Move Away or Stay Put
- Phillip D. Szuromi
Microcontact printing (μCP) of thiols on gold surfaces makes it feasible to create intricate patterns quickly and at low cost, but one limitation of this method in many applications is that the thiol molecules tend to diffuse into the bare regions of the gold surface. Trying to restrict the spreading by backfilling the bare spots in a follow-up step can blur pattern boundaries through prolonged exposure to solvent.
Dameron et al. show that the preadsorption of 1-adamantanethiol (AD) on gold surfaces creates a well-ordered but weakly bound layer that can be displaced by long-chain thiols, such as 1-decanethiol, that are transferred to the surface with a μCP stamp. By tuning the concentration of alkanethiols on the stamp and the contact time, patterns can be formed without the problem of lateral mixing of the adjacent self-assembled monolayers (SAMs). — PDS
Nano Lett. 10.1021/nl050981j (2005).
- MOLECULAR BIOLOGY
Me Instead of U
- Guy Riddihough
Small interfering (si)RNAs and micro (mi)RNAs play a central role in RNA silencing phenomena in which RNAs complementary to the si/miRNA are targeted for cleavage and destruction, translational silencing, or are (presumably) used as markers for directing heterochromatin formation. Much is known about the biogenesis of si/miRNAs, but what happens to them afterward?
In Arabidopsis, the HEN1 protein, implicated in RNA silencing, has been shown to add a methyl group to the 3' ends of miRNAs. Results from Li et al. show that Hen1 has a much wider scope, methylating many Arabidopsis siRNAs at their 3' ends, too. In the absence of HEN1, the unmethylated miRNAs and siRNAs have several uridine (U) residues added to their 3' ends, indicating that methylation interferes with uridylation. Intriguingly, it is the sense strand of the miRNA:miRNA* duplex that preferentially has a U tail added, hinting that the addition might occur after passage through the RISC complex, when the antisense miRNA* strand has already been jettisoned. The authors propose that methylation may stabilize small RNAs, a speculation supported by the previous observation that cleaved mRNA targets have also been observed to be U-tailed. — GR
Curr. Biol. 15, 1501 (2005).
Mergers and Acquisitions
- Paula A. Kiberstis
Many people living with diabetes for an extended time eventually develop a complication called diabetic neuropathy, a form of nerve damage that affects the extremities with symptoms that range from tingling and numbness to severe pain. Although many hypotheses have been proposed to explain how this nerve damage arises, the underlying mechanisms remain poorly understood.
A new study identifies an unexpected cellular culprit. From an analysis of rodent models, Terashima et al. find that diabetic neuropathy is accompanied by an aberrant fusion of bone marrow-derived (BMD) cells to neurons in the sciatic nerve and dorsal root ganglion. The fusion, which appears to involve a distinct subset of BMD cells that are marked by inappropriate expression of proinsulin, disrupts calcium handling in the neurons and triggers their premature death. The authors speculate that the diabetic state likely induces inappropriate gene expression in the BMD cells, producing molecules (such as tumor necrosis factor- α) that may be toxic to neurons and to the hybrid cells. Although BMD cells are often viewed in a favorable light for their potential therapeutic applications in repairing tissue damage, this study suggests that in certain contexts these cells may in fact be harmful. — PAK
Proc. Natl. Acad. Sci. U.S.A. 102, 12525 (2005).
- CLIMATE SCIENCE
Poring over the Past
- H. Jesse Smith
The concentration of CO2 in the atmosphere is understood to be a primary controller of climate, and high values are thought to be the main cause of a number of extended warm periods over the geological history of Earth. Additionally, atmospheric CO2 exerts a fundamental influence on the carbonate chemistry of the ocean, due to the solubility of CO2 in seawater, and therefore on calcifying marine organisms. A direct record of atmospheric CO2 concentration is available for less than the past 1 million years, so earlier periods must be studied by modeling or via proxies.
Haworth et al. use measurements of the density of stomata, the pores through which gas exchange occurs in plant leaves, in an extinct conifer to estimate the partial pressure of atmospheric CO2 during the mid-Cretaceous. This technique takes advantage of the observation that stomatal density is negatively correlated to the concentration of CO2 in the air. They find that CO2 was between 560 and 1200 parts per million over that period, values that fall on the low side of the range of previous estimates based on other techniques and are compatible with other evidence for relatively cool mid-Cretaceous climates. — HJS
Geology 33, 749 (2005).
Some Like It Hot
- Gilbert J. Chin
Ever since atomic-resolution models of enzymes from thermophilic organisms appeared a decade ago, one question has been how these macromolecules are able to function (that is, remain flexible) while maintaining their integrity (that is, remain stable) at temperatures approaching 100°C. Some of the explanations offered are an increase (relative to their mesophilic cousins) in the number of salt bridges and/or hydrogen bonds, a tighter packing of the hydrophobic core, and a higher percentage of amino acids incorporated into α helices and α sheets.
Berezovsky and Shakhnovich have carried out unfolding simulations on matched proteins from mesophiles and thermophiles, and performed comparative genome-based analysis of mesophilic and thermophilic bacteria and archaea. They find two solutions for thriving at high temperatures: make protein structure more compact by optimizing relatively weak interactions globally or engineer a few strong interactions into the sequence. They suggest that archaeal thermophiles (Pyrococcus furiosus) were favored by starting off long ago with more designable proteins that could be adapted to the primordial hothouse, whereas bacterial thermophiles (Thermotoga maritima) that entered hot environments later on were forced to reinforce their proteins with staples (salt bridges or perhaps disulfides). — GJC
Proc. Natl. Acad. Sci. U.S.A. 102, 12742 (2005).
Oxides as Reductants
- Jake S. Yeston
High-valent metal-oxo compounds are often used to mediate or catalyze oxidations of organic substrates. Nolin et al. have pursued the counterintuitive approach of using a rhenium-oxo complex to catalyze reduction. Rather than transferring oxygen to a hydrocarbon, the Re=O group facilitates hydride transfer from a silane to an imine. Unlike most catalysts used for this type of reaction, the Re complex is already in a high oxidation state and therefore fully stable in the open atmosphere. By appending a chiral bis(oxazoline) derivative to the Re center, the authors achieved enantioselective reductions of a broad range of aromatic imines under air at room temperature, with yields of 50 to 90% and very high enantiomeric excesses (92 to >99%). The imine nitrogens were protected with phosphinyl groups that could then be removed hydrolytically after reduction. The catalyst selectively reacts with the imine group even in the presence of esters and olefins, leading to a variety of chiral amines of potential use as pharmaceutical precursors. — JSY
J. Am. Chem. Soc. 10.1021/ja050831a (2005).
Neuropeptide-Mediated Receptor Trafficking
- Elizabeth M. Adler
Opioid receptors on pain-sensing neurons mediate the inhibitory effects of opiates on pain. The δ-opioid receptor, which is sorted into large dense-core vesicles (LDCVs) that carry secreted neuropeptides, is inserted into the membrane in response to opioid agonists or neuronal firing. Guan et al. noted that, in dorsal root ganglion neurons containing substance P, δ-opioid receptors colocalized with the neurotransmitter substance P in LDCVs, but in mice lacking preprotachykinin A gene, which encodes substance P and other tachykinin peptides, the receptors were absent from the vesicles. By expressing different portions of the substance P precursor, the authors determined that the δ-opioid receptor sorting signal was in the substance P domain and that sorting into LDCVs depended on the interaction of the signal with the third extracellular loop of the opioid receptor. Stimulus-dependent membrane insertion of the δ-opioid receptor was attenuated in preprotachykinin A-knockout mice, and both δ-opioid receptor-mediated spinal analgesia and morphine tolerance were eliminated. Thus, these results suggest an intriguing link between pain pathways (substance P) and analgesia (opioid receptor). — EMA
Cell 122, 619 (2005).