Editors' Choice

Science  04 Jun 2004:
Vol. 304, Issue 5676, pp. 1415

    Ferroelectric Lithography

    1. Marc S. Lavine

    Much like a pen on a piece of paper or a stick dragged through sand on a beach, probe microscopy methods have been used to pattern substrates, either through the deposition of molecules or by scratching the substrate. Arrays of probes can pattern with more than one “ink,” but there are limits to the complexity of the patterns that can be formed. By combining a ferroelectric substrate with redox chemical reactions, Kalinin et al. show that they can sequentially fabricate complex metal patterns. Using either barium titanate or lead zirconate titanate as their substrates, through the application of a local electric field, domains were produced with different orientations of the ferroelectric polarization. When subject to light above the bandgap wavelength, electron-hole pairs form according to the local ferroelectric polarization, and thus when immersed in a solution containing metal ions, they will be preferentially deposited on the positively oriented domains. Ag, Rh, Pd, Pt, and Au were successfully applied, and structures using many metals and functional organics could be built through a series of patterning and photoreduction cycles. — MSL

    Adv. Mater. 16, 795 (2004).


    Healthy Appetite

    1. Paula A. Kiberstis

    Since its discovery 5 years ago, the stomach-derived peptide ghrelin has been the subject of intense research. Dubbed the “hunger hormone,” ghrelin stimulates food intake and body weight gain when administered to rodents, possibly through direct action on the brain. These observations prompted speculation that pharmacological inhibitors of ghrelin production would be valuable drugs for the treatment of obesity.

    To study the physiological role of ghrelin, Wortley et al. generated ghrelin-deficient mice. Surprisingly, the mutant mice showed normal food intake, basal metabolic rate, and body weight. In contrast to wild-type mice, however, ghrelin-deficient mice on a high-fat diet burned more fat than carbohydrate, suggesting that ghrelin may play a role in regulating the metabolic substrates used for the maintenance of energy balance. In a complementary study, Sun et al. found that mice deficient in the receptor for ghrelin also showed no major abnormalities in food intake or body composition. Together, the studies indicate that ghrelin is not an essential regulator of appetite, and its role in body weight regulation may be more complex than previously envisaged. — PAK

    Proc. Natl. Acad. Sci. U.S.A. 101, 8227; 4679 (2004)


    Snakeheads: Coming Down the Mountains

    1. Linda Rowan

    Snakeheads (Channidae) are air-breathing freshwater fish that can walk on the land and jump in the water. These large fish (0.3 to 1.8 m long) have heavy bones and sharp teeth. Unfortunately, they are predatory and have become a problem in North America, where they have been introduced accidentally and could decimate native species.

    An excellent fossil record of this robust fish indicates an origin in Pakistan at least 50 million years ago (Ma). Böhme tracked their migration into western Eurasia about 17 Ma and into Africa and eastern Asia about 8 Ma. In nature, extant snakeheads are restricted to African and Asian regions of high precipitation with temperatures greater than 20°C. Using these climatic restrictions, the author inferred that their migration about 17 Ma fits with a northward shift of the Intertropical Convergence Zone, and their migration about 8 Ma fits with the development of the Asian monsoon—two climatic shifts related to the uplift of the Alps, Pyrenees, and Himalayas. Thus, the mobility of the snakeheads traces paleoclimate and past tectonics. — LR

    Geology 32, 393 (2004).


    The Long and the Short of It

    1. Stephen J. Simpson

    Over a human lifetime, the immune system becomes dominated by an aging lymphocyte population, with the source of new cells diminishing and the existing pool being preserved to fight infection. As with any cell, the normal life span of a lymphocyte is marked by the gradual shortening of its telomeres, eventually resulting in replicative senescence of the cell. However, it is likely that this process is differentially regulated in T lymphocytes, depending on whether they are slowly dividing naïve T cells, short-lived highly proliferating effectors, or long-lived memory cells.

    Reed et al. looked at memory cell differentiation in humans who had previously been vaccinated with BCG. After injection of a second antigen, T cells responded vigorously at the site of challenge in the skin, acquiring an activated memory phenotype as they proliferated. Compared with other circulating T cells in these people, the responding cells displayed as much as eight times the level of telomere reduction 3 weeks after vaccination— the amount that would normally be seen in a resting cell over 1 year. Type 1 interferons present at the site of the response were largely responsible for the elevated telomere erosion, apparently through inhibition of the enzyme telomerase, which normally maintains telomere ends. — SJS

    J. Exp. Med. 199, 1433 (2004).


    Surfaces That Shake Faster

    1. Phil D. Szuromi

    The atoms at the surface of a solid are normally expected to have enhanced vibrational amplitudes, especially in the components normal to the surface, because fewer bonds constrain their movement in that direction. Typically, the increase is about 40 to 50% of the bulk value, but Van Hove notes that three surfaces—α-Al2O3(0001), α-Ga(010), and reconstructed Si(111)-(2×1)—have root mean square displacements double that of the bulk value, and at 90 K for water ice (0001), the increase may be as much as triple the bulk value. The author suggests that for these surfaces, the “back bonds” that hold the outermost layer in place are almost perpendicular to the surface plane, and that the vibrations are primarily soft bending modes rather than stretching modes. Such enhanced vibrations could play a role in surface pre-melting and catalysis. — PDS

    J. Chem. Phys.B 10.1021/jp040047x (2004).


    Prepare for Invasion

    1. Stella M. Hurtley

    An important factor in the relative seriousness of cancer is the invasiveness of the constituent tumor cells causing metastasis. Eustace et al. used two independent in vitro proteomic screens on fibrosarcoma cells in an attempt to define cell surface proteins involved in cellular invasiveness. In both screens, a molecular chaperone protein isoform, HSP90α, was found to be involved. HSP90α was expressed on the surface of invasive cells, where it interacted with matrix metalloproteinase 2 (MMP2), the protease implicated in digesting the extracellular matrix during tumor invasion. By inhibiting extracellular HSP90α, the activity of MMP2 was reduced and so was cellular invasiveness. Both fibrosarcoma and breast cancer cells express HSP90α on the cell surface. The authors suggest that impermeant inhibitors of HSP90α might be able to inhibit tumor invasiveness without affecting the important intracellular functions of other HSP90 isoforms. — SMH

    Nature Cell Biol. 10.1038/ncb1131 (2004)

  7. STKE

    A New Spin on an Old Cycle

    1. Elizabeth M. Adler

    The citric acid cycle, in which fuel molecules are broken down to yield energy and CO2, takes place in the mitochondria. However, citric acid cycle intermediates are found in the blood at micromolar concentrations, where their levels are controlled by absorption and extrusion by the kidneys, as well as by respiration and metabolism. He et al. isolated a compound that activated cells expressing the orphan heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) GPR91, which was identified as the citric acid cycle intermediate succinate. When applied to mammalian cells stably expressing human GPR91, succinate elicited increases in intracellular calcium and inositol phosphate, activated extracellular signal-regulated kinase, and inhibited adenosine 3',5'-monophosphate production. These data, together with an observed sensitivity to pertussis toxin, indicate that succinate stimulation of GPR91 activates at least two G protein-mediated signaling pathways (Gi or Go and Gq). A second citric acid cycle intermediate, α-ketoglutarate, activated a Gq pathway through the closely related orphan GPCR GPR99. The mRNAs for GPR91 and GPR99 are predominantly localized in the kidney, and intravenous injection of succinate elicited increases in plasma renin activity and mean arterial blood pressure in rats; in mice, the effect of succinate on blood pressure depended on GPR91 expression. Thus, succinate and α-ketoglutarate serve as ligands for GPR91 and GPR99, respectively, and succinate may thereby link cell metabolism and blood pressure regulation. — EMA

    Nature 429, 188 (2004).

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