Nature Biotechnology pp 808 - 812 and pp 750 - 751

Paper-making is an environmentally damaging process involving the use of some very toxic chemicals. These chemicals are needed to remove lignin---a tough polymer imparting strength and rigidity to trees---from the wood pulp. In this issue, Vincent Chiang and his colleagues have provided a potential solution by producing trees that are greatly reduced in their lignin content and that also grow faster than their natural counterparts. The authors believe that these trees will not only require less harsh chemical treatments to process them into paper pulp, but may also produce more wood per acre, with important commercial and environmental implications.

Using a genetic engineering approach called antisense, in which the messenger RNA of a specific gene is targeted by a complementary RNA sequence, Chiang and his colleagues aimed to lower production of a gene encoding a key enzyme in the lignin biosynthetic pathway, 4-coumarate:coenzyme A ligase (4CL). By specifically targeting a 4CL type that is located in the woody part of the tree, but not in the epidermis of stems and leaves, they succeeded in lowering lignin production without affecting the production of other beneficial 4CL byproducts, such as photoprotective and antibiotic flavonoids. Unexpectedly, they also found that the growth of the aspen transgenic trees was significantly enhanced. Their findings could potentially lead to higher wood production per area of land, which could be important for conserving natural forests and reducing the environmental impact of forestry. When applied to more economically important trees, such as eucalyptus and pine, the technology could also have a significant impact on forestry---an industry that represents more than 1% of the world economy.

Nature Biotechnology pp 813 - 816

Anyone who has had a bout of flu knows that high temperature and fever often presage illness. Now an analogous phenomenon in plants has been exploited by researchers to predict infection in tobacco before any other outward disease symptoms are detectable on the plants. Using an infrared video imager, researchers at the University of Ghent in Belgium have noted temperature hot spots around virus-infected leaves eight hours before any signs of disease are visible. Their infrared technology could be useful for rapidly diagnosing plant pathogen infection, studying plant--pathogen interactions, and ultimately selecting pathogen-resistant plants in crop-breeding programs.

Dominique Van Der Straeten and her colleagues had previously noted that the accumulation of salicylic acid, a defense molecule produced by plants in response to infection, appears to affect leaf temperature. In the present study, they confirm that the accumulation of salicyclic acid in the leaves of tobacco plants infected with tobacco mosaic virus results in local temperature elevations of 0.3--0.4†C that can easily be imaged using a high-resolution infrared camera. When they looked at the phenomenon more closely, the temperature hike appeared to be due to the closure of stomata---pores on the leaf surface that regulate the release of water (rather like human sweat glands). Salicylic acid appears to induce stomata closure, thereby preventing water loss and leading to the rise in temperature. The authors suggest that the nondestructive and predictive aspects of the approach will be of wide use for the early detection of plant diseases.

Nature Biotechnology pp 768 - 774 and p 749

Matrix metalloproteinase (MMP) inhibitors show considerable promise as anticancer agents as MMP enzymes are involved in both the production of new blood vessels and the promotion of tumor invasion and metastasis. Unfortunately, the broad specificity of MMP inhibitors currently in trials has resulted in unacceptable side effects, such as severe joint and muscle pain, as well as disappointing efficacy. In this issue, Renata Pasqualini and her colleagues identify a tiny peptide that not only selectively targets tumor blood vessels, but also specifically inhibits MMP-2 and MMP-9---MMPs that are intimately associated with tumor growth and invasion. As Judah Folkman writes in an accompanying commentary, therapeutics based on this peptide might prove useful alternatives to broad MMP inhibitors currently in trials.

Using a method termed phage panning, in which peptides of interest are expressed on the coats of bacterial viruses (phage) and then screened for their binding affinity to MMP-9, Pasqualini's team identified four types of peptide sequence. Of these, a cyclic, soluble peptide CTTHWGFTLC showed potent inhibitory activity against MMP-2 and MMP-9 in vitro, but had little effect on other MMPs or serine proteases. When the investigators studied the ability of CTTHWGFTLC to affect the migration of blood-vessel-derived endothelial cells or tumor cells, the peptide inhibited migration of all types of human and mouse cells. What's more, CTTHWGFTLC prevented tumor growth and metastases when injected into mice, significantly improving the survival of tumor-bearing animals. As only tumor blood vessels, rather than other tissues, are targeted by the peptide, CTTHWGFTLC-based drugs appear to have a very promising therapeutic potential.

Nature Biotechnology pp 763 - 767

Although current confocal microscope approaches allow the visualization of live specimens, the high-intensity light they employ often causes damage and reduces the viability of cells or organisms under examination. Now, Jayne Squirrell and her colleagues have used a relatively new approach, termed two-photon laser scanning microscopy, to generate high-resolution images without affecting the developmental competence of mammalian embryos. They show that they can view live hamster embryos under the microscope, reimplant them into animals, and generate live offspring with no apparent developmental defects---a feat almost impossible for traditional techniques. Squirrell believes the approach will be useful for tracking cell migration and gene expression during embryonic development and may one day allow cancer researchers and clinicians to study cancer cell metastases through living tissue.

Current confocal microscopy approaches use standard, single-photon fluorescence. Although this is an effective way of visualizing specimens, the high-energy photons used to excite the fluorescent chemical (fluorophore) often cause damage to living cells and tissues, making prolonged observation impossible. Two-photon microscopy, in contrast, excites the fluorophore using two or more lower energy, longer wavelength infrared photons. Although this approach requires more photons to illuminate the specimen, damaging two-photon "hits" occur in only a limited focal plane on the slide, whereas the majority of the specimen receives only single-photon "hits," which are less damaging. Repeating the process through successive focal planes allowed Squirrell to reconstruct a three-dimensional image. Because the two-photon approach is much less damaging than single-photon microscopy, the specimen can be imaged over hours or even days. Squirrell cautions that the lasers used are still quite expensive and only available in a few facilities; however, the approach shows considerable promise as an alternative to standard confocal microscopy approaches in use today.