Monday, September 26, 2011

Hot off the presses! Sep 27 Curr Biol

The Sep 27 issue of the Curr Biol is now up on Pubget (About Curr Biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

  • Why do people riot?
    - Curr Biol 21(18):R673-R676 (2011)
    The rioting and looting that occurred in English cities at the beginning of August has provoked contradictory responses from politicians. Now academic research is looking into what happened and why. Michael Gross investigates.
  • Debashish Bhattacharya
    - Curr Biol 21(18):R676-R677 (2011)
  • Visual crowding
    - Curr Biol 21(18):R678-R679 (2011)
  • Bioluminescent aposematism in millipedes
    - Curr Biol 21(18):R680-R681 (2011)
    Bioluminescence — the ability of organisms to emit light — has evolved about 40–50 times independently across the tree of life [1]. Many different functions for bioluminescence have been proposed, for example, mate recognition, prey attraction, camouflage, and warning coloration. Millipedes in the genus Motyxia produce a greenish-blue light at a wavelength of 495 nm that can be seen in darkness [2]. These detritivores defend themselves with cyanide, which they generate internally and discharge through lateral ozopores [3]. Motyxia are an ideal model system to investigate the ecological role of bioluminescence because they are blind, thus limiting their visual signalling to other organisms, for example predators. While the biochemical mechanisms underlying Motyxia bioluminescence have been studied in detail [2] and [4] , its adaptive significance remained unknown [5] and [6] . We here show that bioluminescence has a single evolutionary origin in millipedes a! nd it serves as an aposematic warning signal to deter nocturnal mammalian predators. Among the numerous examples of bioluminescence, this is the first field experiment in any organism to demonstrate that bioluminescence functions as a warning signal. Video Abstract The editors of Current Biology welcome correspondence on any article in the journal, but reserve the right to reduce the length of any letter to be published. All Correspondence containing data or scientific argument will be refereed. Queries about articles for consideration in this format should be sent by e-mail to View Within Article
  • Prestin links extrinsic tuning to neural excitation in the mammalian cochlea
    - Curr Biol 21(18):R682-R683 (2011)
    The sensory hair cells of amniote hearing organs are usually distributed in tonotopic array from low to high frequencies and are very sensitively and sharply tuned to acoustic stimulation. Frequency tuning and tonotopicity of non-mammalian auditory hair cells is due largely to intrinsic properties of the hair cells [1], but frequency tuning and tonotopic organisation of the mammalian cochlea has an extrinsic basis in the basilar membrane (BM); a spiralling ribbon of collagen-rich extracellular matrix that decreases in stiffness from the high-frequency base of the cochlea to the low-frequency apex [2] and [3] . Sensitive frequency tuning is due to amplification, which specifically boosts low-level input to the mechanosensitive hair cells at their tonotopic location to overcome viscous damping [1] , [2] and [3] . In non-mammalian hearing organs, at least, amplification is attributed to calcium-mediated hair bundle motion [1]. In the mammalian cochlea, amplificatio! n is the remit of the sensory-motor outer hair cells (OHCs), located within the organ of Corti to exercise maximum mechanical effect on the motion of the BM and transmit cochlear responses to the adjacent sensory inner hair cells (IHCs) and, consequently, to the auditory nerve [1] , [2] and [3] (Figure 1A). OHCs behave like piezoelectric actuators, developing forces along their long axis in response to changes in membrane potential [2]. These forces are due to voltage-dependent conformational changes in the motor molecule prestin, which is densely distributed in the OHC lateral membranes [2].
  • Baby Brain: Training Executive Control in Infancy
    - Curr Biol 21(18):R684-R685 (2011)
    A recent study shows that a relatively short period of cognitive training can improve infants' ability to sustain and flexibly deploy attention. Thus, it appears important aspects of cognition can be modified using 'brain-training' techniques at an early age.
  • Plant Sex Chromosomes: A Non-Degenerated Y?
    - Curr Biol 21(18):R685-R688 (2011)
    Animal Y chromosomes have undergone chromosome-wide degeneration in response to a lack of recombination, and ancient Ys contain few functional genes. Recent research suggests that plant Y chromosomes may evolve differently and retain most of their ancestral genes.
  • Chromosome Segregation: Spindle Mechanics Come To Life
    - Curr Biol 21(18):R688-R690 (2011)
    Chromosome segregation is a mechanical process, and the spindle generates, and is subject to, mechanical force. A recent study probes how the mechanical architecture of the spindle allows it to maintain mechanical integrity despite these forces.
  • Tissue Polarity: PCP Inheritance Ensured by Selective Mitotic Endocytosis
    - Curr Biol 21(18):R690-R692 (2011)
    Recent findings report the selective internalization of core planar cell polarity components during mitosis followed by cell-non-autonomous polarized recycling. This novel mechanistic model explains how tissue polarity is inherited in daughter cells of proliferative tissue.
  • Protein Degradation: BAGging Up the Trash
    - Curr Biol 21(18):R692-R695 (2011)
    Cells efficiently uncover and degrade proteins that are misfolded. However, we know very little about what cells do to protect themselves from mislocalized proteins. A new study reveals a novel quality control pathway that recognizes and degrades secretory pathway proteins that have failed to target to the endoplasmic reticulum.
  • Affective Neuroscience: Tracing the Trace of Fear
    - Curr Biol 21(18):R695-R696 (2011)
    The trace of fear has been elusive and difficult to discern in the human brain. Researchers have come up with a clever new way to track it down.
  • Autophagy: Cells SNARE Selves
    - Curr Biol 21(18):R697-R699 (2011)
    Autophagosomes sequester cytosolic constituents and deliver this cargo to lysosomes for destruction. Two groups now report that autophagosome maturation requires homotypic membrane fusion catalyzed by SNARE proteins.
  • It's All Life History
    - Curr Biol 21(18):R700 (2011)
  • On the Programmed/Non-Programmed Nature of Ageing within the Life History
    - Curr Biol 21(18):R701-R707 (2011)
    Understanding why and how senescence evolved is of great importance in investigating the multiple, complex mechanisms that influence the course of ageing in humans and other organisms. Compelling arguments eliminate the idea that death is generally programmed by genes for ageing, but there is still a widespread tendency to interpret data in terms of loosely defined 'age regulation', which does not usually make either evolutionary or mechanistic sense. This review critically addresses the role of natural selection in shaping ageing within the life history and examines the implications for research on genetic pathways that influence the life span. It is recognised that in exceptional circumstances the possibility exists for selection to favour limiting survival. In acknowledging that, at least in theory, ageing might occasionally be adaptive, however, the high barriers to validating actual instances of adaptive ageing are made clear.
  • Primates and the Evolution of Long, Slow Life Histories
    - Curr Biol 21(18):R708-R717 (2011)
    Primates are characterized by relatively late ages at first reproduction, long lives and low fertility. Together, these traits define a life-history of reduced reproductive effort. Understanding the optimal allocation of reproductive effort, and specifically reduced reproductive effort, has been one of the key problems motivating the development of life-history theory. Because of their unusual constellation of life-history traits, primates play an important role in the continued development of life-history theory. In this review, I present the evidence for the reduced reproductive effort life histories of primates and discuss the ways that such life-history tactics are understood in contemporary theory. Such tactics are particularly consistent with the predictions of stochastic demographic models, suggesting a key role for environmental variability in the evolution of primate life histories. The tendency for primates to specialize in high-quality, high-variability food! items may make them particularly susceptible to environmental variability and explains their low reproductive-effort tactics. I discuss recent applications of life-history theory to human evolution and emphasize the continuity between models used to explain peculiarities of human reproduction and senescence with the long, slow life histories of primates more generally.
  • Ecological and Evolutionary Consequences of Linked Life-History Stages in the Sea
    - Curr Biol 21(18):R718-R725 (2011)
    Naturalists and scientists have been captivated by the diversity of marine larval forms since they were discovered following the advent of the microscope. Because they often bear little resemblance to adults, larvae were identified initially as new life forms, classified into different groups based on the similarity of their body plans and given new names that are still with us today. The radically different body plans and lifestyles of marine larvae and adults have led most investigators historically to study the two phases of complex life cycles in isolation. More recently, important ecological insights have sprung from taking a holistic view of marine life cycles. Meanwhile, the evolutionary (phenotypic and genetic) links among life-history phases remain less appreciated. In this review, our objective is to evaluate the evolutionary links within marine life cycles, and explore their ecological and evolutionary consequences. We provide a brief overview of marine life! histories, discuss the phenotypic and genetic links between the two phases of the life cycle and pose challenges to advance our understanding of the evolutionary constraints acting on marine life histories.
  • The Origins and Evolution of Vertebrate Metamorphosis
    - Curr Biol 21(18):R726-R737 (2011)
    Metamorphosis, classically defined as a spectacular post-embryonic transition, is well exemplified by the transformation of a tadpole into a frog. It implies the appearance of new body parts (such as the limbs), the resorption of larval features (such as the tail) and the remodelling of many organs (such as the skin or the intestine). In vertebrates, metamorphosis has been well characterized in anuran amphibians, where thyroid hormones orchestrate the intricate and seemingly contradictory changes observed at the cellular and tissue levels. Thyroid hormones control a complex hierarchical cascade of target genes via binding to specific receptors, TRα and TRβ, ligand-activated transcription factors belonging to the nuclear receptor superfamily. Metamorphosis is actually widespread in the vertebrates, though quite diverse in the way it manifests in a particular species. Furthermore, evolutionary and ecological variations of this key event, from paedomorphosis to dire! ct development, provide an excellent illustration of how tinkering with a control pathway can lead to divergent life histories. The study of invertebrate chordates has also shed light on the origin of metamorphosis. The available data suggest that post-embryonic remodelling governed by thyroid hormones is an ancestral feature of chordates. According to this view, metamorphosis of the anurans is an extreme example of a widespread life history transition.
  • Polyphenism in Insects
    - Curr Biol 21(18):R738-R749 (2011)
    Polyphenism is the phenomenon where two or more distinct phenotypes are produced by the same genotype. Examples of polyphenism provide some of the most compelling systems for the study of epigenetics. Polyphenisms are a major reason for the success of the insects, allowing them to partition life history stages (with larvae dedicated to feeding and growth, and adults dedicated to reproduction and dispersal), to adopt different phenotypes that best suit predictable environmental changes (seasonal morphs), to cope with temporally heterogeneous environments (dispersal morphs), and to partition labour within social groups (the castes of eusocial insects). We survey the status of research on some of the best known examples of insect polyphenism, in each case considering the environmental cues that trigger shifts in phenotype, the neurochemical and hormonal pathways that mediate the transformation, the molecular genetic and epigenetic mechanisms involved in initiating and mai! ntaining the polyphenism, and the adaptive and life-history significance of the phenomenon. We conclude by highlighting some of the common features of these examples and consider future avenues for research on polyphenism.
  • Coordinating Growth and Maturation — Insights from Drosophila
    - Curr Biol 21(18):R750-R757 (2011)
    Adult body size in higher animals is dependent on the amount of growth that occurs during the juvenile stage. The duration of juvenile development, therefore, must be flexible and responsive to environmental conditions. When immature animals experience environmental stresses such as malnutrition or disease, maturation can be delayed until conditions improve and normal growth can resume. In contrast, when animals are raised under ideal conditions that promote rapid growth, internal checkpoints ensure that maturation does not occur until juvenile development is complete. Although the mechanisms that regulate growth and gate the onset of maturation have been investigated for decades, the emerging links between childhood obesity, early onset puberty, and adult metabolic disease have placed a new emphasis on this field. Remarkably, genetic studies in the fruit fly Drosophila melanogaster have shown that the central regulatory pathways that control growth and the timing of s! exual maturation are conserved through evolution, and suggest that this aspect of animal life history is regulated by a common genetic architecture. This review focuses on these conserved mechanisms and highlights recent studies that explore how Drosophila coordinates developmental growth with environmental conditions.
  • Hormone Signaling and Phenotypic Plasticity in Nematode Development and Evolution
    - Curr Biol 21(18):R758-R766 (2011)
    Phenotypic plasticity refers to the ability of an organism to adopt different phenotypes depending on environmental conditions. In animals and plants, the progression of juvenile development and the formation of dormant stages are often associated with phenotypic plasticity, indicating the importance of phenotypic plasticity for life-history theory. Phenotypic plasticity has long been emphasized as a crucial principle in ecology and as facilitator of phenotypic evolution. In nematodes, several examples of phenotypic plasticity have been studied at the genetic and developmental level. In addition, the influence of different environmental factors has been investigated under laboratory conditions. These studies have provided detailed insight into the molecular basis of phenotypic plasticity and its ecological and evolutionary implications. Here, we review recent studies on the formation of dauer larvae in Caenorhabditis elegans, the evolution of nematode parasitism and th! e generation of a novel feeding trait in Pristionchus pacificus. These examples reveal a conserved and co-opted role of an endocrine signaling module involving the steroid hormone dafachronic acid. We will discuss how hormone signaling might facilitate life-history and morphological evolution.
  • Macroparasite Life Histories
    - Curr Biol 21(18):R767-R774 (2011)
    Parasites and parasitism is common. Worm macroparasites have evolved life-history traits that allow them to successfully transmit between spatially and temporally separated patches of host resource and to survive within these environments. Macroparasites have common life-history strategies to achieve this, but these general themes are modified in a myriad of ways related to the specific biology of their hosts. Parasite life histories are also dynamic, responding to conditions inside and outside of hosts, and they continue to evolve, especially in response to our attempts to control them and the harm that they cause.
  • Life Histories of Symbiotic Rhizobia and Mycorrhizal Fungi
    - Curr Biol 21(18):R775-R785 (2011)
    Research on life history strategies of microbial symbionts is key to understanding the evolution of cooperation with hosts, but also their survival between hosts. Rhizobia are soil bacteria known for fixing nitrogen inside legume root nodules. Arbuscular mycorrhizal (AM) fungi are ubiquitous root symbionts that provide plants with nutrients and other benefits. Both kinds of symbionts employ strategies to reproduce during symbiosis using host resources; to repopulate the soil; to survive in the soil between hosts; and to find and infect new hosts. Here we focus on the fitness of the microbial symbionts and how interactions at each of these stages has shaped microbial life-history strategies. During symbiosis, microbial fitness could be increased by diverting more resources to individual reproduction, but that may trigger fitness-reducing host sanctions. To survive in the soil, symbionts employ sophisticated strategies, such as persister formation for rhizobia and revers! al of spore germination by mycorrhizae. Interactions among symbionts, from rhizobial quorum sensing to fusion of genetically distinct fungal hyphae, increase adaptive plasticity. The evolutionary implications of these interactions and of microbial strategies to repopulate and survive in the soil are largely unexplored.
  • Nuclear and Genome Dynamics in Multinucleate Ascomycete Fungi
    - Curr Biol 21(18):R786-R793 (2011)
    Genetic variation between individuals is essential to evolution and adaptation. However, intra-organismic genetic variation also shapes the life histories of many organisms, including filamentous fungi. A single fungal syncytium can harbor thousands or millions of mobile and potentially genotypically different nuclei, each having the capacity to regenerate a new organism. Because the dispersal of asexual or sexual spores propagates individual nuclei in many of these species, selection acting at the level of nuclei creates the potential for competitive and cooperative genome dynamics. Recent work in Neurospora crassa and Sclerotinia sclerotiorum has illuminated how nuclear populations are coordinated for fungal growth and other behaviors and has revealed both molecular and physical mechanisms for preventing and policing inter-genomic conflict. Recent results from population-level genomic studies in a variety of filamentous fungi suggest that nuclear exchange between myc! elia and recombination between heterospecific nuclei may be of more importance to fungal evolution, diversity and the emergence of newly virulent strains than has previously been recognized.
  • Autophagy and Lipid Metabolism Coordinately Modulate Life Span in Germline-less C. elegans
    - Curr Biol 21(18):1507-1514 (2011)
    Background The cellular recycling process of autophagy is emerging as a key player in several longevity pathways in Caenorhabditis elegans. Here, we identify a role for autophagy in long-lived animals lacking a germline and show that autophagy and lipid metabolism work interdependently to modulate aging in this longevity model. Results Germline removal extends life span in C. elegans via genes such as the lipase LIPL-4; however, less is known of the cellular basis for this life-span extension. Here, we show that germline loss induces autophagy gene expression via the forkhead box A (FOXA) transcription factor PHA-4 and that autophagy is required to extend longevity. We identify a novel link between autophagy and LIPL-4, because autophagy is required to maintain high lipase activity in germline-deficient animals. Reciprocally, lipl-4 is required for autophagy induction. Coordination between autophagy and lipolysis is further supported by the finding that inhibition of TOR (target of rapamycin), a major negative regulator of autophagy, induces lipl-4 expression, and TOR levels are reduced in germline-less animals. TOR may therefore function as a common upstream regulator of both autophagy and lipl-4 expression in germline-less animals. Importantly, we find that the link between autophagy and LIPL-4 is releva! nt to longevity, because autophagy is induced in animals overexpressing LIPL-4 and autophagy is required for their long life span, recapitulating observations in germline-less animals. Conclusions Collectively, our data offer a novel mechanism by which autophagy and the lipase LIPL-4 interdependently modulate aging in germline-deficient C. elegans by maintaining lipid homeostasis to prolong life span.
  • Molecular Organization of Drosophila Neuroendocrine Cells by Dimmed
    - Curr Biol 21(18):1515-1524 (2011)
    Background In Drosophila, the basic-helix-loop-helix protein DIMM coordinates the molecular and cellular properties of all major neuroendocrine cells, irrespective of the secretory peptides they produce. When expressed by nonneuroendocrine neurons, DIMM confers the major properties of the regulated secretory pathway and converts such cells away from fast neurotransmission and toward a neuroendocrine state. Results We first identified 134 transcripts upregulated by DIMM in embryos and then evaluated them systematically using diverse assays (including embryo in situ hybridization, in vivo chromatin immunoprecipitation, and cell-based transactivation assays). We conclude that of eleven strong candidates, six are strongly and directly controlled by DIMM in vivo. The six targets include several large dense-core vesicle (LDCV) proteins, but also proteins in non-LDCV compartments such as the RNA-associated protein Maelstrom. In addition, a functional in vivo assay, combining transgenic RNA interference with MS-based peptidomics, revealed that three DIMM targets are especially critical for its action. These include two well-established LDCV proteins, the amidation enzyme PHM and the ascorbate-regenerating electron transporter cytochrome b561-1. The third key DIMM target, CAT-4 (CG13248), has not previously been associated with peptide neurosecretion—it encodes a putative cationic amino acid! transporter, closely related to the Slimfast arginine transporter. Finally, we compared transcripts upregulated by DIMM with those normally enriched in DIMM neurons of the adult brain and found an intersection of 18 DIMM-regulated genes, which included all six direct DIMM targets. Conclusions The results provide a rigorous molecular framework with which to describe the fundamental regulatory organization of diverse neuroendocrine cells.
  • Hedgehog Signaling Regulates Nociceptive Sensitization
    - Curr Biol 21(18):1525-1533 (2011)
    Background Nociceptive sensitization is a tissue damage response whereby sensory neurons near damaged tissue enhance their responsiveness to external stimuli. This sensitization manifests as allodynia (aversive withdrawal to previously nonnoxious stimuli) and/or hyperalgesia (exaggerated responsiveness to noxious stimuli). Although some factors mediating nociceptive sensitization are known, inadequacies of current analgesic drugs have prompted a search for additional targets. Results Here we use a Drosophila model of thermal nociceptive sensitization to show that Hedgehog (Hh) signaling is required for both thermal allodynia and hyperalgesia following ultraviolet irradiation (UV)-induced tissue damage. Sensitization does not appear to result from developmental changes in the differentiation or arborization of nociceptive sensory neurons. Genetic analysis shows that Hh signaling acts in parallel to tumor necrosis factor (TNF) signaling to mediate allodynia and that distinct transient receptor potential (TRP) channels mediate allodynia and hyperalgesia downstream of these pathways. We also demonstrate a role for Hh in analgesic signaling in mammals. Intrathecal or peripheral administration of cyclopamine (CP), a specific inhibitor of Sonic Hedgehog signaling, blocked the development of analgesic tolerance to morphine (MS) or morphine antinociception in standard assays of inflammatory pain in rats and synergistically augmented and sustained morphine analges! ia in assays of neuropathic pain. Conclusions We demonstrate a novel physiological role for Hh signaling, which has not previously been implicated in nociception. Our results also identify new potential therapeutic targets for pain treatment.
  • Arg Kinase Regulates Epithelial Cell Polarity by Targeting β1-Integrin and Small GTPase Pathways
    - Curr Biol 21(18):1534-1542 (2011)
    Background Establishment and maintenance of epithelial cell polarity is regulated in part by signaling from adhesion receptors. Loss of cell polarity is associated with multiple pathologies including the initiation and progression of various cancers. The β1-integrin adhesion receptor plays a role in the regulation of cell polarity; however, the identity of the signaling pathways that modulate β1-integrin function and connect it to the regulation of polarity pathways remains largely unknown. Results The present work identifies a role for Arg, a member of the Abl family nonreceptor tyrosine kinases, in the regulation of adhesive signals and epithelial cell polarity. In a three-dimensional cell culture model, activation of Arg kinase leads to a striking inversion of apical-basal polarity. In contrast, loss of Arg function impairs the establishment of a polarized epithelial cyst structure. Activated Arg kinase disrupts β1-integrin signaling and localization and impairs Rac1-mediated laminin assembly. Disruption of β1-integrin function by active Arg results in altered distribution of selected polarity complex components mediated in part by Rap1 GTPase signaling. Whereas polarity inversion is partially rescued by a constitutively active Rap1, Rac1-dependent laminin assembly is not, indicating that Rap1 and Rac1 signal independently during epithelial polarity. Conclusions These findings suggest that modulation of Arg kinase function may contribute not only to normal epithelial polarity regulation but also may promote pathologies associated with loss of cell polarity.
  • Training Attentional Control in Infancy
    - Curr Biol 21(18):1543-1547 (2011)
    Several recent studies have reported that cognitive training in adults does not lead to generalized performance improvements [ [1] and [2] ], whereas many studies with younger participants (children 4 years and older) have reported distal transfer [ [3] and [4] ]. This is consistent with convergent evidence [ [5] , [6] , [7] and [8] ] for greater neural and behavioral plasticity earlier in development. We used gaze-contingent paradigms to train 11-month-old infants on a battery of attentional control tasks. Relative to an active control group, and following only a relatively short training period, posttraining assessments revealed improvements in cognitive control and sustained attention, reduced saccadic reaction times, and reduced latencies to disengage visual attention. Trend changes were also observed in spontaneous looking behavior during free play, but no change was found in working memory. The amount of training correlated with the degree of improvement ! on some measures. These findings are to our knowledge the first demonstration of distal transfer following attentional control training in infancy. Given the longitudinal relationships identified between early attentional control and learning in academic settings [ [9] and [10] ], and the causal role that impaired control of attention may play in disrupting learning in several disorders [ [11] , [12] , [13] and [14] ], the current results open a number of avenues for future work.
  • Regulation of Sexual Plasticity in a Nematode that Produces Males, Females, and Hermaphrodites
    - Curr Biol 21(18):1548-1551 (2011)
    The mechanisms by which new modes of reproduction evolve remain important unsolved puzzles in evolutionary biology. Nematode worms are ideal for studying the evolution of mating systems because the phylum includes both a large range of reproductive modes and large numbers of evolutionarily independent switches [ [1] and [2] ]. Rhabditis sp. SB347, a nematode with sexual polymorphism, produces males, females, and hermaphrodites [3]. To understand how the transition between mating systems occurs, we characterized the mechanisms that regulate female versus hermaphrodite fate in Rhabditis sp. SB347. Hermaphrodites develop through an obligatory nonfeeding juvenile stage, the dauer larva. Here we show that by suppressing dauer formation, Rhabditis sp. SB347 develops into females. Conversely, larvae that under optimal growth conditions develop into females can be respecified toward hermaphroditic development if submitted to dauer-inducing conditions. These results are of si! gnificance to understanding the evolution of complex mating systems present in parasitic nematodes.
  • A Shift in Sensory Processing that Enables the Developing Human Brain to Discriminate Touch from Pain
    - Curr Biol 21(18):1552-1558 (2011)
    When and how infants begin to discriminate noxious from innocuous stimuli is a fundamental question in neuroscience [1]. However, little is known about the development of the necessary cortical somatosensory functional prerequisites in the intact human brain. Recent studies of developing brain networks have emphasized the importance of transient spontaneous and evoked neuronal bursting activity in the formation of functional circuits [ [2] and [3] ]. These neuronal bursts are present during development and precede the onset of sensory functions [ [4] and [5] ]. Their disappearance and the emergence of more adult-like activity are therefore thought to signal the maturation of functional brain circuitry [ [2] and [4] ]. Here we show the changing patterns of neuronal activity that underlie the onset of nociception and touch discrimination in the preterm infant. We have conducted noninvasive electroencephalogram (EEG) recording of the brain neuronal activity in respo! nse to time-locked touches and clinically essential noxious lances of the heel in infants aged 28–45 weeks gestation. We show a transition in brain response following tactile and noxious stimulation from nonspecific, evenly dispersed neuronal bursts to modality-specific, localized, evoked potentials. The results suggest that specific neural circuits necessary for discrimination between touch and nociception emerge from 35–37 weeks gestation in the human brain.
  • An Essential Protein that Interacts with Endosomes and Promotes Movement of the SHORT-ROOT Transcription Factor
    - Curr Biol 21(18):1559-1564 (2011)
    Plant cells can communicate through the direct transport of transcription factors [ [1] , [2] , [3] , [4] , [5] , [6] and [7] ]. One of the best-studied examples of this phenomenon is SHORT-ROOT (SHR), which moves from the stele cells into the endodermis and root tip of Arabidopsis, where it specifies endodermal cell identity and stem cell function, respectively [ [8] , [9] and [10] ]. In the endodermis, SHR upregulates the transcription factors SCARECROW (SCR) [2] and JACKDAW (JKD), which in turn inhibit movement of SHR from the endodermis [11]. Although much is known about the regulatory pathways that mediate expression and activity of SHR [ [1] , [8] , [9] , [10] , [11] , [12] , [13] and [14] ], little is known about the factors that promote its movement or the movement of other transcription factors. We have identified a novel protein, SHORT-ROOT INTERACTING EMBRYONIC LETHAL (SIEL), that interacts with SHR, CAPRICE (CPC), TARGET OF MONOPTEROUS 7 (! TMO7), and AGAMOUS-LIKE 21 (AGL21). Null alleles of SIEL are embryonic lethal. Hypomorphic alleles produce defects in root patterning and reduce SHR movement. Surprisingly, both SHR and SCR regulate expression of SIEL, so that siel/scr and siel/shr double mutants have extremely disorganized roots. SIEL localizes to the nucleus and cytoplasm of root cells where it is associated with endosomes. We propose that SIEL is an endosome-associated protein that promotes intercellular movement.
  • Continental Shelf-Wide Response of a Fish Assemblage to Rapid Warming of the Sea
    - Curr Biol 21(18):1565-1570 (2011)
    Climate change affects marine biological processes from genetic to ecosystem levels [ [1] , [2] and [3] ]. Recent warming in the northeast Atlantic [ [4] and [5] ] has caused distributional shifts in some fish species along latitudinal and depth gradients [ [6] and [7] ], but such changes, as predicted by climate envelope models [8], may often be prevented because population movement requires availability of suitable habitat. We assessed the full impacts of warming on the commercially important European continental shelf fish assemblage using a data-driven Eulerian (grid-based) approach that accommodates spatial heterogeneity in ecological and environmental conditions. We analyzed local associations of species abundance and community diversity with climatic variables, assessing trends in 172 cells from records of >100 million individuals sampled over 1.2 million km2 from 1980–2008. We demonstrate responses to warming in 72% of common species, with three times ! more species increasing in abundance than declining, and find these trends reflected in international commercial landings. Profound reorganization of the relative abundance of species in local communities occurred despite decadal stability in the presence-absence of species. Our analysis highlights the importance of focusing on changes in species abundance in established local communities to assess the full consequences of climate change for commercial fisheries and food security.
  • The Snail Repressor Inhibits Release, Not Elongation, of Paused Pol II in the Drosophila Embryo
    - Curr Biol 21(18):1571-1577 (2011)
    The development of the precellular Drosophila embryo is characterized by exceptionally rapid transitions in gene activity, with broadly distributed maternal regulatory gradients giving way to precise on/off patterns of gene expression within a one-hour window, between two and three hours after fertilization [1]. Transcriptional repression plays a pivotal role in this process, delineating sharp expression patterns (e.g., pair-rule stripes) within broad domains of gene activation. As many as 20 different sequence-specific repressors have been implicated in this process, yet the mechanisms by which they silence gene expression have remained elusive [2]. Here we report the development of a method for the quantitative visualization of transcriptional repression. We focus on the Snail repressor, which establishes the boundary between the presumptive mesoderm and neurogenic ectoderm [3]. We find that elongating Pol II complexes complete transcription after the onset of Snail ! repression. As a result, moderately sized genes (e.g., the 22 kb sog locus) are fully silenced only after tens of minutes of repression. We propose that this "repression lag" imposes a severe constraint on the regulatory dynamics of embryonic patterning and further suggest that posttranscriptional regulators, like microRNAs, are required to inhibit unwanted transcripts produced during protracted periods of gene silencing.
  • Organization of the Smallest Eukaryotic Spindle
    - Curr Biol 21(18):1578-1583 (2011)
    In metazoans, plants, and fungi, the spindle checkpoint delays mitosis until each chromosome is attached to one or more of its own kinetochore microtubules (kMTs). Some unicellular eukaryotes, however, have been reported to have fewer kMTs than chromosomes [ [1] , [2] , [3] , [4] and [5] ]. If this is the case, it is unclear how the spindle checkpoint could be satisfied. In the vast majority of the previous studies, mitotic cells were chemically fixed at room temperature, but this does not always preserve dynamic and/or small structures like spindle MTs and kinetochores [6]. Indeed, later higher-resolution studies have reversed some earlier claims [ [7] , [8] , [9] , [10] and [11] ]. Here we show that in Ostreococcus tauri (the smallest eukaryote known), mitosis does involve fewer spindle microtubules than chromosomes. O. tauri cultures were enriched for mitotic cells, high-pressure frozen, and then imaged in 3D both in plastic and in a near-native ("frozen! -hydrated") state through electron tomography. Mitotic cells have a distinctive intranuclear heterochromatin-free "spindle tunnel" with approximately four short and occasionally one long, incomplete (unclosed) microtubule at each end of the spindle tunnel. Because other aspects of O. tauri's spindle checkpoint seem typical, these data suggest that O. tauri's 20 chromosomes are physically linked and segregated as just one or a small number of groups.
  • HURP Regulates Chromosome Congression by Modulating Kinesin Kif18A Function
    - Curr Biol 21(18):1584-1591 (2011)
    Chromosome biorientation and congression during mitosis require precise control of microtubule dynamics [ [1] , [2] , [3] and [4] ]. The dynamics of kinetochore microtubules (K-MTs) are regulated by a variety of microtubule-associated proteins (MAPs) [ [4] , [5] , [6] , [7] , [8] and [9] ]. Recently, a MAP known as HURP (hepatoma upregulated protein) was identified [ [10] , [11] and [12] ]. During mitosis, Ran-guanosine 5′-triphosphate (RanGTP) releases HURP from the importin β inhibitory complex and allows it to localize to the kinetochore fiber (k-fiber) [ [12] and [13] ]. HURP stabilizes k-fibers and promotes chromosome congression [ [12] , [14] and [15] ]. However, the molecular mechanism underlying the role of HURP in regulating chromosome congression remains elusive. Here, we show that overexpression of the N-terminal microtubule binding domain (1–278 aa, HURP278) of HURP induces a series of mitotic defects that mimic the effects of Kif18! A depletion. In addition, coimmunoprecipitation and bimolecular fluorescence complementation assays identify Kif18A as a novel interaction partner of HURP. Furthermore, quantitative results from live-cell imaging analyses illustrate that HURP regulates Kif18A localization and dynamics at the plus end of K-MTs. Lastly, misaligned chromosomes in HURP278-overexpressing cells can be partially rescued by the overexpression of Kif18A. Our results demonstrate in part the regulatory mechanism for Kif18A during chromosome congression and provide new insights into the mechanism of chromosome movement at the metaphase plate.

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