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Current Biology
Journal Prestige (SJR): 4.296
Citation Impact (citeScore): 5
Number of Followers: 256  
 
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ISSN (Print) 0960-9822
Published by Elsevier Homepage  [3157 journals]
  • Male-Specific Conditioned Pain Hypersensitivity in Mice and Humans
    • Abstract: Publication date: Available online 10 January 2019Source: Current BiologyAuthor(s): Loren J. Martin, Erinn L. Acland, Chulmin Cho, Wiebke Gandhi, Di Chen, Elizabeth Corley, Basil Kadoura, Tess Levy, Sara Mirali, Sarasa Tohyama, Sana Khan, Leigh C. MacIntyre, Erika N. Carlson, Petra Schweinhardt, Jeffrey S. MogilSummaryPain memories are hypothesized to be critically involved in the transition of pain from an acute to a chronic state. To help elucidate the underlying neurobiological mechanisms of pain memory, we developed novel paradigms to study context-dependent pain hypersensitivity in mouse and human subjects, respectively. We find that both mice and people become hypersensitive to acute, thermal nociception when tested in an environment previously associated with an aversive tonic pain experience. This sensitization persisted for at least 24 hr and was only present in males of both species. In mice, context-dependent pain hypersensitivity was abolished by castrating male mice, pharmacological blockade of the hypothalamic-pituitary-adrenal axis, or intracerebral or intrathecal injections of zeta inhibitory peptide (ZIP) known to block atypical protein kinase C (including the protein kinase Mζ isoform). In humans, men, but not women, self-reported higher levels of stress when tested in a room previously associated with tonic pain. These models provide a new, completely translatable means for studying the relationship between memory, pain, and stress.
       
  • Dynamic Construction of Reduced Representations in the Brain for
           Perceptual Decision Behavior
    • Abstract: Publication date: Available online 10 January 2019Source: Current BiologyAuthor(s): Jiayu Zhan, Robin A.A. Ince, Nicola van Rijsbergen, Philippe G. SchynsSummaryOver the past decade, extensive studies of the brain regions that support face, object, and scene recognition suggest that these regions have a hierarchically organized architecture that spans the occipital and temporal lobes [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14], where visual categorizations unfold over the first 250 ms of processing [15, 16, 17, 18, 19]. This same architecture is flexibly involved in multiple tasks that require task-specific representations—e.g. categorizing the same object as “a car” or “a Porsche.” While we partly understand where and when these categorizations happen in the occipito-ventral pathway, the next challenge is to unravel how these categorizations happen. That is, how does high-dimensional input collapse in the occipito-ventral pathway to become low dimensional representations that guide behavior' To address this, we investigated what information the brain processes in a visual perception task and visualized the dynamic representation of this information in brain activity. To do so, we developed stimulus information representation (SIR), an information theoretic framework, to tease apart stimulus information that supports behavior from that which does not. We then tracked the dynamic representations of both in magneto-encephalographic (MEG) activity. Using SIR, we demonstrate that a rapid (∼170 ms) reduction of behaviorally irrelevant information occurs in the occipital cortex and that representations of the information that supports distinct behaviors are constructed in the right fusiform gyrus (rFG). Our results thus highlight how SIR can be used to investigate the component processes of the brain by considering interactions between three variables (stimulus information, brain activity, behavior), rather than just two, as is the current norm.
       
  • A New Spiralian Phylogeny Places the Enigmatic Arrow Worms among
           Gnathiferans
    • Abstract: Publication date: Available online 10 January 2019Source: Current BiologyAuthor(s): Ferdinand Marlétaz, Katja T.C.A. Peijnenburg, Taichiro Goto, Noriyuki Satoh, Daniel S. RokhsarSummaryChaetognaths (arrow worms) are an enigmatic group of marine animals whose phylogenetic position remains elusive, in part because they display a mix of developmental and morphological characters associated with other groups [1, 2]. In particular, it remains unclear whether they are a sister group to protostomes [1, 2], one of the principal animal superclades, or whether they bear a closer relationship with some spiralian phyla [3, 4]. Addressing the phylogenetic position of chaetognaths and refining our understanding of relationships among spiralians are essential to fully comprehend character changes during bilaterian evolution [5]. To tackle these questions, we generated new transcriptomes for ten chaetognath species, compiling an extensive phylogenomic dataset that maximizes data occupancy and taxonomic representation. We employed inference methods that consider rate and compositional heterogeneity across taxa to avoid limitations of earlier analyses [6]. In this way, we greatly improved the resolution of the protostome tree of life. We find that chaetognaths cluster together with rotifers, gnathostomulids, and micrognathozoans within an expanded Gnathifera clade and that this clade is the sister group to other spiralians [7, 8]. Our analysis shows that several previously proposed groupings are likely due to systematic error, and we propose a revised organization of Lophotrochozoa with three main clades: Tetraneuralia (mollusks and entoprocts), Lophophorata (brachiopods, phoronids, and ectoprocts), and a third unnamed clade gathering annelids, nemerteans, and platyhelminthes. Consideration of classical morphological, developmental, and genomic characters in light of this topology indicates secondary loss as a fundamental trend in spiralian evolution.
       
  • Filopodome Mapping Identifies p130Cas as a Mechanosensitive Regulator of
           Filopodia Stability
    • Abstract: Publication date: Available online 10 January 2019Source: Current BiologyAuthor(s): Guillaume Jacquemet, Aki Stubb, Rafael Saup, Mitro Miihkinen, Elena Kremneva, Hellyeh Hamidi, Johanna IvaskaSummaryFilopodia are adhesive cellular protrusions specialized in the detection of extracellular matrix (ECM)-derived cues. Although ECM engagement at focal adhesions is known to trigger the recruitment of hundreds of proteins (“adhesome”) to fine-tune cellular behavior, the components of the filopodia adhesions remain undefined. Here, we performed a structured-illumination-microscopy-based screen to map the localization of 80 target proteins, linked to cell adhesion and migration, within myosin-X-induced filopodia. We demonstrate preferential enrichment of several adhesion proteins to either filopodia tips, filopodia shafts, or shaft subdomains, suggesting divergent, spatially restricted functions for these proteins. Moreover, proteins with phosphoinositide (PI) binding sites are particularly enriched in filopodia. This, together with the strong localization of PI(3,4)P2 in filopodia tips, predicts critical roles for PIs in regulating filopodia ultra-structure and function. Our mapping further reveals that filopodia adhesions consist of a unique set of proteins, the filopodome, that are distinct from classical nascent adhesions, focal adhesions, and fibrillar adhesions. Using live imaging, we observe that filopodia adhesions can give rise to nascent adhesions, which, in turn, form focal adhesions. We demonstrate that p130Cas (BCAR1) is recruited to filopodia tips via its C-terminal Cas family homology domain (CCHD) and acts as a mechanosensitive regulator of filopodia stability. Finally, we demonstrate that our map based on myosin-X-induced filopodia can be translated to endogenous filopodia and fascin- and IRSp53-mediated filopodia.
       
  • A Translaminar Genetic Logic for the Circuit Identity of Intracortically
           Projecting Neurons
    • Abstract: Publication date: Available online 10 January 2019Source: Current BiologyAuthor(s): Esther Klingler, Andres De la Rossa, Sabine Fièvre, Karthikeyan Devaraju, Philipp Abe, Denis JabaudonSummaryNeurons of the neocortex are organized into six radial layers, which have appeared at different times during evolution, with the superficial layers representing a more recent acquisition. Input to the neocortex predominantly reaches superficial layers (SL, i.e., layers (L) 2-4), while output is generated in deep layers (DL, i.e., L5-6) [1]. Intracortical connections, which bridge input and output pathways, are key components of cortical circuits because they allow the propagation and processing of information within the neocortex. Two main types of intracortically projecting neurons (ICPN) can be distinguished by their axonal features: L4 spiny stellate neurons (SSN) with short axons projecting locally within cortical columns [2, 3, 4, 5], and SL and DL long-range projection neurons, including callosally projecting neurons (CPNSL and CPNDL) [5, 6]. Here, we investigate the molecular hallmarks that distinguish SSN, CPNSL, and CPNDL and relate their transcriptional signatures with their output connectivity. Specifically, taking advantage of the presence of CPN in both SL and DL, we identify lamina-independent genetic hallmarks of a constant projection motif (i.e., interhemispheric projection). By performing unbiased transcriptomic comparisons between CPNSL, CPNDL and SSN, we provide specific molecular profiles for each of these populations and show that target identity supersedes laminar position in defining ICPN transcriptional diversity. Together, these findings reveal a projection-based organization of transcriptional programs across cortical layers, which we propose reflects conserved strategy to protect canonical circuit structure (and hence function) across a diverse range of neuroanatomies.Graphical Graphical abstract for this article
       
  • All-or-None Context Dependence Delineates Limits of FEF Visual Target
           Selection
    • Abstract: Publication date: Available online 10 January 2019Source: Current BiologyAuthor(s): Veronica E. Scerra, M. Gabriela Costello, Emilio Salinas, Terrence R. StanfordSummaryChoices of where to look are informed by perceptual judgments, which locate objects of current value or interest within the visual scene. This perceptual-motor transform is partly implemented in the frontal eye field (FEF), where visually responsive neurons appear to select behaviorally relevant visual targets and, subsequently, saccade-related neurons select the movements required to look at them. Here, we use urgent decision-making tasks to show (1) that FEF motor activity can direct accurate, visually informed choices in the complete absence of prior target-distracter discrimination by FEF visual responses and (2) that such discrimination by FEF visual cells shows an all-or-none reliance on the presence of stimulus attributes strongly associated with saliency-driven attentional allocation. The present findings suggest that FEF visual target selection is specific to visual judgments made on the basis of saliency and may not play a significant role in guiding saccadic choices informed solely by feature content.
       
  • Dynamics of Free and Chromatin-Bound Histone H3 during Early Embryogenesis
    • Abstract: Publication date: Available online 10 January 2019Source: Current BiologyAuthor(s): Yuki Shindo, Amanda A. AmodeoSummaryDuring zygotic genome activation (ZGA), the chromatin environment undergoes profound changes, including the formation of topologically associated domains, refinements in nucleosome positioning on promoters, and the emergence of heterochromatin [1, 2, 3, 4]. In many organisms, including Drosophila, ZGA is associated with the end of a period of extremely rapid, exponential cleavage divisions that are facilitated by large maternally provided pools of nuclear components. It is therefore imperative that we understand how the supply of chromatin components relative to the exponentially increasing demand affects nuclear and chromatin composition during early embryogenesis. Here, we examine the nuclear trafficking and chromatin dynamics of histones during the cleavage divisions in Drosophila using a photo-switchable H3-Dendra2 reporter. We observe that total H3-Dendra2 in the nucleus decreases with each cleavage cycle. This change in nuclear composition is due to depletion of large pools (>50%) of free protein that are present in the early cycles. We find that the per nucleus import rate halves with each cycle and construct a mathematical model in which increasing histone demand determines the dynamics of nuclear H3 supply. Finally, we show that these changes in H3 availability correspond to a large (∼40%) reduction in global H3 occupancy on the chromatin, which is compensated by the increased incorporation of H3.3. The observed changes in free nuclear H3 and chromatin composition may contribute to the cell-cycle slowing, changes in chromatin structure, and the onset of transcription associated with this developmental stage.
       
  • The Genomic Footprints of the Fall and Recovery of the Crested Ibis
    • Abstract: Publication date: Available online 10 January 2019Source: Current BiologyAuthor(s): Shaohong Feng, Qi Fang, Ross Barnett, Cai Li, Sojung Han, Martin Kuhlwilm, Long Zhou, Hailin Pan, Yuan Deng, Guangji Chen, Anita Gamauf, Friederike Woog, Robert Prys-Jones, Tomas Marques-Bonet, M. Thomas P. Gilbert, Guojie ZhangSummaryHuman-induced environmental change and habitat fragmentation pose major threats to biodiversity and require active conservation efforts to mitigate their consequences. Genetic rescue through translocation and the introduction of variation into imperiled populations has been argued as a powerful means to preserve, or even increase, the genetic diversity and evolutionary potential of endangered species [1, 2, 3, 4]. However, factors such as outbreeding depression [5, 6] and a reduction in available genetic diversity render the success of such approaches uncertain. An improved evaluation of the consequence of genetic restoration requires knowledge of temporal changes to genetic diversity before and after the advent of management programs. To provide such information, a growing number of studies have included small numbers of genomic loci extracted from historic and even ancient specimens [7, 8]. We extend this approach to its natural conclusion, by characterizing the complete genomic sequences of modern and historic population samples of the crested ibis (Nipponia nippon), an endangered bird that is perhaps the most successful example of how conservation effort has brought a species back from the brink of extinction. Though its once tiny population has today recovered to>2,000 individuals [9], this process was accompanied by almost half of ancestral loss of genetic variation and high deleterious mutation load. We furthermore show how genetic drift coupled to inbreeding following the population bottleneck has largely purged the ancient polymorphisms from the current population. In conclusion, we demonstrate the unique promise of exploiting genomic information held within museum samples for conservation and ecological research.
       
  • Reprogramming Cdr2-Dependent Geometry-Based Cell Size Control in Fission
           Yeast
    • Abstract: Publication date: Available online 10 January 2019Source: Current BiologyAuthor(s): Giuseppe Facchetti, Benjamin Knapp, Ignacio Flor-Parra, Fred Chang, Martin HowardSummaryHow cell size is determined and maintained remains unclear, even in simple model organisms. In proliferating cells, cell size is regulated by coordinating growth and division through sizer, adder, or timer mechanisms or through some combination [1, 2]. Currently, the best-characterized example of sizer behavior is in fission yeast, Schizosaccharomyces pombe, which enters mitosis at a minimal cell size threshold. The peripheral membrane kinase Cdr2 localizes in clusters (nodes) on the medial plasma membrane and promotes mitotic entry [3]. Here, we show that the Cdr2 nodal density, which scales with cell size, is used by the cell to sense and control its size. By analyzing cells of different widths, we first show that cdr2+ cells divide at a fixed cell surface area. However, division in the cdr2Δ mutant is more closely specified by cell volume, suggesting that Cdr2 is essential for area sensing and supporting the existence of a Cdr2-independent secondary sizer mechanism more closely based on volume. To investigate how Cdr2 nodes may sense area, we derive a minimal mathematical model that incorporates the cytoplasmic kinase Ssp1 as a Cdr2 activator. The model predicts that a cdr2 mutant in an Ssp1 phosphorylation site (cdr2-T166A) [4] should form nodes whose density registers cell length. We confirm this prediction experimentally and find that thin cells now follow this new scaling by dividing at constant length instead of area. This work supports the role of Cdr2 as a sizer factor and highlights the importance of studying geometrical aspects of size control.Graphical Graphical abstract for this article
       
  • Climate Change May Affect Fatal Competition between Two Bird Species
    • Abstract: Publication date: Available online 10 January 2019Source: Current BiologyAuthor(s): Jelmer M. Samplonius, Christiaan BothSummaryClimate warming has altered phenologies of many taxa [1, 2], but the extent differs vastly between [3, 4] and within trophic levels [5, 6, 7]. Differential adjustment to climate warming within trophic levels may affect coexistence of competing species, because relative phenologies alter facilitative and competitive outcomes [8, 9], but evidence for this is scant [10, 11]. Here, we report on two mechanisms through which climate change may affect fatal interactions between two sympatric passerines, the resident great tit Parus major and the migratory pied flycatcher Ficedula hypoleuca, competing for nest sites. Spring temperature more strongly affected breeding phenology of tits than flycatchers, and tits killed more flycatchers when flycatcher arrival coincided with peak laying in the tits. Ongoing climate change may diminish this fatal competition if great tit and flycatcher phenologies diverge. However, great tit density increased after warm winters, and flycatcher mortality was elevated when tit densities were higher. Consequently, flycatcher males in synchronous and high-tit-density years suffered mortality by great tits of up to 8.9%. Interestingly, we found no population consequences of fatal competition, suggesting that mortality predominantly happened among surplus males. Indeed, late-arriving males are less likely to find a partner [12], and here we show that such late arrivers are more likely to die from competition with great tits. We conclude that our breeding population is buffered against detrimental effects of competition. Nevertheless, we expect that if buffers are diminished, population consequences of interspecific competition may become apparent, especially after warm winters that are benign to resident species.Video Graphical Graphical abstract for this article
       
  • Microtubules and Neurodegeneration: The Tubulin Code Sets the Rules of the
           Road
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): J. Chloë BulinskiSummaryTwo recent papers demonstrate that the ‘tubulin code’ — the pattern of chemical modifications of tubulin along a microtubule — is disrupted upon deletion or mutation of an enzyme, called CCP1, that removes one of these modifications. Ablation of CCP1 interferes with mitochondrial transport and causes human neurodegenerative disease, which may be amenable to pharmacological therapies.
       
  • Chromosomes: Keeping Centromeric Chromatin Tidy through S Phase
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): Jennine M. Dawicki-McKenna, Ben E. BlackSummaryThe centromere, the chromosomal locus where the kinetochore is assembled in mitosis, is defined epigenetically, and its location must be remembered with each cell cycle. Recent studies elucidate how centromere identity is faithfully maintained despite challenges imposed by DNA replication.
       
  • Larval Development: Making Ants into Soldiers
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): H. Frederik NijhoutSummaryMany ant species have complex caste systems, with reproductive queens and sterile workers, which often play distinct roles in the maintenance and defense of the colony. A new study sheds light on how these worker caste systems evolved and the mechanisms by which totipotent larvae give rise to the alternative adult castes.
       
  • Exocytosis: A New Exocyst Movie
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): Kunrong Mei, Wei GuoSummaryUsing genome editing and advanced light microscopy, a recent study has offered new insights into the dynamic assembly and disassembly of the exocyst complex during vesicle tethering and membrane fusion.
       
  • Working Memory: Why You Didn’t Trip on that Rock
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): Daniel S. MarigoldSummaryOnce an animal steps over an obstacle with its forelimbs, the obstacle is no longer visible. The posterior parietal cortex appears to maintain an obstacle representation in working memory through phasic and sustained activity to allow for appropriate hindlimb elevation.
       
  • Pseudokinases: Flipping the ATP for AMPylation
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): Lee BardwellSummaryThe crystal structure of SelO, a pseudokinase previously presumed to be inactive, reveals an ATP cofactor sitting in the active site in a flipped orientation compared with canonical kinases, leading to the discovery of an unexpected catalytic activity for this ancient enzyme.
       
  • Evolution: How Many Phenotypes Do Regulatory Mutations Affect'
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): Gavin Rice, Mark RebeizSummaryMutations in gene regulatory regions are thought to play an important role in the evolution of morphological structures. This is largely due to their minimal pleiotropic effects, limiting their impact to one particular body part. A recent study finds that one such regulatory mutation may affect two particular morphological structures.
       
  • Gustation and Olfaction: The Importance of Place and Time
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): Lindsey Czarnecki, Alfredo FontaniniSummaryAnimals can smell odors from the external environment or from their mouth via two routes: orthonasal and retronasal, respectively. Little is known about how the brain processes orthonasal and retronasal odors associated with taste, but a new study has revealed an important role for the gustatory cortex in such odor processing.
       
  • Biotremology: The Sound of One Egg Cracking
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): Peggy S.M. HillSummaryIn many animals, eggs within a clutch emerge more or less at the same time. A new study identifies vibrations of eggs cracking open as the cue that triggers synchronous emergence in an insect.
       
  • No evidence for a magnetite-based magnetoreceptor in the lagena of pigeons
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): E. Pascal Malkemper, Daniel Kagerbauer, Lyubov Ushakova, Simon Nimpf, Paul Pichler, Christoph D. Treiber, Martin de Jonge, Jeremy Shaw, David A. KeaysSummaryIt is well established that an array of avian species sense the Earth’s magnetic field and use this information for orientation and navigation. While the existence of a magnetic sense can no longer be disputed, the underlying cellular and biophysical basis remains unknown. It has been proposed that pigeons exploit a magnetoreceptor based on magnetite crystals (Fe3O4) that are located within the lagena [1], a sensory epithelium of the inner ear. It has been hypothesised that these magnetic crystals form a bed of otoconia that stimulate hair cells transducing magnetic information into a neuronal impulse. We performed a systematic high-sensitivity screen for iron in the pigeon lagena using synchrotron X-ray fluorescence microscopy coupled with the analysis of serial sections by transmission electron microscopy. We find no evidence for extracellular magnetic otoconia or intracellular magnetite crystals, suggesting that if an inner ear magnetic sensor does exist it relies on a different biophysical mechanism.
       
  • Female-biased stranding in Magellanic penguins
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): Takashi Yamamoto, Ken Yoda, Gabriela S. Blanco, Flavio QuintanaSummaryMagellanic penguins (Spheniscus magellanicus) have been reported to become stranded along the coasts of northern Argentina, Uruguay and southern Brazil during the austral winter 1, 2, 3. This location is more than a thousand kilometers distant from their northernmost breeding colony in northern Patagonia. Curiously, females typically outnumber males at stranding sites (approximately three females per male) [2]. To date, no conspicuous sex differences have been reported in their migratory movements [3], although records are lacking during the peak stranding season. Consequently, the reason(s) for the female-biased stranding remain unknown, despite the growing necessity for understanding their behavior outside the breeding season [3]. We recorded at-sea distributions of Magellanic penguins throughout the non-breeding period using animal-borne data loggers and found that females reached more northern areas than males and did not dive as deep during winter (Figure 1). Such sexual differences in spatial domains might be driven by mechanisms related to sexual size dimorphism, such as the avoidance of intraspecific competition for food resources [4], differences in thermal habitat preference [5] or differences in the ability to withstand the northward-flowing ocean circulation [6]. Individual penguins that winter in northern areas are likely to be at greater risk of natural [7] and anthropogenic threats [8], and probably more so in females, as more females than males tend to frequent areas closer to the sites where penguins strand. Our results highlight the importance of understanding the spatial domains of each sex throughout the annual cycle that are associated with different mortality risks.
       
  • Hybridogenesis
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): Guillaume Lavanchy, Tanja SchwanderSummaryHybridogenesis is an unusual form of reproduction that is found in hybrids between different species. It involves the selective transmission of one of the parental genomes, while the other one is renewed by mating with the corresponding species. It is seen as a form of sexual parasitism, in which the hybridogenetic genome gains a twofold transmission advantage and exploits the reproductive effort of another species.
       
  • Ascetosporea
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): David Bass, Georgia M. Ward, Fabien Burki
       
  • Mark Blumberg
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): Mark Blumberg
       
  • A vision for historical biogeography
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): Nathan A. Jud
       
  • Beneficial bugs
    • Abstract: Publication date: 7 January 2019Source: Current Biology, Volume 29, Issue 1Author(s): Michael GrossSummaryMuch maligned as parasites, pests and disease vectors, insects in the order Hemiptera (true bugs and allies) and related groups are rarely appreciated and insufficiently understood. They have important roles to play in their ecosystems, while some serve biological pest control and others could even help medicine with new bioactives. Michael Gross reports.
       
  • Extended Flight Bouts Require Disinhibition from GABAergic Mushroom Body
           Neurons
    • Abstract: Publication date: Available online 3 January 2019Source: Current BiologyAuthor(s): Steffy B. Manjila, Maria Kuruvilla, Jean-Francois Ferveur, Sanjay P. Sane, Gaiti HasanSummaryInsect flight is a complex behavior that requires the integration of multiple sensory inputs with flight motor output. Although previous genetic studies identified central brain monoaminergic neurons that modulate Drosophila flight, neuro-modulatory circuits underlying sustained flight bouts remain unexplored. Certain classes of dopaminergic and octopaminergic neurons that project to the mushroom body, a higher integrating center in the insect brain, are known to modify neuronal output based on contextual cues and thereby organismal behavior. This study focuses on how monoaminergic modulation of mushroom body GABAergic output neurons (MBONs) regulates the duration of flight bouts. Octopaminergic neurons in the sub-esophageal zone stimulate central dopaminergic neurons (protocerebral anterior medial, PAM) that project to GABAergic MBONs. Either inhibition of octopaminergic and dopaminergic neurons or activation of GABAergic MBONs reduces the duration of flight bouts. Moreover, activity in the PAM neurons inhibits the GABAergic MBONs. Our data suggest that disinhibition of the identified neural circuit very likely occurs after flight initiation and is required to maintain the “flight state” when searching for distant sites, possibly related to food sources, mating partners, or a suitable egg-laying site.Video Graphical Graphical abstract for this article
       
  • Bidirectional Propagation of Signals and Nutrients in Fungal Networks via
           Specialized Hyphae
    • Abstract: Publication date: Available online 3 January 2019Source: Current BiologyAuthor(s): Stefanie S. Schmieder, Claire E. Stanley, Andrzej Rzepiela, Dirk van Swaay, Jerica Sabotič, Simon F. Nørrelykke, Andrew J. deMello, Markus Aebi, Markus KünzlerSummaryIntercellular distribution of nutrients and coordination of responses to internal and external cues via endogenous signaling molecules are hallmarks of multicellular organisms. Vegetative mycelia of multicellular fungi are syncytial networks of interconnected hyphae resulting from hyphal tip growth, branching, and fusion. Such mycelia can reach considerable dimensions and, thus, different parts can be exposed to quite different environmental conditions. Our knowledge about the mechanisms by which fungal mycelia can adjust nutrient gradients or coordinate their defense response to fungivores is scarce, in part due to limitations in technologies currently available for examining different parts of a mycelium over longer time periods at the microscopic level. Here, we combined a tailor-made microfluidic platform with time-lapse fluorescence microscopy to visualize the dynamic response of the vegetative mycelium of a basidiomycete to two different stimuli. The microfluidic platform allows simultaneous monitoring at both the colony and single-hypha level. We followed the dynamics of the distribution of a locally administered nutrient analog and the defense response to spatially confined predation by a fungivorous nematode. Although both responses of the mycelium were constrained locally, we observed long-distance propagation for both the nutrient analog and defense response in a subset of hyphae. This propagation along hyphae occurred in both acropetal and basipetal directions and, intriguingly, the direction was found to alternate every 3 hr in an individual hypha. These results suggest that multicellular fungi have, as of yet, undescribed mechanisms to coordinate the distribution of nutrients and their behavioral response upon attack by fungivores.Graphical Graphical abstract for this article
       
  • Diminished Jak/STAT Signaling Causes Early-Onset Aging Defects in Stem
           Cell Cytokinesis
    • Abstract: Publication date: Available online 3 January 2019Source: Current BiologyAuthor(s): Kari F. Lenhart, Benjamin Capozzoli, Gwen S.D. Warrick, Stephen DiNardoSummaryTissue renewal becomes compromised with age. Although defects in niche and stem cell behavior have been implicated in promoting age-related decline, the causes of early-onset aging defects are unknown. We have identified an early consequence of aging in germline stem cells (GSCs) in the Drosophila testis. Aging disrupts the unique program of GSC cytokinesis, with GSCs failing to abscise from their daughter cells. Abscission failure significantly disrupts both self-renewal and the generation of differentiating germ cells. Extensive live imaging and genetic analyses show that abscission failure is due to inappropriate retention of F-actin at the intercellular bridges between GSC-daughter cells. Furthermore, F-actin is regulated by the Jak/STAT pathway—increasing or decreasing pathway activity can rescue or exacerbate the age-induced abscission defect, respectively. Even subtle decreases to STAT activity are sufficient to precociously age young GSCs and induce abscission failure. Thus, this work has identified the earliest age-related defect in GSCs and has revealed a unique role for an established niche signaling pathway in controlling stem cell cytokinesis and in regulating stem cell behavior with age.Graphical Graphical abstract for this article
       
  • Ciliary Beating Compartmentalizes Cerebrospinal Fluid Flow in the Brain
           and Regulates Ventricular Development
    • Abstract: Publication date: Available online 3 January 2019Source: Current BiologyAuthor(s): Emilie W. Olstad, Christa Ringers, Jan N. Hansen, Adinda Wens, Cecilia Brandt, Dagmar Wachten, Emre Yaksi, Nathalie Jurisch-YaksiSummaryMotile cilia are miniature, propeller-like extensions, emanating from many cell types across the body. Their coordinated beating generates a directional fluid flow, which is essential for various biological processes, from respiration to reproduction. In the nervous system, ependymal cells extend their motile cilia into the brain ventricles and contribute to cerebrospinal fluid (CSF) flow. Although motile cilia are not the only contributors to CSF flow, their functioning is crucial, as patients with motile cilia defects develop clinical features, like hydrocephalus and scoliosis. CSF flow was suggested to primarily deliver nutrients and remove waste, but recent studies emphasized its role in brain development and function. Nevertheless, it remains poorly understood how ciliary beating generates and organizes CSF flow to fulfill these roles. Here, we study motile cilia and CSF flow in the brain ventricles of larval zebrafish. We identified that different populations of motile ciliated cells are spatially organized and generate a directional CSF flow powered by ciliary beating. Our investigations revealed that CSF flow is confined within individual ventricular cavities, with little exchange of fluid between ventricles, despite a pulsatile CSF displacement caused by the heartbeat. Interestingly, our results showed that the ventricular boundaries supporting this compartmentalized CSF flow are abolished during bodily movement, highlighting that multiple physiological processes regulate the hydrodynamics of CSF flow. Finally, we showed that perturbing cilia reduces hydrodynamic coupling between the brain ventricles and disrupts ventricular development. We propose that motile-cilia-generated flow is crucial in regulating the distribution of CSF within and across brain ventricles.Graphical Graphical abstract for this article
       
  • Encoding of Odor Fear Memories in the Mouse Olfactory Cortex
    • Abstract: Publication date: Available online 3 January 2019Source: Current BiologyAuthor(s): Claire Meissner-Bernard, Yulia Dembitskaya, Laurent Venance, Alexander FleischmannSummaryOdor memories are exceptionally robust and essential for animal survival. The olfactory (piriform) cortex has long been hypothesized to encode odor memories, yet the cellular substrates for olfactory learning and memory remain unknown. Here, using intersectional, cFos-based genetic manipulations (“Fos tagging”), we show that olfactory fear conditioning activates sparse and distributed ensembles of neurons in the mouse piriform cortex. We demonstrate that chemogenetic silencing of these Fos-tagged piriform ensembles selectively interferes with odor fear memory retrieval but does not compromise basic odor detection and discrimination. Furthermore, chemogenetic reactivation of piriform neurons that were Fos tagged during olfactory fear conditioning causes a decrease in exploratory behavior, mimicking odor-evoked fear memory recall. Together, our experiments identify specific ensembles of piriform neurons as critical components of an olfactory fear memory trace.
       
  • Kinesin-3 Responds to Local Microtubule Dynamics to Target Synaptic Cargo
           Delivery to the Presynapse
    • Abstract: Publication date: Available online 3 January 2019Source: Current BiologyAuthor(s): Pedro Guedes-Dias, Jeffrey J. Nirschl, Nohely Abreu, Mariko K. Tokito, Carsten Janke, Maria M. Magiera, Erika L.F. HolzbaurSummaryNeurons in the CNS establish thousands of en passant synapses along their axons. Robust neurotransmission depends on the replenishment of synaptic components in a spatially precise manner. Using live-cell microscopy and single-molecule reconstitution assays, we find that the delivery of synaptic vesicle precursors (SVPs) to en passant synapses in hippocampal neurons is specified by an interplay between the kinesin-3 KIF1A motor and presynaptic microtubules. Presynaptic sites are hotspots of dynamic microtubules rich in GTP-tubulin. KIF1A binds more weakly to GTP-tubulin than GDP-tubulin and competes with end-binding (EB) proteins for binding to the microtubule plus end. A disease-causing mutation within KIF1A that reduces preferential binding to GDP- versus GTP-rich microtubules disrupts SVP delivery and reduces presynaptic release upon neuronal stimulation. Thus, the localized enrichment of dynamic microtubules along the axon specifies a localized unloading zone that ensures the accurate delivery of SVPs, controlling presynaptic strength in hippocampal neurons.Graphical Graphical abstract for this article
       
  • Photogeometric Cues to Perceived Surface Shading
    • Abstract: Publication date: Available online 3 January 2019Source: Current BiologyAuthor(s): Phillip J. Marlow, Scott W.J. Mooney, Barton L. AndersonSummaryThe human visual system is remarkably adept at extracting the three-dimensional (3D) shape of surfaces from images of smoothly shaded surfaces (shape from shading). Most research into this remarkable perceptual ability has focused on understanding how the visual system derives a specific representation of 3D shape when it is known (or assumed) that shading and self-occluding contours are the sole causes of image structure [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11]. But there is an even more fundamental problem that must be solved before any such analysis can take place: how does the visual system determine when it’s viewing a shaded surface' Here, we present theoretical analyses showing that there is statistically reliable information generated along the bounding contours of smoothly curved surfaces that the visual system uses to identify surface shading. This information can be captured by two photogeometric constraints that link the shape of bounding contours to the distributions of shading intensity along the contours: one that links shading intensity to the local orientations along bounding contours and a second that links shading intensity to bounding contour curvature. We show that these constraints predict the perception of shading for surfaces with smooth self-occluding contours and a widely studied class of bounding contours (planar cuts). The results provide new insights into the information that the visual system exploits to distinguish surface shading from other sources of image structure and offer a coherent explanation of the influence of bounding contours on the perception of surface shading and 3D shape.
       
  • The Hippo Pathway Regulates Caveolae Expression and Mediates Flow Response
           via Caveolae
    • Abstract: Publication date: Available online 27 December 2018Source: Current BiologyAuthor(s): Valentina Rausch, Jonathan R. Bostrom, Jiwon Park, Isabel R. Bravo, Yi Feng, David C. Hay, Brian A. Link, Carsten G. HansenSummaryThe Hippo pathway plays major roles in development, regeneration, and cancer. Its activity is tightly regulated by both diffusible chemical ligands and mechanical stimuli. The pathway consists of a series of kinases that can control the sub-cellular localization and stability of YAP or TAZ, homologous transcriptional co-factors. Caveolae, small (60–100 nm) bulb-like invaginations of the plasma membrane, are comprised predominantly of caveolin and cavin proteins and can respond to mechanical stimuli. Here, we show that YAP/TAZ, the major transcriptional mediators of the Hippo pathway, are critical for expression of caveolae components and therefore caveolae formation in both mammalian cells and zebrafish. In essence, without YAP/TAZ, the cell loses an entire organelle. CAVEOLIN1 and CAVIN1, the two essential caveolar genes, are direct target genes of YAP/TAZ, regulated via TEA domain (TEAD) transcription factors. Notably, YAP/TAZ become nuclear enriched and facilitate target gene transcription in cells with diminished levels of caveolae. Furthermore, caveolar-mediated shear stress response activates YAP/TAZ. These data link caveolae to Hippo signaling in the context of cellular responses to mechanical stimuli and suggest activity-based feedback regulation between components of caveolae and the outputs of the Hippo pathway.Graphical Graphical abstract for this article
       
  • Ferrets as a Model for Higher-Level Visual Motion Processing
    • Abstract: Publication date: Available online 27 December 2018Source: Current BiologyAuthor(s): Augusto A. Lempel, Kristina J. NielsenSummaryFerrets are a major developmental animal model due to their early parturition. Here we show for the first time that ferrets could be used to study development of higher-level visual processes previously identified in primates. In primates, complex motion processing involves primary visual cortex (V1), which generates local motion signals, and higher-level visual area MT, which integrates these signals over more global spatial regions. Our data show similar transformations in motion signals between ferret V1 and higher-level visual area PSS, located in the posterior bank of the suprasylvian sulcus. We found that PSS neurons, like MT neurons, were tuned for stimulus motion and showed strong suppression between opposing direction inputs. Most strikingly, PSS, like MT, exhibited robust global motion signals when tested with coherent plaids—the classic test for motion integration across multiple moving elements. These PSS responses were described well by computational models developed for MT. Our findings establish the ferret as a strong animal model for development of higher-level visual processing.
       
  • Egg-Cracking Vibration as a Cue for Stink Bug Siblings to Synchronize
           Hatching
    • Abstract: Publication date: Available online 27 December 2018Source: Current BiologyAuthor(s): Jun Endo, Takuma Takanashi, Hiromi Mukai, Hideharu NumataSummaryEgg clutches of many animals hatch synchronously due to parental control [1, 2] or environmental stimulation [3, 4]. In contrast, in some animals, embryos actively synchronize their hatching timing with their siblings to facilitate adaptive behavior in sibling groups, such as mass migration [5, 6]. These embryos require synchronization cues that are detectable from eggs and indicative of when the siblings hatch, such as pre-hatching vocalizations in birds and crocodiles [7, 8]. Previous studies, using methods including artificial presentation of non-specific mechanical stimuli, demonstrated that vibrations or other mechanical forces caused by sibling movements are cues used by some turtles and insects [9, 10, 11, 12, 13]. However, there is no evidence about which movements of tiny embryos or hatchlings, among multiple possibilities, can generate mechanical cues actually detectable through eggs. Here, we show that embryos of the brown marmorated stink bug, Halyomorpha halys, synchronize hatching by responding to single pulsed vibrations generated when siblings crack open their eggshells. An egg-cracking vibration seems to be transmitted to distant eggs within a clutch while still maintaining its function as a cue, thus leading to the highly synchronized hatching pattern previously reported [14]. In this species, it is possible that embryos attempt to hatch with short lags after earlier-hatched siblings to avoid egg cannibalism by them [14]. The present study illustrates the diversity of social-information use by animal embryos for success in the sibling group.Graphical Graphical abstract for this article
       
  • Ectopic Activation of the Spindle Assembly Checkpoint Signaling Cascade
           Reveals Its Biochemical Design
    • Abstract: Publication date: Available online 27 December 2018Source: Current BiologyAuthor(s): Chu Chen, Ian P. Whitney, Anand Banerjee, Carlos Sacristan, Palak Sekhri, David M. Kern, Adrienne Fontan, Geert J.P.L. Kops, John J. Tyson, Iain M. Cheeseman, Ajit P. JoglekarSummarySwitch-like activation of the spindle assembly checkpoint (SAC) is critical for accurate chromosome segregation and for cell division in a timely manner. To determine the mechanisms that achieve this, we engineered an ectopic, kinetochore-independent SAC activator: the “eSAC.” The eSAC stimulates SAC signaling by artificially dimerizing Mps1 kinase domain and a cytosolic KNL1 phosphodomain, the kinetochore signaling scaffold. By exploiting variable eSAC expression in a cell population, we defined the dependence of the eSAC-induced mitotic delay on eSAC concentration in a cell to reveal the dose-response behavior of the core signaling cascade of the SAC. These quantitative analyses and subsequent mathematical modeling of the dose-response data uncover two crucial properties of the core SAC signaling cascade: (1) a cellular limit on the maximum anaphase-inhibitory signal that the cascade can generate due to the limited supply of SAC proteins and (2) the ability of the KNL1 phosphodomain to produce the anaphase-inhibitory signal synergistically, when it recruits multiple SAC proteins simultaneously. We propose that these properties together achieve inverse, non-linear scaling between the signal output per kinetochore and the number of signaling kinetochores. When the number of kinetochores is low, synergistic signaling by KNL1 enables each kinetochore to produce a disproportionately strong signal output. However, when many kinetochores signal concurrently, they compete for a limited supply of SAC proteins. This frustrates synergistic signaling and lowers their signal output. Thus, the signaling activity of unattached kinetochores will adapt to the changing number of signaling kinetochores to enable the SAC to approximate switch-like behavior.
       
  • Historical Genomes Reveal the Genomic Consequences of Recent Population
           Decline in Eastern Gorillas
    • Abstract: Publication date: Available online 27 December 2018Source: Current BiologyAuthor(s): Tom van der Valk, David Díez-del-Molino, Tomas Marques-Bonet, Katerina Guschanski, Love DalénSummaryMany endangered species have experienced severe population declines within the last centuries [1, 2]. However, despite concerns about negative fitness effects resulting from increased genetic drift and inbreeding, there is a lack of empirical data on genomic changes in conjunction with such declines [3, 4, 5, 6, 7]. Here, we use whole genomes recovered from century-old historical museum specimens to quantify the genomic consequences of small population size in the critically endangered Grauer’s and endangered mountain gorillas. We find a reduction of genetic diversity and increase in inbreeding and genetic load in the Grauer’s gorilla, which experienced severe population declines in recent decades. In contrast, the small but relatively stable mountain gorilla population has experienced little genomic change during the last century. These results suggest that species histories as well as the rate of demographic change may influence how population declines affect genome diversity.
       
  • Three-Dimensionally Preserved Appendages in an Early Cambrian Stem-Group
           Pancrustacean
    • Abstract: Publication date: Available online 27 December 2018Source: Current BiologyAuthor(s): Dayou Zhai, Javier Ortega-Hernández, Joanna M. Wolfe, Xianguang Hou, Chunjie Cao, Yu LiuSummaryPancrustaceans boast impressive diversity, abundance, and ecological impact in the biosphere throughout the Phanerozoic [1]. Molecular clock estimates suggest an early Cambrian divergence for pancrustaceans [2, 3]. Despite the wealth of Palaeozoic exceptional fossiliferous deposits [4, 5, 6, 7], the early evolution of Pancrustacea remains elusive given the difficulty of recognizing synapomorphies between Cambrian forms and extant representatives. Although early studies suggested crustacean affinities for Cambrian bivalved euarthropods [8, 9, 10, 11], this view has fallen out of favor by recent reappraisals of their morphology [12, 13, 14, 15, 16]. The best evidence for total-group pancrustaceans comes from Cambrian microfossils preserved as three-dimensional phosphatic replicates in Orsten-type assemblages [4, 17, 18, 19] or as “small carbonaceous fossils” (SCFs) [20, 21]. Although these taphonomic windows capture minute morphology enabling detailed comparisons with extant representatives, these microfossils are limited to larval stages (Orsten) or recalcitrant fragmentary remains (SCFs) restricting their phylogenetic precision [5, 12, 19, 20, 22, 23]. We employed X-ray computed tomography [24] to reveal the three-dimensionally appendage morphology of the Chengjiang bivalved euarthropod Ercaicunia multinodosa [25] from the early Cambrian of China. E. multinodosa possesses characters uniquely shared with extant crustaceans, including differentiated tritocerebral antennae and epipodite-bearing biramous trunk appendages. Similarities between E. multinodosa with clypecaridids [9], waptiids [16] and hymenocarines [11, 14] suggest that these euarthropods may also possess similarly differentiated appendages, but these details are obstructed by the limits of preservation of compacted macrofossils. E. multinodosa illuminates the early evolution of pancrustacean appendage differentiation and represents the oldest unequivocal crown-group mandibulate known from complete macrofossils [22].Graphical Graphical abstract for this article
       
  • Swing Velocity Profiles of Small Limbs Can Arise from Transient Passive
           Torques of the Antagonist Muscle Alone
    • Abstract: Publication date: Available online 20 December 2018Source: Current BiologyAuthor(s): Arndt von Twickel, Christoph Guschlbauer, Scott L. Hooper, Ansgar BüschgesSummaryIn large limbs, changing motor neuron activity typically controls within-movement velocity. For example, sequential agonist-antagonist-agonist motor neuron firing typically underlies the slowing often present at the end of human reaches. In physiological movements of large limbs, antagonistic muscle passive torque is generally negligible. In small limbs, alternatively, passive torques can determine limb rest position, generate restoring movements to it, and decrease agonist-generated movement amplitude and velocity maxima. These observations suggest that, in small limbs, passive forces might also control velocity changes within movements. We investigated this issue in stick insect middle leg femur-tibia (FT) joint. During swing, the FT joint extensor muscle actively shortens and the flexor muscle passively lengthens. As in human reaching, after its initial acceleration, FT joint velocity continuously decreases. We measured flexor passive forces during imposed stretches spanning the ranges of FT joint angles, angular velocities, and movement amplitudes present in leg swings. The viscoelastic “transient” passive force that occurs during and soon after stretch depended on all three variables and could be tens of times larger than the “steady-state” passive force commonly measured long after stretch end. We combined these data, the flexor and extensor moment arms, and an existing extensor model to simulate FT joint swing. To measure only passive (flexor) muscle-dependent effects, we used constant extensor activations in these simulations. In simulations using data from ten flexor muscles, flexor passive torque could always produce swings with, after swing initiation, continuously decreasing velocities. Antagonist muscle passive torques alone can thus control within-movement velocity.
       
  • Retronasal Odor Perception Requires Taste Cortex, but Orthonasal Does Not
    • Abstract: Publication date: Available online 20 December 2018Source: Current BiologyAuthor(s): Meredith L. Blankenship, Maria Grigorova, Donald B. Katz, Joost X. MaierSummarySmells can arise from a source external to the body and stimulate the olfactory epithelium upon inhalation through the nares (orthonasal olfaction). Alternatively, smells may arise from inside the mouth during consumption, stimulating the epithelium upon exhalation (retronasal olfaction). Both ortho- and retronasal olfaction produce highly salient percepts, but the two percepts have very different behavioral implications. Here, we use optogenetic manipulation in the context of a flavor preference learning paradigm to investigate differences in the neural circuits that process information in these two submodalities of olfaction. Our findings support a view in which retronasal, but not orthonasal, odors share processing circuitry commonly associated with taste. First, our behavioral results reveal that retronasal odors induce rapid preference learning and have a potentiating effect on orthonasal preference learning. Second, we demonstrate that inactivation of the insular gustatory cortex selectively impairs expression of retronasal preferences. Thus, orally sourced (retronasal) olfactory input is processed by a brain region responsible for taste processing, whereas externally sourced (orthonasal) olfactory input is not.
       
  • Stable Delay Period Representations in the Posterior Parietal Cortex
           Facilitate Working-Memory-Guided Obstacle Negotiation
    • Abstract: Publication date: Available online 20 December 2018Source: Current BiologyAuthor(s): Carmen Wong, Stephen G. LomberSummaryIn complex environments, information about surrounding obstacles is stored in working memory (WM) and used to coordinate appropriate movements for avoidance. In quadrupeds, this WM system is particularly important for guiding hindleg stepping, as an animal can no longer see the obstacle underneath the body following foreleg clearance. Such obstacle WM involves the posterior parietal cortex (PPC), as deactivation of area 5 incurs WM deficits, precluding successful avoidance. However, the neural underpinnings of this involvement remain undefined. To reveal the neural substrates of this behavior, microelectrode arrays were implanted to record neuronal activity in area 5 during an obstacle WM task in cats. Early in the WM delay, neurons were modulated generally by obstacle presence or more specifically in relation to foreleg step height. Thus, information about the obstacle or about foreleg clearance can be retained in WM. In a separate set of neurons, this information was recalled later in the delay in order to plan subsequent hindleg stepping. Such early and late delay period signals were temporally bridged by neurons exhibiting obstacle-modulated activity sustained throughout the delay. These neurons represented a specialized subset of all recorded neurons, which maintained stable information coding across the WM delay. Ultimately, these various patterns of task-related modulation enable stable representations of obstacle-related information within the PPC to support successful WM-guided obstacle negotiation in the cat.
       
  • Myosin-18B Promotes the Assembly of Myosin II Stacks for Maturation of
           Contractile Actomyosin Bundles
    • Abstract: Publication date: Available online 20 December 2018Source: Current BiologyAuthor(s): Yaming Jiu, Reena Kumari, Aidan M. Fenix, Niccole Schaible, Xiaonan Liu, Markku Varjosalo, Ramaswamy Krishnan, Dylan T. Burnette, Pekka LappalainenSummaryCell adhesion, morphogenesis, mechanosensing, and muscle contraction rely on contractile actomyosin bundles, where the force is produced through sliding of bipolar myosin II filaments along actin filaments. The assembly of contractile actomyosin bundles involves registered alignment of myosin II filaments and their subsequent fusion into large stacks. However, mechanisms underlying the assembly of myosin II stacks and their physiological functions have remained elusive. Here, we identified myosin-18B, an unconventional myosin, as a stable component of contractile stress fibers. Myosin-18B co-localized with myosin II motor domains in stress fibers and was enriched at the ends of myosin II stacks. Importantly, myosin-18B deletion resulted in drastic defects in the concatenation and persistent association of myosin II filaments with each other and thus led to severely impaired assembly of myosin II stacks. Consequently, lack of myosin-18B resulted in defective maturation of actomyosin bundles from their precursors in osteosarcoma cells. Moreover, myosin-18B knockout cells displayed abnormal morphogenesis, migration, and ability to exert forces to the environment. These results reveal a critical role for myosin-18B in myosin II stack assembly and provide evidence that myosin II stacks are important for a variety of vital processes in cells.Graphical Graphical abstract for this article
       
  • Novelty, Salience, and Surprise Timing Are Signaled by Neurons in the
           Basal Forebrain
    • Abstract: Publication date: Available online 20 December 2018Source: Current BiologyAuthor(s): Kaining Zhang, Charles D. Chen, Ilya E. MonosovSummaryThe basal forebrain (BF) is a principal source of modulation of the neocortex [1, 2, 3, 4, 5, 6] and is thought to regulate cognitive functions such as attention, motivation, and learning by broadcasting information about salience [2, 3, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19]. However, events can be salient for multiple reasons—such as novelty, surprise, or reward prediction errors [20, 21, 22, 23, 24]—and to date, precisely which salience-related information the BF broadcasts is unclear. Here, we report that the primate BF contains at least two types of neurons that often process salient events in distinct manners: one with phasic burst responses to cues predicting salient events and one with ramping activity anticipating such events. Bursting neurons respond to cues that convey predictions about the magnitude, probability, and timing of primary reinforcements. They also burst to the reinforcement itself, particularly when it is unexpected. However, they do not have a selective response to reinforcement omission (the unexpected absence of an event). Thus, bursting neurons do not convey value-prediction errors but do signal surprise associated with external events. Indeed, they are not limited to processing primary reinforcement: they discriminate fully expected novel visual objects from familiar objects and respond to object-sequence violations. In contrast, ramping neurons predict the timing of many salient, novel, and surprising events. Their ramping activity is highly sensitive to the subjects’ confidence in event timing and on average encodes the subjects’ surprise after unexpected events occur. These data suggest that the primate BF contains mechanisms to anticipate the timing of a diverse set of important external events (via ramping activity) and to rapidly deploy cognitive resources when these events occur (via short latency bursting).
       
  • Ventral Tegmental Dopamine Neurons Participate in Reward Identity
           Predictions
    • Abstract: Publication date: Available online 20 December 2018Source: Current BiologyAuthor(s): Ronald Keiflin, Heather J. Pribut, Nisha B. Shah, Patricia H. JanakSummaryDopamine (DA) neurons in the ventral tegmental area (VTA) and substantia nigra (SNc) encode reward prediction errors (RPEs) and are proposed to mediate error-driven learning. However, the learning strategy engaged by DA-RPEs remains controversial. RPEs might imbue predictive cues with pure value, independently of representations of their associated outcome. Alternatively, RPEs might promote learning about the sensory features (the identity) of the rewarding outcome. Here, we show that, although both VTA and SNc DA neuron activation reinforces instrumental responding, only VTA DA neuron activation during consumption of expected sucrose reward restores error-driven learning and promotes formation of a new cue→sucrose association. Critically, expression of VTA DA-dependent Pavlovian associations is abolished following sucrose devaluation, a signature of identity-based learning. These findings reveal that activation of VTA- or SNc-DA neurons engages largely dissociable learning processes with VTA-DA neurons capable of participating in outcome-specific predictive learning, and the role of SNc-DA neurons appears limited to reinforcement of instrumental responses.
       
  • Y Chromosome Sequences Reveal a Short Beringian Standstill, Rapid
           Expansion, and early Population structure of Native American Founders
    • Abstract: Publication date: Available online 20 December 2018Source: Current BiologyAuthor(s): Thomaz Pinotti, Anders Bergström, Maria Geppert, Matt Bawn, Dominique Ohasi, Wentao Shi, Daniela R. Lacerda, Arne Solli, Jakob Norstedt, Kate Reed, Kim Dawtry, Fabricio González-Andrade, Cesar Paz-y-Miño, Susana Revollo, Cinthia Cuellar, Marilza S. Jota, José E. Santos, Qasim Ayub, Toomas Kivisild, José R. SandovalSummaryThe Americas were the last inhabitable continents to be occupied by humans, with a growing multidisciplinary consensus for entry 15–25 thousand years ago (kya) from northeast Asia via the former Beringia land bridge [1, 2, 3, 4]. Autosomal DNA analyses have dated the separation of Native American ancestors from the Asian gene pool to 23 kya or later [5, 6] and mtDNA analyses to ∼25 kya [7], followed by isolation (“Beringian Standstill” [8, 9]) for 2.4–9 ky and then a rapid expansion throughout the Americas. Here, we present a calibrated sequence-based analysis of 222 Native American and relevant Eurasian Y chromosomes (24 new) from haplogroups Q and C [10], with four major conclusions. First, we identify three to four independent lineages as autochthonous and likely founders: the major Q-M3 and rarer Q-CTS1780 present throughout the Americas, the very rare C3-MPB373 in South America, and possibly the C3-P39/Z30536 in North America. Second, from the divergence times and Eurasian/American distribution of lineages, we estimate a Beringian Standstill duration of 2.7 ky or 4.6 ky, according to alternative models, and entry south of the ice sheet after 19.5 kya. Third, we describe the star-like expansion of Q-M848 (within Q-M3) starting at 15 kya [11] in the Americas, followed by establishment of substantial spatial structure in South America by 12 kya. Fourth, the deep branches of the Q-CTS1780 lineage present at low frequencies throughout the Americas today [12] may reflect a separate out-of-Beringia dispersal after the melting of the glaciers at the end of the Pleistocene.
       
  • Noemi Controls Production of Flavonoid Pigments and Fruit Acidity and
           Illustrates the Domestication Routes of Modern Citrus Varieties
    • Abstract: Publication date: Available online 20 December 2018Source: Current BiologyAuthor(s): Eugenio Butelli, Concetta Licciardello, Chandrika Ramadugu, Marie Durand-Hulak, Alessandra Celant, Giuseppe Reforgiato Recupero, Yann Froelicher, Cathie MartinSummaryIn citrus, the production of anthocyanin pigments requires the activity of the transcriptional activator Ruby. Consequently, loss-of-function mutations in Ruby result in an anthocyaninless phenotype [1]. Several citrus accessions, however, have lost the ability to produce these pigments despite the presence of wild-type Ruby alleles. These specific mutants have captivated the interest of botanists and breeders for centuries because the lack of anthocyanins in young leaves and flowers is also associated with a lack of proanthocyanidins in seeds and, most notably, with an extreme reduction in fruit acidity (involving about a three-unit change in pH). These mutants have been defined collectively as “acidless” [2, 3, 4]. We have identified Noemi, which encodes a basic helix-loop-helix (bHLH) transcription factor and which controls these apparently unrelated processes. In accessions of Citron, limetta, sweet lime, lemon, and sweet orange, acidless phenotypes are associated with large deletions or insertions of retrotransposons in the Noemi gene. In two accessions of limetta, a change in the core promoter region of Noemi is associated with reduced expression and increased pH of juice, indicating that Noemi is a major determinant of fruit acidity. The characterization of the Noemi locus in a number of varieties of Citron indicates that one specific mutation is ancient. The presence of this allele in Chinese fingered Citrons and in those used in the Sukkot Jewish ritual [5] illuminates the path of domestication of Citron, the first citrus species to be cultivated in the Mediterranean. This allele has been inherited in Citron-derived hybrids with long histories of cultivation.Graphical Graphical abstract for this article
       
  • Plasticity and Adaptation in Adult Binocular Vision
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Zeynep Başgöze, Allyson P. Mackey, Emily A. CooperSummaryUnderstanding the relationship between changes in sensory perception and functional/structural changes in the brain is a major endeavor in the field of systems neuroscience. Progress in this area holds the potential to reveal how the brain adapts to the demands of a complex and changing environment, as well as to assist with the development of therapeutic interventions to reverse the negative effects of abnormal experience. The cells and circuits that make up the mammalian visual system provide a unique scientific test-bed for studying brain plasticity, thanks to the rich literature on their basic organization and similarity across a range of species. In this minireview, we highlight recent advances in the study of plasticity in adult binocular vision, emphasizing the importance of considering changes that occur over different timescales. We discuss key new insights, significant open questions, and how this research is leading to a broader understanding of the ways that the adult brain maintains a robust ability for adaptation and change.
       
  • Metacognitive Failure as a Feature of Those Holding Radical Beliefs
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Max Rollwage, Raymond J. Dolan, Stephen M. FlemingSummaryWidening polarization about political, religious, and scientific issues threatens open societies, leading to entrenchment of beliefs, reduced mutual understanding, and a pervasive negativity surrounding the very idea of consensus [1, 2]. Such radicalization has been linked to systematic differences in the certainty with which people adhere to particular beliefs [3, 4, 5, 6]. However, the drivers of unjustified certainty in radicals are rarely considered from the perspective of models of metacognition, and it remains unknown whether radicals show alterations in confidence bias (a tendency to publicly espouse higher confidence), metacognitive sensitivity (insight into the correctness of one’s beliefs), or both [7]. Within two independent general population samples (n = 381 and n = 417), here we show that individuals holding radical beliefs (as measured by questionnaires about political attitudes) display a specific impairment in metacognitive sensitivity about low-level perceptual discrimination judgments. Specifically, more radical participants displayed less insight into the correctness of their choices and reduced updating of their confidence when presented with post-decision evidence. Our use of a simple perceptual decision task enables us to rule out effects of previous knowledge, task performance, and motivational factors underpinning differences in metacognition. Instead, our findings highlight a generic resistance to recognizing and revising incorrect beliefs as a potential driver of radicalization.
       
  • Signal Transduction: Magnesium Manifests as a Second Messenger
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Alessandra Stangherlin, John S. O’NeillSummaryMg2+ is an essential ion for the cell but whether it can act as a bona fide second messenger has long been questioned. A recent study supports this hypothesis and shows a signalling role for Mg2+ in GABA-mediated neuronal maturation.
       
  • Symbiosis: Plasmodesmata Link Root-Nodule Organogenesis with Infection
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Caroline GutjahrSummaryDuring the establishment of root-nodule symbioses between plants and nitrogen-fixing rhizobia, nodule organogenesis in the inner cortex needs to be precisely coordinated with the rhizobial infection site at the root epidermis. A new study shows that rhizobia induce localized callose turnover at plasmodesmata to allow spatiotemporal synchronization of the two processes through symplastic connections.
       
  • Monkey Memory: Rehearsal Emerges for Novel Images When Familiarity Cues
           Fade
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Michael J. BeranSummaryIt was thought that, when monkeys use familiarity cues to aid recognition memory, they do not engage working memory. A new study shows that, when the value of those familiarity cues is attenuated, monkeys rehearse novel images like familiar ones, a striking parallel with human working memory.
       
  • Neuroscience: Great Expectations at the Speech–Language
           Interface
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Andrew J. Anderson, Michael P. Broderick, Edmund C. LalorSummaryHow heard speech is transformed into words in the brain remains poorly understood. New research reveals signals in auditory cortex that reflect predictions the brain makes in transforming phonetic information into words.
       
  • Ecology: Termite Patterning at Multiple Scales
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Corina E. TarnitaSummaryA vast and ancient array of regularly spaced dirt mounds — the result of termite activities— has been discovered in Brazil. Might this inform our understanding of general mechanisms of spatial patterning at different scales'
       
  • Active Sensing: Constancy Requires Change
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Volker Hofmann, Maurice J. ChacronSummaryWe constantly generate movements in order to enhance our ability to perceive the external environment. New research on electric fish has used augmented reality to demonstrate that animals dynamically regulate their movements to maintain variability in their sensory input.
       
  • Speciation: On the Scent of Mate Discrimination Genes
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Jennifer M. Coughlan, Daniel R. MatuteSummaryAnimals use smell to recognize individuals from their own species and find suitable mates. A study of female chemical cues in two species of fruit flies uses a creative genetic strategy to identify an allele that is involved in species recognition and may play an important role in keeping these species apart in nature.
       
  • Neuroscience: To Eat or to Sleep'
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Isabel De Araujo Salgado, Michael J. KrashesSummaryEnergy and sleep homeostasis are entwined, each capable of exerting priority based on need. The identification of central nodes involved in the appropriate orchestration of these systems is critical to our understanding of how the brain regulates behavior.
       
  • Ecology: Luck, Scarcity, and the Fate of Populations
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Philip A. StephensSummaryAn animal’s choice of diet plays a large part in determining whether it will find food during a period of searching. This has profound implications for the likelihood of reproductive success or starvation and many other important questions in ecology.
       
  • Drosophila: Where the Wild Flies Are
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Marianthi Karageorgi, Teruyuki Matsunaga, Noah K. WhitemanSummaryDrosophila melanogaster is a human commensal and dietary generalist. A new study in its ancestral range in Africa finds that wild Drosophila melanogaster are specialists on marula fruit — fruits cached in caves by Pleistocene humans.
       
  • Stroking modulates noxious-evoked brain activity in human infants
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Deniz Gursul, Sezgi Goksan, Caroline Hartley, Gabriela Schmidt Mellado, Fiona Moultrie, Amy Hoskin, Eleri Adams, Gareth Hathway, Susannah Walker, Francis McGlone, Rebeccah SlaterSummaryA subclass of C fibre sensory neurons found in hairy skin are activated by gentle touch [1] and respond optimally to stroking at ∼1–10 cm/s, serving a protective function by promoting affiliative behaviours. In adult humans, stimulation of these C-tactile (CT) afferents is pleasant, and can reduce pain perception [2]. Touch-based techniques, such as infant massage and kangaroo care, are designed to comfort infants during procedures, and a modest reduction in pain-related behavioural and physiological responses has been observed in some studies [3]. Here, we investigated whether touch can reduce noxious-evoked brain activity. We demonstrate that stroking (at 3 cm/s) prior to an experimental noxious stimulus or clinical heel lance can attenuate noxious-evoked brain activity in infants. CT fibres may represent a biological target for non-pharmacological interventions that modulate pain in early life.
       
  • Ethical seed sourcing is a key issue in meeting global restoration targets
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Paul G. Nevill, Adam T. Cross, Kingsley W. DixonSummaryThe global demand for restoration has increased orders of magnitude in the last decade, and hundreds of thousands of tonnes of native seed are required to feed this restoration engine [1] (Figure 1). But where are all the seeds required by restoration going to come from' Wild seed resources continue to be depleted by habitat loss, land degradation and climatic change, and over-collection of seed from wild populations threatens to erode these resources further. Ethical seed sourcing for restoration now represents a core issue in responsible restoration practice. Solutions include the introduction of regulatory frameworks controlling seed sourcing from wild populations, the development of seed farming capacity and advancement of seed enhancement technologies and precision delivery systems reducing seed wastage.
       
  • Plasmodesmata and the symplast
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Christine FaulknerSummaryMulticellular organisms rely on cell-to-cell communication and resource exchange to coordinate the various diverse processes involved in growth, development, and environmental responses across tissues and organs. Most complex multicellular organisms have highly organised and specialised anatomies, which develop by processes underpinned by regulated mechanisms for intercellular coordination. Indeed, in 1897 Wilhelm Pfeffer noted that for a plant to coordinate its physiological responses across the whole, there must be continuity throughout the entire organism, and that connections between cells must transport material and messages between tissues. Intercellular communication is an integral factor in any tissue-wide or organ-wide process in a multicellular organism.
       
  • Cynipid gall wasps
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Scott P. Egan, Glen R. Hood, Ellen O. Martinson, James R. Ott
       
  • Niels C. Rattenborg
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Niels C. Rattenborg
       
  • Ancient genomes of the Americas
    • Abstract: Publication date: 17 December 2018Source: Current Biology, Volume 28, Issue 24Author(s): Michael GrossSummaryIn an extraordinary series of migrations, the descendants of a group of Siberians that had crossed into Alaska spread into North and South America. Now evidence from more than 70 ancient DNA samples provides details of the migrations. Genomes also show how the first Americans coped with dramatically different climates and how they co-evolved with new staple crops, including the potato. Michael Gross reports.
       
  • Competition for Space Induces Cell Elimination through Compaction-Driven
           ERK Downregulation
    • Abstract: Publication date: Available online 13 December 2018Source: Current BiologyAuthor(s): Eduardo Moreno, Léo Valon, Florence Levillayer, Romain LevayerSummaryThe plasticity of developing tissues relies on the adjustment of cell survival and growth rate to environmental cues. This includes the effect of mechanical cues on cell survival. Accordingly, compaction of an epithelium can lead to cell extrusion and cell death. This process was proposed to contribute to tissue homeostasis but also to facilitate the expansion of pretumoral cells through the compaction and elimination of the neighboring healthy cells. However, we know very little about the pathways that can trigger apoptosis upon tissue deformation, and the contribution of compaction-driven death to clone expansion has never been assessed in vivo. Using the Drosophila pupal notum and a new live sensor of ERK, we show first that tissue compaction induces cell elimination through the downregulation of epidermal growth factor receptor/extracellular signal regulated kinase (EGFR/ERK) pathway and the upregulation of the pro-apoptotic protein Hid. Those results suggest that the sensitivity of EGFR/ERK pathway to mechanics could play a more general role in the fine tuning of cell elimination during morphogenesis and tissue homeostasis. Second, we assessed in vivo the contribution of compaction-driven death to pretumoral cell expansion. We found that the activation of the oncogene Ras in clones can downregulate ERK and activate apoptosis in the neighboring cells through their compaction, which eventually contributes to Ras clone expansion. The mechanical modulation of EGFR/ERK during growth-mediated competition for space may contribute to tumor progression.Graphical Graphical abstract for this article
       
  • Timed Collinear Activation of Hox Genes during Gastrulation Controls the
           Avian Forelimb Position
    • Abstract: Publication date: Available online 13 December 2018Source: Current BiologyAuthor(s): Chloe Moreau, Paolo Caldarelli, Didier Rocancourt, Julian Roussel, Nicolas Denans, Olivier Pourquie, Jerome GrosSummaryLimb position along the body is highly consistent within one species but very variable among vertebrates. Despite major advances in our understanding of limb patterning in three dimensions, how limbs reproducibly form along the antero-posterior axis remains largely unknown. Hox genes have long been suspected to control limb position; however, supporting evidences are mostly correlative and their role in this process is unclear. Here, we show that limb position is determined early in development through the action of Hox genes. Dynamic lineage analysis revealed that, during gastrulation, the forelimb, interlimb, and hindlimb fields are progressively generated and concomitantly patterned by the collinear activation of Hox genes in a two-step process. First, the sequential activation of Hoxb genes controls the relative position of their own collinear domains of expression in the forming lateral plate mesoderm, as demonstrated by functional perturbations during gastrulation. Then, within these collinear domains, we show that Hoxb4 anteriorly and Hox9 genes posteriorly, respectively, activate and repress the expression of the forelimb initiation gene Tbx5 and instruct the definitive position of the forelimb. Furthermore, by comparing the dynamics of Hoxb genes activation during zebra finch, chicken, and ostrich gastrulation, we provide evidences that changes in the timing of collinear Hox gene activation might underlie natural variation in forelimb position between different birds. Altogether, our results that characterize the cellular and molecular mechanisms underlying the regulation and natural variation of forelimb positioning in avians show a direct and early role for Hox genes in this process.Graphical Graphical abstract for this article
       
  • Allatostatin-C/AstC-R2 Is a Novel Pathway to Modulate the Circadian
           Activity Pattern in Drosophila
    • Abstract: Publication date: Available online 13 December 2018Source: Current BiologyAuthor(s): Madelen M. Díaz, Matthias Schlichting, Katharine C. Abruzzi, Xi Long, Michael RosbashSummarySeven neuropeptides are expressed within the Drosophila brain circadian network. Our previous mRNA profiling suggested that Allatostatin-C (AstC) is an eighth neuropeptide and specifically expressed in dorsal clock neurons (DN1s). Our results here show that AstC is, indeed, expressed in DN1s, where it oscillates. AstC is also expressed in two less well-characterized circadian neuronal clusters, the DN3s and lateral-posterior neurons (LPNs). Behavioral experiments indicate that clock-neuron-derived AstC is required to mediate evening locomotor activity under short (winter-like) and long (summer-like) photoperiods. The AstC-Receptor 2 (AstC-R2) is expressed in LNds, the clock neurons that drive evening locomotor activity, and AstC-R2 is required in these neurons to modulate the same short photoperiod evening phenotype. Ex vivo calcium imaging indicates that AstC directly inhibits a single LNd. The results suggest that a novel AstC/AstC-R2 signaling pathway, from dorsal circadian neurons to an LNd, regulates the evening phase in Drosophila.Graphical Graphical abstract for this article
       
  • A Tree Ortholog of SHORT VEGETATIVE PHASE Floral Repressor Mediates
           Photoperiodic Control of Bud Dormancy
    • Abstract: Publication date: Available online 13 December 2018Source: Current BiologyAuthor(s): Rajesh Kumar Singh, Pal Miskolczi, Jay P. Maurya, Rishikesh P. BhaleraoSummaryPerennials in boreal and temperate ecosystems display seasonally synchronized growth. In many tree species, prior to the advent of winter, exposure to photoperiods shorter than a critical threshold for growth (short days; SDs) induces growth cessation, culminating in the formation of an apical bud that encloses the shoot apical meristem and arrested leaf primordia [1, 2, 3, 4]. Following growth cessation, subsequent exposure to SDs induces transition to dormancy in the shoot apex [5]. Establishment of dormancy is crucial for winter survival and is characterized by the inability of the shoot meristem to respond to growth-promotive signals [6]. Recently, SDs were shown to induce bud dormancy by activating the abscisic acid (ABA) pathway. ABA upregulates expression of CALLOSE SYNTHASE 1 (CALS1) and suppresses glucanases that break down callose to induce the blockage of intracellular conduits (plasmodesmata; PDs) with callosic plugs called “dormancy sphincters” that by restricting access to growth-promotive signals promote dormancy [7]. However, components downstream of ABA in dormancy regulation remain largely unknown, and thus there are significant gaps in our understanding of photoperiodic control of bud dormancy. Here we demonstrate that SVL, orthologous to Arabidopsis floral repressor SHORT VEGETATIVE PHASE (SVP), is a mediator of photoperiodic control of dormancy downstream of the ABA pathway in hybrid aspen. SVL downregulation impairs dormancy, whereas SVL overexpression suppresses dormancy defects resulting from ABA insensitivity. Downstream, SVL induces callose synthase expression and negatively regulates the gibberellic acid (GA) pathway to promote dormancy, thus revealing the regulatory module mediating photoperiodic control of dormancy by ABA.
       
  • Predominant Striatal Input to the Lateral Habenula in Macaques Comes from
           Striosomes
    • Abstract: Publication date: Available online 13 December 2018Source: Current BiologyAuthor(s): Simon Hong, Satoko Amemori, Emily Chung, Daniel J. Gibson, Ken-ichi Amemori, Ann M. GraybielSummaryStriosomes, neurochemically specialized modules in the striatum, are thought to be nodes in circuits extending, via basal ganglia pathways, from mood-related neocortical regions to dopamine-containing neurons of the substantia nigra. Yet striosomes have remained beyond the reach of electrophysiological methods to identify them, especially in non-human primates. Such work is needed for translational as well as for basic science. Here we introduce a method to identify striosomes on-line in awake, behaving macaques. We combined electrical microstimulation of the striatum with simultaneous electrophysiological recording in the lateral habenula (LHb) followed by immunohistochemistry. We demonstrate that striosomes provide the predominant striatal input to the macaque pallido-habenular circuit, which is known to function in relation to reinforcement signaling. Further, our experiments suggest that striosomes from different striatal regions may convergently influence the lateral habenula. This work now opens the way to defining the functions of striosomes in behaving primates in relation to mood, motivation, and action.
       
  • Neandertal Introgression Sheds Light on Modern Human Endocranial
           Globularity
    • Abstract: Publication date: Available online 13 December 2018Source: Current BiologyAuthor(s): Philipp Gunz, Amanda K. Tilot, Katharina Wittfeld, Alexander Teumer, Chin Yang Shapland, Theo G.M. van Erp, Michael Dannemann, Benjamin Vernot, Simon Neubauer, Tulio Guadalupe, Guillén Fernández, Han G. Brunner, Wolfgang Enard, James Fallon, Norbert Hosten, Uwe Völker, Antonio Profico, Fabio Di Vincenzo, Giorgio Manzi, Janet KelsoSummaryOne of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1, 2, 3, 4]. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture [4, 5]. However, in the absence of fossil brain tissue, the underlying neuroanatomical changes as well as their genetic bases remain elusive. To better understand the biological foundations of modern human endocranial shape, we turn to our closest extinct relatives: the Neandertals. Interbreeding between modern humans and Neandertals has resulted in introgressed fragments of Neandertal DNA in the genomes of present-day non-Africans [6, 7]. Based on shape analyses of fossil skull endocasts, we derive a measure of endocranial globularity from structural MRI scans of thousands of modern humans and study the effects of introgressed fragments of Neandertal DNA on this phenotype. We find that Neandertal alleles on chromosomes 1 and 18 are associated with reduced endocranial globularity. These alleles influence expression of two nearby genes, UBR4 and PHLPP1, which are involved in neurogenesis and myelination, respectively. Our findings show how integration of fossil skull data with archaic genomics and neuroimaging can suggest developmental mechanisms that may contribute to the unique modern human endocranial shape.
       
  • GABA-Induced Intracellular Mg2+ Mobilization Integrates and Coordinates
           Cellular Information Processing for the Maturation of Neural Networks
    • Abstract: Publication date: Available online 6 December 2018Source: Current BiologyAuthor(s): Ryu Yamanaka, Yutaka Shindo, Kohji Hotta, Koji Suzuki, Kotaro OkaSummaryCells simultaneously utilize different intracellular signaling systems to process environmental information [1, 2, 3, 4]. The magnesium ion (Mg2+) is recognized as a multitarget analog regulator that performs many roles, such as circadian timekeeping, due to the following properties: (1) it influences wide-ranging biological processes, (2) its concentration is tightly controlled within a narrow sub-millimolar range, and (3) its intracellular dynamics are slow and long lasting [5, 6, 7, 8, 9, 10, 11]; its regulatory manner is not all-or-none in contrast to the switch-like signal transduction by the well-established second messenger Ca2+ [12]. Recent studies, however, have reported another role for Mg2+ as a second messenger in immune cells—i.e., a switching system for cellular states [13, 14]. These multifaceted characteristics of Mg2+ raise the question of how Mg2+ processes information and how common its role is as a signaling molecule. We focused on the trophic effects of γ-aminobutyric acid (GABA) and its developmental transition, the molecular basis of which also remains poorly understood despite its evolutionarily well-conserved roles [15, 16, 17, 18, 19]. Here, we show that in neurons, GABAA receptor signaling, whose action is excitatory, triggers Mg2+ release from mitochondria specifically at early developmental stages, and that released Mg2+ stimulates the CREB and mTOR signaling pathways, thereby facilitating structural and functional maturation of neural networks. We found that cytosolic Mg2+ fluctuations within physiological ranges is enough to crucially regulate ERK, CREB, and mTOR activities. Together, intracellular Mg2+ physiologically integrates and coordinates cellular information, and Mg2+ is a novel signal transducer for organizing neural networks.Graphical Graphical abstract for this article
       
  • Wild African Drosophila melanogaster Are Seasonal Specialists on
           Marula Fruit
    • Abstract: Publication date: Available online 6 December 2018Source: Current BiologyAuthor(s): Suzan Mansourian, Anders Enjin, Erling V. Jirle, Vedika Ramesh, Guillermo Rehermann, Paul G. Becher, John E. Pool, Marcus C. StensmyrSummaryAlthough the vinegar fly Drosophila melanogaster is arguably the most studied organism on the planet, fundamental aspects of this species’ natural ecology have remained enigmatic [1]. We have here investigated a wild population of D. melanogaster from a mopane forest in Zimbabwe. We find that these flies are closely associated with marula fruit (Sclerocarya birrea) and propose that this seasonally abundant and predominantly Southern African fruit is a key ancestral host of D. melanogaster. Moreover, when fruiting, marula is nearly exclusively used by D. melanogaster, suggesting that these forest-dwelling D. melanogaster are seasonal specialists, in a similar manner to, e.g., Drosophila erecta on screw pine cones [2]. We further demonstrate that the main chemicals released by marula activate odorant receptors that mediate species-specific host choice (Or22a) [3, 4] and oviposition site selection (Or19a) [5]. The Or22a-expressing neurons—ab3A—respond strongly to the marula ester ethyl isovalerate, a volatile rarely encountered in high amounts in other fruit. We also show that Or22a differs among African populations sampled from a wide range of habitats, in line with a function associated with host fruit usage. Flies from Southern Africa, most of which carry a distinct allele at the Or22a/Or22b locus, have ab3A neurons that are more sensitive to ethyl isovalerate than, e.g., European flies. Finally, we discuss the possibility that marula, which is also a culturally and nutritionally important resource to humans, may have helped the transition to commensalism in D. melanogaster.Graphical Graphical abstract for this article
       
  • Calretinin Neurons in the Midline Thalamus Modulate Starvation-Induced
           Arousal
    • Abstract: Publication date: Available online 6 December 2018Source: Current BiologyAuthor(s): Ruifang Hua, Xu Wang, Xinfeng Chen, Xinxin Wang, Pengcheng Huang, Pengcheng Li, Wei Mei, Haohong LiSummaryOrchestration of sleep and feeding behavior is essential for organismal health and survival. Although sleep deprivation promotes feeding and starvation suppresses sleep, the underlying neural mechanisms remain largely unknown. Here, we showed that starvation in mice potently promoted arousal and activated calretinin neurons (CR+) in the paraventricular thalamus (PVT). Direct activation of PVTCR+ neurons promoted arousal, and their activity was necessary for starvation-induced sleep suppression. Specifically, the PVTCR+-bed nucleus of the stria terminalis (BNST) circuit rapidly initiated arousal. Selective inhibition of BNST-projecting PVT neurons opposed arousal during starvation. Taken together, our results define a cell-type-specific neural circuitry modulating starvation-induced arousal and coordinating the conflict between sleeping and feeding.
       
  • Bi-directional Control of Walking Behavior by Horizontal Optic Flow
           Sensors
    • Abstract: Publication date: Available online 6 December 2018Source: Current BiologyAuthor(s): Christian Busch, Alexander Borst, Alex S. MaussSummaryMoving animals experience constant sensory feedback, such as panoramic image shifts on the retina, termed optic flow. Underlying neuronal signals are thought to be important for exploratory behavior by signaling unintended course deviations and by providing spatial information about the environment [1, 2]. Particularly in insects, the encoding of self-motion-related optic flow is well understood [1, 2, 3, 4, 5]. However, a gap remains in understanding how the associated neuronal activity controls locomotor trajectories. In flies, visual projection neurons belonging to two groups encode panoramic horizontal motion: horizontal system (HS) cells respond with depolarization to front-to-back motion and hyperpolarization to the opposite direction [6, 7], and other neurons have the mirror-symmetrical response profile [6, 8, 9]. With primarily monocular sensitivity, the neurons’ responses are ambiguous for different rotational and translational self-movement components. Such ambiguities can be greatly reduced by combining signals from both eyes [10, 11, 12] to determine turning and movement speed [13, 14, 15, 16]. Here, we explore the underlying functional logic by optogenetic HS cell manipulation in tethered walking Drosophila. We show that de- and hyperpolarization evoke opposite turning behavior, indicating that both direction-selective signals are transmitted to descending pathways for course control. Further experiments reveal a negative effect of bilaterally symmetric de- and hyperpolarization on walking velocity. Our results are therefore consistent with a functional architecture in which the HS cells’ membrane potential influences walking behavior bi-directionally via two decelerating pathways.Graphical Graphical abstract for this article
       
  • Persisting Worldwide Seabird-Fishery Competition Despite Seabird Community
           Decline
    • Abstract: Publication date: Available online 6 December 2018Source: Current BiologyAuthor(s): David Grémillet, Aurore Ponchon, Michelle Paleczny, Maria-Lourdes D. Palomares, Vasiliki Karpouzi, Daniel PaulySummaryFisheries transform marine ecosystems and compete with predators [1], but temporal trends in seabird-fishery competition had never been assessed on a worldwide scale. Using catch reconstructions [2] for all fisheries targeting taxa that are also seabird prey, we demonstrated that average annual fishery catch increased from 59 to 65 million metric tons between 1970–1989 and 1990–2010. For the same periods, we estimated that global annual seabird food consumption decreased from 70 to 57 million metric tons. Despite this decrease, we found sustained global seabird-fishery food competition between 1970–1989 and 1990–2010. Enhanced competition was identified in 48% of all areas, notably the Southern Ocean, Asian shelves, Mediterranean Sea, Norwegian Sea, and Californian coast. Fisheries generate severe constraints for seabird populations on a worldwide scale, and those need to be addressed urgently. Indeed, seabirds are the most threatened bird group, with a 70% community-level population decline across 1950–2010 [3].Graphical Graphical abstract for this article
       
  • The Muskox Lost a Substantial Part of Its Genetic Diversity on Its Long
           Road to Greenland
    • Abstract: Publication date: Available online 6 December 2018Source: Current BiologyAuthor(s): Charles Christian Riis Hansen, Christina Hvilsom, Niels Martin Schmidt, Peter Aastrup, Peter J. Van Coeverden de Groot, Hans Redlef Siegismund, Rasmus HellerSummaryThe muskox (Ovibos moschatus) is the largest terrestrial herbivore in the Arctic and plays a vital role in the tundra ecosystem [1, 2, 3, 4]. Its range, abundance, and genetic diversity have declined dramatically over the past 30,000 years [5]. Two subspecies are recognized, but little is known about the genetic structure and how this relates to the species history. One unresolved question is how and when the species dispersed into its present range, notably the present strongholds in the Canadian archipelago and Greenland. We used genotyping by sequencing (GBS) data from 116 muskox individuals and genotype likelihood-based methods to infer the genetic diversity and distribution of genetic variation in the species. We identified a basal split separating the two recognized subspecies, in agreement with isolation of the muskox into several refugia in the Nearctic around 21,000 years ago [6], near the last glacial maximum (LGM). In addition, we found evidence of strong, successive founder effects inflicting a progressive loss of genetic diversity as the muskox colonized the insular High Arctic from an unknown Nearctic origin. These have resulted in exceptionally low genetic diversity in the Greenlandic populations, as well as extremely high genetic differentiation among regional populations. Our results highlight the need for further investigations of genetic erosion in Nearctic terrestrial mammals, of which several show similar colonization histories in the High Artic.Graphical Graphical abstract for this article
       
  • Parrot Genomes and the Evolution of Heightened Longevity and Cognition
    • Abstract: Publication date: Available online 6 December 2018Source: Current BiologyAuthor(s): Morgan Wirthlin, Nicholas C.B. Lima, Rafael Lucas Muniz Guedes, André E.R. Soares, Luiz Gonzaga P. Almeida, Nathalia P. Cavaleiro, Guilherme Loss de Morais, Anderson V. Chaves, Jason T. Howard, Marcus de Melo Teixeira, Patricia N. Schneider, Fabrício R. Santos, Michael C. Schatz, Maria Sueli Felipe, Cristina Y. Miyaki, Alexandre Aleixo, Maria P.C. Schneider, Erich D. Jarvis, Ana Tereza R. Vasconcelos, Francisco ProsdocimiSummaryParrots are one of the most distinct and intriguing groups of birds, with highly expanded brains [1], highly developed cognitive [2] and vocal communication [3] skills, and a long lifespan compared to other similar-sized birds [4]. Yet the genetic basis of these traits remains largely unidentified. To address this question, we have generated a high-coverage, annotated assembly of the genome of the blue-fronted Amazon (Amazona aestiva) and carried out extensive comparative analyses with 30 other avian species, including 4 additional parrots. We identified several genomic features unique to parrots, including parrot-specific novel genes and parrot-specific modifications to coding and regulatory sequences of existing genes. We also discovered genomic features under strong selection in parrots and other long-lived birds, including genes previously associated with lifespan determination as well as several hundred new candidate genes. These genes support a range of cellular functions, including telomerase activity; DNA damage repair; control of cell proliferation, cancer, and immunity; and anti-oxidative mechanisms. We also identified brain-expressed, parrot-specific paralogs with known functions in neural development or vocal-learning brain circuits. Intriguingly, parrot-specific changes in conserved regulatory sequences were overwhelmingly associated with genes that are linked to cognitive abilities and have undergone similar selection in the human lineage, suggesting convergent evolution. These findings bring novel insights into the genetics and evolution of longevity and cognition, as well as provide novel targets for exploring the mechanistic basis of these traits.
       
  • Geckos Race Across the Water’s Surface Using Multiple Mechanisms
    • Abstract: Publication date: Available online 6 December 2018Source: Current BiologyAuthor(s): Jasmine A. Nirody, Judy Jinn, Thomas Libby, Timothy J. Lee, Ardian Jusufi, David L. Hu, Robert J. FullSummaryAcrobatic geckos can sprint at high speeds over challenging terrain [1], scamper up the smoothest surfaces [2], rapidly swing underneath leaves [3], and right themselves in midair by swinging only their tails [4, 5]. From our field observations, we can add racing on the water’s surface to the gecko’s list of agile feats. Locomotion at the air-water interface evolved in over a thousand species, including insects, fish, reptiles, and mammals [6]. To support their weight, some larger-legged vertebrates use forces generated by vigorous slapping of the fluid’s surface followed by a stroke of their appendage [7, 8, 9, 10, 11, 12], whereas smaller animals, like arthropods, rely on surface tension to walk on water [6, 13]. Intermediate-sized geckos (Hemidactylus platyurus) fall squarely between these two regimes. Here, we report the unique ability of geckos to exceed the speed limits of conventional surface swimming. Several mechanisms likely contribute in this intermediate regime. In contrast to bipedal basilisk lizards [7, 8, 9, 10], geckos used a stereotypic trotting gait with all four limbs, creating air cavities during slapping to raise their head and anterior trunk above water. Adding surfactant to the water decreased velocity by half, confirming surface tension’s role. The superhydrophobic skin could reduce drag during semi-planing. Geckos laterally undulated their bodies, including their submerged posterior trunk and tail, generating thrust for forward propulsion, much like water dragons [14] and alligators [15]. Geckos again remind us of the advantages of multi-functional morphologies providing the opportunity for multiple mechanisms for motion.Graphical Graphical abstract for this article
       
  • Tooth Loss Precedes the Origin of Baleen in Whales
    • Abstract: Publication date: Available online 29 November 2018Source: Current BiologyAuthor(s): Carlos Mauricio Peredo, Nicholas D. Pyenson, Christopher D. Marshall, Mark D. UhenSummaryWhales use baleen, a novel integumentary structure, to filter feed; filter feeding itself evolved at least five times in tetrapod history but demonstrably only once in mammals [1]. Living baleen whales (mysticetes) are born without teeth, but paleontological and embryological evidence demonstrate that they evolved from toothed ancestors that lacked baleen entirely [2]. The mechanisms driving the origin of filter feeding in tetrapods remain obscure. Here we report Maiabalaena nesbittae gen. et sp. nov., a new fossil whale from early Oligocene rocks of Washington State, USA, lacking evidence of both teeth and baleen. The holotype possesses a nearly complete skull with ear bones, both mandibles, and associated postcrania. Phylogenetic analysis shows Maiabalaena as crownward of all toothed mysticetes, demonstrating that tooth loss preceded the evolution of baleen. The functional transition from teeth to baleen in mysticetes has remained enigmatic because baleen decays rapidly and leaves osteological correlates with unclear homology; the oldest direct evidence for fossil baleen is ∼25 million years younger [3] than the oldest stem mysticetes (∼36 Ma). Previous hypotheses for the origin of baleen [4, 5] are inconsistent with the morphology and phylogenetic position of Maiabalaena. The absence of both teeth and baleen in Maiabalaena is consistent with recent evidence that the evolutionary loss of teeth and origin of baleen are decoupled evolutionary transformations, each with a separate morphological and genetic basis [2, 6]. Understanding these macroevolutionary patterns in baleen whales is akin to other macroevolutionary transformations in tetrapods such as scales to feathers in birds.
       
  • Rapid Transformation from Auditory to Linguistic Representations of
           Continuous Speech
    • Abstract: Publication date: Available online 29 November 2018Source: Current BiologyAuthor(s): Christian Brodbeck, L. Elliot Hong, Jonathan Z. SimonSummaryDuring speech perception, a central task of the auditory cortex is to analyze complex acoustic patterns to allow detection of the words that encode a linguistic message [1]. It is generally thought that this process includes at least one intermediate, phonetic, level of representations [2, 3, 4, 5, 6], localized bilaterally in the superior temporal lobe [7, 8, 9]. Phonetic representations reflect a transition from acoustic to linguistic information, classifying acoustic patterns into linguistically meaningful units, which can serve as input to mechanisms that access abstract word representations [10, 11]. While recent research has identified neural signals arising from successful recognition of individual words in continuous speech [12, 13, 14, 15], no explicit neurophysiological signal has been found demonstrating the transition from acoustic and/or phonetic to symbolic, lexical representations. Here, we report a response reflecting the incremental integration of phonetic information for word identification, dominantly localized to the left temporal lobe. The short response latency, approximately 114 ms relative to phoneme onset, suggests that phonetic information is used for lexical processing as soon as it becomes available. Responses also tracked word boundaries, confirming previous reports of immediate lexical segmentation [16, 17]. These new results were further investigated using a cocktail-party paradigm [18, 19] in which participants listened to a mix of two talkers, attending to one and ignoring the other. Analysis indicates neural lexical processing of only the attended, but not the unattended, speech stream. Thus, while responses to acoustic features reflect attention through selective amplification of attended speech, responses consistent with a lexical processing model reveal categorically selective processing.
       
  • Closed-Loop Control of Active Sensing Movements Regulates Sensory Slip
    • Abstract: Publication date: Available online 29 November 2018Source: Current BiologyAuthor(s): Debojyoti Biswas, Luke A. Arend, Sarah A. Stamper, Balázs P. Vágvölgyi, Eric S. Fortune, Noah J. CowanSummaryActive sensing involves the production of motor signals for the purpose of acquiring sensory information [1, 2, 3]. The most common form of active sensing, found across animal taxa and behaviors, involves the generation of movements—e.g., whisking [4, 5, 6], touching [7, 8], sniffing [9, 10], and eye movements [11]. Active sensing movements profoundly affect the information carried by sensory feedback pathways [12, 13, 14, 15] and are modulated by both top-down goals (e.g., measuring weight versus texture [1, 16]) and bottom-up stimuli (e.g., lights on or off [12]), but it remains unclear whether and how these movements are controlled in relation to the ongoing feedback they generate. To investigate the control of movements for active sensing, we created an experimental apparatus for freely swimming weakly electric fish, Eigenmannia virescens, that modulates the gain of reafferent feedback by adjusting the position of a refuge based on real-time videographic measurements of fish position. We discovered that fish robustly regulate sensory slip via closed-loop control of active sensing movements. Specifically, as fish performed the task of maintaining position inside the refuge [17, 18, 19, 20, 21, 22], they dramatically up- or downregulated fore-aft active sensing movements in relation to a 4-fold change of experimentally modulated reafferent gain. These changes in swimming movements served to maintain a constant magnitude of sensory slip. The magnitude of sensory slip depended on the presence or absence of visual cues. These results indicate that fish use two controllers: one that controls the acquisition of information by regulating feedback from active sensing movements and another that maintains position in the refuge, a control structure that may be ubiquitous in animals [23, 24].Graphical Graphical abstract for this article
       
  • Centromere DNA Destabilizes H3 Nucleosomes to Promote CENP-A Deposition
           during the Cell Cycle
    • Abstract: Publication date: Available online 29 November 2018Source: Current BiologyAuthor(s): Manu Shukla, Pin Tong, Sharon A. White, Puneet P. Singh, Angus M. Reid, Sandra Catania, Alison L. Pidoux, Robin C. AllshireSummaryActive centromeres are defined by the presence of nucleosomes containing CENP-A, a histone H3 variant, which alone is sufficient to direct kinetochore assembly. Once assembled at a location, CENP-A chromatin and kinetochores are maintained at that location through a positive feedback loop where kinetochore proteins recruited by CENP-A promote deposition of new CENP-A following replication. Although CENP-A chromatin itself is a heritable entity, it is normally associated with specific sequences. Intrinsic properties of centromeric DNA may favor the assembly of CENP-A rather than H3 nucleosomes. Here we investigate histone dynamics on centromere DNA. We show that during S phase, histone H3 is deposited as a placeholder at fission yeast centromeres and is subsequently evicted in G2, when we detect deposition of the majority of new CENP-ACnp1. We also find that centromere DNA has an innate property of driving high rates of turnover of H3-containing nucleosomes, resulting in low nucleosome occupancy. When placed at an ectopic chromosomal location in the absence of any CENP-ACnp1 assembly, centromere DNA appears to retain its ability to impose S phase deposition and G2 eviction of H3, suggesting that features within centromere DNA program H3 dynamics. Because RNA polymerase II (RNAPII) occupancy on this centromere DNA coincides with H3 eviction in G2, we propose a model in which RNAPII-coupled chromatin remodeling promotes replacement of H3 with CENP-ACnp1 nucleosomes.
       
  • Direct Electrical Stimulation of Lateral Orbitofrontal Cortex Acutely
           Improves Mood in Individuals with Symptoms of Depression
    • Abstract: Publication date: Available online 29 November 2018Source: Current BiologyAuthor(s): Vikram R. Rao, Kristin K. Sellers, Deanna L. Wallace, Morgan B. Lee, Maryam Bijanzadeh, Omid G. Sani, Yuxiao Yang, Maryam M. Shanechi, Heather E. Dawes, Edward F. ChangSummaryMood disorders cause significant morbidity and mortality, and existing therapies fail 20%–30% of patients. Deep brain stimulation (DBS) is an emerging treatment for refractory mood disorders, but its success depends critically on target selection. DBS focused on known targets within mood-related frontostriatal and limbic circuits has been variably efficacious. Here, we examine the effects of stimulation in orbitofrontal cortex (OFC), a key hub for mood-related circuitry that has not been well characterized as a stimulation target. We studied 25 subjects with epilepsy who were implanted with intracranial electrodes for seizure localization. Baseline depression traits ranged from mild to severe. We serially assayed mood state over several days using a validated questionnaire. Continuous electrocorticography enabled investigation of neurophysiological correlates of mood-state changes. We used implanted electrodes to stimulate OFC and other brain regions while collecting verbal mood reports and questionnaire scores. We found that unilateral stimulation of the lateral OFC produced acute, dose-dependent mood-state improvement in subjects with moderate-to-severe baseline depression. Stimulation suppressed low-frequency power in OFC, mirroring neurophysiological features that were associated with positive mood states during natural mood fluctuation. Stimulation potentiated single-pulse-evoked responses in OFC and modulated activity within distributed structures implicated in mood regulation. Behavioral responses to stimulation did not include hypomania and indicated an acute restoration to non-depressed mood state. Together, these findings indicate that lateral OFC stimulation broadly modulates mood-related circuitry to improve mood state in depressed patients, revealing lateral OFC as a promising new target for therapeutic brain stimulation in mood disorders.
       
  • In Toto Imaging of Dynamic Osteoblast Behaviors in Regenerating
           Skeletal Bone
    • Abstract: Publication date: Available online 29 November 2018Source: Current BiologyAuthor(s): Ben D. Cox, Alessandro De Simone, Valerie A. Tornini, Sumeet P. Singh, Stefano Di Talia, Kenneth D. PossSummaryOsteoblasts are matrix-depositing cells that can divide and heal bone injuries. Their deep-tissue location and the slow progression of bone regeneration challenge attempts to capture osteoblast behaviors in live tissue at high spatiotemporal resolution. Here, we have developed an imaging platform to monitor and quantify individual and collective behaviors of osteoblasts in adult zebrafish scales, skeletal body armor discs that regenerate rapidly after loss. Using a panel of transgenic lines that visualize and manipulate osteoblasts, we find that a founder pool of osteoblasts emerges through de novo differentiation within one day of scale plucking. These osteoblasts undergo division events that are largely uniform in frequency and orientation to establish a primordium. Osteoblast proliferation dynamics diversify across the primordium by two days after injury, with cell divisions focused near, and with orientations parallel to, the scale periphery, occurring coincident with dynamic localization of fgf20a gene expression. In posterior scale regions, cell elongation events initiate in areas soon occupied by mineralized grooves called radii, beginning approximately 2 days post injury, with patterned osteoblast death events accompanying maturation of these radii. By imaging at single-cell resolution, we detail acquisition of spatiotemporally distinct cell division, motility, and death dynamics within a founder osteoblast pool as bone regenerates.Graphical Graphical abstract for this article
       
  • Nonverbal Working Memory for Novel Images in Rhesus Monkeys
    • Abstract: Publication date: Available online 29 November 2018Source: Current BiologyAuthor(s): Ryan J. Brady, Robert R. HamptonSummaryHuman working memory is greatly facilitated by linguistic representations—for example, by verbal rehearsal and by verbal recoding of novel stimuli. The absence of language in nonhumans raises questions about the extent to which nonhuman working memory includes similar mechanisms. There is strong evidence for rehearsal-like active maintenance in working memory when monkeys are tested with highly familiar stimuli, but not when tested with novel stimuli, suggesting that working memory depends on the existence of previously encoded representations. This difference in working memory for familiar and novel images may exist because, lacking language, monkeys cannot recode novel stimuli in a way that permits active maintenance in working memory. Alternatively, working memory for novel images may have been present, but behaviorally silent, in earlier studies. In tests with novel images, the high familiarity of to-be-remembered stimuli compared to never-before-seen distractors may be such a strong determinant of recognition performance that evidence of working memory is obscured. In the current study, we developed a technique for attenuating the utility of relative familiarity as a mnemonic signal in recognition tests with novel stimuli. In tests with novel images, we observed impairments of memory by concurrent cognitive load and delay interval that indicate actively maintained working memory. This flexibility in monkey working memory suggests that monkeys may recode unfamiliar stimuli to facilitate working memory and establishes new parallels between verbal human working memory and nonverbal nonhuman primate working memory.
       
  • Tissue-Specific cis-Regulatory Divergence Implicates eloF in Inhibiting
           Interspecies Mating in Drosophila
    • Abstract: Publication date: Available online 29 November 2018Source: Current BiologyAuthor(s): Peter A. Combs, Joshua J. Krupp, Neil M. Khosla, Dennis Bua, Dmitri A. Petrov, Joel D. Levine, Hunter B. FraserSummaryReproductive isolation is a key component of speciation. In many insects, a major driver of this isolation is cuticular hydrocarbon pheromones, which help to identify potential intraspecific mates [1, 2, 3]. When the distributions of related species overlap, there may be strong selection on mate choice for intraspecific partners [4, 5, 6, 7, 8, 9] because interspecific hybridization carries significant fitness costs [10]. Drosophila has been a key model for the investigation of reproductive isolation; although both male and female mate choices have been extensively investigated [6, 11, 12, 13, 14, 15, 16], the genes underlying species recognition remain largely unknown. To explore the molecular mechanisms underlying Drosophila speciation, we measured tissue-specific cis-regulatory divergence using RNA sequencing (RNA-seq) in D. simulans × D. sechellia hybrids. By focusing on cis-regulatory changes specific to female oenocytes, the tissue that produces cuticular hydrocarbons, we rapidly identified a small number of candidate genes. We found that one of these, the fatty acid elongase eloF, broadly affects the hydrocarbons present on D. sechellia and D. melanogaster females, as well as the propensity of D. simulans males to mate with them. Therefore, cis-regulatory changes in eloF may be a major driver in the sexual isolation of D. simulans from multiple other species. Our RNA-seq approach proved to be far more efficient than quantitative trait locus (QTL) mapping in identifying candidate genes; the same framework can be used to pinpoint candidate drivers of cis-regulatory divergence in traits differing between any interfertile species.
       
  • Control of Xenopus Tadpole Locomotion via Selective Expression of Ih in
           Excitatory Interneurons
    • Abstract: Publication date: Available online 29 November 2018Source: Current BiologyAuthor(s): Laurence D. Picton, Keith T. Sillar, Hong-Yan ZhangSummaryLocomotion relies on the coordinated activity of rhythmic neurons in the hindbrain and spinal cord and depends critically on the intrinsic properties of excitatory interneurons. Therefore, understanding how ion channels sculpt the properties of these interneurons, and the consequences for circuit function and behavior, is an important task. The hyperpolarization-activated cation current, Ih, is known to play important roles in shaping neuronal properties and for rhythm generation in many neuronal networks. We show in stage 42 Xenopus laevis frog tadpoles that Ih is strongly expressed only in excitatory descending interneurons (dINs), an important ipsilaterally projecting population that drives swimming activity. The voltage-dependent HCN channel blocker ZD7288 completely abolished a prominent depolarizing sag potential in response to hyperpolarization, the hallmark of Ih, and hyperpolarized dINs. ZD7288 also affected dIN post-inhibitory rebound firing, upon which locomotor rhythm generation relies, and disrupted locomotor output. Block of Ih also unmasked an activity-dependent ultraslow afterhyperpolarization (usAHP) in dINs following swimming, mediated by a dynamic Na/K pump current. This usAHP, unmasked in dINs by ZD7288, resulted in suprathreshold stimuli failing to evoke swimming at short inter-swim intervals, indicating an important role for Ih in maintaining swim generation capacity and in setting the post-swim refractory period of the network. Collectively, our data suggest that the selective expression of Ih in dINs determines specific dIN properties that are important for rhythm generation and counteracts an activity-dependent usAHP to ensure that dINs can maintain coordinated swimming over a wide range of inter-swim intervals.
       
 
 
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