Monday, April 11, 2011

Hot off the presses! Apr 12 curr biol

The Apr 12 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:

  • Regenerative medicine spoilt for choice
    - curr biol 21(7):R235-R237 (2011)
    Embryonic stem cells, induced pluripotent cells, transdifferentiated cells – there is now a wide range of options for medical researchers trying to regenerate disease-affected tissues and organs. But which approach will win the day, and can science policy keep up with the bioethical implications of rapid progress? Michael Gross investigates.
  • Velvet worms
    - curr biol 21(7):R238-R240 (2011)
  • Tony Hyman
    - curr biol 21(7):R240-R242 (2011)
  • Lateral gene transfer
    - curr biol 21(7):R242-R246 (2011)
    The four disparate images shown in Figure 1 have this in common: each represents a radical adaptation that would not have happened had lateral gene transfer (LGT), also known as horizontal gene transfer (HGT), not been the powerful evolutionary force we now know it to be. Those who study the phenomenon are still struggling to quantitatively assess LGT as a process or processes and accommodate its implications for how patterns in nature should be represented — such as the existence of definable species or a meaningful universal Tree of Life. But all agree that the exchange of genetic information across species lines — which is how we will define LGT in this primer — is far more pervasive and more radical in its consequences than we could have guessed just a decade ago. Both prokaryotes (bacteria and archaea) and eukaryotes have experienced LGT, though its potential as a source of novel adaptations and as a challenge to phylogenetics are so far more obvious and bet! ter understood for prokaryotes, as are the mechanisms by which it is effected.
  • Bitter taste induces nausea
    - curr biol 21(7):R247-R248 (2011)
    Nausea is the most characteristic negative experience that typically accompanies toxin-induced illness. Because most plant-derived toxins taste bitter, there is a rational link between bitter tasting compounds in the mouth and nausea that often results from their ingestion. It is surprising then that there are no experimental data demonstrating this connection. There are, however, data consistent with this notion. For example, people who are the most sensitive to bitter stimuli are more prone to motion sickness [1], and bitter taste sensitivity and pregnancy associated nausea are positively related, a response postulated to protect the fetus from poisoning [2]. Moreover, we know that bitter taste slows gastric emptying, a correlate of nausea [3]. Bitter taste is strongly sensed by the glossopharyngeal and vagus nerves [4], which innervate the posterior oral cavity and the gastrointestinal tract, respectively. The two projection fields of these sensory nerves are immedi! ately adjacent within the nucleus of the solitary tract as well as in other brain relays [5], thus establishing a neuro-anatomical substrate for taste inputs to influence gastrointestinal states. Here, we report the first direct demonstration that bitter taste stimulation, but not sweet, salty, or umami taste, induces nausea, showing that the body not only detects potential toxins but anticipates their ingestion by inducing a prophylactic aversive state.
  • Synthetic Biology: Modulating the MAP Kinase Module
    - curr biol 21(7):R249-R251 (2011)
    In a recent study, the MAP kinase module involved in many human cancers has been reconstructed in yeast, in order to tinker with its behavior.
  • Auditory Neuroscience: Temporal Anticipation Enhances Cortical Processing
    - curr biol 21(7):R251-R253 (2011)
    A recent study shows that expectation about the timing of behaviorally-relevant sounds enhances the responses of neurons in the primary auditory cortex and improves the accuracy and speed with which animals respond to those sounds.
  • Hybridization: Expressing Yourself in a Crowd
    - curr biol 21(7):R254-R255 (2011)
    What happens to the expression of homeologous gene copies during the formation of new allopolyploid hybrids and their subsequent evolution? Recent studies have shown that hybridisation may relax transcriptional regulation and enable subsequent allopolyploid generations to develop novel patterns of parental gene expression.
  • Cytoskeletal Regulation: Sorting Out Stress Fibers with Tropomyosin
    - curr biol 21(7):R255-R256 (2011)
    Mechanisms governing the specification and function of non-muscle actomyosin structures, such as contractile rings and stress fibers, are poorly understood. An interesting new study now sheds some light on this topic by examining the role of tropomyosin in stress fiber organization.
  • Genomic Imprinting: An Obsession with Depilatory Mice
    - curr biol 21(7):R257-R259 (2011)
    Excessive grooming in mice has been promoted as a model of human obsessive-compulsive disorders. A recent paper adds Grb10 to the list of genes with effects on behavioral hair loss, with the added twist that this time the gene is imprinted.
  • Visual Perception: Bizarre Contours Go Against the Odds
    - curr biol 21(7):R259-R260 (2011)
    A new study shows that the brain sometimes invents visual contours even when they would be highly unlikely to occur in the real world. This presents a challenge to theories assuming that the brain prefers the most probable interpretation of the retinal image.
  • Chromosome Segregation: A Kinetochore Missing Link Is Found
    - curr biol 21(7):R261-R263 (2011)
    During mitosis the kinetochore assembles on centromeric chromatin. The component that connects the chromatin-associated inner domain to the microtubule-binding outer domain has eluded researchers. Two new studies identify a conserved molecular linkage between the inner and outer kinetochore.
  • Auditory Neuroscience: How to Stop Tinnitus by Buzzing the Vagus
    - curr biol 21(7):R263-R265 (2011)
    Recent observations linking the vagus nerve to plasticity in the central nervous system could pave the way to new treatments for one of the most common and intractable disorders of the auditory system.
  • Quantitative Variation in Autocrine Signaling and Pathway Crosstalk in the Caenorhabditis Vulval Network
    - curr biol 21(7):527-538 (2011)
    Background Biological networks experience quantitative change in response to environmental and evolutionary variation. Computational modeling allows exploration of network parameter space corresponding to such variations. The intercellular signaling network underlying Caenorhabditis vulval development specifies three fates in a row of six precursor cells, yielding a quasi-invariant 3°3°2°1°2°3° cell fate pattern. Two seemingly conflicting verbal models of vulval precursor cell fate specification have been proposed: sequential induction by the EGF-MAP kinase and Notch pathways, or morphogen-based induction by the former. Results To study the mechanistic and evolutionary system properties of this network, we combine experimental studies with computational modeling, using a model that keeps the network architecture constant but varies parameters. We first show that the Delta autocrine loop can play an essential role in 2° fate specification. With this autocrine loop, the same network topology can be quantitatively tuned to use in the six-cell-row morphogen-based or sequential patterning mechanisms, which may act singly, cooperatively, or redundantly. Moreover, different quantitative tunings of this same network can explain vulval patterning observed experimentally in C. elegans, C. briggsae, C. remanei, and C. brenneri. We experimentally validate model predictions, such as interspecific differences in isolated vulval precursor cell behavior and in spatial regulation of Notch activity. Conclusions Our study illustrates how quantitative variation in the same network comprises developmental patterning modes that were previously considered qualitatively distinct and also accounts for evolution among closely related species.
  • A Molecular Pathway for Myosin II Recruitment to Stress Fibers
    - curr biol 21(7):539-550 (2011)
    Background Cell migration and morphogenesis are driven by both protrusive and contractile actin filament structures. The assembly mechanisms of lamellipodial and filopodial actin filament arrays, which provide the force for plasma membrane protrusions through actin filament treadmilling, are relatively well understood. In contrast, the mechanisms by which contractile actomyosin arrays such as stress fibers are generated in cells, and how myosin II is specifically recruited to these structures, are not known. Results We demonstrate that four functionally distinct tropomyosins are required for assembly of stress fibers in cultured osteosarcoma cells. Tm1, Tm2/3, and Tm5NM1/2 stabilize actin filaments at distinct stress fiber regions. In contrast, Tm4 promotes stress fiber assembly by recruiting myosin II to stress fiber precursors. Elimination of any one of the tropomyosins fatally compromises stress fiber formation. Importantly, Dia2 formin is critical to stress fiber assembly by nucleating Tm4-decorated actin filaments at the cell cortex. Myosin II is specifically recruited through a Tm4-dependent mechanism to the Dia2-nucleated filaments, which subsequently assemble endwise with Arp2/3-nucleated actin filament structures to yield contractile stress fibers. Conclusions These experiments identified a pathway, involving Dia2- and Arp2/3-promoted actin filament nucleation and several functionally distinct tropomyosins, that is required for generation of contractile actomyosin arrays in cells.
  • Transcriptomic Shock Generates Evolutionary Novelty in a Newly Formed, Natural Allopolyploid Plant
    - curr biol 21(7):551-556 (2011)
    New hybrid species might be expected to show patterns of gene expression intermediate to those shown by parental species [[1] and [2]]. "Transcriptomic shock" may also occur, in which gene expression is disrupted; this may be further modified by whole genome duplication (causing allopolyploidy) [[3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15] and [16]]. "Shock" can include instantaneous partitioning of gene expression between parental copies of genes among tissues [[16], [17], [18] and [19]]. These effects have not previously been studied at a population level in a natural allopolyploid plant species. Here, we survey tissue-specific expression of 144 duplicated gene pairs derived from different parental species (homeologs) in two natural populations of 40-generation-old allotetraploid Tragopogon miscellus (Asteraceae) plants. We compare these results with patterns of allelic expression in both in vitro "hybrids" and hand-crossed F1 hyb! rids between the parental diploids T. dubius and T. pratensis, and with patterns of homeolog expression in synthetic (S1) allotetraploids. Partitioning of expression was frequent in natural allopolyploids, but F1 hybrids and S1 allopolyploids showed less partitioning of expression than the natural allopolyploids and the in vitro "hybrids" of diploid parents. Our results suggest that regulation of gene expression is relaxed in a concerted manner upon hybridization, and new patterns of partitioned expression subsequently emerge over the generations following allopolyploidization.
  • Reward Improves Long-Term Retention of a Motor Memory through Induction of Offline Memory Gains
    - curr biol 21(7):557-562 (2011)
    In humans, training in which good performance is rewarded or bad performance punished results in transient behavioral improvements [[1], [2] and [3]]. The relative effects of reward and punishment on consolidation and long-term retention, critical behavioral stages for successful learning [[4] and [5]], are not known. Here, we investigated the effects of reward and punishment on these different stages of human motor skill learning. We studied healthy subjects who trained on a motor task under rewarded, punished, or neutral control conditions. Performance was tested before and immediately, 6 hr, 24 hr, and 30 days after training in the absence of reward or punishment. Performance improvements immediately after training were comparable in the three groups. At 6 hr, the rewarded group maintained performance gains, whereas the other two groups experienced significant forgetting. At 24 hr, the reward group showed significant offline (posttraining) improvements, whereas the ! other two groups did not. At 30 days, the rewarded group retained the gains identified at 24 hr, whereas the other two groups experienced significant forgetting. We conclude that training under rewarded conditions is more effective than training under punished or neutral conditions in eliciting lasting motor learning, an advantage driven by offline memory gains that persist over time.
  • RAF Inhibitor-Induced KSR1/B-RAF Binding and Its Effects on ERK Cascade Signaling
    - curr biol 21(7):563-568 (2011)
    RAF kinase inhibitors can induce ERK cascade signaling by promoting dimerization of RAF family members in the presence of oncogenic or normally activated RAS [[1], [2] and [3]]. This interaction is mediated by a dimer interface region in the RAF kinase domain that is conserved in members of the ERK cascade scaffold family, kinase suppressor of RAS (KSR) [[4] and [5]]. In this study, we find that most RAF inhibitors also induce the binding of KSR1 to wild-type and oncogenic B-RAF proteins, including V600E B-RAF, but promote little complex formation between KSR1 and C-RAF. The inhibitor-induced KSR1/B-RAF interaction requires direct binding of the drug to B-RAF and is dependent on conserved dimer interface residues in each protein, but, unexpectedly, is not dependent on binding of B-RAF to activated RAS. Inhibitor-induced KSR/B-RAF complex formation can occur in the cytosol and is observed in normal mouse fibroblasts, as well as a variety of human cancer cell lines. Stri! kingly, we find that KSR1 competes with C-RAF for inhibitor-induced binding to B-RAF and, as a result, alters the effect of the inhibitors on ERK cascade signaling.
  • Habitat Complexity Drives Experimental Evolution of a Conditionally Expressed Secondary Sexual Trait
    - curr biol 21(7):569-573 (2011)
    The conditional expression of alternative phenotypes underlies the production of almost all life history decisions and many dichotomous traits [[1], [2], [3], [4], [5] and [6]], including male alternative reproductive morphs and behavioral tactics [7]. Changes in tactic fitness should lead to evolutionary shifts in developmental switch points that underlie tactic expression [8]. We used experimental evolution to directly test this hypothesis by rearing ten generations of the male-dimorphic mite Rhizoglyphus echinopus in either simple or three-dimensionally complex habitats that differed in their effects on morph fitness. In R. echinopus, fighter males develop weapons used for killing rivals, whereas scrambler males do not [9]. Populations evolving in complex 3D habitats, where fighters had reduced fitness, produced fewer fighters because the switch point for fighter development evolved to a larger critical body size. Both the reduced mobility of fighter males and the a! ltered spatial distribution of potential mates and rivals in the complex habitat were implicated in the evolutionary divergence of switch point between the habitats. Our results demonstrate how abiotic factors like habitat complexity can have a profound effect on evolution through sexual selection.
  • Decoupling of Activation and Effector Binding Underlies ARF6 Priming of Fast Endocytic Recycling
    - curr biol 21(7):574-579 (2011)
    The small GTP-binding protein ADP-ribosylation factor 6 (ARF6) controls the endocytic recycling pathway of several plasma membrane receptors. We analyzed the localization and GDP/GTP cycle of GFP-tagged ARF6 by total internal reflection fluorescent microscopy. We found that ARF6-GFP associates with clathrin-coated pits (CCPs) at the plasma membrane in a GTP-dependent manner in a mechanism requiring the adaptor protein complex AP-2. In CCP, GTP-ARF6 mediates the recruitment of the ARF-binding domain of downstream effectors including JNK-interacting proteins 3 and 4 (JIP3 and JIP4) after the burst recruitment of the clathrin uncoating component auxilin. ARF6 does not contribute to receptor-mediated clathrin-dependent endocytosis. In contrast, we found that interaction of ARF6 and JIPs on endocytic vesicles is required for trafficking of the transferrin receptor in the fast, microtubule-dependent endocytic recycling pathway. Our findings unravel a novel mechanism of separ! ation of ARF6 activation and effector function, ensuring that fast recycling may be determined at the level of receptor incorporation into CCPs.
  • Compensatory Neural Reorganization in Tourette Syndrome
    - curr biol 21(7):580-585 (2011)
    Children with neurological disorders may follow unique developmental trajectories whereby they undergo compensatory neuroplastic changes in brain structure and function that help them gain control over their symptoms [[1], [2], [3], [4], [5] and [6]]. We used behavioral and brain imaging techniques to investigate this conjecture in children with Tourette syndrome (TS). Using a behavioral task that induces high levels of intermanual conflict, we show that individuals with TS exhibit enhanced control of motor output. Then, using structural (diffusion-weighted imaging) brain imaging techniques, we demonstrate widespread differences in the white matter (WM) microstructure of the TS brain that include alterations in the corpus callosum and forceps minor (FM) WM that significantly predict tic severity in TS. Most importantly, we show that task performance for the TS group (but not for controls) is strongly predicted by the WM microstructure of the FM pathways that lead to th! e prefrontal cortex and by the functional magnetic resonance imaging blood oxygen level-dependent response in prefrontal areas connected by these tracts. These results provide evidence for compensatory brain reorganization that may underlie the increased self-regulation mechanisms that have been hypothesized to bring about the control of tics during adolescence.
  • The Phosphorylation State of an Aurora-Like Kinase Marks the Length of Growing Flagella in Chlamydomonas
    - curr biol 21(7):586-591 (2011)
    Flagella and cilia are structurally polarized organelles whose lengths are precisely defined, and alterations in length are related to several human disorders [[1] and [2]]. Intraflagellar transport (IFT) and protein signaling molecules are implicated in specifying flagellar and ciliary length [[3], [4], [5] and [6]], but evidence has been lacking for a flagellum and cilium length sensor that could participate in active length control or establishment of structural polarity. Previously, we showed that the phosphorylation state of the aurora-like protein kinase CALK in Chlamydomonas is a marker of the absence of flagella. Here we show that CALK phosphorylation state is also a marker for flagellar length. CALK is phosphorylated in cells without flagella, and during flagellar assembly it becomes dephosphorylated. Dephosphorylation is not simply a consequence of initiation of flagellar assembly or of time after experimentally induced flagellar loss, but instead requires fl! agella to be assembled to a threshold length. Analysis of cells with flagella of varying lengths shows that the threshold length for CALK dephosphorylation is 6 μm (half length). Studies with short and long flagellar mutants indicate that cells detect absolute rather than relative flagellar length. Our results demonstrate that cells possess a mechanism for translating flagellar length into a posttranslational modification of a known flagellar regulatory protein.
  • NompC TRP Channel Is Essential for Drosophila Sound Receptor Function
    - curr biol 21(7):592-597 (2011)
    The idea that the NompC TRPN1 channel is the Drosophila transducer for hearing has been challenged by remnant sound-evoked nerve potentials in nompC nulls [[1], [2], [3], [4] and [5]]. We now report that NompC is essential for the function of Drosophila sound receptors and that the remnant nerve potentials of nompC mutants are contributed by gravity/wind receptor cells. Ablating the sound receptors reduces the amplitude and sensitivity of sound-evoked nerve responses, and the same effects ensued from mutations in nompC. Ablating the sound receptors also suffices to abolish mechanical amplification, which arises from active receptor motility [[6] and [7]], is linked to transduction [8], and also requires NompC [9]. Calcium imaging shows that the remnant nerve potentials in nompC mutants are associated with the activity of gravity/wind receptors and that the sound receptors of the mutants fail to respond to sound. Hence, Drosophila sound receptors require NompC for mecha! nical signal detection and amplification, demonstrating the importance of this transient receptor potential channel for hearing and reviving the idea that the fly's auditory transducer might be NompC.
  • Amphiastral Mitotic Spindle Assembly in Vertebrate Cells Lacking Centrosomes
    - curr biol 21(7):598-605 (2011)
    The role of centrosomes and centrioles during mitotic spindle assembly in vertebrates remains controversial. In cell-free extracts and experimentally derived acentrosomal cells, randomly oriented microtubules (MTs) self-organize around mitotic chromosomes and assemble anastral spindles [[1], [2] and [3]]. However, vertebrate somatic cells normally assemble a connected pair of polarized, astral MT arrays—termed an amphiaster ("a star on both sides" [4])—that is formed by the splitting and separation of the microtubule-organizing center (MTOC) well before nuclear envelope breakdown (NEB) [5]. Whether amphiaster formation requires splitting of duplicated centrosomes is not known. We found that when centrosomes were removed from living vertebrate cells early in their cell cycle, an acentriolar MTOC reassembled, and, prior to NEB, a functional amphiastral spindle formed. Cytoplasmic dynein, dynactin, and pericentrin are all recruited to the interphase aMTOC, and the! activity of kinesin-5 is needed for amphiaster formation. Mitosis proceeded on time and these karyoplasts divided in two. However, 35% of aMTOCs failed to split and separate before NEB, and these entered mitosis with persistent monastral spindles. Chromatin-associated RAN-GTP—the small GTPase Ran in its GTP bound state—could not restore bipolarity to monastral spindles, and these cells exited mitosis as single daughters. Our data reveal the novel finding that MTOC separation and amphiaster formation does not absolutely require the centrosome, but, in its absence, the fidelity of bipolar spindle assembly is highly compromised.
  • Intracellular Transport by an Anchored Homogeneously Contracting F-Actin Meshwork
    - curr biol 21(7):606-611 (2011)
    Actin-based contractility orchestrates changes in cell shape underlying cellular functions ranging from division to migration and wound healing [[1], [2], [3], [4] and [5]]. Actin also functions in intracellular transport, with the prevailing view that filamentous actin (F-actin) cables serve as tracks for motor-driven transport of cargo [[1] and [6]]. We recently discovered an alternate mode of intracellular transport in starfish oocytes involving a contractile F-actin meshwork that mediates chromosome congression [7]. The mechanisms by which this meshwork contracts and translates its contractile activity into directional transport of chromosomes remained open questions. Here, we use live-cell imaging with quantitative analysis of chromosome trajectories and meshwork velocities to show that the 3D F-actin meshwork contracts homogeneously and isotropically throughout the nuclear space. Centrifugation experiments reveal that this homogeneous contraction is translated in! to asymmetric, directional transport by mechanical anchoring of the meshwork to the cell cortex. Finally, by injecting inert particles of different sizes, we show that this directional transport activity is size-selective and transduced to chromosomal cargo at least in part by steric trapping or "sieving." Taken together, these results reveal mechanistic design principles of a novel and potentially versatile mode of intracellular transport based on sieving by an anchored homogeneously contracting F-actin meshwork.
  • An Early Cambrian Hemichordate Zooid
    - curr biol 21(7):612-616 (2011)
    Hemichordates are known as fossils from at least the earliest mid-Cambrian Period (ca. 510 Ma) and are well represented in the fossil record by the graptolithinid pterobranchs ("graptolites"), which include the most abundantly preserved component of Paleozoic macroplankton [1]. However, records of the soft tissues of fossil hemichordates are exceedingly rare and lack clear anatomical details [2]. Galeaplumosus abilus gen. et sp. nov. from the lower Cambrian of China [3], an exceptionally preserved fossil with soft parts, represents by far the best-preserved, the earliest, and the largest hemichordate zooid from the fossil record; it provides new insight into the evolution of the group. The fossil is assigned to the pterobranch hemichordates on the basis of its morphological similarity to extant representatives. It has a zooidal tube (coenecium) with banding throughout comparable to that in the extant pterobranchs and a zooid with paired annulated arms bearing paire! d rows of annulated tentacles; it also displays a putative contractile stalk. G. abilus demonstrates stasis in pterobranch morphology, mode of coenecium construction, and probable feeding mechanism over 525 million years.
  • Males Use Multiple, Redundant Cues to Detect Mating Rivals
    - curr biol 21(7):617-622 (2011)
    Across many species, males exhibit plastic responses when they encounter mating rivals [1]. The ability to tailor responses to the presence of rivals allows males to increase investment in reproduction only when necessary. This is important given that reproduction imposes costs [2] that limit male reproductive capacity, particularly when sperm competition occurs [[3] and [4]]. Fruitfly (Drosophila melanogaster) males exposed to rivals subsequently mate for longer and thus accrue fitness benefits under increased competition [5], in line with theory [[6] and [7]]. Here, we show that male D. melanogaster detect rivals by using a suite of cues and that the resulting responses lead directly to significant fitness benefits. We used multiple techniques to systematically remove auditory, olfactory, tactile, and visual cues, first singly and then in all possible combinations. No single cue alone was sufficient to allow males to detect rivals. However, the perception of any two ! cues from sound, smell, or touch permitted males to detect and respond adaptively to rivals through increased offspring production. Vision was only of marginal importance in this context. The findings indicate adaptive redundancy through the use of multiple, but interchangeable, cues. We reveal the robust mechanisms by which males assess their socio-sexual environment to precisely attune responses via the expression of plastic behavior.
  • Highly Selective Tuning of a Silkworm Olfactory Receptor to a Key Mulberry Leaf Volatile
    - curr biol 21(7):623 (2011)
  • Control of Local Rho GTPase Crosstalk by Abr
    - curr biol 21(7):623 (2011)

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