Hot off the presses! Sep 29 Curr Biol

The Sep 29 issue of the Curr Biol is now up on Pubget (About Curr Biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• US rethinks forestry plans
  - Curr Biol 19(18):R829-R830 (2009)
  Cyrus Martin looks at proposals to buttress the United States' National Forest Service in the wake of fires and other challenges.
• Arctic honey pot
  - Curr Biol 19(18):R830-R831 (2009)
  Melting ice is increasing opportunities for local people. Nigel Williams reports.
• Uncertainty principles
  - Curr Biol 19(18):R831-R832 (2009)
  The general elections in Germany have been more open than ever, with five main parties likely to be in the new Bundestag. So what are their policies for science, and the environment? Michael Gross reports.
• GM food ban worries
  - Curr Biol 19(18):R833 (2009)
  The increasing cost of non-GM foods is worrying British supermarkets. Nigel Williams reports.
• Darwin's last big problem
  - Curr Biol 19(18):R834-R835 (2009)
  Robert May, new president of the British Science Association, has highlighted the issue of the biological basis of co-operation. Nigel Williams reports.
• Anniversary send-offs
  - Curr Biol 19(18):R835-R836 (2009)
  Darwin celebrations continue apace. Nigel Williams reports.
• Gilles Laurent
  - Curr Biol 19(18):R837-R838 (2009)
  
• Mycorrhizal networks
  - Curr Biol 19(18):R838-R839 (2009)
  
• The Fungi
  - Curr Biol 19(18):R840-R845 (2009)
  
• Cellular Allometry: The Spindle in Development and Inheritance
  - Curr Biol 19(18):R846-R847 (2009)
  Recent studies have demonstrated a correlation between cell size and the behaviors of the cytoskeletal division machinery during embryogenesis, giving insight into how a core cellular process is modulated over the course of development.
• Perceptual Decisions: From Sensory Signals to Behavior
  - Curr Biol 19(18):R847-R849 (2009)
  Recent non-invasive studies in humans provide new insights into the timing of perceptual decision making and show that integrated sensory evidence is represented in motor areas well before a behavioral response.
• Meiosis: Making a Synaptonemal Complex Just Got Easier
  - Curr Biol 19(18):R849-R851 (2009)
  In preparation for meiosis, chromosomes go through several massive structural transitions, including chromosome fragmentation, pairing and synapsis. A checkpoint factor and a SUMO ligase collaborate to keep things in order.
• Vision: Thinking Globally, Acting Locally
  - Curr Biol 19(18):R851-R854 (2009)
  The global structure of images profoundly influences how we see their local detail, consistent with activity in primary visual cortex being disambiguated via feedback from later visual areas.
• Fly Memory: A Mushroom Body Story in Parts
  - Curr Biol 19(18):R855-R857 (2009)
  Recent studies on the compartmentalization of fly mushroom bodies show that learning and memory in Drosophila are not as simple as might be expected for an organism with such a tiny brain.
• Bacterial Evolution: Dynamic Genomes and the Power of Transformation
  - Curr Biol 19(18):R857-R859 (2009)
  Virulence and avirulence genes carried on large, unstable pathogenicity islands (PAI) strongly influence the course and fate of host–pathogen interactions. A recent study shows how one such PAI can be rapidly transferred between two closely related bacteria via transformation in vivo, and how this horizontal gene transfer affects the fitness of the recipient strain.
• Memory Consolidation: Tracking Transfer with Functional Connectivity
  - Curr Biol 19(18):R860-R862 (2009)
  Every day we store memories of innumerable new experiences. Our extraordinary ability to retrieve so many of them at a later time is due in no small part to the consolidation of these memories, a process that continues offline long after the experiences themselves are over.
• Olfaction: When Nostrils Compete
  - Curr Biol 19(18):R862-R864 (2009)
  In vision, alternating percepts occur when two different visual stimuli are presented separately to the two eyes. By analogy, simultaneous presentation of two different odorants separately to the two nostrils has now been shown to cause alternating odor percepts, an effect termed 'binaral rivalry'.
• Integrating Genomes, Brain and Behavior in the Study of Songbirds
  - Curr Biol 19(18):R865-R873 (2009)
  Songbirds share some essential traits but are extraordinarily diverse, allowing comparative analyses aimed at identifying specific genotype–phenotype associations. This diversity encompasses traits like vocal communication and complex social behaviors that are of great interest to humans, but that are not well represented in other accessible research organisms. Many songbirds are readily observable in nature and thus afford unique insight into the links between environment and organism. The distinctive organization of the songbird brain will facilitate analysis of genomic links to brain and behavior. Access to the zebra finch genome sequence will, therefore, prompt new questions and provide the ability to answer those questions.
• The archipelago Tumor Suppressor Gene Limits Rb/E2F-Regulated Apoptosis in Developing Drosophila Tissues
  - Curr Biol 19(18):1503-1510 (2009)
  Background The Drosophila archipelago gene (ago) encodes the specificity component of a ubiquitin ligase that targets the cyclin E and dMyc proteins for degradation. Its human ortholog, Fbw7, is commonly lost in cancers, suggesting that failure to degrade ago/Fbw7 targets drives excess tissue growth. Results We find that ago loss induces hyperplasia of some organs but paradoxically reduces the size of the adult eye. This reflects a requirement for ago to restrict apoptotic activity of the rbf1/de2f1 pathway adjacent to the eye-specific morphogenetic furrow (MF): ago mutant cells display elevated de2f1 activity, express the prodeath dE2f1 targets hid and rpr, and undergo high rates of apoptosis. These phenotypes are dependent on rbf1, de2f1, hid, and the rbf1/de2f1 regulators cyclin E and dacapo but are independent of dp53. A transactivation-deficient de2f1 allele blocks MF-associated apoptosis of ago mutant cells but does not retard their clonal overgrowth, indicating that intact de2f1 function is required for the death but not overproliferation of ago cells. Epidermal growth factor receptor (EGFR) and wingless (wg) alleles also modify the ago apoptotic phenotype, indicating that these pathways may modulate the underlying sensitivity of ago mutant cells to apoptotic signals. Conclusions These data show that ago loss requires a collaborating block in cell death to efficiently drive tissue overgrowth and that this conditional phenotype reflects a role for ago in restricting apoptotic output of the rbf1/de2f1 pathway. Moreover, the susceptibility of ago mutant cells to succumb to this apoptotic program appears to depend on local variations in extracellular signaling that could thus determine tissue-specific fates of ago mutant cells.
• Cell-Cycle Control by Physiological Matrix Elasticity and In Vivo Tissue Stiffening
  - Curr Biol 19(18):1511-1518 (2009)
  Background A number of adhesion-mediated signaling pathways and cell-cycle events have been identified that regulate cell proliferation, yet studies to date have been unable to determine which of these pathways control mitogenesis in response to physiologically relevant changes in tissue elasticity. In this report, we use hydrogel-based substrata matched to biological tissue stiffness to investigate the effects of matrix elasticity on the cell cycle. Results We find that physiological tissue stiffness acts as a cell-cycle inhibitor in mammary epithelial cells and vascular smooth muscle cells; subcellular analysis in these cells, mouse embryonic fibroblasts, and osteoblasts shows that cell-cycle control by matrix stiffness is widely conserved. Remarkably, most mitogenic events previously documented as extracellular matrix (ECM)/integrin-dependent proceed normally when matrix stiffness is altered in the range that controls mitogenesis. These include ERK activity, immediate-early gene expression, and cdk inhibitor expression. In contrast, FAK-dependent Rac activation, Rac-dependent cyclin D1 gene induction, and cyclin D1-dependent Rb phosphorylation are strongly inhibited at physiological tissue stiffness and rescued when the matrix is stiffened in vitro. Importantly, the combined use of atomic force microscopy and fluorescence imaging in mice shows that comparable increases in tissue stiffness occur at sites of cell proliferation ! in vivo. Conclusions Matrix remodeling associated with pathogenesis is in itself a positive regulator of the cell cycle through a highly selective effect on integrin-dependent signaling to FAK, Rac, and cyclin D1.
• Fpr3 and Zip3 Ensure that Initiation of Meiotic Recombination Precedes Chromosome Synapsis in Budding Yeast
  - Curr Biol 19(18):1519-1526 (2009)
  Background Homolog pairing, synaptonemal complex (SC) assembly (chromosome synapsis), and crossover recombination are essential for successful meiotic chromosome segregation. A distinguishing feature of meiosis in budding yeast and mammals is that synapsis between homologs depends upon recombination; however, the molecular basis for this contingency is not understood. Results We show here that the yeast proline isomerase Fpr3 and the small ubiquitin-like modifier (SUMO) ligase Zip3 ensure that SC assembly is dependent upon recombination initiation. When Fpr3 and Zip3 are absent, synapsis occurs even in a mutant that fails to initiate recombination and homolog pairing. Fpr3 and Zip3 appear to specifically prevent synapsis initiation at centromeric sites. This result is consistent with previous observations of SC proteins localizing to centromeres prior to and independent of meiotic recombination initiation. Finally, we show that without Fpr3 and Zip3 activities, the synapsis initiation components Zip2 and Zip4 are dispensable for chromosome synapsis. Conclusions Fpr3 and Zip3 represent parallel pathways that function in a checkpoint-like manner to ensure that chromosome synapsis is contingent on the initiation of recombination. We propose that, during normal meiosis, Zip2 and Zip4 act downstream of recombination signals to oppose Fpr3- and Zip3-mediated inhibitions to initiating SC assembly at centromeres. These data suggest a role for centromeres in coordinating major meiotic chromosomal events and draw an interesting parallel between yeast centromeres and C. elegans pairing centers.
• Emergence of a New Gene from an Intergenic Region
  - Curr Biol 19(18):1527-1531 (2009)
  It is generally assumed that new genes would arise by gene duplication mechanisms, because the signals for regulation and transcript processing would be unlikely to evolve in parallel with a new gene function [1] and [2]. We have identified here a transcript in the house mouse (Mus musculus) that has arisen within the past 2.5–3.5 million years in a large intergenic region. The region is present in many mammals, including humans, allowing us to exclude the involvement of gene duplication, transposable elements, or other genome rearrangements, which are typically found for other cases of newly evolved genes [3], [4], [5], [6], [7] and [8]. The gene has three exons, shows alternative splicing, and is specifically expressed in postmeiotic cells of the testis. The transcript is restricted to species within the genus Mus and its emergence correlates with indel mutations in the 5′ regulatory region of the transcript. A recent selective sweep is associated with the transc! ript region in M. m. musculus populations. A knockout in the laboratory strain BL6 results in reduced sperm motility and reduced testis weight. Our results show that cryptic signals for transcript regulation and processing exist in intergenic regions and can become the basis for the evolution of a new functional gene.
• Neurons in Posterior Cingulate Cortex Signal Exploratory Decisions in a Dynamic Multioption Choice Task
  - Curr Biol 19(18):1532-1537 (2009)
  In dynamic environments, adaptive behavior requires striking a balance between harvesting currently available rewards (exploitation) and gathering information about alternative options (exploration) [1], [2], [3] and [4]. Such strategic decisions should incorporate not only recent reward history, but also opportunity costs and environmental statistics. Previous neuroimaging [5], [6], [7] and [8] and neurophysiological [9], [10], [11], [12] and [13] studies have implicated orbitofrontal cortex, anterior cingulate cortex, and ventral striatum in distinguishing between bouts of exploration and exploitation. Nonetheless, the neuronal mechanisms that underlie strategy selection remain poorly understood. We hypothesized that posterior cingulate cortex (CGp), an area linking reward processing, attention [14], memory [15] and [16], and motor control systems [17], mediates the integration of variables such as reward [18], uncertainty [19], and target location [20] that underlie! this dynamic balance. Here we show that CGp neurons distinguish between exploratory and exploitative decisions made by monkeys in a dynamic foraging task. Moreover, firing rates of these neurons predict in graded fashion the strategy most likely to be selected on upcoming trials. This encoding is distinct from switching between targets and is independent of the absolute magnitudes of rewards. These observations implicate CGp in the integration of individual outcomes across decision making and the modification of strategy in dynamic environments.
• Walking Straight into Circles
  - Curr Biol 19(18):1538-1542 (2009)
  Common belief has it that people who get lost in unfamiliar terrain often end up walking in circles. Although uncorroborated by empirical data, this belief has widely permeated popular culture. Here, we tested the ability of humans to walk on a straight course through unfamiliar terrain in two different environments: a large forest area and the Sahara desert. Walking trajectories of several hours were captured via global positioning system, showing that participants repeatedly walked in circles when they could not see the sun. Conversely, when the sun was visible, participants sometimes veered from a straight course but did not walk in circles. We tested various explanations for this walking behavior by assessing the ability of people to maintain a fixed course while blindfolded. Under these conditions, participants walked in often surprisingly small circles (diameter < 20 m), though rarely in a systematic direction. These results rule out a general explanation in term! s of biomechanical asymmetries or other general biases [1], [2], [3], [4], [5] and [6]. Instead, they suggest that veering from a straight course is the result of accumulating noise in the sensorimotor system, which, without an external directional reference to recalibrate the subjective straight ahead, may cause people to walk in circles.
• Cultural Confusions Show that Facial Expressions Are Not Universal
  Jack RE Blais C Scheepers C Schyns PG Caldara R - Curr Biol 19(18):1543-1548 (2009)
  Central to all human interaction is the mutual understanding of emotions, achieved primarily by a set of biologically rooted social signals evolved for this purpose—facial expressions of emotion. Although facial expressions are widely considered to be the universal language of emotion [1], [2] and [3], some negative facial expressions consistently elicit lower recognition levels among Eastern compared to Western groups (see [4] for a meta-analysis and [5] and [6] for review). Here, focusing on the decoding of facial expression signals, we merge behavioral and computational analyses with novel spatiotemporal analyses of eye movements, showing that Eastern observers use a culture-specific decoding strategy that is inadequate to reliably distinguish universal facial expressions of "fear" and "disgust." Rather than distributing their fixations evenly across the face as Westerners do, Eastern observers persistently fixate the eye region. Using a model information ! sampler, we demonstrate that by persistently fixating the eyes, Eastern observers sample ambiguous information, thus causing significant confusion. Our results question the universality of human facial expressions of emotion, highlighting their true complexity, with critical consequences for cross-cultural communication and globalization.
• Cell-Size-Dependent Spindle Elongation in the Caenorhabditis elegans Early Embryo
  - Curr Biol 19(18):1549-1554 (2009)
  Cell size is one of the critical parameters controlling the size of intracellular structures. A well-known example is the constant nuclear-to-cytoplasmic ratio (N/C ratio) [1], [2], [3], [4] and [5]. The length of the metaphase spindle is proportional to cell size, but it has an upper limit during early embryogenesis [6]. During anaphase, the mitotic spindle elongates and delivers the centrosomes and sister chromatids near the centers of the nascent daughter cells. Here, we quantified the relationship between spindle elongation and cell size in the early embryo of Caenorhabditis elegans and propose possible models for cell-size-dependent spindle elongation. Quantitative measurements revealed that the extent and speed of spindle elongation are correlated with cell size throughout early embryogenesis. RNAi knockdown of Gα proteins and their regulators revealed that the spindles failed to fully elongate and that the speed of spindle elongation was almost constant regardl! ess of cell size. Our results suggest that spindle elongation is controlled by two qualitatively distinct mechanisms, i.e., Gα-dependent and -independent modes of elongation. Simulation analyses revealed that the constant-pulling model and the force-generator-limited model reproduced the dynamics of the Gα-independent and Gα-dependent mechanisms, respectively. These models also explain how the set length of spindles is achieved.
• Optic Flow Processing for the Assessment of Object Movement during Ego Movement
  - Curr Biol 19(18):1555-1560 (2009)
  The vast majority of research on optic flow (retinal motion arising because of observer movement) has focused on its use in heading recovery and guidance of locomotion. Here we demonstrate that optic flow processing has an important role in the detection and estimation of scene-relative object movement during self movement. To do this, the brain identifies and globally discounts (i.e., subtracts) optic flow patterns across the visual scene—a process called flow parsing. Remaining motion can then be attributed to other objects in the scene. In two experiments, stationary observers viewed radial expansion flow fields and a moving probe at various onscreen locations. Consistent with global discounting, perceived probe motion had a significant component toward the center of the display and the magnitude of this component increased with probe eccentricity. The contribution of local motion processing to this effect was small compared to that of global processing (experimen! t 1). Furthermore, global discounting was clearly implicated because these effects persisted even when all the flow in the hemifield containing the probe was removed (experiment 2). Global processing of optic flow information is shown to play a fundamental role in the recovery of object movement during ego movement.
• Binaral Rivalry between the Nostrils and in the Cortex
  - Curr Biol 19(18):1561-1565 (2009)
  When two different images are presented to the two eyes, we perceive alternations between seeing one image and seeing the other. Termed binocular rivalry, this visual phenomenon has been known for over a century [1] and has been systematically studied in recent years at both the behavioral and neural levels [2]. A similar phenomenon has been documented in audition [3]. Here we report the discovery of alternating olfactory percepts when two different odorants are presented to the two nostrils. This binaral rivalry involves both cortical and peripheral (olfactory receptor) adaptations. Our discovery opens up new avenues to explore the workings of the olfactory system and olfactory awareness.
• Motor-Independent Targeting of CLASPs to Kinetochores by CENP-E Promotes Microtubule Turnover and Poleward Flux
  - Curr Biol 19(18):1566-1572 (2009)
  Efficient chromosome segregation during mitosis relies on the coordinated activity of molecular motors with proteins that regulate kinetochore attachments to dynamic spindle microtubules [1]. CLASPs are conserved kinetochore- and microtubule-associated proteins encoded by two paralog genes, clasp1 and clasp2, and have been previously implicated in the regulation of kinetochore microtubule dynamics [2], [3] and [4]. However, it remains unknown how CLASPs work in concert with other proteins to form a functional kinetochore microtubule interface. Here we have identified mitotic interactors of human CLASP1 via a proteomic approach. Among these, the microtubule plus-end-directed motor CENP-E [5] was found to form a complex with CLASP1 that colocalizes to multiple structures of the mitotic apparatus in human cells. We found that CENP-E recruits both CLASP1 and CLASP2 to kinetochores independently of its motor activity or the presence of microtubules. Depletion of CLASPs or C! ENP-E by RNA interference in human cells causes a significant and comparable reduction of kinetochore microtubule poleward flux and turnover rates and rescues spindle bipolarity in Kif2a-depleted cells. We conclude that CENP-E integrates two critical functions that are important for accurate chromosome movement and spindle architecture: one relying directly on its motor activity, and the other involving the targeting of key microtubule regulators to kinetochores.
• Wnt11/5a Complex Formation Caused by Tyrosine Sulfation Increases Canonical Signaling Activity
  - Curr Biol 19(18):1573-1580 (2009)
  Wnt signaling plays important roles in embryonic development, tissue differentiation, and cancer [1], [2], [3], [4], [5], [6] and [7]. In both normal and malignant tissue, Wnt family members are often expressed combinatorially [8], [9], [10] and [11], although the significance of this is not understood. We recently showed that Wnt11 and Wnt5a are both required for the initiation of embryonic axis formation and that the two proteins physically interact with each other [12]. However, little is known about the mechanism or biological significance of Wnt-Wnt protein interaction. Here we show in three assays, with Xenopus oocytes, mouse L cells, and human embryonic stem cells, that secreted Xenopus Wnt11/5a complexes have more canonical Wnt signaling activity than secreted Wnt11 or Wnt5a acting alone. We demonstrate that the sulfation activity of tyrosylprotein sulfotransferase-1 (TPST-1) is required for Xenopus dorsal axis formation and that O-sulfation of specific tyrosin! e residues is necessary for the interaction of Wnt11 with Wnt5a and for enhanced canonical signaling activity. These findings demonstrate a novel aspect of Wnt biology—Wnt family member interaction that depends on tyrosyl sulfation.
• Buildup of Choice-Predictive Activity in Human Motor Cortex during Perceptual Decision Making
  - Curr Biol 19(18):1581-1585 (2009)
  Simple perceptual decisions are ideally suited for studying the sensorimotor transformations underlying flexible behavior [1] and [2]. During perceptual detection, a noisy sensory signal is converted into a behavioral report of the presence or absence of a perceptual experience [3]. Here, we used magnetoencephalography (MEG) to link the dynamics of neural population activity in human motor cortex to perceptual choices in a "yes/no" visual motion detection task. We found that (1) motor response-selective MEG activity in the "gamma" (64–100 Hz) and "beta" (12–36 Hz) frequency ranges predicted subjects' choices several seconds before their overt manual response; (2) this choice-predictive activity built up gradually during stimulus viewing toward both "yes" and "no" choices; and (3) the choice-predictive activity in motor cortex reflected the temporal integral of gamma-band activity in motion-sensitive area MT during stimulus viewing. Because gamma! -band activity in MT reflects visual motion strength [4], these findings suggest that, during motion detection, motor plans for both "yes" and "no" choices result from continuously accumulating sensory evidence. We conclude that frequency-specific neural population activity at the cortical output stage of sensorimotor pathways provides a window into the mechanisms underlying perceptual decisions.
• Bacterial Evolution by Genomic Island Transfer Occurs via DNA Transformation In Planta
  - Curr Biol 19(18):1586-1590 (2009)
  Our understanding of the evolution of microbial pathogens has been advanced by the discovery of "islands" of DNA that differ from core genomes and contain determinants of virulence [1] and [2]. The acquisition of genomic islands (GIs) by horizontal gene transfer (HGT) is thought to have played a major role in microbial evolution. There are, however, few practical demonstrations of the acquisition of genes that control virulence, and, significantly, all have been achieved outside the animal or plant host. Loss of a GI from the bean pathogen Pseudomonas syringae pv. phaseolicola (Pph) is driven by exposure to the stress imposed by the plant's resistance response [3]. Here, we show that the complete episomal island, which carries pathogenicity genes including the effector avrPphB, transfers between strains of Pph by transformation in planta and inserts at a specific att site in the genome of the recipient. Our results show that the evolution of bacterial pathogens by ! HGT may be achieved via transformation, the simplest mechanism of DNA exchange. This process is activated by exposure to plant defenses, when the pathogen is in greatest need of acquiring new genetic traits to alleviate the antimicrobial stress imposed by plant innate immunity [4].