Hot off the presses! Aug 09 Curr Biol

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Latest Articles Include:

• Copy numbers count for autism
  - Curr Biol 21(15):R571-R573 (2011)
  Among the elusive genetic causes for autism, copy number variations are emerging as an important factor. Testing for these might help parents determine the risk of recurrence. Michael Gross reports.
• Brown algae
  - Curr Biol 21(15):R573-R575 (2011)
  
• John Ross
  - Curr Biol 21(15):R575-R576 (2011)
  
• Acquisition of an animal gene by microsporidian intracellular parasites
  - Curr Biol 21(15):R576-R577 (2011)
  Parasites have adapted to their specialised way of life by a number of means, including the acquisition of genes by horizontal gene transfer. These newly acquired genes seem to come from a variety of sources, but seldom from the host, even in the most intimate associations between obligate intracellular parasite and host [1]. Microsporidian intracellular parasites have acquired a handful of genes, mostly from bacteria, that help them take energy from their hosts or protect them from the environment [2] and [3]. To date, however, no animal genes have been documented in any microsporidian genome. Here, we have surveyed the genome of the microsporidian Encephalitozoon romaleae, which parasitises arthropods for evidence of animal genes. We found one protein-encoding gene that is absent from publicly available sequence data from other microsporidia. The gene encodes a component of the purine salvage pathway, and has been independently acquired by other parasites through hor! izontal gene transfer from other donors. In this case, however, the gene shows a very strong phylogenetic signal for arthropod origin.
• Anhydrobiosis: The Model Worm as a Model?
  - Curr Biol 21(15):R578-R579 (2011)
  Summay New work now shows that the dauer larvae of Caenorhabditis elegans can survive anhydrobiotically. The genetic tractability of this model organism may be useful in studying how organisms survive when losing most or all of their water.
• Associative Memory: Without a Trace
  - Curr Biol 21(15):R579-R581 (2011)
  Some transient sensory stimuli can cause prolonged activity in the brain. Trace conditioning experiments can reveal the time over which these lasting representations can be utilized and where they reside.
• Adaptive Introgression: The Seeds of Resistance
  - Curr Biol 21(15):R581-R583 (2011)
  Populations of the European house mouse have acquired resistance to anticoagulant pesticides from a closely related species. This discovery improves our understanding of the circumstances in which interspecific genetic exchange is likely to facilitate adaptation.
• Cognitive Neuroscience: Swapping Bodies in the Brain
  - Curr Biol 21(15):R583-R585 (2011)
  A recent study has found that activity in multisensory brain areas, namely the premotor cortex, intraparietal cortex and the putamen, mirrors the vividness of ownership over a mannequin, induced by the body-swap illusion.
• Tissue Remodeling: Making Way for Cellular Invaders
  - Curr Biol 21(15):R585-R587 (2011)
  Cellular invasion through protein matrices is a critical process during epithelial–mesenchymal transitions. A recent study of Caenorhabditis elegans vulval development reports a novel invasive mechanism in which cells coordinate spatially restricted degradation and sliding of a basement membrane during cellular ingression and tissue formation.
• Microbial Genomics: E. coli Relatives Out of Doors and Out of Body
  - Curr Biol 21(15):R587-R589 (2011)
  Genome comparisons have shown that several clades of Escherichia isolated primarily from non-host habitats are adapted to life outside of hosts, and that these very close relatives of E. coli have historically not shared environments with gut-associated E. coli.
• Parahippocampal Cortex: Translating Vision into Space
  - Curr Biol 21(15):R589-R591 (2011)
  Two recent imaging studies have shed new light on information representation in human parahippocampal cortex. Despite their different approaches, the two studies both support the view that this brain region represents space at an elementary level.
• Evolution of Development: Diversified Dorsoventral Patterning
  - Curr Biol 21(15):R591-R594 (2011)
  Patterning of the dorsoventral axis by graded BMP signaling is conserved in the evolution of animals. However, this system has also proven to be highly adaptable, as is now highlighted by its short-range function in the leech Helobdella.
• Centrosome Size: Scaling Without Measuring
  - Curr Biol 21(15):R594-R596 (2011)
  Centrosome size is controlled by a limiting component mechanism in which a fixed quantity of precursor protein is divided up among however many centrosomes are present. This simple scheme explains size control and scaling of centrosomes relative to cell volume.
• Cell Migration: PKA and RhoA Set the Pace
  - Curr Biol 21(15):R596-R598 (2011)
  A new study shows that protein kinase A (PKA) activity establishes a signaling loop that governs protrusion–retraction cycles in migrating cells. PKA activity near the leading edge of protrusions phosphorylates RhoA and inhibits its activity via increased association with RhoGDI.
• Cell Division Orientation in Animals
  - Curr Biol 21(15):R599-R609 (2011)
  Cell division orientation during animal development can serve to correctly organize and shape tissues, create cellular diversity or both. The underlying cellular mechanism is regulated spindle orientation. Depending on the developmental context, extrinsic signals or intrinsic cues control the correct orientation of the mitotic spindle. Cell geometry has been known to be another determinant of spindle orientation and recent results have shed new light on the link between cellular shape and cell division orientation. The importance of controlling spindle orientation is manifested in neurodevelopmental defects such as microcephaly, tumor initiation as well as defects in tissue architecture and cell fate misspecification. Here, we summarize the role of oriented cell division during animal development and also outline the cellular and molecular mechanisms in selected invertebrate and vertebrate systems.
• Ancient Hybridization and an Irish Origin for the Modern Polar Bear Matriline
  - Curr Biol 21(15):1251-1258 (2011)
  Background Polar bears (Ursus maritimus) are among those species most susceptible to the rapidly changing arctic climate, and their survival is of global concern. Despite this, little is known about polar bear species history. Future conservation strategies would significantly benefit from an understanding of basic evolutionary information, such as the timing and conditions of their initial divergence from brown bears (U. arctos) or their response to previous environmental change. Results We used a spatially explicit phylogeographic model to estimate the dynamics of 242 brown bear and polar bear matrilines sampled throughout the last 120,000 years and across their present and past geographic ranges. Our results show that the present distribution of these matrilines was shaped by a combination of regional stability and rapid, long-distance dispersal from ice-age refugia. In addition, hybridization between polar bears and brown bears may have occurred multiple times throughout the Late Pleistocene. Conclusions The reconstructed matrilineal history of brown and polar bears has two striking features. First, it is punctuated by dramatic and discrete climate-driven dispersal events. Second, opportunistic mating between these two species as their ranges overlapped has left a strong genetic imprint. In particular, a likely genetic exchange with extinct Irish brown bears forms the origin of the modern polar bear matriline. This suggests that interspecific hybridization not only may be more common than previously considered but may be a mechanism by which species deal with marginal habitats during periods of environmental deterioration.
• Limiting Amounts of Centrosome Material Set Centrosome Size in C. elegans Embryos
  - Curr Biol 21(15):1259-1267 (2011)
  Background The ways in which cells set the size of intracellular structures is an important but largely unsolved problem [1]. Early embryonic divisions pose special problems in this regard. Many checkpoints common in somatic cells are missing from these divisions, which are characterized by rapid reductions in cell size and short cell cycles [2]. Embryonic cells must therefore possess simple and robust mechanisms that allow the size of many of their intracellular structures to rapidly scale with cell size. Results Here, we study the mechanism by which one structure, the centrosome, scales in size during the early embryonic divisions of C. elegans. We show that centrosome size is directly related to cell size and is independent of lineage. Two findings suggest that the total amount of maternally supplied centrosome proteins could limit centrosome size. First, the combined volume of all centrosomes formed at any one time in the developing embryo is constant. Second, the total volume of centrosomes in any one cell is independent of centrosome number. By increasing the amount of centrosome proteins in the cell, we provide evidence that one component that limits centrosome size is the conserved pericentriolar material protein SPD-2 [3], which we show binds to and targets polo-like kinase 1 [[3] and [4]] to centrosomes. Conclusions We propose a limiting component hypothesis, in which the volume of the cell sets centrosome size by limiting the total amount of centrosome components. This idea could be a general mechanism for setting the size of intracellular organelles during development.
• The RWP-RK Factor GROUNDED Promotes Embryonic Polarity by Facilitating YODA MAP Kinase Signaling
  - Curr Biol 21(15):1268-1276 (2011)
  Background The division of plant zygotes is typically asymmetric, generating daughter cells with different developmental fates. In Arabidopsis, the apical daughter cell produces the proembryo, whereas the basal daughter cell forms the mostly extraembryonic suspensor. Establishment of apical and basal fates is known to depend on the YODA (YDA) mitogen-associated protein (MAP) kinase cascade and WUSCHEL-LIKE HOMEOBOX (WOX) homeodomain transcription factors. Results Mutations in GROUNDED (GRD) cause anatomical defects implying a partial loss of developmental asymmetry in the first division. Subsequently, suspensor-specific WOX8 expression disappears while proembryo-specific ZLL expression expands in the mutants, revealing that basal fates are confounded. GRD encodes a small nuclear protein of the RWP-RK family and is broadly transcribed in the early embryo. Loss of GRD eliminates the dominant effects of hyperactive YDA variants, indicating that GRD is required for YDA-dependent signaling in the embryo. However, GRD function is not regulated via direct phosphorylation by MAP kinases, and forced expression of GRD does not suppress the effect of yda mutations. In a strong synthetic interaction, grd;wox8;wox9 triple mutants arrest as zygotes or one-cell embryos lacking apparent polarity. Conclusions The predicted transcription factor GRD acts cooperatively with WOX homeodomain proteins to establish embryonic polarity in the first division. Like YDA, GRD promotes zygote elongation and basal cell fates. GRD function is required for YDA-dependent signaling but apparently not regulated by the YDA MAP kinase cascade. Similarity of GRD to Chlamydomonas MID suggests a conserved role for small RWP-RK proteins in regulating the transcriptional programs of generative cells and the zygote.
• The Arabidopsis RWP-RK Protein RKD4 Triggers Gene Expression and Pattern Formation in Early Embryogenesis
  - Curr Biol 21(15):1277-1281 (2011)
  Morphogenesis of seed plants commences with highly stereotypical cell division sequences in early embryogenesis [[1] and [2]]. Although a small number of transcription factors and a mitogen-activated protein (MAP) kinase cascade have been implicated in this process [[3], [4], [5], [6], [7] and [8]], pattern formation in early embryogenesis remains poorly understood. We show here that the Arabidopsis RKD4, a member of the RWP-RK motif-containing putative transcription factors [9], is required for this process. Loss-of-function rkd4 mutants were defective in zygotic cell elongation, as well as subsequent cell division patterns. As expected from this mutant phenotype, RKD4 was transcribed preferentially in early embryos. RKD4 possessed functional characteristics of transcription factors and was able to ectopically induce early embryo-specific genes when overexpressed in seedlings. Strikingly, induced overexpression of RKD4 primed somatic cells for embryogenesis independen! tly of external growth regulators. These results reveal that RKD4 is a novel key regulator of the earliest stage of plant development.
• A New Molecular Logic for BMP-Mediated Dorsoventral Patterning in the Leech Helobdella
  - Curr Biol 21(15):1282-1288 (2011)
  Bone morphogenetic protein (BMP) signaling is broadly implicated in dorsoventral (DV) patterning of bilaterally symmetric animals [[1], [2] and [3]], and its role in axial patterning apparently predates the birth of Bilateria [[4], [5], [6] and [7]]. In fly and vertebrate embryos, BMPs and their antagonists (primarily Sog/chordin) diffuse and interact to generate signaling gradients that pattern fields of cells [[8], [9] and [10]]. Work in other species reveals diversity in essential facets of this ancient patterning process, however. Here, we report that BMP signaling patterns the DV axis of segmental ectoderm in the leech Helobdella, a clitellate annelid (superphylum Lophotrochozoa) featuring stereotyped developmental cell lineages, but the detailed mechanisms of DV patterning in Helobdella differ markedly from fly and vertebrates. In Helobdella, BMP2/4s are expressed broadly, rather than in dorsal territory, whereas a dorsally expressed BMP5–8 specifies dorsal fat! e by short-range signaling. A BMP antagonist, gremlin, is upregulated by BMP5–8 in dorsolateral, rather than ventral territory, and yet the BMP-antagonizing activity of gremlin is required for normal ventral cell fates. Gremlin promotes ventral fates without disrupting dorsal fates by selectively inhibiting BMP2/4s, not BMP5–8. Thus, DV patterning in the development of the leech revealed unexpected evolutionary plasticity of the conserved BMP patterning system, presumably reflecting its adaptation to different modes of embryogenesis.
• Crosstalk between Nodal/Activin and MAPK p38 Signaling Is Essential for Anterior-Posterior Axis Specification
  - Curr Biol 21(15):1289-1295 (2011)
  Nodal/activin signaling plays a key role in anterior-posterior (A-P) axis formation by inducing the anterior visceral endoderm (AVE), the extraembryonic signaling center that initiates anterior patterning in the embryo. Here we provide direct evidence that the mitogen-activated protein kinase (MAPK) p38 regulates AVE specification through a crosstalk with the Nodal/activin signaling pathway. We show that p38 activation is directly stimulated by Nodal/activin and fails to be maintained upon inhibition of this pathway both in vivo and in vitro. In turn, p38 strengthens the Nodal signaling response by phosphorylating the Smad2 linker region and enhancing the level of Smad2 activation. Furthermore, we demonstrate that this p38 amplification loop is essential for correct specification of the AVE in two ways: first, by showing that inhibiting p38 activity in 5.5 days postcoitum embryo cultures leads to a switch from AVE to an extraembryonic visceral endoderm cell identity, a! nd second, by demonstrating that genetically reducing p38 activity in a Nodal-sensitive background leads to a failure of AVE specification in vivo. Collectively, our results reveal a novel role for p38 in regulating the threshold of Nodal signaling and propose a new mechanism by which A-P axis development can be reinforced during early embryogenesis.
• Adaptive Introgression of Anticoagulant Rodent Poison Resistance by Hybridization between Old World Mice
  - Curr Biol 21(15):1296-1301 (2011)
  Polymorphisms in the vitamin K 2,3-epoxide reductase subcomponent 1 (vkorc1) of house mice (Mus musculus domesticus) can cause resistance to anticoagulant rodenticides such as warfarin [[1], [2] and [3]]. Here we show that resistant house mice can also originate from selection on vkorc1 polymorphisms acquired from the Algerian mouse (M. spretus) through introgressive hybridization. We report on a polymorphic introgressed genomic region in European M. m. domesticus that stems from M. spretus, spans >10 Mb on chromosome 7, and includes the molecular target of anticoagulants vkorc1 [[1], [2], [3] and [4]]. We show that in the laboratory, the homozygous complete vkorc1 allele of M. spretus confers resistance when introgressed into M. m. domesticus. Consistent with selection on the introgressed allele after the introduction of rodenticides in the 1950s, we found signatures of selection in patterns of variation in M. m. domesticus. Furthermore, we detected adaptive protein e! volution of vkorc1 in M. spretus (Ka/Ks = 1.54–1.93) resulting in radical amino acid substitutions that apparently cause anticoagulant tolerance in M. spretus as a pleiotropic effect. Thus, positive selection produced an adaptive, divergent, and pleiotropic vkorc1 allele in the donor species, M. spretus, which crossed a species barrier and produced an adaptive polymorphic trait in the recipient species, M. m. domesticus.
• The Circe Principle Explains How Resource-Rich Land Can Waylay Pollinators in Fragmented Landscapes
  - Curr Biol 21(15):1302-1307 (2011)
  Global declines in pollinators, associated with land-use change [[1], [2], [3], [4], [5] and [6]] and fragmentation [[7], [8], [9] and [10]], constitute a serious threat to crop production and biodiversity [11]. Models investigating impacts of habitat fragmentation on pollen flow have categorized landscapes simply in terms of habitat and nonhabitat. We show that pollen flow depends strongly on types of land use between habitat fragments. We used paternity analysis of seeds and a combination of circuit and general linear models to analyze pollen flow for the endangered tree Gomortega keule (Gomortegaceae) [12] in the fragmented Central Chile Biodiversity Hotspot [13]. Pollination probability was highest over pine plantation, moderate over low-intensity agriculture and native forest, and lowest over clearfells. Changing the proportions of the land uses over one kilometer altered pollination probability up to 7-fold. We explain our results by the novel "Circe principle.! " In contrast to models where land uses similar to native habitat promote pollinator movement, pollinators may actually be waylaid in resource-rich areas between habitat patches. Moreover, pollinators may move with higher probability between habitat patches separated by some resource-poor land uses. Pollination research in fragmented landscapes requires explicit recognition of the nature of the nonhabitat matrix, rather than applying simple binary landscape models.
• A Maternal Factor Unique to Ascidians Silences the Germline via Binding to P-TEFb and RNAP II Regulation
  - Curr Biol 21(15):1308-1313 (2011)
  Suppression of zygotic transcription in early embryonic germline cells is tightly linked to their separation from the somatic lineage. Many invertebrate embryos utilize localized maternal factors that are successively inherited by the germline cells for silencing the germline. Germline quiescence has also been associated with the underphosphorylation of Ser2 of the C-terminal domain (CTD-Ser2) of RNA polymerase II [[1], [2] and [3]]. Here, using the ascidian Halocynthia roretzi, we identified a first deuterostome example of a maternally localized factor, posterior end mark (PEM), which globally represses germline transcription. PEM knockdown resulted in ectopic transcription and ectopic phosphorylation of CTD-Ser2 in the germline. Overexpression of PEM abolished all transcription and led to the underphosphorylation of CTD-Ser2 in the somatic cells. PEM protein was reiteratively detected in the nucleus of the germline cells and coimmunoprecipitated with CDK9, a componen! t of posterior transcription elongation factor b (P-TEFb). These results suggest that nonhomologous proteins, PEM and Pgc of Drosophila [[3], [4] and [5]] and PIE-1 of C. elegans [[1], [6] and [7]], repress germline gene expression through analogous functions: by keeping CTD-Ser2 underphosphorylated through binding to the P-TEFb complex. The present study is an interesting example of evolutionary constraint on how a mechanism of germline silencing can evolve in diverse animals.
• Divergent Strategies for Controlling the Nuclear Membrane Satisfy Geometric Constraints during Nuclear Division
  - Curr Biol 21(15):1314-1319 (2011)
  Eukaryotes segregate chromosomes in "open" or "closed" mitosis, depending on whether their nuclear envelopes (NEs) break down or remain intact. Here we show that the control of the nuclear surface area may determine the choice between these two modes. The dividing nucleus does not expand its surface in the fission yeast Schizosaccharomyces japonicus, confining the mitotic spindle and causing it to buckle. The NE ruptures in anaphase, releasing the compressive stress and allowing chromosome segregation. Blocking the NE expansion in the related species Schizosaccharomyces pombe that undergoes closed mitosis induces spindle buckling and collapse in the absence of an intrinsic NE rupture mechanism. We propose that scaling considerations could have shaped the evolution of eukaryotic mitosis by necessitating either nuclear surface expansion or the NE breakdown.
• An In Vivo Assay of Synaptic Function Mediating Human Cognition
  - Curr Biol 21(15):1320-1325 (2011)
  The contribution of dopamine to working memory has been studied extensively [[1], [2] and [3]]. Here, we exploited its well characterized effects [[1], [2] and [3]] to validate a novel human in vivo assay of ongoing synaptic [[4] and [5]] processing. We obtained magnetoencephalographic (MEG) measurements from subjects performing a working memory (WM) task during a within-subject, placebo-controlled, pharmacological (dopaminergic) challenge. By applying dynamic causal modeling (DCM), a Bayesian technique for neuronal system identification [6], to MEG signals from prefrontal cortex, we demonstrate that it is possible to infer synaptic signaling by specific ion channels in behaving humans. Dopamine-induced enhancement of WM performance was accompanied by significant changes in MEG signal power, and a DCM assay disclosed related changes in synaptic signaling. By estimating the contribution of ionotropic receptors (AMPA, NMDA, and GABAA) to the observed spectral response, w! e demonstrate changes in their function commensurate with the synaptic effects of dopamine. The validity of our model is reinforced by a striking quantitative effect on NMDA and AMPA receptor signaling that predicted behavioral improvement over subjects. Our results provide a proof-of-principle demonstration of a novel framework for inferring, noninvasively, neuromodulatory influences on ion channel signaling via specific ionotropic receptors, providing a window on the hidden synaptic events mediating discrete psychological processes in humans.
• The C. elegans Touch Response Facilitates Escape from Predacious Fungi
  - Curr Biol 21(15):1326-1330 (2011)
  Predator-prey interactions are vital determinants in the natural selection of behavioral traits. Gentle touch to the anterior half of the body of Caenorhabditis elegans elicits an escape response in which the animal quickly reverses and suppresses exploratory head movements [[1] and [2]]. Here, we investigate the ecological significance of the touch response in predator-prey interactions between C. elegans and predacious fungi that catch nematodes using constricting hyphal rings. We show that the constricting rings of Drechslerella doedycoides catch early larval stages with a diameter similar to the trap opening. There is a delay between the ring entry and ring closure, which allows the animal to withdraw from the trap before being caught. Mutants that fail to suppress head movements in response to touch are caught more efficiently than the wild-type. This demonstrates that the coordination of motor programs allows C. elegans to smoothly retract from a fungal noose and! evade capture. Our results suggest that selective pressures imposed by predacious fungi have shaped the evolution of C. elegans escape behavior. Video Abstract To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon below Download this Video (14646 K)
• Trehalose Renders the Dauer Larva of Caenorhabditis elegans Resistant to Extreme Desiccation
  - Curr Biol 21(15):1331-1336 (2011)
  Water is essential for life on Earth. In its absence, however, some organisms can interrupt their life cycle and temporarily enter an ametabolic state, known as anhydrobiosis [1]. It is assumed that sugars (in particular trehalose) are instrumental for survival under anhydrobiotic conditions [2]. However, the role of trehalose remained obscure because the corresponding evidence was purely correlative and based mostly on in vitro studies without any genetic manipulations of trehalose metabolism. In this study, we used C. elegans as a genetic model to investigate molecular mechanisms of anhydrobiosis. We show that the C. elegans dauer larva is a true anhydrobiote: under defined conditions it can survive even after losing 98% of its body water. This ability is correlated with a several fold increase in the amount of trehalose. Mutants unable to synthesize trehalose cannot survive even mild dehydration. Light and electron microscopy indicate that one of the major functions! of trehalose is the preservation of membrane organization. Fourier-transform infrared spectroscopy of whole worms suggests that this is achieved by preserving homogeneous and compact packing of lipid acyl chains. By means of infrared spectroscopy, we can now distinguish a "dry, yet alive" larva from a "dry and dead" one.