text: Digital Rights and Respecting OpinionsDexomega1/11/14 8:00amFiled to: RantSteamDigital RightsTAYClassicDex's Corner715EditPromoteShare to KinjaGo to permalink What's bringing this on? In short, a certain discussion in an innocuous article yesterday. I quickly saw a basic opinion dog-piled by a bunch of people with some really strange arguments. Even worse, I saw him essentially getting called a Luddite. This is ridiculous and you all know it. Advertisement Want me to be honest? He's not wrong about digital rights. Not by a long shot.Now that 60% of you have gone to the comments to talk about how I hate gaming and the glorious paradise of fuzzily-defined digital ownership, I can talk to the rest of you critically. Advertisement I love Steam and online retailers. I love them to death. I get games cheap, play them where I want, and I can have more games than ever. The problem is that we've descended into a cycle of ignorance surrounding how little we legally own these binary bits. While retailers might say that we will get to keep our games when they go out of business, their legal documents tell a very different and vague story.Does this make me right? No, it doesn't. I'm not going to be so arrogant as to think I'm the only right one here. We'll get to that.I have three basic points to make here: my view on digital rights, how we are doing this to help you, and how respect should be applied to these discussions.Digital Rights: Are We Being Too Soft?As gamers, it seems like we've lost our interest firmly establishing our right to own what we do. The discussion started when the OP posted his wish to have tangible product in the form of physical media, he was instantly ridiculed for it. Since when did owning something earn you the right to be ridiculed? Advertisement Sponsored I don't see this in the movie industry, the music industry, or in the book industry. This epidemic of licensing is heavily favoring video games and everyone seems to just accepted this as reality. I can rip my DVDs, download my iTunes music as MP3s, and even get some of my e-books in their raw data format, so why the hell is it such a sin to be interested in the same in the gaming industry? There are some companies like GOG are taking this one to heart and I love them for it. They'll give us DRM-free titles that I can back up free and clear with no legal repercussions and I respect them greatly for doing so. I get games with them at every chance so I can support this line of thinking. Advertisement There are those in the audience right now that are about to point out that you can back up your games from Steam. Well... no you really can't. You can back up the raw data for the game, but you don't own it... not by a long shot. I'll turn to the Steam Subscriber Agreement, that we've all said yes to, to explain this.2. LICENSESA. General Software LicenseSteam and your Subscription(s) require the automatic download and installation of Software onto your computer. Valve hereby grants, and you accept, a limited, terminable, non-exclusive license and right to use the Software for your personal, non-commercial use (except where commercial use is expressly allowed herein or in the applicable Subscription Terms) in accordance with this Agreement, including the Subscription Terms. The Software is licensed, not sold. Your license confers no title or ownership in the Software. To make use of the Software, you must have a Steam Account and you may be required to be running the Steam client and maintaining a connection to the Internet.For reasons that include, without limitation, system security, stability, and multiplayer interoperability, Steam may need to automatically update, pre-load, create new versions of or otherwise enhance the Software and accordingly, the system requirements to use the Software may change over time. You consent to such automatic updating. You understand that this Agreement (including applicable Subscription Terms) does not entitle you to future updates, new versions or other enhancements of the Software associated with a particular Subscription, although Valve may choose to provide such updates, etc. in its sole discretion.This section explicitly gives Valve the ability to deny users further updates to the games they own. Okay, I'm fine with that. Well, except for that one part about "Valve hereby grants, and you accept, a limited, terminable, non-exclusive license" and that part about "no title or ownership", but I can deal with that if I know how it gets terminated.F. Ownership of SoftwareAll title, ownership rights and intellectual property rights in and to the Software and any and all copies thereof, are owned by Valve US and/or its or its affiliates' licensors. All rights are reserved, except as expressly stated herein. The Software is protected by copyright laws, international copyright treaties and conventions and other laws. The Software contains certain licensed materials and Valve's and its affiliates' licensors may protect their rights in the event of any violation of this Agreement.Oh, my games are solely owned by Valve US. We have no rights to the data at all. Huh, well okay... that's fine I guess. Advertisement B. LIMITATION OF LIABILITYTO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, NEITHER VALVE, ITS LICENSORS, NOR ITS OR THEIR AFFILIATES, NOR ANY OF VALVE'S SERVICE PROVIDERS, SHALL BE LIABLE IN ANY WAY FOR LOSS OR DAMAGE OF ANY KIND RESULTING FROM THE USE OR INABILITY TO USE STEAM, YOUR ACCOUNT, YOUR SUBSCRIPTIONS AND THE SOFTWARE INCLUDING, BUT NOT LIMITED TO, LOSS OF GOODWILL, WORK STOPPAGE, COMPUTER FAILURE OR MALFUNCTION, OR ANY AND ALL OTHER COMMERCIAL DAMAGES OR LOSSES. IN NO EVENT WILL VALVE BE LIABLE FOR ANY INDIRECT, INCIDENTAL, CONSEQUENTIAL, SPECIAL, PUNITIVE OR EXEMPLARY DAMAGES, OR ANY OTHER DAMAGES ARISING OUT OF OR IN ANY WAY CONNECTED WITH STEAM, THE SOFTWARE, THE SUBSCRIPTIONS, AND ANY INFORMATION AVAILABLE IN CONNECTION THEREWITH, OR THE DELAY OR INABILITY TO USE THE SOFTWARE, SUBSCRIPTIONS OR ANY INFORMATION, EVEN IN THE EVENT OF VALVE'S OR ITS AFFILIATES' FAULT, TORT (INCLUDING NEGLIGENCE), STRICT LIABILITY, BREACH OF CONTRACT, OR BREACH OF VALVE'S WARRANTY AND EVEN IF VALVE HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES. THESE LIMITATIONS AND EXCLUSIONS REGARDING DAMAGES APPLY EVEN IF ANY REMEDY FAILS TO PROVIDE ADEQUATE RECOMPENSE.[...]C. NO GUARANTEESNEITHER VALVE NOR ITS AFFILIATES GUARANTEE CONTINUOUS, ERROR-FREE, VIRUS-FREE OR SECURE OPERATION AND ACCESS TO STEAM, THE SOFTWARE, YOUR ACCOUNT AND/OR YOUR SUBSCRIPTIONS(S) OR ANY INFORMATION AVAILABLE IN CONNECTION THEREWITH.Hmm, okay. They've also explicitly destroyed your right to take them to court over any loss of ability to use your account/games. They then followed it up by clarifying that they won't guarantee us access to our software "continuously", which essentially means that they don't guarantee said right at all. They then follow these two wham lines up with a bit of vagueness: Advertisement C. Termination by ValveValve may cancel your Account or any particular Subscription(s) at any time in the event that (a) Valve ceases providing such Subscriptions to similarly situated Subscribers generally, or (b) you breach any terms of this Agreement (including any Subscription Terms or Rules of Use). In the event that your Account or a particular Subscription is terminated or cancelled by Valve for a violation of this Agreement or improper or illegal activity, no refund, including of any Subscription fees or of any unused funds in your Steam Wallet, will be granted.That was... rather vague. I'm no lawyer, but case A seems pretty weird. I can see you using that in several situations where you shouldn't if you're good enough at your job. Advertisement The core of the problem here though is that Valve has firmly established that they own this data, not you. Any attempt to use the raw data without Steam's authentication automatically means you're breaking this agreement. Essentially, if Steam shuts down and you crack open the games after it does, the legal holding company for what remains of Valve can slap you and your contemporaries with a breach of agreement lawsuit. Unlikely? Yes. Possible? Definitely.That's the problem. The poor definitions of our digital rights are requiring us to bank off the goodwill of companies rather than have clearly defined boundaries. It's setting a really stupid legal precedent that people aren't talking about enough.We Aren't Doing This For Ourselves:The OP was asked why he was doing this several times. Things along the lines of "you won't be around when this is actually a problem". GIF ...What? Advertisement Advertisement I'm not sitting here writing this because I want to defend anyone or to attack Valve and online retailers, I'm doing this for you.I know, it's a weird concept. Look guys, I'm here on this rant to defend you. If there is ever an online service that shuts down and locks out its users, I don't want to have been another person who gleefully stuck my head in the sand and pretended like it wouldn't happen... I want to have been the guy that went down in history as a stupid Luddite that tried to defend those people's right to their games.Everyone deserves a right to what they've paid for in some capacity and I want to advocate that position until the very end.Respect (Because I Apparently Need to Talk About This):Come on guys. This is just sad. The discussion OP came in with at least a decent opinion and then everyone made him out to be the bad guy. There are always many opinions on a situation and this entire discussion was a bunch of malformed arguments and terrible insults. It was really a sight that I hate to see in a community that should be acting like... a community. I feel stupid for having to even include a section like this but it somehow became necessary. Just because you have an opinion doesn't make you right. There was a distinct air of arrogance coming from several parties in this discussion on the whole. The OP didn't start off by saying that your way was terrible or by explicitly calling out Steam users for being sheep or something, and yet many felt the need to get on-board the flame train and proceeded to do it to him. Advertisement He was called backwards, basically a Luddite by some, and his opinion was generally mocked and met with ridiculous commentary. Many people made reference to promises by Valve to give us our games despite there being distinct legal ammunition to not have to do so. Even more made reference to how this is just how the all-digital age is supposed to be. GIF ...What? Advertisement Nothing is ever set in stone like that, especially in this evolving world. The discussion OP and I share a common interest in trying to change the way people look at digital ownership and apparently that's enough to get us ridiculed. The OP and I have different approaches to the problem, but it doesn't make either of us wrong. You aren't wrong either.The truth is that there is no real way to tell what the "right" future is. The all-digital world could very well be a license world, I don't know. Until that happens though, I'll keep pulling for our rights to our content. Advertisement In short, don't act arrogant in when you enter a discussion. When you see an opinion like this, approach it as objectively as you can and try to see their side. Nothing is inherently "incorrect" in this world. Working against the norms doesn't make you "wrong".I thought we learned about this in preschool, I really did. Be kind and respectful. I didn't see much of that at all in this discussion.Conclusion:The discussion OP might have come on pretty strong there, but he isn't wrong by any means. There is some really weird legal vagueness going on here and gamers somehow became fine with this. It's even gotten so bad that people attack others for merely trying to hold onto physical media, the simplest way to establish ownership. Advertisement We should be demanding that companies actually define these things in their legal documents instead of just counting on things to work out. This is a strange world and ambiguity is likely to lead us to strange places. Dismissing people for not getting on the all-digital bandwagon before we've gotten this point across is ridiculous. I'd much rather enter an all-digital market after we've managed to define these fuzzy legal boundaries.Counting on companies to just give you things is presumptuous on your part. The Steam Subscriber Agreement is a legally binding document that you should be taking seriously, anything less is insulting to all parties. Take this seriously or the companies won't take you seriously. Advertisement Be proactive, not reactive. Be knowledgeable, not ignorant. Most of all, don't be disrespectful to your fellow commenters, everyone loses in that situation.The discussion in question, now that you should know what not to do. This article was made in response to my increasing displeasure with the "Hakuna matata!" attitude of the video gaming community with respect to all-digital rights. More importantly, it is also addressing the air of disrespect that many seem to have for opinions. Be kind, respectful, and approach the discussion with objectivity. Advertisement I'd like to apologize to my Anime Marathon viewers for using the time I had allotted to write my next review to instead be allocated to this. I'll get it out soon.You can see all my articles on Dex's Corner.Reply7 repliesLeave a reply


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Once the cheering, perhaps as much a matter of relief for at last having the beginnings of a real agreement as anything else, dies down, a process of years-long pressuring, prodding, chivvying, and inspiring will take place. Or, perhaps better put, it had damn well better take place if this planet is going to remain habitable for humanity.
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by Daniel Potaczek in EpiBeat
Epigenetic regulation is thought to be one of the most important mechanisms contributing to the development and clinical course of chronic immunological diseases like allergies and asthma. DNA methylation has been extensively studied in this context, which has not been a case of histone modifications such as histone acetylation or methylation.
Early epigenetic studies from our lab conducted in mouse models demonstrated a role for histone acetylation in mediating bacteria-induced protection ag........ Read more »
Harb H, Alashkar Alhamwe B, Garn H, Renz H, & Potaczek DP. (2016) Recent developments in epigenetics of pediatric asthma. Current opinion in pediatrics, 28(6), 754-763. PMID: 27662207
Harb, H., Amarasekera, M., Ashley, S., Tulic, M., Pfefferle, P., Potaczek, D., Martino, D., Kesper, D., Prescott, S., & Renz, H. (2016) Epigenetic Regulation in Early Childhood: A Miniaturized and Validated Method to Assess Histone Acetylation. International Archives of Allergy and Immunology, 168(3), 173-181. DOI: 10.1159/000442158
Harb, H., Raedler, D., Ballenberger, N., Böck, A., Kesper, D., Renz, H., & Schaub, B. (2015) Childhood allergic asthma is associated with increased IL-13 and FOXP3 histone acetylation. Journal of Allergy and Clinical Immunology, 136(1), 200-202. DOI: 10.1016/j.jaci.2015.01.027
Stefanowicz, D., Lee, J., Lee, K., Shaheen, F., Koo, H., Booth, S., Knight, D., & Hackett, T. (2015) Elevated H3K18 acetylation in airway epithelial cells of asthmatic subjects. Respiratory Research, 16(1). DOI: 10.1186/s12931-015-0254-y
Harb, H., & Renz, H. (2015) Update on epigenetics in allergic disease. Journal of Allergy and Clinical Immunology, 135(1), 15-24. DOI: 10.1016/j.jaci.2014.11.009
by Tina Bianco-Miotto in EpiBeat
The placenta is a unique organ as it is an extra-embryonic tissue primarily regulated by the fetal genome and shared between mother and fetus. However, it is a transient organ that is only needed throughout pregnancy and gestation and then is discarded after delivery. The essential role of the placenta in pregnancy is unquestionable but, surprisingly, as highlighted by the NIH NICHD Human Placenta Project (https://www.nichd.nih.gov/research/HPP/Pages/default.aspx), it is the human organ we know ........ Read more »
Mayne BT, Leemaqz SY, Smith AK, Breen J, Roberts CT, & Bianco-Miotto T. (2016) Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation. Epigenomics. PMID: 27894195
Bianco-Miotto T, Mayne BT, Buckberry S, Breen J, Rodriguez Lopez CM, & Roberts CT. (2016) Recent progress towards understanding the role of DNA methylation in human placental development. Reproduction (Cambridge, England), 152(1). PMID: 27026712
Ehrlich M, Gama-Sosa MA, Huang LH, Midgett RM, Kuo KC, McCune RA, & Gehrke C. (1982) Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic acids research, 10(8), 2709-21. PMID: 7079182
Fuke C, Shimabukuro M, Petronis A, Sugimoto J, Oda T, Miura K, Miyazaki T, Ogura C, Okazaki Y, & Jinno Y. (2004) Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Annals of human genetics, 68(Pt 3), 196-204. PMID: 15180700
Novakovic B, Yuen RK, Gordon L, Penaherrera MS, Sharkey A, Moffett A, Craig JM, Robinson WP, & Saffery R. (2011) Evidence for widespread changes in promoter methylation profile in human placenta in response to increasing gestational age and environmental/stochastic factors. BMC genomics, 529. PMID: 22032438
Price EM, Cotton AM, Peñaherrera MS, McFadden DE, Kobor MS, & Robinson W. (2012) Different measures of "genome-wide" DNA methylation exhibit unique properties in placental and somatic tissues. Epigenetics, 7(6), 652-63. PMID: 22531475
Schroeder DI, Blair JD, Lott P, Yu HO, Hong D, Crary F, Ashwood P, Walker C, Korf I, Robinson WP.... (2013) The human placenta methylome. Proceedings of the National Academy of Sciences of the United States of America, 110(15), 6037-42. PMID: 23530188
Robinson WP, & Price EM. (2015) The human placental methylome. Cold Spring Harbor perspectives in medicine, 5(5). PMID: 25722473
Fogarty NM, Burton GJ, & Ferguson-Smith AC. (2015) Different epigenetic states define syncytiotrophoblast and cytotrophoblast nuclei in the trophoblast of the human placenta. Placenta, 36(8), 796-802. PMID: 26008948
Marioni RE, Shah S, McRae AF, Chen BH, Colicino E, Harris SE, Gibson J, Henders AK, Redmond P, Cox SR.... (2015) DNA methylation age of blood predicts all-cause mortality in later life. Genome biology, 25. PMID: 25633388
by Barbara Banelli in EpiBeat
MicroRNAs (miRNAs) are non-coding RNAs, roughly 22 nucleotides in size that are central and negative regulators of gene expression. They exert their functions through base-pairing with the 3'UTR of mRNAs and block expression at the transcriptional and post-transcriptional levels, depending on the perfect or imperfect match in sequences between miRNAs and their target genes. miRNAs are central nodes in a variety of biological processes like cell proliferation, apoptosis, migration and dif........ Read more »
Parodi F, Carosio R, Ragusa M, Di Pietro C, Maugeri M, Barbagallo D, Sallustio F, Allemanni G, Pistillo MP, Casciano I.... (2016) Epigenetic dysregulation in neuroblastoma: A tale of miRNAs and DNA methylation. Biochimica et biophysica acta, 1859(12), 1502-1514. PMID: 27751904
by Tushar Tomar in EpiBeat
Ovarian cancer is the most lethal gynecologic malignancy. After epigenomic analysis of patient tumors, aberrant DNA methylation patterns are universally observed in the most abundant histological subtype of ovarian cancer, high-grade serous ovarian cancer (HGSOC). These epigenetic modifications like DNA methylation are known to frequently affect gene regulation involved in cancer-related processes. Since epigenetic alterations are reversible in nature, these changes have emerged as attractive ta........ Read more »
Tomar T, de Jong S, Alkema NG, Hoekman RL, Meersma GJ, Klip HG, van der Zee AG, & Wisman GB. (2016) Genome-wide methylation profiling of ovarian cancer patient-derived xenografts treated with the demethylating agent decitabine identifies novel epigenetically regulated genes and pathways. Genome medicine, 8(1), 107. PMID: 27765068
Alkema NG, Wisman GB, van der Zee AG, van Vugt MA, & de Jong S. (2016) Studying platinum sensitivity and resistance in high-grade serous ovarian cancer: Different models for different questions. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 55-69. PMID: 26830315
Hidalgo M, Amant F, Biankin AV, Budinská E, Byrne AT, Caldas C, Clarke RB, de Jong S, Jonkers J, Mælandsmo GM.... (2014) Patient-derived xenograft models: an emerging platform for translational cancer research. Cancer discovery, 4(9), 998-1013. PMID: 25185190
Alkema NG, Tomar T, Duiker EW, Jan Meersma G, Klip H, van der Zee AG, Wisman GB, & de Jong S. (2015) Biobanking of patient and patient-derived xenograft ovarian tumour tissue: efficient preservation with low and high fetal calf serum based methods. Scientific reports, 14495. PMID: 26440065
by Iris Oliva Rodriguez in EpiBeat
Apolipoprotein A5 gene (APOA5) is one of the genes implicated in contributing to a predisposition for hypertriacylglycerolaemia (HTG), a complex polygenic pathology that is highly influenced by environment. Hypertriacylglycerolaemia is characterized by having high circulating triacylglycerol levels and is a significant risk factor for cardiovascular disease and atherosclerosis. This genetic predisposition has an inherited component (based on polymorphisms) as well as an acquired component regu........ Read more »
Oliva, I., Guardiola, M., Vallve, J., Ibarretxe, D., Plana, N., Masana, L., Monk, D., & Ribalta, J. (2016) APOA5 genetic and epigenetic variability jointly regulate circulating triacylglycerol levels. Clinical Science, 130(22), 2053-2059. DOI: 10.1042/CS20160433
by Enrico Avvedimento in EpiBeat
DNA methylation is a biological clock that ticks with age, and numerous studies have been able to construct age-prediction models based on methylation status. However in somatic cells, DNA methylation is highly polymorphic – though this is not always appreciated in genome wide studies because coverage is often limited and variants below 10% usually escape detection. In an effort to clarify the origin of somatic DNA methylation heterogeneity and the impact it has on chromatin domains and ge........ Read more »
Russo, G., Landi, R., Pezone, A., Morano, A., Zuchegna, C., Romano, A., Muller, M., Gottesman, M., Porcellini, A., & Avvedimento, E. (2016) DNA damage and Repair Modify DNA methylation and Chromatin Domain of the Targeted Locus: Mechanism of allele methylation polymorphism. Scientific Reports, 33222. DOI: 10.1038/srep33222
Cuozzo, C., Porcellini, A., Angrisano, T., Morano, A., Lee, B., Pardo, A., Messina, S., Iuliano, R., Fusco, A., Santillo, M.... (2007) DNA Damage, Homology-Directed Repair, and DNA Methylation. PLoS Genetics, 3(7). DOI: 10.1371/journal.pgen.0030110
Morano, A., Angrisano, T., Russo, G., Landi, R., Pezone, A., Bartollino, S., Zuchegna, C., Babbio, F., Bonapace, I., Allen, B.... (2013) Targeted DNA methylation by homology-directed repair in mammalian cells. Transcription reshapes methylation on the repaired gene. Nucleic Acids Research, 42(2), 804-821. DOI: 10.1093/nar/gkt920
Landan, G., Cohen, N., Mukamel, Z., Bar, A., Molchadsky, A., Brosh, R., Horn-Saban, S., Zalcenstein, D., Goldfinger, N., Zundelevich, A.... (2012) Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues. Nature Genetics, 44(11), 1207-1214. DOI: 10.1038/ng.2442
by Lara Ianov in EpiBeat
Estradiol (E2) influences a number of processes that are important for maintaining healthy brain function, including memory. The ability of E2 to protect the brain and enhance or maintain memory function depends on the interaction of E2 with different estrogen receptors.1 In particular, the expression of estrogen receptor alpha (ERα) has been linked to synaptic plasticity, inflammation, and neuroprotection.2-5 Thus, it may be important that expression of ERα in the hippocampus, a bra........ Read more »
Ianov L, Kumar A, & Foster TC. (2016) Epigenetic regulation of estrogen receptor α contributes to age-related differences in transcription across the hippocampal regions CA1 and CA3. Neurobiology of aging, 79-85. PMID: 27776265
Bean LA, Ianov L, & Foster TC. (2014) Estrogen receptors, the hippocampus, and memory. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry, 20(5), 534-45. PMID: 24510074
Adams MM, Fink SE, Shah RA, Janssen WG, Hayashi S, Milner TA, McEwen BS, & Morrison JH. (2002) Estrogen and aging affect the subcellular distribution of estrogen receptor-alpha in the hippocampus of female rats. The Journal of neuroscience : the official journal of the Society for Neuroscience, 22(9), 3608-14. PMID: 11978836
Benedusi V, Meda C, Della Torre S, Monteleone G, Vegeto E, & Maggi A. (2012) A lack of ovarian function increases neuroinflammation in aged mice. Endocrinology, 153(6), 2777-88. PMID: 22492304
Merchenthaler I, Dellovade TL, & Shughrue PJ. (2003) Neuroprotection by estrogen in animal models of global and focal ischemia. Annals of the New York Academy of Sciences, 89-100. PMID: 14993043
Zhang QG, Raz L, Wang R, Han D, De Sevilla L, Yang F, Vadlamudi RK, & Brann DW. (2009) Estrogen attenuates ischemic oxidative damage via an estrogen receptor alpha-mediated inhibition of NADPH oxidase activation. The Journal of neuroscience : the official journal of the Society for Neuroscience, 29(44), 13823-36. PMID: 19889994
Bean LA, Kumar A, Rani A, Guidi M, Rosario AM, Cruz PE, Golde TE, & Foster TC. (2015) Re-Opening the Critical Window for Estrogen Therapy. The Journal of neuroscience : the official journal of the Society for Neuroscience, 35(49), 16077-93. PMID: 26658861
Zhang QG, Han D, Wang RM, Dong Y, Yang F, Vadlamudi RK, & Brann DW. (2011) C terminus of Hsc70-interacting protein (CHIP)-mediated degradation of hippocampal estrogen receptor-alpha and the critical period hypothesis of estrogen neuroprotection. Proceedings of the National Academy of Sciences of the United States of America, 108(35). PMID: 21808025
Han X, Aenlle KK, Bean LA, Rani A, Semple-Rowland SL, Kumar A, & Foster TC. (2013) Role of estrogen receptor α and β in preserving hippocampal function during aging. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33(6), 2671-83. PMID: 23392694
by David Schecter in EpiBeat
Cancer metastasis occurs when cancer cells leave a primary tumor and invade other tissues. Generally, this leads to a poor prognosis for patients. Underlying epigenetic mechanisms of tumor progression are poorly understood but are of great interest for developing new approaches of treatment in the clinic. Cancer etiology is highly correlated with alterations in the histone code1-5 and protein methyltransferases are frequently dysregulated in cancer, implicating them as compelling novel targets f........ Read more »
Chen H, Lorton B, Gupta V, & Shechter D. (2016) A TGFβ-PRMT5-MEP50 axis regulates cancer cell invasion through histone H3 and H4 arginine methylation coupled transcriptional activation and repression. Oncogene. PMID: 27270440
Chi P, Allis CD, & Wang GG. (2010) Covalent histone modifications--miswritten, misinterpreted and mis-erased in human cancers. Nature reviews. Cancer, 10(7), 457-69. PMID: 20574448
Sawan, Carla. (2010) Histone Modifications and Cancer. Adv Genet, 57-85. DOI: 10.1016/B978-0-12-380866-0.60003-4
Stopa N, Krebs JE, & Shechter D. (2015) The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond. Cellular and molecular life sciences : CMLS, 72(11), 2041-59. PMID: 25662273
Cha B, & Jho EH. (2012) Protein arginine methyltransferases (PRMTs) as therapeutic targets. Expert opinion on therapeutic targets, 16(7), 651-64. PMID: 22621686
Sebova K, & Fridrichova I. (2010) Epigenetic tools in potential anticancer therapy. Anti-cancer drugs, 21(6), 565-77. PMID: 20436342
Yang, Y., & Bedford, M. (2012) Protein arginine methyltransferases and cancer. Nature Reviews Cancer, 13(1), 37-50. DOI: 10.1038/nrc3409
Yang XJ, & Seto E. (2008) Lysine acetylation: codified crosstalk with other posttranslational modifications. Molecular cell, 31(4), 449-61. PMID: 18722172
Greenblatt SM, Liu F, & Nimer SD. (2016) Arginine methyltransferases in normal and malignant hematopoiesis. Experimental hematology, 44(6), 435-41. PMID: 27026282
Wilczek C, Chitta R, Woo E, Shabanowitz J, Chait BT, Hunt DF, & Shechter D. (2011) Protein arginine methyltransferase Prmt5-Mep50 methylates histones H2A and H4 and the histone chaperone nucleoplasmin in Xenopus laevis eggs. The Journal of biological chemistry, 286(49), 42221-31. PMID: 22009756
Ho MC, Wilczek C, Bonanno JB, Xing L, Seznec J, Matsui T, Carter LG, Onikubo T, Kumar PR, Chan MK.... (2013) Structure of the arginine methyltransferase PRMT5-MEP50 reveals a mechanism for substrate specificity. PloS one, 8(2). PMID: 23451136
Burgos ES, Wilczek C, Onikubo T, Bonanno JB, Jansong J, Reimer U, & Shechter D. (2015) Histone H2A and H4 N-terminal tails are positioned by the MEP50 WD repeat protein for efficient methylation by the PRMT5 arginine methyltransferase. The Journal of biological chemistry, 290(15), 9674-89. PMID: 25713080
Chan-Penebre E, Kuplast KG, Majer CR, Boriack-Sjodin PA, Wigle TJ, Johnston LD, Rioux N, Munchhof MJ, Jin L, Jacques SL.... (2015) A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nature chemical biology, 11(6), 432-7. PMID: 25915199
Liu F, Cheng G, Hamard PJ, Greenblatt S, Wang L, Man N, Perna F, Xu H, Tadi M, Luciani L.... (2015) Arginine methyltransferase PRMT5 is essential for sustaining normal adult hematopoiesis. The Journal of clinical investigation, 125(9), 3532-44. PMID: 26258414
Ikushima H, & Miyazono K. (2010) TGFbeta signalling: a complex web in cancer progression. Nature reviews. Cancer, 10(6), 415-24. PMID: 20495575
Lamouille, S., Xu, J., & Derynck, R. (2014) Molecular mechanisms of epithelial–mesenchymal transition. Nature Reviews Molecular Cell Biology, 15(3), 178-196. DOI: 10.1038/nrm3758
by Eliza Bacon in EpiBeat
DNA methylation and hydroxymethylation are well-established key players in gene regulation. Although many would agree that 5hmC also plays a critical role, there is still some debate over whether it serves a functional role, or is merely an artifact of DNA de-methylation. Even still, other intermediates of de-methylation are actively being investigated. In a recent paper by Iuilaro et al. 2016, a group of scientists argue that 5-formlycytosine (5fC), an intermediate of DNA de-methylation, is a s........ Read more »
Iurlaro M, McInroy GR, Burgess HE, Dean W, Raiber EA, Bachman M, Beraldi D, Balasubramanian S, & Reik W. (2016) In vivo genome-wide profiling reveals a tissue-specific role for 5-formylcytosine. Genome biology, 17(1), 141. PMID: 27356509
by Blair McCallie in EpiBeat
Aneuploidy is the leading cause of miscarriage, stillbirth, and congenital birth defects and occurs as a result of errors during meiotic or mitotic cell division.1 As a woman ages, the probability of an aneuploid conception significantly rises, to roughly 50% by the age of 40.2 Only a fraction of full aneuploidies, primarily trisomies, will develop past the first trimester. This is in contrast to monosomies that almost never implant or result in an ongoing pregnancy. DNA methylation is an epi........ Read more »
McCallie BR, Parks JC, Patton AL, Griffin DK, Schoolcraft WB, & Katz-Jaffe MG. (2016) Hypomethylation and Genetic Instability in Monosomy Blastocysts May Contribute to Decreased Implantation Potential. PloS one, 11(7). PMID: 27434648
Hassold T, Hall H, & Hunt P. (2007) The origin of human aneuploidy: where we have been, where we are going. Human molecular genetics. PMID: 17911163
Grewal, S. (2003) Heterochromatin and Epigenetic Control of Gene Expression. Science, 301(5634), 798-802. DOI: 10.1126/science.1086887
Messerschmidt DM, Knowles BB, & Solter D. (2014) DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes , 28(8), 812-28. PMID: 24736841
Kahlem, P. (2004) Transcript Level Alterations Reflect Gene Dosage Effects Across Multiple Tissues in a Mouse Model of Down Syndrome. Genome Research, 14(7), 1258-1267. DOI: 10.1101/gr.1951304
by Louis Cicchini in EpiBeat
Human papillomaviruses (HPV) are a diverse group of small double-stranded DNA viruses with specific mucosal or cutaneous tropisms. It is estimated that up to 80% of sexually active individuals will become infected with HPV sometime in their lifetime, making HPV the most prevalent sexually transmitted infection. HPVs can be further divided into high- and low-risk genotypes, based on their oncogenic potential. High-risk HPVs are implicated as causal in nearly 100% of cervical cancers, approximatel........ Read more »
Cicchini L, Westrich JA, Xu T, Vermeer DW, Berger JN, Clambey ET, Lee D, Song JI, Lambert PF, Greer RO.... (2016) Suppression of Antitumor Immune Responses by Human Papillomavirus through Epigenetic Downregulation of CXCL14. mBio, 7(3). PMID: 27143385
Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A.... (2011) The mutational landscape of head and neck squamous cell carcinoma. Science (New York, N.Y.), 333(6046), 1157-60. PMID: 21798893
Anayannis NV, Schlecht NF, & Belbin TJ. (2015) Epigenetic Mechanisms of Human Papillomavirus-Associated Head and Neck Cancer. Archives of pathology , 139(11), 1373-8. PMID: 25978766
Cancer Genome Atlas Network. (2015) Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature, 517(7536), 576-82. PMID: 25631445
Burgers WA, Blanchon L, Pradhan S, de Launoit Y, Kouzarides T, & Fuks F. (2007) Viral oncoproteins target the DNA methyltransferases. Oncogene, 26(11), 1650-5. PMID: 16983344
Schlecht NF, Kulaga S, Robitaille J, Ferreira S, Santos M, Miyamura RA, Duarte-Franco E, Rohan TE, Ferenczy A, Villa LL.... (2001) Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA, 286(24), 3106-14. PMID: 11754676
A nucleosome is constituted by positively charged histone proteins and negatively charged DNA. Methylation as well as other covalent modifications on DNA and histones ( together also called epigenetic modifications or marks) play important roles in the regulation of chromatin structure and function. TET (Ten-Eleven Translocation) proteins were identified as 5mC oxidases which not only generate new 5mC oxidative derivates (5hmC, 5caC and 5fC) but also initiate active or passive DNA demethylation1........ Read more »
Kong L, Tan L, Lv R, Shi Z, Xiong L, Wu F, Rabidou K, Smith M, He C, Zhang L.... (2016) A primary role of TET proteins in establishment and maintenance of De Novo bivalency at CpG islands. Nucleic acids research. PMID: 27288448
Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L.... (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science (New York, N.Y.), 324(5929), 930-5. PMID: 19372391
He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L.... (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science (New York, N.Y.), 333(6047), 1303-7. PMID: 21817016
Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, & Zhang Y. (2011) Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science (New York, N.Y.), 333(6047), 1300-3. PMID: 21778364
Zhang, H., Zhang, X., Clark, E., Mulcahey, M., Huang, S., & Shi, Y. (2010) TET1 is a DNA-binding protein that modulates DNA methylation and gene transcription via hydroxylation of 5-methylcytosine. Cell Research, 20(12), 1390-1393. DOI: 10.1038/cr.2010.156
Ehrlich M. (2002) DNA methylation in cancer: too much, but also too little. Oncogene, 21(35), 5400-13. PMID: 12154403
Cedar H, & Bergman Y. (2009) Linking DNA methylation and histone modification: patterns and paradigms. Nature reviews. Genetics, 10(5), 295-304. PMID: 19308066
Easwaran H, Johnstone SE, Van Neste L, Ohm J, Mosbruger T, Wang Q, Aryee MJ, Joyce P, Ahuja N, Weisenberger D.... (2012) A DNA hypermethylation module for the stem/progenitor cell signature of cancer. Genome research, 22(5), 837-49. PMID: 22391556
Lian CG, Xu Y, Ceol C, Wu F, Larson A, Dresser K, Xu W, Tan L, Hu Y, Zhan Q.... (2012) Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell, 150(6), 1135-46. PMID: 22980977
Tan L, & Shi YG. (2012) Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development (Cambridge, England), 139(11), 1895-902. PMID: 22569552
by Aniruddha Chatterjee in EpiBeat
Phenotypic differences between males and females of a species are referred to as sexual dimorphism. Sexual dimorphism manifests not only in morphological traits, but also in physiological and behavioural traits. In organisms that do not have sex chromosomes, males and females are both derived from a nearly identical genome. Such is the case in zebrafish. Despite being such an important model for biological research, the mechanism of sex determination still remains a mystery. Many believe environ........ Read more »
Chatterjee, A., Lagisz, M., Rodger, E., Zhen, L., Stockwell, P., Duncan, E., Horsfield, J., Jeyakani, J., Mathavan, S., Ozaki, Y.... (2016) Sex differences in DNA methylation and expression in zebrafish brain: a test of an extended 'male sex drive' hypothesis. Gene. DOI: 10.1016/j.gene.2016.05.042
Connallon T, & Knowles LL. (2005) Intergenomic conflict revealed by patterns of sex-biased gene expression. Trends in genetics : TIG, 21(9), 495-9. PMID: 16039005
Ellegren, H., & Parsch, J. (2007) The evolution of sex-biased genes and sex-biased gene expression. Nature Reviews Genetics, 8(9), 689-698. DOI: 10.1038/nrg2167
Chatterjee A, Ozaki Y, Stockwell PA, Horsfield JA, Morison IM, & Nakagawa S. (2013) Mapping the zebrafish brain methylome using reduced representation bisulfite sequencing. Epigenetics, 8(9), 979-89. PMID: 23975027
Chatterjee A, Stockwell PA, Horsfield JA, Morison IM, & Nakagawa S. (2014) Base-resolution DNA methylation landscape of zebrafish brain and liver. Genomics data, 342-4. PMID: 26484126
Chatterjee A, Leichter AL, Fan V, Tsai P, Purcell RV, Sullivan MJ, & Eccles MR. (2015) Erratum: A cross comparison of technologies for the detection of microRNAs in clinical FFPE samples of hepatoblastoma patients. Scientific reports, 13505. PMID: 26328756
Gagnidze K, Weil ZM, & Pfaff DW. (2010) Histone modifications proposed to regulate sexual differentiation of brain and behavior. BioEssays : news and reviews in molecular, cellular and developmental biology, 32(11), 932-9. PMID: 20836091
by Gregg E. Homanics in EpiBeat
Mice born to alcohol exposed fathers were resistant to stress-induced drinking. Read more on today's EpiBeat!... Read more »
Rompala GR, Finegersh A, & Homanics GE. (2016) Paternal preconception ethanol exposure blunts hypothalamic-pituitary-adrenal axis responsivity and stress-induced excessive fluid intake in male mice. Alcohol (Fayetteville, N.Y.), 19-25. PMID: 27286933
Parkinson's disease (PD) is the second most frequent neurodegenerative disease, affecting 1-2% of the population over 55 years of age. The main pathological feature of PD is the progressive death of neurons located in the midbrain that produce the neurotransmitter dopamine. These neurons modulate the activity of a collection of ...
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Södersten E, Feyder M, Lerdrup M, Gomes AL, Kryh H, Spigolon G, Caboche J, Fisone G, & Hansen K. (2014) Dopamine signaling leads to loss of polycomb repression and aberrant gene activation in experimental parkinsonism. PLoS genetics, 10(9). PMID: 25254549
Birkmayer W, & Hornykiewicz O. (1998) The effect of l-3,4-dihydroxyphenylalanine (. Parkinsonism , 4(2), 59-60. PMID: 18591089
Obeso, J., Olanow, C., & Nutt, J. (2000) Levodopa motor complications in Parkinson's disease. Trends in Neurosciences. DOI: 10.1016/S1471-1931(00)00031-8
Feyder M, Bonito-Oliva A, & Fisone G. (2011) L-DOPA-Induced Dyskinesia and Abnormal Signaling in Striatal Medium Spiny Neurons: Focus on Dopamine D1 Receptor-Mediated Transmission. Frontiers in behavioral neuroscience, 71. PMID: 22028687
Greengard, P. (2001) The Neurobiology of Slow Synaptic Transmission. Science, 294(5544), 1024-1030. DOI: 10.1126/science.294.5544.1024
Feyder M, Södersten E, Santini E, Vialou V, LaPlant Q, Watts EL, Spigolon G, Hansen K, Caboche J, Nestler EJ.... (2014) A Role for Mitogen- and Stress-Activated Kinase 1 in L-DOPA-Induced Dyskinesia and ∆FosB Expression. Biological psychiatry. PMID: 25193242
Santini E, Valjent E, Usiello A, Carta M, Borgkvist A, Girault JA, Hervé D, Greengard P, & Fisone G. (2007) Critical involvement of cAMP/DARPP-32 and extracellular signal-regulated protein kinase signaling in L-DOPA-induced dyskinesia. The Journal of neuroscience : the official journal of the Society for Neuroscience, 27(26), 6995-7005. PMID: 17596448
Di Croce, L., & Helin, K. (2013) Transcriptional regulation by Polycomb group proteins. Nature Structural , 20(10), 1147-1155. DOI: 10.1038/nsmb.2669
Gehani SS, Agrawal-Singh S, Dietrich N, Christophersen NS, Helin K, & Hansen K. (2010) Polycomb group protein displacement and gene activation through MSK-dependent H3K27me3S28 phosphorylation. Molecular cell, 39(6), 886-900. PMID: 20864036
Epigenetics refers to changes in gene regulation that are do not related to changes in the primary sequence of DNA. It can be reversible and heritable throughout cell division, and its regulation is characterized by several modifications, such as DNA methylation and post-translational changes in the histone proteins. In addition, ...
The post Imprinting, epigenetic markers and assisted reproductive technologies (ARTs) appeared first on EpiBeat.
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Franco MM, Prickett AR, & Oakey RJ. (2014) The Role of CCCTC-Binding Factor (CTCF) in Genomic Imprinting, Development, and Reproduction. Biology of reproduction. PMID: 25297545
Franco MM, Fagundes NS, Michalczechen-Lacerda VA, Caixeta ES, de Castro Rodrigues F, Machado GM, Ferreira AR, & Dode MA. (2014) Characterisation of the methylation pattern in the intragenic CpG island of the IGF2 gene in Bos taurus indicus cumulus cells during in vitro maturation. Journal of assisted reproduction and genetics, 31(1), 115-20. PMID: 24174298
Carvalho JO, Michalczechen-Lacerda VA, Sartori R, Rodrigues FC, Bravim O, Franco MM, & Dode MA. (2012) The methylation patterns of the IGF2 and IGF2R genes in bovine spermatozoa are not affected by flow-cytometric sex sorting. Molecular reproduction and development, 79(2), 77-84. PMID: 22128039
Fagundes NS, Michalczechen-Lacerda VA, Caixeta ES, Machado GM, Rodrigues FC, Melo EO, Dode MA, & Franco MM. (2011) Methylation status in the intragenic differentially methylated region of the IGF2 locus in Bos taurus indicus oocytes with different developmental competencies. Molecular human reproduction, 17(2), 85-91. PMID: 20833870
Aberrant epigenetic status resulting in dysregulation of gene expression is a hallmark of many cancers and other diseases. In the last decade, countless time and energy has been spent in efforts to develop drugs targeting DNA methylation and histone modifications. To date however, none of these epigenetic drugs are sequence ...
The post Artificial Transcription Factors – A new class of epigenetic drug appeared first on EpiBeat.
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Grimmer MR, Stolzenburg S, Ford E, Lister R, Blancafort P, & Farnham PJ. (2014) Analysis of an artificial zinc finger epigenetic modulator: widespread binding but limited regulation. Nucleic acids research, 42(16), 10856-68. PMID: 25122745
More than 35% of the U.S. population is considered clinically obese (body mass index of > 30), while 68% of the U.S. is considered overweight (body mass index of > 25) 1. Obesity is known to have adverse health effects, impacting the risk and prognosis for a number of diseases, ...
The post Obesogens: The epigenetic interaction between nature and nurture on risk of obesity appeared first on EpiBeat.
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Ogden CL, Carroll MD, Kit BK, & Flegal KM. (2014) Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA, 311(8), 806-14. PMID: 24570244
Hu FB. (2011) Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes care, 34(6), 1249-57. PMID: 21617109
McCormick DP, Sarpong K, Jordan L, Ray LA, & Jain S. (2010) Infant obesity: are we ready to make this diagnosis?. The Journal of pediatrics, 157(1), 15-9. PMID: 20338575
Klimentidis, Y., Beasley, T., Lin, H., Murati, G., Glass, G., Guyton, M., Newton, W., Jorgensen, M., Heymsfield, S., Kemnitz, J.... (2010) Canaries in the coal mine: a cross-species analysis of the plurality of obesity epidemics. Proceedings of the Royal Society B: Biological Sciences, 278(1712), 1626-1632. DOI: 10.1098/rspb.2010.1890
Milagro FI, Mansego ML, De Miguel C, & Martínez JA. (2013) Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives. Molecular aspects of medicine, 34(4), 782-812. PMID: 22771541
Prior LJ, & Armitage JA. (2009) Neonatal overfeeding leads to developmental programming of adult obesity: you are what you ate. The Journal of physiology, 587(Pt 11), 2419. PMID: 19483248
Grün F, & Blumberg B. (2007) Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis. Reviews in endocrine , 8(2), 161-71. PMID: 17657605
Grün F, & Blumberg B. (2006) Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology, 147(6 Suppl). PMID: 16690801
Grün F, & Blumberg B. (2009) Minireview: the case for obesogens. Molecular endocrinology (Baltimore, Md.), 23(8), 1127-34. PMID: 19372238
Janesick A, & Blumberg B. (2011) Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity. Birth defects research. Part C, Embryo today : reviews, 93(1), 34-50. PMID: 21425440
Snedeker SM, & Hay AG. (2012) Do interactions between gut ecology and environmental chemicals contribute to obesity and diabetes?. Environmental health perspectives, 120(3), 332-9. PMID: 22042266
Somm E, Schwitzgebel VM, Toulotte A, Cederroth CR, Combescure C, Nef S, Aubert ML, & Hüppi PS. (2009) Perinatal exposure to bisphenol a alters early adipogenesis in the rat. Environmental health perspectives, 117(10), 1549-55. PMID: 20019905
Chamorro-García R, Sahu M, Abbey RJ, Laude J, Pham N, & Blumberg B. (2013) Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal exposure to the obesogen tributyltin in mice. Environmental health perspectives, 121(3), 359-66. PMID: 23322813
Manikkam M, Tracey R, Guerrero-Bosagna C, & Skinner MK. (2013) Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PloS one, 8(1). PMID: 23359474
Grün F, Watanabe H, Zamanian Z, Maeda L, Arima K, Cubacha R, Gardiner DM, Kanno J, Iguchi T, & Blumberg B. (2006) Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates. Molecular endocrinology (Baltimore, Md.), 20(9), 2141-55. PMID: 16613991
Skinner MK, Manikkam M, Tracey R, Guerrero-Bosagna C, Haque M, & Nilsson EE. (2013) Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity. BMC medicine, 228. PMID: 24228800
Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, Rodford J, Slater-Jefferies JL, Garratt E, Crozier SR.... (2011) Epigenetic gene promoter methylation at birth is associated with child's later adiposity. Diabetes, 60(5), 1528-34. PMID: 21471513
Herskind AM, McGue M, Iachine IA, Holm N, Sørensen TI, Harvald B, & Vaupel JW. (1996) Untangling genetic influences on smoking, body mass index and longevity: a multivariate study of 2464 Danish twins followed for 28 years. Human genetics, 98(4), 467-75. PMID: 8792824
Schuster-Böckler, B., & Lehner, B. (2012) Chromatin organization is a major influence on regional mutation rates in human cancer cells. Nature, 488(7412), 504-507. DOI: 10.1038/nature11273
Atherosclerosis is an inflammatory disease of the arterial walls, and is the major cause of heart attack and stroke. Atherosclerosis is localized to curves and branches in the vasculature where disturbed blood flow (d-flow) is able to alter gene expression and induce endothelial cell (EC) dysfunction. Our lab's work focuses on the mechanism by which ...
The post Endothelial DNA Methylation Goes With the Flow appeared first on EpiBeat.
... Read more »
Dunn J, Qiu H, Kim S, Jjingo D, Hoffman R, Kim CW, Jang I, Son DJ, Kim D, Pan C.... (2014) Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis. The Journal of clinical investigation. PMID: 24865430
Nam D, Ni CW, Rezvan A, Suo J, Budzyn K, Llanos A, Harrison D, Giddens D, & Jo H. (2009) Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis. American journal of physiology. Heart and circulatory physiology, 297(4). PMID: 19684185
Ni CW, Qiu H, Rezvan A, Kwon K, Nam D, Son DJ, Visvader JE, & Jo H. (2010) Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow. Blood, 116(15). PMID: 20551377
Gerhard A. Coetzee, Wange Lu, Peggy Farnham USC Genome-wide association studies (GWAS) have revealed numerous single-nucleotide polymorphisms (SNPs) where allelic frequencies differ between cases and controls of many complex diseases (NHGRI GWA Catalog). In the last decade 6,696 genetic associations of 598 traits have been reported in 16,770 papers (up to 2013). Despite these impressive ...
The post SNP-SNP here, SNP-SNP there, everywhere a SNP-SNP, old McDonald had a GWAS…… appeared first o........ Read more »
Hazelett DJ, Rhie SK, Gaddis M, Yan C, Lakeland DL, Coetzee SG, Ellipse/GAME-ON consortium, Practical consortium, Henderson BE, Noushmehr H.... (2014) Comprehensive functional annotation of 77 prostate cancer risk loci. PLoS genetics, 10(1). PMID: 24497837
Eeles RA, Olama AA, Benlloch S, Saunders EJ, Leongamornlert DA, Tymrakiewicz M, Ghoussaini M, Luccarini C, Dennis J, Jugurnauth-Little S.... (2013) Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nature genetics, 45(4), 385. PMID: 23535732
Visscher PM, Brown MA, McCarthy MI, & Yang J. (2012) Five years of GWAS discovery. American journal of human genetics, 90(1), 7-24. PMID: 22243964
Ecker JR, Bickmore WA, Barroso I, Pritchard JK, Gilad Y, & Segal E. (2012) Genomics: ENCODE explained. Nature, 489(7414), 52-5. PMID: 22955614
Coetzee SG, Rhie SK, Berman BP, Coetzee GA, & Noushmehr H. (2012) FunciSNP: an R/bioconductor tool integrating functional non-coding data sets with genetic association studies to identify candidate regulatory SNPs. Nucleic acids research, 40(18). PMID: 22684628
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text:
canvas's impl of this function is the same as nsFrame's:
*** Bug 373724 has been marked as a duplicate of this bug. ***
There's a small difference, http://mxr.mozilla.org/seamonkey/source/layout/generic/nsHTMLCanvasFrame.cpp#260 does an argument check. Is there a reason for this? Or can we just merge them?
You're looking at the seamonkey tree, I'm not sure exactly what that is but in mozilla-central nsHTMLCanvasFrame doesn't override GetContentForEvent. So this is fixed.


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|Sleepy John Estes
Drawing from the Document Catalogue, this double CD features the early recordings of the Tennessee country blues singer and guitarist Sleepy John Estes. Sleepy John Estes was born in Ripley, Tennessee in January 1899, the son of sharecroppers. He lost the sight of one eye as a child. He learned to play a homemade "cigarbox" guitar and by 1919 he was performing on the streets alongside the mandolin playing 11 year old James "Yank" Rachel. John's recording career for Victor commenced in just a month before the stock market crash in September 1929. His debut "The Girl I Love, She Got Long Curly Hair" was the biggest selling of Estes's early records. He recorded a further 15 sides for Victor before the Depression halted his recording career he was not back in the studio until July 1935. He was an influential singer and songwriter, he wrote about people and his own experiences. Down South Blues tells of the effect of the Depression on himself and others living in Memphis. John continued to record until 1940 and after a break of 20 years he like so many other bluesmen became involved in the 60s Folk/Blues revival. Includes informative booklet notes by Gary Atkinson.


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Audi Sport Quattro S1 E2 "Maximum Attack" - 1985 1000 Lakes Rally
Stig Blomqvist and Hannu Mikkola flying through the finish country side in there Audi Sport Quattro E2's. Stig would go on to finish the rally in 2nd place while Hannu retired his sport quattro after a troubled rally. Group B rally.
Group B Rally 1000 Lakes Finland 1986
WRC 600hp Group B Rally Supercars. The ULTIMATE Group B Rally, The 1000 Lakes Rally 1986. 3 x Works Martini Lancia Delta S4 3 x Works Peugeot 205T16 E2 3 x Works MG Metro 6R4
Group B Monsters in Finland - with pure engine sounds (1000 Lakes Rally 1983-1986)
Pure engine sounds mix of the notorious Group B rally monsters in action in the fast & flowing gravel roads of the 1000 Lakes Rally in Finland (1983-1986). Winners of 1000 Lakes Rally in the Group B era: 1983: Mikkola, Hannu Audi quattro A2 1984: Vatanen, Ari Peugeot 205 turbo 16 1985: Salonen, Timo Peugeot 205 turbo 16 E2 1986: Salonen, Timo Peugeot 205 turbo 16 E2
1000 Lakes Rally 1985 - SS1 Laajavuori Live
Alen has a rough jump and Henri Toivonen crashes to ditch but continues.


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The Biostatistics Core will provide essential biostatistical support to investigators on the Northwest Prostate Cancer SPORE. This Core will link study design, data collection, measurement, and analysis to the critical hypotheses and questions of the Northwest Prostate Cancer SPORE through the following Specific Aims: 1. Study Design: Define study hypotheses, study populations and experimental parameters to answer the research questions of interest, reduce systematic bias and ensure a high likelihood of detection of biologically meaningful effects. 2. Analysis and Interpretation: Identify and implement state-of-the-art quantitative methods to address the scientific questions of interest and provide valid statistical inferences about the evidence supporting the various study hypotheses. Provide necessary bioinformatics expertise for study interpretation. 3. Methods Development: Where appropriate statistical methods are inadequate or lacking, devise and implement novel quantitative approaches to address study questions of interest. During the prior funding periods, the Biostatistics Core played an integral role in the collection, validation and analysis of data for SPORE projects. Our experience has shown that involvement of statisticians from the concept phase yields studies that are better designed, more likely to answer the scientific questions of interest, and, ultimately, more compelling in their conclusions. Therefore the Core will continue to function though close collaboration with investigators from the beginning through the life of each SPORE study. The Biostatistics Core operates from within the Biostatistics Program at the FHCRC. Investigators on the Core play leadership roles on funded studies and programs whose missions overlap considerably with that of the Core. These include the Data management and Coordinating Center for the Early Detection Research Network, and the Program in Computational Biology and Bioinformatics at the FHCRC. Access to and collaboration with these programs will enhance the Core's ability to address analytic questions raised by SPORE studies using cutting-edge, and, if necessary, novel techniques.
|Kuo, Kevin F; Hunter-Merrill, Rachel; Gulati, Roman et al. (2015) Relationships between times to testosterone and prostate-specific antigen rises during the first off-treatment interval of intermittent androgen deprivation are prognostic for castration resistance in men with nonmetastatic prostate cancer. Clin Genitourin Cancer 13:6-Oct
|Lam, Hung-Ming; Vessella, Robert L; Morrissey, Colm (2014) The role of the microenvironment-dormant prostate disseminated tumor cells in the bone marrow. Drug Discov Today Technol 11:41-7
|True, Lawrence D (2014) Methodological requirements for valid tissue-based biomarker studies that can be used in clinical practice. Virchows Arch 464:257-63
|Sprenger, Cynthia C T; Plymate, Stephen R (2014) The link between androgen receptor splice variants and castration-resistant prostate cancer. Horm Cancer 5:207-17
|Montgomery, Bruce; Cheng, Heather H; Drechsler, James et al. (2014) Glucocorticoids and prostate cancer treatment: friend or foe? Asian J Androl 16:354-8
|O'Hurley, Gillian; Prencipe, Maria; Lundon, Dara et al. (2014) The analysis of serum response factor expression in bone and soft tissue prostate cancer metastases. Prostate 74:306-13
|Tarnow, Carolin; Engels, Géraldine; Arendt, Annika et al. (2014) TMPRSS2 is a host factor that is essential for pneumotropism and pathogenicity of H7N9 influenza A virus in mice. J Virol 88:4744-51
|Barnett, Christine M; Heinrich, Michael C; Lim, Jeong et al. (2014) Genetic profiling to determine risk of relapse-free survival in high-risk localized prostate cancer. Clin Cancer Res 20:1306-12
|Mostaghel, Elahe A; Plymate, Stephen R; Montgomery, Bruce (2014) Molecular pathways: targeting resistance in the androgen receptor for therapeutic benefit. Clin Cancer Res 20:791-8
|Chéry, Lisly; Lam, Hung-Ming; Coleman, Ilsa et al. (2014) Characterization of single disseminated prostate cancer cells reveals tumor cell heterogeneity and identifies dormancy associated pathways. Oncotarget 5:9939-51
Showing the most recent 10 out of 227 publications


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2 Timothy 3:16 - All scripture [is] given by inspiration of God, and [is] profitable for doctrine, for reproof, for correction, for instruction in righteousness:
Matthew 24:35 - Heaven and earth shall pass away, but my words shall not pass away.
Colossians 3:16 - Let the word of Christ dwell in you richly in all wisdom; teaching and admonishing one another in psalms and hymns and spiritual songs, singing with grace in your hearts to the Lord.
Proverbs 4:20-22 - My son, attend to my words; incline thine ear unto my sayings. (Read More...)
Hebrews 4:12 - For the word of God [is] quick, and powerful, and sharper than any twoedged sword, piercing even to the dividing asunder of soul and spirit, and of the joints and marrow, and [is] a discerner of the thoughts and intents of the heart.
Proverbs 3:1-35 - My son, forget not my law; but let thine heart keep my commandments: (Read More...)
Proverbs 30:5-6 - Every word of God [is] pure: he [is] a shield unto them that put their trust in him. (Read More...)
John 12:48 - He that rejecteth me, and receiveth not my words, hath one that judgeth him: the word that I have spoken, the same shall judge him in the last day.
Psalms 119:103 - How sweet are thy words unto my taste! [yea, sweeter] than honey to my mouth!
Psalms 119:105 - NUN. Thy word [is] a lamp unto my feet, and a light unto my path.
Topics and verses are auto-generated from user searches. If a verse or topic does not belong, please contact us. Some scripture references/categories courtesy of Open Bible .info under CC BY 3.0
Related Bible Dictionary Terms:
Word of God Word The
Search the King James Version (KJV) for more references about Gods Word...
Bible Verses About God
Bible Verses About Children
Bible Verses About Divorce


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More Videos...
Black GTS Dodge Viper Lapping @ Dunnville Autodrome
Take a quick lap in a gorgeous Dodge GTS Viper
Racing The Talon & Lowering A Mustang
We wake up in the morning and do some drag racing. Then proceed to lower A Mustang. Wing: http://www.ebay.com/itm/Haggard-Garage-Miata-Prototype-Wing-/262018457747?h ash=item3d01846093&vxp=mtr Drive Time: https://www.youtube.com/user/DriveTimeProductions
MotorWeek | Retro Review: '89 Eagle Talon TSI
A good friend of mine and I test drove his dad's brand new one once...without permission. This is a tribute to that.
Talon vs. Viper Run 2
Talon still on 34lbs. 50-150 roll.


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Creative Professional / Graphic Designer / Art Director – Always workin' on some ill shit. http://felone.fi | http://about.me/felone
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The world No 1 Lee Chong Wei claimed his first All-England title with victory over the Japanese underdog Kenichi Tago yesterday.
Lee prevailed 21-19 21-19 at Birmingham's National Indoor Arena to become the first non-Chinese men's singles winner since 2003 and only the second Malaysian champion in 44 years. The unseeded Tago showed spirit to save two match points but Lee, who has struggled to win major titles throughout his career, finished the job and overcame a psychological barrier with a good body shot.
Tine Rasmussen of Denmark won her second All England Open women's singles title, avenging her loss to top-seeded Wang Yihan last year at Birmingham National Indoor Arena by winning 21-14, 18-21, 21-19 in front of a 7,000-capacity crowd.
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Slow PunctureLast updated at 12:01AM, March 26 2016
The government is neglecting its promises to cyclists
David Cameron must take personal responsibility for the safety of cyclists and promote the measures needed to make Britain's streets safer, he is told in a letter today from 40 cross-party MPs.
The Conservative, Liberal Democrat and Labour MPs are calling on Mr Cameron to use his speech at the Conservative Party conference, which begins in Birmingham on Sunday, to address the rising death toll of cyclists on Britain's roads.
Mr Cameron, who was often pictured riding his bicycle while in Opposition, acknowledged the need for improved cycle safety in the House of Commons earlier this year, but the MPs are asking him to provide personal leadership in seeing that the necessary measures are implemented.
A cross-party inquiry into cycle safety starts this autumn, when a panel of MPs and peers will hear expert evidence from engineers, road safety groups, civil servants from the departments for transport, health and education and the Treasury.
The letter states: "We the undersigned call on you as Prime Minister to use your speech at Conservative Party conference to make clear that this nation of cyclists can count on your personal leadership in studying the inquiry's findings and promoting the measures needed to get more people cycling in Britain.
"Leadership, commitment and investment across Government in new policies and infrastructure are all that can reverse this trend of innocent lives lost and encourage more people to ride their bikes."
Signatories include Zac Goldsmith, the Conservative MP, Tim Farron, the Liberal Democrat MP and party president and the Labour MPs Ben Bradshaw and Dame Tessa Jowell. It is also signed by the Shadow Transport Secretary Maria Eagle, who pledged that the Labour manifesto for the 2015 general election would adopt in full the measures set out in The Times Cities Fit for Cycling campaign.
Britain's success in cycling at the Olympic and Paralympic Games has boosted enthusiasm for cycling in this country, but September was also the deadliest month for cyclists on the roads, with 15 fatalities, bringing the death toll this year to 89 victims.
The letter states: "The success of GB cyclists was a marvel to behold at London 2012 and the so-called 'Wiggins' effect' has seen a huge boost for cycling as a clean, sustainable and inherently safe way to travel in the UK.
"But it was also during the Games that a commuting cyclist, 28-year-old Dan Harris, was crushed to death beneath the wheels of a bus outside the Olympic Park; a bitter reminder that much more needs to be done to make the streets safer for cyclists."
Figures from the Department for Transport confirm that cycling has become more dangerous. The rate of death or serious injury rose by 15 per cent last year even though the number of cyclists rose by only 1 per cent.
The letter, organised by the Liberal Democrat MP Julian Huppert, the Labour MP Ian Austin and the Conservative MP Sarah Wollaston of the All-Party Parliamentary Cycling Group, calls on the Transport Secretary, Patrick McLoughlin, to use his conference speech to outline the department's plans for cycle safety.
The letter adds: "It is not enough to acknowledge that the death toll for cyclists is unacceptable. The economic and social benefits of cycling in improving public health, tackling child obesity, reducing congestion and pollution are being lost due to inaction."
RBS 6 Nations stars on how they come together as a team to succeed
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Speed of European monetary union has left capital markets in the slow lane
The government is neglecting its promises to cyclists
The cycling and walking investment strategy pledges £300 million over five years, which is less than 14 per cent of the recommended amount
A minister labelled cyclists "the biggest challenge for a commuter", as the number found guilty of neglect of traffic directions more than doubled
Mary Bowers, 31, who has been left with severe brain damage after suffering "appalling" injuries, will need to receive care for the rest of her life
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The Brawley Wildcats volleyball team won Friday's neutral tournament match against Sanger by a score of 2-0.
Game Details: Beach City Invitational
The Brawley Wildcats volleyball team scored 2 points and limited the host Sanger Apaches to 0 in the Wildcats non-league victory on Friday.
The Wildcats now have a 6-1 record. They put it on the line next when they travel to Service for a non-league game on Friday, September 25. Brawley will confront a Cougars team coming off a 3-0 non-league loss to Mission Hills (San Marcos, CA). The Cougars record now stands at 3-5.
The Apaches (1-6) will now prepare for their game against University City (San Diego, CA). The Centurions enter the non-league game with a 8-4 record. In their last game, University City dropped by Mead (Spokane, WA), 2-0, in a non-league game.


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Zyprexa, generic Olanzapine, is an atypical antipsychotic medication used in the treatment of bipolar disorder, schizophrenia, and treatment resistant depression.

Commonly Reported Side Effects of Zyprexa

Common side effects of Zyprexa include:

Sleepiness or excessive sleeping

Dizziness

Dry mouth

Lack of energy

Increased appetitie

Tremor

Hard or infrequent stools

Change in behavior

Restlessness

Be sure to consult your doctor if any of these side effects bother you or are persistent. Also, there are some more unique side effects that teenagers may experience with Zyprexa -- be sure to review these with your doctor.

Potential Serious Side Effects with Zyprexa

One important and serious side effect of Zyprexa is significant weight gain, which is often a huge reason why a patient stops their medication. In addition, Zyprexa can also increase blood sugar levels, which can put a person at risk for developing diabetes. Zyprexa may also increase a person's cholesterol levels. All of these factors can increase a person's risk of heart disease. This is why it's important to review a exercise and nutritional plan with your doctor while on Zyprexa -- to help minimize these side effects.

A rare but very dangerous side effect of Zyprexa is neuroleptic malignant syndrome, or NMS. Signs of NMS include muscle rigidity, confusion, high fever, increased blood pressure and heart rate, and abnormal heart rhythms.

Tardive dyskinesia (TD) is another potentially irreversible, involuntary movement that may develop. Although the risk of tardive dyskinesia is lower when compared to typical or first generation antipsychotics.

In addition, it has been reported that people on Zyprexa may have an increased sensitivity to heat due to reduced sweating. So be sure to drink plenty of water, especially in hot weather or before and after exercising.

Other potential serious side effects include seizures, dizziness or fainting when changing positions (like going from a sitting to standing position), problems swallowing, and an increased risk of transient ischemic attacks and strokes in elderly people with dementia-related psychosis.

What if My Doctor Prescribes Zyprexa?

It's important to first inform your doctor of all your medications -- this includes prescription, herbals, vitamins, or any over-the-counter medications. Some medications interact with Zyprexa, and may cause serious side effects or require that your doctor alter your dose. Also, never start or stop Zyprexa without seeking the advice of your doctor -- this is for your safety and well-being

It's also important to give your doctor a complete medical history, including all your medical problems and any allergies. For example, tell your doctor if you are lactose-intolerant, as Zyprexa tablets contain lactose. Also, tell your doctor if you drink alcohol, as alcohol should not be used when taking Zyprexa.

Finally, when on Zyprexa, take it at the same time everyday. If you accidentally forget a dose, take it as soon as you remember -- unless, it's almost time for the next dose anyway. Then skip it, and take your regular dose as scheduled. Do not take two doses of Zyprexa at the same time. If you are unsure about your timing, call your doctor to be safe.

Sources:

Eli Lily and Company. US Food and Drug Administration. (2009). Medication Guide: Zyprexa. Retrieved January 30th 2016.

Nashed MG, Restivo MR & Taylor VH. Olanzapine-induced weight gain in patients with bipolar I disorder: A meta-analysis. Prim Care Companion CNS Disord. 2011;13(6):PCC

DISCLAIMER: The information in this site is for educational purposes only. It should not be used as a substitute for personal care by a licensed physician. Please see your doctor for diagnosis and treatment of any concerning symptoms or medical condition.


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ATLANTA -- Jeff Francoeur, who turned down a football scholarship at Clemson to play baseball, showed Wednesday night that he knows something about a third sport.
"I think it's just part of being a golfer; I put a spin on the sand wedge," Francoeur said in explaining his eighth-inning, run-scoring bloop double that gave the Atlanta Braves the lead in their 4-3 win over the Washington Nationals.
Francoeur, a former Atlanta-area high school star who was called up from Double-A Mississippi on July 7, had three hits and drove in two runs in his first start against a right-handed pitcher.
Braves manager Bobby Cox said it didn't matter that two of Francoeur's hits were bloopers.
"What he's done, he's put the ball in play, and when you do that you give yourself a chance," Cox said. "That's the name of the game -- put it in play."
Atlanta wasted a 3-1 lead in the eighth, then went ahead in the bottom half against Gary Majewski (2-2).
Chipper Jones singled with two outs and stole second, and Adam LaRoche was intentionally walked. Francoeur blooped a double into shallow center, allowing Jones to score the go-ahead run.
"I was just lucky to hit it in the right place," Francoeur said.
Francoeur also gave the Braves a 2-1 lead with a fourth-inning single.
Dan Kolb (3-6) won despite giving up two key hits in the eighth, and Chris Reitsma finished for his 11th save in 15 chances.
Atlanta, which won the first two games of the three-game series, opened a two-game lead in the NL East, its largest margin since the Braves led by 2½ games after play on May 15.
The Nationals held a team meeting after the game.
Washington is 6-15 since leading the NL East by 5½ games on July 2.
Asked if he is angry and frustrated, Washington manager Frank Robinson said: "A little bit of all of the above. ... We're not playing winning baseball."
Robinson said the meeting "was something I had to do, get it off my chest, and I did it."
Francoeur is hitting .433, and Cox said after the game the rookie will start again Thursday when the Braves face right-hander Ryan Drese.
Francoeur had been sharing time with fellow rookie Ryan Langerhans in right field. Langerhans will move to left field Thursday as Cox rests a third rookie outfielder, Kelly Johnson, who is hitting only .224.
"I'm having a blast," Francoeur said. "I'm looking forward to it. It will be good to get to start two days in a row, especially against a right-hander."
Tim Hudson gave up one run and five hits in seven innings, handing his bullpen a 3-1 lead.
John Foster walked Brad Wilkerson and Jose Vidro leading off the eighth, prompting Cox to bring in Kolb. Jose Guillen and Nick Johnson hit RBI singles, bringing boos from the crowd of 40,625.
Washington's Esteban Loaiza gave up three runs -- two earned -- and seven hits in six-plus innings.
Wilkerson led off the game with a triple to the right-field corner and scored on Guillen's single. The Nationals loaded the bases before Vinny Castilla grounded into an inning-ending double play.
Marcus Giles hit a solo homer in the fourth, and Andruw Jones followed with a high pop fly that Johnson and Vidro lost in the lights and fell at least 15 feet from the first baseman for an easy double. Francoeur singled through the pitcher's legs with two outs for a 2-1 lead.
"I don't know why they couldn't see it," Robinson said of the pop fly.
Francoeur led off the seventh with a bloop single that shortstop Cristian Guzman appeared to lose in the lights, and Loaiza threw the ball into the outfield on Brian McCann's bunt for an error. With Julio Franco at the plate, reliever Joey Eischen threw a run-scoring wild pitch.
"I think we hit one ball hard all night -- Giles' home run," Chipper Jones said. "Everything else was a blooper."
There was a 27-minute rain delay in the top of the third inning. ... Chipper Jones stole his second base of the season in the eighth inning. ... Nick Johnson was 2-for-3 in his second game since being activated from the disabled list.


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Home Page > Companies > TEAM BUILDING TOURS > Rally Murder Party in 2CV
Customized Duration
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A2 after only a very short time立刻/马上
He replied very quickly. 他马上就回复了。
More examples
- She quickly left the chorus for a starring role.
- The plane climbed quickly to a height of 30 000 feet.
- Police quickly closed off the area.
- Christmas comes round so quickly!
- You don't need to eat so quickly! It's not a competition.


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