This Week in Science

Science  19 Nov 2010:
Vol. 330, Issue 6007, pp. 1019
  1. Wiping Out Memories


      Inhibition of fear responses can be unexpectedly reversed even when a subject is perfectly safe. This can lead to inappropriate reactions to a fear-associated trigger, such as a bright light or loud noise. This type of reaction appears to underpin posttraumatic stress disorder, but there is little understanding of when training to inhibit fear may fail or succeed. Using a combination of electrophysiology and behavioral training in mice, Clem and Huganir (p. 1108, published online 28 October) observed that fear conditioning increased synaptic transmission by calcium-permeable AMPA receptors into the part of the brain that controls emotional responses (the amygdala). This effect lasted for about a week, during which the fearful memories could be erased if the animals were trained to reduce conditioned fear responses. Postmortem brain slices showed that the fear-induced synaptic changes also reversed, except in transgenic mice with a mutant subunit of the AMPA receptor.

    1. Regulating Migration

        The migration of cells around the body is an important factor in cancer development and the establishment of infection. Movement is induced by small proteins called chemokines, and so for a specific function, migration is controlled by a relevant chemokine binding to its respective receptor. This family of receptors is known as guanine (G) protein–coupled receptors, which span cell membranes to mediate between external signals from chemokines and internal mechanisms. The chemokine receptor CXCR4 is implicated in many types of cancer and in infection, and Wu et al. (p. 1066, published online 7 October; see the Report by Chien et al.) report on a series of crystal structures obtained for CXCR4 bound to small molecules. In every case, the same homodimer structure was observed, suggesting that the interface is functionally relevant. These structures offer insights into the interactions between CXCR4 and its natural chemokine, as well as with the virus HIV-1.

      1. Moving Carbon

          During the last glacial maximum, approximately 23,000 years ago, both the atmosphere and the terrestrial biosphere contained much less carbon than in the immediately preindustrial era. The carbon must have been stored in the deep ocean, and the transfer of carbon to the air and land during deglaciation must have affected the carbonate chemistry and carbon isotopic composition of the sea. Yu et al. (p. 1084) estimated how deep-water carbonate concentrations changed over the course of the last deglaciation and combined their results with 13C/12C data to show that carbon released by the deep ocean between 17.5 and 14.5 thousand years ago mostly stayed in the atmosphere as CO2, while between 14 and 10 thousand years ago, a substantial fraction was absorbed by the terrestrial biosphere.

        1. Quantum Connection

            A system that is quantum mechanically entangled with another distant system can be predicted by measuring the distant system. This form of “action-at-a-distance,” or nonlocality, seemingly contradicts Heisenberg's uncertainty principle, which is one of the fundamental aspects of quantum mechanics. Oppenheim and Wehner (p. 1072) show that the degree of nonlocality in quantum mechanics is actually determined by the uncertainty principle. The unexpected connection between nonlocality and uncertainty holds true for other physical theories besides quantum mechanics.

          1. Finely Tracking Flow

              Magnetic resonance imaging (MRI) is in principle well-suited for tracking flow dynamics in microfluidic channels. However, multiple channels tend to be arrayed on much larger substrates, and MRI coils large enough to enclose the whole assembly do not have the sensitivity required to resolve an intimate picture of any one channel. Bajaj et al. (p. 1078, published online 7 October; see the Perspective by Utz and Landers) present an imaging protocol in which the spins of the fluid molecules in a microfluidic chip are first tagged by a conventionally sized coil and then analyzed downstream using a more sensitive and smaller coil through which the fluid flows incrementally after leaving the microfluidic device.

            1. Enhanced Strain Sensitivity

                The ability to measure tiny deformations in length is useful for many disciplines, from large-scale structural engineering to DNA analysis with optical tweezers. The most sensitive strain sensors are those using optical interferometers, which can detect small changes at the scale of visible wavelengths. Using an optical frequency comb to stabilize the output of a diode laser, and as a highly accurate ruler to determine small changes in length of an optic fiber sensor, Gagliardi et al. (p. 1081, published online 28 October) showed that sensitivity can be enhanced by several orders of magnitude. Such combined technology should provide for a new generation of high-performance sensors.

              1. Silicon Leakage

                  CREDIT: ELLWOOD ET AL.

                  Silicon is a major structural component of many marine organisms, whose chemistry is affected by oceanic nutrient distributions. To constrain nutrient changes since the last glacial period, Ellwood et al. (p. 1088, published online 21 October) measured the isotopic compositions of silicon obtained from the skeletons of deep-sea sponges found in deep cores from the Atlantic and Pacific sectors of the Southern Ocean and compared them to the silicon signatures in the skeletons of modern sponges. The results indicate that nutrient redistribution, related to iron fertilization from dust deposition, boosted the growth of organisms that transferred silicon to mid-latitudes during the last glacial period.

                1. Tweaking Dopamine Reception

                    Dopamine modulates many cognitive and emotional functions of the human brain by activating G protein–coupled receptors. Antipsychotic drugs that block two of the receptor subtypes are used to treat schizophrenia but have multiple side effects. Chien et al. (p. 1091; see the Research Article by Wu et al.) resolved the crystal structure of one receptor in complex with a small-molecule inhibitor at 3.15 angstrom resolution. Homology modeling with other receptor subtypes might be a promising route to reveal potential structural differences that can be exploited in the design of selective therapeutic inhibitors having fewer side effects.

                  1. Germinal Center Survival

                      The humoral immune response, which comprises antibodies secreted by B lymphocytes, is critical for protection against pathogens. In response to infection, B lymphocytes proliferate and differentiate into antibody-producing effector cells. After an infection clears, a small number of cells persist as memory B cells; however, the survival signals that regulate effector and memory B lymphocyte generation are not well understood. To probe this question, Vikstrom et al. (p. 1095, published online 7 October) deleted prosurvival genes in activated, antigen-specific B cells during a T lymphocyte–dependent immune response in mice. They found that a specific programmed cell death inhibitor, known as Mcl1, was required for the formation of germinal-center B cells (an effector cell population) and memory B cells but not for their maintenance. Dysregulation of the B cell responses mediated by Mcl1 may be a trigger for lymphomagenesis.

                    1. Turncoat Aphids

                        CREDIT: RYUICHI KOGA

                        Aphid color has consequences for the fate of the wearer: Coccinellid beetles prefer to eat red ones and parasitoid wasps attack green ones. What might happen if aphids could change color and outwit their predators? Tsuchida et al. (p. 1102) have found that a subpopulation of the pea aphid can do this, but not without help from a previously unknown species of bacterium that lives intimately with the aphid as an endosymbiont and makes red aphids turn green. The bacterium interferes with host pigment biosynthesis—itself borrowed from fungi long ago in evolution—to stimulate blue-green pigment production as the aphid larva matures, turning the red nymph into a green adult. The ecological consequences of this about-turn of color have yet to be tested, but other studies have shown a variety of effects on aphid behavior mediated by endosymbionts in response to adaptation to different food plants, temperature tolerance, and predator avoidance.

                      1. Piggybacking on Cancer Genes

                          Transposons are mobile segments of DNA that can insert in or near important genes to cause mutations that disrupt gene function. Rad et al. (p. 1104, published online 14 October) adapted a mutagenic transposon called Piggybac, originally derived from a moth, into a tool for discovery of cancer-causing genes in mice. Mobilization of Piggybac in mice was associated with the development of leukemias and solid tumors. In many instances the causative mutations, which were identified by mapping the Piggybac integration sites, were within genes not previously implicated in cancer.

                        1. Orientation Columns

                            In the brain's visual cortex, certain neurons respond to vertical lines and others to horizontal lines, with a range in between. Such orientation of neurons tends to be organized in columns reflecting similar responses, and the columns are organized in pinwheels representing the range of responses. Kaschube et al. (p. 1113, published online 4 November; see the Perspective by Miller) looked at the organization of orientation columns in diverse placental mammals and discovered a similarity of organizational principles.

                          1. Common Themes

                              Both plants and animals need to be able to distinguish between their own tissues and the cells and tissues of an invading pathogen. Across kingdoms there exists a range of pattern recognition systems that have become integral to the evolution of innate immune responses. Ronald and Beutler (p. 1061) synthesize recent intellectual progress to bring insights into shared features of animal immunology and plant pathology.

                            1. Speeding Electron Transfer Between Proteins

                                Compared to those observed in photosynthetic proteins, electron transfer rates between other large biomolecules, such as myoglobin and cytochrome b5, are very slow. Xiong et al. (p. 1075) show that modifying the acidic amino acid residues in the binding surface of myoglobin to lysine changes the distribution of structures to ones that favor faster electron transfer from the zinc porphyrin in myoglobin to the heme iron of cytochrome b5. The rates observed are within an order of magnitude of those observed for the initial step of charge separation in photosynthesis and provide valuable data for scientists interested in designing reactive proteins.

                              1. Theory of Growth Control

                                  Although quantitative studies of growth in bacterial cultures have been made for over 50 years, the relationship between cell proliferation and gene expression has not been clear. Scott et al. (p. 1099; see the Perspective by Lerman and Palsson) have revealed that mass per cell exponentially increased with linear increases in growth rate and that ribosome abundance increased linearly with growth rate depending on the rate of translation. Hence, the systems properties of the biological processes involved in growth can be derived without any molecular understanding of their basis and can be used to establish fundamental properties for the design of biotechnological procedures.

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