This Week in Science

Science  26 Jun 2009:
Vol. 324, Issue 5935, pp. 1613
  1. P Granule Conundrum


      In many organisms, the presumptive germ cells can be distinguished from somatic cells by the presence of distinctive cytoplasmic granules. In Caenorhabditis elegans, these P granules are more or less uniformly distributed in the oocyte and one-cell stage of the fertilized egg. By the end of the first cleavage, however, the anterior cell is essentially free of P granules, whereas the posterior cell still displays a prominent population of granules. Exactly how this process occurs and whether it involves directed migration of the granules is unclear. Now Brangwynne et al. (p. 1729, published online 21 May; see the Perspective by Le Goff and Lecuit) provide evidence that localization occurs by a quite different mechanism, controlled dissolution and condensation of granule components. This type of cytoplasmic remodeling by physicochemical mechanisms can now be looked for in other cellular and developmental systems.

    1. Winner Takes All?

        Competition between individual cells plays a role in normal animal development and cell homeostasis. Johnston (p. 1679) reviews two situations of cell competition in Drosophila, one involving epithelial cells in the wing and another involving germline or somatic stem cells. “Loss” in cell competition is evidenced by the “weaker” cell's death or displacement. On the other hand, winners may engulf the loser or display enhanced proliferation. Competitive interactions allow cells to sense and eliminate poor-quality cells during development.

      1. Molecular Fire Quencher

          Cage-shaped molecular assemblies can regulate the reactivity of smaller molecules trapped within them. Mal et al. (p. 1697) extend this approach to enable the protection of elemental white phosphorus (P4), a substance that rapidly ignites on contact with oxygen. The tetrahedral cages self-assemble in aqueous solution through coordination of six ligands to four iron ions, and efficiently capture phosphorus from a suspension. The water-soluble host-guest constructs were stable in air for at least 4 months, but released intact P4 rapidly on displacement by added benzene.

        1. CO on a Chip

            Microfluidics technology has facilitated remarkable miniaturization of chemical synthesis platforms; through electrically gated solution flow and mixing, molecular reactions can be carried out on chips several centimeters across. When it comes to more fundamental dynamics studies, though, which involve probing gas-phase molecules in specific quantum mechanical states, the experiments still tend to require much larger interaction areas. Meek et al. (p. 1699) take a step toward miniaturization in this latter regime by demonstrating the isolation of a cold gas-phase beam of CO molecules just above a microelectrode-decorated chip. The technique relies on rapidly modulated electric fields that trap and then slow down the incoming molecules through dipole interactions. Once brought to a stop, the molecules can be held on the chip for a discrete period and then released to a detector.

          1. Flower Functionalization


              The development of the specialized cells that make up the female reproductive unit in flowering plants, the gametophyte, requires the hormone auxin. However, auxin's function and movement to and within these cells are unclear. Pagnussat et al. (p. 1684, published online 4 June; see the Perspective Friedman) provide evidence that auxin is synthesized at specific positions within the female gametophyte and exerts a positional effect and that a gradient of auxin controls patterning of these specialized cells.

            1. Going Faster

                The concentrations of most tropospheric pollutants and trace gases are kept in check by their reactions with hydroxyl radicals (OH). OH is a short-lived, highly reactive species that is produced in the atmosphere by photochemical processes, and regenerated in the chain of chemical reactions that follows the oxidative destruction of those molecules. These regeneration mechanisms were thought to be fairly well understood, but now Hofzumahaus et al. (p. 1702, published online 4 June) present evidence of a pathway not previously recognized. In a study of atmospheric composition in the Pearl River Delta, a highly polluted region of China, greatly elevated OH concentrations were observed without the correspondingly high levels of ozone expected from current models. Thus, OH concentrations may be augmented by a process that speeds the regeneration of OH without producing ozone.

              1. Two's a Crowd

                  The process by which males and females compete to maximize their individual fitness also affects the fitness of their offspring. Sexual selection largely results from polyandry (multiple mating by females), and several competing hypotheses attempt to explain the evolution of polyandry. Bilde et al. (p. 1705) staged double mating experiments in seed beetles to distinguish between the theories underlying cryptic female choice and sexual antagonism. Contrary to expectation, males of high genetic quality, as measured on the basis of the number of offspring sired when singly mated to a female, consistently produced fewer offspring when females were doubly mated to males of both high and low genetic quality. Thus, postmating sexual selection can favor male genotypes with low fitness, and females risk genetic costs when mating with multiple males.

                1. Of Life, Limb, and a Small RNA

                    Gene expression in mammals is controlled not only by proteins but by small noncoding RNAs called microRNAs. The involvement of these RNAs provides powerful clues about the molecular origins of human diseases and how they might be treated. Ischemic diseases arise from an inadequate blood supply. Bonauer et al. (p. 1710, published online 21 May) find that a specific microRNA that is expressed in the cells lining blood vessels (called miR-92a) functions to repress the growth of new blood vessels. MiR-92a probably acts through effects on expression of integrins, proteins involved in cell adhesion and migration. In mouse models in which an inadequate blood supply had caused damage either to heart or limb muscle, therapeutic inhibition of miR-92a led to an increase in blood vessel density in the damaged tissues and enhanced functional recovery.

                  1. Ras, STAT3, and Transformation

                      The STAT (signal transducer and activator of transcription) proteins are activated in response to receptor stimulation and act in the nucleus to regulate gene expression. Gough et al. (p. 1713) found that STAT3 functioned in transformation of cells by the oncogene Ras. However, this activity was maintained in mutants of STAT that fail to activate transcription. Instead, the active STAT3 appeared to be associated with mitochondria. Furthermore, modified STAT3 targeted to the mitochondria promoted transformation by Ras, and mitochondrial function was disrupted in Ras-transformed cells lacking STAT3. Such transformation-specific effects of STAT3 could be a useful target in developing anticancer therapies.

                    1. Cuprate Analysis

                        CREDIT: PUSHP ET AL.

                        Despite more than 20 years of intensive effort, the mechanism providing superconductivity in the cuprates remains elusive and contentious, partly because the cuprates are inhomogeneous. Scanning tunneling spectroscopy (STS) and high-resolution, angle-resolved photoemission spectroscopy provide energy and momentum information about the excitations in the high-temperature cuprate superconductors. Pushp et al. (p. 1689, published online 4 June) provide a STS study of the cuprate Bi2Sr2CaCu2O8+δ over a range of doping levels and temperatures. This methodology for analyzing the spectra takes into account the inhomogeneity and may provide insight into how a superconducting pairing mechanism evolves from the parent insulating state.

                      1. Green for Diatoms

                          Diatoms account for 20% of global carbon fixation and, together with other chromalveolates (e.g., dinoflagellates and coccolithophorids), represent many thousands of eukaryote taxa in the world's oceans and on the tree of life. Moustafa et al. (p. 1724; see the Perspective by Dagan and Martin) have discovered that the genomes of diatoms are highly chimeric, with about 10% of their nuclear genes being of foreign algal origin. Of this set of 1272 algal genes, 253 were, as expected, from a distant red algal secondary endosymbiont, but more than 1000 of the genes were derived from green algae and predated the red algal relationship. These protist taxa are important not only for genetic and genomic investigations but also for their potential in biofuel and nanotechnology applications and in global primary productivity in relation to climate change.

                        1. BDNF and Drug Dependence

                            Brain-derived neurotrophic factor (BDNF) is a growth factor involved in neuronal plasticity that is expressed after chronic administration of drugs of abuse and may play a crucial role in chronic opiate effects. Vargas-Perez et al. (p. 1732, published online 28 May) found that BDNF was directly involved in the switching mechanism in the ventral tegmental area, from an opiate-naïve, dopamine-independent drug reward substrate to an opiate-dependent, dopamine-dependent motivational substrate. In the ventral tegmental area, BDNF changed the action of GABA-A receptors from inhibitory to excitatory. This change led to behavioral changes that defined a neurobiological boundary between the acute phase of drug-taking and addiction.

                          1. NMR Under Stormy Conditions

                              Nuclear magnetic resonance spectroscopy is immensely useful for molecular characterization. However, the resolution necessary for making fine structural distinctions relies on sample isolation in a surrounding magnetic field that exhibits minimal variation in space and time over the course of the measurement; this requirement limits the range of materials that can be easily probed. Pelupessy et al. (p. 1693) present an approach that circumvents the need for spatiotemporal field homogeneity by detecting coherence transfer among coupled spins. Whereas prior methods have compensated for heterogeneity by applying corrective magnetic fields, this technique relies on the inherent insensitivity of the measured coherences to changes in the local magnetic environment and thus can be applied without prior knowledge of the field variation profile.

                            1. Integrating Organ Induction

                              During animal development, multiple signaling pathways specify the induction of organ progenitors such as those in the pancreas and liver. Wandzioch and Zaret (p. 1707) investigated how three signaling pathways converge on the earliest genes specifying these organs. Within hours, multiple changes were observed in the inductive network with different signals operating in parallel. The findings may help to explain the incomplete programming seen in various stem cell differentiation protocols.

                            2. Synthetic Centromere

                                Every eukaryotic chromosome must have a centromere where the cell division machinery latches onto each chromosome pair to ensure an even apportioning of the genetic material between daughter cells. The characteristic (but not conserved) repeat sequences associated with most centromeres are thought to be required to induce an RNA interference (RNAi) response and thereby promote the formation of heterochromatin, needed for centromere function. Kagansky et al. (p. 1716) now show in fission yeast that these outer repeat sequences can be replaced in their entirety by very short sequences that recruit an enzyme, Clr4, which promotes the formation of heterochromatin in the absence of RNAi. Thus, flanking heterochromatin, regardless of its derivation, is all that is required for the formation of a functional centromere.

                              1. Transcriptional Regulation Gets More Complicated

                                  Sequence preferences of DNA binding proteins are a primary mechanism by which cells interpret the genome. A central goal in genome biology is to identify regulatory sequences in the genome; however, few proteins' DNA binding specificities have been characterized comprehensively. Badis et al. (p. 1720, published online 14 May) studied 104 known and predicted transcription factors (TFs), spanning 22 structural classes, in the mouse genome. While traditional models of TF binding sites are based on a single collection of highly similar DNA sequences, binding profiles were represented better by multiple motifs. Roughly half of the TFs recognized distinct primary and secondary motifs that are different from each other. At least some of these interaction modes appeared to be attributable to biophysically distinct protein conformations, adding to the complexity of transcriptional regulation.

                                1. Opening the Portico

                                    Escherichia coli diacylglycerol kinase (DAGK) represents a family of integral membrane phosphotransferases that function in prokaryotic-specific metabolic pathways. Van Horn et al. (p. 1726) determined the structure of the 40-kilodalton functional homotrimer of E. coli DAGK by solution nuclear magnetic resonance spectroscopy. Each monomer comprises three transmembrane helices. The third transmembrane helix from each subunit is domain-swapped to pack against the first and second transmembrane helices from an adjacent subunit. These three helices frame a portico-like membrane-submerged cavity that contains residues critical for activity in close proximity to residues critical for folding. The structure provides insight into the determinants of lipid substrate specificity and phosphotransferase activity.