This Week in Science

Science  28 Aug 2009:
Vol. 325, Issue 5944, pp. 1043
  1. Hidden Pockets of Resistance


      Groups of bacteria indulge in gene swapping at frequencies correlated with prevailing selection pressures and phylogenetic relatedness. When assaulted by antibiotics, antibiotic resistance genes become favored currency for exchange among bacteria. During sequencing of human gut microflora, Sommer et al. (p. 1128) found a very large reservoir of distinct genes that, when put into Escherichia coli, conferred resistance to a wide range of drugs. By contrast, analysis of the culturable aerobic gut microbiome, which constitutes a tiny fraction of the entire gut flora, revealed resistance genes highly similar to those harbored by human pathogens. Although there is a risk of novel modes of antibiotic resistance emerging from this reservoir, because they are evolutionarily distant, gene transfer between pathogens and the poorly known majority of the microbiome might actually be quite restricted.

    1. Toward New Scaffolds

        Most existing antibiotics are derived from a small number of core molecular structures or scaffolds. As more and more pathogens emerge that are resistant to existing antibiotics, Fischbach and Walsh (p. 1089) review why renewed efforts must be made to find not only new antibiotics but new scaffolds. Approaches in the areas of natural products, synthesis, and target-based discovery are all yielding promising antibiotics candidates. The battle against resistance should also involve researching narrow-spectrum antibiotics and using combination therapies to extend the usefulness of drugs with high intrinsic resistance rates.

      1. Adapting Coat Color

          Simple phenotypic changes can often be the target of selection—for example, variations in coat color that provide protection against detection by predators. Linnen et al. (p. 1095) explore the underlying molecular mechanisms behind the production of pale deer mice living on the light-colored Nebraska Sand Hills. The mice that live on the sand are significantly lighter in color than conspecifics living nearby on darker soils. This lighter color was found to be due to de novo changes at the Agouti coat color locus. Thus, rapid adaptive change does not always rely on preexisting genetic variation.

        1. Mind the Pseudogap

            Below the transition temperature, an energy gap opens in superconductors, which effectively protects the superconducting phase. Above the transition temperature, the gap closes, creating excitations and a loss of superconductivity. In the high-temperature superconducting cuprates, however, the gap persists above the transition temperature. Understanding the electronic structure of this pseudogap region is important in understanding the mechanism of superconductivity in the cuprates. Lee et al. (p. 1099; see the Perspective by Norman) use high-resolution, temperature-dependent scanning tunneling microscopy to reveal that the pseudogap regime is an incoherent (or phase-disordered) d-wave superconductor.

          1. Atomic Imaging Within Adsorbed Molecules

              CREDIT: GROSS ET AL.

              Scanning tunneling microscopy provides atomic resolution images of surfaces and adsorbed atoms, but imaging atoms within an organic molecule adsorbed on a surface is difficult because contrast is lacking in the states that determine the tunneling current. Atomic force microscopy should be able to resolve atoms through changes in short-range chemical forces, but resolution is lost if the scanning tip undergoes modifications or if it moves the molecule. Gross et al. (p. 1110) show that in situ functionalization of the tip—for example, with CO—can dramatically improve the resolution of images of pentacene molecules adsorbed on conducting surfaces, like copper, and nonconductors, like NaCl.

            1. More Than the Sum of the Parts

                The radiative output of the Sun varies distinctly with the 11-year cycle of sunspots, although the change in energy output is small—less than a tenth of a percent in magnitude. Nevertheless, that small variation produces changes in sea surface temperatures two or three times as large as it should, and the mechanism by which this occurs has remained unclear. Meehl et al. (p. 1114; see the news story by Kerr) employ three global, coupled climate models to simulate this phenomenon. Two mechanisms appear to act in conjunction to cause this ocean response: a change in the abundance of stratospheric ozone owing to fluctuations of shortwave solar forcing; and a coupled surface ocean-atmosphere response. This combination of effects enhances precipitation maxima, reduces low-latitude cloud cover, and lowers the temperature of surface waters in the tropical Pacific Ocean, resulting in the larger warm-to-cold variation.

              1. “Rapid” Recovery

                  The Permian-Triassic extinction 252 million years ago was Earth's most severe biotic crisis since the Precambrian and is thought to have depressed diversity in its wake for millions of years. Brayard et al. (p. 1118; see the Perspective by Marshall and Jacobs) show, however, that ammonoids, a large group of marine organisms that were severely affected, recovered remarkably quickly. Only 1 million years after the extinction, ammonoids had recovered to levels higher than in the Permian, compared with the 10-million-year biotic recovery period for other benthic organisms. The Triassic recovery seems to include several cycles, but the immediate recovery of ammonoids may have left them as one of the most diverse groups in the earliest Triassic.

                1. Restoring Oysters

                    Populations and wild fisheries of native oyster species have collapsed worldwide because of overfishing and habitat destruction, resulting in severe ecosystem alteration and degradation. Expensive restoration efforts have met with little success, leading to the introduction of non-native oyster species in an attempt to recover lost economic and ecological benefits. In the Chesapeake Bay on the U.S. East Coast, eastern oyster landings and population abundance have plummeted to approximately 1% of historical levels, despite considerable expensive attempts to restore the fishery. Schulte et al. (p. 1124, published online 30 July) present field evidence of a successful restoration of a large metapopulation of native oysters in the Great Wicomico River, a tributary on the western shore of the Chesapeake Bay. The metapopulation is composed of a network of reef complexes spanning 35 hectares and comprises an estimated 185 million live native oysters of 1-year-old juveniles and 2- and 3-year-old adults.

                  1. Treg Responses to Eos

                      CREDIT: PAN ET AL.

                      CD4+ regulatory T cells (Tregs) are critical for keeping our immune system in check: They prevent immune responses from getting out of hand and keep autoimmunity at bay. By activating the expression of some genes and turning off expression of others, the master regulatory transcription factor of Tregs, Foxp3, endows these cells with the appropriate gene expression program to mediate their suppressive effects. Pan et al. (p. 1142, published online 20 August) now demonstrate that the transcription factor Eos is selectively required for Foxp3-mediated gene suppression in mice. Genes normally suppressed by Foxp3 in Tregs remained “on” when Eos expression was suppressed, whereas genes activated by Foxp3 were unaffected. Treg function was also affected by Eos suppression. With half their genetic program disrupted, these cells resembled an intermediate between Tregs and conventional CD4+ T cells—unable to suppress immune responses properly and partially responsive to T cell–activating stimulation.

                    1. Beat It

                        Primary cilia are specialized organelles that serve important sensory functions in many different tissues and cells, and defects in their structure and function underlie a variety of genetic diseases. In contrast to primary cilia, motile cilia serve a mechanical function. For example, the cilia on airway epithelia remove inhaled material from the lung. Shah et al. (p. 1131, published online 23 July; see the cover; see the Perspective by Kinnamon and Reynolds) now show that these classic motile cilia are also chemosensory. The motile cilia on airway epithelia contain bitter-taste receptors and their associated signaling machinery. Moreover, application of bitter substances triggers an elevation of intracellular Ca2+ levels and increases cilia beat frequency. Thus, in airway epithelia, bitter-taste receptors may be able to detect noxious substances entering the airways and initiate an autonomous defensive mechanism designed to accelerate elimination of the offending compound.

                      1. Tapping the Mitochondrial Proteome

                          Mitochondria produce the energy that cells need to survive, function, and divide. A growing list of human disorders has been traced to defects in mitochondrial function. About 300 mammalian mitochondrial proteins are functionally uncharacterized, and Hao et al. (p. 1139, published online 23 July) reasoned that the most highly conserved proteins within this group might provide insights into human disease. A combination of bioinformatics, yeast genetics, biochemistry, and human genetics was used to show that a previously uncharacterized mitochondrial protein (Sdh5) is required for the activity of respiratory complex II. Inactivating mutations in the human gene encoding SDH5 were found in individuals with hereditary paraganglioma, a rare neuroendocrine tumor. Thus, analysis of a mitochondrial protein in yeast has revealed a human tumor susceptibility gene.

                        1. Tuning Carbon Nanotube Resonances

                            Nanoscale resonators can be used in sensing and for processing mechanical signals. Single-walled carbon nanotubes have potential design advantages as resonators in that their oscillatory motion could be coupled to electron transport (see the Perspective by Hone and Deshpande). Steele et al. (p. 1103, published online 23 July) and Lassagne et al. (p. 1107, published online 23 July) report that the resonance frequency of a suspended single-walled carbon nanotube can be excited when operated as a single-electron transistor at low temperatures. Electrostatic forces are set up when the carbon nanotubes charge and discharge. The resonance frequency depends on applied voltages, and the coupling is strong enough to drive the mechanical motion into the nonlinear response regime. Differences in the responses of the devices in the two studies reflect in part the different quality factors of the resonators and different cryogenic temperatures.

                          1. Assessing Ecological Restoration

                              In the wake of the Millennium Ecosystem Assessment, the analysis of ecosystem services, and their relationship to biodiversity, has become one of the most rapidly developing research themes in environmental science. At the same time, ecological restoration is widely being implemented as a response to environmental degradation and biodiversity loss. Rey Benayas et al. (p. 1121, published online 30 July) link these themes in a meta-analysis of the impacts of ecological restoration actions on provision of ecosystem services and biodiversity conservation. The analysis of 89 published restoration projects worldwide establishes that ecological restoration does, in general, have positive impacts on both biodiversity and provision of ecosystem services. These effects are especially marked in the tropics. Thus, ecological restoration actions may indeed deliver benefits, both in terms of biodiversity conservation and supporting human livelihoods.

                            1. Regulating Akt

                                The protein kinase Akt is activated in response to receptor-activated generation of the signaling second messenger phosphatidylinositol 3,4,5-trisphosphate and has roles in regulation of diverse processes from metabolism and cell survival to transcription and tumorigenesis. Yang et al. (p. 1134; see the Perspective by Restuccia and Hemmings) report a previously unrecognized mode of regulation of Akt: covalent modification of Akt by linkage to lysine 63 of ubiquitin molecules. Such ubiquitination of Akt promotes localization to the cell membrane and consequent activation in cells stimulated with growth factors. TRAF6 (TNF receptor–associated factor 6) was implicated as the E3 ubiquitin ligase that mediates ubiquitination of Akt. Ubiquitination of Akt may influence its role in cancer cells: A mutant form of Akt associated with human cancer showed increased ubiquitination, and depletion of TRAF6 decreased tumorigenicity of a prostate cancer cell line in a mouse cancer model.