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Preview: PLoS Biology: New Articles

PLOS Biology: New Articles



A Peer-Reviewed Open-Access Journal



Updated: 2018-02-20T23:45:45Z

 



(XML) Design of synthetic bacterial communities for predictable plant phenotypes

2018-02-20T22:00:00Z

by Sur Herrera Paredes, Tianxiang Gao, Theresa F. Law, Omri M. Finkel, Tatiana Mucyn, Paulo José Pereira Lima Teixeira, Isaí Salas González, Meghan E. Feltcher, Matthew J. Powers, Elizabeth A. Shank, Corbin D. Jones, Vladimir Jojic, Jeffery L. Dangl, Gabriel Castrillo

Specific members of complex microbiota can influence host phenotypes, depending on both the abiotic environment and the presence of other microorganisms. Therefore, it is challenging to define bacterial combinations that have predictable host phenotypic outputs. We demonstrate that plant–bacterium binary-association assays inform the design of small synthetic communities with predictable phenotypes in the host. Specifically, we constructed synthetic communities that modified phosphate accumulation in the shoot and induced phosphate starvation–responsive genes in a predictable fashion. We found that bacterial colonization of the plant is not a predictor of the plant phenotypes we analyzed. Finally, we demonstrated that characterizing a subset of all possible bacterial synthetic communities is sufficient to predict the outcome of untested bacterial consortia. Our results demonstrate that it is possible to infer causal relationships between microbiota membership and host phenotypes and to use these inferences to rationally design novel communities.(image)



(XML) Vocal development through morphological computation

2018-02-20T22:00:00Z

by Yisi S. Zhang, Asif A. Ghazanfar

The vocal behavior of infants changes dramatically during early life. Whether or not such a change results from the growth of the body during development—as opposed to solely neural changes—has rarely been investigated. In this study of vocal development in marmoset monkeys, we tested the putative causal relationship between bodily growth and vocal development (without the need to invoke neural growth). During the first two months of life, the spontaneous vocalizations of marmosets undergo (1) a gradual disappearance of context-inappropriate call types and (2) an elongation in the duration of context-appropriate contact calls. We hypothesized that both changes are the natural consequences of lung growth and do not require any changes at the neural level. To test this idea, we first present a central pattern generator model of marmoset vocal production to demonstrate that lung growth can affect the temporal and oscillatory dynamics of neural circuits via sensory feedback from the lungs. Lung growth qualitatively shifted vocal behavior in the direction observed in real marmoset monkey vocal development. We then empirically tested this hypothesis by placing the marmoset infants in a helium–oxygen (heliox) environment in which air is much lighter. This simulated a reversal in development by decreasing the effort required to respire, thus increasing the respiration rate (as though the lungs were smaller). The heliox manipulation increased the proportions of inappropriate call types and decreased the duration of contact calls, consistent with a brief reversal of vocal development. These results suggest that bodily growth alone can play a major role in shaping the development of vocal behavior.(image)



(XML) A damped oscillator imposes temporal order on posterior gap gene expression in Drosophila

2018-02-16T22:00:00Z

by Berta Verd, Erik Clark, Karl R. Wotton, Hilde Janssens, Eva Jiménez-Guri, Anton Crombach, Johannes Jaeger

Insects determine their body segments in two different ways. Short-germband insects, such as the flour beetle Tribolium castaneum, use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar fly Drosophila melanogaster, determine all segments simultaneously through a hierarchical cascade of gene regulation. Gap genes constitute the first layer of the Drosophila segmentation gene hierarchy, downstream of maternal gradients such as that of Caudal (Cad). We use data-driven mathematical modelling and phase space analysis to show that shifting gap domains in the posterior half of the Drosophila embryo are an emergent property of a robust damped oscillator mechanism, suggesting that the regulatory dynamics underlying long- and short-germband segmentation are much more similar than previously thought. In Tribolium, Cad has been proposed to modulate the frequency of the segmentation oscillator. Surprisingly, our simulations and experiments show that the shift rate of posterior gap domains is independent of maternal Cad levels in Drosophila. Our results suggest a novel evolutionary scenario for the short- to long-germband transition and help explain why this transition occurred convergently multiple times during the radiation of the holometabolan insects.(image)



(XML) Fruit flies are multistable geniuses

2018-02-14T22:00:00Z

by Christopher C. Pack, Jamie C. Theobald

Our sensory systems have evolved to provide us with information about the external world. Such information is useful only insofar as it leads to actions that enhance fitness, and thus, the link between sensation and action has been thoroughly studied in many species. In insects, for example, specific visual stimuli lead to highly stereotyped responses. In contrast, humans can exhibit a wide range of responses to the same stimulus, as occurs most notably in the phenomenon of multistable perception. On this basis, one might think that humans have a fundamentally different way of generating actions from sensory inputs, but Toepfer et al. show that flies show evidence of multistable perception as well. Specifically, when confronted with a sensory stimulus that can yield different motor responses, flies switch from one response to another with temporal dynamics that are similar to those of humans and other animals. This suggests that the mechanisms that give rise to the rich repertoire of sensory experience in humans have correlates in much simpler nervous systems.(image)



(XML) Identification of FAM173B as a protein methyltransferase promoting chronic pain

2018-02-14T22:00:00Z

by Hanneke L. D. M. Willemen, Annemieke Kavelaars, Judith Prado, Mirjam Maas, Sabine Versteeg, Lara J. J. Nellissen, Jeshua Tromp, Rafael Gonzalez Cano, Wenjun Zhou, Magnus E. Jakobsson, Jędrzej Małecki, George Posthuma, Abdella M. Habib, Cobi J. Heijnen, Pål Ø. Falnes, Niels Eijkelkamp

Chronic pain is a debilitating problem, and insights in the neurobiology of chronic pain are needed for the development of novel pain therapies. A genome-wide association study implicated the 5p15.2 region in chronic widespread pain. This region includes the coding region for FAM173B, a functionally uncharacterized protein. We demonstrate here that FAM173B is a mitochondrial lysine methyltransferase that promotes chronic pain. Knockdown and sensory neuron overexpression strategies showed that FAM173B is involved in persistent inflammatory and neuropathic pain via a pathway dependent on its methyltransferase activity. FAM173B methyltransferase activity in sensory neurons hyperpolarized mitochondria and promoted macrophage/microglia activation through a reactive oxygen species–dependent pathway. In summary, we uncover a role for methyltransferase activity of FAM173B in the neurobiology of pain. These results also highlight FAM173B methyltransferase activity as a potential therapeutic target to treat debilitating chronic pain conditions.(image)



(XML) Correction: The Compartmentalized Bacteria of the Planctomycetes-Verrucomicrobia-Chlamydiae Superphylum Have Membrane Coat-Like Proteins

2018-02-14T22:00:00Z

by Rachel Santarella-Mellwig, Josef Franke, Andreas Jaedicke, Mátyás Gorjánácz, Ulrike Bauer, Aidan Budd, Iain W. Mattaj, Damien P. Devos

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(XML) Multi-stability with ambiguous visual stimuli in Drosophila orientation behavior

2018-02-13T22:00:00Z

by Franziska Toepfer, Reinhard Wolf, Martin Heisenberg

It is widely accepted for humans and higher animals that vision is an active process in which the organism interprets the stimulus. To find out whether this also holds for lower animals, we designed an ambiguous motion stimulus, which serves as something like a multi-stable perception paradigm in Drosophila behavior. Confronted with a uniform panoramic texture in a closed-loop situation in stationary flight, the flies adjust their yaw torque to stabilize their virtual self-rotation. To make the visual input ambiguous, we added a second texture. Both textures got a rotatory bias to move into opposite directions at a constant relative angular velocity. The results indicate that the fly now had three possible frames of reference for self-rotation: either of the two motion components as well as the integrated motion vector of the two. In this ambiguous stimulus situation, the flies generated a continuous sequence of behaviors, each one adjusted to one or another of the three references.(image)



(XML) How the microbiome challenges our concept of self

2018-02-09T22:00:00Z

by Tobias Rees, Thomas Bosch, Angela E. Douglas

Today, the three classical biological explanations of the individual self––the immune system, the brain, the genome––are being challenged by the new field of microbiome research. Evidence shows that our resident microbes orchestrate the adaptive immune system, influence the brain, and contribute more gene functions than our own genome. The realization that humans are not individual, discrete entities but rather the outcome of ever-changing interactions with microorganisms has consequences beyond the biological disciplines. In particular, it calls into question the assumption that distinctive human traits set us apart from all other animals––and therefore also the traditional disciplinary divisions between the arts and the sciences.(image)



(XML) Catecholamines alter the intrinsic variability of cortical population activity and perception

2018-02-08T22:00:00Z

by Thomas Pfeffer, Arthur-Ervin Avramiea, Guido Nolte, Andreas K. Engel, Klaus Linkenkaer-Hansen, Tobias H. Donner

The ascending modulatory systems of the brain stem are powerful regulators of global brain state. Disturbances of these systems are implicated in several major neuropsychiatric disorders. Yet, how these systems interact with specific neural computations in the cerebral cortex to shape perception, cognition, and behavior remains poorly understood. Here, we probed into the effect of two such systems, the catecholaminergic (dopaminergic and noradrenergic) and cholinergic systems, on an important aspect of cortical computation: its intrinsic variability. To this end, we combined placebo-controlled pharmacological intervention in humans, recordings of cortical population activity using magnetoencephalography (MEG), and psychophysical measurements of the perception of ambiguous visual input. A low-dose catecholaminergic, but not cholinergic, manipulation altered the rate of spontaneous perceptual fluctuations as well as the temporal structure of “scale-free” population activity of large swaths of the visual and parietal cortices. Computational analyses indicate that both effects were consistent with an increase in excitatory relative to inhibitory activity in the cortical areas underlying visual perceptual inference. We propose that catecholamines regulate the variability of perception and cognition through dynamically changing the cortical excitation–inhibition ratio. The combined readout of fluctuations in perception and cortical activity we established here may prove useful as an efficient and easily accessible marker of altered cortical computation in neuropsychiatric disorders.(image)



(XML) Empirical evidence that metabolic theory describes the temperature dependency of within-host parasite dynamics

2018-02-07T22:00:00Z

by Devin Kirk, Natalie Jones, Stephanie Peacock, Jessica Phillips, Péter K. Molnár, Martin Krkošek, Pepijn Luijckx

The complexity of host–parasite interactions makes it difficult to predict how host–parasite systems will respond to climate change. In particular, host and parasite traits such as survival and virulence may have distinct temperature dependencies that must be integrated into models of disease dynamics. Using experimental data from Daphnia magna and a microsporidian parasite, we fitted a mechanistic model of the within-host parasite population dynamics. Model parameters comprising host aging and mortality, as well as parasite growth, virulence, and equilibrium abundance, were specified by relationships arising from the metabolic theory of ecology. The model effectively predicts host survival, parasite growth, and the cost of infection across temperature while using less than half the parameters compared to modeling temperatures discretely. Our results serve as a proof of concept that linking simple metabolic models with a mechanistic host–parasite framework can be used to predict temperature responses of parasite population dynamics at the within-host level.(image)



(XML) A case for conserving common species

2018-02-07T22:00:00Z

by Emmanuel A. Frimpong

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(XML) The jaguar and the PhD

2018-02-07T22:00:00Z

by Sergio Avila-Villegas

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(XML) Neutrophils kill the parasite Trichomonas vaginalis using trogocytosis

2018-02-06T22:00:00Z

by Frances Mercer, Shek Hang Ng, Taylor M. Brown, Grace Boatman, Patricia J. Johnson

T. vaginalis, a human-infective parasite, causes the most common nonviral sexually transmitted infection (STI) worldwide and contributes to adverse inflammatory disorders. The immune response to T. vaginalis is poorly understood. Neutrophils (polymorphonuclear cells [PMNs]) are the major immune cell present at the T. vaginalis–host interface and are thought to clear T. vaginalis. However, the mechanism of PMN clearance of T. vaginalis has not been characterized. We demonstrate that human PMNs rapidly kill T. vaginalis in a dose-dependent, contact-dependent, and neutrophil extracellular trap (NET)-independent manner. In contrast to phagocytosis, we observed that PMN killing of T. vaginalis involves taking “bites” of T. vaginalis prior to parasite death, using trogocytosis to achieve pathogen killing. Both trogocytosis and parasite killing are dependent on the presence of PMN serine proteases and human serum factors. Our analyses provide the first demonstration, to our knowledge, of a mammalian phagocyte using trogocytosis for pathogen clearance and reveal a novel mechanism used by PMNs to kill a large, highly motile target.(image)



(XML) Resurrection and resilience of the rarest butterflies

2018-02-06T22:00:00Z

by Nick M. Haddad

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(XML) Witnessing extinction in real time

2018-02-06T22:00:00Z

by Karen R. Lips

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(XML) Conservation stories from the front lines

2018-02-05T22:00:00Z

by Liza Gross, Annaliese Hettinger, Jonathan W. Moore, Liz Neeley

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(XML) Parallel trends in cortical gray and white matter architecture and connections in primates allow fine study of pathways in humans and reveal network disruptions in autism

2018-02-05T22:00:00Z

by Basilis Zikopoulos, Miguel Ángel García-Cabezas, Helen Barbas

Noninvasive imaging and tractography methods have yielded information on broad communication networks but lack resolution to delineate intralaminar cortical and subcortical pathways in humans. An important unanswered question is whether we can use the wealth of precise information on pathways from monkeys to understand connections in humans. We addressed this question within a theoretical framework of systematic cortical variation and used identical high-resolution methods to compare the architecture of cortical gray matter and the white matter beneath, which gives rise to short- and long-distance pathways in humans and rhesus monkeys. We used the prefrontal cortex as a model system because of its key role in attention, emotions, and executive function, which are processes often affected in brain diseases. We found striking parallels and consistent trends in the gray and white matter architecture in humans and monkeys and between the architecture and actual connections mapped with neural tracers in rhesus monkeys and, by extension, in humans. Using the novel architectonic portrait as a base, we found significant changes in pathways between nearby prefrontal and distant areas in autism. Our findings reveal that a theoretical framework allows study of normal neural communication in humans at high resolution and specific disruptions in diverse psychiatric and neurodegenerative diseases.(image)



(XML) Making America great again requires acting on scientific knowledge

2018-02-05T22:00:00Z

by Elizabeth A. Hadly

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(XML) With a pinch of extra salt—Did predatory protists steal genes from their food?

2018-02-02T22:00:00Z

by Laura Czech, Erhard Bremer

The cellular adjustment of Bacteria and Archaea to high-salinity habitats is well studied and has generally been classified into one of two strategies. These are to accumulate high levels either of ions (the “salt-in” strategy) or of physiologically compliant organic osmolytes, the compatible solutes (the “salt-out” strategy). Halophilic protists are ecophysiological important inhabitants of salt-stressed ecosystems because they are not only very abundant but also represent the majority of eukaryotic lineages in nature. However, their cellular osmostress responses have been largely neglected. Recent reports have now shed new light on this issue using the geographically widely distributed halophilic heterotrophic protists Halocafeteria seosinensis, Pharyngomonas kirbyi, and Schmidingerothrix salinarum as model systems. Different approaches led to the joint conclusion that these unicellular Eukarya use the salt-out strategy to cope successfully with the persistent high salinity in their habitat. They accumulate various compatible solutes, e.g., glycine betaine, myo-inositol, and ectoines. The finding of intron-containing biosynthetic genes for ectoine and hydroxyectoine, their salt stress–responsive transcription in H. seosinensis, and the production of ectoine and its import by S. salinarum come as a considerable surprise because ectoines have thus far been considered exclusive prokaryotic compatible solutes. Phylogenetic considerations of the ectoine/hydroxyectoine biosynthetic genes of H. seosinensis suggest that they have been acquired via lateral gene transfer by these bacterivorous Eukarya from ectoine/hydroxyectoine-producing food bacteria that populate the same habitat.(image)



(XML) Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics

2018-02-01T22:00:00Z

by Andreas Sagner, Zachary B. Gaber, Julien Delile, Jennifer H. Kong, David L. Rousso, Caroline A. Pearson, Steven E. Weicksel, Manuela Melchionda, S. Neda Mousavy Gharavy, James Briscoe, Bennett G. Novitch

During tissue development, multipotent progenitors differentiate into specific cell types in characteristic spatial and temporal patterns. We addressed the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN) progenitors differentiate more rapidly than other progenitors. Using single cell transcriptomics, we defined the transcriptional changes associated with the transition of neural progenitors into MNs. Reconstruction of gene expression dynamics from these data indicate a pivotal role for the MN determinant Olig2 just prior to MN differentiation. Olig2 represses expression of the Notch signaling pathway effectors Hes1 and Hes5. Olig2 repression of Hes5 appears to be direct, via a conserved regulatory element within the Hes5 locus that restricts expression from MN progenitors. These findings reveal a tight coupling between the regulatory networks that control patterning and neuronal differentiation and demonstrate how Olig2 acts as the developmental pacemaker coordinating the spatial and temporal pattern of MN generation.(image)



(XML) Contrasting impacts of competition on ecological and social trait evolution in songbirds

2018-01-31T22:00:00Z

by Jonathan P. Drury, Joseph A. Tobias, Kevin J. Burns, Nicholas A. Mason, Allison J. Shultz, Hélène Morlon

Competition between closely related species has long been viewed as a powerful selective force that drives trait diversification, thereby generating phenotypic diversity over macroevolutionary timescales. However, although the impact of interspecific competition has been documented in a handful of iconic insular radiations, most previous studies have focused on traits involved in resource use, and few have examined the role of competition across large, continental radiations. Thus, the extent to which broad-scale patterns of phenotypic diversity are shaped by competition remain largely unclear, particularly for social traits. Here, we estimate the effect of competition between interacting lineages by applying new phylogenetic models that account for such interactions to an exceptionally complete dataset of resource-use traits and social signaling traits for the entire radiation of tanagers (Aves, Thraupidae), the largest family of songbirds. We find that interspecific competition strongly influences the evolution of traits involved in resource use, with a weaker effect on plumage signals, and very little effect on song. Our results provide compelling evidence that interspecific exploitative competition contributes to ecological trait diversification among coexisting species, even in a large continental radiation. In comparison, signal traits mediating mate choice and social competition seem to diversify under different evolutionary models, including rapid diversification in the allopatric stage of speciation.(image)



(XML) Role of the AP-5 adaptor protein complex in late endosome-to-Golgi retrieval

2018-01-30T22:00:00Z

by Jennifer Hirst, Daniel N. Itzhak, Robin Antrobus, Georg H. H. Borner, Margaret S. Robinson

The AP-5 adaptor protein complex is presumed to function in membrane traffic, but so far nothing is known about its pathway or its cargo. We have used CRISPR-Cas9 to knock out the AP-5 ζ subunit gene, AP5Z1, in HeLa cells, and then analysed the phenotype by subcellular fractionation profiling and quantitative mass spectrometry. The retromer complex had an altered steady-state distribution in the knockout cells, and several Golgi proteins, including GOLIM4 and GOLM1, were depleted from vesicle-enriched fractions. Immunolocalisation showed that loss of AP-5 led to impaired retrieval of the cation-independent mannose 6-phosphate receptor (CIMPR), GOLIM4, and GOLM1 from endosomes back to the Golgi region. Knocking down the retromer complex exacerbated this phenotype. Both the CIMPR and sortilin interacted with the AP-5–associated protein SPG15 in pull-down assays, and we propose that sortilin may act as a link between Golgi proteins and the AP-5/SPG11/SPG15 complex. Together, our findings suggest that AP-5 functions in a novel sorting step out of late endosomes, acting as a backup pathway for retromer. This provides a mechanistic explanation for why mutations in AP-5/SPG11/SPG15 cause cells to accumulate aberrant endolysosomes, and highlights the role of endosome/lysosome dysfunction in the pathology of hereditary spastic paraplegia and other neurodegenerative disorders.(image)



(XML) The importance of being second

2018-01-29T22:00:00Z

by The PLOS Biology Staff Editors

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(XML) Hot mitochondria?

2018-01-25T22:00:00Z

by Nick Lane

Mitochondria generate most of the heat in endotherms. Given some impedance of heat transfer across protein-rich bioenergetic membranes, mitochondria must operate at a higher temperature than body temperature in mammals and birds. But exactly how much hotter has been controversial, with physical calculations suggesting that maximal heat gradients across cells could not be greater than 10−5 K. Using the thermosensitive mitochondrial-targeted fluorescent dye Mito Thermo Yellow (MTY), Chrétien and colleagues suggest that mitochondria are optimised to nearly 50 °C, 10 °C hotter than body temperature. This extreme value questions what temperature really means in confined far-from-equilibrium systems but encourages a reconsideration of thermal biology.(image)



(XML) Mitochondria are physiologically maintained at close to 50 °C

2018-01-25T22:00:00Z

by Dominique Chrétien, Paule Bénit, Hyung-Ho Ha, Susanne Keipert, Riyad El-Khoury, Young-Tae Chang, Martin Jastroch, Howard T. Jacobs, Pierre Rustin, Malgorzata Rak

In endothermic species, heat released as a product of metabolism ensures stable internal temperature throughout the organism, despite varying environmental conditions. Mitochondria are major actors in this thermogenic process. Part of the energy released by the oxidation of respiratory substrates drives ATP synthesis and metabolite transport, but a substantial proportion is released as heat. Using a temperature-sensitive fluorescent probe targeted to mitochondria, we measured mitochondrial temperature in situ under different physiological conditions. At a constant external temperature of 38 °C, mitochondria were more than 10 °C warmer when the respiratory chain (RC) was fully functional, both in human embryonic kidney (HEK) 293 cells and primary skin fibroblasts. This differential was abolished in cells depleted of mitochondrial DNA or treated with respiratory inhibitors but preserved or enhanced by expressing thermogenic enzymes, such as the alternative oxidase or the uncoupling protein 1. The activity of various RC enzymes was maximal at or slightly above 50 °C. In view of their potential consequences, these observations need to be further validated and explored by independent methods. Our study prompts a critical re-examination of the literature on mitochondria.(image)



(XML) Correction: Regulating toxic chemicals for public and environmental health

2018-01-25T22:00:00Z

by The PLOS Biology Staff

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(XML) Evolution of mitotic spindle behavior during the first asymmetric embryonic division of nematodes

2018-01-22T22:00:00Z

by Aurore-Cécile Valfort, Caroline Launay, Marie Sémon, Marie Delattre

Asymmetric cell division is essential to generate cellular diversity. In many animal cells, the cleavage plane lies perpendicular to the mitotic spindle, and it is the spindle positioning that dictates the size of the daughter cells. Although some properties of spindle positioning are conserved between distantly related model species and different cell types, little is known of the evolutionary robustness of the mechanisms underlying this event. We recorded the first embryonic division of 42 species of nematodes closely related to Caenorhabditis elegans, which is an excellent model system to study the biophysical properties of asymmetric spindle positioning. Our recordings, corresponding to 128 strains from 27 Caenorhabditis and 15 non-Caenorhabditis species (accessible at http://www.ens-lyon.fr/LBMC/NematodeCell/videos/), constitute a powerful collection of subcellular phenotypes to study the evolution of various cellular processes across species. In the present work, we analyzed our collection to the study of asymmetric spindle positioning. Although all the strains underwent an asymmetric first cell division, they exhibited large intra- and inter-species variations in the degree of cell asymmetry and in several parameters controlling spindle movement, including spindle oscillation, elongation, and displacement. Notably, these parameters changed frequently during evolution with no apparent directionality in the species phylogeny, with the exception of spindle transverse oscillations, which were an evolutionary innovation at the base of the Caenorhabditis genus. These changes were also unrelated to evolutionary variations in embryo size. Importantly, spindle elongation, displacement, and oscillation each evolved independently. This finding contrasts starkly with expectations based on C. elegans studies and reveals previously unrecognized evolutionary changes in spindle mechanics. Collectively, these data demonstrate that, while the essential process of asymmetric cell division has been conserved over the course of nematode evolution, the underlying spindle movement parameters can combine in various ways. Like other developmental processes, asymmetric cell division is subject to system drift.(image)



(XML) Unique properties of TCR-activated p38 are necessary for NFAT-dependent T-cell activation

2018-01-22T22:00:00Z

by Muhammad S. Alam, Matthias M. Gaida, Subrata Debnath, Harichandra D. Tagad, Lisa M. Miller Jenkins, Ettore Appella, M. Jubayer Rahman, Jonathan D. Ashwell

Nuclear factor of activated T cells (NFAT) transcription factors are required for induction of T-cell cytokine production and effector function. Although it is known that activation via the T-cell antigen receptor (TCR) results in 2 critical steps, calcineurin-mediated NFAT1 dephosphorylation and NFAT2 up-regulation, the molecular mechanisms underlying each are poorly understood. Here we find that T cell p38, which is activated by an alternative pathway independent of the mitogen-activated protein (MAP) kinase cascade and with different substrate specificities, directly controls these events. First, alternatively (but not classically) activated p38 was required to induce the expression of the AP-1 component c-Fos, which was necessary for NFAT2 expression and cytokine production. Second, alternatively (but not classically) activated p38 phosphorylated NFAT1 on a heretofore unidentified site, S79, and in its absence NFAT1 was unable to interact with calcineurin or migrate to the nucleus. These results demonstrate that the acquisition of unique specificities by TCR-activated p38 orchestrates NFAT-dependent T-cell functions.(image)



(XML) Identification of osmoadaptive strategies in the halophile, heterotrophic ciliate Schmidingerothrix salinarum

2018-01-22T22:00:00Z

by Lea Weinisch, Steffen Kühner, Robin Roth, Maria Grimm, Tamara Roth, Daili J. A. Netz, Antonio J. Pierik, Sabine Filker

Hypersaline environments pose major challenges to their microbial residents. Microorganisms have to cope with increased osmotic pressure and low water activity and therefore require specific adaptation mechanisms. Although mechanisms have already been thoroughly investigated in the green alga Dunaliella salina and some halophilic yeasts, strategies for osmoadaptation in other protistan groups (especially heterotrophs) are neither as well known nor as deeply investigated as for their prokaryotic counterpart. This is not only due to the recent awareness of the high protistan diversity and ecological relevance in hypersaline systems, but also due to methodological shortcomings. We provide the first experimental study on haloadaptation in heterotrophic microeukaryotes, using the halophilic ciliate Schmidingerothrix salinarum as a model organism. We established three approaches to investigate fundamental adaptation strategies known from prokaryotes. First, proton nuclear magnetic resonance (1H-NMR) spectroscopy was used for the detection, identification, and quantification of intracellular compatible solutes. Second, ion-imaging with cation-specific fluorescent dyes was employed to analyze changes in the relative ion concentrations in intact cells. Third, the effect of salt concentrations on the catalytic performance of S. salinarum malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICDH) was determined. 1H-NMR spectroscopy identified glycine betaine (GB) and ectoine (Ect) as the main compatible solutes in S. salinarum. Moreover, a significant positive correlation of intracellular GB and Ect concentrations and external salinity was observed. The addition of exogenous GB, Ect, and choline (Ch) stimulated the cell growth notably, indicating that S. salinarum accumulates the solutes from the external medium. Addition of external 13C2-Ch resulted in conversion to 13C2-GB, indicating biosynthesis of GB from Ch. An increase of external salinity up to 21% did not result in an increase in cytoplasmic sodium concentration in S. salinarum. This, together with the decrease in the catalytic activities of MDH and ICDH at high salt concentration, demonstrates that S. salinarum employs the salt-out strategy for haloadaptation.(image)



(XML) Hippo signaling controls cell cycle and restricts cell plasticity in planarians

2018-01-22T22:00:00Z

by Nídia de Sousa, Gustavo Rodríguez-Esteban, Jose Ignacio Rojo-Laguna, Emili Saló, Teresa Adell

The Hippo pathway plays a key role in regulating cell turnover in adult tissues, and abnormalities in this pathway are consistently associated with human cancers. Hippo was initially implicated in the control of cell proliferation and death, and its inhibition is linked to the expansion of stem cells and progenitors, leading to larger organ size and tumor formation. To understand the mechanism by which Hippo directs cell renewal and promotes stemness, we studied its function in planarians. These stem cell–based organisms are ideal models for the analysis of the complex cellular events underlying tissue renewal in the whole organism. hippo RNA interference (RNAi) in planarians decreased apoptotic cell death, induced cell cycle arrest, and could promote the dedifferentiation of postmitotic cells. hippo RNAi resulted in extensive undifferentiated areas and overgrowths, with no effect on body size or cell number. We propose an essential role for hippo in controlling cell cycle, restricting cell plasticity, and thereby preventing tumoral transformation.(image)