One of alternative forms of the same gene
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We are back with more exciting IDWeek 2024 content. In this episode, Breakpoints hostesses Drs. Erin McCreary, Julie Ann Justo, Jeannette Bouchard, and Megan Klatt highlight more of our favorite sessions and posters at IDWeek, this episode is a must listen if you are an IDWeek nerd like us! References: Perret et al. Application of OpenAI GPT-4 for the retrospective detection of catheter-associated urinary tract infections in a fictitious and curated patient data set. 10.1017/ice.2023.189 Wiemken et al. Assisting the infection preventionist: Use of artificial intelligence for health care–associated infection surveillance. 10.1016/j.ajic.2024.02.007 Leekha et al. Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study. 10.1136/bmjqs-2023-016831 Diekema et al. Are Contact Precautions "Essential" for the Prevention of Healthcare-associated Methicillin-Resistant Staphylococcus aureus? 10.1093/cid/ciad571 Martin et al. Contact precautions for MRSA and VRE: where are we now? A survey of the Society for Healthcare Epidemiology of America Research Network. 10.1017/ash.2024.350 Browne et al. Investigating the effect of enhanced cleaning and disinfection of shared medical equipment on health-care-associated infections in Australia (CLEEN): a stepped-wedge, cluster randomised, controlled trial. 10.1016/S1473-3099(24)00399-2 Protect trial: Decolonization in Nursing Homes to Prevent Infection and Hospitalization. 10.1056/NEJMoa2215254 Aldardeer et al. Early Versus Late Antipseudomonal β-Lactam Antibiotic Dose Adjustment in Critically Ill Sepsis Patients With Acute Kidney Injury: A Prospective Observational Cohort Study. 10.1093/ofid/ofae059 Schmiemann et al. Effects of a multimodal intervention in primary care to reduce second line antibiotic prescriptions for urinary tract infections in women: parallel, cluster randomised, controlled trial. 10.1136/bmj-2023-076305 Vernacchio et al. Improving Short Course Treatment of Pediatric Infections: A Randomized Quality Improvement Trial. 10.1542/peds.2023-063691 Advani et al. Bacteremia From a Presumed Urinary Source in Hospitalized Adults With Asymptomatic Bacteriuria. 10.1001/jamanetworkopen.2024.2283 Saif et al. Clinical decision support for gastrointestinal panel testing. 10.1017/ash.2024.15 Bekker et al. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. 10.1056/NEJMoa2407001 Montini et al. Short Oral Antibiotic Therapy for Pediatric Febrile Urinary Tract Infections: A Randomized Trial. 10.1542/peds.2023-062598 Nielsen et al. Oral versus intravenous empirical antibiotics in children and adolescents with uncomplicated bone and joint infections: a nationwide, randomised, controlled, non-inferiority trial in Denmark. 10.1016/S2352-4642(24)00133-0 Kaasch et al. Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial. 10.1016/S1473-3099(23)00756-9 AMIKINHAL: Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia. 10.1056/NEJMoa2310307 PROPHY-VAP: Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial. 10.1016/S2213-2600(23)00471-X AVENIR: Azithromycin to Reduce Mortality — An Adaptive Cluster-Randomized Trial. 10.1056/NEJMoa2312093 Thomas et al. Comparison of Two High-Dose Versus Two Standard-Dose Influenza Vaccines in Adult Allogeneic Hematopoietic Cell Transplant Recipients. 10.1093/cid/ciad458 Schuster et al. The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial. 10.1093/cid/ciad534 Mahadeo et al. Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial. 10.1016/S1470-2045(23)00649-6 Khoury et al. Third-party virus-specific T cells for the treatment of double-stranded DNA viral reactivation and posttransplant lymphoproliferative disease after solid organ transplant. 10.1016/j.ajt.2024.04.009 Spec et al. MSG-15: Super-Bioavailability Itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses—A Multicenter, Open-Label, Randomized Comparative Trial. 10.1093/ofid/ofae010
Speed of Light by Stefan DurhamSpeed of Light is a sci-fi fantasy love story filled with information about the human psyche and experience. The story has three main characters: Zenthaus, Mazaya, and Allele.Zenthaus is a heroic figure who embarks on a journey to liberate or rescue a slave girl and her daughter from captivity. Mazaya the slave girl, also a princess that comes from a rare and unique royal bloodline, gives birth to Allele, the star seed who is chosen to restore balance and prosperity to a world full of darkness.It's an adventure that causes these characters to learn life lessons and to find fulfillment in those lessons, a documentary of parables and allegories that hold an even deeper meaning and message when you read it. It is a hero's journey that delves into the struggles that we all face throughout life, followed by justice, transformation, and the balance between light and darkness, diving headfirst into addressing the anxieties of life. Here you will find digestible facts about the author's personal life, not just the ones that preserve his image, but a really intimate and detailed description of his shadow self--the parts that are dark, mysterious, and difficult to understand. These are life lessons that we can all benefit from tremendously. These characters represent different aspects of the author's personality. This adventure is suspenseful, romantic, highly vibrational, and energetically abundant, breaking through the illusions of our reality, helping others to see the truth about themselves.Stefan Durham was brought up in performing arts with his family in Colorado Springs, CO. These different forms of art include, martial arts, culinary arts and songwriting. His first book "Speed of Light", also considered a work of art, is part of a Sc-fi series that will continue to grow and inspire for many years to come. In this Light Speed series, we will explore the universe's answer to the negativity that forces its way through the barrier of our consciousness and into our reality. https://www.amazon.com/Speed-Light-Stefan-Durham/dp/B0C6B2HWL7http://www.MainspringBooks.com https://www.newmansprings.com/release/?book=speedoflight&fbclid=IwY2xjawFmVdxleHRuA2FlbQIxMAABHXo3s-8TCQfBsgItSURCgOySIVEFTiMLA2NNqtrjrI3PyMLrjQbpvjPaJw_aem_HV0SS5UB3kKvz3ugfiTK6whttp://www.bluefunkbroadcasting.com/root/twia/10324sdmsb.mp3
Genetics can be intricate, no doubt. With millions of mutations present in every human, one might wonder why not everyone is impacted by pathogenic diseases. The Patient Empowerment Program aims to assist you in grasping the fundamental concepts of various mutations and how they function, paving the way for you to enhance your understanding of genetics. Delve into the diverse array of disease-causing mutations, their characteristics, and explore which mutations could potentially be addressed through ASO treatment in this concluding episode of Advanced Genetics.On This Episode We Discuss:The nature of a SNPPre-mature-m-RNA effectsIndels can disrupt the reading frameDefining Alleles, Homozygous, Heterozygous, and Compound HeterozygousThe difference between whole exome and genome sequencingHow we, at n-Lorem, decide which patients are amendable to ASO treatmentsHow we design ASOs to take advantage of different post-RNA binding mechanismsMechanisms: Non-allele selective RNAse H1, Allele-selective RNAse H1, and Splicing ASOs
Es gibt über viel zu schwärmen: Julian hat anscheinend bei Die Tagebücher der Apothekerin Lukas nicht zu viel versprochen, Lukas hat mit der schrägen Mystery-Serie Migi & Dali seinen Geheimtipp des Jahres gefunden und Frieren - Nach dem Ende der Reise begeistert beide auf allen Ebenen. Während Eminence in Shadow Staffel 2 und 100 Girlfriends bei Julian höher im Kurs steht, hatte Lukas mehr Spaß bei den nun endlich erschienenen, abschließenden Episoden von Zom 100. Enttäuschungen waren bei der Menge an Anime aber leider auch zu erwarten: Für Julian konnte selbst Eurobeat nicht MF Ghost retten, Firefighter Daigo war nicht hitzebeständig genug für Lukas' Hottakes und über Kizuna no Allele will Lukas komischerweise nicht reden...
Listen to our thoughts on the newest season! Lots of good anime. What did you all think? 00:00 Intro 02:00 Alice Gear Aegis Expansion 02:44 Ao no Orchestra 04:23 The Aristocrat’s Otherworldly Adventure 05:00 The Café Terrace and Its Goddesses 06:23 Dead Mount Death Play 07:15 Kizuna no Allele 08:08 THE MARGINAL SERVICE 09:23 My … Continue reading Kaiseki Anime Ep. 122 — Spring 2023 Seasonal Impressions →
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.12.536672v1?rss=1 Authors: Fujiwara, Y., Saito, K., Sun, F., Inoue, E., Schimenti, J., Okada, Y., Handel, M. A. Abstract: An unbiased screen for discovering novel genes for fertility identified the spcar3, spermatocyte arrest 3, mutant phenotype. The spcar3 mutation identified a new allele of the Setx gene, encoding senataxin, a DNA/RNA helicase that regulates transcription termination by resolving DNA/RNA hybrid R-loop structures. Although mutations in the human SETX gene cause neural disorders, Setxspcar3 mutant mice do not show any apparent neural phenotype, but instead exhibit male infertility and female subfertility. Histology of the Setxspcar3 mutant testes revealed absence of spermatids and mature spermatozoa in the seminiferous tubules. Cytological analysis of chromosome spread preparations of the Setxspcar3 mutant spermatocytes revealed normal synapsis, but aberrant DNA damage in the autosomes, and defective formation of the sex body. Furthermore, Setxspcar3 testicular cells exhibited abnormal accumulation of R-loops compared to wild type testicular cells. Transient expression assays identified regions of the senataxin protein required for sub-nuclear localization. Together, these results not only confirm that senataxin is required for normal meiosis and spermatogenesis but also provide a new resource for determination of its role in maintaining R-loop formation and genome integrity. 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/2023.04.07.536031v1?rss=1 Authors: Balasooriya, G. I., Spector, D. L. Abstract: Spatiotemporal gene regulation is fundamental to the biology of diploid cells. Therefore, effective communication between two alleles and their geometry in the nucleus is important. However, the mechanism that fine-tunes the expression from each of the two alleles of an autosome is enigmatic. Establishing an allele-specific gene expression visualization system in living cells, we show that alleles of biallelically expressed Cth and Ttc4 genes are paired prior to acquiring monoallelic expression. We found that active alleles of monoallelic genes are preferentially localized at Sun1-enriched domains at the nuclear periphery. These peripherally localized active DNA loci are enriched with adenine-thymidine-rich tandem repeats that interact with Hnrnpd and reside in a Hi-C-defined A compartment within the B compartment. Our results demonstrate the biological significance of T1A3 tandem repeat sequences in genome organization and how the regulation of gene expression, at the level of individual alleles, relates to their spatial arrangement. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
AniTAY Podcast Spring 2023 Seasonal Preview Spring is finally here along with a gamut of new anime. I also have too much fun editing this podcast. This episode's members: Requiem, Gugsy, TheMamaLuigi and Raitzeno with Thatsmapizza handling the editing duties. The AniTAY Podcast is a bi-weekly podcast brought to you every other Wednesday. It is available on all your favorite podcast services! If you like us, be sure to subscribe to your favorite service and give us 5 stars! Your support is much appreciated and will help us grow and continue to provide this style of content. Intro: 0:00 - 2:06 Housekeeping: 2:06 - 6:29 New Seasonal Shows: The Galaxy Next Door: 6:30 - 8:28 Alice Gear Aegis Expansion: 8:29 - 10:49 Ao no Orchestra: 10:50 - 15:09 Birdie Wing S2: 15:10 - 17:27 Chibi Godzilla: 17:28 - 18:51 Death Mount Death Play: 18:52 - 22:49 Demon Slayer, Swordsmith Village Arc: 22:50 - 25:18 Dr. Stone S3: 25:19 - 27:04 Edens Zero S2: 27:05 - 29:39 Hell's Paradise: 29:40 - 32:08 Insomniacs After School: 32:09 - 34:05 Cheat Skill in Another World: 34:06 - 38:08 Summon to Another World for a Second Time: 38:09 - 41:08 In Another World with My Smartphone S2: 41:09 - 43:42 What God Does in a World Without Gods: 43:43 - 45:56 Mobile Suit Gundam - The Witch from Mercury S2: 45:57 - 47:27 Kizuna no Allele: 47:28 - 49:25 KONOSUBA - An Explosion on This Wonderful World: 49:26 - 51:42 Kuma Kuma Kuma Bear S2: 51:43 - 55:04 Magical Destroyers: 55:05 - 58:03 Mashle - Magic and Muscles: 58:04 - 1:01:39 The Cafe Terrace and its Goddesses: 1:01:40 - 1:02:51 Mix S2: 1:02:52 - 1:06:07 My Clueless First Friend: 1:06:08 - 1:08:33 My Home Hero: 1:08:34 - 1:10:30 My One Hit Kill Sister: 1:10:31 - 1:12:40 Opus Colors: 1:12:41 - 1:13:34 Oshi no Ko: 1:13:35 - 1:17:02 Otaku Elf: 1:17:03 - 1:18:37 Ranking of Kings S2: 1:18:38 - 1:20:58 Pokemon 2023: 1:20:59 - 1:24:21 Rokudo's Bad Girls: 1:24:22 - 1:26:25 Sacrificial Princess and the King of Beasts: 1:26:26 - 1:27:54 Skip and Loafer: 1:27:55 - 1:30:34 Heavenly Delusion: 1:30:35 - 1:32:45 Ancient Magus Bride S2: 1:32:46 - 1:36:00 The Aristocrat's Other Worldly Adventure: 1:36:01 - 1:38:14 The Dangers in My Heart: 1:38:15 - 1:40:01 The Idolm@ster Cinderella Girls: U149: 1:40:02 - 1:40:52 The Legendary Hero is Dead: 1:40:53 - 1:43:19 The Marginal Service: 1:43:20 - 1:45:28 Why Raeliana Ended Up at the Duke's Mansion: 1:45:29 - 1:48:24 Tokyo Mew Mew S2: 1:48:25 - 1:50:11 Tonikawa - Over the Moon for You: 1:50:12 - 1:52:07 Too Cute Crisis: 1:52:08 - 1:54:05 Tousouchuu - Great Mission: 1:54:06 - 1:56:54 World Dai Star: 1:56:54 - 1:57:50 Yamada-Kun to Lv999 no Koi wo Suru: 1:57:51 - 2:01:05 Yuri is My Job!: 2:01:06 - 2:02:28 Movies/OVAs/Shorts: 2:02:29 - 2:05:56 Shows AniTAY is Excited for: 2:05:57 - 2:09:56 Outro: 2:09:56 - End Missed the previous episode of the AniTAY Podcast? Check it out here: https://medium.com/anitay-official/anitay-podcast-s8-e4-attack-on-titan-season-40-final-mix-championship-edition-part-2-section-a-54b5f5be48c2
The SLICK haplotype, originally identified in Senepol cattle, has been introduced into Holsteins. Inheritance of the SLICK1 allele of the prolactin receptor gene improves thermotolerance of lactating Holstein cows under humid heat stress conditions.Dr. Anna Denicol of the University of California-Davis, along with her research group, recently published a study on whether pre- and postweaning Holstein heifers carrying the SLICK1 allele would show physiological responses indicative of higher tolerance to heat stress in high- and low-humidity climates. In this video, Dr. Phil Cardoso talks with Dr. Denicol about her work.Links to papers and other sources mentioned in this podcast--------------------------------------------------------------- Carmickle et al. 2022, Physiological responses of Holstein calves and heifers carrying the SLICK1 allele to heat stress in California and Florida dairy farms.https://www.journalofdairyscience.org/article/S0022-0302(22)00527-6/fulltextDOI: 10.3168/jds.2022-22177Dikmen et al. 2014, The SLICK hair locus derived from Senepol cattle confers thermotolerance to intensively managed lactating Holstein cows.https://www.journalofdairyscience.org/article/S0022-0302(14)00457-3/fulltextDOI: 10.3168/jds.2014-8087Sosa et al. 2021, Inheritance of the SLICK1 allele of PRLR in cattle.https://onlinelibrary.wiley.com/doi/10.1111/age.13145DOI: 10.1111/age.13145Vapometer to measure the speed of water leaving the skinhttps://delfintech.com/products/vapometer/
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.14.516364v1?rss=1 Authors: Hua, L., Gao, F., Xia, X., Guo, Q., Zhao, Y., Yuan, Z. Abstract: To date, no reliable biomarkers are available that link individual-specific functional connectivity and patients' individualized symptoms for early detection and prediction of Alzheimer's disease (AD) in elderly people with specific genotypes. Meanwhile, functional magnetic resonance imaging (MRI) and machine learning are promising tools that can reveal the relationships between brain and behavior at individual level towards predicting the transition to AD. In this study, individual-specific functional connectivity was constructed in elderly participants with Apolipoprotein E (APOE) {varepsilon}4 allele (N = 120) and without APOE {varepsilon}4 allele (N = 115), respectively. In particular, machine learning based on a recursive feature selection technique was carried out to track multiple clinical symptoms among differing genotypes at individual level from normal aging (NA) and AD. It was found that the captured neuroimaging features in both APOE genotyping groups were able to distinguish the changes of clinical symptoms from NA to AD. Besides, our findings illustrated that the connections between individual-specific functional regions exhibited significantly higher correlation between estimated and observed scores in multiple clinical symptoms than those from atlas-based functional connectivity for both APOE genotyping groups, while no significant performance was detected when the data of two APOE genotyping groups were combined for the estimation models. Further, individual-specific between-network connectivity constitutes a major contributor for accessing cognitive symptoms in both APOE genotyping groups. Therefore, this study demonstrated the essential role of individual variation in cortical functional anatomy and the significance in combining brain and behavior for improving the accuracy in detection and prediction of AD in elderly people with specific genotypes. 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/2022.11.07.515284v1?rss=1 Authors: Sadikoglou, E., Domingo-Fernandez, D., Savytska, N., Fernandes, N., Rizzu, P., Illarionova, A., Strauss, T., Schwarz, S., Kodamullil, A., Hoeglinger, G., Dhingra, A., Heutink, P. Abstract: The microtubule associated protein tau (MAPT) chromosome 17q21.31 locus lies within a region of high linkage disequilibrium (LD) conferring two extended haplotypes commonly referred to as H1 and H2. The major haplotype, H1 has been genetically associated with an increased risk for multiple neurodegenerative disorders, including Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), APOE epsilon4-negative Alzheimer`s disease (AD) and Parkinson`s disease (PD). The mechanism causing this increased risk is largely unknown. Here, we investigated the role of Mild Chronic Oxidative Stress (MCOS) in neurogenin 2 (NGN2) induced neurons (iNeurons) derived from iPS (induced pluripotent stem cells) from carriers of both haplotypes. We identified that iNeurons of the H1 homozygous haplotype showed an increased susceptibility to MCOS compared to homozygous H2 carriers, leading to cell death through ferroptosis. We performed a cellular screen in H1 iNeurons using a FDA-approved Drug Library and identified candidate molecules that rescued the increased susceptibility to MCOS and prevented ferroptosis in H1 iNeurons. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
This week on the Roach Koach Podcast we begin Jenny's slow exit from the show with her first album pick, Point of Origin by Allele. Why did Jenny pick this album? Did Jenny get academic with her research? Does this album have enough screams? What is Matt's relationship with the film Garden State? Most importantly, does Allele belong in the Nu-Metal Canon? Listen and find out!Rate and review Roach Koach on iTunes! We'd appreciate it! Questions about the show? Have album recommendations? Just want to say hi? We'd love to hear from you! Contact the show @RoachKoach on Twitter, Roach Koach on Facebook , Roach Koach on Instagram, or send an email to RoachKoachPodcast at Gmail. Support the show over on our Patreon.
Nari & the Boys leave Taybury in good hands, traveling north to retrieve their hidden airship from the Free Peoples of Allele on this first leg of their trek to visit Nari's people in the mountains and to seek a cure for Rousse. Also, Pine judges a science fair, Rousse prays to a god with no followers, Ebi inspires the rising generation, and Nari finds a familiar hiding spot. Join the 12 Sided Guys on Discord! https://discord.gg/SJZnpCCx6N Support us at patreon.com/12sidedguys for extra content including bonus episodes, DM notes, and more! Additional sound effects from zapsplat.com and tabletopaudio.com. Additional music by Jonathan Shaw. Find more of his music at www.jshaw.co.uk.
What does it mean for something to be finely-tuned? Does fine-tuning extend beyond our own man-made systems and into biology and the universe itself? If so, what or who has done the fine-tuning? Robert J. Marks, Ola Hössjer, and Daniel Diaz discuss the concept of fine-tuning. Show Notes 00:02:17 | Introducing Ola Hössjer and Daniel Diaz 00:04:39 | No Free… Source
There is a month and a week left until the summer solstice, and the time when the days begin growing shorter. Until then, there are now over 14 hours of sunlight in the section of the Earth on the day when the May 16 edition of Charlottesville Community Engagement is produced. That’s enough time to ensure that this newsletter and podcast at least tries to bring as much information as possible. I’m your host, Sean Tubbs. On today’s program:Charlottesville Planning Commission recommends a seven-story building on Jefferson Park AvenueA fatal crash on U.S. 29 near Greenbrier Road has claimed the life of a Charlottesville manAn Augusta County elections official is the latest appointee to the State Board of ElectionsA quick update on COVID-19 from the UnivToday’s first shout-out goes to LEAPWe’re now well into spring, and many of us may have already turned on our air conditioning units for the first in months. To see what you can do to get the most out of your home, contact LEAP, your local energy nonprofit, to schedule a home energy assessment this month - just $45 for City and County residents. LEAP also offers FREE home weatherization to income- and age-qualifying residents. If someone in your household is age 60 or older, or you have an annual household income of less than $74,950, you may qualify for a free energy assessment and home energy improvements such as insulation and air sealing. Sign up today to lower your energy bills, increase comfort, and reduce energy waste at home!COVID cases still increasing; UVA Health urges renewed maskingAs the week begins, the Virginia Department of Health this morning reports a seven-day average for new COVID-19 cases at 2,750 a day and the seven-day percent positivity has increased to 14.6 percent. The actual amount of spread is likely higher due to the number of home tests that have become common as a first diagnosis for many people. “There are many people calling saying they’re COVID positive and importantly and interestingly, a fair number of those people have been vaccinated,” said Dr. Costi Sifri, the director of hospital epidemiology for the University of Virginia Health System. With more cases in the community, UVA officials say its time to take precautions again.“Personally I’m masking back up and I think a lot of people are making the decision,” said Wendy Horton, the CEO of the UVA Health System. “It’s people that have been really careful, been vaccinated, and I think we’re just in this interesting time where we’re really tired of masking but I think it’s alive and well. We know it. We see it in our workforce. We see it in our patients.” The latest COVID model from the UVA Biocomplexity Institute was released on Friday. “Models forecast a significant surge of cases in the coming weeks,” reads the model. “Case rates are not expected to reach levels seen during the January wave. But they will likely exceed those seen in pre-Omicron waves.” Dr. Sifri said ebbs and flows are likely to continue as COVID-19 continues to transition from pandemic to endemic. He said the same public health advice exists. “In a period of time like now where we’re starting to see a surge in cases, this is the time to say okay, in this time and place right now, wearing a mask is helpful to prevent transmission,” Dr. Sifri said. “It’s also important because with COVID it still remains the case that probably half or more than half of cases are in people who are asymptomatic or have such mild symptoms that they don’t recognize that they’re sick.” This week the Virginia Department of Health is retiring several dashboards and ways of reporting COVID. People who seek to know cases by vaccination status will need to go to the Centers for Disease Control website. Cases and Deaths by Date Reported will also be phased out. The changes will take place on May 19. The VDH already has stopped reporting cases by locality on its website. Learn more about the changes on their website.Fatal crash on Seminole TrailAlbemarle County police are investigating the cause of a fatal crash last night in the 1200 block of U.S. 29 near Greenbrier Drive. Thirty-six-year old Justin Michael Tilghman of Charlottesville died at the scene of the crash which happened at 9:21 p.m. last night. The driver of a second vehicle was taken to the University of Virginia hospital. The Albemarle County Police Department’s Fatal Crash Reconstruction Team is leading the investigation. This is the fourth fatality on Albemarle County roads so far in 2022. Augusta County official named to State Board of ElectionsGovernor Glenn Youngkin has named a member of the Augusta County Board of Elections to serve on the Virginia State Board of Elections. Youngkin named Georgia K. Alvis-Long to the position. A press release identifies her occupation as a registered nurse instructor. Under Virginia law, the State Board of Elections is a five-member body that will have three members from the political party that won the Governor’s mansion in the last election. “Each political party entitled to an appointment may make and file recommendations with the Governor for the appointment,” reads Section 24.2-102 of Virginia Code.Alvis-Long fills a position left by the resignation of Jamilah D. LeCruise. For more recent appointments, take a look at the full release. Second shout-out: Charlottesville Jazz Society spotlighting benefit show for UkraineIn today’s second subscriber supported shout-out. The Charlottesville Jazz Society is spotlighting a benefit event to support the people of Ukraine at the Whiskey Jar this Wednesday from 6:30 p.m. to 10:30 p.m. Young jazz students near the besieged city of Mariupol sent guitarist Royce Campbell a plea to help, and several area musicians have jumped into help. Vocalist Monica Worth has organized the event, and Campbell will play for Ukraine with bassist Andre La Vell and drummer Jim Howe. Many of Charlottesville’s best jazz musicians will sit in. Donations will be collected and sent to Global Giving’s Ukraine Crisis Relief Fund, and you can also go ahead and support this effort with a payment online. That’s We Play for Ukraine at the Whiskey Jar this Wednesday from 6:30 p.m. to 10:30 p.m. Divided Planning Commission approves seven-story building on Jefferson Park Avenue A divided Charlottesville Planning Commission voted 4-3 on May 10 to recommend that City Council approve a special use permit for additional height and density for a seven-story U-shaped building at 2005 Jefferson Park Avenue. They’ve also recommended reducing parking requirements by 22 percent over what would otherwise be required.“The [special use permit] is required to accommodate a development being proposed for 119-units of multifamily dwellings within one building with underground parking,” said city planner Matt Alfele. This project was filed after the city adopted a new Comprehensive Plan and Future Land Use Map created as part of the Charlottesville Plans Together initiative, which is still underway. There are currently 17 units across multiple structures across the property. “The Future Plan Use Map, the Comprehensive Plan that we went through, is increasing density and increasing density in certain areas of the city, and this area of the city is one that is looking to increase density and to increase density at especially this scale is going to create a big building,” Alfele said. The developer would pay $500,000 into the city’s affordable housing fund rather than provide required affordable units on-site or at another location nearby. They’ll build 125 parking spaces in an underground garage with access on Washington Avenue. Residents would not be eligible to park on that street or Observatory due to restricted parking. The building would be seven stories taller from JPA and would be five stories tall at the back. “The biggest concern I think staff had was the rear elevation, the five story building going down into the mainly single-family, two-family neighborhood,” Allele said. This request comes after City Council adopted a new Comprehensive Plan with a Future Land Use Map that encourages more residential density, but before the new zoning rules have been written. “Do you happen to know and can you remind me what in our Future Land Use map, what this area is designated as, and what the by-right height would be in that corridor?” asked City Councilor Michael Payne. “This is Urban Mixed Use Corridor and the height is five stories or up to eight at key intersections,” Alfele said. “This is one of the areas where our Comprehensive Plan land use conflicts with our current zoning because our Comprehensive land use map is anticipating our zoning changing. The Future Land Use Map measures in stories and not feet.” Under the existing zoning, the structure could be 35 feet tall without a permit. This is one of the areas that will be clarified in the zoning rewrite. The term “key intersection” is also currently not defined. Payne pointed out the Comprehensive Plan seeks to encourage more units that would be rented to people below market. “The framework that we’ve adopted for that is that if we’re going above the by-right height, the reason we’re doing that is to have an inclusionary zoning program that’s going to required affordable housing as part of that,” Payne said. Payne also suggested $500,000 as an affordable housing contribution would not go far. “I know it’s their choice and we don’t have any control over it but I would just note for the record that we got an affordable housing report that included data on the total subsidy needed to construct a new affordable unit, and I can’t remember the exact number but I know in Virginia that total subsidy to build one new unit could be around $300,000,” Payne said. Charlottesville Mayor Lloyd Snook noted that there had been a lot of concerns during the Future Land Use Map from other neighborhoods such as North Downtown, but he had not heard much from the JPA neighborhood at that time.“The one area where it seemed clear that everyone was willing to agree we should have increased density was along JPA yet there was no basically no public discussion of that fact,” Snook said. Until the rezoning is finalized, individual applications like this are the forum for how the city will look in the future. The project will need a certificate of appropriateness from the Entrance Corridor Review Board, which is also the Planning Commission. They’ll get to influence the design. The developer said the area was already predominantly occupied by renters, and that this level of density is served by transit. “We are one block away in each direction from the trolley stops,” said Erin Hannegan with Mitchell + Matthews Architects and Planners. Hannegan acknowledged the Future Land Use Map designation of Urban Mixed Use Corridor and said this project meets the goals of the Comprehensive Plan.“The further definition is ‘higher intensity mixed-use development’ for this area and that’s exactly what we’re trying to do,” Hannegan said. “A higher intensity development. Mixed use is not allowed under the R-3 mixed-use currently designated.” Hannegan acknowledged that the new building would be out of scale with what is currently there, but anticipated the future conditions of JPA.“This building might be taller than its current neighbors but it won’t be out of character with the future implementation of the Comprehensive Plan and the implementation of the vision that’s been in the works for over 20 years for this particular neighborhood,” Hannegan said. At the public hearing, Nina Barnes of the Jefferson Park Avenue Neighborhood Association said the Comprehensive Plan compels Council and the Planning Commission to take adverse effects into account when considering a special use permit. “Adverse impacts may include traffic or parking congestion, undue density and population, and massing and scale,” Barnes said. “This project has adverse effects in all of these ways.”Barnes said the seven-story building would block the sun from existing one and two story buildings.Ellen Contini-Morava said the staff reports seemed to be in favor of the developer, and noted the gap between an adopted Comprehensive Plan and older zoning. She said this undermines the spirit of the Cville Plans Together Initiative. “This application treats the rezoning that’s proposed in the Future Land Use Map as if it were already in place,” Contini-Morava said. “This application not only aims to short-circuit the rezoning process but even requests a height that is two stories higher than the five stories suggested in the Future Land Use Map for the JPA corridor.” Fifeville resident Matthew Gillikin spoke for the group Livable Cville, which is not a registered entity with the State Corporation Commission but is active in promoting higher density in the community. Gillikin said the answer to affordability in Charlottesville is more housing. “And the developer is planning to contribute nearly $500,000 to the Charlottesville affordable housing fund as a condition to build,” Gillikin said. “This will fund groups like [Charlottesvile Redevelopment and Housing Authority], LEAP, [Albemarle Housing Improvement Program], [Piedmont Housing Alliance], and Habitat for Humanity in the work to address local housing issues.” Gillikin said approval of this project would prevent students from moving into local neighborhoods such as Tenth and Page and Fifeville. These units would have no affordability provisions. For comparisons let’s look at the Standard, another building designed by Mitchell + Matthews Architects. According to their website, the lowest rent for a room in a four-bedroom unit goes for $1,029 a month. Double occupancy in a single bedroom in a three bedroom unit can go for $845 a month. One and two bedroom units in the Standard are sold out. Pricing is not available online for the Flats at West Village. The Lark on Main has a one bedroom unit with a study for $1,879 a month. A room in a four bedroom, four bathroom costs $955 a month. Garage parking is an extra $100. Commission discussionAfter the public hearing, Commissioner Hosea Mitchell said he supported the project, but did want the massing to be a little more consistent with the rest of the neighborhoods. “We do need more housing in Charlottesville and we do a bit of relief valve,” Mitchell said. “We need housing in Charlottesville that is closer to UVA so that the housing that is further away from UVA can be used by the rest of our citizenry,” Mitchell said. Commissioner Taneia Dowell said if the developer is going to additional density based on the future zoning for the property, the spirit of the Affordable Housing Plan must also be honored. “That’s where I’m really having some heartburn,” Dowell said. “If we’re going to go off future endeavors for this project and this special use permit, then we need to go off future endeavors for everything related to this.” Commissioner Jody Lahendro said he could not support this level of density in the area and especially with a building with that much massing. He said the Comprehensive Plan also calls for development on Entrance Corridors to be compatible with existing neighborhoods. “I am not in favor of sacrificing a long term neighborhood for providing student housing for the University,” Lahendro said. “I think the people who have lived here and the single-family homes in this neighborhood deserve… we can’t just pretend that they’re not there.” Commissioner Rory Stolzenberg said he was reviewing the permit request under existing rules and not looking ahead to the new zoning. Quoting the standards of review, he noted that the Commission must review whether a proposal would be “harmonious with existing patterns of use and development in the neighborhood.”“But it will shock you guys to learn that harmonious is not actually defined in the code so the question I think before us is whether a five-story building can co-exist near or next to even smaller buildings including detached houses,” Stolzenberg said. “I’d note there’s already a four and a half story building at the head of the street.” Bill Palmer is with the Office of the Architect at the University of Virginia and sits as a non-voting member of the Planning Commission. He said UVA is not in an era where they are being required by the Commonwealth of Virginia to increase enrollment. According to the UVA office of Institutional Research and Analytics, there was an on-Grounds enrollment in Fall 2021 of 16,793 undergraduates and 6,928 graduate students. (enrollment data)“If you look at our official projects, they are flat,” Palmer said. Palmer said UVA is building additional housing on Grounds, including a second new structure in the Brandon Avenue Corridor. He also said the UVA initiative to build up to 1,500 new affordable units in the community includes a site further down from 2005 JPA in Albemarle County at the Piedmont housing site. “In terms of having affordable housing close in the future, that will be a place where the University is trying to provide something,” Palmer said. Council thoughtsCouncil will have the final decision, but did not vote during what is their first reading.Councilor Payne said he was frustrated that the affordability rules of the future are not yet in place. “This happened with another [special use permit] a few weeks ago where we’re in this strange situation where we’re sort of evaluating the Future Land Use Map and zoning map rewrite in mind, but if we’re using that in our evaluation, that will include our framework of inclusionary zoning and affordable housing overlays which are critical to the success of that plan for affordable housing,” Payne said. Councilor Brian Pinkston said he is learning toward support because it did provide more housing close to the University of Virginia. “I’m not able to fully articulate how we square that with point number one which is whether it is harmonious,” Pinkston said. “To some degree I think harmoniousness might be in the eye of the beholder. I will say that in terms of how the design was laid out and that you have seven stories in the front and five stories in the back, I thought there was some care and attention to trying to integrate into the neighborhood.” Snook also said he had issues with the word “harmonious” and said the traditional form of land use control known as “Euclidean zoning” is not good at dealing with change. “It doesn’t allow for us to grow gradually from a little bit of density to a little bit more density,” Snook said. “It allows us to say okay, we’re going to rezone the entire block of the entire neighborhood but it doesn’t let us go bit by bit.” As the Entrance Corridor Review Board, the Planning Commission voted unanimously on a motion to acknowledge there would be an adverse impact, but those impacts can be mitigated through the design process. As the Planning Commission, they consider a motion made by Stolzenberg to recommend approval. The was 4-3 with Stolzenberg, Mitchell, Habbab, and Commission Chair Lyle Solla-Yates voting in favor. Lahendro joined Dowell and Commissioner Liz Russell in voting no. Help Ting help support Town Crier productions!For one year now, Town Crier Productions has had a promotional offering through Ting!Are you interested in fast internet? Visit this site and enter your address to see if you can get service through Ting. If you decide to proceed to make the switch, you’ll get:Free installationSecond month of Ting service for freeA $75 gift card to the Downtown MallAdditionally, Ting will match your Substack subscription to support Town Crier Productions, the company that produces this newsletter and other community offerings. So, your $5 a month subscription yields $5 for TCP. Your $50 a year subscription yields $50 for TCP! The same goes for a $200 a year subscription! All goes to cover the costs of getting this newsletter out as often as possible. Learn more here! 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Botanists demonstrate a novel, effective approach to allele discovery in diverse accessions using a draft reference genome from a single species. You can read this online at https://www.botany.one/2021/10/allele-mining-could-help-improve-forage-grasses/ You can read the original research at https://doi.org/10.1093/aob/mcab101
There are many examples in biology of the incredible fine-tuning of life. On this episode of Mind Matters, you’ll learn about fine-tuning, population genetics, and probability as Robert J. Marks speaks with Ola Hössjer and Daniel Díaz. Show Notes 00:47 | Introducing Dr. Daniel Díaz 01:00 | Introducing Dr. Ola Hössjer 01:14 | Fine-tuning in biology 07:15 | A cellular… Source
Welcome to My AP Biology Thoughts podcast, my name is Shriya and I am your host for episode 5 called “Population Genetics: Central Dogma, Allele Frequency Equation and Gene Pools.” Today we will be discussing the definitions of all of those concepts as well as a few examples to go along with them. Then, we will connect all of that to the overarching topic of evolution. Hope you enjoy! Segment 1: Introduction to Population Genetics: Central Dogma, Allele Frequency Equation and the Gene PoolIntroduce the episode topic Include definitions and vocabulary Will be discussing the topic of population genetics which is the study of genetic variation within a population and looking into changes in the frequencies of genes and alleles in populations over time Natural selection is one of the most influential factors that can affect a population's genetic composition Central dogma of biology is when the instructions contained in DNA are converted into a functional product, a phenotype DNA, contains the genes that determine who you are, and proteins determine the structure and function of all your cells It describes the two-step process, transcription and translation, of how information in genes flow into proteins, creating a string of amino acids called polypeptides The DNA has the information which is used by the RNA to make the proteins The Allele Frequency Equation: an allele is a version of a gene and a heritable unit that controls a particular feature of an organism The allele frequency refers to how often a particular allele appears in a population An equation called the Hardy-Weinberg equation is used to calculate the genetic variation in a population: p^2 + 2pq + q^2 p^2 and q^2 are the allele frequencies of the homozygous recessive and homozygous dominant, and 2pq is the allele frequency of the heterozygous genotypes To get p and q individually, you calculate actual/total # of alleles With this knowledge, you are able to calculate the total allele frequencies using the equation p + q = 1 The gene pool is calculated using the equation just mentioned, p + q = 1 since it is the sum of both allele frequencies A gene pool is the collection of different genes within an interbreeding population, and refers to its genetic diversity The larger the gene pool, the greater genetic diversity, and the better a population is able to withstand environmental challenges Segment 2: Examples of Population GeneticsHave a natural transition into an example… no need to say “segment 2” Provide detailed example(s) of your topic This first example is a depiction of the central dogma and the different processes at work from Khan Academy DNA directs the construction of the chain of amino acids through transcription, which is when the DNA sequence of a gene is copied to make an RNA molecule During the second process, translation, mRNA is decoded to specify the amino acids of the polypeptide chain Overall, information flows from DNA to RNA to a protein, and this directional flow is why it is the central dogma of molecular biology An example using pea plants demonstrates how to calculate the allele frequency of a population using the total number of alleles and fractions There are 9 pea plants, meaning 18 total alleles 6 of them are homozygous dominant (WW), 1 is heterozygous (Ww), and 2 are homozygous recessive (ww) To calculate p and q, set up fractions and convert them into percentages There are 13 copies of the W allele and 5 copies of the w allele, so the allele frequencies for each are 72% and 28% respectively If you notice, they add up to 1, or 100% To show a gene pool, here is a picture of butterflies of 3 different colors: orange, white, brown You can see the diversity in the population through the different allele combinations: AA (brown), Aa(orange), aa (white) Segment 3: Digging Deeper into Population GeneticsHow does this topic fit into the greater picture of evolution? The...
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.11.377978v1?rss=1 Authors: Gursoy, G., Lu, N., Wagner, S., Gerstein, M. Abstract: With the recent increase in RNA sequencing efforts using large cohorts of individuals, studying allele-specific gene expression is becoming increasingly important. Here, we report that, despite not containing explicit variant information, a list of allele-specific gene names of an individual is enough to recover key variants and link the individual back to their genome or phenotype. This creates a privacy conundrum. Copy rights belong to original authors. Visit the link for more info
In dieser Folge geht es um 1) eine Studie, die untersucht, welche Bedeutung Schüler der Sexualität, Rekombination und Meiose zuschreiben (bitte nicht als "Diss" verstehen:) Es ist in den Lehrplänen (noch) nicht anders verankert...@Bildungsministerium...) 2) wie man die Bedeutung der Phänomene aus Sicht der Evolution erweitern sollte 3) folgende Übungsaufgaben: 1. Zeichne schematisch eine diploide Zelle mit dem Chromosomensatz 2n=6 2. .Beschrifte ein homologes Chromosomenpaar und markiere Chromosomen mütterlichen Ursprungs rot, väterlichen Ursprungs grün. 3.Zeichne diese Zelle im Stadium der Metaphase I der Meiose und stelle dabei ein Crossing over dar. 4.Gib alle möglichen Keimzellen an, die aus dieser Zelle entstehen könnten. 5.Was sind Allele? 6.Zähle alle Mutationstypen auf, die du kennst. Fachbegriffe: Meiose, Rekombination, Crossing over, Mutation, Reifeteilung I, Metaphase I, Variationen (ursprünglich erbliche Varietäten), 2n, diploid, 1n, haploid, Äquatorialebene, Allel (angedeutet auch bei Minute ...), interchromosomale und intrachromosomale Rekombination. PS: Das X-Chromosom ist übrigens heterlog zu dem Y-Chromosom:) PPS: Korrektur: Das Crossing over findet meist schon in der Prophase I statt. Schicke dein Feedback an biologopodcast@googlemail.com Hinterlasse eine Bewertung bei iTunes, wenn dir der Podcast etwas bringt.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.01.322362v1?rss=1 Authors: Miller, B., Morse, A., Borgert, J. E., Liu, Z., Sinclair, K., Gamble, G., Zou, F., Newman, J., Leon-Novelo, L., Marroni, F., McIntyre, L. Abstract: Allelic imbalance (AI) occurs when alleles in a diploid individual are differentially expressed and indicates cis acting regulatory variation. What is the distribution of allelic effects in a natural population? Are all alleles the same? Are all alleles distinct? Tests of allelic effect are performed by crossing individuals and comparing expression between alleles directly in the F1. However, a crossing scheme that compares alleles pairwise is a prohibitive cost for more than a handful of alleles as the number of crosses is at least (n2-n)/2 where n is the number of alleles. We show here that a testcross design followed by a hypothesis test of AI between testcrosses can be used to infer differences between non-tester alleles, allowing n alleles to be compared with n crosses. Using a mouse dataset where both testcrosses and direct comparisons have been performed, we show that ~75% of the predicted differences between non-tester alleles are validated in a background of ~10% differences in AI. The testing for AI involves several complex bioinformatics steps. BASE is a complete bioinformatics pipeline that incorporates state-of-the-art error reduction techniques and a flexible Bayesian approach to estimating AI and formally comparing levels of AI between conditions. The modular structure of BASE has been packaged in Galaxy, made available in Nextflow and sbatch on github (https://github.com/McIntyre-Lab/BASE_2020). In the mouse data, the direct test identifies more cis effects than the testcross. Cis-by-trans interactions with trans-acting factors on the X contributing to observed cis effects in autosomal genes in the direct cross remains a possible explanation for the discrepancy. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.22.262709v1?rss=1 Authors: Zhou, X., Barkley-Levenson, A., Montilla-Perez, P., Telese, F., Palmer, A. A. Abstract: Methamphetamine is a widely abused psychostimulant. In a previous genome-wide association study (GWAS), we identified a locus that influenced the stimulant response to methamphetamine. That locus was also an eQTL for the gene Azi2. Based on those findings, we hypothesized that heritable differences in the expression of Azi2 were causally related to the differential response to methamphetamine. In this study, we created a mutant Azi2 allele that caused lower Azi2 expression and enhanced the locomotor response to methamphetamine; however, based on the GWAS findings, we had expected lower Azi2 to decrease rather than increase the stimulant response to methamphetamine. We then sought to explore the mechanism by which Azi2 influenced methamphetamine sensitivity. A recent publication had reported that the 3UTR of Azi2 mRNA downregulates the expression of Slc6a3, which encodes the dopamine transporter (DAT), which is a key target of methamphetamine. We evaluated the relationship between Azi2/Azi2 3UTR and Slc6a3 expression in the VTA in the mutant Azi2 mice and in a new cohort of CFW mice. We did not observe any correlation between Azi2 and Slc6a3 in the VTA in either cohort. However, RNA sequencing confirmed that the Azi2 mutation altered Azi2 expression and also revealed a number of potentially important genes and pathways that were regulated by Azi2, including the metabotropic glutamate receptor group III pathway and nicotinic acetylcholine receptor signaling pathway. Our results support a role for Azi2 in methamphetamine sensitivity; however, the exact mechanism does not appear to involve regulation of Slc6a3 and thus remains unknown. Copy rights belong to original authors. Visit the link for more info
#FATS LIPIDS AND #CHOLESTEROL - #CARNIVORE ROUNDTABLE 1: Isn't saturated fat bad for you? 2: Isn't dietary cholesterol bad for you? What about serum cholesterol? Any thoughts on statins? 3: What are the best fats to eat? And the worst? All content mentioned in the video is linked below. Let us know if you have suggestions for topics, guests and questions for our future episodes! BE SURE TO LIKE, SUBSCRIBE AND TURN ON THE BELL NOTIFICATION! TIMESTAMPS: [0:24] Guest introduction: J Gulinello [4:49] Isn't saturated fat bad for you? [10:56] What is a hyper-responder? [19:58] Isn't dietary cholesterol bad for you? [23:52] Side effects of statins [28:23] Reading bloodwork, ratios, relevance of triglycerides, HDL, LDL [45:07] Cait's bloodwork [52:26] Cait's diet [53:32] J's diet [1:01:27] Dangers of Seed Oils [1:05:40] Safest fats for cooking NUTRITION AND FITNESS RESOURCES MENTIONED IN THIS EPISODE: Referred to by J Gulinello: -High cholesterol may protect against infections and atherosclerosis https://academic.oup.com/qjmed/article/96/12/927/1533176 -Better Memory Functioning Associated With Higher Total and Low-Density Lipoprotein Cholesterol Levels in Very Elderly Subjects Without the Apolipoprotein e4 Allele https://pubmed.ncbi.nlm.nih.gov/18757771/ -High Cholesterol Level Is Essential for Myelin Membrane Growth https://pubmed.ncbi.nlm.nih.gov/15793579/ -Associations of Fats and Carbohydrate Intake With Cardiovascular Disease and Mortality in 18 Countries From Five Continents (PURE): A Prospective Cohort Study https://pubmed.ncbi.nlm.nih.gov/28864332/ -Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort https://link.springer.com/article/10.1007%2Fs00125-015-3528-5 -High ratio of triglycerides to hdl-cholesterol predicts extensive coronary disease https://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000400003 Diet Doctor (Swedish MD promoting keto/low carb high fat whole foods diets for health and disease prevention): -Saturated Fat: https://www.dietdoctor.com/low-carb/saturated-fat -Red Meat: https://www.dietdoctor.com/low-carb/red-meat BMJ Meta-analysis on hyperlipidemia and mortality in MI and Heart Failure - Lower Mortality with Hyperlipidemia: -https://bmjopen.bmj.com/content/bmjopen/9/12/e028638.full.pdf Dietary saturated fat and heart disease: a narrative review (“The AHA stance regarding the strength of the evidence for the recommendation to limit SFAs for heart disease prevention may be overstated and in need of reevaluation.”) -https://academic.oup.com/nutritionreviews/article-abstract/78/6/474/5678770 The Causal Conundrum: The Diet-Heart Debates and the Management of Uncertainty in American Medicine (Diet-Heart Hypothesis History) -https://academic.oup.com/jhmas/article/70/2/218/776256 Unlocking Your Body's Fat Burning Potential and Sinister Seed Oils Dr. Cate Shanahan -https://www.youtube.com/watch?v=0hwj3FPZLl8 Vegetable Oils: The Hidden Killer - Chris Knobbe, MD - Peak Human podcast #78 w/ Brian Sanders -https://www.youtube.com/watch?v=JqPlyJbvGsk Paleomedicina/Zsofia Clemens website: -https://www.paleomedicina.com/en GUEST SOCIAL MEDIA: -J GULINELLO: https://www.instagram.com/perpetualhealthco/ CARNIVORE ROUNDTABLE SOCIAL MEDIA: -INSTAGRAM: https://www.instagram.com/CarnivoreRoundtable/ -FACEBOOK: https://www.facebook.com/CarnivoreRoundtable/ -YOUTUBE: https://tinyurl.com/CarnivoreRoundtable HOST INSTAGRAM ACCOUNTS: -ALYSHA: https://www.instagram.com/FatFuelled -CAIT: http://instagram.com/CaitMizzi -DAN & PETRA: https://www.instagram.com/TheMeaters -VAJID: https://www.instagram.com/LamborghiniKhan/
Dr. Daniel Claassen discusses his paper, "Genotyping Single Nucleotide Polymorphisms for Allele-Selective Therapy in Huntington Disease". Show References: Paper: https://ng.neurology.org/content/6/3/e430 Podcast: https://neurology.libsyn.com/website
In the first segment, Dr. Jason Crowell talks with Dr. Daniel Claassen about his Neurology: Genetics paper on genotyping single nucleotide polymorphisms for allele-selective therapy in Huntington disease. In the second part of the podcast, Dr. Jeffrey Ratliff focuses his discussion with Dr. Roseanne Dobkin on telephone-based CBT for depression in patients with Parkinson disease. Disclosures can be found at Neurology.org. No CME this week: Interviews based on articles from Neurology: Clinical Practice®, Neurology® Genetics, and Neurology® Neuroimmunology & Neuroinflammation are excluded from the CME program.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.20.162859v1?rss=1 Authors: Parmhans, N., Fuller, A. D., Nguyen, E., Chuang, K., Swygart, D. I., Wienbar, S. R., Lin, T., Kozmik, Z., Dong, L., Schwartz, G. W., Badea, T. C. Abstract: Members of the POU4F/Brn3 transcription factor family have an established role in the development of retinal ganglion cell types (RGCs), the projection sensory neuron conveying visual information from the mammalian eye to the brain. Our previous work using sparse random recombination of a conditional knock-in reporter allele expressing Alkaline Phosphatase (AP) and intersectional genetics had identified three types of Pou4f3/Brn3c positive (Brn3c+) RGCs. Here, we describe a novel Brn3cCre mouse allele generated by serial Dre to Cre recombination. We use this allele to explore the expression overlap of Brn3c with Brn3a and Brn3b and the dendritic arbor morphologies and visual stimulus properties of Brn3c+ RGC types. Furthermore, we explore Brn3c-expressing brain nuclei. Our analysis reveals a much larger number of Brn3c+ RGCs and more diverse set of RGC types than previously reported. The majority of RGCs having expressed Brn3c during development are still Brn3c positive in the adult, and all of them express Brn3a while only about half express Brn3b. Intersection of Brn3b and Brn3c expression highlights an area of increased RGC density, similar to an area centralis, corresponding to part of the binocular field of view of the mouse. Brn3c+ neurons and projections are present in multiple brain nuclei. Brn3c+ RGC projections can be detected in the Lateral Geniculate Nucleus (LGN), Pretectal Area (PTA) and Superior Colliculus (SC) but also in the thalamic reticular nucleus (TRN), a visual circuit station that was not previously described to receive retinal input. Most Brn3c+ neurons of the brain are confined to the pretectum and the dorsal midbrain. Amongst theses we identify a previously unknown Brn3c+ subdivision of the deep mesencephalic nucleus (DpMe). Thus, our newly generated allele provides novel biological insights into RGC type classification, brain connectivity and midbrain cytoarchitectonic, and opens the avenue for specific characterization and manipulation of these structures. Copy rights belong to original authors. Visit the link for more info
Malaria continues to be a major health hazard throughout the tropical and subtropical regions of the world. There were 228 million cases of malaria in 2018 and over 400,000 deaths. Malaria is a mosquito-borne infectious disease spread by 40 of the world’s 3,500 mosquito species. So, efforts to control mosquito populations are the primary strategy […]
KribenGovender, is a Food Scientist, Register Nutritionist and Founder of Nourishme Organics, a company specialising in Guth Health focused products. With an honours degree in Applied Science (Food Science and Technology) and 20+ years of food industry experience, Kriben intimately understands the interaction between diet and the gut microbiome. He is the host of one of Australia’s leading nutrition podcasts - The Gut Health Gurus Podcast, where he frequently interviews gut health experts from around the world.Kriben currently oversees Australia’s premier Gut Health Facebook Group- The Nourishme Organics Gut Health Gurus, with more than 11,000 gut health enthusiasts! He also co-founded, Allele, a whole genome metagenomics DNA based stool testing company. What you will learn from this episode: 1) The importance of gut health in improving anxiety, depression, and overall mental health 2) How to make kefir at home 3) What are the different kinds of fermented foods that can improve your gut health 4) What kinds of bacteria are present in the fermented foods that help optimize our health 5) How to understand what strains of bacteria are present in your gut microbiome How to learn more about our guest: Instagram: @kribengovender https://www.nourishmeorganics.com.au/ https://www.podcast.nourishmeorganics.com.au/ https://www.facebook.com/groups/nourishmeorganics/ https://www.allele.com.au/ Please enjoy, share, rate and review our podcast and help us bring the message about precision health care to the world!
Progeria is an extremely rare genetic disease that practically speeds up time. It affects young children who get it due to a mutation from a very specific Gene, the LMNA gene. Tune in for more!ScrubCaps: A Health and Medical Podcast Every Monday!Visit my Website: https://www.brainontheloose.comLeave a Review on Apple Podcasts: https://podcasts.apple.com/us/podcast/scrubcaps-a-health-and-medical-podcast/id1442030058References: https://www.progeriaresearch.org/about-progeria/ https://ghr.nlm.nih.gov/condition/hutchinson-gilford-progeria-syndrome https://www.mayoclinic.org/diseases-conditions/progeria/diagnosis-treatment/drc-20356043 Support the show (http://patreon.com/ Nathanhidajatscrubcaps)
Question: For someone who is homozygous for the H63D allele of the iron- and hemochromatosis-related HFE gene, if ferritin is low but transferrin saturation is high, should they still donate blood? H63D is one of the genes that predisposes to hemochromatosis, a condition of iron overload. Most clinicians who work in this area do not consider the H63D allele to be a concern because it's less severe. With that said, most people who are progressive on the iron research front do believe it's a concern. There is literature showing that people can get clinical hemochromatosis from it and you don't have to get clinically hemochromatosis to be worried about iron overload. My opinion on this is going to be different than someone who is an expert clinician, but is not immersing themselves deeply in the physiological literature about how this works. I don't have the skills that they have in triaging and filtering who’s ideal for what treatment and looking at large numbers of people that do one or another treatment and knowing intuitively what happens in those — but what I do have is I have immersed myself very deeply in the physiology. So the way that I look at this is as follows: iron saturation is an estimate of your transferrin saturation. It's a cheaper way to estimate it than to actually measure transferrin saturation, so it's much more common to get iron saturation. But let's assume that we're talking about actual transferrin saturation or that iron saturation is a good metric of it. That's your short-term iron storage. Ferritin is your long-term iron storage. The defect in the H63D allele, same for the C282Y allele of the HFE gene, the two moderate and severe hemochromatosis alleles. Allele is a variant of the gene. In normal physiology what happens is transferrin acts as a gauge of your iron status. The normal physiological levels are between 30 and 40 percent. Now being 41 percent doesn't mean you have a disease, we're not talking about diagnosis here, we're talking about understanding the physiology. Mechanistically this is designed so that as you go from 30 to 40 percent and especially as you go over 40 percent that communicates the signal to a hormonal system that says you have more iron than you need. So you ramp down iron absorption and you ramp up ferritin. Why do you ramp up ferritin? Because you have more than you need in your short-term storage, so that's when you put it into your long-term storage. Also, because ferritin is a protective response that prevents you from having free iron. Free iron is bad because it feeds pathogens and it makes infections worse. Free iron is bad because it causes oxidative stress and causes wear and damage on your tissues. And so to avoid free iron you ramp up ferritin while you take down your absorption from food at the same time. And now is that a problem at all? You could debate that, but if you're just talking, if you're not talking about diagnosis and you're talking about wellness, and you're talking about health management then… What I would want to do myself in that situation is I would first of all not let the ferritin go under 20, and if it's going near there I would be getting a CBC to make sure I'm not making myself anemic. And so I would not stop donating blood just because the ferritin is going down 60, 50, 40, I would consider it a gray area, it would be my preference to focus on the transferrin saturation and get it consistently under 40%. You get the pinprick to look at your serum iron levels, they're not going to let you donate blood if you're actually in the danger zone of anemia. So I would get the CBC to be proactive about it. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/02/24/ask-anything-nutrition-feb-17-2019/ If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a
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Nels and Vincent trace the origins of Saccharomyces cerevisiae strains used to make beer, and find that ales and lagers are made with yeasts that were derived from those used to make European grape wine and Asian rice wine. Hosts: Nels Elde and Vincent Racaniello Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiEVO Origins of beer yeasts (PLoS Biol) Chateau Jiahu beer Time stamps by Jolene. Thanks! Science Picks Nels - Population fluctuations in 10 biggest cities Vincent - 1.7 million year old rhino tooth (original Nature paper) Music on TWiEVO is performed by Trampled by Turtles Send your evolution questions and comments to twievo@microbe.tv
This bonus track is brought to you from the ALLELE seminar series on evolution at the University of Alabama. Dr. Chakrabarty presents his talk, "Making evolution accessible to everyone"; for more information on his research check out SoS Episode 28 "The Fishy Perspective".
“The Sausage of Science Podcast with Cara & Chris” From the Public Relations Committee of the Human Biology Association SoS26- “Live" on Lactation with Katie Hinde In episode 26, we go “live” from a talk with Dr. Katie Hinde as part of the ALLELE series at the University of Alabama. Dr. Hinde discusses her path to anthropology and answers student questions on a number of her latest articles. A few selected topics include: non-human primate shock at seeing toes, recent developments in the field, human lactation, and the microbiome. Dr. Hinde is an Associate Professor at Arizona State University in the Center for Evolution and Medicine and School for Human Evolution and Social Change. Her current research investigates how variation in mother’s milk and behavioral care influences infant outcomes from post-natal life and into adulthood, and subsequent generations. For more information on Dr. Hinde’s work, check out her ASU webpage https://isearch.asu.edu/profile/2740008, her blog “Mammals Suck...Milk!” http://mammalssuck.blogspot.com/, or get in touch with her via email at Katie.Hinde@asu.edu, or on twitter @Mammals_Suck. The articles discussed in this week talk can be found at the following links: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512713/ -Milk bioactives may manipulate microbes to mediate parent–offspring conflict and https://www.researchgate.net/profile/Amanda_Dettmer/publication/299579964_Nonhuman_Primate_Models_of_Mental_Health/links/5706ad1e08aed73c8548a305/Nonhuman-Primate-Models-of-Mental-Health.pdf?origin=publication_detail The Sausage of Science is produced by Cara Ocobock and Chris Lynn, with assistance from Junior Service Fellow Caroline Owens for the Public Relations Committee of the Human Biology Association. The song in the soundbed is “Always Lyin’” by the Morning Shakes. Contact the Sausage of Science and Human Biology Association: Facebook: https://www.facebook.com/groups/humanbiologyassociation Website:http://humbio.org/, Twitter: @HumBioAssoc Michaela Howells, Public Relations Committee Chair, Email: howellsm@uncw.edu Cara Ocobock, Website: https://sites.nd.edu/cara-ocobock/, Email:cocobock@nd.edu, Twitter:@CaraOcobock Chris Lynn, Website:http://cdlynn.people.ua.edu/, Email:cdlynn@ua.edu, Twitter:@Chris_Ly Caroline Owens, Email: cowens8@emory.edu, Twitter: @careowens
If you are interested in the low-carb, moderate protein, high-fat, ketogenic diet, then this is the podcast for you. We zero in exclusively on all the questions people have about how being in a state of nutritional ketosis and the effects it has on your health. There are a lot of myths about keto floating around out there and our two amazing co-hosts are shooting them down one at a time. Keto Talk is co-hosted by 10-year veteran health podcaster and international bestselling author Jimmy Moore from “Livin’ La Vida Low-Carb” and Pittsburgh, PA functional medicine practitioner Dr. Will Cole from DrWillCole.com who thoroughly share from their wealth of experience on the ketogenic lifestyle each and every Thursday. We love hearing from our fabulous Ketonian listeners with new questions–send an email to Jimmy at livinlowcarbman@charter.net. And if you’re not already subscribed to the podcast on iTunes and listened to the past episodes, then you can do that and leave a review HERE. Listen in today as Jimmy and Will answer your keto questions in Episode 106. .YOUR NEW KETO DIET ALLY NOTICE OF DISCLOSURE: Paid sponsorship HERE’S WHAT JIMMY AND WILL TALKED ABOUT IN EPISODE 106: HOT TOPICS: 1. How does eating more dietary fat (as part of a low-carb, moderate protein approach) tap into helping your body burn stored body fat? 2. How does caffeine impact blood sugar and insulin levels? Does it raise insulin levels? 3. How can you possibly have higher levels of ketones (in nutritional ketosis) with elevated blood glucose levels? What’s going on? 4. What is the impact of consuming the erythritol in keto desserts on gut health? 5. What makes ketone levels fluctuate so dramatically throughout the day? -- Yes, bacon really is killing us -- We learn nothing about nutrition, claim medical students -- Fit ’n Fat Grill promises high flavor, low-carbs MAKE KETO EASIER WITH FBOMB NOTICE OF DISCLOSURE: Paid sponsorship -- Will a ketogenic diet help speed up the recovery process for my upcoming jaw surgery? Jimmy and Will, I am a registered dietitian who is an advocate for the keto diet since starting it for myself nine months ago. I am working diligently on influencing others in my profession about the health benefits of nutritional ketosis. Keto Talk has helped me stay on top of what is happening in the world of keto so I can be armed with the knowledge to pass along to my RD colleagues. Recently I had braces put into my mouth in preparation for jaw surgery coming in the Fall. This will include my mouth being banded together for a few weeks after surgery which would thus limit the types of foods I could eat or drink. Do you have any input about what my recovery will be like being in a state of ketosis vs. if I wasn’t ketogenic? I would assume inflammation would be lower on keto, but is there any research showing how much quicker healing will take place? My wife does not eat keto and has hinted several times that she wants me to just eat whatever post-surgery so I keep my energy up and have an enjoyable experience. I’m not wanting to lose any more weight in this, but the faster recovery would be a bonus. Thanks for the help, Casey -- STUDY: How to Time Your Meals to Control Blood Sugar -- Direct link to study 1. Is it possible to heal my Type 2 diabetes through a ketogenic diet and lifestyle change alone without going back on medications again? Hello Jimmy and Dr. Cole, I am a 38-year old male with Type 2 diabetes. I am 6'3" and currently weigh 307 pounds. I started keto at the beginning of the year and have lost 25 pounds so far. I stopped taking all my diabetes medications on am only on blood pressure medication at the moment. My blood glucose numbers run between 155-200 no matter what time of day I check it. I have been implementing intermittent fasting with keto for the past month. So my question for you guys is this: Did I stop taking my medications for controlling Type 2 diabetes too soon? I was taking 1000mg metformin twice a day, 20mg glipizide twice a day, 10 units of lantis per day. I feel so amazing on keto and never want to go back to eating any other way. Do I need to go back on the medications for a short period of time until I heal a little more or will my body heal with a ketogenic diet and lifestyle changes over time? Most shocking to me when when my doctor told me I’d be on medication for the rest of my life and that diet and lifestyle don’t make a difference with Type 2 diabetes. In fact, one of his nurses told me that I was not insulin resistant. How the heck can a Type 2 diabetic NOT be insulin resistant? The idea of going back on these prescriptions that force me to eat more carbohydrates to counteract their effects is frustrating to me. Can you help me figure this out? Thank you for any advice you can give, Matt THE PERFECT KETO SUPPLEMENT USE COUPON CODE LLVLC FOR 15% OFF NOTICE OF DISCLOSURE: Paid sponsorship 2. Does having an ApoE4 require me to reduce my saturated fat intake to prevent the atherogenic small dense LDL particles from developing? Hi Jimmy and Will, I have an ApoE4 that researchers say makes me more susceptible to having higher LDL cholesterol as well as an increased risk for developing heart disease. I eat LCHF and although my LDL-C is high (150) my Small LDL-P count is low at 129 and I’m solidly in Pattern A. My question for you guys is this: Should I be avoiding saturated fats like coconut oil and replacing them with monounsaturated fats like avocados? Will the saturated fats increase the number of small dense LDL particles even though my triglycerides are low? Thanks for your help with this one! Bryan 3. Does the gluconeogenesis that happens from consuming too much protein apply also to the protein found in eggs and plant proteins? Greetings you guys, I bought Keto Clarity at Barnes and Noble last week and have read about a third of it so far. When you refer to gluconeogenesis, does that apply to just to meats or is it to eggs and even plant-based proteins as well? Or are the proteins found in eggs and plants different than those in animal-based sources? I’ve always wondered why I never did well on the Atkins diet and this excessive protein issues seems to be the answer I’ve been looking for. Look forward to hearing your answer about my questions. Brian KETO TALK MAILBOX -- Does dietary fat that makes you feel good and happy while eating it spike dopamine in the same way that consuming sugar does? Is this good or bad? Hi Jimmy and Dr. Cole, It’s very easy for me to wrap my head around and understand the spike in dopamine that takes place in your brain when you consume sugar. But a goofy thought ran through my head and it made me wonder if dietary fat could have the exact same effect in a fat-adapted person. I know that when I eat fat I always feel really good and happy. So does that mean I had a spike in dopamine? And if so, what are the ramifications for a ketogenic dieter if that is indeed happening? Thanks for being there, Jeff BECOME A NUTRITIONAL THERAPY PRACTITIONER Sign up by February 2018 for the 9-month program NOTICE OF DISCLOSURE: Paid sponsorship Apple Podcasts reviews: LINKS MENTIONED IN EPISODE 106 – SUPPORT OUR SPONSOR: Staying in ketosis just got easier – Your new keto-diet ally (Enter MOORE15 at checkout for fifteen percent off your first order.) – SUPPORT OUR SPONSOR: Drop an FBOMB for the freshest, high-quality fats from JimmyLovesFBomb.com (Get 10% off your first food order with coupon code “JIMMYLOVESFBOMB”) – SUPPORT OUR SPONSOR: Jump start your ketogenic diet with PerfectKeto.com/Jimmy (USE PROMO CODE LLVLC FOR 15% OFF) – SUPPORT OUR SPONSOR: Become A Nutritional Therapy Practitioner – We learn nothing about nutrition, claim medical students – Fit ’n Fat Grill promises high flavor, low-carbs – Yes, bacon really is killing us – STUDY: How to Time Your Meals to Control Blood Sugar – Jimmy Moore from “Livin’ La Vida Low-Carb” – DR. Will Cole D.C. from DrWillCole.com
Dr. Nina Jablonski is Evan Pugh Professor of Anthropology at Penn State University. She is a primatologist and paleoanthropologist but has also become among the foremost experts in the world on the biology and evolution of human skin pigmentation. She is author of Living Color: The Biological and Social Meaning of Skin Color (2012) and Skin: A Natural History (2006). Dr. Jablonski was interviewed by Chris, along with Jo Weaver and Erik Peterson, while in Tuscaloosa, AL to give a lecture for the ALLELE speaker series. The interview was recorded by Jim Bindon. Jo, Erik, and Jim produce the Speaking of Race podcast, and we shared portions of the interview. Learn more about Dr. Jablonski’s research and teaching at her department webpage: anth.la.psu.edu/people/ngj2. Contact Nina Jablonski: Ngj2@psu.edu. Get info about the Finding Your Roots program she develops and runs with Henry Louis Gates www.findingyourroots.la.psu.edu/ Tmw119@psu.edu Find more information about the UA ALLELE series: evolution.ua.edu/. Nina Jablonski’s full lecture with video will be posted on the ALLELE Vimeo site: vimeo.com/channels/allele/videos Contact Us: www.facebook.com/groups/humanbiologyassociation humbio.org/ twitter.com/HumBioAssoc Michaela Howells is Chair of the Publicity Committee, howellsm@uncw.edu. Cara & Chris are committee members and produce this show: Cara Ocobock www.albany.edu/anthro/72074.php cocobock@albany.edu twitter.com/CaraOcobock Chris Lynn cdlynn.people.ua.edu/ cdlynn@ua.edu twitter.com/Chris_Ly Interview engineered by Jim Bindon. Lecture recorded by UA’s eTech. Mixing and editing by Chris. Music by the Morning Shakes. “Sausage of Science” logo by Lux Lynn (LuxL1312@gmail.com).
Dr. Nina Jablonski is Evan Pugh Professor of Anthropology at Penn State University. She is a primatologist and paleoanthropologist but has also become among the foremost experts in the world on the biology and evolution of human skin pigmentation. She is author of Living Color: The Biological and Social Meaning of Skin Color (2012) and Skin: A Natural History (2006). Dr. Jablonski was interviewed by Chris, along with Jo Weaver and Erik Peterson, while in Tuscaloosa, AL to give a lecture for the ALLELE speaker series. The interview was recorded by Jim Bindon. Jo, Erik, and Jim produce the Speaking of Race podcast, and we shared portions of the interview. Learn more about Dr. Jablonski’s research and teaching at her department webpage: http://anth.la.psu.edu/people/ngj2. Contact Nina Jablonski: Ngj2@psu.edu. Get info about the Finding Your Roots program she develops and runs with Henry Louis Gates http://www.findingyourroots.la.psu.edu/ Tmw119@psu.edu Find more information about the UA ALLELE series: http://evolution.ua.edu/. Nina Jablonski’s full lecture with video will be posted on the ALLELE Vimeo site: https://vimeo.com/channels/allele/videos Contact Us: https://www.facebook.com/groups/humanbiologyassociation http://humbio.org/ https://twitter.com/HumBioAssoc Michaela Howells is Chair of the Publicity Committee, howellsm@uncw.edu. Cara & Chris are committee members and produce this show: Cara Ocobock http://www.albany.edu/anthro/72074.php cocobock@albany.edu https://twitter.com/CaraOcobock Chris Lynn http://cdlynn.people.ua.edu/ cdlynn@ua.edu https://twitter.com/Chris_Ly Interview engineered by Jim Bindon. Lecture recorded by UA’s eTech. Mixing and editing by Chris. Music by the Morning Shakes. “Sausage of Science” logo by Lux Lynn (LuxL1312@gmail.com).
I talk about allele-specific expression: why it arises and how it can be reliably detected. Sections: The biology of allele-specific expression (2:17) Detecting allele-specific expression with RNA-seq (7:46) Mapping and sequencing biases (16:39) The experiment in yeast (19:47) Statistical models (21:44) Links: A powerful and flexible statistical framework for testing hypotheses of allele-specific gene expression from RNA-seq data Supplemenal information Effect of read-mapping biases on detecting allele-specific expression from RNA-sequencing data The talk by John Marioni The blog post explaining the RSEM model
Main Topic: Pastor Scott Thom revisits creation vs. evolution Question: 17:06 - Is evolution the study of Allele or Gene Frequencies? NoOtherDoctrine.org CrossFellowship.org CCFCollege.com LeadershipFromTheCross.com
Hosts: Nels Elde and Vincent Racaniello Guest: Nitin Phadnis Nitin joins Nels and Vincent to explain how he identified a gene that is responsible for male inviability in hybrids from a cross between two species of fruit flies. Links for this episode Cell cycle regulation gene causes hybrid inviability in fruit fly (Science) Phadnis laboratory Phadnis laboratory on Facebook Gene for new species discovered (UNews) Tardigrade HGT disputed (bioRxiv) Photo credit: Lee J. Siegel, University of Utah Science Picks Nels - Watercolor of Darwin and crewVincent - SpaceX rocket landing (Verge and ArsTechnica) Nitin - 120th anniversary of Roentgen's first X-ray Music on TWiEVO is performed by Trampled by Turtles Send your evolution questions and comments to twievo@microbe.tv
One of the lectures in the ALLELE series (Alabama Lectures on Life's Evolution. This lecture focuses on the importance of Wallace as a co-discoverer of natural selection.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 17/19
Schizophrenia is one of the most frequent psychiatric disorders and is associated with a substantial part of worldwide disease burdon1. The clinical symptoms of patients with schizophrenia can be separated into positive symptoms such as halluciations and delusions as well as negative symptoms such as cognitive impairments, apathy, blunted affect and social withdrawal2. It has been suggested that understanding the underlying pathophysiological processes that give rise to these symptoms is a crucial step for the development of efficient treatment for schizophrenia3. In the presented work two aspects of the clinical symptomatology of schizophrenia are analyzed with respect to their potential neurobiological correlate. Following the dopamine-hypothesis, patients with schizophrenia exhibit an increase in dopaminergic neurotransmission in the striatum which might be related to the experience of positive symptoms4,5. In the first publication evidence for this dopamine-hypothesis from in-vivo neuroimaging studies was investigated in a comprehensive meta-analysis. Results are in the line with the dopamine-hypothesis and point to an increase of striatal presynaptic dopamine synthesis in schizophrenia: - Howes OD*, Kambeitz J*, Kim E, Stahl D, Slifstein M, Abi-Dargham A*, Kapur S* (2012): The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry 69: 776–786. * these authors contributed equally ISI Web of Knowledge: Archives of General Psychiatry (now: JAMA Psychiatry) impact factor 2012: 13.77 5-year impact factor 2012: 14.47 Ranked 3rd of all psychiatry journals The negative symptoms of schizophrenia such as cognitive impairments have frequently been associated with changes of cerebral gray matter in numerous brain regions including the hippocampus6–9. In the second publication, effects of a potential risk-gene on the hippocampus are analyzed. Results indicate reduced hippocampal structure and function in carriers of the met-allele of the BDNF polymorphism val(66)met: - Kambeitz JP*, Bhattacharyya S*, Kambeitz-Ilankovic LM, Valli I, Collier DA, McGuire P (2012): Effect of BDNF val(66)met polymorphism on declarative memory and its neural substrate: a meta-analysis. Neurosci Biobehav Rev 36: 2165–2177. * these authors contributed equally ISI Web of Knowledge: Neuroscience and Biobehavioral Reviews impact factor 2012: 9.44 5-year impact factor 2012: 9.92 Ranked 12th of all neurosciences journals
Dr. Gregory Retallack, an expert in fossil plants and soil and a professor of geological sciences at the University of Oregon, presented at The University of Alabama’s 2013-2014 ALLELE Lecture series discussing major innovations in the evolution of vegetation and how changes in organisms can affect world climate. The 2013-2014 ALLELE series is supported by UA’s College of Arts and Sciences and the departments of anthropology, biological sciences, communicative disorders, geological sciences, philosophy and religious studies.
Hosts: Vincent Racaniello, Dickson Despommier, Rich Condit, and Kathy Spindler The TWiVome dissect the finding that interferon lambda alleles predict the outcome of hepatitis C virus infection. Links for this episode Interferon lambda and HCV outcome (Cell Host Micr) Laser capture microdissection (Wikipedia) HCV dependent fluorescent reporter (Nat Biotech) Bats and viruses (PLoS Path) White nose syndrome (PLoS Path) Mouse phenome database Letters read on TWiV 273 Weekly Science Picks Rich - Think like a scientist (one, two); Science controversiesDickson - Visualization challenge 2013Vincent - Orphan BlackKathy - Alberta worm invasion project Listener Pick of the Week Timothy - How do vaccines cause autism?Anne - Luke Jerram's glass virusesJim - NLM Communications Engineering BranchSteve - Synapse by synapseJacob - Tiny technology creates a buzz Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv
In The Naked Scientists Guide to Genetics, Simon Bishop explores some common genetics terms, meets a creature from the depths of the sea floor, and befriends a family of fancy rats! The terms DNA, genes, chromosomes and inheritance are explored PLUS are humans really 50% banana? Music featured: Adventure, Darling by Gillicuddy http://freemusicarchive.org/music/gillicuddy/; Dan-O, at http://danosongs.com. Like this podcast? Please help us by supporting the Naked Scientists
In The Naked Scientists Guide to Genetics, Simon Bishop explores some common genetics terms, meets a creature from the depths of the sea floor, and befriends a family of fancy rats! The terms DNA, genes, chromosomes and inheritance are explored PLUS are humans really 50% banana? Music featured: Adventure, Darling by Gillicuddy http://freemusicarchive.org/music/gillicuddy/; Dan-O, at http://danosongs.com. Like this podcast? Please help us by supporting the Naked Scientists
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 14/19
Für ein genetisches Modell B-Raf(V600E)-mutierter Darmkrebszellen und korrespondierender Wildtyp-Zellen wurde erstmalig in Deutschland das Somatic Cell Gene Targeting eingesetzt. Dabei konnte demonstriert werden, dass RKO eine Oncogene Addiction bezüglich der BRAF-Mutation aufweist. Als weitere B-Raf(V600E)-abhängige Effekte wurden die Selbstversorgung mit Wachstumssignalen (Self-Sufficiency of Growth Signals) und die Resistenz gegen Apoptose in dem Modell festgestellt. Darüber hinaus war die proliferative Kontaktinhibition in V600E-mutierten Klonen durch eine verstärkte Akt-Phosphorylierung aufgehoben und wurde nach Knockout der mutierten Allele im Wildtyp-Zellklon RBW-1 wieder hergestellt. Somit konnten vier zentrale Merkmale der Onkogenität dem mutierten B-Raf(V600E) zugeordnet werden. Andere onkogene Mechanismen waren dagegen vermutlich aufgrund einer Mutation der PI3-Kinase auch in BRAF-Wildtyp-Zellen noch intakt. So waren das Wachstum unter guten Kulturbedingungen und eine verstärkte Expression des EGF-Rezeptors unter Mangelbedingungen nicht vom BRAF-Mutationsstatus abhängig. Außerdem behielten Wildtyp-Zellen ihre Immortalisierung bei und zeigten weiterhin kein relevantes Auftreten von Seneszenz. Es wurden neue Spleißvarianten des BRAF-Gens gefunden und basal charakterisiert. Die alternativen Transkripte zeigten keine Kinase-Aktivität und waren in einem Ausmaß nachweisbar, das eine physiologische Bedeutung vermuten lässt. Hinsichtlich der Herkunft-Allele alternativer Isoformen und den Ursachen für das Auftreten alternativen Spleißens wurden neue Erkenntnisse gewonnen, die zudem die Interpretation publizierter Daten erleichtern. Es wurde gezeigt, dass die durch E-Cadherin vermittelten Zellkontakte essentiell für die epitheliale Komponente der intestinalen Barriere sind. Darüber hinaus wurde der Einfluss von E-Cadherin auf die Ausreifung sekretierender Zellen im Darm ermittelt und damit ein weiterer entscheidender Mechanismus der Abwehr bakterieller Invasionen aufgeklärt.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 14/19
Morbus Fabry wird X-chromosomal vererbt und führt durch einen Defekt des lysosomalen Enzyms α-Galaktosidase A zu einer Störung im Glykosphingolipid-Katabolismus. Neutrale Glykosphingolipide, v.a. Gb3 (Globotriaosylceramid), akkumulieren in Lysosomen verschiedenster Gewebe. Mit zunehmender Ablagerung dieser Stoffe im Gefäßendothel und in den Organen kommt es zur Ausprägung der Krankheitssymptome. In der Kindheit beginnt die Erkrankung häufig mit Akroparästhesien und Angiokeratomen. Im weiteren Verlauf treten dann die lebenslimitierenden Manifestationen dieser Erkrankung auf, wie terminale Niereninsuffizienz und, durch Ischämie- und Infarktereignisse, Myokardinfarkt und zerebrale Ischämie. Im Gegensatz zur überwiegenden Mehrzahl anderer X-gebundener Erkrankungen zeigen bei Morbus Fabry nahezu alle heterozygoten Mutationsträgerinnen im Laufe der Zeit klinische Manifestationen dieser Erkrankung, teils in gleich schwerer Form wie männliche Patienten. Da bisherige Hypothesen davon ausgingen, dass eine Verschiebung der X-Inaktivierung zugunsten des mutierten GLA-Allels am Auftreten von Symptomen bei heterozygoten Fabry-Mutationsträgerinnen beteiligt sei, wurden die X-Inaktivierungsmuster von durch Mutationsanalyse gesicherten Morbus Fabry-Patientinnen mit Hilfe des Androgenrezeptor-Tests untersucht. Bei diesem Assay wird genomische DNA mit methylierungssensitiven Restriktionsenzymen inkubiert. Diese verdauen nur die unmethylierte DNA des aktiven X-Chromosoms, so dass in der anschließenden PCR-Amplifikation eines hochpolymorphen CAG-Repeats im Exon 1 des Androgenrezeptor-Gens lediglich Allele des inaktiven X-Chromosoms amplifiziert werden. Nach der automatisierten Auswertung mittels Fragmentanalyse, ermöglicht durch einen mit einem Fluoreszenzfarbstoff markierten PCR-Primer, zeigt das Verhältnis der zwei Androgenrezeptor-Allele zueinander die relative Häufigkeit eines jeden Allels auf dem aktiven oder inaktiven X-Chromosom in den Zellen des untersuchten Materials. Erstmals wurden im Rahmen der vorliegenden Arbeit die X-Inaktivierungsmuster heterozygoter Mutationsträgerinnen von Morbus Fabry im Vergleich zu einem nichtverwandten Kontrollkollektiv untersucht. 13 (46%) der 28 Fabry-Mutationsträgerinnen zeigten eine random X-Inaktivierung, 10 (36%) eine moderate Verschiebung der X-Inaktivierung und 5 (18%) eine ausgeprägte Verschiebung der X-Inaktivierung zugunsten eines Allels. Es zeigte sich kein statistisch signifikanter Unterschied zu den Inaktivierungsmustern gleichaltriger Kontrollen (p = 0,669). Segregationsanalysen konnten anhand der Familien von sechs Frauen mit ausgeprägter oder moderater Verschiebung der X-Inaktivierung durchgeführt werden. Hier zeigte sich bei vier dieser Frauen eine Verschiebung der X-Inaktivierung zugunsten des Wildtyp GLA-Allels, während bei zwei weiteren eine Verschiebung zugunsten des mutierten Allels in Leukozyten erkennbar war. Bei jeder der Fabry-Patientinnen war sowohl der klinische Schweregrad der Erkrankung mittels MSSI (Mainz Severity Score Index), einem detaillierten Scoring-System für Morbus Fabry, als auch die Enzymaktivität der α-Galaktosidase A bestimmt worden. Eine Korrelation zwischen dem Ausmaß der X-Inaktivierung in Leukozyten heterozygoter Fabry-Mutationsträgerinnen und deren klinischen oder biochemischen Krankheitsparametern konnte jedoch nicht nachgewiesen werden. In dieser Studie konnte gezeigt werden, dass heterozygote Fabry-Patientinnen random X-Inaktivierungsmuster ähnlich denen gesunder Frauen aufweisen. Anhand unserer Daten konnte nicht belegt werden, dass das Auftreten und der Schweregrad der Erkrankung bei der Mehrzahl der heterozygoten Fabry-Patientinnen auf eine Verschiebung der X-Inaktivierung zugunsten des mutierten Allels als Pathomechanismus zurückzuführen ist. X-Inaktivierungsstudien können jedoch dazu beitragen, jene Frauen frühzeitig herauszufiltern, welche aufgrund einer bei ihnen möglicherweise rascher progredient verlaufenden Erkrankung von einer sehr teuren Enzymersatztherapie am meisten profitieren könnten.
Dr. Scott M. Williams discusses his manuscript "Increased Variance in Germline Allele-Specific Expression of APC Associates With Colorectal Cancer." To view the print version of this abstract go to http://bit.ly/vTAn0W.
Objective: The common single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity-associated gene (FTO) is associated with obesity. As genetic variants associated with weight regulation might also be implicated in the etiology of eating disorders, we evaluated whether SNP rs9939609 is associated with bulimia nervosa (BN) and anorexia nervosa (AN). Methods: Association of rs9939609 with BN and AN was assessed in 689 patients with AN, 477 patients with BN, 984 healthy non-population-based controls, and 3,951 population-based controls (KORA-S4). Based on the familial and premorbid occurrence of obesity in patients with BN, we hypothesized an association of the obesity risk A-allele with BN. Results: In accordance with our hypothesis, we observed evidence for association of the rs9939609 A-allele with BN when compared to the non-population-based controls (unadjusted odds ratio (OR) = 1.142, one-sided 95% confidence interval (CI) 1.001-infinity; one-sided p = 0.049) and a trend in the population-based controls (OR = 1.124, one-sided 95% CI 0.932-infinity; one-sided p = 0.056). Interestingly, compared to both control groups, we further detected a nominal association of the rs9939609 A-allele to AN (OR = 1.181, 95% CI 1.027-1.359, two-sided p = 0.020 or OR = 1.673, 95% CI 1.101-2.541, two-sided p = 0.015,). Conclusion: Our data suggest that the obesity-predisposing FTO allele might be relevant in both AN and BN. Copyright (C) 2012 S. Karger GmbH, Freiburg
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 12/19
Die Schizophrenie ist eine schwerwiegende psychiatrische Störung, von der weltweit etwa 1% der Bevölkerung betroffen ist. Die multifaktorielle Ätiopathogenese der Erkrankung ist noch weitgehend ungeklärt, wobei eine genetisch bedingte Vulnerabilität im Mittelpunkt steht. Dabei wird von einem polygenen Erbgang ausgegangen, wobei die risikomodulierenden Genvarianten bei verschiedenen Personen möglicherweise in unterschiedlicher Ausprägung vorliegen und für die Erkrankung prädisponieren. Bei der Suche nach kausalen chromosomalen Loci wurden bislang mehrere Gene mit jeweils nur geringen Beiträgen zu Entstehung und Ausprägung der Schizophrenie identifiziert. Dennoch sind die Anzahl der prädisponierenden Genloci, das von jedem Genort übertragene anteilige Risiko sowie epistatische Effekte derzeit unbekannt. Ein Grund für die inkonsistente Ergebnislage wird in der ätiologischen Heterogenität der klinisch-psychiatrischen Diagnose Schizophrenie gesehen. Das Konzept der Endophänotpyen bzw. intermediärer Phänotypen bietet eine Möglichkeit ätiologisch homogenere Subgruppen zu bilden. Endophänotypen sind zeitstabile, quantitativ messbare neurobiologische Korrelate. Es wird angenommen, dass ihre Ätiologie homogener und ihre genetische Determination weniger komplex ist als diejenige klinischer Krankheitsphänotypen. RGS4 ist ein Kandidatengen für Schizophrenie, das auf Chromosom 1 lokalisiert ist, in einer Region, die mit Schizophrenie gekoppelt zu sein scheint. Die Relation von RGS4 zur Pathogenese der Schizophrenie erscheint plausibel, da RGS4-Proteine die zeitliche Koordination und die Dauer der Signaltransduktion spezifischer Neurotransmittersysteme regulieren, die in der Pathophysiologie und der Behandlung der Schizophrenie eine Rolle spielen. Die Expression von RGS4 ist im Neokortex hoch und bei schizophrenen Patienten signifikant reduziert. In mehreren Assoziationsstudien (familienbasierte- und Fall-Kontroll-Designs) wurde ein signifikanter Zusammenhang unterschiedlicher RGS4-Polymorphismen und der Schizophrenie berichtet, wobei die Ergebnislage in Bezug auf die krankheitsassoziierten Single Nucleotide Polymorphisms (SNPs), Allele und Haplotypen inkonsistent ist. In der vorliegenden Fall-Kontroll-Assoziationsstudie wurde der Zusammenhang von sechs Basenaustauschpolymorphismen des RGS4-Gens und der Schizophrenie an 504 Schizophreniepatienten sowie 1315 deutschstämmigen Kontrollprobanden untersucht. In einer Subgruppe von 102 Patienten und 248 gesunden Kontrollprobanden wurde auch der Zusammenhang der sechs RGS4-Polymorphismen und neuropsychologischen Endophänotypen untersucht. Hierzu wurden die Patienten und Kontrollprobanden mit einer umfassenden neuropsychologischen Testbatterie untersucht. Die sechs SNPs (rs951436, rs951439, rs2661319, rs2842030, rs10759 und rs2063142) wurden mittels iPLEX genotypisiert und die Massen anschließend im MALDI-TOF Massenspektrometer analysiert. Signifikante Assoziationen der untersuchten RGS4-Polymorphismen konnten in dieser Arbeit sowohl mit dem Phänotypen Schizophrenie als auch mit dem neuropsychologischen Endophänotypen verbales Gedächtnis gefunden werden. Drei der untersuchten RGS4-Polymorphismen (rs951436, rs951439, rs2063142) waren mit Schizophrenie assoziiert, ein weiterer (rs10759) zeigte eine Tendenz zur Assoziation. In der Endophänotypen-Studie wurde eine signifikante Assoziation zwischen dem Marker rs2661319 und dem Faktor verbales Gedächtnis gefunden. In einem nächsten Schritt wurde untersucht, ob die Untertests bzw. Indizes, die den Faktor verbales Gedächtnis bilden, ebenfalls mit den analysierten RGS4-Polymorphismen assoziiert sind. Vier RGS4-Marker (951436, rs2661319, rs2842030, rs10759) zeigten eine Assoziation mit unterschiedlichen Indizes des Faktors verbales Gedächtnis, ein Marker (rs2063142) war tendenziell mit einem Index assoziiert. Die durchgeführte Haplotypenanalyse konnte diese Befunde bestätigen. Interessanterweise war das jeweilige C-Allel der Marker rs951436 und rs951439 sowohl mit Schizophrenie als auch mit einer schlechteren Leistung in einem Index assoziiert. Die Resultate der vorliegenden Untersuchung deuten auf einen Zusammenhang des RGS4-Gens sowohl mit Schizophrenie als auch mit dem neuropsychologischen Endophänotypen verbales Gedächtnis hin. Aufgrund der insgesamt jedoch inkonsistenten Ergebnislage im Hinblick auf krankheitsassoziierte SNPs, Allele und Haplotypen des RGS4-Gens sind weitere Studien nötig, um die mit Schizophrenie assoziierten RGS4-Polymorphismen zu identifizieren. Erst wenn die Identifikation der Genvarianten gelungen ist, die mit dem Risiko an Schizophrenie zu erkranken assoziiert sind, können in einem nächsten Schritt die bislang unbekannten molekularen Signalwege untersucht werden, durch deren Kenntnis eine kausale Therapie der Erkrankung ermöglicht würde.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 10/19
Pemphigoid gestationis ist eine seltene blasenbildende Autoimmundermatose unklarer Ätiologie, die ausschließlich im Zusammenhang mit Schwangerschaften oder schwangerschaftsassoziierten Tumoren beobachtet wird. Als Autoantigen konnte das Transmembranprotein Kollagen-Typ-XVII, ein Strukturelement der Hemidesmosomen der dermoepidermalen Junktionszone, identifiziert werden. Der selbstlimitierende Krankheitsverlauf und die hohe Rezidivneigung bei Folgeschwangerschaften deuten auf eine pathogenetische Rolle schwangerschaftsspezifischer Veränderungen endokriner sowie immunologischer Faktoren hin. Es besteht darüber hinaus eine Assoziation mit den MHC-Klasse-II-Antigenen HLA-DR3 und -DR4 bei den Patientinnen sowie mit dem väterlichen Haplotypen HLA-DR2. HLA-G ist ein nicht-klassisches MHC-Klasse-Ib-Molekül, das hauptsächlich von den extravillösen Trophoblasten der Plazenta exprimiert wird. Es gibt zahlreiche Hinweise darauf, dass HLA-G an der fetomaternalen Grenzzone durch Interaktion mit Rezeptoren auf natürlichen Killerzellen, B- und T-Lymphozyten und antigenpräsentierenden Zellen maßgeblich an der Tolerierung des semiallogenen Feten durch die mütterliche Immunabwehr beteiligt ist. Es wird postuliert, dass HLA-G auch an pathologischen Prozessen ausserhalb der Schwangerschaft, wie etwa Autoimmun- und Tumorerkrankungen, beteiligt sein könnte. HLA-G weist im Gegensatz zu den klassischen HLA-Klasse-I-Genen einen stark beschränkten Polymorphismus auf. In dieser Arbeit wurde erstmals eine mögliche Assoziation zwischen Polymorphismen im HLA-G-Gen und in der HLA-G-Promotorregion mit dem Pemphigoid gestationis untersucht. Ein potentiell funktioneller 14-bp-Insertions-Deletions-Polymorphismus in Exon 8 von HLA-G (rs1704) sowie vier Einzelnukleotidpolymorphismen der Promotorregion (rs1736936, rs1632947, rs1632946, rs1233334) wurden in einem Kollektiv, welches 18 Pemphigoid-gestationis-Patientinnen umfasst, genotypisiert und mit einem Kontrollkollektiv bestehend aus 52 gesunden Blutspenderinnen verglichen. Aufgrund der bekannten Assoziation von Pemphigoid gestationis mit dem Haplotyp HLA-DR2 wurden auch Kinder und Partner der Pemphigoid-gestationis- Patientinnen hinsichtlich dieser Polymorphismen typisiert und mit dem Kontrollkollektiv verglichen. Sofern DNA-Proben von kompletten Familien gewonnen werden konnten, wurden die Ergebnisse der Typisierung in Stammbaumdiagrammen dargestellt. Der 14-bp-Insertions-Deletions-Polymorphismus war in früheren Studien bereits mit anderen schwangerschaftsassoziierten Krankheitsbildern sowie mit der blasenbildenden Autoimmundermatose Pemphigus vulgaris in Zusammenhang gebracht worden. In den hier untersuchten Kollektiven der Pemphigoid-gestationis-Patientinnen und ihrer Angehörigen konnte keine statistisch signifikante Assoziation zum Pemphigoid gestationis nachgewiesen werden. Auffällig war jedoch eine sehr deutliche relative Häufung des in der Allgemeinbevölkerung seltener vorkommenden Insertionsallels in der Patientinnengruppe. Zu Grunde liegend könnte ein bekanntes starkes Kopplungsungleichgewicht zwischen dem mütterlichen Risikoallel für Pemphigoid gestationis, HLA-DR3, und einem für die 14-bp-Insertionsvariante kodierenden HLA-G-Allel sein. Die vier untersuchten Einzelnukleotidpolymorphismen der Promotorregion von HLA-G zeichnen sich durch ihre Lage innerhalb oder in der Nähe funktioneller Elemente und/oder eine bereits bekannte klinische Assoziation aus. Drei der untersuchten Polymorphismen (rs1736936, rs1632947, rs1632946) befanden sich in einem nahezu vollständigen Kopplungsungleichgewicht. Beim statistischen Vergleich der untersuchten Kollektive zeigte sich für die drei gekoppelten Einzelnukleotidpolymorphismen eine grenzwertig signifikante Assoziation bzw. eine Tendenz in Richtung einer Assoziation bestimmter väterlicher Allele und Genotypen mit dem Pemphigoiod gestationis (die p-Werte lagen zwischen 0,05 und 0,07). Für den Einzelnukleotidpolymorphismus rs1233334 konnte ebenfalls ein deutlicher Trend hin zu bestimmten väterlichen und kindlichen Genotypenkonstellationen im Vergleich zum Kontrollkollektiv ausgemacht werden (p-Werte zwischen 0,07 und 0,09). Die Ergebnisse der vorliegenden Arbeit deuten auf eine mögliche Assoziation der untersuchten Polymorphismen im HLA-G-Gen bei Vätern und Kindern von Pemphigoid-gestationis-Patientinnen mit dem Erkrankungsrisiko der Frauen im untersuchten Kollektiv hin. Es bleibt weiterführenden Studien überlassen, diese Ergebnisse an einem größeren Patientinnen- und Angehörigenkollektiv zu vergleichen und so möglicherweise zur Klärung der Ätiopathogenese dieser seltenen Autoimmunerkrankung beizutragen.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 03/06
Die in dieser Dissertation präsentierten Ergebnisse tragen aus dem Blickwinkel der Evolutionsbiologie zu unserem Verständnis der Regulation von Genexpression bei. Ich verwende einen bestens bekannten Modellorganismus, die Fruchtfliege Drosophila melanogaster, nicht nur als Objekt der Beobachtung, sondern auch als ein genetisches Manipulationswerkzeug, und untersuche drei verschiedene Aspekte des Prozesses, durch den die in der DNA gespeicherte Information förmlich „entfesselt“ oder umgesetzt wird zu biologischem Sinn, letztlich also zu Form und Funktion. In Kapitel 1 zeige ich zunächst, dass eine Inaktivierung des X-Chromosomes (und somit Genregulation auf chromosomaler Ebene) in der männlichen Keimbahn von D. melanogaster stattfindet. Im Gegensatz zur X-Inaktivierung in weiblichen Säugetieren, wo dies in den somatischen Zellen als Mechanismus zur Dosiskompensation auftritt, ist diese Art der Inaktivierung auf die Spermatogenese beschränkt und wurde wahrscheinlich während der Genomevolution als eine Möglichkeit etabliert, schädliche Auswirkungen in Zusammenhang mit Sexualantagonismus zu umgehen. Durch P-Element-vermittelte Keimbahntransformation erhielt ich fast 50 unabhängige Insertionen eines testisspezifischen Reportergenkonstrukts und untersuchte die dazugehörigen Reportergenaktivitäten durch Messung der Enzymaktivität und durch quantitative RT-PCR. Autosomale Insertionen dieses Konstrukts zeigten das erwartete Muster hoher männchen- und testisspezifischer Expression. Insertionen auf dem X-Chromosom zeigten dagegen wenig bzw. gar keine Expression des Transgens. Da die X-chromosomalen Insertionen die euchromatischen Abschnitte des Chromosoms abdeckten (bestimmt durch inverse PCR), konnte eine systematische Bevorzugung bestimmter Regionen bei Insertionen, die ein Fehlen von Expression auf dem X-Chromosom hätte erklären können, ausgeschlossen werden. Der Effekt scheint eine globale Eigenschaft des X-Chromosomes zu sein. Lediglich die Testisspezifität des transgenen Konstrukts ist für das Erscheinen des Effekts erforderlich, was somit eine Selektionshypothese für die X-Inaktivierung erhärtet sowie einige Beobachtungen erklären könnte, die im Zusammenhang mit der Verteilung von im Männchen und Testis exprimierten Genen im Drosophila-Genom gemacht wurden. In Kapitel 2 untersuche ich dann mutmaßliche cis-regulatorische Sequenzen und ihr Vermögen, allelspezifische Genexpression zu steuern. Nachdem Microarray-Studien umfangreiche Variabilität im Primärmerkmal Genexpression in unterschiedlichsten Taxa aufgedeckt haben, ist eine naheliegende Frage, mit der sich Evolutionsbiologen konfrontiert sehen, die nach der dieser Variabilität zugrunde liegenden genetischen Quelle. Neben epigenetischen Mechanismen gibt es einen Disput darüber, ob regulatorische Sequenzen nahe des exprimierten Gens (cis-Faktoren) und anderswo im Genom kodierte Faktoren (trans-Faktoren) einen qualitativ und quantitativ unterschiedlichen Beitrag zur Variabilität der Genexpression liefern. Hierzu wählte ich ein Gen von D. melanogaster, das nachweislich konsistente Expressionsunterschiede zwischen afrikanischen und nicht-afrikanischen („kosmopolitischen“) Stämmen zeigt, und klonierte die entsprechenden stromaufwärts flankierend gelegenen Teile jeweils in ein bakterielles Reportergenkonstrukt, um – nach erfolgreicher Integration ins Fruchtfliegengenom – direkt die von ihnen gesteuerte Auswirkung auf die Genexpression zu vergleichen. Der beobachtete Effekt war klein, jedoch signifikant, und zeigte sich nur in transgenen Fliegen, die ein X-Chromosom des afrikanischen Ausgangsstammes besaßen. Dies legt den Schluss nahe, dass zusätzlich zu den cis-regulatorischen Faktoren auch noch trans-Faktoren (vor allem auf dem X-Chromosom) zu dem zwischen den Stämmen beobachteten Expressionsunterschied beitragen. Letztendlich untersuche ich in Kapitel 3 das Phänomen des Codon bias durch seinen Zusammenhang mit Genexpression. Aufgrund der Redundanz des genetischen Codes werden viele der proteinogenen Aminosäuren durch mehr als ein Codon kodiert. Dies ermöglicht es, synonyme Codons in einer kodierenden Gensequenz auszutauschen, ohne dabei die Aminosäurensequenz des kodierten Polypeptids zu verändern. Ob dies Konsequenzen für die produzierte Proteinmenge hat (Translationseffizienz) ist Gegenstand dieses Kapitels. Ich verglich dabei die von zwei Allelen des Gens Alkoholdehydogenase (Adh) (von D. melanogaster) vermittelte Enzymaktivität direkt miteinander, welche sich in sieben Leucin-Codons unterschieden. Es ergab sich nahezu kein Unterschied in der ADH-Enzymaktivität, obwohl eines der Allele aus gänzlich optimalen Leucin-Codons bestand und das andere sieben suboptimale Leucin-Codons enthielt. Da Letzteres die Wildtypform von Adh war, legen die Ergebnisse den Schluss nahe, dass das Adh-Gen in seiner Leucin-Codonzusammensetzung (und vielleicht auch in seiner Codonzusammensetzung allgemein) bereits ausreichend optimiert ist. Weitere Versuche, die Zahl der optimalen Leucin-Codons zu erhöhen, können sogar einen Negativeffekt hinsichtlich der Enzymproduktion haben; dies möglicherweise aufgrund einer Sättigung des tRNA-Pools und/oder der Konsequenzen veränderter mRNA-Sekundärstrukturen.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 07/19
Die Untersuchung genetischer Prädispositionsfaktoren in der Ätiologie der chronisch-entzündlichen Darmerkrankungen (CED) führte zur Identifikation von zahlreichen so genannten Suszeptibilitätsgenen, die eine Rolle in der Pathophysiologie der CED spielen könnten. Im Jahre 2001 wurde das so genannte NOD2-/CARD15-Gen in der perizentrischen Region des Chromosoms 16 identifiziert. Drei Hauptmutationen in diesem 12 Exons umfassenden Gen konnten mit einem Morbus Crohn (MC) assoziiert werden (c.2104C>T (p.R702W) in Exon 4, c.2722G>C (p.G908R) in Exon 8 und c.3020insC (p.1007fs) in Exon 11). Ist ein Allel durch eine dieser Mutationen verändert, so ist im Vergleich zur Normalbevölkerung das relative Risiko, an einem Morbus Crohn zu erkranken, ungefähr dreimal so hoch. Im Falle einer Veränderung beider CARD15-Allele steigt das Erkrankungsrisiko sogar um das 30 bis 40fache. Weiterhin konnte in klinischen Studien gezeigt werden, dass diese CARD15-Mutationen mit einer rascheren Progression der Erkrankung und mit einem penetrierenden und stenosierenden Verlauf assoziiert sind. Ziel der im Rahmen dieser Doktorarbeit durchgeführten Studien war es, die genetischen Analysen für den Kliniker nutzbar zu machen und die Bedeutung der Genotypisierung in der klinischen Diagnostik und Therapieplanung genauer zu definieren. Ein weiteres Hauptinteresse war die Identifizierung genetisch determinierter Subpopulationen von CED-Patienten, die ein homogenes Krankheitsbild aufweisen. Da sich in verschiedenen Studien zeigte, dass gerade homozygote und zusammengesetzt heterozygote Merkmalsträger von CARD15-Mutationen unter einer besonders schweren CED leiden, sollte eine effektive und auch in der täglichen Routine leicht anwendbare Detektionsstrategie entwickelt werden, um solche Patienten einfach identifizieren zu können. Durch die Untersuchung der drei Hauptmutationen des CARD15-Gens (p.R702W, p.G908R und p.1007fs) bei 445 CED-Patienten und eine anschließend durchgeführte Genotyp-Phänotyp-Korrelation konnte solch eine Population von Hochrisiko-Patienten identifiziert werden, die für die Insertionsmutation p.1007fs homozygot war. Dabei handelt es sich um die größte je in der Literatur veröffentlichte Subkohorte von MC-Patienten (n = 19) mit diesem Genotyp, die durch ein sehr homogenes Krankheitsbild charakterisiert war. Alle Betroffenen litten unter einem progressiv verlaufenden Morbus Crohn mit der häufigen Notwendigkeit einer operativen Intervention, und sie mußten mit Immunsuppressiva behandelt werden, um eine Remission der Erkrankung zu erreichen. In einer weiteren Studie wurde eine zweite Subgruppe von CED-Patienten identifiziert, die ebenfalls unter einer raschen Progression der Erkrankung litt. Es handelte sich dabei um zusammengesetzt heterozygote Merkmalsträger, deren zweite, seltenere Mutation durch eine limitierte DNA-Sequenzanalyse der Exons 4, 5, 6, 8 und 11 des CARD15-Gens detektiert werden konnte. Durch diese Detektionsstrategie war es theoretisch möglich, bis zu 96,6 % der bis dahin beschriebenen mutierten Allele effektiv zu identifizieren. Von den acht neuen CARD15-Varianten spielt die Mehrheit wahrscheinlich eine Rolle in der Pathophysiologie der CED. Im Rahmen einer ebenfalls am Universitätsklinikum München-Grosshadern durchgeführten prospektiven doppelblinden Studie sollte anschließend anhand des Phänotyps der CED-Patienten der assoziierte Genotyp vorhergesagt werden. Hierbei konnte die Insertionsmutation p.1007fs als Vorhersagewert für einen stenosierenden Verlauf des Morbus Crohn im terminalen Ileum identifiziert werden. Trotz kontroverser Diskussionen über den wirklichen Nutzen und die Konsequenzen der Kenntnis des CARD15-Mutationsstatus eines CED-Patienten im klinischen Alltag, d. h. für die Diagnostik und eventuell für die weitere Therapieplanung, scheint bei Betrachtung der Ergebnisse der im Rahmen dieser Doktorarbeit durchgeführten Studien eine Genotypisierung von CED-Patienten durchaus sinnvoll zu sein. Angesichts der Häufigkeiten und der Lokalisation der CARD15-Mutationen ist sicherlich eine initiale Fokussierung auf die drei Hauptmutationen des CARD15-Gens (p.R702W, p.G908R und p.1007fs) zum Beispiel mittels RLFP-Analysen sinnvoll. Eine Untersuchung weiterer Regionen des CARD15-Gens durch Sequenzierung der DNA ist vorzugsweise bei Patienten angebracht, die sich bereits in jungen Jahren mit einem schweren Krankheitsbild präsentieren. Insgesamt können nur etwa 20 % der genetischen Prädisposition für einen Morbus Crohn durch CARD15-Mutationen erklärt werden, wobei zwischen 35 und 45 % der MC-Patienten Träger von CARD15-Mutationen sind. Demzufolge müssen Veränderungen in weiteren Suszeptibilitätsgenen für die genetische Prädisposition verantwortlich sein. Seit der Erstbeschreibung des CARD15-Gens wurden dementsprechend weitere Gene bzw. Genveränderungen beschrieben, die ebenfalls eine Rolle in der Entstehung einer CED spielen könnten. DLG5, SCL22A4 und SLC22A5, Gene der HLA-Region, CARD4 und TLR4 sind solche potentiellen Suszeptibilitätsgene.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 01/06
Das Ziel der Arbeit bestand darin, anhand molekulargenetischer Untersuchungen das krankheitsverursachende Gen für das Myoklonus-Dystonia-Syndrom (MDS) in den vorliegenden MDS-Familien zu identifizieren. Außerdem sollte die Vererbung dieses Gens und die molekularen Ursachen seiner allelspezifischen Expression analysiert werden, um einen Beitrag zur Erforschung der genetischen Ursachen des MDS zu leisten. Mit einem positionellen Klonierungsansatz sollte das krankheitsverursachende Gen für das MDS identifiziert werden. Kopplungsanalysen des MDS auf Chr. 7q21 - 22 waren dafür eine wesentliche Voraussetzung. In der Kandidatenregion sollten mit Hilfe eines Annotationsprogramms bekannte und neue Gene identifiziert und eine vollständige Transkriptkarte von diesem Bereich erstellt werden. Neu vorhergesagte Gene mussten experimentell verifiziert und vervollständigt werden. Eine Mutationsanalyse der identifizierten Kandidatengene für das MDS sollte vorgenommen werden. Die Vererbung des MDS erfolgte nach einem dominanten Erbschema, das jedoch keine vollständige Penetranz besitzt. Familienstammbaumanalysen zeigten, dass die Transmission der Erkrankung abhängig vom Geschlecht des krankheitsübertragenden Elternteils ist. Daher sollte eine mögliche genomische Prägung des in MDS-Patienten mutierten Gens in genomischer DNA und auf transkriptioneller Ebene untersucht werden. Die differentielle Methylierung von Cytosinen in CpG-Dinukleotiden ist ein epigenetischer Mechanismus zur Prägung von Genen und kann der Identifizierung geprägter Gene dienen. Die Etablierung der genomischen Bisulfitsequenzierung war die Voraussetzung, um den Methylierungsstatus von CpG-Dinukleotiden im Promotorbereich von SGCE in Lymphoblasten und Gehirngewebe zu analysieren. Die maternale Prägung des SGCE-Gens sollte auf Expressionsebene verifiziert werden. Eine monoallelische Expression des SGCE-Gens wurde in cDNA von genomisch heterozygoten SGCE-Mutationsträgern untersucht. Die differentielle Expression der elterlichen Allele sollte in cDNAs uniparentaler Disomien von Chromosom 7 überprüft werden. Da einige geprägte Gene physikalisch gekoppelt vorliegen, wurden benachbarte Gene auf monoallelische Expression analysiert. Um einen besseren Einblick in die Vererbung des MDS zu bekommen, sollte der Fall einer maternalen Transmission näher untersucht werden, der im Widerspruch zu einer maternalen Prägung des Krankheitsgens steht.
Background: For a diploid organism such as human, the two alleles of a particular gene can be expressed at different levels due to X chromosome inactivation, gene imprinting, different local promoter activity, or mRNA stability. Recently, imbalanced allelic expression was found to be common in human and can follow Mendelian inheritance. Here we present a method that employs real competitive PCR for allele-specific expression analysis. Results: A transcribed mutation such as a single nucleotide polymorphism ( SNP) is used as the marker for allele-specific expression analysis. A synthetic mutation created in the competitor is close to a natural mutation site in the cDNA sequence. PCR is used to amplify the two cDNA sequences from the two alleles and the competitor. A base extension reaction with a mixture of ddNTPs/ dNTP is used to generate three oligonucleotides for the two cDNAs and the competitor. The three products are identified and their ratios are calculated based on their peak areas in the MALDI-TOF mass spectrum. Several examples are given to illustrate how allele-specific gene expression can be applied in different biological studies. Conclusions: This technique can quantify the absolute expression level of each individual allele of a gene with high precision and throughput.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 01/19
Die hier vorliegende Arbeit stellt ein neues Mausmodell vor, mit dem der Einfluß von IgE in der Entstehung einer Allergie und die Folgen vermehrter IgE-Produktion in-vivo untersucht werden können. Erreicht wurde dies durch eine definierte Mutation im Erbgut von Mäusen. Mittels homologer Rekombination wurde durch ein knock-in-Verfahren eines der beiden g1-Allele im Immunglobulingenlocus durch die Sequenz, die für den IgE-Isotyp codiert, ersetzt.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 01/06
Ustilago maydis ist der Erreger des Maisbeulenbrands. Vorraussetzung für eine erfolgreiche Infektion sind Fusion zweier kompatibler, haploider Zellen und die folgende Ausbildung eines dikaryotischen Filaments. Diese Prozesse werden durch die beiden Paarungstyploci a und b kontrolliert. Der a-Locus kodiert für ein biallelisches Pheromon/Pheromonrezeptor-System, das die Zell/Zell-Erkennung und die Zellfusion reguliert. Die folgende pathogene Entwicklung wird durch den multiallelischen b-Locus kontrolliert, der für zwei Homeodomänenproteine kodiert, bW und bE. Nach der Fusion der haploiden Sporidien können sich bE/bW-Heterodimere ausschließlich aus bW und bE-Proteinen unterschiedlicher Allele bilden. Diese regulieren das filamentöse Wachstum, die Penetration der Pflanzenoberfläche, das Wachstum in der Pflanze und die Tumorinduktion. Das Ziel dieser Arbeit war es, regulatorische Gene aus U.maydis zu identifizieren, die an der Kontrolle der b-abhängigen, pathogenen Entwicklung beteiligt sind. Es wurde versucht, in einem direkten Selektionsprozess haploide, pathogene Stämme zu isolieren, die aus einer REMI-Mutagenese hervorgingen. Um eine möglichst breite Mutagenese zu erreichen, wurde eine neuartige Mutagenesestrategie angewandt, die neben Geninaktivierung ("loss of function") auch eine mögliche Aktivierung der Genexpression der betroffenen Loci ("gain of function") berücksichtigte. In einer weiteren UV-Mutagenese wurden durch Nutzung von egl1 als Reportergen Stämme isoliert, die EG-Aktivität zeigten. Die Expression des b-abhängigen, aber vermutlich nicht direkt durch das bE/bW-Heterodimer regulierten Gens egl1 sollte dabei eine Mutation in einem regulatorischen Gen anzeigen, das wiederum unter der Kontrolle von b stehen könnte. Es wurde angenommen, dass die interessantesten Stämme neben egl1 weitere b-abhängige Gene exprimieren. Eine komplexe Deregulation der Genexpression b-abhängiger Gene in haploiden Zellen sollte die Zentralität des betroffenen Regulators innerhalb der b-Regulationskaskade anzeigen. Die Komplementation des Stammes MR9-1 führte zur Isolierung eines regulatorischen Gens. hda1 kodiert für ein Protein mit signifikanter Homologie zu Histondeacetylasen und ist an der Kontrolle der differentiellen Genexpression in haploiden und dikaryotischen Zellen, und später an der Sporenentwicklung im Tumor entscheidend beteiligt. Hda1 wirkt in haploiden Zellen nicht als genereller Regulator der Genexpression, sondern bestimmt ein spezifisches Set von hda1-abhängigen Genen, das sich vornehmlich aus b-abhängigen Genen und den b-Genen selbst zusammensetzt. Haploide ∆hda1-Stämme vollziehen nicht die pathogene Entwicklung; nur dikaryotische ∆hda1-Zellen führen zur Tumorentwicklung, leiten jedoch nicht die Bildung von Sporen im Tumorgewebe ein. Funktionelle und biochemische Analysen zeigen in haploiden Zellen einen hochmolekularen Hda1-Komplex, der vermutlich den Aufbau einer höher geordneten Chromatinstruktur an regulatorischen Sequenzen bestimmt. Vermutlich kann Hda1 über einen Deacetylierungsmechanismus regulatorischer Sequenzen zur Repression b-abhängiger Gene führen.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 01/06
Diese Arbeit bietet einen Einblick in die Variabilität von Phagengenomen und die Anpassungsfähigkeit des Systems Phage. Dazu wurde die modulare Architektur der Phagengenome unter verschiedenen Gesichtspunkten analysiert: • In einer natürlichen Phagenpopulation aus Naturisolaten von Salmonella typhimurium wurde die Modulzusammensetzung innerhalb einer bestimmten Gruppe von Genen, der Lysisgenkassette, untersucht. Hierbei existiert prinzipiell ein großes Variationspotential, das jedoch in der Natur bei weitem nicht in dem Maße genutzt wird, wie es auf Grund der Anzahl der existierenden modularen Allele zu erwarten wäre. Offensichtlich spielen auch Selektionsvor- oder -nachteile eines Allels oder einer Allelkombination, der zeitliche Aspekt sowie die jeweilige Isolationsbedingung des Phagen eine Rolle. • Durch Simulation von Superinfektionen unter Laborbedingungen wurde die Häufigkeit untersucht, mit der unterschiedliche superinfizierende Phagen durch Rekombination auf den Genpool eines Prophagen zurückgreifen. In diesem Zusammenhang wird die Rolle der zweiten Immunitätsregion ImmI von P22 untersucht. • Zur Untersuchung der Evolution bei Phagen im klassischen Sinn auf Nukleotidebene wurden die Gene 3 der Verpackungsregion verschiedener lambdoider Phagen analysiert. Insgesamt zeigt sich, dass trotz des enormen Variationspotentials, das den lambdoiden Phagen aufgrund der Vielzahl der nachgewiesenen Allele in den einzelnen Kassetten zur Verfügung steht, insgesamt bis heute nur ein geringer Teil der theoretisch denkbaren Modulkombinationen nachgewiesen werden konnte.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 01/06
Das Zytomegalievirus der Maus (MCMV) zählt zur Familie der Herpesviridae und hat verschiedene Strategien entwickelt, um dem Immunsystem des Wirts zu entgehen. Einer dieser Mechanismen beeinflusst die Antigenpräsentation durch MHC-Klasse-I-Moleküle und wird durch das virale Genprodukt von m152 vermittelt. Dieses kodiert für ein Glykoprotein von 40 kDa Größe und wird in dieser Arbeit m152/gp40 genannt. M152/gp40 blockiert den Transport von MHC-Klasse-I-Molekülen zur Zelloberfläche und erkennt nur Moleküle der Maus, nicht aber des Menschen. Diese speziesspezifische Erkennung von MHC-Klasse-IMolekülen ist bisher nur für m152/gp40 bekannt und es wurden daher in der vorliegenden Arbeit Eigenschaften von MHC-Klasse-I-Molekülen untersucht, welche diese Speziesspezifität begründen. Es konnte gezeigt werden, dass die Spezies des gebundenen ß2- Mikroglobulins, sowie die Anzahl der Glykosylierungen der schweren Kette keinen Einfluss auf die Erkennung von MHC-Klasse-I-Antigenen durch m152/gp40 haben. Die Eigenschaft von m152/gp40, MHC-Klasse-I-Moleküle des Menschen nicht zurückzuhalten, wurde genutzt, um mit Hilfe chimärer MHC-Klasse-I-Moleküle den Bereich, der von m152/gp40 erkannt wird, einzugrenzen. Dieser liegt hauptsächlich in der a1-Domäne, weil die a2- Domäne nur eine schwache Retention bewirkt. Zwar können MHC-Klasse-I-Moleküle, die nur den luminalen Bereich umfassen, von m152/gp40 zurückgehalten werden, doch akkumulieren diese im ER und nicht im „ER-Golgi intermediate compartment“ (ERGIC) / cis-Golgi, wie Wildtyp-H-2Kb. Es wird diskutiert, ob dies ein Hinweis auf einen aktiven Transportmechanismus von MHC-Klasse-I-Molekülen aus dem ER ins ERGIC ist. Neben der Untersuchung der Funktion von m152/gp40 aufgrund der Expression des Gens allein, wurde der Einfluss der drei viralen Genprodukte von m04, m06 und m152 auf die MHC-Klasse-I-Oberflächenexpression mit Hilfe von MCMV-Deletionsmutanten untersucht. Anhand der Analyse der Oberflächenexpression verschiedener MHC-Klasse-I-Allele nach Infektion mit Wildtyp-MCMV oder MCMV-Mutanten konnte gezeigt werden, dass in MCMV nur m06/gp48 und m152/gp40 die Oberflächenexpression von MHC-Klasse-IMolekülen reduzieren. Von den untersuchten Allelen werden H-2Kb und H-2Kk nur schwach zurückgehalten. Es wurde gezeigt, dass dies auf die Funktion von m04/gp34 zurückzuführen ist, wobei m04/gp34 generell die Funktion von m152/gp40 und kaum die Funktion von m06/gp48 behindert. Für weitere Allele konnte gezeigt werden, dass diese unterschiedlich stark von den einzelnen viralen Proteinen zurückgehalten werden. So wird H-2Dd nur von m06/gp48 und m152/gp40 gemeinsam gut zurückgehalten, wohingegen H-2Db von m152/gp40 alleine gut zurückgehalten wird. Eine mögliche Rolle der unterschiedlichen Oberflächenexpression von MHC-Klasse-I-Allelen nach MCMV-Infektion für die Inhibition von NK-Zellen wird diskutiert.