Podcasts about SMAD

The 2 Gordons welcome you as always to a mix of whisky fun, fact, and features.  Their irregular section entitled, An Insider's Guide this week stars John McElwee who has been taking tourists around Scotland for over 25 years and now specializes in whisky tourism.  The best distillery tours, the most interesting spots to drink a dram and his favourite tipple are just some of the areas covered in a fascinating insight to one of the great whisky jobs out there.  The 2 Gordon's talk about the Campbletown and Feis Isle Festivals while looking at some of the other great whisky festivals of the world.   Anders Nostrom chairman of SMAD one of Swedens largest whisky clubs explains just how long it takes to pour for 170 guests in Borlange!  And there's just time to play the legendary game You Have Arrived at Your Whisky Destination!   It is a whisky show but not as you know it!  Slainte`

Tenis, ciclismo y fútbol playa en ascenso. En Cúcuta se disputó la Billie Jean King Cup, tras una semana de competición, Argentina y Colombia consiguieron su clasificación al play off del Grupo Mundial. Emiliana Arango, María Fernanda Herazo, Yuliana Lizarazu y María Paulina Pérez fueron responsables para que el país acuda a la siguiente fase en el mes de noviembre. Por otro lado, Jhonatan Restrepo fue campeón del Giro della Città Metropolitana di Reggio Calabria, con esta victoria, el colombiano consiguió su séptimo triunfo en su carrera profesional. La Selección Colombia de Fútbol Playa quedó campeona del Acapulco Beach Soccer Cup 2023 (Cuadrangular amistoso). No obstante, el descenso se presentó dentro del FPC. El partido entre Atlético Nacional y América de Cali fue reprogramado debido a los disturbios provocados por la barra brava 'Los Del Sur' y a los que intervino el SMAD. La información deportiva colombiana y del exterior aquí en Tono Deportivo, ¡bienvenidos!

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.25.530017v1?rss=1 Authors: Lee, H., Aylward, A. J., Pearse, R. V., Hsieh, Y.-C., Augur, Z. M., Benoit, C. R., Chou, V., Knupp, A., Pan, C., Goberdhan, S., Duong, D. M., Seyfried, N. T., Bennett, D. A., Klein, H.-U., De Jager, P. L., Menon, V., Young, J. E., Young-Pearse, T. L. Abstract: SORL1 is strongly implicated in the pathogenesis of Alzheimer's disease (AD) through human genetic studies that point to an association of reduced SORL1 levels with higher risk for AD. To interrogate the role(s) of SORL1 in human brain cells, SORL1 null iPSCs were generated, followed by differentiation to neuron, astrocyte, microglia, and endothelial cell fates. Loss of SORL1 led to alterations in both overlapping and distinct pathways across cell types, with the greatest effects in neurons and astrocytes. Intriguingly, SORL1 loss led to a dramatic neuron-specific reduction in APOE levels. Further, analyses of iPSCs derived from a human aging cohort revealed a neuron-specific linear correlation between SORL1 and APOE RNA and protein levels, a finding validated in human post-mortem brain. Pathway analysis implicated intracellular transport pathways and TGF{beta}/SMAD signaling in the function of SORL1 in neurons. In accord, enhancement of retromer-mediated trafficking and autophagy rescued elevated phospho-tau observed in SORL1 null neurons but did not rescue APOE levels, suggesting that these phenotypes are separable. Stimulation and inhibition of SMAD signaling modulated APOE RNA levels in a SORL1-dependent manner. These studies provide a mechanistic link between two of the strongest genetic risk factors for AD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

#Lutherhiersteheich #Hauptstadtinsider #JanPeterLuther #DNEWS24 #DDR #SED #Blockparteien #Blockflöten Vor 33 Jahren bekam die Mauer Löcher. Das Ende der SED-Diktatur in der DDR wurde eingeläutet. Plötzlich traten CDU, LDPD, NDPD und die DBD, von den Bürgern als "Block-Flöten" verspottet, in das Licht der Öffentlichkeit. Diese Parteien hatten gemeinsam mit der SED, die aus der Fusion von KPD und SPD entstanden war, den von der SMAD vorgeschriebenen "Antifaschistisch-demokratischen Block", zu dem auch der Gewerkschaftsbund FDGB und die FDJ gehörten, gebildet. Welche Rolle spielte das Mehr-Parteien-System in der DDR? Hauptstadt-Insider Jan Peter Luther im DNEWSTV24-Podcast „Luther – hier stehe ich!“. DNEWS24 Den Hauptstadtinsider "Luther - hier stehe ich!" – überall, wo es gute Podcasts zu hören gibt. #Hauptstadtinsider

Great blog post from @Mike Mattera at @Akamai! That diagram.. @greeningofstreaming Great blog post from @Mike Mattera at @Akamai! That diagram.. @greeningofstreaming

In this week's episode we'll learn more about salvage therapy with nivolumab plus or minus ICE (or NICE) for Hodgkin lymphoma, discuss the role of BMP2/SMAD pathway activation in leukemic transformation, and learn more about the role of zinc in T-cell reconstitution after transplantation.

Have you ever felt scared? I sure have. It can be really hard to feel scared feelings, and it can be confusing, too. Like, I know I'm scared of falling into quicksand, and being turned into a bagel (again), and I'm definitely afraid of being chased by Australian crocodiles! But I can feel scared even when none of those things are actually happening.  Sometimes I get scared just imagining scary things. I worry about things that might happen, and then I start thinking about how unfair it would be if they did happen, and then I get upset because those things shouldn't happen but I don't know how to keep them from happening, and then my face gets hot and my breathing gets fast, and then I feel really SMAD—scared and mad!In today's special episode, Vac and I are both feeling SMAD. But we talk through it together and that helps us feel a little better. Promising to be kind to each other and to all of our friends in the Neighborhood helps us feel a little better, too. If you're feeling scared or SMAD or any other big feelings, I hope you'll talk to a trusted grown-up about them. And I hope you know how much Vac and I—and everyone in the Neighborhood—cares about you and wants you to feel safe. We love you. So much.Scotty

FEATURED GUESTS: Leah Guzman, ATR-BC supports creatives with healing and manifesting their desires utilizing art media through art therapy services and coaching. She's written 3 art therapy books, “The Art of Healing and Manifesting: Creative Exercises to Living an Abundant Life, “Essential Art Therapy Exercises: Effective Techniques to Manage Anxiety, Depression, and PTSD”, and a children's book, “RAD is SMAD!!” . Her signature program, Art of Healing and Manifesting, supports creatives by healing any emotional wounds and transforming energy to be your most authentic self. She focuses on the law of attraction, spirituality, and cognitive-behavioral art therapy techniques. She also is the founder of the monthly art making group, Creative Soul Society. It's an honor for her to have helped thousands of individuals find more joy, wealth, and peace in their lives through her books, and individual & group programs. LISTEN & LEARN: How Leah uses the Chakras to organize the creative process of manifesting. What is manifesting and how it relates to healing. The importance of intentional design in life and in product creation. The role of consistent showing up in building your creative offering as a practitioner. RESOURCES MENTIONED ON THE SHOW: www.leahguzman.com hello@leahguzman.com Free Visualization offering https://leahguzman.com/true-you-visualization-opt-in Creative Soul Online Retreat Facebook Group The Art of Healing and Manifesting: Creative Exercises to Living an Abundant Life, Essential Art Therapy Exercises: Effective Techniques to Manage Anxiety, Depression, and PTSD RAD is SMAD!!

Leah Guzman is a Board-Certified Art Therapist who has written three books on art therapy: (1) “The Art of Healing and Manifesting: Creative Exercises to Living an Abundant Life, (2) “Essential Art Therapy Exercises: Effective Techniques to Manage Anxiety, Depression, and PTSD”, and a children's book, (3) “RAD is SMAD!!” You can find these books here: (1): https://leahguzman.com/the-art-of-healing-and-manifesting-book-and-oracle-deck (2):https://www.amazon.com/gp/product/B08589QCTM/ref=dbs_a_def_rwt_hsch_vapi_tkin_p1_i0 (3): https://www.amazon.com/Rad-Smad-Leah-Guzman/dp/1564923827 Join us as we discuss art therapy and the courses Leah offers. Leah's website: https://leahguzman.com/Note: Information contained in this video is for educational purposes only and is not intended as a substitute for treatment or consultation with a mental health professional or business consultant.

I'm Back ! I apologize for my absence but I seriously needed to take some time to myself . I'm good and well as well as everyone around me . I want to thank you all for sticking w/me as I go on this journey of healing and getting my mental health together . Joining me today is Karina x Erica . They are the hosts of Single Moms After Dark - The Podcast ( Coming Soon ) . In todays episode , the ladies of SMAD talk to us about their up and coming podcast as well as some of the positive and negative effects that they endure from being single mothers ! ✨ Coffee & Apple Juice - The Podcast ✨ Coffee & Apple Juice - The Podcast Consist Of Adult Discussions About Issues Known To Grown Folks ! Your Hosts , Aisha Hadiya Share Her Views & Opinions On Topics Surrounding The Culture . . . ☕️ buymeacoffee.com/CAJPodcast ☕️

ما تيسر من سورة المطففين - تجويد عالي الجودة - عبر الباسط عبد الصمد - نفس طويل - Surah Al-mutafifin - Al-moutaffifin - Abdul basit Abdul Smad - Long Breath Meditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sportMeditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sport

ما تيسر من سورة عبس - تجويد عالي الجودة - عبر الباسط عبد الصمد - نفس طويل - Surah Abasa - Abdul basit Abdul Smad - Long Breath Meditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sportMeditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sport

سورة الغاشية - تجويد عالي الجودة - عبد الباسط عبد الصمد - نفس طويل Beautiful recitation of Surah alghashiya - al ghashiya - al ghachiya - Abdul basit Abdul Smad - Long Breath Meditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sportMeditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sport

سورة الطارق - تجويد عالي الجودة - عبد الباسط عبد الصمد - نفس طويل Beautiful recitation of Surah Attarik - Attariq _ at-taqriq - Abdul basit Abdul Smad - Long Breath Meditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sportMeditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sport

سورة الغاشية - تجويد عالي الجودة - عبد الباسط عبد الصمد - نفس طويل Beautiful recitation of Surah alghashiya - al ghashiya - al ghachiya - Abdul basit Abdul Smad - Long Breath Meditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sportMeditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sport

ما تيسر من سورة القيامة - تجويد عالي الجودة - عبر الباسط عبد الصمد - نفس طويل - Surah alqiyama - Abdul basit Abdul Smad - Long Breath Meditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sportMeditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sport

ما تيسر من سورة النبأ - تجويد عالي الجودة - عبر الباسط عبد الصمد - نفس طويل - Surah Annabaa - Abdul basit Abdul Smad - Long Breath Meditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sportMeditation, Relaxation, life balance, good life, Islam, peace, chill, chill out. decompress, de-stress, loosen up, mellow (out), unwind, mental health treatment, reduce stress, thereby improving health conditions, Inner peace, How to organize, Breathing dalliance, frolic, frolicking, recreation, fun, play, rollicking, mind sport

Episode spécial "chronologie des médias" cette semaine du 7 juillet 2021 avec la mise en application à partir du 1er juillet de la directive SMAD. On y cmmente égalment le film sud-africain "Moffie", de Oliver Hermanus. Une très bonne semaine à tous !

Au programme de ce 62ème épisode de Netflixers, le podcast francophone dédié à Netflix et à la SVOD en général : 00:02:17 : Actus du secteur SVOD français et mondial. On revient sur l'achat par Amazon d'un lot de football qui va avoir des répercussions sur le secteur audiovisuel français, sur la nouvelle boutique de Netflix, le festival de Cannes et la publication du décret SMAD et ce qu'elle signifie pour le futur et la nouvelle chronologie des médias mais aussi les renouvellements, annulations et renouvannulations du mois chez Netflix ainsi qu'une sélection des meilleurs projets annoncés chez Netflix. 01:11:43 : Nos recommandations de juin : On y parle de "Skater girl", "Carnaval", "Awake", "Good on Paper", "Un papa hors pair", "This is Pop" (s1), "Le Cap des Manchots" (S1), "Trois soeurs dans les starting blocks", "Three identical strangers", "Lupin" (P2), "Katla" (s1), "Ca croustille", "The Handmaid's tale" (finale S4), "Hannah Montana" (S1), "Loki" (S1), "Luca", "Love death and robots" (S2), "The Wilds", "Mixte", "Frontière verte", "Scrubs" ainsi que vos recos. 02:11:50 : Sur Netflix France en juillet 2021. Gros tour d'horizon des ajouts tiers et Originals annoncés sur Netflix France le mois prochain. Vous pouvez retrouver cette liste mise à jour dans cet article : https://medium.com/le-futur-de-la-distribution-de-films-en-france/tous-les-ajouts-netflix-originals-de-2021-sur-netflix-france-31060028ca25 Pour vous les Netflixos : Le devoir du mois prochain choisi par Nivrae est "Le guide de la famille parfaite" qui sera dispo le 14 juillet. N'hésitez pas à nous donner votre avis dessus en nous mentionnant sur Twitter @filmsdelover, ou sur le Discord de l'émission dont l'adresse est ci-dessous. Nous avons un Discord avec toutes les dernières infos sur Netflix, des conversations, des débats sur Netflix mais aussi sur les autres services SVOD dispos en France : https://discord.gg/N4Vmd5n (Merci Kris_Mery de l'administrer et de l'avoir créé) Intermèdes audio :"Ruby, tombée du nid" dispo en novembre / "Skater girl", dispo / "Outer banks" (S2) dispo le 30 juillet. Intervenants : Hélène (https://www.twitter.com/nivrae) Damien (https://www.twitter.com/Damien_srsly) Présenté par Frédéric (https://www.twitter.com/filmsdelover).

EPISODE 35 | A Field Guide to Aliens For images and many videos, check this episode and its dedicated playlist on our YouTube channel. "The aliens" are not one group, but many, often with competing goals and motivations. Starting back in 1946, the Russians compiled a handbook for elite KGB and SMERSH agents on 58 separate alien races that visit our planet. Some are nice and some are not very nice at all. They all seem to think the Earth is a special place, however, even if many of them really just couldn't care less about us humans at all. Or so says an internet marketing guy who "found" a copy of this book and claims it's all real, including pictures of the aliens taken from movies and video games. One thing's for sure - it's a helluva story. SECTIONS 03:26 - Gil Carlson markets to the masses 05:01 - Background on the handbook, Dante Santori translates/writes it 09:10 - Origin Story - The Anunnaki made humans, helped by the Kurs and Zeta Reticulans, then the Reptilians messed everything up 14:29 - Nice Guy Aliens - Grays, Nordics and others 15:05 - "Grays" - Solipsi Rai, Afim ("Afim Spiantsy"), Akart, Jefok ("The Peacekeepers"), Moovianthan-Kayphik("The Shining Ones") 19:30 - "Nordics" - Pleyadiyans, 2017 20:43 - The Council of Five - El-Manouk; Orela, Ginvo, Egarot, Redan & Emerther 22:30 - "Humanoids" - Graysli, Ramay, Smad, Vinnytvary 24:21 - "Reptoids" - Tengri-Tengri, Tisar-3 26:00 - Boo-Hiss: The Bad Guys - Not just Reptilians 26:19 - The Reptilians - The intergalactic villains 28:13 - The Maitre Alliance - Maitre, X5-Tykut, Mazarek, Jighantik, Kyllimir-Auk 31:02 - Other Jerk Aliens - Alcohbata, Caraveldi, Dorsay, Dries, Indugutk ("Tall White"), Kiily-Tokurt, Hav-Hannuae-Kondras (intergalactic vampires), Lang ("fairies"), Negumak ("Gnomopo"), Tanzany 38:02 - A Message for Us - The Ramay & Jefok have told us about the creator ("She"), the First Race, interstellar feminism 40:48 - Weird Tidbits from Aliens - Unified Field Theory, the Philadelphia Experiment, Area 51 43:44 - The Earth is special, humans may or may not be (but we are pretty weird) 45:41 - Go Forth and Create a Media Empire Music by Fanette Ronjat More on this stuff: Blue Planet Project (good one) Blue Planet Project (alien one) Books by Gil Carlson Book of Alien Races: Secret Russian KGB Book of Alien Races Book of Alien Races online Mass Effect alien races Saddam's Stargate and Taskforce 20 episode The Lucifer Project(s) - Big Scary in Sky! episode Magic Carpet Ride - UFOs & the New Age episode Harvesters from "Independence Day" Truth Control alien forums Follow us on social for extra goodies: Facebook (including upcoming conspiracy-themed events) Twitter YouTube (extra videos on the topic, Old Time Radio shows, music playlists and more) Other Podcasts by Derek DeWitt DIGITAL SIGNAGE DONE RIGHT - Winner of 2021 AVA Digital Award Gold & 2020 Communicator Award of Excellence for Podcasts and on numerous top 10 podcast lists.  PRAGUE TIMES - A city is more than just a location - it's a kaleidoscope of history, places, people and trends. This podcast looks at Prague, in the center of Europe, from a number of perspectives, including what it is now, what is has been and where it's going. It's Prague THEN, Prague NOW, Prague LATER.

Tras el paro nacional ya con un mes en Colombia, se muestra una evidente violencia y desobediencia al no cumplir el decreto de no ingresar a los barrios la orden era liberar las calles principales si embargo se evidenció lo contrario --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app

Las jornadas de movilización continúan en Cali. Este domingo los puntos de protesta que siguen activos en la ciudad fueron escenario de conciertos y encuentros pacíficos, como en Meléndez, donde estuvo RFI. “Buenas noches para toda la comunidad que todos los días nos acompaña en nuestra velatón”, dice una mujer al micrófono: estamos en el punto de resistencia de Meléndez, calificado como uno de los barrios más peligrosos del sur de Cali, epicentro de las protestas. Una nueva velatón (homenaje con velas) convoca esta noche a un grupo de personas, en su mayoría jóvenes, que cumplen 19 días en resistencia. Luz, reconocida lideresa de paz de esta esquina de Cali, suma su voz a las de hombres y mujeres que en 20 puntos de levantamiento de esta ciudad se mantienen en pie de lucha, y ellos dicen, de defensa: “Es gracias a ustedes como comunidad, que nos ayudan a cuidarnos”, enfatiza Luz. Las pancartas hablan de los 42 muertos que según la ONG Temblores ha dejado la represión policial, de los cientos de desaparecidos, de las 16 víctimas de agresión sexual. Pero se habla en especial de Alison que, con 17 años, fue detenida arbitrariamente en Popayán por cuatro agentes de la policía antidisturbios –el SMAD, y manoseada frente a las cámaras de testigos. Horas después, Alison, hija paradójicamente de un intendente de la policía, dejó en redes sociales un mensaje con la denuncia y se quitó la vida. “Hasta lloramos de felicidad” Al otro lado de la calle, mujeres se activan para que la olla comunitaria garantice que ninguno de los jóvenes enfrente la noche con el hambre que en su mayoría padecieron gran parte de su vida: “Hasta lloramos de felicidad, de ver cómo tanta gente colaboró para que esta olla comunitaria siguiera en pie”, cuenta una mujer. Con el paso de las horas algunos regresan a sus casas. Chicos y chicas siguen en las barricadas, alrededor de pequeñas fogatas. “¿Para mi qué significa estar en primera línea? Significa sacar la cara por mi país y por mis derechos”, dice un joven, mientras una muchacha explica que lucha “por cada compañero a quien le han apagado la voz”. El próximo miércoles los manifestantes volverán a paralizar la ciudad. Mientras tanto las negociaciones con los representantes del paro están lejos de lograr el desmonte de estos puntos de resistencia. Hay muchos mártires y demasiada desconfianza. Y sobre todo, una juventud unida como nunca antes y decidida a resistir, hasta cambiar la historia.

La réforme de l’audiovisuel qui revient avec un projet de loi, au Parlement, visant à protéger les œuvres du piratage, mais aussi un décret pour obliger les plateformes comme Netflix à investir dans la production française et européenne. Vous vous souvenez peut-être qu’une grande loi sur l’audiovisuel avait été annoncée pour avril 2020, avant d’être abandonnée en raison de la crise sanitaire. Elle revient aujourd’hui avec deux réformes importantes. L’une vise à lutter contre le piratage, l’autre cherche à mieux assurer le financement des œuvres de télévision et de cinéma en demandant à Netflix ou Amazon Prime de consacrer près du quart de leurs revenus en France au soutien à la production dans l’Hexagone. Alors concernant le piratage, il y a deux mesures clés dans le projet de loi qui arrivera la semaine prochaine au Sénat. La première, c’est la fusion du CSA et de l’Hadopi, l’autorité de protection des œuvres, avec la création de l’Autorité de régulation des communications, l’Arcom, pour mieux assurer la protection et la régulation des programmes diffusés. En corollaire, on pourra exiger des fournisseurs d’accès à Internet qu’ils bloquent l’accès à des contenus piratés ou à des retransmissions sportives illicites. Pourront ainsi être bloqués non seulement les plateformes de piratage, mais aussi leurs sites miroirs. En revanche, et cela lui est reproché par une société d’auteurs, la SACD, le gouvernement n’a pas voulu envoyer devant les tribunaux le consommateur pirate multirécidiviste qui pourra se contenter de payer une amende à l’Arcom. Pas question de rallumer une guerre culturelle avec les jeunes comme au moment de la loi Hadopi, en 2009. 85 % du catalogue d’œuvres audiovisuelles à des productions françaises ou européennes Concernant le décret Smad maintenant, sur les services de médias audiovisuels, il est prévu d’imposer des obligations aux géants comme Netflix de soutenir la création française de séries, de films ou de documentaires. Ce sera à hauteur de 20 % du chiffre d’affaires en France de ces plateformes et même de 25 % si elles bénéficient d’une diffusion des films plus tôt par rapport à la sortie en salles. En outre, ces géants devront en principe consacrer 85 % de leur catalogue d’œuvres audiovisuelles à des productions françaises ou européennes. Mais là, la Commission européenne estime que le gouvernement est allé trop loin dans la défense de l’exception culturelle en favorisant un peu trop les sociétés de production françaises et en excluant les producteurs contrôlés par des étrangers. La France, c’est vrai, cherche à protéger son patrimoine audiovisuel : elle va aussi demander une déclaration préalable avant toute cession d’un catalogue d’œuvres à l’étranger. Et certains espèrent qu’elle profitera de sa présidence de l’Union européenne, en 2022, pour promouvoir l’idée d’une autorisation obligatoire si l’on veut céder Studio Canal ou Pathé à un Chinois ou un Américain.

We talk about and the Willowbrook State School and the Beechworth Asylum. He's gross. --- Support this podcast: https://anchor.fm/spookyshit-pod/support

Confira o novo podcast do Núcleo de saúde mental, cognição e comportamento (NEPSI), do curso de Psicologia UFPel. A idealização e locução deste episódio foi realizada pela graduanda em psicologia Eduarda Magalhães em conjunto com os demais extensionistas. Esta ação faz parte do Projeto de Extensão do NEPSI, sob a coordenação geral dos professores Tiago Munhoz e Mateus Levandowski e coordenação acadêmica de Vanessa Marques. Se você gostou desse conteúdo, não se esqueça de compartilhar. Para acompanhar as próximas atividades do NEPSI, acesse nosso site e curta nossa página no Facebook e Instagram. Até o próximo episódio! REFERÊNCIAS Abjaude SAR, Pereira LB, Zanetti MOB, Pereira LRL. How do social media influence mental health? SMAD, Rev Eletrônica Saúde Mental Álcool Drog. 2020;16(1):1-3.doi:https://dx.doi.org/10.11606/issn.1806-6976.smad.2020.0089. MOROMIZATO, Maíra Sandes et al . O Uso de Internet e Redes Sociais e a Relação com Indícios de Ansiedade e Depressão em Estudantes de Medicina. Rev. bras. educ. med., Rio de Janeiro, v. 41, n. 4, p. 497-504, Dec. 2017. Disponível em: . Acesso em 14 Out. 2020. Doi: https://doi.org/10.1590/1981-52712015v41n4rb20160118. SOUZA, Karlla; CUNHA, Mônica. Impactos do uso das redes sociais virtuais na saúde mental dos adolescentes: uma revisão sistemática da literatura. Revista Educação, Psicologia e Interfaces, v. 3, n.3, p. 204-2017, dez. 2019. Doi: https://doi.org/10.37444/issn-2594-5343.v3i3.156 --- Send in a voice message: https://anchor.fm/nepsi-ufpel/message

Cabô é agora! Brunão, GG e Slow vão encerrar a 1ª temporada da nossa série de drogas, dessa vez toda a História, contexto social, química e filosofias da Ayahuasca! Vem com a gente! Tempo de duração: 1h27/min Link do APOIA.SE: https://apoia.se/zicast   Conheça o grupo Ayahuasca Tiuaco: Telefone: (11) 99156-3205 Saiba mais no eBook Uma Colher de Chá do Mestre Tiuaco em: www.agbook.com.br Referências: SANTOS, Rafael Guimarães dos. AYAHUASCA: neuroquímica e farmacologia. SMAD, Rev. Eletrônica Saúde Mental Álcool Drog. (Ed. port.),  Ribeirão Preto ,  v. 3, n. 1, fev.  2007 .    COSTA, Maria Carolina Meres; FIGUEIREDO, Mariana Cecchetto; CAZENAVE, Silvia de O. Santos. Ayahuasca: uma abordagem toxicológica do uso ritualístico. Rev. psiquiatr. clín.,  São Paulo ,  v. 32, n. 6, p. 310-318,  Dec.  2005 .  TROMBONI, Marco. O uso ritual da ayahuasca. Mana,  Rio de Janeiro ,  v. 9, n. 2, p. 211-215,  Oct.  2003 .   Mande sua opinião, xingamento ou correção para nosso e-mail que o e a gente lê mesmo: republicazicast@gmail.com Arte da vitrine: GG REDES SOCIAIS: Twitch: zicast_podcast Youtube: ZiCast Insta: @zicast twitter: @republicazicast Facetruck: /ZiCast Apoia.se: https://apoia.se/zicast See omnystudio.com/listener for privacy information.

In this episode we cover:Why should African-American women know specifically about TNBC?What can AA women do and where can they go to arm themselves with knowledge regarding TNBC?What is the Black Breast Cancer Alliance?The importance of choosing life in every thing that you do!Know your HER story—what's your health issue?Changing your life will require you to let go of your dependencies.What is SMAD?---Sisters Making A Difference. Create your own group of supporters who can share valuable resources with each other.Don't wait till you are told you are going to die to find your purpose. Your peace is non-negotiable. Finding your filter for dealing with stress to get to peace.Ricki Fairley is an 8-year Stage 3A survivor/thriver of TNBC. She is spearheading a movement to address #BlackBreastCancer as a disease that warrants special attention and focus by Pharma. Ricki's personal purpose, passion, mission, ministry and blessing is to raise awareness, fundraise for a cure for breast cancer and support and coach what she calls her “Breastie” sisters through their breast cancer experience. Ricki is building a movement and the Black Breast Cancer Alliance to address Black Breast Cancer as a unique and special disease state, with the overall goal of reducing the mortality rate for Black women. Ricki founded and serves as co-host for “The Doctor Is In,” a weekly live web series on the BlackDoctor.org Facebook page. She serves on the Board of Trustees for the Triple Negative Breast Cancer Foundation where she spearheads the Marketing Committee and directs multicultural outreach. She established a presence for the Foundation in African American targeted media/social media vehicles. She is a board member for the Center for Healthcare Innovation, a non-profit research and educational institute making healthcare more equitable. She also serves as an Ambassador and Advisor for the Live Humanly Campaign and works with companies to provide the patient advocate voice for breast cancer drug development. She serves on the National Accreditation Program for Breast Centers (NAPBC) Advocacy and Outreach Committee, and the CDC Advisory Committee on Breast Cancer in Young Women. She writes regularly for BlackDoctor.org, Black Health Matters, the Cincinnati Herald and the Black Press.Email: rickifairley@gmail.comBrand/Organization Name: DOVE MarketingWebsite: dove.marketingTOUCH, The Black Breast Cancer AllianceFacebook, Twitter, Instagram: @TouchBBCAFacebook: Ricki FairleyTwitter: @rickidove Instagram: @rickidove 

Au programme de ce 53ème épisode de Netflixers, le podcast francophone dédié à Netflix et à la SVOD en général : 00:02 : Actus du secteur SVOD français et mondial. Les suites de l'affaire "Moulanne", de l'affaire "Mignonne", les résultats des Emmy Awards, la possible vente envisagée de Quibi, les petits jeux de lobbys entre Netflix et le gouvernement français sur la question de l'application du décret SMAD, les chamboulements à la tête de Netflix, mais aussi les renouvellements, annulations et renouvannulations du mois chez Netflix ainsi qu'une sélection des meilleurs projets annoncés chez Netflix. 00:45 : Nos recommandations de septembre : On y parle de "Les phénomènes", "Enola Holmes", "Coup de foudre garanti", "Le Diable Tout le temps", "Derrière nos écrans de fumée", "En t'attendant : l'espoir figé", "Julie and the Phantoms", "Aggretsuko : Saison 3", "Sing On! États-Unis", "Chaque chose à sa place avec Clea et Joanna" (Home Edit), "Mission déco : Saison 1", "Sing On! Allemagne", "Mylène Farmer l'Ultime Création", "Je veux juste en finir", "Sons of Anarchy (en cours, S2), "The Boys" (S2), "The Purge" (S2), "Les voyageurs du temps" (S1) 01:56 : Sur Netflix France en octobre 2020. Gros tour d'horizon des ajouts tiers et Originals annoncés sur Netflix France en octobre 2020. Vous pouvez retrouver cette liste mise à jour dans cet article : https://medium.com/le-futur-de-la-distribution-de-films-en-france/tous-les-ajouts-netflix-originals-de-2020-sur-netflix-france-b2912d08b9cb Pour vous les Netflixos : Le devoir du mois prochain choisi par Nivrae est "Pour l'amour de Ginny" qui sera dispo le 9 octobre. N'hésitez pas à nous donner votre avis dessus en nous mentionnant sur Twitter @filmsdelover, ou sur le Discord de l'émission dont l'adresse est ci-dessous. Nous avons un Discord avec toutes les dernières infos sur Netflix, des conversations, des débats sur Netflix mais aussi sur les autres services SVOD dispos en France : https://discord.gg/N4Vmd5n (Merci Kris_Mery de l'administrer et de l'avoir créé) Intermèdes audio :"Lupin dans l'ombre d'Arsène" dispo en janvier 2021 / "Barbarians", dispo en octobre / "Quelqu'un doit mourir" dispo en octobre. Intervenants : Hélène (https://www.twitter.com/nivrae) Damien (https://www.twitter.com/damien_srsly) Présenté par Frédéric (https://www.twitter.com/filmsdelover). Bonus : Cet épisode n'est pas vraiment soutenu par le cinéma français en fait. C'est comme ça.

From Angela Lei's poetry book: "Lights in the Dark" Section: Black Chronicles --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/angela-lei/support

We interviewed and pried into the personal life of Youtuber Jimmy Zhang. Enjoy our Valentine's special! So much thanks to Jimmy for joining us and being a lot of fun.

The girls go into detail about their new romantic interests. Megan has a man from Poland that she met in New York, Jacqueline has fallen for a hotel security guard, and Abby has a typical Tinder boy that turned into something more. The ladies also discuss cuffing szn and answer some of your questions as always.

The ladies talk about basic sex ed, share some dirty facts, and would like to remind you all to clean your dicks and pussies. They wanna teach you how to stay clean and safe while getting down & dirty with a lover or friend or whatever.

The girls pry into Youtuber/Singer/Business owner David Choi's life and ruin the image that we grew up to know and love back in the late 2000's when Youtube was first on the rise. So much thanks to David Choi, who is a listener and fan of SMAD, for joining us on this episode and letting us lightly expose him.

Looks like it's CUFFING SZN! Just kidding, not for the SMAD girls, unfortunately. The ladies talk about the difficulties of finding actual love in LA, how you shouldn't be ashamed to hoe around, how guys shouldn't be afraid of a girl's past, intimate vs. rough sex, and other random bs.

Cindy S.H.:                         Hi. Welcome to Discover CircRes, the monthly podcast of the American Heart Association's journal Circulation Research. I'm your host, Cindy St. Hilaire, and my goal is to bring you highlights of articles published in the Circ Research Journal as well as have in-depth conversations with senior scientists and the junior trainees who have led the most exciting discoveries in our current issues. Today is our premier episode, so I want to take some time to introduce myself, give you a little bit of background about the history of the journal, and then have a conversation with our new editor in chief, Dr. Jane Freedman, and my social media editor partner in crime, Dr. Milka Koupenova. Cindy S.H.:                         First, a little bit about me. I'm an assistant professor of medicine and bioengineering at the University of Pittsburgh. My lab is part of the division of cardiology and we're also a member of the Pittsburgh Heart, Lung and Blood Vascular Medicine Institute. I'm still a relatively new PI. I'm still learning as I go. One of the strengths of being a new PI in the current time is the amazing network we have through social media, whether it's through listening to podcasts or through Twitter or through select groups like one of my favorites, New PI Slack. Really one of my personal goals of starting this podcast for Circ Research is to have a career development angle. Because career development is so fresh in my mind and it's really something I want to incorporate into this podcast, we're hoping we can reach out to more junior trainees through these mediums. Really that's the impetus for Dr. Freedman wanting to have specific social media editors at the Circulation Research Journal. Cindy S.H.:                         I'm very honored to be the first host of this podcast and I'm very excited for this opportunity. As a team, Milka and I hope to expose the larger community to not only the most current and exciting discoveries in cardiovascular research but also a behind-the-scenes look of what it takes to get high-impact research done and published and planned and funded, and also talk about some of the maybe the non-bench aspects of this job, the networking, the behind-the-scenes look that really you learn on the fly as you go. Hopefully we can expose more people to these on-the-fly things in a slightly more rigorous manner. Cindy S.H.:                         Before I go into the articles summarized in this week's podcast, I want to give a very big thank you to Ruth Williams. Ruth is the person who writes the content of the In This Issue which is featured in every issue of the journal Circulation Research, and that content is extremely helpful in deciding which articles we're going to focus on in this podcast and also for helping me form the conversations and discussions. Thank you, Ruth, for all your hard work. Cindy S.H.:                         Now I'm going to highlight three articles that were featured in the June 21st issue of Circulation Research. The first is entitled Relationship Between Serum Alpha-Tocopherol and Overall and Cause-Specific Mortality: A 30-Year Prospective Cohort Analysis. The first author is Jiaqi Huang and the corresponding author is Demetrius Albanes , who are both at the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, which is at the NIH in Bethesda, Maryland. Alpha-tocopherol is the more formal name for vitamin E, and vitamin E is an essential fat-soluble vitamin. By essential, that means that while your body absolutely needs it, it does not produce it itself. Therefore we need to consume products containing vitamin E. We do that by eating vegetable oils, nuts, seeds, whole grains and certain fruits and vegetables. Previously, population-based studies have shown inconsistent associations between circulating vitamin E and risk of overall death or death due to specific diseases such as cancer and cardiovascular disease. Cindy S.H.:                         To look more closely at cause-specific mortality, Huang and colleagues studied a cohort of close to 30,000 Finnish men, which is a huge study. Added to that, these men were in their 50s and 60s at the start of the study and then continued for the next 30 years of their life to be in this study. It's frankly an amazing achievement to keep that many individuals enrolled. From approximately 24,000 deaths, so about 80% of the original cohort, the authors adjusted for factors such as age and confounding things like smoking. They found that vitamin E levels were inversely associated with the risk of death from a variety of causes. What that means is that higher levels of vitamin E associated with lower risk of death. All of those causes of death that they found were cardiovascular disease, heart disease, stroke, cancer, and respiratory disease. This large prospective cohort analysis provides very strong evidence that higher vitamin E levels means greater protection. Cindy S.H.:                         It's really interesting to note though that this data did not seem to associate with a reduced risk of death by diabetes or, for that matter, injury and accidents, which I guess kind of makes sense. The authors say these results indicate that vitamin E may influence longevity, but they also highlight the need for further studies, specifically in more ethnically diverse populations and of course in women, because we all know a major limiting factor of a majority of cardiovascular studies is the fact that often there are just not enough women in these studies. But really that's a push now to include not only women but more ethnically and geographically diverse populations. Cindy S.H.:                         The second article I want to highlight is titled Mitochondria Are a subset of Extracellular Vesicles Released by Activated Monocytes and Induce Type I IFN and TNF Responses in Endothelial Cells . The first authors are Florian Puhm and Taras Afonyushkin , and the senior author is Christopher Binder. All three are in the Department of Laboratory Medicine, the Medical University of Vienna, in Vienna, Austria. This group is also part of the Research Center of Molecular Medicine of the Austrian Academy of Sciences. Cindy S.H.:                         I want to talk about this paper because I found that title extremely provocative. Extracellular vesicles or microvesicles are small particles that can be released from cells. These particles can act as cell-cell communicators. They can hold a variety of substances such as proteins and micro RNAs and minerals and all sorts of things that are derived from inside the cell. The matrix vesicle is then budded off. Matrix vesicles released from monocytes after bacterial LPS stimulation, so a stimulus that induces an inflammatory response, these matrix vesicles have been shown to contain mitochondrial proteins. Mitochondrial DNA-containing matrix vesicles have been reported in the mouse model of inflammation. From this premise, from these prior studies, Dr. Puhm and colleagues hypothesized that the mitochondrial content of matrix vesicles might actively contribute to pro-inflammatory effects. Cindy S.H.:                         What they then did was show that monocytic cells release free mitochondria and also matrix vesicles that contain mitochondria within them. These free and matrix vesicle-encapsulated mitochondria were shown to drive enothelial cells to induce inflammatory cytokines such as TNF-alpha and interferon. These circulating matrix vesicles were collected also in human volunteers that were injected with this same inflammatory substance, LPS. These circulating matrix vesicles isolated from humans also induced endothelial cell cytokine production. Very interestingly, inhibition of the mitochondrial activity drastically reduced the pro-inflammatory capacity of these matrix vesicles. Cindy S.H.:                         Together, this result suggests that the released mitochondria, whether it's free or whether it's encapsulated in a matrix vesicle, may be a key player in certain inflammatory diseases. This study shows that in addition to their central role in cellular metabolism, mitochondria, whether encapsulated or free, can actively participate in an inflammatory response in a cell other than the cell it was native in, which is just intriguing to think about. This work provides new insight to the contribution of mitochondria to the content and biological activity of extracellular vesicles. It also might suggest that perhaps targeting mitochondria and their release may represent a novel point for therapeutic intervention in inflammatory pathologies. Cindy S.H.:                         The last article I want to highlight is titled Macrophage Smad3 Protects the Infarcted Heart, Stimulating Phagocytosis and Regulating Inflammation . The first author is Bijun Chen and the senior author is Nikolaos Frangogiannis . When tissues are injured, there is localized increase in the cytokine TGF-beta. However, depending on conditions, this TGF-beta can function to stimulate macrophages to adopt either pro-inflammatory or anti-inflammatory phenotypes. To complicate matters more, the signaling pathway for both the pro- and anti-inflammatory phenotypes involves activation of the intracellular signaling protein Smad3. Inflammation, whether too much or too little, can influence the outcome of injuries, including injuries such as myocardial infarctions. An infarction, for those of you unfamiliar with the term, is a localized area of dead tissue and that results from a lack of blood supply. In this case, an infarction, a myocardial infarction, is essentially a heart attack that stops blood flow through the coronaries and causes death in the cardiac tissue and cells. Cindy S.H.:                         The authors hypothesized that in the infarcted myocardium, activation of TGF-beta and Smad signaling and macrophages may regulate repair and remodeling. They had a very specific question about a very specific cell type in the context of the whole heart. To address the role of Smad3, they utilized mice that were engineered to lack Smad3 in the myeloid lineage which produces macrophage cells. They found that these mice with myeloid cell-specific deletion of Smad3 had reduced survival compared to control mice. Additionally, the hearts from the animals with the myeloid cell-specific deletion of Smad3 exhibited increased adverse remodeling and greater impairment of function. That's a really interesting finding. The heart tissue itself was the same. All that was different were the cells of the myeloid lineage. Then to dig after what cells were mediating this effect, the investigators moved on to in vitro studies. They found that Smad3-lacking cells themselves showed reduced phagocytic activity, sustained expression of pro-inflammatory genes, and reduced production of anti-inflammatory mediators when compared with control macrophages. Cindy S.H.:                         In summary, these results suggest Smad3 is necessary for macrophages in the area of the infarction to transition to an anti-inflammatory phagocytic phenotype that protects against excess remodeling. However, we cannot go after global inhibition of Smad3 as a potential therapy post myocardial infarction, and that's because inhibition of Smad3 in cardiomyocytes is actually protective against the infarction. Inhibition in a macrophage is bad, but inhibition in a cardiomyocyte is good. Any potential Smad3-modifying therapies really needs to be designed to be cell type-specific and be able to be deployed to activate that cell type. Cindy S.H.:                         In addition to science, I love history. I thought I would take this opportunity of the first podcast to share with you a little bit of history about the Journal of Circulation Research. Circulation Research is now in its 66th year, but its origins can be traced to 1944. That was when the AHA established a council that was attempting to organize its research arm and its professional program arms. The AHA journal Circulation was already in existence, but in 1951 the executive committee decided to launch a basic research supplement, and it was called just that: Circulation Basic Research Supplement. But a few years later, Circulation Research was to be its own publication because of the interest and the excitement around the basic research supplements. The quote that I'm going to read is from that first executive committee meeting and there they wanted Circulation Research to be the authoritative new journal for investigators of basic sciences as they apply to the heart and circulation. Cindy S.H.:                         It's a fun little subgroup that they list after that. They list in anatomy, biology, biochemistry, morphology, which I just think is so neat to think about, pathology, physics, pharmacology, and others. It's interesting to think about what that would be today if we were now finding this journal. Biochemistry, genetics, molecular biology. It's fun to think about how much science has changed since they began this journal. Really the broader goal was to integrate and disseminate new knowledge. Leading that was Dr. Carl Wiggers, who was the first editor in chief of Circ Research. At the time, he was the head of physiology at Western Reserve University, and he's often referred to as the dean of physiology, as his research really provided much of the fundamental knowledge regarding the pressures in the heart and the vessels of the body and how they interact. Cindy S.H.:                         I actually went back and looked at some of the first titles in Volume One, Issue One, of Circ Research. It's really kind of neat. Some of them could be completely relevant today. I'm just going to read a few. Nucleotide Metabolism and Cardiac Activity, Fundamental Differences in the Reactivity of Blood Vessels in Skin Compared to Those in the Muscle. That was at the VRIC the other day. Haemodynamic Studies of Tricuspid Stenosis of Rheumatic Origin. Reading these for the first time I actually got chills because my two themes of my lab are both in that first Volume One, Issue One, of that journal. I study the extracellular nucleotide aCD73 and its impact on vascular homeostasis. I also study calcific aortic valve disease and are hugely curious about the role of inflammation and things like rheumatic heart disease in the progression of the disease. It's amazing how much science has changed, but yet how so much has stayed the same. Cindy S.H.:                         Dr. Wiggers wrote a few gems, a few quotes in his biography that I want to share with you. I find them inspiring and also humbling. The first is, "Research is a gamble in which the laws of chance favor the loser. The loser must remain a good sport," which I think is perfect to think about in science. I really wish I had read that after my first RO1 was triaged. The next two are more about the science writing and I think they're great not only for when we're thinking about papers but also grants. The first is, "Readers are greatly influenced in their judgment of a research project by literary style. A poor presentation can easily damage the best investigation," which is so true. No matter how good your science is, if you can't communicate it, it doesn't matter. And lastly, "A good paper, like a good glass of beer, should be neither largely foam nor flat. It should have just the right amount of head of foam to make it palatable." Cindy S.H.:                         With these nuggets of wisdom, we're now going to talk with Drs. Jane Freedman, who's now the editor in chief of Circ Research, and Dr. Milka Koupenova, who is the social media editor. Before I really introduce Jane, I want to recognize all of the former editors in chief of Circ Research, Dr. Carl Wiggers, Dr. Carl Schmidt, Dr. Eugene Landis, Dr. Julius Comroe, Dr. Robert Berne, Dr. Brian Hoffman, Dr. Francis Abboud, Dr. Harry Fozzard, Dr. Stephen Vatner, Dr. Eduardo Marbán, Dr. Roberto Bolli, and now Dr. Jane Freedman. Welcome, Jane. Thank you so much for this opportunity and congratulations on your new position. Dr. Freedman:                   Thank you very much. Cindy S.H.:                         I was wondering if you could just introduce yourself to the listeners and give us a little bit about your background. Dr. Freedman:                   Sure. I am the Budnitz Professor of Medicine at the University of Massachusetts, and I originally became interested in a scientific career while attending Yale University where I was both an architecture and geology major. Cindy S.H.:                         Interesting. Dr. Freedman:                   Yes, very interesting. Then, not exactly knowing what I wanted to do, I worked for a year as a research assistant for my later-to-be mentor Dr. Joe Loscalzo at Brigham and Women's Hospital. There one day he sent me up to the intensive care unit and said we need to get a tube of blood from someone who was in the throes of having a myocardial infarction. Really at that point I became hooked. Why was that person having a heart attack, and using their blood how could I figure out whether they would live, die, do well, not do well, or yield new things that might help us cure or diagnose people with heart attacks later on? After that. I went to Tufts Medical School. I did my residency and cardiology fellowship at Brigham and Women's Hospital and the Massachusetts General Hospital. After working at several different places, I have wound up at the University of Massachusetts where I am in the Division of Cardiology and where my laboratory currently resides. Cindy S.H.:                         Excellent. As the new editor in chief, what do you see as your vision for the journal? Dr. Freedman:                   I'm in a very fortunate position to be taking over a wonderful journal from an incredibly dedicated group of editors and associate editors and other supportive editors. Scientific pursuits and reporting and publications are really evolving at a rapid clip, so we hope to have several things happen over the next few years to survive and thrive. The first thing is we hope to define and expand Circulation Research's scientific identity. We want to extend its already outstanding portfolio of science that really demonstrates how elegant basic and translational mechanisms and pathways are part of a greater web of cardiovascular disease and stroke. This will include an increasingly diverse group of basic and translational sciences and they'll touch on both fundamental studies as well as how they translate to human disease. We also want to continue to pursue the excellence that Circulation Research already epitomizes and we want to extend its brand both to an increasingly diverse group of members, both nationally and internationally. Dr. Freedman:                   Circulation Research already has really wonderful publication metrics such as turnaround time, time to review, and we hope to maintain that so as to be a journal of choice for an increasingly growing number of investigators. We would also very much like to have greater interface with the American Heart Association. A lot of the research on our pages is funded by the American Heart Association, and the majority of science that the American Heart Association currently funds is basic cardiovascular science. We hope to have greater interface and help our users of the journal understand what the American Heart Association can do for them and for their scientific pursuits. Dr. Freedman:                   Last and very importantly, we really want to attract early and mid-career investigators to the journal. We already have some really nice programs that the previous editorship has started, such as Meet The First Author, but we would also like to be a site for education of how you can review papers, have a junior editor program and other types of programs that will help early and mid-career investigators in their future. One of the ways we're going to be doing that is to have enhanced social media programs. Cindy S.H.:                         Great. I really like that idea of having the junior editors because I think the best learning experience I had about how to write a grant did not happen until I actually served on a study section, because it was there you actually can understand all of those comments you got on your first grant that was triaged and why they were said. I think that is a key and really important aspect. Dr. Freedman:                   That's a perfect analogy because you want to remove the black box that people think is happening when they send their manuscripts in. There's so many reasons why manuscripts succeed and don't succeed, and we really do want to be as transparent as possible and we do want to educate investigators as much as possible about the process. Cindy S.H.:                         Actually, could you maybe tell us a little bit about that process? I made all my figures, I formatted my paper according to the instructions, I hit submit. Black box. What happens? What's the next step? Dr. Freedman:                   What's the next step? Cindy S.H.:                         What do you do? What does an editor in chief actually do? Dr. Freedman:                   I do have to say that none of this would happen, especially in the incredibly quick turnaround time, if we didn't have amazing support and help in our office that happens to be in Baltimore. The people there are just incredible. They make sure that papers move through. It's really 24/7. Our group has not been at it for very long, but I know Dr. Bolli's group as well as our group, people are handling manuscripts as fast as they really come in. We see the manuscript, they get quality checked. We try not to be too onerous with the first steps. Then typically they go to one of the associate or deputy editors who will handle them to send out for review. Cindy S.H.:                         Is that based on keywords or the title or how is that decided? Dr. Freedman:                   Sometimes it's based on keywords, so careful with your keywords. A lot of times, because each of the associate editors has an area of expertise that hopefully covers what your science is interested in, they will know experts in the field. We very heavily rely on our editorial board. We have an amazing editorial board at Circulation Research, and amazing contributions from the BCBS council. These individuals have over the years and currently provided just tireless and unsung, devoted help to making the journal run smoothly. It's a pretty quick turnaround time. Then the decision made based on the reviews of the article. Occasionally articles come in and they're not suitable for the journal because they're not what we perceive as what our readers would be interested in. Sometimes those articles don't go up for review. We don't want to keep them caught up, so we send them back right away. Dr. Freedman:                   When the articles come back in with the reviews, we're going to be discussing them at a weekly meeting. Other viewpoints will weigh in, and then we make a decision whether it's an accept, whether it's a revise, whether it needs a lot more science. That's called a de novo. Sometimes we think it's more suitable for one of the other 11 American Heart Journals and we might suggest that you consider sending it to that journal and we consult with that journal's editor. Cindy S.H.:                         Interesting. All that happens with about 14 days. Dr. Freedman:                   That's supposed to happen with 14 days. Cindy S.H.:                         It does pretty regularly based on the stats. That's amazing. One of the initiatives you mentioned was really the role of social media. Now I would like to introduce Dr Milka Koupenova, who is the co social media editor alongside me. Before I let Milka talk, I really have to be honest and say that my graduate school days were some of the best of my life. It was in part because Milka I were both in the same lab. We overlapped by a couple of years under the amazing mentorship of Dr. Katya Ravid. Every time we get together, all we'd talk about was how can we be like Katya? Maybe someday we'll actually have a podcast where we can get Katya in here and actually record all her nuggets of wisdom. Dr. Koupenova:                 I think the same thing about Katya. Cindy S.H.:                         How can it be more like Katya? But for now, Milka, welcome. Thank you. If you could just introduce yourself and give us a little bit about your background. Dr. Koupenova:                 Hi, everybody. My name is Milka Koupenova. I am an assistant professor at University of Massachusetts Medical School. Briefly about me, as Cindy mentioned, I did my PhD at Boston University and I studied at that time metabolism in atherosclerosis. Then I had this great opportunity to join this lab in thrombosis that studied these little cell fragments called platelets, which I knew something but not that much about. I joined Dr. Freedman lab as a postdoctoral fellow, and actually my interest evolved to be very much in platelet immunobiology and how platelets may contribute to thrombotic disease during viral infections. Luckily for me, I had two angels that I wanted to be. One of them was Katya Ravid, as you mentioned, and the other one was Dr. Freedman. Both set up a great example of scientists and how to do science in life. Cindy S.H.:                         Wonderful. Excellent. Thank you. I won't lie. I don't know if you feel this way. I definitely feel a little nervous about being a social media editor. I'm talking in a room to a box with a microphone on me and I don't know who's going to be listening. That's also exciting for me too. I get to disseminate all this cool knowledge and share our basic research with this huge audience. What are you most nervous about and excited about? Dr. Koupenova:                 You're doing the podcast, so I don't have to worry about that, that that particular part. I am quite excited actually about everything that's going to surround popularizing the science at Circulation Research. I think in the time that we live in and when social media is a huge part of our life, we definitely need to engage the community, scientific or lay, and communicate our ideas. I'm super excited about the creative part behind how we are going to achieve this via various social medias. Cindy S.H.:                         Can you talk about the platforms that you plan on using? Dr. Koupenova:                 We currently are using Twitter and Facebook. Please follow us on Twitter and Facebook. And we are going to launch Instagram. Find us, follow us, engage us. That will be great. You can always send us messages and like us, retweet whatever you decide. Cindy S.H.:                         Give podcast feedback on Twitter. Nice comments only. Dr. Koupenova:                 We'd like to hear your comments and we'd like to hear what you envision in certain cases when it comes to your Circulation Research, because this is your journal as much as it is ours. We're here for you. In addition to popularize and advertise the wonderful science that we're publishing in Circ Research, we want you to be engaged. We want you to be able to advertise in your own work and to think of it as something that you own and something you need to communicate to the rest of the world. That is one of the things that we want to do. Dr. Koupenova:                 Finally I'm going to echo on what Dr. Freedman said, is we want to attract truly early career and young investigators and help them be involved, help them own their science and help them communicate their ideas. That's pretty much what our social media platform is and we are going to evolve with you. That is perhaps one of the challenges. Cindy S.H.:                         I think one of the most interesting aspects, at least in academia as I see it, is really the role of self-promotion. It's something you're never taught and it's something that you don't really appreciate until you go to that conference. I remember my first conference as a new PI, I was standing there and I'm just like, "Okay, these are all other PIs. How are they all in groups? How does everybody know each other? Why are they all friends already?" It takes a lot of guts and you have to inject yourself. "Hi. I'm Cindy St. Hilaire and I'm new. Please be my friend," essentially, essentially. But it's important and I really liked the fact that when your journal is published you have that little button, share on Twitter, share on Facebook. I think that's really important. It helps you practice that self-promotion and can help really allow you to embrace your extrovert when you know how to. Dr. Koupenova:                 That's exactly what I was going to point out. Scientists or physician scientists, or physician scientists perhaps are a bit better. But as scientists we're very much introverted. But social media gives you a platform that it's not cheesy to popularize and communicate. Then you see those people on conferences and then you have your little group without- Cindy S.H.:                         It's amazing how many Twitter friends I have. "Oh, I met you on Twitter. It's so nice to meet you in real life." Dr. Koupenova:                 It's a new generation. We at Circ Research want to evolve with it. Is that correct, Dr. Freedman? Dr. Freedman:                   That is correct. Thank you very much. Cindy S.H.:                         It's exciting times. I guess maybe this is a question for all of us to talk about, but how do you think we can, number one, attract people to science, attract diverse people to science, and then really keep them in science and how do you think we can use Circ Research and also the social media aspects of Circ Research to do that? Dr. Freedman:                   I think, first of all, people have to see themselves in the journal. The journal, I think the first point I talked about, about being inclusive, inclusive types of people, way people consume science, types of science. We really want people to feel like Circ Research isn't just a journal that puts out scientific papers, but is a forum. It's a forum for them to exchange ideas and it's a forum for them to understand better about their scientific careers. Cindy S.H.:                         Great. Thank you. This has been an amazing first podcast. I'm so happy to share it with the two of you and I'm super excited for this opportunity. Again, Jane, I want to congratulate you on your new position as editor in chief and I can't help but mention as the first female editor in chief. That's a wonderful, wonderful thing. Cindy S.H.:                         You can find us on Twitter. The handle is @CircRes, at C-I-R-C-R-E-S. We're also on Instagram using the same name, C-I-R-C-R-E-S. We hope to hear from you there. Cindy S.H.:                         Thank you for listening. I'm your host, Cindy St. Hilaire, and this is Discover CircRes, your source for the most up-to-date and exciting discoveries in basic cardiovascular research.

Jane Ferguson:                Hello, welcome to Getting Personal: Omics of the Heart, Episode 22. This is a podcast from Circulation: Genomic and Precision Medicine, and the AHA Council on Genomic and Precision Medicine. I am Jane Ferguson and it's November 2018.                                            Our first article comes from Carlos Vanoye, Alfred George and colleagues from Northwestern University Feinberg School of Medicine and is entitled, High Throughput Functional Evaluation of KCNQ1 Decrypts Variance of Unknown Significance.                                            So a major growing problem in clinical genomics is that following the identification of a variant that is potentially linked to a disease phenotype, without further interrogation, it's really hard to make sense of the functional significance of that variant. Right now, the large number of variants of unknown significance lead to confusion for patients and clinicians alike. To allow for accurate diagnoses and the best treatment plans, we need a way to be able to screen variants to assess their function in a fast and cost-effective manner.                                            In this paper, the authors decided to focus in the KCNQ1 gene, a cardiac ion channel, which can affect arrhythmias. They aim to assess whether a novel high-throughput functional evaluation strategy could identify functional mutations, as well as an in vitro electrophysiological approach. Which is effective, but expensive and time-consuming. Their approach capitalized on an existing automated electrophysiological recording platform that had originally had been developed for drug discovery essays.                                            They selected 78 variants in KCNQ1 and assessed their function using the High-Throughput platform, which coupled high efficiency, cell electroporation with automated plain or patch clamp recording. They compared the results to traditional electrophysiological essays and find a high rate of concordance between the two methods. Overall, they were able to reclassify over 65% of the variants tested, with far greater efficiency than traditional methods.                                            While this method will not work for all genes and phenotypes, the authors have demonstrated an efficient method for functional interrogation of variants. Which may greatly accelerate discovery and conditions such as Long QT or other congenital arrhythmias.                                            The next paper, Nocturnal Atrial Fibrillation Caused by Mutations in KCND2 Encoding Poor Forming Alpha Subunit of the Cardiac KV 4.2 Potassium Channel, comes from Max Drabkin, Ohad Birk, and colleagues at Soroka University Medical Center in Israel. This paper also focuses on cardiac ion channels and the role of mutations in atrial fibrillation.                                            In a family with early-onset peroxisomal AF across three generations, whole XM sequencing revealed a variant in KCND2 encoding the KV 4.2 Potassium Channel, which segregated consistent with autosomal dominant heredity. This variant resulted in a replacement of a conserved [inaudible] residue with an arginine. To investigate functional consequences of this novel variant, they conducted experiments in xenopos laevis oocytes and found that there is decreased voltage depended channel and activation and impaired formation of the KV 4.2 Homotetramer and the KV 4.2, KV 4.3 Heterotetramer.                                            Overall, this study shows that a novel mutation in a conserved Protein kinase C Phosphorylation site within the KV 4.2 Potassium Channel underlies the phenotypes observed in a family of peroxisomal atrial fibrillation. The targeting Atrial KV 4.2 might be an effective therapeutic avenue.                                            Next up, Michael Levin and Scott Damrauer and colleagues from the University of Pennsylvania published an article entitled, Genomic Risks Stratification Predicts All-Cause Mortality After Cardiac Catheterization.                                            They were interested in understanding the utility of polygenic risk scores for disease prediction. They constructed a genome Y genetic risk score for CAD and applied it to individuals from the Penn Medicine Bio-bank who had undergone Coronary angiography and genotyping.                                            They included over 139,000 variants for the 1,500 ancestry subjects who were included and classified them as high or low polygenic risk. Individuals who were classified as high polygenic risk were shown to have higher risk of All-Cause mortality than low polygenic risk individuals despite no differences in traditional risk factor profiles. This was particularly evident in individuals with high genetic risk but no evidence of angiographic CAD.                                            Adding the polygenic risk score to a traditional risk assessment model was able to improve prediction of five year All-Cause mortality. Highlighting the utility of a polygenic score and underscoring traditional risk factors do not yet fully capture mortality risk.                                            The next article entitled, "Bio-marker Glycoprotein Acetyls is Associated with the Risk of A Wide Spectrum of Incident Diseases and Stratifies Mortality Risk in Angiography Patients" comes from Johannes Kettunen, Scott Ritchie, Peter Würtz and colleagues from the University of Oulu Finland.                                            GlycA is a circulating biomarker that reflects the amount of Glycated proteins in the circulation. It has been associated with cardiovascular disease, Type 2 Diabetes, and all-cause mortality. In this paper, the authors used electronic health record data from over 11,000 adults from the finish general population previously included in the "FINRISK" and "Dilgom" studies and they tested for a associations between GlycA and 468 different health outcomes over an 8-12 year follow up. They report new associations between GlycA and multiple conditions including incident alcoholic liver disease, chronic renal failure, glomerular diseases, chronic obstructive pulmonary disease, inflammatory polyarthric disease and hypertension.                                            These associations held true even after adjusting for CRP suggesting that GlycA represents an independent biological contributor to inflammation and disease. Their findings highlight potential utility for GlycA as a biomarker of many diseases and underscore the importance future functional and mechanistic studies to understand how GlycA is linked to disease risk.                                            Our last original research article entitled, "Tissue Specific Differential Expression of Novel Jeans and Long Intergenic Non-coding RNAs in Humans with Extreme Response to Endotoxic glycemia comes from Jane Ferguson, Murdock Riley, and colleagues from Vanderbilt University, Columbia University, and the University of Pennsylvania. That first author is none other than me, so I'm not unbiased reader of this particular manuscript, but I'd like to tell you a little bit about it anyway.                                            We were interested in understanding the transcriptional changes that occur in tissues during acute inflammation. As part of the genetics of evoked responses to Niacin and Endotoxemia, or gene study, we recruited healthy individuals and performed an inpatient endotoxin challenge where we administered a low dose of LPS and looked at the systemic inflammatory response. Individuals vary greatly in the degree of their inflammatory response to LPS and we identified high and low responders, men and women, of African and European ancestry, who had responses in the top or bottom 10% for cytokines and fever.                                            We conducted RNA seek and adipose tissue in 25 individuals and CD-14 positive monosites for 15 individuals in pre and two or four hours post LPS samples. We found that the differences in transcriptional response between high or low responders are mostly explained by magnitude rather than discrete sets of genes.                                            So some core genes were altered similarly, in both groups, but overall the high responders mounted a large transcription of response to LPS or low responders rather than mounting an anti-inflammatory response actually just barely responded on the transcription level. We saw clear tissue specificity between manosites and adipose tissue we identified several long non-coding RNAs that were up or down regulated in response to LPS and validated these independent samples one of these link RNAs which we have now named Monosite LPs induced link RNA regulator vile six or Mahler Isle six, with highly regulated by LPs and monosites but not in adipose tissue.                                            We [inaudible] THP-1 monosites and find a significant effect on iOS six expression suggesting that this is a novel link RNA that regulates Isle six expression in manosites potentially through a cd-86 dependent pathway. Overall our data revealed tissue specific transcriptional of changes that correlate with clinical inflammatory responses and highlight the role of specifically incarnate and inflammatory response.                                            Next up is a research letter entitled "Reduced Sodium Current in Native Cardiomyocytes of a Regatta Syndrome Patient Associated with Beta Two Central Mutation" published by Constance Schmidt, Felix Wiedmann, Ibrahim El-Battrawy, Dierk Thomas, and co-authors from University Hospital Heidelberg. They obtained cardiomyocytes from a patient with Regatta Syndrome previous whole XM sequencing had implicated a variant in the Beta Two Syntrophin or "SNTB2" gene as potentially causal in this individual. Expression analysis showed lower SNTB2 expression and atrial tissue of the affected individual compared with controls.                                            They performed electrophysiology on the Microcytes and found reduced peak sodium density and reduced late sodium current. They co-express wild type or mutant SNTB2 in heck 293 T cells and [inaudible] with the cardiac sodium channel NAV-1.5 and found a significant effect on binding which adversely affected sodium currents. This study nicely demonstrates the functional effect of this SNTB2 mutation underlying Regatta Syndrome in this patient.                                            A second research letter comes from A.T. van den Hoven and Jolien Roos- Hesselink and colleagues from Erasmus University Medical Center in the Netherlands and is entitled "Aortic Dimensions and Clinical Outcome in Patients with SMAD three mutations, they were interested in understanding how the Aortic dilation comment individuals with SMAD three mutations compared to individuals with other syndrome and causes of Aortic dilation.                                            In 28 patients with SMAD three mutations, there were significant growth in the Sinotubular Junction the ascending Aorta on the diaphragm over an average of 10 years of follow up at reads far higher population averages but lower than might be seen in other syndromes, such as [inaudible]. Intensive management and preventive surgery and many of the patients prevented any mortality in this group.                                            Rounding out this issue is a clinical letter entitled "Concealed Arrhythmogenic  Right Ventricular Cardiomyopathy in Sudden unexplained Cardiac Death events from Jodie Ingles, Chris Semsarian, and colleagues from the University of Sydney, Australia. They report on for clinical cases where individuals presented in early adulthood with unexplained cardiac arrest, which was later found to be attributable to mutations in the PKP2 gene. PKP2 or, Plakophilin 2, encodes an integral component of the Desmosome, which is important and Cell-Cell adhesion. Further PKP2 is involved in transcriptional activation of genes controlling intracellular calcium cycling. This gene has been implicated arrhythmogenic right ventricular cardiomyopathy in individuals with cardiac structural abnormalities. These four cases where unrelated individuals were all fans to have loss of function variants and PKP2 underlying sudden cardiac death or events, despite structurally normal hearts. This prompts questions on the clinical management of such cases of concealed ARVC.                                            That's all from us for November, thanks to all of you out there listening. We'll be back in December for the final episode of 2018.                                            This podcast was brought to you by Circulation Genomic and Precision Medicine and the American Heart Association Council on Genomic and Precision Medicine. This program is copyright American Heart Association 2018.                                             

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.                                                 Is there a unique lipoprotein profile for incident peripheral artery disease as opposed to coronary or cerebral vascular disease? Well, you're just gonna have to wait for our feature discussion to find out. That's coming right up after these summaries.                                                 Our first original paper this week tells us that gene variance known to be associated with idiopathic and peripartum cardiomyopathy are also associated with preeclampsia. First and corresponding author Dr Gammill from University of Washington and colleagues studied 181 participants with confirmed preeclampsia from the Preeclampsia Registry in BioBank. Saliva samples were collected for DNA isolation and whole exome sequencing was performed to detect rare variants in 43 genes known to be associated with cardiomyopathy.                                                 Results were compared with data from two controlled groups, unrelated women with a gynecological disorder, sequence using the same methods and instruments, as well as published variant data from 33,000 subjects in the Exome Aggregation Consortium.                                                 The results showed that women who developed preeclampsia are more likely to carry protein altering mutations in genes associated with cardiomyopathy, particularly, the TTN gene which encodes the sarcomeric protein titin. Thus, detecting these gene variants may allow more specific diagnosis, classification, counseling and management of women at risk.                                                 Prior trials have shown that nonsteroidal anti-inflammatory drugs or NSAIDS confer cardiovascular risk. Now this has been postulated to be due to enhanced formation of methyl arginines in the kidney that would limit the action of nitric oxide throughout the vasculature. However, the next original paper in this week's journal suggests that this may not be correct. First author, Dr Ricciotti, corresponding author, Dr FitzGerald from University of Pennsylvania Perelman School of Medicine and colleagues, used multiple genetic and pharmacological approaches to disrupt the COX 2 pathway in mice and analyze plasma from patients taking NSAIDS.                                                 However, they did not observe an increase in methyl arginines. In contrast, they did observe an increase in plasma asymmetric dimethylarginine or EDMA in mice-rendered hypertensive by infusion of angiotensin II at a dose that also caused renal impairment. After a four week washout period following the infusion of angiotensin II, blood pressure, creatinine, and ADMA levels all fell back to normal levels.                                                 Celecoxib-treated mice also exhibited increased ADMA and plasma creatinine in response to infusion of angiotensin II and their levels also returned to normal thereafter. Thus, it seems likely that the previous reported elevations in ADMA reflected renal dysfunction rather than a direct consequence of COX 2 deletion or inhibition. The authors end by suggesting that the most plausible mechanism by which NSAIDS confer a cardiovascular risk, is by suppression of COX 2 derived cardioprotective prostaglandins such as Prostacyclin rather than by enhanced formation of methyl arginines.                                                 The next original paper identifies new targets with the potential to prevent vascular malformations in patients with hereditary hemorrhagic telangiectasia. Co-corresponding authors, Dr Ola and Eichmann from Yale University School of Medicine and colleagues looked at SMAD4, which is a downstream effector of transforming growth factor-beta/bone morphogenetic protein family ligands that signal via activin-like kinase receptors.                                                 The authors generated a tamoxifen inducible postnatal endo-fetal specific SMAD for a mutant mouse and showed that SMAD4 prevented flow-induced arterial venous malformations by inhibiting casein kinase II. The uncovered pathways provided novel targets for the treatment of vascular lesions in hereditary hemorrhagic telangiectasia related juvenile polyposis patients carrying SMAD4 mutations.                                                 The next original paper provides important data for the accurate diagnosis of long QT syndrome. Long QT syndrome can be a challenging diagnosis partly because the optimal method for QT assessment is not unequivocally established. QT experts advocate manual measurements with a tangent or threshold method.                                                 In today's paper, first and corresponding author, Dr Vink from Academic Medical Center University of Amsterdam and colleagues, aimed to assess similarities and differences between these two methods of QT interval analysis among 1,484 patients with a confirmed pathogenic variant in either KCNQ1, KCNH2 or SNC5A genes from 265 families. Both QT measurement methods yielded a high inter and intra reader validity and a high diagnostic accuracy.                                                 Using the same current guideline cutoff of QTC interval 480 milliseconds, both methods had similar specificity but yielded a different sensitivity. QTC interval cutoff values for the QT measured by the tangent method was lower compared to that measured by the threshold method. Plus, values were different depending on the correction for heart rate, age, and sex.                                                 The authors provided an adjusted cutoff values specified for method, correction formula, age, and sex. In addition, a freely accessible online probability calculator for long QT syndrome at www.QTcalculator.org has been made available as an aid in the interpretation of the QT interval.                                                 The next original paper demonstrates for the first time that thrombin mediated signaling may play a role in diet-induced atherogenesis. Co-first authors, Dr Raghavan and Singh, corresponding author Dr Rao from University of Tennessee Health Science Center and colleagues, used a mouse model of diet-induced atherosclerosis and molecular biological approaches and explored the role of thrombin and its G protein coupled receptor signaling in diet-induced atherosclerosis.                                                 They found that thrombin-induced CD36 expression and foam cell formation required protease activated receptor 1, G alpha 12, Pyk2, GAB 1, and protein kinase C theta dependent activating transcription factor 2 activation. Thus, inhibition of thrombin G protein coupled receptor signaling could be a promising target for the development of new drugs in reducing the risk of diet-induced atherogenesis.                                                 The next study provides insights into the long- term association of LDL cholesterol with coronary heart disease mortality in individuals at low tenure risks of atherosclerotic cardiovascular disease. First and corresponding author, Dr Abdullah, from VA North Texas Medical Center and UT Southwestern Medical Center and colleagues studied more than 36,000 subjects in the Cooper Clinic Longitudinal Study cohort who are at low tenure estimated risk of atherosclerotic cardiovascular disease. In other words, a low tenure risk of less than 7.5%. They've followed these patients for more than two decades.                                                 Results showed that LDL cholesterol and non-HDL cholesterol at or above 160 milligrams per deciliter were independently associated with a 50 to 80% increased relative risk of cardiovascular disease mortality. The associations between LDL cholesterol and cardiovascular disease mortality were more robust when follow up was extended beyond the traditional 10 year estimated risk period.                                                 The associations remain significant in those with an estimated tenure atherosclerotic cardiovascular disease risk of less than 5%. These data suggests that LDL cholesterol levels at or above 160 milligrams per deciliter in individuals deemed to be at low tenure atherosclerotic cardiovascular risk are associated with worse long term cardiovascular disease mortality. These findings, along with other observational data and data extrapolated from clinical trials, support further consideration of appropriate LDL cholesterol thresholds for lipid lowering interventions in individuals categorized as low short-term risk.                                                 The final paper this week uncovers a novel therapeutic target for the prevention and treatment of thoracic aortic aneurysms. First author, Dr Nogi, corresponding author Dr Shimokawa from Tohoku University Graduate School of Medicine and colleagues, used genetically modified mice to show a pathogenic role of the small GTP binding protein, GDP dissociation stimulator in the development of angiotensin 2 induced thoracic aortic aneurysms and dissection. Down regulation of this protein contributed to dysfunction of aortic smooth muscle cells and hence oxidative stress, and matrix metalloproteinase activities in the pathogenesis of thoracic aortic aneurysms and dissection.                                                 Local over expression of this small GTB binding protein GDP dissociation stimulator around the thoracic aorta inhibited aortic dilatation and rupture in deficient mice. And that wraps it up for this week's summaries. Now for our feature discussion.                                                 Atherosclerosis has been considered a systemic process, meaning that when we see a disease in one vascular bed, we assume that that's a risk marker for disease in other vascular territories, and that they share pathophysiology, they share risk factors. However, if we think about it, the prior studies have all been sort of focusing on coronary and cerebral vascular disease, but today's feature paper changes that a bit because it addresses a key knowledge gap in peripheral artery disease risk, and interestingly suggests that there may be a unique lipid profile that's related to peripheral artery disease.                                                 This is gonna be an exciting discussion and I have the first author, Dr Aaron Aday from Vanderbilt University Medical Center currently. We have our editorialist, Dr Parag Joshi from UT Southwestern, and our associate editor, Dr Anand Rohatgi from UT Southwestern. Welcome gentlemen and Aaron, could we start with you sharing about your study? Dr Aaron Aday:                 So, as you mentioned, a lot of the previous epidemiologic data on atherosclerosis have been primarily in coronary artery disease and stroke, and when we looked at peripheral artery disease or PAD, there seemed to be some subtle differences. So for instance, total cholesterol on HTL cholesterol seemed to be the strongest risk factors for future peripheral artery disease and in terms of LDL cholesterol, the data are somewhat mixed. Some have found a weak association, some have actually found no association. And so building on that, we wanted to see if using nuclear magnetic resonance spectroscopy, we could elucidate more details about the litho protein pathways associated with peripheral artery disease.                                                 And we did this in the women's health study which is a prospective cohort study of women free of cardiovascular disease, the baseline, they were aged 45 and older. And what we've found in terms of the standards with their profiles, we again found that there was no association between LDL cholesterol and future peripheral artery disease, whereas certain standard lipid measures like HDL cholesterol were strongly associated with PAD, and then using the Endemol spectroscopy tool, we found that actually, small LDL particles and total LDL particles were concentrations of both of those markers, were strong risk factors for future PAD and other measures like total HDL particle concentration were even more strongly associated with future PAD than coronary artery disease.                                                 So essentially the signature associated with future peripheral artery disease, had some important differences than that for a composite of coronary artery disease and stroke. Dr Carolyn Lam:                Aaron thanks for that. That's beautifully described and just so intriguing. Parag, could you tell us how should we be thinking about results like this? Dr Parag Joshi:                   It's a great paper and it really highlights a new and unique approach in that we ... Peripheral artery disease as an isolated incident event is fairly understudied I guess we could say and so, this is a really nice paper to start choosing out some of the risk factors for that. I think overall, when we think of peripheral arterial disease in general, I think historically, we've thought of it as similar pathophysiology, you know LDL particles and perhaps other particles depositing in the arterial space. But this does highlight some important differences that might exist and I think one of those seems to be that maybe this is more a signature of elevated remnant lipoproteins or triglyceride rich remnant lipoproteins, small dent LDL particles, low HDL, that sort of metabolic syndrome type patterns that we look at as a high risk factor that may be more contributory to peripheral artery disease than coronary disease, or at least more specific to peripheral artery disease.                                                 I guess one of my main questions about that from your work Aaron is, how can we be sure this isn't just a pre-clinical marker of diabetic patients which we know have this type of pattern? Dr Aaron Aday:                 Sure, it's certainly a possibility. I think what's notable in the cohort, at least a time enrollment. And there was a very little diabetes and actually there was a much greater prevalent of metabolic syndrome. So in my mind, it may be more of a metabolic syndrome specific marker rather than necessarily down the diabetes pathway, but it's certainly something that needs to be explored further. Dr Parag Joshi:                   I wonder whether women's health studies such a healthy cohort that I wonder if this is picking up some signal before the answer to diabetes or as you said, metabolic syndrome, you know which certainly suggests an insulin resistance pattern and we know the association of diabetes with peripheral artery disease is stronger and so I wonder if this may be a sort of earlier way of picking that up. Dr Aaron Aday:                 It may be. I think one thing to notice is the outcome of peripheral artery disease that we're using. So it is symptomatic disease. So, we're not picking up a lot of ulcers that are developing in the future, it's more the claudication and then people who've undergone revascularization. Certainly diabetics have both of those as well but I think that may suggest it's not fully unexplained by developing diabetes than peripheral artery disease further down the line. Dr Parag Joshi:                   Yeah that's a great point. Dr Carolyn Lam:                Yeah great questions, great thoughts. Anand, what about you? Did you have questions too? Dr Anand Rohatgi:            I think from my perspective and thinking about it for circulation and its readership, we found this really interesting for several reasons. Number one, I think is, as you all have discussed, peripheral arterial disease just is not as well characterized and you can see that here in over 25,000 people, add about a 100 a bed, so I think in younger folk, it takes a lot of people to study, to be able to really understand kind of the pathophysiology of peripheral arterial disease.                                                 The other thing that they think they really shed some light on is how this is happening in women in particular and in women, of course as we know have been understudied in all cardiovascular diseases, but in particular, diseases like this which are less common. It's really insightful to see that these lipid abnormalities in women are contributing to peripheral arterial disease more so than your typical LDL cholesterol management and interestingly enough, most of the women who had PAD events in this study, did not have other cardiovascular events.                                                 They really just had PAD events exclusively and I thought that was really intriguing, and the use of this advanced lipoprotein testing, this NMR modality has been very useful in terms of biology and research, and I think that's the case here where we really go under the hood Carolyn, as you said, and get kind of deep dive, the lipid metalobles on abnormalities. And I think Parag and Aaron hit the nail in the head that this is really capturing an insulin resistance of phenotype and what I really liked about this is, instead of studying people who are 70, 80 years old and a lot of things are sort of clustering, a lot of diseases are clustering and they're manifesting all at the same time, it's very hard to tease apart the effective age.                                                 Here, we captured women in their 50s and middle aged, just as they have kind of gone through menopause and this adverse metabolite's phenotype starts to rise in women. And then we could follow them over time and see what the natural history of that is, and the women who have this phenotype go on to have this devastating consequence, this peripheral arterial disease. One of the questions I had then, Aaron for you is, what do you think the implications are from these findings? Does it mean that in terms of diagnostics, we should be doing more advanced testings looking at LDL and HDL type particles with NMR or some other mortality? Does it change therapies with new therapies beings studies right now? What do you think the implications are from your work? Dr Aaron Aday:                 That's important right. I think you mentioned this and I see the inter marked tool in this study, is really a way to try to dig further into the biology of peripheral artery disease as a form of atherosclerosis. I think that we already know patients who are extremely high risk or PAD, those are patients with diabetes, smoking history, metabolic syndrome et cetera., and as you can see in a patient population in 28,000 middle aged women who are pretty healthy, we only had just over a 100 PAD events.                                                 So, I think even if you were to scale this up in terms of cost, I'm not sure that that would necessarily be a viable option for patients, but I think it does suggest that truly focusing on LDL in a very high-risk patient population, meaning patients with PAD, or we may not be fully addressing their risk. And so I think this is a need to highlight that important gap, think about other therapeutic options and we'll soon have ongoing trials, triglyceride low in therapy that may be particularly beneficial in this patient population and so that's how I see this being used. Dr Anand Rohatgi:            That makes a lot of sense and particular because in middle aged women like this, your standard risk score algorithms will not really capture that they're at increased risk, even if they smoke, just because they're women and they're younger and so, I think this really is a call to arms to more refined risk assessment in these women. Dr Parag Joshi:                   Aaron, do you think there's actually a difference in the biology in the peripheral arteries compared to the coronary and cerebral vascular beds, or is there data to kind of look at that or maybe histopathological data to look at that? Dr Aaron Aday:                 We know there's a lot of overlaps, so I don't wanna suggest that PAD is not a former atherosclerosis. I think one limitation is that the primary animal model for PAD is the hyperCKemia model. That doesn't fully recapitulate what's happening in a limb with PAD and so I think that has been one limitation in understanding the biology. But I think what we're starting to see in some clinical trials that have come out in the last couple of years or starting to see a somewhat different signal for therapies in patients with PAD so for instance, in 48, we actually saw that there was a greater benefit to LDL lower [inaudible 00:21:00] inhibitors than for coronary disease. We now have the compass trial results, again, more events, higher risk among these patients but for their benefit, add on River Oxodine therapy, we've seen lymph events or lymph signals in the SGLP2 inhibitor trials. So, I think we're starting to get a sense that there may be something else on top of the traditional ascariasis biology that may be a potential target on down the road. Dr Parag Joshi:                   I think it's really a fascinating biological question of how these different territories might actually differ in their pathophysiology. I think it's a really a nice time to look at this. Also I think, Anand and Aaron both mentioned ongoing trials. The omega 3 fatty acid trials I think reduce it, will be soon to be presented and hopefully published in the next month or so. It would be nice to see if they evaluate peripheral events in that group, I'm sure they will. Dr Carolyn Lam:                Indeed, these have been just such great thoughts and discussion. Nothing really much to add there. I suppose I could say something cheeky like for the first time, and I never thought I'd say it on the podcast, I feel kind of bad that there are no men included in this trial but anyway, I just learnt so much from this. I just wanna thank you gentlemen for a great discussion.                                                 Thank you, listeners, for joining us today and don't forget to tune in again next week to Circulation on the Run.

You know the name, you've accepted the payment method. But, did you know that Paypal has a team of people focused solely on Small Business advocacy and public policy? Joining us today on the Small Business Show is Paul Disselkoen, Paypal Public Relations Specialist. Paul is charged with getting the voices of Small Business owners heard by politicians that are setting public policy that impacts Small Businesses throughout the country. Join your hosts Dave Hamilton and Shannon Jean to learn about what Paypal is doing to insure that it's not just the big companies that are sending lobbyists to Washington. You'll get a chance to find out about the Paypal Small Merchant Advisory Delegation and how YOU can join and get your message heard and get some great publicity for your Small Business. Paul takes us through the role that Paypal plays in helping to set policies that are favorable for Small Business owners and discusses the types of businesses they are looking for to connect with lawmakers locally, as well as in their annual trip to D.C. to connect with legislators on Capitol Hill. Listen in to learn more and find out how you can join the Small Merchant Advisory Board to protect and promote your Small Business. After the show, click over to the Small Business Support Group to share your thoughts about the show! Chapters/Timestamps 00:00:00 Small Business Show #124 June 21, 2017 00:00:49 Paul Disselkoen, PayPal Government Relations Specialist 00:02:45 Small Business Merchant Advocacy Delegation (SMAD) 00:03:48 Lobbying for Small Business - getting the voice of Small Business owners heard 00:05:26 Introducing SMB owners to their representatives in govt. 00:08:17 How do businesses join SMAD? Finding good stories from passionate SMB owners 00:09:28 What makes a good SMAD member? 00:11:09 Use PayPal to vet overseas suppliers 00:12:38 Using SMAD to overcome challenges Paypal SMB research report 00:17:00 Thought leaders in the Small Business area 00:18:21 PayPal hosts local events for Small Business Owners as well as trips to D.C. 00:19:24 Small Business Pitted Together with Politics 00:21:52 PayPal Public Policy on Twitter 00:24:05 Check the “Join” Link at PayPal.com/publicpolicy 00:24:34 SBS Outtro

Bob Mutchler returns to give us the low down on the NoPolio! rally. http://www.nopolio.orgAlso, the dangers of SMAD. If you'd like to help support Long Riders Radio, please visit our Patreon page. Thank you!

Das zugunsten von Matrix Metalloproteinasen (MMP) verschobene Proteasen/Inhibitoren-Verhältnis begründet unter anderem die Malignität von Nierenzellkarzinomen. „Tissue Inhibitor of Metalloproteinases 1“ (TIMP-1), ein löslicher Gewebeinhibitor für Metalloproteinasen der extrazellulären Matrix, kontrolliert die Aktivität von MMP durch 1:1 stochiometrische Bindung. Durch Fusion von humanen TIMP-1 mit einem Glykosylphosphatidylinositol- (GPI-)Anker wird die TIMP-1-Aktivität von der extrazellulären Matrix auf die Zelloberfläche verschoben und eine lokale Applikation von definierten TIMP-1-Konzentrationen ermöglicht. Mit TIMP-1-GPI behandelte Nierenkarzinomzellen zeigten im Vergleich zu Vehikel und nativen TIMP-1-Kontrollgruppen signifikant erhöhte Apoptose- und reduzierte Proliferationsraten. Ziel der Arbeit ist mithilfe von transkriptomischem Profiling und Signaltransduktionsweg-Mapping verantwortliche Genregulationsmechanismen für TIMP-1-GPI-spezifische Effekte zu identifizieren. Mithilfe dieser Techniken zeigten wir, dass eine TIMP-1-GPI-Behandlung zu einer signifikanten Änderung der Regulation von „Inhibitor der DNA Bindung“ (ID), TGF-β/SMAD und BMP Signaltransduktionswege führte. Die unterdrückte ID-Proteinexpression ist auf die durch TIMP-1-GPI gehemmte proteolytische Aktivierung von pro-TGF-β1 und dadurch verursachte reduzierte TGF-β1-Signalaktivität zurückzuführen. Eine mögliche Erklärung für die Überlegenheit von TIMP-1-GPI gegenüber nativem TIMP-1 ist die fokale Konzentration auf der Zelloberfläche, die eine effektivere Hemmung von autosezernierten TGF-β1 ermöglicht. Diese besonderen Eigenschaften von TIMP-1-GPI könnten in der Therapie von Nierenzellkarzinomen als Adjuvanz bei der modernen chirurgischen Nierenteilresektion oder bei der Therapie mit Angiogenese-Hemmern zunutze gemacht werden, um mögliche Tumorrezidive zu verhindern.

There was a dude recently who challenged atheists to prove god does not exist.  To illustrate the flaw in this thinking, I'm reminded of an old debate blog I did years ago.  A far less charismatic person gave me the exact same challenge.  This brought about a new religion I made up that involved a dragon in my pants, and the Super Mega Awesome Dragon, later dubbed the SMAD. Why is the demand to prove a negative stupid?  Why should extraordinary claims require extraordinary evidence?  Why does no one believe I have a dragon in my pants when no one can prove I don't have a dragon? Plus your calls. The SMAD aprroves

Tissue inhibitor of metalloproteinase 1 (TIMP-1) controls matrix metalloproteinase activity through 1:1 stoichiometric binding. Human TIMP-1 fused to a glycosylphosphatidylinositol (GPI) anchor (TIMP-1–GPI) shifts the activity of TIMP-1 from the extracellular matrix to the cell surface. TIMP-1–GPI treated renal cell carcinoma cells show increased apoptosis and reduced proliferation. Transcriptomic profiling and regulatory pathway mapping were used to identify the potential mechanisms driving these effects. Significant changes in the DNA binding inhibitors, TGF-β1/SMAD and BMP pathways resulted from TIMP-1–GPI treatment. These events were linked to reduced TGF-β1 signaling mediated by inhibition of proteolytic processing of latent TGF-β1 by TIMP-1–GPI.

Background: Bone Morphogenetic Protein (BMP)-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described. Methods: BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT)-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8) expression was quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-beta induced epithelial-to-mesenchymal transition (EMT), expression of TGF-beta receptor type I (TGF-beta RI) and phosphorylated Smad 2 (pSmad 2) as well as on TNF-alpha induced apoptosis of proximal tubular cells. Results: BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml) were able to reverse TNF-alpha-induced apoptosis and TGF-beta-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-beta RI. In addition, BMP-7 was able to reverse TGF-beta-induced phosphorylation of Smad 2. Conclusions: The findings suggest a protective role for BMP-7 by counteracting the TGF-beta and TNF-alpha-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease.

Oberst Tjulpanov stand seit 1945 der sowjetischen Besatzungsbehörde vor, welche die Parteien und gesellschaftlichen Organisationen, die Propaganda- und Publikationsorgane sowie den Kulturbetrieb in der Sowjetzone aufbaute und anleitete. In kurzen Abständen verfasste er schriftliche Berichte an seine Vorgesetzten in Berlin-Karlshorst, die diese meist nach Moskau weiterleiteten. Viele seiner Berichte gelangten zu Stalin, dem die deutschen Angelegenheiten äußerst wichtig waren. 1948 überprüfte eine hochrangige Untersuchungskommission des ZK der KPdSU die Tätigkeit Tjulpanovs und fasste seine zwischen 1945 und 1948 erstellten Stellungnahmen in einem Gesamtbericht zusammen. Dr. Gerhard Wettig hat diesen geheimen Bericht in einem Moskauer Archiv gefunden und mit Förderung der Bundesstiftung Aufarbeitung gemeinsam mit Dr. Wladislaw Hedeler ins Deutsche übersetzt, eingeleitet und kommentiert. Buchvorstellung und Diskussion mit Dr. Jörg Morré (Direktor des Deutsch-Russischen Museums Berlin-Karlshorst) und Dr. Gerhard Wettig (Historiker und Osteuropaexperte).

Oberst Tjulpanov stand seit 1945 der sowjetischen Besatzungsbehörde vor, welche die Parteien und gesellschaftlichen Organisationen, die Propaganda- und Publikationsorgane sowie den Kulturbetrieb in der Sowjetzone aufbaute und anleitete. In kurzen Abständen verfasste er schriftliche Berichte an seine Vorgesetzten in Berlin-Karlshorst, die diese meist nach Moskau weiterleiteten. Viele seiner Berichte gelangten zu Stalin, dem die deutschen Angelegenheiten äußerst wichtig waren. 1948 überprüfte eine hochrangige Untersuchungskommission des ZK der KPdSU die Tätigkeit Tjulpanovs und fasste seine zwischen 1945 und 1948 erstellten Stellungnahmen in einem Gesamtbericht zusammen. Dr. Gerhard Wettig hat diesen geheimen Bericht in einem Moskauer Archiv gefunden und mit Förderung der Bundesstiftung Aufarbeitung gemeinsam mit Dr. Wladislaw Hedeler ins Deutsche übersetzt, eingeleitet und kommentiert. Buchvorstellung und Diskussion mit Dr. Jörg Morré (Direktor des Deutsch-Russischen Museums Berlin-Karlshorst) und Dr. Gerhard Wettig (Historiker und Osteuropaexperte).