bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addressing challenges of high spatial resolution, UHF field fMRI for group analysis of higher-order cognitive tasks; an inter-sensory task directing attention between visual and somatosensory domains
Authors: Aquino Kevin M. , Sokoliuk Rodika , Pakenham Daisie , Panchuelo Rosa Sanchez , Hanslmayr Simon , Mayhew Stephen D. , Mullinger Karen J. , Francis Susan T. 
Published: July 2018

AbstractFunctional MRI at ultra-high field (UHF, ≥7T) provides significant increases in BOLD contrast-to-noise ratio (CNR) compared with conventional field strength (3T), and has been exploited for reduced field-of-view, high spatial resolution mapping of primary sensory areas. Applying these high spatial resolution methods to investigate whole brain functional responses to higher-order cognitive tasks leads to a number of challenges, in particular how to perform robust group-level statistical analyses.This study addresses these challenges using an inter-sensory cognitive task which modulates top-down attention at graded levels between the visual and somatosensory domains. At the individual level, highly focal functional activation to the task and task difficulty (modulated by attention levels) were detectable due to the high CNR at UHF. However, to assess group level effects, both anatomical and functional variability must be considered during analysis. We demonstrate the importance of surface over volume normalization and the requirement of no spatial smoothing when assessing highly focal activity. Using novel group analysis on anatomically parcellated brain regions, we show that in higher cognitive areas (parietal and dorsal-lateral-prefrontal cortex) fMRI responses to graded attention levels were modulated quadratically, whilst in visual cortex and VIP, responses were modulated linearly. These group fMRI responses were not seen clearly using conventional second-level GLM analyses, illustrating the limitations of a conventional approach when investigating such focal responses in higher cognitive regions which are more anatomically variable. The approaches demonstrated here complement other advanced analysis methods such as multi-variate pattern analysis, allowing UHF to be fully exploited in cognitive neuroscience.
Cryo-EM Reveals Ligand Induced Allostery Underlying InsP3R Channel Gating
Authors: Fan Guizhen , Baker Mariah R. , Wang Zhao , Seryshev Alexander B. , Ludtke Steven J. , Baker Matthew L. , Serysheva Irina I. 
Published: July 2018

AbstractInositol-1,4,5-trisphosphate receptors (InsP3Rs) are cation channels that mobilize Ca2+from intracellular stores in response to a wide range of cellular stimuli. The paradigm of InsP3R activation is the coupled interplay between binding of InsP3and Ca2+that switches the ion conduction pathway between closed and open states to enable the passage of Ca2+through the channel. However, the molecular mechanism of how the receptor senses and decodes ligand-binding signals into gating motion remains unknown. Here we present the electron cryo-microscopy structure of InsP3R1 from rat cerebellum determined to 4.1 Å resolution in the presence of activating concentrations of Ca2+and adenophostin A (AdA), a structural mimetic of InsP3and the most potent known agonist of the channel. Comparison with the 3.9 Å-resolution structure of InsP3R1 in the Apo-state, also reported herein, reveals the binding arrangement of AdA in the tetrameric channel assembly and striking ligand-induced conformational rearrangements within cytoplasmic domains coupled to the dilation of a hydrophobic constriction at the gate. Together, our results provide critical insights into the mechanistic principles by which ligand-binding allosterically gates InsP3R channel.
Asgard archaea are diverse, ubiquitous, and transcriptionally active microbes
Authors: Cai Mingwei , Liu Yang , Zhou Zhichao , Yang Yuchun , Pan Jie , Gu Ji-Dong , Li Meng 
Published: July 2018

AbstractAsgard is a newly proposed archaeal superphylum. Phylogenetic position of Asgard archaea and its relationships to the origin of eukaryotes is attracting increasingly research interest. However, in-depth knowledge of their diversity, distribution, and activity of Asgard archaea remains limited. Here, we used phylogenetic analysis to cluster the publicly available Asgard archaeal 16S rRNA gene sequences into 13 subgroups, including five previously unknown subgroups. These lineages were widely distributed in anaerobic environments, with the majority of 16S rRNA gene sequences (92%) originating from sediment habitats. Co-occurrence analysis revealed potential relationships between Asgard, Bathyarchaeota, and Marine Benthic Group D archaea. Genomic analysis suggested that Asgard archaea are potentially mixotrophic microbes with divergent metabolic capabilities. Importantly, metatranscriptomics confirmed the versatile lifestyles of Lokiarchaeota and Thorarchaeota, which can fix CO2using the tetrahydromethanopterin Wood-Ljungdahl pathway, perform acetogenesis, and degrade organic matters. Overall, this study broadens the understandings of Asgard archaea ecology, and also provides the first evidence to support a transcriptionally active mixotrophic lifestyle of Asgard archaea, shedding light on the potential roles of these microorganisms in the global biogeochemical cycling.
A new normalization for the Nanostring nCounter gene expression assay
Authors: Molania Ramyar , Gagnon-Bartsch Johann A. , Dobrovic Alexander , Speed Terence P 
Published: July 2018

AbstractThe Nanostring nCounter gene expression assay uses molecular barcodes and single molecule imaging to detect and count hundreds of unique transcripts in a single reaction. These counts need to be normalized to adjust for the amount of sample, variations in assay efficiency, and other factors. Most users adopt the normalization approach described in the nSolver analysis software, which involves background correction based on the observed values of negative control probes, a within-sample normalization using the observed values of positive control probes and normalization across samples using reference (housekeeping) genes. Here we present a new normalization method, Removing Unwanted Variation-III (RUV-III), which makes vital use of technical replicates and suitable control genes. We also propose an approach using pseudo-replicates when technical replicates are not available. The effectiveness of RUV-III is illustrated on four different data sets. We also offer suggestions on the design and analysis of studies involving this technology.
On the molecular filters in cochlea transduction
Authors: Goussev Valeri 
Published: July 2018

AbstractThe article is devoted to the specific consideration of the cochlear transduction for the low level sound intensities, which correspond to the regions near the perception threshold. The basic cochlea mechanics is extended by the new concept of the molecular filters, which allows us to discuss the transduction mechanism on the molecular level in the space-time domain. The molecular filters are supposed to be built on the set of the stereocilia of every inner hair cell. It is hypothesized that the molecular filters are the sensors in the feedback loop, which includes also outer hair cells along with the tectorial membrane and uses the zero compensation method to evaluate the traveling wave shape on the basilar membrane. Besides the compensation, the feedback loop, being spatially distributed along the cochlea, takes control over the tectorial membrane strain field generated by the outer hair cells, and implements it as the mechanism for the automatic gain control in the sound transduction.
Two central pattern generators from the crab, Cancer borealis, respond robustly and differentially to extreme extracellular pH
Authors: Haley Jessica A. , Hampton David , Marder Eve 
Published: July 2018

AbstractAnimals and their neuronal circuits must maintain function despite significant environmental fluctuations. The crab, Cancer borealis, experiences daily changes in ocean temperature and pH. Here, we describe the effects of extreme changes in extracellular pH – from pH 5.5 to 10.4 – on two central pattern generating networks, the stomatogastric and cardiac ganglia of C. borealis. Given that the physiological properties of ion channels are known to be sensitive to pH within the range tested, it is surprising that these rhythms generally remained robust from pH 6.1 to pH 8.8. Unexpectedly, the stomatogastric ganglion was more sensitive to acid while the cardiac ganglion was more sensitive to base. Considerable animal-to-animal variability was likely a consequence of similar network performance arising from variable sets of underlying conductances. Together, these results illustrate the potential difficulty in generalizing the effects of environmental perturbation across circuits, even within the same animal.AbbreviationsSTGstomatogastric ganglionCGcardiac ganglionCPGcentral pattern generatorABAnterior BursterPDPyloric DilatorLPLateral PyloricPYPyloricSCSmall CellLCLarge Celllvnlateral ventricular nerveANOVAanalysis of variancePTXpicrotoxinIPSPinhibitory post-synaptic potentialLGLateral GastricMGMedial GastricLPGLateral Posterior GastricGMGastric MillDGDorsal GastricAMAnterior MedianInt1Interneuron 1mvnmedial ventricular nervedgndorsal gastric nervelgnlateral gastric nerveioninferior oesophageal nerveICInferior CardiacVDVentricular DilatorMCN1Modulatory Commissural Neuron 1VCNVentral Cardiac NeuronCPN2Commissural Projection Neuron 2CoGcommissural ganglionKDEkernel density estimateIQRinterquartile rangeCIconfidence interval
Evolutionary parallelisms of pectoral and pelvic network-anatomy from fins to limbs
Authors: Esteve-Altava Borja , Pierce Stephanie E. , Molnar Julia L. , Johnston Peter , Diogo Rui , Hutchinson John R. 
Published: July 2018

ABSTRACTPectoral and pelvic lobe-fins transformed into fore- and hindlimbs during the Devonian period, enabling the water-to-land transition in tetrapods. In the timespan of ~60 million years, transitional forms evolved, spanning a wide range of morphologies. Here we traced the evolution of well-articulated appendicular skeletons across the fins-to-limbs transition, using a network-based approach and phylogenetic tools to quantify and compare topological features of skeletal anatomy of fins and limbs. We show that the topological arrangement of bones in the pectoral and pelvic appendages evolved in parallel during the fins-to-limbs transition, occupying overlapping regions of the morphospace, following a directional mode of evolution, and decreasing their disparity over time. We identify the presence of digits as the morphological novelty triggering significant topological changes that clearly discriminated limbs from fins. The origin of digits caused an evolutionary shift towards appendages that were less densely and heterogeneously connected, but more assortative and modular. Topological disparity likewise decreased for both appendages: for the pectoral appendage, until the origin of amniotes; for the pelvic appendage, until a time concomitant with the earliest-known tetrapod tracks. Finally, we tested and rejected the presence of a pectoral-pelvic similarity bottleneck for the network-anatomy of appendages at the origin of tetrapods. We interpret our findings in the context of a dynamic compromise between possibly different functional demands in pectoral and pelvic appendages during the water-to-land transition and a shared developmental program constraining the evolvability of limbs.
SMRT long reads and Direct Label and Stain optical maps allow the generation of a high-quality genome assembly for the European barn swallow (Hirundo rustica rustica)
Authors: Formenti Giulio , Chiara Matteo , Poveda Lucy , Francoijs Kees-Jan , Bonisoli-Alquati Andrea , Canova Luca , Gianfranceschi Luca , Stephen Horner David , Saino Nicola 
Published: July 2018

ABSTRACTBackgroundThe barn swallow (Hirundo rustica) is a migratory bird that has been the focus of a large number of ecological, behavioural and genetic studies. To facilitate further population genetics and genomic studies, here we present a reference genome assembly for the European subspecies (H. r. rustica).FindingsAs part of the Genome10K (G10K) effort on generating high quality vertebrate genomes, we have assembled a highly contiguous genome assembly using Single Molecule Real-Time (SMRT) DNA sequencing and several Bionano optical map technologies. We compared and integrated optical maps derived both from the Nick, Label, Repair and Stain and from the Direct Label and Stain (DLS) technologies. As proposed by Bionano, the DLS more than doubled the scaffold N50 with respect to the nickase. The dual enzyme hybrid scaffold led to a further marginal increase in scaffold N50 and an overall increase of confidence in the scaffolds. After removal of haplotigs, the final assembly is approximately 1.21 Gbp in size, with a scaffold N50 value of over 25.95 Mbp.ConclusionsThis high-quality genome assembly represents a valuable resource for further studies of population genetics and genomics in the barn swallow, and for studies concerning the evolution of avian genomes. It also represents one of the very first genomes assembled by combining SMRT long-read sequencing with the new Bionano DLS technology for scaffolding. The quality of this assembly demonstrates the potential of this methodology to substantially increase the contiguity of genome assemblies.
Dynamic functional connectivity changes in dementia with Lewy bodies and Alzheimer’s disease
Authors: Schumacher Julia , Peraza Luis R. , Firbank Michael , Thomas Alan J. , Kaiser Marcus , Gallagher Peter , O’Brien John T. , Blamire Andrew M. , Taylor John-Paul 
Published: July 2018

AbstractWe studied the dynamic functional connectivity profile of dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) and the relationship between dynamic connectivity and the temporally transient symptoms of cognitive fluctuations and visual hallucinations in DLB.Resting state fMRI data from 31 DLB, 29 AD, and 31 healthy control participants were analysed using dual regression to determine between-network functional connectivity. We used a sliding window approach followed by k-means clustering and dynamic network analyses to study dynamic functional connectivity changes associated with AD and DLB. Network measures that showed significant group differences were tested for correlations with clinical symptom severity.AD and DLB patients spent more time than controls in sparse connectivity configurations with absence of strong positive and negative connections and a relative isolation of motor networks from other networks. Additionally, DLB patients spent less time in a more strongly connected state and the variability of global brain network efficiency was reduced in DLB compared to controls. However, there were no significant correlations between dynamic connectivity measures and clinical scores.The loss of global efficiency variability in DLB might indicate the presence of an abnormally rigid brain network and the lack of economical dynamics, factors which could contribute to an inability to respond appropriately to situational demands. However, the absence of significant clinical correlations indicates that the severity of transient cognitive symptoms such as cognitive fluctuations and visual hallucinations might not be directly related to these dynamic connectivity changes observed during a short resting state scan.
Genome-wide association meta-analysis of cocaine dependence: Shared genetics with comorbid conditions
Authors: Cabana-Domínguez Judit , Shivalikanjli Anu , Fernàndez-Castillo Noèlia , Cormand Bru 
Published: July 2018

AbstractCocaine dependence is a complex psychiatric disorder that is highly comorbid with other psychiatric traits. Twin and adoption studies suggest that genetic variants contribute substantially to cocaine dependence susceptibility, which has an estimated heritability of 65-79%. Here we performed a meta-analysis of genome-wide association studies of cocaine dependence using four datasets from the dbGaP repository (2,085 cases and 4,293 controls, all of them selected by their European ancestry). Although no genome-wide significant hits were found in the SNP-based analysis, the gene-based analysis identified HIST1H2BD as associated with cocaine-dependence (10% FDR). This gene is located in a region on chromosome 6 enriched in histone-related genes, previously associated with schizophrenia (SCZ). Furthermore, we performed LD Score regression analysis with comorbid conditions and found significant genetic correlations between cocaine dependence and SCZ, ADHD, major depressive disorder (MDD) and risk taking. We also found, through polygenic risk score analysis, that all tested phenotypes can significantly predict cocaine dependence status: SCZ (R2=2.28%; P=1.21e-26), ADHD (R2=1.39%; P=4.5e-17), risk taking (R2=0.60%; P=2.7e-08), MDD (R2=1.21%; P=4.35e-15), children’s aggressiveness (R2=0.3%; P=8.8e-05) and antisocial behavior (R2=1.33%; P=2.2e-16). To our knowledge, this is the largest reported cocaine dependence GWAS meta-analysis in European-ancestry individuals. We identified suggestive associations in regions that may be related to cocaine dependence and found evidence for shared genetic risk factors between cocaine dependence and several comorbid psychiatric traits. However, the sample size is limited and further studies are needed to confirm these results.
How many individuals share a mitochondrial genome?
Authors: Andersen Mikkel M , Balding David J 
Published: July 2018

AbstractMitochondrial DNA (mtDNA) is useful to assist with identification of the source of a biological sample, or to confirm matrilineal relatedness. Although the autosomal genome is much larger, mtDNA has an advantage for forensic applications of multiple copy number per cell, allowing better recovery of sequence information from degraded samples. In addition, biological samples such as fingernails, old bones, teeth and hair have mtDNA but little or no autosomal DNA. The relatively low mutation rate of the mitochondrial genome (mitogenome) means that there can be large sets of matrilineal-related individuals sharing a common mitogenome. Here we present the mitolina simulation software that we use to describe the distribution of the number of mitogenomes in a population that match a given mitogenome, and investigate its dependence on population size and growth rate, and on a database count of the mitogenome. Further, we report on the distribution of the number of meioses separating pairs of individuals with matching mitogenome. Our results have important implications for assessing the weight of mtDNA profile evidence in forensic science, but mtDNA analysis has many non-human applications, for example in tracking the source of ivory. Our methods and software can also be used for simulations to validate models of population history in human or non-human populations.Author SummaryThe maternally-inherited mitochondrial DNA (mtDNA) represents only a small fraction of the human genome, but mtDNA profiles are important in forensic science, for example when a biological evidence sample is degraded or when maternal relatedness is questioned. For forensic mtDNA analysis, it is important to know how many individuals share a mtDNA profile. We present a simulation model of mtDNA profile evolution, implemented in open-source software, and use it to describe the distribution of the number of individuals with matching mitogenomes, and their matrilineal relatedness. The latter is measured as the number of mother-child pairs in the lineage linking two matching individuals. We also describe how these distributions change when conditioning on a count of the profile in a frequency database.
Individual differences in cortical processing speed predict cognitive abilities: a model-based cognitive neuroscience account
Authors: Schubert Anna-Lena , Nunez Michael D. , Hagemann Dirk , Vandekerckhove Joachim 
Published: July 2018

AbstractPrevious research has shown that individuals with greater cognitive abilities display a greater speed of higher-order cognitive processing. These results suggest that speeded neural information-processing may facilitate evidence accumulation during decision making and memory updating and thus yield advantages in general cognitive abilities. We used a hierarchical Bayesian cognitive modeling approach to test the hypothesis that individual differences in the velocity of evidence accumulation mediate the relationship between neural processing speed and cognitive abilities. We found that a higher neural speed predicted both the velocity of evidence accumulation across behavioral tasks as well as cognitive ability test scores. However, only a small part of the association between neural processing speed and cognitive abilities was mediated by individual differences in the velocity of evidence accumulation. The model demonstrated impressive forecasting abilities by predicting 36% of individual variation in cognitive ability test scores in an entirely new sample solely based on their electrophysiological and behavioral data. Our results suggest that individual differences in neural processing speed might affect a plethora of higher-order cognitive processes, that only in concert explain the large association between neural processing speed and cognitive abilities, instead of the effect being entirely explained by differences in evidence accumulation speeds.
Local adaptation under gene flow: Recombination, conditional neutrality and genetic trade-offs shape genomic patterns inArabidopsis lyrata
Authors: Hämälä Tuomas , Savolainen Outi 
Published: July 2018

AbstractShort-scale local adaptation is a complex process involving selection, migration and drift. The expected effects on the genome are well grounded in theory, but examining these on an empirical level has proven difficult, as it requires information about local selection, demographic history and recombination rate variation. Here, we use locally adapted and phenotypically differentiatedArabidopsis lyratapopulations from two altitudinal gradients in Norway to test these expectations at the whole-genome level. Demography modelling indicates that populations within the gradients diverged less than 2000 years ago and that the sites are connected by gene flow. The gene flow estimates are, however, highly asymmetric with migration from high to low altitudes being several times more frequent thanvice versa. To detect signatures of selection for local adaptation, we estimate patterns of lineage specific differentiation among these populations. Theory predicts that gene flow leads to concentration of adaptive loci in areas of low recombination; a pattern we observe in both lowland-alpine comparisons. Although most selected loci display patterns of conditional neutrality, we found indications of genetic trade-offs, with one locus particularly showing high divergence and signs of selection in both populations. Our results further suggest that resistance to solar radiation is an important adaptation to alpine environments, while vegetative growth and bacterial defense are indicated as selected traits in the lowland habitats. These results provide insights into genetic architectures and evolutionary processes driving local adaptation under gene flow. We also contribute to understanding of traits and biological processes underlying alpine adaptation in northern latitudes.