Podcasts about elongation

Hosted by Chris Beckett & Shane Ludtke, two amateur astronomers in Saskatchewan. actualastronomy@gmail.com * July 1st - Today is Canada Day    Mars 4° below Moon this morning * July 2nd - Uranus 4° below Moon this morning * July 3rd - Jupiter 5° below Moon this morning * July 4th - is Independence Day in the USA and the 970th anniversary of the Crab Supernova Explosion * July 4th is also New Moon * July 5th - Earth is at Aphelion * July 6th - Ceres at Opposition Mag. 7.3 * July 7th Mercury 3° below the Moon this evening    Spot Arcturus with the unaided eye this week * July 13th - first Quarter Moon * July 14th - Lunar Straight Wall visible this evening * July 15th - Mars 0.6° below Uranus this morning * July 16th - Comet Shoemaker-Levy 9 crashed into Jupiter 30 years ago! * July 21st - Full Moon    Asteroid 40 Harmonia at Opposition, Mag. 9.4 * July 22nd- Mercury at greatest Elongation this evening at 27° from the Sun    Jupiter appears in the morning sky around 2:30 am PDT with only 1 Satellite Callisto Visible. * July 27th Last Quarter Moon * July 29th - Uranus 4° below Moon this morning. * July 30th - Mars 5° below the Moon this morning * July 31st - ZHR=25 best seen in predawn hours today and tomorrow.   We've added a new way to donate to 365 Days of Astronomy to support editing, hosting, and production costs.  Just visit: https://www.patreon.com/365DaysOfAstronomy and donate as much as you can! Share the podcast with your friends and send the Patreon link to them too!  Every bit helps! Thank you! ------------------------------------ Do go visit http://www.redbubble.com/people/CosmoQuestX/shop for cool Astronomy Cast and CosmoQuest t-shirts, coffee mugs and other awesomeness! http://cosmoquest.org/Donate This show is made possible through your donations.  Thank you! (Haven't donated? It's not too late! Just click!) ------------------------------------ The 365 Days of Astronomy Podcast is produced by the Planetary Science Institute. http://www.psi.edu Visit us on the web at 365DaysOfAstronomy.org or email us at info@365DaysOfAstronomy.org.

March 24, 2024: Mercury is at its best evening appearance of the year for northern hemisphere sky watchers.  The Full (Worm) moon occurs tonight. See the accompanying article - 2024, March 24: Mercury at Greatest Elongation, Worm Moon --- Send in a voice message: https://podcasters.spotify.com/pod/show/jeffrey-l-hunt/message Support this podcast: https://podcasters.spotify.com/pod/show/jeffrey-l-hunt/support

In this Podcast Astrid Rijkenhuizen discusses  'Neurologic deficits and surgical treatment in a horse affected with internal carotid artery tortuous elongation'

January 12, 2024:  Before daybreak, spot Mercury at greatest elongation, to the lower left of Morning Star Venus. See the accompanying article - 2024, January 12:  Spot Mercury at Greatest Elongation near Venus --- Send in a voice message: https://podcasters.spotify.com/pod/show/jeffrey-l-hunt/message Support this podcast: https://podcasters.spotify.com/pod/show/jeffrey-l-hunt/support

December 4, 2023: The moon is with Leo high in the southern sky before sunrise.  Mercury's visibility is limited at this evening greatest elongation. See the accompanying article - 2023, December 4: Leo Moon, Mercury at Greatest Elongation --- Send in a voice message: https://podcasters.spotify.com/pod/show/jeffrey-l-hunt/message Support this podcast: https://podcasters.spotify.com/pod/show/jeffrey-l-hunt/support

Emmy Wisz a research fellow at the Maria Mitchell Association discusses Venus at greatest elongation west. The second planet from the Sun, Venus will be appearing at its greatest elongation west point on October 23 and it will be visible in the early morning eastern sky before sunrise. 

October 23, 2023: Venus moves to its farthest angular distance from the sun today, known as greatest elongation.  During morning twilight, the Morning Star passes Leo's Chertan. See the accompanying article 2023, October 23: Venus at Greatest Elongation --- Send in a voice message: https://podcasters.spotify.com/pod/show/jeffrey-l-hunt/message Support this podcast: https://podcasters.spotify.com/pod/show/jeffrey-l-hunt/support

September 21, 2023: Mercury is putting on its best morning display of the year in the eastern sky.  The nearly half-full moon is in front of Ophiuchus, above Scorpius. See the accompanying article 2023, September 21: Mercury Near Greatest Elongation, Evening Ophiuchan Moon --- Send in a voice message: https://podcasters.spotify.com/pod/show/jeffrey-l-hunt/message Support this podcast: https://podcasters.spotify.com/pod/show/jeffrey-l-hunt/support

Hosted by Chris Beckett & Shane Ludtke, two amateur astronomers in Saskatchewan. actualastronomy@gmail.com   August 1st - Full Moon 2nd - Saturn 2-degrees above the Moon in VERY EARLY ie 1 am morning Sky 8th  - Last quarter Moon  Jupiter 3-degrees below Moon in early morning sky 10th - Mercury at greatest Elongation 27-degrees in Evening Sky - tough in very bright dusky sky 10 Hygiea at opposition m=9.6 Hygiea is a major asteroid and possible dwarf planet located in the main asteroid belt. With a diameter of 434 kilometres and a mass estimated to be 3% of the total mass of the belt, it is the fourth-largest asteroid in the Solar System by both volume and mass. Annibale de Gasparis discovered Hygiea on 12 April 1849.  Named after the Greek Goddess of Health. On Aquarius Capricornus Border. 13th & 14th - Perseid Meteor Shower Peaks in the early morning hours on these mornings 15th - Old Moon Challenge - You'll see a sliver of a Moon in morning twilight. 16th -  New Moon / Young Crescent Moon possible in evening twilight 18th - Mars 2-degrees below and right of Moon in evening twilight 24th - First Quarter - Lunar Straight Wall visible - Moon Occults ANtares this evening What is an Occultation? From here the Moon Passes in front of Antares in the Daylight sky just a few minutes before Sunset, around 8pm, however, the Moon is readily visible in the daytime around 1st quarter and with the Moon as a guide you might find Antares. We can easily see the reveal at about 9pm when it's dark. 26th - Asteroid 8 Flora at opposition m= 8.3 Discovered by J. R. Hind on 18 October 1847. The name Flora was proposed by John Herschel, from Flora, the Latin goddess of flowers and gardens. Morning Sky Eastern Taurus. 27th - Saturn at opposition - rings are closing in a little…look like little ears when we viewed them in Grasslands. 30th - Full Moon and Saturn 2 degrees above and right of the Moon in evening sky   We've added a new way to donate to 365 Days of Astronomy to support editing, hosting, and production costs.  Just visit: https://www.patreon.com/365DaysOfAstronomy and donate as much as you can! Share the podcast with your friends and send the Patreon link to them too!  Every bit helps! Thank you! ------------------------------------ Do go visit http://www.redbubble.com/people/CosmoQuestX/shop for cool Astronomy Cast and CosmoQuest t-shirts, coffee mugs and other awesomeness! http://cosmoquest.org/Donate This show is made possible through your donations.  Thank you! (Haven't donated? It's not too late! Just click!) ------------------------------------ The 365 Days of Astronomy Podcast is produced by the Planetary Science Institute. http://www.psi.edu Visit us on the web at 365DaysOfAstronomy.org or email us at info@365DaysOfAstronomy.org.

105.ਬਾਂਹ ਦਾ ਲੰਬਾ ਹੋਣਾ, ਕਸਰ ਜਾਂ ਕਿਰਪਾ?What does arm elongation signify?

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.27.546809v1?rss=1 Authors: Devarakonda, P. M., Sarmiento, V., Heaslip, A. T. Abstract: Toxoplasma gondii contains an essential plastid organelle called the apicoplast that is necessary for fatty acid, isoprenoid, and heme synthesis. Perturbations affecting apicoplast function or inheritance lead to parasite death. The apicoplast is a single copy organelle and therefore must be divided so that each daughter parasite inherits an apicoplast during cell division. In this study we identify new roles for F-actin and an unconventional myosin motor, TgMyoF, in this process. First, loss of TgMyoF and actin lead to an accumulation of apicoplast vesicles in the cytosol indicating a role for this actomyosin system in apicoplast protein trafficking or morphological integrity of the organelle. Second, live cell imaging reveals that during division the apicoplast is highly dynamic, exhibiting branched, U-shaped and linear morphologies that are dependent on TgMyoF and actin. In parasites where movement was inhibited by the depletion of TgMyoF, the apicoplast fails to associate with the parasite centrosomes. Thus, this study provides crucial new insight into mechanisms controlling apicoplast-centrosome association, a vital step in the apicoplast division cycle, which ensures that each daughter inherits a single apicoplast. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Why would you undergo neck elongation? This procedure, which works to stretch out the neck, causes pain and takes a lot of dedication. It's natural to wonder why anyone would go through the process. But look closer, and you'll realize that how neck elongation is perceived varies widely from person to person. Some cultures have a rich history of neck elongation practices. In many cases, the reasons why people elongate their necks are related to tradition. #NeckElongation #bodymodification #weirdhistory #culturalpractices #tradition Learn more about your ad choices. Visit podcastchoices.com/adchoices

April 11, 2023: Jupiter is at solar conjunction.  The sun is between Earth and Jupiter.  Mercury is at its farthest from the sun in the evening sky.  Venus continues its display with the Pleiades. This episode is also available as a blog post: 2023, April 11: Jupiter Conjunction, Mercury at Greatest Elongation --- Send in a voice message: https://podcasters.spotify.com/pod/show/jeffrey-l-hunt/message Support this podcast: https://podcasters.spotify.com/pod/show/jeffrey-l-hunt/support

 Dr. Gillian Eggleston of the Audubon Sugar Institute at the LSU AgCenter talks about Crystal Elongation & Molasses Problems in the 2022 Louisiana Sugarcane Grinding Season at the 2023 winter meeting of the American Society of Sugar Cane Technologists and the American Sugar Cane League in Baton Rouge. 

In this episode of the Epigenetics Podcast, we caught up with Karen Arndt from the University of Pittsburgh to talk about her work on transcription elongation control by the Paf1 complex. Karen Arndt and her lab investigate the process of transcriptional elongation and how RNA polymerase II overcomes obstacles like nucleosomes. One of the proteins that helps overcome those obstacles is the Paf1 complex. This complex associates with the transcribing polymerase and helps in modifying the chromatin template by ubiquitinating Histone H2B and methylating Histone H3.   References Squazzo, S. L., Costa, P. J., Lindstrom, D. L., Kumer, K. E., Simic, R., Jennings, J. L., Link, A. J., Arndt, K. M., & Hartzog, G. A. (2002). The Paf1 complex physically and functionally associates with transcription elongation factors in vivo. The EMBO journal, 21(7), 1764–1774. https://doi.org/10.1093/emboj/21.7.1764 Van Oss, S. B., Shirra, M. K., Bataille, A. R., Wier, A. D., Yen, K., Vinayachandran, V., Byeon, I. L., Cucinotta, C. E., Héroux, A., Jeon, J., Kim, J., VanDemark, A. P., Pugh, B. F., & Arndt, K. M. (2016). The Histone Modification Domain of Paf1 Complex Subunit Rtf1 Directly Stimulates H2B Ubiquitylation through an Interaction with Rad6. Molecular cell, 64(4), 815–825. https://doi.org/10.1016/j.molcel.2016.10.008 Cucinotta, C. E., Hildreth, A. E., McShane, B. M., Shirra, M. K., & Arndt, K. M. (2019). The nucleosome acidic patch directly interacts with subunits of the Paf1 and FACT complexes and controls chromatin architecture in vivo. Nucleic acids research, 47(16), 8410–8423. https://doi.org/10.1093/nar/gkz549 Hildreth, A. E., Ellison, M. A., Francette, A. M., Seraly, J. M., Lotka, L. M., & Arndt, K. M. (2020). The nucleosome DNA entry-exit site is important for transcription termination and prevention of pervasive transcription. eLife, 9, e57757. https://doi.org/10.7554/eLife.57757   Related Episodes Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard) H3K4me3, SET Proteins, Isw1, and their Role in Transcription (Jane Mellor)   Contact Epigenetics Podcast on Twitter Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Active Motif on Twitter Active Motif on LinkedIn Email: podcast@activemotif.com

Zu Ehren Rudolf Virchows  - Wir alle sind aus Zellen gemacht. Genau um diese kleinste Einheit unseres Körpers dreht sich die folgende Quadrologie. In dieser Folge soll es quasi um die wichtigste Zutat zur Zellneuschöpfung gehen: Die Verdopplung der DNA. Wie viele Seiten ihr pro Stunde kopieren müsstet, um diesen Prozess zu vollziehen und viele spannende, wie auch witzige Facts gibts hier! (00:00) - Einführung und Grundlagen (12:11) - Initiation (17:14) - Elongation und Termination (35:48) - Hemmstoffe Für die Inhalte in diesem Podcast übernehmen wir keine Gewähr. Der Podcast kann den Besuch von Vorlesungen nicht ersetzen. Wir empfehlen das Studium von einschlägiger Fachliteratur über den Inhalt des Podcasts hinaus.

In this episode... Adrian is joined by one of Sofeast's senior engineers, Paul Adams, who will take us through 7 key tests that importers who are developing new metal and/or plastic products and checking that their quality remains on target after production should consider to check and validate certain critical points in materials, components, and products, such as their hardness, durability, and chemical makeup.  He explains what each test is, the equipment used, the industries and products that use them, and more, so you can decide if they're right for your product.   Show Sections 00:00 - Greetings. 01:04 - Introducing Paul Adams. 02:56 - Today's topic: The tests most importers should consider performing on their hard goods and why. Namely: Tensile test Impact test Hardness test Flexural test (bend test) Chemical analysis Fatigue testing Creep test These are NOT in order of importance. 05:44 - Test 1: Tensile test 16:20 - Why importers should have an understanding of test machine types. 17:20 - Test 2: Impact test. 25:46 - Test 3: Hardness test. 34:21 - Test 4: Flexural test (bend test). 42:06 - Test 5: Chemical analysis. 49:46 - Test 6: Fatigue testing. 57:09 - Test 7: Creep test. 1:04:26 - Summary of tests covered & wrapping up.   Related content... Need help with testing? Sofeast can help you devise and perform appropriate testing such as those outlined here on your materials/parts/product in our own lab: Reliability & Durability Testing (Products & Packaging in a China lab) What's the real Cost of Poor Quality and Reliability? [Podcast] What To Do If Your Electronic Product Contains Unreliable Components? When and Why a Product Failure Analysis is Required [Podcast] How to Reduce Your Product Return Rate? [Podcast] Content from Paul about selecting and testing common thermoplastics Checking Steel's Properties [Video playlist including many tests] Silicone Rubber Properties Testing (Tensile strength, Elongation, & Tear strength) [Video] How To Test Silicone Hardness? [Video] Plastic Testing [Video playlist including many tests] How Reliability Testing Is Critical To Obtaining Great Mass-Produced Products CTQ Components: How Component Engineers Manage Their Quality List of testing laboratories in China Product Reliability Testing | 7 FAQs   Get in touch with us Connect with us on LinkedIn Send us a tweet @sofeast Prefer Facebook? Check us out on FB Contact us via Sofeast's contact page Subscribe to our YouTube channel   Subscribe to the podcast  There are more episodes to come, so remember to subscribe! You can do so in your favorite podcast apps here and don't forget to give us a 5-star rating, please: Apple Podcasts Spotify Stitcher Google Podcasts TuneIn Amazon Podcasts Deezer iHeartRADIO PlayerFM Listen Notes Podcast Addict Podchaser

January 29, 2023: Mercury is at its greatest angular separation from the sun during morning twilight. After sundown, look for four planets and the gibbous moon near the Pleiades star cluster. This episode is also available as a blog post: 2023, January 29: Mercury, Greatest Elongation, Evening Moon, Pleiades --- Send in a voice message: https://anchor.fm/jeffrey-l-hunt/message Support this podcast: https://anchor.fm/jeffrey-l-hunt/support

Mercury's at greatest elongation and near Venus. Jupiter and Saturn are easy evening sights. So is Mars. Earth's at solstice. These are the longest days of the year as measured by high noon to high noon.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.11.516046v1?rss=1 Authors: Pfannenstein, A., Macara, I. G. Abstract: Mammary glands contain branched networks of ducts and alveoli that function to produce milk for offspring. While the murine luminal epithelium is organized as a cellular monolayer, it originates from multilayered structures called terminal end buds (TEB). The TEBs generate ducts of monolayered epithelial cells as they invade the fat pad but little is known about underlying mechanisms. While apoptosis provides a plausible mechanism for cavitation of the ductal lumen it does not account for elongation of ducts behind the TEBs. Our spatial calculations suggest that most cells in TEBs need to intercalate into the outermost luminal layer and that this migration of cells is the primary driver of cavitation and ductal elongation. To study the progression of multilayered to monolayered epithelium, we developed a quantitative cell culture assay that determines the efficiency of intercalation into an epithelial monolayer. Using this tool, we verified that loss of adherens junctions prevents stable integration of cells into monolayers, consistent with previous data in cultured cells and in primary tissue. Interestingly, tight junction (TJ) proteins also play a key role in this integration process. Although loss of the ZO1 TJ protein in intercalating cells suppresses intercalation, loss of ZO1 in the monolayer has the reverse effect, promoting intercalation even though ZO1 is not necessary for establishment of TJs. ZO1 positive puncta form between cells and the monolayer, which then resolves into a new intercellular boundary as intercalation proceeds. ZO1 loss also reduces engraftment when cells are transplanted into the mammary gland via intraductal injection. We further show that intercalation is dependent on dynamic cytoskeletal rearrangements in both the existing monolayer and intercalating cells. These data identify luminal cell rearrangements necessary for mammary gland development and suggest a molecular mechanism for integration of cells into an existing monolayer. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

October 8, 2022: Mercury is at greatest elongation today and visible before sunrise. The nearly full moon is with Jupiter after sundown. This episode is also available as a blog post: 2022, October 8: Mercury, Greatest Elongation, Moon with Jupiter --- Send in a voice message: https://anchor.fm/jeffrey-l-hunt/message Support this podcast: https://anchor.fm/jeffrey-l-hunt/support

Today we are talking about elongation, why it's important for your scoliosis, and what forms of elongation you want to stay away from if you don't want to end up with a back spasm! Interested in working together on your scoliosis with Scolio-Pilates? Schedule a FREE discovery call here: https://schedulethescoliotherapist.as.me/Learn more about scoliosis therapy here: https://mindfulmovementptpilates.com/scoliosis-therapyGet my BEST Sleep Positions for Scoliosis FREEBIE here: https://mindfulmovementptpilates.com/newsletterInterested in working together on your scoliosis with Scolio-Pilates? Schedule a FREE discovery call here: https://schedulethescoliotherapist.as.me/Learn more about scoliosis therapy here: https://mindfulmovementptpilates.com/scoliosis-therapyGet my BEST Sleep Positions for Scoliosis FREEBIE here: https://mindfulmovementptpilates.com/newsletter

PT, PTA, AT – this podcast may help you meet your continuing education requirements. Access Relias Academy to review course certificate information. In this episode, we talk with Danielle Vernon, PT, ISST/BSPTS Schroth Scoliosis Specialist about how to treat adults with scoliosis using a 3-dimensional approach vs. the traditional 2-dimensional approach many practitioners are accustomed to. (00:30) Introduction (03:00) Why an Interest in Scoliosis? (06:20)  The Schroth Method: A Brief History (09:50)  Why More Adults are Seeking Treatment for Scoliosis (10:50)  Patient Empowerment and Self-Referral (12:24) Reducing the Need for Surgery (16:07) Scoliosis: Not Only a Childhood Condition (19:26) Adult-Onset Scoliosis: Terminology and Pathophysiology (22:26) Recognizing Scoliosis and the Primary Curve (26:06) Why a 3-Dimensional Treatment Approach Is Not Common Practice          (30:30) Best Practice to Address Primary Curves (32:04) Common Presentations: Signs and Symptoms (33:46) Addressing Scoliosis Post-Surgery (35:20) Treatment Guidelines for Non-Surgical Patients: 5 Principles (37:20) Avoiding Surgery: How Time-Sensitive Is Our Treatment? (39:34) Why Not Traditional Interventions? (40:29) Elongation and Active Traction (42:44) Key Considerations for a 3-D Treatment Program (48:00) Expected Outcomes Without Scoliosis-Specific Intervention (49:24) Post-Surgery Considerations (50:32) What About Bracing? (51:05) Suggestions for Improving Proficiency with Scoliosis (52:48) Conclusion The content for this course was created by Danielle Vernon, PT, ISST/BSPTS Schroth scoliosis specialist. The content for this course was created by Wendy Phillips, PT, BSPT Here is how Relias can help you earn continuing education credits:  Access your Relias Library offered by your employer to see course certificate information and exam;  or  Access the continuing education library for clinicians at Relias Academy Review the course certificate information, and if eligible, you can purchase the course to access the course exam and receive your certificate. Learn more about Relias at www.relias.com.   Legal Disclaimer: The content of Stretch: Relias Rehab Therapy Education is provided only for educational and training purposes for healthcare professionals. The educational material provided in this podcast should not be used as medical advice to treat any medical condition in either yourself or others. Resources The International Scientific Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT) Guidelines (2016): https://scoliosisjournal.biomedcentral.com/articles/10.1186/s13013-017-0145-8

Important subjects that often get overlooked. --- Send in a voice message: https://anchor.fm/dick-chasse/message

References Dr. Guerra lecture material Nutr J. 2014; 13: 17. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

March 20, 2022: Spring arrives this morning at 10:33 a.m. CDT and Venus is at greatest elongation earlier in the morning. Morning planets Venus, Mars, and Saturn are in the east-southeast before sunrise. This episode is also available as a blog post: 2022, March 20: Spring Arrives, Venus at Greatest Elongation --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/jeffrey-l-hunt/message Support this podcast: https://anchor.fm/jeffrey-l-hunt/support

Pediatric surgeons Dr. Daniel Von Allmen and Dr. Todd Ponsky from Cincinnati children's Hospital discussing the technique for treating long gap esophageal atresia. For additional info please visit: https://www.youtube.com/c/CincinnatiChildrens/featured https://www.jpedsurg.org/article/S0022-3468(15)00181-5/fulltext

January 6, 2022: Planet Mercury nears its evening greatest elongation. It appears in the evening sky, with a crescent moon, Jupiter, and Saturn. Venus sets soon after sundown. Mars is in the southeast before sunup. This episode is also available as a blog post: https://whenthecurveslineup.com/2021/12/07/2022-january-6-mercury-nears-greatest-elongation/ --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/jeffrey-l-hunt/support

October 29, 2021: Venus reaches its greatest elongation from the sun. It is in the evening sky with Jupiter and Saturn. The crescent moon and Mercury are in the eastern sky before sunrise. This episode is also available as a blog post: https://whenthecurveslineup.com/2021/10/22/2021-october-29-venus-greatest-elongation/ --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/jeffrey-l-hunt/support

Das Skript findest du hier! Wie wird die mRNA eigentlich übersetzt? Bzw. translatiert? Gemeinsam mit Fiona (Specialguest! Juhu!!) besprechen wir: 1) Welche Eigenschaften hat der genetische Code? 2) Wie liest man die Codesonne? 3) Was passiert bei den Schritten der Translation? (Inititiation, Elongation, Termination) Viel Freude beim Lernen! #proteinbiosynthese #translation #biolernen #initiation #elongation #termination #ribosom #mRNA #proteine #genetischercode #biostudium #abi2022 #abi2023 #biologieunterricht

September 13, 2021: Mercury reaches greatest elongation tonight. It is a challenge to see in the bright twilight. This episode is also available as a blog post: https://whenthecurveslineup.com/2021/09/03/2021-september-13-mercury-at-greatest-elongation/ --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/jeffrey-l-hunt/support

Dr. Laurie talks with a urologist about the ways men are trying to "grow their members". You'll also hear answers to listener submitted questions, and get Dr. Laurie's take on "Sex in the News".

Megalithic Marvels founder Dee Olson sits down with author & explorer Hugh Newman to discuss the mystery surrounding the Olmec civilization & their strange artifacts. SHOW NOTES Instagram: Perspolis photo Youtube Video Version Music: “Designer Synth” is by iMovie and is licensed under a Creative Commons Attribution license and is provided in the iMovie App from Apple, Inc."

All about spotting Mercury, a rare sight in the sky!

Elongation et kyste de l l'ovaire

Elongation et kyste de l l'ovaire

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.11.378570v1?rss=1 Authors: Nie, L., Pike, A. C., Pascoa, T. C., Bushell, S. R., Quigley, A., Ruda, G. F., Chu, A., Cole, V., Speedman, D., Moreira, T., Shrestha, L., Mukhopadhyay, S. M., Burgess-Brown, N. A., Love, J. D., Brennan, P. E., Carpenter, E. P. Abstract: Very long chain fatty acids (VLCFAs) are essential building blocks for synthesis of the ceramides and sphingolipids required for nerve, skin and retina function and 3-keto acyl-CoA synthases (ELOVL elongases) perform the first step in the FA elongation cycle. Although ELOVLs are implicated in common diseases including insulin resistance, hepatic steatosis and Parkinson's, their underlying molecular mechanisms are unknown. Here we report the structure of the human ELOVL7 elongase, which includes an inverted transmembrane barrel structure surrounding a 35 [A] long tunnel containing a covalently-attached product analogue. The structure reveals the substrate binding sites in the tunnel and an active site deep in the membrane including the canonical ELOVL HxxHH sequence. This indicates a ping-pong mechanism for catalysis, involving unexpected covalent histidine adducts. The unusual substrate-binding arrangement and chemistry suggest mechanisms for selective ELOVL inhibition, relevant for diseases where VLCFAs accumulate such as X-linked adrenoleukodystrophy. Copy rights belong to original authors. Visit the link for more info

Caoimhe & MJ discuss the fourth chapter of Journey to the West, in which Sun Wukong demands a promotion.As usual expect fights and violence throughout the episode and the episode also has some digressions that briefly touch on phrenology between 20:15 and 22:47 and a joke about BDSM sex practises at 26:08 and 28:00.Links:Episode artwork from A Modern Journey to the West (1865) by Tsukioka Yoshitoshi.Giant Buddha, Giant Ears on National Geographic.Throwing Embroidered Ball on Omeida.Follow Caoimhe, MJ and this podcast on Twitter, follow MJ on Instagram and follow Caoimhe on the Fediverse.Check out Hysteria Ireland on Facebook.I forgot about it while recording the episode but embroidered balls specifically as a courtship ritual will show up again in a future chapter.

Der Sternenpodcast März 2020 Ihr Audioguide für die Sterne. Ob zuhause mit der Sternkarte oder unterwegs unter freiem Himmel - Planetariumsdirektor Thomas Kraupe führt Sie zu den interessantesten Sternbildern und Himmelsereignissen - jeden Monat neu und kostenlos. Hier können Sie den Podcast bequem über Soundcloud, Spotify oder iTunes anhören oder die mp3-Audio-Datei direkt herunterladen. Dieser Podcast des Planetarium Hamburg wird Ihnen in Zusammenarbeit mit dem Hamburger Abendblatt präsentiert - mit freundlicher Unterstützung unserer Audio-Partner Prime Time Studios und Audio Consulting Group. Frühlingsnächte mit “Supermond” und planetaren Rendezvous Am 20.März um 4 Uhr 50 Mitteleuropäischer Zeit kreuzt die Sonne im „Frühlingspunkt“ die Äquatorebene unserer Erde nordwärts. Mit dieser „Tag- und Nachtgleiche“ beginnt auf der Nordhalbkugel der Erde der Frühling und auf der Südhalbkugel der Herbst. Und bereits am 29.März, dem letzten Sonntag des Monats, werden zur vermeintlich besseren Ausnutzung dieses Tageslichts die Uhren wieder eine Stunde vorgestellt, die Sommerzeit beginnt. Rekordverdächtiger Abendstern Bereits in der Abenddämmerung zieht der “Abendstern” Venus alle Blicke auf sich. Kein Stern leuchtet auch nur annähernd so hell wie dieser Planet, der uns in diesem Monat auf 100 Millionen Kilometer nahe kommt. Der Sonne eilt er im aufsteigenden Teil des Tierkreises voraus - von den Fischen in den Widder und weiter in den Stier. Während der Abendstern zu Monatsbeginn um kurz nach 22 Uhr untergeht, bleibt er Ende März bis weit nach 24 Uhr Sommerzeit über dem Westhorizont und ist somit mehr als 4 Stunden lang zu sehen. Am 24.März erreicht Venus mit 46 Grad Winkelabstand zur Sonne im Widder ihre “größte östliche Elongation”. Mondlauf und ein tierischer Sternenhimmel Nach 21 Uhr tauschen „links“ vom Abendstern im Südwesten die vertrauten Sterne des Orions auf. Auffällig ist dabei, dass die drei markanten Gürtelsterne am späten Abend auf gleicher Höhe stehen, parallel zum Horizont im Westen. Links davon, im Südwesten, funkelt Sirius - und rechts davon, fast auf gleicher Höhe, das rötliche Auge des Stiers, der Stern Aldebaran. Schön anzuschauen ist in dieser Himmelsgegend der abendliche Lauf des zunehmenden Mondes am Monatsende: Vom 28. bis 31.März zieht er an Venus und den Plejaden im Stier vorbei und steigt hoch hinauf, über dem Orion in die Zwillinge. “Supermond” am 9.März Am 9.März erreicht der Mond nur wenige Stunden nach seinem Durchgang durch den erdnächsten Bahnpunkt im Sternbild Jungfrau die Vollmondstellung. Für solche Vollmonde, die nahe der Erdnähe stattfinden, hat sich seit einigen Jahren die Bezeichnung „Supermond“eingebürgert. Ein solcher Supermond ist allerdings nur um rund 7% größer und lediglich 15% heller als ein durchschnittlicher Vollmond - der Unterschied ist also kaum erkennbar. Das große Planetentripel am Ende der Nacht Es lohnt sich, bei klarer Sicht gegen 5 Uhr frühmorgens aufzustehen, um zu verfolgen, wie unser äußerer Nachbarplanet Mars bis zum 20.März immer näher an den fernen Riesenplaneten Jupiter heranrückt und dann knapp südlich an ihm vorbeizieht. Saturn steht dann nur 7 Grad links neben dem Planetenpaar. Am 18. und 19.März erweist auch der abnehmende Mond dem Planetentrio seine Referenz und gesellt sich dazu - ein prächtiges Bild, das uns da gegen 5 Uhr morgens geboten wird! Am letzten Monatstag überholt Mars, dann bereits im Sternbild Steinbock, auch den fast gleichhellen Saturn. Leider ist dies im Norden Deutschlands nur sehr horizontnah zu sehen. Ein Artikel von Prof. Thomas W. Kraupe, Astronom und Direktor des Planetarium Hamburg

Der Sternenpodcast Februar 2020 Ihr Audioguide für die Sterne. Ob zuhause mit der Sternkarte oder unterwegs unter freiem Himmel - Planetariumsdirektor Thomas Kraupe führt Sie zu den interessantesten Sternbildern und Himmelsereignissen - jeden Monat neu und kostenlos. Dieser Podcast des Planetarium Hamburg wird Ihnen in Zusammenarbeit mit dem Hamburger Abendblatt präsentiert - mit freundlicher Unterstützung unserer Audio-Partner Prime Time Studios und Audio Consulting Group. Im Februar zeigt sich der Winterhimmel noch einmal in seiner ganzen Pracht - und gleich mehrere Planeten und ein Stern haben ihren großen Auftritt! Der Aufstieg des „Abendsterns“ Schon kurz nach Sonnenuntergang leuchtet Venus als heller „Superstar“ über dem Westhorizont. Sie wandert östlich der Sonne durch den Tierkreis und rückt in den kommenden Wochen immer näher an unsere Erde heran. Venus reflektiert an ihrer dichten Wolkenhülle so viel Sonnenlicht, dass sie heller als alle Sterne leuchtet. Ende Februar geht sie erst um 22 Uhr unter, rund vier Stunden nach der Sonne. Vom 25. bis 27. rückt die Mondsichel an Venus heran und zieht bis 28.Februar an ihr vorbei - ein herrliches Bild in der Abenddämmerung! Merkurs kurze Abendshow Zu Beginn des Monats zeigt sich auch Merkur in der Abenddämmerung. Am 10.Februar erreicht er mit 18 Grad Winkelabstand zur Sonne seine „größte östliche Elongation“ erreicht. Am besten, man hält bereits etwa eine halbe Stunde nach Sonnenuntergang Ausschau. Dies ist sein bester Auftritt am Abendhimmel in diesem Jahr. Spätestens ab der Monatsmitte verschwindet der scheue Planet wieder im Glanz der Sonne. Die wichtigsten Sternbilder am Februarhimmel Wie eine große Vorfahrtstafel leuchten über Venus und Merkur im Westen noch die Sterne des „Herbstvierecks“. Im Osten, ist längst das schönste Sternbild des Frühlings emporgestiegen – der Löwe, der gegen 1 Uhr morgens seine größte Höhe im Süden erreicht. Am 9.Februar, wenige Stunden nach Vollmond, prangt die Mondkugel knapp über Regulus, dem „Herzstern“ des Löwen. Hoch über unseren Köpfen funkelt der helle Stern Capella im Fuhrmann. Er markiert den nördlichsten Stern des „Wintersechsecks“, dessen funkelnde Pracht den gesamten südlichen Himmelsbereich einnimmt. Der südlichste Stern in dem Sternensextett des Winters ist Sirius im Sternbild „Großer Hund“, der gegen 21 Uhr über der Südrichtung funkelt und erst nach Mitternacht im Südwesten untergeht. Unübersehbar - fast wie ein Schmetterling - wirkt daneben die Figur des Orion: Eine auffällige Kette von drei gleichhellen Sternen bildet den Gürtel des Jägers, jeweils zwei helle Sterne darüber und darunter die Schultern bzw. die Füße der Jägergestalt. Was ist los mit Beteigeuze? Seit vergangenen Oktober blicken abertausende von Sternfreunden Nacht für Nacht zu Beteigeuze, dem östlichen Schulterstern des Orion, denn dieser Stern hat in nur wenigen Wochen deutlich an Helligkeit verloren. Nicht nur Rigel, sondern auch Bellatrix, der westliche Schulterstern des Orion, ist nun heller als er. Selten kann man so leicht die Änderungen verfolgen, wie sie sogar im Leben eines Sterns geschehen. Beteigeuze steht kurz vor seinem Karriereende als Stern. Dies hat auch Folgen für seinen Außenbereich - der Stern pulsiert - sein Durchmesser, variiert unregelmäßig zwischen dem rund 500- bis 900-fachen des Sonnendurchmessers. Bald sind die Tage des Sterns gezählt. Der Stern wird zusammenbrechen und in einer katastrophalen Supernova-Explosion vergehen. Beteigeuze befindet sich kurz vor diesem Endstadium und könnte in nur wenigen zigtausend Jahren explodieren. Noch ist es nicht so weit - aber es ist schon packend, mit bloßem Auge den allmählichen Todeskampf dieses Sterns aus sicheren 650 Lichtjahren Entfernung zu verfolgen. Ein Artikel von Prof. Thomas W. Kraupe, Astronom und Direktor des Planetarium Hamburg

How is string different when hit with and not being hit with?

The Spokesmen Cycling Podcast Time Space Elongation, Marxist Geographers, Biking While Black: In Conversation With John Stehlin Episode 234 Saturday 11th January 2020 SPONSOR: Jenson USA HOST: Carlton Reid GUEST: John Stehlin, assistant professor at University of North Carolina at Greensboro, USA, author of "Cyclescapes of the Unequal City." NOTES: The-spokesmen.com

I call rope elongation the silent killer. Most people don't understand how rope stretch in their systems can often introduce risk. Careful understanding of fall lines can help you decide where to go or how to protect a pitch.

Vollmond kennt jeder. Aber gibt es auch eine Vollerde? Und was hat die Vollvenus mit Galileo Galilei und der Revolution unseres Weltbilds zu tun? In der heutigen Folge des Sternengeschichten-Podcast geht es um die Phasen der Himmelskörper!

Mitochondria are often described as molecular power stations of the cell as they generate most of the energy that drives cellular processes. Mitochondria are eukaryotic organelles with bacterial origin that contain an extra-nuclear source of genetic information. Although most mitochondrial proteins are encoded in the nucleus, the mitochondrial genome still encodes key components of the oxidative phosphorylation machinery that is the major source for cellular adenosine 5’-triphosphate (ATP). The mitochondrial genome is transcribed by a singlesubunit DNA-dependent RNA polymerase (RNAP) that is distantly related to the RNAP of bacteriophage T7. Unlike its T7 homolog, mitochondrial RNA polymerase (mtRNAP) relies on two transcription factors, TFAM and TFB2M, to initiate transcription. The previously solved structure of free mtRNAP has revealed a unique pentatricopeptide repeat (PPR) domain, a N-terminal domain (NTD) that resembles the promoter-binding domain of T7 RNAP and a C-terminal catalytic domain (CTD) that is highly conserved in T7 RNAP. The CTD adopts the canonical right-hand fold of polymerases of the pol A family, in which its ‘thumb’, ‘palm’ and ‘fingers’ subdomains flank the active center. Since the structure represents an inactive “clenched” conformation with a partially closed active center, only limited functional insights into the mitochondrial transcription cycle have been possible so far. This work reports the first crystal structure of the functional human mtRNAP elongation complex, determined at 2.65 Å resolution. The structure reveals a 9-base pair DNA-RNA hybrid formed between the DNA template and the RNA transcript and one turn of DNA both upstream and downstream of the hybrid. Comparisons with the distantly related T7 RNAP indicate conserved mechanisms for substrate binding and nucleotide incorporation, but also strong mechanistic differences. Whereas T7 RNAP refolds during the transition from initiation to elongation, mtRNAP adopts an intermediary conformation that is capable of elongation without NTD refolding. The intercalating hairpin that melts DNA during mtRNAP and T7 RNAP initiation additionally promotes separation of RNA from DNA during mtRNAP elongation. The structure of the mtRNAP elongation complex (this work) and free mtRNAP (previously published) demonstrate that mtRNAP represents an evolutionary intermediate between singlesubunit and multisubunit polymerases. Furthermore, it illustrates the adaption of a phage-like RNAP to a new role in mitochondrial gene expression.

Hosts: Vincent Racaniello, Rich Condit, and Kathy Spindler Vincent, Rich and Kathy discuss mechanisms of protein synthesis and regulation in virus-infected cells. Links for this episode: Slides for this episode (pdf) T7 ribosomal binding sites (CSH Symp Quant Biol) Tinkering with translation (CSH Persp) Translation at nexus of infection and immunity (Cell Host Microbe) Viral subversion of protein synthesis machinery (Nat Rev Micr) Weekly Science Picks Kathy - Vaccine-preventable outbreaksRich -  To Catch a Virus by John Booss and Marilyn J. AugustVincent - This is Water by David Foster Wallace Listener Pick of the Week Jon - Confessions of a converted lecturer by Eric MazurPeter - FameLab Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

Enterobacteria have evolved several strategies to survive the acidic environment of the gastrointestinal tract. One of the acid stress resistance systems is the Cad system in Escherichia coli, which is induced by low pH and in the presence of external lysine. It consists of CadA, which catalyzes the decarboxylation of lysine to cadaverine, the lysine/cadaverine antiporter CadB and the pH sensing transcriptional regulator CadC. Moreover, the lysine permease LysP inhibits the induction of cadBA expression when lysine is absent, and the small histon-like molecule H-NS acts as repressor for both cadBA and cadC transcription. Additionally, a random mutagenesis approach revealed that a deletion in yjeK leads to highly reduced cadaverine production. YjeK acts as 2,3-lysine aminomutase (LAM) while catalyzing the isomerization of (S)-α-lysine to (R)-β-lysine. The truncated lysyl-tRNA synthetase YjeA uses (R)-β-lysine as substrate to post-translationally modify and to activate the translation elongation factor EF-P at a conserved lysine residue (K34). EF-P and its ortholog eukaryotic initiation factor 5A (eIF5A) have been investigated for more than thirty years, but their roles in translation remained enigmatic. In this work the role of active EF-P in the Cad system was investigated in more detail. Reduced cadBA expression in ΔyjeA, ΔyjeK642-1029 and Δefp mutants was linked to impaired CadC translation. As the translation of cadA and cadB was EF-P independent, a general role of EF-P in translation could be excluded. The identification of CadC as first direct target for EF-P in E. coli allowed further investigations on the role of EF-P in translation. Determining the β-galactosidase activities of CadC´-LacZ translational fusions of increasing CadC length in efp- and efp+ cells revealed that EF-P is required for translation of the sequence found between codon 108 and 158 in cadC. This region comprises a cluster of three consecutive prolines (Pro120-Pro121-Pro122). Substitution of these prolines by alanines diminished EF-P dependency. Remarkably, cells harboring the CadC-PPPIP/AAAIS variant revealed cadBA expression even under non-inducing conditions. Thus, EF-P tightly controls the CadC copy number, which is crucial for stress dependent regulation of the Cad system. In order to investigate the work mechanism of EF-P in more detail, EF-P independent CadC´-LacZ hybrids were employed to artificially introduce prolines. Three consecutive prolines were sufficient for EF-P dependency, regardless of the codon or the context. The proline-rich proteins AmiB, FlhC, Flk, NlpD, RzoR, TonB and UvrB also showed EF-P dependent expression. Thus, the recognition of three consecutive prolines by EF-P is a general mechanism and not limited to CadC. Dr. Agata Starosta of the group of Dr. Daniel Wilson (Gene Center, LMU Munich) confirmed ribosomal stalling at polyproline-stretches in samples lacking EF-P with in vitro translation assays. Finally it was investigated, if EF-P expression and modification could be stress-dependently regulated. In this work first hints are given that the efp promoter contains a repressor site, and that expression of yjeA and yjeK is dependent on the pH of the medium and the presence of the small RNA binding protein Hfq. This leads to the suggestion that small regulatory RNAs are also involved in regulation of the EF-P modification enzymes. In conclusion, the results obtained in this work reveal a new regulatory mechanism by EF-P dependent translation. 100-1000´s of polyproline rich proteins exist in bacteria, archaea and eukaryotes. Therefore, EF-P and its orthologs aIF5A and eIF5A most likely play an important role in the adjustment of copy numbers of proteins with different functions in all kingdoms of life.

Aspergillus fumigatus is a saprophytic mold that naturally inhabits the soil. Asexual reproduction yields hardy conidia that circulate in the air and are inhaled daily by humans. The fungus seems not to have evolved distinct mechanisms of pathogenicity, but is capable of responding to many stressful environmental cues present in its naturally harsh niche. The robust conidia present no problem to a fully functioning immune system, but if the innate immune system is compromised, the conidia can become activated and differentiate within the lung tissue to form invasive and disseminating hyphae. The resulting disease is called aspergillosis and is difficult to detect and to treat. To date, scientists have yet to find the factor(s) missing during immunosuppression that allow a healthy patient to easily dispose of A. fumigatus. We explored two possibilities: the production of neutrophil extracellular traps (NETs) and the release of IFN-γ by natural killer (NK) cells. We report here that NETs alone cannot kill the fungus, but do inhibit polar growth. Elongation of hyphal tips is abrogated due to zinc starvation, likely a consequence of the zinc-chelating, NETs-associated protein calprotectin. NK cells alone are also incapable of fungicidal activity, but their release of IFN-γ upon contact with A. fumigatus abrogates hyphal growth by a yet unknown mechanism. In vitro studies of the innate immune response, though helpful, are far from representative of the in vivo response. Neither NETs nor IFN-γ alone can manage Aspergillus infection, but in combination, these and other immune assaults certainly can. The difficulty lies in identifying the precise combination of immune cells and cytokine milieu that in a healthy individual prevent infection. Additionally, we explored mechanisms by which the fungus responds to stress, namely the HOG MAPK pathway, historically involved in osmotic stress response. In filamentous fungi, certain stress signals are sensed by a cytoplasmic hybrid histidine kinase sensor and then passed through the HOG system via phosphorylation. We identified the putative hybrid sensor kinase in A. fumigatus, and generated a corresponding knockout mutant. The ΔtcsC mutant was indeed sensitive to osmotic stress, and resistant to the phenolpyrrole fungicide fludioxonil. In the wild type the addition of either osmotic stress or fludioxonil resulted in SakA phosphorylation and translocation to the nucleus. SakA, the Hog1 homolog in A. fumigatus, is located at the end of the HOG pathway, confirming the role of TcsC as the cytoplasmic sensor upstream of SakA. In hypoxia, on farnesol, and in high concentrations of divalent cations the ΔtcsC mutant exhibited a striking “fluffy” phenotype characterized by the production of tremendous aerial hyphae and little or no differentiation, i.e., no conidiation. Though the ΔtcsC mutant showed no change in virulence compared to wild type, components of the TcsC signalling pathway remain promising targets for antifungal agents.

Gary continues the conversation on Mars Rx with Adam Gainsburg of Soulsign. We cover the brightest apparition of Mars for the next two years. Then Gary relates this to Mercury and his upcoming retrograde transformation. Lots of insights packed into a relatively short show!

Wed, 20 Jul 2011 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/13249/ https://edoc.ub.uni-muenchen.de/13249/1/Chanarat_Sittinan.pdf Chanarat, Sittinan ddc:540, ddc:50

Mon, 25 Oct 2010 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/13046/ https://edoc.ub.uni-muenchen.de/13046/1/Schmidt_Thorsten.pdf Schmidt, Thorsten ddc:570, ddc:500, Fakultät für Biologie

Molekülmechanische (MM) Molekulardynamik-(MD)-Simulationen sollen eine virtuelle Realität von Makromolekülen im Computer erschaffen. Dabei zeigten sorgfältige Tests wiederholt, dass die bisherigen MM-Kraftfelder nur bedingt geeignet sind, um experimentelle Referenzdaten zu reproduzieren. In vielen Fällen sind die Mängel der Beschreibung auf die Vernachlässigung von nicht-additiven Effekten, insbesondere der elektrostatischen Polarisation, zurückzuführen. Das Wassermolekül ist stark polarisierbar und muss in MD-Simulationen von Biomolekülen einbezogen werden. Aus diesem Grund werden im ersten Teil meiner Arbeit die Effekte von externen elektrischen Feldern auf Wassermoleküle untersucht. In polarisierbaren MM-Modellen für Wasser wird das induzierte Dipolmoment zumeist an das Feld am Ort des Sauerstoffatoms gekoppelt – die Elektronendichte eines realen Wassermoleküls reagiert aber auf ein Volumenmittel des Feldes. Es wird gezeigt, dass im Gegensatz bisherigen Meinung, das elektrische Feld, dem ein Wassermolekül im Volumenwasser ausgesetzt ist, nicht homogen, sondern selbst auf dem kleinen Volumen, welches das Molekül einnimmt, hochgradig inhomogen ist. Die Feldinhomogenität ist aber dergestalt, dass sie durch eine mittlere Feldinhomogenität beschrieben werden kann. Deshalb ist das mittlere Feld annähernd proportional zum Feld am Ort des Sauerstoffatoms und kann daraus mit Hilfe eines Skalierungsfaktors berechnet werden. Das skalierte Feld kann dann zur Berechnung des Dipolmoments von punkt-polarisierbaren Wassermodellen herangezogen werden. Es wird außerdem gezeigt, dass die Polarisierbarkeit, die als Proportionalitätskonstante bei der Berechnung des Dipolmoments auftaucht, in der flüssigen Phase den gleichen Wert wie bei isolierten Wassermolekülen hat, obwohl ihre Geometrie dort von der Gasphasengeometrie abweicht. Dies ist darauf zurückzuführen, dass sich für die spezifische Geometrieänderung, die beim Transfer in die flüssige Phase beobachtet wird, zwei Beiträge zur Polarisierbarkeit gegenseitig aufheben. Diese Beiträge resultieren allgemein aus der Elongation der Bindungslängen und der Kompression des Bindungswinkels. Die Frage, ob der Einsatz eines solchen polarisierbaren Kraftfeldes die Beschreibung von Makromolekülen, wie beispielsweise Proteinen, verbessert, kann nur durch Vergleich mit dem Experiment beantwortet werden. Infrarotspektren sind hoch sensitiv bezüglich lokaler elektrischer Felder und wären deshalb eine gute Referenz. Theoretische Vorhersagen solcher Spektren sind allerdings nur für eine der in Proteinen auftretenden Banden – und auch hier nur bedingt – möglich. Der zweite Teil dieser Dissertation beschäftigt sich deshalb mit der Entwicklung eines Kraftfelds zur Berechnung aller Schwingungsbanden des Proteinrückgrats. Hier wird der Einfluss der lokalen elektrischen Felder auf die Stärke der kovalenten Bindungen explizit berücksichtigt. Aufbauend auf einer Vorabversion eines solchen Kraftfelds wird eine Methode entwickelt, um Schwingungsspektren mit spektroskopischer Genauigkeit, d.h. mit Fehlern im Bereich von wenigen Wellenzahlen, vorherzusagen. Der minimale Parametersatz, der zur korrekten Beschreibung dieser Schwingungsspektren notwendig ist, wird identifiziert, und die entbehrlichen Parameter werden eliminiert. Anhand des Moleküls N-Methylacetamid wird demonstriert, dass das neue Kraftfeld in der Lage ist, solvatochrome Verschiebungen für verschiedene polare Lösungsmittel gut zu reproduzieren.

Learn about the earliest journeys of our ancestors revealed by archaeogenetics (0:50),  a versatile transcription elongation factor with several key functions in the cell (11:12) and an oncoprotein and its many partners, which are involved in leukemia (16:21).

Fri, 17 Jul 2009 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/11254/ https://edoc.ub.uni-muenchen.de/11254/1/Andrecka_Joanna.pdf Andrecka, Joanna ddc:540, ddc:500, Fakultät für Chemie und

Polyglutaminerkrankungen sind neurodegenerative Erkrankungen mit fatalem Verlauf, die sich durch selektive neuronale Degeneration und die Bildung intrazellulärer Aggregate auszeichnen. Verursacht werden sie durch eine Expansion einer Polyglutaminsequenz in einem für die Erkrankung spezifischen Protein, die Fehlfaltung und Aggregation des entsprechenden Proteins bewirkt. Die Aggregation wirkt dabei neurotoxisch, wobei Toxizität hauptsächlich durch lösliche Intermediate des Aggregationsprozesses vermittelt wird. Zur Untersuchung der frühen Aggregationsphase und der späteren Elongationsphase wurden in dieser Arbeit verschiedene fluoreszenzbasierte Methoden etabliert. Mit Hilfe dieser Methoden konnte gezeigt werden, dass nach proteolytischer Spaltung von GST-Htt-Exon1 das Monomer eine Konformationsumlagerung durchmacht, die von einer Dimerisierung oder Oligomerisierung gefolgt wird. Dimere oder Oligomere bilden dabei eine kompakte Struktur aus. Wachstum der Fibrillen erfolgt durch Anlagerung von Monomeren oder einer anderen bisher nicht identifizierten Spezies. Durch Distanzmessungen innerhalb verschiedener Spezies konnte gezeigt werden, dass unlösliche Spezies eine kompakte Struktur aufweisen, die spezifisch für unlösliche Spezies ist. Lösliche Spezies liegen dagegen in einer expandierteren Konformation vor. Molekulare Chaperone üben oftmals eine protektive Funktion auf Neuronen in neurodegenerativen Erkrankungen aus. In dieser Arbeit wurde untersucht, inwieweit das eukaryontische Chaperonin TRiC, das in einem RNA-interference screen als potentieller Suppressor der Huntingtin-Aggregation identifiziert wurde, Aggregation modulieren kann. Gereinigtes TRiC hat keinen Einfluss auf die frühe Phase der Htt-Exon1-Aggregation, vielmehr inhibiert es die Elongation von fibrillären Strukturen, indem es mit Htt-Exon1-Oligomeren interagiert. Diese Interaktion ist transient und ATP-unabhängig. Im Gegensatz dazu interagiert TRiC in Kooperation mit dem Hsp70/40-System mit Htt-Exon1-Monomeren und verhindert die Nukleation der Aggregation. Stattdessen wird ein „gefaltetes“ Htt-Exon1-Produkt mit einer neuartigen Konformation gebildet, das löslich, nicht-fibrillär und nicht-toxisch ist und ~500 kDa-Oligomere ausbildet. Diese Interaktion ist kooperativ, sequentiell und benötigt ATP, ähnelt also der kooperativen Interaktion von TRiC und Hsp70/40 in der de novo-Proteinfaltung und stellt möglicherweise einen natürlichen Faltungsweg für Huntingtin dar.

RNA polymerase II (RNAP II) transiently associates with many different proteins and multiprotein complexes during the mRNA transcription cycle, which includes three phases, initiation, elongation, and termination. This thesis describes structural studies of two factors that facilitate transcription through chromatin. The heterodimeric Saccharomyces cerevisiae elongation factor Spt4-Spt5 (human DSIF) has been identified by biochemical and genetic approaches to help RNAP II transcribe through chromatin. It is assumed that Spt4-Spt5 pauses RNAP II to open a time window for capping enzyme recruitment and addition of a cap to the 5'-end of the nascent RNA. The preparation of milligram quantities of soluble Spt4-Spt5 variants that are suited for structural studies has been achieved. Several strategies to resolve the structure of the RNAP II–Spt4-Spt5 complex were unsuccessful, possibly indicating an intrinsic flexibility of the complex. In addition, there is now evidence for direct links between chromatin modification and transcription elongation. A major player in this process is the histone lysine methyltransferase Set2 which has a modular structure. The catalytic activity of Set2 is mediated by the SET [Su(var)3-9, Enhancer of Zeste, Trithorax] domain. During mRNA elongation, the SRI (Set2 Rpb1-interacting) domain of Set2 binds to the phosphorylated CTD (carboxyl-terminal domain) of RNAP II. The NMR solution structure of yeast Set2 SRI domain has been determined. The structure reveals a novel CTD-binding fold consisting of a left-handed three-helix bundle. Unexpectedly, the SRI domain fold resembles the structure of an RNA polymerase-interacting domain in sigma factors that mediate transcription initiation in bacteria (domain sigma2 in sigma70). NMR titration experiments show that the SRI domain binds a Ser2/Ser5-phosphorylated CTD peptide comprising two heptapeptide repeats and three flanking NH2-terminal residues. Amino acid residues that show strong chemical shift perturbations upon CTD binding cluster in two regions on the SRI surface. The results will enable a detailed analysis of the specific CTD interactions underlying the coupling of transcription and chromatin modification by Set2.

This thesis describes crystal structures of complete, 12-subunit yeast RNA polymerase II (Pol II) in complex with a synthetic transcription bubble and product RNA, with an NTP substrate analogue, and in complex with the transcription elongation factor TFIIS. The structure of the Pol II-transcription bubble-RNA complex reveals incoming template and non-template DNA, a seven base-pair DNA-RNA hybrid, and three nucleotides each of separating DNA and RNA. Based on this structure, those parts of Pol II were identified which are involved in separating template DNA from non-template DNA before the active site, and DNA from product RNA at the upstream end of the DNA-RNA hybrid. In both instances, strand separation can be explained by Pol II-induced duplex distortions. Only parts of the complete transcription bubble present in the complexes are ordered in the crystal structure, explaining the way in which high processivity of Pol II is reconciled with rapid translocation along the DNA template. The presence of an NTP substrate analogue in a conserved putative pre-insertion site was unveiled in a Pol II-transcription bubble-RNA complex crystal soaked with the substrate analogue GMPCPP. The structure of the Pol II-TFIIS complex was obtained from Pol II crystals soaked with TFIIS. TFIIS extends from the Pol II surface to the active site and complements the active site with two essential and invariant acidic residues for hydrolytic RNA cleavage. TFIIS also induces extensive structural changes in Pol II that reposition nucleic acids, in particular RNA, near the active centre. These results support the idea that Pol II contains a single tuneable active site for RNA polymerisation and cleavage. The technical obstacles imposed by crystal structure determination of large, transient protein-DNA-RNA complexes were overcome by two novel, fluorescence-based assays to monitor and optimise the composition of the crystals. Both assays are not limited to Pol II complexes, but can serve as a general tool for the crystallographic community.