Current Biology

Infant Neural Sensitivity to Dynamic Eye Gaze Is Associated with Later Emerging Autism.

Publication Date: 2012 Jan 24 PMID: 22285033
Authors: Elsabbagh, M. - Mercure, E. - Hudry, K. - Chandler, S. - Pasco, G. - Charman, T. - Pickles, A. - Baron-Cohen, S. - Bolton, P. - Johnson, M. H.
Journal: Curr Biol

Autism spectrum disorders (henceforth autism) are diagnosed in around 1% of the population [1]. Familial liability confers risk for a broad spectrum of difficulties including the broader autism phenotype (BAP) [2, 3]. There are currently no reliable predictors of autism in infancy, but characteristic behaviors emerge during the second year, enabling diagnosis after this age [4, 5]. Because indicators of brain functioning may be sensitive predictors, and atypical eye contact is characteristic of the syndrome [6-9] and the BAP [10, 11], we examined whether neural sensitivity to eye gaze during infancy is associated with later autism outcomes [12, 13]. We undertook a prospective longitudinal study of infants with and without familial risk for autism. At 6-10 months, we recorded infants' event-related potentials (ERPs) in response to viewing faces with eye gaze directed toward versus away from the infant [14]. Longitudinal analyses showed that characteristics of ERP components evoked in response to dynamic eye gaze shifts during infancy were associated with autism diagnosed at 36 months. ERP responses to eye gaze may help characterize developmental processes that lead to later emerging autism. Findings also elucidate the mechanisms driving the development of the social brain in infancy.

post to: CiteULike

Mcm10 Plays a Role in Functioning of the Eukaryotic Replicative DNA Helicase, Cdc45-Mcm-GINS.

Publication Date: 2012 Jan 24 PMID: 22285032
Authors: Watase, G. - Takisawa, H. - Kanemaki, M. T.
Journal: Curr Biol

Eukaryotic DNA replication is initiated at multiple origins of replication, where many replication proteins assemble under the control of the cell cycle [1]. A key process of replication initiation is to convert inactive Mcm2-7 to active Cdc45-Mcm-GINS (CMG) replicative helicase [2]. However, it is not known whether the CMG assembly would automatically activate its helicase activity and thus assemble the replisome. Mcm10 is an evolutionally conserved essential protein required for the initiation of replication [3, 4]. Although the roles of many proteins involved in the initiation are understood, the role of Mcm10 remains controversial [5-9]. To characterize Mcm10 in more detail, we constructed budding yeast cells bearing a degron-fused Mcm10 protein that can be efficiently degraded in response to auxin. In the absence of Mcm10, a stable CMG complex was assembled at origins. However, subsequent translocation of CMG, replication protein A loading to origins, and the intra-S checkpoint activation were severely diminished, suggesting that origin unwinding is defective. We also found that Mcm10 associates with origins during initiation in an S-cyclin-dependent kinase- and Cdc45-dependent manner. Thus, Mcm10 plays an essential role in functioning of the CMG replicative helicase independent of assembly of a stable CMG complex at origins.

post to: CiteULike

Rapid Establishment of Genetic Incompatibility through Natural Epigenetic Variation.

Publication Date: 2012 Jan 24 PMID: 22285031
Authors: Durand, S. - Bouche, N. - Perez Strand, E. - Loudet, O. - Camilleri, C.
Journal: Curr Biol

Epigenetic variation is currently being investigated with the aim of deciphering its importance in both adaptation and evolution [1]. In plants, epimutations can underlie heritable phenotypic diversity [2-4], and epigenetic mechanisms might contribute to reproductive barriers between [5] or within species [6]. The extent of epigenetic variation begins to be appreciated in Arabidopsis [7], but the origin of natural epialleles and their impact in the wild remain largely unknown. Here we show that a genetic incompatibility among Arabidopsis thaliana strains is related to the epigenetic control of a pair of duplicate genes involved in fitness: a transposition event results in a rearranged paralogous structure that causes DNA methylation and transcriptional silencing of the other copy. We further show that this natural, strain-specific epiallele is stable over numerous generations even after removal of the duplicated, rearranged gene copy through crosses. Finally, we provide evidence that the rearranged gene copy triggers de novo DNA methylation and silencing of the unlinked native gene by RNA-directed DNA methylation. Our findings suggest an important role of naturally occurring epialleles originating from structural variation in rapidly establishing genetic incompatibilities following gene duplication events.

post to: CiteULike

Kinase Activity of Fission Yeast Mph1 Is Required for Mad2 and Mad3 to Stably Bind the Anaphase Promoting Complex.

Publication Date: 2012 Jan 24 PMID: 22281223
Authors: Zich, J. - Sochaj, A. M. - Syred, H. M. - Milne, L. - Cook, A. G. - Ohkura, H. - Rappsilber, J. - Hardwick, K. G.
Journal: Curr Biol

Defects in chromosome segregation result in aneuploidy, which can lead to disease or cell death [1, 2]. The spindle checkpoint delays anaphase onset until all chromosomes are attached to spindle microtubules in a bipolar fashion [3, 4]. Mad2 is a key checkpoint component that undergoes conformational activation, catalyzed by a Mad1-Mad2 template enriched at unattached kinetochores [5]. Mad2 and Mad3 (BubR1) then bind and inhibit Cdc20 to form the mitotic checkpoint complex (MCC), which binds and inhibits the anaphase promoting complex (APC/C). Checkpoint kinases (Aurora, Bub1, and Mps1) are critical for checkpoint signaling, yet they have poorly defined roles and few substrates have been identified [6-8]. Here we demonstrate that a kinase-dead allele of the fission yeast MPS1 homolog (Mph1) is checkpoint defective and that levels of APC/C-associated Mad2 and Mad3 are dramatically reduced in this mutant. Thus, MCC binding to fission yeast APC/C is dependent on Mph1 kinase activity. We map and mutate several phosphorylation sites in Mad2, producing mutants that display reduced Cdc20-APC/C binding and an inability to maintain checkpoint arrest. We conclude that Mph1 kinase regulates the association of Mad2 with its binding partners and thereby mitotic arrest.

post to: CiteULike

New insights in human memory interference and consolidation.

Publication Date: 2012 Jan 24 PMID: 22280913
Authors: Robertson, E. M.
Journal: Curr Biol

Learning new facts and skills in succession can be frustrating because no sooner has new knowledge been acquired than its retention is being jeopardized by learning another set of skills or facts. Interference between memories has recently provided important new insights into the neural and psychological systems responsible for memory processing. For example, interference not only occurs between the same types of memories, but can also occur between different types of memories, which has important implications for our understanding of memory organization. Converging evidence has begun to reveal that the brain produces interference independently from other aspects of memory processing, which suggests that interference may have an important but previously overlooked function. A memory's initial susceptibility to interference and subsequent resistance to interference after its acquisition has revealed that memories continue to be processed 'off-line' during consolidation. Recent work has demonstrated that off-line processing is not limited to just the stabilization of a memory, which was once the defining characteristic of consolidation; instead, off-line processing can have a rich diversity of effects, from enhancing performance to making hidden rules explicit. Off-line processing also occurs after memory retrieval when memories are destabilized and then subsequently restabalized during reconsolidation. Studies are beginning to reveal the function of reconsolidation, its mechanistic relationship to consolidation and its potential as a therapeutic target for the modification of memories.

post to: CiteULike

Developmental biology: taking flight.

Publication Date: 2012 Jan 24 PMID: 22280912
Authors: Roy, S. - Vijayraghavan, K.
Journal: Curr Biol

Powered flight was first mastered by insects, many millions of years ago. Now, studies with the fruit fly Drosophila melanogaster reveal the critical role of a conserved transcription factor in programming the development of specialized flight muscles.

post to: CiteULike

Sexual signaling: climatic carry-over.

Publication Date: 2012 Jan 24 PMID: 22280911
Authors: Vitousek, M. N. - Dor, R. - Safran, R. J.
Journal: Curr Biol

A long term study of warblers in the Himalayas reveals a surprising contrast in the effects of warm springs as opposed to warm summers on a signaling trait, emphasizing the need to consider year-round influences of the environment on morphological variation.

post to: CiteULike

Cell polarization: mechanical switch for a chemical reaction.

Publication Date: 2012 Jan 24 PMID: 22280910
Authors: Verkhovsky, A. B.
Journal: Curr Biol

Anterior-posterior polarity in the Caenorhabditis elegans zygote depends on two groups of PAR proteins, as well as on cortical flow. Recent work now demonstrates that this polarization results from a transition in a bistable reaction-diffusion system of PAR proteins that is triggered by cortical flow.

post to: CiteULike

Auditory neuroscience: how to encode microsecond differences.

Publication Date: 2012 Jan 24 PMID: 22280909
Authors: Koppl, C.
Journal: Curr Biol

Minute differences between the time of arrival of a sound at the two ears are used by humans and animals to locate the source. New in vivo recordings have shed light on how auditory neurons solve the problem of resolving microsecond time differences.

post to: CiteULike

Epigenetic inheritance: what news for evolution?

Publication Date: 2012 Jan 24 PMID: 22280908
Authors: Hunter, B. - Hollister, J. D. - Bomblies, K.
Journal: Curr Biol

Whether epigenetic variation is important in adaptive evolution has been contentious. Two recent studies in Arabidopsis thaliana significantly add to our understanding of genome-wide variation and stability of an epigenetic mark, and thus help pave the path for realistically incorporating epigenetics into evolutionary theory.

post to: CiteULike

Motor proteins: Kinesin can replace Myosin.

Publication Date: 2012 Jan 24 PMID: 22280907
Authors: Scheffler, K. - Tran, P. T.
Journal: Curr Biol

Directional transport of specific cargos is tuned to specific molecular motors and specific cytoskeletal tracks. Myosin V transports its cargo on actin cables, whereas kinesin or dynein transport their cargo on microtubules. A recent study shows that an engineered kinesin can substitute for myosin V and its cargo-specific transport and subsequent cellular functions.

post to: CiteULike

Animal cognition: chimpanzee alarm calls depend on what others know.

Publication Date: 2012 Jan 24 PMID: 22280906
Authors: Seyfarth, R. M. - Cheney, D. L.
Journal: Curr Biol

After a wild chimpanzee encounters a model of a dangerous snake, whether or not he gives an alarm call depends on his perception of another individual's knowledge.

post to: CiteULike

Cell polarity: tension quenches the rear.

Publication Date: 2012 Jan 24 PMID: 22280905
Authors: Mogilner, A. - Zhu, J.
Journal: Curr Biol

A combination of biophysical perturbations and computer simulations shows that leading edge protrusion in crawling cells increases membrane tension, which constrains the protruding front to one side of the cell, thereby maintaining its polarity.

post to: CiteULike

Motor development: activity matters after all.

Publication Date: 2012 Jan 24 PMID: 22280904
Authors: Wenner, P.
Journal: Curr Biol

Developing spinal networks are constructed through the integration of local microcircuits and the ongoing incorporation of later-developing neurons. This process is dependent on neuronal activity prior to synaptogenesis.

post to: CiteULike

Spike sorting.

Publication Date: 2012 Jan 24 PMID: 22280903
Authors: Quiroga, R. Q.
Journal: Curr Biol

post to: CiteULike

Oncogene addiction.

Publication Date: 2012 Jan 24 PMID: 22280902
Authors: Settleman, J.
Journal: Curr Biol

post to: CiteULike

Disrupted Circadian Rhythms in a Mouse Model of Schizophrenia.

Publication Date: 2012 Jan 18 PMID: 22264613
Authors: Oliver, P. L. - Sobczyk, M. V. - Maywood, E. S. - Edwards, B. - Lee, S. - Livieratos, A. - Oster, H. - Butler, R. - Godinho, S. I. - Wulff, K. - Peirson, S. N. - Fisher, S. P. - Chesham, J. E. - Smith, J. W. - Hastings, M. H. - Davies, K. E. - Foster, R. G.
Journal: Curr Biol

Sleep and circadian rhythm disruption has been widely observed in neuropsychiatric disorders including schizophrenia [1] and often precedes related symptoms [2]. However, mechanistic basis for this association remains unknown. Therefore, we investigated the circadian phenotype of blind-drunk (Bdr), a mouse model of synaptosomal-associated protein (Snap)-25 exocytotic disruption that displays schizophrenic endophenotypes modulated by prenatal factors and reversible by antipsychotic treatment [3, 4]. Notably, SNAP-25 has been implicated in schizophrenia from genetic [5-8], pathological [9-13], and functional studies [14-16]. We show here that the rest and activity rhythms of Bdr mice are phase advanced and fragmented under a light/dark cycle, reminiscent of the disturbed sleep patterns observed in schizophrenia. Retinal inputs appear normal in mutants, and clock gene rhythms within the suprachiasmatic nucleus (SCN) are normally phased both in vitro and in vivo. However, the 24 hr rhythms of arginine vasopressin within the SCN and plasma corticosterone are both markedly phase advanced in Bdr mice. We suggest that the Bdr circadian phenotype arises from a disruption of synaptic connectivity within the SCN that alters critical output signals. Collectively, our data provide a link between disruption of circadian activity cycles and synaptic dysfunction in a model of neuropsychiatric disease.

post to: CiteULike

Neural Locus of Color Afterimages.

Publication Date: 2012 Jan 18 PMID: 22264612
Authors: Zaidi, Q. - Ennis, R. - Cao, D. - Lee, B.
Journal: Curr Biol

After fixating on a colored pattern, observers see a similar pattern in complementary colors when the stimulus is removed [1-6]. Afterimages were important in disproving the theory that visual rays emanate from the eye, in demonstrating interocular interactions, and in revealing the independence of binocular vision from eye movements. Afterimages also prove invaluable in exploring selective attention, filling in, and consciousness. Proposed physiological mechanisms for color afterimages range from bleaching of cone photopigments to cortical adaptation [4-9], but direct neural measurements have not been reported. We introduce a time-varying method for evoking afterimages, which provides precise measurements of adaptation and a direct link between visual percepts and neural responses [10]. We then use in vivo electrophysiological recordings to show that all three classes of primate retinal ganglion cells exhibit subtractive adaptation to prolonged stimuli, with much slower time constants than those expected of photoreceptors. At the cessation of the stimulus, ganglion cells generate rebound responses that can provide afterimage signals for later neurons. Our results indicate that afterimage signals are generated in the retina but may be modified like other retinal signals by cortical processes, so that evidence presented for cortical generation of color afterimages is explainable by spatiotemporal factors that modify all signals.

post to: CiteULike

Divergence, Convergence, and the Ancestry of Feral Populations in the Domestic Rock Pigeon.

Publication Date: 2012 Jan 18 PMID: 22264611
Authors: Stringham, S. A. - Mulroy, E. E. - Xing, J. - Record, D. - Guernsey, M. W. - Aldenhoven, J. T. - Osborne, E. J. - Shapiro, M. D.
Journal: Curr Biol

Domestic pigeons are spectacularly diverse and exhibit variation in more traits than any other bird species [1]. In The Origin of Species, Charles Darwin repeatedly calls attention to the striking variation among domestic pigeon breeds-generated by thousands of years of artificial selection on a single species by human breeders-as a model for the process of natural divergence among wild populations and species [2]. Darwin proposed a morphology-based classification of domestic pigeon breeds [3], but the relationships among major groups of breeds and their geographic origins remain poorly understood [4, 5]. We used a large, geographically diverse sample of 361 individuals from 70 domestic pigeon breeds and two free-living populations to determine genetic relationships within this species. We found unexpected relationships among phenotypically divergent breeds as well as convergent evolution of derived traits among several breed groups. Our findings also illuminate the geographic origins of breed groups in India and the Middle East and suggest that racing breeds have made substantial contributions to feral pigeon populations.

post to: CiteULike

Attenuated Boundary Extension Produces a Paradoxical Memory Advantage in Amnesic Patients.

Publication Date: 2012 Jan 18 PMID: 22264610
Authors: Mullally, S. L. - Intraub, H. - Maguire, E. A.
Journal: Curr Biol

BACKGROUND: When we view a scene, we construct an internal representation of the scene that extends beyond its given borders. This cognitive phenomenon is revealed by a subsequent memory error when we confidently misremember the extended scene instead of the original. This effect is known as "boundary extension" and is apparent in adults, children, and babies. RESULTS: Here we show that seven patients with selective bilateral hippocampal damage and amnesia, who cannot imagine spatially coherent scenes, displayed attenuated levels of boundary extension on three separate measures. Paradoxically, this reduced boundary extension resulted in better memory for the stimuli compared with matched control participants, because the patients' recall was less encumbered by the boundary extension error. A further test revealed that although patients could generate appropriate semantic, conceptual, and contextual information about what might be beyond the view in a scene, their representation of the specifically spatial aspect of extended scenes was markedly impoverished. CONCLUSIONS: The patients' superior memory performance betrayed a fundamental deficit in scene processing. Our findings indicate that the hippocampus supports the internal representation of scenes and extended scenes when they are not physically in view, and this may involve providing a spatial framework in scenes. We suggest that interference with the ability to internally represent space may prevent the construction of spatially coherent scenes, with possible consequences for navigation, recollection of the past, and imagination of the future, which depend on this function.

post to: CiteULike

A Role for Metaphase Spindle Elongation Forces in Correction of Merotelic Kinetochore Attachments.

Publication Date: 2012 Jan 18 PMID: 22264609
Authors: Choi, S. H. - McCollum, D.
Journal: Curr Biol

During mitosis, equal segregation of chromosomes depends on proper kinetochore-microtubule attachments. Merotelic kinetochore orientation, in which a single kinetochore binds microtubules from both spindle poles [1], is a major cause of chromosome instability [2], which is commonly observed in solid tumors [3, 4]. Using the fission yeast Schizosaccharomyces pombe, we show that a proper force balance between kinesin motors on interpolar spindle microtubules is critical for correcting merotelic attachments. Inhibition of the plus-end-directed spindle elongation motors kinesin-5 (Cut7) and kinesin-6 (Klp9) reduces spindle length, tension at kinetochores, and the frequency of merotelic attachments. In contrast, merotely is increased by deletion of the minus-end-directed kinesin-14 (Klp2) or overexpression of Klp9. Also, Cdk1 regulates spindle elongation forces to promote merotelic correction by phosphorylating and inhibiting Klp9. The role of spindle elongation motors in merotelic correction is conserved, because partial inhibition of the human kinesin-5 homolog Eg5 using the drug monastrol reduces spindle length and lagging chromosome frequency in both normal (RPE-1) and tumor (CaCo-2) cells. These findings reveal unexpected links between spindle forces and correction of merotelic attachments and show that pharmacological manipulation of spindle elongation forces might be used to reduce chromosome instability in cancer cells.

post to: CiteULike

Measuring Internal Representations from Behavioral and Brain Data.

Publication Date: 2012 Jan 18 PMID: 22264608
Authors: Smith, M. L. - Gosselin, F. - Schyns, P. G.
Journal: Curr Biol

The study of internal knowledge representations is a cornerstone of the research agenda in the interdisciplinary study of cognition. An influential proposal assumes that the brain uses its internal knowledge of the external world to constrain, in a top-down manner, high-dimensional sensory data into a lower-dimensional representation that enables perceptual decisions and other higher-level cognitive functions [1-9]. This proposal relies on a precise formulation of the observer-specific internal knowledge (i.e., the internal representations, or models) that guides reduction of the high-dimensional retinal input onto a low-dimensional code. Here, we directly revealed the content of subjective internal representations by instructing five observers to detect a face in the presence of only white noise, to force a pure top-down, knowledge-based task. We used reverse correlation methods to visualize each observer's internal representation that supports detection of an illusory face. Using reverse correlation again, this time applied to observers' electroencephalogram activity, we established where and when in the brain specific internal knowledge conceptually interprets the input white noise as a face. We show that internal representations can be reconstructed experimentally from behavioral and brain data, and that their content drives neural activity first over frontal and then over occipitotemporal cortex.

post to: CiteULike

Myosin IIIB Uses an Actin-Binding Motif in Its Espin-1 Cargo to Reach the Tips of Actin Protrusions.

Publication Date: 2012 Jan 18 PMID: 22264607
Authors: Merritt, R. C. - Manor, U. - Salles, F. T. - Grati, M. - Dose, A. C. - Unrath, W. C. - Quintero, O. A. - Yengo, C. M. - Kachar, B.
Journal: Curr Biol

Myosin IIIA (MYO3A) targets actin protrusion tips using a motility mechanism dependent on both motor and tail actin-binding activity [1]. We show that myosin IIIB (MYO3B) lacks tail actin-binding activity and is unable to target COS7 cell filopodia tips, yet is somehow able to target stereocilia tips. Strikingly, when MYO3B is coexpressed with espin-1 (ESPN1), a MYO3A cargo protein endogenously expressed in stereocilia [2], MYO3B targets and carries ESPN1 to COS7 filopodia tips. We show that this tip localization is lost when we remove the ESPN1 C terminus actin-binding site. We also demonstrate that, like MYO3A [2], MYO3B can elongate filopodia by transporting ESPN1 to the polymerizing end of actin filaments. The mutual dependence of MYO3B and ESPN1 for tip localization reveals a novel mechanism for the cell to regulate myosin tip localization via a reciprocal relationship with cargo that directly participates in actin binding for motility. Our results are consistent with a novel form of motility for class III myosins that requires both motor and tail domain actin-binding activity and show that the actin-binding tail can be replaced by actin-binding cargo. This study also provides a framework to better understand the late-onset hearing loss phenotype in patients with MYO3A mutations.

post to: CiteULike

Peripheral and Central Inputs Shape Network Dynamics in the Developing Visual Cortex In Vivo.

Publication Date: 2012 Jan 18 PMID: 22264606
Authors: Siegel, F. - Heimel, J. A. - Peters, J. - Lohmann, C.
Journal: Curr Biol

Spontaneous network activity constitutes a central theme during the development of neuronal circuitry [1, 2]. Before the onset of vision, retinal neurons generate waves of spontaneous activity that are relayed along the ascending visual pathway [3, 4] and shape activity patterns in these regions [5, 6]. The spatiotemporal nature of retinal waves is required to establish precise functional maps in higher visual areas, and their disruption results in enlarged axonal projection areas (e.g., [7-10]). However, how retinal inputs shape network dynamics in the visual cortex on the cellular level is unknown. Using in vivo two-photon calcium imaging, we identified two independently occurring patterns of network activity in the mouse primary visual cortex (V1) before and at the onset of vision. Acute manipulations of spontaneous retinal activity revealed that one type of network activity largely originated in the retina and was characterized by low synchronicity (L-) events. In addition, we identified a type of high synchronicity (H-) events that required gap junction signaling but were independent of retinal input. Moreover, the patterns differed in wave progression and developmental profile. Our data suggest that different activity patterns have complementary functions during the formation of synaptic circuits in the developing visual cortex.

post to: CiteULike

Rapid, Repeated, and Clustered Loss of Duplicate Genes in Allopolyploid Plant Populations of Independent Origin.

Publication Date: 2012 Jan 18 PMID: 22264605
Authors: Buggs, R. J. - Chamala, S. - Wu, W. - Tate, J. A. - Schnable, P. S. - Soltis, D. E. - Soltis, P. S. - Barbazuk, W. B.
Journal: Curr Biol

The predictability of evolution is debatable, with recent evidence suggesting that outcomes may be constrained by gene interaction networks [1]. Whole-genome duplication (WGD; polyploidization-ubiquitous in plant evolution [2]) provides the opportunity to evaluate the predictability of genome reduction, a pervasive feature of evolution [3, 4]. Repeated patterns of genome reduction appear to have occurred via duplicated gene (homeolog) loss in divergent species following ancient WGD [5-9], with evidence for preferential retention of duplicates in certain gene classes [8-10]. The speed at which these patterns arise is unknown. We examined presence/absence of 70 homeologous loci in 59 Tragopogon miscellus plants from five natural populations of independent origin; this allotetraploid arose approximately 80 years ago via hybridization between diploid parents and WGD [11]. Genes were repeatedly retained or lost in clusters, and the gene ontology categories of the missing genes correspond to those lost after ancient WGD in the same family (Asteraceae; sunflower family) [6] and with gene dosage sensitivity [8]. These results provide evidence that the outcomes of WGD are predictable, even in 40 generations, perhaps due to the connectivity of gene products [8, 10, 12]. The high frequency of single-allele losses detected and low frequency of changes fixed within populations provide evidence for ongoing evolution.

post to: CiteULike

Spread of Social Information and Dynamics of Social Transmission within Drosophila Groups.

Publication Date: 2012 Jan 18 PMID: 22264604
Authors: Battesti, M. - Moreno, C. - Joly, D. - Mery, F.
Journal: Curr Biol

Understanding how behavioral diversity arises and is maintained is central to evolutionary biology. Genetically based inheritance has been a predominant research focus of the last century; however, nongenetic inheritance, such as social transmission, has become a topic of increasing interest [1]. How social information impacts behavior depends on the balance between information gathered directly through personal experience versus that gleaned through social interactions and on the diffusion of this information within groups [2, 3]. We investigate how female Drosophila melanogaster use social information under seminatural conditions and whether this information can spread and be maintained within a group, a prerequisite for establishing behavioral transmission [4]. We show that oviposition site choice is heavily influenced by previous social interactions. Naive observer flies develop a preference for the same egg-laying medium as experienced demonstrator flies conditioned to avoid one of two equally rewarding media. Surprisingly, oviposition site preference was socially transmitted from demonstrators to observers even when they interacted in a cage with only unflavored, pure agar medium, and even when the observer flies had previous personal experience with both rewarding media. Our findings shed light on the diffusion process of social information within groups, on its maintenance, and ultimately, on the roots of behavioral local adaptation.

post to: CiteULike

CRAC Channels Drive Digital Activation and Provide Analog Control and Synergy to Ca(2+)-Dependent Gene Regulation.

Publication Date: 2012 Jan 11 PMID: 22245003
Authors: Kar, P. - Nelson, C. - Parekh, A. B.
Journal: Curr Biol

Ca(2+)-dependent gene expression is critical for cell growth, proliferation, plasticity, and adaptation [1-3]. Because a common mechanism in vertebrates linking cytoplasmic Ca(2+) signals with activation of protein synthesis involves the nuclear factor of activated T cells (NFAT) family of transcription factors [4, 5], we have quantified protein expression in single cells following physiological Ca(2+) signals by using NFAT-driven expression of a genetically encoded fluorescent protein. We find that gene expression following CRAC channel activation is an all-or-nothing event over a range of stimulus intensities. Increasing agonist concentration recruits more cells but each responding cell does so in an essentially digital manner. Furthermore, Ca(2+)-dependent gene expression shows both short-term memory and strong synergy, where two pulses of agonist, which are ineffectual individually, robustly activate gene expression provided that the time interval between them is short. Such temporal filtering imparts coincidence detection to Ca(2+)-dependent gene activation. The underlying molecular basis mapped to time-dependent, nonlinear accumulation of nuclear NFAT. Local Ca(2+) near CRAC channels has to rise above a threshold level to drive gene expression, providing analog control to the digital activation process and a means to filter out fluctuations in background noise from activating transcription while ensuring robustness and high fidelity in the excitation-transcription coupling mechanism.

post to: CiteULike

Lead Transformation to Pyromorphite by Fungi.

Publication Date: 2012 Jan 11 PMID: 22245002
Authors: Rhee, Y. J. - Hillier, S. - Gadd, G. M.
Journal: Curr Biol

Lead (Pb) is a serious environmental pollutant in all its chemical forms [1]. Attempts have been made to immobilize lead in soil as the mineral pyromorphite using phosphate amendments (e.g., rock phosphate, phosphoric acid, and apatite [2-5]), although our work has demonstrated that soil fungi are able to transform pyromorphite into lead oxalate [6, 7]. Lead metal, an important structural and industrial material, is subject to weathering, and soil contamination also occurs through hunting and shooting [8, 9]. Although fungi are increasingly appreciated as geologic agents [10-12], there is a distinct lack of knowledge about their involvement in lead geochemistry. We examined the influence of fungal activity on lead metal and discovered that metallic lead can be transformed into chloropyromorphite, the most stable lead mineral that exists. This is of geochemical significance, not only regarding lead fate and cycling in the environment but also in relation to the phosphate cycle and linked with microbial transformations of inorganic and organic phosphorus. This paper provides the first report of mycogenic chloropyromorphite formation from metallic lead and highlights the significance of this phenomenon as a biotic component of lead biogeochemistry, with additional consequences for microbial survival in lead-contaminated environments and bioremedial treatments for Pb-contaminated land.

post to: CiteULike

Maternal control of nutrient allocation in plant seeds by genomic imprinting.

Publication Date: 2012 Jan 24 PMID: 22245001
Authors: Costa, L. M. - Yuan, J. - Rouster, J. - Paul, W. - Dickinson, H. - Gutierrez-Marcos, J. F.
Journal: Curr Biol

Imprinted genes are commonly expressed in mammalian placentas and in plant seed endosperms, where they exhibit preferential uniparental allelic expression. In mammals, imprinted genes directly regulate placental function and nutrient distribution from mother to fetus [1-4]; however, none of the >60 imprinted genes thus far reported in plants have been demonstrated to play an equivalent role in regulating the flow of resources to the embryo [5-7]. Here we show that imprinted Maternally expressed gene1 (Meg1) in maize [8] is both necessary and sufficient for the establishment and differentiation of the endosperm nutrient transfer cells located at the mother:seed interface. Consistent with these findings, Meg1 also regulates maternal nutrient uptake, sucrose partitioning, and seed biomass yield. In addition, we generated an imprinted and nonimprinted synthetic Meg1 ((syn)Meg1) dosage series whereby increased dosage and absence of imprinting both resulted in an unequal investment of maternal resources into the endosperm. These findings highlight dosage regulation by genomic imprinting as being critical for maintaining a balanced distribution of maternal nutrients to filial tissues in plants, as in mammals. However, unlike in mammals, Meg1 is a maternally expressed imprinted gene that surprisingly acts to promote rather than restrict nutrient allocation to the offspring.

post to: CiteULike

CDK-Dependent Potentiation of MPS1 Kinase Activity Is Essential to the Mitotic Checkpoint.

Publication Date: 2012 Jan 11 PMID: 22245000
Authors: Morin, V. - Prieto, S. - Melines, S. - Hem, S. - Rossignol, M. - Lorca, T. - Espeut, J. - Morin, N. - Abrieu, A.
Journal: Curr Biol

Accurate chromosome segregation relies upon a mitotic checkpoint that monitors kinetochore attachment toward opposite spindle poles before enabling chromosome disjunction [1]. The MPS1/TTK protein kinase is a core component of the mitotic checkpoint that lies upstream of MAD2 and BubR1 both at the kinetochore and in the cytoplasm [2, 3]. To gain insight into the mechanisms underlying the regulation of MPS1 kinase, we undertook the identification of Xenopus MPS1 phosphorylation sites by mass spectrometry. We mapped several phosphorylation sites onto MPS1 and we show that phosphorylation of S283 in the noncatalytic region of MPS1 is required for full kinase activity. This phosphorylation potentiates MPS1 catalytic efficiency without impairing its affinity for the substrates. By using Xenopus egg extracts depleted of endogenous MPS1 and reconstituted with single point mutants, we show that phosphorylation of S283 is essential to activate the mitotic checkpoint. This phosphorylation does not regulate the localization of MPS1 to the kinetochore but is required for the recruitment of MAD1/MAD2, demonstrating its role at the kinetochore. Constitutive phosphorylation of S283 lowers the number of kinetochores required to hold the checkpoint, which suggests that CDK-dependent phosphorylation of MPS1 is essential to sustain the mitotic checkpoint when few kinetochores remain unattached.

post to: CiteULike

The HSF-like Transcription Factor TBF1 Is a Major Molecular Switch for Plant Growth-to-Defense Transition.

Publication Date: 2012 Jan 24 PMID: 22244999
Authors: Pajerowska-Mukhtar, K. M. - Wang, W. - Tada, Y. - Oka, N. - Tucker, C. L. - Fonseca, J. P. - Dong, X.
Journal: Curr Biol

BACKGROUND: Induction of plant immune responses involves significant transcription reprogramming that prioritizes defense over growth-related cellular functions. Despite intensive forward genetic screens and genome-wide expression-profiling studies, a limited number of transcription factors have been found that regulate this transition. RESULTS: Using the endoplasmic-reticulum-resident genes required for antimicrobial protein secretion as markers, we identified a heat-shock factor-like transcription factor that specifically binds to the TL1 (GAAGAAGAA) cis element required for the induction of these genes. Surprisingly, plants lacking this TL1-binding factor, TBF1, respond normally to heat stress but are compromised in immune responses induced by salicylic acid and by microbe-associated molecular pattern, elf18. Genome-wide expression profiling indicates that TBF1 plays a key role in the growth-to-defense transition. Moreover, the expression of TBF1 itself is tightly regulated at both the transcriptional and translational levels. Two upstream open reading frames encoding multiple aromatic amino acids were found 5' of the translation initiation codon of TBF1 and shown to affect its translation. CONCLUSIONS: Through this unique regulatory mechanism, TBF1 can sense the metabolic changes upon pathogen invasion and trigger the specific transcriptional reprogramming through its target genes expression.

post to: CiteULike

Marine Viruses Exploit Their Host's Two-Component Regulatory System in Response to Resource Limitation.

Publication Date: 2012 Jan 24 PMID: 22244998
Authors: Zeng, Q. - Chisholm, S. W.
Journal: Curr Biol

Phosphorus (P) availability, which often limits productivity in marine ecosystems, shapes the P-acquisition gene content of the marine cyanobacteria Prochlorococcus [1-4] and its viruses (cyanophages) [5, 6]. As in other bacteria, in Prochlorococcus these genes are regulated by the PhoR/PhoB two-component regulatory system that is used to sense and respond to P availability and is typical of signal transduction systems found in diverse organisms [7]. Replication of cyanophage genomes requires a significant amount of P, and therefore these phages could gain a fitness advantage by influencing host P acquisition in P-limited environments. Here we show that the transcription of a phage-encoded high-affinity phosphate-binding protein gene (pstS) and alkaline phosphatase gene (phoA)-both of which have host orthologs-is elevated when the phages are infecting host cells that are P starved, relative to P-replete control cells. We further show that the phage versions of these genes are regulated by the host's PhoR/PhoB system. This not only extends this fundamental signaling mechanism to viruses but is also the first example of regulation of lytic phage genes by nutrient limitation in the host. As such, it reveals an important new dimension of the intimate coevolution of phage, host, and environment in the world's oceans.

post to: CiteULike

Sperm storage.

Publication Date: 2012 Jan 10 PMID: 22240479
Authors: Orr, T. J. - Zuk, M.
Journal: Curr Biol

post to: CiteULike

Mechanisms of autophagosome biogenesis.

Publication Date: 2012 Jan 10 PMID: 22240478
Authors: Rubinsztein, D. C. - Shpilka, T. - Elazar, Z.
Journal: Curr Biol

Autophagy is a unique membrane trafficking process whereby newly formed membranes, termed phagophores, engulf parts of the cytoplasm leading to the production of double-membraned autophagosomes that get delivered to lysosomes for degradation. This catabolic pathway has been linked to numerous physiological and pathological conditions, such as development, programmed cell death, cancer, pathogen infection, neurodegenerative disorders, and myopathies. In this review, we will focus on recent studies in yeast and mammalian systems that have provided insights into two critical areas of autophagosome biogenesis - the source of the autophagosomal membranes, and the mechanisms regulating the fusion of the edges of the double-membraned phagophores to form autophagosomes.

post to: CiteULike

Neurogenesis: premature mitotic entry lets cleavage planes take off!

Publication Date: 2012 Jan 10 PMID: 22240477
Authors: Singh, P. - Cabernard, C.
Journal: Curr Biol

Mutations in the gene microcephalin/MCPH1 result in the neurodevelopmental disease microcephaly. A recent report provides evidence that MCPH1 controls neuroprogenitor entry into mitosis via the Chk1-Cdc25b centrosome maturation pathway.

post to: CiteULike

Brain organization: wiring economy works for the large and small.

Publication Date: 2012 Jan 10 PMID: 22240476
Authors: Stevens, C. F.
Journal: Curr Biol

The highest-resolution test to date of the wire minimization hypothesis has found that this principle works well for brain regions with a volume just over 400 mum(3). What is the wire minimization hypothesis, and why should anyone care about it?

post to: CiteULike

Binocular vision: the eyes add and subtract.

Publication Date: 2012 Jan 10 PMID: 22240475
Authors: Kingdom, F. A.
Journal: Curr Biol

Our two eyes' views of the outside world are slightly different, providing the basis for stereopsis. A new study has found evidence that the human visual system has separately adaptable channels for adding and subtracting the neural signals from the two eyes, supporting an unconventional view of the initial stages of stereopsis.

post to: CiteULike

Human microbiome: a genetic bazaar for microbes?

Publication Date: 2012 Jan 10 PMID: 22240474
Authors: Langille, M. G. - Meehan, C. J. - Beiko, R. G.
Journal: Curr Biol

A recent study suggests that lateral gene transfer has been particularly intense among human-associated microbes. What can this tell us about our relationship with our internal microbial world?

post to: CiteULike

Visual cognition: rats compare shapes among the crowd.

Publication Date: 2012 Jan 10 PMID: 22240473
Authors: Cruz-Martin, A. - Huberman, A. D.
Journal: Curr Biol

Rats can discriminate simple shapes visually, even if they are moved around, made smaller, or partially covered up; the strategy they use may help shed light on human brain mechanisms for discriminating complex features, such as faces.

post to: CiteULike

Thermoregulation: an orphan receptor finds its way in the cold.

Publication Date: 2012 Jan 10 PMID: 22240472
Authors: Swoap, S. J.
Journal: Curr Biol

The hypometabolic state of torpor is a widely utilized and well-orchestrated response to food shortage. A new study shows that the melatonin-related orphan receptor GPR50 plays an important function in metabolic regulation for entry into torpor.

post to: CiteULike

Wound healing: calcium flashes illuminate early events.

Publication Date: 2012 Jan 10 PMID: 22240471
Authors: Wood, W.
Journal: Curr Biol

What are the earliest signals produced at a wound edge that mobilise epithelial cells to heal the wound? Live analysis of wound healing in the worm Caenorhabditis elegans shows that calcium may be the key early trigger.

post to: CiteULike

Polarization vision: Drosophila enters the arena.

Publication Date: 2012 Jan 10 PMID: 22240470
Authors: Hardie, R. C.
Journal: Curr Biol

Two new studies introduce the power of Drosophila genetics to polarization vision, revealing distinct photoreceptor inputs to polarotactic behaviour mediated by dorsal and ventral eye regions.

post to: CiteULike

Genetic rediscovery of an 'extinct' Galapagos giant tortoise species.

Publication Date: 2012 Jan 10 PMID: 22240469
Authors: Garrick, R. C. - Benavides, E. - Russello, M. A. - Gibbs, J. P. - Poulakakis, N. - Dion, K. B. - Hyseni, C. - Kajdacsi, B. - Marquez, L. - Bahan, S. - Ciofi, C. - Tapia, W. - Caccone, A.
Journal: Curr Biol

Genes from recently extinct species can live on in the genomes of extant individuals of mixed ancestry. Recently, genetic signatures of the giant Galapagos tortoise once endemic to Floreana Island (Chelonoidis elephantopus) were detected within eleven hybrid individuals of otherwise pure Chelonoidis becki on Volcano Wolf, Isabela Island [1]. Movement of tortoises between islands by pirate and whaling ships was not uncommon during the 1800s [2], representing a likely mechanism by which individuals from Floreana were translocated to northern Isabela, despite being presumed extinct soon after Charles Darwin's historic voyage to the Galapagos Islands in 1835. These eleven hybrid individuals with C. elephantopus ancestry were thought to be the last genetic vestiges of a unique evolutionary lineage in the wild. Here, we report that reproductively mature purebred tortoises of the recently 'extinct'C. elephantopus from Floreana Island are very likely still alive today, as identified and tracked through the genetic footprints left in the genomes of very recent hybrid offspring on Volcano Wolf. If found, these purebred C. elephantopus individuals could constitute core founders of a captive breeding program directed towards resurrecting this species.

post to: CiteULike

The RhoGAP Domain of CYK-4 Has an Essential Role in RhoA Activation.

Publication Date: 2012 Jan 5 PMID: 22226748
Authors: Loria, A. - Longhini, K. M. - Glotzer, M.
Journal: Curr Biol

Cytokinesis in animal cells is mediated by a cortical actomyosin-based contractile ring. The GTPase RhoA is a critical regulator of this process as it activates both nonmuscle myosin and a nucleator of actin filaments [1]. The site at which active RhoA and its effectors accumulate is controlled by the microtubule-based spindle during anaphase [2]. ECT-2, the guanine nucleotide exchange factor (GEF) that activates RhoA during cytokinesis, is regulated by phosphorylation and subcellular localization [3-5]. ECT2 localization depends on interactions with CYK-4/MgcRacGAP, a Rho GTPase-activating protein (GAP) domain containing protein [5, 6]. Here we show that, contrary to expectations, the Rho GTPase-activating protein (GAP) domain of CYK-4 promotes activation of RhoA during cytokinesis. Furthermore, we show that the primary phenotype caused by mutations in the GAP domain of CYK-4 is not caused by ectopic activation of CED-10/Rac1 and ARX-2/Arp2. However, inhibition of CED-10/Rac1 and ARX-2/Arp2 facilitates ingression of weak cleavage furrows. These results demonstrate that a GAP domain can contribute to activation of a small GTPase. Furthermore, cleavage furrow ingression is sensitive to the balance of contractile forces and cortical tension.

post to: CiteULike

An ARF6/Rab35 GTPase Cascade for Endocytic Recycling and Successful Cytokinesis.

Publication Date: 2012 Jan 24 PMID: 22226746
Authors: Chesneau, L. - Dambournet, D. - Machicoane, M. - Kouranti, I. - Fukuda, M. - Goud, B. - Echard, A.
Journal: Curr Biol

Cytokinesis bridge instability leads to binucleated cells that can promote tumorigenesis in vivo [1]. Membrane trafficking is crucial for animal cell cytokinesis [2-8], and several endocytic pathways regulated by distinct GTPases (Rab11, Rab21, Rab35, ARF6, RalA/B) [9-16] contribute to the postfurrowing steps of cytokinesis. However, little is known about how these pathways are coordinated for successful cytokinesis. The Rab35 GTPase controls a fast endocytic recycling pathway and must be activated for SEPTIN cytoskeleton localization at the intercellular bridge, and thus for completion of cytokinesis [12]. Here, we report that the ARF6 GTPase [17, 18] negatively regulates Rab35 activation and hence the Rab35 pathway. Human cells expressing a constitutively activated, GTP-bound ARF6 mutant display identical endocytic recycling and cytokinesis defects as those observed upon overexpression of the inactivated, GDP-bound Rab35 mutant. As a molecular mechanism, we identified the Rab35 GAP EPI64B as an effector of ARF6 in negatively regulating Rab35 activation. Unexpectedly, this regulation takes place at clathrin-coated pits, and activated ARF6 reduces Rab35 loading into the endocytic pathway. Thus, an effector of an ARF protein is a GAP for a downstream Rab protein, and we propose that this hierarchical ARF/Rab GTPase cascade controls the proper activation of a common endocytic pathway essential for cytokinesis.

post to: CiteULike

A vesicular transport pathway shuttles cargo from mitochondria to lysosomes.

Publication Date: 2012 Jan 24 PMID: 22226745
Authors: Soubannier, V. - McLelland, G. L. - Zunino, R. - Braschi, E. - Rippstein, P. - Fon, E. A. - McBride, H. M.
Journal: Curr Biol

Mitochondrial respiration relies on electron transport, an essential yet dangerous process in that it leads to the generation of reactive oxygen species (ROS). ROS can be neutralized within the mitochondria through enzymatic activity, yet the mechanism for steady-state removal of oxidized mitochondrial protein complexes and lipids is not well understood. We have previously characterized vesicular profiles budding from the mitochondria that carry selected cargo [1]. At least one population of these mitochondria-derived vesicles (MDVs) targets the peroxisomes; however, the fate of the majority of MDVs was unclear. Here, we demonstrate that MDVs carry selected cargo to the lysosomes. Using a combination of confocal and electron microscopy, we observe MDVs in steady state and demonstrate that they are stimulated as an early response to oxidative stress, the extent of which is determined by the respiratory status of the mitochondria. Delivery to the lysosomes does not require mitochondrial depolarization and is independent of ATG5 and LC3, suggesting that vesicle delivery complements mitophagy. Consistent with this, ultrastructural analysis of MDV formation revealed Tom20-positive structures within the vesicles of multivesicular bodies. These data characterize a novel vesicle transport route between the mitochondria and lysosomes, providing insights into the basic mechanisms of mitochondrial quality control.

post to: CiteULike

Functional evidence for a dual route to amygdala.

Publication Date: 2012 Jan 24 PMID: 22209532
Authors: Garrido, M. I. - Barnes, G. R. - Sahani, M. - Dolan, R. J.
Journal: Curr Biol

The amygdala plays a central role in evaluating the behavioral importance of sensory information. Anatomical subcortical pathways provide direct input to the amygdala from early sensory systems and may support an adaptively valuable rapid appraisal of salient information [1-3]. However, the functional significance of these subcortical inputs remains controversial [4]. We recorded magnetoencephalographic activity evoked by tones in the context of emotionally valent faces and tested two competing biologically motivated dynamic causal models [5, 6] against these data: the dual and cortical models. The dual model comprised two parallel (cortical and subcortical) routes to the amygdala, whereas the cortical model excluded the subcortical path. We found that neuronal responses elicited by salient information were better explained when a subcortical pathway was included. In keeping with its putative functional role of rapid stimulus appraisal, the subcortical pathway was most important early in stimulus processing. However, as often assumed, its action was not limited to the context of fear, pointing to a more widespread information processing role. Thus, our data supports the idea that an expedited evaluation of sensory input is best explained by an architecture that involves a subcortical path to the amygdala.

post to: CiteULike

Wild chimpanzees inform ignorant group members of danger.

Publication Date: 2012 Jan 24 PMID: 22209531
Authors: Crockford, C. - Wittig, R. M. - Mundry, R. - Zuberbuhler, K.
Journal: Curr Biol

The ability to recognize other individuals' mental states-their knowledge and beliefs, for example-is a fundamental part of human cognition and may be unique to our species. Tests of a "theory of mind" in animals have yielded conflicting results [1-3]. Some nonhuman primates can read others' intentions and know what others see, but they may not understand that, in others, perception can lead to knowledge [1-3]. Using an alarm-call-based field experiment, we show that chimpanzees were more likely to alarm call in response to a snake in the presence of unaware group members than in the presence of aware group members, suggesting that they recognize knowledge and ignorance in others. We monitored the behavior of 33 individuals to a model viper placed on their projected travel path. Alarm calls were significantly more common if the caller was with group members who had either not seen the snake or had not been present when alarm calls were emitted. Other factors, such as own arousal, perceived risk, or risk to receivers, did not significantly explain the likelihood of calling, although they did affect the call rates. Our results suggest that chimpanzees monitor the information available to other chimpanzees and control vocal production to selectively inform them.

post to: CiteULike

A multivariate approach reveals the behavioral templates underlying visual discrimination in rats.

Publication Date: 2012 Jan 10 PMID: 22209530
Authors: Vermaercke, B. - Op de Beeck, H. P.
Journal: Curr Biol

Although rodents are the first-choice animal model in the life sciences, they are rarely used to study higher visual functions. It is unclear to what extent rodents follow complex visual strategies to solve visual object recognition and discrimination tasks [1-5]. We report the performance of rats in a visual discrimination task applying the multivariate "Bubbles" paradigm previously used in highly visual species such as humans, monkeys, and pigeons [6-8]. We demonstrate a relationship between accuracy and local occlusion of stimuli by bubbles, as such revealing the strategies or "templates" that underlie visual discrimination behavior. Performance was guided by relatively simple, screen-centered templates as well as more adaptive templates reflecting context dependency and tolerance for changes in stimulus position. These findings demonstrate the complexity of visual strategies followed by rats and reveal interesting similarities (e.g., potential for position tolerance) as well as differences (overall efficiency of visual processing) compared to primates. In conclusion, this study illustrates the feasibility of investigating visual cognition in rats with multivariate behavioral paradigms, with the ultimate aim to use a comparative approach to explore the anatomical and neurophysiological basis of vision, also for those visual abilities that are traditionally studied in humans and monkeys. VIDEO ABSTRACT:

post to: CiteULike

The Papaver Self-Incompatibility Pollen S-Determinant, PrpS, Functions in Arabidopsis thaliana.

Publication Date: 2012 Jan 24 PMID: 22209529
Authors: de Graaf, B. H. - Vatovec, S. - Juarez-Diaz, J. A. - Chai, L. - Kooblall, K. - Wilkins, K. A. - Zou, H. - Forbes, T. - Franklin, F. C. - Franklin-Tong, V. E.
Journal: Curr Biol

Many angiosperms use specific interactions between pollen and pistil proteins as "self" recognition and/or rejection mechanisms to prevent self-fertilization. Self-incompatibility (SI) is encoded by a multiallelic S locus, comprising pollen and pistil S-determinants [1, 2]. In Papaver rhoeas, cognate pistil and pollen S-determinants, PrpS, a pollen-expressed transmembrane protein, and PrsS, a pistil-expressed secreted protein [3, 4], interact to trigger a Ca(2+)-dependent signaling network [5-10], resulting in inhibition of pollen tube growth, cytoskeletal alterations [11-13], and programmed cell death (PCD) [14, 15] in incompatible pollen. We introduced the PrpS gene into Arabidopsis thaliana, a self-compatible model plant. Exposing transgenic A. thaliana pollen to recombinant Papaver PrsS protein triggered remarkably similar responses to those observed in incompatible Papaver pollen: S-specific inhibition and hallmark features of Papaver SI [11-15]. Our findings demonstrate that Papaver PrpS is functional in a species with no SI system that diverged approximately 140 million years ago [16]. This suggests that the Papaver SI system uses cellular targets that are, perhaps, common to all eudicots and that endogenous signaling components can be recruited to elicit a response that most likely never operated in this species. This will be of interest to biologists interested in the evolution of signaling networks in higher plants.

post to: CiteULike

Natural Variation in Biogenesis Efficiency of Individual Arabidopsis thaliana MicroRNAs.

Publication Date: 2012 Jan 24 PMID: 22206705
Authors: Todesco, M. - Balasubramanian, S. - Cao, J. - Ott, F. - Sureshkumar, S. - Schneeberger, K. - Meyer, R. C. - Altmann, T. - Weigel, D.
Journal: Curr Biol

Like protein-coding genes, loci that produce microRNAs (miRNAs) are generally considered to be under purifying selection [1-3], consistent with miRNA polymorphisms being able to cause disease [4]. Nevertheless, it has been hypothesized that variation in miRNA genes may contribute to phenotypic diversity [1, 3, 5, 6]. Here we demonstrate that a naturally occurring polymorphism in the MIR164A gene affects leaf shape and shoot architecture in Arabidopsis thaliana, with the effects being modified by additional loci in the genome. A single base pair substitution in the miRNA complementary sequence alters the predicted stability of the miRNA:miRNA( *) duplex. It thereby greatly reduces miRNA accumulation, probably because it interferes with precursor processing. We demonstrate that this is not a rare exception and that natural strains of Arabidopsis thaliana harbor dozens of similar polymorphisms that affect processing of a wide range of miRNA precursors. Our results suggest that natural variation in miRNA biogenesis resulting from cis mutations is a common contributor to phenotypic variation in plants.

post to: CiteULike

A neuronal network switch for approach/avoidance toggled by appetitive state.

Publication Date: 2012 Jan 24 PMID: 22197246
Authors: Hirayama, K. - Gillette, R.
Journal: Curr Biol

Concrete examples of computation and implementation of cost/benefit decisions at the level of neuronal circuits are largely lacking. Such decisions are based on appetitive state, which is the integration of sensation, internal state, and memory. Value-based decisions are accessible in neuronal circuitry of simple systems [1]. In one such system, the predatory sea slug Pleurobranchaea, appetite is readily quantified in behavior [2] and related to approach/avoidance decision [3]. Moreover, motor aspects of feeding and turning can be observed as fictive motor output in the isolated central nervous system (CNS) [4, 5]. Here we found that the excitation state of the feeding motor network both manifested appetitive state and controlled expression of orienting versus avoidance. In isolated CNSs, spontaneous feeding network activity varied proportionally to donor feeding thresholds. CNSs from low- and high-feeding-threshold donors expressed fictive orienting or avoidance, respectively, in response to brief stimulation of sensory nerves. Artificially exciting the feeding network converted fictive avoidance to orienting. Thus, the feeding network embodied appetitive state and toggled approach/avoidance decision by configuring response symmetry of the premotor turn network. A resulting model suggests a basic cost/benefit decision module from which to consider evolutionary elaboration of the circuitry to serve more intricate valuation processes in complex animals.

post to: CiteULike

Cleavage Furrow Organization Requires PIP(2)-Mediated Recruitment of Anillin.

Publication Date: 2012 Jan 10 PMID: 22197245
Authors: Liu, J. - Fairn, G. D. - Ceccarelli, D. F. - Sicheri, F. - Wilde, A.
Journal: Curr Biol

Cell division is achieved by a plasma membrane furrow that must ingress between the segregating chromosomes during anaphase [1-3]. The force that drives furrow ingression is generated by the actomyosin cytoskeleton, which is linked to the membrane by an as yet undefined molecular mechanism. A key component of the membrane furrow is anillin. Upon targeting to the furrow through its pleckstrin homology (PH) domain, anillin acts as a scaffold linking the actomyosin and septin cytoskeletons to maintain furrow stability (reviewed in [4, 5]). We report that the PH domain of anillin interacts with phosphatidylinositol phosphate lipids (PIPs), including PI(4,5)P(2), which is enriched in the furrow. Reduction of cellular PI(4,5)P(2) or mutations in the PH domain of anillin that specifically disrupt the interaction with PI(4,5)P(2), interfere with the localization of anillin to the furrow. Reduced expression of anillin disrupts symmetric furrow ingression that can be restored by targeting ectopically expressed anillin to the furrow using an alternate PI(4,5)P(2) binding module, a condition where the septin cytoskeleton is not recruited to the plasma membrane. These data demonstrate that the anillin PH domain has two functions: targeting anillin to the furrow by binding to PI(4,5)P(2) to maintain furrow organization and recruiting septins to the furrow.

post to: CiteULike

A Genome-wide SNP Genotyping Array Reveals Patterns of Global and Repeated Species-Pair Divergence in Sticklebacks.

Publication Date: 2012 Jan 10 PMID: 22197244
Authors: Jones, F. C. - Chan, Y. F. - Schmutz, J. - Grimwood, J. - Brady, S. D. - Southwick, A. M. - Absher, D. M. - Myers, R. M. - Reimchen, T. E. - Deagle, B. E. - Schluter, D. - Kingsley, D. M.
Journal: Curr Biol

Genes underlying repeated adaptive evolution in natural populations are still largely unknown. Stickleback fish (Gasterosteus aculeatus) have undergone a recent dramatic evolutionary radiation, generating numerous examples of marine-freshwater species pairs and a small number of benthic-limnetic species pairs found within single lakes [1]. We have developed a new genome-wide SNP genotyping array to study patterns of genetic variation in sticklebacks over a wide geographic range, and to scan the genome for regions that contribute to repeated evolution of marine-freshwater or benthic-limnetic species pairs. Surveying 34 global populations with 1,159 informative markers revealed substantial genetic variation, with predominant patterns reflecting demographic history and geographic structure. After correcting for geographic structure and filtering for neutral markers, we detected large repeated shifts in allele frequency at some loci, identifying both known and novel loci likely contributing to marine-freshwater and benthic-limnetic divergence. Several novel loci fall close to genes implicated in epithelial barrier or immune functions, which have likely changed as sticklebacks adapt to contrasting environments. Specific alleles differentiating sympatric benthic-limnetic species pairs are shared in nearby solitary populations, suggesting an allopatric origin for adaptive variants and selection pressures unrelated to sympatry in the initial formation of these classic vertebrate species pairs.

post to: CiteULike

Emergence of patterned activity in the developing zebrafish spinal cord.

Publication Date: 2012 Jan 24 PMID: 22197243
Authors: Warp, E. - Agarwal, G. - Wyart, C. - Friedmann, D. - Oldfield, C. S. - Conner, A. - Del Bene, F. - Arrenberg, A. B. - Baier, H. - Isacoff, E. Y.
Journal: Curr Biol

BACKGROUND: Developing neural networks display spontaneous and correlated rhythmic bursts of action potentials that are essential for circuit refinement. In the spinal cord, it is poorly understood how correlated activity is acquired and how its emergence relates to the formation of the spinal central pattern generator (CPG), the circuit that mediates rhythmic behaviors like walking and swimming. It is also unknown whether early, uncorrelated activity is necessary for the formation of the coordinated CPG. RESULTS: Time-lapse imaging in the intact zebrafish embryo with the genetically encoded calcium indicator GCaMP3 revealed a rapid transition from slow, sporadic activity to fast, ipsilaterally correlated, and contralaterally anticorrelated activity, characteristic of the spinal CPG. Ipsilateral correlations were acquired through the coalescence of local microcircuits. Brief optical manipulation of activity with the light-driven pump halorhodopsin revealed that the transition to correlated activity was associated with a strengthening of ipsilateral connections, likely mediated by gap junctions. Contralateral antagonism increased in strength at the same time. The transition to coordinated activity was disrupted by long-term optical inhibition of sporadic activity in motoneurons and ventral longitudinal descending interneurons and resulted in more neurons exhibiting uncoordinated activity patterns at later time points. CONCLUSIONS: These findings show that the CPG in the zebrafish spinal cord emerges directly from a sporadically active network as functional connectivity strengthens between local and then more distal neurons. These results also reveal that early, sporadic activity in a subset of ventral spinal neurons is required for the integration of maturing neurons into the coordinated CPG network.

post to: CiteULike

Semaphorin and Eph Receptor Signaling Guide a Series of Cell Movements for Ventral Enclosure in C. elegans.

Publication Date: 2012 Jan 10 PMID: 22197242
Authors: Ikegami, R. - Simokat, K. - Zheng, H. - Brown, L. - Garriga, G. - Hardin, J. - Culotti, J.
Journal: Curr Biol

BACKGROUND: In the last stage of the Caenorhabditis elegans body wall closure, an open pocket in the epidermis is closed by the migration of marginal epidermal P/pocket cells to the ventral midline. The cellular and molecular mechanisms of this closure remain unknown. RESULTS: Cells within the pocket align to form a bridge for migration of contralateral P cell pair P9/10 L,R (and neighboring P cells) to the midline. Bridge formation involves rearrangement of five sister pairs of PLX-2/plexin and VAB-1/Eph receptor expressing "plexin band" cells, of which three pairs form a scaffold for bridge assembly and two pairs form the bridge. Bridge formation requires VAB-1 kinase-dependent extension of presumptive bridge cells over scaffold cells toward the ventral midline. An unassembled vab-1 null mutant bridge obstructs P cell migration, which is largely overcome by plexin band expression of VAB-1 or VAB-1(delC) (a kinase deletion of VAB-1). VAB-1 also functions redundantly with MAB-20/semaphorin to prevent perdurant gaps between sister plexin band cells that block P cell migration. CONCLUSIONS: The Eph receptor mediates cellular extensions required for bridge formation, independently facilitates P cell migration to the midline, and functions redundantly with PLX-2/plexin to prevent gaps in the bridge used for P9/10 cell migration in body wall closure.

post to: CiteULike

Children's Development of Self-Regulation in Speech Production.

Publication Date: 2012 Jan 24 PMID: 22197241
Authors: Macdonald, E. N. - Johnson, E. K. - Forsythe, J. - Plante, P. - Munhall, K. G.
Journal: Curr Biol

Species-specific vocalizations fall into two broad categories: those that emerge during maturation, independent of experience, and those that depend on early life interactions with conspecifics. Human language and the communication systems of a small number of other species, including songbirds, fall into this latter class of vocal learning. Self-monitoring has been assumed to play an important role in the vocal learning of speech [1-3] and studies demonstrate that perception of your own voice is crucial for both the development and lifelong maintenance of vocalizations in humans and songbirds [4-8]. Experimental modifications of auditory feedback can also change vocalizations in both humans and songbirds [9-13]. However, with the exception of large manipulations of timing [14, 15], no study to date has ever directly examined the use of auditory feedback in speech production under the age of 4. Here we use a real-time formant perturbation task [16] to compare the response of toddlers, children, and adults to altered feedback. Children and adults reacted to this manipulation by changing their vowels in a direction opposite to the perturbation. Surprisingly, toddlers' speech didn't change in response to altered feedback, suggesting that long-held assumptions regarding the role of self-perception in articulatory development need to be reconsidered.

post to: CiteULike

A Role for the Melatonin-Related Receptor GPR50 in Leptin Signaling, Adaptive Thermogenesis, and Torpor.

Publication Date: 2012 Jan 10 PMID: 22197240
Authors: Bechtold, D. A. - Sidibe, A. - Saer, B. R. - Li, J. - Hand, L. E. - Ivanova, E. A. - Darras, V. M. - Dam, J. - Jockers, R. - Luckman, S. M. - Loudon, A. S.
Journal: Curr Biol

The ability of mammals to maintain a constant body temperature has proven to be a profound evolutionary advantage, allowing members of this class to thrive in most environments on earth. Intriguingly, some mammals employ bouts of deep hypothermia (torpor) to cope with reduced food supply and harsh climates [1, 2]. During torpor, physiological processes such as respiration, cardiac function, and metabolic rate are severely depressed, yet the neural mechanisms that regulate torpor remain unclear [3]. Hypothalamic responses to energy signals, such as leptin, influence the expression of torpor [4-7]. We show that the orphan receptor GPR50 plays an important role in adaptive thermogenesis and torpor. Unlike wild-type mice, Gpr50(-/-) mice readily enter torpor in response to fasting and 2-deoxyglucose administration. Decreased thermogenesis in Gpr50(-/-) mice is not due to a deficit in brown adipose tissue, the principal site of nonshivering thermogenesis in mice [8]. GPR50 is highly expressed in the hypothalamus of several species, including man [9, 10]. In line with this, altered thermoregulation in Gpr50(-/-) mice is associated with attenuated responses to leptin and a suppression of thyrotropin-releasing hormone. Thus, our findings identify hypothalamic circuits involved in torpor and reveal GPR50 to be a novel component of adaptive thermogenesis in mammals.

post to: CiteULike

Flying Drosophila orient to sky polarization.

Publication Date: 2012 Jan 10 PMID: 22177905
Authors: Weir, P. T. - Dickinson, M. H.
Journal: Curr Biol

Insects maintain a constant bearing across a wide range of spatial scales. Monarch butterflies and locusts traverse continents [1, 2], and foraging bees and ants travel hundreds of meters to return to their nests [1, 3, 4], whereas many other insects fly straight for only a few centimeters before changing direction. Despite this variation in spatial scale, the brain region thought to underlie long-distance navigation is remarkably conserved [5, 6], suggesting that the use of a celestial compass is a general and perhaps ancient capability of insects. Laboratory studies of Drosophila have identified a local search mode in which short, straight segments are interspersed with rapid turns [7, 8]. However, this flight mode is inconsistent with measured gene flow between geographically separated populations [9-11], and individual Drosophila can travel 10 km across desert terrain in a single night [9, 12, 13]-a feat that would be impossible without prolonged periods of straight flight. To directly examine orientation behavior under outdoor conditions, we built a portable flight arena in which a fly viewed the natural sky through a liquid crystal device that could experimentally rotate the polarization angle. Our findings indicate that Drosophila actively orient using the sky's natural polarization pattern.

post to: CiteULike

Genetic dissection reveals two separate retinal substrates for polarization vision in Drosophila.

Publication Date: 2012 Jan 10 PMID: 22177904
Authors: Wernet, M. F. - Velez, M. M. - Clark, D. A. - Baumann-Klausener, F. - Brown, J. R. - Klovstad, M. - Labhart, T. - Clandinin, T. R.
Journal: Curr Biol

BACKGROUND: Linearly polarized light originates from atmospheric scattering or surface reflections and is perceived by insects, spiders, cephalopods, crustaceans, and some vertebrates. Thus, the neural basis underlying how this fundamental quality of light is detected is of broad interest. Morphologically unique, polarization-sensitive ommatidia exist in the dorsal periphery of many insect retinas, forming the dorsal rim area (DRA). However, much less is known about the retinal substrates of behavioral responses to polarized reflections. SUMMARY: Drosophila exhibits polarotactic behavior, spontaneously aligning with the e-vector of linearly polarized light, when stimuli are presented either dorsally or ventrally. By combining behavioral experiments with genetic dissection and ultrastructural analyses, we show that distinct photoreceptors mediate the two behaviors: inner photoreceptors R7+R8 of DRA ommatidia are necessary and sufficient for dorsal polarotaxis, whereas ventral responses are mediated by combinations of outer and inner photoreceptors, both of which manifest previously unknown features that render them polarization sensitive. CONCLUSIONS: Drosophila uses separate retinal pathways for the detection of linearly polarized light emanating from the sky or from shiny surfaces. This work establishes a behavioral paradigm that will enable genetic dissection of the circuits underlying polarization vision.

post to: CiteULike

Cross-generational effects of climate change on expression of a sexually selected trait.

Publication Date: 2012 Jan 10 PMID: 22177903
Authors: Scordato, E. S. - Bontrager, A. L. - Price, T. D.
Journal: Curr Biol

Sexually selected traits and early breeding are often correlated with quality in birds: individuals that breed earlier in the season have more elaborate traits and raise more surviving offspring [1, 2]. As global climate warms, breeding date for many temperate birds is advancing [3, 4], but we lack corresponding information on climate-induced variation in sexual selection. Here, we investigated influences of climate on a sexually selected plumage trait in a Himalayan warbler (Phylloscopus humei). We found that when spring is warm, birds breed early. Subsequent to an early-breeding year, adults express relatively large sexually selected traits and rear offspring that also develop large traits. The positive effects of early breeding, plus the across-year correlation between parent and offspring cohorts, predict that warmer climates should lead to increases in trait size. However, trait size has not increased over the past 25 years, even though mean breeding date has advanced. We show that whereas warm springs have positive effects on trait size, warm summers have negative effects due to increased feather wear. Apparent stasis in the size of a sexually selected trait thus masks large, conflicting influences of climate change. Continued climate warming has the potential to affect the honesty of sexual signals, as trait expression and condition become increasingly disassociated.

post to: CiteULike

Serotonin Signaling Is Required for Wnt-Dependent GRP Specification and Leftward Flow in Xenopus.

Publication Date: 2012 Jan 10 PMID: 22177902
Authors: Beyer, T. - Danilchik, M. - Thumberger, T. - Vick, P. - Tisler, M. - Schneider, I. - Bogusch, S. - Andre, P. - Ulmer, B. - Walentek, P. - Niesler, B. - Blum, M. - Schweickert, A.
Journal: Curr Biol

In vertebrates, most inner organs are asymmetrically arranged with respect to the main body axis [1]. Symmetry breakage in fish, amphibian, and mammalian embryos depends on cilia-driven leftward flow of extracellular fluid during neurulation [2-5]. Flow induces the asymmetric nodal cascade that governs asymmetric organ morphogenesis and placement [1, 6, 7]. In the frog Xenopus, an alternative laterality-generating mechanism involving asymmetric localization of serotonin at the 32-cell stage has been proposed [8]. However, no functional linkage between this early localization and flow at neurula stage has emerged. Here, we report that serotonin signaling is required for specification of the superficial mesoderm (SM), which gives rise to the ciliated gastrocoel roof plate (GRP) where flow occurs [5, 9]. Flow and asymmetry were lost in embryos in which serotonin signaling was downregulated. Serotonin, which we found uniformly distributed along the main body axes in the early embryo, was required for Wnt signaling, which provides the instructive signal to specify the GRP. Importantly, serotonin was required for Wnt-induced double-axis formation as well. Our data confirm flow as primary mechanism of symmetry breakage and suggest a general role of serotonin as competence factor for Wnt signaling during axis formation in Xenopus.

post to: CiteULike

Perceived direction of motion determined by adaptation to static binocular images.

Publication Date: 2012 Jan 10 PMID: 22177901
Authors: May, K. A. - Zhaoping, L. - Hibbard, P. B.
Journal: Curr Biol

In Li and Atick's [1, 2] theory of efficient stereo coding, the two eyes' signals are transformed into uncorrelated binocular summation and difference signals, and gain control is applied to the summation and differencing channels to optimize their sensitivities. In natural vision, the optimal channel sensitivities vary from moment to moment, depending on the strengths of the summation and difference signals; these channels should therefore be separately adaptable, whereby a channel's sensitivity is reduced following overexposure to adaptation stimuli that selectively stimulate that channel. This predicts a remarkable effect of binocular adaptation on perceived direction of a dichoptic motion stimulus [3]. For this stimulus, the summation and difference signals move in opposite directions, so perceived motion direction (upward or downward) should depend on which of the two binocular channels is most strongly adapted, even if the adaptation stimuli are completely static. We confirmed this prediction: a single static dichoptic adaptation stimulus presented for less than 1 s can control perceived direction of a subsequently presented dichoptic motion stimulus. This is not predicted by any current model of motion perception and suggests that the visual cortex quickly adapts to the prevailing binocular image statistics to maximize information-coding efficiency.

post to: CiteULike

Mosquitoes Cool Down during Blood Feeding to Avoid Overheating.

Publication Date: 2012 Jan 10 PMID: 22177900
Authors: Lahondere, C. - Lazzari, C. R.
Journal: Curr Biol

Temperature is one of the most important factors affecting the life of insects [1]. For instance, high temperatures can have deleterious effects on insects' physiology. Therefore, many of them have developed various strategies to avoid the risk of thermal stress [2]. They can seek a fresher environment or adjust their water loss, but hematophagous insects, such as mosquitoes, must confront the issue of thermal stress at each feeding event on a warm-blooded host [3]. To better understand to what extent mosquitoes are exposed to thermal stress while feeding, we conducted a real-time infrared thermographic analysis of mosquitoes' body temperature during feeding on both warm blood and sugar solution. First, our results highlighted differences in temperature between the body parts of the mosquito (i.e., heterothermy) during blood intake, but not during sugar meals. We also found that anopheline mosquitoes can decrease their body temperature during blood feeding thanks to evaporative cooling of fluid droplets, which are excreted and maintained at the end of the abdomen. This mechanism protects the insect itself, probably as well as the sheltered microorganisms, both symbionts and parasites, from thermal stress. These findings constitute the first evidence of thermoregulation among hematophagous insects and explain the paradox of fresh blood excretion during feeding.

post to: CiteULike

When correlation implies causation in multisensory integration.

Publication Date: 2012 Jan 10 PMID: 22177899
Authors: Parise, C. V. - Spence, C. - Ernst, M. O.
Journal: Curr Biol

Inferring which signals have a common underlying cause, and hence should be integrated, represents a primary challenge for a perceptual system dealing with multiple sensory inputs [1-3]. This challenge is often referred to as the correspondence problem or causal inference. Previous research has demonstrated that spatiotemporal cues, along with prior knowledge, are exploited by the human brain to solve this problem [4-9]. Here we explore the role of correlation between the fine temporal structure of auditory and visual signals in causal inference. Specifically, we investigated whether correlated signals are inferred to originate from the same distal event and hence are integrated optimally [10]. In a localization task with visual, auditory, and combined audiovisual targets, the improvement in precision for combined relative to unimodal targets was statistically optimal only when audiovisual signals were correlated. This result demonstrates that humans use the similarity in the temporal structure of multisensory signals to solve the correspondence problem, hence inferring causation from correlation.

post to: CiteULike

The rpd3 core complex is a chromatin stabilization module.

Publication Date: 2012 Jan 10 PMID: 22177115
Authors: Chen, X. F. - Kuryan, B. - Kitada, T. - Tran, N. - Li, J. Y. - Kurdistani, S. - Grunstein, M. - Li, B. - Carey, M.
Journal: Curr Biol

The S. cerevisiae Rpd3 large (Rpd3L) and small (Rpd3S) histone deacetylase (HDAC) complexes are prototypes for understanding transcriptional repression in eukaryotes [1]. The current view is that they function by deacetylating chromatin, thereby limiting accessibility of transcriptional factors to the underlying DNA. However, an Rpd3 catalytic mutant retains substantial repression capability when targeted to a promoter as a LexA fusion protein [2]. We investigated the HDAC-independent properties of the Rpd3 complexes biochemically and discovered a chaperone function, which promotes histone deposition onto DNA, and a novel activity, which prevents nucleosome eviction but not remodeling mediated by the ATP-dependent RSC complex. These HDAC-independent activities inhibit Pol II transcription on a nucleosomal template. The functions of the endogenous Rpd3 complexes can be recapitulated with recombinant Rpd3 core complex comprising Sin3, Rpd3, and Ume1. To test the hypothesis that Rpd3 contributes to chromatin stabilization in vivo, we measured histone H3 density genomewide and found that it was reduced at promoters in an Rpd3 deletion mutant but partially restored in a catalytic mutant. Importantly, the effects on H3 density are most apparent on RSC-enriched genes [3]. Our data suggest that the Rpd3 core complex could contribute to repression via a novel nucleosome stabilization function.

post to: CiteULike