b, leading to increase in ATP and ROS reduction in HEK293T cells. Our findings reveal a previously unrecognized mechanism for uptaking and delivering functional extracellular miRNAs into mitochondria. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

song llc delivery zen copy li pathway functional wang mir zhang atp rna mitochondria liang xu jiang uptake rong microrna depleting biorxiv mirnas cytochrome

Small Molecule Inducers of Neuroprotective miR-132 Identified by HTS-HTS in Human iPSC-derived Neurons

Play Episode Listen Later Nov 1, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.01.514550v1?rss=1 Authors: Nguyen, L. D., Wei, Z., Silva, M. C., Barberan-Soler, S., Rabinovsky, R., Muratore, C. R., Stricker, J. M. S., Hortman, C., Young-Pearse, T. L., Haggarty, S. J., Krichevsky, A. M. Abstract: MicroRNAs (miRNAs) are short RNAs that regulate fundamental biological processes. miR-132, a key miRNA with established functions in Tau homeostasis and neuroprotection, is consistently downregulated in Alzheimer's disease (AD) and other tauopathies. miR-132 overexpression rescues neurodegenerative phenotypes in several AD models. To complement research on miRNA-mimicking oligonucleotides targeting the central nervous system, we developed a high-throughput-screen coupled high-throughput-sequencing (HTS-HTS) in human induced pluripotent stem cell (iPSC)-derived neurons to identify small molecule inducers of miR-132. We discovered that cardiac glycosides, which are canonical sodium-potassium ATPase inhibitors, selectively upregulated miR-132 in the sub-M range. Coordinately, cardiac glycoside treatment downregulated total and phosphorylated Tau in rodent and human neurons and protected against toxicity by glutamate, N-methyl-D-aspartate, rotenone, and A{beta} oligomers. In conclusion, we identified small-molecule drugs that upregulated the neuroprotective miR-132 and ameliorated neurodegenerative phenotypes. Our dataset also represents a comprehensive resource for discovering small molecules that modulate specific miRNAs for therapeutic purposes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

llc alzheimer's disease copy wei mir identified tau molecule neurons derived stricker rnas ipsc biorxiv neuroprotective atpase mirnas

Cortical miR-709 links glutamatergic signaling to NREM sleep EEG slow waves in an activity-dependent manner

Play Episode Listen Later Sep 26, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.24.508386v1?rss=1 Authors: Kompotis, K., Mang, G., Hubbard, J. T., Jimenez, S., Emmenegger, Y., Polysopoulos, C., Hor, C. N., Wigger, L., Hebert, S. S., Mongrain, V., Franken, P. Abstract: MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression that have been implicated in a plethora of neuronal processes. Nevertheless, their role in regulating brain activity in the context of sleep has so far received little attention. To test their involvement, we deleted mature miRNAs in post-mitotic neurons at two developmental ages, i.e., in early adulthood using conditional Dicer knockout (cKO) mice and in adult mice using an inducible conditional Dicer cKO (icKO) line. In both models, electroencephalographic (EEG) activity was affected and the response to sleep deprivation (SD), altered; while rapid-eye-movement sleep (REMS) rebound was compromised in both, EEG delta (1-4 Hz) power during non-REM sleep (NREMS) was reduced in cKO mice and increased in icKO mice. We subsequently investigated the effects of SD on the miRNA transcriptome and found that the expression of 48 forebrain miRNAs was affected, in particular, the activity-dependent miRNA miR-709. In vivo inhibition of miR-709 in the brain increased EEG power during NREMS in the slow-delta (0.75-1.75 Hz) range, particularly after periods of prolonged wakefulness. Transcriptome analysis of primary cortical neurons in vitro revealed that miR-709 regulates endosomal trafficking and glutamatergic receptor activity. A subset of the genes involved in glutamatergic transmission was affected also in the cortices of sleep-deprived, miR-709-inhibited mice. Our data implicate miRNAs in the regulation of EEG activity and indicate that miR-709 links neuronal excitability during wakefulness to brain synchrony during sleep, likely through the regulation of endosomal trafficking and glutamatergic signaling. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Can microRNAs in the Bloodstream Signal Cognitive Decline?

Play Episode Listen Later Sep 21, 2022 6:37

Listen to a blog summary about a trending research paper published by Aging (Aging-US as the cover of Volume 14, Issue 17, entitled, "Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative Aging Study.” __________________________________________ Can factors in our bloodstream tell us about our cognitive abilities or predict cognitive decline later in life? Among individuals with dementias, including Alzheimer's disease (AD), studies have identified extracellular microRNAs (miRNAs) as potential biomarkers of cognitive impairment. In cognitively normal individuals, however, this association has not yet been fully investigated. “Understanding the functions of miRNAs in the earliest stages of cognitive decline will expand our knowledge on the biology of prodromal AD and the roles of circulating miRNAs in neurodegenerative diseases and could result in identification of therapeutic targets to guide drug development [17].” In a new research paper, published on the cover of Volume 14, Issue 17, of Aging (listed as “Aging (Albany NY)” by Medline/PubMed and “Aging-US” by Web of Science), researchers Nicole Comfort, Haotian Wu, Peter De Hoff, Aishwarya Vuppala, Pantel S. Vokonas, Avron Spiro, Marc Weisskopf, Brent A. Coull, Louise C. Laurent, Andrea A. Baccarelli, and Joel Schwartz from Columbia University Mailman School of Public Health, University of California San Diego, VA Boston Healthcare System, Boston University School of Medicine, and Harvard TH Chan School of Public Health investigated expression levels of extracellular miRNAs circulating in blood plasma taken from cognitively normal men and the association between these miRNAs and cognitive function. Their secondary goal was to investigate the genes and biological pathways associated with miRNAs linked to cognitive function or decline. The research paper was published on September 6, 2022, and entitled, “Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative Aging Study.” Full blog - https://aging-us.org/2022/09/can-micrornas-in-the-bloodstream-signal-cognitive-decline/ DOI - https://doi.org/10.18632/aging.204268 Corresponding author - Nicole Comfort - nicole.comfort@columbia.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204268 Press release - https://aging-us.com/news_room/Extracellular-microRNA-and-cognitive-function-in-a-prospective-cohort-of-older-men Keywords - aging, plasma, extracellular RNA, RNA-seq, microRNA, cognitive decline, cognitive impairment 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/agingus LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Press Release: Extracellular microRNA and Cognitive Function in Older Men

Play Episode Listen Later Sep 15, 2022 4:35

A new research paper was published on the cover of Aging (Aging-US) Volume 14, Issue 17, entitled, “Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative Aging Study.” Aging-related cognitive decline is an early symptom of Alzheimer's disease and other dementias, and on its own can have substantial consequences on an individual's ability to perform important everyday functions. Despite increasing interest in the potential roles of extracellular microRNAs (miRNAs) in central nervous system (CNS) pathologies, there has been little research on extracellular miRNAs in early stages of cognitive decline. In a new study, researchers Nicole Comfort, Haotian Wu, Peter De Hoff, Aishwarya Vuppala, Pantel S. Vokonas, Avron Spiro, Marc Weisskopf, Brent A. Coull, Louise C. Laurent, Andrea A. Baccarelli, and Joel Schwartz from Columbia University Mailman School of Public Health, University of California San Diego, VA Boston Healthcare System, Boston University School of Medicine, and Harvard TH Chan School of Public Health leveraged the longitudinal Normative Aging Study (NAS) cohort to investigate associations between plasma miRNAs and cognitive function among cognitively normal men. “In a cohort of older men from Massachusetts, we investigated associations between plasma miRNAs and global cognition and rate of global cognitive decline measured by the MMSE.” Full press release - https://aging-us.net/2022/09/15/aging-extracellular-microrna-and-cognitive-function-in-a-prospective-cohort-of-older-men-the-veterans-affairs-normative-aging-study/ DOI: https://doi.org/10.18632/aging.204268 Corresponding Author: Nicole Comfort – nicole.comfort@columbia.edu Keywords: plasma, extracellular RNA, RNA-seq, microRNA, cognitive decline, cognitive impairment Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204268 About Aging-US: Launched in 2009, Aging (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 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 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/agingus LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, contact media@impactjournals.com.

Death induced by survival gene elimination (DISE) contributes to neurotoxicity in Alzheimer's disease

Play Episode Listen Later Sep 10, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.08.507157v1?rss=1 Authors: Paudel, B., Jeong, S.-Y., Martinez, C. P., Rickman, A., Haluck-Kangas, A., Bartom, E. T., Frederiksen, K., Affaneh, A., Kessler, J. A., Mazzulli, J. R., Murmann, A. E., Rogalski, E., Geula, C., Ferreira, A., Heckmann, B. L., Green, D. R., Sadleir, K. R., Vassar, R., Peter, M. E. Abstract: BackgroundAlzheimers disease (AD) is characterized by progressive neurodegeneration, but the specific events that cause cell death remain poorly understood. Death Induced by Survival gene Elimination (DISE) is a recently discovered powerful cell death mechanism mediated by short (s) RNAs including micro (mi) RNAs acting through the RNA induced silencing complex (RISC). G-rich 6mer seed sequences in the sRNAs (position 2-7) target hundreds of C-rich seed matches in genes essential for cell survival resulting in the simultaneous activation of multiple cell death pathways. The RISC of most cells is occupied by miRNAs with nontoxic 6mer seeds, which may protect them from DISE by blocking loading of toxic sRNAs. However, during aging when miRNA expression decreases, toxic sRNAs may enter the RISC more readily leaving cells primed for DISE. Whether DISE contributes to neuronal loss in a neurodegenerative disease such as AD has not been evaluated. MethodsUsing Ago precipitation and RNAseq (Ago-RP-Seq) combined with SPOROS, a recently developed bioinformatics pipeline to analyze small RNAseq data with respect to 6mer seed toxicity, we analyzed RISC bound sRNAs (R-sRNAs) in in vitro models and in the brains of multiple in vivo AD mouse models, aged mice, and AD patients. ResultsWe find that in in vitro cell line studies, in mouse models that show neurodegeneration, and in the aging brain R-sRNAs shift to more toxic seeds. In contrast, in cells that survived in post-mortem brains of AD patients and the brains of "SuperAgers", individuals over age 80 who have superior memory performance, R-sRNAs shift to more nontoxic seeds, supporting a protective function of miRNAs. ConclusionOur data provide first evidence of a contribution of DISE to the neurotoxicity seen in AD suggesting that increasing the levels of protective miRNAs in the brain or blocking the activity of toxic R-sRNAs could lead to a novel way of treating the disease. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

MicroRNA-218 instructs proper assembly of hippocampal networks

medical treatments diagnosis fertility expression infertility pcos insulin insulin resistance natural remedies glucose metabolism mirnas

Play Episode Listen Later Aug 25, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.08.24.505085v1?rss=1 Authors: Taylor, S., Kobayashi, M., Vilella, A., Tiwari, D., Zolboot, N., Hartzell, A., Girgiss, C., Abaci, Y., De Sanctis, C., Bellenchi, G. C., Darnell, R. B., Gross, C., Zoli, M., Berg, D. K., Lippi, G. Abstract: The assembly of the mammalian brain is orchestrated by temporally coordinated waves of gene expression. A key aspect of this developmental program is mediated at the post-transcriptional level by microRNAs (miRNAs). Deletion of neuronal enriched miRNAs induces strong developmental phenotypes, and multiple reports have found altered levels of miRNAs in patients with neurodevelopmental disorders. However, cellular and molecular mechanisms used by miRNAs to instruct proper brain development remain largely unexplored. Here, through multiple screens, we identified miR-218 as a critical regulator of hippocampal assembly in mice. MiR-218 is highly expressed in the hippocampus and enriched in both excitatory principal neurons and GABAergic inhibitory interneurons. Transient inhibition of miR-218 in early life results in an adult brain with heightened network activity and a predisposition to seizures. We used RNA-seq and FACS-seq (fluorescence-activated cell sorting followed by RNA-seq) to identify global and cell type-specific changes in gene expression in the absence of miR-218 and narrow down which altered developmental processes would lead to long-term network instability. We find that miR-218 inhibition results in the disruption of early depolarizing GABAergic signaling, structural defects in dendritic spines, and altered intrinsic membrane excitability. Finally, conditional knockout of miR-218 in interneurons, but not pyramidal neurons is sufficient to recapitulate the effects on long-term stability. Taken together, the data suggest that miR-218 orchestrates hippocampal network assembly to produce a stable network in the adult, primarily by regulating interneuron function in early postnatal life. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

proper gross berg copy networks assembly mir rna darnell facs kobayashi transient deletion tiwari instructs microrna zoli hartzell lippi biorxiv gabaergic vilella hippocampal mirnas micrornas mirnas

09:PCOS and the Insulin Effect

The PCOS Repair Podcast

Play Episode Play 37 sec Highlight Listen Later Jun 10, 2022 11:37

Medical research has shown that Insulin resistance is a primary factor for over 70% of women with PCOS and yet most women I work with and talk to have been told by their doctor that their blood sugar is fine and that they are not insulin resistant. So what's the deal with insulin and PCOS and is it something that you should be addressing in order to reverse your PCOS? Well, my friend that is what this episode is all about so hit play to listen now!The insulin effect Notice how I didn't say insulin resistance. There is a big difference and it is really important to understand the importance of the insulin effect if you want to reverse your PCOS naturally. that I want you to understand. So what is insulin and how does it affect your PCOS hormones?When you eat something it is broken down and released into your body as glucose (that's another name for blood sugar). So by choosing the foods you eat smartly and combining certain foods to lessen their insulin effect you can greatly improve your PCOS hormones. In this episode, you will learn about what foods worsen the insulin effect and your PCOS (spoiler alert….it's not just sugar). And more importantly, you will learn what foods will help to improve your insulin effect and assist you in reversing your PCOS…..and it doesn't require you to never eat certain foods again. When you are armed with the food knowledge packed into this episode you will be able to make serious progress toward reversing your PCOS! Are you ready? Go ahead and listen to this episode where I not only share how insulin is working in your body but some simple actionable steps to use this information to heal your PCOS naturally! Happy listening! Resources Mentioned can be found on the Episode webpage:Reset Your Hormones with The PCOS DetoxGet your FREE copy of the PCOS Fertility Meal guideTake the PCOS Root cause quiz to learn what your body needs to healMedical Journal References for this Episode - see the podcast page for this episode here: Adipocyte Insulin Resistance in PCOS: Relationship With GLUT-4 Expression and Whole-Body Glucose Disposal and β-Cell FunctionAssociation of Insulin Resistance and Elevated Androgen Levels with Polycystic Ovarian Syndrome (PCOS): A Review of LiteratureThe Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism RevisitedThe role of miRNAs in polycystic ovary syndrome with insulin resistanceReview of Novel Potential Insulin Resistance Biomarkers in PCOS Patients—The Debate Is Still OpenTo Assess the Association between Glucose Metabolism and Ectopic Lipid Content in Different Clinical Classifications of PCOSAll Women With PCOS Should Be Treated For Insulin Resistance

EP109 Compuestos y beneficios de la leche humana

María Lactanz

Play Episode Listen Later Apr 25, 2022 61:31

Atributos de la leche humana (LH), funciones, composición y beneficio de sus macros: lípidos, carbohidratos, proteínas, y micronutrientes y otros compuestos. Células anti inflamatorias, anti cuerpos, comparación con leche bovina, programación metabólica, dinamismo de la LH. Mirnas, beneficios clínicos en pediatría, para la mamá y bebé. Todo esto y más, con nuestro invitado experto, el Dr. Raúl Garza Bulnes Datos de contacto: Celular: 8182873734 E-mail: raulgarzabulnes@me.com

ra humana beneficios celular l'h atributos la leche compuestos mirnas

Epigenetics and Epitranscriptomics in Cancer (Manel Esteller)

Epigenetics Podcast

Play Episode Listen Later Feb 24, 2022 34:02

In this episode of the Epigenetics Podcast, we caught up with Manel Esteller, Director of the Josep Carreras Leukemia Research Institute to talk about his work on Epigenetics and Epitranscriptomics in Cancer. The focus of Manel Esteller's research career and the focus of his current team is to characterize the epigenome and epitranscriptome of cancer cells in comparison to healthy cells, and their interplay. Ultimately, their goal is to use this knowledge to develop new therapies for cancer. Key achievements from the Esteller lab began with the discovery of the first miRNA that undergoes specific cancer-methylation associated silencing. The team further identified many more miRNAs that also play a role in cancer. Next to miRNAs, Manel Esteller studied the influence of lncRNAs, enhancers and DNA methylation on cancer development and progression, insights that may be used to develop cancer biomarkers and potential treatments. References Guil, S., Soler, M., Portela, A., Carrère, J., Fonalleras, E., Gómez, A., Villanueva, A., & Esteller, M. (2012). Intronic RNAs mediate EZH2 regulation of epigenetic targets. Nature Structural & Molecular Biology, 19(7), 664–670. https://doi.org/10.1038/nsmb.2315 Vizoso, M., Ferreira, H. J., Lopez-Serra, P., Carmona, F. J., Martínez-Cardús, A., Girotti, M. R., Villanueva, A., Guil, S., Moutinho, C., Liz, J., Portela, A., Heyn, H., Moran, S., Vidal, A., Martinez-Iniesta, M., Manzano, J. L., Fernandez-Figueras, M. T., Elez, E., Muñoz-Couselo, E., … Esteller, M. (2015). Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR. Nature Medicine, 21(7), 741–750. https://doi.org/10.1038/nm.3863 Agrelo, R., Cheng, W.-H., Setien, F., Ropero, S., Espada, J., Fraga, M. F., Herranz, M., Paz, M. F., Sanchez-Cespedes, M., Artiga, M. J., Guerrero, D., Castells, A., von Kobbe, C., Bohr, V. A., & Esteller, M. (2006). Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proceedings of the National Academy of Sciences of the United States of America, 103(23), 8822–8827. https://doi.org/10.1073/pnas.0600645103 Lopez-Serra, P., Marcilla, M., Villanueva, A., Ramos-Fernandez, A., Palau, A., Leal, L., Wahi, J. E., Setien-Baranda, F., Szczesna, K., Moutinho, C., Martinez-Cardus, A., Heyn, H., Sandoval, J., Puertas, S., Vidal, A., Sanjuan, X., Martinez-Balibrea, E., Viñals, F., Perales, J. C., … Esteller, M. (2014). A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect. Nature Communications, 5, 3608. https://doi.org/10.1038/ncomms4608 Rosselló-Tortella, M., Llinàs-Arias, P., Sakaguchi, Y., Miyauchi, K., Davalos, V., Setien, F., Calleja-Cervantes, M. E., Piñeyro, D., Martínez-Gómez, J., Guil, S., Joshi, R., Villanueva, A., Suzuki, T., & Esteller, M. (2020). Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer. Proceedings of the National Academy of Sciences of the United States of America, 117(34), 20785–20793. https://doi.org/10.1073/pnas.2003358117 Castro de Moura, M., Davalos, V., Planas-Serra, L., Alvarez-Errico, D., Arribas, C., Ruiz, M., Aguilera-Albesa, S., Troya, J., Valencia-Ramos, J., Vélez-Santamaria, V., Rodríguez-Palmero, A., Villar-Garcia, J., Horcajada, J. P., Albu, S., Casasnovas, C., Rull, A., Reverte, L., Dietl, B., Dalmau, D., … Esteller, M. (2021). Epigenome-wide association study of COVID-19 severity with respiratory failure. EBioMedicine, 66, 103339. https://doi.org/10.1016/j.ebiom.2021.103339 Related Episodes CpG Islands, DNA Methylation, and Disease (Sir Adrian Bird) Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard) Cancer and Epigenetics (David Jones) Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

miR-106b Suppresses Pathological Retinal Angiogenesis

Fraunhofer-Podcast: Forschung erleben – Zukunft hören

Play Episode Listen Later Dec 2, 2021 1:24

Aging-US published a Special Collection on Eye Disease which included "miR-106b suppresses pathological retinal angiogenesis" which reported that microRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. Here, the authors show that expression of the miR-106b-25 cluster is negatively regulated by the unfolded protein response pathway of protein kinase RNA-like ER kinase in a mouse model of neovascular AMD. They demonstrate that therapeutic delivery of miR-106b to the retina with lentiviral vectors protects against aberrant retinal angiogenesis in two distinct mouse models of pathological retinal neovascularization. Dr. Przemyslaw Sapieha and Dr. Vincent De Guire said, "Age-related macular degeneration (AMD) is a common [1] and complex [2, 3] disease of aging and the leading cause of irreversible loss of sight in elderly people." Early forms of AMD are characterized by subretinal lipoproteinaceous deposits, local attrition of photoreceptors and loss of visual sensitivity. Late forms of AMD are defined by geographic atrophy and/or pathologic choroidal neovascularization characterized by vascular sprouting from the choriocapillaris into the neural retina or subretinal space. Sustained reduction in retinal VEGF levels can lead to neurotoxicity and degeneration of RPE-choriocapillaris in mouse models. Importantly, assessment by fundus photography and fundus fluorescein angiography of patients on anti-VEGF therapy showed accelerated development of geographic atrophy. These findings justify the need for continued exploration of novel therapeutic interventions. Given that several inflammatory and growth factors in addition to VEGF are associated with the pathogenesis of NV AMD, a multi-targeted approach is warranted. The authors previously elucidated a specific miRNA signature in the vitreous and plasma of patients with NV AMD and observed a disease-associated increase in miR-146a and a decrease in miR-106b and miR-152. Interestingly, within this cohort, they found that both vitreous- and plasma-based miR-146a/miR-106b ratios had greater than 90% discriminatory power for classification of patients with NV AMD with an area under the receiver operating characteristic curve of 0,977 in vitreous humour and 0,915 in plasma, suggesting potential for a blood-based diagnostic. The Sapieha/De Guire Research Team concluded in their Aging-US Research Output that there are efforts to devise therapeutics that simultaneously inhibit several factors involved in retinal vascular disease given the clinical success of compounds such as Aflibercept. miRNAs regulate translation of multiple genes and hence may be considered as multi-target inhibitors. Their potential to mitigate retinal disease will grow as comprehensive landscapes of miRNAs in health and disease are established. Preclinical studies are underway for mimics or inhibition of specific miRNAs. Full Text - https://www.aging-us.com/article/202404/text Correspondence to: Przemyslaw Sapieha email: mike.sapieha@umontreal.ca and Vincent De Guire email: vdeguire.hmr@ssss.gouv.qc.ca Keywords: age related macular degeneration, miR-106b, PERK, choroidal neovascularization, angiogenesis About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

er llc mir amd rna sustained perk rpe pathological fulltext special collections retinal rnas vegf eye disease preclinical suppresses micrornas angiogenesis mirnas

Hoffnungsträger RNA

Play Episode Listen Later Oct 22, 2021 19:12

Die Begriffe DNA und RNA kennen viele Menschen schon aus dem Biologieunterricht. Dass RNAs auch als Wirk- und Impfstoffe eingesetzt werden können, war vor der Corona-Pandemie jedoch den wenigsten bekannt. Aber was genau steckt dahinter? Weiß auch jeder, welche Eigenschaften Ribonukleinsäure hat und warum gerade RNA-Moleküle die Entwicklung eines Impfstoffs gegen COVID-19 in ungewöhnlich kurzer Zeit ermöglicht haben? In der Wissenschaft ist das Potenzial von RNAs schon seit 30 Jahren kein Geheimnis mehr. Doch nicht nur in der Impfstoffentwicklung spielt die RNA-Forschung eine Rolle. 00:00 Hoffnungsträger RNA 01:29 Was ist RNA? 02:16 Wie funktioniert RNA? 03:18 Was ist mRNA, MessengerRNA? 04:42 Wie lässt sich RNA gegen Krankheiten einsetzen? 07:07 Die Hoffnungen in RNA sind berechtigt 08:29 RNA universell einsetzbar 10:03 Grundlagenforschung und angewandte Forschung 12:01 RNA gegen Krebs und Herzkreislauferkrankungen 16:14 Translation und automatisierte Medikamentenentwicklung Prof. Dr. Dr. med. Thomas Thum, Institutsleiter des Fraunhofer-Instituts für Toxikologie und Experimentelle Medizin ITEM (Hannover), arbeitet mit so genannten miRNAs – nicht-kodierenden RNA-Molekülen, deren Rolle bis vor einigen Jahren noch völlig unklar war. Mit seinem Team hat er neue therapeutische Angriffspunkte identifiziert und darauf aufbauend RNA-basierte Therapien für Patienten mit Herzinsuffizienz entwickelt und diese bereits erstmals klinisch erprobt. miRNAs haben großes Potenzial für die Entwicklung neuer diagnostischer Biomarker und Therapien – nicht nur für Herz-Kreislauf- sondern auch viele andere Erkrankungen. Warum die RNA-Forschung nicht nur Hoffnungsträger für den medizinischen Fortschritt, sondern gleichzeitig ein hervorragendes Beispiel für die Translation vom Labor zur Therapie ist, erläutert Prof. Thum im Fraunhofer-Podcast. Der mit dem Paul-Martini-Preis ausgezeichnete Kardiologe forscht seit Jahren an Therapien mit Hilfe von RNA und hat diese bereits erfolgreich gegen Herzinsuffizienz eingesetzt. FuE-Schwerpunkte von Prof. Thomas Thum https://www.item.fraunhofer.de/de/angebot/neue-institutsleitung-fraunhofer-item-2021.html Prof. Thum erhält Paul-Martini-Preis Neue Behandlung bei chronischer Herzschwäche: Institutsleiter des Fraunhofer ITEM erhält Paul-Martini-Preis 2021 https://www.item.fraunhofer.de/de/presse-medien/presseinformationen/institutsleiter-thum-erhaelt-paul-martini-preis-2021.html Website Fraunhofer ITEM https://www.item.fraunhofer.de/

Table Of Contents: Volume 12, Issue #17

Play Episode Listen Later Aug 18, 2021 7:38

Listen to the latest oncology-focused research published in this week's issue of Oncotarget, Volume 12, Issue 17. https://www.oncotarget.com/archive/v12/i17/ Research Paper (Cover) - “Scent test using Caenorhabditis elegans to screen for early-stage pancreatic cancer” https://doi.org/10.18632/oncotarget.28035 Research Paper - “The role of circulating miRNAs and CA19-9 in pancreatic cancer diagnosis” https://doi.org/10.18632/oncotarget.28038 Research Paper - “Diverse transcriptional regulation and functional effects revealed by CRISPR/Cas9-directed epigenetic editing” https://doi.org/10.18632/oncotarget.28037 Research Paper - “The protective role of Prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion” https://doi.org/10.18632/oncotarget.28041 Research Paper - “Quantitative difference of oral pathogen between individuals with gastric cancer and individuals without cancer” https://doi.org/10.18632/oncotarget.28034 Research Paper - “Exosomal and non-exosomal miRNA expression levels in patients with HCV-related cirrhosis and liver cancer” https://doi.org/10.18632/oncotarget.28036 Review- “Role of microRNAs in glioblastoma” https://doi.org/10.18632/oncotarget.28039 Editorial - “Mantle cell lymphoma patients in first relapse: we pretty much know what to do” https://doi.org/10.18632/oncotarget.27980 (PDF Download) Editorial - “UBE2T: A new molecular regulator of cancer stemness in hepatocellular carcinoma” https://doi.org/10.18632/oncotarget.28033 (PDF Download) Research Perspective - “Hypofractionation: less is more?” https://doi.org/10.18632/oncotarget.28023 Keywords - Caenorhabditis elegans, pancreatic cancer, microRNA, biomarkers, DNA methylation, acute lung injury (ALI), periodontal disease, gastric cancer, miRNA, liver cancer, glioblastoma, cancer, science, research, oncology About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

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Aging-US: MiR - 513b - 5p Represses Autophagy by Targeting PIK3R3

university research italy medicine pennsylvania cancer treating romania promising rna principal investigators ferrara bucharest md anderson rnas microrna calin kimmel center mirnas

Play Episode Listen Later Aug 17, 2021 3:14

Aging-US published "MiR-513b-5p represses autophagy during the malignant progression of hepatocellular carcinoma by targeting PIK3R3" which reported MiR-513b-5p repressed liver cancer cell proliferation, migration/invasion, and induced apoptosis in vitro. Crucially, miR-513b-5p attenuated tumor growth of liver cancer cells in vivo. In the mechanical investigation, the authors identified that PIK3R3 mRNA 3′UTR was targeted by miR-513b-5p and miR-513b-5p suppressed PIK3R3 expression. PIK3R3 overexpression partly reversed miR-513b-5p-mediated autophagy, proliferation, and apoptosis of liver cancer cells. Consequently, they concluded in their Aging-US Research Output that miR-513b-5p repressed autophagy during the malignant progression of HCC by targeting PIK3R3. MiR-513b-5p may be applied as a therapeutic target for HCC. Dr. Rongjun Nie from The Guangxi Medical University said, "Liver cancer is a prevalent malignancy and the principal reason for tumor mortality globally, in which hepatocellular carcinoma (HCC) depicts 70–85% of the entire liver carcinoma weight." As the previous studies, autophagy is a crucial process during liver cancer development and a potential therapeutic target for liver cancer therapy, but the mechanisms are poorly understood. PIK3R3 acts as an oncogene of various cancers, containing glioma, lung cancer, and gastric cancer. As several miRNAs are involved in the modulation of autophagy in HCC and based on the crucial role of miR-513b-5p in cancer development, the authors selected miR-513b-5p as an example to evaluate its function in autophagy during liver cancer progression. In the present study, they were interested in the miR-513b-5p function in the modulation of autophagy during liver cancer progression. They demonstrated that miR-513b-5p attenuated autophagy during the malignant progression of liver cancer by targeting PIK3R3. The Nie Research Team concluded in their study, "miR-513b-5p repressed autophagy during the malignant progression of HCC by targeting PIK3R3. MiR-513b-5p may be applied as a therapeutic target for HCC." Sign up for free Altmetric alerts about this article DOI - https://doi.org/10.18632/aging.203135 Full Text - https://www.aging-us.com/article/203135/text Correspondence to: Rongjun Nie email: nrj2001@163.com Keywords: hepatocellular carcinoma, autophagy, progression, miR-513b-5p, PIK3R3 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

llc targeting mir liver crucially autophagy hcc utr mirnas altmetric

George Calin, MD Discusses Promising Research on Small RNAs in Treating Cancers

Finding Genius Podcast

Play Episode Listen Later Jul 21, 2021 32:50

Dr. George Calin holds M.D. and Ph.D. degrees from Carol Davila University of Medicine in Bucharest, Romania. He completed cancer genomics training at the University of Ferrara in Italy and was a post-doctor fellow at the Kimmel Center in Pennsylvania. The focus of his work is exploring new RNA therapeutic options for cancer patients. Click on play to learn: Why research on non-coding RNAs is important and what makes them special. How studies of ultraconserved gene sequences led to the discovery of distinct signatures in human cancers. How combinatorial therapeutics for small RNAs shows promise in treating cancers. Dr. Calin is the Principal Investigator at the Calin Laboratory at MD Anderson. He is currently working on all aspects of molecular biology and biomarkers with a focus on deadly cancers such as ovarian, gastric, colon, pancreatic, and cholangiocarcinoma. It has become evident in recent cancer research that the genomic complexity of cancer cells is more significant than originally assumed. For more than 30 years, the focus was on the development and testing of new gene therapy strategies involving protein-coding genes. The research done by Dr. Calin and his colleagues has led to the concept that small non-coding RNAs knowns as microRNA genes (miRNAs) are involved in the production of human tumors. His research also showed that another family of ncRNAs, ultraconserved genes (UCGs) plays a role in cancer initiation, progression, and the mechanisms of a predisposition to cancer. Looking to the future, the results of the studies of miRNAs and ncRNAs has led to the possibilities of combinatorial therapeutics that are customized for a specific cancer patient. Dr. Calin believes that there is a strong need to focus on the early diagnosis of cancer which has the potential to increase the survival of cancer patients significantly. To learn more visit: mdanderson.org/research Episode also available on Apple Podcasts: apple.co/30PvU9C

50. Early Diagnosis of Pancreatic Cancer via ML & Treatment for Alzheimer's - Siya Goel

Drop the STEM podcast

Play Episode Listen Later Jun 7, 2021 47:04

Siya Goel @_siyagoel_ is a passionate researcher in biology and computer science!

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Stroke Alert March 2021

Stroke Alert

Play Episode Listen Later Mar 12, 2021 17:08

On Episode 2 of the Stroke Alert podcast, host Dr. Negar Asdaghi highlights two featured articles from the March 2021 issue of Stroke. This episode also features a conversation with Dr. Joan Montaner from Neurovascular Research Laboratory at the Universitat Autònoma in Barcelona, Spain, to discuss his article “D-Dimer as Predictor of Large Vessel Occlusion in Acute Ischemic Stroke.” Dr. Negar Asdaghi: Can your microRNA profile predict your future risk of stroke? Is stroke that wake-up call to finally live a healthier lifestyle, better diet, exercise more, and stop smoking? Can a simple blood test improve our clinical predictive models for presence of a large vessel occlusion in patients with suspected ischemic stroke? We have the answers and much more in today's podcast. You're listening to Stroke Alert. Stay with us. Dr. Negar Asdaghi: From the Editorial Board of Stroke, welcome to the Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami, Miller School of Medicine, and the host of the monthly Stroke Alert Podcast. In today's podcast, I'm going to interview the senior author of the study on the values of D-dimer and predicting the presence of large vessel occlusion in stroke. But first with these two articles. Dr. Negar Asdaghi: DNA noncoding sequences and introns, once thought to represent the, quote, junk DNA, quote, have been found to play an important role in the modulation of gene expression at the post transcriptional level through coding for regulatory molecules, such as microRNAs, or miRNA. Whether the presence of certain miRNAs can signal a future risk of development of stroke is unknown. In their paper titled “Circulatory MicroRNAs as Potential Biomarkers for Stroke Risk: The Rotterdam Study,” Dr. Michelle Mens and colleagues from the Department of Neurology, University Medical Center, in Rotterdam, Netherlands, discuss their findings related to microRNA samples collected between 2002 and 2005 from over 1900 stroke-free participants of the Rotterdam Study. Participants were assessed for incident stroke through continuous monitoring of medical records until January 1, 2016. Dr. Negar Asdaghi: At baseline, using next-generation sequencing, they measured expression levels of over 2083 miRNAs in plasma samples. During a mean follow-up of close to 10 years, the incidence of stroke was 7% in their study population, and they found, in total, 39 miRNAs were at least nominally related with that incidence of stroke. In their fully adjusted model, they found significant association between expression level of three particular microRNAs and risk of stroke, with the hazard ratio ranging between 1.1 to 2.6. Interestingly, the area under the curve for the longitudinal predictive models improved when the miRNA data was added to the vascular risk factor model. And in conclusion, they found miRNA 6124, 5196-5p and 4292 were associated with future risk of stroke in their population. The elevated levels of these miRNAs may serve as plasma biomarkers for predicting future risk of stroke in combination with other known vascular risk factors for stroke. Dr. Negar Asdaghi: So, speaking of vascular risk factors, let's move on to our second paper for today's podcast. There's a growing emphasis on adherence with pharmaceutical interventions, such as diabetic and blood pressure treatments, statin therapy, to control the risk factors for stroke and prevent recurrent vascular events. All the while, the non-pharmaceutical interventions, such as smoking cessation, diet control, and increased physical activity, seem to represent the somewhat easy or implied aspect of our secondary preventive efforts. But how well are stroke survivors doing with regards to making these healthy lifestyle modifications? In the March issue of Stroke, Dr. Chelsea Liu and colleagues from Johns Hopkins School of Public Health presented their findings on lifestyle and behavioral changes pertaining to cardiovascular health in the study titled, “Change in Life's Simple 7 Measure of Cardiovascular Health After Incident Stroke: The REGARDS Study.” Dr. Negar Asdaghi: So, this was a population-based, epidemiological study of over 7,000 stroke-free participants between 2003 and 2007, who had data on Life's Simple 7, what the author called “LS7 measures,” which studied seven different domains. Four of them behavioral, including smoking, diet, physical activity, body mass index, and three medication-controlled, including blood pressure, total cholesterol, and fasting glucose, both at study entry and their follow-up visit. At which point, either they did not have a stroke or had an ischemic stroke and were included if that stroke had happened more than one year before the follow-up visit. And so the study authors hypothesized that those with a stroke would have had a significant improvement in their Life's Simple 7 data poststroke as compared to the stroke-free participants. Dr. Negar Asdaghi: But what they found was completely the opposite. At 10 years follow-up, a total of 149 patients had suffered a stroke in their study. On a scale of zero to 14 at study entry, all participants scored low or relatively low in these seven simple measures, but those participants who would ultimately suffer a stroke scored significantly lower at baseline. What was alarming, though, was that after adjusting for all confounders, at follow-up, participants who had experienced an ischemic stroke showed a significantly further decline in their total LS7 score at 10-year follow-up. And the greatest declines were noted in behavioral domains, most notably physical activity and diet scores. The authors noted a non-significant improvement, in other words, improvement in weight in the BMI score among stroke survivors, but they caution that that may indeed be actually related to muscle loss, a downstream effect of decreased physical activity poststroke, rather than representing active dietary interventions with weight loss. So, in summary, this important paper highlights, on a population level, the urgent need for behavioral interventions to improve secondary prevention after a stroke event up and beyond our efforts to improve medication adherence. Dr. Negar Asdaghi: So now moving on from secondary preventative measures to the acute phase, our next paper discusses ways in which we can improve our diagnostic accuracy in the acute setting. Identification of large vessel occlusions is the first step in determining patients' eligibility for endovascular thrombectomy, a highly effective treatment to improve outcomes in acute ischemic stroke. But without vascular imaging, which may not be readily available in the small or community hospitals, the decision to transfer patients to thrombectomy-capable centers is entirely dependent on clinical scales, which, as we all know, may have suboptimal sensitivity and specificity. So the question is, could a simple blood test improve the predictive capabilities of our current clinical scales for presence of a target LVO, or large vessel occlusion? Joining me now is Dr. Joan Montaner from Neurovascular Research Laboratory at the Universitat Autònoma in Barcelona, who is the senior author of the study titled “D-Dimer as Predictor of Large Vessel Occlusion in Acute Ischemic Stroke.” Good morning, Joan, all the way from the sunny Florida to the beautiful Barcelona. Good to have you with us, and thank you for joining us. Dr. Joan Montaner: Hello. Nice to talk with you on blood biomarkers for stroke management. Dr. Negar Asdaghi: Thank you, Joan. Your study touches on the importance of improving the ways in which the systems of care are set up in triage and transfer of patients with thrombectomy-capable centers. Can you please tell us briefly about the stroke systems of care in Catalonia where you practice and where your study is based out of? And what clinical scales are currently used for transfer of patients with suspected acute stroke to a comprehensive stroke center? Dr. Joan Montaner: Yes, Catalonia, it's a region of about 7.5 million inhabitants. And when we did this study, most of the comprehensive stroke centers were located in Barcelona itself, in the capital. So it's true that there are several areas of the region that are far away from Barcelona. It took more than two hours to bring some patients from those distant regions to Barcelona. That's why we began to use these clinical scales that you are talking about. Mainly they are RACE, it's like a simplification of the NIHSS subscale. And, in fact, a large study RACE card that was presented last year in the European Stroke Conference was done to try to see if we could, by using these scales, RACE, select the right patients to come directly to the thrombectomy centers instead of going to the closest hospital. But, unfortunately, the results were neutral. So, we were a little bit disappointed, and we think, as you were saying, that these neurological scales are suboptimal, probably not enough sensitivity and specificity for identifying LVO. That's why we think that these biomarkers could improve the accuracy of those scales. Dr. Negar Asdaghi: Perfect. I totally agree with you. And now, before you tell us about the biomarkers, can you just briefly tell us about the Stroke-Chip study, your study population, and what prompted you to look at these various biomarkers that you addressed in the paper? Dr. Joan Montaner: Stroke-Chip was a lot, it was really a massive collaborative effort among all the public hospitals in this network here in Catalonia. We were able to collect more than 1,300 patients in this particular study that we are talking about. Dr. Anna Ramos-Pachón and Elena Cancio were leading the analysis on the relation of these biomarkers with LVO. But I have to say that this was not the original intention of our study. Really, and perhaps we were naive at that time, we were looking for biomarkers to differentiate ischemia from hemorrhagic strokes or from stroke mimicking conditions to try to give TPA or TNK in the ambulance. But, as I was saying, perhaps that was a little bit naive, and we know how difficult that would be and perhaps with some liabilities. That's why it came this idea of, "Well, if we use those markers, not for giving a drug in the ambulance, but for doing triage and sending the patient to the right hospital, that could be more simple and more useful even." Dr. Negar Asdaghi: Thank you very much. Can you briefly tell us about the study? What were your inclusion criteria? Dr. Joan Montaner: Well, in this study, we selected all consecutive acute stroke patients attending the stroke unit of all these hospitals. We were including all stroke suspicions, if their symptoms onset happened within six hours. So, it's really hyperacute patients. And we were able to collect, like this, more than 1,300 patients. And then at the hospital, with the angio CT or duplex, we were able to categorize those with LVO, and we measured a panel of different biomarkers in the blood stream of those patients and trying to associate which of these markers were related with having or not having an LVO. Dr. Negar Asdaghi: Very interesting. So tell us, please, your study's main finding? Dr. Joan Montaner: The main finding, what we liked more, let's say, of our results was that some of those markers, specifically NT-proBNP and D-dimer, were really high among patients with a large vessel occlusion. When we combined these results, for example, having high levels of D-dimer, those patients above fourth quartile of D-dimer with more stroke severity, patients with NIH of more than 10, the accuracy was really good. It was very specific, 93% specificity, 34% sensitivity, to predict an LVO. So this means that without almost any mistake, you select more than one third of the patients that have an LVO, that could be very useful. To bring those patients, we were talking from far away of these thrombectomy centers, to the right place. And perhaps we could be doing a thrombectomy one or two hours before with these technologies. Dr. Negar Asdaghi: Perfect. So basically, just to reiterate what you're saying, is that D-dimer, as non-specific as it is and as important as it is to note that it can be elevated in the setting of aging or increase NIH Stroke Scale severity, this increase in D-dimer noted in patients with LVO was just not a factor of just age simply or increased severity of the stroke scale. Can you tell us about your multivariate analysis and what other factors you adjusted for in your final model? Dr. Joan Montaner: You are right that D-dimer can be modified by many things, as you were saying. That's why we took a lot of care about the multivariate analysis and all factors, all clinical factors that were related with LVO were included in the model. And finally, only eight NIH Stroke Scale scores D-dimer and the vast history of atrial fibrillation were included in the model. Odds ratio for D-dimer was 1.59 that I think it's quite acceptable. And it's true that in that model, NT-proBNP was not included anymore, probably because it's related with a fee. So, that's something interesting if perhaps in the ambulance, you don't know about the story, the history of a patient, of a fee, we could use NT-proBNP, so I think this opens the possibility of using different clinical neurological scales biomarkers in combination to make the prediction of LVO. Dr. Negar Asdaghi: Yes. Very, very exciting results for sure. So what is our main takeaway from your study? Are we thinking that D-dimer or a particular level of elevations of D-dimer will one day become the, quote, Troponin equivalent of LVO for stroke? Dr. Joan Montaner: Well, it sounds nice, but I know it's several technical issues here. You are right that there is variability among labs in the measurement of D-dimer so now what we are doing is really, in a prospective study called BIO-FAST in the south of Spain, in Seville, in a large network of ambulances, we are measuring D-dimer, but in a rapid fashion with a rapid point of care test in the ambulance itself. We think that we are not going to have a magic biomarker. Not that Troponin you are talking about. Probably we need to combine it with others. We think that the marker of brain damage would add a lot on top of D-dimer, probably D-dimer is very good for the clot burden, but we think other markers could improve the accuracy of the test. And we are measuring them together with these. Our dream would be really to have cost utility study in the future and to see if really we are able to randomize patients based on these biomarkers in the ambulance, will have an impact on outcome if we are able really to do thrombectomies much faster. Dr. Negar Asdaghi: Well, we certainly look forward to covering your future studies on this topic of biomarkers. Dr. Joan Montaner, thank you for joining us and congratulations on your work. Dr. Joan Montaner: Thanks a lot. Dr. Negar Asdaghi: And this concludes our podcast. Don't forget to check online for the full list of publications, including two papers on the state of pediatric thrombectomy and a study on the association between stroke and subsequent risk of suicide that are published online ahead of their presentations at the International Stroke Conference. Until our next podcast, stay alert with Stroke Alert.

Network based multifactorial modelling of miRNA-target interactions

Play Episode Listen Later Nov 17, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.16.384826v1?rss=1 Authors: Ari Yuka, S., Yilmaz, A. Abstract: Competing endogenous RNA (ceRNA) regulations and crosstalk between various types of non-coding RNA in human is an important and under-explored subject. Several studies have pointed out that an alteration in miRNA:target interaction can result in unexpected changes due to indirect and complex interactions. In this paper, we defined a new network-based model that incorporates miRNA:ceRNA interactions with expression values and then calculates network-wide effects after perturbation in expression level of element(s) while utilizing miRNA interaction factors such as seed type, binding energy. We have carried out analysis of large scale miRNA:target networks from breast cancer patients. Highly perturbing genes identified by our approach coincide with breast cancer associated genes and miRNAs. Our network-based approach helps unveiling the crosstalk between node elements in miRNA:target network where abundance of targets leading to sponge effect is taken into account. The model has potential to reveal unforeseen and unpredicted regulations which are only evident when considered in network context. Our tool is scalable and can be plugged in with emerging miRNA effectors such as circRNAs, lncRNAs and available as R package ceRNAnetsim https://www.bioconductor.org/packages/release/bioc/html/ceRNAnetsim.html . Copy rights belong to original authors. Visit the link for more info

network target copy interactions rna modelling yilmaz biorxiv mirnas multifactorial lncrnas

In silico analysis of single nucleotide polymorphisms (SNPs) in human C-C chemokine receptor type five (CCR5) gene

Play Episode Listen Later Nov 16, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.14.382739v1?rss=1 Authors: Ali Hassan, A., Ibrahim, M. E. Abstract: Chemokines are small transmembrane proteins with immune surveillance and immune cell recruitment functions. the expression of CCR5 gene affects virus production and viral load(1). The CCR5 gene contains two introns, three exons, and two promoters, and it is necessary as a co-receptor for the entry of the macrophage-tropic HIV strains. Mutations in the coding region of CCR5 affect the protein structure, which will affect production, chemokine binding, transport, signaling and expression of the CCR5 receptor. SNPs within CCR5 gene were retrieved from ensemble database. Coding SNPs were analyzed using SNPnexus. Coding non-synonymous SNPs in CCR5 binding domains with Viral gp120 were analyzed using SIFT, PolyPhen and I-mutant tools. Project HOPE then used to modelled the 3D structure of the protein resulting from these SNPs. Non-coding SNPs that affects miRNAs in 3' rejoin were analyzing using PolymiRTS. SNPs that affect transcription factor binding were analyzed using regulomeDB. (178) non-synonyms missense SNPs were found to have deleterious and damaging effect on the structure and function of the protein. In CCR5 binding domains with Viral gp120: 3 SNPs rs145061115, rs199824195 and rs201797884 were found to affect both structure and function and stability of chemokine protein. The 2 SNPs rs185691679 and rs199722070 has a role in disruption and creation of the target sites in miRNA seeds due to their high conservation score. Mutations in CCR5 gene may explain and represent the molecular basis of the resistance to HIV infection. Copy rights belong to original authors. Visit the link for more info

3d viral hiv copy coding mutation receptor sift snps project hope biorxiv ccr5 mirnas type five chemokine single nucleotide polymorphisms

emiRIT: A text-mining based resource for microRNA information

Play Episode Listen Later Nov 6, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.05.370593v1?rss=1 Authors: Roychowdhury, D., Gupta, S., Qin, X., Arighi, C. N., Vijay-Shanker, K. Abstract: Motivation: microRNAs (miRNAs) are essential gene regulators and their dysregulation often leads to diseases. Easy access to miRNA information is crucial for interpreting generated experimental data, connecting facts across publications, and developing new hypotheses built on previous knowledge. Here, we present emiRIT, a text mining-based resource, which presents miRNA information mined from the literature through a user-friendly interface. Results: We collected 149,233 miRNA-PubMed ID pairs from Medline between January 1997 to May 2020. emiRIT currently contains miRNA-gene regulation (60,491 relations); miRNA-disease (cancer) (12,300 relations); miRNA-biological process and pathways (23,390 relations); and circulatory miRNAs in extracellular locations (3,782 relations). Biological entities and their relation to miRNAs were extracted from Medline abstracts using publicly available and in-house developed text mining tools, and the entities were normalized to facilitate querying and integration. We built a database and an interface to store and access the integrated data, respectively. Conclusion: We provide an up-to-date and user-friendly resource to facilitate access to comprehensive miRNA information from the literature on a large-scale, enabling users to navigate through different roles of miRNA and examine them in a context specific to their information needs. To assess our resource's information coverage, in the absence of gold standards, we have conducted two case studies focusing on the target and differential expression information of miRNAs in the context of diseases. Database URL: https://research.bioinformatics.udel.edu/emirit/ Copy rights belong to original authors. Visit the link for more info

resource copy biological gupta qin microrna medline biorxiv text mining mirnas

Computational prediction of SARS-CoV-2 encoded miRNAs and their putative host targets

Play Episode Listen Later Nov 3, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.02.365049v1?rss=1 Authors: Verma, S., Dwivedy, A., Kumar, N., Biswal, B. K. Abstract: Background: Over the past two decades, there has been a continued research on the role of small non-coding RNAs including microRNAs (miRNAs) in various diseases. Studies have shown that viruses modulate the host cellular machinery and hijack its metabolic and immune signaling pathways by miRNA mediated gene silencing. Given the immensity of coronavirus disease 19 (COVID-19) pandemic and the strong association of viral encoded miRNAs with their pathogenesis, it is important to study Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) miRNAs. Results: To address this unexplored area, we identified 8 putative novel miRNAs from SARS-CoV-2 genome and explored their possible human gene targets. A significant proportion of these targets populated key immune and metabolic pathways such as MAPK signaling pathway, maturity-onset diabetes of the young, Insulin signaling pathway, endocytosis, RNA transport, TGF-{beta} signaling pathway, to name a few. The data from this work is backed up by recently reported high-throughput transcriptomics datasets obtains from SARS-CoV-2 infected samples. Analysis of these datasets reveal that a significant proportion of the target human genes were down-regulated upon SARS-CoV-2 infection. Conclusions: The current study brings to light probable host metabolic and immune pathways susceptible to viral miRNA mediated silencing in a SARS-CoV-2 infection, and discusses its effects on the host pathophysiology. Copy rights belong to original authors. Visit the link for more info

covid-19 predictions studies analysis copy targets sars cov kumar insulin rna computational rnas encoded tgf biorxiv mirnas mapk putative micrornas mirnas results to

An Algorithmic framework for genome-wide identification of Sugarcane (Saccharum officinarum)-encoded microRNA Targets against SCBV

Play Episode Listen Later Oct 25, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.25.353821v1?rss=1 Authors: Ashraf, M. A., Feng, X., Hu, X., Ashraf, F., Shen, L., Zhang, S. Abstract: Sugarcane Bacilliform Virus (SCBV) is considered an economically the most damaging pathogen for sugarcane production worldwide. Three ORFs are characterized in a single molecule of circular, ds-DNA genome of the SCBV, encoding for hypothetical protein (ORF1), DNA binding protein (ORF2) and Polyprotein (ORF3). The study was aimed to predict and comprehensively evaluate sugarcane miRNAs for the silencing of SCBV genome using in-silico algorithms. Computational methods were used for prediction of candidate miRNAs from sugarcane (S. officinarum L.) to silence the expression of SCBV genes through translational inhibition by mRNA cleavage. Mature sugarcane miRNAs were retrieved and were assessed to hybridization with the SCBV genome. A total of fourteen potential candidate miRNAs from sugarcane were computed by all the algorithms used for the silencing of SCBV. A consensus of three algorithms predicts hybridization sites of sof-miR159e at common locus 5534. The miRNA-mRNA interaction was estimated by computing free-energy of miRNA-mRNA duplex using RNAcofold algorithm. Regulatory network of predicted candidate miRNAs of sugarcane with SCBV ORFs, generated using Circos, identify novel targets. Consequently, detecting and discarding inefficient amiRNAs prior to cloning would help suppressed mutants faster. The efficacy of predicted candidate miRNAs was evaluated to test the survival rate of the in vitro amiRNA-mediated effective badnaviral silencing and resistance in sugarcane cultivars. Copy rights belong to original authors. Visit the link for more info

High precision in microRNA prediction: a novel genome-wide approach based on convolutional deep residual networks

deep predictions wide networks precision genome residual rnas microrna biorxiv mirnas convolutional

Play Episode Listen Later Oct 25, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.23.352179v1?rss=1 Authors: Yones, C. A., Raad Macchiaroli, J., Bugnon, L., Milone, D. H., Stegmayer, G. Abstract: Motivation: MicroRNAs (miRNAs) are small non-coding RNAs that have a key role in the regulation of gene expression. The importance of miRNAs is widely acknowledged by the community nowadays, and the precise prediction of novel candidates with computational methods is still very needed. This could be done by searching homologous with sequence alignment tools, but this will be restricted only to sequences very similar to the known miRNA precursors (pre-miRNAs). Furthermore, other important properties of pre-miRNAs, such as the secondary structure, are not taken into account by these methods. Many machine learning approaches were proposed in the last years to fill this gap, but these methods were tested in very controlled conditions, which are not fulfilled, for example, when predicting in newly sequenced genomes, where no miRNAs are known. If these methods are used under real conditions, the precision achieved is far from the one published. Results: This work provides a novel approach for dealing with the computational prediction of pre-miRNAs: a convolutional deep residual neural network. The proposed model has been tested on several complete genomes of animals and plants, achieving a precision up to 5 times higher than other approaches at the same recall rates. Also, a novel validation methodology is used to ensure that the performance reported can be achieved when using the method on new unknown species. Availability: To provide fast an easy access to mirDNN, a web demo is available in http://sinc.unl.edu.ar/web-demo/mirdnn/. It can process fasta files with multiple sequences to calculate the prediction scores, and can generate the nucleotide importance plots. The full source code of this project is available at http://sourceforge.net/projects/sourcesinc/files/mirdnn Contact: cyones@sinc.unl.edu.ar Copy rights belong to original authors. Visit the link for more info

From miRNA target gene network to miRNA function: miR-375 might regulate apoptosis and actin dynamics in the heart muscle via Rho-GTPases-dependent pathways

Play Episode Listen Later Oct 21, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.20.344556v1?rss=1 Authors: Osmak, G., Kiselev, I., Baulina, N., Favorova, O. Abstract: MicroRNAs (miRNAs) are short single-stranded non-coding RNA molecules, which are involved in regulation of main biological processes, such as apoptosis, cell proliferation and differentiation, through sequence-specific interaction with target mRNAs. In this study we propose a workflow for predicting miRNAs function by analyzing the structure of the network of their target genes. This workflow was applied to study the functional role of miR-375 in the heart muscle (myocardium), since this miRNA was previously shown to be associated with heart diseases and data on its function in myocardium are mostly unclear. We identified PIK3CA, RHOA, MAPK3, PAFAH1B1, CTNNB1, MYC, PRKCA, ERBB2, and CDC42 as key genes in the miR-375 regulated network and predicted the possible function of miR-375 in the heart muscle, consisting mainly in the regulation of the Rho-GTPases-dependent signalling pathways. We implemented our algorithm for miRNA function prediction into Python module, which is available at GitHub (https://github.com/GJOsmak/miRNET). Copy rights belong to original authors. Visit the link for more info

network target muscle copy dynamics function pathways python mir github dependent regulate rna real housewives of atlanta actin apoptosis myc biorxiv mrnas mirnas pik3ca ctnnb1 erbb2 gtpases cdc42

Randy Schekman Part 3: How Human Cells Secrete Small RNAs in Extracellular Vesicles

iBiology Videos

Play Episode Listen Later Oct 17, 2020 38:41

Schekman outlines exosome biogenesis. Exosomes are extracellular vesicles released by the cell, and in contrast to intracellular vesicles, exosomes contain small molecules of RNA. Schekman's laboratory characterized the RNAs contained in exosomes and showed the importance of Ybx1 protein for the recruitment of certain miRNAs into exosomes.

rna exosomes rnas secrete extracellular human cells mirnas vesicles randy schekman

Differential gene expression in the interactome of the Human Dopamine transporter in the context of Parkinson's disease

Play Episode Listen Later Oct 12, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.12.336388v1?rss=1 Authors: NAVARRO, R. C., Ligia Scott, A., Allison Philot, E., Atencio, L., Fernandez Ponce, C., Aroca Martinez, G., Cadena Bonfanti, A., Gomez Escorcia, l., Navarro Quiroz, E. Abstract: Abstract: Background: The human dopamine transporter is the main regulator of dopamine tone and an intricate network exists to regulate the expression, conformation, and kinetics of the hDAT. hDAT dysfunction is directly related to Parkinson's disease. The objective of this work is to evaluate the differential gene expression in the interactome of the Dopamine transporter in the context of Parkinson's disease. Methods:To do this, we evaluated hDAT interaction data in string-db, mint.bio, IntAct, reactome, hprd and BioGRID, subsequently, data was obtained from the differential gene expression of mRNA and miRNAs for this hDAT interactome in the context of PD. Results: The analysis of the differential expression changes of genes of the hDAT interactome in tissues of patients with PD compared with tissues of individuals without PD, allowed to identify an expression pattern of 32 components of the hDAT interactome, of which 31 presented a negative change proportion in PD. Conclusions: We found a total of 90 miRNAs that could regulate the expression of 27 components of the hDAT interactome, at the same time, 39 components of the hDAT interactome may participate in 40 metabolic pathways. Together, these findings show a systematic effect on the hDAT-mediated dopamine internalization process in patients with Parkinson's, which would contribute to a greater susceptibility to neuronal oxidative stress in PD patients. Copy rights belong to original authors. Visit the link for more info

context parkinson copy dopamine mrna pd transporter intact differential parkinson's disease gene expression atencio biorxiv mirnas methods to

Oncotarget - Exosomes Secreted Under Hypoxia Enhance Stemness In Ewing's Sarcoma

Play Episode Listen Later Oct 8, 2020 4:08

The cover for issue 40 of Oncotarget features Figure 5, "miR-210 silences the proapoptosis member CASP8AP2," by Kling, et al. which reported that hypoxic Ewing's sarcoma cells release exosomes that promote sphere formation, a stem-like phenotype, in EWS cells by enhancing survival. Analysis of the hypoxic exosomal miRNA cargo identified a HIF-1α regulated miRNA, miR-210, as a potential mediator of sphere formation in cells exposed to hypoxic exosomes. The knockdown of HIF-1α in hypoxic EWS cells led to decreased exosomal miR-210 levels and reduced the capacity of hypoxic exosomes to form spheres. Inhibition of miR-210 in hypoxic spheres attenuated sphere formation and overexpression of miR-210 in normoxic spheres significantly enhanced the number of EWS spheres. Together, the findings in this Oncotarget study suggest that hypoxic exosomes promote stemness in EWS cells by delivering enriched miR-210 that is capable of down-regulating apoptotic pathways, resulting in the survival of cells with increased sphere formation. Dr. Shantaram S. Joshi from The University of Nebraska Medical Center said, "Ewing's sarcoma (EWS) is an aggressive and highly malignant bone tumor that develops in children and adolescents." HIF -1α has been demonstrated to regulate tumor formation and stem cell survival in hypoxic cancer cells by inhibiting apoptosis. Emerging evidence indicates intercellular communication between tumor cells in hypoxic and normoxic regions contributes to functional differences associated with hypoxic tumors. Other reports demonstrated that shCD99 EWS-derived exosomes could transfer enriched miR-34a to recipient EWS cells and stimulate neural differentiation while in another study, EWS-derived exosomes carrying EZH2 mRNA could be delivered intact to mesenchymal stem cells. Studies in other cancer models investigating the role of hypoxic exosomes have provided insight into how hypoxic tumors can secrete exosomes that propagate an aggressive phenotype in cells outside the hypoxic niche. Exosomes released from hypoxic prostate cancer cells enhanced sphere formation in normoxic cells, but the authors were unable to elucidate a mechanism describing how hypoxic exosomes promote stemness in normoxic cells. The Joshi Research Team concluded in their Oncotarget Research Paper that this study describes a mechanism whereby EWS cells under hypoxic conditions release exosomes that enhance stemness in EWS cells. The authors identified a hypoxia regulated miRNA significantly expressed in hypoxic cells and HypoxicEXO and characterized a potential target that facilitates an apoptotic pathway critical to sphere formation. Ongoing studies are investigating the role of HIF-1α on regulating EWS stemness and together, the authors future aim is to investigate how HIF-1α selectively modulates the packaging of miRNAs into HypoxicEXO, and validate additional miRNAs that promote aggressive hypoxic phenotypes. Sign up for free Altmetric alerts about this article DOI - https://doi.org/10.18632/oncotarget.27702 Full text - https://www.oncotarget.com/article/27702/text/ Correspondence to - Shantaram S. Joshi - ssjoshi@unmc.edu Keywords - exosomes, hypoxia, Ewing's sarcoma, stemness, miR-210 About Oncotarget Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget 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 please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105

university llc soundcloud reddit figure studies emerging analysis ongoing enhance mir ewing joshi correspondence kling inhibition hypoxia nebraska medical center exosomes ews hif mirnas secreted altmetric oncotarget ewing's sarcoma

CancerMIRNome: a web server for interactive analysis and visualization of cancer miRNome data

レアジョブ英会話 Daily News Article Podcast

Play Episode Listen Later Oct 5, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.04.325670v1?rss=1 Authors: Li, R., Qu, H., Wang, S., Wang, X., Cui, Y., Yu, L., Chater, J. M., Zhou, R., Jia, Q., Traband, R., Yuan, D., Zhu, J., Zhong, W.-D., Jia, Z. Abstract: MicroRNAs (miRNAs), which play critical roles in gene regulatory networks, have emerged as promising biomarkers for a variety of human diseases, including cancer. In particular, circulating miRNAs that are secreted into circulation exist in remarkably stable forms, and have enormous potential to be leveraged as non-invasive diagnostic biomarkers for early cancer detection. The vast amount of miRNA expression data from tens of thousands of samples in various types of cancers generated by The Cancer Genome Atlas (TCGA) and circulating miRNA data produced by many large-scale circulating miRNA profiling studies provide extraordinary opportunities for the discovery and validation of miRNA signatures in cancer. Novel and user-friendly tools are desperately needed to facilitate the data mining of such valuable cancer miRNome datasets. To fill this void, we developed CancerMIRNome, a web server for interactive analysis and visualization of cancer miRNome data based on TCGA and public circulating miRNome datasets. A series of cutting-edge bioinformatics tools and functions have been packaged in CancerMIRNome, allowing for a pan-cancer analysis of a miRNA of interest across multiple cancer types and a comprehensive analysis of cancer miRNome at the dataset level. The CancerMIRNome web server is freely available at http://bioinfo.jialab-ucr.org/CancerMIRNome. Copy rights belong to original authors. Visit the link for more info

data cancer copy visualizations wang interactive yuan yu zhou zhu jia cui zhong webserver biorxiv chater mirnas tcga

Scientists Discover Possible Hair Loss Treatment

Play Episode Listen Later Sep 22, 2020 2:02

Scientists from the North Carolina State University discovered a specific molecule that stimulates hair growth. At present, hair loss is treated with very expensive transplants and medications that require frequent application. However, many of the current methods are often ineffective. This prompted the researchers to explore alternative means to stimulate hair growth. They conducted an experiment with dermal papillae (DP) cells, which are cells that control the development of hair follicles, and discovered the molecule that signals hair growth. This molecule is a type of MicroRNA (MiRNA), which are molecules that regulate communication. For the experiment, the researchers took samples of the DP cells and cultivated them in the lab. To activate the cells, they created an environment similar to the area around the hair where the cells are normally found. Once the cultured cells were activated, the researchers transplanted them on mice with bald spots. Results showed that after 15 days, the mice that underwent transplant regrew 90% of their hair. The researchers found that the DP cells had a certain type of MiRNA that stimulated hair growth. According to lead author Ke Cheng, the DP cells they cultivated showed great promise as a treatment for baldness. However, they need to be grown, preserved, and then injected into the scalp. In contrast, MiRNAs can be used in topical treatments like creams and lotions. Cheng believes that medication made with MiRNA molecules can have an effect similar to DP cell treatments while posing fewer problems. The researchers are planning to analyze MiRNAs in future studies.

health english discover dna treatments scientists results dp cheng hair loss north carolina state university mirnas

An evolutionarily acquired microRNA shapes development of mammalian cortical projections

Play Episode Listen Later Sep 8, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.08.286955v1?rss=1 Authors: Diaz, J. L., Siththanandan, V., Lu, V., Gonzalez-Nava, N., Pasquina, L., MacDonald, J., Woodworth, M. B., Ozkan, A., Nair, R., He, Z., Sahni, V., Sarnow, P., Palmer, T. D., Macklis, J., Tharin, S. Abstract: The corticospinal tract is unique to mammals and the corpus callosum is unique to placental mammals (eutherians). The emergence of these structures is thought to underpin the evolutionary acquisition of complex motor and cognitive skills. Corticospinal motor neurons (CSMN) and callosal projection neurons (CPN) are the archetypal projection neurons of the corticospinal tract and corpus callosum, respectively. Although a number of conserved transcriptional regulators of CSMN and CPN development have been identified in vertebrates, none are unique to mammals and most are co-expressed across multiple projection neuron subtypes. Here, we discover seventeen CSMN-enriched microRNAs (miRNAs), fifteen of which map to a single genomic cluster that is exclusive to eutherians. One of these, miR-409-3p, promotes CSMN subtype identity in part via repression of LMO4, a key transcriptional regulator of CPN development. In vivo, miR-409-3p is sufficient to convert deep-layer CPN into CSMN. This is the first demonstration of an evolutionarily acquired miRNA in eutherians that refines cortical projection neuron subtype development. Our findings implicate miRNAs in the eutherians increase in neuronal subtype and projection diversity, the anatomic underpinnings of their complex behavior. Copy rights belong to original authors. Visit the link for more info

development copy projections shapes mir macdonald acquired nair woodworth cortical microrna mammalian cpn biorxiv evolutionarily mirnas micrornas mirnas

MiREDiBase: a manually curated database of editing events in microRNAs

Play Episode Listen Later Sep 6, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.04.283689v1?rss=1 Authors: Marceca, G. P., Distefano, R., Tomasello, L., Lagana, A., Russo, F., Calore, F., Romano, G., Bagnoli, M., Gasparini, P., Ferro, A., Acunzo, M., Ma, Q., Croce, C. M., Nigita, G. Abstract: MicroRNAs (miRNAs) are a class of regulatory small non-coding RNAs that modulate gene expression. As such, miRNAs are indirectly involved in most cellular mechanisms, including cell differentiation, proliferation, survival, and homeostasis. Several different mechanisms finely regulate miRNA expression levels and functions. Among these, miRNA editing is a type of epitranscriptomic modification that alters the original nucleotide sequence of selected miRNAs, possibly influencing their conformational state and target-binding ability. To date, adenosine-to-inosine (A-to-I) and cytosine-to-uracil (C-to-U) RNA editing are recognized as the "canonical" editing types, with the A-to-I type being the predominant one. A comprehensive resource explicitly dedicated to miRNA editing data collection is still missing. Here we present MiREDiBase, a manually curated catalog of editing events in miRNAs. Overall, the current version includes 3059 unique A-to-I and C-to-U editing sites occurring in 626 human miRNA transcripts and three different species of non-human primates. Each editing event is provided with essential information and key relevant details, including biological sample, detection method, enzyme-dependent affinity, editing level, and biological function. Editing events in human mature miRNAs were provided with miRNA-target predictions and enrichment analysis. Minimum free energy structures were inferred for editing events falling into pre-miRNA regions, aiming to help users to interpret the biological information. MiREDiBase represents a valuable tool for cell biology and biomedical research, continuously updated, improved, and expanded with new data from the literature. MiREDiBase is available at https://ncrnaome.osumc.edu/miredibase. Copy rights belong to original authors. Visit the link for more info

events editing copy minimum russo databases romano ferro curated distefano croce rnas calore micrornas gasparini tomasello biorxiv bagnoli lagana mirnas acunzo

BrumiR: A toolkit for de novo discovery of microRNAs from sRNA-seq data.

Play Episode Listen Later Aug 7, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.07.240689v1?rss=1 Authors: Moraga, C., Sanchez, E., Galvao Ferrarini, M., Gutierrez, R. A., Vidal, E. A., Sagot, M.-F. Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that are key players in the regulation of gene expression. In the last decade, with the increasing accessibility of high-throughput sequencing technologies, different methods have been developed to identify miRNAs, most of which rely on pre-existing reference genomes. However, when a reference genome is absent or is not of high quality, such identification becomes more difficult. In this context, we developed BrumiR, an algorithm that is able to discover miRNAs directly and exclusively from sRNA-seq data. We benchmarked BrumiR with datasets encompassing animal and plant species using real and simulated sRNA-seq experiments. The results demonstrate that BrumiR reaches the highest recall for miRNA discovery, while at the same time being much faster and more efficient than the state-of-the-art tools evaluated. The latter allows BrumiR to analyze a large number of sRNA-seq experiments, from plants or animals species. Moreover, BrumiR detects additional information regarding other expressed sequences (sRNAs, isomiRs, etc.), thus maximizing the biological insight gained from sRNA-seq experiments. Finally, when a reference genome is available, BrumiR provides a new mapping tool (BrumiR2ref) that performs an a posteriori exhaustive search to identify the precursor sequences. The code of BrumiR is freely available at https://github.com/camoragaq/BrumiR. Copy rights belong to original authors. Visit the link for more info

data discovery copy sanchez toolkit gutierrez vidal de novo rnas micrornas biorxiv srna mirnas srnas

Integrated Bioinformatics Analysis Deciphering the microRNA Regulation in Protein-Protein Interaction Network in Lung Adenocarcinoma

PaperPlayer biorxiv genetics

Play Episode Listen Later Aug 4, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.01.232306v1?rss=1 Authors: Sengupta, P., Saha, S., Maji, M., Ghosh, M. Abstract: Background: The architecture of the protein-protein interaction (PPI) network in any organism relies on their gene expression signature. microRNAs (miRNAs) have recently emerged as major post transcriptional regulators that control PPI by targeting mainly untranslated regions of the gene encoding proteins. Here, we aimed to unveil the role of miRNAs in the PPI network for identifying potential molecular targets for lung adenocarcinoma (LUAD). Materials and methods: The expression profiles of miRNAs and mRNAs were collected from the NCBI Gene Expression Omnibus (GEO) database (GSE74190 and GSE116959). Abnormally expressed mRNAs from the data were appointed to construct a PPI network and hence incorporated with the miRNA-mRNA regulatory network. The miRNAs and mRNAs in this network were subjected to functional enrichment. Through the network analysis, hubs were identified and their mutation rate and probability of cooccurrence were calculated. Results: We identified 17 miRNAs and 429 mRNAs signature for differentially altered transcriptome in LUAD. The combined miRNA-mRNA regulatory network exhibited scale-free characteristics. Network analysis showed 5 miRNA (including hsa-miR-486-5p, hsa-miR-200b-5p, and hsa-miR-130b-5p) and 10 mRNA (including ASPM, CCNB1, TTN, TPX2, and BIRC5) which expressively contribute in the LUAD. We further investigated the hub genes and noticed that ASPM and TTN had the maximum rate of mutation and possessed a high tendency of cooccurrence in LUAD. Conclusion: This study provides a unique network approach to the exploration of the underlying molecular mechanism in LUAD. Identified mRNAs and miRNAs may therefore, serve as significant prognostic predictors and therapeutic targets. Copy rights belong to original authors. Visit the link for more info

KH domain containing RNA-binding proteins coordinate with microRNAs to regulate Caenorhabditis elegans development

Play Episode Listen Later Aug 4, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.03.235127v1?rss=1 Authors: Haskell, D., Zinovyeva, A. Abstract: microRNAs (miRNAs) and RNA binding proteins (RBPs) regulate gene expression at the post-transcriptional level, but the extent to which these key regulators of gene expression coordinate and the precise mechanisms of their coordination are not well understood. RNA binding proteins often have recognizable RNA binding domains that correlate with specific protein function. Recently, several RBPs containing K Homology (KH) RNA binding domains were shown to work with miRNAs to regulate gene expression, raising the possibility that KH domains may be important for coordinating with miRNA pathways in gene expression regulation. To ascertain whether additional KH domain proteins functionally interact with miRNAs during Caenorhabditis elegans development, we knocked down twenty-four genes encoding KH-domain proteins in several miRNA sensitized genetic backgrounds. Here, we report that a majority of the KH domain-containing genes genetically interact with multiple miRNAs and Argonaute alg-1. Interestingly, two KH domain genes, predicted splicing factors sfa- and asd-2, genetically interacted with all of the miRNA mutants tested, while other KH domain genes exhibited functional interactions only with specific miRNAs. Our domain architecture and phylogenetic relationship analyses of the C. elegans KH domain-containing proteins revealed potential groups that may share both structure and function. Collectively, we show that many C. elegans KH domain RBPs functionally interact with miRNAs, suggesting direct or indirect coordination between these two classes of post-transcriptional gene expression regulators. Copy rights belong to original authors. Visit the link for more info

development copy domain binding collectively regulate rna proteins kh coordinate micrornas biorxiv elegans caenorhabditis mirnas argonaute

Dr Axel Heiser: Research to find new Covid test and light technology to combat virus

Early Edition with Kate Hawkesby

Play Episode Listen Later Jul 16, 2020 4:52

Research to find a new method to detect Covid-19 infection before the onset of symptoms and the development of a new light sterilisation method to kill the virus on surfaces and in the air are being led by AgResearch.Funded by the Government, the research is part of New Zealand's response to the Covid-19 pandemic.The first research aims to identify Covid-19 cases within hours of infection. The project will focus on finding a molecular pattern that signals a human body's response to the virus."The current testing methods for Covid-19 are detecting the viral RNA, but the virus needs to grow for a few days until its RNA can be found in the samples taken for the test," said AgResearch principal scientist Dr Axel Heiser.Dr Gale Brightwell and post-doctoral scientist Shuyan Wu working on the light sterilisation research. Photo / Supplied."We want to measure what we call microRNA molecules (miRNAs). The body's cells make thousands of different miRNAs to control their response to diseases."Scientists at the crown research institute will be joined by other experts from ESR and the University of Otago.The method involving detection of patterns relating to miRNAs has been used successfully to diagnose cattle infected with Johne's Disease.Scientist Sandeep Gupta said the aim was to discover the miRNAs immediately after virus infection and to find a pattern that was specific to the presence of Covid-19."We can then develop a test that detects this pattern and therefore tells us the disease is present within hours of infection in otherwise asymptomatic people," Gupta said."This test will make targeted contact tracing far more effective and could help make long quarantine measures unnecessary for people travelling to NZ."AgResearch said if proven effective, this diagnostic method would have a test trialled and potentially made available within a year to 18 months.The second research aims to develop a unique technology that uses different forms of light to kill the virus causing Covid-19 and other harmful viruses.AgResearch scientists will work with counterparts from Massey University and the Christchurch firm Energylight Group Ltd on this.Team leader Dr Gale Brightwell said they would look at combing ultraviolet light with blue light, through LEDs (light emitting diodes) for the antiviral treatment."Once we have proven the light combination is effective, there will be potential to move to develop and test prototype combinations for commercial light fittings that can sterilise surfaces, disinfect circulating air, and treat parcels/baggage – all with minimal management day to day," Brightwell said."Examples could be for use in airports, shopping malls and public toilets."Brightwell says another major advantage of light sanitisation over other sterilisation methods is that it is not known to result in micro-organisms developing resistance to the treatment.An AgResearch spokesman said it was leading these projects because it has relevant knowledge and expertise, and scientists leading both projects are based in Palmerston North.The organisation received funding of $250,000 for the early detection research and $300,000 for the lighting technology project.

Functional and molecular early enteric biomarkers for Parkinson's disease in mice and men

Play Episode Listen Later Jun 8, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.06.136556v1?rss=1 Authors: Gries, M., Christmann, A., Schulte, S., Weyland, M., Rommel, S., Martin, M., Baller, M., Roeth, R., Schmitteckert, S., Unger, M., Liu, Y., Sommer, F., Muehlhaus, T., Schroda, M., Timmermans, J.-P., Pintelon, I., Rappold, G. A., Britschgi, M., Lashuel, H., Menger, M. D., Laschke, M. W., Niesler, B., Schaefer, K.-H. Abstract: Parkinson's disease (PD) usually has a late clinical onset. The lack of early biomarkers for the disease represents a major challenge for developing timely treatment interventions. Here, we use an alpha-synuclein-overexpressing transgenic (Th-1-SNCA-A30P) mouse model of PD to identify appropriate candidate markers in the gut for early stages of PD before hallmark symptoms begin to manifest. A30P mice did not show alterations in gait parameters at 2 months of age, and these mice were therefore defined as pre-symptomatic A30P mice (psA30P). We discovered early functional motility changes in the gut and early molecular dysregulations in the myenteric plexus of psA30P mice by comparative protein and miRNA profiling and cell culture experiments. We found that the proteins neurofilament light chain, vesicle-associated membrane protein 2 and calbindin 2, together with the miRNAs that regulate them, are potential biomarkers of early PD that may facilitate timely treatment and/or prevention of PD in men. Copy rights belong to original authors. Visit the link for more info

sommer copy functional mice pd molecular liu baller schaefer biomarkers schulte unger parkinson's disease rommel timmermans menger biorxiv weyland enteric mirnas

Oncotarget: Anticancer Effect Of Physical Activity Is Mediated

Play Episode Listen Later Jun 3, 2020 3:47

Volume 11, Issue 22 of Oncotarget reported that the goal of this study was to explore the involvement of mi RNAs in beneficial effects exerted by physical activity in breast cancer prevention. The levels of extracellular mi RNAs were evaluated in blood plasma before and after structured exercise by means of microarray analysis of 1,900 mi RNAs identifying mostly modulated mi RNAs. The different expressions of two mi RNAs involved in breast cancer progression, i. e. up-regulation of mi R-206 and down-regulation of anti-miR-30c, were the most striking effects induced by exercise. The biological effects of these mi RNAs were investigated in MCF-7 human breast cancer cells. The evaluation of these mi RNAs in the blood can be used as non-invasive biomarkers for breast cancer prevention. Dr. Alessandra Pulliero from the Department of Health Sciences at The University of Genoa said, "The relevance of structured exercise for public health has been addressed by the World Health Organization, and its lack is estimated to be the main risk factor for 21–25% of breast and colon cancer cases, 27% of diabetes cases, and 30% of ischemic heart disease cases." Breast cancer survivors engaging in structured exercise increase the drainage of lymph from their upper limbs, thereby decreasing the side effects of mastectomy, significantly lowering their risk of cancer relapse and improving their immune functions. Structured exercise improves insulin resistance, reduces hyperinsulinaemia and reduces the risk for diabetes, which could explain the link between increased structured exercise and reduced risk for these cancers. Recent findings indicate that women with a history of breast cancer who engage in more than 9 metabolic equivalent h/week of structured exercise after a breast cancer diagnosis had a significantly lower risk of death or breast cancer recurrence than women who were physically inactive. Incubation of MCF-7 estrogen-responsive breast cancer cells and MDA-MB-231 triple-negative breast cancer cells treated with post-exercise serum, from both healthy volunteers and operated cancer patients resulted in a reduction of breast cancer cell viability in comparison with breast cancer cells incubated with pre-exercise sera. Accordingly, the authors analyzed circulating mi RNAs expression profiles before and after structured exercise and evaluated their potential anti-cancer properties in breast cancer cells. The Pulliero Research Team concluded in their Oncotarget Research Article, "this study provides evidence that miRNA modulation is a specific molecular mechanism through which structured exercise exerts preventive effects against cancer. The possibility of using these two miRNAs for breast cancer prevention is of interest. MicroRNA as delivered by lipid nanoparticles has been already been effective in mice in preventing NNK induced lung cancer [46]. However, insofar no similar experiments exist as far as concern breast cancer prevention. Moreover, the evaluation of miR-206 and anti-miR-30c levels in the blood of breast cancer patients could be useful as non-invasive biomarkers in guiding future strategies for cancer prevention." DOI - https://doi.org/10.18632/oncotarget.27609 Full text - https://www.oncotarget.com/article/27609/text/ Correspondence to - Alessandra Pulliero - alessandra.pulliero@unige.it About Oncotarget Oncotarget is a weekly, peer-reviewed, open-access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget 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 please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

Deep sncRNA-seq of the PPMI cohort to study Parkinson's disease progression

Play Episode Listen Later Jun 1, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.01.127092v1?rss=1 Authors: Kern, F., Fehlmann, T., Violich, I., Alsop, E., Hutchins, E., Kahraman, M., Grammes, N. L., Guimaraes, P., Backes, C., Poston, K., Casey, B., Balling, R., Geffers, L., Krueger, R., Galasko, D., Mollenhauer, B., Meese, E., Wyss-Coray, T., Craig, D. W., Van Keuren-Jensen, K., Keller, A. Abstract: Coding and non-coding RNAs have diagnostic and prognostic importance in Parkinson's diseases (PD). We studied circulating small non-coding RNAs (sncRNAs) in 7,003 samples from two longitudinal PD cohorts (Parkinson's Progression Marker Initiative (PPMI) and Luxembourg Parkinson's Study (NCER-PD)) and modelled their influence on the transcriptome. First, we sequenced sncRNAs in 5,450 blood samples of 1,614 individuals in PPMI. The majority of 323 billion reads (59 million reads per sample) mapped to miRNAs. Other covered RNA classes include piRNAs, rRNAs, snoRNAs, tRNAs, scaRNAs, and snRNAs. De-regulated miRNAs were associated with the disease and disease progression and occur in two distinct waves in the third and seventh decade of live. Originating mostly from a characteristic set of immune cells they resemble a systemic inflammation response and mitochondrial dysfunction, two hallmarks of PD. By profiling 1,553 samples from 1,024 individuals in the NCER-PD cohort using an independent technology, we validate relevant findings from the sequencing study. Finally, network analysis of sncRNAs and transcriptome sequencing of the original cohort identified regulatory modules emerging in progressing PD patients. Copy rights belong to original authors. Visit the link for more info

Cooperative action of miR-124 and ISX9 in instructing direct reprogramming of mouse astrocytes to induced-neurons in vitro and in vivo

Play Episode Listen Later Jun 1, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.01.127126v1?rss=1 Authors: Papadimitriou, E., Koutsoudaki, P. N., Karamitros, T., Karagkouni, D., Chroni-Tzartou, D., Margariti, M., Gkemisis, C., Xingi, E., Thanou, I., Tzartos, S. J., Hatzigeorgiou, A. G., Thomaidou, D. Abstract: miR-124 plays a major regulatory role in neurogenesis and neuronal differentiation during brain development through control of its multiple non-neuronal targets and has therefore been employed in direct reprogramming protocols supplementary to neurogenic TFs, and other miRNAs to enhance neurogenic conversion. However, its capacity to instruct neurogenic conversion of astrocytes and its independent mechanism of direct reprogramming action have been poorly investigated. Aim of the study was to investigate whether miR-124 is a master-regulatory reprogramming agent, potent to drive direct reprogramming of astrocytes to induced-neurons (iNs) on its own and to elucidate its mechanism of reprogramming action. To this end we overexpressed miR-124 either alone or in combination with the small neurogenic compound ISX9 both in vitro and in in vivo in a mouse mechanical cortical trauma model and analyzed their mechanism of reprogramming action. Our data indicate that miR-124 and ISX9 exhibit both unique and convergent molecular contributions in the reprogramming process to iNs. miR-124 is a potent driver of the astrocytic reprogramming switch of astrocytes towards an immature neuronal fate by repressing genes regulating astrocytic function, among which we identified the RNA-binding protein Zfp36l1 as a novel miR-124 direct target. We also provide evidence that ISX9 greatly improves both miR-124-induced reprogramming efficiency and functional maturation of iNs. Importantly, miR-124 either alone or along with ISX9 is potent to guide direct neuronal reprogramming of reactive astrocytes to iNs of cortical identity in vivo, a novel finding confirming the robust direct reprogramming action of the two molecules in activated astrocytes in vivo. Copy rights belong to original authors. Visit the link for more info

action copy mouse aim vivo mir rna ins induced cooperative reprogramming neurons vitro instructing tfs biorxiv astrocytes mirnas

TWiV 580: Noncoding RNA with Chris Sullivan

This Week in Virology

Play Episode Listen Later Dec 29, 2019 96:27

From the University of Texas at Austin, Vincent and Rich speak with Chris Sullivan about his work on miRNAs encoded in the genomes of polyomaviruses and papillomaviruses, and how an RNA triphosphatase restricts hepatitis C virus replication. Hosts: Vincent Racaniello and Rich Condit Guest: Chris Sullivan Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode Sullivan lab Virus-encoded miRNAs in papillomaviruses (PLoS Path) Murine polyomavirus miRNA promotes viruria (J Virol) DUSP11 helps XRN restrict hepatitis C virus (PNAS) Timestamps by Jolene. Thanks! Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv

university texas rich viruses viral factor rna restriction hepatitis virology chris sullivan microrna rnai papillomavirus mirnas twiv noncoding

TWiV 580: Noncoding RNA with Chris Sullivan

This Week in Virology

Play Episode Listen Later Dec 29, 2019 96:27

university texas rich viruses viral factor rna restriction hepatitis virology chris sullivan microrna rnai papillomavirus mirnas twiv noncoding

Development of a predictive miRNA signature for breast cancer risk among high-risk women