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Integration with YouTube's podcast API, the latest Castro app update; what is happening with my downloads stats? How to find out what is up when you see those ups and downs; real time news about Gaana; talking about what's up with section 230; answering more questions about YouTube and podcasts; clean vs explicit; formatting your podcast shownotes; another mean and median download update!
Integration with YouTube's podcast API, the latest Castro app update; what is happening with my downloads stats? How to find out what is up when you see those ups and downs; real time news about Gaana; talking about what's up with section 230; answering more questions about YouTube and podcasts; clean vs explicit; formatting your podcast shownotes; another mean and median download update!
In the In Conversation With series, a part of the free DDW podcast, DDW speaks with members of the drug discovery industry about their work and how it helps turn science into business. In this episode, Megan Thomas is in conversation with Steve Worland, CEO of eFFECTOR. eFFECTOR is a company targeting three distinct targets central to the eIF4F translation initiation complex: MNK, eIF4A and eIF4E. Each of these targets regulates distinct sets of genes in cancer and immune cells. Dr Worland has significant experience as a scientist and C-suite level executive/entrepreneur, and today speaks about how Selective Translation Regulator Inhibitors (STRIs) are unique to other cancer treatments, the future of the industry as well as the significance of pharma collaboration in the development process. You can find the Drug Discovery World Podcast on Spotify, Google Play and Apple Podcasts.
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I read from effective to effervesce. Effector https://en.wikipedia.org/wiki/Effector_(biology) The word of the episode is "effervesce". Theme music from Jonah Kraut https://jonahkraut.bandcamp.com/ Merchandising! https://www.teepublic.com/user/spejampar "The Dictionary - Letter A" on YouTube "The Dictionary - Letter B" on YouTube "The Dictionary - Letter C" on YouTube "The Dictionary - Letter D" on YouTube Featured in a Top 10 Dictionary Podcasts list! https://blog.feedspot.com/dictionary_podcasts/ Backwards Talking on YouTube: https://www.youtube.com/playlist?list=PLmIujMwEDbgZUexyR90jaTEEVmAYcCzuq dictionarypod@gmail.com https://www.facebook.com/thedictionarypod/ https://www.threads.net/@dictionarypod https://twitter.com/dictionarypod https://www.instagram.com/dictionarypod/ https://www.patreon.com/spejampar https://www.tiktok.com/@spejampar 917-727-5757
This week's podcast is sponsored by Vetter.On this week's episode, we have a conversation with Steve Worland, CEO of eFFECTOR Therapeutics.eFFECTOR is a clinical-stage biopharmaceutical company pioneering the development of a new class of oncology drugs referred to as STRIs (selective translation regulation inhibitors). eFFECTOR's STRI product candidates target the eIF4F complex and its activating kinase, mitogen-activated protein kinase interacting kinase (MNK). The eIF4F complex is a central node where two of the most frequently mutated signaling pathways in cancer, the PI3K-AKT and RAS-MEK pathways, converge to activate the translation of select mRNA into proteins that are frequent culprits in key disease-driving processes. The company's product candidates are designed to act on a single protein that drives the expression of a network of functionally related proteins, including oncoproteins and immunosuppressive proteins in T cells, that together control tumor growth, survival and immune evasion. The lead product candidate, tomivosertib, is an MNK inhibitor currently being evaluated in KICKSTART, a randomized, double-blind, placebo-controlled phase 2b trial of tomivosertib in combination with pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC). Zotatifin, eFFECTOR's inhibitor of eIF4A, is currently being evaluated in phase 2a expansion cohorts in certain biomarker-positive solid tumors, including ER+ breast cancer and KRAS-mutant NSCLC. eFFECTOR has a global collaboration with Pfizer to develop inhibitors of a third target, eIF4E.
In the 24th episode of our Immunology 101 series, Ash and Jatin discuss the various effector functions of Antibodies
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.24.550339v1?rss=1 Authors: Shaughnessy, R., Serres, M., Escot, S., Hammich, H., Cuvelier, F., Salles, A., Rocancourt, M., Verdon, Q., Gaffuri, A.-L., Sourigues, Y., Malherbe, G., Velikovsky, L., Chardon, F., Tinevez, J.-Y., Callebaut, I., Formstecher, E., Houdusse, A., David, N., Pylypenko, O., Echard, A. Abstract: Cilia protrude from the cell surface and play critical roles in intracellular signaling, environmental sensing and development. Actin-dependent contractility and intracellular trafficking are both required for ciliogenesis, but little is known about how these processes are coordinated. Here, we identified a Rac1- and Rab35-binding protein with a truncated BAR domain that we named MiniBAR (aka KIAA0355/GARRE) which plays a key role in ciliogenesis. MiniBAR colocalizes with Rac1 and Rab35 at the plasma membrane and on intracellular vesicles trafficking to the ciliary base and exhibits remarkable fast pulses at the ciliary membrane. MiniBAR depletion leads to short cilia resulting from abnormal Rac-GTP/Rho-GTP levels, increased acto-myosin-II-dependent contractility together with defective trafficking of IFT88 and ARL13B into cilia. MiniBAR-depleted zebrafish embryos display dysfunctional short cilia and hallmarks of ciliopathies including left-right asymmetry defects. Thus, MiniBAR is a unique dual Rac and Rab effector that controls both actin cytoskeleton and membrane trafficking for ciliogenesis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.12.548606v1?rss=1 Authors: Oliveira, M. M., Mohamed, M. S., Elder, M. K., Banegas-Morales, K., Mamcarz, M., Lu, E. H., Golhan, E. A. N., Navrange, N., Chatterjee, S., Abel, T., Klann, E. Abstract: Neuronal protein synthesis is required for long-lasting plasticity and long-term memory consolidation. Dephosphorylation of eukaryotic initiation factor 2 is one of the key translational control events that is required to increase de novo protein synthesis that underlies long-lasting plasticity and memory consolidation. Here, we interrogate the molecular pathways of translational control that are triggered by stimulation of neurons with brain-derived neurotrophic factor (BDNF), which results in eIF2 dephosphorylation and de novo protein synthesis. Primary rodent neurons exposed to BDNF displayed elevated translation, but not transcription, of GADD34, which facilitates eIF2 dephosphorylation and subsequent de novo protein synthesis. Furthermore, GADD34 requires G-actin generated by cofilin to dephosphorylate eIF2 and enhance protein synthesis. Finally, GADD34 is required for the BDNF-induced translation of synaptic plasticity-related proteins. Overall, we provide evidence that neurons repurpose GADD34, an effector of the Integrated Stress Response, as an orchestrator of rapid increases in eIF2-dependent translation in response to plasticity-inducing stimuli. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Influencers often inspire or guide the actions of others by posting about something (such as a consumer product or service) that they use or endorse based on brand partnerships. And today's episode is a sure shot response to Sue Duffield's recent "Effector" award of Top Influencer, but what she initially read was "Influenza!" The most all-inclusive definition of an influencer is a person who has the ability to influence others. So, a politician making a speech, a business expert leading a seminar, and a celebrity endorsing a product are all technically influencers, and yes even pastors, singers and keynote speakers. An infectious personality, like Sue, may know a lot, but an individual still needs the ability to advocate, sell and drum up enthusiasm. Influencers normally have high engagement rates with their audience (in person or on-line), taking on a hands-on approach with their people, showing great care, and always looking to serve their needs to better understand them. So, just how important is it to be an effective influencer for the Kingdom's sake? Everything. Let Jesus shine SO much in your life that you're infectious and that you get reports of your influence - from all generations. www.sueduffield.com
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.10.536314v1?rss=1 Authors: Gherman, S., Markowitz, N., Tostaeva, G., Espinal, E., Mehta, A. D., O'Connell, R. G., Kelly, S. P., Bickel, S. Abstract: Neural representations of perceptual decision formation that are abstracted from specific motor requirements have previously been identified in humans using non-invasive electrophysiology, however, it is currently unclear where these originate in the brain. Here, we capitalized on the high spatiotemporal precision of intracranial EEG to localize such abstract decision signals. Presurgical epilepsy patients judged the direction of random-dot stimuli and responded either with a speeded button press (N=23), or vocally, after a randomized delay (N=11). We found a widely distributed motor-independent network of regions where high-frequency activity exhibited key characteristics consistent with evidence accumulation, including a gradual build-up that was modulated by the strength of the sensory evidence, and an amplitude that predicted subjects' choice accuracy and response time. Our findings offer a new view on the brain networks governing human decision making. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Object Worship launches on all major podcast platforms on March 30th, with new episodes of season one arriving every two weeks. To listen directly, go to oldbloodnoise.com/objectworship
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.23.533139v1?rss=1 Authors: Cocom-Chan, B., Khakzad, H., Valencia-Gallardo, C., Zarrouk, Y., Tran Van Nhieu, G. Abstract: Vinculin is a component of focal adhesions strengthening integrin receptors association to the actin cytoskeleton during mechanotransduction. While vinculin activation leading to its association with actin filaments has been particularly studied, the role and mechanism of vinculin oligomerization remain unclear. The Shigella IpaA effector binds to vinculin to promote efficient bacterial invasion of host cells. Unlike canonical activating ligand, IpaA interacts with the vinculin subdomains D1 and D2 via its three Vinculin Binding Sites (VBSs), promoting major allosteric changes leading to D1D2 domain-mediated trimerization. Here, we built on structural models of allosteric conformers of D1D2:IpaA complexes to design mutations and analyzed their effects on IpaA-induced trimer formation using native gel shift assays. We show that charge inversions, mutations affecting polar interactions at residues in D1D2 interfacing IpaA VBS3 and targeting a distal putative coiled-coil motif in D2 reduced the rates of D1D2 trimer formation. Introduction of these mutations in full-length vinculin led to a decrease in the number and size of focal adhesions, with distinct elongated focal adhesions associated with the coiled-coil mutation. These findings suggest that IpaA hijacks a cell endogenous head-domain mediated vinculin oligomerization process involved in the maturation of focal adhesion. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
In part 2 of a 2-part series, Dr. Claudia Zbrzeski discusses the relevant labs, imaging, and EEG data seen in ICANS, as well as prevention and treatment strategies.
In part 1 of a 2-part series, Dr. Andy (Ho Wing) Chan discusses the clinical recognition and diagnosis of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.27.530266v1?rss=1 Authors: Raj, D., Nair, A. V., Sharma, J., Prakash, S., Kaushik, A., Basu, S., Sahu, S., Singh, S., Bhosale, V., Chandra, T., Ghoshal, U. C., Dasgupta, A., Siddiqi, M. I., Gupta, S. K., Chakravortty, D., Ammanathan, V., LAHIRI, A. Abstract: Intracellular Salmonella resides and multiplies in cholesterol-rich specialized compartment called Salmonella-containing vacuoles (SCVs) and avoids fusion with acidic lysosomes. Given, lysosomes are primary organelle that redistributes LDL derived cholesterol to other organelles; we questioned how lysosomal cholesterol can be transported to SCV. We demonstrate here that peroxisomes are recruited to SCVs in human primary macrophages, epithelial cells and functions as pro-bacterial organelles. Further, this interaction is assisted by SseI, a Salmonella effector protein containing mammalian peroxisome targeting sequence. SseI localizes to peroxisome, interacts and activates a host Ras GTPase, ARF-1 on the peroxisome membrane. Activation of ARF-1 leads to recruitment of phosphatidylinsolitol-5-phosphate-4 kinase to generate phosphatidylinsolitol-4-5-bisphosphate on peroxisomes. Accordingly, the {Delta}sseI strain showed reduced virulence in cell lines and during mice infection. Taken together, our work identified a fascinating mechanism by which a pathogen targets host organelles via its secretory effectors and exploits host metabolic intermediates for its intracellular proliferation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
In this bonus episode Associate Editor, Dr. Helen Heslop discusses Banked Allogeneic Immune Effector Cells with Blood Author Dr. Jeffrey Miller.
References Authentic Biochemistry Podcast Immunoepigenetics lectures XXIX-XXX1 Dr. Guerra's intermediary metabolism and bioenergetics lectures Nature. 2019 Jul; 571(7765): 403–407 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
What if most of difficulties we have in our life are caused by the lack of acknowledgment of how different we already are? Sweet friends and listeners, the time has come for us to stop making ourselves less and giving ourselves up for the judgments coming from the world around us. Trying to live by other people's standards and considerations of what's right and wrong will never work for you. It will never be enough for you. Plus, it puts you in a constant state of reaction to whatever someone else thinks. How effective can you actually be when you let others' reactions determine your choices? Join our host, Sarah Grandinetti, and our amazingly different guest, Cara Wright, while they explore how it is actually imperative to claim, own, and acknowledge the gift and power of your difference. To not change who you are so that others can be comfortable. And, to be willing to approach every new adventure with as much vulnerability as we can while never giving ourselves up. Do you desire to be at the effect of your environment or be the effector of it? Take aways - Interrupt the judgment pattern of wrongness by asking: what's right about me I'm not getting? - Be willing to honor you, stop pretending that you are normal and the same as anyone else. You Are Different. - Ask: Is this choice going to create the future I'm asking for?
Сергей Сова, фронтенд-инженер в Selzy и мэйнтейнер Effector'а, в гостях у Андрея Смирнова из Frontend Weekend. Про подход в автоматизации тестирования AvitoTech читайте в Playbook: http://bit.ly/3jsPRyP 00:00 Начало 00:36 Чем можешь быть известен моей аудитории? 01:13 Соседское соглашение в Авито 02:05 Почему даунгрейднулся с руководителя до фронтендера? 04:40 Как пришёл в программирование и попал во фронтенд? 10:04 Сложно ли дался переход в тимлиды и руководители? 13:02 Почему заинтересовался Эффектором и как стал его мэйнтейнером? 18:52 Как февральские события повлияли на распорядок дня и поддержку Эффектора? 23:10 Как и зачем придумал три связанных стартапа и в каком они состоянии? 31:20 Что означает быть в core-команде feature-sliced design и зачем это тебе? 34:31 Почему важна архитектура во фронтенде и встречал ли примеры хорошей? 37:18 Зачем был создан подкаст «Под куполом» и почему он такой личный? 40:05 Что с ютуб-каналом и на что делаешь ставку в будущем подобном творчестве? 43:29 Кем бы ты стал, если бы не стал разработчиком? 45:17 Почему стоит приехать в Пятигорск? 46:35 Тяжело ли дался вынужденный переезд в Ереван? 50:30 В чём сейчас главная проблема современного IT? 51:09 Готовим вместе с фронтенд-разработчиком 53:40 Совет от Серёжи Ссылки по теме: 1) Личный сайт Серёжи – https://sova.dev/ 2) Обсуждаемый выпуск подкаста «307 пакетов» с Серёжей – https://youtu.be/QtsH31LD79c 3) Выпуск блога «Съебастьян» про переезд Серёжи в Ереван – https://youtu.be/s6atItVtGxE 4) Подкаст «Под Куполом» – https://podcast.ru/1586738556 5) Выпуск Подлодки про архитектуру во фронтенде – https://podlodka.io/286 6) Гитхаб Эффектора – https://github.com/effector/effector
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.31.525875v1?rss=1 Authors: Rodriguez-Silvestre, P., Laub, M., Davies, A. K., Schessner, J. P., Krawczyk, P. A., Tuck, B. J., McEwan, W. A., Borner, G. H. H., Kozik, P. Abstract: During initiation of antiviral and antitumour T cell-mediated immune responses, dendritic cells (DCs) cross-present exogenous antigens on MHC class I. Cross-presentation relies on the unique leakiness of endocytic compartments in DCs, whereby internalised proteins escape into the cytosol for proteasome-mediated generation of MHC I-binding peptides. Given that type 1 conventional DCs excel at cross-presentation, we searched for cell-type specific effectors of endocytic escape. We devised an escape assay suitable for genetic screening and identified a pore-forming protein, perforin-2, as a dedicated effector exclusive to cross-presenting cells. Perforin-2 is recruited to antigen-containing compartments, where it undergoes maturation, releasing its pore-forming domain. Mpeg1-/- mice fail to efficiently prime CD8+ T cells to cell-associated antigens, revealing an important role of perforin-2 in cytosolic entry of antigens during cross-presentation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Dr. Rachna Malani discusses the potential neurotoxicity associated with CAR-T therapy.
Dr. Derek Stitt talks with Dr. Rachna Malani, about the potential neurotoxicity associated with CAR-T therapy.
Der Smart Flex Effector ist ein Ausgleichselement mit aktiver Messfunktion in sechs Freiheitsgraden. Er erhöht die Präzision, z.B. bei Handlingsrobotern und erschließt ganz neue Einsatzgebiete für Industrieroboter und kartesische Systeme. Mehr zum SFE https://www.boschrexroth.com/de/de/produkte/produktgruppen/lineartechnik/smart-flex-effector Wir sagen Danke zu unserem Partner, dem Deutschen Robotik Verband https://www.robotikverband.de Fragen oder Ideen zur Robotik in der Industrie? helmut@robotikpodcast.de oder robert@robotikpodcast.de
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.26.513940v1?rss=1 Authors: Gordon, E. M., Chauvin, R. J., Van, A. N., Rajesh, A., Nielsen, A., Newbold, D. J., Lynch, C. J., Seider, N. A., Krimmel, S. R., Scheidter, K. M., Monk, J., Miller, R. L., Metoki, A., Montez, D. F., Zheng, A., Elbau, I., Madison, T., Nishino, T., Myers, M. J., Kaplan, S., D'Andrea, C. B., Demeter, D. V., Feigelis, M., Barch, D. M., Smyser, C. D., Rogers, C. E., Zimmerman, J., Botteron, K. N., Pruett, J. R., Willie, J. T., Brunner, P., Shimony, J. S., Kay, B. P., Marek, S., Norris, S. A., Gratton, C., Sylvester, C. M., Power, J. D., Liston, C., Greene, D. J., Roland, J. L., Petersen, S. E., Rai Abstract: Primary motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down precentral gyrus from foot to face representations1,2. The motor homunculus has remained a textbook pillar of functional neuroanatomy, despite evidence for concentric functional zones3 and maps of complex actions4. Using our highest precision functional magnetic resonance imaging (fMRI) data and methods, we discovered that the classic homunculus is interrupted by regions with sharpy distinct connectivity, structure, and function, alternating with effector-specific (foot, hand, mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, and to prefrontal, insular, and subcortical regions of the Cingulo-opercular network (CON), critical for executive action5 and physiological control6, arousal7, and processing of errors8 and pain9. This inter-digitation of action control-linked and motor effector regions was independently verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant, child) precision fMRI revealed potential cross-species analogues and developmental precursors of the inter-effector system. An extensive battery of motor and action fMRI tasks documented concentric somatotopies for each effector, separated by the CON-linked inter-effector regions. The inter-effector regions lacked movement specificity and co-activated during action planning (coordination of hands and feet), and axial body movement (e.g., abdomen, eyebrows). These results, together with prior work demonstrating stimulation-evoked complex actions4 and connectivity to internal organs (e.g., adrenal medulla)10, suggest that M1 is punctuated by an integrative system for implementing whole-body action plans. Thus, two parallel systems intertwine in motor cortex to form an integrate-isolate pattern: effector-specific regions (foot, hand, mouth) for isolating fine motor control, and a mind-body interface (MBI) for the integrative whole-organism coordination of goals, physiology, and body movement. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
An increasingly reasonable question for the musician is the approach to effects pedals. Do I go the traditional route, building a pedal board with specific pedals for specific tones or do I instead consider an all in one multi-effects device? Things have changed a lot in the last decade. The sound quality from multi-effectors has improved massively as has the overall quality of the effects. Latency is not the problem it once was, and digital processing makes it nigh impossible to tell the original pedal from its digital alternative. Let's look at pros and cons of both routes.
In cancer, the rigorous translational machinery of the human body goes haywire, causing an overproduction of proteins that fuel the growth and spread of tumors, as well as enabling them to evade the immune system. Effector Therapeutics is developing a new class of cancer therapies called selective translation regulator inhibitors, or STRIs, that can inhibit the production of proteins that drive a cancer. We spoke to Steve Worland, president and CEO of Effector, about the company's new class of therapies, how they target a central node where two major cancer signaling pathways converge, and how they pack the punch of a combination therapy in a single drug.
Today we'll learn more about the risk of subsequent malignancies in patients treated with genetically modified immune effector cells, discuss how p53 immunohistochemistry can be a global readout for TP53 alterations in AML, and uncover the role of CD19-negative CD22-positive B-cell progenitors in immune escape from CD19-directed therapies.
A new year brings new libraries and state machines, so if you'd rather not be confused, this episode's for you. In this one, the team covers React's most significant improvements, how to avoid losing your mind over state machines, and what libraries to peruse in 2022. In This Episode Why React's improvements made THIS feature irrelevant for most cases The team's solution for people wanting more than just juggling API's all day (and why it's a big win for storage and data migration) If you're into spreadsheets, we bet you'll LOVE using THIS library Want to learn a new, intuitive library in 2022? Jack's got you covered How to avoid the NIGHTMARE of complication with state machines Sponsors Top End Devs (https://topenddevs.com/) Raygun | Click here to get started on your free 14-day trial (https://raygun.com/?utm_medium=podcast&utm_source=reactroundup&utm_campaign=devchat&utm_content=homepage) Coaching | Top End Devs (https://topenddevs.com/coaching) Links useSWR (https://swr.vercel.app/) React Query (https://react-query.tanstack.com/) RTK Query Overview | Redux Toolkit (https://redux-toolkit.js.org/rtk-query/overview) Recoil (https://recoiljs.org/) Jotai (https://jotai.org/) Zustand (https://zustand.surge.sh/) GitHub - pmndrs/valtio (https://github.com/pmndrs/valtio) Akita | Reactive State Management (https://datorama.github.io/akita/) Effector (https://effector.dev/) Picks Jack- AirPods Max - Apple (https://www.apple.com/airpods-max/) Paige- Watch The Witcher | Netflix Official Site (https://www.netflix.com/title/80189685) TJ- Sonic the Hedgehog (https://www.imdb.com/title/tt3794354/)
Dr. Steve Worland is President and CEO of eFFECTOR Therapeutics a pioneer in the Genomics 3.0 category putting to work the research on selective translation regulator inhibitors (STRIs) and the key ways that cancer cells change their behavior and also change the immune system. Steve says, "There are two revolutions in cancer in the last 10 to 15 years-- targeted therapies and immunotherapies. And we think STRIs is a third way to compliment one or both of those. And really with the idea here is that you could control a cancer for a long period of time. It's very hard to completely eradicate every tumor and every cancer cell in your body. "But if you can restore control, your immune system can control the cancer. Hopefully, patients can live for years knowing they have the disease but not having it debilitate their daily life." #eFFECTORTherapeutics #NSCLC #STRIs #cancer #SPAC eFFECTOR.com Download the transcript here
Dr. Steve Worland is President and CEO of eFFECTOR Therapeutics a pioneer in the Genomics 3.0 category putting to work the research on selective translation regulator inhibitors (STRIs) and the key ways that cancer cells change their behavior and also change the immune system. Steve says, "There are two revolutions in cancer in the last 10 to 15 years-- targeted therapies and immunotherapies. And we think STRIs is a third way to compliment one or both of those. And really with the idea here is that you could control a cancer for a long period of time. It's very hard to completely eradicate every tumor and every cancer cell in your body. "But if you can restore control, your immune system can control the cancer. Hopefully, patients can live for years knowing they have the disease but not having it debilitate their daily life." #eFFECTORTherapeutics #NSCLC #STRIs #cancer #SPAC eFFECTOR.com Listen to the podcast here
J Immunol August 1, 2017, 199 (3) 874-884 Ann Rev Cell Dev Biol 2018. 34:111-136 Blood. 2016 Apr 14;127(15):1930-9 J BiolChem. 2017 Aug 25; 292(34): 14292–14307 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
In life sometimes we are affected by our current circumstances and allow ourselves to feel like there is no other way. The answer is to switch your pattern of thinking from being affected to becoming an effector.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.28.356139v1?rss=1 Authors: Ahmad, S., Tsang, K. K., Sachar, K., Quentin, D., Tashin, T. M., Bullen, N. P., Raunser, S., McArthur, A. G., Prehna, G., Whitney, J. C. Abstract: Type VI secretion systems facilitate the delivery of antibacterial effector proteins between neighbouring Gram-negative bacteria. A subset of these effectors harbor N-terminal transmembrane domains (TMDs) implicated in effector translocation across the target cell membrane. However, the abundance and distribution of these TMD-containing effectors has remained unknown. Here we report the discovery of prePAAR, a conserved motif found in over 6,000 putative TMD-containing effectors. Based on their differing sizes and number of TMDs these effectors fall into two distinct classes that are unified by their requirement for a member of the Eag family of T6SS chaperones for export. Co-crystal structures of class I and class II effector TMD-chaperone complexes from Salmonella Typhimurium and Pseudomonas aeruginosa, respectively, reveals that Eag chaperones mimic transmembrane helical packing to stabilize effector TMDs. In addition to participating in the chaperone-TMD interface, we find that prePAAR functions to facilitate proper folding of the downstream PAAR domain, which is required for effector interaction with the T6SS spike. Taken together, our findings define the mechanism of chaperone-assisted secretion of a widespread family of T6SS membrane protein effectors. Copy rights belong to original authors. Visit the link for more info
Cell therapy involves the transplantation of viable cells into a patient in order to trigger a medicinal effect. CAR-T is... The post Advances in CAR-T and cellular therapy from EBMT 2020: MSCs, clinical trial updates and gene-edited effector cells appeared first on VJHemOnc.
Cell therapy involves the transplantation of viable cells into a patient in order to trigger a medicinal effect. CAR-T is... The post Advances in CAR-T and cellular therapy from EBMT 2020: MSCs, clinical trial updates and gene-edited effector cells appeared first on VJHemOnc.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.16.300624v1?rss=1 Authors: Zhang, S., Wang, Y., Zhu, X., Song, L., Ma, E., McDonough, J., Fu, H., Cambi, F., Grinspan, J., Guo, F. Abstract: Promoting oligodendrocyte differentiation represents a promising option for remyelination therapy for treating the demyelinating disease multiple sclerosis (MS). The Wnt effector TCF7l2 was upregulated in MS lesions and had been proposed to inhibit oligodendrocyte differentiation. Recent data suggest the opposite yet underlying mechanisms remain elusive. Here we unravel a previously unappreciated function of TCF7l2 in controlling autocrine bone morphogenetic protein (BMP4)-mediated signaling. Disrupting TCF7l2 results in oligodendroglial-specific BMP4 upregulation and canonical BMP4 signaling activation in vivo. Mechanistically, TCF7l2 binds to Bmp4 gene regulatory element and directly represses its transcriptional activity. Functionally, enforced TCF7l2 expression promotes oligodendrocyte differentiation by reducing autocrine BMP4 secretion and dampening BMP4 signaling. Importantly, compound genetic disruption demonstrates that oligodendroglial-specific BMP4 deletion rescues arrested oligodendrocyte differentiation elicited by TCF7l2 disruption in vivo. Collectively, our study reveals a novel connection between TCF7l2 and BMP4 in oligodendroglial lineage and provides new insights into augmenting TCF7l2 for promoting remyelination in demyelinating disorders such as MS. Copy rights belong to original authors. Visit the link for more info
В этом выпуске у нас в гостях был Илья Лесик, соорганизатор tver.io, сооснователь Lessmess и Additivka, автор библиотеки react-figma Контакты Илья: Twitter: https://twitter.com/ilialesik Сайт: https://lesik.dev/ Шоуноты: ⁃ Из C++ и Java в JavaScript (02:00) ⁃ О работе в lessmess.agency (05:02) ⁃ Effector или Redux? Проблемы state manager'ов текущего поколения (06:20) ⁃ Об образовательном проекте Additivka (21:48) ⁃ Обучение 3d-печати через настольную игру (24:00) ⁃ react-figma: рендеринг мокапов фирмы при помощи react-компонентов (26:48) ⁃ Об основании и текущем положении дел в Tver.IO (36:16) ⁃ О жизни в Твери (44:30) Доп. cсылки: Lessmess Agency - lessmess.agency Образовательный проект “Additivka” - https://additivka.ru/ 3D-печать в помощь врачам - https://makersvscovid.ru/ Effector - https://github.com/zerobias/effector Tver.IO - https://tver.io/ Youtube-канал Tver.IO - https://www.youtube.com/c/TverIO?sub_confirmation=1 Обсуждение стейт менеджеров - https://www.youtube.com/watch?v=cUSyJk6k2rk React-figma - https://github.com/react-figma/react-figma Использование OpenAI вместе с react-figma - https://twitter.com/sonnylazuardi/status/1282626069095280642 Telegram—канал CSSSR: https://t.me/csssr Twitter CSSSR: https://twitter.com/csssr_dev Telegram ведущего: https://t.me/sgolovin Twitter ведущего: https://twitter.com/_sgolovin Telegram редакции: https://t.me/Vindizh Twitter редакции: https://twitter.com/Vindizh
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.03.234963v1?rss=1 Authors: Black, M. H., Osinski, A., Gradowski, M., Servage, K. A., Pawłowski, K., Tagliabracci, V. S. Abstract: ADP-ribosyltransferases (ARTs) are a widespread superfamily of enzymes frequently employed in pathogenic strategies of bacteria. Legionella pneumophila, the causative agent of Legionnaires disease, has acquired over 330 translocated effectors that showcase remarkable biochemical and structural diversity. Here we took a bioinformatic approach to search the Legionella effector repertoire for additional divergent members of the ART superfamily and identified an ART domain in Lpg0181. We show that L. pneumophila Lpg0181 targets a specific class of 120-kDa NAD+-dependent glutamate dehydrogenase (GDH) enzymes found in fungi and protists, including many natural hosts of Legionella. Lpg0181 targets a conserved arginine residue in the NAD+ -binding pocket of GDH, thereby blocking oxidative deamination of glutamate. While intracellular pathogens employ diverse virulence mechanisms to overcome host-limited nutrient availability, Lpg0181 is to the best of our knowledge the first example of a Legionella effector which directly targets a host metabolic enzyme. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.31.231399v1?rss=1 Authors: Zhou, Y., Bravo, J. P. K., Taylor, H. N., Steens, J., Jackson, R. N., Staals, R. H. J., Taylor, D. W. Abstract: We reveal the structure of a type IV-B CRISPR effector (Csf) complex at 3.9 a resolution using cryo-electron microscopy. The complex resembles the type III-A CRISPR Csm effector complex, but lacks subunits for RNA processing and target DNA cleavage, and is surprisingly assembled upon heterogeneous non-CRISPR RNA. These findings provide the first glimpse into the assembly and function of enigmatic type IV CRISPR systems. Copy rights belong to original authors. Visit the link for more info
The Latest Malaria News, in 60 Seconds. Enhancing antibody induction may improve the protective efficacy of RTS,S and researchers find that more gametocytes are produced when human infection is initiated by blood-stage parasites compared to mosquito bite. More: www.fightmalaria.uk/MalariaMinute
Marty Wolff and PSA’s Mike McHale discuss solving challenging and unique material handling applications with CEO Carl Vause of Soft Robotics (www.softroboticsinc.com). Soft Robotics offers robotic gripping systems made of highly compliant material that can safely and effectively grasp items of varying size, shape and weight with the same tool. Soft Robotics specializes in handling material that previously could only be picked up with the human hand and is not suitable for traditional foam compression or vacuum suction cup end effector solutions. Carl and Mike also discuss staffing small businesses with a variety of talent and partnering with a network of resources within the automation and manufacturing industries to help adapt to ever changing customer needs and grow the business.
At just 23 years old, Karl O'Brien has built his social media company into a global brand employing 8 people. Karl shares his views on selecting your clients, not letting your clients choose you. As a young entrepreneur, Karl started his first venture in his bedroom before using his college years to rapidly grow his business. We chat about habits that help him perform at the highest level and how he seeks mentors to avoid repeating their mistakes.
Nels and Vincent look at the intracellular bacteria Legionella from an evolutionary perspective: the role of gene acquisition and reshuffling from plants, animals, fungi, and archaea in the emergence of human pathogens. Hosts: Nels Elde and Vincent Racaniello Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiEVO Over 18,000 effectors in Legionella genome (PNAS) Carmen Buchrieser lab Howard Shuman Science Picks Nels - Science in Film (twitter) Vincent - Lunar Eclipse 101 Music on TWiEVO is performed by Trampled by Turtles Send your evolution questions and comments to twievo@microbe.tv
[easy_media_download url=”http://archive.org/download/BestEffector/LDP614.mp3″] On today’s podcast Lou and Andrea go over the highlights ... Read More
Dr. Jack West reviews provocative biomarker results on the IMpower150 trial that tested atezolizumab with carboplatin/paclitaxel +/- bevacizumab & revealed strongest benefit of atezo in those with T effector gene signature high expression or high PD-L1.
The author and audience of Hebrews are not known for sure. Apollos is a possible candidate for the authorship of Hebrews. Some believe Prisca wrote Hebrews. In Hebrews 6, the people are instructed in the Christian faith. In Hebrews 10 we find the people were faithful through a time of suffering. The suffering of the people is causing some concern. Consider that the main theme is a warning not to neglect so great a salvation. In Hebrews 2 we have the conversion of the audience. In Hebrews 3:1-6 we are shown that Jesus is superior to Moses and the Prophets. Hebrews 9-10 contains Jesus as the Final Sacrifice and Effector of Redemption. Hebrews shows us that Jesus is the final Word and fulfillment of prophecy. Explore that there are warning sections between sections that celebrate Jesus. The first warning is Hebrews 2:1-4 which is in-between Jesus as superior to the angels and to Moses. The second warning is in Hebrews 3:7 -4:13 in-between Jesus as superior to Moses and Jesus as the Great High Priest. The third warning is in Hebrews 5:11-6:12 which is in-between Jesus as Great High Priest and after the order of Melchizedek. The forth warning is in Hebrews 10:22-36 which is in-between the superior New Covenant and Faith Hall of Fame.
On this edition of Nuthin But Fantasy hosts Andrea LaMont and Phil Naessens discuss Andrea's published article in the 2017 Fantasy Baseball Guide called "The Effector" and whether or not drafting an effector is a good idea or not, the NFBC Leagues and how to be successful in them, dead to me Fantasy Baseball players and much more.
Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin The TWiP trio solve the case of the bug bites all in a row, and talk about a secreted Toxoplasma protein that is central to the parasite's manipulation of host cells. Subscribe to TWiP (free) in iTunes, Google Play Music, by the RSS feed or by email Links for this episode: Pigeon mites feed on humans at night (EPA) Secreted Toxoplasma protein (mBio) Image credit Letters read on TWiP 111 This episode is sponsored by CuriosityStream, a subscription streaming service that offers over 1,400 documentaries and nonfiction series from the world's best filmmakers. Get unlimited access starting at just $2.99 a month, and for our audience, the first two months are completely free if you sign up at curiositystream.com/microbe and use the promo code MICROBE. Case Study for TWiP 111 82 yo woman living in Washington Heights NYC 10 days of watery diarrhea, not smelly, does not float. Wakes her up at night. No fever, sweats at night. Losing some weight, appetite. No recent travel. Born in DR early 1930s, moved to US age 30. Sometimes goes back but not for several years. Springtime. Lives with extended family, only one sick. Eats whole assortment of cooked foods, rice, beans, fresh fruits. Drinks tap water. Not working. No pets. Stays mostly inside. History of reflux, high blood pressure, cognitive decline, diagnosed with temporal giant cell arteritis. Put on prednisone, doing better. Has had gall bladder removed. HIV negative. Extended family works in city, no taxi drivers. Belly uncomfortable for >week. Temp 38.1, BP 116/78, HR 105, breathing 12/min. Exam: looks ill, has diffusely tender abdomen, decreased bowel sounds. Liver, spleen not enlarged. Oriented. Has rash on abdomen: odd patchy distribution, looks like multiple thumbprints, front of belly, extending from umbilicus. White count 8, 78 polys, 14 lymphs, 4 mono, 1 eosinophil. Sodium 129, BUN 15, Creat 0.6. Urine histoplasma negative, TB test negative. Send your case diagnosis, questions and comments to twip@microbe.tv
The author and audience of Hebrews are not known for sure. Apollos is a possible candidate for the authorship of Hebrews. Some believe Prisca wrote Hebrews. In Hebrews 6, the people are instructed in the Christian faith. In Hebrews 10 we find the people were faithful through a time of suffering. The suffering of the people is causing some concern. Consider that the main theme is a warning not to neglect so great a salvation. In Hebrews 2 we have the conversion of the audience. In Hebrews 3:1-6 we are shown that Jesus is superior to Moses and the Prophets. Hebrews 9-10 contains Jesus as the Final Sacrifice and Effector of Redemption. Hebrews shows us that Jesus is the final Word and fulfillment of prophecy. Explore that there are warning sections between sections that celebrate Jesus. The first warning is Hebrews 2:1-4 which is in-between Jesus as superior to the angels and to Moses. The second warning is in Hebrews 3:7 -4:13 in-between Jesus as superior to Moses and Jesus as the Great High Priest. The third warning is in Hebrews 5:11-6:12 which is in-between Jesus as Great High Priest and after the order of Melchizedek. The forth warning is in Hebrews 10:22-36 which is in-between the superior New Covenant and Faith Hall of Fame.
The TWiM crew ponders the question of how a bacterium finds its middle when dividing, then divulge the transfer of interbacterial antagonism genes to eukaryotes, where they may function in innate defense. Links for this episode: Size independent symmetric division (Nat Commun) How does a bacterium find its middle? (Nat Struct Biol) Genes transferred from bacteria augment eukaryotic defenses (Cell) Antibacterial gene transfer (eLife) Letters read on TWiM #98 on TWiM 98 Visit microbeworld.org/twim for complete shownotes and more.
Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 05/06
Tue, 20 May 2014 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/17729/ https://edoc.ub.uni-muenchen.de/17729/1/Ruppert_Raphael.pdf Ruppert, Raphael Hubert ddc:540, ddc:500, Fakultät für Chemi
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 16/19
The Gram-negative bacterium Legionella pneumophila naturally parasitises environmental amoebae, but is also able to infect human alveolar macrophages in a mechanistically similar manner. This can result in the mild "Pontiac fever", a flu-like illness, or a potentially lethal pneumonia termed Legionnaires' disease". Crucial for establishing an intracellular replication niche is the Icm/Dot type IV secretion system (T4SS), which translocates approximately 300 different "effector" proteins into the host cell. These substrates enhance uptake efficiency into phagocytes and direct formation of a replication-permissive compartment, called the Legionella-containing vacuole (LCV), and ultimately the egress of the bacteria. Some of the effectors interfere with small GTPases, phosphoinositide metabolism or the ubiquitination machinery, and modulate host cell signalling and vesicle trafficking. We developed a method to isolate intact LCVs by using immuno-magnetic separation with an LCV-specific antibody followed by density gradient centrifugation. Proteomic analysis of the purified phagosomes together with findings of previous studies showed, that the vacuoles harbour markers of the endosomal network, associate with mitochondria, early secretory vesicles and the endoplasmic reticulum, but avoid fusion with lysosomes. Our investigations of the novel L. pneumophila effector RidL revealed that the LCV also communicates with the retrograde vesicle trafficking pathway of infected cells. This pathway recycles amongst others acid-hydrolase receptors, such as the cation-independent mannose 6-phosphate receptor (CIMPR), from the tubular endosomal network back to the trans-Golgi. This transport requires the multiprotein "retromer" complex, which consists of two major subunits: the heterotrimeric cargo-selective subcomplex comprising the proteins Vps26, Vps29 and Vps35 and the membrane-deforming heterodimeric subcomplex composed of any combination of the phosphoinositide (PI)-binding sorting nexins SNX1 or SNX2 plus SNX5 or SNX6. Pull-down experiments with lysates of RAW 264.7 macrophages or D. discoideum amoebae revealed Vps26, Vps29 and Vps35 to be retained by the then uncharacterised protein RidL, which represented an intriguing, novel effector interaction. Like most T4SS substrate mutants, L. pneumophila lacking ridL showed no phenotype for growth in liquid AYE medium and uptake into phagocytes compared to wild-type bacteria. However, intracellular replication was strongly impaired for the mutant strain in several host cell lines. RidL is preferentially expressed in the late post-exponential growth phase and translocated in an T4SS-dependent manner at early time-points of the infection, suggesting a role shortly after the uptake of the bacteria. The effector exhibited a bipolar localisation on the LCV membrane, but upon overexpression the protein covered the entire vacuole. Interestingly, RidL bound the lipid phosphatidylinositol 3-phosphate (PtdIns(3)P), a known eukaryotic endosomal membrane anchor, and also specifically bound to the retromer subunit Vps29. Although the protein had no effect on the acquisition of Vps26, Vps29 and Vps35, the percentage of LCVs positive for the retrograde cargo receptors CIMPR or sortilin was reduced in presence of RidL, suggesting interference with the retrograde transport pathway. Furthermore, significantly less SNX1- and SNX2-positive LCVs were detected in cells infected with wild-type L. pneumophila compared to the ridL mutant strain. Moreover, RidL competed with SNX1 for binding at PtdIns(3)P-positive membranes. To directly examine the influence of RidL on retrograde trafficking, the retromer-dependent transport of cholera and Shiga toxin inside cells was analysed in macrophages infected with wild-type or ridL L. pneumophila, and in HeLa cells ectopically producing RidL, respectively. In both cases, the trafficking was inhibited by RidL, and for cholera toxin the transport was arrested at the endosomal stage. In line with these findings, siRNA knockdown experiments revealed that a functional retrograde pathway restricted intracellular growth of L. pneumophila. Taken together, we postulate that RidL (Retromer interactor decorating LCVs) inhibits retrograde trafficking at endosomes by binding to the retromer subunit Vps26 and/or by competition with sorting nexins, thus promoting intracellular replication of L. pneumophila. Collectively, the results obtained in this thesis shed light on the host factor composition of LCVs and provide mechanistic insights into a novel L. pneumophila effector protein.
Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, and Kathy Spindler Vincent, Dickson, Alan, and Kathy review clearance of simian immunodeficiency virus infection from macaques by immunization with SIV proteins encoded in a rhesus cytomegalovirus vector. Links for this episode: Immune clearance of SIV infection (Nature) Rhesus CMV vectors (Nature Medicine) Types of memory T cells (WikiPedia) Goldilocks approach to vaccines (Scilogs) Chimeric HA influenza vaccine (J Virol) Influenza vaccine matched vs mismatched (BMC Medicine) Letters read on TWiV 254 Weekly Science Picks Dickson - The Man Who Planted Trees by Jean GionoKathy - A boy and his atom and Moving Atoms (YouTube)Alan - It is pitch dark and Get Lamp (YouTube)Vincent - Who's afraid of peer review? (Science) Listener Pick of the Week Maren - Hello Maestro (episodes on YouTube)Ayesha - Why you don't f****** love scienceJon - A Capella Science (YouTube) Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv
Pirate Station #600 , по-своему Юбилейный выпуск встречал сразу двух дорогих гостей : сильнейшего игрока на Молдавской днб сцене и нередкого гостя ПС dj FLADE и интересного деятеля сцены из Санкт - петербурга dj EVOQUE, громко заявившего о себе подкастами, звучащими на радиостанциях разных стран ... Оба гостя представили отличный вайб, балансируя на разных гранях mainstream drum'n'bass!!! Я в свою очередь поиграл два небольших микса, один из которых был посвящен современным джангл настроениям, а второй -обозревал интересные дабки,новинки и просто откровения тру или неожиданных героев сцены! dj FLADE guestmix: 01. Submatik - Stories Can Wait (Virtual Riot Remix) 02. Infuze - Back To Reality 03. S.P.Y. - Hammer In My Heart (feat. Diane Charlemaghe) (Black Sun Empire Remix) 04. Trippcore - Circles 05. Stereo Killaz - Human 2 Hero 06. Fred V & Grafix - Purple Gates 07. Hadouken! - Bad Signal (The Prototypes Remix) 08. Task Horizon & Kriteria - Letting Go (Remix) 09. Tantrum Desire - Guided Rhytm 10. 12th Planet & Flinch - The End Is Near Part 1 (Dirtyphonics Remix) 11. Danny Byrd - Love You Like This 12. Mediks, Texas - Fast Lane 13. J.Rabbit - Daddy Issues (Jayline Deep Abuse Remix) 14. Rockwell feat. Kito & Sam Frank - Childhood Memories (Metrik Remix) 15. Arctica, Skunkshaft - Butcher Comes To You (DnB Remix) 16. Jumpshot, Jahdan Blackkamoore - Headstrong (Liondub Jungle Remix) 17. Zero Method - Cold War 18. Disept - Time Shift 19. BCee - Generations (S.P.Y Remix) GVOZD mix1: 1. Нейромонах Феофан - мужицкая силушка (free) 2. Bones ft Gregory Isaacs - number one sound (Jungle Expeditions) 3. David Boomah ft tenor Fly (Aries rmx) - sound ago dead (V dub) 4. Johnny Osbourne(Marcus Visionary rmx) - rock it tonight (Lion Dub International) 5. Aries and Gold ft Cowboy Ranger & 2nice(Run Tingz Cru rmx) - my sound (N1 in the dance)(Run Tingz) 6. Dialect and Kosine ft King General - got to be conscious (Jungle Alliance) 7. Tenor Fly and Run Tingz Cru - Don man sound (Run Tingz Cru dirty rmx) (Run Tingz) 8. Seba - balance of power (Secret Operations) + tease 9. Jayline - do you like jungle (Soundbully Audio) EVOQUE guest mix: 1. Ayah Marar - The Raver 2. Drumsound & Bassline Smith feat. Hadouken! - Daylight (Club Mix) 3. Wilkinson - Direction (Original Mix) 4. Bingo Players feat. Far East Movement - Get Up (Rattle) (The Prototypes Remix) 5. Black&White - Get Ya Hands Up (Toronto Is Broken Remix) 6. Ben Howard - Only Love (Roni Size Remix) 7. Fred V & Grafix - Purple Gates 8. Loadstar - Black & White (Ft. Benny Banks - Hamilton Remix) 9. Tantrum Desire - Guided Rhythm 10. Trippcore - Leave Me Alone 11. Dimension - Children (Rollz Remix) 12. iLL Audio - Never Be The Same (Rollz Remix) 13. Brains - Blazin (GRiD rmx) 14. Mat Zo & Porter Robinson - Easy (Mediks Bootleg) GVOZD mix2: 1. Billain - boogie (Bad Taste dub) 2. Biopssia, Effector - breakdown (You So Fat) 3. Melleefresh vs Deadmau5 (Dank mix) - sex slave (Play digital) 4. Major Look - no hope city (Six Blade rmx) (Cold Blooded) 5. Koven - more than you (DC Breaks rmx) (Viper) 6. Flo Rida - i cry (Henri V bootleg) 7. Jaydan - party rocker (Smokin Riddim) 8. Paradox - crate logic (Samurai) 9. Peshay - funkster (Liquid V dub)
Pirate Station #600 , по-своему Юбилейный выпуск встречал сразу двух дорогих гостей : сильнейшего игрока на Молдавской днб сцене и нередкого гостя ПС dj FLADE и интересного деятеля сцены из Санкт - петербурга dj EVOQUE, громко заявившего о себе подкастами, звучащими на радиостанциях разных стран ... Оба гостя представили отличный вайб, балансируя на разных гранях mainstream drum'n'bass!!! Я в свою очередь поиграл два небольших микса, один из которых был посвящен современным джангл настроениям, а второй -обозревал интересные дабки,новинки и просто откровения тру или неожиданных героев сцены! dj FLADE guestmix: 01. Submatik - Stories Can Wait (Virtual Riot Remix) 02. Infuze - Back To Reality 03. S.P.Y. - Hammer In My Heart (feat. Diane Charlemaghe) (Black Sun Empire Remix) 04. Trippcore - Circles 05. Stereo Killaz - Human 2 Hero 06. Fred V & Grafix - Purple Gates 07. Hadouken! - Bad Signal (The Prototypes Remix) 08. Task Horizon & Kriteria - Letting Go (Remix) 09. Tantrum Desire - Guided Rhytm 10. 12th Planet & Flinch - The End Is Near Part 1 (Dirtyphonics Remix) 11. Danny Byrd - Love You Like This 12. Mediks, Texas - Fast Lane 13. J.Rabbit - Daddy Issues (Jayline Deep Abuse Remix) 14. Rockwell feat. Kito & Sam Frank - Childhood Memories (Metrik Remix) 15. Arctica, Skunkshaft - Butcher Comes To You (DnB Remix) 16. Jumpshot, Jahdan Blackkamoore - Headstrong (Liondub Jungle Remix) 17. Zero Method - Cold War 18. Disept - Time Shift 19. BCee - Generations (S.P.Y Remix) GVOZD mix1: 1. Нейромонах Феофан - мужицкая силушка (free) 2. Bones ft Gregory Isaacs - number one sound (Jungle Expeditions) 3. David Boomah ft tenor Fly (Aries rmx) - sound ago dead (V dub) 4. Johnny Osbourne(Marcus Visionary rmx) - rock it tonight (Lion Dub International) 5. Aries and Gold ft Cowboy Ranger & 2nice(Run Tingz Cru rmx) - my sound (N1 in the dance)(Run Tingz) 6. Dialect and Kosine ft King General - got to be conscious (Jungle Alliance) 7. Tenor Fly and Run Tingz Cru - Don man sound (Run Tingz Cru dirty rmx) (Run Tingz) 8. Seba - balance of power (Secret Operations) + tease 9. Jayline - do you like jungle (Soundbully Audio) EVOQUE guest mix: 1. Ayah Marar - The Raver 2. Drumsound & Bassline Smith feat. Hadouken! - Daylight (Club Mix) 3. Wilkinson - Direction (Original Mix) 4. Bingo Players feat. Far East Movement - Get Up (Rattle) (The Prototypes Remix) 5. Black&White - Get Ya Hands Up (Toronto Is Broken Remix) 6. Ben Howard - Only Love (Roni Size Remix) 7. Fred V & Grafix - Purple Gates 8. Loadstar - Black & White (Ft. Benny Banks - Hamilton Remix) 9. Tantrum Desire - Guided Rhythm 10. Trippcore - Leave Me Alone 11. Dimension - Children (Rollz Remix) 12. iLL Audio - Never Be The Same (Rollz Remix) 13. Brains - Blazin (GRiD rmx) 14. Mat Zo & Porter Robinson - Easy (Mediks Bootleg) GVOZD mix2: 1. Billain - boogie (Bad Taste dub) 2. Biopssia, Effector - breakdown (You So Fat) 3. Melleefresh vs Deadmau5 (Dank mix) - sex slave (Play digital) 4. Major Look - no hope city (Six Blade rmx) (Cold Blooded) 5. Koven - more than you (DC Breaks rmx) (Viper) 6. Flo Rida - i cry (Henri V bootleg) 7. Jaydan - party rocker (Smokin Riddim) 8. Paradox - crate logic (Samurai) 9. Peshay - funkster (Liquid V dub)
Background: Ralstonia solanacearum is a soil-borne beta-proteobacterium that causes bacterial wilt disease in many food crops and is a major problem for agriculture in intertropical regions. R. solanacearum is a heterogeneous species, both phenotypically and genetically, and is considered as a species complex. Pathogenicity of R. solanacearum relies on the Type III secretion system that injects Type III effector (T3E) proteins into plant cells. T3E collectively perturb host cell processes and modulate plant immunity to enable bacterial infection. Results: We provide the catalogue of T3E in the R. solanacearum species complex, as well as candidates in newly sequenced strains. 94 T3E orthologous groups were defined on phylogenetic bases and ordered using a uniform nomenclature. This curated T3E catalog is available on a public website and a bioinformatic pipeline has been designed to rapidly predict T3E genes in newly sequenced strains. Systematical analyses were performed to detect lateral T3E gene transfer events and identify T3E genes under positive selection. Our analyses also pinpoint the RipF translocon proteins as major discriminating determinants among the phylogenetic lineages. Conclusions: Establishment of T3E repertoires in strains representatives of the R. solanacearum biodiversity allowed determining a set of 22 T3E present in all the strains but provided no clues on host specificity determinants. The definition of a standardized nomenclature and the optimization of predictive tools will pave the way to understanding how variation of these repertoires is correlated to the diversification of this species complex and how they contribute to the different strain pathotypes.
Background: Prostate smooth muscle tone is regulated by alpha 1-adrenoceptor-induced contraction and cAMP-mediated relaxation. EPAC is an effector of cAMP, being involved in smooth muscle relaxation and cell cycle control outside the lower urinary tract. Here, we investigated the expression and function of EPAC in human prostate tissues from patients undergoing radical prostatectomy. Results: mRNA and protein expression of EPAC was detected in all prostate tissues by RT-PCR and Western blot analysis. Immunoreactivity was observed in stromal cells, and colocalized with immunofluorescence for a-smooth muscle actin and calponin. Under normal conditions, noradrenaline-or phenylephrine-induced contraction of prostate strips in the organ bath was not affected by the EPAC activator pCPT (SP-8-pCPT-2'-O-Me-cAMPS.NA) (30 mu M). However, when the cyclooxygenase inhibitor indomethacin (50 mu M) was added, EPAC activators pCPT and OME (8-CPT-2'-O-Me-cAMP.Na) (30 mu M) significantly reduced contractions by low concentrations of phenylephrine. These effects were not observed on noradrenaline-induced contraction. OME and pCPT caused phosphorylation of the transcription factor Elk1 in prostate tissues. Elk1 activation was confirmed by EMSA (electrophoretic mobility shift assay), where OME and pCPT incresed Elk1 binding to a specific DNA probe. Conclusions: EPAC activation may reduce alpha 1-adrenergic prostate contraction in the human prostate, although this effect is masked by cyclooxygenases and beta-adrenoceptors. A main EPAC function in the human prostate may be the regulation of the transcription factor Elk1.
Aptamers are oligonucleotides that can bind to various nonnucleic acid molecular targets in a high affinity and specificity. As an emerging class of therapeutic agents, aptamers offer an unparalleled advantage over other classes of therapeutic agents: the possibility to rationally regulate the therapeutic activity of aptamers.
Предпоследний эфир Пиратской Станции 2012 ... Первая часть отчета за год: мейнстрим и андеграунд треки, хорошо зарекомендовавшие себя как в шоу, так и на танцполах ... Ставьте на репит и не прекращайте этот музыкальный трип!with love! ) GVOZD: 1. Zardonic, Counterstrike, Gein and Robyn Kaos - revolution (Big riddim) 2. Effector - revival (Amunnition) 3. Noisia and Phace - imperial (Vision) 4. Blokhe4d - bang the drum (Bad Taste) 5. Freqax - political crime (Yellow Stripe) 6. Ulterior Motive ft. Codebreaker - its on (Subtitles) 7. Miditacia - mad planet (Close 2 Death) 8. Hadouken - parasite (Break rmx)(MOS) 9. Phace - stresstest (Neosignal) 10. Paranoic Del - vibration (dub) 11. Crissy Criss - more than ever vip (Technique) 12. Alex Curly - sun night (dub) 13. TC - tap ho (TC) 14. E.Decay and Soulpride - out of my mind (Formation) 15. Medics - outbreak (Audio Porn) 16. Slogun and iOh - magic (Heavy Artillery) 17. Loadstar - second skin (Ram) 18. High Contrast - the agony and extasy (Hospital) 19. Sway - level up (Blame rmx) 20. dj Marky and SPY - last night (Innerground) 21. dj Chap ft Iriann Joyce - midnight love (dRamatic and dbAudio rmx)(Liquid V) 22. Die and Break - grand funk hustle (Digital Soundboy) 23. Slynk - bad duppy walk (Jungle Cakes) 24. Krafty Kuts & Featurecast - monkey dance (Ed Solo jungle rmx) 26. Bladerunner - feel for you (Dread) 27. Fada - ecru (Alphacut dub) 28. L33 - robot (Sculpture) 29. Locksem - not as we know it 30. Dub Phyzix and mc Fox- never been (Critical) 31. Secret Panda Society - relentless () 32. Kove - stellar (Viper) 33. Netsky - love has gone (Hospital) 34. Pendulum - island (Internationale bootleg) 35. John B - robot lover (GMorozov rmx)(Beta) 36. LXC - i know you (Bustle ) 37. Subwave - aeeeh (Metalheads)
Предпоследний эфир Пиратской Станции 2012 ... Первая часть отчета за год: мейнстрим и андеграунд треки, хорошо зарекомендовавшие себя как в шоу, так и на танцполах ... Ставьте на репит и не прекращайте этот музыкальный трип!with love! ) GVOZD: 1. Zardonic, Counterstrike, Gein and Robyn Kaos - revolution (Big riddim) 2. Effector - revival (Amunnition) 3. Noisia and Phace - imperial (Vision) 4. Blokhe4d - bang the drum (Bad Taste) 5. Freqax - political crime (Yellow Stripe) 6. Ulterior Motive ft. Codebreaker - its on (Subtitles) 7. Miditacia - mad planet (Close 2 Death) 8. Hadouken - parasite (Break rmx)(MOS) 9. Phace - stresstest (Neosignal) 10. Paranoic Del - vibration (dub) 11. Crissy Criss - more than ever vip (Technique) 12. Alex Curly - sun night (dub) 13. TC - tap ho (TC) 14. E.Decay and Soulpride - out of my mind (Formation) 15. Medics - outbreak (Audio Porn) 16. Slogun and iOh - magic (Heavy Artillery) 17. Loadstar - second skin (Ram) 18. High Contrast - the agony and extasy (Hospital) 19. Sway - level up (Blame rmx) 20. dj Marky and SPY - last night (Innerground) 21. dj Chap ft Iriann Joyce - midnight love (dRamatic and dbAudio rmx)(Liquid V) 22. Die and Break - grand funk hustle (Digital Soundboy) 23. Slynk - bad duppy walk (Jungle Cakes) 24. Krafty Kuts & Featurecast - monkey dance (Ed Solo jungle rmx) 26. Bladerunner - feel for you (Dread) 27. Fada - ecru (Alphacut dub) 28. L33 - robot (Sculpture) 29. Locksem - not as we know it 30. Dub Phyzix and mc Fox- never been (Critical) 31. Secret Panda Society - relentless () 32. Kove - stellar (Viper) 33. Netsky - love has gone (Hospital) 34. Pendulum - island (Internationale bootleg) 35. John B - robot lover (GMorozov rmx)(Beta) 36. LXC - i know you (Bustle ) 37. Subwave - aeeeh (Metalheads)
НЕ забываем оставлять комменты и ставить+!!!Треклист гостевого!01 Marcin 'Cedyn' Czartynski- Factory Music1 (OST Painkiller) 02 Noisia feat. Eminem - Block Control (VIP) 03 TriaMer - Algorythm Of Death (Original mix) 04 Mystification feat. Replicator - Fantasy (Original mix) 05 Zardonic feat. Replicator - Ten Commandments (Original mix) 06 TRN18 feat. Terror[east] - Crowd (Original mix) 07 The Outside Agency feat. SPL- Separateways (Original mix) 08 TRN18- Fucking Hell (Original mix) 09 Broken Note - Channel Zero (Original mix) 10 C.V.I. feat. Terror[east]- Specnaz (Original mix) 11 Mystification- Plastic Mortality (Original mix) 12 Zardonic- Nexus Polaris (Original mix) 13 Counterstrike feat. Magna Karta- Interface (Original mix) 14 Counterstrike- Deathstar (Forbidden Society Remix) 15 Hallucinator- Mosh (Original Mix) 16 Dark Concept- Different Heaven (Original Mix) 17 Imprintz- Remain (Original Mix) 18 Effector- 2012 (Original Mix) 19 Telemetrik feat. Hyx- The Bane (Original Mix) 20 Telemetrik- Myglightyear (Original Mix)
НЕ забываем оставлять комменты и ставить+!!!Треклист гостевого!01 Marcin 'Cedyn' Czartynski- Factory Music1 (OST Painkiller) 02 Noisia feat. Eminem - Block Control (VIP) 03 TriaMer - Algorythm Of Death (Original mix) 04 Mystification feat. Replicator - Fantasy (Original mix) 05 Zardonic feat. Replicator - Ten Commandments (Original mix) 06 TRN18 feat. Terror[east] - Crowd (Original mix) 07 The Outside Agency feat. SPL- Separateways (Original mix) 08 TRN18- Fucking Hell (Original mix) 09 Broken Note - Channel Zero (Original mix) 10 C.V.I. feat. Terror[east]- Specnaz (Original mix) 11 Mystification- Plastic Mortality (Original mix) 12 Zardonic- Nexus Polaris (Original mix) 13 Counterstrike feat. Magna Karta- Interface (Original mix) 14 Counterstrike- Deathstar (Forbidden Society Remix) 15 Hallucinator- Mosh (Original Mix) 16 Dark Concept- Different Heaven (Original Mix) 17 Imprintz- Remain (Original Mix) 18 Effector- 2012 (Original Mix) 19 Telemetrik feat. Hyx- The Bane (Original Mix) 20 Telemetrik- Myglightyear (Original Mix)
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 04/06
T cells directed against brain antigens are generally held to play a crucial role in the initiation of multiple sclerosis (MS). This was deduced from experimental autoimmune encephalomyelitis (EAE). In this model for MS, T cells reactive for myelin antigens induced a severe paralytic disease upon transfer to healthy syngeneic recipients. Intriguingly, the disease does not start immediately upon transfer of the pathogenic effector T cells. Instead, as earlier studies have shown, the effector T cells attack their target organ only after having migrated in the periphery through secondary lymphoid organs. The aim of the project was to characterize the functional properties of these migrating encephalitogenic T cells during the course of EAE and to identify biological pathways which determine their migratory behaviour and pathogenic potential. To this end, average linkage hierarchical clustering, pathway and gene ontology (GO) analyses of transcriptomes from cultured and ex vivo-isolated myelin basic protein-reactive T cells (TMBP cells) were performed. At the time of transfer, encephalitogenic T cells in vitro are maximally activated, i.e. they exhibit a prominent upregulation of cell cycle genes such as cyclin A2 (CCNA2) and cyclin B2 (CCNB2) among others. In contrast, T cells isolated from spleen 3 days post transfer, downregulated activation markers such as interleukin 2 receptor (IL2R) and interferon γ (IFNγ), and at the same time upregulated migration specific genes such as CC-chemokine receptor 1 (CCR1), CC-chemokine receptor 2 (CCR2) and CC-chemokine receptor 5 (CCR5). Hierarchical cluster analysis revealed that several transcription regulators known for inhibiting cell cycle progression such as krüppel-like factor 4 (KLF4), B-cell translocation gene 2 (BTG2) and transducer of ERBB2, 1 (TOB1) were clustered together with cell cycle and migration genes. Overexpression of KLF4 in T cells not only inhibited G1/S phase progression of the cell cycle but additionally induced upregulation of CCR2 and CCR5. A novel tetraspan membrane protein called epithelial membrane protein (EMP1), was found to be up regulated in ex vivo-isolated effector T cells. Overexpression of EMP1 in encephalitogenic T cells influenced the migratory behaviour of effector T cells both in vitro and in vivo. EMP1 enhanced T cell motility within the extracellular matrix milieu in vitro and promoted T cell migration from the connective tissue to lymph nodes in vivo resulting in an accelerated onset of EAE. In conclusion, gene expression profiling of encephalitogenic T cells revealed interesting genome wide transcriptomic changes and established a correlation between cell cycle progression and cell migration. As a result, in silico analysis put forth several interesting candidate genes that hold promise as potential targets for therapeutic intervention.
Hello In this edition of the podcast I will discuss a paper published by Stemberger and collaborators in the journal Immunity called "A single naive CD8+ T cells precursor can develop into diverse effector and memory subset" vol 27, pag 987 of December 2007. In this very interesting paper the authors redraw the concepts of memory T cells differentiation from naive T cells, developping a successfull model of transfer of an single naive T cell precursor. The paper shows that this single antigen specific naive T cell precursor can give rise to an diversified memory T cell responses including all subsets (central memory (CD62L positive, CD127 posit) and effector memory (CD62L negative, CD127 positive) T cells) upon antigen challenge. Importantly the kind of memory responses were equivalent in frequency to the ones generated by the host mice (containing a normal size naive pool of antigen specific T cells) against an antigenic protein. See you next time. PS: The audio has "clicks" artifacts that I don't know the origin. I apologize for that.
Mon, 1 Jan 1979 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6771/1/6771.pdf Koszinowski, Ulrich H.; Simon, M. M. ddc:610, Medizin
Sat, 1 Jan 1977 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6960/1/6960.pdf Ertl, Hildegund; Koszinowski, Ulrich H.