My Labonews

Optimizing the sensory characteristics and acceptance of canned cat food: use of a human taste panel. Link

Man I really love this chart. Should be expanded though!
Tastes Like Chicken?, Joe Staton, Museum of Comparative Zoology, Harvard University.

Well you may be interested that I just co-authored my first scientific publication. It's nothing like a first author, I know, still it is a decent journal (Human Molecular Genetics) and a nice reward for my internship in Harvard last year.
A hypomorphic allele of Tsc2 highlights the role of TSC1/TSC2 in signaling to AKT and models mild human TSC2 alleles.[Pubmed]

So much to do, I almost forgot telling you about this years' Ig Nobel prizes, sponsored and organized by Improbable Research. Here are the winning publications:

• NUTRITION PRIZE: "The Role of Auditory Cues in Modulating the Perceived Crispness and Staleness of Potato Chips," Massimiliano Zampini and Charles Spence, Journal of Sensory Studies, vol. 19, October 2004,  pp. 347-63.
• PEACE PRIZE:  "The Dignity of Living Beings With Regard to Plants. Moral Consideration of Plants for Their Own Sake" 
• BIOLOGY PRIZE:  "A Comparison of Jump Performances of the Dog Flea, Ctenocephalides canis (Curtis, 1826) and the Cat Flea, Ctenocephalides felis felis (Bouche, 1835)," M.C. Cadiergues, C. Joubert, and M. Franc, Veterinary Parasitology, vol. 92, no. 3, October 1, 2000, pp. 239-41.
• MEDICINE PRIZE:  "Commercial Features of Placebo and Therapeutic Efficacy," Rebecca L. Waber; Baba Shiv; Ziv Carmon; Dan Ariely, Journal of the American Medical Association, March 5, 2008; 299: 1016-1017. Definitely my favorite one... the authors demonstrated that expensive fake medicine is doing better than cheap fake medicine.
• COGNITIVE SCIENCE PRIZE: "Intelligence: Maze-Solving by an Amoeboid Organism," Toshiyuki Nakagaki, Hiroyasu Yamada, and Ágota Tóth, Nature, vol. 407, September 2000, p. 470.
• ECONOMICS PRIZE: "Ovulatory Cycle Effects on Tip Earnings by Lap Dancers: Economic Evidence for Human Estrus?" Geoffrey Miller, Joshua M. Tybur, Brent D. Jordan, Evolution and Human Behavior, vol. 28, 2007, pp. 375-81.
• LITERATURE PRIZE: "You Bastard: A Narrative Exploration of the Experience of Indignation within Organizations," David Sims, Organization Studies, vol. 26, no. 11, 2005, pp. 1625-40.
  

Riding along the earlier placebo post, here's another interesting publication:
Crum AJ Langer EJ. Mind-Set Matters: Exercise and the Placebo Effect. Psychological Science 18(2) 165-171, 2007.
What the authors basically did was to divide two groups of cleaning ladies from an hotel who were actively getting a lot of exercise by doing all of their usual work. However, most did not perceive this to be exercise at the beginning of the study. They then chose one group and taught them about all the active work they were doing, burning so and so many calories by vacuum cleaning, making the beds etc... The other group did not receive this (truthful) information. After 4 weeks, the authors measured some objective health measures like weight, body fat, body mass index, waist-to-hip ratio and blood pressure. The group knowing about all the good exercise they were getting had better results in all of these categories after only 4 weeks, while the other did not. Is it really as simple as that?

Wouldn't it be jolly good if we'd decide what we consume by irrelevant criteria such as quality? Well, the more expensive the wine, the better it tastes. Are we realy that easy to fool?

Link: http://www.apa.org/journals/features/psp7761121.pdf

Worth a reading: Abstract: People tend to hold overly favorable views of their abilities in many social and intellectual domains. The authors suggest that this overestimation occurs, in part, because people who are unskilled in these domains suffer a dual burden: Not only do these people reach erroneous conclusions and make unfortunate choices, but their incompetence robs them of the metacognitive ability to realize it. Across 4 studies, the authors found that participants scoring in the bottom quartile on tests of humor, grammar, and logic grossly overestimated their test performance and ability. Although their test scores put them in the 12th percentile, they estimated themselves to be in the 62nd. Several analyses linked this miscalibration to deficits in metacognitive skill, or the capacity to distinguish accuracy from error. Paradoxically, improving the skills of participants, and thus increasing their metacognitive competence, helped them recognize the limitations of their abilities. GET the full Paper.
(Via)

Sometimes I wish I were in medicine. They can publish anything! VIA

Ott et al. Intestinal obstruction after ingestion of a beer-filled condom at the Munich Octoberfest. The American journal of gastroenterology (2003) vol. 98 (2) pp. 512-3 

Link: http://researchblogging.org

Here's the link to a very promising project I've read about only now in The Questionable Authority Blog. I'm eager to participate myself! Quoting: 

Do you like to read about new developments in science and other fields? Are you tired of "science by press release"? Research Blogging is your place. Research Blogging allows readers to easily find blog posts about serious peer-reviewed research, instead of just news reports and press releases.
How it works: Bloggers -- often experts in their field -- find exciting new peer-reviewed research they'd like to share. They write thoughtful posts about the research for their blogs. Bloggers register with us and use a simple one-line form to create a snippet of code to place in their posts. This snippet not only notifies our site about their post, it also creates a properly formatted research citation for their blog. Our software automatically scans registered blogs for posts containing our code snippet. When it finds them, it indexes them and displays them on our front page -- thousands of posts from hundreds of blogs, in one convenient place, organized by topic. The quality of the posts listed on our site is monitored by the member bloggers. If a post doesn't follow our guidelines, it is removed from our database. Borderline cases may be discussed in our forums. We also provide bloggers with an icon they can use to show when they're talking about a peer-reviewed work that they've read and analyzed closely. There are already hundreds of blog posts using the icon, and we're working on a way to make them even easier to find. If you're a blogger who writes about serious research, Research Blogging offers you a way to distinguish your serious posts from news, politics, family, bagpipes, and so on. We can direct your regular readers -- and new readers -- to the posts you've worked the hardest to create. All you need to get started is a blog and our guidelines... and a peer-reviewed research report that you'd like to discuss.

 

Just for fun, if you like to read some scientific nonsense:

• Scott et al. Naming the Loch Ness monster. Nature (1975) No need to comment there, still amazing that it made a 3 page paper publication in Nature!!!
• Mullis et al. Cosmological Significance of Time Reversal. Nature (1968): Written by Kary Mullis, who later received the Nobel prize for his contributions to the PCR reaction. He apparently wrote this completely lunatic article while being on LSD, interestingly it was published, in Nature too (what does this tell us about Nature)! After a 1993 win in Chemistry for inventing the PCR gene-copying technique, Mullis became a beach bum, a surfer and nearly a witness for O.J. Simpson. [Time]. More in his book Dancing Naked in the Mind Field here.

We all know that biologists can be very geeky sometimes, especially when it comes to advertisements in scientific journals... Well this one is no exception!

- Stephan Wullschleger, Robbie Loewith, and Michael N. Hall, - DOI 10.1016/j.cell.2006.01.016 - Cell 124, February 10, 2006 - Elsevier Inc. -

TOR or target of rapamycin is a 280 kDa Ser/Thr kinase belonging to the phosphatidylinositol kinase-related kinase (PIKK), integrating important cues from a cells environment (such as growth factors via PI3K/IGF) and regulating the cells growth (when and where) and metabolism among others, suggesting its implication in cancer, autoimmunity, metabolic disorders and cardiovascular disease. There are two major TOR complexes, TORC1, containing either TOR1 or TOR2 in yeast or mTOR in mammals and which is sensitive to rapamycin, and TORC2,containing TOR2 in yeast and mTOR in mammals and which is responsible for actin polymerization. TOR was first identified in two mutations in Saccharomyces cerevisiae making them resistant to the growth inhibiting properties of rapamycin, the same experiment showing that rapamycin inhibits TOR by forming a complex with peptidyl-prolyl cis/trans isomerase FKBP12 and binding to its N-terminal binding site (FR. So far, every examined eucaryotic genome contains at least one copy of the TOR gene, some yeast strains containing two.
Raptor, a 150kDa protein, is one of the better known components associated with mTOR in TORC1, containing a highly conserved N-ter domain, and several HEAT and WD40 repeats. It seems possible that there are more than one interaction site between those two molecules. Raptor seems to work positively in mTOR signaling as its knockout simulates rapamycin treatment.
mLST8 is a 36kDa protein, containing multiple WD40 repeats and binding the kinase domain of mTOR.
mTOR is connected to the Pl3K pathway via the TSC1-TSC2 heterodimer, where TSC2 acts as GAP (GTPase-activating protein) for Rheb which in its turn binds to the kinase domain of mTOR.
Amino acid starvation leads to rapid dephosphorylation of mTORC1 effectors S6K1 and 4E-BP1.
mTORC1 senses the energy status of the cell via the AMP-activated protein kinase (AMPK). AMPK gets activated by AICAR and inhibits phosphorylation of S6K1 and 4E-BP1. AMPK also phosphorylates TSC2, thereby inhibiting mTORC1 signaling.
Tumor suppressor LKB1 is an upstream kinase for AMPK.
TORC1 senses hypoxia through REDD1 an REDD2 which are activate by HIF1. REDD's inhibiting function towards mTOR is located downstream to Akt and upstream of TSC1-TSC2 and is independent of LKB1-AMPK.
DNA damage activates p53 and inhibits mTOR via AMPK-TSC2.
mTOR also has a redox sensor in its FATC domain.
mTORC1 controls translation via S6K1 (which phosphorylates 40S ribosomal protein S6) and 4E-BP1.
TOR controls Pol1 via RRN3/TIF1A (an important initiation factor).
Quoting:“There seems to be a negative feedback loop between the TSC-mTOR-S6K1 pathway to the upstream, insulin-responding IRS-PI3K-PDK1-Akt pathway”.
Recent studies suggest that tumors are sensitive to mTORC1 inhibitation if they show defective activation in the PI3K pathway.

-Ines Raineri, Daniel Wegmueller, Brigitte Gross, Ulrich Certa and Christoph Moroni - Nucleic Acids Research, 2004, Vol. 32, No. 4 1279-1288 - DOI: 10.1093/nar/gkh282 -

In this paper, the authors investigated the effect on mRNA stability by targeting siRNAs against AU-bindin proteins. More precisely, they targeted AUF1 isoforms (arising through differential splicing) along with HuR and BRF1 in HT1080 cells with GFP linked to a terminal 3' ARE (AU-rich element). AUF1 not only affects mRNA stability but is also involved in telomere maintainance and transcriptional activation. AREs influence mRNA stability by inducing rapid shortening of the poly-A tail, leading to exosomal degradation. Targeting HuR decreased fluorescence, whereas BRF1 increased it, with no effect shown in treating both isoforms, suggesting an antagonistic control of ARE-mRNA stability. Interestingly, downregulating all 4 isoforms did not show any effects, whereas selective targeting of p40AUF1/p45AUF1 did so. This suggests that relative levels of the different isoforms influences the net mRNA stability rather than the total AUF1 level.

- Esther Conde, Barbara Angulo, Moying Tang, ManuelMorente, Juan Torres-Lanzas, Angel Lopez-Encuentra, Fernando Lopez-Rios, and Montserrat Sanchez-Cespedes - Clinical Cancer Research 2006;711 12(3) February 1, 2006 - www.aacrjournals.org -

A number of patients with lung adenocarcinomas present activating mutations in the EGFR gene. These mutations can make the cells sensitive to tyrosine kinase inhibitor treatment. To study the molecular characteristics of these mutations, the authors sequenced several carcinomas and cancer cell lines, assessed the number of copies of the EGFR and the ErbB2 genes by FISH and the levels of several downstream genes by immunohistochemistry. They found amplification of the EGFR in 14% of the cases, mutations in EGFR in 13% and an increase of mTOR signaling in comparison with wt EGFR, indicated by an increase of S6 proteins. Also it was shown that EGFR mutations do not coexist with amplification in ErbB2 amplification in lung adenocarcinomas.

– Georg Stoecklin, Marco Colombi, Ines Raineri, Sabrina Leuenberger, Michel Mallaun, Martin Schmidlin, Brigitte Gross, Min Lu, Toshio Kitamura, Christoph Moroni – The EMBO Journal Vol.21 No.17 pp. 4709-4718, 2002 -

The ARE (AU-rich element) is a cis-regulatory element in the 3'UTR of proteins like cytokines and growth factors, marking the mRNA for a rapid decay, as the expression of these genes should normally be at a very low level.Upon signaling via the c-jun, p38 MAPK and PI3K pathways regulates the stability of their mRNA, and after the activation phase, rapid decay in restored. This is important as a deregulation of ARE mRNA stability can contribute to the formation of cancer and inflammation. Several AU binding proteins (AUBPs) have already been identified, and the aim of this work was to identify those proteins that exert an effect of the mRNA turnover. Therefor they engineered a cell line with a fusion of GFP and IL3. This a good indicator for mRNA stability because of the AREs in the 3'UTR of IL3. This cell line was mutagenized and the results screened for an overexpression of GFP. 3 cell lines were found with in trans mutations of the ARE pathway, and the researchers managed to identify the gene responsible in one of the mutants via retroviral cDNA library transfer and subsequent PCR of the clone presenting a successfully restored mRNA decay. This gene was BRF1 or butyrate response factor-1. These results were backed up by siRNA silencing experiments.