Hot off the presses! Apr 28 Curr Biol

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Latest Articles Include:

• Meat eating on the block
  - Curr Biol 19(8):R305-R306 (2009)
  The row is growing over the contribution of humans' eating preferences to damage to the environment. Nigel Williams reports.
• G20 fears
  - Curr Biol 19(8):R306-R307 (2009)
  In spite of global plaudits, many people are concerned about the lack of environmental targets in the summit's conclusion. Nigel Williams reports.
• Dolphin surprise
  - Curr Biol 19(8):R307-R308 (2009)
  A large new population of rare Irrawaddy dolphins has just been described. Nigel Williams reports.
• Firing back
  - Curr Biol 19(8):R308 (2009)
  The Australian bush is already regenerating after record fires, reports Nigel Williams.
• Slavery driven
  - Curr Biol 19(8):R309-R310 (2009)
  A new book argues that Darwin's evolutionary ideas were powered by a moral passion. Nigel Williams reports.
• Tetsuro Matsuzawa
  - Curr Biol 19(8):R310-R312 (2009)
  
• Birthday presence
  - Curr Biol 19(8):R312 (2009)
  
• Below the Convergence
  - Curr Biol 19(8):R313-R314 (2009)
  
• Bird head stabilization
  - Curr Biol 19(8):R315-R316 (2009)
  
• Anolis lizards
  - Curr Biol 19(8):R316-R318 (2009)
  
• Dinosaurs
  - Curr Biol 19(8):R318-R323 (2009)
  
• Filling-in afterimage colors between the lines
  - Curr Biol 19(8):R323-R324 (2009)
  It is known that when a colored surface is viewed for some time and a blank screen is presented afterwards, an afterimage can be perceived in the complementary color. Color appearances in afterimages are due to adaptation of retinal cones and they are especially vivid when contours, presented after the adapting image, coincide with the blurred edges of the afterimage [1]. We report here that one and the same colored stimulus can induce multiple, differently colored afterimages, and that colored afterimages can also be perceived at regions that were not adapted to color. The observed filling-in of afterimage colors strongly depends on contours presented after the colored stimulus, revealing color–contour interactions that resemble filling-in of 'real' colors.
• Group Behaviour: Leadership by Those in Need
  - Curr Biol 19(8):R325-R327 (2009)
  A new model of animal group behaviour shows that, when the need to reach a target outweighs the costs of splitting from the group, a minority of the most 'needy' individuals become the leaders of large groups.
• Cell Division: Breaking Up Is Easy to Do
  - Curr Biol 19(8):R327-R328 (2009)
  How did cells divide before protein machines evolved? A new study shows that bacteria can reproduce without the division machinery, supporting the idea that primordial cells could have divided using physical mechanisms alone.
• Memory Networks: Answering the Call of the Hippocampus
  - Curr Biol 19(8):R329-R330 (2009)
  Without the hippocampus, experiences disappear without a memory trace. A recent study shows that changing synaptic strength within the hippocampus alters circuit function in widely distributed brain networks.
• DNA Repair: A RIDDLE at a Double-Strand Break
  - Curr Biol 19(8):R331-R333 (2009)
  Ubiquitin is known to accumulate at the sites of DNA damage. The identification of a new ubiquitin ligase, RIDDLIN, provides evidence for a ubiquitin-signalling cascade that regulates the assembly of an important DNA repair complex at a DNA double-strand break.
• Fungal Morphogenesis: Some Like It Hot
  - Curr Biol 19(8):R333-R334 (2009)
  The ability to reversibly convert between budding yeast-like and filamentous hyphal forms is important for the virulence of Candida albicans. A new study now provides insight into the relationship between environmental temperature and the signalling mechanisms that regulate morphogenesis in this fungal pathogen.
• Organelle Division: Dynamin-Related Proteins in Apicomplexans
  - Curr Biol 19(8):R334-R336 (2009)
  Establishing an infection within a host requires efficient invasion and division. In the intracellular parasite Toxoplasma gondii, these functions are mediated by dynamin-related proteins with a unique evolutionary history.
• Critical Periods: Motion Sensitivity Is Early in All Areas
  - Curr Biol 19(8):R336-R338 (2009)
  Recent work shows that global motion sensitivity, a property of extrastriate cortex, can be altered by early visual deprivation, while binocularity, a property of primary visual cortex, is still plastic. This contradicts the hypothesis that critical periods end later at higher levels of the system.
• Animal Navigation: A Wake-Up Call for Homing
  - Curr Biol 19(8):R338-R339 (2009)
  Many animals seem to know their location even when far from home. Evidence variously implicates odors or magnetic fields. The most consistent olfactory results, however, may not mean what we think.
• Animal Evolution: Once upon a Time
  - Curr Biol 19(8):R339-R341 (2009)
  The evolutionary relationships between the earliest branches of the animal kingdom – bilaterians, cnidarians, ctenophores, sponges and placozoans – are contentious. A new phylogenomic analysis suggests a return to old ideas.
• Hsp90 Orchestrates Temperature-Dependent Candida albicans Morphogenesis via Ras1-PKA Signaling
  - Curr Biol 19(8):621-629 (2009)
  Background Hsp90 is an environmentally contingent molecular chaperone that influences the form and function of diverse regulators of cellular signaling. Hsp90 potentiates the evolution of fungal drug resistance by enabling crucial cellular stress responses. Here we demonstrate that in the leading fungal pathogen of humans, Candida albicans, Hsp90 governs cellular circuitry required not only for drug resistance but also for the key morphogenetic transition from yeast to filamentous growth that is crucial for virulence. This transition is normally regulated by environmental cues, such as exposure to serum, that are contingent upon elevated temperature to induce morphogenesis. The basis for this temperature dependence has remained enigmatic. Results We show that compromising Hsp90 function pharmacologically or genetically induces a transition from yeast to filamentous growth in the absence of external cues. Elevated temperature relieves Hsp90-mediated repression of the morphogenetic program. Hsp90 regulates morphogenetic circuitry by repressing Ras1-PKA signaling. Modest Hsp90 compromise enhances the phenotypic effects of activated Ras1 signaling whereas deletion of positive regulators of the Ras1-PKA cascade blocks the morphogenetic response to Hsp90 inhibition. Consistent with the requirement for morphogenetic flexibility for virulence, depletion of C. albicans Hsp90 attenuates virulence in a murine model of systemic disease. Conclusions Hsp90 governs the integration of environmental cues with cellular signaling to orchestrate fungal morphogenesis and virulence, suggesting new therapeutic strategies for life-threatening infectious disease. Hsp90's capacity to govern a key developmental program in response to temperature change provides a new mechanism that complements the elegant repertoire that organisms utilize to sense temperature.
• Tdrd6 Is Required for Spermiogenesis, Chromatoid Body Architecture, and Regulation of miRNA Expression
  - Curr Biol 19(8):630-639 (2009)
  Background Chromatoid bodies (CBs) are characteristic spermatid organelles, which were suggested to function in RNA storage and small RNA processing but whose functions remain largely unknown. CB components include Mili, Miwi, and Tudor domain proteins such as Tdrd6, whose contribution to CB structure and function is elusive. Results We determined gametogenesis stage- and male-specific expression and localization of Tdrd6, identified a C-terminally truncated form as predominant after meiosis I, and demonstrated direct physical interaction of Tdrd6 with the CB components Mili and Miwi. Development from round into elongated spermatids is abrogated in Tdrd6−/− mice. Their round spermatids bear "ghost" CBs, whose architecture is greatly disrupted. Mael, Miwi, and Mvh do not localize to the Tdrd6-deficient CBs, but retrotransposons are not significantly activated. However, more than 50 miRNAs are more abundant in Tdrd6−/− testes, as are exemplary pre- and pri-miRNAs. Conclusion We conclude that Tdrd6 is essential for spermiogenesis, for CB structure, and for proper mature and precursor miRNA expression.
• Mili Interacts with Tudor Domain-Containing Protein 1 in Regulating Spermatogenesis
  - Curr Biol 19(8):640-644 (2009)
  Piwi proteins are essential for germline development, stem cell self-renewal, epigenetic regulation, and transposon silencing [1], [2], [3], [4], [5], [6] and [7]. They bind to a complex class of small noncoding RNAs called Piwi-interacting RNAs (piRNAs) [8]. Mammalian Piwi proteins such as Mili are localized in the cytoplasm of spermatogenic cells, where they are associated with a germline-specific organelle called the nuage or its derivative, the chromatoid body, as well as with polysomes [9]. To investigate the molecular mechanisms mediated by Mili, we searched for Mili-interacting proteins. Here, we report that Mili specifically interacts with Tudor domain-containing protein 1 (Tdrd1), a germline protein that contains multiple Tudor domains [10] and [11]. This RNA-independent interaction is mediated through the N-terminal domain of Mili and the N-terminal region of Tdrd1 containing the myeloid Nervy DEAF-1 (MYND) domain and the first two Tudor domains. In addition,! Mili positively regulates the expression of the Tdrd1 mRNA. Furthermore, Mili and Tdrd1 mutants share similar spermatogenic defects. However, Tdrd1, unlike Mili, is not required for piRNA biogenesis. Our results suggest that Mili interacts with Tdrd1 in the nuage and chromatoid body. This interaction does not contribute to piRNA biogenesis but represents a regulatory mechanism that is critical for spermatogenesis.
• Development of Global Motion Perception Requires Early Postnatal Exposure to Patterned Light
  - Curr Biol 19(8):645-649 (2009)
  The accurate representation of the motion of external objects is one of the more important tasks of the visual areas of the brain because motion by itself can provide sufficient information for discriminating visual forms and hence breaking camouflage. Whereas the analysis of the motion of single small elements can occur in primary visual cortex (V1), the perception of a common direction of global motion of some visual elements among many is supported by extrastriate cortical areas [1] and [2]. Humans treated for binocular congenital cataracts afterward exhibit extreme deficits of global motion, but after monocular cataracts, the deficits are minimal [3]. These observations suggest a need for normal early patterned visual experience through at least one eye for global motion perception to develop in a typical fashion. We investigated this role for early experience and its timing on kittens that were deprived of light or patterned light at different ages. Such deprivati! on in the first 6 weeks resulted in long-lasting (>2 yr) profound deficits of perception of global motion but no apparent effects on the perception of simple unidirectional motion. Contrary to current opinion, sensitive periods to visual deprivation in primary and extrastriate cortex may be of similar duration.
• Activational Rather Than Navigational Effects of Odors on Homing of Young Pigeons
  - Curr Biol 19(8):650-654 (2009)
  Olfaction plays many well-established roles in vertebrate sensory perception [1] and [2]. More controversial is the claim that olfactory cues underlie the large-scale geographic "map" sense used by birds and other vertebrates [3] and [4]. The most common procedure used to investigate the role of odors in avian homing is to experimentally produce anosmia and/or block access to natural odors [4] and [5]. Although by no means universal in their results, many of these experiments have shown disorientation and/or decreased homing success [6], [7] and [8], generally interpreted as evidence for the olfactory map hypothesis. Here, in addition to control (CO) birds exposed to natural odors and birds deprived of odors ("no odor"; NO) during displacement to unfamiliar release sites, we included a group exposed to artificial odors ("novel odors"; NV) that could not provide navigational information [9]. Although all groups had access to natural odors at release sites, t! he vanishing bearings of NO birds were disoriented, whereas those of NV birds were homeward oriented and indistinguishable from those of CO birds. These findings show that odors, rather than providing navigational information, activate a nonolfactory path integration system.
• Reduced Effectiveness of Selection Caused by a Lack of Recombination
  - Curr Biol 19(8):655-660 (2009)
  Genetic recombination associated with sexual reproduction is expected to have important consequences for the effectiveness of natural selection. These effects may be evident within genomes, in the form of contrasting patterns of molecular variation and evolution in regions with different levels of recombination. Previous work reveals patterns that are consistent with a benefit of recombination for adaptation at the level of protein sequence: both positive selection for adaptive variants and purifying selection against deleterious ones appear to be compromised in regions of low recombination [1], [2], [3], [4], [5], [6], [7], [8], [9], [10] and [11]. Here, we re-examine these patterns by using polymorphism and divergence data from the Drosophila dot chromosome, which has a long history of reduced recombination. To avoid confounding selection and demographic effects, we collected these data from a species with an apparently stable demographic history, Drosophila american! a. We find that D. americana dot loci show several signatures of ineffective purifying and positive selection, including an increase in the rate of protein evolution, an increase in protein polymorphism, and a reduction in the proportion of amino acid substitutions attributable to positive selection.
• Gestures Orchestrate Brain Networks for Language Understanding
  - Curr Biol 19(8):661-667 (2009)
  Although the linguistic structure of speech provides valuable communicative information, nonverbal behaviors can offer additional, often disambiguating cues. In particular, being able to see the face and hand movements of a speaker facilitates language comprehension [1]. But how does the brain derive meaningful information from these movements? Mouth movements provide information about phonological aspects of speech [2] and [3]. In contrast, cospeech gestures display semantic information relevant to the intended message [4], [5] and [6]. We show that when language comprehension is accompanied by observable face movements, there is strong functional connectivity between areas of cortex involved in motor planning and production and posterior areas thought to mediate phonological aspects of speech perception. In contrast, language comprehension accompanied by cospeech gestures is associated with tuning of and strong functional connectivity between motor planning and produ! ction areas and anterior areas thought to mediate semantic aspects of language comprehension. These areas are not tuned to hand and arm movements that are not meaningful. Results suggest that when gestures accompany speech, the motor system works with language comprehension areas to determine the meaning of those gestures. Results also suggest that the cortical networks underlying language comprehension, rather than being fixed, are dynamically organized by the type of contextual information available to listeners during face-to-face communication.
• VE-Cadherin-Mediated Cell-Cell Interaction Suppresses Sprouting via Signaling to MLC2 Phosphorylation
  Abraham S Yeo M Montero-Balaguer M Paterson H Dejana E Marshall CJ Mavria G - Curr Biol 19(8):668-674 (2009)
  During new blood vessel formation, the cessation of angiogenic sprouting is necessary for the generation of functional vasculature. How sprouting is halted is not known, but it is contemporaneous with the development of stable intercellular junctions [1]. We report that VE-cadherin, which is responsible for endothelial adherens junction organization [2] and [3], plays a crucial role in the cessation of sprouting. Abrogating VE-cadherin function in an organotypic angiogenesis assay and in zebrafish embryos stimulates sprouting. We show that VE-cadherin signals to Rho-kinase-dependent myosin light-chain 2 phosphorylation, leading to actomyosin contractility [4], which regulates the distribution of VE-cadherin at cell-cell junctions. VE-cadherin antagonizes VEGFR2 signaling, and consequently, inhibition of VE-cadherin, Rho-kinase, or actomyosin contractility leads to VEGF-driven, Rac1-dependent sprouting. These findings suggest a novel mechanism by which cell-cell adhesio! n suppresses Rac1-dependent migration and sprouting by increasing actomyosin contractility at cell junctions.
• MST2- and Furry-Mediated Activation of NDR1 Kinase Is Critical for Precise Alignment of Mitotic Chromosomes
  - Curr Biol 19(8):675-681 (2009)
  The precise alignment of chromosomes on the metaphase plate prior to the onset of anaphase is essential for ensuring equal segregation of sister chromatids into two daughter cells, and defects in this process potentially cause chromosome instability and tumor progression [1], [2] and [3]. NDR1 is an evolutionarily conserved serine/threonine kinase whose activity is regulated by MST kinases, Furry (Fry), and MOB [4]. Although the NDR1 signaling pathway is implicated in cell division and morphogenesis in yeast and invertebrates [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15] and [16], the mechanisms of NDR1 activation and the functional significance of the NDR1 pathway in mammalian cells are largely unknown. Here, we show that NDR1 is required for accurate chromosome alignment at metaphase in HeLa cells; depletion of NDR1, Fry, or MST2 caused mitotic chromosome misalignment. Chromosome misalignment in MST2-depleted cells was corrected by expression of ac! tive NDR1. The kinase activity of NDR1 increased in early mitotic phase and was dependent on Fry and MST2. We also provide evidence that Fry binds to microtubules, localizes on the spindle, acts as a scaffold that binds to both NDR1 and MOB2, and synergistically activates NDR1 with MOB2. Our findings suggest that MST2-, Fry-, and MOB2-mediated activation of NDR1 is crucial for the fidelity of mitotic chromosome alignment in mammalian cells.
• Spatial Orienting Biases in the Decimal Numeral System
  - Curr Biol 19(8):682-687 (2009)
  Humans map numbers upon a mental number line (MNL) on which small integers are placed to the left of larger ones [1], [2], [3], [4], [5], [6], [7], [8] and [9]. Here, we show that human adults systematically shift the subjective midpoints of number intervals away from the borders separating contiguous tens along the MNL. Number intervals are erroneously bisected further to the right the closer they are to the left starting point of the tens and further to the left the closer they are to the right endpoint of the tens. Similarly, right-brain-damaged patients neglecting the left side of the MNL [10], [11] and [12] show enhanced pathological rightward deviation in the bisection of number intervals located toward the left starting point of the tens and reduced deviation for intervals located toward the right endpoint of the tens. These data disclose the effects that the recursive grouping of symbolic decimal numerals within the tens has brought on the phylogenetically and ! ontogenetically foregoing spatial representation of magnitudes [13], [14], [15] and [16].
• Regulation of Hox Gene Activity by Transcriptional Elongation in Drosophila
  - Curr Biol 19(8):688-693 (2009)
  Hox genes control the anterior-posterior patterning of most metazoan embryos. Their sequential expression is initially established by the segmentation gene cascade in the early Drosophila embryo [1]. The maintenance of these patterns depends on the Polycomb group (PcG) and trithorax group (trxG) complexes during the remainder of the life cycle [2]. We provide both genetic and molecular evidence that the Hox genes are subject to an additional tier of regulation, i.e., at the level of transcription elongation. Both Ultrabithorax (Ubx) and Abdominal-B (Abd-B) genes contain stalled or paused RNA polymerase II (Pol II) even when silent [3] and [4]. The Pol II elongation factors Elongin-A and Cdk9 are essential for optimal Ubx and Abd-B expression. Mitotic recombination assays suggest that these elongation factors are also important for the regulation of Notch-, EGF-, and Dpp-signaling genes. Stalled Pol II persists in tissues where Ubx and Abd-B are silenced by the PcG comp! lex. We propose that stalling fosters both the rapid induction and precise silencing of Hox gene expression during development.
• In Vivo Protein Architecture of the Eukaryotic Kinetochore with Nanometer Scale Accuracy
  - Curr Biol 19(8):694-699 (2009)
  The kinetochore is a macromolecular protein machine [1] that links centromeric chromatin to the plus ends of one or more microtubules (MTs) and segregates chromosomes during cell division. Its core structure consists of eight multicomponent protein complexes, most of which are conserved in all eukaryotes. We use an in vivo two-color fluorescence microscopy technique to determine, for the first time, the location of these proteins along the budding yeast kinetochore axis at nanometer resolution. Together with kinetochore protein counts [2] and [3], these localizations predict the 3D protein architecture of a metaphase kinetochore-microtubule attachment and provide new functional insights. We also find that the kinetochore becomes much shorter in anaphase as metaphase tension is lost. Shortening is due mainly to a decrease in the length of the Ndc80 complex, which may result either from intramolecular bending of the Ndc80 complex at the kink within the stalk region of th! e Ndc80-Nuf2 dimer [4] and [5] or from a change in its orientation relative to the microtubule axis. Conformational changes within the Ndc80 and Mtw1 complexes may serve as mechanical cues for tension-dependent regulation of MT attachment and the spindle-assembly checkpoint. The geometry of the core structure of the budding yeast kinetochore reported here is remarkably similar to that found in mammalian kinetochores, indicating that kinetochore structure is conserved in eukaryotes with either point or regional centromeres.
• Enhanced Arrestin Facilitates Recovery and Protects Rods Lacking Rhodopsin Phosphorylation
  - Curr Biol 19(8):700-705 (2009)
  G protein-coupled receptors (GPCRs) are the largest family of signaling proteins expressed in every cell in the body and are targeted by the majority of clinically used drugs [1]. GPCR signaling, including rhodopsin-driven phototransduction, is terminated by receptor phosphorylation followed by arrestin binding [2]. Genetic defects in receptor phosphorylation and excessive signaling by overactive GPCR mutants result in a wide variety of diseases, from retinal degeneration to cancer [3], [4], [5] and [6]. Here, we tested whether arrestin1 mutants with enhanced ability to bind active unphosphorylated rhodopsin [7], [8], [9] and [10] can suppress uncontrolled signaling, bypassing receptor phosphorylation by rhodopsin kinase (RK) and replacing this two-step mechanism with a single-step deactivation in rod photoreceptors. We show that in this precisely timed signaling system with single-photon sensitivity [11], an enhanced arrestin1 mutant partially compensates for defects ! in rhodopsin phosphorylation, promoting photoreceptor survival, improving functional performance, and facilitating photoresponse recovery. These proof-of-principle experiments demonstrate the feasibility of functional compensation in vivo for the first time, which is a promising approach for correcting genetic defects associated with gain-of-function mutations. Successful modification of protein-protein interactions by appropriate mutations paves the way to targeted redesign of signaling pathways to achieve desired functional outcomes.
• Phylogenomics Revives Traditional Views on Deep Animal Relationships
  - Curr Biol 19(8):706-712 (2009)
  The origin of many of the defining features of animal body plans, such as symmetry, nervous system, and the mesoderm, remains shrouded in mystery because of major uncertainty regarding the emergence order of the early branching taxa: the sponge groups, ctenophores, placozoans, cnidarians, and bilaterians. The "phylogenomic" approach [1] has recently provided a robust picture for intrabilaterian relationships [2] and [3] but not yet for more early branching metazoan clades. We have assembled a comprehensive 128 gene data set including newly generated sequence data from ctenophores, cnidarians, and all four main sponge groups. The resulting phylogeny yields two significant conclusions reviving old views that have been challenged in the molecular era: (1) that the sponges (Porifera) are monophyletic and not paraphyletic as repeatedly proposed [4], [5], [6], [7], [8] and [9], thus undermining the idea that ancestral metazoans had a sponge-like body plan; (2) that the m! ost likely position for the ctenophores is together with the cnidarians in a "coelenterate" clade. The Porifera and the Placozoa branch basally with respect to a moderately supported "eumetazoan" clade containing the three taxa with nervous system and muscle cells (Cnidaria, Ctenophora, and Bilateria). This new phylogeny provides a stimulating framework for exploring the important changes that shaped the body plans of the early diverging phyla.
• Regulation of Hox Gene Activity by Transcriptional Elongation in Drosophila
  - Curr Biol 19(8):713 (2009)