bluuebunny/crossref_metadata_2025 huggingface dataset:
Wave reflection and transmission in multiply stented blood vessels
Authors: Papathanasiou T. K. , Movchan A. B. , Bigoni D.
Published: June 2017

Closed circulatory systems display an exquisite balance between vascular elasticity and viscous fluid effects, to induce pulse-smoothing and avoid resonance during the cardiac cycle. Stents in the arterial tree alter this balance through stiffening and because a periodic structure is introduced, capable of interacting with the fluid in a complex way. While the former feature has been investigated, the latter received no attention so far. But periodic structures are the building blocks of metamaterials, known for their ‘non-natural’ behaviour. Thus, the investigation of a stent's periodic microstructure dynamical interactions is crucial to assess possible pathological responses. A one-dimensional fluid–structure interaction model, simple enough to allow an analytical solution for situations of interest involving one or two interacting stents, is introduced. It is determined: (i) whether or not frequency bands exist in which reflected blood pulses are highly increased and (ii) if these bands are close to the characteristic frequencies of arteries and finally, (iii) if the internal structure of the stent can sensibly affect arterial blood dynamics. It is shown that, while the periodic structure of an isolated stent can induce anomalous reflection only in pathological conditions, the presence of two interacting stents is more critical, and high reflection can occur at frequencies not far from the physiological values.
Ultrasonic defect characterization using parametric-manifold mapping
Authors: Velichko A. , Bai L. , Drinkwater B. W.
Published: June 2017

The aim of ultrasonic non-destructive evaluation includes the detection and characterization of defects, and an understanding of the nature of defects is essential for the assessment of structural integrity in safety critical systems. In general, the defect characterization challenge involves an estimation of defect parameters from measured data. In this paper, we explore the extent to which defects can be characterized by their ultrasonic scattering behaviour. Given a number of ultrasonic measurements, we show that characterization information can be extracted by projecting the measurement onto a parametric manifold in principal component space. We show that this manifold represents the entirety of the characterization information available from far-field harmonic ultrasound. We seek to understand the nature of this information and hence provide definitive statements on the defect characterization performance that is, in principle, extractable from typical measurement scenarios. In experiments, the characterization problem of surface-breaking cracks and the more general problem of elliptical voids are studied, and a good agreement is achieved between the actual parameter values and the characterization results. The nature of the parametric manifold enables us to explain and quantify why some defects are relatively easy to characterize, whereas others are inherently challenging.
Addressing the discrepancy of finding the equilibrium melting point of silicon using molecular dynamics simulations
Authors: Chavoshi Saeed Zare , Xu Shuozhi , Goel Saurav
Published: June 2017

We performed molecular dynamics simulations to study the equilibrium melting point of silicon using (i) the solid–liquid coexistence method and (ii) the Gibbs free energy technique, and compared our novel results with the previously published results obtained from the Monte Carlo (MC) void-nucleated melting method based on the Tersoff-ARK interatomic potential (Agrawal
et al. Phys. Rev. B
72
, 125206. (
doi:10.1103/PhysRevB.72.125206
)). Considerable discrepancy was observed (approx. 20%) between the former two methods and the MC void-nucleated melting result, leading us to question the applicability of the empirical MC void-nucleated melting method to study a wide range of atomic and molecular systems. A wider impact of the study is that it highlights the bottleneck of the Tersoff-ARK potential in correctly estimating the melting point of silicon.
Extensional channel flow revisited: a dynamical systems perspective
Authors: Marques Francisco , Meseguer Alvaro , Mellibovsky Fernando , Weidman Patrick D.
Published: June 2017

Extensional self-similar flows in a channel are explored numerically for arbitrary stretching–shrinking rates of the confining parallel walls. The present analysis embraces time integrations, and continuations of steady and periodic solutions unfolded in the parameter space. Previous studies focused on the analysis of branches of steady solutions for particular stretching–shrinking rates, although recent studies focused also on the dynamical aspects of the problems. We have adopted a dynamical systems perspective, analysing the instabilities and bifurcations the base state undergoes when increasing the Reynolds number. It has been found that the base state becomes unstable for small Reynolds numbers, and a transitional region including complex dynamics takes place at intermediate Reynolds numbers, depending on the wall acceleration values. The base flow instabilities are constitutive parts of different codimension-two bifurcations that control the dynamics in parameter space. For large Reynolds numbers, the restriction to self-similarity results in simple flows with no realistic behaviour, but the flows obtained in the transition region can be a valuable tool for the understanding of the dynamics of realistic Navier–Stokes solutions.
Glacial survival of trophically linked boreal species in northern Europe
Authors: Quinzin Maud C. , Normand Signe , Dellicour Simon , Svenning Jens-Christian , Mardulyn Patrick
Published: June 2017

Whether non-arctic species persisted in northern Europe during the Last Glacial Maximum (LGM) is highly debated. Until now, the debate has mostly focused on plants, with little consideration for other groups of organisms, e.g. the numerous plant-dependent insect species. Here, we study the late-Quaternary evolution of the European range of a boreo-montane leaf beetle,Gonioctena intermedia, which feeds exclusively on the boreal and temperate treesPrunus padusandSorbus aucuparia. Using species distribution models, we estimated the congruence between areas of past and present suitable climate for this beetle and its host plants. Then we derived historical hypotheses from the congruent range estimates, and evaluated their compatibility with observed DNA sequence variation at five independent loci. We investigated compatibility using computer simulations of population evolution under various coalescence models. We find strong evidence for range modifications in response to late-Quaternary climate changes, and support for the presence of populations ofG. intermediain northern Europe since the beginning of the last glaciation. The presence of a co-dependent insect in the region through the LGM provides new evidence supporting the glacial survival of cold-tolerant tree species in northern Europe.
Motorboat noise impacts parental behaviour and offspring survival in a reef fish
Authors: Nedelec Sophie L. , Radford Andrew N. , Pearl Leanne , Nedelec Brendan , McCormick Mark I. , Meekan Mark G. , Simpson Stephen D.
Published: June 2017

Anthropogenic noise is a pollutant of international concern, with mounting evidence of disturbance and impacts on animal behaviour and physiology. However, empirical studies measuring survival consequences are rare. We use a field experiment to investigate how repeated motorboat-noise playback affects parental behaviour and offspring survival in the spiny chromis (Acanthochromis polyacanthus), a brooding coral reef fish. Repeated observations were made for 12 days at 38 natural nests with broods of young. Exposure to motorboat-noise playback compared to ambient-sound playback increased defensive acts, and reduced both feeding and offspring interactions by brood-guarding males. Anthropogenic noise did not affect the growth of developing offspring, but reduced the likelihood of offspring survival; while offspring survived at all 19 nests exposed to ambient-sound playback, six of the 19 nests exposed to motorboat-noise playback suffered complete brood mortality. Our study, providing field-based experimental evidence of the consequences of anthropogenic noise, suggests potential fitness consequences of this global pollutant.
Chimpanzees, bonobos and children successfully coordinate in conflict situations
Authors: Sánchez-Amaro Alejandro , Duguid Shona , Call Josep , Tomasello Michael
Published: June 2017

Social animals need to coordinate with others to reap the benefits of group-living even when individuals' interests are misaligned. We compare how chimpanzees, bonobos and children coordinate their actions with a conspecific in a Snowdrift game, which provides a model for understanding how organisms coordinate and make decisions under conflict. In study 1, we presented pairs of chimpanzees, bonobos and children with an unequal reward distribution. In the critical condition, the preferred reward could only be obtained by waiting for the partner to act, with the risk that if no one acted, both would lose the rewards. Apes and children successfully coordinated to obtain the rewards. Children used a ‘both-partner-pull’ strategy and communicated during the task, while some apes relied on an ‘only-one-partner-pulls' strategy to solve the task, although there were also signs of strategic behaviour as they waited for their partner to pull when that strategy led to the preferred reward. In study 2, we presented pairs of chimpanzees and bonobos with the same set-up as in study 1 with the addition of a non-social option that provided them with a secure reward. In this situation, apes had to actively decide between the unequal distribution and the alternative. In this set-up, apes maximized their rewards by taking their partners' potential actions into account. In conclusion, children and apes showed clear instances of strategic decision-making to maximize their own rewards while maintaining successful coordination.
Tetranychus urticae
mites do not mount an induced immune response against bacteria
Authors: Santos-Matos Gonçalo , Wybouw Nicky , Martins Nelson E. , Zélé Flore , Riga Maria , Leitão Alexandre B. , Vontas John , Grbić Miodrag , Van Leeuwen Thomas , Magalhães Sara , Sucena Élio
Published: June 2017

The genome of the spider mite
Tetranychus urticae
, a herbivore, is missing important elements of the canonical
Drosophila
immune pathways necessary to fight bacterial infections. However, it is not known whether spider mites can mount an immune response and survive bacterial infection. In other chelicerates, bacterial infection elicits a response mediated by immune effectors leading to the survival of infected organisms. In
T. urticae
, infection by either
Escherichia coli
or
Bacillus megaterium
did not elicit a response as assessed through genome-wide transcriptomic analysis. In line with this, spider mites died within days even upon injection with low doses of bacteria that are non-pathogenic to
Drosophila
. Moreover, bacterial populations grew exponentially inside the infected spider mites. By contrast,
Sancassania berlesei
, a litter-dwelling mite, controlled bacterial proliferation and resisted infections with both Gram-negative and Gram-positive bacteria lethal to
T. urticae
. This differential mortality between mite species was absent when mites were infected with heat-killed bacteria. Also, we found that spider mites harbour in their gut 1000-fold less bacteria than
S. berlesei
. We show that
T. urticae
has lost the capacity to mount an induced immune response against bacteria, in contrast to other mites and chelicerates but similarly to the phloem feeding aphid
Acyrthosiphon pisum
. Hence, our results reinforce the putative evolutionary link between ecological conditions regarding exposure to bacteria and the architecture of the immune response.
Three-month-old human infants use vocal cues of body size
Authors: Pietraszewski David , Wertz Annie E. , Bryant Gregory A. , Wynn Karen
Published: June 2017

Differences in vocal fundamental (
F
0
) and average formant (
F
n
) frequencies covary with body size in most terrestrial mammals, such that larger organisms tend to produce lower frequency sounds than smaller organisms, both between species and also across different sex and life-stage morphs within species. Here we examined whether three-month-old human infants are sensitive to the relationship between body size and sound frequencies. Using a violation-of-expectation paradigm, we found that infants looked longer at stimuli inconsistent with the relationship—that is, a smaller organism producing lower frequency sounds, and a larger organism producing higher frequency sounds—than at stimuli that were consistent with it. This effect was stronger for fundamental frequency than it was for average formant frequency. These results suggest that by three months of age, human infants are already sensitive to the biologically relevant covariation between vocalization frequencies and visual cues to body size. This ability may be a consequence of developmental adaptations for building a phenotype capable of identifying and representing an organism's size, sex and life-stage.
Evidence for strategic cooperation in humans
Authors: Burton-Chellew Maxwell N. , El Mouden Claire , West Stuart A.
Published: June 2017

Humans may cooperate strategically, cooperating at higher levels than expected from their short-term interests, to try and stimulate others to cooperate. To test this hypothesis, we experimentally manipulated the extent an individual's behaviour is known to others, and hence whether or not strategic cooperation is possible. In contrast with many previous studies, we avoided confounding factors by preventing individuals from learning during the game about either pay-offs or about how other individuals behave. We found clear evidence for strategic cooperators—just telling some individuals that their groupmates would be informed about their behaviour led to them tripling their initial level of cooperation, from 17 to 50%. We also found that many individuals play as if they do not understand the game, and their presence obscures the detection of strategic cooperation. Identifying such players allowed us to detect and study strategic motives for cooperation in novel, more powerful, ways.
Global biogeography since Pangaea
Authors: McIntyre Sarah R. N. , Lineweaver Charles H. , Groves Colin P. , Chopra Aditya
Published: June 2017

The break-up of the supercontinent Pangaea around 180 Ma has left its imprint on the global distribution of species and resulted in vicariance-driven speciation. Here, we test the idea that the molecular clock dates, for the divergences of species whose geographical ranges were divided, should agree with the palaeomagnetic dates for the continental separations. Our analysis of recently available phylogenetic divergence dates of 42 pairs of vertebrate taxa, selected for their reduced ability to disperse, demonstrates that the divergence dates in phylogenetic trees of continent-bound terrestrial and freshwater vertebrates are consistent with the palaeomagnetic dates of continental separation.
Life or death: disease-tolerant coral species activate autophagy following immune challenge
Authors: Fuess Lauren E. , Pinzón C Jorge H. , Weil Ernesto , Grinshpon Robert D. , Mydlarz Laura D.
Published: June 2017

Global climate change has increased the number and severity of stressors affecting species, yet not all species respond equally to these stressors. Organisms may employ cellular mechanisms such as apoptosis and autophagy in responding to stressful events. These two pathways are often mutually exclusive, dictating whether a cell adapts or dies. In order to examine differences in cellular response to stress, we compared the immune response of four coral species with a range of disease susceptibility. Using RNA-seq and novel pathway analysis, we were able to identify differences in response to immune stimulation between these species. Disease-susceptible species
Orbicella faveolata
activated pathways associated with apoptosis. By contrast, disease-tolerant species
Porites porites
and
Porites astreoides
activated autophagic pathways. Moderately susceptible species
Pseudodiploria strigosa
activated a mixture of these pathways. These findings were corroborated by apoptotic caspase protein assays, which indicated increased caspase activity following immune stimulation in susceptible species. Our results indicate that in response to immune stress, disease-tolerant species activate cellular adaptive mechanisms such as autophagy, while susceptible species turn on cell death pathways. Differences in these cellular maintenance pathways may therefore influence the organismal stress response. Further study of these pathways will increase understanding of differential stress response and species survival in the face of changing environments.
Indirect effects of ocean acidification drive feeding and growth of juvenile crown-of-thorns starfish,
Acanthaster planci
Authors: Kamya Pamela Z. , Byrne Maria , Mos Benjamin , Hall Lauren , Dworjanyn Symon A.
Published: June 2017

The indirect effects of changing climate in modulating trophic interactions can be as important as the direct effects of climate stressors on consumers. The success of the herbivorous juvenile stage of the crown-of-thorns starfish (COTS),
Acanthaster planci,
may be affected by the impacts of ocean conditions on its crustose coralline algal (CCA) food. To partition the direct effects of near future ocean acidification on juvenile COTS and indirect effects through changes in their CCA food, COTS were grown in three pH
T
levels (7.9, 7.8, 7.6) and fed CCA grown at similar pH levels. Consumption of CCA by COTS was bolstered when the COTS were grown in low pH and when they were fed CCA grown in low pH regardless of the pH in which the COTS were reared. COTS fed CCA grown at pH 7.6 grew fastest, but the pH/
p
CO
2
that the COTS were reared in had no direct effect on growth. Ocean acidification conditions decreased the C : N ratio and carbonate levels in the CCA. Bolstered growth in COTS may be driven by enhanced palatability, increased nutritive state and reduced defences of their CCA food. These results indicate that near future acidification will increase the success of early juvenile COTS and boost recruitment into the coral-eating life stage.
SNVPhyl: a single nucleotide variant phylogenomics pipeline for microbial genomic epidemiology
Authors: Petkau Aaron , Mabon Philip , Sieffert Cameron , Knox Natalie C. , Cabral Jennifer , Iskander Mariam , Iskander Mark , Weedmark Kelly , Zaheer Rahat , Katz Lee S. , Nadon Celine , Reimer Aleisha , Taboada Eduardo , Beiko Robert G. , Hsiao William , Brinkman Fiona , Graham Morag , Van Domselaar Gary
Published: June 2017

The recent widespread application of whole-genome sequencing (WGS) for microbial disease investigations has spurred the development of new bioinformatics tools, including a notable proliferation of phylogenomics pipelines designed for infectious disease surveillance and outbreak investigation. Transitioning the use of WGS data out of the research laboratory and into the front lines of surveillance and outbreak response requires user-friendly, reproducible and scalable pipelines that have been well validated. Single Nucleotide Variant Phylogenomics (SNVPhyl) is a bioinformatics pipeline for identifying high-quality single-nucleotide variants (SNVs) and constructing a whole-genome phylogeny from a collection of WGS reads and a reference genome. Individual pipeline components are integrated into the Galaxy bioinformatics framework, enabling data analysis in a user-friendly, reproducible and scalable environment. We show that SNVPhyl can detect SNVs with high sensitivity and specificity, and identify and remove regions of high SNV density (indicative of recombination). SNVPhyl is able to correctly distinguish outbreak from non-outbreak isolates across a range of variant-calling settings, sequencing-coverage thresholds or in the presence of contamination. SNVPhyl is available as a Galaxy workflow, Docker and virtual machine images, and a Unix-based command-line application. SNVPhyl is released under the Apache 2.0 license and available at http://snvphyl.readthedocs.io/ or at https://github.com/phac-nml/snvphyl-galaxy.
A Guide to Analysis and Reconstruction of Serial Block Face Scanning Electron Microscopy Data
Authors: Cocks E. , Taggart M. , Rind F.C. , White K.
Published: June 2017

Serial block face scanning electron microscopy (SBF-SEM) is a relatively new technique that allows the acquisition of serially sectioned, imaged and digitally aligned ultrastructural data. There is a wealth of information that can be obtained from the resulting image stacks but this presents a new challenge for researchers - how to computationally analyse and make best use of the large data sets produced. One approach is to reconstruct structures and features of interest in 3D. However the software programs can appear overwhelming, time consuming and not intuitive for those new to image analysis. There are a limited number of published articles that provide sufficient detail on how to do this type of reconstruction. Therefore the aim of this paper is to provide a detailed step-by-step protocol, videos and explanation on the types of analysis and programs that can be used. To showcase the programs, skeletal muscle from fetal and adult guinea pigs were used. The tissue was processed using the heavy metal protocol developed specifically for SBFSEM. Trimmed resin blocks were placed into a Zeiss Sigma SEM incorporating the Gatan 3View and the resulting image stacks were analysed in 3 different programs, Fiji, Amira and MIB, using a range of tools available for segmentation. The results from the image analysis comparison show that the analysis tools are often more suited to a type of structure. For example larger structures, such as nuclei and cells, can be segmented using interpolation, which speeds up analysis; single contrast structures, such as the nucleolus, can be segmented using the contrast-based thresholding tools. Knowing the nature of the tissue and its specific structures (complexity, contrast, if there are distinct membranes, size) will help to determine the best method for reconstruction and thus maximising output from valuable tissue.
Plasmids, Viruses, And Other Circular Elements In Rat Gut
Authors: Jørgensen Tue Sparholt , Hansen Martin Asser , Xu Zhuofei , Tabak Michael A. , Sørensen Søren J , Hansen Lars Hestbjerg
Published: June 2017

Circular DNA such as plasmids and some viruses is the major source of genetic variation in bacteria and thus has the same important evolutionary function as sexual reproduction in eukaryotic species: It allows dissemination of advantageous traits through bacterial populations. Here, we present the largest collection of novel complete extrachromosomal genetic elements to date, and compare the diversity, distribution, and content of circular sequences from 12 rat cecum samples from the pristine Falkland Islands and Danish hospital sewers, two environments with contrasting anthropogenic impact. Using a validated pipeline, we find 1,869 complete, circular, non-redundant sequences, of which only 114 are previously described. While sequences of similar size from the two environments share general features, the size distribution of the elements between environments differs significantly, with hospital sewer samples hosting larger circular elements than Falkland Island samples, a possible consequence of the massive anthropogenic influence in the hospital sewer environment. Several antibiotic resistance genes have been identified with a notably larger diversity in hospital sewer samples than in Falkland Islands samples in concordance with expectations. Our findings suggest that even though sequences of similar length carry similar traits, the mobilome of rat gut bacteria are affected by human activities in that sewer rats have larger elements and more diverse large elements than pristine island rats. More than 1000 novel and not classified small sequences was identified and hint the existence of a biological unit not previously described on a community level.

List of figures

Sampling sites and Rat gut anatomy

Rarefaction curves of circular elements

Elements shared between environments

Size distribution plots of rep, mob, stab, capsid carrying elements.

Graphical representation of representative elements

Replication genes content, diversity

Rep_2 plasmid replication gene phylogeny

Table Resfams findings

List of appendices

basic statistics table

Phylogeny of plasmid replication genes

List of known plasmids and circular sequences found in 1869 elements

Automatic identification of identical circular elements with different breaking points

Test of separation of plasmids and viruses based on predicted, annotated genes

No false positive circular sequences from MG1655 genomic sequencing.
The consequences of polyandry for sibship structures, distributions of relationships and relatedness, and potential for inbreeding in a wild population
Authors: Germain Ryan R. , Arcese Peter , Reid Jane M.
Published: June 2017

The evolutionary benefits of simultaneous polyandry (female multiple mating within a single reproductive event) remain elusive. One potential benefit could arise if polyandry alters sibship structures and consequent relationships and relatedness among females’ descendants, and thereby intrinsically reduces future inbreeding risk (the ‘indirect inbreeding avoidance hypothesis’). However such effects have not been quantified in naturally complex reproductive systems that also encompass iteroparity, overlapping generations, sequential polyandry, and polygyny. We used long-term social and genetic pedigree data from song sparrows (Melospiza melodia) to quantify cross-generational consequences of simultaneous polyandry for offspring sibship structures and distributions of relationships and relatedness among possible mates. Simultaneous polyandry decreased full-sibships and increased half-sibships on average, but such effects varied among females and were smaller than would occur in the absence of sequential polyandry or polygyny. Further, while simultaneous polyandry decreased the overall frequencies of possible matings among adult full-sibs, it increased the frequencies of possible matings among adult half-sibs and more distant relatives. These results imply that the intrinsic consequences of simultaneous polyandry for inbreeding risk could cause weak indirect selection on polyandry, but the magnitude and direction of such effects will depend on complex interactions with other mating system components and the form of inbreeding depression.
Design Principles of Lambda’s Lysis/Lysogeny Decision vis-a-vis Multiplicity of Infection
Authors: Wadhwa Dinkar
Published: June 2017

Bacteriophage lambda makes a decision between lysis and lysogeny based on the number of coinfecting phages, namely the multiplicity of infection (MoI): lysis at low MoIs; lysogeny at high MoIs. Here, by evaluating various rationally designed models on their ability a) to make the lytic decision at MoI of 1 and the lysogeny decision at MoI of 2, b) to exhibit bistability at both MoIs, and c) to perform accurately in the presence of noise, it is demonstrated that lambda’s lysis/lysogeny decision is based on three features, namely a) mutual repression, b) cooperative positive autoregulation of CI, and c) cooperative binding of the activator protein, not basal expression, triggering positive autoregulatory loop of CI. Cro and CI are sufficient to acquire the first two features. CII is required to acquire the third feature. The quasi-minimal two-protein model for the switch is justified by showing its qualitative equivalence, except for Cro repression ofpRM, to the lambda’s gene regulatory network responsible for the decision. A three-protein simplified version of the lambda’s switch is shown to possess all the three design features. Bistability at MoI of 1 is responsible for lysogen stability, whereas bistability at MoI of 2 imparts stability to lytic development post-infection and especially during prophage induction.
Visual pathways from the perspective of cost functions and multi-task deep neural networks
Authors: Scholte H. Steven , Losch Max M. , Ramakrishnan Kandan , de Haan Edward H.F. , Bohte Sander M.
Published: June 2017

Vision research has been shaped by the seminal insight that we can understand the higher-tier visual cortex from the perspective of multiple functional pathways with different goals. In this paper, we try to give a computational account of the functional organization of this system by reasoning from the perspective of multi-task deep neural networks. Machine learning has shown that tasks become easier to solve when they are decomposed into subtasks with their own cost function. We hypothesize that the visual system optimizes multiple cost functions of unrelated tasks and this causes the emergence of a ventral pathway dedicated to vision for perception, and a dorsal pathway dedicated to vision for action. To evaluate the functional organization in multi-task deep neural networks, we propose a method that measures the contribution of a unit towards each task, applying it to two networks that have been trained on either two related or two unrelated tasks, using an identical stimulus set. Results show that the network trained on the unrelated tasks shows a decreasing degree of feature representation sharing towards higher-tier layers while the network trained on related tasks uniformly shows high degree of sharing. We conjecture that the method we propose can be used to analyze the anatomical and functional organization of the visual system and beyond. We predict that the degree to which tasks are related is a good descriptor of the degree to which they share downstream cortical-units.
Non-classical estrogen signaling inhibits melanoma and improves response to PD-1 blockade
Authors: Natale Christopher A. , Li Jinyang , Zhang Junqian , Dahal Ankit , Stanger Ben Z. , Ridky Todd W.
Published: June 2017

Female sex and pregnancy are associated with reduced risk of melanoma and improved stage specific survival; however, the mechanism underlying this apparent clinical benefit is unknown. We previously discovered that pregnancy-associated 17β-estradiol drives melanocyte differentiation by activating the nonclassical G-protein coupled estrogen receptor (GPER). Here, we show that pregnancy inhibits melanoma, and that transient GPER activation induces long-term changes in melanocytes, which are associated with increased cellular differentiation and resistance to melanoma. A selective GPER agonist induced c-Myc protein degradation, slowed tumor growth, and inhibited expression of immune suppressive proteins including PD-L1, suggesting that GPER signaling may render melanoma cells more vulnerable to immunotherapy. Systemically delivered GPER agonist was well tolerated, and cooperated synergistically with PD-1 blockade in melanoma-bearing mice to dramatically extend survival. These results thus define GPER as a target for differentiation-based melanoma therapy.

Significance

Immune checkpoint inhibitors including αPD-1 induce durable remissions in only 30% of patients with advanced melanoma. This work demonstrates that αPD-1 efficacy is significantly improved by systemic delivery of a selective agonist of the nonclassical estrogen receptor, GPER, which drives melanoma differentiation and renders tumors more vulnerable to the immune system.
Impairment of zebrafish reproduction upon exposure to melengestrol acetate
Authors: Xiong Kewen , Zhong Chunyun , Wang Xin
Published: June 2017

Synthetic progestins contamination is common in the aquatic ecosystem, which may lead to serious health problem on aquatic animals. Melengestrol acetate (MGA) has been detected in the aquatic environment; however, its potential effects on fish reproduction are largely unclear. Here, we aimed to investigate the endocrine disruption and impact of MGA on zebrafish reproduction. Six-month old reproductive zebrafish were exposed to four nominal concentrations of MGA (1,10, 100 and 200 ng/L) for 15 days. Treatment with MGA reduced the egg production with a significant decrease at 200 ng/L. The circulating concentrations of estradiol and testosterone in female zebrafish or 11-keto testosterone in male zebrafish were significantly diminished compared to the non-exposed control fish. The early embryonic development or hatching rates were unaffected during the MGA exposure. Our results indicated that MGA was a potent endocrine disruptor in fish and the fish reproduction could be impaired even during a short-term exposure to MGA.
Bystro: rapid online variant annotation and natural-language filtering at whole-genome scale
Authors: Kotlar Alex V. , Trevino Cristina E. , Zwick Michael E. , Cutler David J. , Wingo Thomas S.
Published: June 2017

Accurately selecting relevant alleles in large sequencing experiments remains technically challenging. Bystro (https://bystro.io/) is the first online, cloud-based application that makes variant annotation and filtering accessible to all researchers for terabyte-sized whole-genome experiments containing thousands of samples. Its key innovation is a general-purpose, natural-language search engine that enables users to identify and export alleles and samples of interest in milliseconds. The search engine dramatically simplifies complex filtering tasks that previously required programming experience or specialty command-line programs. Critically, Bystro’s annotation and filtering capabilities are orders of magnitude faster than previous solutions, saving weeks of processing time for large experiments.
Cooling Induced by Uphill Energy Transport in Plant Photosystems
Authors: Sen Koel , Bhattacharya Abhishek , Singha Santiswarup , Dasgupta Maitrayee , Dasgupta Anjan Kr
Published: June 2017

The uphill energy transfer in photosystems implies input energy at higher wavelength leading to energy output at lower wavelength. Briefly, energy is uphill transported from photosystem I (PSI) to photosystem II (PSII), the latter having a lower wavelength emission. This uphill energy transport involves absorption of thermal energy from the surroundings. While such cooling effects have been reported in laser systems we report for the first time a white light driven cooling in thylakoid suspension. The cooling of the surrounding medium by appropriate illumination was illustrated using thermal measurements. Again cooling is inhibited by agents like 3-(3,4-Dichlorophenyl)-1,1-dimethylurea,that block the linear electron flow between the photocenters, implying a dependence of the cooling on interplay between such centers. Furthermore, it is possible to modulate the cooling pattern by addition of external agents like nanopaticles, some favoring further cooling (e.g., Ag nanoparticle) and some like Au or chlorophyll nanoparticles, showing insignificant or even reverse trends. Interestingly, the cooling is invariably associated with the 77K spectra of the thylakoid suspension. With reference to the dark control, an agent causing cooling always increases PSII to PSI ratio and vice versa i.e.,the uphill energy transport. Importantly, the cooling effect, apart from its import role in plant physiology can be exploited artificially for energy saving in post-harvest or food preservation.
Nitric oxide sensing by chlorophylla
Authors: Bhattacharya Abhishek , Biswas Pranjal , Kar Puranjoy , Roychoudhury Piya , Basu Sankar , Ghosh Sanjay , Panda Kaustab , Pal Ruma , Dasgupta Anjan Kr.
Published: June 2017

Nitric oxide (NO) acts as a signalling molecule that has direct and indirect regulatory roles in various functional processes in biology, though in plant kingdom its role is relatively unexplored. One reason for this is the fact that sensing of NO is always challenging. There are very few probes that can classify the different NO species. The present paper proposes a simple but straightforward way for sensing different NO species using chlorophyll, the source of inspiration being hemoglobin that serves as a NO sink in most mamalian system. The proposed method is able to classify NO from DETA-NONOate or (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1,2-diolate, nitrite, nitrate and S-nitrosothiol or SNO. This discrimination is carried out by chlorophylla(chl a) at nano molar (nM) order of sensitivity and at 293K to 310K. Molecular docking reveals the differential binding behaviour of NO and SNO with chlorophyll, the predicted binding affinity matching with the experimental observation. Additional expreiments with diverse range of cyanobacteria reveals that apart from spectroscopic approach the proposed sensing module can be used in microscopic inspection of NO speices. Binding of NO is sensitive to tempertaure and static magnetic field. This provides additional support to the involvement of the porphyrin ring structure to the NO sensing process. This also broadens the scope of the sensing methods as hinted in the text.
Stepwise approach to oocyte depletion inSrymutated XY female mice
Authors: Sakashita Akihiko , Wakai Takuya , Kawabata Yukiko , Nishimura Chiaki , Sotomaru Yusuke , Kono Tomohiro
Published: June 2017

Little is known regarding the mechanisms underlying infertility in male-to-female sex-reversed females. To gain a better understanding of germ cell dysfunction in this condition, we produced XYsry−-females via the CRISPR/Cas9 system in C57BL/6 inbred strain mice. Mutant mice showed severe attrition of germ cells during foetal development, resulting in depletion of ovarian germ cells before sexual maturation. Comprehensive transcriptome analysis of embryonic day 13.5 primordial germ cells (PGCs) and postnatal day 1 oocytes demonstrated that XYsry−-PGCs had already deviated from the developmental process at the mitotic stage. In addition, XYsry−-oocytes resulted in meiotic disruption and developmental failure, and the genes related to these processes were significantly changed. This grievous disruption, which caused germ cell deterioration in XYsry−-females, was shown to proceed from the germ cells themselves. These results provide novel insight into the germ cell depletion of sex-reversed mice as well as into disorders of sex differentiation in human, such as ‘Swyer syndrome’, wherein patients present as typical females albeit with an XY karyotype and infertile.
Isolation and functional characterization of the rat Thyroglobulin gene upstream enhancer region
Authors: Christophe-Hobertus Christiane , Christophe Daniel
Published: June 2017

We report here the isolation and functional characterization of the as yet undescribed rat Thyroglobulin gene upstream enhancer element.
Pre-dispersal conditions and presence of opposite sex modulate density dependence and sex bias of dispersal
Authors: Mishra Abhishek , Tung Sudipta , Sruti V.R. Shree , Sadiq Mohammed Aamir , Srivathsa Sahana , Dey Sutirth
Published: June 2017

Density-dependent dispersal (DDD) has been demonstrated in many species and has several ecological and evolutionary consequences. Yet we know little about how robust DDD is to the various conditions experienced by individuals. In this study, we use three independent experiments on laboratory populations ofDrosophila melanogasterto examine the effects of pre-dispersal adult density, sex of the dispersers and presence of mates on the robustness of DDD patterns. We show that DDD can be greatly affected by both pre-dispersal density and interaction between the sexes. Moreover, the direction of sex-biased dispersal can reverse completely due to an interaction between the pre-dispersal and dispersal densities. We also show that interaction between the sexes can lead to negative DDD at the population level, even if, by themselves, neither sex exhibits DDD. Finally, we discuss potential implications of our results for processes like evolutionary rescue from extinctions and genetic divergence of populations.
Non-canonical secondary structures arising from non-B-DNA motifs are determinants of mutagenesis
Authors: Georgakopoulos-Soares Ilias , Morganella Sandro , Jain Naman , Hemberg Martin , Nik-Zainal Serena
Published: June 2017

Somatic mutations show variation in density across cancer genomes. Previous studies have shown that chromatin organization and replication time domains are correlated with and thus predictive of this variation1,2,3,4,5. Here, we analyse 1,809 whole-genome sequences from nine cancer types6,7,8to show that a subset of repetitive DNA sequences called non-B motifs that predict non-canonical secondary structure formation9,10,11,12can independently account for variation in mutation density. However, combined with epigenetic factors and replication timing, the variance explained can be improved to 43-76%. Intriguingly, ~2-fold mutation enrichment is observed directly within non-B motifs, is focused on exposed structural components, and is dependent on physical properties that are optimal for secondary structure formation. Therefore, there is mounting evidence that secondary structures arising from non-B motifs are not simply associated with increased mutation density, they are possibly causally implicated. Our results suggest that they are determinants of mutagenesis and increase the likelihood of recurrent mutations in the genome13,6. This analysis calls for caution in the interpretation of recurrent mutations and highlights the importance of taking non-B motifs, that can simply be inferred from the reference sequence, into consideration in background models of mutability henceforth.
Learn to Track: Deep Learning for Tractography
Authors: Poulin Philippe , Côté Marc-Alexandre , Houde Jean-Christophe , Petit Laurent , Neher Peter F. , Maier-Hein Klaus H. , Larochelle Hugo , Descoteaux Maxime
Published: June 2017

We show that deep learning techniques can be applied successfully to fiber tractography. Specifically, we use feed-forward and recurrent neural networks to learn the generation process of streamlines directly from diffusion-weighted imaging (DWI) data. Furthermore, we empirically study the behavior of the proposed models on a realistic white matter phantom with known ground truth. We show that their performance is competitive to that of commonly used techniques, even when the models are used on DWI data unseen at training time. We also show that our models are able to recover high spatial coverage of the ground truth white matter pathways while better controlling the number of false connections. In fact, our experiments suggest that exploiting past information within a streamline's trajectory during tracking helps predict the following direction.
Genetic contribution to two factors of neuroticism is associated with affluence, better health, and longer life
Authors: Hill W David , Weiss Alexander , McIntosh Andrew M , Gale Catharine R , Deary Ian J
Published: June 2017

Neuroticism is a personality trait that describes the tendency to experience negative emotions. Individual differences in neuroticism are moderately stable across much of the life course1; the trait is heritable2-5, and higher levels are associated with psychiatric disorders6-8, and have been estimated to have an economic burden to society greater than that of substance abuse, mood, or anxiety disorders9. Understanding the genetic architecture of neuroticism therefore has the potential to offer insight into the causes of psychiatric disorders, general wellbeing10, and longevity. The broad trait of neuroticism is composed of narrower traits, or factors. It was recently discovered that, whereas higher scores on the broad trait of neuroticism are associated with earlier death, higher scores on a ‘worry/vulnerability’ factor are associated with living longer11. Here, we examine the genetic architectures of two neuroticism factors—worry/vulnerability and anxiety/tension—and how they contrast with the architecture of the general factor of neuroticism. We show that, whereas the polygenic load for general factor of neuroticism is associated with an increased risk of coronary artery disease (CAD), major depressive disorder, and poorer self-rated health, the genetic variants associated with high levels of the anxiety/tension and worry/vulnerability factors are associated with affluence, higher cognitive ability, better self-rated health, and longer life. We also identify the first genes associated with factors of neuroticism that are linked with these positive outcomes that show no relationship with the general factor of neuroticism.
Mcm10 functions to isomerize CMG-DNA for replisome bypass of DNA blocks
Authors: Langston Lance D. , Mayle Ryan , Schauer Grant D. , Yurieva Olga , Zhang Daniel , Yao Nina Y. , Georgescu Roxana , O’Donnell Michael E.
Published: June 2017

Replicative helicases of all cell types are rings that unwind DNA by steric exclusion in which the helicase ring only encircles the tracking strand, excluding the other strand outside the ring. Steric exclusion mediated unwinding enables helicase rings to bypass blocks on the strand that is excluded from the central channel. Unlike other replicative helicases, eukaryotic CMG encircles duplex DNA at a forked junction and is stopped by a block on the non-tracking (lagging) strand. This report demonstrates that Mcm10, an essential replication protein unique to eukaryotes, binds CMG and enables the replisome to bypass blocks on the non-tracking strand, implying that Mcm10 isomerizes the CMG-DNA complex to position only one strand through the central channel. A similar CMG-DNA isomerization is needed at the origin for head-to-head CMGs to bypass one another during formation of bidirectional replication forks.
Networks around entrepreneurs: gendering in China and countries around the Persian Gulf
Authors: Bertelsen Rasmus Gjedssø , Ashourizadeh Shayegheh , Jensen Kent Wickstrøm , Schøtt Thomas , Cheng Yuan
Published: June 2017

Purpose

Entrepreneurs are networking with others to get advice for their businesses. The networking differs between men and women; notably, men are more often networking for advice in the public sphere and women are more often networking for advice in the private sphere. The purpose of this study is to account for how such gendering of entrepreneurs’ networks of advisors differs between societies and cultures.

Design/methodology/approach

Based on survey data from the Global Entrepreneurships Monitor, a sample of 16,365 entrepreneurs is used to compare the gendering of entrepreneurs’ networks in China and five countries largely located around the Persian Gulf, namely Yemen, Iran, Saudi Arabia, Qatar and the United Arab Emirates.

Findings

Analyses show that female entrepreneurs tend to have slightly larger private sphere networks than male entrepreneurs. The differences between male and female entrepreneurs’ networking in the public sphere are considerably larger. Societal differences in the relative prominence of networking in the public and private spheres, and the gendering hereof, correspond well to cultural and socio-economic societal differences. In particular, the authors found marked differences among the religiously conservative and politically autocratic Gulf states.

Research limitations/implications

As a main limitation to this study, the data disclose only the gender of the entrepreneur, but not the gender of each advisor in the network around the entrepreneur. Thus, the authors cannot tell the extent to which men and women interact with each other. This limitation along with the findings of this study point to a need for further research on the extent to which genders are structurally mixed or separated as entrepreneurs network for advice in the public sphere. In addition, the large migrant populations in some Arab states raise questions of the ethnicity of entrepreneurs and advisors.

Originality/value

Results from this study create novel and nuanced understandings about the differences in the gendering of entrepreneurs’ networking in China and countries around Persian Gulf. Such understandings provide valuable input to the knowledge of how to better use the entrepreneurial potential from both men and women in different cultures. The sample is fairly representative of entrepreneur populations, and the results can be generalized to these countries.