SCIENCE & TECHNOLOGY CONCENTRATES
STRONGER CERAMICS VIA 3-D PRINTING
TARGETING PRETERM LABOR
Additive manufacturing methods are widely used to make intricately shaped products from polymers and metals. Three-dimensional printed ceramics, however, which could benefit aeronautics and thermal protection systems, are much less common because of challenges imposed by many ceramics’ very high melting points. The limited range of products made this way is formed by using a gluelike material to bind ceramic powders or by fusing them with a laser. But those methods are slow and typically yield porous products that are weak and prone to cracking. Zak C. Eckel, Tobias A. Schaedler, and coworkers at the R&D firm HRL Laboratories may have a solution. The team has shown that various monomers can be cured with ultraviolet light in a 3-D printer to form intricately shaped polymer structures that can be pyrolyzed to yield strong, nonporous ceramic products (Science 2016, DOI: 10.1126/ science.aad2688). For example, from siloxane-based resins, the team formed silicon oxycarbide products that exhibit higher strength than ceramic foams of similar density.—MJ
About 15 million babies are born preterm each year, according to the World Health Organization. And current therapies don’t work well at preventing preterm birth. Evidence suggests that increases in intracellular Ca2+ levels help induce contractions, but blocking the main calcium channel doesn’t prolong gestation. David N. Cornfield of Stanford University and coworkers now show that a nonselective calcium channel, transient receptor potential vanilloid 4 (TRPV4), plays a role in controlling contractions in uterine tissue (Sci. Transl. Med. 2015, DOI: 10.1126/scitranslmed. aad0376). Expression of this protein in uterine cell membranes increases as pregnancy progresses. Uterine contractility decreases when TRPV4 is blocked and increases when it’s stimulated. In a mouse model of preterm labor, blocking TRPV4 delayed the onset of labor. The team gave pregnant mice RU-486 to chemically induce contractions. Giving the mice the TRPV4 antagonist HC 067047 delayed delivery of the pups. On the basis of these results, the researchers propose that TRPV4 may be a potential therapeutic target for preventing preterm labor.—CHA
CLEARING CELL JUNK IN ALZHEIMER’S In neurodegenerative diseases, certain proteins misfold and clump in the brain. A study of mice reports that aggregated tau—a protein associated with Alzheimer’s disease—can impair the function of cells’ proteasomes, garbage disposals that cells use to break down H misfolded proteins. N Ramping up the O O activity of proteasomes with a small CH3O molecule overcame Rolipram this impairment, leading to fewer tau aggregates and improved cognitive function. Natura Myeku of Columbia University and colleagues studied genetically engineered mice that express a tau protein prone to aggregate. Proteasomes isolated from these mice had less protein-dicing activity than those from normal animals. The team thinks that tau gloms on to the complex and disrupts its function. To help proteasomes overcome this disruption, the researchers turned to rolipram, a compound that triggers a path-
way that phosphorylates the proteasome, a mechanism known to increase proteasome activity. When given to four- to fivemonth-old engineered mice, the molecule led to more active proteasomes, fewer tau aggregates, and improved spatial memory, compared with control mice (Nat. Med. 2015, DOI: 10.1038/nm.4011).—MT
GENE TWEAKING BOOSTS SPLICEOSTATIN SYNTHESIS Pfizer scientists have reprogrammed an engineered microbe to improve the fermentation yield of the promising cancer drug thailanstatin A, a crucial step in its further development as a chemotherapy agent (Metab. Eng. 2015, DOI: 10.1016/j. ymben.2015.11.003). Thailanstatin A is a member of the spliceostatin family of bacterial natural products that interact with the spliceosome, the protein-RNA hybrid complex that is responsible for editing mRNA before the ribosome uses it to make proteins. Misregulation of mRNA splicing and mutations in the splicing machinery are associated with several cancers, and spliceostatins can put a halt to the problems. Alessandra S. Eustáquio and colleagues previously developed a biosynthetic pathway to make more potent and stable spliceostatins, but it was limited to producing 60 mg/L of thailanstatin A. The team found a bottleneck in the pathway, which they alleviated by increasing the expression of a gene to improve selective CEN.ACS.ORG
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formation of a key hydroxyl group. The reprogramming helped increase production to 2.5 g/L, a level sufficient to support clinical trials.—SR
NANOSCALE PATTERNING VIA BLOCK COPOLYMERS An advance in formulating block copolymers (BCPs) may help electronics manufacturers exploit BCP films for making ever smaller circuit features via photolithography (Nano Lett. 2015, DOI: 10.1021/ acs.nanolett.5b04602). BCPs can spontaneously form patterns with nanosized features on surfaces. But controlling those patterns is challenging. A BCP with a low χ value, a measure of the blocks’ tendency to segregate, generally cannot form patterns with features smaller than 10 nm. High-χ BCPs can form sub-10-nm features. But the difference in surface energy between the blocks of a high-χ BCP typically causes the blocks to stack parallel to the surface, which buries the pattern, making it useless. For lithographic patterning, the blocks must line up perpendicular to the surface. Dow Chemical’s Phillip D. Hustad and coworkers have shown that using a small amount of a second BCP can solve the alignment problem. One of that BCP’s blocks balances the surface tension that drives the main BCP’s blocks to lie down on the surface, causing them instead to align vertically. The other block keeps the second BCP anchored firmly on top of the main BCP, ensuring that its blocks remain aligned vertically.—MJ
