Editors' Choice

Science  28 May 2004:
Vol. 304, Issue 5675, pp. 1213

    Brightly Glows the Sexy Parasite

    In plants, and a few groups of microorganisms, Ca2+- dependent protein kinases (CDPKs) translate externally triggered calcium signals into cellular responses. Plasmodium malaria parasites have many CDPKs, and intracellular Ca2+ regulates the parasite's sexual development. Billker et al. looked at the process of Plasmodium gametocyte differentiation, after consumption of parasitized blood by mosquitoes, using a parasite reporter strain engineered to contain a fluorescent cytosolic calcium sensor. Within seconds of entering the mosquito gut, parasite differentiation starts. Host-derived xanthurenic acid shifts the microbial cytosolic pH from 7.4 to pH 8.0, triggering a Ca2+ burst that activates CDPK, possibly via guanylyl cyclase. Fifteen minutes later fertilization occurs. It appears that the type of CDPK programs male and female development, with CDPK4 apparently being male-specific. Importantly, CDPKs do not occur in the mammalian hosts of malaria parasites, making them interesting targets for anti-malarial drug discovery. — CA

    Cell 117, 503 (2004


    Fat Busters!

    Blood vessels are needed to support human tissues, and white adipose tissue is no exception. In fact, the formation of new blood vessels, a process called angiogenesis, spurs the expansion of white adipose tissue. Now Kolonin et al. show that destroying the supporting blood vessel network for white fat cells promotes loss of white adipose tissue in obese mice. The authors identified a specific marker for blood vessels that feed white adipose tissue, prohibitin. Using in vivo phage display, they identified a prohibitin-binding peptide, which was then linked to a proapoptotic peptide. Mice that were obese as the result of being fed a high-calorie diet were injected with the chimeric peptide. After nearly 1 month of treatment, white fat mass was reduced and normal body weight was restored without toxic side effects. Because human prohibitin is similar to the mouse molecule, it may be possible to design obesity therapies based either on the targeted delivery of drugs to fat or on the selective destruction of fat-associated blood vessels. — LDC

    Nature Med. 10.108/nm1048 (2004).


    The Quadruple Jump

    Rather like metal wires conduct electrons, photonic wires conduct light via transfers of excited-state energy. Heilemann et al. have designed a DNA-based wire that uses Förster resonance energy transfer across four donor-acceptor pairs of chromophores, such that excitation of Rhodamine Green at 488 nm (violet) results in emission from Atto 680 at 705 nm (red); in between, energy passes through tetramethylrhodamine, Atto 590, and LightCycler Red. The dyes are spaced 3.4 nm apart by attaching them to short DNA strands at 10-nucleotide (nt) intervals, and then hybridizing these short pieces to a 60-nt backbone. The maximal efficiency is about 90%, but a number of factors combine to lower the yield when measured in bulk. On the other hand, single-molecule spectroscopy uncovers the heterogeneity, with each spot exhibiting a predominant emission through only one of the five chromophores. Confirmation that the energy is transferred stepwise comes from prolonged excitation of single molecules, which results in sequential photobleaching and a shift in the emission from the red back toward the blue. — GJC

    J. Am. Chem. Soc. 10.1021/ja049351u (2004).


    Strained Stacking

    Both CdSe/ZnSe quantum wells and quantum dots (QDs) have been examined in detail, with one possible use as yellow, blue, or green light-emitting devices. Fabrication using QDs should produce devices that will have a lower lasing threshold and be less susceptible to defect-induced degradation effects than those produced using quantum wells. One challenge, though, is to assemble the QDs so that they have a uniform size distribution and periodic ordering. Stacking layers of dots with a separation layer of matrix material is effective for ordering in III-V compounds, because the strain induced by the lattice mismatch leads to heterogeneous nucleation of the subsequent layers of dots. Schmidt et al. used grazing incidence small-angle x-ray scattering to see if both vertical and lateral coupling of the dots occur in a CdSe system, which is a II-VI material. They grew the first layer of CdSe dots on a ZnSe buffer layer, but then used ZnSSe as the matrix material in order to avoid stacking fault formation. For a fixed spacer layer, they observed ordering when 10 and 5 layers were grown, but not for 3 layers. Similarly, when they kept the number of layers thick, they observed ordering only for the smaller spacer layer thicknesses. These observations confirm the idea that the initial QD layer acts as a seed layer for subsequent growth and thus drives the ordering process. By tuning the induced lattice strain, it should be possible to optimize the growth of the QD array. — MSL

    Appl. Phys. Lett. 84, 4367 (2004).


    Shifting into Reverse

    The right-handed DNA helix can be changed into left-handed Z-DNA by complexation with achiral agents such as metal ions or polyamines such as spermine. Similarly, synthetic helical polymers have been synthesized that can change helicity with changes in temperature. Miyake et al. show that a small CoII complex can reverse its helical sense in the presence of an achiral molecule, the relatively small nitrate anion. An x-ray structure shows that a chiral tetradendate ligand coordinates CoII with two amine nitrogens and two amide oxygen atoms in a λcis-α configuration. In solution, addition of nitrate switches the sign of the molecule's circular dichroism (CD) signal, whereas ClO4 and BF4 anions had no effect. Two equivalents of nitrate were needed to completely reverse the CD spectrum and convert the molecule to the δ isomer. Binding of nitrate to the amide hydrogen creates steric repulsions that destabilize the λ isomer. Unlike many other systems that show helical inversion, the kinetically labile CoII complex undergoes this transition rapidly (in under 1 min) at room temperature. — PDS

    J. Am. Chem. Soc. 10.1021/ja049130o(2004).


    Assessing Sediment Age

    Marine sediments, one of the most important sources of paleoclimatic and paleoceanographic data for the past 50,000 years, are often difficult to date by radiocarbon analysis. This is because they contain a wide variety of organic compounds of different carbon ages, so a unique date of deposition is typically impossible to determine. One way to overcome this problem is by determining the radiocarbon age of a single type of molecule of known origin, called a biomarker. Such a method has become technically possible only since the development of accelerated mass spectrometry in the 1980s. The question remains: Which types of biomarkers are best suited to provide accurate sediment ages? Smittenberg et al. address this question by conducting a survey of radiocarbon ages of a variety of compounds found in independently dated sediments from Saanich Inlet, Canada. Good ages were provided by one particular kind of molecule, crenarchaeol. Other biomarkers had more variable ages, and so were less useful for dating purposes. This confirms the idea that the microscopic, single-celled marine organisms, the Crenarchaeota, which produce this biomarker, used dissolved inorganic carbon as their carbon source. — HJS

    Paleoceanography 19, PA2012, 10.1029/2003PA000927 (2004).

  7. STKE

    Slit and Robo in Kidney Formation

    During development appropriate signals guide particular groups of cells to produce intricate organs, such as kidneys, but somehow don't influence other cells that might make supernumerary organs. Normally, each kidney develops from a single bud (the ureteric bud) that grows from a tubelike structure known as the nephric duct. This budding occurs in response to glial-derived neurotrophic factor (GDNF) secreted from adjacent mesenchymal tissue. The secreted ligand, Slit2, and its receptor, Robo2, are best known for their role in transmitting chemorepellent signals that guide migration of developing neurons. Grieshammer et al. now find that in mice lacking the Slit2 gene kidney development is disrupted, and three or more ureteric buds are often formed. Robo2 knockout animals had similar defects, indicating that failure of Slit-Robo signaling accounted for the problem. When Slit was absent, GDNF was produced in a larger area of the nephrogenic mesenchyme, which may explain the extended formation of multiple buds from the nephric duct. The mechanism by which Slit2-Robo2 signaling restricts GDNF expression remains unclear, but appears to be distinct from that underlying the known chemorepellent effects. — LBR

    Dev. Cell 6, 709 (2004).