Podcasts about murine

Play Episode Listen Later Aug 2, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.31.551374v1?rss=1 Authors: Ishioka, M., Nihashi, Y., Sunagawa, Y., Umezawa, K., Shimosato, T., Kagami, H., Morimoto, T., Takaya, T. Abstract: An 18-base myogenetic oligodeoxynucleotide (myoDN), iSN04, acts an anti-nucleolin aptamer and induces myogenic differentiation of skeletal muscle myoblasts. This study investigated the effect of iSN04 on murine embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). In the undifferentiated state, iSN04 inhibited the proliferation of ESCs and iPSCs but did not affect the expression of pluripotent markers. In the differentiating condition, iSN04 treatment of ESCs/iPSCs from day 5 onward dramatically induced the differentiation into Nkx2-5+ beating cardiomyocytes with upregulation of Gata4, Isl1, and Nkx2-5, whereas iSN04 treatment from earlier stages completely inhibited cardiomyogenesis. RNA sequencing revealed that iSN04 treatment from day 5 onward contributes to the generation of cardiac progenitors by modulating the Wnt signaling pathway. Immunostaining showed that iSN04 suppressed the cytoplasmic translocation of nucleolin and restricted it to the nucleoli. These results demonstrate that nucleolin inhibition by iSN04 facilitates the terminal differentiation of cardiac mesoderm into cardiomyocytes, but interferes with the differentiation of early mesoderm into the cardiac lineage. This is the first report on the generation of cardiomyocytes from pluripotent stem cells using a DNA aptamer. Since iSN04 did not induce hypertrophic responses in primary-cultured cardiomyocytes, iSN04 would be useful and safe for the regenerative therapy of heart failure using stem cell-derived cardiomyocytes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Bioactive effects of natural and novel unnatural tropolone sesquiterpenoids in a murine cell model of renal interstitial fibroblasts

Play Episode Listen Later Jul 19, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.19.549646v1?rss=1 Authors: Bergmann, T. C., Menssen, M., Schotte, C., Cox, R. J., Lee-Thedieck, C. Abstract: Fungal specialized metabolites often exhibit a wide range of potent bioactivities, with tropolone sesquiterpenoids (TS) representing a promising family with a variety of known bioactive properties. Here, we investigated bioactive properties of the novel TS compounds 4- hydroxyxenovulene B 4, 4-dehydroxy-norpycnidione 5 and the structurally-related compounds 4-hydroxy-norxenovulene B 6, and xenovulene B 3, for which no bioactive effects have been reported yet. We detected compound-specific changes in cell shapes and ramification patterns that were strongly correlated in samples treated with structurally-similar compounds and related to the tropolone moieties present on the molecule. The number of tropolone moieties per molecule had a significant influence on survival of FAIK3-5 cells, with an increased cytotoxic effect observed with the dual-substituted compounds compared to the monotropolones. Treatment with eupenifeldin 2, compound 4 and 5 demonstrated versatile influences on cellular behaviour and can reduce EPO content in hypomethylated FAIK3-5 cells. Monotropolone 5 showed significantly reduced proliferation with low cytotoxic effects and could serve as a potential compound for further (pre-)clinical drug testing for cancer treatment. Our results bring us one step closer to linking the molecular structures of bioactive TS compounds to their biological effects and may improve their potential for clinical applications. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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ImmunoEpigenetics91. WTAP conditional deletion via LoxPCre controlled by FoxP3 obtains a Treg phenotype incapable of supressing murine spontaneous colitis. DJGPhD. 15.7.23. Authentic Biochemistry.

Authentic Biochemistry

Play Episode Listen Later Jul 15, 2023 29:59

Reference Nature Immunology 2022. volume 23, pages 1208–1221. --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message

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Intra-Articular Sprouting Of Nociceptors Accompanies Progressive Osteoarthritis: Comparative Evidence In Four Murine Models

Play Episode Listen Later Jul 2, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.30.547216v1?rss=1 Authors: Obeidat, A. M., Ishihara, S., Li, J., Lammlin, L., Junginger, L., Maerz, T., Miller, R. J., Miller, R., Malfait, A.-M. Abstract: Objective: Knee joints are densely innervated by nociceptors. Sprouting of nociceptors has been reported in late-stage osteoarthritis (OA), both in human knees and in rodent models. Here, we sought to describe progressive nociceptor remodeling in four mouse models of knee OA, capturing early and late-stage disease. Methods: Sham surgery, destabilization of the medial meniscus (DMM), partial meniscectomy (PMX), or non-invasive anterior cruciate ligament rupture (ACLR) was performed in the right knee of 10-12-week old male C57BL/6 NaV1.8-tdTomato mice. Mice were euthanized (1) 4, 8 or 16 weeks after DMM or sham surgery; (2) 4 or 12 weeks after PMX or sham; (3) 1 or 4 weeks after ACLR injury or sham. Additionally, a cohort of naive male wildtype mice was evaluated at 6 and 24 months. Twenty-m thick mid-joint cryosections were assessed qualitatively and quantitatively for NaV1.8+ and PGP9.5+ innervation. Cartilage damage (using a modified OARSI score), synovitis, and osteophytes were assessed blindly. Results: Progressive OA developed in the medial compartment after DMM, PMX, and ACLR. Synovitis and associated neo-innervation by nociceptors peaked in early-stage OA. In the subchondral bone, channels containing sprouting nociceptors appeared early, and progressed with worsening joint damage. Two-year old mice developed primary OA in both the medial and the lateral compartment, accompanied with neuroplasticity in the synovium and the subchondral bone. All 4 models had an increased nerve signal in osteophytes. Conclusion: Anatomical neuroplasticity of nociceptors was observed in association with joint damage in 4 distinct mouse models, suggesting that it is intrinsic to OA pathology. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Modeling the cell-type specific mesoscale murine connectome with anterograde tracing experiments

Play Episode Listen Later May 3, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.02.539079v1?rss=1 Authors: Koelle, S., Mastrovito, D., Whitesell, J. D., Hirokawa, K. E., Zeng, H., Meila, M., Harris, J. A., Mihalas, S. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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A single-cell atlas of the aging murine ovary

Play Episode Listen Later Apr 29, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.29.538828v1?rss=1 Authors: Isola, J., Ocanas, S. R., Hubbart, C., Ko, S., Ali Mondal, S., Hense, J., Schneider, A., Kovats, S., Freeman, W. M., Stout, M. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Leveraging the power of 3D brain-wide imaging and mapping tools for brain injury research in murine models

Play Episode Listen Later Apr 28, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.27.537761v1?rss=1 Authors: Anwer, M., LeDue, J., Wang, Z., Wang, S., Cheng, W. H., Burdyniuk, M., Cheung, H., Fan, J., Barron, C., Cripton, P. A., Cembrowski, M. S., Rossi, F., Murphy, T. H., Wellington, C. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Proteomic analysis of peripheral nerve myelin during murine aging

Play Episode Listen Later Apr 28, 2023

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

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Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury

Play Episode Listen Later Apr 13, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.13.536755v1?rss=1 Authors: Helbing, D. L., Haas, F., Cirri, E., Rahnis, N., Dau, T. T. D., Sacramento, E. K., Oraha, N., Boehm, L., Morrison, H., Bauer, R. Abstract: Preconditioning with LPS induces neuroprotection against subsequent cerebral ischemic injury, mainly involving innate immune pathways. Microglia are CNS-resident immune cells that respond early to danger signals through memory-like differential reprogramming. However, the cell-specific molecular mechanisms underlying preconditioning are not fully understood. To elucidate the distinct molecular mechanisms of preconditioning on microglia, we compared these cell-specific proteomic profiles in response to LPS preconditioning and without preconditioning and subsequent transient focal brain ischemia and reperfusion, using an established mouse model of transient focal brain ischemia and reperfusion. A proteomic workflow, based on isolated microglia obtained from mouse brains by cell sorting and coupled to mass spectrometry for identification and quantification, was applied. Our data confirm that LPS preconditioning induces marked neuroprotection, as indicated by a significant reduction in brain infarct volume. The established brain cell separation method was suitable for obtaining an enriched microglial cell fraction for valid proteomic analysis. The results show a significant impact of LPS preconditioning on microglial proteome patterns by type I interferons, presumably driven by the interferon cluster regulator proteins Stat1/2. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Molecular Consequences of Peripheral Influenza A Infection on Cell Populations in the Murine Hypothalamus

Play Episode Listen Later Mar 7, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.06.530999v1?rss=1 Authors: Lemcke, R., Egebjerg, C., Berendtsen, N. T., Egerod, K. L., Thomsen, A. R., Pers, T. H., Christensen, J. P., Kornum, B. R. Abstract: Infection with Influenza A virus (IAV) causes the well-known symptoms of the flu, including fever, loss of appetite and excessive sleepiness. These responses, mediated by the brain, will normally disappear once the virus is cleared from the system, but a severe respiratory virus infection may cause long-lasting neurological disturbances. These include encephalitis lethargica and narcolepsy. The mechanisms behind such long lasting changes are unknown. The hypothalamus is a central regulator of the homeostatic response during a viral challenge. To gain insight into the neuronal and non-neuronal molecular changes during an IAV infection, we intranasally infected mice with an H1N1 virus and extracted the brain at different time points. Using single-nucleus RNA sequencing (snRNA-seq) of the hypothalamus, we identify transcriptional effects in all identified cell populations. The snRNA-seq data showed the most pronounced transcriptional response at 3 days past infection, with a strong downregulation of genes across all cell types. General immune processes were mainly impacted in microglia, the brain resident immune cells, where we found increased numbers of cells expressing pro-inflammatory gene networks. In addition, we found that most neuronal cell populations downregulated genes contributing to the energy homeostasis in mitochondria and protein translation in the cytosol, indicating potential reduced cellular and neuronal activity. This might be a preventive mechanism in neuronal cells to avoid intracellular viral replication and attack by phagocytosing cells. This is complemented by increased activity of microglia monitoring their surroundings. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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The Role of HERG channel in the Secretion of Glucagon-Like Peptide-1 (GLP-1) from Murine Intestinal L-Cells

Play Episode Listen Later Mar 1, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.28.530535v1?rss=1 Authors: ang, J.-K., Liu, C., Yuan, Y.-, Xie, R.-R., Wang, H. Abstract: HERG ion channel is a member of the Voltage-gated potassium (Kv) channels. A reduction in HERG function reduces potassium efflux during repolarization. Previous research has shown that patients with long QT syndrome due to HERG mutations have increased secretion of the hormone glucagon-like peptide-1 (GLP-1). However, the role of HERG in GLP-1 secretion remains uncertain. Here we report that HERG is expressed in GLP-1-producing L-cells in rodent intestinal epithelium. In a mouse L-cell model (GLUTag cell line), downregulation of HERG significantly prolonged action potential duration, increased intracellular calcium concentration, and stimulated GLP-1 secretion after exposure to nutrients. These findings suggest that HERG in the intestine plays a direct role in GLP-1 secretion and may be a potential target for diabetes treatment. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Shared inflammatory glial cell signature after brain injury, revealed by spatial, temporal and cell-type-specific profiling of the murine cerebral cortex

Talking Out Your Glass podcast

Play Episode Listen Later Feb 27, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.24.529840v1?rss=1 Authors: Koupourtidou, C., Schwarz, V., Aliee, H., Frerich, S., Fischer-Sternjak, J., Bocchi, R., Simon-Ebert, T., Dichgans, M., Goetz, M., Theis, F. J., Ninkovic, J. Abstract: Traumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability and the development of secondary neurodegenerative diseases. A holistic understanding of the mechanisms controlling the responses of specific cell types and their crosstalk is required to develop an efficient strategy for better regeneration. Here, we combined spatial and single-cell transcriptomics to chart the transcriptomic signature of the injured murine cerebral cortex, and identified specific states of astrocytes, microglia, and oligodendrocyte precursor cells contributing to this signature. Interestingly, these cellular populations share a large fraction of injury-regulated genes, including inflammatory programs downstream of the innate immune-associated pathways Cxcr3 and Tlr1/2. Systemic manipulation of these pathways decreased the reactivity state of glial cells associated with poor regeneration. The functional relevance of the newly discovered shared signature of glial cells highlights the importance of our resource enabling comprehensive analysis of early events after brain injury. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Nathan Sandberg: Pioneering Vitrigraph Kiln, Techniques, Artwork

Play Episode Listen Later Feb 17, 2023 73:53

Capitalizing on the ways glass can be arranged in and flows from a crucible, Nathan Sandberg creates reproducible decorative cane and murrine using the Vitrigraph Kiln. His work showcases these elements in a variety of artistic applications and furnishings. When not in his North Portland studio creating work or getting ready for an exhibition, Sandberg can be found presenting modern, innovative curriculum in kilnformed glass at a wide variety of studios and schools around the globe. In 2003, Sandberg received his BFA in glass and ceramics from Southern Illinois University, Carbondale. After working at private glassblowing studios and independently furthering his education in kiln-glass, he joined Bullseye Glass Co. in 2005. As a member of the company's Research & Education team, he taught and developed courses and online educational videos as well as assisted visiting artists. Beginning at the Bullseye factory in 2009, the artist began exploring modern Vitrigraph methods that have become the primary techniques used in the creation of his work. Sandberg creates glass panes that are full of movement and repeated patterns that gently guide the viewer's eyes through the work. He states: “Our world is complex. And I realize that occasionally we simply need a pleasant view in order to escape some of the ugliness and take ourselves somewhere healthier, even if only for a moment.” In 2012, Sandberg founded Nathans LLC. This educational entrepreneurship helped establish him as one of the top kiln-glass educators in the world, sending him on teaching adventures from Santa Fe to Zurich and Australia to Norway. In 2015, Nathans LLC moved out of the basement and into a proper studio space in the Kenton neighborhood of North Portland. Today, Sandberg uses OnGrade Studio as his home base and can be found there relentlessly producing work for exhibitions and developing new curriculum to teach on the road and online. Using primarily glass, Sandberg's installations commonly make use of other materials such as wood, metal and concrete. His artwork can be found in private and public collections around the world and has received critical recognition through awards, exhibitions, and art fairs, including Glazen Huis in Lommel, Belgium, 2nd Place Non-Functional, Academic Award WG@BE3: E-merge, Bullseye Connection Gallery and SOFA Chicago. Sandberg worked with Gabriela Wilson as part of an Instructor Collaborative Residency at The Studio of the Corning Museum of Glass in September 2019. The duo explored the traditional hot shop methods of pulling cane to compare and contrast the process with Vitrigraph methods. Currently, Sandberg operates an 8' x 10' waterjet two days a week and says this equipment will revolutionize what is possible in kilnformed glass. The artist is also in the design phase of a glass shingle backsplash for a 30-foot-tall residential waterfall project. His artwork will be on view at Guardino Gallery in Portland in September 2023 and in October at the Pittsburgh Glass Center with Amanda Simmons, Nancy Callan, Mel Douglas and Corey Pemberton in an exhibition titled Pattern.

Boldine modulates glial transcription and functional recovery in a murine model of contusion spinal cord injury

Play Episode Listen Later Feb 15, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.15.528337v1?rss=1 Authors: Toro, C. A., Johnson, K. E., Hansen, J., Siddiq, M. M., Vasquez, W., Zhao, W., Graham, Z. A., Saez, J. C., Iyengar, R., Cardozo, C. P. Abstract: Membrane channels such as connexins (Cx), pannexins (Panx) and P2X7 receptors (P2X7R) are permeable to calcium ions and other small molecules such as ATP and glutamate. Release of ATP and glutamate through these channels is a key mechanism driving tissue response to traumas such as spinal cord injury (SCI). Boldine, an alkaloid isolated from the Chilean boldo tree, blocks both Cx hemichannels (HC) and Panx. To test if boldine could improve function after SCI, boldine or vehicle was administered to treat mice with a moderate severity contusion-induced SCI. Boldine led to greater spared white matter and increased locomotor function as determined by the Basso Mouse Scale and horizontal ladder rung walk tests. Boldine treatment reduced immunostaining for markers of activated microglia (Iba1) and astrocytic (GFAP) markers while increasing that for axon growth and neuroplasticity (GAP-43). Cell culture studies demonstrated that boldine blocked glial HC, specifically Cx26 and Cx30, in cultured astrocytes and blocked calcium entry through activated P2X7R. RT-qPCR studies showed that boldine treatment reduced expression of the chemokine Ccl2, cytokine IL-6 and microglial gene CD68, while increasing expression of the neurotransmission genes Snap25 and Grin2b, and Gap-43. Bulk RNA sequencing (of the spinal cord revealed that boldine modulated a large number of genes involved in neurotransmission in in spinal cord tissue just below the lesion epicenter at 14 days after SCI. Numbers of genes regulated by boldine was much lower at 28 days after injury. These results indicate that boldine treatment ameliorates injury and spares tissue to increase locomotor function. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

TGFB1 Induces Fetal Reprogramming and Enhances Intestinal Regeneration

Play Episode Listen Later Jan 13, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.13.523825v1?rss=1 Authors: Chen, L., Dupre, A., Qiu, X., Pellon-Cardenas, O., Walton, K. D., Wang, J., Perekatt, A. O., Hu, W., Spence, J. R., Verzi, M. P. Abstract: The adult gut epithelium has a remarkable ability to recover from damage. To achieve cellular therapies aimed at restoring and/or replacing defective gastrointestinal tissue, it is important to understand the natural mechanisms of tissue regeneration. We employed a combination of high throughput sequencing approaches, mouse genetic models, and murine and human organoid models, and identified a role for TGFB signaling during intestinal regeneration following injury. At 2 days following irradiation (IR)-induced damage of intestinal crypts, a surge in TGFB1 expression is mediated by monocyte/macrophage cells at the location of damage. Depletion of macrophages or genetic disruption of TGFB-signaling significantly impaired the regenerative response following irradiation. Murine intestinal regeneration is also characterized by a process where a fetal transcriptional signature is induced during repair. In organoid culture, TGFB1-treatment was necessary and sufficient to induce a transcriptomic shift to the fetal-like/regenerative state. The regenerative response was enhanced by the function of mesenchymal cells, which are also primed for regeneration by TGFB1. Mechanistically, integration of ATAC-seq, scRNA-seq, and ChIP-seq suggest that a regenerative YAP-SOX9 transcriptional circuit is activated in epithelium exposed to TGFB1. Finally, pre-treatment with TGFB1 enhanced the ability of primary epithelial cultures to engraft into damaged murine colon, suggesting promise for the application of the TGFB-induced regenerative circuit in cellular therapy. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Multiparametric senescent cell phenotyping reveals CD24 osteolineage cells as targets of senolytic therapy in the aged murine skeleton

Play Episode Listen Later Jan 13, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.12.523760v1?rss=1 Authors: Doolittle, M. L., Saul, D., Kaur, J., Rowsey, J. L., Vos, S. J., Pavelko, K. D., Farr, J. N., Monroe, D., Khosla, S. Abstract: Senescence drives organismal aging, yet the deep characterization of senescent cells in vivo remains incomplete. Here, we applied mass cytometry by time-of-flight (CyTOF) using carefully validated antibodies to analyze senescent cells at single-cell resolution. We used multiple criteria to identify senescent mesenchymal cells that were growth arrested and resistant to apoptosis (p16+/Ki67-/BCL-2+; p16KB cells). These cells were highly enriched for senescence-associated secretory phenotype (SASP) and DNA damage markers and were strongly associated with age. p16KB cell percentages were also increased in CD24+ osteolineage cells, which exhibited an inflammatory SASP in aged mice and were robustly cleared by both genetic and pharmacologic senolytic therapies. Following isolation, CD24+ skeletal cells exhibited growth arrest, SA-beta gal positivity, and impaired osteogenesis in vitro. These studies thus provide a new approach using multiplexed protein profiling by CyTOF to define senescent mesenchymal cells in vivo and identify a highly inflammatory, senescent CD24+ osteolineage population cleared by senolytics. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Novel Antibody Drug Conjugate Improves Murine Acute Myeloid Leukemia

Oncotarget

Play Episode Listen Later Jan 5, 2023 7:57

Listen to a blog summary of a trending research paper published by Oncotarget: "Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model." _________________________________________________________ The average age of patients with acute myeloid leukemia (AML) is 67 years old. Older adults generally have a lower tolerance for treatments that exhibit high off-target toxicity. Additionally, chemotherapy-relapsed or -refractory (R/R) AML patients are often at an advanced stage of disease and are therefore more likely to have comorbidities that may reduce their tolerance for harsh treatments. Thus, pharmaceutical AML drugs with high efficacy and low toxicity are in high demand. Antibody drug conjugates (ADCs) are emerging as promising therapeutic approaches to more safely treat hematological malignancies by reducing side effects. ADCs are designed to decrease damage to healthy tissues by specifically targeting tumor-associated antigens attached to cancer cells. “Antibody drug conjugates (ADC) are one of the modalities that aims to dissociate drug efficacy from toxicity. ADC consists of three components: antibody specific for tumor associated antigen, drug linker and cytotoxic payload.” ASTELLAS PHARMA Recently, researchers from Astellas Pharma Inc. (a pharmaceutical company in Japan) developed ASP1235—a novel ADC that targets Fms-like tyrosine kinase 3 (FLT3). In more than 90% of AML patients, FLT3 is overexpressed on leukemic blasts. ASP1235 is designed to target FLT3-positive leukemia cells and deliver the cytotoxic drug payload to these cells. However, this drug alone was found to have only a mild effect on AML cells, prompting researchers to assess the efficacy of ASP1235 in combination with other drugs. In a new study, Astellas Pharma researchers Hirofumi Tsuzuki, Tatsuya Kawase, Taisuke Nakazawa, Masamichi Mori, and Taku Yoshida investigated the efficacy of ASP1235 combined with venetoclax (an anti-apoptotic agent) and azacitidine (a DNA methyltransferase inhibitor) in an experimental mouse model of AML. Their research paper was published in Oncotarget on December 20, 2022, and entitled, “Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model.” Full blog: https://www.oncotarget.org/2023/01/04/novel-antibody-drug-conjugate-improves-murine-acute-myeloid-leukemia/ DOI: https://doi.org/10.18632/oncotarget.28331 Corresponding author: Hirofumi Tsuzuki - hirofumi.tsuzuki@astellas.com Keywords: acute myeloid leukemia (AML), ASP1235, antibody drug conjugate (ADC), venetoclax, azacitidine About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

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Salmonella actively modulates TFEB in murine macrophages in a growth-phase and time-dependent manner

Play Episode Listen Later Dec 4, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.03.518968v1?rss=1 Authors: Inpanathan, S., Ospina-Escobar, E., Cho, Y. H., Porco, N., Choy, C. H., McPhee, J. B., Botelho, R. J. Abstract: The transcription factor TFEB promotes lysosomal and autophagic capacity in response to stresses like amino acid depletion. Additionally, TFEB drives expression of immune-responsive and immuno-protective genes in response to LPS, phagocytosis, and bacteria such as Escherichia coli (E. coli) and Staphylococcus aureus. Consistent with a role for TFEB in promoting immunity and bactericidal activity, intracellular pathogens like Mycobacterium and Salmonella appear to repress TFEB, whereas compounds that promote TFEB production or activity enhance macrophage killing of Salmonella. Intriguingly, Salmonella enterica sv. Typhimurium (S. Typhimurium) was observed to actively stimulate TFEB, implying a benefit to Salmonella during infection. To better understand the relationship between S. Typhimurium infection and TFEB, we assessed if S. Typhimurium regulated TFEB in murine macrophages in a manner dependent on infection conditions. Here, we show that macrophages that engulfed late-logarithmic grown Salmonella accumulated and maintained nuclear TFEB, comparable to macrophages that engulfed E. coli. In contrast, stationary-phase S. Typhimurium infection of macrophages actively delayed TFEB nuclear mobilization over the first hour of infection. The delay in TFEB nuclear mobilization was not observed in macrophages that engulfed heat-killed stationary-phase Salmonella, or Salmonella lacking functional SPI-1 and SPI-2 type three secretion systems. S. Typhimurium mutated in the master virulence regulator phoP or the secreted effector genes sifA, and sopD also showed normal TFEB nuclear translocation. Interestingly, while E. coli survived better in Tfeb-/- macrophages, S. Typhimurium growth was similar in wild-type and Tfeb-/- macrophages. Yet, priming macrophages with phagocytosis enhanced the killing of Salmonella in wild-type, but not in Tfeb-/- macrophages. Collectively, S. Typhimurium seems to orchestrate TFEB in a manner dependent on infection conditions, while conditions that disturb this context-dependent control of TFEB, such as forcing activation of TFEB seems to be detrimental to Salmonella survival. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Deep RNA-seq of male and female murine sensory neuron subtypes after nerve injury

Play Episode Listen Later Nov 22, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.21.516781v1?rss=1 Authors: Barry, A. M., Zhao, N., Yang, X., Bennett, D. L., Baskozos, G. Abstract: Dorsal root ganglia (DRG) neurons have been well described for their role in driving both acute and pain. Although nerve injury is known to cause transcriptional dysregulation, how this differs across neuronal subtypes and the impact of sex is unclear. Here, we study the deep transcriptional profiles of multiple murine DRG populations in early and late pain states while considering sex. We have exploited currently available transgenics to label numerous subpopulations for fluorescent activated cell sorting (FACS) and subsequent transcriptomic analysis. Using bulk tissue samples, we are able to circumvent the issues of low transcript coverage and drop-outs seen with single cell datasets. This increases our power to detect novel and even subtle changes in gene expression within neuronal subtypes and discuss sexual dimorphism at the neuronal subtype level. We have curated this resource into an accessible database for other researchers (https://livedataoxford.shinyapps.io/drg-directory/). We see both stereotyped and unique subtype signatures in injured states after nerve injury at both an early and late timepoint. While all populations contribute to a general injury signature, subtype enrichment changes can also be seen. Within populations, there is not a strong intersection of sex and injury, but previously unknown sex differences in naive states- particularly in AB-RA + Ad-LTMRs - still contribute to differences in injured neurons. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Rate of neuronal turnover in the healthy adult murine myenteric ganglia varies with ganglia size

Play Episode Listen Later Nov 14, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.14.516462v1?rss=1 Authors: Gorecki, A. M., Singh, A., Zhang, C., Gurumurthy, R., Kulkarni, S. Abstract: Major gastrointestinal and systemic functions are regulated by the Enteric Nervous System (ENS), whose cells are organized in interconnected clusters or ganglia to form plexuses in the gut wall. Previously, we showed that neuronal turnover, driven by overall equal rates of neurogenesis and neuronal loss, is an important homeostatic mechanism that maintains the larger myenteric plexus of the healthy adult ENS. While this process maintains neuronal numbers, whether it occurs at the same rate across the two sexes, in different regions and within ganglia that contain a diversity of neuronal numbers remains unknown. Here, by using antibodies against the DNA replication marker phospho-Histone H3 and against the pan-neuronal marker Hu to detect new-born neurons, we observe that while the proportions of new-born myenteric neurons are conserved irrespective of the region or sex in the healthy small intestine, they are inversely correlated with ganglia size. In contrast, by using antibodies against the apoptosis marker Cleaved Caspase 3 and Hu, we found that proportions of apoptotic neurons were directly correlated with ganglia size. Our observations on the unequal rate of neuronal turnover across ganglia, where smaller ganglia are more neurogenic and larger ganglia are more apoptotic, suggests that the myenteric ganglia are plastic in nature. These results provide further insight into the dynamic nature of the adult ENS. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

healthy dna llc adult copy singh zhang turnover hu ens kulkarni neuronal varies biorxiv ganglia murine

Integrated transcriptome and lineage analyses reveal novel catecholaminergic cardiomyocytes contributing to the cardiac conduction system in murine heart

Play Episode Listen Later Nov 4, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.04.515095v1?rss=1 Authors: Sun, T., Grassam-Rowe, A., Pu, Z., Ren, H., An, Y., Guo, X., Hu, W., Liu, Y., Li, Y., Liu, Z., Kou, K., Ou, X., Chen, T., Fan, X., Liu, Y., Tu, S., He, Y., Ren, Y., Chen, A., Shang, Z., Xia, Z., Miquerol, L., Smart, N., Zhang, H., Tan, X., Shou, W., Lei, M. Abstract: Cardiac conduction system (CCS) morphogenesis is essential for correct heart function yet is incompletely understood. Here we established the transcriptional landscape of cell types populating the developing heart by integrating single-cell RNA sequencing and spatial enhanced resolution omics-sequencing (Stereo-seq). Stereo-seq provided a spatiotemporal transcriptomic cell fate map of the murine heart with a panoramic field of view and in situ cellular resolution of the CCS. This led to the identification of a previously unrecognized cardiomyocyte population expressing dopamine beta-hydroxylase (Dbh+-CMs), which is closely associated with the CCS in transcriptomic analyses. To confirm this finding, genetic fate mapping by using DbhCre/Rosa26-tdTomato reporter mouse line was performed with Stereo-seq, RNAscope, and immunohistology. We revealed that Dbh+-derived CMs first emerged in the sinus venosus at E12.5, then populated the atrial and ventricular CCS components at E14.5, with increasing abundance towards perinatal stages. Further tracing by using DbhCFP reporter and DbhCreERT/Rosa26-tdTomato inducible reporter, we confirmed that Dbh+-CMs are mostly abundant in the AVN and ventricular CCS and this persists in the adult heart. By using DbhCre/Rosa26-tdTomato/Cx40-eGFP compound reporter line, we validated a clear co-localization of tdTomato and eGFP signals in both left and right ventricular Purkinje fibre networks. Finally, electrophysiological optogenetic study using cell-type specific Channelrhodopsin2 (ChR2) expression further elucidated that Dbh+-derived CMs form a functional part of the ventricular CCS and display similar photostimulation-induced electrophysiological characteristics to Cx40CreERT/ChR2- tdTomato CCS components. Thus, by utilizing advanced transcriptomic, mouse genetic, and optogenetic functional analyses, our study provides new insights into mammalian CCS development and heterogeneity by revealing novel Dbh+-CMs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

The matrisome of the murine and human dorsal root ganglion: a transcriptomal approach

Play Episode Listen Later Oct 24, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.22.513341v1?rss=1 Authors: Vroman, R., Hunter, R., Wood, M. J., Davis, O. C., Malfait, Z., George, D. S., Ren, D., Tavares-Ferreira, D., Price, T. J., Malfait, A.-M., Malfait, F., Miller, R. E., Syx, D. Abstract: The extracellular matrix (ECM) is a dynamic structure composed of a large number of molecules that can be divided into six different categories and are collectively called the matrisome. The ECM plays pivotal roles in physiological and pathological processes in many tissues, including the nervous system. Intriguingly, alterations in ECM molecules/pathways are often associated with painful human conditions and murine experimental pain models. Nevertheless, mechanistic insight into the interplay of normal or defective ECM and pain is largely lacking. To expand the knowledge on ECM composition and synthesis in the peripheral nervous system, we used a transcriptomal approach to investigate the expression and cellular origin of matrisome genes in murine and human dorsal root ganglia (DRG), containing the cell bodies of sensory neurons. Bulk RNA sequencing data showed that over 60% of all matrisome genes were expressed in both murine and human DRG, with proportionally more core matrisome genes (glycoproteins, collagens, and proteoglycans) expressed compared to matrisome-associated genes (ECM-affiliated genes, ECM regulators and secreted factors). Examination of the cellular origin of matrisome expression by single cell RNA sequencing on murine DRG revealed that core matrisome genes, especially collagens, were expressed by vascular leptomeningeal-like (fibroblast) cell types whereas matrisome-associated genes were mainly expressed by neuronal cell types. We analyzed cell-cell communication networks with the CellChat R package and predicted an important role for the Collagen signaling pathway in connecting vascular cell types and nociceptors in murine tissue, which we confirmed by analysis of spatial transcriptomic data from human DRG. RNAscope in situ hybridization and immunohistochemistry confirmed expression of collagens in fibroblasts surrounding nociceptors in human DRG. This study supports the idea that the DRG matrisome may contribute to neuronal signaling in both mouse and human. The identification of the cellular distribution of murine and human matrisome genes provides a framework to study the role of the ECM in peripheral nervous tissue and its effects on pain signaling. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

price llc wood root copy examination rna collagen ecm intriguingly dorsal drg biorxiv ganglion murine

Single-nuclei transcriptomics of mammalian prion diseases identifies dynamic gene signatures shared between species

california texas flea murine rickettsia erin scott

Play Episode Listen Later Sep 15, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.13.507650v1?rss=1 Authors: Dimitriadis, A., Zhang, F., Murphy, T., Trainer, T., Jaunmuktane, Z., Schmidt, C., Nazari, T., Linehan, J., Brandner, S., Collinge, J., Mead, S., Vire, E. Abstract: Mammalian prion diseases are fatal and transmissible neurological conditions caused by the propagation of prions, self-replicating multimeric assemblies of misfolded forms of host cellular prion protein (PrP). The most common human form of the disease, sporadic Creutzfeldt-Jakob disease (sCJD), typically presents as a rapidly progressive dementia and has no effective treatments. Prion diseases are transmissible to laboratory rodents affording unprecedented opportunities to understand neurodegeneration in its evolving stages. Murine models are especially useful in prion research as they develop bona fide prion disease and recapitulate all biochemical and neuropathological hallmarks of human prion disease. Despite extensive studies investigating the changes in transcriptional profiles in prion diseases the mechanisms by which prion diseases induce cellular toxicity, including changes in gene expression profiles are yet to be fully characterized. This is at least in part because confounding effects related to brain cellular heterogeneity have not been resolved. Here, we took advantage of the recent developments in single-cell technologies and performed an unbiased whole-transcriptome single-nucleus transcriptomic analysis in prion disease. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

single disease trainers shared dynamic copy schmidt species zhang prp signatures identifies vire linehan mammalian prion biorxiv creutzfeldt jakob brandner murine scjd

Episode 16 - Erin Scott

Jack The Lad Podcast

Play Episode Listen Later Apr 29, 2022 96:18

Erin Scott contracted a rare bacterial disease called Murine typhus, which is a Flea-borne disease caused by a bacteria called Rickettsia typhi. She was admitted to hospital whereupon they placed her into an induced coma due to the organ failure. She then required years of speech therapy as a part of the aftermath of this life changing condition which is most commonly found in California and Texas.

Murine MI Sizing with 2D and 4D Echocardiography

AJP-Heart and Circulatory Podcasts

Play Episode Listen Later Apr 6, 2022 21:13

While echocardiography is commonly used to assess cardiac structure and function in mouse models of heart disease, can this non-invasive technique also be used to accurately measure infarct size? Listen as Deputy Editor Dr. Zamaneh Kassiri (University of Alberta) interviews co-authors Dr. Erin Mulvihill (University of Ottawa) and Dr. Craig Goergen (Purdue University), along with content expert Dr. Daniele Panetta (Institute of Clinical Physiology CNR - Pisa). Dann et al. measured and monitored infarct size by comparing and contrasting 2-D echo imaging results with 4-D echo imaging results in a myocardial infarction mouse model. 4-D ultrasound imaging allowed the authors to measure the entire volume of the left ventricle throughout the cardiac cycle, as well as analyze the progression of asymmetric ventricular remodeling. In addition, this work illustrates how authors from two different academic institutions found a novel way to collaborate during the COVID-19 pandemic and ensuing international travel restrictions. The study by Dann et al. provides a unique visualization of the infarct in 3-D, which then allowed for volumetric analysis to use contouring of the heart to produce dynamic strain maps. Listen as we discuss how the innovative imaging modalities utilized by Dann et al. allow researchers to focus on animal specific differences as well as the inclusion of both female and male animals for robust rigor and reproducibility. Melissa M. Dann, Sydney Q. Clark, Natasha A. Trzaskalski, Conner C. Earl, Luke E. Schepers, Serena M. Pulente, Ebonee N. Lennord, Karthik Annamalai, Joseph M. Gruber, Abigail D. Cox, Ilka Lorenzen-Schmidt, Richard Seymour, Kyoung-Han Kim, Craig J. Goergen, and Erin E. Mulvihill Quantification of murine myocardial infarct size using 2-D and 4-D high-frequency ultrasound Am J Physiol Heart Circ Physiol, published February 8, 2022. DOI: doi.org/10.1152/ajpheart.00476.2021

covid-19 ottawa doi sizing richard seymour echocardiography murine

JACC: Basic to Translational Science - Implications of Iron Deficiency in STEMI Patients and in a Murine Model of Myocardial Infarction

JACC Speciality Journals

Play Episode Listen Later Jul 26, 2021 6:22

Commentary by Dr. Douglas Mann

model patients basic commentary implications iron deficiency stemi myocardial infarction translational science jacc murine

The Gary Null Show - 07.02.21

The Gary Null Show

Play Episode Listen Later Jul 2, 2021 59:10

Sunflower peptide as 'template' for potential analgesic Medical University of Vienna (Austria), June 28, 2021 A naturally occurring peptide in sunflower seeds was synthetically optimised and has now been identified as a potential drug for treating abdominal pain or inflammation (in the gastrointestinal tract, abdominal area and/or internal organs). That is the finding of an international study led by Christian Gruber from MedUni Vienna's Institute of Pharmacology (Center for Physiology and Pharmacology), which was conducted jointly with the University of Queensland and Flinders University in Australia and has now been published. The scientific aim of the study is to find analgesics that are only active in the periphery and do not cross the blood-brain barrier, as an alternative to commonly used synthetic opioids. Gruber explains the background: "Morphine was one of the first plant-based medicines and was isolated from the dried latex of poppies more than 200 years ago. It binds to opioid receptors in the brain and is still regarded as the main pillar of pain therapy. However, there is a high risk of opioid addiction, and an overdose - as a result of this strong dependency - inhibits the breathing centre in the brain, which can result in respiratory depression and, in the worst case, in death." For this reason, researchers throughout the world are trying to make analgesics safer and to find active drug molecules that do not have the typical opioid side-effects. Sunflower extracts were to some extent used in traditional medicine for their anti-inflammatory and analgesic properties. In the current study, the scientists from Austria and Australia, primarily PhD student Edin Muratspahi?, isolated the plant molecule that may be responsible for this effect. Medicinal chemistry methods were then used to optimise the so-called sunflower trypsin inhibitor-1 (SFTI-1), one of the smallest naturally occurring cyclic peptides, by 'grafting' an endogenous opioid peptide into its scaffold. A total of 19 peptides were chemically synthesized based on the original SFTI-1 blueprint and pharmacologically tested. "One of these variants turned out to be our lead candidate for as potential innovative analgesic molecule, especially for pain in the gastrointestinal tract or in the peripheral organs. This peptide is extremely stable, highly potent and its action is restricted to the body's periphery. Its use is therefore expected to produce fewer of the typical side-effects associated with opioids," point out Gruber and Muratspahi?. The mode-of-action of the peptide is via the so-called kappa opioid receptor; this cellular protein is a drug target for pain relief, but is often associated with mood disorders and depression. The sunflower peptide does not act in the brain, hence there is much less risk of dependency or addiction. Furthermore, it selectively activates only the molecular signalling pathway that influences pain transmission but does not cause the typical opioid side-effects. The data of the animal model in the current study are very promising: the scientists see great potential for using this peptide in the future to develop a safe medication - which could be administered orally in tablet form - to treat pain in the gastrointestinal tract, and this drug could potentially also be used for related painful conditions, e.g. for inflammatory bowel disease. Using Nature's blueprint The research of this MedUni Vienna laboratory led by Christian Gruber exploits the concept of using Nature's blueprint to develop optimised drugs. "We are searching through large databases containing genetic information of plants and animals, decoding new types of peptide molecules and studying their structure, with a view to testing them pharmacologically on enzymes or membrane receptors and ultimately utilizing them in the disease model," explains Gruber. Finally, potential drug candidates are chemically synthesised in a slightly modified form based on the natural blueprint, to obtain optimised pharmacological properties. Study associates organic food intake in childhood with better cognitive development Analysis of multiple prenatal and childhood environmental risk factors suggests that poor nutrition, house crowding and indoor air pollution are associated with poorer cognitive function Barcelona Institute for Global Health (Spain), July 1, 2021 A study analysing the association between a wide variety of prenatal and childhood exposures and neuropsychological development in school-age children has found that organic food intake is associated with better scores on tests of fluid intelligence (ability to solve novel reasoning problems) and working memory (ability of the brain to retain new information while it is needed in the short term). The study, published in Environmental Pollution, was conceived and designed by researchers at the Barcelona Institute for Global Health (ISGlobal)--a centre supported by the "la Caixa" Foundation--and the Pere Virgili Health Research Institute (IISPV-CERCA). The explanation for this association may be that "healthy diets, including organic diets, are richer than fast food diets in nutrients necessary for the brain, such as fatty acids, vitamins and antioxidants, which together may enhance cognitive function in childhood," commented lead author Jordi Júlvez, a researcher at IISPV-CERCA who works closely with ISGlobal. The study also found that fast food intake, house crowding and environmental tobacco smoke during childhood were associated with lower fluid intelligence scores. In addition, exposure to fine particulate matter (PM2.5) indoors was associated with lower working memory scores. The study, titled "Early life multiple exposures and child cognitive function: A multi-centric birth cohort study in six European countries", used data on 1,298 children aged 6-11 years from six European country-specific birth cohorts (United Kingdom, France, Spain, Greece, Lithuania and Norway). The researchers looked at 87 environmental factors the children were exposed to in utero (air pollution, traffic, noise, various chemicals and lifestyle factors) and another 122 factors they were exposed to during childhood. A Pioneering Study The aim of the study was to analyse the influence of these exposures on the development and maturation of the human brain, since during childhood the brain is not yet fully developed for efficient defence against environmental chemicals and is particularly sensitive to toxicity, even at low levels that do not necessarily pose a risk to a healthy mature brain. The originality of the study lies in its use of an exposome approach, i.e. the fact that it takes into account the totality of exposures rather than focusing on a single one. This approach aims to achieve a better understanding of the complexity of multiple environmental exposures and their simultaneous effect on children's neurodevelopment. Another strength of the study, which analyses cohorts from six European countries, is its diversity, although this factor also poses the additional challenge of cultural differences, which can influence exposure levels and cognitive outcomes. Notable Associations The study found that the main determinants of fluid intelligence and working memory in children are organic diet, fast food diet, crowdedness of the family home, indoor air pollution and tobacco smoke. To date, there has been little research on the relationship between type of diet and cognitive function, but fast food intake has been associated with lower academic development success and some studies have also reported positive associations between organic diets and executive function scores. "In our study," explained Júlvez, "we found better scores in fluid intelligence and working memory with higher organic food intake and lower fast food intake." In contrast, exposure to tobacco smoke and indoor PM2.5 during childhood may negatively affect cognitive function by enhancing pro-inflammatory reactions in the brain. Still, according to Júlvez, it is worth bearing in mind that "the number of people living together in a home is often an indicator of the family's economic status, and that contexts of poverty favour less healthy lifestyles, which in turn may affect children's cognitive test scores". Some Surprising Findings The study also found some unexpected associations, which could be explained by confounding and reverse causality. For example, a positive association was found between childhood exposure to perfluorooctane sulfonic acid (PFOS) and cognitive function, even though PFOS is considered an endocrine disruptor that may alter thyroid function and negatively influence cognitive development. The study forms part of the large European project Human Early-Life Exposome (HELIX), as does another recent paper that used the same exposome and the same participants but looked at symptoms of attention deficit hyperactivity disorder (ADHD) and childhood behavioural problems. "We observed that several prenatal environmental pollutants (indoor air pollution and tobacco smoke) and lifestyle habits during childhood (diet, sleep and family social capital) were associated with behavioural problems in children," explained Martine Vrijheid, last author of the study and head of ISGlobal's Childhood and Environment programme. "One of the strengths of this study on cognition and the earlier study on behavioural problems is that we systematically analysed a much wider range of exposure biomarkers in blood and urine to determine the internal levels in the model and that we analysed both prenatal and childhood exposure variables," concluded Vrijheid. Extract of mulberry leaves partially restores the composition of intestinal microbiota and strengthens liver glycogen fragility in diabetic rats Macau University of Science and Technology (China), June 28, 2021 According to news reporting out of Macau, People's Republic of China, research stated, “Mulberry leaf as a traditional Chinese medicine is able to treat obesity, diabetes, and dyslipidemia. It is well known that diabetes leads to intestinal microbiota dysbiosis.” Our news journalists obtained a quote from the research from the Macau University of Science and Technology, “It is also recently discovered that liver glycogen structure is impaired in diabetic animals. Since mulberry leaves are able to improve the diabetic conditions through reducing blood glucose level, it would be interesting to investigate whether they have any positive effects on intestinal microbiota and liver glycogen structure. In this study, we first determined the bioactive components of ethanol extract of mulberry leaves via high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS). Murine animal models were divided into three groups, normal Sprague-Dawley (SD) rats, high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic rats, and HFD/STZ-induced rats administered with ethanol extract of mulberry leaves (200 mg/kg/day). Composition of intestinal microbiota was analyzed via metagenomics by sequencing the V3-V4 region of 16S rDNAs. Liver glycogen structure was characterized through size exclusion chromatography (SEC). Both Student's t-test and Tukey's test were used for statistical analysis. A group of type 2 diabetic rat models were successfully established. Intestinal microbiota analysis showed that ethanol extract of mulberry leaves could partially change intestinal microbiota back to normal conditions. In addition, liver glycogen was restored from fragile state to stable state through administration of ethanol extract of mulberry leaves. This study confirms that the ethanol extract of mulberry leaves (MLE) ameliorates intestinal microbiota dysbiosis and strengthens liver glycogen fragility in diabetic rats.” According to the news editors, the research concluded: “These finding can be helpful in discovering the novel therapeutic targets with the help of further investigations.” Supplemental antioxidants may reduce exacerbations in cystic fibrosis University of Colorado, July 2, 2021 An antioxidant-enriched vitamin may decrease respiratory exacerbations in people with cystic fibrosis(CF), according to new research published online iin the American Journal of Respiratory and Critical Care Medicine. In "Effects of an Antioxidant-Enriched Multivitamin in Cystic Fibrosis: Randomized, Controlled, Multicenter Trial," Scott D. Sagel, MD, PhD, a professor of pediatrics at Children's Hospital Colorado and director of the University of Colorado Cystic Fibrosis Center, and coauthors report a 50 percent reduced risk of time to the first exacerbation requiring antibiotics in those receiving the supplemental antioxidants. During the 16-week study of 73 patients (36 received supplemental antioxidants), 53 percent of the antioxidant-treated group experienced 28 exacerbations, compared to 68 percent of the control group who experienced 39 exacerbations. The researchers also found that supplemental antioxidants increased circulating antioxidant concentrations of beta-carotene, coenzyme Q10, gamma-tocopherol (a form of vitamin E) and lutein and transiently decreased inflammation (at 4 weeks, but not 16 weeks) as measured by two blood-based biomarkers of inflammation, calprotectin and myeloperoxidase (MPO). People with CF typically experience chronic bacterial infections, which lead to inflammation and the release of "vast amounts of reactive oxygen species in the airways," the authors wrote. Normally, they added, the body would marshal an antioxidant defense to neutralize this oxidant stress, but CF is characterized by dietary antioxidant deficiencies. This contributes to an oxidant-antioxidant imbalance and more inflammation, which leads to lung damage and a progressive loss of lung function. "Improving antioxidant status in CF is an important clinical goal and may have a positive effect on health," Dr. Sagel said. "Oral antioxidant formulations had been tested in CF with mixed results. However, there had not been a well-designed randomized controlled trial of an antioxidant 'cocktail' that included multiple antioxidants in a single formulation." This phase 2 trial, conducted at 15 CF centers affiliated with the CF Foundation Therapeutics Development Network, enrolled patients who were 10 years and older (average age 22 years), with pancreatic insufficiency, which causes malabsorption of antioxidants. Participants had an FEV1, the measure of how much air can be forcefully exhaled in one second, between 40 and 100 percent of what would be predicted, based on age, gender, height and a range of other characteristics. Patients in the control group received a multivitamin without antioxidant enrichment. The two groups tolerated their vitamins equally well, and there were no differences in adverse events between the two groups. The study did not meet its primary endpoint: change in sputum MPO concentration over 16 weeks. The authors chose sputum MPO "rather than another marker of airway inflammation such as neutrophil elastase because MPO generates reactive oxidant species as part of its function in innate host defense mechanisms, and is considered by many a marker of oxidative stress." "While the antioxidant supplement did not appear to exert sustained anti-inflammatory effects, we believe its effect on time to first pulmonary exacerbation was significant and clinically meaningful," Dr. Sagel said, adding that the improvement in antioxidant status alone may justify its use. "Developing safe and effective anti-inflammatory treatments remains a key priority of the CF community." Maternal diets rich in Omega-3 fatty acids may protect offspring from breast cancer Marshall University School of Medicine, June 28, 2021 According to researchers at Marshall University, a maternal diet rich in Omega-3 fatty acids protects from breast cancer development in offspring. In a new studyrecently published by Frontiers in Cell and Developmental Biology, researchers noted a significant difference in mice from mothers that were fed a diet rich in canola oil, compared with mothers fed a diet rich in corn oil. A maternal Omega 3-rich diet affected genome-wide epigenetic landscape changes in offspring and potentially modulated gene expression patterns. Dr. Ata Abbas, a former postdoctoral research fellow in Marshall's Department of Biological Sciences, headed a research team under the leadership of Dr. Philippe Georgel in the College of Science. Research was done in the Cell Differentiation and Development Center at Marshall as part of a collaborative effort with the Joan C. Edwards School of Medicine's Department of Biochemistry and Microbiology, under the leadership of Dr. W. Elaine Hardman. Researchers noticed a three-week delay in mortality in mice whose mothers were fed canola oil versus corn oil. The early delay in mortality was significantly different, but the ultimate overall survival rate was not. Eventually, all the mice developed tumors, but the ones fed canola oil had tumors that were slower-growing and smaller than the mice fed corn oil. Translated to human time scale, the duration of the protective effect linked to the maternal diet would be equivalent to several months (Sengupta et al., 2016). This study is among a body of work done by Marshall University scientists and others looking at the link between Omega-3 fatty acids and reduced incidence of various types of cancer including, but not restricted to, Chronic Lymphocytic Leukemia and Diffuse Large B-Cell Lymphoma. "The issue of parental diet and inter-generational transmission has become an important field of research; however, the mode of action often remains partially elusive," said Georgel, a professor in the Department of Biological Sciences at Marshall. "The MU research group focused on 'epigenetic' aspects of trans-generational transmission to explain the reported role of Omega-3 fatty acids. Epigenetics involves changes in gene expression which are not linked to changes in genetic sequences. These results have the potential to promote the design of simple changes in diet which would allow for reduced onset of various types of cancer, not only for the individuals using that diet but also for their offspring." Compounds found in green tea and wine may block formation of toxic metabolites Tel Aviv University (Israel), July 2, 2021 A new Tel Aviv University study suggests there is hope of treating certain inborn congenital metabolic diseases -- a hope found in green tea and in red wine. Most people with inherited metabolic disorders are born with a defective gene that results in a critical enzyme deficiency. In the absence of a cure, many patients with inborn congenital metabolic disorders must adhere to a strict and demanding diet their entire lives. This new research finds that certain compounds found naturally in green tea and red wine may block the formation of toxic metabolites. The research was led by Prof. Ehud Gazit of TAU's Faculty of Life Sciences and his doctoral student Shira Shaham-Niv. It was published in the Nature group journal Communications Chemistry. The researchers considered two compounds: (1) epigallocatechin gallate, known as EGCG, found naturally in green tea, which has attracted attention within the medical community for its potential health benefits; and (2) tannic acid, found in red wine, which is known to prevent the formation of toxic amyloid structures that cause neurodegenerative disorders such as Alzheimer's and Parkinson's disease. "In the case of inborn congenital metabolic diseases, the body does not produce a vital metabolic enzyme," Shaham-Niv said. "As a result, metabolites -- substances that are, among other things, the building blocks of DNA and proteins -- accumulate in the body. Such uncontrolled accumulation is toxic and can cause severe developmental and mental disorders. "Our new study demonstrates once again the ability of nature to produce the best candidate of drugs to treat some of the worst human maladies." Collectively, this group of disorders constitutes a significant portion of pediatric genetic diseases. The disease phenylketonuria (PKU), which produces the aggregation of the metabolite phenylalanine, is one common inborn metabolic disease. Infants with PKU must adhere to a strict diet free of phenylalanine for the rest of their lives. If they don't, they may face severe debilitating developmental problems. "But this is an incredibly difficult task, since phenylalanine is found in most of the food products that we consume," Shaham-Niv said. "The avoidance of certain substances is the only way to prevent the debilitating long-term effects of inborn congenital metabolic disorders. We hope that our new approach will facilitate the development of new drugs to treat these disorders." The new research is based on two previous studies conducted at Prof. Gazit's TAU laboratory. In the first study, phenylalanine was shown to be capable of self-assembly and of forming amyloid structures like those seen in Alzheimer's, Parkinson's and other neurodegenerative diseases. In the second study, by Shaham-Niv, other metabolites that accumulate in other inborn congenital metabolic diseases were also shown to undergo self-assembly processes and form toxic amyloid aggregates. "Both studies led to an overhaul in the research community's understanding of metabolic diseases," Shaham-Niv said. "In our new study, we examined whether the molecules identified in past studies on Alzheimer's disease and other amyloid diseases, which are known to inhibit the formation of amyloid aggregates, could also help counteract the amyloid formation process of metabolites in metabolic diseases." The new research focused on EGCG and tannic acid using test tubes and culture cell systems. The two substances were tested on three metabolites related to three innate metabolic diseases: adenine, cumulative tyrosine and phenylalanine. The results were promising. Both tannic acid and EGCG were effective in blocking the formation of toxic amyloid structures. The researchers also used computer simulations to verify the mechanism driving the compounds. "We are entering a new era of understanding the role and the importance of metabolites in various diseases, including metabolic diseases, neurodegenerative diseases and even cancer," Shaham-Niv concluded. "The tools we have developed are ground-breaking and have tremendous potential to help a wide range of patients in the future." People with fibromyalgia are substituting CBD for opioids to manage pain University of Michigan, June 24, 2021 Fibromyalgia is one of many chronic pain conditions that remains stubbornly difficult to treat. As the ravages of the opioid epidemic lead many to avoid these powerful painkillers, a significant number of people with fibromyalgia are finding an effective replacement in CBD-containing products, finds a new Michigan Medicine study. CBD, short for cannabidiol, is the second most common cannabinoid in the cannabis plant, and has been marketed for everything from mood stabilization to pain relief, without the intoxicating effects produced by the most common cannabinoid, THC. THC, which stands for delta-9-tetrahydrocannabinol, is the ingredient in marijuana that causes people to feel high. The cannabis industry has exploded, aided by the legalization of medical and recreational marijuana in states around the United States and the removal of hemp-derived CBD from Schedule 1 status--reserved for drugs with no currently accepted medical use and a high potential for abuse--at the federal level. Previous research shows that some people substitute medical cannabis (often with high concentrations of THC) for opioids and other pain medications, reporting that cannabis provides better pain relief and fewer side effects. However, there is far less data on CBD use. "CBD is less harmful than THC, as it is non-intoxicating and has less potential for abuse," said Kevin Boehnke, Ph.D., a research investigator in the Department of Anesthesiology and the Chronic Pain and Fatigue Research Center. "If people can find the same relief without THC's side effects, CBD may represent a useful as a harm reduction strategy." Boehnke and his team surveyed people with fibromyalgia about their use of CBD for treatment of chronic pain. "Fibromyalgia is not easy to treat, often involving several medications with significant side effects and modest benefits," Boehnke explained. "Further, many alternative therapies, like acupuncture and massage, are not covered by insurance." For this study, the team focused on 878 people with fibromyalgia who said they used CBD to get more insight into how they used CBD products. The U-M team found that more than 70% of people with fibromyalgia who used CBD substituted CBD for opioids or other pain medications. Of these participants, many reported that they either decreased use or stopped taking opioids and other pain medications as a result. "I was not expecting that level of substitution," said Boehnke, noting that the rate is quite similar to the substitution rate reported in the medical cannabis literature. People who said they used CBD products that also contained THC had higher odds of substitution and reported greater symptom relief. Yet the finding that products containing only CBD also provided pain relief and were substituted for pain medications is promising and merits future study, noted Boehnke. The team noted that much of the widespread use of CBD is occurring without physician guidance and in the absence of relevant clinical trials. "Even with that lack of evidence, people are using CBD, substituting it for medication and doing so saying it's less harmful and more effective," he said. Boehnke stressed the need for more controlled research into how CBD may provide these benefits, as well as whether these benefits may be due to the placebo effect. Clinically, opening up lines of discussion around CBD use for chronic pain is imperative, said Boehnke, for medication safety reasons as well as for "enhancing the therapeutic alliance and improving patient care."

united states university children australia israel china science technology france college phd research nature colorado michigan chinese european dna medicine spain united kingdom developing institute environment patients md adhd prof childhood improving greece alzheimer's disease norway cbd sec austria researchers parkinson omega faculty queensland mu thc oral infants chronic pain liver controlled physiology lithuania composition life sciences biochemistry collectively sunflowers epigenetics cf fibromyalgia microbiology respiratory medicinal gruber pharmacology biological sciences tau tel aviv university intestinal anesthesiology vrijheid morphine mulberry critical care medicine marshall university flinders university lcms developmental biology scott d development center vienna austria mle sengupta hospital colorado michigan medicine pfos mpo chronic lymphocytic leukemia pku egcg hplc murine stz hfd fev1 gary null tukey

Vigyan Patrika S2 EP20: Role of mycobacterial histidine biosynthesis in murine tubercular infection and pathogenesis

Bio Patrika Podcast

Play Episode Listen Later Apr 27, 2021 6:49

This episode is also available as a blog post: http://biopatrika.com/2021/04/27/interview-mycobacterial-histidine-biosynthesis-infection-tuberculosis/

infection pathogenesis patrika murine biosynthesis mycobacterial

Let's Duet: Nuisance in Narringarten EP 22

duet barnaby nuisance murine

Play Episode Listen Later Apr 21, 2021 56:27

Barnaby catches a glimpse of the impossible, and no I don't mean Murine finally being nice to him. His mom seems to be laying dormant in some kind of crystalline structure. All the boys need to do is get through this room without crushing any of the glass pieces and make it through to the other side.

Let's Duet: Tales of Taela EP 15

Play Episode Listen Later Feb 17, 2021 61:48

Murine and Ocker are getting more and more acquainted with their all too pleasant surroundings. Before they head out, they decide to check out some of the local quirky shop keeps. One of which who might be responsible for all of their terrible nightmares! Uh oh whats that all about?

tales duet murine

Let's Duet: Tales of Taela EP 14

Play Episode Listen Later Feb 10, 2021 45:43

Finally the crew come face to face with director Valen. The mysterious...masked dog man they've been searching for this whole time. Ocker and Murine are given a choose your own adventure brochure with 3 vastly different locales. Each one holds hints, tips and tricks to finding Valen's treasure trove. But first, its been a really long luxury boat cruise ride and the boys need some rest. They head over to their see through cabins and plan how to really give it to Wren.

tales duet valen murine

Let's Duet: Tales of Taela EP 13

Play Episode Listen Later Feb 3, 2021 49:26

Murine has been knocked out once again and finds himself surround by a bunch of friendly siphonophore....tendrils? He can't help himself but reach for them tasty tasty nugs and ends up running into a new friend in the void! Though, they seem to know about as much as Murine about what is going on here. Guess it's time to hunt more into through the endless nightmare.

tales duet murine

Let's Duet: Tales of Taela EP 5

Play Episode Listen Later Nov 27, 2020 58:36

Uh oh, looks like Ocker and Murine are in a bind again. Who would have guessed that Mynmir wasn't that much of an upstanding dude. Some would even say, he doesn't stand up at all, cause he's a werewolf, so he's on all fours. Pesky werewolves always mucking things up, you know how it is. Luckily, past adventures of slaying deities and unspeakable monstrosities have made Ocker and Murine a dexterous duo. Still got to work on that upper body strength though.

tales duet pesky murine

Comprehensive characterization of migration profiles of murine cerebral cortical neurons during development using FlashTag labeling

development migration copy comprehensive profiles hashimoto shin cerebral labeling kubo neurons characterization ishii cortical kasai nakajima biorxiv murine

Play Episode Listen Later Oct 5, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.05.317925v1?rss=1 Authors: Yoshinaga, S., Shin, M., Kitazawa, A., Ishii, K., Tanuma, M., Kasai, A., Hashimoto, H., Kubo, K.-i., Nakajima, K. Abstract: In mammalian cerebral neocortex, different regions have different cytoarchitecture, neuronal birthdates and functions. In most regions, neuronal migratory profiles have been speculated similar to each other based on observations using thymidine analogues. Few reports investigated regional migratory differences from mitosis at the ventricular surface. Here, in mice, we applied FlashTag technology, in which dyes are injected intraventricularly, to describe migratory profiles. We revealed a mediolateral regional difference in migratory profiles of neurons that is dependent on the developmental stages, e.g., neurons labeled at E12.5-15.5 reached their destination earlier dorsomedially than dorsolaterally even where there were underlying ventricular surfaces, reflecting sojourning below the subplate. This difference was hardly recapitulated by thymidine analogues, which visualize neurogenic gradient, suggesting biological significance different from neurogenic gradient. These observations advance understanding of cortical development, portraying strength of FlashTag in studying migration, and are thus a resource for studies of normal and abnormal neurodevelopment. Copy rights belong to original authors. Visit the link for more info

Probing Causality of the Brainstem-Hypothalamic Murine Models of Sleep-Wake Regulation

models regulation copy determination probing causality cortical billard brainstem hypothalamic alloway biorxiv murine sleep wake

Play Episode Listen Later Sep 22, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.21.306456v1?rss=1 Authors: Bahari, F., Billard, M. W., Kimbugwe, J., Curay, C., Watson, G. D. R., Alloway, K. D., Gluckman, B. J. Abstract: Sleep-wake regulation is thought to be governed by interactions among several nuclei in midbrain, pons, and hypothalamic regions. Determination of the causal role of these nuclei in state transitions requires simultaneous measurements from the nuclei with sufficient spatial and temporal resolution. We obtained long-term experimental single- and multi-unit measurements simultaneously from multiple nuclei of the putative hypothalamic and brainstem sleep-wake regulatory network in freely behaving rats. Cortical and hippocampal activity, along with head acceleration were also acquired to assess behavioral state. We found that although the average activity of cell groups during states matches the patterns presented previously in brief recordings of individual nuclei in head-fixed animals, the firing rates with respect to cortical and behavioral signs of state transitions differ in critical ways. Our findings pose fundamental questions about the neural mechanisms that maintain specific states and the neural interactions that lead to the emergence of new states. Copy rights belong to original authors. Visit the link for more info

Origins of 1f-like tissue oxygenation fluctuations in the murine cortex

origins copy tissue cortex fluctuations oxygenation biorxiv murine

Play Episode Listen Later Sep 20, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.18.303164v1?rss=1 Authors: Zhang, Q., Gheres, K. W., Drew, P. J. Abstract: The concentration of oxygen in the brain spontaneously fluctuates, and the power distribution in these fluctuations has 1/f-like dynamics. Though these oscillations have been interpreted as being driven by neural activity, the origins of these 1/f-like oscillations is not well understood. Here, to gain insight of the origin of the 1/f-like oxygen fluctuations, we investigated the dynamics of tissue oxygenation and neural activity in awake behaving mice. We found that oxygen signal recorded from the cortex of mice had 1/f-like spectra. However, band-limited power in the local field potential, did not show corresponding 1/f-like fluctuations. When local neural activity was suppressed, the 1/f-like fluctuations in oxygen concentration persisted. Two-photon measurements of erythrocyte spacing fluctuations ("stalls") and mathematical modelling show that stochastic fluctuations in erythrocyte flow and stalling could underlie 1/f-like dynamics in oxygenation. These results show discrete nature of erythrocytes and their irregular flow, rather than neural activity, could drive 1/f-like fluctuations in tissue oxygenation. Copy rights belong to original authors. Visit the link for more info

Differential effect of ethanol intoxication on peripheral markers of cerebral injury in murine blunt TBI

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Play Episode Listen Later Sep 20, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.18.303396v1?rss=1 Authors: li, z., zhang, j., halbgebauer, s., chandrasekar, a., rehman, r., ludolph, a. c., boeckers, t. m., huber-lang, m., otto, m., Roselli, F., olde Heuvel, f. Abstract: Blood-based biomarkers have proven to be a reliable measure of traumatic brain injury (TBI) severity and outcome, in both murine models and patients. In particular, neuron-specific enolase (NSE) and neurofilament light (NFL) have been investigated in the clinical setting post injury. Ethanol intoxication (EI) remains a significant comorbidity in TBI, with 30-40% of patients having a positive blood alcohol level (BAC) post TBI. The effect of ethanol on blood-based biomarkers on the prognosis and diagnosis of TBI remain unclear. In this study, we investigated the effect of EI on NSE and NFL and their correlation with blood-brain barrier (BBB) integrity in a murine model of TBI. We have used ultra-sensitive single molecule array technology (SIMOA) and ELISA methods to measure NFL, NSE and Claudin-5 concentrations in plasma 3h post TBI. We showed that both NFL and NSE were increased 3h post TBI. However, ethanol blood concentrations only showed an inverse correlation with NSE, but not NFL. Claudin-5 levels were increased post injury, but no difference was detected in EI. The Claudin-5 increase post TBI was correlated with NFL, but not with NSE. Thus, the data indicate that ethanol has a confined effect on biomarker release in the bloodstream and neuronal biomarkers reflect a different pathophysiology upon TBI. Copy rights belong to original authors. Visit the link for more info

nfl injury copy ei bbb blunt tbi cerebral markers bac peripheral differential ethanol intoxication heuvel nse biorxiv murine

Establishment of murine hybridoma cells producing antibodies against spike protein of SARS-CoV-2

Play Episode Listen Later Aug 29, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.29.272963v1?rss=1 Authors: Antipova, N. V., Larionova, T. D., Shakhparonov, M. I., Pavlyukov, M. S. Abstract: In 2020 the world faced the pandemic of COVID-19 - severe acute respiratory syndrome caused by a new type of coronavirus named SARS-CoV-2. To stop the spread of the disease, it is crucial to create molecular tools allowing to investigate, diagnose and treat COVID-19. One of such tools are monoclonal antibodies (mAbs). In this study we describe the development of hybridoma cells that can produce mouse mAbs against receptor binding domain of SARS-CoV-2 spike (S) protein. These mAbs are able to specifically detect native and denaturized S protein in all tested applications including immunoblotting, immunofluorescence staining and enzyme-linked immunosorbent assay. In addition, we showed that the obtained mAbs decreased infection rate of human cells by SARS-CoV-2 pseudovirus particles in in vitro experiments. Finally, we determined the amino acid sequence of light and heavy chains of the mAbs. This information will allow to use the corresponding peptides to establish genetically engineered therapeutic antibodies. To date multiple mAbs against SARS-CoV-2 proteins have been established, however due to the restrictions caused by pandemic, it is imperative to have a local source of the antibodies suitable for researches and diagnostics of COVID-19. Moreover, as each mAb has a unique binding sequence, bigger sets of various antibodies will allow to detect SARS-CoV-2 proteins even if the virus acquires novel mutations. Copy rights belong to original authors. Visit the link for more info

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Emergence of Non-Canonical Parvalbumin-Containing Interneurons in Hippocampus of a Murine Model of Type I Lissencephaly

Play Episode Listen Later Aug 21, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.21.262014v1?rss=1 Authors: Ekins, T. G., Mahadevan, V. G., Zhang, Y., D'Amour, J., Petros, T., McBain, C. J. Abstract: Type I lissencephaly is a neuronal migration disorder caused by haploinsuffiency of the LIS1 gene and is characterized in humans by agyria, mislamination of brain structures, developmental delays, and epilepsy. Here, we investigate the impact of LIS1 mutation on the cellular migration, morphophysiology, microcircuitry and genomics of mouse hippocampal CA1 parvalbumin-containing inhibitory interneurons (PV+INTs). We find that WT PV+INTs consist of two physiological subtypes (80% fast-spiking (FS), 20% non-fast-spiking (NFS)) and four morphological subtypes (basket, axo-axonic, bistratified, radiatum-targeting). We also discover that cell-autonomous mutations within interneurons disrupts morphological development of PV+INTs and results in the emergence of a non-canonical 'intermediate spiking (IS)' subset of PV+INTs. In the GlobalLis mutant, IS/NFS cells become the dominant PV+INT subtypes (56%) and the percentage of FS cells shrinks to 44%. We also find that IS/NFS cells are prone to entering depolarizing block, causing them to temporarily lose the ability to initiate action potentials and control network excitation, potentially promoting seizures. Finally, single-cell nuclear RNAsequencing of PV+INTs revealed several misregulated genes related to morphogenesis, cellular excitability, and synapse formation. Copy rights belong to original authors. Visit the link for more info

model copy emergence zhang fs canonical hippocampus petros mcbain nfs biorxiv mahadevan murine ca1

Starburst amacrine cells amplify optogenetic visual restoration through gap junctions in the murine retina