This Week in Science

Science  27 Apr 2007:
Vol. 316, Issue 5824, pp. 511
  1. Micromanaging the Immune System


    Micro-RNAs (miRNAs) are abundant small RNA species that have emerged as key regulators in many biological processes. Rodriguez et al. (p. 608; see the news story by Couzin) observed that mice deficient in miRNA-155 develop spontaneous inflammation of the lungs and have accompanying defects in antigen presentation, as well as T cell and B cell function. Exploring the same miRNA, Thai et al. (p. 604; see the news story by Couzin) observed a similar T and B cell deficiency that resulted in a suboptimal response of the germinal center, which is needed for T cell-mediated antibody production. Although both studies provide some evidence for how this miRNA mediates its effects, the next important step will be to identify the precise mechanism and critical target genes involved.

  2. Solving Nanoscale Structure

    For many materials, if you can grow sufficiently large, high-quality crystals, there are many tools for determining the crystal structure, and in some cases the process can be fully automated. However, for materials that have structural features that are inherently nanoscale (such as cages in zeolites) or that may not be fully crystalline, the solution of the phase problem is more daunting. Billinge and Levin (p. 561) review recent progress in this area and note the benefits of greater integration of data through complex modeling from a wide of range of direct and indirect methods that probe both bulk and local details.

  3. Disappearing in the Twilight Zone

    Most of the organic carbon produced in the sunlit upper layer of the ocean is recycled (remineralized) as dead organisms sink to greater depths, but there is considerable uncertainty about how efficient this remineralization process is in the ocean's “twilight zone” (depths between the bottom of the euphotic zone and about 1000 meters). Buesseler et al. (p. 567, see the cover) have used neutrally buoyant sediment traps that can sample sinking particles more faithfully than traps moored in fixed spots that are subject to strong cross-flow from ocean currents. The transfer efficiency of sinking particulate organic matter differed by more than a factor of 2 between the two sites examined; this difference is poorly represented in present biogeochemical models.

  4. Life Without Dynamin


    Dynamin 1 is a neuron-specific guanosine triphosphatase involved in the endocytic recycling of synaptic vesicle membranes. Ferguson et al. (p. 570; see the Perspective by Robinson) created genetically engineered mice lacking dynamin 1 and found, surprisingly, that they contained functional synapses and had limited postnatal viability. However, the synapses of these dynamin 1 knockouts contained branched, tubular plasma membrane invaginations capped by clathrin-coated pits, consistent with dynamin 1's proposed role in clathrin-coated vesicle scission. Also, after strong stimulation, synaptic vesicle endocytosis was severely impaired but could resume efficiently upon stimulus termination. This finding reveals the existence of a dynamin 1-independent mechanism that can support limited synaptic vesicle endocytosis.

  5. Mimicking Hydrogenase

    Hydrogenase enzymes rely on the cooperation of two metal centers in their active sites (either iron, or iron and nickel) to break down H2 into protons and electrons. In contrast, effective synthetic H2 cleavage catalysts tend to be monometallic, and the mechanisms underlying hydrogenase efficiency remain only loosely understood. Ogo et al. (p. 585; see the Perspective by Rauchfuss) have enhanced the mechanistic picture by synthesizing an active-site model, consisting of ruthenium and nickel centers, that replicates the enzyme's essential feature of heterolytically cleaving H2 in water at room temperature. The reaction liberates a proton and leaves behind a paramagnetic hydride-bridged Ni-Ru complex, the structure of which the authors confirmed using neutron diffraction.

  6. Sudden Death of Entanglement

    Quantum information processing relies on the constituent parts, the qubits, forming entangled states and remaining coherent. The quantum features of many systems decay uniformly as the result of decoherence, which arises from the unavoidable coupling to the environment, and much effort has been directed to extend the coherence time of these qubits. However, Almeida et al. (p. 579; see the Perspective by Eberly and Yu) show that under particular circumstances where there is even only a partial loss of coherence of each qubit, entanglement can be suddenly and completely lost. These results should mark an important consideration in the design and operation of future quantum information networks.

  7. The Heart of Stress Responses

    Two myosin heavy chain (MHC) genes are expressed in opposing manners in the mouse heart; βMHC is expressed embryonically, whereas αMHC is up-regulated postnatally. Cardiac stress shifts this ratio toward βMHC with negative effects on cardiac function, and previous work has identified microRNAs (miRNAs) as possible regulators of cardiac growth and function. Van Rooij et al. (p. 575, published online 22 March) now show that miR-208, which is encoded by an intron of the αMHC gene, is a cardiac-specific regulator of βMHC is expressed embryonically, whereas αMHC is up-regulated postnatally. Cardiac stress shifts this ratio toward βMHC expression in response to stress and hypothyroidism in the heart. Deletion of the coding region of miR-208 resulted in inhibition of βMHC expression and a reduced stress response in the heart. Thus, miR-208 may act through thyroid signaling to regulate βMHC expression, possibly by repressing expression of the thyroid receptor co-regulator THRAP1.

  8. Volcanic Release of Buried Greenhouse Gases


    The Paleocene-Eocene thermal maximum (PETM) about 55 million years ago was marked by a rapid emission of greenhouse gases (either CO2 or methane) during a period of a few thousand years that increased global temperatures by 5° to 10°C. However, the trigger for this sudden event has been uncertain. Storey et al. (p. 587; see the news story by Kerr) date a volcanic layer that overlies the marine sections marking the PETM and a volcanic ash at the top of a massive volcanic sequence in Greenland and Europe that likely erupted within about 300,000 years, marking the beginning of the opening of the Northern Atlantic Ocean. The dates are identical within error, implying that timing of the PETM overlaps that of the volcanic sequence. Massive intrusion of basalt into carbonaceous sediments may have released methane or CO2 to the atmosphere, perhaps explaining at least some of the causes of the PETM.

  9. Selfish Genes, Pushy Genotypes

    In the past few years, transgenic mosquitoes have been developed with significantly lower ability to transmit dengue and malaria based on the action of single “effector” transgenes. These genotypes are exciting, but they are of little practical use without a gene-drive mechanism to force them to high frequencies in natural populations of the pathogen-vectoring mosquito species. Chen et al. (p. 597, published online 29 March; see the 30 March news story by Enserink) provide one potential drive mechanism that is expected to be very efficient at quickly increasing the frequency of nonvectoring genotypes. They engineered a maternal-effect selfish drive element in Drosophila by using RNA interference against essential, maternally supplied RNAs and rescue by a zygotically expressed gene. This modification, which provides the capacity to move to fixation after introduction in only about 10 generations, may provide a route by which wild insect populations can be replaced with insects unable to transmit disease.

  10. Modeling Human Leukemia in Mice

    Mouse models have been a mainstay of leukemia research for two decades and have provided many important insights into the physiological roles of genes that cause or suppress the disease. One limitation of these models, however, is that the leukemias typically originate from mouse rather than human hematopoietic cells, thereby precluding analysis of the human cell types that initiate the disease. Barabé et al. (p. 600) have created a new mouse model in which acute myeloid and lymphoid leukemias arise from primitive human hematopoietic cells expressing an MLL (mixed-lineage leukemia) fusion oncogene. The leukemias in these mice show many features of the human diseases. The authors identified the leukemia-initiating cell and studied its evolution during disease progression.

  11. Radical Development

    Recently, chiral amines have proven useful as catalysts for adding a diverse range of functional groups enantioselectively to aldehydes and ketones. In general, the catalysts react with the substrate at the CO position and enhance its reactivity either toward nucleophiles (through iminium formation) or toward electrophiles (through enamine formation). Beeson et al. (p. 582, published online 29 March) find that by using a one-electron oxidant in tandem with an amine catalyst, they can create a radical species intermediate between these two extremes, which reacts efficiently with less polar hydrocarbon reagents. Specifically, they achieve highly selective asymmetric α-addition of allyl groups to aldehydes, and also show preliminary results for asymmetric α-arylations.

  12. Maintaining the Blood Supply

    Stem cells, and later progenitor cells, provide the steady resupply of blood throughout life, and successful bone marrow transplants depend on engraftment of just such cells. Gupta et al. (p. 590) have now identified a protein, Nov, that is required for function of these early cells in the pathway toward human hematopoiesis. Previous studies of Nov implicated its function in tumor suppression, wound-healing, and angiogenesis.

  13. Differential Responses to Change

    Understanding how organisms respond to genetic or environmental perturbations requires quantitative measurements across multiple levels of biological information. Ishii et al. (p. 593, published online 22 March; see the Perspective by Sauer et al.) used a variety of technologies to measure gene expression, protein levels, metabolite concentrations, and reaction fluxes in order to study the response of Escherichia coli to growth rates and genetic deletions. Although E. coli responds to changes in the environment by regulating the level of enzyme expression to keep metabolite levels stable, messenger RNA and protein levels do not change in response to most gene disruptants. Instead, there are likely changes in the structure of the metabolic network that keep the levels of most metabolites stable.

  14. An Antigenic Route Planner

    Antigenic peptides are presented to T cells from two sources: Proteins generated inside the cell (as in the case of virally infected cells or tumor cells) or from an extracellular pool. In the latter situation, class II major histocompatibility complex (MHC) molecules on antigen-presenting cells (APCs) present peptide fragments to CD4+ helper T cells, whereas MHC class I molecules display peptides to CD8+ T cells in a process known as cross-presentation. Burgdorf et al. (p. 612) reveal that the two pathways for presenting peptides from the same extracellular antigen are determined by the mode of antigen uptake by the APC. For class I restricted presentation, surface mannose receptors routed antigen to the stable early endosome compartment, where peptides could meet MHC class I molecules. In contrast, pinocytosis of the same antigen directed it to the lysosomal compartment for presentation by class II MHC. The findings will help resolve questions about how APCs activate and modulate different arms of the T cell response.

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