In This Issue
CHEMISTRY
Improved organic solar cells
Although the efficiency of organic solar cells is not yet high enough to render them commercially practical, they offer several attractions over crystalline silicon wafer cells. The organic cells are cheap, flexible, and could be manufactured in a “roll-to-roll” printing process. One barrier to higher efficiency organic cells is that, electrons can leak to the anode instead of flowing to the cathode in the highest-performing organic cells. Previous research has shown that this unavoidable limitation occurs when a phase-separated blend of a polymeric electron donor (P3HT) and an electron acceptor (PCBM) both make contact with the anode. In the past, this leakage was partially suppressed by interposing an electron-resistive, hole-conducting polymer layer (PEDOT:PSS) between the active organic blend and the anode. Michael Irwin et al. report that fabricating this layer from an inorganic semiconductor, NiO instead of PEDOT:PSS, improves solar cell efficiency from 4.0% to 5.2%. NiO is ideal, the authors say, because it is a p-type semiconductor and its conduction band minimum lies well above the lowest unoccupied molecular orbitals of P3HT and PCBM, creating a barrier to electron transport. The authors obtained optimum results with a 10-nm layer of NiO, which is sufficiently thin to be optically transparent. — K.M.
Architecture of the organic solar cell.
“p-Type semiconducting nickel oxide as an efficiency-enhancing anode interfacial layer in polymer bulk-heterojuction solar cells” by Michael D. Irwin, D. Bruce Buchholz, Alexander W. Hains, Robert P. H. Chang, and Tobin J. Marks (see pages 2783–2787)
GEOLOGY, ECOLOGY
You are what you drink
The isotopic makeup of each strand of human hair tells the story of where a person is from and where he or she has been. James Ehleringer et al. analyzed isotope ratios of hydrogen and water in human hair samples and found a close match between the ratios in hair and the local tap water. Isotope ratios of hydrogen and oxygen in water vary geographically throughout the United States and, because water is incorporated into the hair-forming protein, keratin, the water a person drinks leaves an isotopic signature in his or her hair. The authors visited 65 cities in the United States and collected hair samples from barbershops to compare with samples of local tap water, and found an 85% correlation between the isotope ratios in the hair and the tap water, without controlling for the origin of individuals or the origin of their food sources. The authors combined these results with known isotope distributions in the U.S. water supply to create a map of the country predicting where an individual has been based on the isotopic makeup of their hair. Even a single hair, the study shows, can be used for analysis, suggesting that the results could be a useful new tool for forensics. — C.E.
Predicted average hydrogen isotope ratios of human scalp hair.
“Hydrogen and oxygen isotope ratios in human hair are related to geography” by James R. Ehleringer, Gabriel J. Bowen, Lesley A. Chesson, Adam G. West, David W. Podlesak, and Thure E. Cerling (see pages 2788–2793)
CELL BIOLOGY
Stem cells tailored to individual patients
Patient-specific embryonic stem cells could generate biological therapeutics and tissues free from immunological burdens. However, the use of stem cells depends on the availability of pluripotent cells that can develop into all three embryonic tissue layers: ectoderm, endoderm, and mesoderm. William Lowry et al. developed a method to induce human dermal fibroblasts to revert into pluripotent stem cells. The authors transduced fibroblasts obtained from a single neonatal source with four transcription factors previouslyshown to “reprogram” rodent cells: Oct4, Sox2, C-Myc, and Klf4. These proteins have been extensively studied for their roles in cell proliferation, differentiation, survival, and the regulation of embryonic development. The induced pluripotent stem cells shared a nearly identical gene expression profile with two established human embryonic stem cell lines. Karyotypic analyses demonstrated that the reprogramming did not produce or require chromosomal alterations. The authors found that induced cells differentiated into all three embryonic germ layers, indicating their pluripotency. Application of this approach has potential to ameliorate human disease on a patient-by-patient basis, generating an unlimited supply of biocompatible pluripotent stem cells, according to the authors. — F.A.
Partial (green) and completely reprogrammed pluripotent stem cells (red).
“Generation of human induced pluripotent stem cells from dermal fibroblasts” by W. E. Lowry, L. Richter, R. Yachechko, A. D. Pyle, J. Tchieu, R. Sridharan, A. T. Clark, and K. Plath (see pages 2883–2888)
MEDICAL SCIENCES
Selectively targeting cancerous proteins
A single amino acid change in the BRAF protein is the most common cancer-causing protein kinase mutation. The mutation can lead to increased drug resistance and a more severe disease course. James Tsai et al. report on the discovery and preclinical evaluation of a compound that selectively acts on the form of the protein found in tumors, while sparing cells with the normal form. The authors' screening procedure identified PLX4720 as a potent inhibitor of the BRAF-V600E protein. The compound inhibited BRAF-V600E at a low concentration, with weaker effects on the wild-type protein and minimal effect on other protein kinases. The authors also tested the compound in cultured melanoma cells and mice. They found that the compound selectively caused cells with the BRAF-V600E mutation to enter cell cycle arrest or undergo apoptosis without harming normal cells. In mice with human melanoma xenografts, oral PLX4720 slowed or halted, and in some cases reversed, tumor growth, without toxicity to the mice. The authors say that PLX4720 is a promising candidate for human clinical trials, and that their study provides support for using scaffold-based screening to develop highly specific inhibitors against additional kinases involved in human malignancies and other diseases. — P.D.
Chemical structure of PLX4720.
“Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity” by James Tsai, John T. Lee, Weiru Wang, Jiazhong Zhang, Hanna Cho, Shumeye Mamo, Ryan Bremer, Sam Gillette, Jun Kong, Nikolas K. Haass, Katrin Sproesser, Ling Li, Keiran S. M. Smalley, Daniel Fong, Yong-Liang Zhu, Adhirai Marimuthu, Hoa Nguyen, Billy Lam, Jennifer Liu, Ivana Cheung, Julie Rice, Yoshihisa Suzuki, Catherine Luu, Calvin Settachatgul, Rafe Shellooe, John Cantwell, Sung-Hou Kim, Joseph Schlessinger, Kam Y. J. Zhang, Brian L. West, Ben Powell, Gaston Habets, Chao Zhang, Prabha N. Ibrahim, Peter Hirth, Dean R. Artis, Meenhard Herlyn, and Gideon Bollag (see pages 3041–3046)
MICROBIOLOGY
Aging bacteria shoulder the burden
Although bacteria do not get gray hair and wrinkles, they do age. One facet of this aging is the accumulation of cellular damage in the form of protein aggregates. When bacteria divide, one new daughter cell inherits a pole (membrane and cell surface components) that is older than the one inherited by its sibling. Cells arising from the new pole grow faster than the mother cell (rejuvenation), whereas the old pole cells grow more slowly (aging). However, which population inherits the cellular damage, and how it affects those cells, remains unclear. Ariel Lindner et al. show that bacteria use an asymmetric strategy to divvy up cellular damage. The authors tagged a chaperone protein (IbpA) involved in aggregate processing to track the inheritance of protein aggregates in the bacterium Escherichia coli. The authors discovered that, when these bacteria divided, protein aggregates were shunted to the daughter cell that inherits the older pole, which significantly reduces reproductive ability (aging). The results suggest that, at least in bacteria, evolution has devised a mechanism to shift the burden of cellular damage to the older generation, ensuring the perpetuation of the population. — M.M.
Protein aggregates (green) within an E. coli microcolony.
“Asymmetric segregation of protein aggregates is associated with cellular aging and rejuvenation” by Ariel B. Lindner, Richard Madden, Alice Demarez, Eric J. Stewart, and François Taddei (see pages 3076–3081)
