Showing posts sorted by relevance for query latest:Current Biology. Sort by date Show all posts
Showing posts sorted by relevance for query latest:Current Biology. Sort by date Show all posts

Thursday, May 14, 2009

Hot off the presses! May 12 Curr Biol

The May 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:

  • Working for John Maddox
    - Current Biology 19(9):R343-R344 (2009)
  • Green shoots
    - Current Biology 19(9):R345-R346 (2009)
    While the UK government presents a budget hoped to tackle economic as well as environmental challenges, other countries have taken the lead in harnessing the economic interventions for ecological gains. Michael Gross reports.
  • Adam's antics
    - Current Biology 19(9):R346-R347 (2009)
    Mediawatch: The activities of Adam, a new robotic laboratory tool, came under scrutiny. Bernard Dixon reports.
  • Down the food chain
    - Current Biology 19(9):R347-R348 (2009)
    Fisheries are increasingly targeting smaller and more unusual species as traditional targets decline and the demand for feed for farmed fish increases. Nigel Williams reports.
  • Polar pressures
    - Current Biology 19(9):R349-R350 (2009)
    The Arctic ice is thinning and tourists are presenting a growing problem in the increasingly fragile Antarctic environment. Nigel Williams reports.
  • High-level twitter
    - Current Biology 19(9):R350-R351 (2009)
    A new study finds that a social bird responds to the position from which it receives information. Nigel Williams reports.
  • Panda rebuild
    - Current Biology 19(9):R351 (2009)
  • Michael Young
    - Current Biology 19(9):R352-R353 (2009)
  • Mauthner cells
    - Current Biology 19(9):R353-R355 (2009)
  • Orchestration of the immune response by dendritic cells
    - Current Biology 19(9):R355-R361 (2009)
  • A simple non-specific chemical signal mediates defence behaviour in a specialised ant–plant mutualism
    - Current Biology 19(9):R361-R362 (2009)
    Specialist 'plant-ants' defend their ant-plant hosts from herbivores in exchange for rewards, including shelter and food [1]. Many of these symbiotic associations are obligate mutualisms, in which ant fitness is strongly tied to host protection. Protection should be enhanced by efficient detection of attacking herbivores [1], [2] and [3]. How information about herbivore presence could be communicated from plant to ant has been little studied. In several systems, plant extracts have been shown to induce increased ant patrolling [2] and [3], but the compounds eliciting ant defence have never been identified. We have characterized the volatile compounds emitted by damaged leaves of a specialized ant-plant and demonstrated in field experiments the identity of chemicals that induce plant-protective behaviour.
  • Aging: Shall We Take the High Road?
    - Current Biology 19(9):R363-R364 (2009)
    For ectotherms, lifespan is increased at low temperature and decreased at high temperature. A new study in Caenorhabditis elegans shows that thermosensory neurons can counteract the effects of high temperature on lifespan by controlling the activity of a steroid signaling pathway.
  • Behavioural Ecology: Cuckolder Eggs Come First
    - Current Biology 19(9):R364-R366 (2009)
    In mixed paternity broods, extra-pair offspring often perform better than their maternal half-siblings. This has been interpreted as evidence for genetic benefits of female promiscuity, but a new study shows that the difference in fitness may be largely due to a non-genetic, maternal effect.
  • Animal Behaviour: Feeding the Superorganism
    - Current Biology 19(9):R366-R368 (2009)
    Insect societies are often described as superorganisms, and there are many functional parallels between organisms and superorganisms. Elegant work using ants shows that nutrient regulation, which occurs in many non-social animals, can also occur at the colony-level.
  • Mating-System Evolution: Genies from a Bottleneck
    - Current Biology 19(9):R369-R370 (2009)
    Evolutionary shifts from outcrossing to selfing have been frequent in plants, but little is known about how this occurs. Two new studies of the same species point to a recent bottleneck that coincided with one such shift.
  • Neurobiology: Reconstructing the Neural Control of Leg Coordination
    - Current Biology 19(9):R371-R373 (2009)
    Walking is adaptable because the timing of movements of individual legs can be varied while maintaining leg coordination. Recent work in stick insects shows that leg coordination set by interactions of pattern generating circuits can be overridden by sensory feedback.
  • Multisensory Integration: Frequency Tuning of Audio-Tactile Integration
    - Current Biology 19(9):R373-R375 (2009)
    Multisensory information can be crucial, yet in many circumstances we have little, if any, awareness of the effects of multisensory inputs on what appear to be entirely unisensory perceptions. A recent study shows robust effects of auditory input on tactile frequency discriminations and that this auditory cross-sensory interference has specific tuning.
  • Necrosis: C-Type Lectins Sense Cell Death
    - Current Biology 19(9):R375-R378 (2009)
    Recent studies have shown that C-type lectins, a family of surface receptors known to recognize microbial carbohydrate moieties, also sense products from dying cells and transduce inflammatory signals that modulate the immune system.
  • Social Learning: What Do Drosophila Have to Offer?
    - Current Biology 19(9):R378-R380 (2009)
    The recent finding that female Drosophila copy the mate-choice criteria of other females introduces a mainstream model species to the study of how animals use social information.
  • Signaling Pathways Regulating Zebrafish Lateral Line Development
    - Current Biology 19(9):R381-R386 (2009)
    The lateral line organ is a mechanosensory organ of fish and amphibians that detects changes in water flow. The lateral line organ of zebrafish has been used as a model for cell polarity and collective cell migration as well as hair cell loss and regeneration. A combination of genetic tools and live imaging has allowed dissection of signaling pathways that regulate these processes. Here, we summarize recent findings on the roles of the FGF, Wnt/beta-catenin, and Notch pathways in the initial formation of the posterior lateral line primordium, as well as during organ patterning, migration, cell fate specification and hair cell regeneration.
  • Regulation of the Longevity Response to Temperature by Thermosensory Neurons in Caenorhabditis elegans
    - Current Biology 19(9):715-722 (2009)
    Background Many ectotherms, including C. elegans, have shorter life spans at high temperature than at low temperature. High temperature is generally thought to increase the "rate of living" simply by increasing chemical reaction rates. In this study, we questioned this view and asked whether the temperature dependence of life span is subject to active regulation. Results We show that thermosensory neurons play a regulatory role in the temperature dependence of life span. Surprisingly, inhibiting the function of thermosensory neurons by mutation or laser ablation causes animals to have even shorter life spans at warm temperature. Thermosensory mutations shorten life span by decreasing expression of daf-9, a gene required for the synthesis of ligands that inhibit the DAF-12, a nuclear hormone receptor. The short life span of thermosensory mutants at warm temperature is completely suppressed by a daf-12(-) mutation. Conclusions Our data suggest that thermosensory neurons affect life span at warm temperature by changing the activity of a steroid-signaling pathway that affects longevity. We propose that this thermosensory system allows C. elegans to reduce the effect that warm temperature would otherwise have on processes that affect aging, something that warm-blooded animals do by controlling temperature itself.
  • aPKC Phosphorylates Miranda to Polarize Fate Determinants during Neuroblast Asymmetric Cell Division
    - Current Biology 19(9):723-729 (2009)
    Background Asymmetric cell divisions generate daughter cells with distinct fates by polarizing fate determinants into separate cortical domains. Atypical protein kinase C (aPKC) is an evolutionarily conserved regulator of cell polarity. In Drosophila neuroblasts, apically restricted aPKC is required for segregation of neuronal differentiation factors such as Numb and Miranda to the basal cortical domain. Whereas Numb is polarized by direct aPKC phosphorylation, Miranda asymmetry is thought to occur via a complicated cascade of repressive interactions (aPKC −| Lgl −| myosin II −| Miranda). Results Here we provide biochemical, cellular, and genetic data showing that aPKC directly phosphorylates Miranda to exclude it from the cortex and that Lgl antagonizes this activity. Miranda is phosphorylated by aPKC at several sites in its cortical localization domain and phosphorylation is necessary and sufficient for cortical displacement, suggesting that the repressive-cascade model is incorrect. In investigating key results that led to this model, we found that Y-27632, a Rho kinase inhibitor used to implicate myosin II, efficiently inhibits aPKC. Lgl3A, a nonphosphorylatable Lgl variant used to implicate Lgl in this process, inhibits the formation of apical aPKC crescents in neuroblasts. Furthermore, Lgl directly inhibits aPKC kinase activity. Conclusions Miranda polarization during neuroblast asymmetric cell division occurs by displacement from the apical cortex by direct aPKC phosphorylation. Rather than mediating Miranda cortical displacement, Lgl instead promotes aPKC asymmetry by regulating its activity. The role of myosin II in neuroblast polarization, if any, is unknown.
  • Public Versus Personal Information for Mate Copying in an Invertebrate
    - Current Biology 19(9):730-734 (2009)
    Organisms require information to make decisions about fitness-affecting resources, such as mates. Animals may extract "personal information" about potential mates by observing their physical characteristics or extract additional "public information" by observing their mating performance [1]. Mate copying by females [2], [3], [4], [5] and [6] is a form of public information use that may reduce uncertainty about male quality, allowing more adaptive choices [2]. Experimental studies have produced evidence that female mate copying occurs in several species of fish [3], birds [5], [6] and [7], and mammals [8], including humans [9]. We report the first evidence that a female invertebrate can exploit public information to select mates. In a first experiment, Drosophila melanogaster female prospectors increased their time in the attraction zones of poor-condition males, but not of good-condition males, after having observed them with a model female. This suggests that ! females appraised prospective mates by exploiting public information and did so mainly when it contrasted with personal information. In a second experiment, prospector females preferably mated with males of the color type they had previously observed copulating over males of the rejected color type, suggesting that female Drosophila can generalize socially learned information. The complexity of Drosophila decision-making suggests an unprecedented level of cognition in invertebrates. Our findings have implications for evolution given that socially learned mate preferences may lead to reproductive isolation, setting the stage for speciation [10].
  • Audiovisual Integration of Speech in a Bistable Illusion
    - Current Biology 19(9):735-739 (2009)
    Visible speech enhances the intelligibility of auditory speech when listening conditions are poor [1], and can modify the perception of otherwise perfectly audible utterances [2]. This audiovisual perception is our most natural form of communication and one of our most common multisensory phenomena. However, where and in what form the visual and auditory representations interact is still not completely understood. Although there are longstanding proposals that multisensory integration occurs relatively late in the speech-processing sequence [3], considerable neurophysiological evidence suggests that audiovisual interactions can occur in the brain stem and primary sensory cortices [4] and [5]. A difficulty testing such hypotheses is that when the degree of integration is manipulated experimentally, the visual and/or auditory stimulus conditions are drastically modified [6] and [7]; thus, the perceptual processing within a modality and the corresponding processing loads ! are affected [8]. Here, we used a bistable speech stimulus to examine the conditions under which there is a visual influence on auditory perception in speech. The results indicate that visual influences on auditory speech processing, at least for the McGurk illusion, necessitate the conscious perception of the visual speech gestures, thus supporting the hypothesis that multisensory speech integration is not completed in early processing stages.
  • Communal Nutrition in Ants
    - Current Biology 19(9):740-744 (2009)
    Studies on nonsocial insects have elucidated the regulatory strategies employed to meet nutritional demands [1], [2] and [3]. However, how social insects maintain the supply of an appropriate balance of nutrients at both a collective and an individual level remains unknown. Sociality complicates nutritional regulatory strategies [4], [5] and [6]. First, the food entering a colony is collected by a small number of workers, which need to adjust their harvesting strategy to the demands for nutrients among individuals within the colony [4], [5], [6] and [7]. Second, because carbohydrates are used by the workers and proteins consumed by the larvae [7], [8], [9], [10], [11], [12], [13] and [14], nutritional feedbacks emanating from both must exist and be integrated to determine food exploitation by foragers [4], [5], [6], [15] and [16]. Here, we show that foraging ants can solve nutritional challenges for the colony by making intricate adjustments to their feeding behavior a! nd nutrient processing, acting both as a collective mouth and gut. The amount and balance of nutrients collected and the precision of regulation depend on the presence of larvae in the colony. Ants improved the macronutrient balance of collected foods by extracting carbohydrates and ejecting proteins. Nevertheless, processing excess protein shortened life span—an effect that was greatly ameliorated in the presence of larvae.
  • Motion Aftereffects Transfer between Touch and Vision
    - Current Biology 19(9):745-750 (2009)
    Current views on multisensory motion integration assume separate substrates where visual motion perceptually dominates tactile motion [1] and [2]. However, recent neuroimaging findings demonstrate strong activation of visual motion processing areas by tactile stimuli [3], [4], [5] and [6], implying a potentially bidirectional relationship. To test the relationship between visual and tactile motion processing, we examined the transfer of motion aftereffects. In the well-known visual motion aftereffect, adapting to visual motion in one direction causes a subsequently presented stationary stimulus to be perceived as moving in the opposite direction [7] and [8]. The existence of motion aftereffects in the tactile domain was debated [9], [10] and [11], though robust tactile motion aftereffects have recently been demonstrated [12] and [13]. By using a motion adaptation paradigm, we found that repeated exposure to visual motion in a given direction produced a tactile motion a! ftereffect, the illusion of motion in the opponent direction across the finger pad. We also observed that repeated exposure to tactile motion induces a visual motion aftereffect, biasing the perceived direction of counterphase gratings. These crossmodal aftereffects, operating both from vision to touch and from touch to vision, present strong behavioral evidence that the processing of visual and tactile motion rely on shared representations that dynamically impact modality-specific perception.
  • Seminal Fluid Protein Allocation and Male Reproductive Success
    - Current Biology 19(9):751-757 (2009)
    Postcopulatory sexual selection can select for sperm allocation strategies in males [1] and [2], but males should also strategically allocate nonsperm components of the ejaculate [3] and [4], such as seminal fluid proteins (Sfps). Sfps can influence the extent of postcopulatory sexual selection [5], [6] and [7], but little is known of the causes or consequences of quantitative variation in Sfp production and transfer. Using Drosophila melanogaster, we demonstrate that Sfps are strategically allocated to females in response to the potential level of sperm competition. We also show that males who can produce and transfer larger quantities of specific Sfps have a significant competitive advantage. When males were exposed to a competitor male, matings were longer and more of two key Sfps, sex peptide [8] and ovulin [9], were transferred, indicating strategic allocation of Sfps. Males selected for large accessory glands (a major site of Sfp synthesis) produced and transferr! ed significantly more sex peptide, but not more ovulin. Males with large accessory glands also had significantly increased competitive reproductive success. Our results show that quantitative variation in specific Sfps is likely to play an important role in postcopulatory sexual selection and that investment in Sfp production is essential for male fitness in a competitive environment.
  • ICIS and Aurora B Coregulate the Microtubule Depolymerase Kif2a
    - Current Biology 19(9):758-763 (2009)
    Kinesins in the mitotic spindle play major roles in determining spindle shape, size, and bipolarity, although specific regulation of these kinesins at distinct locations on the spindle is poorly understood. So that the forces that are required for spindle bipolarity are balanced, microtubule-depolymerizing kinesins are tightly regulated. Aurora B kinase phosphorylates the neck regions of the kinesin-13 family microtubule depolymerases Kif2a and mitotic centromere-associated kinesin (MCAK) and inhibits their depolymerase activities. How they are reactivated and how this is controlled independently on different kinetochore fibers is unknown. We show that inner centromere Kin-I stimulator (ICIS), which stimulates the related depolymerase MCAK, can reactivate Kif2a after Aurora B inhibition. When antibodies that block the ability of ICIS to activate Kif2a are injected into cells, monopolar spindles are generated. This phenotype is rescued by coinjection of anti-Nuf2 antibo! dies. We have performed a structure-function analysis of the ICIS protein and find that the N terminus of ICIS binds Aurora B and its regulators INCENP and TD60, whereas a central region binds MCAK, Kif2a, and microtubules, suggesting a scaffold function for ICIS. These data argue that ICIS and the chromosomal passenger complex (CPC) regulate Kif2a depolymerase activity.
  • Host Mixing and Disease Emergence
    - Current Biology 19(9):764-767 (2009)
    Recent cases of emergent diseases have renewed interest in the evolutionary and ecological mechanisms that promote parasite adaptation to novel hosts [1], [2], [3], [4], [5] and [6]. Crucial to adaptation is the degree of mixing of original, susceptible hosts, and novel hosts. An increase in the frequency of the original host has two opposing effects on adaptation: an increase in the supply of mutant pathogens with improved performance on the novel host [7], [8] and [9]; and reduced selection to infect novel hosts, caused by fitness costs commonly observed to be associated with host switching [10], [11], [12], [13], [14], [15], [16] and [17]. The probability of disease emergence will therefore peak at intermediate frequencies of the original host. We tested these predictions by following the evolution of a virus grown under a range of different frequencies of susceptible (original) and resistant (novel) host bacteria. Viruses that evolved to infect resistant hosts were! only detected when susceptible hosts were at frequencies between 0.1% and 1%. Subsequent experiments supported the predictions that there was reduced selection and mutation supply at higher and lower frequencies, respectively. These results suggest that adaptation to novel hosts can occur only under very specific ecological conditions, and that small changes in contact rates between host species might help to mitigate disease emergence.
  • Bcl-2 Proteins EGL-1 and CED-9 Do Not Regulate Mitochondrial Fission or Fusion in Caenorhabditis elegans
    - Current Biology 19(9):768-773 (2009)
    The Bcl-2 family proteins are critical apoptosis regulators that associate with mitochondria and control the activation of caspases. Recently, both mammalian and C. elegans Bcl-2 proteins have been implicated in controlling mitochondrial fusion and fission processes in both living and apoptotic cells. To better understand the potential roles of Bcl-2 family proteins in regulating mitochondrial dynamics, we carried out a detailed analysis of mitochondria in animals that either lose or have increased activity of egl-1 and ced-9, two Bcl-2 family genes that induce and inhibit apoptosis in C. elegans, respectively. Unexpectedly, we found that loss of egl-1 or ced-9, or overexpression of their gene products, had no apparent effect on mitochondrial connectivity or mitochondrial size. Moreover, loss of ced-9 did not affect the mitochondrial morphology observed in a drp-1 mutant, in which mitochondrial fusion occurs but mitochondrial fission is defective, or in a fzo-1 mutant,! in which mitochondrial fission occurs but mitochondrial fusion is restricted, suggesting that ced-9 is not required for either the mitochondrial fission or fusion process in C. elegans. Taken together, our results argue against an evolutionarily conserved role for Bcl-2 proteins in regulating mitochondrial fission and fusion.
  • Five siRNAs Targeting Three SNPs May Provide Therapy for Three-Quarters of Huntington's Disease Patients
    - Current Biology 19(9):774-778 (2009)
    Among dominant neurodegenerative disorders, Huntington's disease (HD) is perhaps the best candidate for treatment with small interfering RNAs (siRNAs) [1], [2], [3], [4], [5], [6], [7], [8] and [9]. Invariably fatal, HD is caused by expansion of a CAG repeat in the Huntingtin gene, creating an extended polyglutamine tract that makes the Huntingtin protein toxic [10]. Silencing mutant Huntingtin messenger RNA (mRNA) should provide therapeutic benefit, but normal Huntingtin likely contributes to neuronal function [11], [12] and [13]. No siRNA strategy can yet distinguish among the normal and disease Huntingtin alleles and other mRNAs containing CAG repeats [14]. siRNAs targeting the disease isoform of a heterozygous single-nucleotide polymorphism (SNP) in Huntingtin provide an alternative [15], [16], [17], [18] and [19]. We sequenced 22 predicted SNP sites in 225 human samples corresponding to HD and control subjects. We find that 48% of our patient population is heteroz! ygous at a single SNP site; one isoform of this SNP is associated with HD. Several other SNP sites are frequently heterozygous. Consequently, five allele-specific siRNAs, corresponding to just three SNP sites, could be used to treat three-quarters of the United States and European HD patient populations. We have designed and validated selective siRNAs for the three SNP sites, laying the foundation for allele-specific RNA interference (RNAi) therapy for HD.
  • A Novel Peptide Mediates Aggregation and Migration of Hemocytes from an Insect
    - Current Biology 19(9):779-785 (2009)
    Insect blood cells (hemocytes) comprise an essential arm of the immune system [1], [2], [3], [4], [5], [6] and [7]. Several factors mediating recognition and phagocytosis of foreign intruders by hemocytes have been identified, but the mechanisms regulating hemocyte movement remain fragmentary. Embryonic hemocytes from Drosophila migrate along stereotypical routes in response to chemotactic signals from PVF ligands, members of the platelet-derived growth factor family [8], [9], [10], [11] and [12]. Embryonic and larval hemocytes also accumulate at external wounds [11], [12] and [13], but PVFs are not required for this response, suggesting involvement by other, unknown factors. Here we report the identification of hemocyte chemotactic peptide (HCP) from the moth Pseudaletia separata and present evidence that it stimulates aggregation and directed movement of phagocytic hemocytes. Spatiotemporal studies revealed that HCP is expressed in both epidermal cells and hemocytes,! whereas structure-function studies identified post-translational modifications important for activity. HCP also shares similarities with another group of cytokines from moths called ENF peptides [14], [15], [16] and [17]. Taken together, our results identify HCP as a chemotactic cytokine that enhances clotting at wound sites in larvae.
  • In Vivo Detection of Residues Required for Ligand-Selective Activation of the S-Locus Receptor in Arabidopsis
    - Current Biology 19(9):786-791 (2009)
    The self-incompatibility response of crucifers is a barrier to fertilization in which arrest of pollen tube development is mediated by allele-specific interactions between polymorphic receptors and ligands encoded by the S-locus haplotype. Activation of stigma-expressed S-locus receptor kinase (SRK) [1] by pollen coat-localized S-locus cysteine-rich (SCR) ligand [2], [3], [4] and [5] and the resulting rejection of pollen occurs only if receptor and ligand are encoded by the same S haplotype [4], [6], [7] and [8]. To identify residues within the SRK extracellular domain (eSRK) that are required for its ligand-selective activation, we assayed chimeric receptors and receptor variants containing substitutions at polymorphic sites in Arabidopsis thaliana [9] and [10]. We show that only a small number of the not, vert, similar100 polymorphic residues in eSRK are required for ligand-specific activation of self-incompatibility in vivo. These essential residues occur in two non! contiguous clusters located at equivalent positions in the two variants tested. They also correspond to sites showing elevated levels of substitutions in other SRKs, suggesting that these residues could define self-incompatibility specificity in most SRKs. The results demonstrate that the majority of eSRK residues that show signals of positive selection and previously surmised to function as specificity determinants are not essential for specificity in the SRK-SCR interaction.
  • Maternal Effects Contribute to the Superior Performance of Extra-Pair Offspring
    - Current Biology 19(9):792-797 (2009)
    The explanation for extra-pair mating in female birds remains poorly understood and contentious [1], [2], [3], [4], [5], [6] and [7]. Several leading hypotheses propose that females benefit indirectly by enhancing the genetic quality of their offspring, through good genes or genetic compatibility effects [1], [8] and [9]. Supporting this idea, recent studies have identified a range of fitness-related traits for which extra-pair offspring (EPO) are superior to their within-pair (WP) half-siblings [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20] and [21]. However, such performance differences may result from nongenetic maternal effects if EPO are positioned earlier in the laying order and benefit from the advantages of earlier hatching [22] and [23]. Here we show that EPO are larger, heavier, and more likely to fledge than their WP half-siblings in a population of blue tits, Cyanistes caeruleus. However, extra-pair paternity declined markedly with laying ! order, resulting in EPO generally hatching earlier. After correcting for variation in hatch time, none of the observed disparities between EPO and their WP half-siblings remained significant. These findings indicate that phenotypic comparisons between maternal half-siblings must consider potential hatching-order effects and suggest that the evidence for genetic benefits from extra-pair copulation may be less compelling than currently accepted. Moreover, the overrepresentation of EPO early in the laying order may help explain female extra-pair mating.
  • Enhanced Arrestin Facilitates Recovery and Protects Rods Lacking Rhodopsin Phosphorylation
    - Current Biology 19(9):798 (2009)
  • Regulation of the Longevity Response to Temperature by Thermosensory Neurons in Caenorhabditis elegans
    - Current Biology 19(9):798 (2009)

Thursday, March 17, 2011

Hot off the presses! Mar 18 Cell

The Mar 18 issue of the Cell is now up on Pubget (About Cell): 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:

  • In This Issue
    - cell 144(6):827, 829 (2011)
    In thinking about complexity, it's frequently invoked that the whole is greater than the sum of its parts. This notion serves as one of the motivating principles of systems biology, which seeks to understand the emergent properties of complex biological systems. Among many biologists, systems biology is also synonymous with the use of particular approaches, including high-throughput techniques, large-scale integration of datasets, and computational modeling to probe system behaviors. There is indeed little doubt that the recent growth of the field has been fueled by the massive expansion in the amount of data being generated in the biological sciences—first from genome sequencing and more recently from such sources as transcriptomics, proteomics, and high-throughput imaging. Given this rising tide of data, there is an urgent need for new ways of analyzing large datasets and for conceptualizing biological complexity. It is in this context that we present our 2011 Spec! ial Review Issue on systems biology. The overarching goal of this collection is to highlight biological insights revealed by the quantitative and computational approaches associated with systems biology. To accomplish this, the issue includes topics that span vastly different size and time scales, from protein-protein interactions to disease models, from transcriptional dynamics to evolutionary processes. For the issue's diversity, depth, and thought-provoking insights, we would like to thank the many distinguished authors and reviewers who generously contributed their time and effort. In reading the issue, we hope that you will find that the collection, like biological systems, is more than the sum of its individual parts, providing a new perspective on this rapidly changing field.
  • Control of Biomolecule Abundance
    - cell 144(6):831, 833 (2011)
    Like any company that manages its resources with an eye on profitability, a cell regulates its constituent biomolecules, compensating for changes in internal function, external conditions, and sector or organismal trends. This issue's Select focuses on new findings that reveal broad insights into how dynamic changes in RNAs and proteins are made and how those changes impact cellular function and fitness.
  • Systems Biology: What's the Next Challenge?
    - cell 144(6):837-838 (2011)
  • Systems Biology: Evolving into the Mainstream
    - cell 144(6):839-841 (2011)
    Systems approaches to biology are steadily widening their reach, but the road to integration and acceptance has been fraught with skepticism and technical hurdles. Interdisciplinary research teams at systems biology centers around the globe are working to win over the critics.
  • Don't Fear the Command Line!
    - cell 144(6):842-843 (2011)
  • Network News: Innovations in 21st Century Systems Biology
    - cell 144(6):844-849 (2011)
    A decade ago, seminal perspectives and papers set a strong vision for the field of systems biology, and a number of these themes have flourished. Here, we describe key technologies and insights that have elucidated the evolution, architecture, and function of cellular networks, ultimately leading to the first predictive genome-scale regulatory and metabolic models of organisms. Can systems approaches bridge the gap between correlative analysis and mechanistic insights?
  • The Cell in an Era of Systems Biology
    - cell 144(6):850-854 (2011)
    The increasing use of high-throughput technologies and computational modeling is revealing new levels of biological function and organization. How are these features of systems biology influencing our view of the cell?
  • Informing Biological Design by Integration of Systems and Synthetic Biology
    - cell 144(6):855-859 (2011)
    Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields.
  • Boosting Signal-to-Noise in Complex Biology: Prior Knowledge Is Power
    - cell 144(6):860-863 (2011)
    A major difficulty in the analysis of complex biological systems is dealing with the low signal-to-noise inherent to nearly all large biological datasets. We discuss powerful bioinformatic concepts for boosting signal-to-noise through external knowledge incorporated in processing units we call filters and integrators. These concepts are illustrated in four landmark studies that have provided model implementations of filters, integrators, or both.
  • Principles and Strategies for Developing Network Models in Cancer
    - cell 144(6):864-873 (2011)
    The flood of genome-wide data generated by high-throughput technologies currently provides biologists with an unprecedented opportunity: to manipulate, query, and reconstruct functional molecular networks of cells. Here, we outline three underlying principles and six strategies to infer network models from genomic data. Then, using cancer as an example, we describe experimental and computational approaches to infer "differential" networks that can identify genes and processes driving disease phenotypes. In conclusion, we discuss how a network-level understanding of cancer can be used to predict drug response and guide therapeutics.
  • Modeling the Cell Cycle: Why Do Certain Circuits Oscillate?
    - cell 144(6):874-885 (2011)
    Computational modeling and the theory of nonlinear dynamical systems allow one to not simply describe the events of the cell cycle, but also to understand why these events occur, just as the theory of gravitation allows one to understand why cannonballs fly in parabolic arcs. The simplest examples of the eukaryotic cell cycle operate like autonomous oscillators. Here, we present the basic theory of oscillatory biochemical circuits in the context of the Xenopus embryonic cell cycle. We examine Boolean models, delay differential equation models, and especially ordinary differential equation (ODE) models. For ODE models, we explore what it takes to get oscillations out of two simple types of circuits (negative feedback loops and coupled positive and negative feedback loops). Finally, we review the procedures of linear stability analysis, which allow one to determine whether a given ODE model and a particular set of kinetic parameters will produce oscillations.
  • Impulse Control: Temporal Dynamics in Gene Transcription
    - cell 144(6):886-896 (2011)
    Regulatory circuits controlling gene expression constantly rewire to adapt to environmental stimuli, differentiation cues, and disease. We review our current understanding of the temporal dynamics of gene expression in eukaryotes and prokaryotes and the molecular mechanisms that shape them. We delineate several prototypical temporal patterns, including "impulse" (or single-pulse) patterns in response to transient environmental stimuli, sustained (or state-transitioning) patterns in response to developmental cues, and oscillating patterns. We focus on impulse responses and their higher-order temporal organization in regulons and cascades and describe how core protein circuits and cis-regulatory sequences in promoters integrate with chromatin architecture to generate these responses.
  • Signaling from the Living Plasma Membrane
    - cell 144(6):897-909 (2011)
    Our understanding of the plasma membrane, once viewed simply as a static barrier, has been revolutionized to encompass a complex, dynamic organelle that integrates the cell with its extracellular environment. Here, we discuss how bidirectional signaling across the plasma membrane is achieved by striking a delicate balance between restriction and propagation of information over different scales of time and space and how underlying dynamic mechanisms give rise to rich, context-dependent signaling responses. In this Review, we show how computer simulations can generate counterintuitive predictions about the spatial organization of these complex processes.
  • Cellular Decision Making and Biological Noise: From Microbes to Mammals
    - cell 144(6):910-925 (2011)
    Cellular decision making is the process whereby cells assume different, functionally important and heritable fates without an associated genetic or environmental difference. Such stochastic cell fate decisions generate nongenetic cellular diversity, which may be critical for metazoan development as well as optimized microbial resource utilization and survival in a fluctuating, frequently stressful environment. Here, we review several examples of cellular decision making from viruses, bacteria, yeast, lower metazoans, and mammals, highlighting the role of regulatory network structure and molecular noise. We propose that cellular decision making is one of at least three key processes underlying development at various scales of biological organization.
  • Measuring and Modeling Apoptosis in Single Cells
    - cell 144(6):926-939 (2011)
    Cell death plays an essential role in the development of tissues and organisms, the etiology of disease, and the responses of cells to therapeutic drugs. Here we review progress made over the last decade in using mathematical models and quantitative, often single-cell, data to study apoptosis. We discuss the delay that follows exposure of cells to prodeath stimuli, control of mitochondrial outer membrane permeabilization, switch-like activation of effector caspases, and variability in the timing and probability of death from one cell to the next. Finally, we discuss challenges facing the fields of biochemical modeling and systems pharmacology.
  • Control of the Embryonic Stem Cell State
    - cell 144(6):940-954 (2011)
    Embryonic stem cells and induced pluripotent stem cells hold great promise for regenerative medicine. These cells can be propagated in culture in an undifferentiated state but can be induced to differentiate into specialized cell types. Moreover, these cells provide a powerful model system for studies of cellular identity and early mammalian development. Recent studies have provided insights into the transcriptional control of embryonic stem cell state, including the regulatory circuitry underlying pluripotency. These studies have, as a consequence, uncovered fundamental mechanisms that control mammalian gene expression, connect gene expression to chromosome structure, and contribute to human disease.
  • Pattern, Growth, and Control
    - cell 144(6):955-969 (2011)
    Systems biology seeks not only to discover the machinery of life but to understand how such machinery is used for control, i.e., for regulation that achieves or maintains a desired, useful end. This sort of goal-directed, engineering-centered approach also has deep historical roots in developmental biology. Not surprisingly, developmental biology is currently enjoying an influx of ideas and methods from systems biology. This Review highlights current efforts to elucidate design principles underlying the engineering objectives of robustness, precision, and scaling as they relate to the developmental control of growth and pattern formation. Examples from vertebrate and invertebrate development are used to illustrate general lessons, including the value of integral feedback in achieving set-point control; the usefulness of self-organizing behavior; the importance of recognizing and appropriately handling noise; and the absence of "free lunch." By illuminating such pri! nciples, systems biology is helping to create a functional framework within which to make sense of the mechanistic complexity of organismal development.
  • Evolution of Gene Regulatory Networks Controlling Body Plan Development
    - cell 144(6):970-985 (2011)
    Evolutionary change in animal morphology results from alteration of the functional organization of the gene regulatory networks (GRNs) that control development of the body plan. A major mechanism of evolutionary change in GRN structure is alteration of cis-regulatory modules that determine regulatory gene expression. Here we consider the causes and consequences of GRN evolution. Although some GRN subcircuits are of great antiquity, other aspects are highly flexible and thus in any given genome more recent. This mosaic view of the evolution of GRN structure explains major aspects of evolutionary process, such as hierarchical phylogeny and discontinuities of paleontological change.
  • Interactome Networks and Human Disease
    - cell 144(6):986-998 (2011)
    Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here, we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease.
  • SnapShot: Protein-Protein Interaction Networks
    - cell 144(6):1000-1000.e1 (2011)

Monday, July 18, 2011

Hot off the presses! Jul 19 Dev Cell

The Jul 19 issue of the Dev Cell is now up on Pubget (About Dev Cell): 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:

  • A Decade of Developmental Cell
    - Dev Cell 21(1):1 (2011)
  • Shifting Patterns: Merging Molecules, Morphogens, Motility, and Methodology
    - Dev Cell 21(1):2-4 (2011)
    We highlight crucial technological progress of the past ten years that permits quantitative analysis of cellular behavior. Adapting these methods to the study of embryogenesis will be essential to advance our understanding of development in the coming decade.
  • Bridging Structure and Process in Developmental Biology through New Imaging Technologies
    - Dev Cell 21(1):5-10 (2011)
    Many unexpected discoveries in developmental biology have depended on advancement of imaging technologies to visualize developmental processes as they unfold across multiple spatial and temporal scales. This essay surveys the recent advances in imaging, highlighting emerging capabilities with an eye toward those poised to have the greatest impact on developmental biology.
  • Can a Systems Perspective Help Us Appreciate the Biological Meaning of Small Effects?
    - Dev Cell 21(1):11-13 (2011)
    The study of dramatic phenotypes has been pivotal to elucidating biological mechanisms. Effectively approaching low-magnitude quantitative phenotypes, a common outcome of systematic loss-of-function studies, will be critical for understanding how individual components of cells interact to generate functioning systems.
  • Beyond Stereospecificity: Liquids and Mesoscale Organization of Cytoplasm
    - Dev Cell 21(1):14-16 (2011)
    The cytoplasm is not a homogenous solution but instead consists of large dynamic assemblies that arise from transient molecular interactions. Some of these structures have been shown to represent liquid droplets of concentrated protein and RNA. Liquid phase separation of cytoplasm may be a fundamental principle of cytoplasmic organization.
  • Enhancers: From Developmental Genetics to the Genetics of Common Human Disease
    - Dev Cell 21(1):17-19 (2011)
    In mammals, long-range gene regulation became apparent through simple Mendelian disease genetics in human and developmental genetics in the mouse. Can the insights into gene control, provided by the study of these enhancers, help us understand the functional significance of sequence variation associated with common/complex human disease and quantitative traits?
  • The Impact of Developmental Biology on Pluripotent Stem Cell Research: Successes and Challenges
    - Dev Cell 21(1):20-23 (2011)
    Research on developmental pathways in model organisms provides key information on how to isolate, maintain, and differentiate human pluripotent stem cells. However, details of developmental pathways differ even across mammalian species. Full realization of the potential of stem cells will require more direct studies of human or primate developmental biology.
  • Self-Organization of Animal Tissues: Cadherin-Mediated Processes
    - Dev Cell 21(1):24-26 (2011)
    Animal cells are capable of self-organizing into multicellular tissues, and important players in this process are cadherin receptors. Through the homophilic interactions of cadherins, cells adhere to one another. Cells can also dynamically change shapes or positions within tissue layers via cadherin-cytoskeleton interactions and become arranged into various architectures.
  • Taking a Developmental Perspective on Systems Biology
    - Dev Cell 21(1):27-28 (2011)
    Developmental biologists understand how different cells contribute to organ function and how cellular components work together to produce a phenotype. These insights need to be more widely applied to systems biology. Another challenge is to incorporate real-time imaging and develop computational approaches to model biological phenomena in four dimensions.
  • Drosophila as a Model for Interorgan Communication: Lessons from Studies on Energy Homeostasis
    - Dev Cell 21(1):29-31 (2011)
    Current studies of physiological communication between Drosophila organs are beginning to address the fundamental problem of how nutrients regulate organismal growth, stem cell behavior, immunity, and aging. Advances in the Drosophila genetic tool kit will allow the design of genetic screens to systematically identify factors involved in organ communication.
  • Protein Evolution in Cell and Tissue Development: Going Beyond Sequence and Transcriptional Analysis
    - Dev Cell 21(1):32-34 (2011)
    Studies of animal evolution often focus on sequence and transcriptional analysis, based on an assumption that the evolution of development is driven by changes in gene expression. We argue that biochemical and cell biological approaches are also required, because sequence-conserved proteins can have different biochemical, cellular, and developmental properties.
  • A Hitchhiker's Guide to Mechanobiology
    - Dev Cell 21(1):35-47 (2011)
    More than a century ago, it was proposed that mechanical forces could drive tissue formation. However, only recently with the advent of enabling biophysical and molecular technologies are we beginning to understand how individual cells transduce mechanical force into biochemical signals. In turn, this knowledge of mechanotransduction at the cellular level is beginning to clarify the role of mechanics in patterning processes during embryonic development. In this perspective, we will discuss current mechanotransduction paradigms, along with the technologies that have shaped the field of mechanobiology.
  • Forward and Reverse Genetic Approaches for the Analysis of Vertebrate Development in the Zebrafish
    - Dev Cell 21(1):48-64 (2011)
    The development of facile forward and reverse genetic approaches has propelled the deconvolution of gene function in biology. While the origins of these techniques reside in the study of single-cell or invertebrate organisms, in many cases these approaches have been applied to vertebrate model systems to gain powerful insights into gene function during embryonic development. This perspective provides a summary of the major forward and reverse genetic approaches that have contributed to the study of vertebrate gene function in zebrafish, which has become an established model for the study of animal development.
  • Developmental Genetics and New Sequencing Technologies: The Rise of Nonmodel Organisms
    - Dev Cell 21(1):65-76 (2011)
    Much of developmental biology in the past decades has been driven by forward genetic studies in a few model organisms. We review recent work with relatives of these species, motivated by a desire to understand the evolutionary and ecological context for morphological innovation. Unfortunately, despite a number of shining examples, progress in nonmodel systems has often been slow. The current revolution in DNA sequencing has, however, enormous potential in extending the reach of genetics. We discuss how developmental biology will benefit from these advances, particularly by increasing the universe of study species.
  • The ESCRT Pathway
    - Dev Cell 21(1):77-91 (2011)
    Multivesicular bodies (MVBs) deliver cargo destined for degradation to the vacuole or lysosome. The ESCRT (endosomal sorting complex required for transport) pathway is a key mediator of MVB biogenesis, but it also plays critical roles in retroviral budding and cytokinetic abscission. Despite these diverse roles, the ESCRT pathway can be simply seen as a cargo-recognition and membrane-sculpting machine viewable from three distinct perspectives: (1) the ESCRT proteins themselves, (2) the cargo they sort, and (3) the membrane they deform. Here, we review ESCRT function from these perspectives and discuss how ESCRTs may drive vesicle budding.
  • Mitochondria in Apoptosis: Bcl-2 Family Members and Mitochondrial Dynamics
    - Dev Cell 21(1):92-101 (2011)
    Mitochondria participate in apoptosis through a range of mechanisms that vary between vertebrates and invertebrates. In vertebrates, they release intermembrane space proteins, such as cytochrome c, to promote caspase activation in the cytosol. This process is the result of the loss of integrity of the outer mitochondrial membrane caused by proapoptotic members of the Bcl-2 family. This event is always accompanied by a fissioning of the organelle. Fission of mitochondria has also been reported to participate in apoptosis in Drosophila and Caenorhabditis elegans. However, in these organisms, mitochondrial membrane permeabilization does not occur and the mechanism by which mitochondrial dynamics participates in cell death remains elusive.
  • Mitotic Spindle Orientation in Asymmetric and Symmetric Cell Divisions during Animal Development
    - Dev Cell 21(1):102-119 (2011)
    The orientation of the mitotic spindle has been proposed to control cell fate choices, tissue architecture, and tissue morphogenesis. Here, we review the mechanisms regulating the orientation of the axis of division and cell fate choices in classical models of asymmetric cell division. We then discuss the mechanisms of mitotic spindle orientation in symmetric cell divisions and its possible implications in tissue morphogenesis. Many recent studies show that future advances in the field of mitotic spindle orientation will arise from combinations of physical perturbation and modeling with classical genetics and developmental biology approaches.
  • Planar Cell Polarity: Coordinating Morphogenetic Cell Behaviors with Embryonic Polarity
    - Dev Cell 21(1):120-133 (2011)
    Planar cell polarization entails establishment of cellular asymmetries within the tissue plane. An evolutionarily conserved planar cell polarity (PCP) signaling system employs intra- and intercellular feedback interactions between its core components, including Frizzled, Van Gogh, Flamingo, Prickle, and Dishevelled, to establish their characteristic asymmetric intracellular distributions and coordinate planar polarity of cell populations. By translating global patterning information into asymmetries of cell membranes and intracellular organelles, PCP signaling coordinates morphogenetic behaviors of individual cells and cell populations with the embryonic polarity. In vertebrates, by polarizing cilia in the node/Kupffer's vesicle, PCP signaling links the anteroposterior to left-right embryonic polarity.
  • Notch Ligand Ubiquitylation: What Is It Good For?
    - Dev Cell 21(1):134-144 (2011)
    In the first volume of Developmental Cell, it was reported that the classic Drosophila neurogenic gene neuralized encodes a ubiquitin ligase that monoubiquitylates the Notch ligand Delta, thus promoting Delta endocytosis. A requirement for ligand internalization by the signal-sending cell, although counterintuitive, remains to date a feature unique to Notch signaling. Ten years and many ubiquitin ligases later, we discuss sequels to these three papers with an eye toward reviewing the development of ideas for how ligand ubiquitylation and endocytosis propel Notch signaling.
  • Extracellular Movement of Signaling Molecules
    - Dev Cell 21(1):145-158 (2011)
    Extracellular signaling molecules have crucial roles in development and homeostasis, and their incorrect deployment can lead to developmental defects and disease states. Signaling molecules are released from sending cells, travel to target cells, and act over length scales of several orders of magnitude, from morphogen-mediated patterning of small developmental fields to hormonal signaling throughout the organism. We discuss how signals are modified and assembled for transport, which routes they take to reach their targets, and how their range is affected by mobility and stability.
  • Drosophila Stem Cell Niches: A Decade of Discovery Suggests a Unified View of Stem Cell Regulation
    - Dev Cell 21(1):159-171 (2011)
    The past decade of research on Drosophila stem cells and niches has provided key insights. Fly stem cells do not occupy a special "state" based on novel "stem cell genes" but resemble transiently arrested tissue progenitors. Moreover, individual stem cells and downstream progenitors are highly dynamic and dispensable, not tissue bulwarks. Niches, rather than fixed cell lineages, ensure tissue health by holding stem cells and repressing cell differentiation inside, but not outside. We review the five best-understood adult Drosophila stem cells and argue that the fundamental biology of stem cells and niches is conserved between Drosophila and mice.
  • The Cellular Basis for Animal Regeneration
    - Dev Cell 21(1):172-185 (2011)
    The ability of animals to regenerate missing parts is a dramatic and poorly understood aspect of biology. The sources of new cells for these regenerative phenomena have been sought for decades. Recent advances involving cell fate tracking in complex tissues have shed new light on the cellular underpinnings of regeneration in Hydra, planarians, zebrafish, Xenopus, and Axolotl. Planarians accomplish regeneration with use of adult pluripotent stem cells, whereas several vertebrates utilize a collection of lineage-restricted progenitors from different tissues. Together, an array of cellular strategies—from pluripotent stem cells to tissue-specific stem cells and dedifferentiation—are utilized for regeneration.

Thursday, July 16, 2009

Hot off the presses! Aug 01 Nat Rev Genet

The Aug 01 issue of the Nat Rev Genet is now up on Pubget (About Nat Rev Genet): 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: