Podcasts about C24

Hier geht es zu den 3,5 Empfehlungen: TR: http://traderepublic.investresearch.net (*) C24: http://c24.investresearch.net (*) WillBe: https://bit.ly/willbe (*) Geldmarkt ETF: https://youtu.be/twqKd9Uhn9c

Send us a Text Message.Expect to get the everyday perspective on which is harder CrossfIT or BJJ, how CrossFit transfers to BJJ, how off the mat conditioning can elevate your grappling, what to prioritise in the gym, advice on motivation and much more. Jason is the founder and CEO of NCFIT GYMS, TRAIN HARD online training, and the host of the JASON KHALIPA PODCAST. He is a CROSSFIT GAMES CHAMPION, 3X TEAM USA CROSSFIT MEMBER and BJJ Brown Belt.Extra Stuff:Insta - https://www.instagram.com/jasonkhalipaWebsite - https://www.jasonkhalipa.comTrain Hard App - https://www.th.fit00:00 What's Harder BJJ or CrossFit08:50 BJJ Competing15:14 Importance of Off-Mat S&C24:10 What to Prioritise 31:59 Strength or Mobility39:31 BJJ Training Partners44:51 Nutrition & Businesses50:36 Advice on Motivation#mentalhealth #bjj #bjjlifestyle #jiujitsu #jiujitsulifestyle #crossfit #worldsfittest #family Need a chat? Here's some options

In dieser Podcastfolge nehmen wir das C24 Girokonto genauer unter die Lupe. Seit mehr als einem halben Jahr nutzt Thomas den aktuellen Testsieger unseres Girokontovergleichs und wir haben viele Fragen dazu erhalten. Deshalb schauen wir uns nun das C24 Girokonto, die Karten- und Tagesgeldangebote genauer an. Außerdem beantworten wir die Frage, ob es sich hierbei um eine echte Alternative zu N26 handelt. Wir beleuchten die Vor- und Nachteile von C24, werfen einen Blick auf die App und gehen durch den Registrierungsprozess. Viel Spaß beim Zuhören! ➡️ Zur LINKBOX (Links zu unseren Produkten und Werbepartnern): https://www.finanzfluss.de/podcast-linkbox/ ℹ️ Weitere Infos zur Folge: Diese Folge als Video: https://www.youtube.com/watch?v=odl5k-kVv7o Girokonto-Vergleich: https://www.finanzfluss.de/vergleich/girokonto/ Finanzfluss Copilot: https://www.finanzfluss.de/copilot/ C24 Konto (+75€ Bonus bei Kontoeröffnung und Kontoumzug): https://link.finanzfluss.de/go/c24-smart *

Die aktuellen Wirtschaftsnachrichten mit Michael WeylandThema heute:    Nächste Stufe im Einlagenwettbewerb: Erste Bank in Deutschland zahlt 4,0 Prozent für Neu- und Bestandskunden im Tagesgeld   Das Geschäft mit klassischen Bankeinlagen stellt auch im laufenden Jahr 2023 weiterhin das vermutlich wichtigste Produktfeld aus Sicht vieler Kreditinstitute dar. Die im Vergleich zum allgemeinen Zinsniveau nach wie vor zurückhaltende Weitergabe der Marktveränderungen am eigenen Bestand beschert vielen Kreditinstituten hohe Erträge, die aufgrund meist nicht vorhandener Wechselbarrieren jedoch einer latenten Abwanderungsgefahr unterliegen. Unter diesem Gesichtspunkt muss aufmerksam zur Kenntnis genommen werden, dass mit der Einführung eines neuen Angebots der C24 Bank erneut eine kritische Preisschwelle überschritten wurde, wie man von der globalen Strategieberatung Simon-Kucher erfährt. Seit nun mehr als einem Jahr beschäftigt die sich vollziehende Zinswende die deutschen Kreditinstitute. Bislang dürfte das Zwischenfazit über die bisherigen Auswirkungen aus Sicht der überwiegenden Mehrheit der Institute positiv ausfallen. Neun Leitzinserhöhungen in Folge innerhalb eines Jahres haben den Konditionenbeitrag passiv zurückkehren und die operativen Erträge weiter steigen lassen. Gleichzeitig ist inzwischen vielerorts deutlich spürbar, dass höher verzinste Angebote im Wettbewerb auf Kundenseite wahrgenommen und zunehmend nachgefragt werden. Das neue Angebot der C24 Bank in Höhe von 4,0 Prozent für reguläres Tagesgeld könnte erneut zu einer verstärkten Kundenwahrnehmung führen und den Druck auf bereits etablierte Institute erhöhen.Eine bereits im November 2022 durchgeführte Kundenstudie der globalen Strategieberatung Simon-Kucher konnte zeigen, dass insbesondere bei Zinsprodukten sogenannte Schwellenpreise existieren. Werden diese überschritten, steigt die Attraktivität aus Kundensicht sprunghaft an, was zu einem ebenso sprunghaften Anstieg der zu erwartenden Kundenreaktionen führt. Mit dieser Tatsache sahen sich beispielsweise viele Institute konfrontiert, als aufgrund des Tagesgeldangebots von 3,00 Prozent der ING im April 2023 erstmals in größerem Umfang Einlagen von Kunden zur ING umgeschichtet wurden. Dass es bei einem Zinssatz von 3,00 Prozent eine deutliche Reaktionsschwelle gibt, zeigt auch die Anfang 2023 veröffentlichte Privatkundenstudie. Die nun von der C24 angebotenen 4,00 Prozent sind gemäß dieser Kundenstudie wiederum als Reaktionsschwelle anzusehen, insbesondere dann, wenn weitere Wettbewerber diesem Angebot folgen. Diesen Beitrag können Sie nachhören oder downloaden unter:

一、思想問題：當神的同在進入我的生活、家庭、工作中，會帶來什麼改變？ 二、鑰節： 68:5 神在他的聖所作孤兒的父，作寡婦的伸冤者。 68:6 神叫孤獨的有家，使被囚的出來享福；惟有悖逆的住在乾燥之地。 神的聖所不只是敬拜之處、讚美之處，奉獻之處、更是充滿憐憫的地方。最軟弱無助的人，他們所需要的不是社會福利，不是經濟補助，他們最大的需要是有一個家，可以得享真正的美福，可以有個父親，可以有一位保護申冤者，這些是今日教會的責任。願我們一起打造神的家，有什麼是我們可以行動的？ 三、經文結構： A1-2 神刑罰惡人：使惡人逃跑消滅。 A'3-6 神顧念義人：使孤兒寡婦歡喜快樂。 →B7-10 神顧念百姓：8震動天地（西奈山），9堅固疲乏者，10施恩給困苦者。 →B'11-23 神勝過外邦：11婦女得勝；14、17震動天地，趕散列王（17西奈山）；19拯救我們。 →→C24-28 神選民敬拜神：24神進入聖所，26神是以色列的源頭。 →→C'29-35 列國君王敬拜神：29獻貢物給聖殿，33神是駕行諸天的主。 四、結構亮光： 本篇背景很類似約櫃起行時所發出的歌頌（可參見撒下6:12，民10:35），歡迎約櫃進入聖所，更象徵著歡迎神進入百姓當中。 本篇採AA'BB'CC'的直線結構，採惡人與義人、百姓與外邦的對比，再再顯示神對百姓的顧念。而vv.1-2對外邦從刑罰，到vv.11-23戰勝外邦，到vv.29-35列國的君王可以敬拜神，更逐步彰顯神對萬民的心意。 A的部分： vv.1-2願神興起，約櫃象徵著神的同在，神施行奇事，把一切抵擋神、攻擊百姓的勢力、仇敵完全消滅。 vv.3-6則是轉眼看見神對義人的顧念，特別是對孤兒寡婦的照顧，關於本篇所提到的聖所，是v.5顧念需要者的地方，是v.17充滿神大能的地方，是v.24讚美神的地方，是v.29萬民奉獻的地方，是v.35百姓敬畏神、神賜能力之地。教會應當是充滿愛心、大能、讚美、奉獻、敬拜之處，因著神的顧念我們可以歡喜快樂。 B的部分： vv.7-10回首過去神如何顧念百姓，v.8從西奈山立約開始，在曠野中一路的保護、同在，v.7雲柱火柱的恩典，v.9降下水源給曠野中的人，v.10神賜恩惠給困苦人、疲乏人。 而vv.11-23則是神戰勝外邦的軍隊。以色列中充滿困苦疲乏之人、婦女，但是外邦有v.12統兵，v.14列王，v.16多峰多嶺、氣勢磅礡的山，但是神就讓v.12婦女勝過君王，過去如何以大能震動天地向選民啟示，今日就以天地震動來擊打外邦（v.14）。巴珊山是神的山，可以翻譯成「巍峨的山、高大的山，但是卻成為被神征服的山」，一切抵擋神的勢力，無法在神面前站立得住。v.16這些高山斜看，就是輕視、藐視神的山，但神就是揀選了錫安山，就是勝過一切抵擋的勢力。 v.18被以弗所書4:4引用，提到神為我們預備了屬靈的恩賜，賜下最寶貴的聖靈給我們。v.20神為我們施行救恩，v.22把我們從外邦海中帶回來，勝過敵人。 C的部分： vv.24-28 在得勝之後，就是約櫃進入聖殿來敬拜的時候，充滿了歡呼讚美的聲音，所有以色列人都要稱頌神，這是舊約中我們所熟悉的部分。 而vv.29-35則是神對外邦的心意，神不只是勝過外邦君王，神更是渴望所有外邦人可以進入聖殿來奉獻（v.29），一起來向神歌唱（v.32）、向神禱告（v.31），把一切的榮耀歸給神（v.34），神期待外邦也可以蒙恩得救。這在舊約並不明顯，但是到了新約，清楚地看見外邦人歸主，一同加入敬拜神的行列。 五、反省問題： 這裡所描繪的聖殿（教會）的景象是否是我所經歷的？在我的教會生活中，是否充滿愛心、能力、讚美、奉獻、敬拜？ 神揀選西奈山並不是因西奈山偉大，而是恩典，我被神揀選是否也是極大的恩典？ 我是否明白神愛世人的心，願意積極使加入福音廣傳的行列？ －－－－－－－－－－－－－－－－ 講員： 貴格會合一堂 徐坤靖牧師 聖經之鑰-各卷書播放清單： https://thfc.pse.is/3epsdf 【聖經之鑰 相關資源】YouTube： https://thfc.pse.is/3cfams電子書： https://thfc.pse.is/3ccluu Powered by Firstory Hosting

This recording has been made during a trip in south Morocco. A band was performing some traditional Moroccan music from Sahara, for a group of tourists. You can hear drums (including qraqeb), a string instrument (a guembri, I guess), and men singing. Kindly recorded in September 2015 by Laurence Luce, with a Yamaha pocketrak C24. Fade in/out applied in Audacity. Recording provided by Kevin Luce via Freesound. This is part of the Obsolete Sounds project, the world's biggest collection of disappearing sounds and sounds that have become extinct – remixed and reimagined to create a brand new form of listening. Explore the whole project at https://citiesandmemory.com/obsolete-sounds

C24 is an independent platform, exploring collaboration as a creative practice. For this episode, the Berlin based founders of Collide24 - Lena Manger and Kevin Moll look in detail at Artist-to Artist collabs, with a glimpse into the NFT world and how it intersects with solo and group works.

Welcome to Ask Stago, the podcast dedicated to provide expert answers to your expert questions in haemostasis.  In today episode, our expert Arnaud Rouvière, Global process – Service manager, will provide us all the current recommendations to establish your Quality control ranges.   As usual, don't forget to send any question you may have to ask@stago.com, we will be glad to answer to it.    Learn more  - Previous mentioned podcast  : Previous episode with Arnaud Rouvière : S1E7 How to determine the mean normal prothrombin time  Learn more about the externalization of your Internal quality controls (eIQC) : S1E3 #3 eIQC and EQA: benefits and differences   Go further with the episode dedicated to the reagent lot conversion : S2E10 - How to manage lot conversion in your daily lab management?  Literature sources:  CLSI Statistical Quality Control for Quantitative Measurement Procedures: Principles and definitions; 4th ed. CLSI guideline C24. Wayne PA: Clinical and Laboratory Standard Institute, 2016.  ISO 15189:2012 – Meical laboratories – requirements for quality and competence  College of American Pathologists. All Common Checklist. Northfield, IL: College of American Pathologists; 2020  Neufassung der Richtlinie der Bundesärztekammer zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen; Rili-BÄK; – Richtlinie der Bundesärztekammer zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen. Dtsch Arztebl Int 2014;111:1583–618. English version: Revision of the “Guideline of the German Medical Association on Quality Assurance in Medical laboratory Examinations – Rili-BAEK”. J Lab Med 2015;39:26–69  Content is scientific and technical in nature. It is intended as an educational tool for laboratory professionals and topics discussed are not intended as recommendations or as commentary on appropriate clinical practice. 

Wenn in Deutschland eine Neobank an den Markt kommt – das hat kaum noch Neuigkeitswert. Wenn aber Check24 eine Bank gründet, dann lohnt es sich genau hinzuschauen. Das Portal bringt als Schwungmasse 15 Millionen Kunden mit, baut mal eben das Kernbankensystem lieber modular selbst, anstatt auf White-Label-Lösungen zu setzen und setzt dank tiefer Taschen zeitweise 70 Entwickler an die Konstruktion der "C24 Bank". Die ist seit Oktober am Markt - und jetzt? Wo will die C24 Bank hin? Warum sitzt sie in Frankfurt und nicht in der Fintech-Metropole Berlin oder am Check24-Standort München? Welche Kunden hat man im Blick? Wie sieht das Geschäftsmodell aus? Und was hat man gelernt in den gut zwei Jahren auf dem Weg von einem weißen Blatt Papier bis zu einer fertigen Bank? Darüber sprechen wir in der heutigen Episode mit Christoph Röttele, dem CEO von Check24. Und der glaubt, dass es tatsächlich noch Segmente gibt, die von hiesigen Banken zu Unrecht ignoriert werden - und kündigt an, dass nun, sechs Monate nach dem "Soft Launch", Marketing und Produktpalette hochgefahren werden.

第10章 第八九災蝗黑暗 1-11 摩西與法老的談判 1-2 神吩咐－神在法老身上行審判，要使以色列後代認識神！ a3-6 摩西：向法老預言蝗災 b7-8 法老：臣僕勸法老聽，問摩西誰要去？ a9 摩西：老少兒女牛羊一起去 b10-11 法老：只有壯年人可去(留下妻小跑不走) 12-20 第八災－蝗蟲 A12 神吩咐－蝗災將至 B13-15 摩西遵行－東風把蝗蟲吹來， C16-20 法老－認罪求饒恕，苦難後神使他心硬 21-29 第九災－黑暗之災 A21 神吩咐－全地黑暗 B22-23 摩西遵行－三天的黑暗，唯有在以色列家有光 C24-29 法老－有條件許可離開，心硬 a24 法老－同意妻兒離開，牛羊要留下 b25-26 摩西－牛羊要帶走獻祭 a27-29 法老拒絕，心硬 結構亮光： 神對法老的審判是逐步加遽的，從外在到身上，從局部到全面，從有逃避的警告到無法逃避的降臨！我們是悔改經歷神憐憫的器皿，還是堅持硬心遭受審判的器皿？ 法老一再表達願意悔改，但是並不是對上帝的順服，而是對災禍的恐懼，因此當災禍一走，馬上原形畢露！當神的管教臨到，而保護卻在以色列民中，這樣鮮明的對比，卻沒有提醒法老自己所作何等的錯誤！我們的悔改是真實還是逃避刑罰？ 鑰節：2 並要叫你將我向埃及人所作的事，和在他們中間所行的神蹟，傳於你兒子和你孫子的耳中，好叫你們知道我是耶和華。」 神所行的神蹟，目的在於使我們知道祂是神，並且是我們世世代代要記得神自己！ 我們的信仰要向下傳遞！所經歷的神蹟，大事，要讓下一代牢牢記在心中！要有具體的事蹟，可見的記號來紀念上帝的作為！求主把這樣紀念神的恩典給我們！ 10:1 耶和華對摩西說：「你進去見法老，我使他和他臣僕的心剛硬，為要在他們中間顯我這些神蹟， 10:2 並要叫你將我向埃及人所作的事，和在他們中間所行的神蹟，傳於你兒子和你孫子的耳中，好叫你們知道我是耶和華。」 10:3 摩西、亞倫就進去見法老，對他說：「耶和華希伯來人的神這樣說：『你在我面前不肯自卑，要到幾時呢？容我的百姓去，好事奉我。 －－－－－－－－－－－－－－－－ 講員： 貴格會合一堂 徐坤靖牧師 聖經之鑰-各卷書播放清單： https://thfc.pse.is/3epsdf 【聖經之鑰 相關資源】 YouTube： https://thfc.pse.is/3cfams 電子書： https://thfc.pse.is/3ccluu Powered by Firstory Hosting

第1章 創造之主 1:1-2 創造的起點 3-31 六日創造 A3-5 第一日；光區分晝夜 B6-8 第二日；空氣區分水 C9-13 第三日：水區分地海，植物受造 A14-19 第四日：光體區分日子 B20-23 第五日：動物受造，水中有魚，空中有鳥 C24-31 第六日：24-25 動物，26-27 造人，28-29 任務，食物 上帝六日創造中，創造的高峰是甚麼？人的受造有甚麼特別之處？感謝神！我們擁有神的形象與樣式，使我們外在有神的樣式、內在有神的榮美，更與主建立最美互動的關係，並且領受頂級的使命，管理大地！ 鑰節：1:26 神說：「我們要照著我們的形象，按著我們的樣式造人，使他們管理海裏的魚、空中的鳥、地上的牲畜和全地，並地上所爬的一切昆蟲。」 1.使無變有的榮耀創造 1-2 2.各按其時的慈愛創造 3-25 3.受造物中人是高峰 26-31 與神共話，親密關係，給予事奉神的榮耀 4.創造中上帝是主角－要紀念他 2:1-3 1:24 神說：「地要生出活物來，各從其類；牲畜、昆蟲、野獸，各從其類。」事就這樣成了。 1:25 於是神造出野獸，各從其類；牲畜，各從其類；地上一切昆蟲，各從其類。神看著是好的。 1:26 神說：「我們要照著我們的形象，按著我們的樣式造人，使他們管理海裏的魚、空中的鳥、地上的牲畜和全地，並地上所爬的一切昆蟲。」 1:27 神就照著自己的形象造人，乃是照著他的形象造男造女。 1:28 神就賜福給他們，又對他們說：「要生養眾多，遍滿地面，治理這地，也要管理海裏的魚、空中的鳥，和地上各樣行動的活物。」 1:29 神說：「看哪，我將遍地上一切結種子的菜蔬和一切樹上所結有核的果子，全賜給你們作食物。 1:30 至於地上的走獸和空中的飛鳥，並各樣爬在地上有生命的物，我將青草賜給牠們作食物。」事就這樣成了。 1:31 神看著一切所造的都甚好。有晚上，有早晨，是第六日。 －－－－－－－－－－－－－－－－ 講員： 貴格會合一堂 徐坤靖牧師 聖經之鑰-各卷書播放清單： https://thfc.pse.is/3epsdf 【聖經之鑰 相關資源】 YouTube： https://thfc.pse.is/3cfams 電子書： https://thfc.pse.is/3ccluu Powered by Firstory Hosting

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.27.223388v1?rss=1 Authors: Luzarowska, U., Russ, A.-K., Joubes, J., Batsale, M., Szymanski, J. J., Thirumalaikumar, V. P., Luzarowski, M., Wu, S., Zhu, F., Endres, N., Khedhayir, S., Schumacher, J., Correa, S. M., Skirycz, A., Fernie, A. R., Li-Beisson, Y., Fusari, C. M., Brotman, Y. Abstract: Due to their sessile lifestyle, plants have evolved unique mechanisms to deal with environmental challenges. Under stress, plant lipids are important as alternative sources of carbon and energy when sugars or starch are limited. Here, we applied combined heat and darkness and extended darkness to a panel of ~ 300 Arabidopsis accessions to study lipid remodeling under carbon starvation. Natural allelic variation at 3-KETOACYL-COENZYME A SYNTHASE4 (KCS4), a gene encoding for an enzyme involved fatty-acid elongation, underlies a differential accumulation of polyunsaturated triacylglycerols (TAGs) under stress. Ectopic expression in yeast and plants proved that KCS4 is a functional enzyme localized in the ER with specificity for C22 and C24 saturated acyl-CoA. Loss-of-function mutants and transient overexpression in planta revealed the role of KCS4 alleles in TAG synthesis and biomass accumulation. The region harboring KCS4 is under high selective pressure. Furthermore, allelic variation at KCS4 correlated with environmental parameters from the locales of Arabidopsis accessions. Our results provide evidence that KCS4 plays a decisive role in the subsequent fate of fatty acids released from chloroplast-membrane lipids under carbon starvation. This work sheds light on both plant response mechanisms to abiotic stress and the evolutionary events shaping the lipidome under carbon starvation. Copy rights belong to original authors. Visit the link for more info

Was steckt aus technischer Perspektive eigentlich hinter einer Bank? In dieser Episode des ITCS Pizzatime Tech-Podcasts blicken wir bereits vor der Veröffentlichung hinter die Kulissen von C24, einer neuen Open Banking Plattform von Check24! Philipp Kemmeter, Profi-Entwickler und Leiter des Versicherungs- und Bankbereichs von Check24, wird Euch einen exklusiven Einblick in die Projektarbeit von C24 ermöglichen. Philipp wird Euch an C24 beispielhaft erklären, wie man aus technischer Perspektive ein Banksystem aufbaut. Hier geht's direkt zur Webseite von C24: https://www.c24.de Werdet außerdem Teil der ITCS-Community und folgt uns auf Social Media unter: itcs_conference (Instagram // Twitter // YouTube). Der ITCS Pizzatime Podcast ist Teil des ITCS – Tech Konferenz, IT Jobmesse & Festival – schnapp dir dein kostenloses Ticket hier: https://www.it-cs.io/ Redaktion: Katharina Bauriedel & Matthias Walenda Produktion: ITCS - Umbeck & Walenda Media GmbH Moderation: Leonie Peyerl

Jordan is a senior in high school in the north burbs of Illinois - she was adopted off of Native American reservation and continues to stand up for her roots. She also stands firm in her faith & her passion for advocacy. On top of all of that, the girl can sing! Her Deats: Her InstagramHer song: INNOCENCEHer podcast: Plans to ProsperOther things mentioned: C24/7: An organization to help families get resources during this time of COVID-19Case for ChristViccino’s Pizza #sliceupyourlife … join in on the conversation wherever you are!Music is by Gillcuddy.http://www.sliceslicebaby.net/slice-up-your-life

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. Dr Greg Hundley:             And I'm Greg Hundley, associate editor as well at Circulation, and director of the Poly Heart Center in Richmond, Virginia, at VCU Health. Well, I'm going to talk about anti-hyperglycemic agents and look at a very important meta-analysis. Dr Carolyn Lam:                Those are the rage: GLP-1 receptor agonists and SGLT-2 inhibitors. But first, let's talk about psychosocial stress and cardiovascular health. So what is the joint impact of multiple stressors on racial or ethnic disparities in cardiovascular health?                                                 Well, this question was tackled by Dr Albert, from University of California San Francisco Center for the Study of Adversity and Cardiovascular Disease and her colleagues. They basically studied more than 25,000 women participating in the women's health study follow-up cohort, and examined the relationship between cumulative psychosocial stress and ideal cardiovascular health as defined by the American Heart Association Strategic 2020 Goals.                                                 As a reminder, this health metric includes smoking, BMI, physical activity, diet, blood pressure, total cholesterol and glucose, and higher levels indicate more ideal cardiovascular health and less cardiovascular risk.                                                 So, they found that both cumulative psychosocial stress and ideal cardiovascular health varied by race or ethnicity. Mean cumulative psychosocial stress scores were higher in Hispanic, Black, and Asian women compared to white women, even after adjusting for age, socioeconomic status and psychological status such as depression and anxiety. The mean ideal cardiovascular health scores remained worse in blacks and better in Asians compared to whites, despite taking into account socioeconomic factors and cumulative psychosocial stress. Dr Greg Hundley:             So Carolyn, how should clinicians incorporate this information in what we do every day? Dr Carolyn Lam:                Although the cumulative psychological stress and socioeconomic status did not fully explain the racial or ethnic differences in ideal cardiovascular health that we saw, clinicians should be informed by these data that psychosocial stressors are social determinants of health that have different prevalence according to race and ethnicity. I think that's what we need to learn. And of course these data support the need for additional work that addresses the joint impact of multiple social determinants of health on cardiovascular disease and in diverse populations. Dr Greg Hundley:             Very good, Carolyn. That was really an interesting article. Well, I'm going to switch gears and talk about the role of red blood cells in promoting vascular calcification. My article is from Dimitrios Tziakas from the Department of Cardiology in Thrace, Alexandropoulos, in Greece.                                                 Now, the presence of extravasated erythrocytes in human atherosclerotic lesions was described several years ago, but little is known about a possible active role of red blood cells during these cardiovascular disease processes. Clinical studies suggest that intraplaque hemorrhage may be associated with the progression of coronary, carotid, and atherosclerotic lesions and degenerative calcific aortic valve stenosis. So, in the present study, the authors examined the contribution of erythrocytes to vascular and valvular lesion progression, focusing on the effects of red blood cells on the osteoblastic transdifferentiation of smooth muscle cells in calcification. Dr Carolyn Lam:                Interesting. So, what did they find? Dr Greg Hundley:             So, lysed erythrocytes, and in particular their membrane faction, enhanced human and murine arterial smooth muscle cell mineralization and vascular aortic ring calcification. Red blood cell membranes injected in the vascular regions of atherosclerotic-prone mice also promoted calcification and red blood cells were found to co-localize with osteoblast like cells in human atherosclerotic plaques, stenotic aortic valves, and abdominal aortic aneurysms. And so, the study demonstrated that intra plaque hemorrhage promotes atherosclerotic and valvular lesion calcification and membranes of extravasated lysed red blood cells appeared to play an important role in the process. The investigators also showed a mechanism, that nitric oxide derived from erythrocyte endothelial nitric oxides synthase is involved, at least in part, in mediating the effects of red blood cells on vascular calcification. Dr Carolyn Lam:                Thanks, Greg. Now back to another, well, clinical paper with the next one asking, do mid-life biomarkers of heart and kidney damage associate with the level of and decline in physical capability with aging? Dr Kuh and colleagues from MRC Unit of Lifelong Health and Aging at University College London used data on 1,736 men and women from the oldest British birth cohort study. And, looked at their walking speed, chair rise speed, balance time, and grip strength. Assessed at ages 60 to 64 and 69 years. They tested the associations between Cystatin C, NT-proBNP, interleukin-6, and E-selectin all at ages 60 to 64 years with their performance at 69 years. And what they found was the lower levels of NT-proBNP in interleukin-6 in middle aged adults were independently associated with better physical capability up to nine years later. And all these associations were stronger than those observed for conventional risk factors: including lipids, blood pressure, and glycemia, and were not explained by the onset of cardio vascular and kidney disease or diabetes. Dr Greg Hundley:             Carolyn, is this saying we should now measure these biomarkers in mid-life? Dr Carolyn Lam:                Ah, before considering the use of NT-proBNP and IL-6 or interleukin-6 for risk stratification, we really do need further research to untangle whether these associations exist because the biomarkers are an integrated measure of accumulated exposures to stressors. Or, whether they are really capturing early an organ damage. Or, whether they are marking additional risk pathways. So, this and more is discussed in a great accompanying editorial entitled "Putting the Measurement of Physical Capacity in Older Adults in its Place". And that's by Dr Kritchevsky from Wake Forest School of Medicine. Dr Greg Hundley:             That's a favorite of my heart, Caroline. The old institution Wake Forest. But, I'm going to switch now and tell you a little bit about plasma ceramides and this is an article from Wei Zhao from the Department of Epidemiology in Population Health at Albert Einstein College of Medicine in Bronx, New York. The study evaluates the role of ceramides and what are those? Well, they're a class of bio-active lipids composed of sphingosines and fatty acids. And are involved in the development of cardiovascular disease. Elevated circulating levels of ceramides have been shown to be associated with increased risk of cardiovascular events, cardiovascular death, and even so, after adjusting for other cardiovascular disease risk factors. Now, interestingly, ceramide metabolism has long been noted to be closely related to HIV infection. But, the relationship has not been fully understood. HIV infected cells may cause enhancement of sphingomyelin volume breakdown and accumulation of intercellular ceramides, whereas intercellular accumulation is associated with enhanced replication of HIV.                                                 So, what did this study do? They evaluated circulating levels of four ceramides species which have been investigated in previous studies of non-HIV populations. And were measured in 737 women and men, 520 HIV infected and 217 HIV uninfected from the Women's Intra-Agency HIV Study and the Multi-Center Aids Cohort Study. And they compared the relationships with the progression of carotid artery disease assessed by B-mode ultrasound over a seven year period. Dr Carolyn Lam:                Interesting approach. So, what did they find? Dr Greg Hundley:             Elevated ceramide levels were associated with anti-retroviral therapy use. Particularly, protease inhibitor use HIV infected individuals. All four ceramides were highly correlated with each other and significantly correlated with total cholesterol and LDL cholesterol. And of note, remember they were measuring four, but C16:0 and C24:1 ceramides rather that C22:0 and C24:0 ceramides were more closely correlated with specific modified activation and inflammation markers and, surface markers of CD4 t-cell activation. Elevated plasma levels of C16:0 and C24:1 ceramides were also associated with progression of carotid artery atherosclerosis. So, in summary, the results of this study provide new information on biological mechanisms that may involve the specific mono-site activation and inflammation beyond cardiovascular disease traditional risk factors like cholesterol levels. For the association between ceramides and CVD, particularly among individuals living with HIV infection. Dr Carolyn Lam:                Fascinating. Thanks, Greg. Now that sets us up for beautifully for our featured discussion. Dr Greg Hundley:             Welcome everyone, to our podcast. My name is Greg Hundley and we've got a very exciting paper for the second part of our program today. With us we have Dr Thomas Zelniker from Brigham and Women's Hospital. And then, also, a guest editor, Dr John McMurray from Glasgow, Scotland. We're going to be discussing a meta-analysis in type 2 diabetic patients. Thomas, can you tell us a little bit about the study population, your design, and what where the outcomes that you saw in this study. Dr Thomas Zelniker:        As you know, the last half decade, members of two drug classes, GLP1 receptor agonists and SGLT2 inhibitors, so our goal was to provide clear context by comparing or contrasting the benefit of these two drug classes, and in particular to investigate the potential heterogeneity in the treatment site between patients with and without atherosclerotic cardiovascular disease. For that reason, we performed meta-analysis of all randomized partially controlled cardiovascular outcome trials of GLP-1 receptor antagonists and SGLT-2 inhibitors. We included data from more than 77,000 patients, nearly 43,000 patients coming from the five GLP-1 receptor antagonist trials and approximately 34,000 patients coming from the three SGLT-2 inhibitor trials. We tried to compare patients with those with known established atherosclerotic cardiovascular disease with those that have multiple risk factors for but no evident ASCVD. And as you can see, our interests included MACE, or major atherosclerotic cardiovascular events, and its individual components, MI, stroke and cardiovascular death. And then we looked at hospitalization for heart failure and progression of kidney disease. The progression of kidney disease was defined as one of the broad composites consisting of new onset of macroalbuminuria, worsening of eGFR, end-stage kidney disease, or death due to renal cause. And then we also had a more narrow kidney outcome which excluded macroalbuminuria. Dr Greg Hundley:             Thomas, did you observe differences in the types of events between the two agents, as they would have impacted hospitalization for heart failure or the progression of renal disease? Dr Thomas Zelniker:        Right. So foremost both trial analyses reduced the risk of MACE, major atherosclerotic events, but the reduction of MACE was actually confined to those patients with atherosclerotic cardiovascular disease. We saw a 40% reduction in patients with known ASCVD, where neither of these groups reduced the risk of MACE in patients with only multiple risk factors but without ASCVD. Now, in terms of the individual components of MACE, both trial analyses reduced the risk of myocardial infarction cardiovascular death but only GLP-1 receptor agonist reduced the risk of stroke. In contrast, as SGLT-2 inhibitors vastly reduced the risk of hospitalization with heart failure by more than 30%, where there was only a non-significant 7% relative risk reduction with GLP-1 receptor antagonist.                                                 GLP-1 receptor antagonists also reduced the broad kidney composite outcome. However, this effect was mainly driven by reduction macroalbuminuria. When excluding macroalbuminuria we found a non-significant relative risk reduction by 8% and this stands in contrast to a very robust relative risk reduction with SGLT-2 inhibitors of more than 45%. Dr Greg Hundley:             Thomas, you mentioned there was a difference in benefit for those with existing cardiovascular disease versus no-known cardiovascular disease upfront. What do you think the reason for that might be, and then did you have the same number of patients in the non-cardiovascular disease group? Did you have enough events in that group? And finally, do you think we might need to follow that patient population a little bit longer in time, to see those events as they didn't have pre-existing cardiovascular disease? Dr Thomas Zelniker:        These are fantastic points. I personally think it's biologically plausible that both drugs and receptors have the same benefit in both patient population to treatment effect may just require more time to become evident in patients with lower risk. You also mentioned a very good point, we had substantially more events in the patient cohort with ASCVD. Dr Greg Hundley:             Very good. So John, we want to turn to you now. Can you help us put those results of this study in perspective? Can you put this into context for us with other published reports using these particular ages? Dr John McMurray:         Certainly Greg, and I'd like to congratulate Thomas on what very important and very timely meta-analysis because, of course, what Thomas and his colleagues have done Greg, is to put all these studies together, to give us what meta-analysis does, which is much more power to look, for example, at components of composite outcomes, and we will in that way compare and contrast the differences and similarities between these two treatments. And as Thomas has mentioned, so interesting differences stand out but there are also some similarities that perhaps were not clear from the individual trials and I suppose the one that would perhaps stand out to me and might not have been realized by many of our readers, is myocardial infarction, that seems to be reduced to pretty much a similar extent by both GLP1 receptor antagonists and SGLT-2 inhibitors.                                                 I think there had perhaps been a view out there from the individual trials, that maybe GLP-1 receptor antagonists have more effect on atherosclerotic events and SGLT-2 inhibitors more effect on heart failure and renal events and to some extent that's true, both agents seem to reduce myocardial infarction to approximately the same extent. Which in itself is interesting, perhaps raises some mechanistic questions. I mean, the differences that stood out is stroke is reduced by GLP-1 receptor antagonists but not by SGLT-2 inhibitors and conversely heart failure which is the opposite, which is by SGLT-2 inhibitors, but not by GLP-1 receptor antagonists in this meta-analysis.                                                 So, I suppose, in summary what this tells us is that these drugs have complementary, perhaps additive cardiovascular benefits. Together, they potentially reduce the whole spectrum of the adverse cardiovascular events that occur in our patients with Type 2 diabetes, especially those who've got established cardiovascular disease. Dr Greg Hundley:             And so, just a last question here, for both Thomas and John, if you're considering in your practice, you have a diabetic patient that's not on these, one of these agents, and they have existing cardiovascular disease, how do you go about considering the addition or the switch to this type of medicine, and what practices do you use to effect that change? Dr Thomas Zelniker:        I guess, looking at patients, so we know that both drug classes have great benefits from MACE, right, but to people on antagonists having also reductions in stroke. So probably the associated risk is in the focus, I would probably rather go with the GLP-1 receptor antagonist. While looking at it from the heart failure perspective, or from the renal perspective, we see obviously bigger advantages attributed to inhibitors. Dr Greg Hundley:             And John, how about you? Dr John McMurray:         I would agree with Thomas' perspective, although I might add just a little caveat which is, of course, that the prevention of heart failure which is what, I think, the clear benefit of SGLT-2 inhibitors is, prevention of heart failure is different to the treatment of heart failure. So, patients at risk of heart failure sadly, an SGLT-2 inhibitor would make sense, but when it comes to patients with established heart failure event, of course we will get that answer because one of the great things about this recent incredible development of new therapies for diabetes, is that now there are now more studies underway including remarkable five trials in patients with different heart failure phenotypes, patients hospitalized, patients in the community, so we will learn a lot more about the use of these drugs, in particular cardiovascular populations. Dr Greg Hundley:             Excellent. I want to thank both Thomas Zelniker from Brigham and Women's Hospital and John McMurray, guest editor from Glasgow, Scotland for helping us work through this just fantastic meta-analysis study pointing us in a new direction for utilizing medications to treat diabetes and those that we see every day, with cardiovascular disease.                                                 On behalf of Carolyn and myself, have a great week and we look forward to seeing you, next week. Dr Carolyn Lam:                This program is copyright American Heart Association, 2019.  

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

DVN005 Limited Edition of 100 Mastered by: Eric Trude released December 29, 2018 C24

Troisième et dernière partie du récit de voyage à New-York, avec un petit tour dans les galeries qui m'ont le plus marqué dans le Gallery District de Chelsea :  La Gagosian Gallery accueillait "Play", une installation de Urs Fischer chorégraphiée par Madeleine Hollander La Crossing Art Gallery présentait les travaux autour des logos de multinationales par Vandana Jain La galerie C24 montrait un ensemble d'oeuvres mixant sculpture et vidéo de l'artiste Katja Lohet A la galerie Unix Gallery, l'étonnante installation "To the victor belongs the spoils" de Jonathan Paul

Salut tout le monde. Voici le 14ème épisode: C24 – jour 13. Retrouvez C24 sur podCloud (suite…)

Salut tout le monde. Voici le 14ème épisode: C24 – jour 13. Retrouvez C24 sur podCloud (suite…)

Coucou tout le monde. Rien que pour vous, voici C24 – jour 5. J’ai eu beaucoup de mal à trouver une musique de fond qui me plaisait, mais grâce à Richoult, qui m’a donné quelques liens, j’ai pu en trouver une. J’aimerais savoir si le format d’épisode court vous plait. J’ai commencé à prendre de l’avance sur le montage des épisodes, comme ça, quand j’aurai fini de tout monter, je pourrai prendre de l’avance sur mon prochain projet. N’hésitez pas à laisser un petit commentaire, pour me dire ce que vous pensez de l’épisode, ou même pour me lancer des petits défis^^ La musique utilisée libre de droit dans cet épisode est: Kevin_MacLeod_-_03_-_Impact_Moderato C24 - Jour 5 844 téléchargements – 4 MB Découvrir cette saga mp3. Sur ce, bonne écoute et à la prochaine.

Coucou tout le monde. Rien que pour vous, voici C24 – jour 5. J’ai eu beaucoup de mal à trouver une musique de fond qui me plaisait, mais grâce à Richoult, qui m’a donné quelques liens, j’ai pu en trouver une. J’aimerais savoir si le format d’épisode court vous plait. J’ai commencé à prendre de l’avance sur le montage des épisodes, comme ça, quand j’aurai fini de tout monter, je pourrai prendre de l’avance sur mon prochain projet. N’hésitez pas à laisser un petit commentaire, pour me dire ce que vous pensez de l’épisode, ou même pour me lancer des petits défis^^ La musique utilisée libre de droit dans cet épisode est: Kevin_MacLeod_-_03_-_Impact_Moderato C24 - Jour 5 ( 4 MB) Cliquez pour télécharger - 1015 téléchargements Découvrir cette saga mp3. Sur ce, bonne écoute et à la prochaine.

Coucou tout le monde. Après moult péripéties comme les révisions de mes partiels et mon casque qui a rendu l’âme, j’ai enfin réussi à sortir cet épisode à peu prêt dans les temps. (^_^) Pour votre plus grand plaisir, voici C24 – jour 4, où comme vous allez l’entendre certaines choses vont commencer à bouger. Plus le temps passe et plus j’essaie de mettre des indices vous permettant de découvrir le secret de l’île, en travaillant sur le sound-design. N’hésitez pas à laisser un petit commentaire, pour me dire ce que vous pensez de l’épisode, ou même pour me lancer des petits défis^^ La musique utilisée libre de droit dans cet épisode est: Jump In Infinity de l’album The Signals par Sergey Cheremisinov. C24 - Jour 4 519 téléchargements – 5 MB Découvrir cette saga mp3. Sur ce, bonne écoute et à la prochaine.

Coucou tout le monde. Après moult péripéties comme les révisions de mes partiels et mon casque qui a rendu l’âme, j’ai enfin réussi à sortir cet épisode à peu prêt dans les temps. (^_^) Pour votre plus grand plaisir, voici C24 – jour 4, où comme vous allez l’entendre certaines choses vont commencer à bouger. Plus le temps passe et plus j’essaie de mettre des indices vous permettant de découvrir le secret de l’île, en travaillant sur le sound-design. N’hésitez pas à laisser un petit commentaire, pour me dire ce que vous pensez de l’épisode, ou même pour me lancer des petits défis^^ La musique utilisée libre de droit dans cet épisode est: Jump In Infinity de l’album The Signals par Sergey Cheremisinov. C24 - Jour 4 ( 5 MB) Cliquez pour télécharger - 688 téléchargements Découvrir cette saga mp3. Sur ce, bonne écoute et à la prochaine.

Coucou tout le monde. Je vous souhaite à tous une très bonne année et que celle-ci soit riche en nouvelles sagas MP3 à écouter. De mon côté, 2017 s’annonce fort remplie, que ce soit en termes de création ou côté personnel. Après un peu plus de 15 jours d’attente, voici le jour 3 de C24. Une fois encore, j’ai essayé d’innover au niveau du sound-design pour que cela soit le plus agréable possible. N’hésitez pas à laisser un petit commentaire, pour me dire ce que vous pensez de l’épisode, ou même pour me lancer des petits défis^^ La musique utilisée libre de droit dans cet épisode est: Magic Forest de Kevin MacLeod. Sur ceux, bonne écoute et à la prochaine. C24 - Jour 3 ( 5 MB) Cliquez pour télécharger - 693 téléchargements

Coucou tout le monde. Je vous souhaite à tous une très bonne année et que celle-ci soit riche en nouvelles sagas MP3 à écouter. De mon côté, 2017 s’annonce fort remplie, que ce soit en termes de création ou côté personnel. Après un peu plus de 15 jours d’attente, voici le jour 3 de C24. Une fois encore, j’ai essayé d’innover au niveau du sound-design pour que cela soit le plus agréable possible. N’hésitez pas à laisser un petit commentaire, pour me dire ce que vous pensez de l’épisode, ou même pour me lancer des petits défis^^ La musique utilisée libre de droit dans cet épisode est:Magic Forest de Kevin MacLeod. Sur ceux, bonne écoute et à la prochaine. C24 - Jour 3 539 téléchargements – 5 MB

Bonjour tout le monde, c’est Villimar ! Je suis heureux de vous présenter, après avoir essayé de prendre en compte tous vos conseils; C24 – jour 2. Pour cela, pour la première fois, j’ai essayé de customiser les bruitages et de faire beaucoup plus d’efforts sur le sound-design. Grace à cela, je trouve que j’ai fait des progrès dans la maîtrise de Cubase et j’espère que ça se verra. Tous vos retours sur les précédents épisodes m’ont fait extrêmement plaisir Bonne écoute et au prochain épisode C24 - Jour 2 572 téléchargements – 5 MB

Bonjour tout le monde, c’est Villimar ! Je suis heureux de vous présenter, après avoir essayé de prendre en compte tous vos conseils; C24 – jour 2. Pour cela, pour la première fois, j’ai essayé de customiser les bruitages et de faire beaucoup plus d’efforts sur le sound-design. Grace à cela, je trouve que j’ai fait des progrès dans la maîtrise de Cubase et j’espère que ça se verra. Tous vos retours sur les précédents épisodes m’ont fait extrêmement plaisir Bonne écoute et au prochain épisode C24 - Jour 2 ( 5 MB) Cliquez pour télécharger - 759 téléchargements

Coucou tout le monde, c’est Villimar, et aujourd’hui je vous présente  jour 1 de C24. Dans ce deuxième épisode, vous allez découvrir le premier jour de survie pour Marianne en milieu hostile. C’est aussi à partir de cet épisode, où l’histoire vous sera contée uniquement à travers son journal de bord tel un podcast. Remerciement à nouveau pour Kanon. En attendant le “jour 2” de C24 qui sortira dans 15 jours, je vous laisse le champs libre pour poster en commentaire vos théories et vos critiques sur ma saga Pour vous aider, j’ai laissé quelques indices que vous pourrez trouver au fil des épisodes. Sur ce, bonne écoute. C24 - Jour 1 817 téléchargements – 4 MB

Coucou tout le monde, c’est Villimar, et aujourd’hui je vous présente  jour 1 de C24. Dans ce deuxième épisode, vous allez découvrir le premier jour de survie pour Marianne en milieu hostile. C’est aussi à partir de cet épisode, où l’histoire vous sera contée uniquement à travers son journal de bord tel un podcast. Remerciement à nouveau pour Kanon. En attendant le “jour 2” de C24 qui sortira dans 15 jours, je vous laisse le champs libre pour poster en commentaire vos théories et vos critiques sur ma saga Pour vous aider, j’ai laissé quelques indices que vous pourrez trouver au fil des épisodes. Sur ce, bonne écoute. C24 - Jour 1 ( 4 MB) Cliquez pour télécharger - 1024 téléchargements

Épisode 006 – Émission du 13 octobre 2015 Au menu cette semaine : Retour sur l’affaire Mike Ward et Jérémie Gabriel (attention langage vulgaire inclus). Je ne parlerais pas du débat des chefs. Pourquoi l’opposition à la loi C24 est de la pure hypocrisie. La toune de la semaine : The Heavy, “Short Change Hero”. Bonne écoute [...]

Phytosterole, die Sterole von Pflanzen, unterscheiden sich von Cholesterol nur durch eine Alkylsubstitution an C24 und eventuell eine Doppelbindung in der Sterol-seitenkette. Trotz vergleichbarer Zufuhr von 200 - 600 mg/d und der großen strukturellen Ähnlichkeit werden von Phytosterolen nur 0,6 - 7%, von Cholesterol jedoch etwa 60% systemisch absorbiert. Phytosterole senken in hohen Dosen (> 2g/d) die Cholesterolabsorption um etwa 30% und die LDL-Cholesterol-Spiegel um bis zu 15% und werden deshalb zunehmend in „funktionellen Lebensmitteln“ vermarktet. Als Mechanismus wurde lange eine rein luminale, physico-chemische Interferenz mit der mizellären Emulgierung von Cholesterol postuliert. Spätestens seit der molekularen Aufklärung der Phytosterolspeicherkrankheit Sitosterolämie als dysfunktionelle Mutationen der apikalen Steroltansportproteine ABCG5/G8 stand fest, dass Phytosterole sehr wohl in Enterozyten aufgenommen, aber durch ABCG5/G8 effektiv ins Darmlumen resezerniert werden. Da ABCG5/8 auch Cholesterol transportieren kann, blieb die intestinale Sterol-Selektivität und -Interaktion weiterhin unklar. In allen Zellen wird ein Cholesterolüberschuss über bestimmte Oxycholesterole signalisiert, die den nukleären Transkriptionsfaktor LXRα aktivieren und so u.a. die Expression des zellulären Cholesterolexporters ABCA1 stimulieren. Dies ließ eine Rolle von Oxycholesterolen oder analogen regulatorischen Oxyphytosterolen bei der enterozytären Sterol-Interaktion und -Selektivität vermuten. Deshalb wurde am humanen Enterozytenmodell Caco-2 das Handling und die Metabolisierung von Phytosterolen und Cholesterol allein und in Kombination verglichen. Sitosterol wurde eindeutig, wenn auch langsamer als Cholesterol, von Enteroyzten akkumuliert, reduzierte aber bei Kombination die Cholesterolabsorption. Dies war teilweise durch Hemmung der apikalen Aufnahme, aber überwiegend der basolateralen Cholesterolsekretion bedingt, unabhängig von der Mizellenbildung, und nicht durch Sättigung einer limitierten Transportkapazität erklärbar. Im humanen Enterozyten und vergleichend in Hepatozyten und Makrophagen wurde deshalb nach potentiell regulatorischen Oxysterolen gesucht. Aus allen Sterolen wurden in diesen Zellen nur die 27-Hydroxy- und 27-Carboxy-Metaboliten gebildet, andere LXR-agonistische Oxysterole waren nicht nachweisbar. Der Umsatz war für Sitosterol und Campesterol abhängig von der Länge der C24-Alkylsubstitution deutlich geringer als für Cholesterol. In Ko-Inkubationen hemmten Phytosterole konzentrations- und C24-alkyl-abhängig die Bildung von 27-OH-Cholesterol. Diese kompetitive Hemmung und die geringe 27-Hydroxylierung von Phytosterolen selbst wurde auch in Präparationen des katalysierenden Enzyms, der an der inneren Mitochondrienwand lokalisierten Cytochrom P450 Oxidase CYP27, direkt gezeigt. Die Bioaktivität der 27-OH-Sterole als LXRα-Agonisten wurde direkt im LXRE-Transaktivierungs-Assay nachgewiesen und die stimulierte Expression von CYP27 und des in Enterozyten nur basolateral lokalisierten Cholesteroltransporters ABCA1 gezeigt. Dementsprechend steigerte 27-OH-Cholesterol auch selektiv die basolaterale, systemische Cholesterolsekretion, während der apikal exprimierte Sterolexporter ABCG8 und die apikale Sterolresekretion unverändert blieben. Umgekehrt hob in Ko- Inkubationen mit Phytosterolen die exogene Substitution eines synthetischen LXRα- Agonisten als Ersatz für das reduzierte endogene 27-OH-Cholesterol die Hemmung der Cholesterolabsorption durch Phytosterole komplett auf und überfuhr die Sterolselektivität. Auch in Tracer-Experimenten mit nanomolaren Phytosterol- und Cholesterolkonzentrationen, die die Aktivierung von LXRα nicht beeinflussen können, konnte keine direkte Sterolselektivität der ABCG5/8 und ABCA1-Transporter nachgewiesen werden. Neben physico-chemischen mizellären Effekten und der allenfalls limitierten direkten Cholesterolpräferenz der Steroltransporter NPC1L1, ABCG5/G8 und ABCA1 wurde für ACAT2, die apikal einströmendes Cholesterol zu >35% verestert und in die ApoBabhängige basolaterale Chylomikronensekretion einschleust, bereits eine relative Sterolselektivität beschrieben. Bei den eigenen Untersuchungen wurde ein neuer Mechanismus auf der regulatorischen Ebene der LXRα-Aktivierung im Enterozyten gefunden: Im Zentrum steht die kompetitive Hemmung des „Cholesterol-Sensors“ CYP27 durch Phytosterole und die nur geringe 27-Hydroxylierung der Phytosterole selbst. Dadurch wird bei gleichzeitigem Einstrom von Phytosterolen und Cholesterol in Enterozyten die Bildung des dominierenden LXRα-Agonisten 27-OH-Cholesterol verhindert. Normaler-weise vermittelt dies über LXR-Aktivierung und Induktion von CYP27, LXRα und ABCA1 eine selbstinduzierbare Komponente der Cholesterolabsorption auf dem ApoA-abhängigen Weg. Der lokale LXRα-Antagonismus von Phytosterolen blockt diese Selbstbahnung, lenkt Cholesterol vermehrt um zur luminalen Resekretion durch die konstitutiv apikal exprimierten ABCG5/8 und trägt auch zur Sterolselektivität bei. In peripheren Makrophagen könnten Phytosterole über Hemmung von CYP27, LXRα und ABCA1 durch Sterol-„Trapping“ die frühe Atherosklerose trotz eher niedriger Cholesterolspiegel bei Sitosterolämie erklären. Ob auch bei ABCG5/G8-Gesunden die unter pharmakologischen Phytosteroldosen erhöhten Plasmaspiegel langfristig zur Phytosterol- und paradoxen Cholesterol-Akkumulation in peripheren Zellen führen können, ist gegenwärtig unklar.

ATP synthase is one of the major photosynthetic complexes that represents one of the smallest molecular motors known in nature. The rotating γ subunit is a key feature of this enzyme. It contains features specific for the chloroplast ATP synthase. In this work the γ subunit has been functionally analyzed in Arabidopsis thaliana. - The nuclear gene atpC1 encoding the γ subunit of the plastid ATP synthase has been inactivated by T-DNA insertion mutagenesis. In the seedling-lethal dpa1 mutant the absence of detectable amounts of the γ subunit destabilizes the entire ATP synthase complex and consequently photophosphorylation is abolished. However, in vivo protein labelling analysis suggests that assemαβ bly of the ATP synthase and subunits into the thylakoid membrane still occurs in dpa1. Further effects of the mutation include an increased light sensitivity of the plants and an altered photosystem II activity. A high non-photochemical quenching develops with increasing actinic light intensity. It has been shown that a high proton gradient is responsible for most quenching (qE). The photoprotective role of qE was further demonstrated in the double mutant dpa1 x psbS in which PsbS, essential factor for qE, is missing. - The expression of a second gene copy, atpC2, is unaltered in dpa1 and is not sufficient to compensate for the lack of atpC1 expression. The two proteins, AtpC1 and AtpC2, share less similarity than AtpC1 of Arabidopsis with γ subunits of other plant species suggesting that the γ subunits so far isolated in other plant species are AtpC1 orthologs. It has been established that AtpC2 is also imported into the chloroplast. Therefore, it is likely that the chloroplast ATP synthase complexes contain both atpC1 and atpC2 encoded γ subunits. However, the atpC2 gene is expressed more than hundred times at a lower level than atpC1 and array data show the differential and tissue specific expression of the two genes. The function of AtpC2 could not be revealed by inactivating the gene. Overexpression of atpC2 in dpa1 generated viable lines with an ATP synthase complex containing only γ2, although wild type phenotype is not completely restored. The second part of this work regarded the optimization of conditions for plastid transformation in Arabidopsis thaliana. An efficient and fast regeneration system from cotyledon protoplasts was established for Arabidopsis thaliana accessions C24, Columbia, and Wassilewskija. Culture conditions and media compositions were optimized for the development of protoplasts embedded in thin alginate layers. The protocol is reproducible, efficient, extremely fast, and regenerated plants are fertile. Thus, this cotyledon-based system could prove useful for studying plant cell and molecular biology in A. thaliana. - The sul gene appeared to be a potential novel candidate as selectable marker for plastid transformation. However, genetic and molecular studies demonstrated that sul can not be used for this purpose. On the other hand a new function of sul appeared. The gene could be the missing marker for mitochondria transformation in higher plants.