Podcasts about Dicer

Kommentar Clemens https://www.youtube.com/watch?v=3Gr5RGs8CKM&t=6s Martins Neujahrsvorsätze Kalorienzähler https://www.yazio.com/ Spitzkohl - Schäler für Kohl https://amzn.to/4fX0HnO Eierschneider! https://amzn.to/4fX0HnO Christian ist ein Nicer Dicer Killer Kitchen Aid Küchenmaschinenaufsatz, Würfelset https://amzn.to/4hC4gkH Weihnachtsfeier Agentur https://www.instagram.com/p/DD4J6pXM3n5/ Gans Game https://www.instagram.com/p/DD_5bxfM7dV/?img_index=1 Weihnachtsburger https://www.instagram.com/p/DEISX6mM00d/ Werbung: FILET20 - DeinGeflügel Kikok den ganzen Januar https://deingefluegel.de/ Kalbsbäckchen https://www.instagram.com/p/DEDECuvsmsd/ Einfach Schweinefilet! https://www.instagram.com/p/DEF_d51slcW/ Sesam-Butter - gerösteter Sesam mit Salz, angestoßen, Butter Dubai-Schokolade von Aldi vom Markt genommen. Martin im Allgäu https://www.instagram.com/p/DEXLouVsODX/ Gyros im Allgäu - Taverna und Bar Stegos https://www.tripadvisor.de/Restaurant_Review-g187316-d27146709-Reviews-Griechische_Taverna_Stego_s-Fussen_Swabia_Bavaria.html Zwiebelrostbraten mit Käsespätzle Entdeckung: Schokoladen-Blaukraut! Wollwurst https://de.wikipedia.org/wiki/Wollwurst Käsespätzle bei Rewe? Spätzlehobel https://amzn.to/3Wmggyv Weißlacker Käse gehört rein! https://bergsennerei.de/produkt/weisslacker/ Gastro auf der Zugspitze Döppekooche Martin https://www.instagram.com/p/DEc70B4MJsf/ Bei Pommes Extra Würze bestellen! Life Hack Eggs Benedict Hack? https://www.instagram.com/p/DESnD8kMuyf/ Jakobsmuscheln in der Schale!!! https://www.instagram.com/p/DEp5srdssHf/

This time our battle rages across the Dreamlands - watch out for Zoogs! Highlights include: - Why would you even go to the Underworld? - The Bhole... sounds shit - I can't wait to DICER this game - Can you make a board game out of ice? Why has nobody done this? - This is the Playmobil of board games - Mark doesn't care whether he's invading a country or a library

"Give me thy grace, good Lord, To set the world at naught;" The 16th and 17th centuries produced a number of men whose courageous faith was accompanied by prodigious learning and literary talent. Among these was St. Thomas More, who wrote poems while languishing in the Tower of London, 1534-1535. Read here are "Lewis the Lost Lover" and "Davey the Dicer", both written in the Tower of London, as well as a meditation written in the margins of More's prayer book while he was imprisoned. Links Lyra Martyrum: The Poetry of the English Martyrs, 1503-1681 https://www.clunymedia.com/product/lyra-martyrum/ Catholic Culture Podcast Ep. 69—Poetry of the English Martyrs, w/ Benedict Whalen: https://www.catholicculture.org/commentary/ep-69-poetry-english-martyrs-benedict-whalen/ Donate at: http://www.catholicculture.org/donate/audio Theme music: 2 Part Invention, composed by Mark Christopher Brandt, performed by Thomas Mirus. ©️2019 Heart of the Lion Publishing Co./BMI. All rights reserved.

In this interview, I'm talking with Heidi Newberg. Her team won a NIAC grant that will investigate building a telescope that will be hunting for Earth-like worlds. The project is called DICER, which stands for Diffractive Interfero Coronagraph Exoplanet Resolver.

In this interview, I'm talking with Heidi Newberg. Her team won a NIAC grant that will investigate building a telescope that will be hunting for Earth-like worlds. The project is called DICER, which stands for Diffractive Interfero Coronagraph Exoplanet Resolver.

It's here! The Internet's most complete list of actors who appeared on both Batman and Star Trek: The Original Series! But... is it totally complete? Look it over and see if there's a relevant actor who isn't listed - then post about him or her in the comments! Some are famous actors in big roles on both, some are extras and uncredited actors, some fall somewhere in between - or had a big role in one show and a bit part in the other. See the entire list at the link below.       Batman Star Trek Stanley Adams Captain Courageous in CATWOMAN GOES TO COLLEGE/BATMAN DISPLAYS HIS KNOWLEDGE Cyrano Jones in THE TROUBLE WITH TRIBBLES Alyce and Rhae Andrece 2nd and 3rd Policewoman in NORA CLAVICLE AND THE LADIES' CRIME CLUB Multiple Alices in I, MUDD Roger C Carmel Colonel Gumm in A PIECE OF THE ACTION/BATMAN'S SATISFACTION Harry Mudd in I, MUDD and MUDD'S WOMEN Ted Cassidy Lurch (window cameo) in THE PENGUIN'S NEST Ruk in WHAT ARE LITTLE GIRLS MADE OF Gorn (voice) in ARENA Balok's puppet (voice) in THE CARBOMITE MANEUVER Elisha Cook Professor Isaacson in ICE SPY/THE DUO DEFY Samuel T. Cogley in COURT MARTIAL Joan Collins The Siren in RING AROUND THE RIDDLER/THE WAIL OF THE SIREN Edith Keeler in THE CITY ON THE EDGE OF FOREVER Yvonne Craig Batgirl in season 3 Marta in WHOM GODS DESTROY John Crawford Printer's Devil in THE BOOKWORM TURNS/WHILE GOTHAM CITY BURNS Commissioner Ferris in THE GALILEO SEVEN Charles Dierkop Dustbag in PENGUIN'S CLEAN SWEEP Morla in WOLF IN THE FOLD Phyllis Douglas Josie Miller in THE JOKER'S LAST LAUGH/THE JOKER'S EPITAPH Yeoman Mears in THE GALILEO SEVEN (shown) Girl #2 in THE WAY TO EDEN Gene Dynarski Benedict in AN EGG GROWS IN GOTHAM/THE YEGG FOES IN GOTHAM Ben in MUDD'S WOMEN Krodak in THE MARK OF GIDEON (shown) Teri Garr Girl outside skating rink in INSTANT FREEZE Roberta Lincoln in ASSIGNMENT: EARTH Frank Gorshin The Riddler in seasons 1 and 3 Commander Belen in LET THAT BE YOUR LAST BATTLEFIELD Lloyd Haynes Lord Chancellor in KING TUT'S COUP/BATMAN'S WATERLOO Lt. Alden in WHERE NO MAN HAS GONE BEFORE Marianna Hill Cleo Patrick THE SPELL OF TUT Helen Noel in DAGGER OF THE MIND Sherry Jackson Pauline in DEATH IN SLOW MOTION/THE RIDDLER'S FALSE NOTION Andrea in WHAT ARE LITTLE GIRLS MADE OF? Jon Lormer Professor Dactyl in HOW TO HATCH A DINOSAUR Dr. Theodore Haskins in THE CAGE Tamar in THE RETURN OF THE ARCHONS Old Man in FOR THE WORLD IS HOLLOW AND I HAVE TOUCHED THE SKY (shown) Lee Meriwether Lisa Carson in KING TUT'S COUP/BATMAN'S WATERLOO (shown); Catwoman in BATMAN: THE MOVIE Losira in THAT WHICH SURVIVES Lawrence Montaigne Mr. Glee in THE JOKER'S LAST LAUGH/THE JOKER'S EPITAPH Decius in BALANCE OF TERROR Stonn in AMOK TIME (shown) Julie Newmar Catwoman in seasons one and two Eleen in FRIDAY'S CHILD Leslie Parrish Dawn Robbins in THE PENGUIN'S A JINX Glacia Glaze in ICE SPY/THE DUO DEFY (shown) Lt. Carolyn Palamas in WHO MOURNS FOR ADONIS? Gil Perkins Henchman in THE JOKER IS WILD, Dicer in THE THIRTEENTH HAT/BATMAN STANDS PAT Cauliflower in RING AROUND THE RIDDLER Jury Foreman in THE JOKE'S ON CATWOMAN (shown) Bluebeard in BATMAN THE MOVIE Slave #3 in BREAD AND CIRCUSES Angelique Pettyjohn 1st Model in A PIECE OF THE ACTION Shahna in THE GAMESTERS OF TRISKELION Malachai Throne False Face in TRUE OR FALSE FACE/HOLY RAT RACE Commodore Jose Mendez in THE MENAGERIE voice of The Keeper in THE CAGE Grace Lee Whitney Neila in KING TUT'S COUP/BATMAN'S WATERLOO Janice Rand in eight Season One episodes and in the movies Meg Wyllie Grandma in BLACK WIDOW STRIKES AGAIN The Keeper in THE CAGE/THE MENAGERIE Honorable mention: Jan Shutan DOZIERVERSE: Lizz in the DICK TRACY pilot Lt. Mira Romaine in THE LIGHTS OF ZETAR Stephen Kandel (writer) BATMAN: TRUE OR FALSE FACE/HOLY RAT RACE, ZODIAC CRIMES 3-parter STAR TREK: I, MUDD and MUDD'S WOMEN INANIMATE OBJECTS Feather robe Worn by Victor Buono as King Tut Worn by William Shatner as Kirk in THE PARADISE SYNDROME The Reactor Catwoman's Cat-Car in THE FUNNY FELINE FELONIES The Jupiter 8 in BREAD AND CIRCUSES

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

Danke liebe Silvia für deine Rückmeldung, die sehr hilfreich ist.

Ihr könnt mir beim Kochen zu hören und beim schneiden von Gemüse auf ganz einfache Art

LIVE FROM SINWEEK! The CinemaSins team gather to spill the tea on what happened in the world of sinning for the week of April 4th, 2022.1) The SinSide Scoop: Thoughts on this week's videos!  Street Fighter (2:44)  Red Notice (6:28)  Love and Monsters (8:54)  Crouching Tiger Hidden Dragon (12:11)  Upgrade (16:37)2) Sin to Win: Deneé hosts a quiz based on the CinemaSins Universe. (21:01)3) The Comment Section: Comments we loved, your emails, and questions from the live audience! (42:15) Oh, and a partially blurred anus!   Want an ad-free pod and other tasty *tot-themed treats? Join the Sinclub! https://www.patreon.com/CinemaSins*tots not included. Advertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy

In dieser Episode sprechen wir über vier Würfelspiele. Manche bekannter, manche weniger, aber alle mit hohem Spaßfaktor.

Some of the CinemaSins B-team gather to spill the tea on what happened in the world of sinning for the week of December 20th, 2021.1) The SinSide Scoop: Thoughts on this week's videos!Fushigi! (2:32)What If Ultron Won? (11:04)Santa Claus is Coming to Town (21:38)Jungle Cruise (30:33)A Christmas Story (41:24)2) Keeping Tabs: Strange moments from the writing process! (51:48)3) The Comment Section: Comments we loved, and your emails! (58:04)4) Beyond the Sins: Some other pop culture we experienced!The Animatrix (1:02:03) Little Darlings (1:06:10) Swan Song (1:12:07) Oh, and a Dicer-shaped pun-shield!Advertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy

Frohes Neues! Wir machen einen Jahresrückblick, um gut ins neue Jahr starten zu können. Außerdem reden wir über unsere neuen Jahresvorsätze. Es bleibt interessant! Wir freuen uns, wieder da zu sein. We are back Bitches!

Este podcast é oferecido por HiDoctor – o software médico mais usado em consultórios e clínicas no país O resumo da semana de 16/11 a 22/11 traz as seguintes publicações: - Tratamento sequencial de terapia e medicamento se mostra eficaz no controle de insônia (JAMA Psychiatry) - Exercício aeróbico estimula expressão da enzima DICER, desencadeando benefícios metabólicos através do aumento da produção de microRNAs (Proceedings of the National Academy of Sciences) - Ácidos graxos ômega-3 circulantes foram associados a menor risco de eventos adversos em pacientes com infarto agudo do miocárdio (Journal of American College of Cardiology) - A maturação do microbioma intestinal durante o primeiro ano de vida contribui para o efeito protetor da fazenda sobre a asma infantil (Nature Medicine) - Pfizer e Bio and Tech concluem estudo de fase 3 da candidata a vacina contra COVID-19, constatando 95% de eficácia (Pfizer) - Estudo descreve a regulação de microRNA pela melatonina no câncer, orientando potenciais terapias para o câncer de mama (Journal of Pineal Research) - Candidata a vacina contra COVID-19 da Moderna é 94,5% eficaz, segundo comunicado de imprensa (Moderna) - Intervenções que reduzem a solidão podem prevenir ou reduzir a depressão em adultos mais velhos (The Lancet Psychiatry) Veja mais notícias em news.med.br.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.19.390161v1?rss=1 Authors: Jonely, M., Singh, R. K., Bass, B., Noriega, R. Abstract: Drosophila melanogaster Dicer-2 is a large, multidomain protein that cleaves double-stranded RNA (dsRNA) into small interfering RNAs in a terminus-dependent manner as part of the RNA interference pathway. We characterize the local binding environment involved in this substrate-selective molecular recognition event by monitoring the time-resolved photophysics of a cyanine dye linked to the dsRNA terminus. We observe substantial changes in the molecular rigidity and local freedom of motion of the probe as a function of distinct conformations of the biomolecular complex between Dicer-2 and dsRNA as a function of dsRNA termini, the presence of regulatory proteins, and the addition of a biochemical energy source (ATP) or a non-hydrolysable equivalent (ATP-{gamma}S). With a clustering analysis based solely on these molecular-scale measures of the local binding environment at the dsRNA terminus, we identify sub-populations of similar conformations that define distinct modes of molecular recognition which are correlated with biochemical activity. These observations reveal the important role of substrate-selective molecular recognition properties for proteins with multiple domains that can bind RNA, regulatory proteins, and cofactors. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.29.319475v1?rss=1 Authors: SINGH, R. K., Jonely, M., Leslie, E., Rejali, N. A., Noriega, R., Bass, B. L. Abstract: Drosophila melanogaster Dicer-2 (dmDcr-2) differentially processes dsRNA with blunt or 2 nucleotide 3{per thousand}-overhanging termini. We investigated the transient kinetic mechanism of these reactions using a rapid reaction stopped-flow technique and time-resolved fluorescence spectroscopy. We found that ATP binding to dmDcr-2{per thousand}s helicase domain impacts the kinetics of dsRNA binding and dissociation in a termini-dependent manner, emphasizing the termini-dependent discrimination of dsRNA on a biologically-relevant time-scale. ATP-hydrolysis mediates local unwinding of dsRNA, and directional translocation on unwound single-stranded RNA, which is concurrent with a slow rewinding prior to dsRNA cleavage. Time-resolved fluorescence anisotropy reveals a nucleotide-dependent change in conformational dynamics of the helicase and Platform.PAZ domains in the nanosecond timescale that is correlated with termini-dependent dsRNA cleavage. Our study delineates kinetic events and transient intermediates for a Dicer-catalyzed reaction, thus establishing a framework for understanding other Dicers and how accessory factors modulate the reaction. Copy rights belong to original authors. Visit the link for more info

This week we go full-on teen slasher in our first ever Patreon shoutout episode! Also, w have a pretty intense tangent about English teachers. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/funsolvedmysteries/message Support this podcast: https://anchor.fm/funsolvedmysteries/support

The CinemaSins B team gather to spill the tea on what happened in the world of sinning for the week of August 24th, 2020. *1) The SinSide Scoop: Thoughts on this week's videos!* * Grey's Anatomy - Bring the Pain (5:54) * Brooklyn Nine-Nine - Jake and Amy (20:20) * BlackPink (37:31) * Fantasy Island (48:15) * Big (58:58) *2) Keeping Tabs: Strange moments from the editing process! (1:14:41)* *3) The Comment Section: Video comments we loved, and your emails! (1:26:09)* *4) Beyond the Sins: Something other pop culture we experienced!* * The New Mutants (1:31:08) * Wicked Things (1:36:19) * The Legends of Monkey (1:39:16) Oh, and Dr. Dicer! Support this podcast at — https://redcircle.com/behindthesins/donations Advertising Inquiries: https://redcircle.com/brands

Further findings into just how much of our speech dogs can understand. An American highway that’s been repaved with recycled plastic. Taika Waititi’s new anti-racist website. Scientists who had to rename human genes due to a Microsoft Excel error. And a smoke detector that wakes you up by spitting wasabi scents in your face.Links:Brain researchers: Dogs process speech just like humans do (Fast Company)America now has a stretch of highway paved with recycled plastic (Optimist Daily)Voice of RacismTaika Waititi’s Voice of Racism is an interactive website revealing the damaging effects of ceaseless micro-aggressions (It’s Nice That)Scientists rename human genes to stop Microsoft Excel from misreading them as dates (The Verge)Sonic Hedgehog, DICER, and the Problem With Naming Genes (Pacific Standard)Wasabi fire alarm a lifesaver for the deaf (Reuters) Wasabi fire alarm scoops Ig Nobel prize for Japanese scientists (The Guardian)

TRENDING TOPIC  George Floyd KILLED BY MINNEAPOLIS POLICE OFFICER DEREK CHAUVIN Racism - Racism is the belief that a particular race is superior or inferior to another, that a person's social and moral traits are predetermined by his or her inborn biological characteristics. THATS AMERICA! SLAVERY FOR 246 YEARS SEGREGATED FOR 89 AND SO CALLED FREE SINCE 1954 How “ lets all be human beings” from a white person Is just another way of saying lets be like the white person and do as i do and be like me. Human/white/American being a synonym Keep me comfortable Lets pretend to be white Cant accept my CULTURE, my hair OR SKIN COLOR, I dont see skin color? BLACK AND PROUD / White privilege OUT OF THE 10 DEADLIST MASS SHOOTING IN AMERICA Dylann Roof (Murdered 9 people / Arrested Peacefully) Route 91 Harvest music festival, Las Vegas, October 2, 2017: 59 killed, 526 injured. ( White Man) Sandy Hook Elementary School, Newtown, Conn., December 2012: 26 killed. (WHITE MAN) First Baptist Church, Sutherland Springs, Texas, November 2017: 26 killed. (WHITE MAN) Luby's Cafeteria, Killeen, Texas, October 1991: 23 killed.(WHITE MAN) Walmart, El Paso, Texas, August 3, 2019: 23 killed, 26 injured.(WHITE MAN) McDonald's, San Ysdiro, Calif., July 1984: 21 killed.(WHITE MAN) Marjory Stoneman Douglas High School, Parkland, Fla., February 2018: 17 killed. (WHITE MAN) University of Texas Tower, Austin, Texas, August 1966: 16 killed around campus. (white man) Questions to white people How much racisms do you face every day? Why is your History is part of the core curriculum yet everyone else is an elective or you get a month? Have you ever felt oppressed? Are you starting to understand why Kepernick is still kneeling? Your american dream was always our nightmare! JUNE AMBROSE POST  SUCIERIA DE NEGRO  Things to never say in bed https://wapa.pe/sexo/1561875-sexualidad-cosas-debes-decir-durante-sexo-pareja-placer Cosas que las mujeres no deben decir en la cama  1-. ¿Puedes apagar la luz?: Esto interrumpirá el apasionado momento y tenlo por seguro que te perderás de lo mejor. Deja que haya luz y libera tus deseos. 2-. Se me olvidó tomar la pastilla: Definitivamente, con esta frase le darás un apagón de inmediato. No habrá ni tres por ciento de ganas. 3-. ¿Ya entró?: ¡Qué roche! Esto puede sonar algo ofensivo para tu pareja, ya que, estarías insinuando que tiene el pene muy pequeño y por eso no lo llegaste a sentir. 4-. ¿Con cuántas mujeres has estado antes?: ¡Nada que ver, no es momento! Este es para que experimenten entre ustedes sin pensar en nadie más. Evita totalmente resucitar a su ex o su pasado. 5-. ¿Tan rápido acabó?: Recontra ofensivo para él al igual que lo anterior. Si es precoz mejor ni se lo digas, por lo meno, no después del sexo, deja que pase un tiempo y convérsalo de una manera más suave. 6-. ¿Te falta mucho?: Mejor espera ni se te ocurra apresurarlo. Relájate y disfruta porque esta pregunta solo lo interrumpirá innecesariamente. 7-. ¡Déjame contestar el teléfono!: Como lo dije en un inicio, ignora todo lo que pueda ocurrir en el exterior porque este es un momento íntimo para ambos. Cero interrupciones. ¿Puedo decir te amo durante el sexo? Depende, pues si realmente lo sientes y estás segura de que es así entonces adelante, pero si solo es una emoción que crees sentir por la intensidad del encuentro íntimo mejor limítate en decirlo. RANT OF THE DAY DEAR MEN -ASKING FOR HELP DOES NOT MAKE YOU A LESS OF A MAN -ADMITTING YOU HAVE MENTAL HEALTH PROBLEMS DOES NOT MAKE YOU LESS OF A MAN -SHOWING YOUR EMOTIONS DO NOT MAKE YOU LESS OF A MAN -DONT LOOK FOR VALIDATION IN YOUR MASCULINITY BY INVOLVING YOURSELF WITH A LOT OF WOMEN -DONT LET ANYONE MAKE YOU FEEL LESS OF A MAN BC YOU CANT LIVE THEIR LIFESTYLE --- Support this podcast: https://anchor.fm/negrosparty/support

In 1581, a young Englishman named Henry Walpole attended the execution of the Jesuit Edmund Campion. As Campion was hung, drawn and quartered, Walpole stood close enough to be spattered with his holy blood. Though Campion's fame in England was already great, Walpole would amplify it further with a splendid, lengthy poem, which became enormously popular among English Catholics—so popular that the man who printed the book had his ears cut off as punishment. In his poem Walpole wrote: We cannot fear a mortal torment, we, This martyr's blood hath moistened all our hearts, Whose parted quarters when we chance to see We learn to play the constant Christian's parts. This was more than wordplay: Two years after Campion's death, Walpole became a priest, and was himself hung for the faith in 1595. St. Henry Walpole was not the only martyr who wrote poems. The 16th and 17th centuries produced a number of men whose courageous faith was accompanied by prodigious learning and literary talent. St. Thomas More wrote poems while languishing in the Tower of London. Another Jesuit martyr, St. Robert Southwell, powerfully influenced the later movement of “metaphysical poetry”, including the greatest Protestant poets of succeeding centuries—such as George Herbert and John Donne. The poetry of the English martyrs has been collected in an anthology called Lyra Martyrum. Benedict Whalen, the editor of the second edition, joins Thomas to discuss these authors, with Catholic Culture Audiobooks' James T. Majewski performing several of their works. Contents [2:08] The historical/literary/educational circumstances that gave us a period of martyr-poets [7:23] Their influence as poets in the succeeding centuries [10:26] St. Robert Southwell's Prefatory Epistle on the purpose of poetry [12:58] All the poets in the first edition of the anthology have since been beatified or canonized [14:29] The martyrdoms of the Jesuit Saints Edmund Campion and Henry Walpole [17:43] St. Henry Walpole, “Upon the Martyrdom of M. Edmund Campion” [30:23] The tradition of meditating on the Four Last Things [33:08] St. Philip Howard, Earl of Arundel, “Meditation upon Heaven” [37:43] St. Thomas More's early poems written for courtly occasions [40:11] More's poems written in the Tower of London: “Lewis the Lost Lover” and “Davy the Dicer” [44:17] The theme of Fortune in medieval and Renaissance philosophy and poetry [47:12] The influence of Latin classics on English verse [49:16] More's influence on English prose [51:29] The life and work of St. Robert Southwell [54:36] St. Robert Southwell, “The Burning Babe” [59:39] “A Child My Choice” [1:05:27] Southwell's conceptual and sonic density: excerpts from “The Nativity of Christ” and “Look Home” [1:09:13] “I Die Alive” [1:12:52] “Mary Magdalen's Complaint at Christ's Death” [1:16:30] The remarkable story of St. Robert Southwell's martyrdom [1:26:10] The appendix of this edition of Lyra Martyrum    Links Lyra Martyrum https://www.clunymedia.com/product/lyra-martyrum/ Benedict Whalen https://www.hillsdale.edu/faculty/benedict-whalen/ Catholic Culture Audiobooks https://www.catholicculture.org/audiobooks This podcast is a production of CatholicCulture.org. If you like the show, please consider supporting us! http://catholicculture.org/donate/audio

Mark and Dale are at GDC so Ellen Burns-Johnson joins us to talk all about Team Building and Game Identities! Join us for this chill evening recording session and discuss the more existential side of game development. If you change a game completely is it still the same game you started with? Stephen builds a house, Ellen is a game feedback therapist and Martha gets lost in the waveform. Mark and Dale are at GDC! The episode of their adventures actually came out *last* week (calendar math) so you can listen to it RIGHT NOW if you haven't already GDC 2019 Special Team Building 0:01:57 Stephen McGregorIRLProductionDicer and Clasp: Dungeon Skedaddle - Stephen's Global Game Jam Team, GGJClaw Breaker - Steam Our episode on topic on Game Writing "Steal this episode."Cat Crib - Ellen's Global Game Jam Team, GGJ Game Identities 0:22:37 Ellen Burns-JohnsonGame DesignProducer Bootcamp: How Saying 'No' Can Help You Make a Better Game - Ruth Tomandl, Oculus Research, GDCRuth Stone, Poet who caught poems on the wind - Wikipedia

Mark and Dale are at GDC so Ellen Burns-Johnson joins us to talk all about Team Building and Game Identities! Join us for this chill evening recording session and discuss the more existential side of game development. If you change a game completely is it still the same game you started with? Stephen builds a house, Ellen is a game feedback therapist and Martha gets lost in the waveform. Mark and Dale are at GDC! The episode of their adventures actually came out *last* week (calendar math) so you can listen to it RIGHT NOW if you haven’t already GDC 2019 Special Team Building 0:01:57 Stephen McGregor Category IRL Production Dicer and Clasp: Dungeon Skedaddle - Stephen's Global Game Jam Team , GGJ Claw Breaker - Steam Our episode on topic on Game Writing "Steal this episode." Cat Crib - Ellen's Global Game Jam Team , GGJ Game Identities 0:22:37 Ellen Burns-Johnson Category Game Design “Producer Bootcamp: How Saying 'No' Can Help You Make a Better Game” - Ruth Tomandl, Oculus Research , (GDC Vault Video) Ruth Stone, Poet who caught poems on the wind - Wikipedia

Minnan toiveet toteutuvat kun tilauslistalle lisätään jo eilisestä asti himottuna ollut vihannesleikkuri! Akilla puolestaan oli aamulla vähän haasteita heräämisen kanssa ja jalkaan päätyivät vähän kyseenalaiset kalsarit. Keskustelua herättävät erilaiset uran vaihdokset ja tämän innostamana Minna ja Aki alkavat melkein vakavissaan harkitsemaan sitä, että ryhtyisivät pyörittämään yhdessä pientä sivubisnestä. Mutta millaista?

Raul Andino joins Vincent and Amy to talk about the finding that a cricket paralysis virus protein restricts RNA-based immunity in insects by regulating the activity and stability of the Argonaute protein. Hosts: Vincent Racaniello and Amy Rosenfeld Guest: Raul Andino Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode TWiV 138: RISCy business with Raul Andino TWiV 33: Live in Philly Viral protein restricts insect immunity (Cell Host Micr) Timestamps by Jolene. Thanks! Weekly Science Picks Amy - Insectropolis Vincent- Genome-edited baby Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv

"Wasser, es ist überall Wasser!". In Folge 4 tickt die Zeitbombe. Unter Hochdruck ballern die Jungs durch ein Potpourri der Themen. Der beste Schokoriegel, Aliens, asiatische All-You-Can-Eat Buffets, Zuschauer-Feedback, Zahnarztbesuche und Müsli. All das bekommt ihr in unter einer Stunde! --- Send in a voice message: https://anchor.fm/spoppin/message

Dr Carolyn Lam:                Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. This week's issue provides much long awaited healthcare resource utilization and cost implications in the MOMENTUM 3 randomized controlled trial of a magnetically levitated cardiac pump in advanced heart failure. All of this coming right up after these summaries.                                                 The first original paper this week provides important mammalian data on the acute effects of phosphodiesterase type 1 inhibition on the heart. Now phosphodiesterase type 1, or PDE1, is known to hydrolyze cyclic AMP and cyclic GMP in the heart. However, what's important to understand is that data from rodents may not be applicable to humans because rodents express mostly the cyclic GMP favoring PDE1A isoform, whereas human hearts predominantly express PDE1C isoform which has a balanced selectivity for cyclic AMP and cyclic GMP.                                                 In today's paper, first author Dr Hashimoto, corresponding author Dr Kass from Johns Hopkins University School of Medicine and colleagues, determined the acute effects of PDE1 inhibition on PDE1C expressing mammals, dogs and rabbits, in normal and failing hearts. They found that selective inhibition of PDE1 with ITI-214 induced positive inotropic, lusitropic, chronotropic, and arterial vasodilatory effects in dogs and rabbits. These effects occurred via cyclic AMP modulation and were observed in failing hearts. ITI-214 contractile increase was insensitive to beta adrenergic blockade or heart rate increase, but inhibited in vivo by adenosine receptor inhibition. Furthermore, isolated myocytes revealed differences between PDE1 and PDE3 inhibition. Wherein PDE3 inhibition, augmented beta receptor agonism and calcium transients, whereas PDE1 inhibition enhanced function without calcium increase. These findings have important clinical implications for ITI-214 which has completed phase 1 trials and may provide a novel therapy for heart failure.                                                 We know that macrophages are involved in foam cell formation in atherosclerotic plaques, but our next paper tells us we may now have a way to therapeutically modify this. Co-corresponding authors Dr Wei and Schober from Ludwig Maximilian's University Munich elucidated the role of microRNA generating enzyme Dicer in macrophage activation during atherosclerosis. They showed that Dicer deletion in macrophages accelerated atherosclerosis in mice, along with enhanced inflammatory response and increased lipid accumulation in lesional macrophages. In vitro, alternative activation was limited, whereas lipid filled foam cell formation was exacerbated in Dicer deficient macrophages due to impaired mitochondrial fatty acid oxidative metabolism. MicroRNA biogenesis promoted the degradation of fatty acids by mitochondrial respiration in macrophages, which in turn reduced intracellular lipid storage and limited atherosclerosis. Thus, reducing foam cell formation in atherosclerotic arteries by enhancing energy metabolism through microRNA mediated fatty acid oxidation may be a promising approach for the treatment of atherosclerosis.                                                 The next study evaluates how aortic stiffening relates to resting cerebral blood flow and cerebral vascular reactivity in older adults. First and corresponding author Dr Jefferson from Vanderbilt Memory and Alzheimer's Center and her colleagues studied participants free of clinical dementia, stroke, or heart failure, including 155 older adults with normal cognition and 115 mild cognitive impairment. They found that greater thoracic aortic stiffening quantified by cardiac magnetic resonance was associated with lower cerebral blood flow in cognitively normal older adults. Aortic stiffening was associated with reduced resting cerebral blood flow in the presence of preserved reactivity and associated vasodilatory capacity, particularly among participants without hypertension. ApoE4, a well-known genetic susceptibility risk factor for Alzheimer's disease, modified the results with stronger effects among carriers in the temporal lobes, where Alzheimer's disease pathology is known to first evolve. In summary, greater aortic stiffening related to lower regional cerebral blood flow and higher cerebral vascular reactivity in cognitively normal older adults, especially among individuals with increased genetic predisposition for Alzheimer's disease. Understanding the association between higher aortic stiffness and compromised brain health, including cerebral hemodynamics, may allow for earlier detection and targeted interventions to prevent or mitigate the onset of more serious cerebral vascular damage associated with greater aortic stiffening.                                                 Aortic valve replacement for aortic stenosis is usually timed according to the development of symptoms, but could the timing be too late once irreversible myocardial scar has developed? Co-first authors Drs Musa and Treibel, corresponding author Dr Greenwood from University of Leeds and their colleagues found that in patients with severe aortic stenosis, focal myocardial fibrosis determined by cardiac magnetic resonance imaging was present in over 50% of patients and was associated with a two-fold higher late mortality. Focal scar was independently associated with all cause and cardiovascular mortality, after both surgical and transcatheter aortic valve replacement. In severe aortic stenosis, late gadolinium enhancement appears to be a useful biomarker of left ventricular remodeling, and its presence is associated with worse long-term outcomes following aortic valve intervention. Thus, in severe aortic stenosis, late gadolinium enhancement may be a useful biomarker of left ventricular remodeling, and its presence may be associated with worse long-term outcomes following aortic valve intervention.                                                 The next study suggests that endogenous factor Xa activity may be irrelevant pharmacodynamic marker to guide Edoxaban dosing in future. First author Dr Yin, corresponding author Dr Giugliano from TIMI Study Group, Brigham and Women's Hospital in Boston, and their colleagues, describe the value of endogenous factor Xa activity as a pharmacodynamic marker, linking Edoxaban concentrations and clinical outcomes in the ENGAGE AF-TIMI 48 trial. They showed that the extent of inhibition of endogenous factor Xa activity was influenced by Edoxaban dosing and clinical characteristics, and was associated with both antithrombotic benefit and risk of bleeding. The implications are that this approach of linking endogenous factor Xa activity to clinical outcomes may be used to guide dose selection in future clinical trials, to monitor patients in certain clinical scenarios, or to define the doses of oral factor Xa inhibitors in patients who require precise anticoagulation therapy.                                                 The next paper describes a novel multi-protein complex that plays a critical role in regulating cardiomyocyte survival. First author Dr Zhang, corresponding author Dr Yan from University of Rochester School of Medicine and Dentistry and colleagues, showed that phosphodiesterase 1C is activated by transient receptor potential canonical channel-3 derived calcium, thereby antagonizing adenosine A2 receptor cyclic GMP signaling and promoting cardiomyocyte death or apoptosis. Targeting these molecules individually, or in combination, may represent a compelling therapeutic strategy for potentiating cardiomyocyte survival.                                                 The final paper demonstrates a molecular link between two well-recognized biomarkers of fibrosis, Galectin-3 and Osteopontin. First author Dr Shirakawa, corresponding author Dr Sano from Keio University School of Medicine and their colleagues, showed that Osteopontin was almost exclusively produced by Galectin-3 high CD206 positive macrophages, which specifically appear in the infarct myocardium after a myocardial infarct. The interleukin-10-STAT3 Galectin-3 axis was essential for Osteopontin producing reparative macrophage polarization after myocardial infarction, and these macrophages contributed to tissue repair by promoting fibrosis and clearance of apoptotic cells. These results therefore suggest that Galectin-3 may contribute to reparative fibrosis in the infarct myocardium by controlling Osteopontin levels. And that brings us to the end of this week's summaries, now for a feature discussion.                                                 Left ventricular assist devices have truly revolutionized our management of advanced heart failure. In fact, these devices have allowed us to keep patients not just as a bridge to transplantation, but as destination therapy. The devices get better and better but also more and more expensive, and the problem is, that places a lot of strain on our healthcare systems. A lot of us are crying out for information on the cost effectiveness of these newer devices, and guess what? We have answers this week with our featured paper.                                                 I am delighted to have with us the first and corresponding author Dr Mandeep Mehra from Brigham and Women's Hospital in Boston, Massachusetts, as well as our senior editor Dr Biykem Bozkurt from Baylor College of Medicine in Houston, Texas. Hello, Mandeep and Biykem! I am so pleased to be talking about a subject really close to all our hearts. Mandeep, could you start by maybe sketching out the actual issue, and maybe reminding our audience what's the difference between the different types of left ventricular assist systems that you compared. Dr Mandeep Mehra:       The era of left ventricular assist devices took a major therapeutic shift when we recognized that we could usher in continuous flow devices. These are devices that generate no peripheral pulse, they do not have systole and diastole. And these devices are small in profile, have very few moving parts, and there are several commercially available devices, two in the United States and up to three worldwide, that bear these characteristics.                                                 The HeartMate II device, which is a continuous flow device that flows blood in an axial format. The HeartWare, or HVAD device, which is a centrifugal flow pump, where the blood comes in and then is ejected at a 90 degree angle. The Jarvik 2000 pump that is still used in some areas, in many regions experimentally, and then the new kid on the block, the HeartMate 3 device, which is a centrifugal flow pump with some very unique technological characteristics. Dr Carolyn Lam:                Nice! And now drumroll, please tell us what you found in your brilliant study this week. Dr Mandeep Mehra:       First, I'd like to remind the audience that the MOMENTUM 3 trial which randomized patients to the HeartMate II versus the HeartMate 3 device, was called MOMENTUM 3 and was a two-year study. We presented the pivotal two year trials results in 366 randomized patients earlier this year in The New England Journal of Medicine, and this study showed that the HeartMate 3 was superior on the primary endpoint when compared to the HeartMate II. The primary endpoint was survival, free of a disabling stroke, or the need to replace the pump surgically for a pump malfunction. And much of that, Carolyn, was driven by the need for replacement of the pump because the HeartMate 3 pump has some unique features that reduce its proclivity for pump thrombosis.                                                 The HeartMate 3 pump is a frictionless pump. It's completely, magnetically, dynamically, born in the rotor. It has wider blood flow paths, so we don't see hemolysis with this pump. And this pump also has an artificial intrinsic pulse that has been created, that pulsates the pump in a 40 beats per minute configuration. So this was the primary trial result, and one of the lucky foresights that we had when we designed the trial was to embed, prospectively, economic analysis within this trial. We recognized that the cost effectiveness related issues and cost configurations with these devices would become very, very important as we scale into today's day and age of healthcare transformation. And the paper that is being presented in Circulation this week, really speaks to the health resource utilization and cost outcomes between the two devices.                                                 We found that the HeartMate 3 pump is actually a cost minimization device, and what that means, Carolyn, is that we have become very used to thinking of new technology as providing incremental costs. So we think that, "Oh, well, what incremental costs should society bear for the benefits as we allocate new technology?" And in this particular trial, what we found is that while the costs of the pump itself, the HeartMate II and the HeartMate 3, were kept the same, which means its operational implant costs were the same, pretty much. We found that the HeartMate 3 pump was associated with a reduction in healthcare resource utilization over two years and with a marked decrease in cost. And in fact, our estimate of cost reduction was in the range of about 65 thousand dollars less, compared to the HeartMate II, in favor of the HeartMate 3. Dr Carolyn Lam:                Wow, Mandeep, first of all, congratulations on these remarkable findings. Biykem, I really have to bring you in here. What do you think of the implications of this? Dr Biykem Bozkurt:         First, I would like to congratulate the authors for a very innovative approach. As Mandeep has stated, they prospectively collected very challenging billing data from the hospitals, and then also did a very complex analysis including the VRG, as well as looking at payer reimbursements for public versus private. And did a variety of subgroup analysis, which I thought was quite helpful in sorting out that perhaps the cost effectiveness was concurrent both from the Medicare, the public, as well as the private, or regardless of the intent for destination versus bridge to transplant.                                                 Probably the most important concept when you look at these close analysis is incremental cost effectiveness ratio, per quality of adjusted life year gained. Now, I do realize the current analysis doesn't allow us to infer the ICER benefit or the incremental cost effectiveness, which I think the investigators are planning to do with a thousand and more patients over a course of two years, which is going to be probably the more definitive. But as it currently stands, with what is provided by Dr Mehra and his colleagues is, we're probably reaching that sweet spot of what is construed as the cost effectiveness ratio of a cost.                                                 Let's say 100 thousand dollars over the course of a year, then I would like to ask Mandeep whether on the prediction will reach that threshold of less than 100 thousand dollars. Because the former studies, looking at the ICER ratios, or incremental cost effectiveness ratios for the DT destination therapies, usually we select somewhere around 200 thousand dollars. And I know that usually that is seen as a prohibited cost, and there was a discussion whether we would be able to reduce the cost by about half, either doing index admission and add subsequent hospitalizations. With the data Dr Mehra and his colleagues have shown, it looks like the re-hospitalization cost is about, approximately half, or reduced by 50%. Mandeep, any thoughts on that, on that sweet spot? Dr Mandeep Mehra:       Yeah. I think, Biykem, you have articulated this extraordinarily well. And for the audience, since it's worldwide, I'd like to place a few things in perspective on how to think of economic modeling. First of all, the point I would make is that this is the first prospectively collected data that we have in the field, and as you pointed out, it was very, very difficult to pull this data together and is still very complex. But let's just think about what ICER really is. It all starts with what we consider to be health utility.                                                 For example, Carolyn, Biykem, and me less so, would have a health utility of 1.0, 1.0 means a perfect health utility number. And I know, Carolyn, you and Biykem are absolutely perfect so you would be a 1.0, I probably am not a 1.0. But a patient with advanced heart failure has a health utility of about .4, so that's only 40% of what is perfect. And when we place ventricular assist devices, whether you place the HeartMate 3 or the HeartMate II, the health utility actually jumps up to about .7. So it's not perfect yet, but it moves all the way up there.                                                 The incremental cost effectiveness ratios of implanting a device over time are calculated based on this health utility benefit, compared to the population of advanced heart failure. And the best current estimates of the HeartMate II are that ICER is about 200 thousand dollars, per quality adjusted life years gained, and this has been done by creating what's known as Markov modeling. A lot of that, by the way, is conjecture, it's not real information. It is predicted information, so one has to take that data with a grain of salt.                                                 Here in this health resource analysis for MOMENTUM 3, we actually looked at actual data. There are some estimates used in this analysis as well, where we did not have accurate billing forms available, but we focused on those things where we had very clear knowledge of the cost of outcomes. For example, we did not look at the costs of outpatient follow-up care. We mainly looked at the cost differences of hospitalizations. And what we essentially found here is that just looking at hospitalizations and differences between the two devices, the cost differential, whether it's Medicare which is public [inaudible 00:20:14], or whether it's commercial. It ranges somewhere between 50 to 65 thousand dollars of difference between the two devices.                                                 Now, if you assume that the ICER for the HeartMate II is accurately at about 200 thousand, and you reduce that ICER by about 50 to 60 thousand, the ICER would naturally come into the range of what you would consider to be about 135 thousand to 150 thousand dollars per quality adjusted life years gained for the HeartMate 3, compared to an advanced heart failure population. Once we look at it from that perspective, as Biykem pointed out, we are getting closer and closer to the societal norms.                                                 At one time-point, society used to think of a quality adjusted life years gained cost of 50 thousand dollars as something that would be acceptable to society, and this was seemingly based on the threshold for what dialysis provides in benefit. And now, we recognize that we have to really expand that to somewhere around 100 thousand more logically, or between 100 and 150 thousand for some technologies. The important thing I would say to you is that, that is society dependent. So what the United States considers to be a reasonable ICER, say 100 to 130 thousand dollars per quality adjusted life years gained, may not be the same that Great Britain would look at, or Sweden would look at, or another country would look at. And each country actually creates their own economic value propositions, and this will have to be taken into account as we think about this data as well. Dr Carolyn Lam:                How cleverly and clearly articulated, thank you so much Mandeep. Just one last question for both you and Biykem, what do you think this implies for moving to less and less advanced heart failure with these left ventricular assist device systems? Biykem? Dr Biykem Bozkurt:         It's an ever-expanding field, and as these devices are becoming smaller, lower profile with lesser complications and more affordable, probably the utilization will likely increase as we have been seeing. As you know, even the percutaneous non-durable device used, as well as our mechanical circulatory support durable devices are definitely increasing utilization. And thus, one may wonder not only the bridge to transplantation, but the destination therapy portfolio, or bridge to decision portfolio, may really increase as these devices become safer and more affordable. Dr Carolyn Lam:                Wow, that's amazing. How about you, Mandeep, what do you think? Dr Mandeep Mehra:       Carolyn, I couldn't have said it any better than what Biykem articulated. I do think that at least in the United States, as we reach the thresholds of cost effectiveness that we as a society accept, we will start to see a lot more widespread utilization, particularly for lifelong therapy or so-called destination therapy. I completely agree with that. I think that moving the needle to the less sicker population is still challenging, because there are complications with these devices that make that slightly difficult.                                                 There was a trial called the REVIVE-IT trial that was stopped midstream largely because of concerns about pump thrombosis, and that trial was looking at taking these devices to a less sick NYHA class 3 population and was stopped midstream. Now that the HeartMate 3 has pretty much resolved the issue of pump thrombosis, and even show a halfing in stroke rates with this device over two years, I think that that portfolio of evidence needs to be reopened. I would caution though, that until we have confirmatory randomized data in those less sick populations, the use to that population should still stay restricted. Dr Carolyn Lam:                I don't think anyone could have said it better than both of you. Thank you so much for this very insightful and balanced conversation.                                                 Thank you so much for listening today. You were listening to Circulation on the Run, and don't forget to tune again next week.  

It's Global Game Jam 2018! In this special jam episode you'll hear field interviews with gamedevs at the Minneapolis Gamecraft site mid-jam as they work on their games. Then your nice hosts talk all about how the weekend went for them and what they each got out of the experience. Martha is a stage manager, Mark can't help but make artistic developer art and Stephen is the GGJ MVP.Stephen's GGJ game: ”Dicer and Clasp: Dungeon Skedaddle”. - Stephen's GGJ Team, GGJMark's GGJ gam: ”CMYK”. - Mark's GGJ Team, GGJMarth's GGJ InterviewsAdia on Twitter. Adia's game: “Jank Escape”Ellen on Twitter. Ellen worked with Stephen on “Dicer and Clasp.”“Intergalactic Transmissing”“Radwave”“Social Anxiety Simulator”“Space Pirate Radio”Charles' wry tweet about the GGJ theme. Global Game Jam 2018 EventsIntergalactic Transmissing found the community at nesdev.com a great resource f…Mark used a very helpful open-source library called VRTK for his GGJ game.Mark used AssetForge to create 3D assets for his GGJ game. Rachel Peterson was a guest on a previous episode. Games Education

It's Global Game Jam 2018! In this special jam episode you'll hear field interviews with gamedevs at the Minneapolis Gamecraft site mid-jam as they work on their games. Then your nice hosts talk all about how the weekend went for them and what they each got out of the experience. Martha is a stage manager, Mark can't help but make artistic developer art and Stephen is the GGJ MVP. Stephen’s GGJ game: ”Dicer and Clasp: Dungeon Skedaddle”. - Stephen's GGJ Team , GGJ Mark’s GGJ gam: ”CMYK”. - Mark's GGJ Team , GGJ Marth's GGJ Interviews Category Events Adia on Twitter. Adia’s game: “Jank Escape” Ellen on Twitter. Ellen worked with Stephen on “Dicer and Clasp.” “Intergalactic Transmissing” “Radwave” “Social Anxiety Simulator” “Space Pirate Radio” Charles’ wry tweet about the GGJ theme. Helpful Links Category Events Intergalactic Transmissing found the community at nesdev.com a great resource f… Mark used a very helpful open-source library called VRTK for his GGJ game. Mark used AssetForge to create 3D assets for his GGJ game. Rachel Peterson was a guest on a previous episode. Games Education

It's Global Game Jam 2018! In this special jam episode you'll hear field interviews with gamedevs at the Minneapolis Gamecraft site mid-jam as they work on their games. Then your nice hosts talk all about how the weekend went for them and what they each got out of the experience. Martha is a stage manager, Mark can't help but make artistic developer art and Stephen is the GGJ MVP. Stephen's GGJ game: ”Dicer and Clasp: Dungeon Skedaddle”. - Stephen's GGJ Team, GGJ Mark's GGJ gam: ”CMYK”. - Mark's GGJ Team, GGJ Marth's GGJ Interviews Adia on Twitter. Adia's game: “Jank Escape” Ellen on Twitter. Ellen worked with Stephen on “Dicer and Clasp.” “Intergalactic Transmissing” “Radwave” “Social Anxiety Simulator” “Space Pirate Radio” Charles' wry tweet about the GGJ theme. Global Game Jam 2018 Events Intergalactic Transmissing found the community at nesdev.com a great resource f… Mark used a very helpful open-source library called VRTK for his GGJ game. Mark used AssetForge to create 3D assets for his GGJ game. Rachel Peterson was a guest on a previous episode. Games Education

Ben tenOever joins the TWiVoli to discuss the evolution of RNA interference and his lab's finding that RNAse III nucleases, needed for the maturation of cellular RNAs, are an ancient antiviral RNA recognition platform in all domains of life. Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler Guest: Ben tenOever Become a patron of TWiV! Links for this episode RNAseIII is an ancient antiviral effector (Nature) Influenza suppression of RNAi (PNAS) Questioning mammalian antiviral RNAi (Nat Micro) Antiviral protection via RdRp (PLoS Path) Evolution of antiviral defense (Cell Host Micr) Letters read on TWiV 450 Weekly Science Picks Ben - Invisible Invaders by Peter Radetsky Kathy - ASV 2017 Virolympics Crossword solved (pdf) and National Museum of the Air Force Rich - Columbia river gorge and Undaunted Courage by Stephen Ambrose Dickson - All the World's Earthquakes Alan - Map of Roman roads Vincent - Brain atlas of fly behavior Listener Pick Rob - Vaccinate Your Kids and Charles Darwin Natural Selection Islam - Self-assembling virus and Virus Patterns Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv

The TWiV Council explores the finding that facial appearance affects science communication, and evidence that RNA interference confers antiviral immunity in mammalian cells. Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, and Kathy Spindler Become a patron of TWiV! Links for this episode JMBE SciComm Issue Facial appearance affects science communication (PNAS) Your face matters to science (virology blog) RNA based antiviral immunity in mammals (Immunity) How mice say nodavirus (TWiV 245) Press release on science meeting gender disparity The Traditional Lecture is Not Dead. I Would Know – I’m A Professor (virology blog) Sound of Silence by Disturbed (YouTube) Letters read on TWiV 449 Weekly Science Picks Kathy - ASV 2017 Virolympics Crossword (pdf) Dickson - The Visible Mouse Alan - Is profitable publishing bad for science? Vincent - Locally Sourced Science Listener Pick Neva - Michael Summers interview and Virus coloring book Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv

Alicja Witek prezentuje to urządzenie, dzięki któremu będziemy w stanie równo pokroić różnego rodzaju składniki do zup czy sałatek.

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, and Kathy Spindler The lovely TWiV team explore evolution of our fecal virome, and the antiviral RNA interference response in the nematode C. elegans.  Become a patron of TWiV! Links for this episode ASM Clinical Virology Symposium Evolution of the human fecal virome (PNAS) Antiviral RNAi response in C. elegans (Curr Biol) Orsay virus (TWiV 123) Broad VSV host range (J Comp Neurol) Image credit Letters read on TWiV 433 This episode is brought to you by Blue Apron. Blue Apron is the #1 fresh ingredient and recipe delivery service in the country. See what’s on the menu this week and get your first 3 meals free with your first purchase – WITH FREE SHIPPING – by going to blueapron.com/twiv Weekly Science Picks Alan - Contact information for Senators and Representatives Kathy - How Tumor Virology Transformed Oncology Dickson - Seven new species of Peacock Spider Vincent - Proposed NIH budget cut and Expensive Oxford Comma Listener Pick Kim - Pigeon Fashion Week (TWiEVO 7) Richard - aeroMorph and Understanding Molecular EvolutionJohnye - Ice Instruments and Fahrenheit and Celsius Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv

Männerabend Stammtisch #15 – Koan Dicer zu Weihnachten! Dennis (@derMaennerabend) spricht heute nacheinander mit Candy (@CandySierks), Thomas (@DerPoppe) und Reinhold (@Big_van_Rocky) über die Ereignisse der letzten Monate, Weihnachten, Silvester und vieles mehr! Unser „Männerabend Stammtisch“ ist auch auf iTunes zu finden (unbedingt abonnieren!) und für alle „nicht Apple User“ gibt es hier (KLICK) den Link […]

This is part two of my interview with Lord Grunge. We recorded this on his front porch in Pittsburgh, on Black Friday. We start the conversation by talking about Grand Buffet’s B-sides record Dicer, and how it later played a hand in them going on tour with Third Eye Blind. We talk about some of Grand Buffet’s later releases, and some of the frustrations they faced upon putting those records out. We discussed making music as an older guy and his new day job as an EMT. Mike Riley’s art this week is an homage to Black Sheep’s Non-Fiction. This episode is hosted by splicetoday.com.

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler The TWiVerinoes discuss the potential for prion spread by plants, global circulation patterns of influenza virus, and the roles of Argonautes and a viral protein in RNA silencing in plants. Links for this episode Prions in plants (Cell Rep) 11:35 Global influenza virus circulation (Nature) 20:40 Rough patch for plant RNA silencing (Lab Times) 29:50 Role of Argonaute proteins in plant viral defense (PLoS Path) 32:15 Rub-inoculation (YouTube) 42:45 Image credit Letters read on TWiV 343 4:00, 1:11:45 Timestamps by Jennifer. Thank you! Weekly Science Picks 1:41:45 Dickson - Global rainfall and snowfall map and A Week in the Life of RainAlan - Automated patch clampKathy - More Women in Science mini LegosRich - The Martian trailerVincent - It's a bug's life Listener Pick of the Week May - p53 by Sue Armstrong Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

RNA interference (RNAi) is a highly conserved process of gene silencing in which Argonaute family proteins are guided by small RNA molecules to complementary targets. In the fission yeast Schizosaccharomyces pombe, RNAi is required for heterochromatin formation at centromeres. Although it seems counterintuitive, pericentromeric heterochromatin in fission yeast is transcribed. The transcripts are processed by RNAi machinery, which is in turn guided back to the pericentromeric repeats by sequence complementarity of the Argonaute-bound small interfering RNA (siRNA) and the nascent transcript. This generates a positive-feedback loop of siRNA amplification that recruits factors required for the assembly of heterochromatin. Previously, it was suggested that a fission yeast class of Dicer-independent small RNAs called primal small RNAs (priRNAs) initiates the positive-feedback loop of siRNA generation and heterochromatin assembly. However, the biogenesis of priRNAs as well as of Dicer-independent small RNAs from other organisms was not well understood. The results presented here identify Triman, a novel 3’-5’ exonuclease that is involved in the final step of biogenesis of both priRNAs and siRNAs in fission yeast. It was observed that Argonaute binds longer priRNA and siRNA precursors from the total RNA fraction. This is followed by the recruitment of Triman to trim 3’ ends of Argonaute-bound small RNAs to the mature size. The final trimming of priRNAs and siRNAs is required for de novo heterochromatin formation at centromeres and the mating-type locus as well as for the maintenance of facultative heterochromatin islands. Furthermore, it was shown that in cells lacking Rrp6, a nuclease subunit of the exosome, RNAi targets various genes across the yeast genome. This demonstrated that the exosome protects the genome against aberrant RNAi. Spurious RNAi targeting in rrp6∆ cells at majority of loci occurs via accumulation of antisense transcripts that are processed into priRNAs in a Triman-dependent manner. These results suggest that Argonaute association with cellular degradation products which are processed into priRNAs might serve as a surveillance mechanism to guard the genome against invading genomic elements (Marasovic et al. 2013).

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler Vincent, Dickson, Alan, Rich, and Kathy review two papers that present evidence for RNA interference as an antiviral immunity mechanism in mammals. Links for this episode: World Polio Day Mole Day John Holland's publications RNAi is antiviral in mammals (Science) Antiviral RNA interference in mammals (Science) RNAi, antiviral after all (Science) Is RNA interference antiviral in mammals? (Cell Host Microbe) Nodamura virus (Nature) Ebolavirus proteins suppress RNAi (J Virol) Illustrated is an siRNA (orange), dicer (top right), and argonaute (bottom) Letters read on TWiV 256 Weekly Science Picks Dickson - Wildlife Photographers of the Year 2013Kathy - John Holland's Emerging Infectious Disease lecture (YouTube)Alan - The worst part is notRich - The Universe in a Single Atom by Dalai Lama (Mind and Life Institute)Vincent - The Truth about T. Rex by Brian Switek Listener Pick of the Week Stephen - International Institute for Species Exploration (Top 10 species choice)  Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

Hosts: Vincent Racaniello and Rich Condit Guests: Robert Krug and Christopher Sullivan Vincent and Rich visit the University of Texas at Austin and meet up with Bob and Chris to talk about their work on influenza virus and microRNAs. Links for this episode: Virus-encoded microRNAs (PLoS Path) microRNA targetomes of polyomavirus (J Virol) Innate and RNAi reciprocal inhibition (Cell) ISG15 pathway (Trends Micro) Role of viral NS1 protein (Virology) Cap-snatching (Cell) Weekly Science Picks Rich - Unraveling BoleroVincent - New botulinum toxin, DURC implications, and inconvenient truths Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

Dendritic cells (DCs) play a key role in the initiation of adaptive immune responses and the maintenance of self-tolerance. Due to their therapeutic potential, understanding the mechanisms that guide DC differentiation and effector functions is important. DC differentiation and activation depends on transcription factor control of stage-specific gene expression. The recent identification of posttranscriptional control of gene expression by microRNAs (miRNAs) has added another layer of gene regulation that might be important in DC biology. We analyzed the miRNA expression profiles of different DC subsets and identified several miRNAs differentially expressed between plasmacytoid DCs (pDCs) and conventional DCs (cDCs). In terms of miRNA expression, pDCs were more closely related to CD4+ T cells than to cDCs. We also observed that pDCs and cDCs preferentially expressed miRNAs associated with lymphoid or myeloid lineage differentiation, respectively. By knocking down miR-221 or miR-222 during in vitro DC differentiation, we obtained a higher pDC frequency. While p27kip1 and c-kit are confirmed miR-221/222 targets, we additionally identified the pDC cell fate regulator E2-2 as a potential miR-221/222 target. Thus, our analysis points to a role for miRNAs in directing and stabilizing pDC and cDC cell fate decisions. To assess the general influence of miRNAs on DCs, we generated mice with a DC-specific conditional knockout of the key miRNA-producing enzyme Dicer. Dicer-deficient mice dis- played no alterations in short-lived spleen and lymph node DCs. However, long-lived epidermal DCs, known as Langerhans cells (LCs), showed increased turnover and apoptosis rates, leading to their progressive loss. Upon stimulation, Dicer-deficient LCs were able to properly upregulate the surface molecules MHC class I and CCR7, but not MHC class II, CD40 and CD86. In consequence, they were incapable of stimulating CD4+ T cell proliferation. The work presented in this thesis indicates a role for miRNAs in DC regulation not covered by transcription factors. Having demonstrated a role for miRNAs in DC lineage fate decisions, as well as in LC homeostasis, maturation and function, we conclude that miRNAs regulate various aspects of DC biology and thereby contribute to the control of adaptive immune responses.

Vincent meets up with Raul Andino in San Francisco to discuss the RNAi-based antiviral defense system of Drosophila, the fruit fly, and how it is antagonized by viruses.

The ability of the Journal of Pathology to provide interesting and useful content to readers and to the field at large has been enhanced by the creation of Virtual Issues, annotated compilations of papers and reviews organized by theme. Here one of the authors of the Virtual Issue John LeQuesne outlines this series and highlights the recently released micro-RNAs Virtual Issue.

As computer and network use becomes more widespread, more people are faced with the problem of making meaning out of large data sets. Big data presents not just technical challenges but time and cost challenges as well. In this episode of Future Lab, we look at two innovative ways, BOINC and Dicer, researchers are developing […]

microRNAs (miRNAs) are small non-coding RNAs of 21-24 nt in size, which are endogenously expressed in higher eukaryotes and play important roles in processes such as tissue development and stress response and in several diseases including cancers. In mammals, miRNAs guide proteins of the Argonaute family (Ago proteins) to partially complementary sequences typically located in the 3’-untranslated regions (3’-UTRs) of specific target mRNAs, leading to translational repression or mRNA degradation. To gain further insight into the function of human miRNAs, we analyzed the protein as well as the RNA composition of miRNA-Ago protein complexes in molecular detail. To identify novel Ago-interacting proteins, we isolated Ago complexes and investigated them by mass spectrometry and co-immunoprecipitation experiments. We found that trinucleotide repeat-containing 6B (TNRC6B), Moloney leukemia virus 10 (MOV10), RNA binding motif protein 4 (RBM4) and Importin 8 (Imp8) interact with human Ago proteins. Moreover, using RNA interference and EGFP and dual luciferase reporter assays, we demonstrated that these factors are required for miRNA function, indicating that we have identified new components of the miRNA pathway. Intriguingly, depletion of Imp8 does not affect the levels of mature miRNAs or the interaction of miRNAs with Ago proteins, but is required for efficient association of Ago-miRNA complexes with their target mRNAs. Thus, Imp8 is the first factor acting at the level of target mRNA binding, establishing a novel layer of regulation for the miRNA pathway. Imp8 is an Importin-β-like protein, which has previously been implicated in nuclear import of substrate proteins. In line with these results, we demonstrated that a detectable fraction of Ago2 localizes to the nucleus of human cells. Moreover, knockdown of Imp8 by RNAi reduces the nuclear signal of Ago2, suggesting that Imp8 affects the nuclear localization of Ago2. Therefore, our data suggest that Imp8 has a dual function both in the cytoplasmic miRNA pathway and in nuclear transport of Ago proteins. To identify small RNAs, which associate with human Ago proteins, we isolated, cloned and sequenced small RNAs bound to Ago1 and Ago2 complexes. In addition to known miRNAs, we found several small RNAs, which derive from small nucleolar RNAs (snoRNAs). We therefore investigated the function of one particular small RNA, which is derived from the snoRNA ACA45 and showed that it functions like a miRNA. Interestingly, this small RNA is processed by the miRNA maturation factor Dicer, but does not require the microprocessor complex that is essential for processing of primary miRNA transcripts. Thus, we have identified a novel biogenesis pathway of a new class of small RNAs that can function like miRNAs. To experimentally identify mRNAs that are stably associated with miRNA-Ago protein complexes, we isolated and analyzed Ago1 and Ago2-bound mRNAs by cloning and sequencing and by microarray hybridization techniques. Using dual luciferase reporter assays, we demonstrated that many Ago-associated mRNAs are indeed miRNA targets. Therefore, we have developed a method allowing for the identification of miRNA target mRNAs from cell lines or tissues of interest independently of computational predictions. In a project that was independent of our studies on Ago protein complexes, we investigated structural and functional requirements for the activity of small interfering RNAs (siRNAs). siRNAs are small double-stranded RNAs of appr. 21 nt in size, which trigger the sequence-specific endonucleolytic degradation of perfectly complementary target transcripts upon binding to Ago2. However, both single strands of a siRNA duplex can potentially have unwanted “off-target effects” by repressing partially complementary target mRNAs through binding to their 3’-UTRs. We therefore developed a method to selectively inhibit the activity of the siRNA strand that is dispensable for target silencing (“passenger strand”) through chemical modification of its 5’-end. This method could be a useful tool for the design of highly specific siRNAs. Taken together, we have analyzed the composition of Ago-miRNA protein complexes by a variety of methods and identified novel protein factors of the miRNA pathway, a novel class of small RNAs as well as a panel of previously unknown miRNA target mRNAs. The techniques for the purification and the analysis of Ago complexes that were developed in this study will provide useful tools for future analyses of miRNA pathway factors, small RNAs and miRNA target mRNAs from any tissue or cell line of interest.