...as in: We got stuck on playing Wii 'till 2AM. Here's the pics!
During my breakfast, I like listening to classical or jazz music. I always tune in on a German radio station that features a good selection of music (right before they turn to the "Wort zum Tag" by some church dude) and it sort of gets me in the right mood. A couple of months ago, I heard a fantastic Jazz song but forgot to look the artist up soon afterward. Then, this Monday they featured another song by the same guy and I immediately grabbed my Moleskine and marked down "Look up Moondog"... which I did, and I came across an very interesting wiki article and album selection on iTunes. Moondog or Louis Thomas Hardin was a blind jazz musician / philosopher / instrument inventor / hobo spending most of his days in the streets of Manhattan wearing his homemade Thor (the god, not the protein, sorry to disappoint you) costume. I can highly recommend him to any avant-garde jazz percussion fan!
In these past months, I could not always find enough time to read as much as I would have liked, however, two noteworthy examples include the following:
- Bad Science by Ben Goldacre, MD, author of a weekly Guardian column and the blog badscience.net. Being a regular reader of his blog, I can still say that much of the themes that Ben touches are well elaborated and researched, much more that a simple blog post could do. I dearly recommend it to anybody interested in the Placebo effect, debunking media healthcare scares, homeopathy and the dark practices of some pharmaceutical companies and bad scientists. It is an interesting book that doesn't necessitate any higher medical training. I must also note however that one can easily see that this is Ben's first book, as the writing can seem slightly incoherent at a couple of passages.
- Phantoms in the Brain by V.S. Ramachandran, MD, PhD. You may remember him from a fantastic TED talk that I posted at some point. Everybody the least bit interested in the mysteries of the human mind, consciousness, phantom pains, hallucinating cartoon characters and more. Very well written, great quotes and many hilarious situations guaranteed! If it weren't for the numerous overly corny sounding deistic allusions that give the impression that the author has to pay tribute to some higher instance (I'm probably exaggerating), the book would even be better. However I must say that the last chapter lost me somewhere in between and seems rather dull compared to the clever writing of the first chapters.
The mTOR (mammalian target of rapamycin) is the pathway I'm working on, and I tried to put some of the recent publications in there. If anybody likes to point out a mistake or has any suggestions, please feel free to do so! This isn't supposed to be a good overview that you'd put in a presentation, rather I tried to put together most of the relevant information I could find, most useful for scientists working on this pathway. There are uncertainties and contradictions, so future work has to be done, especialy regarding the mTorc2 (mTOR complex 2) and its upstream regulators and effectors.
Update v1.01: 28th May 2008 - Amino Acids, Sancak 2008
Update v1.02: 30th May 2008 - Protor->PRR; Ca-dependant; RagGTPase dashed
Update v1.5: 12th June 2008 - New layout; phospho sites; new links
Update v1.6: 8th January 2008 - Revived project, rebuild file from scratch (HDD crash), changed phosphosites and layout, included SGK, PKC, PHLPP, Tel2, PLD1 removed TCTP...
- Gwinn et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Molecular cell (2008) vol. 30 (2) pp. 214-26
- Huang et al. The TSC1-TSC2 complex is required for proper activation of mTOR complex 2. Molecular and cellular biology (2008) pp.
- Panasyuk et al. Ribosomal protein S6 kinase 1 interacts with and is ubiquitinated by ubiquitin ligase ROC1. Biochem Biophys Res Commun(2008) pp.
- Suzuki et al. Tuberous sclerosis complex 2 loss-of-function mutation regulates reactive oxygen species production through Rac1 activation. Biochem Biophys Res Commun (2008) pp.
- Baba et al. Kidney-Targeted Birt-Hogg-Dube Gene Inactivation in a Mouse Model: Erk1/2 and Akt-mTOR Activation, Cell Hyperproliferation, and Polycystic Kidneys. J Natl Cancer Inst (2008) pp.
- Bai et al. Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38. Science (New York, NY) (2007) vol. 318 (5852) pp. 977-80
- Yang et al. Expanding mTOR signaling. Cell Res (2007) pp.
- Pearce et al. Identification of Protor as a novel Rictor-binding component of mTOR complex-2. The Biochemical journal (2007) vol. 405 (3) pp. 513-22
- Land et al. Hypoxia-inducible factor 1alpha is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif. The Journal of biological chemistry (2007) vol. 282 (28) pp. 20534-43
- Guertin et al. Defining the role of mTOR in cancer. Cancer cell (2007) vol. 12 (1) pp. 9-22
- Manning et al. AKT/PKB signaling: navigating downstream. Cell (2007) vol. 129 (7) pp. 1261-74
- Abraham et al. The Mammalian target of rapamycin signaling pathway: twists and turns in the road to cancer therapy. Clinical cancer research : an official journal of the American Association for Cancer Research (2007) vol. 13 (11) pp. 3109-14
- Soulard et al. SnapShot: mTOR signaling. Cell (2007) vol. 129 (2) pp. 434
- Brognard et al. PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. Molecular cell (2007) vol. 25 (6) pp. 917-31
- Zhang et al. S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt. Molecular cell (2006) vol. 24 (2) pp. 185-97
- Baba et al. Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proceedings of the National Academy of Sciences of the United States of America (2006) vol. 103 (42) pp. 15552-7
- Inoki et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell (2006) vol. 126 (5) pp. 955-68
- Sabatini. mTOR and cancer: insights into a complex relationship. Nature reviews Cancer (2006) vol. 6 (9) pp. 729-34
- Shaw et al. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature (2006) vol. 441 (7092) pp. 424-30
- Sarbassov et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Molecular cell (2006) vol. 22 (2) pp. 159-68
- Wullschleger et al. TOR signaling in growth and metabolism. Cell (2006) vol. 124 (3) pp. 471-84
- Gloire et al. The role of SHIP1 in T-lymphocyte life and death. Biochemical Society transactions (2007) vol. 35 (Pt 2) pp. 277-80
- Update: 05/28/08: Sancak et al. The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1. Science (New York, NY) (2008) pp.
- Update: 05/30/08: Gulati et al. Amino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34. Cell metabolism (2008) vol. 7 (5) pp. 456-65
- Update: 06/12/08: Manning. Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. The Journal of cell biology (2004) vol. 167 (3) pp. 399-403
- Update: 06/12/08: Phospho sites: Cellsignal.com
- Update: 06/12/08: Harrington et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. The Journal of cell biology (2004) vol. 166 (2) pp. 213-23
- Update: 06/12/08: Lu et al. Src family protein-tyrosine kinases alter the function of PTEN to regulate phosphatidylinositol 3-kinase/AKT cascades. The Journal of biological chemistry (2003) vol. 278 (41) pp. 40057-66
- Update: 06/12/08: Huang et al. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. The Biochemical journal (2008) vol. 412 (2) pp. 179-90
- Update: 06/12/08: Harvey et al. FOXO-regulated transcription restricts overgrowth of Tsc mutant organs. The Journal of cell biology (2008) vol. 180 (4) pp. 691-6
- Update: 06/12/08: Sofer et al. Regulation of mTOR and cell growth in response to energy stress by REDD1. Molecular and cellular biology (2005) vol. 25 (14) pp. 5834-45
- Update: 01/08/09: Sun et al. Phospholipase D1 is an effector of Rheb in the mTOR pathway. Proceedings of the National Academy of Sciences of the United States of America (2008) vol. 105 (24) pp. 8286-91
- Update: 01/08/09: Yan et al. mTORC2 is the hydrophobic motif kinase for SGK1. The Biochemical journal (2008) vol. 416 (3) pp. e19-21
- Update: 01/08/09: Facchinetti et al. The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. The EMBO Journal (2008) vol. 27 (14) pp. 1932-43
- Update: 01/08/09: Takai et al. Tel2 regulates the stability of PI3K-related protein kinases. Cell (2007) vol. 131 (7) pp. 1248-59
- Update: 01/08/09: Hardie. Neither LKB1 nor AMPK are the direct targets of metformin. Gastroenterology (2006) vol. 131 (3) pp. 973; author reply 974-5
- Update: 01/08/09: Xie et al. Phosphorylation of LKB1 at serine 428 by protein kinase C-zeta is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells. Circulation (2008) vol. 117 (7) pp. 952-62
- Update: 01/08/09: Sapkota et al. Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell growth. The Journal of biological chemistry (2001) vol. 276 (22) pp. 19469-82
- Update: 01/08/09: Gwinn et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Molecular cell (2008) vol. 30 (2) pp. 214-26
It was a good new year's eve we had this year here in Basel. I had concluded that it was time to stay here in Basel for once and so Line and I invite a couple of people over. We prepared a Fondue Bourguignonne Betz style (i.e. beef, lamb, duck, pig and chicken meat, the most powerful garlic mayonnaise you can prepare on this hemisphere and oven roasted potatoes with our famous sour cream / cream cheese sauce), followed by an after mid-night Luxembourgish onion soup with cheese and finally an pineapple ice-cream. Recipies will follow... Here's the pix.
It's Christmas and I'm wondering again whether I should switch to a new camera. Not just any camera, the follow up model to mine, the famous EOS 5D Mark II. Mainly because of some of its newest additions (higher ISO, 1080p video, quiet shutter, auto cleaning, life view micro focusing etc), not because my old one let me down at any point. Of course I could only do it if I can sell my old one for a reasonable price, so (again) I wanted to know if anybody has something in mind. Ebay sells them from 1200 (dubious Taiwan imports) to around 1600 (with more acessories that I can offer), so I guess there is a middleway. The camera is 2 years old, has 5 or 6 batteries (2 brand new, 1 new, 1 ok and 1 bad) and is otherwise in a good (though not mint) condition. So you have my destiny in your hands!
Just got home from the Biozentrum from this year's biochemistry blockcourse party that was organized mostly by Adi, so kudos to him! After both of us kicked out the students and finished cleaning up the mess, I present you, Ladies and Gentlemen, the pictures of the evening. There's plenty of pictures from the PhD Christmas party as well. As you can judge from my previous posts, there's way too much partying going on on our floors, so I guess it will be nice to retreat to the family for the next week or so. So Happy Monkey everyone!
BTW here are the pix...