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CHIMERAS
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- September 10, 2012
- 10:14 AM
- 245 views
The encyclopedia of DNA - Part I
The raw numbers of the human genome: three billion base pairs, of which roughly 1% fall into the 20,000 genes in our genome. So, what's all the extra stuff for?Typing the whole human genome, in 2001, was only the beginning. The next step in disentangling the puzzle was to assign biochemical functions to those three billion base pairs. "The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elemen........ Read more »
The ENCODE Project Consortium. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature. DOI: 10.1038/nature11247
- September 3, 2012
- 06:53 PM
- 287 views
Transcription factories for gene expression: the hard working units of the nucleus
You've probably heard it many times already: if you could stretch out the DNA contained in any one nucleated cell in your body, it would be 2 meters (~6 feet) long. Now imagine packing this 2-meter long molecule into a sphere whose diameter is of the order of a few micrometers, roughly one millionth smaller than a meter. Yes, it's going to be packed in there, yet those genes have to be accessible to the "workers" that come in and perform daily tasks such as gene transcription, replication, and D........ Read more »
Schoenfelder, Stefan, et al. (2010) The transcriptional interactome: gene expression in 3D. . Current Opinion in Genetics . DOI: 10.1016/j.gde.2010.02.002
- August 30, 2012
- 09:51 AM
- 292 views
How chromatin changes are preserved after cell division
DNA is found in the nucleus of every cell, woven around proteins called histones. This complex of DNA and proteins found inside the nucleus is called chromatin. In the past, I dedicated a couple of posts to chromatin rearrangements, how they are used by the cell to silence certain genes, and how epigenetic reprogramming has to happen in order for cells to differentiate during development. I'm still learning how these epigenetic mechanisms work, and today I'd like to share with you a couple new r........ Read more »
Wen Yuan, Tong Wu, Hang Fu, Chao Dai, Hui Wu, Nan Liu, Xiang Li, Mo Xu, Zhuqiang Zhang, Tianhui Niu.... (2012) Dense Chromatin Activates Polycomb Repressive Complex 2 to Regulate H3 Lysine 27 Methylation. Science. DOI: 10.1126/science.1225237
- August 23, 2012
- 01:08 PM
- 247 views
The mystery of the Delta antigen
Now I feel like I should write a spy-fiction story on the delta antigen... Maybe I will... But for now, here's the real story. When in the mid '70s a group of patients in Turin, Italy, presented a particularly virulent form of Hepatitis B (HBV), medical researchers thought they had found a new subtype of the virus. Liver biopsies from infected patients revealed a new antigen, which was thought to be a new protein encoded by HBV. There was a mystery to solve, though: why was the new antigen (call........ Read more »
John Taylor, & Martin Pelchat. (2012) Origin of hepatitis δ virus. Future Medicine. DOI: 10.2217/fmb.10.15
- August 20, 2012
- 09:00 AM
- 403 views
It's not a virus, it's a viroid
A virus is a stretch of DNA or RNA, usually a few thousand bases long, enclosed in a protein shell. Once inside the cell, the RNA or DNA from the virus starts producing viral proteins, which are then used for replication.Now imagine a circular strand of RNA that instead of a few thousand bases comprises a few hundred bases. It doesn't code for proteins, it doesn't come in a shell. And yet it's highly pathogenic and able to reproduce. In plants, that is. A viroid is essentially a circular strand ........ Read more »
Beatriz Navarroa,, Andreas Giselb,, Maria-Elena Rodioa,, Sonia Delgadoc,, Ricardo Floresc,, & Francesco Di Serio. (2012) Viroids: How to infect a host and cause disease without encoding proteins. Biochem. DOI: 10.1016/j.biochi.2012.02.020
- August 16, 2012
- 09:00 AM
- 301 views
What's that gene for, again?
I'm always skeptical when you hear prepositions such as "gene X has function Y," as often there are very complicated mechanisms nestled between the "gene" and the "function/phenotype." If you've been following me over the past year (yes, I've been blogging for a year already, time flies!), we've learned that between-gene interactions (epistasis), and changes in gene expression (epigenetics) can completely change the picture. Recent review on the use of RNA interference have given me additional r........ Read more »
William G. Kaelin Jr. (2012) Use and Abuse of RNAi to Study Mammalian Gene Function. Science, 337(6093), 421-422. DOI: 10.1126/science.1225787
- August 13, 2012
- 09:00 AM
- 269 views
Olympic fever, olympic medicine
Will you be missing the Olympics now that they are finally over? I will. If you enjoyed watching the games, you'll also enjoy the NEJM perspective by David Jones [1], which gives a historical overview of olympic medicine and how it has studied, over the years, the limits of the human body. It's interesting to read how in the 1904 games in St. Louis the marathon winner had taken strychnine sulfate, five eggs, and brandy during the race and still required medical attention afterwards. Fast forward........ Read more »
David S. Jones. (2012) Olympic Medicine. New England Journal of Medicine, 289-292. info:/
- August 2, 2012
- 09:00 AM
- 286 views
The beginning of the end. . . Maybe.
"We share a very special moment - it is the moment when an AIDS-free generation is finally in sight." That's what the US president, Barack Obama, said on July 26. Well, are we?A colleague a few days ago brought to our attention some stunning figures: according to the CDC, of all HIV infected individuals in the US, only 25% are under treatment and hence have the virus under control. Quite striking if you consider that in Sweden instead 85% of HIV-positive individuals are undergoing treatment. The........ Read more »
Diane Havlir, & Chris Beyrer. (2012) The Beginning of the End of AIDS?. New England Journal of Medicine. info:/10.1056/NEJMp1207138
- July 30, 2012
- 09:42 AM
- 384 views
Oedipus's dilemma
I love Greek mythology, and of all myths, Oedipus is probably the one that fascinates me the most. Nothing to do with the fact that it's become a psychiatric hallmark. I love this myth because it always makes me wonder: if somebody came to you and told you they knew with absolute certainty your future (how many years you'll live, what you'll accomplish, etc.), would you want to know? It's a paradox, because that knowledge would affect the future course of action you choose. Think about Laius: he........ Read more »
Nicholas J. Roberts, Joshua T. Vogelstein, Giovanni Parmigiani, Kenneth W. Kinzler, Bert Vogelstein1 and, & Victor E. Velculescu. (2012) The Predictive Capacity of Personal Genome Sequencing. Sci Transl Med 4, 133ra58. DOI: 10.1126/scitranslmed.3003380
- July 23, 2012
- 09:00 AM
- 389 views
The vulnerable banana crop
"What are you doing?""Eating a banana.""Did you know that banana trees are seedless? They only reproduce asexually and hence are all genetically identical."(Me, chewing) "Hmm-mmm.""If a parasite were to kill one, it would kill all of them because there's no genetic variation among the plants."See, this is what you get from growing up with a biologist father. Over a meal, you can learn infinitely many new things, like the fact that shellfish is an unfortunate name for something that really isn't ........ Read more »
Angélique D’Hont,, France Denoeud,, Jean-Marc Aury,, Franc-Christophe Baurens,, Françoise Carreel,, Olivier Garsmeur,, Benjamin Noel,, Stéphanie Bocs,, Gaëtan Droc,, Mathieu Rouard,.... (2012) The banana (Musa acuminata) genome and the evolution of monocotyledonous plants. Nature. DOI: 10.1038/nature11241
- July 16, 2012
- 08:41 AM
- 378 views
An interplay between GO genes and STOP genes optimizes cancer growth
Tumor cells typically have certain genes (called oncogenes) that are either mutated or highly expressed (for example, they can increase in copy number) and that promote tumor growth. Oncogenes often act in combination with silenced tumor suppressor genes -- genes that inhibit tumor development. As the name suggests, if both copies of a tumor suppressor gene are silenced, tumor growth is promoted. To date, there are nearly 500 oncogenes that have been catalogued and whose mutations have been show........ Read more »
Nicole L. Solimini,, Qikai Xu,, Craig H. Merme,, Anthony C. Liang,, Michael R. Schlabach,, Ji Luo,, Anna E. Burrows,, Anthony N. Anselmo,, Andrea L. Bredemeyer,, Mamie Z. Li,.... (2012) Recurrent Hemizygous Deletions in Cancers May Optimize Proliferative Potential. Science. DOI: 10.1126/science.1219580
- July 12, 2012
- 09:00 AM
- 399 views
Stress-induced epigenetic changes last up to four generations in mice
One of the most intriguing aspects of epigenetics is its ability to confer transgenerational changes. General belief used to be that inheritance pertained exclusively to DNA, and that what did not affect DNA could not be inherited. Epigenetics encompasses all molecular "processes that regulate genome activity independent of DNA sequence [1]." It has revolutionized the way we view heritability: epigenetic changes do not alter the DNA sequence, only the way genes are expressed. And yet environment........ Read more »
David Crewsa, Ross Gillettea, Samuel V. Scarpinoa, Mohan Manikkamb, Marina I. Savenkovab, and Michael K. Skinner. (2012) Epigenetic transgenerational inheritance of altered stress responses. PNAS. DOI: 10.1073/pnas.1118514109
- July 9, 2012
- 09:30 AM
- 380 views
A nicotine vaccine could be the key to quit smoking
It's been a while since I last talked about gene therapy, and this recent study gave me the perfect chance to reopen the topic: a research group tested a vaccine against nicotine addiction in mice. But wait... how can a vaccine work against... a molecule? Once inhaled, nicotine reaches the brain within 10-20 seconds. Here, it activates one of the dopaminergic pathways in the brain, which involves the transmission of dopamine from one region of the brain to another. Dopamine is a neurotransmitter........ Read more »
X Y Shen1, F M Orson1,2 and T R Kosten. (2012) Vaccines Against Drug Abuse. Clinical Pharmacology 6(1), 277-70. DOI: 10.1038/clpt.2011.281. DOI: 10.1038/clpt.2011.281
Martin J. Hicks1,, Jonathan B. Rosenberg,, Bishnu P. De1,, Odelya E. Pagovich,, Colin N. Young,, Jian-ping Qiu,, Stephen M. Kaminsky,, Neil R. Hackett,, Stefan Worgall1,, Kim D. Janda,.... (2012) AAV-Directed Persistent Expression of a Gene Encoding Anti-Nicotine Antibody for Smoking Cessation. Sci Transl Med 27 June 2012: Vol. 4, Issue 140, p. 140ra87. DOI: 10.1126/scitranslmed.3003611
- July 5, 2012
- 10:16 AM
- 421 views
Viruses and epigenetics: old tricks, new findings
Different cells express different genes. Which genes are expressed and which, instead, are silenced, is regulated either at the transcriptional or at the post-transcriptional level. In an older post I described how DNA is arranged inside the nucleus and how changes in chromatin (the "yarn" of DNA and other proteins like histone complexes) can affect gene expression. Transcriptional gene regulation happens at the chromatin level, in other words, genes are expressed or silenced due to rearrangemen........ Read more »
Jeang KT. (2012) RNAi in the regulation of mammalian viral infections. BMC biology, 58. PMID: 22734679
Reinhard Kurth,, & Norbert Bannert. (2010) Beneficial and detrimental effects of human endogenous retroviruses. International Journal of Cancer, 126(2), 306-314. DOI: 10.1002/ijc.24902
- July 2, 2012
- 09:00 AM
- 365 views
How commensal bacteria modulate immune responses
As you all probably know by now, I grew up in Europe. One of the first things I noticed when dealing with the health system here in the U.S. is -- no, not insurance. Antibiotics! Yes, I'm old school and believe that antibiotics are over-prescribed in this country. You may find it convenient to carry antibiotic creams in your hiking bag and use it over the tiniest scrapes, or that your house cleaner kills 99.99% of germs, but in the end we may pay a price for that. The paper I'm discussing today ........ Read more »
Michael C. Abt, Lisa C. Osborne, Laurel A. Monticelli, Travis A. Doering, Theresa Alenghat, Gregory F. Sonnenberg, Michael A. Paley, Marcelo Antenus, Katie L. Williams, Jan Erikson, E. John Wherrysend, David Artissend. (2012) Commensal Bacteria Calibrate the Activation Threshold of Innate Antiviral Immunity. Immunity. info:/
- June 29, 2012
- 09:20 AM
- 418 views
Dual-use research of concern
I'm still reading (and very much enjoying) last Friday's Science issue on the flu pandemic. In [1], Anthony Fauci and Francis Collins summarize very well why the flu presents a potential threat: "Influenza viruses have animal reservoirs, especially in birds and pigs. They can undergo extensive genetic changes and even jump species, sometimes resulting in a virus to which humans may be highly vulnerable."Over the last hundred years, this happened four times: in 1918 (the Spanish flu), in 1957 (th........ Read more »
Anthony S. Fauci,, & Francis S. Collins. (2012) Benefits and Risks of Influenza Research: Lessons Learned . Science, 336(6088), 1522-1523. info:/
- June 25, 2012
- 09:00 AM
- 308 views
Flu pandemics: are we prepared?
The first avian flu controversial paper appeared in Nature last April, and the second one just came out in the last issue of Science. For the occasion, Science also published a series of essays from various experts in the field discussing the issues at stake and what we learned. The most fundamental question is: in case of a flu pandemic, are we prepared?Rino Rappuoli and Philip Dormitzer discuss what can be done in the event of a flu pandemic, basing their observations on the lessons learned fr........ Read more »
Rappuoli1, R,, & Dormitzer, P. (2012) Influenza: Options to Improve Pandemic Preparation. Science, 336(6088), 1531-1533. DOI: 10.1126/science.1221466
- June 18, 2012
- 07:35 AM
- 385 views
Chromatin and oncogenesis
DNA is packed inside the nucleus of our cells, folded around proteins in a "yarn" called chromatin. In an older post I discussed how chromatin changes affect gene expression. A recent PNAS paper [1] explores the relationship between chromatin conformational changes and cancer. They studied one family of genes in particular, ERG, which is part of the larger family of genes called ETS. In order to understand the paper I had to learn about this ETS family of genes and, let me tell you, it's quite ........ Read more »
Rickman DS, Soong TD, Moss B, Mosquera JM, Dlabal J, Terry S, Macdonald TY, Tripodi J, Bunting K, Najfeld V.... (2012) Oncogene-mediated alterations in chromatin conformation. Proceedings of the National Academy of Sciences of the United States of America, 109(23), 9083-8. PMID: 22615383
- June 11, 2012
- 07:20 AM
- 500 views
Do rare variants hold the missing answers?
Most DNA is identical across subjects. However, some genes are polymorphic, which means different alleles of the same gene are present across individuals. Since we all have two copies of each gene, individuals who carry two identical copies are called homozygous, and those who carry different copies are called heterozygous. Typically, one allele is most common in the population, the "wild type," and the other ones, present at lower frequencies, are called "mutants." Single-base differences are c........ Read more »
Tennessen, J., Bigham, A., O'Connor, T., Fu, W., Kenny, E., Gravel, S., McGee, S., Do, R., Liu, X., Jun, G.... (2012) Evolution and Functional Impact of Rare Coding Variation from Deep Sequencing of Human Exomes. Science. DOI: 10.1126/science.1219240
- June 7, 2012
- 09:44 AM
- 418 views
Convergence of phenotypes: homoplasy
Most often, trait similarities between different species are an indication of a common phylogeny (homology). However, the opposite is also possible: independent phylogenies can indeed show similarities due to convergence in evolution rather than relatedness. When this occurs, a phenomenon called "homoplasy", it becomes of interest understand what mechanisms determined the convergence in phenotype."Study of the underlying developmental genetic mechanisms may reveal whether the recurrent structure........ Read more »
Wake, D., Wake, M., & Specht, C. (2011) Homoplasy: From Detecting Pattern to Determining Process and Mechanism of Evolution. Science, 331(6020), 1032-1035. DOI: 10.1126/science.1188545
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