Wednesday, December 8, 2010

Hot off the presses! Dec 07 curr biol

The Dec 07 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:

  • Fees hike leads to UK student riot
    - curr biol 20(23):R999-R1000 (2010)
    The UK government's plan to shift the cost of university teaching from the state to the students has led to mass protests and riots. Michael Gross reports.
  • Cool build-up to climate conference
    - curr biol 20(23):R1000-R1001 (2010)
    Rather than agreement, the Cancun talks are expected to be a 'staging post' to a new deal. Nigel Williams reports.
  • Europe's faltering biofuel aims
    - curr biol 20(23):R1002 (2010)
    The drive to shift away from fossil fuels may backfire. Nigel Williams reports.
  • Prize for the HeLa cell story
    - curr biol 20(23):R1003-R1004 (2010)
    A book about Henrietta Lacks, source of the eponymous cells, is top of the list for the prestigious Wellcome Trust's science book prize. Nigel Williams reports.
  • Modified vector attack on dengue
    - curr biol 20(23):R1004-R1005 (2010)
    Genetically modified mosquitoes are showing promise in reducing the occurrence of a serious disease. Nigel Williams reports.
  • Major lionfish hunt launched
    - curr biol 20(23):R1005-R1006 (2010)
  • Lars Chittka
    - curr biol 20(23):R1006-R1008 (2010)
  • Dictyostelium
    - curr biol 20(23):R1008-R1010 (2010)
  • Dreaming and offline memory processing
    - curr biol 20(23):R1010-R1013 (2010)
    The activities of the mind and brain never cease. Although many of our waking hours are spent processing sensory input and executing behavioral responses, moments of unoccupied rest free us to wander through thoughts of the past and future, create daydreams, and imagine fictitious scenarios. During sleep, when attention to sensory input is at a minimum, the mind continues to process information, using memory fragments to create the images, thoughts, and narratives that we commonly call 'dreaming'. Far from being a random or meaningless distraction, spontaneous cognition during states of sleep and resting wakefulness appears to serve important functions related to processing past memories and planning for the future. From single-cell recordings in rodents to behavioral studies in humans, recent studies in the neurosciences suggest a new conception of dreaming as part of a continuum of adaptive cognitive processing occurring across the full range of mind/brain states.
  • Meiotic Checkpoints: Repair or Removal?
    - curr biol 20(23):R1014-R1016 (2010)
    Defects in meiosis can produce different checkpoint responses in female and male animals, suggesting that meiotic checkpoints exhibit sexual dimorphism. A recent study in Caenorhabditis elegans indicates that meiotic checkpoint activation is similar between the sexes and the primary difference lies in the downstream consequences.
  • Adaptive Diversity: Hormones and Metabolism in Freshwaters
    - curr biol 20(23):R1016-R1018 (2010)
    Genes underlying the evolution of morphological traits have recently been identified in a number of model species. In the stickleback, the metabolic adaptations to a freshwater habitat have now been linked to a well-known hormonal system.
  • Heterochromatin Replication: Better Late Than Ever
    - curr biol 20(23):R1018-R1020 (2010)
    Different heterochromatic properties appear on satellite DNA during successive embryonic division cycles in Drosophila. One such property, late replication, precedes HP1 recruitment, is under the control of zygotic transcription, and helps to lengthen S phase.
  • Pollination: Sexual Mimicry Abounds
    - curr biol 20(23):R1020-R1022 (2010)
    Why do plants mimic female insects to attract males for pollination? A new study gives insights into the advantages of sexual mimicry and documents this pollination system for the first time outside the orchid family, in a South African daisy.
  • Male Meiosis: Y Keep It Silenced?
    - curr biol 20(23):R1022-R1024 (2010)
    What drives defective spermatocytes into apoptosis during mid-pachytene? A recent study identifies the first mid-pachytene 'killer' genes: two Y-linked transcription factors, the Zfy1/2 gene pair, must be silenced to avoid apoptosis.
  • Bacterial Cytokinesis: FzlA Frizzes FtsZ Filaments for Fission Force
    - curr biol 20(23):R1024-R1027 (2010)
    Most bacteria divide by assembling filaments of the tubulin-like protein FtsZ into a cytokinetic ring, which then constricts. A recent study suggests that Caulobacter crescentus uses a novel regulator, FzlA, to activate ring constriction by inducing helical bundles of FtsZ filaments.
  • Nuclear Migration: Rock and Roll Facilitated by Dynein and Kinesin
    - curr biol 20(23):R1027-R1029 (2010)
    The nucleus encounters other organelles as well as high cytoplasmic pressures during its migration within the cell. A new study describes how the action of kinesin and dynein motors is coordinated at the nuclear envelope to rock and roll the nucleus in Caenorhabditis elegans.
  • Asymmetric Cell Division: A New Way to Divide Unequally
    - curr biol 20(23):R1029-R1031 (2010)
    It has long been known that cells can divide unequally by shifting the mitotic spindle to one side. Two recent reports identify an alternative way to generate daughter cells of different sizes.
  • Animal Tool-Use
    - curr biol 20(23):R1032-R1039 (2010)
    The sight of an animal making and using a tool captivates scientists and laymen alike, perhaps because it forces us to question some of our ideas about human uniqueness. Does the animal know how the tool works? Did it anticipate the need for the tool and make it in advance? To some, this fascination with tools seems arbitrary and anthropocentric; after all, animals engage in many other complex activities, like nest building, and we know that complex behaviour need not be cognitively demanding. But tool-using behaviour can also provide a powerful window into the minds of living animals, and help us to learn what capacities we share with them — and what might have changed to allow for the incontrovertibly unique levels of technology shown by modern humans.
  • Tension Management in the Kinetochore
    - curr biol 20(23):R1040-R1048 (2010)
    The kinetochore is the protein machine built at the centromere that integrates mechanical force and chemical energy from dynamic microtubules into directed chromosome motion. The kinetochore also provides a powerful signaling function that is able to alter the properties of the spindle checkpoint and initiate a signal transduction cascade that leads to inhibition of the anaphase promoting complex and cell cycle arrest. Together, the kinetochore accomplishes the feat of chromosome segregation with unparalleled accuracy. Errors in segregation lead to Down's syndrome, the most frequent inherited birth defect, pregnancy loss, and cancer. Over a century after the discovery of the kinetochore, an architectural map comprising greater than 100 proteins is emerging. Understanding the architecture and physical biology of the key components provides new insights into how this fascinating machine moves genomes.
  • Developmental Control of Late Replication and S Phase Length
    - curr biol 20(23):2067-2077 (2010)
    Background Fast, early embryonic cell cycles have correspondingly fast S phases. In early Drosophila embryos, forks starting from closely spaced origins replicate the whole genome in 3.4 min, ten times faster than in embryonic cycle 14 and a hundred times faster than in a wing disc. It is not known how S phase duration is regulated. Here we examined prolongation of embryonic S phases, its coupling to development, and its relationship to the appearance of heterochromatin. Results Imaging of fluorescent nucleotide incorporation and GFP-PCNA gave exquisite time resolution of S phase events. In the early S phases, satellite sequences replicated rapidly despite a compact chromatin structure. In S phases 11–13, a delay in satellite replication emerged in sync with modest and progressive prolongation of S phase. In S phase 14, major and distinct delays ordered the replication of satellites into a sequence that occupied much of S phase. This onset of late replication required transcription. Satellites only accumulated abundant heterochromatin protein 1 (HP1) after replicating in S phase 14. By cycle 15, satellites clustered in a compact HP1-positive mass, but replication occurred at decondensed foci at the surface of this mass. Conclusions The slowing of S phase is an active process, not a titration of maternal replication machinery. Most sequences continue to replicate rapidly in successive cycles, but increasing delays in the replication of satellite sequences extend S phase. Although called constitutively heterochromatic, satellites acquire the distinctive features of heterochromatin, compaction, late replication, HP1 binding, and aggregation at the chromocenter, in successive steps coordinated with developmental progress.
  • Meiotic Errors Activate Checkpoints that Improve Gamete Quality without Triggering Apoptosis in Male Germ Cells
    - curr biol 20(23):2078-2089 (2010)
    Background Meiotic checkpoints ensure the production of gametes with the correct complement and integrity of DNA; in metazoans, these pathways sense errors and transduce signals to trigger apoptosis to eliminate damaged germ cells. The extent to which checkpoints monitor and safeguard the genome differs between sexes and may contribute to the high frequency of human female meiotic errors. In the C. elegans female germline, DNA damage, chromosome asynapsis, and/or unrepaired meiotic double-strand breaks (DSBs) activate checkpoints that induce apoptosis; conversely, male germ cells do not undergo apoptosis. Results Here we show that the recombination checkpoint is in fact activated in male germ cells despite the lack of apoptosis. The 9-1-1 complex and the phosphatidylinositol 3-kinase-related protein kinase ATR, sensors of DNA damage, are recruited to chromatin in the presence of unrepaired meiotic DSBs in both female and male germlines. Furthermore, the checkpoint kinase CHK-1 is phosphorylated and the p53 ortholog CEP-1 induces expression of BH3-only proapoptotic proteins in germlines of both sexes under activating conditions. The core cell death machinery is expressed in female and male germlines; however, CED-3 caspase is not activated in the male germline. Although apoptosis is not triggered, checkpoint activation in males has functional consequences for gamete quality, because there is reduced viability of progeny sired by males with a checkpoint-activating defect in the absence of checkpoint function. Conclusions We propose that the recombination checkpoint functions in male germ cells to promote repair of meiotic recombination intermediates, thereby improving the fidelity of chromosome transmission in the absence of apoptosis.
  • Specialization of a Drosophila Capping Protein Essential for the Protection of Sperm Telomeres
    - curr biol 20(23):2090-2099 (2010)
    Background A critical function of telomeres is to prevent fusion of chromosome ends by the DNA repair machinery. In Drosophila somatic cells, assembly of the protecting capping complex at telomeres notably involves the recruitment of HOAP, HP1, and their recently identified partner, HipHop. We previously showed that the hiphop gene was duplicated before the radiation of the melanogaster subgroup of species, giving birth to K81, a unique paternal effect gene specifically expressed in the male germline. Results Here we show that K81 specifically associates with telomeres during spermiogenesis, along with HOAP and HP1, and is retained on paternal chromosomes until zygote formation. In K81 mutant testes, capping proteins are not maintained at telomeres in differentiating spermatids, resulting in the transmission of uncapped paternal chromosomes that fail to properly divide during the first zygotic mitosis. Despite the apparent similar capping roles of K81 and HipHop in their respective domain of expression, we demonstrate by in vivo reciprocal complementation analyses that they are not interchangeable. Strikingly, HipHop appeared to be unable to maintain capping proteins at telomeres during the global chromatin remodeling of spermatid nuclei. Conclusions Our data demonstrate that K81 is essential for the maintenance of capping proteins at telomeres in postmeiotic male germ cells. In species of the melanogaster subgroup, HipHop and K81 have not only acquired complementary expression domains, they have also functionally diverged following the gene duplication event. We propose that K81 specialized in the maintenance of telomere protection in the highly peculiar chromatin environment of differentiating male gametes.
  • Stem Cell Dynamics in Response to Nutrient Availability
    - curr biol 20(23):2100-2105 (2010)
    When nutrient availability becomes limited, animals must actively adjust their metabolism to allocate limited resources and maintain tissue homeostasis [[1], [2] and [3]]. However, it is poorly understood how tissues maintained by adult stem cells respond to chronic changes in metabolism. To begin to address this question, we fed flies a diet lacking protein (protein starvation) and assayed both germline and intestinal stem cells. Our results revealed a decrease in stem cell proliferation and a reduction in stem cell number; however, a small pool of active stem cells remained. Upon refeeding, stem cell number increased dramatically, indicating that the remaining stem cells are competent to respond quickly to changes in nutritional status. Stem cell maintenance is critically dependent upon intrinsic and extrinsic factors that act to regulate stem cell behavior [4]. Activation of the insulin/IGF signaling pathway in stem cells and adjacent support cells in the germline w! as sufficient to suppress stem cell loss during starvation. Therefore, our data indicate that stem cells can directly sense changes in the systemic environment to coordinate their behavior with the nutritional status of the animal, providing a paradigm for maintaining tissue homeostasis under metabolic stress.
  • Disrupting Parietal Function Prolongs Dominance Durations in Binocular Rivalry
    - curr biol 20(23):2106-2111 (2010)
    Human brain imaging studies of bistable perceptual phenomena revealed that frontal and parietal areas are activated during perceptual switches between the two conflicting percepts [[1], [2] and [3]]. However, these studies do not provide information about causality, i.e., whether activity reports a consequence or a cause of the perceptual change. Here we used functional magnetic resonance imaging to individually localize four parietal regions involved in perceptual switches during binocular rivalry in 15 subjects and subsequently disturbed their neural processing and that of a control site using 2 Hz repetitive transcranial magnetic stimulation (TMS) during binocular rivalry. We found that TMS over one of the sites, the right intraparietal sulcus (IPS), prolonged the periods of stable percepts. Additionally, the more lateralized the blood oxygen level-dependent signal was in IPS, the more lateralized the TMS effects were. Lateralization varied considerably across subje! cts, with a right-hemispheric bias. Control replay experiments rule out nonspecific effects of TMS on task performance, reaction times, or eye blinks. Our results thus demonstrate a causal, destabilizing, and individually lateralized effect of normal IPS function on perceptual continuity in rivalry. This is in accord with a role of IPS in perceptual selection, relating its role in rivalrous perception to that in attention [[4], [5] and [6]].
  • Spatial Heterogeneity in the Perception of Face and Form Attributes
    - curr biol 20(23):2112-2116 (2010)
    The identity of an object is a fixed property, independent of where it appears, and an effective visual system should capture this invariance [[1], [2] and [3]]. However, we now report that the perceived gender of a face is strongly biased toward male or female at different locations in the visual field. The spatial pattern of these biases was distinctive and stable for each individual. Identical neutral faces looked different when they were presented simultaneously at locations maximally biased to opposite genders. A similar effect was observed for perceived age of faces. We measured the magnitude of this perceptual heterogeneity for four other visual judgments: perceived aspect ratio, orientation discrimination, spatial-frequency discrimination, and color discrimination. The effect was sizeable for the aspect ratio task but substantially smaller for the other three tasks. We also evaluated perceptual heterogeneity for facial gender and orientation tasks at different ! spatial scales. Strong heterogeneity was observed even for the orientation task when tested at small scales. We suggest that perceptual heterogeneity is a general property of visual perception and results from undersampling of the visual signal at spatial scales that are small relative to the size of the receptive fields associated with each visual attribute.
  • Evidence that Meiotic Sex Chromosome Inactivation Is Essential for Male Fertility
    - curr biol 20(23):2117-2123 (2010)
    The mammalian X and Y chromosomes share little homology and are largely unsynapsed during normal meiosis. This asynapsis triggers inactivation of X- and Y-linked genes, or meiotic sex chromosome inactivation (MSCI) [1]. Whether MSCI is essential for male meiosis is unclear. Pachytene arrest and apoptosis is observed in mouse mutants in which MSCI fails, e.g., Brca1−/−, H2afx−/−, Sycp1−/−, and Msh5−/− [[2] and [3]]. However, these also harbor defects in synapsis and/or recombination and as such may activate a putative pachytene checkpoint [4]. Here we present evidence that MSCI failure is sufficient to cause pachytene arrest. XYY males exhibit Y-Y synapsis and Y chromosomal escape from MSCI without accompanying synapsis/recombination defects [5]. We find that XYY males, like synapsis/recombination mutants, display pachytene arrest and that this can be circumvented by preventing Y-Y synapsis and associated Y gene expression. Pachytene expression of indivi! dual Y genes inserted as transgenes on autosomes shows that expression of the Zfy1/2 paralogs in XY males is sufficient to phenocopy the pachytene arrest phenotype; insertion of Zfy1/2 on the X chromosome where they are subject to MSCI prevents this response. Our findings show that MSCI is essential for male meiosis and, as such, provide insight into the differential severity of meiotic mutations' effects on male and female meiosis.
  • Adaptive Divergence in the Thyroid Hormone Signaling Pathway in the Stickleback Radiation
    - curr biol 20(23):2124-2130 (2010)
    During adaptive radiations, animals colonize diverse environments, which requires adaptation in multiple phenotypic traits [1]. Because hormones mediate the dynamic regulation of suites of phenotypic traits [[2], [3] and [4]], evolutionary changes in hormonal signaling pathways might contribute to adaptation to new environments. Here we report changes in the thyroid hormone signaling pathway in stream-resident ecotypes of threespine stickleback fish (Gasterosteus aculeatus), which have repeatedly evolved from ancestral marine ecotypes [[5], [6], [7] and [8]]. Stream-resident fish exhibit a lower plasma concentration of thyroid hormone and a lower metabolic rate, which is likely adaptive for permanent residency in small streams. The thyroid-stimulating hormone-β2 (TSHβ2) gene exhibited significantly lower mRNA expression in pituitary glands of stream-resident sticklebacks relative to marine sticklebacks. Some of the difference in TSHβ2 transcript levels can be explai! ned by cis-regulatory differences at the TSHβ2 gene locus. Consistent with these expression differences, a strong signature of divergent natural selection was found at the TSHβ2 genomic locus. By contrast, there were no differences between the marine and stream-resident ecotypes in mRNA levels or genomic sequence in the paralogous TSHβ1 gene. Our data indicate that evolutionary changes in hormonal signaling have played an important role in the postglacial adaptive radiation of sticklebacks.
  • Inhibition of Respiration Extends C. elegans Life Span via Reactive Oxygen Species that Increase HIF-1 Activity
    - curr biol 20(23):2131-2136 (2010)
    A mild inhibition of mitochondrial respiration extends the life span of many organisms, including yeast, worms, flies, and mice [[1], [2], [3], [4], [5], [6], [7], [8], [9] and [10]], but the underlying mechanism is unknown. One environmental condition that reduces rates of respiration is hypoxia (low oxygen). Thus, it is possible that mechanisms that sense oxygen play a role in the longevity response to reduced respiration. The hypoxia-inducible factor HIF-1 is a highly conserved transcription factor that activates genes that promote survival during hypoxia [[11] and [12]]. In this study, we show that inhibition of respiration in C. elegans can promote longevity by activating HIF-1. Through genome-wide screening, we found that RNA interference (RNAi) knockdown of many genes encoding respiratory-chain components induced hif-1-dependent transcription. Moreover, HIF-1 was required for the extended life spans of clk-1 and isp-1 mutants, which have reduced rates of respira! tion [[1], [4] and [13]]. Inhibiting respiration appears to activate HIF-1 by elevating the level of reactive oxygen species (ROS). We found that ROS are increased in respiration mutants and that mild increases in ROS can stimulate HIF-1 to activate gene expression and promote longevity. In this way, HIF-1 appears to link respiratory stress in the mitochondria to a nuclear transcriptional response that promotes longevity.
  • Zygotic Resetting of the HISTONE 3 Variant Repertoire Participates in Epigenetic Reprogramming in Arabidopsis
    - curr biol 20(23):2137-2143 (2010)
    In most eukaryotes, the HISTONE 3 family comprises several variants distinguished by their amino acid sequence, localization, and correlation with transcriptional activity [[1], [2] and [3]]. Transgenerational inheritance of epigenetic information carried by histones is still unclear [[4] and [5]]. In addition to covalent histone modifications, the mosaic distribution of H3 variants onto chromatin has been proposed to provide a new level of epigenetic information [6]. To study the transmission of patterns of H3 variants through generations, we combined transcriptional profiling and live imaging of the 13 H3 variants encoded by the Arabidopsis plant genome [7]. In comparison with somatic cells, only a restricted number of H3 variants are present in male and female gametes. Upon fertilization, H3 variants contributed by both gametes are actively removed from the zygote chromatin. The somatic H3 composition is restored in the embryo by de novo synthesis of H3 variants. A ! survey of Arabidopsis homologs of animal H3 chaperones suggests that removal of parental H3 from the zygote nucleus relies on a new mechanism. Our results suggest that reprogramming of parental genomes in the zygote limits the inheritance of epigenetic information carried by H3 variants across generations.
  • SPIKE1 Signals Originate from and Assemble Specialized Domains of the Endoplasmic Reticulum
    - curr biol 20(23):2144-2149 (2010)
    In the leaf epidermis, intricately lobed pavement cells use Rho of plants (ROP) small GTPases to integrate actin and microtubule organization with trafficking through the secretory pathway [[1], [2], [3], [4] and [5]]. Cell signaling occurs because guanine nucleotide exchange factors (GEFs) promote ROP activation and their interactions with effector proteins that direct the cell growth machineries [6]. In Arabidopsis, SPIKE1 (SPK1) is the lone DOCK family GEF [[7] and [8]]. SPK1 promotes polarized growth and cell-cell adhesion in the leaf epidermis; however, its mode of action in cells is not known. Vertebrate DOCK proteins are deployed at the plasma membrane [[9] and [10]]. Likewise, current models place SPK1 activity and/or active ROP at the plant plasma membrane and invoke the localized patterning of the cortical cytoskeleton as the mechanism for shape control [[1], [4], [6] and [11]]. In this paper, we find that SPK1 is a peripheral membrane protein that accumulate! s at, and promotes the formation of, a specialized domain of the endoplasmic reticulum (ER) termed the ER exit site (ERES). SPK1 signals are generated from a distributed network of ERES point sources and maintain the homeostasis of the early secretory pathway. The ERES is the location for cargo export from the ER [12]. Our findings open up unexpected areas of plant G protein biology and redefine the ERES as a subcellular location for signal integration during morphogenesis.
  • GDNF Acts as a Chemoattractant to Support ephrinA-Induced Repulsion of Limb Motor Axons
    - curr biol 20(23):2150-2156 (2010)
    Despite the abundance of guidance cues in vertebrate nervous systems, little is known about cooperation between them [[1], [2] and [3]]. Motor axons of the lateral motor column (LMCL) [[4] and [5]] require two ligand/receptor systems, ephrinA/EphA4 and glial cell line-derived neurotrophic factor (GDNF)/Ret, to project to the dorsal limb [[6], [7] and [8]]. Deletion of either EphA4 or Ret in mice leads to rerouting of a portion of LMCL axons to the ventral limb, a phenotype enhanced in EphA4;Ret double mutants [[7] and [8]]. The guidance errors in EphA4 knockouts were attributed to the lack of repulsion from ephrinAs in the ventral mesenchyme [[6], [7] and [9]]. However, it has remained unclear how GDNF, expressed dorsally next to the choice point [8], acts on motor axons and cooperates with ephrinAs. Here we show that GDNF induces attractive turning of LMCL axons. When presented in countergradients, GDNF and ephrinAs cooperate in axon turning, indicating that the recep! tors Ret and EphA4 invoke opposite effects within the same growth cone. GDNF also acts in a permissive manner by reducing ephrinA-induced collapse and keeping the axons in a growth-competent state. This is the first example of two opposing cues promoting the same trajectory choice at an intermediate target.
  • Cse1l Is a Negative Regulator of CFTR-Dependent Fluid Secretion
    - curr biol 20(23):2157 (2010)
  • Carnivores
    - curr biol 20(23):2157 (2010)

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