Podcasts about polymerization

There are all sorts of molecular tests to tell if you're infected with something specific, but what do you use when you're not sure what you might have? You might use a thermometer as a first step, but wouldn't it be nice if that thermometer was a bit more high tech? In this episode we meet Dr. Nick Meyerson, CEO and co-founder of Darwin Biosciences, who's team is working to develop the “molecular thermometer of the future.” We hear about how this physicist transitioned into molecular biology and then latched onto saliva as a sample of choice to detect early molecular indicator of infection. Nick does a great job of explaining his path leading up to the founding of Darwin Bio, the challenges of founding a company in early 2020, why saliva is their sample of choice, the beautiful simplicity of isothermal amplification methods, and the lesser-known funding routes of working with government agencies like the Defense Threat Reduction Agency (DTRA). Join us as we dive into the molecular nature of non-specific detection of infections, how it's done using no electricity, it's potential applications, and what the future holds for this field. Nick also shares lessons learned and some insights on the value of mentors and a lifelong curiosity. Subscribe to get future episodes as they drop and if you like what you're hearing we hope you'll share a review or recommend the series to a colleague.  Download Transcripts: Speaking of Mol Bio Podcast | Thermo Fisher Scientific - US Visit the Invitrogen School of Molecular Biology to access helpful molecular biology resources and educational content, and please share this resource with anyone you know working in molecular biology.

In this week's episode we'll explore the role of fibrinogen polymerization in thrombosis. Then, we'll discuss preventing CD19-negative relapse after CAR T-cell therapy in acute lymphoblastic leukemia. Finally, we'll learn how increased levels of the RNA-binding protein FUS has been identified as an effector of hematopoietic stem cell aging. 

Prof. Richard Price, Prosthodontist and Biomedical Engineering researcher based in Halifax, Canada is visiting Auckland to present on light curing. See link below for details: https://dentaleducationhub.co.nz/courses/curious-about-curing-everything-you-need-to-know-about-your-curing-light/   He shares freely from his extensive knowledge researching this topic for ~30 years. You will learn something new! Links to his content:  https://rprice.ca Article on the ability of Dentists to light cure simulated restorations- 44.7% failed to deliver the right amount of light to cure a restoration in this study! https://doi.org/10.2341/19-147-C

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.20.549974v1?rss=1 Authors: Boussaty, E. C., Ninoyu, Y., Andrade, L., Li, Q., Ohyama, T., Wahlin, K. J., Manor, U., Friedman, R. A. Abstract: Age-related hearing loss (ARHL) is a common sensory impairment with comlex underlying mechanisms. In our previous study, we performed a meta-analysis of genome-wide association studies (GWAS) in mice and identified a novel locus on chromosome 18 associated with ARHL specifically linked to a 32 kHz tone burst stimulus. Consequently, we investigated the role of Formin Homology 2 Domain Containing 3 (Fhod3), a newly discovered candidate gene for ARHL based on the GWAS results. We observed Fhod3 expression in auditory hair cells (HCs) and primarily localized at the cuticular plate (CP). To understand the functional implications of Fhod3 in the cochlea, we generated Fhod3 overexpression mice (Pax2-Cre+/-; Fhod3Tg/+) (TG) and HC-specific conditional knockout mice (Atoh1-Cre+/-; Fhod3fl/fl) (KO). Audiological assessments in TG mice demonstrated progressive high-frequency hearing loss, characterized by predominant loss of outer HCs and decrease phalloidin intensities of CP. Ultrastructural analysis revealed shortened stereocilia in the basal turn cochlea. Importantly, the hearing and HC phenotype in TG mice were replicated in KO mice. These findings indicate that Fhod3 plays a critical role in regulating actin dynamics in CP and stereocilia. Further investigation of Fhod3-related hearing impairment mechanisms may facilitate the development of therapeutic strategies for ARHL in humans. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.03.539131v1?rss=1 Authors: McCormick, L. A., Cleary, J. M., Hancock, W. O., Rice, L. M. Abstract: GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which the bound nucleotide regulates the strength of tubulin:tubulin interactions is debated. The "self-acting" (cis) model posits that the nucleotide (GTP or GDP) bound to a particular tubulin dictates how strongly that tubulin interacts, whereas the "interface-acting" (trans) model posits that the nucleotide at the interface of two tubulin dimers is the determinant. We identified a testable difference between these mechanisms using mixed nucleotide simulations of microtubule elongation: with self-acting nucleotide plus- and minus-end growth rates decreased in the same proportion to the amount of GDP-tubulin, whereas with interface-acting nucleotide plus-end growth rates decreased disproportionately. We then experimentally measured plus- and minus-end elongation rates in mixed nucleotides and observed a disproportionate effect of GDP-tubulin on plus-end growth rates. Simulations of microtubule growth were consistent with GDP-tubulin binding at and "poisoning" plus-ends but not at minus-ends. Quantitative agreement between simulations and experiments required nucleotide exchange at terminal plus-end subunits to mitigate the poisoning effect of GDP-tubulin there. Our results indicate that the interfacial nucleotide determines tubulin:tubulin interaction strength, thereby settling a longstanding debate over the effect of nucleotide state on microtubule dynamics. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.14.532631v1?rss=1 Authors: Bhanja, A., Lazzaro, M., Upadhyaya, A., Song, W. Abstract: Antigen-induced B-cell receptor (BCR) signaling is critical for initiating and regulating B-cell activation. The actin cytoskeleton plays essential roles in BCR signaling. Upon encountering cell-surface antigens, actin-driven B-cell spreading amplifies signaling, while B-cell contraction following spreading leads to signal attenuation. However, the mechanism by which actin dynamics switch BCR signaling from amplification to attenuation is unknown. Here, we show that Arp2/3-mediated branched actin polymerization is required for B-cell contraction. Contracting B-cells generate centripetally moving actin foci from lamellipodial F-actin networks in the B-cell plasma membrane region contacting antigen-presenting surfaces. Actin polymerization driven by N-WASP, but not WASP, generates these actin foci. N-WASP-dependent actin foci facilitate non-muscle myosin II recruitment to the contact zone to create actomyosin ring-like structures. Furthermore, B-cell contraction increases BCR molecular density in individual clusters, leading to decreased BCR phosphorylation. Increased BCR molecular density reduced levels of the stimulatory kinase Syk, the inhibitory phosphatase SHIP-1, and their phosphorylated forms in individual BCR clusters. These results suggest that N-WASP-activated Arp2/3 generates centripetally moving foci and contractile actomyosin ring-like structures from lamellipodial networks, enabling contraction. B-cell contraction attenuates BCR signaling by pushing out both stimulatory kinases and inhibitory phosphatases from BCR clusters, providing novel insights into actin-facilitated signal attenuation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.23.524173v1?rss=1 Authors: Paukstyte, J., Lopez Cabezas, R. M., Feng, Y., Tong, K., Schnyder, D., Elomaa, E., Gregorova, P., Doudin, M., Sarkka, M., Sarameri, J., Lippi, A., Vihinen, H., Juutila, J., Nieminen, A., Toronen, P., Holm, L., Jokitalo, E., Krisko, A., Huiskonen, J. T., Sarin, P., Hietakangas, V., Picotti, P., Barral, Y., Saarikangas, J. Abstract: Aging is associated with progressive phenotypic changes over time. Virtually all cellular phenotypes are produced by proteins and structural alterations in proteins can lead to age-related diseases. Nonetheless, comprehensive knowledge of proteins undergoing structural-functional changes during cellular aging and their contribution to age-related phenotypes is lacking. Here, we conducted proteome-wide analysis of early age-related protein structural changes in budding yeast using limited proteolysis-mass spectrometry. The results, compiled in online ProtAge-catalog, unravelled age-related functional changes in regulators of translation, protein folding and amino acid metabolism. Mechanistically, we found that folded glutamate synthase Glt1 polymerizes into supramolecular self-assemblies during aging causing breakdown of cellular amino acid homeostasis. Inhibiting Glt1 polymerization by mutating the polymerization interface restored amino acid levels in aged cells, attenuated mitochondrial dysfunction and led to life span extension. Altogether, this comprehensive map of protein structural changes enables identifying novel mechanisms of age-related phenotypes and offers opportunities for their reversal. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.10.523203v1?rss=1 Authors: Busley, A. V., Gutierrez-Gutierrez, O., Hammer, E., Steinegger, M., Boehmer, L., Schroeder, H., Kleinsorge, M., Altmueller, J., Marbach, F., Hasenfuss, G., Zimmermann, W.-H., Wollnik, B., Cyganek, L. Abstract: Noonan syndrome patients harboring causative variants in LZTR1 are particularly at risk to develop severe and early-onset hypertrophic cardiomyopathy. However, the underling disease mechanisms of LZTR1 missense variants driving the cardiac pathology are poorly understood. Hence, therapeutic options for Noonan syndrome patients are limited. In this study, we investigated the mechanistic consequences of a novel homozygous causative variant LZTR1L580P by using patient-specific and CRISPR/Cas9-corrected iPSC-cardiomyocytes. Molecular, cellular, and functional phenotyping in combination with in silico prediction of protein complexes uncovered a unique LZTR1L580P-specific disease mechanism provoking the cardiac hypertrophy. The homozygous variant was predicted to alter the binding affinity of the dimerization domains facilitating the formation of linear LZTR1 polymer chains. The altered polymerization resulted in dysfunction of the LZTR1-cullin 3 ubiquitin ligase complexes and subsequently, in accumulation of RAS GTPases, thereby provoking global pathological changes of the proteomic landscape ultimately leading to cellular hypertrophy. Importantly, uni- or biallelic genetic correction of the LZTR1L580P missense variant rescued the molecular and cellular disease-associated phenotype, providing proof-of-concept for CRISPR-based gene therapies. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.20.513009v1?rss=1 Authors: Zhao, Z., Hong, L., Huang, G., He, Y., Zuo, X., Han, W. Abstract: Cells sense physical cues, such as changes in extracellular matrix (ECM) stiffness, and translate these stimuli into biochemical signals that control various aspects of cellular behavior, thereby facilitating physiological and pathological processes in various organs. Evidence from multiple studies suggests that the anterior vaginal wall stiffness is higher in POP patients than in non-POP patients. Our experiments found that the expression of -smooth muscle actin (-SMA) in the anterior vaginal wall of patients with POP was increased, and the expression of DNMT1 was decreased. We used polyacrylamide gel to simulate matrix stiffening in vitro, and substrate stiffening induced the high expression of myofibroblast markers -SMA and CTGF in L929 cells. Inhibition of DNMT1 promotes fibroblast differentiation into myofibroblasts in vitro. The results of bioinformatics analysis showed that the expression of DNMT1 was significantly correlated with microtubule polymerization-related proteins. The experiment showed that the microtubule polymerization inhibitor nocodazole could eliminate the decrease of DNMT1 expression in fibroblasts induced by high stiffness. We conclude that fibroblasts sense an increase in the stiffness of the surrounding matrix and regulate fibroblast differentiation by regulating the expression of DNA methyltransferase 1 (DNMT1) through the regulation of microtubule polymerization. This study may help to elucidate the complex crosstalk between vaginal fibroblasts and their surrounding matrix in both healthy and pathological conditions, and provide new insights into the implications of potentially targeted phenotypic regulation mechanisms in material-related therapeutic applications. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.12.511969v1?rss=1 Authors: Bogucka-Janczi, K., Harms, G., May-Coissieux, M., Bentires-Alj, M., Thiede, B., Rajalingam, K. Abstract: The actin cytoskeleton is tightly controlled by RhoGTPases, actin binding proteins and nucleation-promoting factors to perform fundamental cellular functions. Here, we show that ERK3, an atypical MAPK, directly acts as a guanine nucleotide exchange factor for Cdc42 and phosphorylates the ARP3 subunit of the ARP2/3 complex at S418 to promote filopodia formation and actin polymerization, respectively. Consistently, depletion of ERK3 prevented both basal and EGF-dependent Rac1 and Cdc42 activation, maintenance of F-actin content, filopodia formation and epithelial cell migration. Further, ERK3 protein binds directly to the purified ARP2/3 complex and augments polymerization of actin in vitro. ERK3 kinase activity is required for the formation of actin-rich protrusions in mammalian cells. These findings unveil a fundamentally unique pathway employed by cells to control actin-dependent cellular functions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Are we headed for war?  East v. West?  NATO v. CTSO? Do the "kings of the earth" want/need a decimated population in order to bring on their false messiah?  Please join Steven and Bonnie as we explore the new procedures of Germany and Chin, the scams of electric energy/health through shots/(planned ?) strikes and banking collapse/the brewing war Eurasian/global war.  Is it God's time to call an end to Satan's rule over this world? The asterisks below indicate I mentioned this issue or video in the talk: *Vaxx a better abortion pill than abortion pill: https://t.me/childcovidvaccineinjuriesuk/2101 *Rabbi tells who's in charge (this link just worked in Chrome): https://twitter.com/thethwarter/status/1565352894140141569 Have never isolated the virus; PCR bogus; why elites gather w/o masks - no threat: https://t.me/AltSkull48/5095 *Funny summary vid, don't miss: https://youtube.com/shorts/NGlhV4pbKtQ?feature=share *Rich buy private jets to avoid airport hassle: https://www.zerohedge.com/markets/european- private-jet-demand-soars-rich-avoid-travel-chaos *Germany introduces digital ID: https://t.me/AltSkull48/5122 *Germany may have armed guards in streets by Oct: https://www.visiontimes.com/2022/08/15/germany-army-patrolling-streets-oct-1.html *Canada - save lives, euthanize yourself: https://www.cbc.ca/news/canada/manitoba/medically-assisted-death-could-save-millions- 1.3947481 *Children in a Chinese quarantine camp scream for food: https://t.me/CovidRedPills/14040 *Clots are self assembling circuits: https://yournews.com/2022/08/31/2405474/shocking- white-embalmer-clots-are-self-assembling/ *No global warming by man per NASA: https://t.me/GeneralMCNews/943 *Armed drones in China: https://t.me/CovidRedPills/14051 CDC changed the protocol for “covid deaths” on death certificate: https://t.me/ungathegreat/4078 *Untested booster ready this fall: https://t.me/DrJaneRuby/7170 *CA residents gas generators because grid is overloaded: https://t.me/ungathegreat/4095 *Margin calls in energy sector: https://www.bloomberg.com/news/articles/2022-09-06/energy- trade-risks-collapsing-over-margin-calls-of-1-5-trillion *Vaxxed glow differently in UV light (new street lights): https://t.me/FlatEarthAndMore/8433 *Purple/blue lights in CA: https://t.me/Flatandmore/222371 *Electric car w/ gas generator on back: https://t.me/ungathegreat/4103 Pfizer's revenue in one graph: https://unga.substack.com/p/pfizer-to-receive-record-high- revenue?sd=pf FEMA being offered to change Death certificate: thevigilantfox.substack.com/p/thats-beyond- fraud-how-fema-bribed *Electric vehicles and lithium batteries: https://t.me/FlatEarthAndMore/8459; https://youtube.com/shorts/XV9ijKAubfU?feature=share; https://threadreaderapp.com/thread/1567538178910994432.html *Pay w/ right hand store: https://t.me/AltSkull48/5151 Old jabs taken off market, new jabs only: https://t.me/childcovidvaccineinjuriesuk/2138 Israeli govt hides risks: https://t.me/childcovidvaccineinjuriesuk/2141 Israeli Population no longer complying: https://t.me/childcovidvaccineinjuriesuk/2142 *Circuits respond to 4G routers: https://rumble.com/v1j38wr-new-nano-circuit-discovery- frequencies-from-phones-laptops-build-circuits.html *“Ribbons” in masks, swabs, “vaccines”: https://www.stewpeters.com/video/2022/08/exclusive-report-shows-live-ribbons-found-on- pcr-test-swabs-from-china/ *Polymerization/ionization: https://t.me/NaturalNewsMedia/2921; https://www.bitchute.com/video/c86em24W5avx/ *Australia school canteens offer bug chips: https://t.me/GeneralMCNews/1033 Huge rise in infant mortality: https://t.me/C19TruthBombs/686; https://thefederalist.com/2022/09/09/cdc-admits-post-vaccine-myocarditis-concerns-that- were-labeled-covid-misinformation-are-legit/ *Climate change - nothing to do w/ man: https://t.me/AltSkull48/5173 *Switzerland to pay heat snitches: https://t.me/AltSkull48/5175; https://www.zerohedge.

The boys are back and fusion is, IN baby! You ever wanna rustle and tussle with the biggest, baddest Pokemon but aren't sure if you're a Rapid Strike Randall or Single Strike Samuel? Then be a Fusion Strike Franklin! Come hear Riley and JW talk through the crazy going ons in the upcoming Fusion Strike set and lay out what you need to know as we approach a new metagame. This episode is sponsored by Manscaped. Use code TAGTEAM for 20% off and free shipping at checkout! You won't want to miss this opportunity to make your Duosion shine.

This chapter has been described from the book "ORGANIC CHEMISTRY", written by Morrison and Boyd

Thank you so much for listening to today's PODCAST EPISODE...

Our party deals with the aftermath of the Feathergale Assault and begins to make their escape. Too effective critical hits, stair falls in heavy armor, and a general disrespect for a bad man's personal space. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/diceytimes/support

Just a single point mutation in the beta-globin gene drives a complex, unrelenting condition characterized by vaso-occlusion, chronic hemolysis, and chronic anemia called hemoglobin S polymerization, as explained here. P-UNB-US-00553 V1

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.17.387142v1?rss=1 Authors: Zhang, W., Kim, C., Tam, C. P., Lelyveld, V., Bala, S., Chaput, J., Szostak, J. W. Abstract: The prebiotic synthesis of ribonucleotides is likely to have been accompanied by the synthesis of noncanonical nucleotides including the threo-nucleotide building blocks of TNA. Here we examine the ability of activated threo-nucleotides to participate in nonenzymatic template-directed polymerization. We find that primer extension by multiple sequential threo-nucleotide monomers can occur but is strongly disfavored relative to ribo-nucleotides. Kinetic, NMR and crystallographic studies suggest that this is due in part to the slow formation of the imidazolium-bridged TNA intermediate in primer extension, and in part because of the greater distance between the attacking RNA primer 3'-hydroxyl and the phosphate of the incoming threo-nucleotide intermediate. Even a single activated threo-nucleotide in the presence of an activated downstream RNA oligonucleotide is added to the primer ten-fold more slowly than an activated ribonucleotide. In contrast, a single activated threo-nucleotide at the end of an RNA primer or in an RNA template results in only a modest decrease in the rate of primer extension, consistent with the minor and local structural distortions revealed by crystal structures. Our results are consistent with a model in which heterogeneous primordial oligonucleotides would, through cycles of replication, have given rise to increasingly homogeneous RNA strands. Copy rights belong to original authors. Visit the link for more info

Polymer chemistry has been one of the main disruptive forces in the last few decades, having a profound impact on materials used in all applications, enabling new technologies and profoundly impacting everyone’s life. Polymers are at the core of modern material science and despite having generated some concerning environmental challenges, it’s hard to imagine a future without them. Dr. Leibfarth is one of the most creative minds in polymer chemistry today and he is leading some incredible innovation in the way these materials are made and applied. He shares a fascinating story of elite collegiate American football, science, inspiration and creativity, as well as where different disciplines converge and provide the disruptive force to change paradigms. Paolo and Frank discuss stereo-controlled polymerization, novel functionalization, exploration of structure-function relationships, as well as Frank's personal and professional growth.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.18.303297v1?rss=1 Authors: Balint, E., Unk, I. Abstract: Polymerase eta (Pol{eta}) is a translesion synthesis DNA polymerase directly linked to cancer development. It can bypass several DNA lesions thereby rescuing DNA damage-stalled replication complexes. We previously presented evidence implicating Saccharomyces cerevisiae Pol{eta} in transcription elongation, and identified its specific RNA extension and translesion RNA synthetic activities. However, RNA synthesis by Pol{eta} proved rather inefficient under conditions optimal for DNA synthesis. Searching for factors that could enhance its RNA synthetic activity, we have identified the divalent cation of manganese. Here we show, that manganese triggers drastic changes in the activity of Pol{eta}. It increases the efficiency of ribonucleoside incorporation into RNA by ~400-2000-fold opposite undamaged DNA, and ~3000 and ~6000-fold opposite TT dimer and 8oxoG, respectively. Importantly, preference for the correct base is maintained with manganese during RNA synthesis. In contrast, activity is strongly impaired, and base discrimination almost lost during DNA synthesis by Pol{eta} with manganese. Moreover, Pol{eta} shows strong preference for manganese during RNA synthesis even at 25-fold excess magnesium concentration. Based on these, we suggest that selective metal cofactor usage plays an important role in determining the specificity of Pol{eta} during synthesis enabling it to function at both replication and transcription. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.26.268748v1?rss=1 Authors: Chou, S. Z., Pollard, T. D. Abstract: We report high resolution cryo-electron microscopy structures of actin filaments with N-1-pyrene conjugated to cysteine 374 and either ADP (3.2 [A]) or ADP-phosphate (3.0 [A]) in the active site. Polymerization buries pyrene in a hydrophobic cavity between subunits along the long-pitch helix with only minor differences in conformation compared with native actin filaments. These structures explain how polymerization increases the fluorescence 20-fold, how myosin and cofilin binding to filaments reduces the fluorescence and how profilin binding to actin monomers increases the fluorescence. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.21.262121v1?rss=1 Authors: Gerak, C. A. N., Cho, S. Y., Kolesnikov, M., Okon, M., Murphy, M. E. P., Sessions, R. B., Roberge, M., McIntosh, L. P. Abstract: ETV6 is an ETS family transcriptional repressor that self-associates by its PNT domain to facilitate cooperative DNA binding. Chromosomal translocations frequently generate constitutively active oncoproteins with the ETV6 PNT domain fused to the kinase domain of one of many protein tyrosine kinases. Although an attractive target for therapeutic intervention, the propensity of the ETV6 PNT domain to polymerize via the tight head-to-tail association of two relatively flat interfaces makes it challenging to identify suitable small molecule inhibitors of this protein-protein interaction. Herein we provide a comprehensive biophysical characterization of the ETV6 PNT domain interaction interfaces to aid future drug discovery efforts and help define the mechanisms by which its self-association mediates transcriptional repression. Using NMR spectroscopy, X-ray crystallography, and molecular dynamics simulations, we demonstrate that ETV6 PNT domain variants with monomerizing mutations adopt very stable helical bundle folds that do not change in conformation upon self-association. Amide hydrogen exchange and surface plasmon resonance-monitored alanine scanning mutagenesis studies identified hot spot regions within the self-association interfaces. These regions include both central hydrophobic residues and flanking salt-bridging residues. Collectively, these studies indicate that small molecules targeted to these hydrophobic or charged regions within the relatively rigid interfaces could potentially serve as orthosteric inhibitors of ETV6 PNT domain polymerization. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.20.258525v1?rss=1 Authors: Gerak, C. A. N., Zhang, S. M., Balgi, A. D., Sadowski, I. J., Sessions, R. B., McIntosh, L. P., Roberge, M. Abstract: ETV6 is an ETS family transcriptional repressor for which head-to-tail polymerization of its PNT domain facilitates cooperative binding to DNA by its ETS domain. Chromosomal translocations frequently fuse the ETV6 PNT domain to one of several protein tyrosine kinases. The resulting chimeric oncoproteins undergo ligand-independent self-association, autophosphorylation, and aberrant stimulation of downstream signaling pathways leading to a variety of cancers. Currently, no small molecules inhibitors of ETV6 PNT domain polymerization are known and no assays targeting PNT domain polymerization have been described. In this study, we developed complementary experimental and computational approaches for identifying such inhibitory compounds. One mammalian cellular approach utilized a mutant PNT domain heterodimer system covalently attached to split Gaussia luciferase fragments. In this protein fragment complementation assay, inhibition of PNT domain heterodimerization reduces luminescence. A yeast assay took advantage of activation of the reporter HIS3 gene upon heterodimerization of mutant PNT domains fused to DNA-binding and transactivation domains. In this two-hybrid screen, inhibition of PNT domain heterodimerization prevents cell growth in medium lacking histidine. The Bristol University Docking Engine (BUDE) was used to identify virtual ligands from the ZINC8 library predicted to bind the PNT domain polymerization interfaces. Over 75 hits from these three assays were tested by NMR spectroscopy for binding to the purified ETV6 PNT domain. Although none were found to bind, lessons learned from this study may facilitate future approaches for developing therapeutics that act against ETV6 oncoproteins by disrupting PNT domain polymerization. Copy rights belong to original authors. Visit the link for more info

For the first time in our show's history, we have produced a hybrid episode. On the first segment, Angie joins us once again to discuss the disturbing Ubisoft allegations that have surfaced in recent weeks. Then, for the rest of the episode, buckle in for a deep dive into Xbox Game Studios with Tyler. Which studios will show games during the Xbox Games Showcase on July 23rd? What about third parties? And how about Microsoft acquiring some more studios, possibly even WB Interactive?Follow us on Twitter: @TTStageFollow our guest Angie on Twitter: @angdacatMusic by Rukunetsu and used with permission.TIMESTAMPS 00:08 - Opening message for this episode. What's up with the structure?05:56 - A candid discussion about the recent Ubisoft allegations.23:39 - What to expect from third-parties during the Xbox Games Showcase.28:12 - A deep dive into Xbox Game Studios and their current projects.54:46 - Future Xbox Game Studios acquistions and WB Interactive rumors.

For the first time in our show's history, we have produced a hybrid episode. On the first segment, Angie joins us once again to discuss the disturbing Ubisoft allegations that have surfaced in recent weeks. Then, for the rest of the episode, buckle in for a deep dive into Xbox Game Studios with Tyler. Which studios will show games during the Xbox Games Showcase on July 23rd? What about third parties? And how about Microsoft acquiring some more studios, possibly even WB Interactive?Follow us on Twitter: @TTStageFollow our guest Angie on Twitter: @angdacatMusic by Rukunetsu and used with permission.TIMESTAMPS 00:08 - Opening message for this episode. What's up with the structure?05:56 - A candid discussion about the recent Ubisoft allegations.23:39 - What to expect from third-parties during the Xbox Games Showcase.28:12 - A deep dive into Xbox Game Studios and their current projects.54:46 - Future Xbox Game Studios acquistions and WB Interactive rumors.

Bathtubs and showers are routinely exposed to shampoos, conditioners, bath oils and other slippery substances and when combined with mineral deposits can create a slippery film. Often referred to as "Polymerization", these films are difficult to remove and are a leading cause of bathtub slip and fall events for the hospitality industry. Greg Wenthe from the Safe Step Company talks about how his company has been safety treating bathtubs and showers for the countries largest hotels.

Can you get plastics from sugar beets? This podcast is the first of six we recorded from a trade fair called Plastteknik Nordic (Nordic plastics technology). Niklas Warlin is a PhD student from Lund University working in the chemistry department on the STEPS-Mistra program.

*slaps top of duel* This bad boy can fit so many Kuribohs in it. This week, Jimmy talks about his side-gig! Tyler talks about something boring! Then, we get into discussing the final part of the duel between Kaiba and Yugi. Things get... surprisingly metal, and emotional? We talk mammoth chest-bursters, fusing zombies to non-zombies, infinite versions of tiny creatures, and brand new strategies that we're convinced Yugi pulled out of his ass. Later, we wax poetic about Link, the Hero of Time, and remind you all to please please please stop touching Millennium Items. They WILL possess you. Does anyone actually know how Polymerization works? Did Kaiba get his evil groove back? Would Big Yugi duel a man in Reno, just to watch him die?

In this episode Mike and Bob discuss a technical topic, and really try to keep it simple. How did we do? Please subscribe to all of our Haz Mat shows: The Haz Mat Guys Podcast, THMG Hot wash, THMG Instructors corner. We also do a weekly round table discussion with experts from around the country live on blab.im under The Haz Mat Guys Nation every Tuesday night at 21:15EST. You can find us on YouTube. Thanks for listening and watching!

Tue, 5 May 2015 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/18313/ https://edoc.ub.uni-muenchen.de/18313/1/Braml_Nicole.pdf Braml, Nicole ddc:540, ddc:500, Fakultät für Chemie und Phar

Wed, 17 Dec 2014 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/19023/ https://edoc.ub.uni-muenchen.de/19023/1/Kaisarly_Dalia.pdf Kaisarly, Dalia Adel Mahmoud

Tue, 1 Oct 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/17517/ https://edoc.ub.uni-muenchen.de/17517/1/Mast_Christof.pdf Mast, Christof ddc:530, ddc:500, Fakultät für Physik

Formin proteins are actin nucleators and elongators which can be found in most eukaryotic cells. In this work, structure-function relationships between yeast formin Bni1p and actin polymerization were studied. In the first part of this work, it was attempted to clone and express formin constructs derived from yeast Bni1p (Saccharomyces cerevisiae), including the key FH2 domain and a modified FH1 domain. Biomathematical models involving both diffusion and concentration-limited actin recruitment kinetics could be tested with such proteins. Cloning was mostly successful, but only the FH2 domain alone was expressed. In the second part of this work, a salt effect on FH2 mediated actin nucleation was discovered by means of pyrene assays and epifluorescence microscopy. Potassium chloride (KCl) is a downregulator of FH2 nucleation activity: a higher KCl concentration leads to a significantly lower actin polymerization speed (kp, m), to a bigger lag time (tlag) and to a bigger t1/2, with the respective actin filament length distributions. The salt effect was shown to be significant in a KCl concentration range from 10 mM to 90 mM at two different FH2 concentration, but not in absence of FH2. The critical KCl concentration is lowered in the presence of FH2. Some initial experiments with sodium chloride point to a non-specific nature of this salt. This is in agreement with the electrostatic nature of the salt effect, which was studied further by computational means: A decrease of the KCl concentration leads to lower binding free energies of the protein-protein interactions in the crystallographically characterized actin-FH2 complex 1Y64. This is especially the case for the electrostatic Coulomb interaction of a specific area ("lasso" site). ANCHOR calculation results of solvent accessible surface areas (SASAs) corroborate the importance of this site. The experimentally found downregulation of FH2 mediated actin nucleation by KCl can therefore be explained by reduced actin recruitment by the FH2 dimer: KCl diminishes the surface charge of FH2 and actin and thus weakens electrostatic Coulomb interactions. In future, this newly discovered salt effect should be considered in experiments on formins, for example when performing in vitro screens for FH2 inhibitors. The relevance of this new salt effect in vivo remains to be demonstrated.

Alkenes may be oxidized to diols by permanganate or by OsO4 catalysis. Metal catalysts provide orbitals that allow simultaneous formation of two bonds from metal to alkene or H2. Coupling such oxidative additions to reductive eliminations, provides a low-energy catalytic path for addition of H2 to an alkene. Such catalytic hydrogenation is often said to involve syn stereochemistry, but the primary literature shows that addition can be anti when allylic rearrangement occurs on the catalyst. Similar oxidative/reductive cycles operate in olefin metathesis and metal-catalyzed polymerization. Careful catalyst design allows control over polymer stereochemistry (tacticity). Polymerizations catalyzed by free-radicals or acids typically lack stereochemical control, but there are ways to control regiochemistry and chain length. Latex, a natural polymer, coagulates to form a rubber ball. Complete course materials are available at the Open Yale Courses website: http://oyc.yale.edu This course was recorded in Spring 2011.

Fri, 14 Jan 2011 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15333/ https://edoc.ub.uni-muenchen.de/15333/1/Haag_Benjamin.pdf Haag, Benjamin

The present work addressed the determination and visualization of the direction and extent of polymerization shrinkage in the light-initiated composite. Hypotheses about the light-cured composite contraction patterns are controversial. With high resolution µCT images, the displacement vector fields are examined and calculated two-dimensionally via an elastic registration algorithm using vector-spline regularization and three-dimensionally with a local rigid registration (block matching) following images segmentation (corresponding traceable fillers in composite). It appears that the light-initiated resin composites do not always shrink toward the light source. Two major contraction patterns were observed: either shrink toward the top-surface (free surface), or toward one side of the cavity wall, in which the bonding was stronger or remained intact. With the proposed methods, it is possible to describe the contraction patterns in great detail. We could demonstrate that the bonding quality to the tooth affects the material movement more than described so far. In addition, the geometry of the cavity also acts as a factor. The continuation of the studies into the interaction of tooth-adhesive-composite indicated the shortcomings and limitations of the current FEA simulation studies. This meant that the assumption of FEA, especially in adhesive systems (i.e., bonding situations and hybridizations), is too perfect and simplificative to interpret the real condition in clinical. The qualitative and quantitative analysis of the shrinkage vector field along with the µCT datasets supply more insight into the shrinkage behavior in real teeth with all their variations of the boundary conditions than with any currently available method. This new approach has the potential to reevaluate and hopefully unify all the currently available hypotheses concerning the extent and orientation of polymerization shrinkage.

Cynthia Reinhart-King explains how substrates play a large role in cell connectivity. The effects on cell assembly are also examined.

Mon, 21 Jul 2008 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/8972/ https://edoc.ub.uni-muenchen.de/8972/1/Visvanathan_Anuradha.pdf.pdf Visvanathan, Anuradha

Lecture 17: This class covers actin polymerization, and an introduction to other parts of the cytoskeleton, such as the intermediate filaments.

Wed, 1 Jan 1992 12:00:00 +0100 http://epub.ub.uni-muenchen.de/4229/ http://epub.ub.uni-muenchen.de/4229/1/061.pdf Enzel, Patricia; Bein, Thomas Enzel, Patricia und Bein, Thomas (1992): Poly(acrylonitrile) chains in zeolite channels. Polymerization and pyrolysis. In: Chemistry of Materials, Vol. 4, Nr. 4: pp. 819-824. Chemie und Phar

Aniline has been polymerized in the three-dimensional channel system of zeolite Y. The monomer was diffused into zeolites with different levels of acidity from hexane solution. Subsequent admission of peroxydisulfate or iodate from aqueous solution yielded the intrazeolite polymers, as demonstrated by FT-IR, electronic absorption data and recovery of the included polymer. With S2O82-, the intrazeolite products are a function of the proton content of the zeolite. Polymer is only formed when a sufficient supply of protons is present in the zeolite host. When neutral iodate solution is used, no polymer is formed in NaY and acid zeolites, but at low pH aniline polymerizes in all zeolites. The open pore system of the zeolite host can be accessed by base such that the intrazeolite protonated polymer is transformed into the corresponding neutral polymer. The polymer chains encapsulated in zeolite hosts represent a new class of low- dimensional electronic materials.

Sun, 1 Jan 1984 12:00:00 +0100 http://epub.ub.uni-muenchen.de/3913/ http://epub.ub.uni-muenchen.de/3913/1/038.pdf Mayr, Herbert; Schneider, Reinhard Mayr, Herbert und Schneider, Reinhard (1984): The efficiency of alkyl halide initiators in carbocationic polymerization. In: Die Makromolekulare Chemie, Rapid Communications, Vol. 5, Nr. 1: pp. 43-46. Chemie und Pharmaz