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Volume 471 Issue 7338, 17 March 2011

The female steroid hormone progesterone is produced by the ovaries and the placenta, and supports gestation and embryogenesis through its actions on a well-characterized nuclear progesterone receptor. But progesterone released by cells surrounding the egg also stimulates sperm cells within the Fallopian tubes and increases their fertilizing ability, and the mechanism of this action of progesterone has remained elusive. Two independent research groups now report that progesterone potently activates CatSper, the principal Ca2+ channel of the sperm flagellum. Their data demonstrate that the CatSper channel or a directly associated membrane protein serves as a novel progesterone receptor that can mediate a fast, non-genomic effect of progesterone at the level of the sperm plasma membrane. These results should help to define the physiological role of progesterone and CatSper in sperm, and could lead to the development of new classes of non-hormonal contraceptives. Illustration by Ren Pascal/Center of Advanced European Study and Research, Bonn, Germany.

Editorial

  • How James Clerk Maxwell made a difference 150 years ago.

    Editorial

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  • Vote to overturn an aspect of climate science marks a worrying trend in US Congress.

    Editorial
  • Scientists studying diseases should be motivated by patients, but not led by them.

    Editorial
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World View

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Research Highlights

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Seven Days

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News

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News Feature

  • When Judy Mikovits found links between chronic fatigue syndrome and a virus, the world took notice. Now, she's caught between the patients who believe her work and the researchers who don't.

    • Ewen Callaway
    News Feature
  • In 1861, James Clerk Maxwell unified electricity, magnetism and light. Experiments under way today could inch physicists closer to combining everything else.

    • M. Mitchell Waldrop
    News Feature
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Comment

  • James Clerk Maxwell's 1861 work on electromagnetism, which unified scientific fields, was driven as much by technology as by abstract theorizing, argues Simon Schaffer.

    • Simon Schaffer
    Comment
  • Combining Maxwell's equations with Einstein's general relativity promises perfect images and cloaking devices, explains Ulf Leonhardt.

    • Ulf Leonhardt
    Comment
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Books & Arts

  • Manfred Milinski enjoys Martin Nowak's paean to the power of cooperation to shape animal and human societies.

    • Manfred Milinski
    Books & Arts
  • Highlights of this season's releases

    Books & Arts
  • An account of the physicist's work reminds Leonard Mlodinow of the gulf between theory and experiment.

    • Leonard Mlodinow
    Books & Arts
  • Today's wariness of reproductive technologies stems from myths, legends and Hollywood, finds Chris Mason.

    • Chris Mason
    Books & Arts
  • A thorough review of how the human head evolved shows how hominins outpaced apes, finds Henry Gee.

    • Henry Gee
    Books & Arts
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Spring Books

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Books & Arts

  • Michael J. Benton finds hope for the future in a study of humanity's cooperation with the environment.

    • Michael J. Benton
    Books & Arts
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Correspondence

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Obituary

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News & Views

  • An enzyme called Dicer is known for its central role in RNA-controlled gene silencing. Mammalian Dicer1, however, also seems to have another function: it maintains visual health by degrading toxic RNA molecules. See Article p.325

    • Gunter Meister
    News & Views
  • Spherical micelles can aggregate into highly organized structures. New micelle arrangements mimic known atomic crystals, both periodic and aperiodic, and provide evidence for a material with 18-fold rotational symmetry.

    • Sharon C. Glotzer
    • Michael Engel
    News & Views
  • Apoptotic cell death is essential for the development of multicellular organisms. Paradoxically, three proteins instrumental in apoptosis also collaborate to preserve life by preventing necrotic cell death. See Letters p.363, p.368 & p.373

    • Marcus E. Peter
    News & Views
  • An approach integrating different data sets has been used to map out seismic-velocity ratios in the crust of western North America. High inferred quartz content correlates with tectonic deformation zones. See Letter p.353

    • Roland Bürgmann
    • Pascal Audet
    News & Views
  • The hormone progesterone rapidly activates intracellular signalling in human sperm, regulating key aspects of their physiology. An ion channel unique to the sperm tail seems to relay progesterone's signal. See Letters p.382 & p.387 See Clarification  p.598

    • Steve Publicover
    • Christopher Barratt
    News & Views
  • The finding that a cobalt oxide insulator's magnetism is similar to that of cuprate superconductors lends support to the popular but contentious idea that stripe-like electronic order is present in the latter materials. See Letter p.341

    • Jan Zaanen
    News & Views
  • New clinical trials report the efficacy of two mechanism-based therapies for treating human pancreatic neuroendocrine tumours. Studies in mouse models have contributed to these success stories, and continue to do so.

    • David Tuveson
    • Douglas Hanahan
    News & Views
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Article

  • Ultracold atoms in optical lattices provide a versatile tool to investigate fundamental properties of quantum many-body systems. This paper demonstrates control at the most fundamental level, using a laser beam and microwave field to flip the spin of individual atoms at specific sites of an optical lattice. The technique should enable studies of entropy transport and the quantum dynamics of spin impurities, the implementation of novel cooling schemes, engineering of quantum many-body phases and various quantum information processing applications.

    • Christof Weitenberg
    • Manuel Endres
    • Stefan Kuhr
    Article
  • In geographic atrophy, a type of macular degeneration, retinal pigmented epithelium (RPE) cells die. This paper finds that DICER1, which processes miRNA precursors, is reduced in RPE from individuals with geographic atrophy. Cell death is not due to loss of miRNA processing, however; rather, the absence of DICER1 allows accumulation of pathological Alu repeat sequence RNAs. This work reveals a novel function of Dicer in degrading Alu RNAs.

    • Hiroki Kaneko
    • Sami Dridi
    • Jayakrishna Ambati
    Article
  • Regulated proteolysis by ATP-dependent proteases have a crucial role in protein quality control in cells. The Clp/Hsp100 proteins of the AAA+ superfamily of ATP-dependent chaperones unfold and translocate proteins into the proteolytic chamber of protease complexes. ClpC requires the adaptor protein MecA for activation and substrate targetting to the ClpCP protease complex. Here, a structural and biochemical analysis is presented of the MecA–ClpC complex revealing organizational principles and providing mechanistic insights into this complex molecular machine.

    • Feng Wang
    • Ziqing Mei
    • Yigong Shi
    Article
  • Here, the X-ray crystal structure of TrkH is solved, a protein that mediates potassium uptake in Vibrio parahaemolyticus, a bacterium. The selectivity filter of the ion transporter is very similar to what is seen in (much simpler) potassium ion channels, but it is significantly shorter. Biochemical studies were performed to explore the molecular basis of K+ selectivity, and it is believed that a novel gating mechanism is involved.

    • Yu Cao
    • Xiangshu Jin
    • Ming Zhou
    Article
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Letter

  • Neutron scattering measurements of spin fluctuations in hole-doped high-Tc copper oxides have revealed an unusual 'hour-glass' feature in the momentum-resolved magnetic spectrum. There is no widely accepted explanation for this feature. One possibility is that it derives from a pattern of alternating spin and charge stripes. Many copper oxides without stripe order, however, also exhibit an hour-glass spectrum. This paper reports the observation of an hour-glass magnetic spectrum in a hole-doped antiferromagnet from outside the family of superconducting copper oxides. The system has stripe correlations and is an insulator, which means its magnetic dynamics can conclusively be ascribed to stripes. The results provide compelling evidence that the hour-glass spectrum in the copper-oxide superconductors arises from fluctuating stripes.

    • A. T. Boothroyd
    • P. Babkevich
    • P. G. Freeman
    Letter
  • The ease with which waves can travel through a disordered system is theoretically encapsulated in the separation and width of the energy levels, or modes, describing that system. However, extracting this information is experimentally challenging due to the spectral overlap of these modes. Here it is shown how these modal properties can be reconstructed from measurements of the 'speckle' pattern of radiation transmitted through a disordered medium.

    • Jing Wang
    • Azriel Z. Genack
    Letter
  • One of the most remarkable global warming events in the history of the Earth was the Palaeocene–Eocene Thermal Maximum (PETM), 56 million years ago, which is thought to have been caused by the release of greenhouse gases from mineral weathering. Several other, less severe warming periods occurred around 6–8 million years after the PETM. This paper shows that these smaller events were brief and surprisingly frequent, to a tempo paced by the Earth's orbit. Their rapid onset and recovery indicates a mechanism primarily dependent on shuffling carbon between the atmosphere and a dissolved, organic form in the ocean, in sharp contrast to the PETM's more sluggish greenhouse gas release from buried carbon reservoirs.

    • Philip F. Sexton
    • Richard D. Norris
    • Samantha Gibbs
    Letter
  • This study uses seismic receiver functions, gravity and surface heat flow measurements to estimate the thickness and seismic velocity ratio, vP/vS, of the continental crust in the western United States. There is a surprising correlation between low crustal vP/vS ratios and both higher lithospheric temperature and Cordilleran deformation. From this it is inferred that the abundance of crustal quartz — the weakest mineral in continental rocks — may lead to a feedback mechanism that strongly influences continental temperature and deformation.

    • Anthony R. Lowry
    • Marta Pérez-Gussinyé
    Letter
  • The amygdala, a brain region important for learning fearful memories, is thought to have a role in generalized anxiety, but the critical subregions and connections are unknown. This paper shows that optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala of rats with channelrhodopsin has an anxiolytic effect, whereas inhibition of the same projection with eNpHR3.0 increases anxiety related behaviours. These effects were not observed with direct optogenetic control of BLA somata themselves, indicating that selective activation of certain connections can have different effects.

    • Kay M. Tye
    • Rohit Prakash
    • Karl Deisseroth
    Letter
  • Caspase-8 mediates apoptosis induced by death receptors. At the same time, this protease is able to prevent RIP-dependent necrosis. Without caspase-8 mice die during their embryonic development. Two papers now show that lethality is not caused by the absence of apoptosis, but by RIP3-dependent necrosis that is unleashed without caspase-8. Mice that lack both caspase-8 and RIP3 develop into viable, immunocompetent, fertile adult mice, but suffer from a progressive lymphoaccumulative disease similar to mice that lack the death receptor CD95. This paper further shows that caspase-8 forms a proteolytically active complex with FLIPL, and that this complex is required for protection against RIP3-dependent necrosis.

    • Andrew Oberst
    • Christopher P. Dillon
    • Douglas R. Green
    Letter
  • Caspase-8 mediates apoptosis induced by death receptors. At the same time, this protease is able to prevent RIP-dependent necrosis. Without caspase-8 mice die during their embryonic development. Two papers now show that lethality is not caused by the absence of apoptosis, but by RIP3-dependent necrosis that is unleashed without caspase-8. Mice that lack both caspase-8 and RIP3 develop into viable, immunocompetent, fertile adult mice, but suffer from a progressive lymphoaccumulative disease similar to mice that lack the death receptor CD95.

    • William J. Kaiser
    • Jason W. Upton
    • Edward S. Mocarski
    Letter
  • Double deficiency of FADD and RIPK1 is shown to rescue the defects in mouse embryonic development and lymphocyte proliferation that are characteristic for mice with single gene deficiencies. This work suggests that the activity of FADD (presumably in conjunction with caspase-8 and c-FLIP) is to keep necrosis in check by causing the cleavage of RIPK1.

    • Haibing Zhang
    • Xiaohui Zhou
    • Jianke Zhang
    Letter
  • Using whole-transcriptome sequencing, this paper identifies recurrent gene translocations in B-cell lymphomas that involve the MHC class II transactivator CIITA. These translocations lead to downregulation of cell surface HLA class II expression and, in the case of some fusion partners, overexpression of CD274/CD273 ligands, which have the potential to reduce the antitumour response against these lymphomas.

    • Christian Steidl
    • Sohrab P. Shah
    • Randy D. Gascoyne
    Letter
  • Progesterone stimulates an increase in Ca2+ levels in human sperm, but the underlying signalling mechanism is poorly understood. Two studies now show that progesterone activates the sperm-specific, pH-sensitive CatSper calcium channel, leading to a rapid influx of Ca2+ ions into the spermatozoa. These results should help to define the physiological role of progesterone and CatSper in sperm, and could lead to the development of new classes of non-hormonal contraceptives.

    • Timo Strünker
    • Normann Goodwin
    • U. Benjamin Kaupp
    Letter
  • Progesterone stimulates an increase in Ca2+ levels in human sperm, but the underlying signalling mechanism is poorly understood. Two studies now show that progesterone activates the sperm-specific, pH-sensitive CatSper calcium channel, leading to a rapid influx of Ca2+ ions into the spermatozoa. These results should help to define the physiological role of progesterone and CatSper in sperm, and could lead to the development of new classes of non-hormonal contraceptives.

    • Polina V. Lishko
    • Inna L. Botchkina
    • Yuriy Kirichok
    Letter
  • During replication, topological stress builds ahead of the polymerase. Current models propose that linear eukaryotic chromosomes are divided into topological domains, and that stress is relieved by the activity of a topoisomerase. Here, it is found that replication stress seems to be present throughout the chromosome, rather than in domains, and that the relief of stress in longer chromosomes is facilitated by the activity of the cohesin/condensin-like Smc5/6 complex as well as by topoisomerase. They propose that the Smc5/6 complex prevent formation of topological tension ahead of the replication fork by promoting fork rotation, leading to the formation of sister chromatin intertwinings behind.

    • Andreas Kegel
    • Hanna Betts-Lindroos
    • Camilla Sjögren
    Letter
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Feature

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News

  • Some senior scientists feel neglected by the National Institutes of Health's grant formula.

    • Kendall Powell
    News
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Futures

  • A world of possibilities.

    • Marissa Lingen
    Futures
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