bluuebunny/crossref_metadata_2025_split huggingface dataset:
SVants – A long-read based method for structural variation detection in bacterial genomes
Authors: Hanson BM , Johnson JS , Leopold SR , Sodergren E , Weinstock GM 
Published: November 2019

AbstractMotivationMobile genetic elements (MGEs) are genetic material that can transfer between bacterial cells and move to new locations within a single bacterial genome. These elements range from several hundred to tens of thousands of bases, and are often bordered by repeat regions, which makes resolving these elements difficult with short-read sequencing data. The development and availability of long-read sequencing technologies has opened up new opportunities in the study of structural variation but there is a lack of bioinformatics tools designed to take advantage of these longer reads.ResultsWe present an assembly-free method for identifying the location of these MGEs when compared to any reference genome (including draft genomes). Using an artificially constructed Escherichia coli genome containing single and tandem-repeats of a Tn9 transposon, we demonstrate the ability of SVants to accurately identify multiple insertion sites as well as count the number of repeats of this MGE. Additionally, we show that SVants accurately identifies the transposon of interest, Tn9, but does not erroneously identify existing IS1 regions present within the chromosome of the E. coli artificial reference.Availability and ImplementationSVants is available as open-source software at https://github.com/EpiBlake/SVants
A cryo-tomography-based volumetric model of the actin core of mouse vestibular hair cell stereocilia lacking plastin 1
Authors: Song Junha , Patterson Roma , Krey Jocelyn F. , Hao Samantha , Wang Linshanshan , Ng Brian , Sazzed Salim , Kovacs Julio , Wriggers Willy , He Jing , Barr-Gillespie Peter G. , Auer Manfred 
Published: November 2019

AbstractElectron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run 13 nm apart in parallel for long distances, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link should anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm. Our models illustrate detailed features of distinct structural domains that are present within the stereocilium.
A generalized machine-learning aided method for targeted identification of industrial enzymes from metagenome: a xylanase temperature dependence case study
Authors: Shahraki Mehdi Foroozandeh , Farhadyar Kiana , Kavousi Kaveh , Azarabad Mohammad Hadi , Boroomand Amin , Ariaeenejad Shohreh , Salekdeh Ghasem Hosseini 
Published: November 2019

AbstractGrowing industrial utilization of enzymes, and the increasing availability of metagenomic data highlights the demand for effective methods of targeted identification and verification of novel enzymes from various environmental microbiota. Xylanases are a class of enzymes with numerous industrial applications and are involved in the degradation of xylose, a component of lignocellulose. Optimum temperature of enzymes are essential factors to be considered when choosing appropriate biocatalysts for a particular purpose. Therefore, in-silico prediction of this attribute is a significant cost and time-effective step in the effort to characterize novel enzymes. The objective of this study was to develop a computational method to predict the thermal dependence of xylanases. This tool was then implemented for targeted screening of putative xylanases with specific thermal dependencies from metagenomic data and resulted in identification of three novel xylanases from sheep and cow rumen microbiota. Here we present TAXyl (Thermal Activity Prediction for Xylanase), a new sequence-based machine learning method that has been trained using a selected combination of various protein features. This random forest classifier discriminates non-thermophilic, thermophilic, and hyper-thermophilic xylanases. Model’s performance was evaluated through multiple iterations of six-fold cross-validations, and it exhibited a mean accuracy of ∼0.79. TAXyl is freely accessible as a web-service.
A geostatistical approach to modelling human Holocene migrations in Europe using ancient DNA
Authors: Racimo Fernando , Woodbridge Jessie , Fyfe Ralph M. , Sikora Martin , Sjögren Karl-Göran , Kristiansen Kristian , Linden Marc Vander 
Published: November 2019

AbstractThe European continent was subject to two major migrations of peoples during the Holocene: the northwestward movement of Anatolian farmer populations during the Neolithic and the westward movement of Yamnaya steppe peoples during the Bronze Age. These movements changed the genetic composition of the continent’s inhabitants, via admixture and population replacement processes. The Holocene was also characterized by major changes in vegetation composition, which altered the environment occupied by the original hunter-gatherer populations. Here, we use a combination of paleogenomics and geostatistical modelling to produce detailed maps of the movement of these populations over time and space, and to understand how these movements impacted the European vegetation landscape. We find that the dilution of hunter-gatherer ancestries and the Yamnaya steppe migration coincided with a reduction in the amount of broad-leaf forest and an increase in the amount of pasture lands in the continent. We also show that climate played a role in these vegetational changes. Additionally, we find that the spread of Neolithic farmer ancestry had a two-pronged wavefront, in agreement with similar findings based on patterns of the cultural spread of farming from radiocarbon-dated archaeological sites. With thousands of ancient genomes publicly available and in production, we foresee that the integration of ancient DNA with geostatistical techniques and large-scale archaeological datasets will revolutionize the study of ancient populations movements, and their effects on local fauna and flora.
TXO: Transcription-Only genetic circuits as a novel cell-free approach for Synthetic Biology
Authors: Millacura Felipe A. , Li Mengxi , Valenzuela-Ortega Marcos , French Christopher E. 
Published: November 2019

AbstractWhile synthetic biology represents a promising approach to solve real-world problems, the use of genetically modified organisms is a cause of legal and environmental concerns. Cell-free systems have emerged as a possible solution but much work is needed to optimize their functionality and simplify their usage for Synthetic Biology. Here we present TXO, transcription-only genetic circuits, independent of translation or post-translation maturation. RNA aptamers are used as reaction output allowing the generation of fast, reliable and simple-to-design transcriptional units. TXO cell-free reactions and their possible applications are a promising new tool for fast and simple bench-to-market genetic circuit and biosensor applications.
The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+T cells
Authors: Kwesi-Maliepaard Eliza Mari , Aslam Muhammad Assad , Alemdehy Mir Farshid , van den Brand Teun , McLean Chelsea , Vlaming Hanneke , van Welsem Tibor , Korthout Tessy , Lancini Cesare , Hendriks Sjoerd , Ahrends Tomasz , van Dinther Dieke , den Haan Joke M.M. , Borst Jannie , de Wit Elzo , van Leeuwen Fred , Jacobs Heinz 
Published: November 2019

AbstractCytotoxic T-cell differentiation is guided by epigenome adaptations but how epigenetic mechanisms control lymphocyte development has not been well defined. Here we show that the histone methyltransferase DOT1L, which marks the nucleosome core on active genes, safeguards normal differentiation of CD8+T cells. T-cell specific ablation ofDot1Lresulted in loss of naïve CD8+T cells and premature differentiation towards a memory-like state, independent of antigen exposure and in a cell-intrinsic manner. Without DOT1L, the memory-like CD8+cells fail to acquire full effector functionsin vitroandin vivo. Mechanistically, DOT1L controlled T-cell differentiation and function by ensuring normal T-cell receptor density and signaling, and by maintaining epigenetic identity, in part by indirectly supporting the repression of developmentally-regulated genes. Through our study DOT1L is emerging as a central player in physiology of CD8+T cells, acting as a barrier to prevent premature differentiation and supporting the licensing of the full effector potential of cytotoxic T cells.
Bladder pressure encoding by near-independent fibre subpopulations — implications for decoding
Authors: Lubba Carl H. , Ouyang Zhonghua , Jones Nick S. , Bruns Tim M. , Schultz Simon R. 
Published: November 2019

AbstractObjectiveWe aim at characterising the encoding of bladder pressure (intravesical pressure) by a population of sensory fibres. This research is motivated by the possibility to restore bladder function in elderly patients or after spinal cord injury using implanted devices, so called bioelectronic medicines. For these devices, nerve-based estimation of intravesical pressure can enable a personalized and on-demand stimulation paradigm, which will be more effective and efficient. In this context, a better understanding of the encoding strategies employed by the body might in the future be exploited by informed decoding algorithms that enable a precise and robust bladderpressure estimation.ApproachTo this end, we apply information theory to microelectrode-array recordings from the cat sacral dorsal root ganglion while filling the bladder, conduct surrogate data studies to augment the data we have, and finally decode pressure in a simple informed approach.Main resultsWe find an encoding scheme by different main bladder neuron types that we divide into three response types (slow tonic, phasic, and derivative fibres). We show that an encoding by different bladder neuron types, each represented by multiple cells, offers reliability through within-type redundancy and high information rates through near-independence of different types. Our subsequent decoding study shows a potentially more robust decoding from mean responses of homogeneous cell pools.SignificanceWe have here, for the first time, analysed the encoding of intravesical pressure by a population of sensory neurons in a principled way using information theory. We show that even a simple adapted decoder can exploit the redundancy in the population to be more robust against cell loss. This work thus paves the way towards principled encoding studies in the periphery and towards a new generation of informed peripheral nerve decoders for bioelectronic medicines.
Brain structural connectivity predicts brain functional complexity: DTI derived centrality accounts for variance in fractal properties of fMRI signal
Authors: Neudorf Josh , Ekstrand Chelsea , Kress Shaylyn , Borowsky Ron 
Published: November 2019

AbstractThe complexity of brain activity has recently been investigated using the Hurst (H) exponent, which describes the extent to which functional magnetic resonance imaging (fMRI) blood oxygen-level dependent (BOLD) activity is self-similar vs. complex. For example, research has demonstrated that fMRI activity is more complex before than after consumption of alcohol and during task than resting state. The measurement of H in fMRI is a novel method that requires the investigation of additional factors contributing to complexity. Graph theory metrics of centrality can assess how centrally important to the brain network each region is, based on diffusion tensor imaging (DTI) counts of probabilistic white matter (WM) tracts. DTI derived centrality was hypothesized to account for the complexity of functional activity, based on the supposition that more sources of information to integrate should result in more complex activity. FMRI BOLD complexity as measured by H was associated with five brain region centrality measures: degree, eigenvector, PageRank, current flow betweenness, and current flow closeness centrality. Multiple regression analyses demonstrated that degree centrality was the most robust predictor of complexity, whereby greater centrality was associated with increased complexity (lower H). Regions known to be highly connected, including the thalamus and hippocampus, notably were among the highest in centrality and complexity. This research has led to a greater understanding of how brain region characteristics such as DTI centrality relate to the novel Hurst exponent approach for assessing brain activity complexity, and implications for future research that employ these measures are discussed.
Modeling Abiotic Niches of Crops and Wild Ancestors Using Deep Learning: A Generalized Approach
Authors: Hulleman W. G. , Vos R. A. 
Published: November 2019

AbstractIntroductionUnderstanding what interactions and environmental factors shape the geographic distribution of species is one of the fundamental questions in ecology and evolution. Insofar as the focus is on agriculturally important species, insight into this is also of applied importance. Species Distribution Modeling (SDM) comprises a spectrum of approaches for establishing correlative models of species (co-)occurrences and geospatial patterns of abiotic environmental variables.MethodsHere, we contribute to this field by presenting a generalized approach for SDM that utilizes deep learning, which offers some improvements over current methods, and by presenting a case study on the habitat suitability of staple crops and their wild ancestors. The approach we present is implemented in a reusable software toolkit, which we apply to an extensive data set of geo-referenced occurrence records for 52 species and 59 GIS layers. We compare the habitat suitability projections for selected, major crop species with the actual extent of their current cultivation.ResultsOur results show that the approach yields especially plausible projections for species with large numbers of occurrences (>500). For the analysis of such data sets, the toolkit provides a convenient interface for using deep neural networks in SDM, a relatively novel application of deep learning. The toolkit, the data, and the results are available as open source / open access packages.ConclusionsSpecies Distribution Modeling with deep learning is a promising avenue for method development. The niche projections that can be produced are plausible, and the general approach provides great flexibility for incorporating additional data such as species interactions.
Amperometric measurements of cocaine cue and novel context-evoked glutamate and nitric oxide release in the nucleus accumbens core
Authors: Siemsen BM , McFaddin JA , Haigh K , Brock AG , Leath MN , Hooker KN , McGonegal LK , Scofield MD 
Published: November 2019

AbstractCue-induced reinstatement of cocaine seeking after self-administration (SA) and extinction relies on glutamate release in the nucleus accumbens core (NAcore), which in turn activates neuronal nitric oxide synthase (nNOS) interneurons. Nitric oxide (NO) is required for structural plasticity in NAcore medium spiny neurons (MSNs), as well as cued cocaine seeking. However, NO release in the NAcore during reinstatement has yet to be directly measured. Further, the temporal relationship between glutamate release, and the induction of a NO response also remains unknown. Using wireless amperometric recordings in awake behaving rat, we quantified the magnitude and temporal dynamics of novel context- and cue-induced reinstatement-evoked glutamate and NO release in the NAcore. We found that re-exposure to cocaine-conditioned stimuli following SA and extinction increased extracellular glutamate, leading to release of NO in the NAcore. In contrast, exposing drug-naïve rats to a novel context led to a lower magnitude rise in glutamate in the NAcore relative to cue-induced reinstatement. Interestingly, novel context exposure evoked a higher magnitude NO response relative to cue-induced reinstatement. Despite differences in magnitude, novel context evoked-NO release in the NAcore was also temporally delayed when compared to glutamate. These results demonstrate a dissociation between the magnitude of cocaine cue- and novel context-evoked glutamate and NO release in the NAcore, yet similarity in the temporal dynamics of their release. Together, these data contribute to a greater understanding of the relationship between glutamate and NO, two neurotransmitters implicated in encoding the valence of distinct contextual stimuli.
Repetition Attenuates the Influence of Recency on Recognition Memory: Behavioral and Electrophysiological Evidence
Authors: Scofield John E. , Price Mason H. , Flores Angélica , Merkle Edgar C. , Johnson Jeffrey D. 
Published: November 2019

ABSTRACTStudies of recognition memory often demonstrate a recency effect on behavioral performance, whereby response times (RTs) are faster for stimuli that were previously presented recently as opposed to more remotely in the past. This relationship between performance and presentation lag has been taken to reflect that memories are accessed by serially searching backwards in time, such that RT indicates the self-terminating moment of such a process. Here, we investigated the conditions under which this serial search gives way to more efficient means of retrieving memories. Event-related potentials (ERPs) were recorded during a continuous recognition task in which subjects made binary old/new judgments to stimuli that were each presented up to four times across a range of lags. Stimulus repetition and shorter presentation lag both gave rise to speeded RTs, consistent with previous findings, and we novelly extend these effects to a robust latency measure of the left parietal ERP effect associated with retrieval success. Importantly, the relationship between repetition and recency was further elucidated, such that repetition attenuated lag-related differences that were initially present in both the behavioral and neural latency data. These findings are consistent with the idea that a serial search through recent memory can quickly be abandoned in favor of relying on more efficient ‘time-independent’ cognitive processes or neural signals.
GluD1 knockout mice with a pure C57BL/6N background show impaired fear memory, social interaction, and enhanced depressive-like behavior
Authors: Nakamoto Chihiro , Kawamura Meiko , Nakatsukasa Ena , Natsume Rie , Takao Keizo , Watanabe Masahiko , Abe Manabu , Takeuchi Tomonori , Sakimura Kenji 
Published: November 2019

AbstractThe GluD1 gene is associated with susceptibility for schizophrenia, autism, depression, and bipolar disorder. However, the function of GluD1 and how it is involved in these conditions remain elusive. In this study, we generated a GluD1-knockout (GluD1-KO) mouse line with a pure C57BL/6N genetic background and performed several behavioral analyses. Compared to a control group, GluD1-KO mice showed no significant anxiety-related behavioral differences, evaluated using behavior in an open field, elevated plus maze, a light-dark transition test, the resident-intruder test of aggression and sensorimotor gating evaluated by the prepulse inhibition test. However, GluD1-KO mice showed (1) hyper locomotor activity in the open field, (2) decreased sociability and social novelty preference in the three-chambered social interaction test, (3) impaired memory in contextual, but not cued fear conditioning tests, and (4) enhanced depressive-like behavior in a forced swim test. Pharmacological studies revealed that enhanced depressive-like behavior in GluD1-KO mice was restored by the serotonin reuptake inhibitors imipramine and fluoxetine, but not the norepinephrine transporter inhibitor desipramine. In addition, biochemical analysis revealed no significant difference in protein expression levels, such as other glutamate receptors in the synaptosome and postsynaptic densities prepared from the frontal cortex and the hippocampus. These results suggest that GluD1 plays critical roles in fear memory, sociability, and depressive-like behavior.
Development of diagnostic SNP markers for quality assurance and control in sweetpotato [Ipomoea batatas (L.) Lam.] breeding programs
Authors: Gemenet Dorcus C , Kitavi Mercy N , David Maria , Ndege Dorcah , Ssali Reuben T , Swanckaert Jolien , Makunde Godwill , Craig Yencho G , Gruneberg Wolfgang , Carey Edward , Mwanga Robert O , Andrade Maria I , Heck Simon , Campos Hugo 
Published: November 2019

AbstractQuality assurance and control (QA/QC) is an essential element of a breeding program’s optimization efforts towards increased genetic gains. Due to auto-hexaploid genome complexity, a low-cost marker platform for routine QA/QC in sweetpotato breeding programs is still unavailable. We used 662 parents of the International Potato Center (CIP)’s global breeding program spanning Peru, Uganda, Mozambique and Ghana, to develop a low-density highly informative single nucleotide polymorphism (SNP) marker set to be deployed for routine QA/QC. Segregation of the selected 30 SNPs (two SNPs per base chromosome) in a recombined breeding population was evaluated using 282 progeny from some of the parents above. The progeny were replicated from in-vitro, screenhouse and field, and the selected SNP-set was confirmed to identify relatively similar mislabeling error rates as a high density SNP-set of 10,159 markers. Six additional trait-specific markers were added to the selected SNP set from previous quantitative trait loci mapping. The 36-SNP set will be deployed for QA/QC in breeding pipelines and in fingerprinting of advanced clones or released varieties to monitor genetic gains in famers fields. The study also enabled evaluation of CIP’s global breeding population structure and the effect of some of the most devastating biotic stresses like sweetpotato virus disease on genetic variation management. These results will inform future deployment of genomic selection in sweetpotato.Key MessageA 36-SNP diagnostic marker set has been developed for quality assurance and control to support global sweetpotato breeding optimization efforts. Breeding population structure is shaped by sweetpotato virus disease prevalence.