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Beaker is Sanford-Burnham Medical Research Institute's science blog, updated frequently to highlight interesting research and news... especially relating to cancer, diabetes, neurodegenerative diseases, rare childhood diseases, stem cells and drug discovery.
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When patients receive a bone marrow transplant, they are getting a new population of hematopoietic stem cells. Fresh stem cells are needed [...]... Read more »
Sieburg HB, Rezner BD, & Muller-Sieburg CE. (2011) Predicting clonal self-renewal and extinction of hematopoietic stem cells. Proceedings of the National Academy of Sciences. info:/10.1073/pnas.1011414108
Cocaine produces its powerful high by stimulating “reward” signals in the brain, sending users back again and again for more. Cocaine gains this effect, in part, by stimulating a receptor called the metabotropic glutamate receptor 2 (mGluR2). Dr. Nicholas Cosford’s group is currently collaborating with Dr. Athina Markou at UC San Diego and Dr. P. [...]... Read more »
Barrett JE. (2010) mGluR2-Positive allosteric modulators: Therapeutic potential for treating cocaine abuse?. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 35(10), 2007-8. PMID: 20711209
Jin X, Semenova S, Yang L, Ardecky R, Sheffler DJ, Dahl R, Conn PJ, Cosford ND, & Markou A. (2010) The mGluR2 positive allosteric modulator BINA decreases cocaine self-administration and cue-induced cocaine-seeking and counteracts cocaine-induced enhancement of brain reward function in rats. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 35(10), 2021-36. PMID: 20555310
Dhanya RP, Sidique S, Sheffler DJ, Nickols HH, Herath A, Yang L, Dahl R, Ardecky R, Semenova S, Markou A.... (2010) Design and Synthesis of an Orally Active Metabotropic Glutamate Receptor Subtype-2 (mGluR2) Positive Allosteric Modulator (PAM) That Decreases Cocaine Self-Administration in Rats. Journal of medicinal chemistry. PMID: 21155570
by Bruce Lieberman in Beaker
Even if you disregarded the taste buds in your mouth and ate a poisonous berry, your digestive system knows better and, as Dr. Timothy Osborne’s research shows, tries to make up for your recklessness.... Read more »
Jeon TI, Seo YK, & Osborne TF. (2011) Gut Bitter Taste Receptor Signaling Induces ABCB1 through a Mechanism Involving CCK. The Biochemical journal. PMID: 21592089
In 2006, a landmark Science paper set a new dogma for reproductive/developmental biology: retinoic acid in the ovaries triggers meiosis in utero, while an enzyme in the testes called Cyp26b1 keeps retinoic acid at bay and prevents meiosis from occurring until after birth. Just one problem – that paradigm is wrong. A recent Nature Communications paper sets the record straight.
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Kumar S, Chatzi C, Brade T, Cunningham TJ, Zhao X, & Duester G. (2011) Sex-specific timing of meiotic initiation is regulated by Cyp26b1 independent of retinoic acid signalling. Nature Communications, 151. PMID: 21224842
Doctors have noticed for decades that people with Down Syndrome seldom develop cancers. Down Syndrome results from an extra copy of chromosome 21, leading scientists to wonder if something about that particular piece of the genome could protect against cancer. A few years ago, researchers at Johns Hopkins University tested that hypothesis. They added several [...]... Read more »
Múnera, J., Ceceña, G., Jedlicka, P., Wankell, M., & Oshima, R. (2011) Ets2 Regulates Colonic Stem Cells and Sensitivity to Tumorigenesis. STEM CELLS, 29(3), 430-439. DOI: 10.1002/stem.599
by Guest Blogger in Beaker
A recent study from the Bodmer lab shows that fruit flies, mice, and humans all share a common molecular pathway that guides heart development and function.... Read more »
Qian L, Wythe JD, Liu J, Cartry J, Vogler G, Mohapatra B, Otway RT, Huang Y, King IN, Maillet M.... (2011) Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species. The Journal of cell biology, 193(7), 1181-96. PMID: 21690310
Roughly 50,000 people in the United States are affected by some type of muscular dystrophy, a condition characterized by debilitating muscle loss. Duchenne muscular dystrophy (DMD), the most common form of the disease, is caused by a mutation in the dystrophin gene. Without dystrophin, the interior muscle fiber frame can’t properly connect to the surrounding [...]... Read more »
Sacco A, Mourkioti F, Tran R, Choi J, Llewellyn M, Kraft P, Shkreli M, Delp S, Pomerantz JH, Artandi SE.... (2010) Short Telomeres and Stem Cell Exhaustion Model Duchenne Muscular Dystrophy in mdx/mTR Mice. Cell. info:/10.1016/j.cell.2010.11.039
Yesterday, we introduced a study in which scientists in Sanford-Burnham’s NCI-Designated Cancer Center and Conrad Prebys Center for Chemical Genomics were looking for compounds that regulate invadopodia, cellular projections that allow cancer cells to invade and metastasize. They used robotic technology and automated microscopy to screen a library of pharmacologically active compounds—compounds already known to [...]... Read more »
Quintavalle, M., Elia, L., Price, J., Heynen-Genel, S., & Courtneidge, S. (2011) A Cell-Based High-Content Screening Assay Reveals Activators and Inhibitors of Cancer Cell Invasion. Science Signaling, 4(183). DOI: 10.1126/scisignal.2002032
by in Beaker
Atherosclerotic plaque is the fatty material that builds up on arterial walls, where it can lead to heart disease and stroke. Atherosclerosis is currently treated with dietary changes, angioplasty (which uses a balloon to move the plaque aside) or more invasive procedures. Using drugs to break up these fatty plaques would be an enticing alternative, [...]... Read more »
Hamzah J, Kotamraju VR, Seo JW, Agemy L, Fogal V, Mahakian LM, Peters D, Roth L, Gagnon MK, Ferrara KW.... (2011) Specific penetration and accumulation of a homing peptide within atherosclerotic plaques of apolipoprotein E-deficient mice. Proceedings of the National Academy of Sciences of the United States of America. PMID: 21482787
The iPS cell approach to regenerative medicine is tantalizing because these cells could be derived from a patient’s own cells and are therefore less likely to face immune rejection. In the past few weeks, however, a slew of papers have indicated that the therapeutic potential of iPS cells might be limited by reprogramming errors and genomic instability. Now an alternative type of reprogrammed stem cell enters the mix. In PNAS, Dr. Evan Snyder and his collaborators outline a method to obtain a ........ Read more »
Kim, K., Lee, H., Jeong, H., Li, J., Teng, Y., Sidman, R., Snyder, E., & Kim, S. (2011) Self-renewal induced efficiently, safely, and effective therapeutically with one regulatable gene in a human somatic progenitor cell. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1019743108
Targeting peptides developed by Dr. Masanobu Komatsu and colleagues could be used to deliver therapeutic compounds and imaging probes directly to lungs affected by pulmonary arterial hypertension (PAH).... Read more »
Urakami T, Järvinen TA, Toba M, Sawada J, Ambalavanan N, Mann D, McMurtry I, Oka M, Ruoslahti E, & Komatsu M. (2011) Peptide-directed highly selective targeting of pulmonary arterial hypertension. The American journal of pathology, 178(6), 2489-95. PMID: 21549345
Alzheimer’s disease is characterized by abnormal proteins that stick together in little globs, disrupting cognitive function (thinking, learning, and memory). These sticky proteins are mostly made up of beta-amyloid peptide. A better understanding of these proteins, how they form, and how they affect brain function will no doubt improve the diagnosis and treatment of Alzheimer’s [...]... Read more »
Qu, J., Nakamura, T., Cao, G., Holland, E., McKercher, S., & Lipton, S. (2011) S-Nitrosylation activates Cdk5 and contributes to synaptic spine loss induced by -amyloid peptide. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1105172108
Since cellular stress due to misfolded proteins in the endoplasmic reticulum (ER) has been implicated in many human diseases, a new appreciation of the cell cycle’s role in this process might help improve our understanding of conditions ranging from Alzheimer’s disease to cancer.... Read more »
Chen M, Gutierrez GJ, & Ronai ZA. (2011) Ubiquitin-recognition protein Ufd1 couples the endoplasmic reticulum (ER) stress response to cell cycle control. Proceedings of the National Academy of Sciences of the United States of America, 108(22), 9119-24. PMID: 21571647
Cells come and go throughout our lifetime. Some live a long time (like brain cells), while others constantly grow, divide and die. Cell death is a process that must be carefully managed – too many cells dying in the brain leads to neurodegenerative diseases like Alzheimer’s, while not enough cell death allows tumors to form. [...]... Read more »
Oberst A, Dillon CP, Weinlich R, McCormick LL, Fitzgerald P, Pop C, Hakem R, Salvesen GS, & Green DR. (2011) Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature. PMID: 21368763
As the United States pauses to observe the 10th anniversary of the September 11th terrorist attacks, we reflect on the research advances that contribute to new counterterrorism measures—understanding anthrax, for example—and the health of our soldiers in Iraq and Afghanistan, including under-studied conditions such as traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD).... Read more »
by Bruce Lieberman in Beaker
It’s an amazing and frightening thought: some of the same genetic signaling that shapes the development of an embryo also drives the spread of cancer. But that’s what a new study by Dr. Sara Courtneidge’s lab suggests. Dr. Courtneidge’s lab primarily studies cancer metastasis—the spread of cancer from a tumor to another part of the [...]... Read more »
Murphy DA, Diaz B, Bromann PA, Tsai JH, Kawakami Y, Maurer J, Stewart RA, Izpisúa-Belmonte JC, & Courtneidge SA. (2011) A Src-Tks5 Pathway Is Required for Neural Crest Cell Migration during Embryonic Development. PloS one, 6(7). PMID: 21799874
Not all cells in a tumor are equal. They have different genes, proteins and behaviors and while some are easily killed, others are more resistant to cell-destroying therapies. In some cancers, a few of these hardier cells are cancer stem cells and they may be the culprits behind tumor formation and drug resistance. Much like [...]... Read more »
Hebbard LW, Maurer J, Miller A, Lesperance J, Hassell J, Oshima RG, & Terskikh AV. (2010) Maternal embryonic leucine zipper kinase is upregulated and required in mammary tumor-initiating cells in vivo. Cancer research, 70(21), 8863-73. PMID: 20861186
Researchers in Dr. Gregg Duester’s lab study retinoic acid, an active form of vitamin A. They want to know how retinoic acid tells the right body parts to form in the right places at the right time in a developing embryo. To figure out retinoic acid’s role, they compare mice with and without the ability [...]... Read more »
Chatzi, C., Brade, T., & Duester, G. (2011) Retinoic Acid Functions as a Key GABAergic Differentiation Signal in the Basal Ganglia. PLoS Biology, 9(4). DOI: 10.1371/journal.pbio.1000609
Bike accidents, C-sections and battlefield wounds can all leave scars. But those are only the scars you can see. Any tissue can scar (not just skin), making scar tissue more than a cosmetic problem. Heart muscle, for example, can scar after a heart attack, and the lungs, kidneys, the liver, and many other tissues can [...]... Read more »
Jarvinen TAH, & Ruoslahti E. (2010) Target-seeking anti-fibrotic compound enhances wound healing and suppresses scar formation in mice. Proceedings of the National Academy of Sciences. info:/
Dr. Daniel Kelly and colleagues show that generating energy from sugar leads to fitter muscles and increased athletic ability in mice.... Read more »
Zhenji Gan, Eileen M. Burkart-Hartman, Dong-Ho Han, Brian Finck, Teresa C. Leone, Emily Y. Smith, Julio E. Ayala, John Holloszy, & Daniel P. Kelly. (2011) The nuclear receptor PPARβ/δ programs muscle glucose metabolism in cooperation with AMPK and MEF2. Genes . info:/doi:10.1101/gad.178434.111
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