Podcasts about 5mc

The Acolyte wirft grosse Schatten voraus! Daher ist diese 5MC ein Leuchtturm der Infos über SW in den nächesten Monaten! Tales of the Empire ist genial und alles andere wird sich daran messen müssen! Deswegen ist eine Analyse angebracht!

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.03.522592v1?rss=1 Authors: Singh, B. N., Tran, H., Kramer, J., Kirishenko, E., Changela, N., Wang, F., Feng, Y., Kumar, D., Tu, M., Liang, S., Lan, J., Bizet, M., Fuks, F., Steward, R. Abstract: Modifications of mRNA, especially methylation of adenosine, have recently drawn much attention. The much rarer modification, 5-hydroxymethylation of cytosine (5hmC), is not well understood and is the subject of this study. Vertebrate Tet proteins are 5-methylcytosine (5mC) hydroxylases enzymes catalyzing the transition of 5mC to 5hmC in DNA and have recently been shown to have the same function in messenger RNAs in both vertebrates and in Drosophila. The Tet gene is essential in Drosophila because Tet knock-out animals do not reach adulthood. We describe the identification of Tet-target genes in the embryo and larval brain by determining Tet DNA-binding sites throughout the genome and by mapping the Tet-dependent 5hmrC modifications transcriptome-wide. 5hmrC-modified sites can be found along the entire transcript and are preferentially located at the promoter where they overlap with histone H3K4me3 peaks. The identified mRNAs are frequently involved in neuron and axon development and Tet knock-out led to a reduction of 5hmrC marks on specific mRNAs. Among the Tet-target genes were the robo2 receptor and its slit ligand that function in axon guidance in Drosophila and in vertebrates. Tet knock-out embryos show overlapping phenotypes with robo2 and are sensitized to reduced levels of slit. Both Robo2 and Slit protein levels were markedly reduced in Tet KO larval brains. Our results establish a role for Tet-dependent 5hmrC in facilitating the translation of modified mRNAs, primarily in developing nerve cells. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

5MC - 5 minute chat - On today's 5 minute chat, we will give you a helpful tool that will help you on your your journey that takes 1 minute to do!!! We have seen many people feel overwhelmed by actually just implementing the plan. No it's not because you're lazy, or that you don't have what it takes. It's about your mindset and since this is one of the biggest hurdles in someones journey, we will be diving deep into mindset in a WAVE of future episodes, so stay tune! 

Domingo XXIII Semana Tiempo Ordinario Rosario de Intercesión Mundial Una voz resuena de lo alto en este día EFFETA ábrete!!! Que nos invita una vez más a dejar que Dios tome el control de nuestras vida... cuanta diferencia existe en nuestro ser cuando dejamos que sea el Señor quien nos oriente, cuando le creemos al Señor y no a las propuestas de este mundo... Hoy el Señor le habla a tu corazón tal vez cansado y agobiado por tantas cosas, pero abrete a la posibilidad de un cambio, de una nueva vida, de algo diferente junto con El...Lee los textos y déjate consolar!!!Is 35, 4-7aSal 145,7-10St 2, 1-5Mc 7, 31-37

Jueves Eucarístico IX Semana Tiempo Ordinario Las noches oscuras como lo dice San Juan De la Cruz son partes fundamentales en el proceso de maduración espiritual. Es ahí cuando se hace ver cómo está nuestro proceso de fe. Hoy los textos nos clarifican como un cristiano debe enfrentar los problemas, las malas noticias o mejor dicho como un cristiano enfrenta los retos desde la Fe...Lee los textos, aprende y actúa...Tb 6, 10-11;7, 1.9-17;8, 4-9Sal 127, 1-5Mc 12, 28-34

Jueves EucarísticoV Semana Tiempo OrdinarioDía de oración por las vocacionesEl proyecto del amor tiene varias facetas unos deciden consagrarse por completo al servicio del Señor en la vida religiosa o sacerdotal otros en cambio buscan en el amor de pareja la manera de servir al Señor. Este proyecto De amor conyugal no es algo que nace de la noche a la mañana...Lee los textos y descubre cuál es el plan De Dios para tu vida de pareja...Gn 2, 18-25Sal 127, 1-5Mc 7, 24-30

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.28.271585v1?rss=1 Authors: Nunn, A., Otto, C., Stadler, P. F., Langenberger, D. Abstract: Whole genome bisulfite sequencing is currently at the forefront of epigenetic analysis, facilitating the nucleotide-level resolution of 5-methylcytosine (5mC) on a genome-wide scale. Specialised software have been developed to accommodate the unique difficulties in aligning such sequencing reads to a given reference, building on the knowledge acquired from model organisms such as human, or Arabidopsis thaliana. As the field of epigenetics expands its purview to non-model plant species, new challenges arise which bring into question the suitability of previously established tools. Herein, nine short-read aligners are evaluated: Bismark, BS-Seeker2, BSMAP, BWA-meth, ERNE-BS5, GEM3, GSNAP, Last, and segemehl. Precision-recall of simulated alignments, in comparison to real sequencing data obtained from three natural accessions, reveals on-balance that BWA-meth and BSMAP are able to make the best use of the data during mapping. The influence of difficult-to-map regions, characterised by deviations in sequencing depth over repeat annotations, is evaluated in terms of the mean absolute deviation of the resulting methylation calls in comparison to a realistic methylome. Downstream methylation analysis is responsive to the handling of multi-mapping reads relative to mapping quality (MAPQ), and potentially susceptible to bias arising from the increased sequence complexity of densely-methylated reads. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.27.223685v1?rss=1 Authors: Greer, C. B., Wright, J., Weiss, J. D., Lazarenko, R. M., Moran, S. P., Zhu, J., Chronister, K. S., Jin, A. Y., Kennedy, A. J., Sweatt, J. D., Kaas, G. A. Abstract: The dynamic regulation of DNA methylation in post-mitotic neurons is necessary for memory formation and other adaptive behaviors. Ten-eleven translocation 1 (TET1) plays a part in these processes by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thereby initiating active DNA demethylation. However, attempts to pinpoint the exact role of the enzyme in the nervous system have been hindered by contradictory findings, perhaps due in part, to a recent discovery that two Tet1 isoforms are differentially expressed from early development into adulthood. Here, we demonstrate that both the shorter transcript (Tet1S) encoding an N-terminally truncated TET1 protein and a full-length Tet1 (Tet1FL) transcript encoding canonical TET1 are co-expressed in the adult brain. We show that Tet1S is the predominantly expressed isoform, and is highly enriched in neurons, whereas Tet1FL is generally expressed at lower levels and more abundant in glia, suggesting their roles are at least partially cell-type specific. Using viral-mediated, isoform- and neuron-specific molecular tools, we find that Tet1S repression enhances, while Tet1FL impairs, hippocampal-dependent memory. In addition, the individual disruption of the two isoforms leads to contrasting changes in basal synaptic transmission and the dysregulation of unique gene ensembles in hippocampal neurons. Together, our findings demonstrate that each Tet1 isoform serves a distinct role in the mammalian brain. Copy rights belong to original authors. Visit the link for more info

Special guest mike joins us to talk about broken records, shitty SE, and the awesome random bullshit of Navy life with the 5MC boys. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/the5mc/support

The 2-oxoglutarate and Fe (II)-dependent ten-eleven translocation (TET) enzymes can oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxycytosine (5caC). Thus, it was hypothesized that this could be a pathway for active DNA demethylation. However, several studies have shown that 5hmC levels accumulate especially in neurons suggesting a role as an epigenetic mark. Nevertheless, the mechanism controlling TET activity and the role of 5hmC are poorly understood. In particular, it is not known how the neuronal TET3 isoform lacking a DNA binding domain is targeted to the DNA. In this study, the role of 5hmC during retinal maturation by genome-wide mapping of 5hmC in immature (postnatal week 2) and mature mouse retina (postnatal week 3) was studied and correlated with expression data. Furthermore, interaction partners of neu-ronal TET3, the main isoform in retinal neurons, were identified. 5hmC accumulates during retinal maturation especially in retinal and neuronal genes. Furthermore, the accumulation of 5hmC is associated with increased transcription. Among the identified proteins the transcriptional repressor REST was identified as a highly enriched TET3-specific interactor. Interestingly, REST was able to enhance TET3 hydroxylase activity. Furthermore, increased 5hmC levels were detected in REST target genes during retinal maturation and overexpression of TET3 activated transcription of REST-target genes. Moreover, NSD3 and two other histone methyltransferases were found to interact with TET3 that are able to mediate H3K36 trimethylation. Finally, it was shown that TET3 is able to enhance NSD3-mediated H3K36 trimethylation to pro-mote transcriptional activation. In conclusion, the data suggests that 5hmC is a stable epigenetic base in retinal neurons that is involved in transcriptional activation. Furthermore, it was shown that 5hmC is generated by TET3 that is recruited to the DNA by transcriptional regulators such as REST in a context-specific manner.

In the mammalian genome, cytosine methylation (5mC) plays a central role in the epigenetic regulation of gene expression and has been implicated in a variety of biological processes, including genome stability, imprinting or differentiation. Compared to other epigenetic marks, DNA methylation has been thought to be relatively stable. However, genome-wide loss of 5mC, or DNA demethylation, has been observed in specific developmental stages and in various types of cancer. The discovery of the TET family of enzymes in 2009 was a watershed moment in comprehending the mechanisms of DNA demethylation. TET proteins oxidize 5mC to 5- hydroxymethylcytosine (5hmC), 5-formlycytosine (5fC) and 5-carboxylcytosine (5caC), which not only serve as key intermediates in active DNA demethylation pathways, but can also act as independent epigenetic marks. In this study, various aspects of TET-mediated DNA demethylation have been intensively investigated. Using quantitative mass-spectrometry-based proteomics readers for the different cytosine derivatives in mouse embryonic stem cells (ESCs), neuronal progenitor cells, and adult mouse brain tissue were identified. Readers for these modifications are only partially overlapping and are dynamic during differentiation. Moreover, the oxidized derivatives of 5mC recruit distinct transcription regulators as well as a large number of DNA repair proteins, implicating DNA damage response as the main pathway contributing to active DNA demethylation. To identify additional non-canonical DNA bases, highly sensitive quantitative mass-spectrometry led to the discovery of 5-hydroxymethyluracil (5hmU) in ESCs. Genomic 5hmU is not generated via deamination of 5hmC, as widely suggested, but through direct oxidation of thymine by TET proteins. In addition, screening for specific 5hmU readers identified different transcriptional and epigenetic factors, implicating that this mark has a specific function in ESCs. So far, only little is known how TET enzymes are regulated and how they are modified by posttranslational modifications (PTMs). Mapping TET phosphorylation and glycosylation sites at amino acid resolution revealed that these PTMs are interdependent and mostly occur at regulatory protein regions. Finally, a reporter gene based assay could demonstrate that in vitro methylation causes gene silencing while subsequent oxidation, resulting in DNA demethylation, leads to gene reactivation in vivo. Different knockout and rescue experiments clearly show that oxidation of methylcytosine by TET proteins and subsequent removal by TDG or NEIL glycosylases and the base excision repair pathway results in reactivation of epigenetically silenced genes. In conclusion, this work provides new insights how TET proteins can set DNA modifications, how these oxidized bases are read by various factors and how TET proteins can be posttranslationally modified. Furthermore, removal of 5mC is achieved through TET-mediated oxidation and depends on the activity of specific glycosylases, which leads to gene reactivation.

The Discussion: Sirius Astronomy and The Knowledge Observatory’s educational outreach and preparation for our dark sky observing weekend in Wales: AstroCamp. The News: In the news we have the latest on the European Space Agency’s ambitious Rosetta spacecraft as it settles into it’s science program at Comet Churyumov Gerasimenko; details of the science payload for NASA’s ‘Curiosity 2’ Mars rover; revealing images of the Pluto system from the New Horizons spacecraft; China’s lunar orbit & spacecraft return mission and turbulent happenings on Uranus (sorry). The 5 Minute Concept: Distant radio sources that reveal unknown monsters from the past, unleashing hell from afar. In this month’s 5MC, Paul takes us billions of light years away from home to explain one of the brightest and most energetic objects in the universe. Quasars. The Interview: This month we return to the most exciting current space mission. In an attempt to understand the life of comets and unlock the secrets of the birth of the solar system, Ralph speaks to the European Space Agency’s Rosetta mission Project Scientist, Matt Taylor. Q&A: Listeners’ questions via email, Facebook & Twitter take us on a journey into the astronomy issues that have always plagued our understanding or stretched our credulity. This month Ralph & Paul answer: Why does Venus rotate retrograde? Dave Bood from Scarborough, UK & Beatriz Caicedo, Guatemala . With the idea that all that is the universe originated in a speck with the big bang, and that the universe is expanding, how is it that things such as galaxies collide? Kurt Green, Chicago Illinois via email. How much would my 20 stone (280lbs) wife weigh on each of the planets in the solar system? Darren Knight .

The Discussion: Enjoying the delights of July’s skies, writing articles for Astronomy magazine, STEM education and Paul becomes a European Space Agency ambassador. The News: In the news we have the Rosetta spacecraft’s approach to the almost unpronounceable comet Churyumov Gerasimenko – revealed to be a binary comet, and the Very Large Telscope in Chile takes a 2.5 year study of a supernova to crack the riddle of how dust is created and survives the extreme temperatures of its birth. The 5 Minute Concept: In this month’s 5MC, Paul looks at the summer phenomenon of noctilucent clouds and asks ‘why is there no record of them before 1885’? The Interview: We welcome back the General Secretary of the International Astronomical Union, Professor Thierry Montmerle to tells us about the International Year of Light, the IAU’s new look communications strategy and their new project to allow the public to name exoplanets and their host stars. Q&A: Listeners’ questions via email, Facebook & Twitter take us on a journey into the astronomy issues that have always plagued our understanding or stretched our credulity. This month Ralph & Paul answer: Oolaaa Martian overlords. Where in your opinions does the solar system truly end. Thanks, your faithful servant Lee? Lee Garner from Norwich, UK. What’s a Vampire Star? @TweetsByLou via Twitter And we finish with the winners of last month’s competition to win three DVD copies of the new film Gagarin – First in Space, and a copy of the book Yuri Gagarin – The First Spaceman.

Happy New Year! The sky guide has Jupiter at its very best, Venus, Saturn & Mars on offer along with the deep sky objects in Orion and Canis Major. The news has a Comet ISON saga round-up, China's Chang'e-3 moon lander, Jupiter's moon Europa spewing water into space & new exoplanet updates. In the 5MC, Paul explains the mystery and awe of Pulsating Stars - Pulsars. Ralph interviews astrophysicist & The Sky at Night host, Dr Chris Lintott. And the Q&A has questions on Martian meteor showers and the difference between open and globular clusters.

We have the planets, meteors showers and moon phases to look out for in December and a look at the deep sky objects in the constellations, Taurus & Gemini. In the news we have Comet ISON at perihelion, a guide to comets, the Indian Mars Orbiter Mission and NASA’s MAVEN both setting sail for Mars and a bizarre asteroid that thinks it’s a comet. In the 5MC, Paul explains the mysterious and awe-inspiring majesty of a familiar object in the night sky – The Orion Nebula. Perfect to listen to as you observe it! We open up our Christmas competition to win a year’s subscription to Astronomy Now magazine and the European Southern Observatory’s 2014 calendar. We have two interviews this month – Dr Gareth Williams, who officially calculated Comet ISON’s trajectory, tells us all about the comet; and Dr Gerhard Schwehm, ESA Project Scientist on the Giotto and Rosetta comet-chasing spacecraft missions. Finally, we answer listeners’ questions about the evidence for ancient alien visitors and the visibility of merging inactive black holes.

This month we have the planets, meteor showers and moon phases to look out for in November and a look at the deep sky objects in the Cetus, Pisces & Sculptor constellations. In the news we have the sad death of Scott Carpenter, the US government shutdown, water in Martian rocks, the completion of ESO’s ALMA  array & ESA's upcoming GAIA mission. In the 5MC, Paul reveals all we know about dark energy: a cosmological constant, a qualtum vacuum energy or quintessence (you decide). We interview Pauline Gagnon from CERN about the Higgs and how we find dark matter, supersymmetry and extra dimensions; and we round off with listeners' questions on rogue planets, the Earth's gravity & observing.

DNA methylation plays a crucial role in the epigenetic control of gene expression during mammalian development and differentiation. Whereas the de novo DNA methyltransferases (Dnmts), Dnmt3a and Dnmt3b, establish DNA methylation patterns during development; Dnmt1 stably maintains DNA methylation patterns during replication. DNA methylation patterns change dynamically during development and lineage specification, yet very little is known about how DNA methylation affects gene expression profiles upon differentiation. Therefore, we determined genome-wide expression profiles during differentiation of severely hypomethylated embryonic stem cells (ESCs) lacking either the maintenance enzyme Dnmt1 (dnmt1-/- ESCs) or all three major Dnmts (dnmt1-/-; dnmt3a-/-, dnmt3b-/- or TKO ESCs), resulting in complete loss of DNA methylation, and assayed their potential to transit in and out of the ESC state. Our results clearly demonstrate that upon initial differentiation to embryoid bodies (EBs), wild type, dnmt1-/- and TKO cells are able to activate differentiation processes. However, transcription profiles of dnmt1-/- and TKO EBs progressively diverge with prolonged EB culture, with dnmt1-/- EBs being more similar to wild type EBs, indicating a higher differentiation potential of dnmt1-/- EBs compared to TKO EBs. Remarkably though, after dissociation of late EBs and further cultivation under pluripotency promoting conditions, both dnmt1-/- and TKO but not wild type cells rapidly revert to expression profiles typical of undifferentiated ESCs. Thus, while DNA methylation is dispensable for the initial activation of differentiation programs, it seems to be crucial for permanently restricting the developmental fate during differentiation. Based on the essential role of Uhrf1 in maintenance DNA methylation, we investigated the structurally highly similar second member of the Uhrf protein family, Uhrf2, whose function in maintenance methylation or other biological processes is completely unknown. Expression analysis of uhrf1 and uhrf2 in various cell lines and tissues revealed a time- and developmental switch in transcript levels of both genes with uhrf1 being highly expressed in undifferentiated, proliferating cells and uhrf2 being predominately expressed in differentiated, non-dividing cells. These opposite expression patterns together with no detectable effect on DNA methylation levels upon knock down of uhrf2 suggests that Uhrf2 is rather involved in maintaining DNA methylation patterns in differentiated cells and points to non-redundant functions of both proteins. The discovery of the “6th base” of the genome, 5-hydroxymethylcytosine (5hmC), resulting from the oxidation of 5mC by the family of Tet dioxygenases (Tet1-3), once again ignited the debate about how DNA methylation marks can be modified and removed. To gain insights into the biological function of this newly identified modification, we developed a sensitive enzymatic assay for quantification of global 5hmC levels in genomic DNA. Similar to 5mC levels, we found that also 5hmC levels dynamically change during differentiation of ESCs to EBs, which correlates with the differential expression of tet1-3. Furthermore, we characterized a novel endonuclease, PvuRts1I that selectively cleaves 5hmC containing DNA and show first data on its application as a tool to map and analyze 5hmC patterns in mammalian genomes. Finally, we investigated designer transcription activator-like effector (dTALEs) proteins targeting the oct4 locus. Our results show that the epigenetic state of the target locus interferes with the ability of dTALEs to activate transcriptionally silent genes, which however can be overcome using dTALEs in combination with low doses of epigenetic inhibitors. In conclusion, this work gives further insights into the biological roles of methylation mark writers (Dnmts), readers (Uhrfs) and modifiers (Tets) and advances our understanding on the function of DNA methylation in the epigenetic control of gene expression during development and cellular differentiation.