Bio-Med Roundup

This month in Bio-Med Roundup:
  • Yu et al. reported the generation of human induced pluripotent stem (iPS) cells, while Hanna et al. showed that symptoms of sickle cell anemia can be ameliorated with iPS cells in a mouse model.
  • Klein et al. found that a gene variant that leads to fewer dopamine receptors impairs a person’s ability to learn from mistakes and inhibits feedback to a brain area that registers negative outcomes.
  • Yin et al. and Dodd et al. described circadian clock feedback mechanisms in plants and animals that incorporate small metabolites and signaling molecules.
  • Berg et al. described a novel carbon dioxide-fixation pathway used by marine Archaea that may be important in global carbon cycling.
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This month’s Bio-Med Roundup is sponsored by: Harvard Business School

Leadership and Strategy in Pharmaceuticals and Biotech, June 1–6, 2008
Leading Science-Based Enterprises, June 15–20, 2008
Consider it “innovation amplification.” When it comes to science-based businesses, the only true way to achieve competitive advantage is by managing innovation. But identifying scientific breakthroughs today that will have the most commercial appeal tomorrow is no easy feat. In response to this challenge, Harvard Business School has developed two highly targeted programs that help leaders of science-based businesses advance scientific knowledge and capture its value. Please visit www.exed.hbs.edu/category/sci.html to learn more.



MOLECULAR BIOLOGY
 
Sensing X Chromosome Pairs Before X Inactivation via a Novel X-Pairing Region of the Xic (7 December 2007)
S. Augui, G. J. Filion, S. Huart, E. Nora, M. Guggiari, M. Maresca, A. F. Stewart, E. Heard
Chromosome contact, the first step of X chromosome inactivation in females, is controlled by a 200-kilobase element upstream of the interaction region.

Orchestration of the DNA-Damage Response by the RNF8 Ubiquitin Ligase (7 December 2007)
N. K. Kolas, J. R. Chapman, S. Nakada, J. Ylanko, R. Chahwan, F. D. Sweeney, S.Panier, M. Mendez, J. Wildenhain, T. M. Thomson et al.
A key ubiquitin ligase builds polyubiquitin chains at radiation-caused DNA lesions, which subsequently recruit other factors necessary for repair.

Serine-7 of the RNA Polymerase II CTD Is Specifically Required for snRNA Gene Expression (14 December 2007)
S. Egloff, D. O’Reilly, R. D. Chapman, A. Taylor, K. Tanzhaus, L. Pitts, D. Eick, S. Murphy
Transcribing RNA Polymerase II Is Phosphorylated at CTD Residue Serine-7 (14 December 2007)
R. D. Chapman, M. Heidemann, T. K. Albert, R. Mailhammer, A. Flatley, M. Meisterernst, E. Kremmer, D. Eick
A serine within a repetitive element of mammalian RNA polymerase II is phosphorylated to modulate transcription and binding of factors for noncoding small nuclear RNAs.
See related Perspective.

Regulation of Replication Fork Progression Through Histone Supply and Demand (21 December 2007)
A. Groth, A. Corpet, A. J. L. Cook, D. Roche, J.Bartek, J. Lukas, G. Almouzni
During chromosome duplication, the chaperone Asf1 coordinates removal of histone proteins from DNA, DNA synthesis, and replacement of histones on the new strands.

Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation (21 December 2007)
S. Vasudevan, Y. Tong, J. A. Steitz
Although they inhibit translation in dividing cells, eukaryotic microRNAs can bind to the 3’-untranslated region of messenger RNAs and activate translation upon cell cycle arrest.
See related Perspective.


STRUCTURAL BIOLOGY/BIOCHEMISTRY

Structure of a Site-2 Protease Family Intramembrane Metalloprotease (7 December 2007)
L. Feng, H. Yan, Z. Wu, N. Yan, Z. Wang, P. D. Jeffrey, Y. Shi
Open and closed structures of an intramembrane protease reveal that it has six segments spanning the membrane and that its zinc active site is accessible only when it is open.

Stabilizing Isopeptide Bonds Revealed in Gram-Positive Bacterial Pilus Structure (7 December 2007)
H. J. Kang, F. Coulibaly, F. Clow, T. Proft, E. N. Baker
The protein pilin contains stabilizing intramolecular lysine-asparagine bonds that help strengthen the hairlike pili used by Gram-positive bacteria to adhere to their host.
See related Perspective.

The Structure of a Human p110α/p85α Complex Elucidates the Effects of Oncogenic PI3Kα Mutations (14 December 2007)
C.-H. Huang, D. Mandelker, O. Schmidt-Kittler, Y. Samuels, V. E. Velculescu, K. W. Kinzler, B. Vogelstein, S. B. Gabelli, L. M. Amzel
Mutations commonly associated with cancer result in disrupted interactions between the domains of a growth-related lipid kinase and alter its regulation or activity.

Combinatorial Synthesis of Peptide Arrays onto a Microchip (21 December 2007)
M. Beyer, A. Nesterov, I. Block, K. König, T. Felgenhauer, S. Fernandez, K. Leibe, G. Torralba, M. Hausmann, U. Trunk et al.
A method of electrically directing amino acids one at a time to precise spots on a microchip can be used for combinatorial in situ synthesis of 40,000 peptides per square centimeter.

Structure of Gαqp63RhoGEF-RhoA Complex Reveals a Pathway for the Activation of RhoA by GPCRs (21 December 2007)
S. Lutz, A. Shankaranarayanan, C. Coco, M. Ridilla, M. R. Nance, C. Vettel, D. Baltus, C. R. Evelyn, R. R. Neubig, T. Wieland, J. J. G. Tesmer
G protein–coupled receptors activate the small GTPase Rho through interaction of the Gαq subunit of the receptor with the exchange factor GEF to relieve inhibition of Rho.


NEUROSCIENCE

Genetically Determined Differences in Learning from Errors (7 December 2007)
T. A. Klein, J. Neumann, M. Reuter, J. Hennig, D. Y. von Cramon, M. Ullsperger
A gene variant that leads to fewer dopamine receptors also prevents people from learning from their mistakes and inhibits feedback to a brain area that registers bad outcomes.

Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase (7 December 2007)
M. M. Behrens, S. S. Ali, D. N. Dao, J. Lucero, G. Shekhtman, K. L. Quick, L. L. Dugan
A psychosis-inducing drug activates a brain inflammatory enzyme system that produces superoxide, which decreases activity in certain GABA-containing interneurons.

Rapid Changes in Throughput from Single Motor Cortex Neurons to Muscle Activity (21 December 2007)
A. G. Davidson, V. Chan, R. O’Dell, M. H. Schieber
As a result of subcortical processes, individual neurons in the motor cortex can quickly switch from controlling motoneurons in the spinal cord to having no effect on them.

Cognitive Recovery in Socially Deprived Young Children: The Bucharest Early Intervention Project (21 December 2007)
C. A. Nelson III, C. H. Zeanah, N. A. Fox, P. J. Marshall, A. T. Smyke, D. Guthrie
In a randomized controlled trial, children in Romania who were raised in foster care showed better cognitive development than did children raised in institutions.


CELL/DEVELOPMENTAL BIOLOGY

DUBA: A Deubiquitinase That Regulates Type I Interferon Production (7 December 2007)
N. Kayagaki, Q. Phung, S. Chan, R. Chaudhari, C. Quan, K. M. O’Rourke, M. Eby, E. Pietras, G. Cheng, J. Fernando Bazan et al.
Interferon secretion in response to viral infection is reduced by an enzyme that removes ubiquitin chains from proteins, an effect that could inhibit autoimmune disease.

Rev-erbα, a Heme Sensor That Coordinates Metabolic and Circadian Pathways (14 December 2007)
L. Yin, N. Wu, J. C. Curtin, M. Qatanani, N. R. Szwergold, R. A. Reid, G. M. Waitt, D. J. Parks, K. H. Pearce, G. B. Wisely, M. A. Lazar
A nuclear receptor is a heme sensor that coordinates circadian and metabolic functions by controlling the expression of a major clock component and the gene for generating sugar.
See related Perspective.

The Arabidopsis Circadian Clock Incorporates a cADPR-Based Feedback Loop (14 December 2007)
A. N. Dodd, M. J. Gardner, C. T. Hotta, K. E. Hubbard, N. Dalchau, J. Love, J.-M. Assie, F. C. Robertson, M. K. Jakobsen, J. Gonçalves et al.
In Arabidopsis, cyclic ADP ribose, a cytoplasmic signaling molecule, modulates the circadian clock, driving periodic Ca2+ release and boosting robustness of the oscillator.
See related Perspective.

Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells (21 December 2007)
J. Yu, M. A. Vodyanik, K. Smuga-Otto, J. Antosiewicz-Bourget, J. L. Frane, S. Tian, J. Nie, G. A. Jonsdottir, V. Ruotti, R. Stewart et al.
Human fibroblasts transfected with four genes exhibit the properties of embryonic stem cells.
See related Perspective.

Treatment of Sickle Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin (21 December 2007)
J. Hanna, M. Wernig, S. Markoulaki, C.-W. Sun, A. Meissner, J. P. Cassady, C. Beard, T. Brambrink, L.-C. Wu, T. M. Townes, R. Jaenisch
Skin cells from a mouse with sickle cell anemia can be genetically reprogrammed to be pluripotent stem cells, then differentiated and used to treat the diseased mouse.
See related Perspective.


GENETICS
 
Engineering Modified Bt Toxins to Counter Insect Resistance (7 December 2007)
M. Soberón, L. Pardo-López, I. López, I. Gómez, B. E. Tabashnik, A. Bravo
Bt toxin, a natural insecticide engineered into plants, can be modified to overcome insect resistance by forming damaging pores in pests independently of its normal receptor.
See related Perspective.


MICROBIOLOGY

A 3-Hydroxypropionate/4-Hydroxybutyrate Autotrophic Carbon Dioxide Assimilation Pathway in Archaea (14 December 2007)
I. A. Berg, D. Kockelkorn, W. Buckel, G. Fuchs
A widespread group of marine Archaea efficiently fix carbon dioxide via a newly described, 16-step metabolic cycle, potentially important for the global carbon budget.
See related Perspective.



This month’s Bio-Med Roundup is sponsored by:
Harvard Business School

At Harvard Business School’s Leading Science-Based Enterprises program, you will discover what it takes to successfully advance products from the research lab to the marketplace. From identifying commercially viable technology and financing its development to attracting top scientific talent and allocating resources across projects, you will emerge with the enterprise models and business strategies you need to identify and commercialize breakthroughs. Come explore the business behind the science. Please visit www.exed.hbs.edu/programs/lsbe/ to learn more.

At Harvard Business School’s Leadership and Strategy in Pharmaceuticals and Biotech program, you will discover what it takes to gain a competitive edge in an ever-shifting marketplace. From understanding global implications and innovating new business models to mitigating risk and analyzing intellectual property issues, you will emerge with the tools and skills you need to develop your own personal leadership model—one that positions you and your organization for a world of change. Become part of the new paradigm. Please visit www.exed.hbs.edu/programs/lspb/ to learn more.