bluuebunny/crossref_metadata_2025 huggingface dataset:
A density functional theory study of the role of functionalized graphene particles as effective additives in power cable insulation
Authors: Song Shuwei , Zhao Hong , Zheng Xiaonan , Zhang Hui , Liu Yang , Wang Ying , Han Baozhong
Published: February 2018

The role of a series of functionalized graphene additives in power cable insulation in suppressing the growth of electrical treeing and preventing the degradation of the polymer matrix has been investigated by density functional theory calculations. Bader charge analysis indicates that pristine, doped or defect graphene could effectively capture hot electrons to block their attack on cross-linked polyethylene (XLPE) because of the π–π conjugated unsaturated structures. Further exploration of the electronic properties in the interfacial region between the additives and XLPE shows that N-doped single-vacancy graphene, graphene oxide and B-, N-, Si- or P-doped graphene oxide have relatively strong physical interaction with XLPE to restrict its mobility and rather weak chemical activity to prevent the cleavage of the C–H or C–C bond, suggesting that they are all potential candidates as effective additives. The understanding of the features of functionalized graphene additives in trapping electrons and interfacial interaction will assist in the screening of promising additives as voltage stabilizers in power cables.
Is countershading camouflage robust to lighting change due to weather?
Authors: Penacchio Olivier , Lovell P. George , Harris Julie M.
Published: February 2018

Countershading is a pattern of coloration thought to have evolved in order to implement camouflage. By adopting a pattern of coloration that makes the surface facing towards the sun darker and the surface facing away from the sun lighter, the overall amount of light reflected off an animal can be made more uniformly bright. Countershading could hence contribute to visual camouflage by increasing background matching or reducing cues to shape. However, the usefulness of countershading is constrained by a particular pattern delivering ‘optimal’ camouflage only for very specific lighting conditions. In this study, we test the robustness of countershading camouflage to lighting change due to weather, using human participants as a ‘generic’ predator. In a simulated three-dimensional environment, we constructed an array of simple leaf-shaped items and a single ellipsoidal target ‘prey’. We set these items in two light environments: strongly directional ‘sunny’ and more diffuse ‘cloudy’. The target object was given the optimal pattern of countershading for one of these two environment types or displayed a uniform pattern. By measuring detection time and accuracy, we explored whether and how target detection depended on the match between the pattern of coloration on the target object and scene lighting. Detection times were longest when the countershading was appropriate to the illumination; incorrectly camouflaged targets were detected with a similar pattern of speed and accuracy to uniformly coloured targets. We conclude that structural changes in light environment, such as caused by differences in weather, do change the effectiveness of countershading camouflage.
Investigating structure–property relationships of biomineralized calcium phosphate compounds as fluorescent quenching–recovery platform
Authors: Wang Liuzheng , He Xiang , Zhang Wei , Liu Yong , Banks Craig E. , Zhang Ying
Published: February 2018

The structure–property relationship between biomineralized calcium phosphate compounds upon a fluorescent quenching–recovery platform and their distinct crystalline structure and surficial functional groups are investigated. A fluorescence-based sensing platform is shown to be viable for the sensing of 8-hydroxy-2-deoxy-guanosine in simulated systems.
Identification of allosteric disulfides from labile bonds in X-ray structures
Authors: Pijning Aster E. , Chiu Joyce , Yeo Reichelle X. , Wong Jason W. H. , Hogg Philip J.
Published: February 2018

Protein disulfide bonds link pairs of cysteine sulfur atoms and are either structural or functional motifs. The allosteric disulfides control the function of the protein in which they reside when cleaved or formed. Here, we identify potential allosteric disulfides in all Protein Data Bank X-ray structures from bonds that are present in some molecules of a protein crystal but absent in others, or present in some structures of a protein but absent in others. We reasoned that the labile nature of these disulfides signifies a propensity for cleavage and so possible allosteric regulation of the protein in which the bond resides. A total of 511 labile disulfide bonds were identified. The labile disulfides are more stressed than the average bond, being characterized by high average torsional strain and stretching of the sulfur–sulfur bond and neighbouring bond angles. This pre-stress likely underpins their susceptibility to cleavage. The coagulation, complement and oxygen-sensing hypoxia inducible factor-1 pathways, which are known or have been suggested to be regulated by allosteric disulfides, are enriched in proteins containing labile disulfides. The identification of labile disulfide bonds will facilitate the study of this post-translational modification.
Fluorescence and photophysical properties of xylene isomers in water: with experimental and theoretical approaches
Authors: Khan Muhammad Farooq Saleem , Wu Jing , Liu Bo , Cheng Cheng , Akbar Mona , Chai Yidi , Memon Aisha
Published: February 2018

A thorough analysis of the photophysical properties involved in electronic transitions in excitation–emission spectra of xylene isomers has been carried out using the time-dependent density functional theory (PBEPBE/6-31 + G(d,p)) method. For the first time a structural and spectroscopic investigation to distinguish isomers of xylene, a widespread priority pollutant, was conducted experimentally and theoretically. The fluorescence properties of xylene isomers (sole and mixture (binary and ternary)) in water were studied. The fluorescence peak intensities of xylenes were linearly correlated to concentration, in the order of
p
-xylene > 
o
-xylene > 
m
-xylene at an excitation/emission wavelength (ex/em) of 260 nm/285 nm for
o
-,
m
-xylene and ex/em 265 nm/290 nm for
p
-xylene at the same concentration. The theoretical excitation/emission wavelengths were at ex/em 247 nm/267 nm, 248 nm/269 nm and 251 nm/307 nm for
o
-,
m
- and
p
-xylene, respectively. The vertical excitation and emission state energies of
p
-xylene (ex/em 4.94 eV/4.03 eV) were lower and the internal conversion energy difference (0.90 eV) was higher than those of
m
-xylene (ex/em 5.00 eV/4.60 eV) (0.4 eV) and
o
-xylene (ex/em 5.02 eV/4.64 eV) (0.377 eV). The order of theoretical emission and oscillator strength (0.0187 > 0.0175 > 0.0339) for
p
-xylene > 
o
-xylene > 
m
-xylene was observed to be in agreement with the experimental fluorescence intensities. These findings provide a novel fast method to distinguish isomers based on their photophysical properties.
Basis and regularity properties of (
p
,
q
)-trigonometric functions and the decay of (
p
,
q
)-Fourier coefficients
Authors: Edmunds David E. , Melkonian Houry
Published: February 2018

The basis and regularity properties of the generalized trigonometric functions

sin

p
,
q

and

cos

p
,
q

are investigated. Upper bounds for the Fourier coefficients of these functions are given. Conditions are obtained under which the functions

cos

p
,
q

generate a basis of every Lebesgue space
L

r

(0,1) with

1
<
r
<
∞

; when
q
is the conjugate of
p
, it is sufficient to require that
p
∈[
p
1
,
p
2
], where
p
1
<2 and
p
2
>2 are calculable numbers. A comparison is made of the speed of decay of the Fourier sine coefficients of a function in Lebesgue and Lorentz sequence spaces with that of the corresponding coefficients with respect to the functions

sin

p
,
q

.

These results sharpen previously known ones.
Mobile assemblies of Bennett linkages from four-crease origami patterns
Authors: Zhang Xiao , Chen Yan
Published: February 2018

This paper deals with constructing mobile assemblies of Bennett linkages inspired by four-crease origami patterns. A transition technique has been proposed by taking the thick-panel form of an origami pattern as an intermediate bridge. A zero-thickness rigid origami pattern and its thick-panel form share the same sector angles and folding behaviours, while the thick-panel origami and the mobile assembly of linkages are kinematically equivalent with differences only in link profiles. Applying this transition technique to typical four-crease origami patterns, we have found that the Miura-ori and graded Miura-ori patterns lead to assemblies of Bennett linkages with identical link lengths. The supplementary-type origami patterns with different mountain–valley crease assignments correspond to different types of Bennett linkage assemblies with negative link lengths. And the identical linkage-type origami pattern generates a new mobile assembly. Hence, the transition technique offers a novel approach to constructing mobile assemblies of spatial linkages from origami patterns.
Diversity change during the rise of tetrapods and the impact of the ‘Carboniferous rainforest collapse’
Authors: Dunne Emma M. , Close Roger A. , Button David J. , Brocklehurst Neil , Cashmore Daniel D. , Lloyd Graeme T. , Butler Richard J.
Published: February 2018

The Carboniferous and early Permian were critical intervals in the diversification of early four-limbed vertebrates (tetrapods), yet the major patterns of diversity and biogeography during this time remain unresolved. Previous estimates suggest that global tetrapod diversity rose continuously across this interval and that habitat fragmentation following the ‘Carboniferous rainforest collapse’ (CRC) drove increased endemism among communities. However, previous work failed to adequately account for spatial and temporal biases in sampling. Here, we reassess early tetrapod diversity and biogeography with a new global species-level dataset using sampling standardization and network biogeography methods. Our results support a tight relationship between observed richness and sampling, particularly during the Carboniferous. We found that subsampled species richness initially increased into the late Carboniferous, then decreased substantially across the Carboniferous/Permian boundary before slowly recovering in the early Permian. Our analysis of biogeography does not support the hypothesis that the CRC drove endemism; instead, we found evidence for increased cosmopolitanism in the early Permian. While a changing environment may have played a role in reducing diversity in the earliest Permian, our results suggest that the CRC was followed by increased global connectivity between communities, possibly reflecting both reduced barriers to dispersal and the diversification of amniotes.
Quantum chemical study of the structure, spectroscopy and reactivity of NO
+
.(H
2
O)

n
=1−5

clusters
Authors: Linton Kirsty A. , Wright Timothy G. , Besley Nicholas A.
Published: February 2018

Quantum chemical methods including Møller–Plesset perturbation (MP2) theory and density functional theory (DFT) have been used to study the structure, spectroscopy and reactivity of NO
+
.(H
2
O)

n
=1−5

clusters. MP2/6-311++G** calculations are shown to describe the structure and spectroscopy of the clusters well. DFT calculations with exchange–correlation functionals with a low fraction of Hartree–Fock exchange give a binding energy of NO
+
.(H
2
O) that is too high and incorrectly predict the lowest energy structure of NO
+
.(H
2
O)
2
, and this error may be associated with a delocalization of charge onto the water molecule directly binding to NO
+
. Ab initio molecular dynamics (AIMD) simulations were performed to study the NO
+
.(H
2
O)
5

H
+
.(H
2
O)
4
+ HONO reaction to investigate the formation of HONO from NO
+
.(H
2
O)
5
. Whether an intracluster reaction to form HONO is observed depends on the level of electronic structure theory used. Of note is that methods that accurately describe the relative energies of the product and reactant clusters did not show reactions on the timescales studied. This suggests that in the upper atmosphere the reaction may occur owing to the energy present in the NO
+
.(H
2
O)
5
complex following its formation.

This article is part of the theme issue ‘Modern theoretical chemistry’.
Accessing the molecular frame through strong-field alignment of distributions of gas phase molecules
Authors: Reid Katharine L.
Published: February 2018

A rationale for creating highly aligned distributions of molecules is that it enables vector properties referenced to molecule-fixed axes (the
molecular frame
) to be determined. In the present work, the degree of alignment that is necessary for this to be achieved in practice is explored. Alignment is commonly parametrized in experiments by a single parameter,

, which is insufficient to enable predictive calculations to be performed. Here, it is shown that, if the full distribution of molecular axes takes a Gaussian form, this single parameter can be used to determine the complete set of alignment moments needed to characterize the distribution. In order to demonstrate the degree of alignment that is required to approach the molecular frame, the alignment moments corresponding to a few chosen values of

are used to project a model molecular frame photoelectron angular distribution into the laboratory frame. These calculations show that

needs to approach 0.9 in order to avoid significant blurring to be caused by averaging.

This article is part of the theme issue ‘Modern theoretical chemistry’.
Identifying Critical Points of Trajectories of Depressive Symptoms From Childhood to Young Adulthood: Evidence of Sex Differences from the Avon Longitudinal Study of Parents and Children (ALSPAC)
Authors: Kwong Alex S. F. , Manley David , Timpson Nicholas J. , Pearson Rebecca M. , Heron Jon , Sallis Hannah , Stergiakouli Evie , Davis Oliver S.P. , Leckie George
Published: February 2018

Depression is a common mental illness associated with increased substance misuse and risk of suicide. Potential risk factors for depression include sex and depressive symptoms in early life, however the mechanisms responsible are not yet understood. Research has focused on late childhood and adolescence as this developmental period may be a modifiable risk factor that prevents or reduces depression at a later stage. It is also important to establish at what ages the level of depression is changing as this will help identify critical points to intervene with treatment. We used multilevel growth-curve models to explore adolescent trajectories of depressive symptoms in the Avon Longitudinal Study of Parents and Children, a UK based pregnancy cohort. Using data from 9301 individuals, trajectories of depressive symptoms were constructed for males and females between 10.6 and 22.8 years old. We calculated the age of peak velocity for depressive symptoms (the age at which depressive symptoms increases most rapidly) and the age of maximum depressive symptoms. Adjusted results suggested that being female was associated with a steeper trajectory compared to being male (per 1 year increase in relation to depressive symptoms: 0.128, SE = 0.035, [95% CI: 0.059, 0.198];p<0.001). We found evidence suggesting that females had an earlier age of peak velocity of depressive symptoms (females 13.7 years old, SE = 0.321, [95% CI: 12.9, 14.4] and males 16.4 years old, SE = 0.096, [95% CI: 16.2, 16.6];p<0.001), but weak evidence of an earlier age of maximum depressive symptoms (p= 0.125). Possible mechanisms that underlie this sex difference include the roles of pubertal development and timing. Using multilevel growth curve models to estimate the age of peak velocity and maximum depressive symptoms for different population subgroups may provide useful knowledge for treating and preventing later depression.
The roles of vision and antennal mechanoreception in hawkmoth flight control
Authors: Dahake Ajinkya , Stöckl Anna , Foster James J. , Sane Sanjay P. , Kelber Almut
Published: February 2018

Flying animals need constant sensory feedback about their body position and orientation for flight control. The visual system provides essential but slow feedback. In contrast, mechanosensory channels can provide feedback at much shorter timescales. How the contributions from these two senses are integrated remains an open question in most insect groups. In Diptera, fast mechanosensory feedback is provided by organs called halteres, and is crucial for the control of rapid flight manoeuvres, while vision controls manoeuvres in lower temporal frequency bands. Here we have investigated the visual-mechanosensory integration in an insect which lacks halteres: the hawkmothMacroglossum stellatarum. They represent a large group of insects that use Johnston’s organs in their antennae to provide mechanosensory feedback on perturbations in body position. High-speed videos of freely-flying hawkmoths hovering at stationary or oscillating artificial flowers showed that positional fidelity during flight was reduced in flagella ablated animals, but was recovered after flagella re-attachment. Our experiments show that antennal mechanosensory feedback specifically mediates fast flight manoeuvres, but not slow ones. Differences in the latency of visual feedback (in different light intensities) affected all antennal conditions equally, suggesting there was no compensatory interaction between antennal and visual feedback under the tested conditions. These results establish the importance of antennal mechanosensors in providing rapid mechanosensory feedback for finer control of flight manoeuvres, acting in parallel to visual feedback.
Detection of Pro-apoptotic BaxΔ2 Proteins in the Human Cerebellum
Authors: Mañas Adriana , Davis Aislinn , Lamerand Sydney , Xiang Jialing
Published: February 2018

BaxΔ2 is a pro-apoptotic protein originally discovered in colon cancer patients with high microsatellite instability. Unlike most pro-apoptotic Bax family members, BaxΔ2 mediates cell death through a non-mitochondrial caspase 8-dependent pathway. In the scope of analyzing the distribution of BaxΔ2 expression in human tissues, we examined a panel of human brain samples. Here, we report 4 cerebellar cases in which the subjects had no neurological disorder or disease documented. We found BaxΔ2 positive cells scattered in all areas of the cerebellum, but most strikingly concentrated in Purkinje cell bodies and dendrites. Two out the four subjects tested had strong BaxΔ2- positive staining in nearly all Purkinje cells; one was mainly negative; and one had various levels of positive staining within the same sample. Further genetic analysis of the Purkinje cell layer, collected by microdissection from two subjects, showed that the samples contained G7 and G9 Bax microsatellite mutations. Both subjects were young and had no diseases reported at the time of death. As the distribution of BaxΔ2 is consistent with that known for Baxa, but in a less ubiquitous manner, these results may imply a potential function of BaxΔ2 in Purkinje cells.
Haplotypes associated to gene expression in breast cancer: can they lead us to the susceptibility markers?
Authors: Edvardsen Hege , Kulle Bettina , Tsalenko Anya , Grenaker Alnӕs Grethe Irene , Ekeberg Johansen Fredrik , Enerly Espen , Vailaya Aditya , Lønning Per-Eystein , Helland Åslaug , Syvänen Ann-Christine , Yakhini Zohar , Børresen-Dale Anne-Lise , Frigessi Arnoldo , Kristensen Vessela N.
Published: February 2018

We have undertaken a systematic haplotype analysis of the positional type of biclusters analysing samples collected from 164 breast cancer patients and 86 women with no known history of breast cancer. We present here the haplotypes and LD patterns in more than 80 genes distributed across all chromosomes and how they differ between cases and controls. We aim by this to 1) identify genes with different haplotype distribution or LD patterns between breast cancer patients and controls and 2) to evaluate the intratumoral mRNA expression patterns in breast cancer associated particularly to the cancer susceptibility haplotypes. A significant difference in haplotype distribution between cases and controls was observed for a total of 35 genes includingABCC1, AKT2, NFKB1, TGFBR2andXRCC4. In addition we see a negative correlation between LD patterns in cases and controls for neighboring markers in 8 genes such asCDKN1A, EPHX1andXRCC1.
Estimating Heritability and Genetic Correlation in Case Control Studies Directly and with Summary Statistics
Authors: Weissbrod Omer , Flint Jonathan , Rosset Saharon
Published: February 2018

Methods that estimate heritability and genetic correlations from genome-wide association studies have proven to be powerful tools for investigating the genetic architecture of common diseases and exposing unexpected relationships between disorders. Many relevant studies employ a case-control design, yet most methods are primarily geared towards analyzing quantitative traits. Here we investigate the validity of three common methods for estimating genetic heritability and genetic correlation. We find that the Phenotype-Correlation-Genotype-Correlation (PCGC) approach is the only method that can estimate both quantities accurately in the presence of important non-genetic risk factors, such as age and sex. We extend PCGC to work with summary statistics that take the case-control sampling into account, and demonstrate that our new method, PCGC-s, accurately estimates both heritability and genetic correlations and can be applied to large data sets without requiring individual-level genotypic or phenotypic information. Finally, we use PCGC-S to estimate the genetic correlation between schizophrenia and bipolar disorder, and demonstrate that previous estimates are biased due to incorrect handling of sex as a strong risk factor. PCGC-s is available athttps://github.com/omerwe/PCGCs.
Fission yeast cells overproducing HSET/KIFC1 provides a useful tool for identification and evaluation of human kinesin-14 inhibitors
Authors: Yukawa Masashi , Yamauchi Tomoaki , Kimura Ken-ichi , Toda Takashi
Published: February 2018

Many cancer cells contain more than two centrosomes, yet these cancer cells can form bipolar spindles and appear to proliferate normally, instead of committing lethal mitoses with multipolar spindles. It is shown that extra centrosomes are clustered into two pseudo-bipolar spindle poles, thereby escaping from multipolarity. Human kinesin-14 (HSET or KIFC1), a minus end-directed motor, plays a crucial role in centrosome clustering and as such, HSET is essential for cell viability only in cancer cells with supernumerary centrosomes, but not in non-transformed cells. Accordingly, HSET is deemed to be an efficient chemotherapeutic target to selectively kill cancer cells. Recently, three HSET inhibitors (AZ82, CW069 and SR31527) have been reported, but their specificity, efficacy and off-target cytotoxicity have not been evaluated rigorously. Here we show that these inhibitors on their own are cytotoxic to fission yeast, suggesting that they have other targets in vivo except for kinesin-14. Nonetheless, intriguingly, AZ82 can neutralize overproduced HSET and partially rescue its lethality. This methodology of protein overproduction in fission yeast provides a convenient, functional assay system by which to screen for not only selective human kinesin-14 inhibitors but also those against other molecules of interest.
Biological and clinical insights from genetics of insomnia symptoms
Authors: Lane Jacqueline M , Jones Samuel , Dashti Hassan S , Wood Andrew R , Aragam Krishna , van Hees Vincent T. , Brumpton Ben , Winsvold Bendik , Wang Heming , Bowden Jack , Song Yanwei , Patel Krunal , Anderson Simon G , Beaumont Robin , Bechtold David A , Cade Brian , Kathiresan Sek , Little Max A , Luik Annemarie I , Loudon Andrew S , Purcell Shaun , Richmond Rebecca C , Scheer Frank AJL , Tyrrell Jessica , Winkelman John ,   HUNT All In Sleep, Strand Linn B , Nielsen Jonas B. , Willer Cristen J. , Redline Susan , Spiegelhalder Kai , Kyle Simon D , Ray David W , Zwart John-Anker , Hveem Kristian , Frayling Timothy M , Lawlor Deborah , Rutter Martin K , Weedon Michael N , Saxena Richa
Published: February 2018

Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes, but underlying pathophysiological processes and causal relationships with disease are poorly understood. Here we identify 57 loci for self-reported insomnia symptoms in the UK Biobank (n=453,379) and confirm their impact on self-reported insomnia symptoms in the HUNT study (n=14,923 cases, 47,610 controls), physician diagnosed insomnia in Partners Biobank (n=2,217 cases, 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n=83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis, phototransduction and muscle development pathways and of genes expressed in multiple brain regions, skeletal muscle and adrenal gland. Evidence of shared genetic factors is found between frequent insomnia symptoms and restless legs syndrome, aging, cardio-metabolic, behavioral, psychiatric and reproductive traits. Evidence is found for a possible causal link between insomnia symptoms and coronary heart disease, depressive symptoms and subjective well-being.

One Sentence Summary

We identify 57 genomic regions associated with insomnia pointing to the involvement of phototransduction and ubiquitination and potential causal links to CAD and depression.
Thermoelectric Heat Exchange and Growth Regulation in a Continuous Yeast Culture
Authors: Latorre-Pérez Adriel , Vilanova Cristina , Alcaina José J , Porcar Manuel
Published: February 2018

We have designed a thermoelectric heat exchanger (TEHE) for microbial fermentations, able to control the temperature of a microbial continuous culture, and produce electric power. The system proved able to stably maintain both the temperature and the optical density of the culture during the exponential, highly productive phase.
Evaluation of redundancy analysis to identify signatures of local adaptation
Authors: Capblancq Thibaut , Luu Keurcien , Blum Michael G.B. , Bazin Eric
Published: February 2018

Ordination is a common tool in ecology that aims at representing complex biological information in a reduced space. In landscape genetics, ordination methods such as principal component analysis (PCA) have been used to detect adaptive variation based on genomic data. Taking advantage of environmental data in addition to genotype data, redundancy analysis (RDA) is another ordination approach that is useful to detect adaptive variation. This paper aims at proposing a test statistic based on RDA to search for loci under selection. We compare redundancy analysis to pcadapt, which is a nonconstrained ordination method, and to a latent factor mixed model (LFMM), which is a univariate genotype-environment association method. Individual-based simulations identify evolutionary scenarios where RDA genome scans have a greater statistical power than genome scans based on PCA. By constraining the analysis with environmental variables, RDA performs better than PCA in identifying adaptive variation when selection gradients are weakly correlated with population structure. Additionally, we show that if RDA and LFMM have a similar power to identify genetic markers associated with environmental variables, the RDA-based procedure has the advantage to identify the main selective gradients as a combination of environmental variables. To give a concrete illustration of RDA in population genomics, we apply this method to the detection of outliers and selective gradients on an SNP data set of Populus trichocarpa (Geraldes et al., 2013). The RDA-based approach identifies the main selective gradient contrasting southern and coastal populations to northern and continental populations in the northwestern American coast.
Disentangling eco-evolutionary effects on trait fixation
Authors: Czuppon Peter , Gokhale Chaitanya S.
Published: February 2018

In population genetics, fixation of traits in a demographically changing population under frequency-independent selection has been extensively analysed. In evolutionary game theory, models of fixation have typically focused on fixed population sizes and frequency-dependent selection. A combination of demographic fluctuations with frequency-dependent interactions such as Lotka-Volterra dynamics has received comparatively little attention. We consider a stochastic, competitive Lotka-Volterra model with higher order interactions between two traits. The emerging individual based model allows for stochastic fluctuations in the frequencies of the two traits and the total population size. We calculate the fixation probability of a trait under differing competition coefficients. This fixation probability resembles qualitatively the deterministic evolutionary dynamics. Furthermore, we partially disentangle the selection effects into their ecological and evolutionary components. We find that changing the evolutionary selection strength also changes the population dynamics and vice versa. Thus, a clean separation of the ecological and evolutionary effects is not possible. The entangled eco-evolutionary processes thus cannot be ignored when determining fixation properties in a co-evolutionary system.
Blue light advances bud burst in branches of three temperate deciduous tree species under short-day conditions
Authors: Brelsford Craig C. , Robson T Matthew
Published: February 2018

During spring, utilising multiple cues allow temperate tree species to coordinate their bud burst and leaf out, at the right moment to capitalise on favourable conditions for photosynthesis. Whilst the effect of blue light (400-500nm) has been shown to increase percentage bud burst of axillary shoots ofRosasp, the effects of blue light on spring-time bud burst of temperate deciduous tree species has not previously been reported. We tested the hypotheses that blue light would advance spring bud burst in temperate tree species, and that late-successional species would respond more than early-successional species, who’s bud burst is primarily determined by temperature. The bud development ofAlnus glutinosa, Betula pendula, andQuercus roburbranches, cut from dormant trees, was monitored under two light treatments of equal photosynthetically active radiation (PAR, 400-700 nm) and temperature, either with or without blue light, under controlled environmental conditions. In the presence of blue light, the mean time required to reach 50% bud burst was reduced by 3.3 days inBetula pendula,6 days inAlnus glutinosa,and 6.3 days inQuercus robur. This result highlights the potential of the blue region of the solar spectrum to be used as an extra cue that could help plants to regulate their spring phenology, alongside photoperiod and temperature. Understanding how plants combine photoreceptor-mediated cues with other environmental cues such as temperature to control phenology is essential if we are to accurately predict how tree species might respond to climate change.

Key Message

An LED spectrum containing blue light advanced bud burst in branches ofBetula pendula, Alnus glutinosaandQuercus roburcompared with a spectrum without blue light in a controlled environment.
The divergence history of European blue mussel species reconstructed from Approximate Bayesian Computation: the effects of sequencing techniques and sampling strategies
Authors: Fraïsse Christelle , Roux Camille , Gagnaire Pierre-Alexandre , Romiguier Jonathan , Faivre Nicolas , Welch John J. , Bierne Nicolas
Published: February 2018

Genome-scale diversity data are increasingly available in a variety of biological systems, and can be used to reconstruct the past evolutionary history of species divergence. However, extracting the full demographic information from these data is not trivial, and requires inferential methods that account for the diversity of coalescent histories throughout the genome. Here, we evaluate the potential and limitations of one such approach. We reexamine a well-known system of mussel sister species, using the joint site frequency spectrum (jSFS) of synonymous mutations computed either from exome capture or RNA-seq, in an Approximate Bayesian Computation (ABC) framework. We first assess the best sampling strategy (number of: individuals, loci, and bins in the jSFS), and show that model selection is robust to variation in the number of individuals and loci. In contrast, different binning choices when summarizing the joint site frequency spectrum, strongly affect the results: including classes of low and high frequency shared polymorphisms can more effectively reveal recent migration events. We then take advantage of the flexibility of ABC to compare more realistic models of speciation, including variation in migration rates through time (i.e. periodic connectivity) and across genes (i.e. genome-wide heterogeneity in migration rates). We show that these models were consistently selected as the most probable, suggesting that mussels have experienced a complex history of gene flow during divergence and that the species boundary is semi-permeable. Our work provides a comprehensive evaluation of ABC demographic inference in mussels based on the coding site frequency spectrum, and supplies guidelines for employing different sequencing techniques and sampling strategies. We emphasize, perhaps surprisingly, that inferences are less limited by the volume of data, than by the way in which they are analyzed.
Sensory neurons sprouting is dependent on osteoclast-derived extracellular vesicles involving the activation of epidermal growth factor receptors
Authors: Neto Estrela , Leitão Luís , Mateus José , Sousa Daniela M. , Conceição Francisco , Alves Cecília J. , Oreffo Richard O. C. , West Jonathan , Aguiar Paulo , Lamghari Meriem
Published: February 2018

The patterning of peripheral innervation is accomplished through the tissue expression, in specific space and timeframe, of attractive or repulsive axonal guidance cues. At the bone microenvironment, neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor, vascular endothelial growth factor, netrin-1 and others were described to regulate the nerve ingrowth towards the bone compartment, by acting directly on receptors expressed at the nerve terminals. Interestingly, besides the gradient of soluble factors, neurons were described to be responsive to extracellular vesicles (EV) derived from myelinating cells and mesenchymal stem cells.

Here we provide evidence on a new mechanism by which peripheral innervation can be coordinated. We show that sensory nerves outgrowth and electric signal propagation are dependent on the EV secreted by osteoclasts, the bone resorbing cells. Furthermore, we demonstrate that the axonal sprouting is achieved through the activation of epidermal-growth factor receptor (EGFR) family signaling pathway. We proved that the EV-depleted osteoclast secretome leads to a significant decrease of neurons firing rate and axonal sprouting, concomitant with a decrease of EGFR/ErbB2 activation levels. Excitingly, the proteomic analysis of the osteoclast-derived EV cargo shows a high correlation with synaptic components reinforcing the role on sensory neurons/osteoclast crosstalk.

Our findings that osteoclast-derived EV hold effect in axonal outgrowth, contributing actively to the dynamics of the sensory neurons sprouting and electrophysiology, is a step toward unraveling target mechanisms to control electrical signal propagation and nerve fibers sprouting and consequently open new avenues for the development of innovative therapies to control bone pain.

Significance Statement

Sensory nerve fibers sprouting in bone pathologies is highly associated with pain. Thus, understanding the mechanisms behind sensory nerves ingrowth, sprouting and electrical activity, within the bone compartment, is essential for improving the strategies to overcome pain in bone disorders. We provide a new mechanism on the sensory nerves sprouting, indicating that the effect is dependent on the extracellular vesicles (EV) released by osteoclasts, through the epidermal growth factor receptor family targeting, by integrin independent pathways. We show different electrophysiology patterns being triggered in the presence of osteoclasts secretome and the abolishment of sensory neurons firing rate in EV-depleted conditions. Overall, our results elucidate novel mechanisms on the peripheral nerves sprouting, essential for pursuing new targets for bone pain therapies.
Inhibitor of apoptosis proteins determine glioblastoma stem-like cells fate depending on oxygen level
Authors: Soubéran Aurélie , Cappaï Jessica , Chocry Mathieu , Nuccio Christopher , Raujol Julie , Colin Carole , Lafitte Daniel , Kovacic Hervé , Quillien Véronique , Baeza-Kallee Nathalie , Rougon Geneviève , Figarella-Branger Dominique , Tchoghandjian Aurélie
Published: February 2018

In glioblastomas, apoptosis inhibitor proteins (IAPs) are involved in apoptotic and non-apoptotic processes. Here we used GDC-0152, a small molecule IAP inhibitor, to explore how IAPs participate in glioblastoma stem-like cell maintenance and fate under both hypoxic and normoxic environments. In hypoxia, IAPs inhibition triggered stem-like cells apoptosis and decreased proliferation in four human glioblastoma cell lines, whereas in normoxia it induced a loss of stemness and differentiation. In addition, we characterized a 3D glioblastoma spheroid model. By using MALDI images we validated that GDC-0152 penetrates in the entire sphere. TOF-SIMS analyses revealed an oxygen gradient correlated with spatial cellular heterogeneity with proliferative and apoptotic cells located close to the hypoxic core and GFAP+cells at the periphery. Notably, Serine-Threonine Kinases activation analysis revealed that oxygen level affects signaling pathways activated by GDC-0152. In hypoxia, IAPs inhibition activated ATR whereas in normoxia it activated NF-κB. Our data brings new mechanistic insights revealing the dual role of IAPs inhibitors like GDC-0152 that are relevant to their therapeutic application in tumors like glioblastomas.
Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities
Authors: Seferovic Maxim , Martín Claudia Sánchez-San , Tardif Suzette D. , Rutherford Julienne , Castro Eumenia C.C. , Li Tony , Hodara Vida L. , Parodi Laura M. , Giavedoni Luis , Layne-Colon Donna , Tamhankar Manasi , Yagi Shigeo , Martyn Calla , Reyes Kevin , Suter Melissa , Aagaard Kjersti M. , Chiu Charles Y. , Patterson Jean L.
Published: February 2018

During its most recent outbreak across the Americas, Zika virus (ZIKV) was surprisingly shown to cause fetal loss and congenital malformations in acutely and chronically infected pregnant women. However, understanding the underlying pathogenesis of ZIKV congenital disease has been hampered by a lack of relevant in vivo experimental models. Here we present a candidate New World monkey model of ZIKV infection in pregnant marmosets that faithfully recapitulates human disease. ZIKV inoculation at the human-equivalent of early gestation caused an asymptomatic seroconversion, induction of type I/II interferon-associated genes and proinflammatory cytokines, and persistent viremia and viruria. Spontaneous pregnancy loss was observed 16-18 days post-infection, with extensive active placental viral replication and fetal neurocellular disorganization similar to that seen in humans. These findings underscore the key role of the placenta as a conduit for fetal infection, and demonstrate the utility of marmosets as a highly relevant model for studying congenital ZIKV disease and pregnancy loss.
Circulating unacylated-ghrelin impairs hippocampal neurogenesis and memory in mice and is altered in human Parkinson's disease dementia
Authors: Hornsby Amanda K E , Santos Vanessa V , Johnston Fionnuala , Roberts Luke D , Stark Romana , Reichenbach Alex , Siervo Mario , Wells Timothy , Andrews Zane B , Burn David J , Davies Jeffrey S
Published: February 2018

Blood-borne factors regulate adult hippocampal neurogenesis (AHN) and cognition in mammals, albeit via mechanisms that are poorly understood. We report that elevating circulating unacylated-ghrelin (UAG), using both pharmacological and genetic methods, reduced hippocampal neurogenesis and plasticity in mice. Spatial memory impairments observed in GOAT-/- mice that lack acyl-ghrelin (AG) but have high levels of UAG, were rescued by treatment with AG. This unexpected finding suggests that the post-translational acylation of ghrelin is an important modulator of neurogenesis and memory in adult mammals. To determine whether this paradigm is relevant to humans we analysed circulating AG:UAG levels in Parkinson's disease (PD) patients diagnosed with dementia (PDD), cognitively intact PD patients and healthy controls. Uniquely, the ratio of plasma AG:UAG was reduced in the PDD cohort and correlated with cognitive performance. Our results identify UAG as a novel regulator of neurogenesis and cognition, and AG:UAG as a circulating diagnostic biomarker of dementia. The findings extend our understanding of adult brain plasticity regulation by circulating factors and suggest that manipulating the post-translational acylation of plasma ghrelin may offer therapeutic opportunities to ameliorate cognitive decline.
Long-range Notch-mediated tissue patterning requires actomyosin contractility
Authors: Hunter Ginger L , He Li , Perrimon Norbert , Charras Guillaume , Giniger Edward , Baum Buzz
Published: February 2018

Dynamic, actin-based protrusions function in cell-cell signaling in a variety of systems. In the dorsal thorax of the developing fly, basal protrusions enable non-neighboring epithelial cells to touch, extending the range over which Notch-mediated lateral inhibition can occur during bristle patterning. Given that actin-based cell protrusions can exert mechanical forces on their environment and Notch receptor activation is mechanically sensitive, how might cytoskeletal contractility contribute to Notch signaling? We identify a pool of basal non-muscle myosin II (myosin II) that regulates protrusion dynamics, promotes Notch signaling, and is required in signal sending and receiving cells for Notch-dependent patterning. We show that interactions between protrusions are extensive and subject to actomyosin contractility. The effects of reducing myosin II activity are more pronounced for protrusion-mediated signaling than for signaling at lateral cell contacts. Together, these results reveal a role for actomyosin contractility in Notch activation, signaling, and patterning in a developmental context.
The national alert-response strategy against cholera in Haiti: a four-year assessment of its implementation
Authors: Rebaudet Stanislas , Bulit Gregory , Gaudart Jean , Michel Edwige , Gazin Pierre , Evers Claudia , Beaulieu Samuel , Abedi Aaron Aruna , Osei Lindsay , Barrais Robert , Pierre Katilla , Moore Sandra , Boncy Jacques , Adrien Paul , Beigbeder Edouard , Guillaume Florence Duperval , Piarroux Renaud
Published: February 2018

Background

A massive cholera epidemic struck Haiti on October 2010. As part of the national cholera elimination plan, the Haitian government, UNICEF and other international partners launched a nationwide alert-response strategy from July 2013. This strategy established a coordinated methodology to rapidly target cholera-affected communities with WaSH (water sanitation and hygiene) response interventions conducted by field mobile teams. An innovative red-orange-green alert system was established, based on routine surveillance data, to weekly monitor the epidemic.

Methodology/Principal findings

We used cholera consolidated surveillance databases, alert records and details of 31,306 response interventions notified by WaSH mobile teams to describe and assess the implementation of this approach between July 2013 and June 2017. Response to red and orange alerts was heterogeneous across the country, but significantly improved throughout the study period so that 75% of red and orange alerts were responded within the same epidemiological week during the 1st semester of 2017. Numbers of persons educated about cholera, houses decontaminated by chlorine spraying, households which received water chlorination tablets and water sources that were chlorinated during the same week as cholera alerts significantly increased. Alerts appeared to be an interesting and simple indicator to monitor the dynamic of the epidemic and assess the implementation of response activities.

Conclusions/Significance

The implementation of a nationwide alert-response strategy against cholera in Haiti was feasible albeit with certain obstacles. Its cost was less than USD 8 million per year. Continuing this strategy seems essential to eventually defeat cholera in Haiti while ambitious long-term water and sanitation projects are conducted in vulnerable areas. It constitutes a core element of the current national plan for cholera elimination of the Haitian Government.
T cell immunity does not age in a long-lived rodent species
Authors: Izraelson M. , Nakonechnaya T.O. , Davydov A.N. , Dronina M.A. , Miskevich D.A. , Mamedov I.Z. , Barbashova L.N. , Shugay M. , Bolotin D.A. , Staroverov D.B. , Kondratyuk E.Y. , Bogdanova E.A. , Lukyanov S. , Shams I. , Britanova O.V. , Chudakov D.M.
Published: February 2018

Numerous studies have demonstrated that the percentage of naïve T cells and diversity of T cell receptor (TCR) repertoire decrease with age, with some findings likewise suggesting that increased repertoire diversity may be associated with longer lifespan and healthy aging. In this work, we have analyzed peripheral TCR diversity from humans, mice, and blind mole-rats (Spalax spp.)—long-lived, hypoxia- and cancer-tolerant rodents. We employed a quantitative approach to TCR repertoire profiling based on 5’RACE with unique molecular identifiers (UMI) to achieve accurate comparison of repertoire diversity, which also required development of specific wet lab protocol and TCR gene reference for Spalax. Our direct comparison reveals a striking phenomenon. Whereas TCR diversity of mice and humans decreases with age, resulting primarily from the shrinkage of the naive T cell pool, Spalax TCR diversity remains stable even for the animals that reach extreme old age (15-17 years). This indicates that T cell immunity does not meaningfully age in long-lived rodents, at least in terms of the classical understanding of immunosenescence, which is associated with the accumulation of large numbers of memory clones. We suggest that the extraordinary longevity of Spalax may be attributable at least in part to the distinctive organization of their T cell immunity. Our findings should therefore encourage a close re-examination of the contribution of immunosenescence to life span in mammals.