Subject: PLOS Biology Volume 17(10) October 2019 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: 8bit


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New Articles in PLOS Biology

PUBLISHED: October 01, 2019 to October 31, 2019


An ecosystem-wide reproductive failure with more snow in the Arctic

In summer 2018, many arctic regions experienced unprecedented large amounts of snow. This Perspective article reports the ecological impacts of this extreme event, and shows that the severe snow conditions resulted in an almost complete reproductive failure across the entire ecosystem. The 2018 may be a rare event, but it also offers a gloomy peep into the future.

The NIH public access policy did not harm biomedical journals

This Perspective article analyzes whether the US National Institutes of Health open access policy, which from 2008 forced open access on thousands of papers, had a detectable effect on the "demography" of biomedical journals.

Community Pages

The NIH Open Citation Collection: A public access, broad coverage resource

In this Community Page article, authors from the National Institutes of Health describe the Open Citation Collection, a public domain citation database that covers articles indexed in PubMed. This free resource is made available through the iCite web interface at and through bulk downloads.

Refining animal research: The Animal Study Registry

This Community Page article presents the Animal Study Registry (, which was launched in January 2019 for pre-registration of animal studies in order to increase transparency and reproducibility of bioscience research and to promote animal welfare.

Meta-Research Article

Predicting translational progress in biomedical research

Fundamental scientific advances can take decades to translate into improvements in human health. This study shows that a machine learning model can accurately predict whether an article is likely to be cited by a future clinical trial or guideline, using as little as two years of post-publication citation data.

Research Articles

Combinatorial mutagenesis of rapidly evolving residues yields super-restrictor antiviral proteins

Antagonistic interactions drive host'virus evolutionary arms-races, often manifesting as recurrent amino acid changes at their protein'protein interaction interfaces. This study shows that evolution-guided combinatorial mutagenesis of a host antiviral protein enhances its restrictive properties, revealing constraints that shape breadth-versus-specificity trade-offs in antiviral proteins.

A neural ensemble correlation code for sound category identification

Animals and humans can readily categorize sounds into behaviorally relevant categories, but the neural mechanisms responsible for category formation are unknown. Neural recordings and modelling reveal that coordinated firing in auditory midbrain circuits provides a robust neural signal for decoding the identity of natural sounds and categories.

Symmetry breaking in the embryonic skin triggers directional and sequential plumage patterning

A survey of plumage patterns and their emergence in Galliformes, ratites, passerines, and penguins shows that their formation depends on a species-specific prepattern in the embryo and demonstrates that universal mechanisms govern the timely emergence of natural patterns in birds.

Alpha oscillations and traveling waves: Signatures of predictive coding?

A predictive coding model explains the spatio-temporal dynamics of alpha oscillations recorded in human brain experiments, including traveling waves whose direction of propagation depends on the cognitive state.

A photoactivatable crosslinking system reveals protein interactions in the Toxoplasma gondii inner membrane complex

The inner membrane complex of the human parasite Toxoplasma gondii is an important organelle involved in motility and replication. This study expands the genetic code of Toxoplasma, allowing the use of photoactivatable unnatural amino acids to uncover interactions within the apicomplexan inner membrane complex.

Human motor cortical beta bursts relate to movement planning and response errors

The dominant cortical signal before and after movement is the beta oscillations over sensorimotor cortex, which are thought to slowly modulate around movement. This study shows that trial-by-trial beta signals are highly dynamic and dominated by short, high-power bursts, whose precise timing is linked to motor behavior.

The developmental Wnt signaling pathway effector beta -catenin/TCF mediates hepatic functions of the sex hormone estradiol in regulating lipid metabolism

Certain hormones and growth factors are known to exert their effects via crosstalk with the Wnt signalling pathway. This study shows that in the liver, the Wnt pathway effector ß-catenin/TCF (a bipartite transcription factor) mediates the role of the female hormone estrogen in maintaining lipid homeostasis, downstream of the G-protein coupled estrogen receptor.

A hormone receptor pathway cell-autonomously delays neuron morphological aging by suppressing endocytosis

Neurons have a lifespan that parallels that of the organism and are largely irreplaceable. Analysis of the nematode "dauer" diapause reveals that state-dependent hormone signaling halts constitutive endocytosis, altering the localization of an actin regulator, thereby suspending dendrite morphogenesis and aging.

Mating induces switch from hormone-dependent to hormone-independent steroid receptor'mediated growth in Drosophila secondary cells

Hormone receptor-dependent growth of secondary cells in the accessory glands of male fruit flies switches to a hormone-independent mechanism after mating, reminiscent of changes seen in advanced prostate cancer in humans.

Cisd2 is essential to delaying cardiac aging and to maintaining heart functions

Cardiomyocytes from young mice lacking the mitochondrial iron-sulfur domain-containing protein Cisd2 show signs of premature aging; conversely, cardiomyocytes from old transgenic mice with a persistently high level of Cisd2 appear "young." This highlights Cisd2 as a novel drug target when developing therapies to delay cardiac aging.

Single-cell RNA sequencing reveals regulatory mechanism for trophoblast cell-fate divergence in human peri-implantation conceptuses

After implantation of the conceptus, trophoblasts undergo dynamic movements and cellular differentiation to generate the placenta, but the mechanisms controlling this process in humans remain elusive. In this study, single-cell RNA-seq of human peri-implantation conceptuses in vitro reveals TBX3 as a key regulator of trophoblast cell-fate divergence.

Spliceosomal Prp8 intein at the crossroads of protein and RNA splicing

A structural study shows that an intein interrupting the critical spliceosomal protein Prp8 in the fungal pathogen Cryptococcus neoformans is inhibited by biologically relevant metals, with implications for the regulation of RNA splicing.

Cell confinement reveals a branched-actin independent circuit for neutrophil polarity

Cells display a high degree of plasticity in migration, but how polarity is organized in different microenvironments has remained unclear. This study uses mechanical perturbations to reveal that migration using actin-rich or bleb-based protrusions are both organized around Rac GTPase.

Dynamic evolution in the key honey bee pathogen deformed wing virus: Novel insights into virulence and competition using reverse genetics

Deformed wing virus, a key pathogen of honey bees, shows rapid diversification after genetic bottlenecks; a novel reverse-genetic system provides insights into the forces that shape virus diversity, suggesting that virus quasi-species diversification may be driven by selection of genotypes capable of evading host RNAi defences.

NF1-cAMP signaling dissociates cell type'specific contributions of striatal medium spiny neurons to reward valuation and motor control

A mouse genetic study reveals that the multifaceted signaling protein neurofibromin (known for its role in the human genetic disease neurofibromatosis type 1) plays a key role in differential routing of motor and reward signals in populations of striatal medium spiny neurons.

Development of neural specialization for print: Evidence for predictive coding in visual word recognition

How a child's brain develops specialization for print is poorly understood. A study of children learning to read Chinese shows that neural specialization for print develops through and is characterized by interactions between regularities of visual inputs and efficiency of top-down predictions.

Sex chromosomes control vertical transmission of feminizing Wolbachia symbionts in an isopod

Microbial endosymbiosis is widespread in animals and relies on efficient vertical transmission through host generations. This study shows that sex chromosomes control vertical transmission of feminizing Wolbachia endosymbionts in an isopod, offering a new perspective on the evolutionary interplay between microbial symbionts and host sex chromosomes.

Autism candidate gene DIP2A regulates spine morphogenesis via acetylation of cortactin

The autism candidate gene DIP2A is known to be involved in the synthesis of acetylated coenzyme A, but its precise role in the brain remains largely unknown. This study shows that loss of DIP2A in mice results in an imbalance in the acetylation of the synaptic protein cortactin, causing defects in spine morphogenesis and synaptic transmission that may establish a link to autism spectrum disorders.

Shaping of a three-dimensional carnivorous trap through modulation of a planar growth mechanism

Many plant and animal organs derive from tissue sheets, but how are they shaped to create the diversity of forms observed in nature? This study uses a combination of imaging and mathematical modelling to show how carnivorous plant traps shape themselves in 3D by a growth framework oriented by tissue polarity, similar to that found in planar leaves.

Walking enhances peripheral visual processing in humans

Cognitive processes are almost exclusively investigated under highly controlled settings in which voluntary body movements are suppressed. New neurophysiological and behavioral data show that processing of peripheral visual input in humans is enhanced during walking.

Molecular basis for the PAM expansion and fidelity enhancement of an evolved Cas9 nuclease

The crystal structures of an evolved Cas9 nuclease, xCas9, in complex with different protospacer adjacent motifs (PAMs) revealed the molecular mechanism for its expanded PAM compatibility and enhanced DNA fidelity.

KHDC3L mutation causes recurrent pregnancy loss by inducing genomic instability of human early embryonic cells

Recurrent pregnancy loss is an important complication in reproductive health, and about 50% of cases remain unexplained. This study shows that KHDC3L safeguards the genomic stability of human early embryonic cells, and damaging mutations in its gene cause recurrent pregnancy loss in humans.

Prepontine non-giant neurons drive flexible escape behavior in zebrafish

Many species execute ballistic escape reactions to avoid imminent danger, but this is not always the best strategy. This study shows that zebrafish rapidly assess the salience of an auditory threat to select either an immediate ballistic response or a delayed and more flexible escape that uses a distinct and newly discovered neural pathway.

Resurrection of the ancestral RH5 invasion ligand provides a molecular explanation for the origin of P. falciparum malaria in humans

This study reveals a molecular pathway by which Plasmodium falciparum malaria arose via zoonotic transfer from gorillas by comparing the host receptor binding properties of extant and "resurrected" ancestral versions of the parasite's erythrocyte invasion ligand RH5.

Dissecting the dynamics of signaling events in the BMP, WNT, and NODAL cascade during self-organized fate patterning in human gastruloids

A self-organizing in vitro model of cell fate decisions during human gastrulation reveals that patterning is controlled by combinatorial dynamics of multiple signaling pathways, rather than by stable gradients.

Experimental evolution reveals a general role for the methyltransferase Hmt1 in noise buffering

Experimental evolution in yeast reveals that the methyltransferase Hmt1 functions as a mediator connecting environmental stimuli to cellular noise; Hmt1-mediated noise buffering is conserved in an evolutionarily distant yeast.

The Hippo pathway integrates PI3K'Akt signals with mechanical and polarity cues to control tissue growth

This study shows that the PI3K-Akt pathway promotes cell proliferation via the Yorkie/YAP transcriptional coactivator in response to mechanical stretching in vivo; the Hippo kinase acts as a key integrator of Akt and mechanical cues to control Yorkie/YAP activity and cell proliferation, with implications for human cancer, in which PI3K-Akt and mechanical forces play key roles in driving cell proliferation and malignancy.

Ratiometric GPCR signaling enables directional sensing in yeast

Cells use surface receptors to decode spatial information from chemical gradients, but accurate decoding is hampered by small cell size and the presence of molecular noise. This study shows that yeast cells decode pheromone gradients by measuring the local ratio of bound to unbound receptors. This mechanism corrects for uneven receptor density at the surface and amplifies the gradient transmitted to downstream components.

Machine learning of human plasma lipidomes for obesity estimation in a large population cohort

Obesity is associated with changes in plasma lipids, but while simple lipid quantification is routinely used, plasma lipids are rarely investigated at the level of individual molecules. A machine learning study based on lipidomes of a total of 1,311 individuals reveals improved associations of plasma lipids with total body fat and fat distribution compared to routine clinical laboratory variables.

Large-scale death of retinal astrocytes during normal development is non-apoptotic and implemented by microglia

A study of the neonatal mouse retina shows that developmental cell death of retinal astrocytes does not occur by apoptosis but is instead mediated by microglia, which kill and engulf astrocytes to effect their developmental removal.

High-throughput micropatterning platform reveals Nodal-dependent bisection of peri-gastrulation'associated versus preneurulation-associated fate patterning

This study describes a method to generate a robust high-throughput micropatterning platform, and uses it to reveal the role played by Nodal signalling in the self-organization of BMP signalling and the consequent fates that arise in micropatterned human embryonic stem cell colonies.

Pervasive and diverse collateral sensitivity profiles inform optimal strategies to limit antibiotic resistance

An experimental evolution study in bacteria offers a new approach to slowing antibiotic resistance by exploiting correlations that occur between evolved resistance levels to currently available drugs. The study reveals a new strategy that balances short-term inhibition of growth with infrequent use of antibiotics intended to steer pathogen populations to a more vulnerable future state.

Phase variation of a signal transduction system controls Clostridioides difficile colony morphology, motility, and virulence

In many bacterial species, a genetically clonal population can generate phenotypic heterogeneity to ensure survival of a subpopulation in the face of sudden environmental stressors. This work shows that the intestinal pathogen Clostridioides difficile introduces heterogeneity into the population through the phase-variable expression of a signal transduction system, resulting in broad changes in physiology, motility, and virulence.

SorCS1-mediated sorting in dendrites maintains neurexin axonal surface polarization required for synaptic function

The membrane trafficking mechanisms that regulate the polarized distribution of synaptic receptors in neurons are poorly understood. This study shows that endosomal sorting in dendrites controls the axonal surface polarization of the synaptic organizer neurexin, which is required for proper presynaptic differentiation and function.

Yeast alpha -arrestin Art2 is the key regulator of ubiquitylation-dependent endocytosis of plasma membrane vitamin B1 transporters

A combination of proteomics, protein modeling, and molecular biology sheds light on how endocytosis of the plasma membrane vitamin B1 transporter Thi7 in yeast is regulated by the a-arrestin Art2.

Cell generation dynamics underlying naive T-cell homeostasis in adult humans

Our pool of naive T cells is critical for protection against new infections and cancers. By measuring remnant 14C from 1960s nuclear bomb blasts that has been incorporated into cellular DNA, this study defines the average age of the naive T-cell pool in healthy adults, revealing the slow, regulated turnover of the naive T-cell pool, supporting its maintenance for a human lifetime.

Short Reports

Somatosensory cortex participates in the consolidation of human motor memory

This study provides direct evidence that learning-related changes to somatosensory cortex are involved in the consolidation of human motor memory. Specifically, transcranial magnetic stimulation applied to somatosensory cortex following motor learning blocks motor memory consolidation, whereas sham stimulation and suppression of activity in primary motor cortex have no adverse effect on retention.

The lunar cycle drives migration of a nocturnal bird

If the fuelling rate of birds varies periodically, it may act as a synchroniser of migrant populations over large spatial scales. Tracking of the nightjar, a long-distance nocturnal migrant bird, reveals that it adjusts its movements in relation to the lunar cycle.

A rotifer-derived paralytic compound prevents transmission of schistosomiasis to a mammalian host

Commensal rotifers living on the intermediate host (snail) of a human parasite (schistosome) produce a factor that paralyzes the schistosome's infective larvae and prevents them from infecting a mammalian definitive host (mouse). Identification of this molecule provides new directions for understanding larval motility and new strategies for preventing schistosome infection.

Song playbacks demonstrate slower evolution of song discrimination in birds from Amazonia than from temperate North America

The use of more than 100 song playback experiments reveals that birds give stronger responses to songs of closely related species in the Amazon than in temperate North America, suggesting that speciation is currently happening more slowly in the species-rich tropics than in species-poor temperate regions.

Historical contingency in the evolution of antibiotic resistance after decades of relaxed selection

Strains of Escherichia coli from the long-term evolution experiment (LTEE) have independently evolved for multiple decades and tens of thousands of generations in the absence of antibiotics; this study shows that evolution and diversification of a single bacterial species in an antibiotic-free environment can render the subsequent evolution of resistance unpredictable.

Mechanical stiffness of reconstituted actin patches correlates tightly with endocytosis efficiency

This study uses in vitro reconstitution of endocytic actin patches and mechanical measurements with chains of superparamagnetic microbeads to reveal a tight correlation between the stiffness of actin networks and the efficiency of endocytosis in yeast.

Methods and Resources

Dynamic enhancers control skeletal muscle identity and reprogramming

The epigenomic basis for the identity and adaptation of different muscle groups is poorly understood. This study reveals chromatin landscapes across muscle groups and their dynamic response to either exercise or overexpression of PPAR gamma coactivator 1 alpha.

Mechanically resolved imaging of bacteria using expansion microscopy

This study describes a new expansion microscopy imaging technique that uses cell wall mechanics as a quantitative and phenotypic imaging contrast, orthogonal to spectral separation, in order to resolve bacterial cells of different species or in distinct physiological states.


Correction: Environmental pollution is associated with increased risk of psychiatric disorders in the US and Denmark

Correction: Selection and characterization of ultrahigh potency designed ankyrin repeat protein inhibitors of C. difficile toxin B

Correction: Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons

Correction: The Naturally Processed CD95L Elicits a c-Yes/Calcium/PI3K-Driven Cell Migration Pathway

Correction: MCC950/CRID3 potently targets the NACHT domain of wild-type NLRP3 but not disease-associated mutants for inflammasome inhibition


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