bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel muon imaging techniques
Authors: Yang Guangliang , Clarkson Tony , Gardner Simon , Ireland David , Kaiser Ralf , Mahon David , Jebali Ramsey Al , Shearer Craig , Ryan Matthew
Published: December 2018

Owing to the high penetrating power of high-energy cosmic ray muons, muon imaging techniques can be used to image large bulky objects, especially objects with heavy shielding. Muon imaging systems work just like CT scanners in the medical imaging field—that is, they can reveal information inside of a target. There are two forms of muon imaging techniques: muon absorption imaging and muon multiple scattering imaging. The former is based on the flux attenuation of muons, and the latter is based on the multiple scattering of muons in matter. The muon absorption imaging technique is capable of imaging very large objects such as volcanoes and large buildings, and also smaller objects like spent fuel casks; the muon multiple scattering imaging technique is best suited to inspect smaller objects such as nuclear waste containers. Muon imaging techniques can be applied in a broad variety of fields, i.e. from measuring the magma thickness of volcanoes to searching for secret cavities in pyramids, and from monitoring the borders of countries checking for special nuclear materials to monitoring the spent fuel casks for nuclear safeguards applications. In this paper, the principles of muon imaging are reviewed. Image reconstruction algorithms such as Filtered Back Projection and Maximum Likelihood Expectation Maximization are discussed. The capability of muon imaging techniques is demonstrated through a Geant4 simulation study for imaging a nuclear spent fuel cask.

This article is part of the Theo Murphy meeting issue ‘Cosmic-ray muography’.
Muons at ISIS
Authors: Hillier A. D. , Lord J. S. , Ishida K. , Rogers C.
Published: December 2018

For the last 30 years, muon experiments at ISIS pulsed neutron and muon facility at the Rutherford Appleton Laboratory, Oxfordshire have been making a significant contribution to a number of scientific fields. The muon facilities at ISIS consist of eight experimental areas. The European Commission Muon facility consists of three experimental areas with a fixed momentum (28 MeV c
−1
). The RIKEN-RAL facility has a variable momentum (17–90 MeV c
−1
) and a choice of negative or positive muons delivering muons to four experimental areas. There is also an area recently used for a muon ionization cooling experiment. In this paper, the ISIS pulsed muon facilities are reviewed, including the beam characteristics that could be useful for muography experiments.

This article is part of the Theo Murphy meeting issue ‘Cosmic-ray muography’.
Metabolically-Driven Maturation of hiPSC-Cell Derived Cardiac Chip
Authors: Huebsch Nathaniel , Charrez Berenice , Siemons Brian , Boggess Steven C. , Wall Samuel , Neiman Gabriel , Charwat Verena , Jæger Karoline H. , Cleres David , Telle Åshild , Lee-Montiel Felipe T. , Jeffreys Nicholas C. , Deveshwar Nikhil , Edwards Andrew , Serrano Jonathan , Snuderl Matija , Stahl Andreas , Tveito Aslak , Miller Evan W. , Healy Kevin E.
Published: December 2018

Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) are a promising in vitro tool for drug development and disease modeling, but their immature electrophysiology limits diagnostic utility. Tissue engineering approaches involving aligned 3D cultures enhance hiPSC-CM structural maturation but are insufficient to induce mature electrophysiology. We hypothesized that mimicking post-natal switching of the heart’s primary ATP source from glycolysis to fatty acid oxidation could enhance electrophysiological maturation of hiPSC-CM. We combined hiPSC-CM with microfabricated culture chambers to form 3D cardiac microphysiological systems (MPS) that enhanced immediate microtissue alignment and tissue specific extracellular matrix (ECM) production. Using Robust Experimental design, we identified a maturation media that improved calcium handling in MPS derived from two genetically distinct hiPSC sources. Although calcium handling and metabolic maturation were improved in both genotypes, there was a divergent effect on action potential duration (APD): MPS that started with abnormally prolonged APD exhibited shorter APD in response to maturation media, whereas the same media prolonged the APD in MPS that started with aberrantly short APD. Importantly, the APD of both genotypes was brought near the range of 270-300ms observed in human left ventricular cardiomyocytes. Mathematical modeling explained these divergent phenotypes, and further predicted the response of matured MPS to drugs with known pro-arrhythmic effects. These results suggest that systematic combination of biophysical stimuli and metabolic cues can enhance the electrophysiological maturation of hiPSC-derived cardiomyocytes. However, they also reveal that maturation-inducing cues can have differential effects on electrophysiology depending on the baseline phenotype of hiPSC-CM. In silico models provide a valuable tool for predicting how changes in cellular maturation will manifest in drug responsiveness.
In vivo microscopy reveals the impact ofPseudomonas aeruginosasocial interactions on host colonization
Authors: Rezzoagli Chiara , Granato Elisa T. , Kümmerli Rolf
Published: December 2018

Pathogenic bacteria engage in social interactions to colonize hosts, which include quorum-sensing-mediated communication and the secretion of virulence factors that can be shared as “public goods” between individuals. While in-vitro studies demonstrated that cooperative individuals can be displaced by “cheating” mutants freeriding on social acts, we know little about social interactions in infections. Here, we developed a live imaging system to track virulence factor expression and social strain interactions in the human pathogenPseudomonas aeruginosacolonizing the gut ofCaenorhabditis elegans. We found that shareable siderophores and quorum-sensing systems are expressed during infections, affect host gut colonization, and benefit nonproducers. However, non-producers were unable to cheat and outcompete producers, probably due to the spatial segregation of strains within the gut. Our results shed new light on bacterial social interactions in infections and reveal potential limits of therapeutic approaches that aim to capitalize on social dynamics between strains for infection control.
Polarized light information modulates sensorimotor decision making in goldfish
Authors: Otero Coronel Santiago , Berón de Astrada Martín , Medan Violeta
Published: December 2018

Animal survival relays on environmental information gathered by their sensory systems. In invertebrates the polarization angle of light is known to provide vital information for a wide range of visual tasks. However, the role of polarization sensitivity in vertebrates remains poorly understood. Here we study if polarization vision enhances threat detection in goldfish. We found that adding a polarization cue to a low intensity contrast looming stimulus biases the type of evasive behavior the animals perform. While low contrast looms mostly evoke subtle alarm reactions, the addition of a polarized cue dramatically increases the probability of eliciting a fast escape maneuver, the C-start response. Goldfish can be startled by polarized light stimuli coming not only from above but also from the sides indicating that polarization sensitivity spans large areas of the retina. In addition, we observed that while low intensity contrast looms preferentially elicit alarm behaviours, high intensity contrast looms rarely induced them, but elicited C-start responses with a high probability. Together, our results show that the addition of a polarized light cue to a low intensity contrast stimulus shifts animal’s decision making from low threshold alarm responses to the higher threshold C-start escape behaviour. This additional visual cue, thus, might aid underwater threat detection and predator avoidance in the animal’s natural environment.

Summary statement

This study gives the first compelling evidence that fish can use polarized light information to improve their decision making in the context of visual threat detection.
Hearing impairment is associated with enhanced neural tracking of the speech envelope
Authors: Decruy Lien , Vanthornhout Jonas , Francart Tom
Published: December 2018

Elevated hearing thresholds in hearing impaired adults are usually compensated by providing amplification through a hearing aid. In spite of restoring hearing sensitivity, difficulties with understanding speech in noisy environments often remain. One main reason is that sensorineural hearing loss not only causes loss of audibility but also other deficits, including peripheral distortion but also central temporal processing deficits. To investigate the neural consequences of hearing impairment in the brain underlying speech-in-noise difficulties, we compared EEG responses to natural speech of 14 hearing impaired adults with those of 14 age-matched normal-hearing adults. We measured neural envelope tracking to sentences and a story masked by different levels of a stationary noise or competing talker. Despite their sensorineural hearing loss, hearing impaired adults showed higher neural envelope tracking of the target than the competing talker, similar to their normal-hearing peers. Furthermore, hearing impairment was related to an additional increase in neural envelope tracking of the target talker, suggesting that hearing impaired adults may have an enhanced sensitivity to envelope modulations or require a larger differential tracking of target versus competing talker to neurally segregate speech from noise. Lastly, both normal-hearing and hearing impaired participants showed an increase in neural envelope tracking with increasing speech understanding. Hence, our results open avenues towards new clinical applications, such as neuro-steered prostheses as well as objective and automatic measurements of speech understanding performance.

Highlights

Adults with hearing impairment can neurally segregate speech from background noise

Hearing loss is related to enhanced neural envelope tracking of the target talker

Neural envelope tracking has potential to objectively measure speech understanding
Plant species and soil type influence rhizosphere bacterial composition and seedling establishment on serpentine soils
Authors: Igwe Alexandria N. , Vannette Rachel L.
Published: December 2018

Root-associated microbial communities influence plant phenotype, growth and local abundance, yet the factors that structure these microbial communities are still poorly understood. California landscapes contain serpentine soils, which are nutrient-poor and high in heavy metals, and distinct from neighboring soils. Here, we surveyed the rhizoplane of serpentine-indifferent plants species growing on serpentine and non-serpentine soils to determine the relative influence of plant identity and soil chemistry on rhizoplane microbial community structure using 16S rRNA metabarcoding. Additionally, we experimentally examined if locally adapted microorganisms enhance plant growth in serpentine soil. Plant species, soil chemistry, and the interaction between them were important in structuring rhizoplane bacterial communities in both the field and experimental soils. In the experiment, rhizoplane microbial community source influenced seedling survival, but plant growth phenotypes measured were largely invariant to microbial community with a few exceptions. Results from the field sampling suggest that plant species associate with specific microbial communities even across chemically distinct soils, and that microbial communities can differentially influence seedling survival on harsh serpentine soils.
Models of archaic admixture and recent history from two-locus statistics
Authors: Ragsdale Aaron P. , Gravel Simon
Published: December 2018

We learn about population history and underlying evolutionary biology through patterns of genetic polymorphism. Many approaches to reconstruct evolutionary histories focus on a limited number of informative statistics describing distributions of allele frequencies or patterns of linkage disequilibrium. We show that many commonly used statistics are part of a broad family of two-locus moments whose expectation can be computed jointly and rapidly under a wide range of scenarios, including complex multi-population demographies with continuous migration and admixture events. A full inspection of these statistics reveals that widely used models of human history fail to predict simple patterns of linkage disequilibrium. To jointly capture the information contained in classical and novel statistics, we implemented a tractable likelihood-based inference framework for demographic history. Using this approach, we show that human evolutionary models that include archaic admixture in Africa, Asia, and Europe provide a much better description of patterns of genetic diversity across the human genome. We estimate that an unidentified, deeply diverged population admixed with modern humans within Africa both before and after the split of African and Eurasian populations, contributing 4-8% genetic ancestry to individuals in world-wide populations.

Author Summary

Throughout human history, populations have expanded and contracted, split and merged, and ex-changed migrants. Because these events affected genetic diversity, we can learn about human history by comparing predictions from evolutionary models to genetic data. Here, we show how to rapidly compute such predictions for a wide range of diversity measures within and across populations under complex demographic scenarios. While widely used models of human history accurately predict common measures of diversity, we show that they strongly underestimate the co-occurence of low frequency mutations within human populations in Asia, Europe, and Africa. Models allowing for archaic admixture, the relatively recent mixing of human populations with deeply diverged human lineages, resolve this discrepancy. We use such models to infer demographic models that include both recent and ancient features of human history. We recover the well-characterized admixture of Neanderthals in Eurasian populations, as well as admixture from an as-yet unknown diverged human population within Africa, further suggesting that admixture with deeply diverged lineages occurred multiple times in human history. By simultaneously testing model predictions for a broad range of diversity statistics, we can assess the robustness of common evolutionary models, identify missing historical events, and build more informed models of human demography.
Macroevolutionary bursts and constraints generate a rainbow in a clade of tropical birds
Authors: Merwin Jon T. , Seeholzer Glenn F. , Smith Brian Tilston
Published: December 2018

Background

Bird plumage exhibits a diversity of colors that serve functional roles ranging from signaling to camouflage and thermoregulation. However, birds must maintain a balance between evolving colorful signals to attract mates, minimizing conspicuousness to predators, and optimizing adaptation to climate conditions. Examining plumage color macroevolution provides a framework for understanding this dynamic interplay over phylogenetic scales. Plumage evolution due to a single overarching process, such as selection, may generate the same macroevolutionary pattern of color variation across all body regions. In contrast, independent processes may partition plumage into sections and produce region-specific patterns. To test these alternative scenarios, we collected color data from museum specimens of an ornate clade of birds, the Australasian lorikeets, using visible-light and UV-light photography, and comparative methods. We predicted that the diversification of homologous feather regions, i.e., patches, known to be involved in sexual signaling (e.g., face) would be less constrained than patches on the back and wings, where new color states may come at the cost of crypsis. Because environmental adaptation may drive evolution towards or away from color states, we tested whether climate more strongly covaried with plumage regions under greater or weaker macroevolutionary constraint.

Results

We found that alternative macroevolutionary models and varying rates best describe color evolution, a pattern consistent with our prediction that different plumage regions evolved in response to independent processes. Modeling plumage regions independently, in functional groups, and all together showed that patches with similar macroevolutionary models clustered together into distinct regions (e.g., head, wing, belly), which suggests that plumage does not evolve as a single trait in this group. Wing patches, which were conserved on a macroevolutionary scale, covaried with climate more strongly than plumage regions (e.g., head), which diversified in a burst.

Conclusions

Overall, our results support the hypothesis that the extraordinary color diversity in the lorikeets was generated by a mosaic of evolutionary processes acting on plumage region subsets. Partitioning of plumage regions in different parts of the body provides a mechanism that allows birds to evolve bright colors for signaling and remain hidden from predators or adapt to local climatic conditions.
New graph-theoretical-multimodal approach using temporal and structural correlations reveal disruption in the thalamo-cortical network in patients with schizophrenia
Authors: Finotteli Paolo , Forlim Caroline Garcia , Dulio Paolo , Klock Leonie , Pini Alessia , Baechle Johanna , Giemsa Patrick , Fuchs Marie , Schoofs Nikola , Montag Christiane , Stoll Laura , Gallinat Juergen , Kuehn Simone
Published: December 2018

Schizophrenia has been understood as a network disease with altered functional and structural connectivity in multiple brain networks compatible to the extremely broad spectrum of psychopathological, cognitive and behavioral symptoms in this disorder. When building brain networks, functional and structural networks are typically modelled independently: functional network models are based on temporal correlations among brain regions, whereas structural network models are based on anatomical characteristics. Combining both features may give rise to more realistic and reliable models of brain networks. In this study, we applied a new flexible graph-theoretical-multimodal model called FD (F, the functional connectivity matrix, and D, the structural matrix) to construct brain networks combining functional, structural and topological information of MRI measurements (structural and resting state imaging) to patients with schizophrenia (N=35) and matched healthy individuals (N=41). As a reference condition, the traditional pure functional connectivity (pFC) analysis was carried out. By using the FD model, we found disrupted connectivity in the thalamo-cortical network in schizophrenic patients, whereas the pFC model failed to extract group differences after multiple comparison correction. We interpret this observation as evidence that the FD model is superior to conventional connectivity analysis, by stressing relevant features of the whole brain connectivity including functional, structural and topological signatures. The FD model can be used in future research to model subtle alterations of functional and structural connectivity resulting in pronounced clinical syndromes and major psychiatric disorders. Lastly, FD is not limited to the analysis of resting state fMRI, and can be applied to EEG, MEG etc.
Binning microbial genomes using deep learning
Authors: Nissen Jakob Nybo , Sønderby Casper Kaae , Armenteros Jose Juan Almagro , Grønbech Christopher Heje , Bjørn Nielsen Henrik , Petersen Thomas Nordahl , Winther Ole , Rasmussen Simon
Published: December 2018

Identification and reconstruction of microbial species from metagenomics wide genome sequencing data is an important and challenging task. Current existing approaches rely on gene or contig co-abundance information across multiple samples andk-mer composition information in the sequences. Here we use recent advances in deep learning to develop an algorithm that uses variational autoencoders to encode co-abundance and compositional information prior to clustering. We show that the deep network is able to integrate these two heterogeneous datasets without any prior knowledge and that our method outperforms existing state-of-the-art by reconstructing 1.8 - 8 times more highly precise and complete genome bins from three different benchmark datasets. Additionally, we apply our method to a gene catalogue of almost 10 million genes and 1,270 samples from the human gut microbiome. Here we are able to cluster 1.3 - 1.8 million extra genes and reconstruct 117 - 246 more highly precise and complete bins of which 70 bins were completely new compared to previous methods. Our method Variational Autoencoders for Metagenomic Binning (VAMB) is freely available at:https://github.com/jakobnissen/vamb
Reactive/proactive aggression specific cortical and subcortical alterations in children and adolescents with disruptive behavior
Authors: Naaijen Jilly , Mulder Leandra M , Ilbegi Shahrzad , Bruijn Sanne de , Kleine-Deters Renee , Dietrich Andrea , Hoekstra Pieter J , Marsman Jan-Bernard C , Aggensteiner Pascal M , Holz Nathalie E , Boettinger Boris , Baumeister Sarah , Banaschewski Tobias , Saam Melanie C , Schulze Ulrike M E , Santosh Paramala J , Sagar-Ouriaghli Ilyas , Mastroianni Mathilde , Fornieles Josefina Castro , Bargallo Nuria , Rosa Mireia , Arango Celso , Penzol Maria J , Werhahn Julia E , Walitza Susanne , Brandeis Daniel , Glennon Jeffrey C , Franke Barbara , Zwiers Marcel P , Buitelaar Jan K
Published: December 2018

Objective

Maladaptive aggression, as present in conduct disorder (CD) and, to a lesser extent, oppositional defiant disorder (ODD), has been associated with structural alterations in various brain regions, such as ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, insula and ventral striatum. Although aggression can be subdivided into reactive and proactive subtypes, no neuroimaging studies have yet investigated if any structural brain alterations are associated with either of the subtypes specifically. Here we investigated this association in predefined regions of interest.

Method

T1-weighted magnetic resonance images were acquired from 158 children and adolescents with aggressive behavior (ODD/CD) and 96 controls in a multi-centre study. Aggression subtypes were assessed by questionnaires. Cortical volume and subcortical volumes and shape were determined using Freesurfer and the FMRIB integrated registration and segmentation tool. Associations between volumes and continuous measures of aggression were established using multilevel linear mixed effects models.

Results

In cases only proactive aggression was negatively associated with amygdala volume (b=−11.82, p=0.05), while reactive aggression was negatively associated with insula volume (b=−46.41, p=0.01). Classical group comparison showed that children and adolescents with aggressive behavior had smaller volumes than controls in (bilateral) ventral striatum (p=0.003), ACC (p=0.01), and vmPFC (p=0.003) with modest effect sizes.

Conclusions

Aggression was associated with reduced volume in brain regions involved in decision making. Negative associations were found between reactive aggression and volumes in regions involved in threat responsivity and between proactive aggression and regions linked to empathy. This provides evidence for aggression subtype-specific alterations in brain structure.
Linking micro and macroevolution in the presence of migration
Authors: Duchen Pablo , Hautphenne Sophie , Lehmann Laurent , Salamin Nicolas
Published: December 2018

The process of speciation is of key importance in evolutionary biology because it shapes macroevolutionary patterns. This process starts at the microevolutionary level, for instance, when two subpopulations evolve towards different phenotypic optima. The speed at which these optima are reached is controlled by the degree of stabilising selection, which pushes a mean trait towards an optimum within subpopulations, and ongoing migration that pulls the mean phenotype away from that optimum. Traditionally, macro phenotypic evolution with selection has been modelled by Ornstein-Uhlenbeck (OU) processes, but these models have ignored the role of migration within species. Here, our goal is to reconcile the processes of micro and macroevolution by modelling migration during speciation. More precisely, we introduce an OU model where migration happens between two subpopulations within a branch of a phylogeny and this migration decreases over time as it happens during speciation. We then use this model to study the evolution of trait means along a phylogeny, as well as the way phenotypic disparity between species changes with successive epochs. We show that ignoring the effect of migration in sampled time-series data leads to a significant underestimation of the selective forces acting upon it. We also show that migration decreases the expected phenotypic disparity between species and we show the effect of migration in the particular case of niche filling. We further introduce a method to jointly estimate selection and migration from time-series data. Our model extends standard results of interactions selection-migration in a microevolutionary time frame across multiple speciation events at a macroevolutionary scale. Our results further proof that not accounting for gene flow has important consequences in inferences at both the micro and macroevolutionary scale.
Deregulation of VEGFR-2 and PGFR expression and microvascular density in a triple-negative model of canine malignant mammary tumors with lymph node or lung metastasis
Authors: dos Anjos Denner Santos , Vital Aline Fernandes , Lainetti Patricia De Faria , Leis-Filho Antonio Fernando , Dalmolin Fabiola , Elias Fabiana , Calazans Sabryna Gouveia , Fonseca-Alves Carlos E
Published: December 2018

Canine mammary tumors (CMT) are the most common cancer in noncastrated female dogs. Interestingly, triple-negative tumors are the most common molecular subtype in female dogs. In this study, we proposed to evaluate the expression of VEGFR-2, PDGFR and microvascular density (MVD) in a group of metastatic and nonmetastatic triple-negative CMT and compare the expression based on clinical parameters. Twenty-six female dogs with triple-negative mammary tumors were divided into three groups: nonmetastatic tumors (NMT) (N=11), tumors with lymph node metastasis (LNM) (N=10) and tumors with lung metastasis (LM) (N=5). We observed increased VEGFR-2 expression in LNM compared with NMT and a positive correlation between tumor grade and VEGFR-2 expression. A positive correlation was noted between VEGFR-2 and PDGFR expression. Regarding microvascular density (MVD), we identified a higher number of vessels in primary tumors with lymph node metastasis and lung metastasis compared with tumors with no metastasis. The primary tumors with lung metastasis exhibited an increased MVD compared with carcinoma with lymph node metastasis. Overall, our results suggest a deregulation of VEGFR-2 and PDGFR and high MVD in metastatic tumors, indicating a role for angiogenesis in tumor progression.
The singularity of Cetacea behaviour parallels the complete inactivation of melatonin gene modules
Authors: Lopes-Marques Monica , Ruivo Raquel , Alves Luís Q. , Sousa Nelson , Machado André M. , Castro L. Filipe C.
Published: December 2018

Melatonin, the hormone of darkness, is a peculiar molecule found in most living organisms. Emerging as a potent broad-spectrum antioxidant, melatonin was repurposed into extra roles such as the modulation of circadian and seasonal rhythmicity: affecting numerous aspects of physiology and behaviour, including sleep entrainment and locomotor activity. Interestingly, the pineal gland—the melatonin synthesising organ in vertebrates—was suggested to be absent or rudimentary in some mammalian lineages, including Cetacea. In Cetacea, pineal regression is paralleled by their unique bio-rhythmicity, as illustrated by the unihemispheric sleeping behaviour and long-term vigilance. Here, we examined the genes responsible for melatonin synthesis (Aanat and Asmt) and signalling (Mtnr1a and Mtnr1b) in 12 toothed and baleen whale genomes. Based on an ample genomic comparison, we deduce that melatonin-related gene modules are eroded in Cetacea.
Wolbachia, Cardinium and climate: an analysis of global data
Authors: Charlesworth J. , Weinert L. A. , Araujo-Jnr. E. V. , Welch J. J.
Published: December 2018

Bacterial secondary symbionts are very common in terrestrial arthropods, but infection levels vary widely among populations. Experiments and within-species comparisons both suggest that environmental temperature might be important in explaining this variation. To investigate the importance of temperature, at broad geographical and taxonomic scales, we extended a global database of terrestrial arthropods screened for Wolbachia and Cardinium. Our final data set contained data from 114,297 arthropods (>2,500 species) screened for Wolbachia and 17,011 arthropods (>800 species) screened for Cardinium, including population samples from 137 different countries, and with mean temperatures varying from - 6.5 to 29.2°C. In insects and relatives, Cardinium infection showed a clear and consistent tendency to increase with temperature. For Wolbachia, a tendency to increase with temperature in temperate climates, is counteracted by reduced prevalence in the tropics, resulting in a weak negative trend overall. We discuss the implications of these results for natural and introduced symbionts, in regions affected by climate change.
Encoding of the Intent to Drink Alcohol by the Prefrontal Cortex is blunted in Rats with a Family History of Excessive Drinking
Authors: Linsenbardt David N. , Timme Nicholas M. , Lapish Christopher C.
Published: December 2018

The prefrontal cortex plays a central role in guiding decision-making, and its function is altered by alcohol use and an individual’s innate risk for excessive alcohol drinking. The primary goal of this work was to determine how neural activity in the prefrontal cortex guides the decision to drink. Towards this goal, the within-session changes in neural activity were measured from medial prefrontal cortex (mPFC) of rats performing a drinking procedure that allowed them to consume or abstain from alcohol in a self-paced manner. Recordings were obtained from rats that either lacked or expressed an innate risk for excessive alcohol intake - Wistar or Alcohol Preferring ‘P’ rats, respectively. Wistar rats exhibited patterns of neural activity consistent with the intention to drink or abstain from drinking, whereas these patterns were blunted or absent in P rats. Collectively, these data indicate that neural activity patterns in mPFC associated with the intention to drink alcohol are influenced by innate risk for excessive alcohol drinking. This observation may indicate a lack of control over the decision to drink by this otherwise well-validated supervisory brain region.
Parsing heterogeneity in autism spectrum disorder and attention-deficit/hyperactivity disorder with individual connectome mapping
Authors: Dajani Dina R , Burrows Catherine A , Nebel Mary Beth , Mostofsky Stewart H , Gates Kathleen M , Uddin Lucina Q
Published: December 2018

Traditional diagnostic systems for mental illnesses define diagnostic categories that are heterogeneous in behavior and underlying neurobiological alterations. The goal of this study was to parse heterogeneity in a core executive function, cognitive flexibility, in children with a range of abilities (N=132; children with autism spectrum disorder [ASD], attention deficit/hyperactivity disorder [ADHD], and typically developing [TD] children) using directed functional connectivity profiles derived from resting-state fMRI data. Brain regions activated in response to a cognitive flexibility task in adults were used guide region-of-interest (ROI) selection to estimate individual connectivity profiles in this study. We expected to find at least three subgroups of children who differed in their network connectivity metrics and symptom measures. Unexpectedly, we did not find a stable or valid subgrouping solution, which suggests that categorical models of the neural substrates of cognitive flexibility in children may be invalid. Results shed light on the validity of conceptualizing the neural substrates of cognitive flexibility categorically in children. Ultimately, this work may provide a foundation for the development of a revised nosology focused on neurobiological substrates of mental illness as an alternative to traditional symptom-based classification systems.
Retinoid X receptor alpha is a spatiotemporally-specific therapeutic target for doxorubicin-induced cardiomyopathy in adult zebrafish
Authors: Ma Xiao , Ding Yonghe , Zhang Hong , Qiu Qi , Dvornikov Alexey V. , Kim Maengjo , Wang Yong , Lowerison Matthew , Herrmann Joerg , Ekker Stephen C. , Hsiai Tzung K. , Lin Xueying , Xu Xiaolei
Published: December 2018

While the genetic suppressor screen is efficient in suggesting therapeutic genes, this strategy has yet to be successful for cardiomyopathies in vertebrates. To develop such a strategy, we recently established a mutagenesis screen platform in zebrafish for systematic discovery of genetic modifiers of doxorubicin-induced cardiomyopathy (DIC). Here, we further revealed both molecular and cellular insights of the first salutary modifier emerged from the screen, i.e.gene-breaking transposon(GBT)0419that affects theretinoid X receptor alpha a(rxraa) gene. First, by rescuing the mutation in tissue-specific manner with multiple Cre-loxP systems, we demonstrated that the endothelial, but not myocardial or epicardial, function ofrxraais primary to this cardioprotective effects. Next, we showed that therxraa-associated salutary effects on DIC were conferred partially by the activation of retinoid acid (RA) signaling. Finally, we identified isotretinoin and bexarotene, 2 US Food and Drug Administration-approved RXRA agonists that are effective in treating adult zebrafish DIC when administered during the early, but not the late, phase of DIC progression. Collectively, we provided the firstin vivogenetic evidence in supportingRXRAas the therapeutic target for DIC, and uncovered a previously unrecognized spatiotemporally-restricted mechanism for this gene-based therapeutic strategy. Our study also justified that searching salutary modifiers via zebrafish mutagenesis screen can be effective in discovering new therapeutic targets for cardiomyopathies.
CarbMetSim:A discrete-event simulator for carbohydrate metabolism in humans
Authors: Goyal Mukul , Aydas Buket , Ghazaleh Husam , Rajasekharan Sanjay
Published: December 2018

This paper describesCarbMetSim, adiscrete-eventsimulator that tracks the blood glucose level of a person in response to a timed sequence of diet and exercise activities.CarbMetSimimplements broader aspects of carbohydrate metabolism in human beings with the objective of capturing the average impact of various diet/exercise activities on the blood glucose level. Key organs (stomach, intestine, portal vein, liver, kidney, muscles, adipose tissue, brain and heart) are implemented to the extent necessary to capture their impact on the production and consumption of glucose. Key metabolic pathways (glucose oxidation, glycolysisandgluconeogenesis) are accounted for in the operation of different organs. The impact of insulin and insulin resistance on the operation of various organs and pathways is captured in accordance with published research.CarbMetSimprovides broad flexibility to configure the insulin production ability, the average flux along various metabolic pathways and the impact of insulin resistance on different aspects of carbohydrate metabolism. The simulator does not yet have a detailed implementation of protein and lipid metabolism.
A Novel Workflow for Health Survey Analysis: Results on the Yazd Health Study (YaHS)
Authors: Heidari Elyas , Balazadeh-Meresht Vahid , Ahmadi Nastaran , Sharifi-Zarchi Ali , Mirzaei Masoud , Sadr-Bafghi Mahmood
Published: December 2018

Health surveys are one of the most prominent sources of information in medical sciences. Analysis of a health survey not only gives information about the inherent features of the population under study but also sheds light on the interactions between different health factors. Even though there has been a multitude of methodologies proposed for survey analysis, many of them are biased towards the previous hypotheses, the fact which may lead to spurious results by neglecting the whole structure of relations among the factors. Here, we proposed our novel workflow on survey analysis. By gathering the previously less-utilized graphical models on survey analysis, newly-proposed methods, and commonly-used tools of prediction and hypothesis testing our workflow provides the medical community with an end-to-end pipeline for comprehensive statistical analysis of health surveys. To demonstrate the functionality of our workflow, we validate it on the Yazd Health Study (YaHS) dataset, in which a questionnaire of 300 questions from 10000 participants associated with 40 laboratory measurements from a subset of 4010 individuals is acquired from the residents of the Yazd greater area of Iran. Many of our findings are aligned with previous medical knowledge. Most of our novel findings are surprisingly observed in the clinics, each of which is potential to raise a promising hypothesis.
A microbial metabolite, Lithocholic acid, suppresses IFN-γ and AhR expression by human cord blood CD4 T cells
Authors: Nikolai Anya , Iwashima MAKIO
Published: December 2018

Vitamin D is a well-known micronutrient that modulates immune responses by epigenetic and transcriptional regulation of target genes, such as inflammatory cytokines. Our group recently demonstrated that the most active form of vitamin D, calcitriol, reduces expression of a transcription factor known as the aryl hydrocarbon receptor (AhR) and inhibits differentiation of a pro-inflammatory T cell subset, Th9. Lithocholic acid (LCA), a secondary bile acid produced by commensal bacteria, is known to bind to and activate the vitamin D receptor (VDR) in a manner comparable to calcitriol. In this study, Naive CD4 T cells were isolated from healthy human umbilical mononuclear cells and were stimulated in the presence or absence of LCA. We determined the effect of LCA on human cord blood T cell activation by measuring IFN-γ production and protein expression of IFN-γ receptor-mediated signaling molecules. We found that LCA reduces production of IFN-γ and decreases phosphorylation of STAT1 as well as expression of AhR, STAT1, and IRF1 by activated human cord blood CD4 T cells. LCA inhibits expression of IFN-γ and reduces its receptor signaling molecules.
Integrating hierarchical statistical models and machine-learning algorithms for ground-truthing drone images of the vegetation: taxonomy, abundance and population ecological models
Authors: Damgaard Christian
Published: December 2018

In order to fit population ecological models, e.g. plant competition models, to new drone-aided image data, we need to develop statistical models that may take the new type of measurement uncertainty when applying machine-learning algorithms into account and quantify its importance for statistical inferences and ecological predictions. Here, it is proposed to quantify the uncertainty and bias of image predicted plant taxonomy and abundance in a hierarchical statistical model that is linked to ground-truth data obtained by the pin-point method. It is critical that the error rate in the species identification process is minimized when the image data are fitted to the population ecological models, and several avenues for reaching this objective are discussed. The outlined method to statistically model known sources of uncertainty when applying machine-learning algorithms may be relevant for other applied scientific disciplines.
An integrated transcriptomics and metabolomics analysis of theCucurbita peponectary implicates key modules of primary metabolism involved in nectar synthesis and secretion
Authors: Solhaug Erik M. , Roy Rahul , Chatt Elizabeth C. , Klinkenberg Peter M. , Mohd-Fadzil Nur-Aziatull , Hampton Marshall , Nikolau Basil J. , Carter Clay J.
Published: December 2018

Nectar is the main reward that flowers offer to pollinators to entice repeated visitation.Cucurbita pepo(squash) is an excellent model for studying nectar biology, as it has large nectaries that produce large volumes of nectar relative to most other species. Squash is also monoecious, having both female and male flowers on the same plant, which allows comparative analyses of nectary function in one individual. Here we report the nectary transcriptomes from both female and male nectaries at four stages of floral maturation. Analysis of these transcriptomes and subsequent confirmatory experiments revealed a metabolic progression in nectaries leading from starch synthesis to starch degradation and to sucrose biosynthesis. These results are consistent with previously published models of nectar secretion and also suggest how a sucrose-rich nectar can be synthesized and secreted in the absence of active transport across the plasma membrane. Non-targeted metabolomic analyses of nectars also confidently identified 40 metabolites in both female and male nectars, with some displaying preferential accumulation in nectar of either male or female flowers. Cumulatively, this study identified gene targets for reverse genetics approaches to study nectary function, as well as previously unreported nectar metabolites that may function in plant-biotic interactions.
Dentate Gyrus Activin Signaling Mediates the Antidepressant Treatment Response
Authors: Gergues Mark M , Yohn Christine N , Levinstein Marjorie R , Samuels Benjamin Adam
Published: December 2018

Antidepressants that target monoaminergic systems, such as selective serotonin reuptake inhibitors (SSRIs), are widely used to treat neuropsychiatric disorders including major depressive disorder, several different anxiety disorders, and obsessive-compulsive disorder. However, these treatments are not ideal because only a subset of patients achieve remission. The reasons why some individuals remit to antidepressant treatments while others do not are unknown. Here, we developed a paradigm to assess antidepressant treatment resistance in mice. Treatment of mice with either chronic corticosterone or chronic social defeat stress effectively induces increased negative valence behaviors. Subsequent chronic treatment with the SSRI fluoxetine reverses these behavioral changes in some, but not all, of the mice, permitting stratification into persistent responders and non-responders to fluoxetine. We found several significant differences in expression of Activin signaling-related genes between responders and non-responders to fluoxetine in the dentate gyrus, a region that we recently reported is critical for the beneficial behavioral effects of fluoxetine. Furthermore, enhancement of Activin signaling in the dentate gyrus converted behavioral non-responders into responders to fluoxetine treatment more effectively than commonly used adjunctive antidepressant treatments, while inhibition of Activin signaling in the dentate gyrus converted responders into non-responders. Taken together, these results demonstrate that the behavioral response to FLX can be bidirectionally modified via targeted manipulations of the dentate gyrus and suggest that molecular- and neural circuit-based modulations of dentate gyrus may provide a new therapeutic avenue for more effective antidepressant treatments or adjunctive therapies.
Impaired social behaviour and molecular mediators of associated neural circuits during chronicToxoplasma gondiiinfection in female mice
Authors: Tyebji Shiraz , Seizova Simona , Garnham Alexandra L , Hannan Anthony J , Tonkin Christopher J
Published: December 2018

Toxoplasma gondii(T. gondii) is a neurotropic parasite that is associated with various neuropsychiatric disorders. Rodents infected withT. gondiidisplay a plethora of behavioural alterations, andToxoplasmainfection in humans has been strongly associated with disorders such as schizophrenia, in which impaired social behaviour is an important feature. Elucidating changes at the cellular level relevant to neuropsychiatric conditions can lead to effective therapies. Here, we compare changes in behaviour during an acute and chronicT. gondiiinfection in female mice. Further, we notice that during chronic phase of infection, mice display impaired sociability when exposed to a novel conspecific. Also, we show thatT. gondiiinfected mice display impaired short-term social recognition memory. However, object recognition memory remains intact. Using c-Fos as a marker of neuronal activity, we show that infection leads to an impairment in neuronal activation in the medial prefrontal cortex, hippocampus as well as the amygdala when mice are exposed to a social environment and a change in functional connectivity between these regions. We found changes in synaptic proteins that play a role in the process of neuronal activation such as synaptophysin, PSD-95 and changes in downstream substrates of cell activity such as cyclic AMP, phospho-CREB and BDNF. Our results point towards an imbalance in neuronal activity that can lead to a wider range of neuropsychiatric problems uponT. gondiiinfection.
Genomic analyses provide insights into genetic architecture of three-way crossbred pigs
Authors: Lin Yu , Tang Qianzi , Li Yan , He Mengnan , Jin Long , Ma Jideng , Wang Xun , Long Keren , Huang Zhiqing , Li Xuewei , Gu Yiren , Li Mingzhou
Published: December 2018

Background

Crossbreeding is effective for improving performance in poultry and livestock, which is mainly attributed to heterosis. For pork production, a classic three-way crossbreeding system of Duroc × (Landrace × Yorkshire) (DLY) is widely used to produce terminal crossbred pigs with stable and prominent performance. Nonetheless, studies on the transmission of genetic information and gene expression pattern of DLY have been limited.

Findings

We analyzed population-scale SNPs based on 30 individuals from these three purebreds and identified 529.93 K SNPs of breed-of-origin of alleles. We also applied whole-genome sequencing of ten individuals from a DLY pig family as well as transcriptome of four representative tissues (adipose, skeletal muscle, heart, and liver) for six DLY individuals. Based on above, we identified a large number of high-confidence ASE genes, among which four ASE genes (KMO,PLIN4,POPDC3andUGT1A6) were found to be shared over all DLY individuals.

Conclusion

We suggest DLY is a more effective strategy of three-way crossbreeding among these three purebreds from genetic aspect. We suppose the numerous breed-of-origin of alleles have close association with improved performance of crossbred individuals. ASE may also play important roles on DLY three-way crossbreeding system. Our findings are valuable for understanding the transmission of genetic information and the gene expression in DLY three-way crossbreeding and may be used to guide breeding and production of pigs in the future.