bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic and genetic variation among three separate introductions of the house sparrow (Passer domesticus) into Australia
Authors: Sheldon E. L. , Schrey A. , Andrew S. C. , Ragsdale A. , Griffith S. C.
Published: April 2018

Invasive populations are often associated with low levels of genetic diversity owing to population bottlenecks at the initial stages of invasion. Despite this, the ability of invasive species to adapt rapidly in response to novel environments is well documented. Epigenetic mechanisms have recently been proposed to facilitate the success of invasive species by compensating for reduced levels of genetic variation. Here, we use methylation sensitive-amplification fragment length polymorphism and microsatellite analyses to compare levels of epigenetic and genetic diversity and differentiation across 15 sites in the introduced Australian house sparrow population. We find patterns of epigenetic and genetic differentiation that are consistent with historical descriptions of three distinct, introductions events. However unlike genetic differentiation, epigenetic differentiation was higher among sample sites than among invasion clusters, suggesting that patterns of epigenetic variation are more strongly influenced by local environmental stimuli or sequential founder events than the initial diversity in the introduction population. Interestingly, we fail to detect correlations between pairwise site comparisons of epigenetic and genetic differentiation, suggesting that some of the observed epigenetic variation has arisen independently of genetic variation. We also fail to detect the potentially compensatory relationship between epigenetic and genetic diversity that has been detected in a more recent house sparrow invasion in Africa. We discuss the potential for this relationship to be obscured by recovered genetic diversity in more established populations, and highlight the importance of incorporating introduction history into population-wide epigenetic analyses.
Large-scale fabrication of porous YBO
3
hollow microspheres with tunable photoluminescence
Authors: Xu Zhenhe , Yu He , Ai Feixue , Zhao Guiyan , Bi Yanfeng , Huang Liangliang , Ding Fu , Sun Yaguang , Gao Yu
Published: April 2018

Hollow lanthanide-doped compounds are some of the most popular materials for high-performance luminescent devices. However, it is challenging to find an approach that can fabricate large-scale and well-crystallized lanthanide-doped hollow structures and that is facile, efficient and of low cost. In this study, YBO
3
: Eu
3+
/Tb
3+
hollow microspheres were fabricated by using a novel multi-step transformation synthetic route for the first time with polystyrene spheres as the template, followed by the combination of a facile homogeneous precipitation method, an ion-exchange process and a calcination process. The results show that the as-obtained YBO
3
: Eu
3+
/Tb
3+
hollow spheres have a uniform morphology with an average diameter of 1.65 µm and shell thickness of about 160 nm. When used as luminescent materials, the emission colours of YBO
3
: Eu
3+
/Tb
3+
samples can be tuned from red, through orange, yellow and green-yellow, to green by simply adjusting the relative doping concentrations of the activator ions under the excitation of ultraviolet light, which might have potential applications in fields such as light display systems and optoelectronic devices.
Photocatalytic degradation properties of α-Fe
2
O
3
nanoparticles for dibutyl phthalate in aqueous solution system
Authors: Liu Yue , Sun Nan , Hu Jianshe , Li Song , Qin Gaowu
Published: April 2018

The phthalate ester compounds in industrial wastewater, as kinds of environmental toxic organic pollutants, may interfere with the body's endocrine system, resulting in great harm to humans. In this work, the photocatalytic degradation properties of dibutyl phthalate (DBP) were investigated using α-Fe
2
O
3
nanoparticles and H
2
O
2
in aqueous solution system. The optimal parameters and mechanism of degradation were discussed by changing the morphology and usage amount of catalysts, the dosage of H
2
O
2
, pH value and the initial concentration of DBP. Hollow α-Fe
2
O
3
nanoparticles showed the highest degradation efficiency when 30 mg of catalyst and 50 µl of H
2
O
2
were used in the DBP solution with the initial concentration of 13 mg l
−1
at pH = 6.5. When the reaction time was 90 min, DBP was degraded 93% for the above optimal parameters. The photocatalytic degradation mechanism of DBP was studied by the gas chromatography–mass spectrometry technique. The result showed that the main degradation intermediates of DBP were
ortho
-phthalate monobutyl ester, methyl benzoic acid, benzoic acid, benzaldehyde, and heptyl aldehyde when the reaction time was 2 h. DBP and its intermediates were almost completely degraded to CO
2
and H
2
O in 12 h in the α-Fe
2
O
3
/ H
2
O
2
/UV system.
Discrepancies in the spiking threshold and frequency sensitivity of nocturnal moths explainable by biases in the canonical auditory stimulation method
Authors: Thevenon Herve , Pfuhl Gerit
Published: April 2018

The auditory stimulation method used in experiments on moth A cell(s) is generally believed to be adequate to characterize the encoding of bat echolocation signals. The stimulation method hosts, though, several biases. Their compounded effects can explain a range of discrepancies between the reported electrophysiological recordings and significantly alter the current interpretation. To test the hypothesis that the bias may significantly alter our current understanding of the moth's auditory transducer characteristics, papers using the same auditory stimulation method and reporting on either spiking threshold or spiking activity of the moth's A cells were analysed. The consistency of the reported data was assessed. A range of corrections issued from best practices and theoretical background were applied to the data in an attempt to re-interpret the data. We found that it is not possible to applya posterioricorrections to all data and bias. However the corrected data indicate that the A cell's spiking may (i) be independent of the repetition rate, (ii) be maximum when detecting long and low-intensity pulses and (iii) steadily reduce as the bat closes on the moth. These observations raise the possibility that a fixed action pattern drives the moths' erratic evasive manoeuvres until the final moment. In-depth investigations of the potential bias also suggest that the auditory transducer's response may be constant for a larger frequency range than thought so far, and provide clues to explain the negative taxis in response to the searching bats' calls detection.
Analytical model of the feto-placental vascular system: consideration of placental oxygen transport
Authors: Mirbod Parisa
Published: April 2018

The placenta is a transient vascular organ that enables nutrients and blood gases to be exchanged between fetal and maternal circulations. Herein, the structure and oxygen diffusion across the trophoblast membrane between the fetal and maternal red blood cells in the feto-placental vasculature system in both human and mouse placentas are presented together as a functional unit. Previous models have claimed that the most efficient fetal blood flow relies upon structures containing a number of ‘conductive’ symmetrical branches, offering a path of minimal resistance that maximizes blood flow to the terminal villi, where oxygen diffusion occurs. However, most of these models have disregarded the actual descriptions of the exchange at the level of the intermediate and terminal villi. We are proposing a ‘mixed model’ whereby both ‘conductive’ and ‘terminal’ villi are presumed to be present at the end of single (in human) or multiple (in mouse) pregnancies. We predict an optimal number of 18 and 22 bifurcation levels in the human and the mouse placentas, respectively. Wherever possible, we have compared our model's predictions with experimental results reported in the literature and found close agreement between them.
The epidemiology of hepatitis C virus in Pakistan: systematic review and meta-analyses
Authors: Al Kanaani Zaina , Mahmud Sarwat , Kouyoumjian Silva P. , Abu-Raddad Laith J.
Published: April 2018

To characterize hepatitis C virus (HCV) epidemiology in Pakistan and estimate the pooled mean HCV antibody prevalence in different risk populations, we systematically reviewed all available records of HCV incidence and/or prevalence from 1989 to 2016, as informed by the Cochrane Collaboration Handbook. This systematic review was reported following the PRISMA guidelines. Populations were classified into six categories based on the risk of exposure to HCV infection. Meta-analyses were performed using DerSimonian and Laird random-effects models with inverse variance weighting. The search identified one HCV incidence study and 341 prevalence measures/strata. Meta-analyses estimated the pooled mean HCV prevalence at 6.2% among the general population, 34.5% among high-risk clinical populations, 12.8% among populations at intermediate risk, 16.9% among special clinical populations, 55.9% among populations with liver-related conditions and 53.6% among people who inject drugs. Most reported risk factors in analytical epidemiologic studies related to healthcare procedures. Pakistan is enduring an HCV epidemic of historical proportions—one in every 20 Pakistanis is infected. HCV plays a major role in liver disease burden in this country, and HCV prevalence is high in all-risk populations. Most transmission appears to be driven by healthcare procedures. HCV treatment and prevention must become a national priority.
Effects of Lewis number on the statistics of the invariants of the velocity gradient tensor and local flow topologies in turbulent premixed flames
Authors: Wacks Daniel , Konstantinou Ilias , Chakraborty Nilanjan
Published: April 2018

The behaviours of the three invariants of the velocity gradient tensor and the resultant local flow topologies in turbulent premixed flames have been analysed using three-dimensional direct numerical simulation data for different values of the characteristic Lewis number ranging from 0.34 to 1.2. The results have been analysed to reveal the statistical behaviours of the invariants and the flow topologies conditional upon the reaction progress variable. The behaviours of the invariants have been explained in terms of the relative strengths of the thermal and mass diffusions, embodied by the influence of the Lewis number on turbulent premixed combustion. Similarly, the behaviours of the flow topologies have been explained in terms not only of the Lewis number but also of the likelihood of the occurrence of individual flow topologies in the different flame regions. Furthermore, the sensitivity of the joint probability density function of the second and third invariants and the joint probability density functions of the mean and Gaussian curvatures to the variation in Lewis number have similarly been examined. Finally, the dependences of the scalar--turbulence interaction term on augmented heat release and of the vortex-stretching term on flame-induced turbulence have been explained in terms of the Lewis number, flow topology and reaction progress variable.
Network integration and limits to social inheritance in vervet monkeys
Authors: Jarrett Jonathan D. , Bonnell Tyler R. , Young Christopher , Barrett Louise , Henzi S. Peter
Published: April 2018

Social networks can be adaptive for members and a recent model (Ilany and Akçay 2016
Nat. Comm.
7
, 12084 (
doi:10.1038/ncomms12084
)) has demonstrated that network structure can be maintained by a simple process of social inheritance. Here, we ask how juvenile vervet monkeys integrate into their adult grooming networks, using the model to test whether observed grooming patterns replicate network structure. Female juveniles, who are philopatric, increased their grooming effort towards adults more than males, although this was not reciprocated by the adults themselves. While more consistent maternal grooming networks, together with maternal network strength, predicted increasing similarity in the patterning of mother–daughter grooming allocations, daughters' grooming networks generally did not match closely those of their mothers. However, maternal networks themselves were not very consistent across time, thus presenting youngsters with a moving target that may be difficult to match. Observed patterns of juvenile female grooming did not replicate the adult network, for which increased association with adults not groomed by their mothers would be necessary. These results suggest that network flexibility, not stability, characterizes our groups and that juveniles are exposed to, and must learn to cope with, temporal shifts in network structure. We hypothesize that this may lead to individual variation in behavioural flexibility, which in turn may help explain why and how variation in sociability influences fitness.
Calcium isotopes offer clues on resource partitioning among Cretaceous predatory dinosaurs
Authors: Hassler A. , Martin J. E. , Amiot R. , Tacail T. , Godet F. Arnaud , Allain R. , Balter V.
Published: April 2018

Large predators are overabundant in mid-Cretaceous continental dinosaur assemblages of North Africa. Such unbalanced ecosystem structure involves, among predatory dinosaurs, typical abelisaurid or carcharodontosaurid theropods co-occurring with long-snouted spinosaurids of debated ecology. Here, we report calcium (Ca) isotope values from tooth enamel (expressed as
δ
44/42
Ca) to investigate resource partitioning in mid-Cretaceous assemblages from Niger (Gadoufaoua) and Morocco (Kem Kem Beds). In both assemblages, spinosaurids display a distinct isotopic signature, the most negative in our dataset. This distinct taxonomic clustering in Ca isotope values observed between spinosaurids and other predators provides unambiguous evidence for niche partitioning at the top of the trophic chains: spinosaurids foraged on aquatic environments while abelisaurid and carcharodontosaurid theropods relied almost exclusively on terrestrial resources.
Do priority effects outweigh environmental filtering in a guild of dominant freshwater macroinvertebrates?
Authors: Little Chelsea J. , Altermatt Florian
Published: April 2018

Abiotic conditions have long been considered essential in structuring freshwater macroinvertebrate communities. Ecological drift, dispersal and biotic interactions also structure communities, and although these mechanisms are more difficult to detect, they may be of equal importance in natural communities. Here, we hypothesized that in 10 naturally replicated headwater streams in eastern Switzerland, locally dominant amphipod species would be associated with differences in environmental conditions. We conducted repeated surveys of amphipods and used a hierarchical joint species distribution model to assess the influence of different drivers on species co-occurrences. The species had unique environmental requirements, but a distinct spatial structure in their distributions was unrelated to habitat. Species co-occurred much less frequently than predicted by the model, which was surprising because laboratory and field evidence suggests they are capable of coexisting in equal densities. We suggest that niche preemption may limit their distribution and that a blocking effect related to the specific linear configuration of streams determines which species colonizes and dominates a given stream catchment, thus suggesting a new solution a long-standing conundrum in freshwater ecology.
Anemone bleaching increases the metabolic demands of symbiont anemonefish
Authors: Norin Tommy , Mills Suzanne C. , Crespel Amélie , Cortese Daphne , Killen Shaun S. , Beldade Ricardo
Published: April 2018

Increased ocean temperatures are causing mass bleaching of anemones and corals in the tropics worldwide. While such heat-induced loss of algal symbionts (zooxanthellae) directly affects anemones and corals physiologically, this damage may also cascade on to other animal symbionts. Metabolic rate is an integrative physiological trait shown to relate to various aspects of organismal performance, behaviour and locomotor capacity, and also shows plasticity during exposure to acute and chronic stressors. As climate warming is expected to affect the physiology, behaviour and life history of animals, including ectotherms such as fish, we measured if residing in bleached versus unbleached sea anemones (
Heteractis magnifica
) affected the standard (i.e. baseline) metabolic rate and behaviour (activity) of juvenile orange-fin anemonefish (
Amphiprion chrysopterus
)
.
Metabolic rate was estimated from rates of oxygen uptake

, and the standard metabolic rate

of anemonefish from bleached anemones was significantly higher by 8.2% compared with that of fish residing in unbleached anemones, possibly due to increased stress levels. Activity levels did not differ between fish from bleached and unbleached anemones. As

reflects the minimum cost of living, the increased metabolic demands may contribute to the negative impacts of bleaching on important anemonefish life history and fitness traits observed previously (e.g. reduced spawning frequency and lower fecundity).
Cortical activation associated with motor preparation can be used to predict the freely chosen effector of an upcoming movement and reflects response time: An fMRI decoding study
Authors: Hirose Satoshi , Nambu Isao , Naito Eiichi
Published: April 2018

Motor action is prepared in the human brain for rapid initiation at the appropriate time. Recent non-invasive decoding techniques have shown that brain activity for action preparation represents various parameters of an upcoming action. In the present study, we demonstrated that a freely chosen effector can be predicted from brain activity measured using functional magnetic resonance imaging (fMRI) before initiation of the action. Furthermore, the activity was related to response time (RT). We measured brain activity with fMRI while 12 participants performed a finger-tapping task using either the left or right hand, which was freely chosen by them. Using fMRI decoding, we identified brain regions in which activity during the preparatory period could predict the hand used for the upcoming action. We subsequently evaluated the relationship between brain activity and the RT of the upcoming action to determine whether correct decoding was associated with short RT. We observed that activity in the supplementary motor area, dorsal premotor cortex, and primary motor cortex measured before action execution predicted the hand used to perform the action with significantly above-chance accuracy (approximately 70%). Furthermore, in most participants, the RT was shorter in trials for which the used hand was correctly predicted. The present study showed that preparatory activity in cortical motor areas represents information about the effector used for an upcoming action, and that well-formed motor representations in these regions are associated with reduced response times.

Highlights

Brain activity measured by fMRI was used to predict freely chosen effectors.

M1/PMd and SMA activity predicted the effector hand prior to action initiation.

Response time was shorter in trials in which effector hand was correctly predicted.

Freely chosen action is represented in the M1/PMd and SMA.

Well-formed preparatory motor representations lead to reduced response time.
A randomised exploratory investigation of the effects of Attention vs Working Memory Training on cognitive performance and everyday functioning following stroke
Authors: Peers Polly V , Astle Duncan E , Duncan John , Murphy Fionnuala , Hampshire Adam , Das Tilak , Manly Tom
Published: April 2018

Difficulties with attention are common following stroke and are associated with poor outcome. Home-based online cognitive training may have to the potential to provide an efficient and effective way to improve attentional functions in such patients. Little work has been carried out to assess the efficacy of this approach in stroke patients, and the lack of studies with active control conditions and rigorous evaluations of cognitive functioning pre and post training means understanding is limited as to whether and how such interventions may be effective. Here we compare the effects of 20 days of active cognitive training using either novel Selective Attention Training (SAT) or commercial Working Memory Training (WMT) programme, versus a waitlist control group, on a wide range of attentional and working memory tasks, as well as on self-reported everyday functioning. We demonstrate separable effects of each of the active training conditions, with SAT leading to improvements in both spatial and non-spatial aspects of attention and WMT leading to improvements only on very closely related working memory tasks. Both training groups reported improvements in everyday functioning, which were associated with improvements in attentional functions, suggesting that improving attention may be of particular importance in maximising functional recovery in this patient group.
First in-human PET study of 3 novel tau radiopharmaceuticals: [11C]RO6924963, [11C]RO6931643, and [18F]RO6958948
Authors: Wong Dean F. , Comley Robert A. , Kuwabara Hiroto , Rosenberg Paul B. , Resnick Susan M. , Ostrowitzki Susanne , Vozzi Cristina , Boess Frank , Oh Esther , Lyketsos Constantine G. , Honer Michael , Gobbi Luca , Klein Gregory , George Noble , Gapasin Lorena , Kitzmiller Kelly , Roberts Josh , Sevigny Jeff , Nandi Ayon , Brasic James , Mishra Chakradhar , Thambisetty Madhav , Mogekar Abhay , Mathur Anil , Albert Marilyn , Dannals Robert F.
Published: April 2018

Background

[11C]RO-963, [11C]RO-643 and [18F]RO-948 (previously referred as [11C]RO6924963, [11C]RO6931643, and [18F]RO6958948, respectively) have been reported as promising PET tracers for tau imaging based on in vitro and preclinical PET data (1,2). Here we describe the first human evaluation of these novel radiotracers.

Methods

Amyloid PET positive Alzheimer’s disease (AD) patients and young healthy subjects (YC) each received two different tau tracers. Dynamic 90 min scans were obtained after bolus injection of [11C]RO-963, [11C]RO-643 or [18F]RO-948. Arterial blood sampling was performed in 11 healthy controls (HC) and 11 AD. Regions were defined on MRI, and PET data were quantified by plasma reference graphical analysis (for VT) and target cerebellum ratio (SUVR60-90). SUVR images were also analyzed voxelwise. Five older healthy subjects (OC) each received two scans with [18F]RO-948 for evaluation of test-retest variability. Four AD subjects received a repeat [18F]RO-948 scan over about 1 year. Six additional HC (3M: 3F; 41-67y) each received one whole body dosimetry scan with [18F]RO-948.

Results

In YC, peak SUV values were observed in the temporal lobe with values of approximately 3.0 for [11C]RO-963, 1.5 for [11C]RO-643 and 3.5 for [18F]RO-948. Over all brain regions and subjects, the trend was that [18F]RO-948 had the highest peak SUV value, followed by [11C]RO-963, and then [11C]RO-643. Regional analysis of SUVR and VT for [11C]RO-643 and [18F]RO-948 clearly discriminated AD and HC groups. Compartmental modeling confirmed that [11C]RO-643 had lower brain entry than both [18F]RO-963 and [18F]RO-948, and [18F]RO-948 showed a better contrast between (predicted) areas of high vs low tau accumulation. Thus, our subsequent analysis focused on [18F]RO-948. Both voxelwise and region-based analysis of [18F]RO-948 binding in HC vs AD revealed multiple areas where AD and HC significantly differed. Of 22 high-binding regions, 13 showed significant group difference (following ANOVA, F=45, p<10-5). Voxelwise analysis also revealed a set of symmetrical clusters where AD>HC (threshold of p<0.001, cluster size k>50).

Conclusions

[18F]RO-948 demonstrates superior characteristics to [11C]RO-643 and [18F]RO-963 for characterization of tau pathology in AD. Regional binding data and kinetic properties of RO-948 compare favorably with existing other tau PET tracers.
Quantifying the risk of local Zika virus transmission in the continental US during the 2015-2016 ZIKV epidemic
Authors: Sun Kaiyuan , Zhang Qian , Pastore-Piontti Ana , Chinazzi Matteo , Mistry Dina , Dean Natalie E. , Rojas Diana P. , Merler Stefano , Poletti Piero , Rossi Luca , Halloran M. Elizabeth , Longini Ira M. , Vespignani Alessandro
Published: April 2018

Background

Local mosquito-borne Zika virus (ZIKV) transmission has been reported in two counties of the continental United State (US), prompting the issuance of travel, prevention, and testing guidance across the continental US. Large uncertainty, however, surrounds the quantification of the actual risk of ZIKV introduction and autochthonous transmission across different areas of the US.

Method

We present a framework for the projection of ZIKV autochthonous transmission in the continental US during the 2015-2016 epidemic, using a data-driven stochastic and spatial epidemic model accounting for seasonal, environmental and detailed population data. The model generates an ensemble of travel-related case counts and simulate their potential to trigger local transmission at individual level.

Results

We estimate the risk of ZIKV introduction and local transmission at the county level and at the 0.025° x 0.025° cell level across the continental US. We provide a risk measure based on the probability of observing local transmission in a specific location during a ZIKV epidemic modeled after the one observed during the years 2015-2016. The high spatial and temporal resolutions of the model allow us to generate statistical estimates of the number of ZIKV introductions leading to local transmission in each location. We find that the risk is spatially heterogeneously distributed and concentrated in a few specific areas that account for less than 1% of the continental US population. Locations in Texas and Florida that have actually experienced local ZIKV transmission are among the places at highest risk according to our results. We also provide an analysis of the key determinants for local transmission, and identify the key introduction routes and their contributions to ZIKV spread in the continental US.

Conclusions

This framework provides quantitative risk estimates, fully captures the stochas-ticity of ZIKV introduction events, and is not biased by the under-ascertainment of cases due to asymptomatic infections. It provides general information on key risk determinants and data with potential uses in defining public health recommendations and guidance about ZIKV risk in the US.
Approaches to maximize sgRNA-barcode coupling in Perturb-seq screens
Authors: Adamson Britt , Norman Thomas M. , Jost Marco , Weissman Jonathan S.
Published: April 2018

Perturb-seq is a platform for single-cell gene expression profiling of pooled CRISPR screens. Like many functional genomics platforms, Perturb-seq relies on lentiviral transduction to introduce perturbation libraries to cells. On this platform, these are barcoded sgRNA libraries. A critical consideration for performing Perturb-seq experiments is uncoupling of barcodes from linked sgRNA expression cassettes, which can occur during lentiviral transduction of co-packaged libraries due to reverse transcriptase-mediated template switching. This problem is common to lentiviral libraries designed with linked variable regions. Here, we demonstrate that recombination between Perturb-seq vectors scrambles linked variable regions separated by 2 kb. This predicts information loss in Perturb-seq screens performed with co-packaged libraries. We also demonstrate ways to address this problem and discuss best practices for single-cell screens with transcriptional readouts.
Hippocampal knockdown of Piwil1 and Piwil2 enhances contextual fear memory in mice
Authors: Leighton Laura J. , Wei Wei , Ratnu Vikram Singh , Li Xiang , Zajaczkowski Esmi L. , Spadaro Paola A. , Khandelwal Nitin , Kumar Arvind , Bredy Timothy W.
Published: April 2018

The Piwi pathway is a conserved gene regulatory mechanism comprised of Piwi-like proteins and Piwi-interacting RNAs, which modulates gene expression via RNA interference and epigenetic mechanisms. The mammalian Piwi pathway has been defined by its role in transposon control during spermatogenesis, and despite an increasing number of studies demonstrating its expression in the nervous system, relatively little is known about its function in neurons or potential contribution to gene regulation in the brain. We have discovered that all three Piwi-like genes are expressed in several regions of the mouse brain, and that simultaneous knockdown of Piwil1 and Piwil2 in the adult mouse hippocampus enhances contextual fear memory without affecting generalised anxiety. Our results implicate the Piwi pathway in control of plasticity-related gene expression in the adult mammalian brain.
Analysis of an open source, closed-loop, realtime system for hippocampal sharp-wave ripple disruption
Authors: Dutta Shayok , Ackermann Etienne , Kemere Caleb
Published: April 2018

Transient neural activity pervades hippocampal electrophysiological activity. During more quiescent states, brief ≈100 ms periods comprising large ≈150–250 Hz oscillations known as sharp-wave ripples (SWR) which co-occur with ensemble bursts of spiking activity, are regularly found in local field potentials recorded from area CA1. SWRs and their concomitant neural activity are thought to be important for memory consolidation, recall, and memory-guided decision making. Temporally-selective manipulations of hippocampal neural activity upon online hippocampal SWR detection have been used as causal evidence of the importance of SWR for mnemonic process as evinced by behavioral and/or physiological changes. However, though this approach is becoming more wide spread, the performance trade-offs involved in building a SWR detection and disruption system have not been explored, limiting the design and interpretation of SWR detection experiments. We present an open source, plug-and-play, online ripple detection system with a detailed performance characterization. Our system has been constructed to interface with an open source software platform, Trodes, and two hardware acquisition platforms, Open Ephys and SpikeGadgets. We show that our in vivo results — approximately 80% detection latencies falling in between ≈20–66 ms with ≈2 ms closed-loop latencies while maintaining <10 false detections per minute — are dependent upon both algorithmic trade-offs and acquisition hardware. We discuss strategies to improve detection accuracy and potential limitations of online ripple disruptions. By characterizing this system in detail, we present a template for analyzing other closed-loop neural detection and perturbation systems. Thus, we anticipate our modular, open source, realtime system will facilitate a wide range of carefully-designed causal closed-loop neuroscience experiments.
Prioritizing putative influential genes in early life cardiovascular disease susceptibility by applying tissue-specific Mendelian randomization
Authors: Taylor Kurt , Davey Smith George , Relton Caroline L , Gaunt Tom R , Richardson Tom G
Published: April 2018

Background

The extent to which changes in gene expression can influence cardiovascular disease risk across different tissue types has not yet been systematically explored. We have developed an analytical framework that integrates tissue-specific gene expression, Mendelian randomization and multiple-trait colocalization to develop functional mechanistic insight into the causal pathway from genetic variant to complex trait.

Methods

We undertook a transcriptome-wide association study in a population of young individuals to uncover genetic variants associated with both nearby gene expression and cardiovascular traits. Two-sample Mendelian randomization was then applied using large-scale datasets to investigate whether changes in gene expression within certain tissue types may influence cardiovascular trait variation. We subsequently performed Bayesian multiple-trait colocalization to further interrogate findings and also gain insight into whether DNA methylation, as well as gene expression, may play a role in disease susceptibility.

Results

Eight genetic loci were associated with changes in gene expression and early life measures of cardiovascular function. Our Mendelian randomization analysis provided evidence of tissue-specific effects at multiple loci, of which the effects at theADCY3andFADS1loci for body mass index and cholesterol respectively were particularly insightful. Multiple trait colocalization uncovered evidence which suggested that changes in DNA methylation at the promoter region upstream ofFADS1/TMEM258may also play a role in cardiovascular trait variation along with gene expression. Furthermore, colocalization analyses were able to uncover evidence of tissue-specificity, most prominantly betweenSORT1expression in liver tissue and cholesterol levels.

Conclusions

Disease susceptibility can be influenced by differential changes in tissue-specific gene expression and DNA methylation. Our analytical framework should prove valuable in elucidating mechanisms in disease, as well as helping prioritize putative causal genes at associated loci where multiple nearby genes may be co-regulated. Future studies which continue to uncover quantitative trait loci for molecular traits across various tissue and cell typse will further improve our capability to understand and prevent disease.
Avoiding misinterpretation of regression lines in allometry: is sexual dimorphism in digit ratio spurious?
Authors: Forstmeier Wolfgang
Published: April 2018

The statistical analysis of allometry (size-dependence of traits) is fraught with difficulty that is often underestimated. In light of some recent controversies about statistical methods and the resulting biological conclusions, I here discuss the interpretation of regression lines and show how to avoid spurious effects. General linear models based on ordinary least square (OLS) regression are often used to quantify sexual dimorphism in a trait of interest that is modelled as a function of sex while controlling for size as a covariate. However, an analysis of artificially generated data where males and females differ in size only, but are otherwise built according to the same principles, shows that the OLS method induces a spurious dimorphism where there is none. Hence, OLS-based general linear models should not be regarded as a fail-proof tool that automatically provides the correct answer to whatever question one has in mind. Here I show how to avoid misinterpretation and how to best proceed with answering the recent debate about sexual dimorphism in digit ratio, a trait that is thought to reflect sex-hormone levels during development. The limited data, currently available to me, suggests that the widely accepted sexual dimorphism in digit ratio might well be only a by-product of an allometric shift in shape, urgently calling for a re-examination in larger data sets on humans and other vertebrates.
CUDA RNAfold
Authors: Langdon W. B. , Lorenz Ronny
Published: April 2018

We add CUDA GPU C program code to RNAfold to enable both it to be run on nVidia gaming graphics hardware and so that many thousands of RNA secondary structures can be computed in parallel. RNAfold predicts the folding pattern for RNA molecules by using O(n3) dynamic programming matrices to minimise the free energy of treating them as a sequence of bases. We benchmark RNAfold on RNA STRAND and artificial sequences of upto 30 000 bases on two GPUs and a GPGPU Tesla. The speed up is variable but up to 14 times.
Agmatine accumulation byPseudomonas aeruginosaclinical isolates confers antibiotic tolerance and dampens host inflammation
Authors: McCurtain Jennifer L. , Gilbertsen Adam J. , Evert Clayton , Williams Bryan J. , Hunter Ryan C.
Published: April 2018

In the cystic fibrosis (CF) airways,Pseudomonas aeruginosaundergoes diverse physiological changes in response to inflammation, antibiotic pressure, oxidative stress and a dynamic bioavailable nutrient pool. These include loss-of-function mutations that result in reduced virulence, altered metabolism and other phenotypes that are thought to confer a selective advantage for long-term persistence. Recently, clinical isolates ofP. aeruginosathat hyperproduce agmatine (decarboxylated arginine) were cultured from individuals with CF. Sputum concentrations of this metabolite were also shown to correlate with disease severity. This raised the question of whether agmatine accumulation might also confer a selective advantage forP. aeruginosa in vivoduring chronic colonization of the lung. Here, we screened a library ofP. aeruginosaCF clinical isolates and found that ~5% of subjects harbored isolates with an agmatine hyperproducing phenotype. Agmatine accumulation was a direct result of mutations inaguA, encoding the arginine deiminase that catalyzes the conversion of agmatine into various polyamines. We also found that agmatine hyperproducing isolates (aguA-) had increased tolerance to the cationic antibiotics gentamicin, tobramycin and colistin relative to their chromosomally complemented strains (aguA+). Finally, we revealed that agmatine diminishes IL-8 production by airway epithelial cells in response to bacterial infection, with a consequent decrease in neutrophil recruitment to the murine airways in an acute pneumonia model. These data highlight a potential new role for bacterial-derived agmatine that may have important consequences for the long-term persistence ofP. aeruginosain the CF airways.
Who is this gene and what does it do? A toolkit for munging transcriptomics data in python
Authors: Fisher Charles K. , Smith Aaron M. , Walsh Jonathan R.
Published: April 2018

Transcriptional regulation is extremely complicated. Unfortunately, so is working with transcriptional data. Genes can be referred to using a multitude of different identifiers and are assigned to an ever increasing number of categories. Gene expression data may be available in a variety of units (e.g, counts, RPKMs, TPMs). Batch effects dominate signal, but metadata may not be available. Most of the tools are written in R. Here, we introduce a library, genemunge, that makes it easier to work with transcriptional data in python. This includes translating between various types of gene names, accessing Gene Ontology (GO) information, obtaining expression levels of genes in healthy tissue, correcting for batch effects, and using prior knowledge to select sets of genes for further analysis. Code for genemunge is freely available on Github.
Ranking genome-wide correlation measurements improves microarray and RNA-seq based global and targeted co-expression networks
Authors: Liesecke Franziska , Daudu Dimitri , Dugé de Bernonville Rodolphe , Besseau Sébastien , Clastre Marc , Courdavault Vincent , de Craene Johan-Owen , Crèche Joel , Giglioli-Guivarc’h Nathalie , Glévarec Gaëlle , Pichon Olivier , Dugé de Bernonville Thomas
Published: April 2018

Co-expression networks are essential tools to infer biological associations between gene products and predict gene annotation. Global networks can be analyzed at the transcriptome wide scale or after querying them with a set of guide genes to capture the transcriptional landscape of a given pathway in a process named Pathway Level Correlation (PLC). A critical step in network construction remains the definition of gene co-expression. In the present work, we compared how Pearson Correlation Coefficient (PCC), Spearman Correlation Coefficient (SCC), their respective ranked values (Highest Reciprocal Rank (HRR)), Mutual Information (MI) and Partial Correlations (PC) performed on global networks and PLCs. This evaluation was conducted on the model plant Arabidopsis thaliana using microarray and differently pre-processed RNA-seq datasets. We particularly evaluated how dataset x distance measurement combinations performed in 5 PLCs corresponding to 4 well described plant metabolic pathways (phenylpropanoid, carbohydrate, fatty acid and terpene metabolisms) and the cytokinin signaling pathway. Our present work highlights how PCC ranked with HRR is better suited for global network construction and PLC with microarray and RNA-seq data than other distance methods, especially to cluster genes in partitions similar to biological subpathways.
Three new dihydro-β-agarofuran sesquiterpenes from the seeds ofMaytenus boaria
Authors: Paz Cristian , Heydenreich Matthias , Schmidt Bernd , Vadra Nahir , Baggio Ricardo
Published: April 2018

As part of a project studying the secondary metabolites extracted from the Chilean flora, we report herein three new β-agarofuran sesquiterpenes, namely (1S,4S,5S,6R,7R,8R,9R,10S)-6-acetoxy-4,9-dihydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepine-5,10-diyl bis(furan-3-carboxylate), C27H32O11, (II), (1S,4S,5S,6R,7R,9S,10S)-6-acetoxy-9-hydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepine-5,10-diyl bis(furan-3-carboxylate), C27H32O10, (III), and (1S,4S,5S,6R,7R,9S,10S)-6-acetoxy-10-(benzoyloxy)-9-hydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepin-5-yl furan-3-carboxylate, C29H34O9, (IV), obtained from the seeds ofMaytenus boariaand closely associated with a recently published relative [Pazet al.(2017).Acta Cryst.C73, 451–457]. In the (isomorphic) structures of (II) and (III), the central decalin system is esterified with an acetate group at site 1 and furoate groups at sites 6 and 9, and differ at site 8, with an OH group in (II) and no substituent in (III). This position is also unsubstituted in (IV), with site 6 being occupied by a benzoate group. The chirality of the skeletons is described as 1S,4S,5S,6R,7R,8R,9R,10Sin (II) and 1S,4S,5S,6R,7R,9S,10Sin (III) and (IV), matching the chirality suggested by NMR studies. This difference in the chirality sequence among the title structures (in spite of the fact that the three skeletons are absolutely isostructural) is due to the differences in the environment of site 8,i.e.OH in (II) and H in (III) and (IV). This diversity in substitution, in turn, is responsible for the differences in the hydrogen-bonding schemes, which is discussed.
Microtubule architecturein vitroand in cells revealed by cryo-electron tomography
Authors: Atherton Joseph , Stouffer Melissa , Francis Fiona , Moores Carolyn A.
Published: April 2018

The microtubule cytoskeleton is involved in many vital cellular processes. Microtubules act as tracks for molecular motors, and their polymerization and depolymerization can be harnessed to generate force. The structures of microtubules provide key information about the mechanisms by which their cellular roles are accomplished and the physiological context in which these roles are performed. Cryo-electron microscopy allows the visualization ofin vitro-polymerized microtubules and has provided important insights into their overall morphology and the influence of a range of factors on their structure and dynamics. Cryo-electron tomography can be used to determine the unique three-dimensional structure of individual microtubules and their ends. Here, a previous cryo-electron tomography study ofin vitro-polymerized GMPCPP-stabilized microtubules is revisited, the findings are compared with new tomograms of dynamicin vitroand cellular microtubules, and the information that can be extracted from such data is highlighted. The analysis shows the surprising structural heterogeneity ofin vitro-polymerized microtubules. Lattice defects can be observed bothin vitroand in cells. The shared ultrastructural properties in these different populations emphasize the relevance of three-dimensional structures ofin vitromicrotubules for understanding microtubule cellular functions.
ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps
Authors: Croll Tristan Ian
Published: April 2018

This paper introducesISOLDE, a new software package designed to provide an intuitive environment for high-fidelity interactive remodelling/refinement of macromolecular models into electron-density maps.ISOLDEcombines interactive molecular-dynamics flexible fitting with modern molecular-graphics visualization and established structural biology libraries to provide an immersive interface wherein the model constantly acts to maintain physically realistic conformations as the user interacts with it by directly tugging atoms with a mouse or haptic interface or applying/removing restraints. In addition, common validation tasks are accelerated and visualized in real time. Using the recently described 3.8 Å resolution cryo-EM structure of the eukaryotic minichromosome maintenance (MCM) helicase complex as a case study, it is demonstrated howISOLDEcan be used alongside other modern refinement tools to avoid common pitfalls of low-resolution modelling and improve the quality of the final model. A detailed analysis of changes between the initial and final model provides a somewhat sobering insight into the dangers of relying on a small number of validation metrics to judge the quality of a low-resolution model.
Comparing the financial reporting quality of Chinese and US public firms
Authors: Brown Kareen , Elayan Fayez A. , Li Jingyu , Liu Zhefeng
Published: April 2018

Purpose

The purpose of this paper is to investigate whether US regulatory actions around reverse mergers (RM) have exerted any spillover effects on the Chinese firms listed in China and whether Chinese firms have exhibited lower financial reporting quality than their US counterparts.

Design/methodology/approach

To test the possible spillover effect, this paper calculates three-day cumulative average abnormal returns (CAAR) and the aggregate CAAR for a series of US regulatory actions in 2010 and 2011. The study then compares the accrual quality, conditional conservatism, and information content of accruals of Chinese firms and US firms.

Findings

The paper documents a spillover effect of US actions around RM on Chinese stocks listed in China. Overall results do not support the perception that Chinese firms have lower financial reporting quality than their US counterparts.

Research limitations/implications

While this study provides evidence consistent with investors perceiving poor financial reporting quality among Chinese firms, that perception is not justified by empirical evidence.

Practical implications

Investors need not be overly concerned about the financial reporting quality among the Chinese firms when they make asset allocation decisions.

Social implications

A reality check is important given that perceptions may be outdated, biased, misleading, and costly.

Originality/value

This study puts the financial reporting quality of Chinese firms into perspective helping global investors assess information risk for optimal resource allocation.