Podcasts about af10

In this episode of the Epigenetics Podcast, we talked with Ani Deshpande from Sanford Burnham Prebys about his work on epigenetic regulation and developing small molecules through high throughput screens for AML. Throughout our discussion, we delve into Dr. Despande's journey into the field of biology and science, tracing his evolution from a literature enthusiast in Mumbai to a dedicated cancer researcher. He reflects on his formative experiences during his PhD at Ludwig Maximilian University in Munich, where she developed murine models for refractory acute myeloid leukemia (AML). We examine these models' contributions to therapeutic discovery and understanding the intricate mechanisms underscoring AML's complexities. Transitioning to his postdoctoral work at Scott Armstrong's lab in Boston, Dr. Despande shares his insights on the importance of epigenetic regulators, such as DOT1L, in leukemias, and how they can serve as strategic therapeutic targets. His ambitious pursuit of translational research is further highlighted through his efforts in developing a conditional knockout mouse model and his collaborative work utilizing CRISPR technology to refine our understanding of epigenetic regulation in cancer pathogenesis. Moreover, we engage in a conversation about the challenges and opportunities that arise when establishing his lab at Sanford Burnham Prebys. Dr. Despande candidly discusses the delicate balance between pursuing topics of genuine interest versus adhering to grant fundability, underlining the tension researchers face in the current scientific landscape. His emphasis on the critical need for innovation within lab settings serves as a motivational call for emerging scientists to venture beyond the established templates that often inhibit groundbreaking discoveries. We conclude our dialogue with an exploration of his recent projects, which involve targeting specific epigenetic modifiers and how his lab's findings can contribute to greater understanding and potential treatments for not only AML but also other pediatric cancers driven by gene fusions. Dr. Despande's insights into the integration of modern technologies, such as CRISPR libraries, exemplify his commitment to pushing the boundaries of cancer research. In addition to discussing his scientific contributions, we touch upon Dr. Despande's foray into podcasting (The Discovery Dialogues), shedding light on his motivation to bridge the communication gap between scientists and the broader public. He articulates his desire to demystify scientific discoveries and promote awareness about the intricate journey of research that lays the groundwork for medical advancements. This multidimensional discussion not only highlights his scientific achievements but also emphasizes the importance of effective science communication in fostering public understanding and appreciation of research.   References Deshpande AJ, Cusan M, Rawat VP, Reuter H, Krause A, Pott C, Quintanilla-Martinez L, Kakadia P, Kuchenbauer F, Ahmed F, Delabesse E, Hahn M, Lichter P, Kneba M, Hiddemann W, Macintyre E, Mecucci C, Ludwig WD, Humphries RK, Bohlander SK, Feuring-Buske M, Buske C. Acute myeloid leukemia is propagated by a leukemic stem cell with lymphoid characteristics in a mouse model of CALM/AF10-positive leukemia. Cancer Cell. 2006 Nov;10(5):363-74. doi: 10.1016/j.ccr.2006.08.023. PMID: 17097559. Deshpande AJ, Deshpande A, Sinha AU, Chen L, Chang J, Cihan A, Fazio M, Chen CW, Zhu N, Koche R, Dzhekieva L, Ibáñez G, Dias S, Banka D, Krivtsov A, Luo M, Roeder RG, Bradner JE, Bernt KM, Armstrong SA. AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes. Cancer Cell. 2014 Dec 8;26(6):896-908. doi: 10.1016/j.ccell.2014.10.009. Epub 2014 Nov 20. PMID: 25464900; PMCID: PMC4291116. Sinha S, Barbosa K, Cheng K, Leiserson MDM, Jain P, Deshpande A, Wilson DM 3rd, Ryan BM, Luo J, Ronai ZA, Lee JS, Deshpande AJ, Ruppin E. A systematic genome-wide mapping of oncogenic mutation selection during CRISPR-Cas9 genome editing. Nat Commun. 2021 Nov 11;12(1):6512. doi: 10.1038/s41467-021-26788-6. Erratum in: Nat Commun. 2022 May 16;13(1):2828. doi: 10.1038/s41467-022-30475-5. PMID: 34764240; PMCID: PMC8586238.   Related Episodes Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard) The Menin-MLL Complex and Small Molecule Inhibitors (Yadira Soto-Feliciano) MLL Proteins in Mixed-Lineage Leukemia (Yali Dou)   Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.30.522239v1?rss=1 Authors: Schmidt, A. R., Shephard, R., Patrick, R. L., Bergeron, S. A. Abstract: As essential components of gene expression networks, transcription factors regulate neural circuit assembly. GS homeobox 1 (gsx1) is expressed in the developing visual system; however, no studies have examined its role in visual system differentiation. In zebrafish, retinal ganglion cell (RGC) axons terminate in ten arborization fields (AFs) in the optic tectum (TeO) and pretectum (Pr). Pretectal AFs (AF1-AF9) mediate distinct and essential visual behaviors, yet we understand very little about their development compared to AF10 in the TeO. Using gsx1 zebrafish mutants, immunohistochemistry, and transgenic lines, we observed that gsx1 is required for vesicular glutamate transporter, slc17a6b, expression in the Pr, but not overall neuron number. gsx1 mutants have normal eye morphology, yet exhibit impaired vision, and a significantly reduced volume of RGC axons innervating the Pr and TeO, including loss of AF7. Consistent with this, prey capture is reduced in gsx1 mutants. Timed laser ablation of slc17a6b-positive neurons reveals that they aide directly in AF7 formation. This work is the first to implicate gsx1 in establishing cell identity and functional neural circuits in the visual system. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PROGRAMA - Amigos Pela Fé. EPISÓDIO - 10. TEMA - O Semeador. APRESENTADOR - Edmilson. DATA - 27 de Julho de 2021.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.19.160804v1?rss=1 Authors: Guggiana Nilo, D. A., Riegler, C., Hübener, M., Engert, F. Abstract: Larval zebrafish (Danio rerio) are an ideal organism to study color vision, as their eye possesses four types of cone photoreceptors, covering most of the visible range and into the UV [1,2]. Additionally, their entire eye and nervous system are accessible to imaging, given they are naturally transparent [3-5]. Relying on this advantage, recent research has found that, through a set of color specific horizontal, bipolar and retinal ganglion cells (RGCs) [6-8], the eye then relays tetrachromatic information to several retino-recipient areas (RAs) [9,10]. The main RA is the optic tectum, receiving 97% of the RGC axons via the neuropil mass termed Arborization Field 10 (AF10) [11,12]. In this work, we aim to understand the processing of color signals at the interface between RGCs and their targets in the brain. We used 2-photon calcium imaging to separately measure the responses of RGCs and neurons in the dorsal brain to stimulation with four different colors in awake animals. We find that color information is widespread throughout the larval brain, with a large variety of color responses among RGCs, and an even greater diversity in their targets. Specific combinations of response types are localized to specific nuclei, but we observe no single color processing structure. In the main interface in this pathway, the connection between Arborization Field 10 and the tectum, we observe key elements of color processing such as enhanced signal decorrelation and improved decoding [13,14]. Finally, when presenting a richer set of stimuli, we identify parallel processing of color, motion and luminance information in the same cells/terminals, evidence of a rich color vision machinery in this small vertebrate brain. Copy rights belong to original authors. Visit the link for more info

Zdravím vás u dalšího dílu!! :) Tentokrát byla hostem moje maminka osobně! Člověk, který mě zná nejdéle na světě..Říkala jsem si- často od vás dostávám otázky ohledně mé minulosti, začátků fitness i závodění.. A kdo vám tohle přiblíží nejlépe, než ten, kdo u toho jednak byl a druhak mě tolik zná..Otázky dopředu maminka nevěděla a celý podcast nemá ANI JEDEN střih :) Vše je upřímné a reálné. Tak, jak jsem to chtěla pro vás uchovat..Padla i témata o kterých jsem nikdy v životě nemluvila a věřím, že i vy tuhle naší otevřenost ohledně mojí minulosti oceníte..  Doufám, že si díl užijete aa ano- mám moderní maminku, která má i Instagram :D Pokud ji chcete sledovat, najdete ji tu: https://www.instagram.com/misafaltova/ ... ➢ Kontakt pro SPOLUPRÁCE: anna.faltova.af@gmail.com http://www.www.annafaltova.cz/ ➢ Instagram: https://www.instagram.com/annafaltova/ ➢ Facebook skupina ,,Silnější spolu" https://www.facebook.com/groups/12234... ......... GALSARI http://www.galsari.com/ FITNESS007 https://www.fitness007.cz/ SWIMMEEZ https://www.swimmeez.cz/  RICH MOVE gumy na trénink http://richmove.cz/ Kód: Af10 pro slevu TÝM BODYHUNTERS https://www.bodyhunters.cz/cs Kód: AF25 pro slevu 25% na všechny programy SUPER EYES Anti Blue Light Brýle https://www.supereyes.org/ Kód: anna10 pro slevu TOP JÍDLO https://top-jidlo.cz/ KRYT ART Kolekce http://www.krytart.cz/annafaltova/

Zdravím vás u dalšího dílu! :) V návaznosti na spoustu krásných reakcí, na mé poslední díly, jak na podcastech, tak na Youtube.. K vám přicházím s novou epizodou o pozávodním stavu a shrnuju v ní 7 mých tipů, jak tenhle kolikrát hodně náročný pozávodní stav zvládnout, třeba o něco lépe.. Jak k věcem přistupovat, pokud vám pozávodní stav dělá problémy, nebo pokud se závoděním i teprve začínáte a pozávodní období je něco, čeho se tak trošku obáváte.. Jde to, jde mít příjemný, pohodový přestup ze závodního "módu" a tady jsou malé tipy ode mě! :)Hodně štěstí a sil všem závodníkům, kteří jsou právě v přípravě! Myslím na vás! :)) Bojujte!A. _________________________ ➢ Kontakt pro SPOLUPRÁCE:anna.faltova.af@gmail.com ......... http://www.www.annafaltova.cz/ ➢ Instagram: https://www.instagram.com/annafaltova/➢ Facebook skupina ,,Silnější spolu"https://www.facebook.com/groups/122343091684831/?ref=bookmarks ......... PODCAST: Cookies 4 DeadliftsiTunes, Spotify, Youtubehttps://www.podparadise.com/Podcast/1455080648 ............................ GALSARIhttp://www.galsari.com/ FITNESS007https://www.fitness007.cz/ SWIMMEEZhttps://www.swimmeez.cz/ .. RICH MOVE gumy na tréninkhttp://richmove.cz/Kód: Af10 pro slevu TÝM BODYHUNTERShttps://www.bodyhunters.cz/csKód: AF25 pro slevu 25% na všechny programy SUPER EYES Anti Blue Light Brýlehttps://www.supereyes.org/Kód: anna10 pro slevu .. TOP JÍDLOhttps://top-jidlo.cz/ KRYT ART Kolekcehttp://www.krytart.cz/annafaltova/

Charles Boutin’s long conspiracy has been fully revealed. The Firewall team dived into the depths of Luna and found the tree that would end all life: the TITAN shadowseed, grown into fruition by Boutin. The ex-PROX-E’s revenge and legacy must be stopped. The Sentinels must destroy Boutin and the thing that he calls his son at all costs. Read the campaign’s epilogue, HOSTEL COMPLEX, here. PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Finale appeared first on The Drunk and The Ugly.

The Lunar Deep Delve is a sunken shaft of hell. The Sentinels have dropped into the festering pit of Boutin’s final play. TITAN has taken root here in the heart of the Moon, and it is up to the Firewall agents to cleanse the corruption with fire. PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 15 appeared first on The Drunk and The Ugly.

The Firewall team spent some time under the radar, investigating their next lead. There is one final account payment on Luna to track down, and the team is scrambling to put together all of the information they’ve uncovered. Charles Boutin, traitor, mastermind, and murderer, is still steps ahead of them. PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 14 appeared first on The Drunk and The Ugly.

Kidnapping, industrial espionage, murder, and grand theft VTOL: just another day on the Moon. The team is now moving on their lead in the city of Nectar. Boutin is still steps ahead of them, and his true plan and intentions have not yet coalesced. Meanwhile, Noah has set off to Clever Hands, the habitat owned by Somatek, following an invitation to take up an ego bounty on a dangerous uplift renegade. Side Chatter PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 13 appeared first on The Drunk and The Ugly.

The Firewall team conducted a security sweep of its own morphs, and discovered some perilously intriguing things. Someone in Firewall has been going to great lengths to instill Griswold with the memories of Richard Connor, Fall Criminal and disgraced Hypercorp CEO. Their motivations are unknown, and the Sentinels are quickly realizing they are even further over their heads than they knew. All in all, it’s been an eventful first day on Luna. Side Chatter PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 12 appeared first on The Drunk and The Ugly.

Charles Boutin is a traitor to Firewall. Known to the organization as PROX-E Klein, he has left Firewall for reasons unknown. He has TITAN tech at his disposal, a seemingly endless set of resources, and motivations that stretch into the dark. And it’s the Sentinel’s team to follow him there. Burned by their organization out of necessity, the Firewall agents must track down Boutin on their own, with whatever allies they choose to make. Side Chatter PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 11 appeared first on The Drunk and The Ugly.

The team, set on tracking down Charles Boutin, began their investigation on Mitre. Sam Franklin discovered that his reporter friend Solemn Zahn was altered by her contact with Charles Boutin, having lost her specific memories of the man. Now, armed with more information about their enemy than they’ve possessed at all during the investigation, the Sentinel team is tracing down Boutin’s private expense account activity, hoping to uncover his true purpose before it is too late. PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 10 appeared first on The Drunk and The Ugly.

The Sentinels have gained a valuable lead on Charles Boutin, the mysterious sponsor of the Red Devil terrorists and the father of a terrifying brand of exsurgents. Firewall has tracked his last location to the station of Mitre, in Luna orbit. PROX-E KING has tasked the Sentinel team with farcasting to Luna and tracking down Boutin. There, the web of conspiracy will unfold and the Sentinels will be plunged into thorough and complete danger. PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 9 appeared first on The Drunk and The Ugly.

The Sentinels walked into hell, and survived. Firewall, desperate to know how they’d done it, forcefully debriefed them. Now, two weeks have passed since the assault on the Red Devils. Mars, having avoided the fires of revolution and destruction, has settled back into its status quo. It’s up to the Sentinels to track down Boutin, find out what he’s planning, and erase him. Side Chatter PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 8 appeared first on The Drunk and The Ugly.

At the end of Act One, the PROX-E KING’s Sentinels walked into hell and survived. They stormed the Red Devil compound, fought off revolutionaries and horrific nightmare creatures, and bested Akinye. Now, Firewall would really appreciate a thorough debriefing. Worth watching: The Facts in the Case of Mister Hollow PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 7 appeared first on The Drunk and The Ugly.

Last session, the Firewall agents earned their salaries. They crashed a mech party, challenged a crime boss to one on one combat, and then impersonated too-rich-for-their-own-blood Hyperelites to gain access to the inner chambers of Skinesthesia. While Noah donned his old personality and spun a web of deceit, John and T.O.M. managed to find the lab where Dr. Worthmeyer was conducting her research. Unfortunately, what was waiting for them was horrific beyond words. The Firewall agents, barely managing to contain the exsurgent threat that had consumed Dr. Worthmeyer, beat a hasty retreat. They managed to cover their trail with some desperate clean-up tactics and composure under pressure, delaying the sure-to-follow investigation and buying themselves precious time. It seems, however, that Akinye is almost ready to make her move. She has a deadly Basilisk hack, TITAN nanotech, and her fingers on the trigger of an unknown number of exsurgents who are ready to pop. Side Chatter PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end […] The post Eclipse Phase – The Thunder and the Whirlwind Episode 6 appeared first on The Drunk and The Ugly.

The Firewall team, having been given some forced downtime, promptly ran smack into a series of increasingly dangerous problems. Someone has deployed a basilisk onto the mesh. Its capabilities, motivations, and intent are unknown. A hypercorp bureaucratic drone was subverted and was apparently used as a puppet to begin some sort of sabotage using recovered TITAN nanotech. PROX-E KING has ordered the Sentinels to make all possible haste to shut down Akinye and her Red Devils terrorist organization. Unfortunately, the spies have almost no information about Akinye or her organization, and their plans, location, or intents. Flying blind, they have to attempt to track down as much information as possible and then make their move, before the Red Devils strike. PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 5 appeared first on The Drunk and The Ugly.

Having survived the TQZ and PROX-E Ghost’s ministrations, the Firewall team — posing as the Red Devils — successfully robbed the Ashoka 22. In a matter of minutes, they breached the train’s security and thoroughly neutralized its mercenary guards, making off with their cargo. During the raid, Sam Franklin, ex-Direct Action mercenary, came knife-to-knife with an old friend. Insisting on a ‘man’s fight,’ he held off the majority of the mercenary team while his Firewall compatriots secured their target cargo. Having completed the first stage of their mission, the Sentinels are being ordered to take some downtime, and stay off the radar while they look into the location of the Red Devils’ homebase. And after all, their favors are coming due. Side Chatter PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 4 appeared first on The Drunk and The Ugly.

The Firewall team is going undercover, posing as Jared Dirac and his team of anonymous Red Devil terrorists. They have received an itinerary of sorts, and have already completed the first task; a daring raid on a TITAN infested settlement on the outskirts of the Titan Quarantine Zone. There, they recovered a strand of dangerous nanotech for the terrorists, and almost lost Griswold Stuart to an attack by the site’s fractal guardians. Having survived their brush with horrific death, the Firewall Sentinels are poised to carry out a robbery on the Ashoka 22, a maglev train carrying a hypercorp’s secret cargo. Side Chatter PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 3 appeared first on The Drunk and The Ugly.

Jared Dirac, the traitor to Firewall, has been captured, intact. Four of the Burner Morphs have been captured (two in less than mint condition.) The VTOL, the weaponry, and the gear from the smuggler’s cave have all been captured. The first step for the Firewall Sentinels will be to parse the information they gathered. Interrogate Dirac, examine the records from the Red Devils, and – carefully – investigate the nanotech, both the secured container and the nanoparticles. From there, drastic steps will have to be taken to shut down the terrorists, and fast. Side Chatter PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by Firewall, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin. Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 2 appeared first on The Drunk and The Ugly.

Mars: 10 years after the Fall. A Firewall sentinel has gone missing two weeks into an undercover mission. Two weeks is not necessarily a red flag for the scanners and vectors until secret Firewall caches across Mars started being very carefully, cautiously, and skillfully raided. PROX-E KING has been informed and taps several new, untested agents to track down the missing and presumed dead sentinel, reacquire their cortical stack, and stop the OpSec leak. But Mars runs thick with blood and betrayal. The sentinel team is setting off on a path whose twists and turns they cannot begin to imagine. Mars will show them fear in a handful of dust. Side Chatter PLAYERS James – TOM (The Optimal Man). An AI programmed in a lunar laboratory, designed to be able to crack any digital protection and retrieve any data (as well as be the best psychotherapist in the known ‘verse). His accent algorithms are slowly degrading. Travis – John Clastion.  Survivor of the Fall, he runs a delivery service on Mars, preferring to use his feet instead of mundane transport. He also knows all about the drugs of the transhuman future and the criminals and cartels that supply them. Kevin – Griswold Stuart. A fork of a former hyperelite from Earth. Griswold Stuart is a 23rd century man, born in a 21st century man’s body, living in an AF10 world.  Reformed by the secretive Firewall organization, he did his best to adapt to his new world and his new place in it.  Formerly a programmer, business executive, and playboy, he is no longer sure of his own memories, much less his identity. Josh – Sam Franklin.  Originally a police officer with a wife, house, and the American Dream.  Left the force when he realized how corrupt it was and signed up with Direct Action.  After a long service that cost him his body and some of his memories, he works freelance for anyone who can pay, looking for his wife and his missing time. Matt – Noah Lucas.  A kangaroo uplift egohunter and x-caster who escaped from Earth during the fall.  Now works towards making sure no uplifts are abused or exploited in the same way he was before the end of the world worked in his favor. The post Eclipse Phase – The Thunder and the Whirlwind Episode 1 appeared first on The Drunk and The Ugly.

The Clathrin Assembly Lymphoid Myeloid leukemia gene (CALM) was first identified as the fusion partner of AF10 in the t(10;11)(p13;q14) translocation. The CALM/AF10 fusion protein plays a crucial role in t(10;11)(p13;q14) associated leukemogenesis. Using the N-terminal half of CALM as a bait in a yeast two-hybrid screen a novel protein named CATS (CALM interacting protein expressed in thymus and spleen) was identified as CALM interacting partner. Multiple tissue Northern blot analysis showed predominant expression of CATS in lymphoid tissues. CATS codes for two protein isoforms of 238 and 248 amino acids. The interaction between CALM and CATS was confirmed by co-immunoprecipitation and colocalization experiments. The CATS interaction domain of CALM was mapped to amino acids 221 to 294 of CALM. This domain is contained in the CALM/AF10 fusion protein. CATS localizes to the nucleus and shows a preference for nucleoli. Expression of CATS was able to markedly increase the nuclear localization of CALM and of the leukemogenic fusion protein CALM/AF10. This effect of CATS seems to be stronger on CALM/AF10 than on CALM. Several monoclonal antibodies against the C-terminus of human CATS were generated. These antibodies recognize both the human and the murine CATS protein. Western blot analyses showed that CATS is strongly expressed in different human leukemia, lymphoma and tumor cell lines but not in resting T-cells. High CATS expression in proliferating cells as well as its nucleolar localization suggest a role of CATS in the control of cell proliferation. In order to gain further insight into CATS function we used CATS as a bait in a yeast two-hybrid screen. Several CATS interacting proteins with apparently unrelated function were identified. Interestingly, on closer scrutiny these proteins could be associated with three key regulatory pathways: signaling, apoptosis and cell cycle control. We discuss in detail the biological relevance of the CATS interaction with the two apoptosis-associated proteins HAX1 and SIVA, the cell cycle regulator KIS and the CALM interacting ribonucleoprotein PCBP1. Our results indicate that the subcellular localization of CALM and CALM/AF10 could depend in part on the presence of CATS with a greater fraction of CALM or CALM/AF10 being present in the nucleus of cells with high CATS expression (e.g. lymphoid cells have high CATS expression). Moreover we provide evidences that CATS function might be tightly linked to cancer initiation and/or progression. The CALM-CATS interaction might thus play an important role in CALM/AF10 mediated leukemogenesis.

The t(10;11)(p13;q14) is a recurring translocation resulting in the fusion of the CALM and AF10 genes. The leukemogenic CALM/AF10 fusion genes codes for a 1595 amino acids protein. This translocation was first identified in a patient with hystiocytic lymphoma and was subsequently found in patients with AML, T-ALL and malignant lymphoma. This translocation is found in younger patients and is associated with a poor prognosis. The CALM/AF10-associated leukemias can exhibit myeloid, lymphoid or mixed lymphoid-meyloid features, indicating a stem cell or an early commited progenitor as the target cell of leukemic transformation. At the present time the target cells in CALM/AF10-associated leukemogenesis are unknown. It is also not known which target genes are up or downregulated by the presence of the CALM/AF10 fusion protein. To answer these questions, the following experiments were performed: 1) Five transgenic mouse lines, two expressing CALM/AF10 under the control of the immunoglobulin heavy chain enhancer promoter and three under the control of the murine proximal Lck promoter were generated. Although the CALM/AF10 expression was confirmed to be present and specific to the cells targeted by the promoters used (B- and T-cell progenitors for IgH and Lck promoters, respectively), the transgenic animals did not show a phenotype that could be detected after meticulous clinical, haematological, immunological, flow cytometrical and immunohistopatological analysis . 2) We performed molecular characterization of several CALM/AF10 patient samples: A group of 13 patients with different types of leukemia: case 1 (AML M2), case 2 (Acute Biphetnotypic leukemia), case 3 (Pre T-ALL), case 4 (Acute Undifferentiated Leukemia), case 5 (PreT-ALL), cases 6 and 7 (ProT-ALL), case 8 (T-ALL), case 9 (AML), case 14 (T-ALL), case 15, 16 and 17 (AML) with a t(10;11) translocation detected by cytogenetic analysis suggesting a CALM/AF10-rearrangement. The samples were analyzed for the presence of the CALM/AF10 and AF10/CALM fusion transcripts by RT-PCR and sequence analysis. All these patients were found to be positive for the CALM/AF10 fusion. In addition, we analyzed a series of twenty-nine patients with T-ALL with T-cell receptor ≥¥ rearrangement. Among these patients, four (case 10 to 13) were positive for the CALM/AF10 fusion transcript, indicating a high incidence of CALM/AF10 fusions in this group of leukemia. Three different breakpoints in CALM at nucleotide 1926, 2091 and a new exon, with 106 bases inserted after nt 2064 of CALM in patient 4 were found. In AF10 four breakpoints were identified: at nucleotide position 424, 589, 883 and 979. In patient 16 we found an extra exon before nt 424 of AF10. In seven patients it was also possible to amplify the reciprocal AF10/CALM fusion transcript (case 1, 3, 4, 8, 9, 10 and 14). There was no correlation between disease phenotype and breakpoint location. Ten CALM/AF10 positive patients were analyzed using oligonucleotide microarrays representing 33,000 different genes (U133 set, Affymetrix). Analysis of microarray gene expression signatures of these patients revealed high expression levels of the polycomb group gene BMI1, the homeobox gene MEIS1 and the HOXA cluster genes HOXA1, HOXA4, HOXA5, HOXA7, HOXA9, and HOXA10. The overexpression of HOX genes seen in these CALM/AF10 positive leukemias is reminiscent to the pattern seen in leukemias with rearrangements of the MLL gene, normal karyotypes and complex aberrant karyotypes suggesting a common effector pathway (i.e. HOX gene deregulation) for these diverse leukemias. In addition, the general pattern of gene expression of CALM/AF10 patients when compared to other leukemia subtypes and to normal bone marrow was dominated by a global downregulation of genes some of them with function identified as related to important molecular mechanisms, such as membrane trafficking, cell growth regulation, proliferation, differentiation and tumor suppression. 3) We cloned CALM/AF10 fusion gene into a vector that allowed us to induce the expression of CALM/AF10 using doxycycline in transiently and stably-transfected NIH3T3 and HEK293 cells. This system will be an important tool to identify direct CALM/AF10 target genes and to answer the question whether continued CALM/AF10 expression is necessary to maintain the CALM/AF10-associated expression pattern.