PLoS Biology: New Articles

Mechanisms and Evolutionary Patterns of Mammalian and Avian Dosage Compensation

2012-05-15T21:00:00Z

by Philippe Julien, David Brawand, Magali Soumillon, Anamaria Necsulea, Angélica Liechti, Frédéric Schütz, Tasman Daish, Frank Grützner, Henrik Kaessmann

As a result of sex chromosome differentiation from ancestral autosomes, male mammalian cells only contain one X chromosome. It has long been hypothesized that X-linked gene expression levels have become doubled in males to restore the original transcriptional output, and that the resulting X overexpression in females then drove the evolution of X inactivation (XCI). However, this model has never been directly tested and patterns and mechanisms of dosage compensation across different mammals and birds generally remain little understood. Here we trace the evolution of dosage compensation using extensive transcriptome data from males and females representing all major mammalian lineages and birds. Our analyses suggest that the X has become globally upregulated in marsupials, whereas we do not detect a global upregulation of this chromosome in placental mammals. However, we find that a subset of autosomal genes interacting with X-linked genes have become downregulated in placentals upon the emergence of sex chromosomes. Thus, different driving forces may underlie the evolution of XCI and the highly efficient equilibration of X expression levels between the sexes observed for both of these lineages. In the egg-laying monotremes and birds, which have partially homologous sex chromosome systems, partial upregulation of the X (Z in birds) evolved but is largely restricted to the heterogametic sex, which provides an explanation for the partially sex-biased X (Z) expression and lack of global inactivation mechanisms in these lineages. Our findings suggest that dosage reductions imposed by sex chromosome differentiation events in amniotes were resolved in strikingly different ways.

Species Interactions Alter Evolutionary Responses to a Novel Environment

2012-05-15T21:00:00Z

by Diane Lawrence, Francesca Fiegna, Volker Behrends, Jacob G. Bundy, Albert B. Phillimore, Thomas Bell, Timothy G. Barraclough

Studies of evolutionary responses to novel environments typically consider single species or perhaps pairs of interacting species. However, all organisms co-occur with many other species, resulting in evolutionary dynamics that might not match those predicted using single species approaches. Recent theories predict that species interactions in diverse systems can influence how component species evolve in response to environmental change. In turn, evolution might have consequences for ecosystem functioning. We used experimental communities of five bacterial species to show that species interactions have a major impact on adaptation to a novel environment in the laboratory. Species in communities diverged in their use of resources compared with the same species in monocultures and evolved to use waste products generated by other species. This generally led to a trade-off between adaptation to the abiotic and biotic components of the environment, such that species evolving in communities had lower growth rates when assayed in the absence of other species. Based on growth assays and on nuclear magnetic resonance (NMR) spectroscopy of resource use, all species evolved more in communities than they did in monocultures. The evolutionary changes had significant repercussions for the functioning of these experimental ecosystems: communities reassembled from isolates that had evolved in polyculture were more productive than those reassembled from isolates that had evolved in monoculture. Our results show that the way in which species adapt to new environments depends critically on the biotic environment of co-occurring species. Moreover, predicting how functioning of complex ecosystems will respond to an environmental change requires knowing how species interactions will evolve.

Human Origins and the Search for “Missing Links”

2012-05-15T21:00:00Z

by Johannes Krause

Adaptive Evolution in Ecological Communities

2012-05-15T21:00:00Z

by Martin M. Turcotte, Michael S. C. Corrin, Marc T. J. Johnson

Understanding how natural selection drives evolution is a key challenge in evolutionary biology. Most studies of adaptation focus on how a single environmental factor, such as increased temperature, affects evolution within a single species. The biological relevance of these experiments is limited because nature is infinitely more complex. Most species are embedded within communities containing many species that interact with one another and the physical environment. To understand the evolutionary significance of such ecological complexity, experiments must test the evolutionary impact of interactions among multiple species during adaptation. Here we highlight an experiment that manipulates species composition and tracks evolutionary responses within each species, while testing for the mechanisms by which species interact and adapt to their environment. We also discuss limitations of previous studies of adaptive evolution and emphasize how an experimental evolution approach can circumvent such shortcomings. Understanding how community composition acts as a selective force will improve our ability to predict how species adapt to natural and human-induced environmental change.

Bet Hedging in Yeast by Heterogeneous, Age-Correlated Expression of a Stress Protectant

2012-05-08T21:00:00Z

by Sasha F. Levy, Naomi Ziv, Mark L. Siegal

Genetically identical cells grown in the same culture display striking cell-to-cell heterogeneity in gene expression and other traits. A crucial challenge is to understand how much of this heterogeneity reflects the noise tolerance of a robust system and how much serves a biological function. In bacteria, stochastic gene expression results in cell-to-cell heterogeneity that might serve as a bet-hedging mechanism, allowing a few cells to survive through an antimicrobial treatment while others perish. Despite its clinical importance, the molecular mechanisms underlying bet hedging remain unclear. Here, we investigate the mechanisms of bet hedging in Saccharomyces cerevisiae using a new high-throughput microscopy assay that monitors variable protein expression, morphology, growth rate, and survival outcomes of tens of thousands of yeast microcolonies simultaneously. We find that clonal populations display broad distributions of growth rates and that slow growth predicts resistance to heat killing in a probabalistic manner. We identify several gene products that are likely to play a role in bet hedging and confirm that Tsl1, a trehalose-synthesis regulator, is an important component of this resistance. Tsl1 abundance correlates with growth rate and replicative age and predicts survival. Our results suggest that yeast bet hedging results from multiple epigenetic growth states determined by a combination of stochastic and deterministic factors.

Yeast Survive by Hedging Their Bets

2012-05-08T21:00:00Z

by Robin Meadows

Bit by Bit: The Darwinian Basis of Life

2012-05-08T21:00:00Z

by Gerald F. Joyce

All known examples of life belong to the same biology, but there is increasing enthusiasm among astronomers, astrobiologists, and synthetic biologists that other forms of life may soon be discovered or synthesized. This enthusiasm should be tempered by the fact that the probability for life to originate is not known. As a guiding principle in parsing potential examples of alternative life, one should ask: How many heritable “bits” of information are involved, and where did they come from? A genetic system that contains more bits than the number that were required to initiate its operation might reasonably be considered a new form of life.

Enhancement of Asynchronous Release from Fast-Spiking Interneuron in Human and Rat Epileptic Neocortex

2012-05-08T21:00:00Z

by Man Jiang, Jie Zhu, Yaping Liu, Mingpo Yang, Cuiping Tian, Shan Jiang, Yonghong Wang, Hui Guo, Kaiyan Wang, Yousheng Shu

Down-regulation of GABAergic inhibition may result in the generation of epileptiform activities. Besides spike-triggered synchronous GABA release, changes in asynchronous release (AR) following high-frequency discharges may further regulate epileptiform activities. In brain slices obtained from surgically removed human neocortical tissues of patients with intractable epilepsy and brain tumor, we found that AR occurred at GABAergic output synapses of fast-spiking (FS) neurons and its strength depended on the type of connections, with FS autapses showing the strongest AR. In addition, we found that AR depended on residual Ca²⁺ at presynaptic terminals but was independent of postsynaptic firing. Furthermore, AR at FS autapses was markedly elevated in human epileptic tissue as compared to non-epileptic tissue. In a rat model of epilepsy, we found similar elevation of AR at both FS autapses and synapses onto excitatory neurons. Further experiments and analysis showed that AR elevation in epileptic tissue may result from an increase in action potential amplitude in the FS neurons and elevation of residual Ca²⁺ concentration. Together, these results revealed that GABAergic AR occurred at both human and rat neocortex, and its elevation in epileptic tissue may contribute to the regulation of epileptiform activities.

Novel Role of NOX in Supporting Aerobic Glycolysis in Cancer Cells with Mitochondrial Dysfunction and as a Potential Target for Cancer Therapy

2012-05-08T21:00:00Z

by Weiqin Lu, Yumin Hu, Gang Chen, Zhao Chen, Hui Zhang, Feng Wang, Li Feng, Helene Pelicano, Hua Wang, Michael J. Keating, Jinsong Liu, Wallace McKeehan, Huamin Wang, Yongde Luo, Peng Huang

Elevated aerobic glycolysis in cancer cells (the Warburg effect) may be attributed to respiration injury or mitochondrial dysfunction, but the underlying mechanisms and therapeutic significance remain elusive. Here we report that induction of mitochondrial respiratory defect by tetracycline-controlled expression of a dominant negative form of DNA polymerase γ causes a metabolic shift from oxidative phosphorylation to glycolysis and increases ROS generation. We show that upregulation of NOX is critical to support the elevated glycolysis by providing additional NAD+. The upregulation of NOX is also consistently observed in cancer cells with compromised mitochondria due to the activation of oncogenic Ras or loss of p53, and in primary pancreatic cancer tissues. Suppression of NOX by chemical inhibition or genetic knockdown of gene expression selectively impacts cancer cells with mitochondrial dysfunction, leading to a decrease in cellular glycolysis, a loss of cell viability, and inhibition of cancer growth in vivo. Our study reveals a previously unrecognized function of NOX in cancer metabolism and suggests that NOX is a potential novel target for cancer treatment.

Regulation of Brain Tumor Dispersal by NKCC1 Through a Novel Role in Focal Adhesion Regulation

2012-05-01T21:00:00Z

by Tomas Garzon-Muvdi, Paula Schiapparelli, Colette ap Rhys, Hugo Guerrero-Cazares, Christopher Smith, Deok-Ho Kim, Lyonell Kone, Harrison Farber, Danielle Y. Lee, Steven S. An, Andre Levchenko, Alfredo Quiñones-Hinojosa

Glioblastoma (GB) is a highly invasive and lethal brain tumor due to its universal recurrence. Although it has been suggested that the electroneutral Na⁺-K⁺-Cl⁻ cotransporter 1 (NKCC1) can play a role in glioma cell migration, the precise mechanism by which this ion transporter contributes to GB aggressiveness remains poorly understood. Here, we focused on the role of NKCC1 in the invasion of human primary glioma cells in vitro and in vivo. NKCC1 expression levels were significantly higher in GB and anaplastic astrocytoma tissues than in grade II glioma and normal cortex. Pharmacological inhibition and shRNA-mediated knockdown of NKCC1 expression led to decreased cell migration and invasion in vitro and in vivo. Surprisingly, knockdown of NKCC1 in glioma cells resulted in the formation of significantly larger focal adhesions and cell traction forces that were approximately 40% lower than control cells. Epidermal growth factor (EGF), which promotes migration of glioma cells, increased the phosphorylation of NKCC1 through a PI3K-dependant mechanism. This finding is potentially related to WNK kinases. Taken together, our findings suggest that NKCC1 modulates migration of glioma cells by two distinct mechanisms: (1) through the regulation of focal adhesion dynamics and cell contractility and (2) through regulation of cell volume through ion transport. Due to the ubiquitous expression of NKCC1 in mammalian tissues, its regulation by WNK kinases may serve as new therapeutic targets for GB aggressiveness and can be exploited by other highly invasive neoplasms.

Competing Sound Sources Reveal Spatial Effects in Cortical Processing

2012-05-01T21:00:00Z

by Ross K. Maddox, Cyrus P. Billimoria, Ben P. Perrone, Barbara G. Shinn-Cunningham, Kamal Sen

Why is spatial tuning in auditory cortex weak, even though location is important to object recognition in natural settings? This question continues to vex neuroscientists focused on linking physiological results to auditory perception. Here we show that the spatial locations of simultaneous, competing sound sources dramatically influence how well neural spike trains recorded from the zebra finch field L (an analog of mammalian primary auditory cortex) encode source identity. We find that the location of a birdsong played in quiet has little effect on the fidelity of the neural encoding of the song. However, when the song is presented along with a masker, spatial effects are pronounced. For each spatial configuration, a subset of neurons encodes song identity more robustly than others. As a result, competing sources from different locations dominate responses of different neural subpopulations, helping to separate neural responses into independent representations. These results help elucidate how cortical processing exploits spatial information to provide a substrate for selective spatial auditory attention.

Disentangling the Benefits of Sex

2012-05-01T21:00:00Z

by Denis Roze

Understanding the evolutionary advantage of sexual reproduction remains one of the most fundamental questions in evolutionary biology. Most of the current hypotheses rely on the fact that sex increases genetic variation, thereby enhancing the efficiency of natural selection; an important body of theoretical work has defined the conditions under which sex can be favoured through this effect. Over the last decade, experimental evolution in model organisms has provided evidence that sex indeed allows faster rates of adaptation. A new study on facultatively sexual rotifers shows that increased rates of sex can be favoured during adaptation to new environmental conditions and explores the cause of this effect. The results provide support for the idea that the benefits of increasing genetic variation may compensate for the short-term costs of sexual reproduction.

The Evolution of Sex Is Favoured During Adaptation to New Environments

2012-05-01T21:00:00Z

by Lutz Becks, Aneil F. Agrawal

Both theory and experiments have demonstrated that sex can facilitate adaptation, potentially yielding a group-level advantage to sex. However, it is unclear whether this process can help solve the more difficult problem of the maintenance of sex within populations. Using experimental populations of the facultatively sexual rotifer Brachionus calyciflorus, we show that rates of sex evolve to higher levels during adaptation but then decline as fitness plateaus. To assess the fitness consequences of genetic mixing, we directly compare the fitnesses of sexually and asexually derived genotypes that naturally occur in our experimental populations. Sexually derived genotypes are more fit than asexually derived genotypes when adaptive pressures are strong, but this pattern reverses as the pace of adaptation slows, matching the pattern of evolutionary change in the rate of sex. These fitness assays test the net effect of sex but cannot be used to disentangle whether selection on sex arises because highly sexual lineages become associated with different allele combinations or with different allele frequencies than less sexual lineages (i.e., “short-” or “long-term” effects, respectively). We infer which of these mechanisms provides an advantage to sex by performing additional manipulations to obtain fitness distributions of sexual and asexual progeny arrays from unbiased parents (rather than from naturally occurring, and thereby evolutionarily biased, parents). We find evidence that sex breaks down adaptive gene combinations, resulting in lower average fitness of sexual progeny (i.e., a short-term disadvantage to sex). As predicted by theory, the advantage to sex arises because sexually derived progeny are more variable in fitness, allowing for faster adaptation. This “long-term advantage” builds over multiple generations, eventually resulting in higher fitness of sexual types.

A Genetic Basis for Mechanosensory Traits in Humans

2012-05-01T21:00:00Z

by Henning Frenzel, Jörg Bohlender, Katrin Pinsker, Bärbel Wohlleben, Jens Tank, Stefan G. Lechner, Daniela Schiska, Teresa Jaijo, Franz Rüschendorf, Kathrin Saar, Jens Jordan, José M. Millán, Manfred Gross, Gary R. Lewin

In all vertebrates hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. There is an extensive literature describing single gene mutations in humans that cause hearing impairment, but there are essentially none for touch. Here we first asked if touch sensitivity is a heritable trait and second whether there are common genes that influence different mechanosensory senses like hearing and touch in humans. Using a classical twin study design we demonstrate that touch sensitivity and touch acuity are highly heritable traits. Quantitative phenotypic measures of different mechanosensory systems revealed significant correlations between touch and hearing acuity in a healthy human population. Thus mutations in genes causing deafness genes could conceivably negatively influence touch sensitivity. In agreement with this hypothesis we found that a proportion of a cohort of congenitally deaf young adults display significantly impaired measures of touch sensitivity compared to controls. In contrast, blind individuals showed enhanced, not diminished touch acuity. Finally, by examining a cohort of patients with Usher syndrome, a genetically well-characterized deaf-blindness syndrome, we could show that recessive pathogenic mutations in the USH2A gene influence touch acuity. Control Usher syndrome cohorts lacking demonstrable pathogenic USH2A mutations showed no impairment in touch acuity. Our study thus provides comprehensive evidence that there are common genetic elements that contribute to touch and hearing and has identified one of these genes as USH2A.

Hear Less, Feel Less: One Mutation Causes Loss of Two Senses

2012-05-01T21:00:00Z

by Richard Robinson

Lipids in HIV's Envelope Help the Virus to Spread

2012-04-24T21:00:00Z

by Caitlin Sedwick

Sialyllactose in Viral Membrane Gangliosides Is a Novel Molecular Recognition Pattern for Mature Dendritic Cell Capture of HIV-1

2012-04-24T21:00:00Z

by Nuria Izquierdo-Useros, Maier Lorizate, F.-Xabier Contreras, Maria T. Rodriguez-Plata, Bärbel Glass, Itziar Erkizia, Julia G. Prado, Josefina Casas, Gemma Fabriàs, Hans-Georg Kräusslich, Javier Martinez-Picado

HIV-1 is internalized into mature dendritic cells (mDCs) via an as yet undefined mechanism with subsequent transfer of stored, infectious virus to CD4⁺ T lymphocytes. Thus, HIV-1 subverts a DC antigen capture mechanism to promote viral spread. Here, we show that gangliosides in the HIV-1 membrane are the key molecules for mDC uptake. HIV-1 virus-like particles and liposomes mimicking the HIV-1 lipid composition were shown to use a common internalization pathway and the same trafficking route within mDCs. Hence, these results demonstrate that gangliosides can act as viral attachment factors, in addition to their well known function as cellular receptors for certain viruses. Furthermore, the sialyllactose molecule present in specific gangliosides was identified as the determinant moiety for mDC HIV-1 uptake. Thus, sialyllactose represents a novel molecular recognition pattern for mDC capture, and may be crucial both for antigen presentation leading to immunity against pathogens and for succumbing to subversion by HIV-1.

Essential Role for miR-196a in Brown Adipogenesis of White Fat Progenitor Cells

2012-04-24T21:00:00Z

by Masaki Mori, Hironori Nakagami, Gerardo Rodriguez-Araujo, Keisuke Nimura, Yasufumi Kaneda

The recent discovery of functional brown adipocytes in adult humans illuminates the potential of these cells in the treatment of obesity and its associated diseases. In rodents, brown adipocyte-like cells are known to be recruited in white adipose tissue (WAT) by cold exposure or β-adrenergic stimulation, but the molecular machinery underlying this phenomenon is not fully understood. Here, we show that inducible brown adipogenesis is mediated by the microRNA miR-196a. We found that miR-196a suppresses the expression of the white-fat gene Hoxc8 post-transcriptionally during the brown adipogenesis of white fat progenitor cells. In mice, miR-196a is induced in the WAT-progenitor cells after cold exposure or β-adrenergic stimulation. The fat-specific forced expression of miR-196a in mice induces the recruitment of brown adipocyte-like cells in WAT. The miR-196a transgenic mice exhibit enhanced energy expenditure and resistance to obesity, indicating the induced brown adipocyte-like cells are metabolically functional. Mechanistically, Hoxc8 targets and represses C/EBPβ, a master switch of brown-fat gene program, in cooperation with histone deacetylase 3 (HDAC3) through the C/EBPβ 3′ regulatory sequence. Thus, miR-196a induces functional brown adipocytes in WAT through the suppression of Hoxc8, which functions as a gatekeeper of the inducible brown adipogenesis. The miR-196a-Hoxc8-C/EBPβ signaling pathway may be a therapeutic target for inducing brown adipogenesis to combat obesity and type 2 diabetes.

Rapid De Novo Evolution of X Chromosome Dosage Compensation in Silene latifolia, a Plant with Young Sex Chromosomes

2012-04-17T21:00:00Z

by Aline Muyle, Niklaus Zemp, Clothilde Deschamps, Sylvain Mousset, Alex Widmer, Gabriel A. B. Marais

Silene latifolia is a dioecious plant with heteromorphic sex chromosomes that have originated only ∼10 million years ago and is a promising model organism to study sex chromosome evolution in plants. Previous work suggests that S. latifolia XY chromosomes have gradually stopped recombining and the Y chromosome is undergoing degeneration as in animal sex chromosomes. However, this work has been limited by the paucity of sex-linked genes available. Here, we used 35 Gb of RNA-seq data from multiple males (XY) and females (XX) of an S. latifolia inbred line to detect sex-linked SNPs and identified more than 1,700 sex-linked contigs (with X-linked and Y-linked alleles). Analyses using known sex-linked and autosomal genes, together with simulations indicate that these newly identified sex-linked contigs are reliable. Using read numbers, we then estimated expression levels of X-linked and Y-linked alleles in males and found an overall trend of reduced expression of Y-linked alleles, consistent with a widespread ongoing degeneration of the S. latifolia Y chromosome. By comparing expression intensities of X-linked alleles in males and females, we found that X-linked allele expression increases as Y-linked allele expression decreases in males, which makes expression of sex-linked contigs similar in both sexes. This phenomenon is known as dosage compensation and has so far only been observed in evolutionary old animal sex chromosome systems. Our results suggest that dosage compensation has evolved in plants and that it can quickly evolve de novo after the origin of sex chromosomes.

Molecular Requirements for Peroxisomal Targeting of Alanine-Glyoxylate Aminotransferase as an Essential Determinant in Primary Hyperoxaluria Type 1

2012-04-17T21:00:00Z

by Krisztián Fodor, Janina Wolf, Ralf Erdmann, Wolfgang Schliebs, Matthias Wilmanns

Alanine-glyoxylate aminotransferase is a peroxisomal enzyme, of which various missense mutations lead to irreversible kidney damage via primary hyperoxaluria type 1, in part caused by improper peroxisomal targeting. To unravel the molecular mechanism of its recognition by the peroxisomal receptor Pex5p, we have determined the crystal structure of the respective cargo–receptor complex. It shows an extensive protein/protein interface, with contributions from residues of the peroxisomal targeting signal 1 and additional loops of the C-terminal domain of the cargo. Sequence segments that are crucial for receptor recognition and hydrophobic core interactions within alanine-glyoxylate aminotransferase are overlapping, explaining why receptor recognition highly depends on a properly folded protein. We subsequently characterized several enzyme variants in vitro and in vivo and show that even minor protein fold perturbations are sufficient to impair Pex5p receptor recognition. We discuss how the knowledge of the molecular parameters for alanine-glyoxylate aminotransferase required for peroxisomal translocation could become useful for improved hyperoxaluria type 1 treatment.

FTIP1 Is an Essential Regulator Required for Florigen Transport

2012-04-17T21:00:00Z

by Lu Liu, Chang Liu, Xingliang Hou, Wanyan Xi, Lisha Shen, Zhen Tao, Yue Wang, Hao Yu

The capacity to respond to day length, photoperiodism, is crucial for flowering plants to adapt to seasonal change. The photoperiodic control of flowering in plants is mediated by a long-distance mobile floral stimulus called florigen that moves from leaves to the shoot apex. Although the proteins encoded by FLOWERING LOCUS T (FT) in Arabidopsis and its orthologs in other plants are identified as the long-sought florigen, whether their transport is a simple diffusion process or under regulation remains elusive. Here we show that an endoplasmic reticulum (ER) membrane protein, FT-INTERACTING PROTEIN 1 (FTIP1), is an essential regulator required for FT protein transport in Arabidopsis. Loss of function of FTIP1 exhibits late flowering under long days, which is partly due to the compromised FT movement to the shoot apex. FTIP1 and FT share similar mRNA expression patterns and subcellular localization, and they interact specifically in phloem companion cells. FTIP1 is required for FT export from companion cells to sieve elements, thus affecting FT transport through the phloem to the SAM. Our results provide a mechanistic understanding of florigen transport, demonstrating that FT moves in a regulated manner and that FTIP1 mediates FT transport to induce flowering.

Project Brainstorm: Using Neuroscience to Connect College Students with Local Schools

2012-04-17T21:00:00Z

by Rafael Romero-Calderón, Elizabeth D. O'Hare, Nanthia A. Suthana, Ashley A. Scott-Van Zeeland, Angela Rizk-Jackson, Aida Attar, Sarah K. Madsen, Cristina A. Ghiani, Christopher J. Evans, Joseph B. Watson

A Blossoming Field of Research: How Florigen Is Transported to Create Flowers

2012-04-17T21:00:00Z

by Charles Q. Choi

Sex Chromosome Equality in Plants

2012-04-17T21:00:00Z

by Robin Meadows

Using Grizzly Bears to Assess Harvest-Ecosystem Tradeoffs in Salmon Fisheries

2012-04-10T21:00:00Z

by Taal Levi, Chris T. Darimont, Misty MacDuffee, Marc Mangel, Paul Paquet, Christopher C. Wilmers

Implementation of ecosystem-based fisheries management (EBFM) requires a clear conceptual and quantitative framework for assessing how different harvest options can modify benefits to ecosystem and human beneficiaries. We address this social-ecological need for Pacific salmon fisheries, which are economically valuable but intercept much of the annual pulse of nutrient subsidies that salmon provide to terrestrial and aquatic food webs. We used grizzly bears, vectors of salmon nutrients and animals with densities strongly coupled to salmon abundance, as surrogates for “salmon ecosystem” function. Combining salmon biomass and stock-recruitment data with stable isotope analysis, we assess potential tradeoffs between fishery yields and bear population densities for six sockeye salmon stocks in Bristol Bay, Alaska, and British Columbia (BC), Canada. For the coastal stocks, we find that both bear densities and fishery yields would increase substantially if ecosystem allocations of salmon increase from currently applied lower to upper goals and beyond. This aligning of benefits comes at a potential cost, however, with the possibility of forgoing harvests in low productivity years. In contrast, we detect acute tradeoffs between bear densities and fishery yields in interior stocks within the Fraser River, BC, where biomass from other salmon species is low. There, increasing salmon allocations to ecosystems would benefit threatened bear populations at the cost of reduced long-term yields. To resolve this conflict, we propose an EBFM goal that values fisheries and bears (and by extension, the ecosystem) equally. At such targets, ecosystem benefits are unexpectedly large compared with losses in fishery yields. To explore other management options, we generate tradeoff curves that provide stock-specific accounting of the expected loss to fishers and gain to bears as more salmon escape the fishery. Our approach, modified to suit multiple scenarios, provides a generalizable method to resolve conflicts over shared resources in other systems.

How Much Lox Is a Grizzly Bear Worth?

2012-04-10T21:00:00Z

by Jonathan Chase

A Novel 3-Hydroxysteroid Dehydrogenase That Regulates Reproductive Development and Longevity

2012-04-10T21:00:00Z

by Joshua Wollam, Daniel B. Magner, Lilia Magomedova, Elisabeth Rass, Yidong Shen, Veerle Rottiers, Bianca Habermann, Carolyn L. Cummins, Adam Antebi

Endogenous small molecule metabolites that regulate animal longevity are emerging as a novel means to influence health and life span. In C. elegans, bile acid-like steroids called the dafachronic acids (DAs) regulate developmental timing and longevity through the conserved nuclear hormone receptor DAF-12, a homolog of mammalian sterol-regulated receptors LXR and FXR. Using metabolic genetics, mass spectrometry, and biochemical approaches, we identify new activities in DA biosynthesis and characterize an evolutionarily conserved short chain dehydrogenase, DHS-16, as a novel 3-hydroxysteroid dehydrogenase. Through regulation of DA production, DHS-16 controls DAF-12 activity governing longevity in response to signals from the gonad. Our elucidation of C. elegans bile acid biosynthetic pathways reveals the possibility of novel ligands as well as striking biochemical conservation to other animals, which could illuminate new targets for manipulating longevity in metazoans.

Steroids as Central Regulators of Organismal Development and Lifespan

2012-04-10T21:00:00Z

by Siu Sylvia Lee, Frank C. Schroeder

Larvae of the nematode Caenorhabditis elegans must choose between reproductive development and dauer diapause. This decision is based on sensing of environmental inputs and dauer pheromone, a small molecule signal that serves to monitor population density. These signals are integrated via conserved neuroendocrine pathways that converge on steroidal ligands of the nuclear receptor DAF-12, a homolog of the mammalian vitamin D receptor and liver X receptor. DAF-12 acts as the main switch between gene expression programs that drive either reproductive development or dauer entry. Extensive studies in the past two decades demonstrated that biosynthesis of two bile acid-like DAF-12 ligands, named dafachronic acids (DA), controls developmental fate. In this issue of PLoS Biology, Wollam et al. showed that a conserved steroid-modifying enzyme, DHS-16, introduces a key feature in the structures of the DAF-12 ligands, closing a major gap in the DA biosynthesis pathway. The emerging picture of DA biosynthesis in C. elegans enables us to address a key question in the field: how are complex environmental signals integrated to enforce binary, organism-wide decisions on developmental fate? Schaedel et al. demonstrated that pheromone and DA serve as competing signals, and that a positive feedback loop based on regulation of DA biosynthesis ensures organism-wide commitment to reproductive development. Considering that many components of DA signaling are highly conserved, ongoing studies in C. elegans may reveal new aspects of bile acid function and lifespan regulation in mammals.

Hormonal Signal Amplification Mediates Environmental Conditions during Development and Controls an Irreversible Commitment to Adulthood

2012-04-10T21:00:00Z

by Oren N. Schaedel, Birgit Gerisch, Adam Antebi, Paul W. Sternberg

Many animals can choose between different developmental fates to maximize fitness. Despite the complexity of environmental cues and life history, different developmental fates are executed in a robust fashion. The nematode Caenorhabditis elegans serves as a powerful model to examine this phenomenon because it can adopt one of two developmental fates (adulthood or diapause) depending on environmental conditions. The steroid hormone dafachronic acid (DA) directs development to adulthood by regulating the transcriptional activity of the nuclear hormone receptor DAF-12. The known role of DA suggests that it may be the molecular mediator of environmental condition effects on the developmental fate decision, although the mechanism is yet unknown. We used a combination of physiological and molecular biology techniques to demonstrate that commitment to reproductive adult development occurs when DA levels, produced in the neuroendocrine XXX cells, exceed a threshold. Furthermore, imaging and cell ablation experiments demonstrate that the XXX cells act as a source of DA, which, upon commitment to adult development, is amplified and propagated in the epidermis in a DAF-12 dependent manner. This positive feedback loop increases DA levels and drives adult programs in the gonad and epidermis, thus conferring the irreversibility of the decision. We show that the positive feedback loop canalizes development by ensuring that sufficient amounts of DA are dispersed throughout the body and serves as a robust fate-locking mechanism to enforce an organism-wide binary decision, despite noisy and complex environmental cues. These mechanisms are not only relevant to C. elegans but may be extended to other hormonal-based decision-making mechanisms in insects and mammals.

A Feedback Loop between Dynamin and Actin Recruitment during Clathrin-Mediated Endocytosis

2012-04-10T21:00:00Z

by Marcus J. Taylor, Marko Lampe, Christien J. Merrifield

Clathrin-mediated endocytosis proceeds by a sequential series of reactions catalyzed by discrete sets of protein machinery. The final reaction in clathrin-mediated endocytosis is membrane scission, which is mediated by the large guanosine triophosphate hydrolase (GTPase) dynamin and which may involve the actin-dependent recruitment of N-terminal containing BIN/Amphiphysin/RVS domain containing (N-BAR) proteins. Optical microscopy has revealed a detailed picture of when and where particular protein types are recruited in the ∼20–30 s preceding scission. Nevertheless, the regulatory mechanisms and functions that underpin protein recruitment are not well understood. Here we used an optical assay to investigate the coordination and interdependencies between the recruitment of dynamin, the actin cytoskeleton, and N-BAR proteins to individual clathrin-mediated endocytic scission events. These measurements revealed that a feedback loop exists between dynamin and actin at sites of membrane scission. The kinetics of dynamin, actin, and N-BAR protein recruitment were modulated by dynamin GTPase activity. Conversely, acute ablation of actin dynamics using latrunculin-B led to a ∼50% decrease in the incidence of scission, an ∼50% decrease in the amplitude of dynamin recruitment, and abolished actin and N-BAR recruitment to scission events. Collectively these data suggest that dynamin, actin, and N-BAR proteins work cooperatively to efficiently catalyze membrane scission. Dynamin controls its own recruitment to scission events by modulating the kinetics of actin and N-BAR recruitment to sites of scission. Conversely actin serves as a dynamic scaffold that concentrates dynamin and N-BAR proteins at sites of scission.