Podcasts about e06

Motorsport 411: 2021 Safari Rally Special Series -Sebastien Ogier 7 time safari rally champion E06 by Capital FM

For an unhinged eighty minute session of inebriated gay screaming, Zach gets uncomfortably drunk and shrieks about the queen of pop with notorious Madonna stan David (@shantytyrelle). They get into ALL OF IT: her best albums, every controversy, Cher, Eurovision, HIV/AIDs, drugs, Kylie Minogue, voguing and pedophilia. Also featuring the cicadas living in David's backyard, way too many shots of tequila and more slurring than you will believe possible from Zach herself. About to change the name of the pod to I'M SO CANCELLED -- reuploaded for quality assurance purposes. impopular.me (s1.E06)

前總統馬英九、陳水扁卸任後都捲上司法案件，台灣第一任直接民選的總統李登輝呢？前總統李登輝所涉及的興票案與國安密帳，跟陳水扁國務機要費，馬英九三中案，其實都有所關聯。今天這一集，我們先來回顧歷史，2000年的總統選舉，若不是李登輝凍省、宋楚瑜被爆出有上億元的秘密帳戶，被國民黨提告疑似侵占黨產，台灣的歷史很有可能就此改變，那次的總統大概不會是陳水扁當選。當時擔任國民黨主席的李登輝，究竟跟這起興票案有什麼關係呢？司法記者這次，又是如何知道李登輝要被傳喚，寫成隔天的頭條新聞呢？【偵查不公開？記者帶你挖內幕 E06】宋楚瑜差點第一次選總統就上　改變台灣政治史的興票案

【READr資料新聞解密E06】疫情風暴裡的數據新聞　開放資料真的是台灣之光嗎？ 或許過了很多年，歷史上仍有一頁會寫道，西元2020年，一種名為COVID-19的病毒重創了全球各國。而細部的史料或許會分享，其中有一個地方，領土或許不大，但卻抱持著滿腔的熱心與謹慎的精神防堵病毒——是的，那就是台灣。台灣連續多日0確診，這樣的好成績背後歸功於許多人的努力。4月底台灣疫情指揮中心成立將屆百日，在這防堵疫情百日的重要日子裡，台灣究竟發生了哪些事？我們可以從哪些數據去分析這次疫情對於台灣與全球的影響呢？閱讀原始報導：武漢肺炎疫情READr作為資料新聞的團隊，也在這段時間長期抗戰中，投身追蹤每天的新增案例進度外，也做了各式各樣大大小小的題目，舉凡5天內口罩實名制系統如何建置的故事，google提出的社區移動報告說了什麼？肺炎對這次往返台灣的航班有什麼影響，甚至對於觀光業有多麽劇烈的衝擊？連前一陣子沸沸揚揚的紐時募資廣告，READr都用了Twitter的轉貼數據，來解析其他國家的人如何看待這件事。沒錯，數據會說話，而讓這些數據說話的，正是背後辛苦的資料記者。這一集邀請到READr的資料新聞記者又如（還會有其他人嗎？），來分享這次肺炎疫情系列報導！節目摘要：01:23 READr的第一個迷惘期，武漢肺炎如何做？資料新聞團隊如何定位？03:14 第一個資料數據小工具如何誕生？後來如何衍生成一系列各式各樣的社群的口罩地圖成果展？後續的數據追蹤怎麼做？08:23 揭開神秘應用「武漢肺炎知識家」的神秘面紗？訓練、建立資料整合的資料庫以供查詢，合作新興媒體中心解答大眾問題。15:00 日常生活問題儘管問，「武漢肺炎知識家」使用門檻卻很高、難以推廣？16:26 從數據出發，深度專題有哪些：觀光產業的生與死。數據怎麼看？哪些數據可以分析？跟SARS的差異在哪？21:28 台灣是新冠疫情優等生？或許不如你想像的那樣！「開放資料」（open data）是什麼？

Are you staying on top of the temperature and the optics of the perceptions of your tone, messaging and content online? Are you keeping in mind that what might feel good in a moment could create problems in the future?Online Reputation Management for your Brand Messaging Optics is the title of The Brand Messaging Podcast Wait What Really OK S6.E06.N109 hosted by Brand Messaging Strategist Loren Weisman. Loren digs in to a series of thoughts to consider and keep in mind when adding content and when commenting online. We are long gone from the days of a private SOS Message in a bottle like The Police Song lyrics. "I'll send an SOS to the world, I hope that someone gets my message in a bottle." These days, our messages and our messaging is far from private and even when we think we are putting something out in the moment, it could be seen by thousands, years later as well as become heavily scrutinized. In this episode, Loren also discusses a brief checklist of ideas to maintain the past, the present and the future of your message and your messaging online. We are living in a time when both incorrect perceptions of your messaging online can turn into major issues for your business and reputation. "We are in a period where comments, posts, shares and even likes can be taken way out of context and create way more issues than they should for businesses and reputations. It is not about managing your reputation online to please everybody, but taking the right steps to reinforce and manage your online reputation can make all the difference for today, tomorrow, next week, next month and next year." S6.E06.N109 of the Wait What Really OK Podcast is called Online Reputation Management for your Brand Messaging Optics. This Brand Messaging Podcast is available on Pandora, iHeartRadio, Spreaker, Spotify, Google Podcasts, Apple Podcasts, and other Podcast Distributors.*******The Brand Messaging Podcast Wait What Really OK is Wait What Really OK is a methodical, comical and informational podcast sharing authentic brand messaging, optics approaches & strategies for honorable authority driven businesses. *******Host, Loren Weisman is a Brand Messaging Strategist and Contributor for FSG Messaging and Optics. Loren focuses on the authenticity, authority, optics, psychology and perceptions of a brand, persona or product. *******FSG Messaging and Optics (Orlando Division) 207 West Plant StreetWinter Garden, Florida, 34777-0991*******LW LinksLW URL: https://lorenweisman.com/Loren’s IMDb: https://imdb.com/name/nm11794652/ Loren's Author Page: https://amazon.com/author/lorenweismanLoren's NewsWire Page: https://www.send2press.com/wire/profile/loren-weisman/*******Brand Messaging Podcast WWROK LinksPodcast Info: http://brandmessagingpodcast.com/Twitter: https://twitter.com/waitwhatreallyOFacebook: https://facebook.com/brandmessagingpodcast/Google: https://brand-messaging-podcast.business.site/Podcast IMDb: https://www.imdb.com/title/tt12847210/Pandora: https://www.pandora.com/podcast/wait-what-really-ok-with-loren-weisman/PC:34213 *******Music Credits: Opening Theme Song“Fully Licensed Wait What Really Ok Theme Song" by RKVC. Copyright 2016 eMbloh Music (ASCAP)/ Cienzo Music (BMI). Administered by Ass Backwards Music (ASCAP)/Bass Ackwards Music (BMI) http://rkvc.net/*******Music Credits: Closing Theme Song“News and Information Podcast Percussion Outro” by Doug Hinrichs. Copyright 2016 Dig And Be Dug Music (BMI).Administered by Bass Ackwards Music (BMI).http://doughinrichs.com/*******Online Reputation Management for your Brand Messaging Optics.

Trapped in the watchtower just won’t do for this group. They were just meant to deliver some supplies and then go home! What can be done? The tower is surrounded and no one seems to be coming to their aid. A large hammer and the promise of blood pudding gives H.A.P.P.Y. a way out….down. ButContinue reading "Adventures in Gebrecan: E06"

Trypp returns Dharruhl to the party after finding him hanging over a rather delicously spiced pot. Kah-Lynn fights her way free from the great drainer and they all make their way back to Boaz to report on all the goings on at Van Sefan Castle. Veiv get’s familiar with her new, probably not evil, gauntletContinue reading "Edge of Desolation: E06"

The Weekend Social brings you the best outtakes from the last seven episodes! Hear your favorite guest hosts like you’ve never heard them before! New and improved! And with new dance moves, bitches!!! •E06 w/ Mr. Clean• 01-Kraft 02-Rock Band 03-Non-binary Tomato 04-I Want My MTV 05-Twist On The Downstroke 06-DBB Weiss 07-Like Trivia To Ulcers •E07 w/ High Gravity• 01-Drummers vs. Flatters 02-Chinese Costco 03-Senior Limpiar 04-The Hot Towel in the Face 05-Nipple Shots 06-I Thought It Was Lube •E08 w/ The Watcher• 01-Inverse Friction 02-Drink Pledge 03-Just Doing Research... 04-Secretive, Secretive or Secretive? 05-Booger Bubble 06-Down to Third Base 07-I Live in a Pirate Ship •E09 w/ ReggaeTron• 01-Oil Can Coincidence 02-Aloha Beaches 03-Farting Inflection Point 04-The ReggaeTron Method 05-Actual Bathroom 06-Rubbing Clay The Wrong Way •E10 w/ Daddy Badger & Tazmann• 01-Dick in Mouth Neck 02-Mira, Stop It 03-Angels Envy and Fireball 04-I Said Swipe Left!!! 05-Brother Badger 06-You Told This Story... 07-E-Money is Upset •E11 w/ Saul Goodman• 01-Stay Away From Stan 02-Smart Shark 03-Smelling What Your Steppin’ In 04-Saul Tastes The Claw 05-Stars And Suffering 06-She’s A Dry Guy 07-I’m Happy That You’re Happy •E12 w/ The Mongoose• 01-Bill Gates, Steve Jobs, Jeff Bezos 02-Lonely Child 03-This is Not A Negotiation 04-What’s an Arcade? 05-Peeing on Grass ••••Contact Us! We want your feedback and ideas!••• Email: TheWeekendSocialPodcast@gmail.com Twitter: The Chisler @fochisel E-Money @emoneytws Facebook: https://www.facebook.com/The-Weekend-Social-Podcast-100412098008836/ Bp7OtWPL5QESw1QXFe5

Quizmaster Dan (from E06) challenged Owen (From E13+E32) in a battle of wits and film knowledge. Loser does their best celebrity impersonation. They join Mark and Scott in a film round since they both do filmy-type stuff. Listen to them discuss (argue) Prometheus, Zooey Deschanel, Jeff Bridges, what it takes to scare a lion and why Owen and Dan think the Edinburgh Zoo is the best place in the world! (The last two points aren't related). Follow the team on Instagram and do the social media thing. Owens music video: https://www.youtube.com/watch?v=JH3LD_8liNs&feature=youtu.be&fbclid=IwAR24DOnjSXoqlUcmA54QMpp9zV0p8y5zcMw5PI0VV3Z-WqnAXcm0rXn3mss You too can find out more about the Edinburgh Zoo here: https://www.edinburghzoo.org.uk/ For any podqast related bits and pieces get in touch at info@goosesquizzes.com. Have a nice day and don't try and sit on peoples legs while they sleep xx

Warum wollen sich ARD und ZDF jetzt “Gemeinwohlmedien” nennen? Was passiert, wenn Politiker Tweets löschen? Und was steckt hinter dem Papageien-Outfit von unserem Bundespräsident Steinmeier? Alles und mehr in E06! (1) Was war eigentlich diese Woche los? (2) Gipfel der Woche: Das Framing Manual von ARD und ZDF (3) Re(tweet) der Woche: Helge Braun und (k)eine Meinung zum Uploadfilter (4) Querkopf der Woche: Frank-Walter Steinmeier entdeckt Instagram für sich

Clique aqui para ouvir o Episódio 150(é só clicar no botão de cima)E eis que conseguimos chegar ao episódio cento e ciquenta! Número redondo que nunca nos passou pela cabeça alcançar....Quis o destino que os nossos ilustres convidados não não tivessem disponibilidade para virem ao programa, mas fica prometido que um dia haverão de vir... e vai ser épico, acreditem!Vamos falar das ultimas jornadas onde o Vitória perdeu fora com o Marítimo e com o Boavista mas ganhou ao Rio Ave em casa, e onde o Beleneneses ganhou ao Feirense e empatou com o Guimarães e o Tondela.Faremos a normal análise à tabela classificativa e uma antevisão da jornada 27 onde o Vitória recebe o Portimonense e o Belenenses vai jogar fora com o Moreirense.Força Vitórrrria! Viva o Belém! Clique aqui para ouvir o Episódio 150Se quiser pode fazer o download do ficheiro e ouvir diretamente no seu computador/device, clicando aqui:Siga-nos no Facebook em:https://www.facebook.com/OsMelhoresAdeptosConfigure o seu leitor de PodCast com o feed em:http://feeds.feedburner.com/OsMelhoresAdeptos

Netflix has a new period drama, set in the '90s, called Everything Sucks. Where does it fall on the spectrum of Stranger Things to Freaks And Geeks? We've asked true '90s kid Stephanie Green to join us and break it down. Around The Dial takes us to Crazy Ex-Girlfriend, The Bachelor, and Chris Rock's new Netflix special, Tambourine. We ponder whether _The New Adventures Of Old Christine_S03.E06, confusingly also called "The New Adventures Of Old Christine," should be inducted into The Canon. Then after naming the week's Winner and Loser, it's on to a Game Time that's been around the world. Check on your Tamagotchi and then join us! Show Topics Lead Topic Everything Sucks Around The Dial Crazy Ex-Girlfriend The Bachelor Chris Rock's new Netflix special, Tambourine The Canon The New Adventures Of Old Christine S03.E06: The New Adventures Of Old Christine Winner And Loser Of The Week The CW Arrested Development alumni Game Time Where In The World Is This Show? Show Notes Stephanie's blog Special Guest: Stephanie Green. See acast.com/privacy for privacy and opt-out information.

Clique aqui para ouvir o Episódio 148(é só clicar no botão de cima)Há quase 3 meses que não gravávamos! Estamos de volta, para falar de tanta coisa que nem sabemos como deu para falar de tanto... desde as direções, os treinadores, as entradas e as saídas, as eliminações nas provas, dos adeptos, da liga, da taça da liga, de modalidades, do futuro... de bola e outras modalidade. Ahhh saudade de ouvir os melhores adeptos...!!Viva o Belém! Força Vitórrrria!Clique aqui para ouvir o Episódio 148Se quiser pode fazer o download do ficheiro e ouvir diretamente no seu computador/device, clicando aqui:Siga-nos no Facebook em:https://www.facebook.com/OsMelhoresAdeptosConfigure o seu leitor de PodCast com o feed em:http://feeds.feedburner.com/OsMelhoresAdeptos

E06.3 That Ain't Right by Albort Einstone

Clique aqui para ouvir o Episódio 135(é só clicar no botão de cima)E mais um programa Os Melhores Adeptos a falar do Vitória e do Belenenses, desta vez com o convidado especial Rodrigo Saraiva, Provedor dos sócios do Belenenses!Vamos ter uma conversa sobre temas atuais do Belenenses e do Vitória. Faremos depois a nossa normal análise à jornada anterior com o Belenenses a vencer em Alvalade o Sporting por 1-3 e o Vitória a perder em Tondela por 2-1. Faremos a normal análise à tabela e a antevisão à jornada 33 com o Belenenses a receber o Feirence e o Vitória a receber o Boavista.OUÇA E DIVULGUE A VOZ DOS VERDADEIROS ADEPTOS DA BOLA!Viva o Belém! Força Vitórrrria!Clique aqui para ouvir o Episódio 135Se quiser pode fazer o download do ficheiro e ouvir diretamente no seu computador/device, clicando aqui:Siga-nos no Facebook em:https://www.facebook.com/OsMelhoresAdeptosConfigure o seu leitor de PodCast com o feed em:http://feeds.feedburner.com/OsMelhoresAdeptos

It’s rare to find an English speaker in Israel who hasn’t heard of the Facebook group Secret Tel Aviv or the man behind it, Jonny Stark. Jonny joined me on Kipp Kong to talk about how he turned a group of a few friends into an over 107,000 member group and Tel Aviv’s online cultural … Continue reading "E06 – Jonny Stark & Secret Tel Aviv"

01. Galantis - No Money (Misha K Remix)02. Tujamo - Drop That Low (When I Dip)03. Miike Snow - Genghis Khan (Hook N Sling Remix)04. Miike Snow - Genghis Khan (Jerry Rekonius Bootleg)05. Dirty Ducks - D.A.N.C.E06. Chocolate Puma - Listen To The Talk07. Major Lazer & DJ Snake feat. M0-Lean On (Merk & Kremont vs Dirty Ducks Remix)08. Steve Aoki - Youth Dem (Turn Up) (feat. Snoop Lion) (Steve Aoki x Garmiani Remix)09. Cash Cash feat. Jacquie Lee - Aftershock (SCNDL Remix)10. Dirty Palm - Ounce11. Alan Walker - Faded (Tungevaag & Raaban Remix)12. Apek & Neeko n Remo - Force13. Jasmine Thompson - Adore (Slamdown Remix)14. Gazlind - Trouble15. Major Lazer - Light It Up (Quintino Remix)16. VINAI - Get Ready Now17. Dj Kuba & Neitan - Rock! (twoloud Edit)18. Swedish House Mafia vs Knife Party - Antidote (TYPE3 Edition)19. Carnage feat. Timmy Trumpet & KSHMR - Toca

[00:00] Intro [01:54] Overwatch not being free-to-play is just fine by Andrew [12:46] Nathan has an announcement [19:05] America Cables [22:49] Ridin' the .wav [30:38] Commercials HERE BE Spoilers! [33:50] Game of Thrones recap (up to S06E05) [48:48] 11.22.63 S01E05 and E06 recap. End of Spoilers [69:13] Star Trek teaser trailer has a bad voice over and a worse font.

Unser Schwerpunkt in E06 sind die Businessnetzwerke Xing und LinkedIn. Das diese beiden Netzwerke heute mehr sind als digitale Visitenkartenboxen haben viele schon verstanden. Wie Ihr die Businessnetzwerke jedoch nutzt um neue Kontakte zu knüpfen, alte Kontakte zu pflegen und um auf Euch aufmerksam zu machen, all das besprechen wir in der heutigen Episode.

Unser Schwerpunkt in E06 sind die Businessnetzwerke Xing und LinkedIn. Das diese beiden Netzwerke heute mehr sind als digitale Visitenkartenboxen haben viele schon verstanden. Wie Ihr die Businessnetzwerke jedoch nutzt um neue Kontakte zu knüpfen, alte Kontakte zu pflegen und um auf Euch aufmerksam zu machen, all das besprechen wir in der heutigen Episode.

[intro music]   Host – Dan Keller Hello, and welcome to Episode Forty-Five of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Dr. Simon Hametner, who discusses the role of iron in multiple sclerosis. But first, here are some of the new items on the MS Discovery Forum.   According to our curated list of the latest scientific articles related to MS, 59 such articles were published last week. To see the list, go to msdiscovery.org and click on Papers. We selected two of those papers as Editors’ Picks. One, published in Nature Reviews Neurology proposes a definition of aggressive multiple sclerosis as well as a treatment algorithm. The other editor’s pick, published in the journal Neurology, reports on a randomized, placebo-controlled study on patients switching from natalizumab to fingolimod, concluding that shorter washout periods may be better.   Our Drug-Development Pipeline includes continually updated information on 44 investigational agents for MS. During the past week we added 3 new trials, we updated information on 2 other trials, and we added 9 other pieces of information. The drugs with important additions and changes are daclizumab, dimethyl fumarate, fingolimod, interferon beta-1a, laquinimod, and natalizumab. To find information on all 44 compounds, visit msdiscovery.org and click first on Research Resources and then on Drug-Development Pipeline   [transition music]   Now to the interview. Dr. Simon Hametner works with Hans Lassmann at the Medical University of Vienna in Austria. We spoke about iron accumulation in MS in cells of the central nervous system and what iron may be doing.   Interviewer – Dan Keller Let's talk about iron and neurodegeneration. What specifically are you looking at?   Interviewee – Simon Hametner We are looking at the formalin-fixed, paraffin-embedded brain tissue from multiple sclerosis patients and controls, and we're looking, for example, at iron in these tissues. We're also looking now at proteins which are engaged in the management of iron in these tissues, for example, now.   MSDF What are you finding different in MS patients that you don't see in healthy people?   Dr. Hametner So we see iron accumulation, for example, in microglia and macrophages in MS, which are related to MS lesions. There are, for example, some MS lesions which have macrophages around those lesions, and we don't see much of iron in macrophages and microglia in healthy control tissue. We also see iron loss in multiple sclerosis because the iron is normally stored in oligodendrocytes in the controls. And this is also the case for MS, but in MS we also see a loss of this iron in the oligodendrocytes, especially at the oligodendrocytes which are closed to MS lesions.   MSDF Do you know the mechanism of why you're seeing these differences in iron?   Dr. Hametner We are now performing the research to find about these mechanisms. We have some prior indications, for example, hephaestin upregulation on oligodendrocytes in the vicinity of the lesions, but these data were not so straightforward. We are now also looking for ferroportin; ferroportin is an iron exporter of glial cells, it's actually ubiquitously expressed in mammalian cells. And all the glial cells also can express ferroportin, and we found it also in the oligodendrocytes; we now undertake this research. We think that oligodendrocytes really upregulate ferroportin and hephaestin in order to export iron.   MSDF Is the iron detrimental?   Dr. Hametner It depends. We don't think that it is, per se, detrimental; we see loads of iron in the deep grey matter nuclei and it seems that the brain can handle that quite well. But if there is even a minor amount of iron in the extracellular space even in the ferrous form – because iron normally is stored in the ferric and the trivalent form in ferritin – but if we see even minor amounts in the ferrous form, then it might be detrimental at very low amounts actually.   MSDF Is this a result or a marker of what's going on, or does it really contribute somehow to the disease?   Dr. Hametner This is a very interesting question. We think that iron really colocalizes or is found and accumulated at sites where things are going on with these lesions which accumulate iron in the microglia and macrophages around them. On the other hand, you can detect it very nicely with magnetic resonance imaging today. So we think that on the one hand it does play a role in the disease pathogenesis, and on the other hand we think that we can detect really these sites of iron accumulation, for example, around MS lesions.   MSDF Are you doing this only on fixed patient tissue, or do you have animal models of this; how are you exploring it?   Dr. Hametner We have this fixed material on the MS, and I think it's really important to also characterize the human material in very detail to perform all the necessary analysis to characterize what's going on in the human tissue. But, of course, as you mentioned animal models, it's very important to look at the EAE models. And collaboration partners have done that from McGill University in Montreal, Juan Zarruk and Sam David, and we are collaborating with them. And actually now they have been looking at some iron transporters and we are looking at exactly the same iron transporters now in the MS tissue. And they have found it in the same cell types, these iron transporters, in the EAE model being upregulated in the course of EAE as we see now in the MS tissues actually. So we really look for confirmation also from animal models from our collaboration partners.   MSDF And does this work with various kinds of animal models, or is it restricted to the EAE?   Dr. Hametner This survey has now been performed on the EAE, so it is a mock EAE actually and that they have performed a relapsing-remitting mock EAE in the chronic EAE model, and they have characterized those proteins, but they also do spinal cord injury models and they have performed a very interesting experiment on iron-loading in macrophages in the course of spinal cord injury where the iron gets into the macrophages possibly from a hemoglobin source from erythrocytes in the traumatic lesional tissue. And we think that regardless of the source of iron, it has these detrimental effects in the macrophages and triggers them to have a pre-inflammatory – or so to speak, M1 state – and are detrimental to the surrounding tissue.   MSDF This is macrophages or also microglia?   Dr. Hametner So in the spinal cord injury model, it was mainly macrophages. In the acute phases of the EAE at the peak of the disease, it was also mainly macrophages, but later they also found iron in the animal model within microglia, as we do also in MS. We have these early lesions where there are a bunch of macrophages in these classical active lesions, and these are mainly macrophages, and if they are iron-loaded, it is in the macrophages. But for the later lesions for these chronic active lesions which have this iron ring around the lesion, we find it also within macrophages but also microglia.   MSDF So does this change the oxidative environment inside the macrophage?   Dr. Hametner That's a good question. We think that it does change something with the macrophages because they seem to die. So we have these dying macrophages in the EAE model, as they have observed it, but in the MS we saw this dystrophic microglia at the lesion edge. So these are microglia which are highly iron-loaded probably for some time, and they have these nice processes. And if these processes get those beads and the process fragmentation and these process budding and blips in the processes, we call them senescent or that dystrophic microglia. And we have indications that this is really related to the iron load of this microglia. And then they get diminished towards the inactive centers of the lesion. So we think that at the edge of chronic active or slowly expanding MS lesions, these get iron-loaded in microglia and they don't handle it quite well, and then they die and get diminished towards the inactive centers.   MSDF So when they die, do they release this and is it affecting other cells?   Dr. Hametner We believe so. We think more or less that it is necessarily released into the extracellular space if an iron-loaded cells just dies by necrosis, or apoptosis, or something in between. So it is just released into the extracellular space. It has to be taken up by other cells; for example, other microglia, or other macrophages, or even astrocytes; it seems that it is really liberated. But, of course, it is hard to say whether iron within a specific microglia has been acquired by some other microglia which has died, or by some oligodendrocyte which has died, or even another source. But the fact is although we are sure that they have really accumulated lots of iron, and given actually the concentration of iron in these microglia and the surrounding tissue, we do think that there must be other sources than only oligodendrocytes by which iron gets into these microglia.   MSDF Where do you go from here? What do you see the steps in the research?   Dr. Hametner  I think it is necessary to characterize these rings around lesions which have these iron-loaded microglia and macrophages, to characterize at which disease phases these rings occur, and, of course, this is very interesting because you can use it in vivo. Because one of the things we are really sure is that we can image iron within microglia at the lesion edge of those lesions very nicely at 7 Tesla of magnetic resonance imaging; we are very sure that this is iron then within microglia and macrophages. And if we can relate pathologically the disease mechanisms or the degenerative actions going on in these lesions to the presence of iron, we then can also relate our in vivo findings from MRI with the things which are going on there, like neural degeneration and demyelination, for example.   MSDF Do you find that the iron-sensitive MRI imaging correlates with duration of the disease or stage or clinical condition?   Dr. Hametner Yes, we think so from our pathological material. So we think that in the progressive stage of MS, there are these lesions which are the slowly-expanding lesions, and they have these chronic activity, chronic demyelinating activity at the lesion edge. And we think it's a typical feature of progressive MS. It remains to be determined whether this also holds true in vivo. If you make an MRI, an iron-sensitive MRI, and you look for iron rings around MS lesions, for example, by susceptibility-weighted imaging or by quantitative susceptibility mapping or even Ultrastar imaging, if you look at these iron rings around lesions, it remains to be determined at which disease phase is, because in the pathological material we have more of the chronic cases and we have very few relapsing-remitting. So we cannot say what's really going on in the relapsing-remitting disease because we don't have this material pathologically.   MSDF Right, you would have to find people in various stages who probably died from something else; they're not going to be advanced MS patients at that point. Is there some relationship of your findings to the idea of oxidative stress?   Dr. Hametner Yes, we have these overactivity for malondialdehyde or E06, which is this antibody against oxidized phospholipids, and we have found actually by working performed partly in this lab that there is a higher activity for oxidative stress of various glial cells in the lesions. But as for the microglial degeneration, we did not see so many microglia being positive for these markers. So the microglia, they seem to die, but we only have these morphological features of dystrophic or senescent microglia actually from the pathological side. On adjacent side, if you stain for iron and you stain for oxidized phospholipids, you see partly that there is a 1:1 colocalization. But we don’t see these always actually.   I think what's really clear is that there is lots of oxidative stress in MS lesions, but even in early MS lesions which on iron stainings don't have so much iron, because on these early lesions we actually see predominant iron loss. If you have a very highly active MS lesion in the early stages, you see iron loss, and you will see also oxidative damage there. So there is also other factors leading to oxidative stress, like NADPH oxidase, for example, the p22phox, the functional subunit of NADPH oxidase, which we have shown in this lab that it is upregulated on macrophages and microglia, but also in the absence of iron.   MSDF What tips the balance between loss and iron accumulation?   Dr. Hametner That's an interesting question, actually a complicated one. You're right, we see on the one hand iron loss, and we see iron accumulation. So in the early stages, we see iron loss around MS lesions, in the MS lesions, because oligodendrocytes try to get rid of their intracellular iron possibly to prevent the iron efflux or iron liberation, which is uncontrolled if there is demyelination and oligodendrocyte degeneration actually. So we think that inflammation in the early phases of the disease leads to this efflux, which we think also involves not only oligodendrocytes, but also astrocytes. So we now think actually that oligodendrocytes probably efflux the iron towards astrocytes, and those astrocytes then might efflux it towards the periphery even. So I think inflammation is an obvious candidate to trigger this upregulation of iron efflux mechanisms.   I think what drives the iron accumulation within the microglia at the lesion edges is a different story. We think that these are two unrelated processes. On the one hand you have these iron loss mechanisms, the iron efflux mechanisms from the oligos leading to iron loss in early MS lesions, and this seems to be a protective phenomenon; this is, so to speak, a protective reaction of the glial cells against oxidative stress. But in later lesions, in chronic active lesions with this iron accumulation within microglia and macrophages, and we don't think that they are really correlated. So we think these are two distinct processes going on in MS, probably even in two distinct phases of the disease.   MSDF Is there anything interesting to add?   Dr. Hametner I think the really crucial question is now to find out about the source of iron for microglia and macrophages, and even to find out about the source of iron for the oligodendrocytes. We are not so sure whether this is really transferrin-bound iron entering the brain and being loaded in oligodendrocytes, as you find it in control tissue, control brains. And we don't think that this is only this iron from the oligodendrocytes which is then loaded into the microglia and macrophages; we think there are additional sources possibly from the vasculature.   MSDF Very good, thank you.   [transition music]   Thank you for listening to Episode Forty-five of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]