bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural sequence evolution and Computational Modeling Approaches of the Complement System in Leishmaniasis
Authors: Ingale Prajakta , Kabra Ritika , Singh Shailza 
Published: September 2018

AbstractThe complement system acts as central arm of innate immunity that is critical to host defense as well as the development of adaptive immunity. The origins of the complement system have so far been traced, which correlates to near to the beginnings of multi-cellular animal life. Owing to the difficulty in obtaining crystal structures of GPCRs in either inactive or active state, accurate structural modeling is still highly desirable for the majority of GPCRs. In an attempt to dissect the conformational changes associated with GPCR activation, computational modeling approaches is being pursued in this paper along with the evolutionary divergence to deal with the structural variability.
Fine tuning of hormonal signaling is linked to dormancy status in sweet cherry flower buds
Authors: Vimont Noémie , Schwarzenberg Adrian , Domijan Mirela , Donkpegan Armel S. L. , Beauvieux Rémi , le Dantec Loïck , Arkoun Mustapha , Jamois Frank , Yvin Jean-Claude , Wigge Philip A. , Dirlewanger Elisabeth , Cortijo Sandra , Wenden Bénédicte 
Published: September 2018

ABSTRACTIn temperate trees, optimal timing and quality of flowering directly depend on adequate winter dormancy progression, regulated by a combination of chilling and warm temperatures. Physiological, genetic and functional genomic studies have shown that hormones play a key role in bud dormancy establishment, maintenance and release. We combined physiological, transcriptional analyses, quantification of abscisic acid (ABA) and gibberellins (GAs), and modelling to further investigate how these signaling pathways are associated with dormancy progression in the flower buds of two sweet cherry cultivars.Our results demonstrated that GA-associated pathways have distinct functions and may be differentially related with dormancy. In addition, ABA levels rise at the onset of dormancy, associated with enhanced expression of ABA biosynthesisPavNCEDgenes, and decreased prior to dormancy release. Following the observations that ABA levels are correlated with dormancy depth, we identifiedPavUG71B6, a sweet cherryUDP-GLYCOSYLTRANSFERASEgene that up-regulates active catabolism of ABA to ABA-GE and may be associated with low ABA content in the early cultivar. Subsequently, we modelled ABA content and dormancy behavior in three cultivars based on the expression of a small set of genes regulating ABA levels. These results strongly suggest the central role of ABA pathway in the control of dormancy progression and open up new perspectives for the development of molecular-based phenological modelling.
Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 are associated with gestational duration
Authors: Liu Xueping , Helenius Dorte , Skotte Line , Beaumont Robin N. , Wielscher Matthias , Geller Frank , Juodakis Julius , Mahajan Anubha , Bradfield Jonathan P. , Lin Frederick T.J. , Vogelezang Suzanne , Bustamante Mariona , Ahluwalia Tarunveer S. , Pitkänen Niina , Wang Carol A. , Bacelis Jonas , Borges Maria C. , Zhang Ge , Bedell Bruce A. , Rossi Robert M. , Skogstrand Kristin , Peng Shouneng ,   Early Growth Genetics (EGG) Consortium,   iPSYCH-BROAD Working Group, Thompson Wesley K. , Appadurai Vivek , Lawlor Debbie A. , Kalliala Ilkka , Power Christine , McCarthy Mark I. , Boyd Heather A. , Marazita Mary L. , Hakonarson Hakon , Hayes M. Geoffrey , Scholtens Denise M. , Rivadeneira Fernando , Jaddoe Vincent W.V. , Vinding Rebecca K. , Bisgaard Hans , Knight Bridget A. , Pahkala Katja , Raitakari Olli , Helgeland Øyvind , Johansson Stefan , Njølstad Pål R. , Fadista João , Schork Andrew , Nudel Ron , Miller Daniel E. , Chen Xiaoting , Weirauch Matthew T. , Mortensen Preben Bo , Børglum Anders D. , Nordentoft Merete , Mors Ole , Hao Ke , Ryckman Kelli K. , Hougaard David M. , Kottyan Leah C. , Pennell Craig E. , Lyytikainen Leo-Pekka , Bønnelykke Klaus , Vrijheid Martine , Felix Janine F. , Lowe William L. , Grant Struan F.A. , Hyppönen Elina , Jacobsson Bo , Jarvelin Marjo-Riitta , Muglia Louis J. , Murray Jeffrey C. , Freathy Rachel M. , Werge Thomas M. , Melbye Mads , Buil Alfonso , Feenstra Bjarke 
Published: September 2018

AbstractThe duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. We conducted a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 was associated with gestational duration; the association was replicated in 9,291 additional infants (combined P = 3.96 × 10−14). Analysis of 15,536 mother-child pairs showed that the association was driven by fetal rather than maternal genotype. Functional experiments showed that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
D.sort: template based automatic spike sorting tool
Authors: Belkhiri Madeny , Kvitsiani Duda 
Published: September 2018

AbstractUnderstanding how populations of neurons represent and compute internal or external variables requires precise and objective metrics for tracing the individual spikes that belong to a given neuron. Despite recent progress in the development of accurate and fast spike sorting tools, the scarcity of ground truth data makes it difficult to settle on the best performing spike sorting algorithm. Besides, the use of different configurations of electrodes and ways to acquire signal (e.g. anesthetized, head fixed, freely behaving animal recordings, tetrode vs. silicone probes, etc.) makes it even harder to develop a universal spike sorting tool that will perform well without human intervention. Some of the prevalent problems in spike sorting are: units separating due to drift, clustering bursting cells, and dealing with nonstationarity in background noise. The last is particularly problematic in freely behaving animals where the noises from the electrophysiological activity of hundreds or thousands of neurons are intermixed with noise arising from movement artifacts. We address these problems by developing a new spike sorting tool that is based on a template matching algorithm. The spike waveform templates are used to perform normalized cross correlation (NCC) with an acquired signal for spike detection. The normalization addresses problems with drift, bursting, and nonstationarity of noise and provides normative scoring to compare different units in terms of cluster quality. Our spike sorting algorithm, D.sort, runs on the graphic processing unit (GPU) to accelerate computations. D.sort is a freely available software package (https://github.com/1804MB/Kvistiani-lab_Dsort).
Novel regression methods for metacognition
Authors: Kristensen Simon Bang , Sandberg Kristian , Bibby Bo Martin 
Published: September 2018

AbstractMetacognition is an important component in basic science and clinical psychology, often studied through complex, cognitive experiments. While Signal Detection Theory (SDT) provides a popular and pervasive framework for modelling responses from such experiments, a shortfall remains that it cannot in a straightforward manner account for the often complex designs. Additionally, SDT does not provide direct estimates of metacognitive ability. This latter shortcoming has recently been sought remedied by introduction of a measure for metacognitive sensitivity dubbed meta-d’. The need for a flexible regression model framework remains, however, which should also incorporate the new sensitivity measure. In the present paper, we argue that a straightforward extension of SDT is obtained by identifying the model with the proportional odds model, a widely implemented, ordinal regression technique. We go on to develop a formal statistical framework for metacognitive sensitivity by defining a model that combines standard SDT with meta-d’ in a latent variable model. We show how this agrees with the literature on meta-d’ and constitutes a practical framework for extending the model. We supply several teoretical considerations on the model, including closed-form approximate estimates of meta-d’ and optimal weighing of response-specific meta-sensitivities. We discuss regression analysis as an application of the obtained model and illustrate our points through simulations. Lastly, we presentR-software that implements the model. Our methods and their implementation extend the computational possibilities of SDT and meta-dand are useful for theoretical and practical researchers of metacognition.
Asymmetry in catalysis by Thermotoga maritima membrane-bound pyrophosphatase demonstrated by a non-phosphorous allosteric inhibitor
Authors: Vidilaseris Keni , Kiriazis Alexandros , Turku Ainoleena , Khattab Ayman , Johansson Niklas G. , Leino Teppo O. , Kiuru Paula S. , af Gennäs Gustav Boije , Meri Seppo , Yli-Kauhaluoma Jari , Xhaard Henri , Goldman Adrian 
Published: September 2018

AbstractMembrane-bound pyrophosphatases are homodimeric integral membrane proteins that hydrolyse pyrophosphate into orthophosphates, coupled to the active transport of protons or sodium ions across membranes. They are important in the life cycle of bacteria, archaea, plants, and protist parasites, but no homologous proteins exist in vertebrates, making them a promising drug target. Here, we report the first non-phosphorous allosteric inhibitor (Ki of 1.8 ± 0.3 μM) of the thermophilic bacterium Thermotoga maritima membrane-bound pyrophosphatase and its bound structure at 3.7 Å resolution together with the substrate analogue imidodiphosphate. The unit cell contains two protein homodimers, each binding a single inhibitor dimer near the exit channel, creating a hydrophobic clamp that inhibits the movement of β-strand 1–2 during pumping, and thus preventing the hydrophobic gate from opening. This asymmetry of inhibitor binding with respect to each homodimer provide the first clear demonstration of asymmetry in the catalytic cycle of membrane-bound pyrophosphatases.
SilentMutations (SIM): a tool for analyzing long-range RNA-RNA interactions in viral genomes and structured RNAs
Authors: Desirò Daniel , Hölzer Martin , Ibrahim Bashar , Marz Manja 
Published: September 2018

ABSTRACTBackgroundA single nucleotide change in the coding region can alter the amino acid sequence of a protein. In consequence, natural or artificial sequence changes in viral RNAs may have various effects not only on protein stability, function and structure but also on viral replication.In recent decades, several tools have been developed to predict the effect of mutations in structured RNAs such as viral genomes or non-coding RNAs. Some tools use multiple point mutations and also take coding regions into account. However, none of these tools was designed to specifically simulate the effect of mutations on viral long-range interactions.ResultsHere, we developedSilentMutations (SIM), an easy-to-use tool to analyze the effect of multiple point mutations on the secondary structures of two interacting viral RNAs. The tool can simulate disruptive and compensatory mutants of two interacting single-stranded RNAs. This allows a fast and accurate assessment of key regions potentially involved in functional long-range RNA-RNA interactions and will eventually help virologists and RNA-experts to design appropriate experiments.SIMonly requires two interacting single-stranded RNA regions as input. The output is a plain text file containing the most promising mutants and a graphical representation of all interactions.ConclusionWe applied our tool on two experimentally validated influenza A virus and hepatitis C virus interactions and we were able to predict potential double mutants forin vitrovalidation experiments.AvailabilityThe source code and documentation ofSIMare freely available at github.com/desiro/silentMutations.
Therapeutic Treatment of Aerosolized Staphylococcal Enterotoxin B in Nonhuman Primates with two Monoclonal Antibodies
Authors: Verreault Daniel , Ennis Jane , Whaley Kevin , Killeen Stephanie Z. , Karauzum Hatice , Aman M.Javad , Holtsberg Rick , Doyle-Meyers Lara , Didier Peter J. , Zeitlin Larry , Roy Chad J. 
Published: September 2018

AbstractStaphylococcal enterotoxin B (SEB) is a protein exotoxin found on the cell surface ofStaphylococcus aureusthat is the source for multiple pathologies in man. When purified and concentrated in aerosol form, SEB can cause an acute and often fatal intoxication, and thus is considered a biological threat agent. There are currently no vaccines or treatments approved for human use. Studies in rodent models of SEB intoxication show that antibody therapy may be a promising treatment strategy, however many have used antibodies only prophylactically or well before any clinical signs of intoxication are apparent. We assessed and compared the protective efficacy of two monoclonal antibodies, Ig121 and c19F1, when administered after aerosol exposure in a uniformly lethal nonhuman primate model of SEB intoxication. Rhesus macaques were challenged using small particle aerosols of SEB, and then were infused intravenously with a single dose of either Ig121 or c19F1 (10 mg/kg) at either 0.5, 2 or 4 hours postexposure. Onset of clinical signs, hematological, and cytokine response in untreated controls confirmed the acute onset and potency of the toxin used in the challenge. All animals administered either Ig121 or c19F1 survived SEB challenge, whereas the untreated controls succumbed to SEB intoxication 30-48 hours postexposure. These results represent the successful therapeuticin vivoprotection by two investigational drugs against SEB in a severe nonhuman primate disease model and punctuate the therapeutic value of monoclonal antibodies hold when faced with treatment options for SEB-induced toxicity in a postexposure setting.One Sentence Summary: Two high-affinity monoclonal antibodies were tested for therapeutic efficacy using a rhesus macaque challenge model of aerosolized SEB
Assessing the blood-host plasticity and dispersal rate of the malaria vector Anopheles coluzzii
Authors: Orsborne James , Furuya-Kanamori Luis , Jeffries Claire L. , Kristan Mojca , Mohammed Abdul Rahim , Afrane Yaw A. , O’Reilly Kathleen , Massad Eduardo , Drakeley Chris , Walker Thomas , Yakob Laith 
Published: September 2018

AbstractDifficulties with observing the dispersal of insect vectors in the field have hampered understanding of several aspects of their behaviour linked to disease transmission. Here, a novel method based on detection of blood-meal sources is introduced to inform two critical and understudied mosquito behaviours: plasticity in the malaria vector’s blood-host choice and vector dispersal. Strategically located collections of Anopheles coluzzii from a malaria-endemic village of southern Ghana showed statistically significant variation in host species composition of mosquito blood-meals. Trialling a new sampling approach gave the first estimates for the remarkably local spatial scale across which host choice is plastic. Using quantitative PCR, the blood-meal digestion was then quantified for field-caught mosquitoes and calibrated according to timed blood digestion in colony mosquitoes. We demonstrate how this new ‘molecular Sella score’ approach can be used to estimate the dispersal rate of blood-feeding vectors caught in the field.
Detection of adaptive divergence in populations of the stream mayflyEphemera strigatawith machine learning
Authors: Li Bin , Yaegashi Sakiko , Carvajal Thaddeus M , Gamboa Maribet , Watanabe Kozo 
Published: September 2018

AbstractAdaptive divergence is a key mechanism shaping the genetic variation of natural populations. A central question linking ecology with evolutionary biology concerns the role of environmental heterogeneity in determining adaptive divergence among local populations within a species. In this study, we examined adaptive the divergence among populations of the stream mayflyEphemera strigatain the Natori River Basin in northeastern Japan. We used a genome scanning approach to detect candidate loci under selection and then applied a machine learning method (i.e. Random Forest) and traditional distance-based redundancy analysis (dbRDA) to examine relationships between environmental factors and adaptive divergence at non-neutral loci. We also assessed spatial autocorrelation at neutral loci to quantify the dispersal ability ofE. strigata. Our main findings were as follows: 1) random forest shows a higher resolution than traditional statistical analysis for detecting adaptive divergence; 2) separating markers into neutral and non-neutral loci provides insights into genetic diversity, local adaptation and dispersal ability and 3)E. strigatashows altitudinal adaptive divergence among the populations in the Natori River Basin.
A systematic review and meta-analysis of the human blood index of the major African malaria vectors
Authors: Orsborne James , Furuya-Kanamori Luis , Jeffries Claire L. , Kristan Mojca , Mohammed Abdul Rahim , Afrane Yaw A. , O’Reilly Kathleen , Massad Eduardo , Drakeley Chris , Walker Thomas , Yakob Laith 
Published: September 2018

AbstractBACKGROUNDThe proportion of mosquito blood-meals that are of human origin, referred to as the ‘human blood index’ or HBI, is a key determinant of malaria transmission. We conducted a systematic review of the HBI for the major African malaria vectors.RESULTSEvidence is presented for higher HBI among Anopheles gambiae (M/S forms and An. coluzzii/An. gambiae s.s. are not distinguished for most studies and therefore combined) as well as An. funestus when compared with An. arabiensis (prevalence odds ratio adjusted for collection location [i.e. indoor or outdoor]: 1.62; 95%CI 1.09-2.42; 1.84; 95%CI 1.35-2.52, respectively). This finding is keeping with the entomological literature which describes An. arabiensis to be more zoophagic than the other major African vectors. However, analysis also revealed that HBI was more associated with location of mosquito captures (R2=0.29) than with mosquito (sibling) species (R2=0.11).CONCLUSIONSOur findings call into question the appropriateness of current methods of assessing host preferences among disease vectors and have important implications for strategizing vector control.
Characterization of deep neural network features by decodability from human brain activity
Authors: Horikawa Tomoyasu , Aoki Shuntaro C. , Tsukamoto Mitsuaki , Kamitani Yukiyasu 
Published: September 2018

AbstractAchievements of near human-level performances in object recognition by deep neural networks (DNNs) have triggered a flood of comparative studies between the brain and DNNs. Using a DNN as a proxy for hierarchical visual representations, our recent study found that human brain activity patterns measured by functional magnetic resonance imaging (fMRI) can be decoded (translated) into DNN feature values given the same inputs. However, not all DNN features are equally decoded, indicating a gap between the DNN and human vision. Here, we present a dataset derived through the DNN feature decoding analyses including fMRI signals of five human subjects during image viewing, decoded feature values of DNNs (AlexNet and VGG19), and decoding accuracies of individual DNN features with their rankings. The decoding accuracies of individual features were highly correlated between subjects, suggesting the systematic differences between the brain and DNNs. We hope the present dataset will contribute to reveal the gap between the brain and DNNs and provide an opportunity to make use of the decoded features for further applications.
Functional Specialization is Independent of Microstructural Variation in Cerebellum but Not in Cerebral Cortex
Authors: Guell Xavier , Schmahmann Jeremy D , Gabrieli John DE 
Published: September 2018

ABSTRACTThe human brain is understood to follow fundamental principles linking form (such as microstructure and anatomical connectivity) to function (perceptual, motor, cognitive, emotional, and other processes). Most of this understanding is based on knowledge of the cerebral cortex, where functional specialization is thought to be closely linked to microstructural variation as well as anatomical connectivity. The Universal Cerebellar Transform (UCT) theory has posited that the cerebellum has a different form-function organization in which microstructure is uniform, and in which functional specialization is determined solely by anatomical connectivity with extracerebellar structures. All cerebellar functions may thus be subserved by a common microstructural - and hence computational - substrate. Here we tested this hypothesis by measuring microstructural variation and functional specialization as indexed by magnetic resonance imaging in 1003 healthy humans. Cerebral cortex exhibited the expected pattern of microstructure-function correlation, but functional specialization was independent of microstructural variation in the cerebellum. These findings support the idea that cerebellar functional specialization is not determined by microstructure, and hence that cerebellar functions may be computationally constant across domains.SIGNIFICANCE STATEMENTThe cerebellum is estimated to contain more than half the neurons in the human brain, is known to be involved in motoric, cognitive, and emotional functions, and is implicated in many neurological and neuropsychological disorders, but remains far less studied than the cerebral cortex. The Universal Cerebellar Transform (UCT) theory posits that one uniform computation underlies all cerebellar functions across multiple domains, but testing that idea has been difficult. Here we find that unlike the cerebral cortex, in which microstructural variation is associated with functional variation, the cerebellum exhibits relatively uniform microstructure across functionally distinct regions. These findings support UCT theory, and draw a sharp distinction between form-function relations in the cerebellum versus the cerebral cortex.
poreTally: run and publish de novo Nanopore assembler benchmarks
Authors: de Lannoy Carlos , Risse Judith , de Ridder Dick 
Published: September 2018

AbstractNanopore sequencing is a novel approach to nucleic acid analysis that generates long, error-prone reads. Since device components, base calling software and best practices for sample preparation are updated frequently and extensively, the nature of the produced data also changes frequently. As a result, peer-reviewed publications on de novo assembly pipeline benchmarking efforts are quickly rendered outdated by the next major improvement to the sequencing platforms. To provide the user community with a faster, more flexible alternative to peer-reviewed benchmark papers for de novo assembly tool performance we constructed poreTally, a comprehensive benchmarking tool. poreTally automatically assembles a given read set using several often-used assembly pipelines, analyzes the resulting assemblies for correctness and continuity, and finally generates a quality report. Results can immediately be shared with peers in a Github/Gitlab repository. Furthermore, we aim to give a more inclusive overview of assembly pipeline performance than any individual research group can, by offering users the possibility to submit their results to a collective benchmarking effort. poreTally is available on Github.