Podcasts about cps1

This week we talk about gene-editing, CRISPR/Cas9, and ammonia.We also discuss the germ line, mad scientists, and science research funding.Recommended Book: The Siren's Call by Chris HayesTranscriptBack in November of 2018, a Chinese scientist named He Jiankui achieved global notoriety by announcing that he had used a relatively new gene-editing technique on human embryos, which led to the birth of the world's first gene-edited babies.His ambition was to help people with HIV-related fertility problems, one of which is that if a parent is HIV positive, there's a chance they could transmit HIV to their child.This genetic modification was meant to confer immunity to HIV to the children so that wouldn't be an issue. And in order to accomplish that immunity, He used a technology called CRISPR/Cas9 to modify the embryos' DNA to remove their CCR5 gene, which is related to immune system function, but relevant to this undertaking, also serves as a common pathway for the HIV-1 virus, allowing it to infect a new host.CRISPR is an acronym that stands for clustered regularly interspaced short palindromic repeats, and that refers to a type of DNA sequence found in all sorts of genomes, including about half of all sequenced bacterial genomes and just shy of 90% of all sequenced archaea genomes.Cas9 stands for CRISPR-associated protein 9, which is an enzyme that uses CRISPR sequences, those repeating, common sequences in DNA strands, to open up targeted DNA strands—and when paired with specific CRISPR sequences, this duo can search for selected patterns in DNA and then edit those patterns.This tool, then, allows researchers who know the DNA pattern representing a particular genetic trait—a trait that moderates an immune system protein that also happens to serve as a convenient pathway for HIV, for instance—to alter or eliminate that trait. A shorthand and incomplete way of thinking about this tool is as a sort of find and replace tool like you have in a text document on your computer, and in this instance, the gene sequence being replaced is a DNA strand that causes a trait that in turn leads to HIV susceptibility.So that's what He targeted in those embryos, and the children those embryos eventually became, who are usually referred to as Lulu and Nana, which are pseudonyms, for their privacy, they were the first gene-edited babies; though because of the gene-editing state of the art at the time, while He intended to render these babies' CCR5 gene entirely nonfunctional, which would replicate a natural mutation that's been noted in some non-gene-edited people, including the so-called Berlin Patient, who was a patient in Germany in the late-90s who was functionally cured of HIV—the first known person to be thus cured—while that's what He intended to do, instead these two babies actually carry both a functional and a mutant copy of CCR5, not just the mutant one, which in theory means they're not immune to HIV, as intended.Regardless of that outcome, which may be less impactful than He and other proponents of this technology may have hoped, He achieved superstardom, briefly, even being named one of the most influential people in the world by Time magazine in 2019. But he was also crushed by controversy, stripped of his license to conduct medical research by the Chinese government, sent to prison for three years and fined 3 million yuan, which is more than $400,000, and generally outcast from the global scientific community for ethical violations, mostly because the type of gene-editing he did wasn't a one-off sort of thing, it was what's called germ-line editing, which means those changes won't just impact Lulu and Nana, they'll be passed on to their children, as well, and their children's children, and so on.And the ethical implications of germ-line editing are so much more substantial because while a one-off error would be devastating to the person who suffers it, such an error that is passed on to potentially endless future generations could, conceivably, end humanity.The error doesn't even have to be a botched job, it could be an edit that makes the edited child taller or more intelligent by some measure, or more resistant to a disease, like HIV—but because this is fringy science and we don't fully understand how changing one thing might change other things, the implications for such edits are massive.Giving someone an immunity to HIV would theoretically be a good thing, then, but if that edit then went on the market and became common, we might see a generation of humans that are immune to HIV, but potentially more susceptible to something else, or maybe who live shorter lives, or maybe who create a subsequent generation who themselves are prone to all sorts of issues we couldn't possibly have foreseen, because we made these edits without first mapping all possible implications of making that genetic tweak, and we did so in such a way that those edits would persist throughout the generations.What I'd like to talk about today is another example of a similar technology, but one that's distinct enough, and which carries substantially less long-term risk, that it's being greeted primarily with celebration rather than concern.—In early August of 2024, a gene-editing researcher at the University of Pennsylvania, Dr. Kiran Musunuru, was asked if there was anything he could do to help a baby that was being treated at the Children's Hospital of Philadelphia for CPS1 deficiency, which manifests as an inability to get rid of the ammonia that builds up in one's body as a byproduct of protein metabolism.We all generate a small amount of ammonia just as a function of living, and this deficiency kept the baby from processing and discarding that ammonia in the usual fashion. As a result, ammonia was building up in its blood and crossing into its brain.The usual method of dealing with this deficiency is severely restricting the suffer's protein intake so that less ammonia is generated, but being a baby, that meant it wasn't able to grow; he was getting just enough protein to survive and was in the 7th percentile for body weight.So a doctor at the Children's Hospital wanted to see if there was anything this gene-editing researcher could do to help this baby, who was at risk of severe brain damage or death because of this condition he was born with.Gene-editing is still a very new technology, and CRISPR and associated technologies are even newer, still often resulting in inaccurate edits, many of which eventually go away, but that also means the intended edit sometimes goes away over time, too—the body's processes eventually replacing the edited code with the original.That said, these researchers, working with other researchers at institutions around the world, though mostly in the US, were able to rush a usually very cumbersome and time-consuming process that would typically take nearly a decade, and came up with and tested a gene-editing approach to target the specific mutation that was causing this baby's problems, and they did it in record time: the original email asking if Dr Musunuru might be able to help arrived in August of 2024, and in late-February of 2025, the baby received his first infusion of the substance that would make the proper edits to his genes; they divided the full, intended treatment into three doses, the first being very small, because they didn't know how the baby would respond to it, and they wanted to be very, very cautious.There were positive signs within the first few weeks, so 22 days later, they administered the second dose, and the third followed after that.Now the research and medical worlds are waiting to see if the treatment sticks; the baby is already up to the 40th percentile in terms of weight for his age, is able to eat a lot more protein and is taking far less medication to help him deal with ammonia buildup, but there's a chance that he may still need a liver transplant, that there might be unforeseen consequences due to that intended edit, or other, accidental edits made by the treatment, or, again, that the edits won't stick, as has been the case in some previous trials.Already this is being heralded as a big success, though, as the treatment seems to be at least partially successful, hasn't triggered any serious, negative consequences, and has stuck around for a while—so even if further treatments are needed to keep the gene edited, there's a chance this could lead to better and better gene-editing treatments in the future, or that such treatments could replace some medications, or be used for conditions that don't have reliable medications in the first place.This is also the first known case of a human of any age being given a custom gene-editing treatment (made especially for them, rather than being made to broadly serve any patient with a given ailment or condition), and in some circles that's considered to be the future of this field, as individually tailored gene-treatments could help folks deal with chronic illnesses and genetic conditions (like cystic fibrosis, Huntington's disease, muscular dystrophy, and sickle cell), but also possibly help fight cancers and similar issues.More immediately, if this treatment is shown to be long-term efficacious for this first, baby patient, it could be applied to other patients who suffer the same deficiency, which afflicts an estimated 1 in 1.3 million people, globally. It's not common then—both parents have to have a mutant copy of a specific gene for their child to have this condition—but that's another reason this type of treatment is considered to be promising: many conditions aren't widespread enough to justify investment in pharmaceuticals or other medical interventions that would help them, so custom-tailored gene-editing could be used, instead, on a case-by-case basis.This is especially true if the speed at which a customized treatment can be developed is sped-up even further, though there are concerns about the future of this field and researchers' ability to up its efficiency as, at least in the US, the current administration's gutting of federal research bodies and funding looks likely to hit this space hard, and previous, similar victories that involved dramatically truncating otherwise ponderous developmental processes—like the historically rapid development of early COVID-19 vaccines—are not looked at favorably by a larger portion of the US electorate, which could mean those in charge of allocating resources and clearing the way for such research might instead pull even more funding and put more roadblocks in place, hobbling those future efforts, rather than the opposite.There are plenty of other researchers and institutions working on similar things around the world, of course, but this particular wing of that larger field may have higher hurdles to leap to get anything done in the coming years, if current trends continue.Again, though, however that larger context evolves, we're still in the early days of this, and there's a chance that this approach will turn out to be non-ideal for all sorts of reasons.The concept of tailored gene-editing therapies is an appealing one, though, as it could replace many existing pharmaceutical, surgical, and similar approaches to dealing with chronic, inherited conditions in particular, and because it could in theory at least allow us to address such issues rapidly, and without needing to mess around with the germ-line, because mutations could be assessed and addressed on a person-by-person basis, those edits staying within their bodies and not being passed on to their offspring, rather than attempting to make genetic customizations for future generations based on the imperfect knowledge and know-how of today's science, and the biased standards and priorities of today's cultural context.Show Noteshttps://www.nejm.org/doi/full/10.1056/NEJMoa2504747https://www.nih.gov/news-events/news-releases/infant-rare-incurable-disease-first-successfully-receive-personalized-gene-therapy-treatmenthttps://www.wired.com/story/a-baby-received-a-custom-crispr-treatment-in-record-time/https://www.wsj.com/tech/biotech/crispr-gene-editing-therapy-philadelphia-infant-8fc3a2c5https://www.washingtonpost.com/science/2025/05/15/crispr-gene-editing-breakthrough/https://www.npr.org/sections/shots-health-news/2025/05/15/nx-s1-5389620/gene-editing-treatment-crispr-inheritedhttps://interestingengineering.com/health/first-personalized-crispr-gene-therapyhttps://www.nature.com/articles/d41586-025-01496-zhttps://www.nytimes.com/2025/05/15/health/gene-editing-personalized-rare-disorders.htmlhttps://www.nytimes.com/2025/05/31/world/asia/us-science-cuts.htmlhttps://www.livescience.com/health/genetics/us-baby-receives-first-ever-customized-crispr-treatment-for-genetic-diseasehttps://en.wikipedia.org/wiki/He_Jiankui_affairhttps://en.wikipedia.org/wiki/CCR5https://en.wikipedia.org/wiki/Berlin_Patienthttps://en.wikipedia.org/wiki/CRISPR_gene_editinghttps://en.wikipedia.org/wiki/CRISPRhttps://pmc.ncbi.nlm.nih.gov/articles/PMC6813942/ This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit letsknowthings.substack.com/subscribe

In the year 20XX, a battle for world domination now begins!! The last featured episode of the 4 Player Beat ‘Em Up miniseries aptly finishes with Capcom's last 2D arcade beat ‘em up, Battle Circuit. Is this the closest we'll ever get to a Cowboy Bebop arcade game? How did an eight-player racing game turn into this four-player beat ‘em up? Who has the worst Elvis impression? Which Capcom system had the best games: CPS1 or CPS2?  In lieu of listener questions we felt inspired to do a Podouken Ranks on the twelve Capcom 2D beat ‘em ups starting with Final Fight and ending with Battle Circuit. Join the Podouken Discord and ask your own questions that could be included in a future episode or tell us why we're wrong to rank your favorite Capcom beat ‘em up dead last: discord.gg/k5vf2Jz You can also like, comment, and subscribe to our YouTube channel where we post our listener question segments and additional content like Podouken Picks: https://www.youtube.com/@podoukenpodcast2716

In the year 20XX, a battle for world domination now begins!! The last featured episode of the 4 Player Beat ‘Em Up miniseries aptly finishes with Capcom's last 2D arcade beat ‘em up, Battle Circuit. Is this the closest we'll ever get to a Cowboy Bebop arcade game? How did an eight-player racing game turn into this four-player beat ‘em up? Who has the worst Elvis impression? Which Capcom system had the best games: CPS1 or CPS2?  In lieu of listener questions we felt inspired to do a Podouken Ranks on the twelve Capcom 2D beat ‘em ups starting with Final Fight and ending with Battle Circuit. Join the Podouken Discord and ask your own questions that could be included in a future episode or tell us why we're wrong to rank your favorite Capcom beat ‘em up dead last: discord.gg/k5vf2Jz You can also like, comment, and subscribe to our YouTube channel where we post our listener question segments and additional content like Podouken Picks: https://www.youtube.com/@podoukenpodcast2716

Sorry X-Men, there's a new longest episode in town. It's time to talk about George Lucas's totally-not-inspired-by-Lord-of-the-Rings fantasy epic (and Capcom arcade game) Willow, which coincidentally (or not) has a new TV series coming out… today!Why are all the names in this movie so awful? Does Val Kilmer make the perfect Madmartigan or would John Cusak have done it better? Did we talk about this movie for almost twice its running time? How does the arcade game reward frugal shopping?Not to miss in this episode: Jarrod references an anime all on his own, we dream up the Forrest Gump video game, discuss the benefits of owning a bone urn, and recap Willow so you can be ready for the new Disney+ series.

Sorry X-Men, there's a new longest episode in town. It's time to talk about George Lucas's totally-not-inspired-by-Lord-of-the-Rings fantasy epic (and Capcom arcade game) Willow, which coincidentally (or not) has a new TV series coming out… today!Why are all the names in this movie so awful? Does Val Kilmer make the perfect Madmartigan or would John Cusak have done it better? Did we talk about this movie for almost twice its running time? How does the arcade game reward frugal shopping?Not to miss in this episode: Jarrod references an anime all on his own, we dream up the Forrest Gump video game, discuss the benefits of owning a bone urn, and recap Willow so you can be ready for the new Disney+ series.

En este programa estaremos conversando sobre uno de los juegos Beat em up mas queridos de la compañía Capcom, el legendario "Cadillacs and Dinosaurs" juego basado en la obra de Mark Schultz "Xenozoic Tales" el cual nos propone un universo post apocalíptico en donde el mundo vuelve a ser habitado por los Dinosaurios. Si hay un aspecto por el cual este juego destaca, es por su maravilloso apartado grafico el cual capta a la perfección el universo en el cual esta basado, sin mencionar además que su banda sonora es impresionante, la que además estaremos repasando a lo largo de todo el programa.

En este programa estaremos conversando sobre el legendario juego y personaje "Captain Commando" personaje que inicialmente fue creado y usado como mascota en Capcom USA para eventualmente, y varios años después, protagonizar su propio juego, el cual además es el primer titulo de arcade de 4 jugadores cooperativo de la compañía.

En este programa estaremos conversando sobre la primera actualización del tan querido Street Fighter II. Repasaremos cuales son las principales novedades y diferencias con respecto a su antecesor, así como también estaremos comentando las razones que llevaron a Capcom a lanzar una actualización por sobre una secuela.

Stasera nell'ottava puntata di RGBar ci è venuto a trovare l'amico Danilo! Parleremo delle consuete news dal mondo del Retrogame, ma anche di denti giapponesi e light novel particolari. Buon Ascolto! Se questo Luglio non ci scioglie prima!★Supporto★► T-Shirt disponibili al seguente link:https://www.retrogamingshop.it/vendita-retrogames/t-shirt-de-i-beceri-videoludici/► Potete sostenerci tramite Amazon cliccando su qualcuno dei seguenti prodotti:OSSC: https://amzn.to/39kJ5jj (link affiliato)Switch HDMI 3x1 4K: https://amzn.to/2vTERl3 (link affiliato)Switch Component: https://amzn.to/3dB610X (link affiliato)Teleprompter: https://amzn.to/3btjINN (link affiliato)Microfono Auna: https://amzn.to/2Uq4ovH (link affiliato)►Abbiamo lanciato un Patreon! Se volete sostenerci andate al seguente link:https://www.patreon.com/IBeceriVideoludici►Per una donazione una tantum: https://www.paypal.me/IBeceriVideoludici★Twitch★► Seguite i nostri stream sul nostro canale Twitch:https://twitch.tv/ibecerivideoludici★Podcast★►Trovate qui il podcast, raggiungeteci per interagire live con noi durante le puntate:https://www.spreaker.com/show/i-beceri-videoludici★Social★►Seguiteci ed interagite con noi:Facebook pagina: https://www.facebook.com/ibecerivideoludici/Facebook gruppo: https://www.facebook.com/groups/621576914890876/Telegram: https://t.me/joinchat/FBFV6BbHbpXTcWQpwHfj2g

En este programa estaremos conversando sobre Ghouls´n Ghosts en su versión lanzada para el sistema CPS1, siendo esta una secuela del original Ghosts´n Goblins, y el cual viene a ser una mejora en todo sentido, tanto en términos gráficos y musicales, como también a nivel de contenido y técnico. Tal fue el éxito de este juego, que se justificaron ports para varios sistemas de la época, como lo son Super Nintendo. Sega Megadrive y X68000, entre otros.

SIRT5 causes deglutarylation and functional activation of glutamate dehydrogenase 1 which is essential to cellular glutaminolysis.Indeed, SIRT5 supports the anaplerotic transamination entry of glutamine and other amino acids as alpho ketoglutarate into the TCA cycle in malignant phenotypes of colorectal cancer via activation of the glutamate dehydrogenase1. Sirt5 is known to regulate the activity of the urea cycle enzyme, carbamoyl phosphate synthase 1 (CPS1). SIRT5 mediated de-glutarylated CPS1 is elevated in activity to maintain urea cycle competency during active amino acid incorporation into the bioenergetic machinery thus promoting the potentiation of tumorigenesis. Science. 2011 Nov11; 334(6057): 806–809 Cell Metab 2014 Apr 1;19(4):605-17. Nat Commun. 2018 Feb7;9(1):545 Cell. 2006 Sep 8;126(5):941-54 Mol Cell. 2013 Jun 6; 50(5): 686–698 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

En este programa estaremos conversando sobre uno de los títulos mas importantes e influyentes del mundo de los videojuegos, Street Fighter II: The World Warrior, juego que no solo significaría el preludio a una larga lista de actualizaciones y ports, sino que ademas también gracias a este titulo, la franquicia en general se convertiría en una de las mas importantes de la compañía Capcom. Y por si fuera poco, es este juego, el que sentaría las bases de lo que conocemos hoy en día como "videojuego de pelea", ya que tras su lanzamiento, prácticamente todos los juegos del genero se basarían en el sistema de Street Fighter II.

MetalFRO and Addicted are joined by the one and only Ser Flash, aka Serraxor, from the Bullet Heaven YouTube series, for a lively discussion about Capcom's U.N. Squadron!

The Mad Gears must pay. We are joined by special guest co-host Chris Antista to discuss Capcom's Final Fight! Capcom goes “huge and cool” to bring us one of the best beat ‘em ups ever made. Who is responsible for the Final Fight/Street Fighter II universe and why is it not who you may think? What part did a French historical novel and manga have in giving us the best political body in video games? Why were severed mammal's feet ever a commercially sold product? How did “stuffing” play a key part in Capcom's game development? You want more? How about the favorite foods of the Final Fight crew, glam metal, Breakfast at Tiffany's, ballads, the chip famine, and Don Frye.

The Mad Gears must pay. We are joined by special guest co-host Chris Antista to discuss Capcom's Final Fight! Capcom goes “huge and cool” to bring us one of the best beat ‘em ups ever made. Who is responsible for the Final Fight/Street Fighter II universe and why is it not who you may think? What part did a French historical novel and manga have in giving us the best political body in video games? Why were severed mammal's feet ever a commercially sold product? How did “stuffing” play a key part in Capcom's game development? You want more? How about the favorite foods of the Final Fight crew, glam metal, Breakfast at Tiffany's, ballads, the chip famine, and Don Frye.

En este capitulo estaremos rememorando una de las sagas mas antiguas de la compañía Capcom, Ghost' n goblins, en su primera entrega para las maquinas de Arcade. Curiosidades, datos del desarrollo del juego y por supuesto como siempre estaremos repasando el increíble soundtrack de este maravilloso juego. No se lo pierdan.

Episode 30 News WELCOME TO YOUR PARTY, SATURN!!! YOU'RE SO OLD NOW (The SJY Community's Top 100 Favorite Saturn Games List) Years Later, Some Can't Tell Who's On Street Fighter II Turbo's Japanese Cartridge Random: Super Mario Land Has Been Ported To The SNES, And It Looks Amazing  Nintendo Was Worried Donkey Kong Country Was "Too 3D" Want to code Amiga games in Assembler? If so then read on! Run out of space? Try these retro computer paper models! #FujiNet – Atari 8-bit Network Adapter The MagPi magazine issue 88 is all about Retro Computing Teenage Mutant Ninja Turtles … of Rage  The “Atari Vault” Collection Just Got Updated To 150 Games Upcoming MiSTer Cores: Sega CD, PlayStation, Jaguar, Cave Arcade, CPS1, and more My exciting holiday features Electronics Boutique 1988 Christmas Catalog Hyper Catalog 4 Review Topic:  Game Boy Interface Game Boy Interface Revisited   Game Club Discussion Vectron Keystone Kapers   New Game Club Games Yie Ar Kung-Fu Daytona USA    Facebook Question(s): Send us you Thanksgiving day retro gaming memories.   Music By: I Love Lightning Bugs

Capcom, a studio and publisher that needs little introduction. From 1984 to 1994, Capcom had developed a solid roster of arcade blockbusters, adult orientated and kid-friendly licensed titles and of course the venerable Street Fighter II. In this episode Alex, Jake and Phil sit down to reminisce about a golden era for Capcom, their high coin-op standards and the brilliant console releases that left a mark that is still with us all today.

Tues 31 May 2016 Asistentes: Adrián Ling twitter.com/AdrianLingSC, Miguel Sandoval twitter.com/aftasher, Rolando Cedillo twitter.com/rolman y Artemi Urbina twitter.com/Artemio 00:00:23 Twinkle Star Sprites 00:12:35 El Shaddai Theme 00:37:00 Okamiden Limited OST Opening Music 01:10:25 Super Puzzle Fighter II Turbo Intro and Sakura 01:40:40 DOOM medley 02:18:40 Thunder Cross: Skywalker 02:53:31 Chip n Dale Rescue Rangers (NES) Music - Zone J 03:16:48 Gomola Speed Stage 1 03:36:41 Magical Quest starring Mickey Mouse.wav 03:57:12 Getsu Fuuma 04:15:44 Ninja Baseball Bat Man - Seattle (Stage 1) 04:31:01 Kirby's Dream Course Medley 04:53:03 Mahou Daisakusen-Stage2 Video de CPS1 por Eduardo Cruz www.youtube.com/watch?v=FAcEneXOWrw

Séptimo episodio de esta primera temporada. En esta edición hablamos de Street Fighter 2 The World Warrior, Arcade de lucha desarrollado por Capcom en 1991 sobre la placa CPS1,clasicazo dónde los haya de los salones recreativos de la época, mítico entre míticos que sentó la base de los fighting games actuales. Comentadnos que os parece el podcast, vuestras impresiones y vivencias sobre este juego en la sección de comentarios.

REJUGANDO THE KING OF DRAGONS Celebramos nuestro 2º aniversario (entre otras cosas) y lo hacemos con un título que lo merece. Uno de los arcade de Capcom que sentaron precedentes. Elfos, Orcos, Magos, Guerreros, Esqueletos y como no, Dragones en un beat'm up legendario de CPS1. Vamos a hablar de Capcom, de Kinu Nishimura, la autora de los ArtWorks, de la música de Shimomura y de otras muchas cosas que giran alrededor del título y su temática. Por supuesto desgranaremos el juego, versiones y leeremos vuestros recuerdos sobre él. Para el próximo episodio toca hablar de DONKEY KONG COUNTRY

REJUGANDO THE KING OF DRAGONS Celebramos nuestro 2º aniversario (entre otras cosas) y lo hacemos con un título que lo merece. Uno de los arcade de Capcom que sentaron precedentes. Elfos, Orcos, Magos, Guerreros, Esqueletos y como no, Dragones en un beat'm up legendario de CPS1. Vamos a hablar de Capcom, de Kinu Nishimura, la autora de los ArtWorks, de la música de Shimomura y de otras muchas cosas que giran alrededor del título y su temática. Por supuesto desgranaremos el juego, versiones y leeremos vuestros recuerdos sobre él. Para el próximo episodio toca hablar de DONKEY KONG COUNTRY

Con un poco más de retraso de lo habitual, os traemos el especial dedicado a una de las mejores placas arcades jamás creadas. Hablamos de la CPS1 de Capcom. Una placa con un catálogo muy variado y lleno de grandes joyas atemporales coronado por el gran Street Fighter II. Además de repasar el catálogo de […]

Nuclear magnetic resonance spectroscopy (NMR) provides robust readouts of many metabolic parameters in one experiment. However, identification of clinically relevant markers in H-1 NMR spectra is a major challenge. Association of NMR-derived quantities with genetic variants can uncover biologically relevant metabolic traits. Using NMR data of plasma samples from 1,757 individuals from the KORA study together with 655,658 genetic variants, we show that ratios between NMR intensities at two chemical shift positions can provide informative and robust biomarkers. We report seven loci of genetic association with NMR-derived traits (APOA1, CETP, CPS1, GCKR, FADS1, LIPC, PYROXD2) and characterize these traits biochemically using mass spectrometry. These ratios may now be used in clinical studies.

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values