bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in non-oscillatory features of the cortical sensorimotor rhythm in Parkinson’s disease across age
Authors: Vinding Mikkel C. , Eriksson Allison , Ting Low Cassia Man , Waldthaler Josefine , Ferreira Daniel , Ingvar Martin , Svenningsson Per , Lundqvist Daniel 
Published: June 2021

AbstractParkinson’s disease (PD) is associated with changes in neural activity in the sensorimotor alpha and beta bands. Using magnetoencephalography (MEG), we investigated the role of spontaneous neuronal activity within the somatosensory cortex in a large cohort of early-to mid-stage PD patients (N = 78) and age- and sex matched healthy controls (N = 60) using source reconstructed resting-state MEG. We quantified features of the time series data in terms of oscillatory alpha power, beta power, and 1/f broadband characteristics using power spectral density, and also characterised transient beta burst events in the time-domain signals. We examined the relationship between these signal features and the patients’ disease state, symptom severity, age, sex, and cortical thickness.PD patients and healthy controls differed on PSD broadband characteristics, with PD patients showing a steeper 1/f exponential slope and higher 1/f offset. PD patients further showed a steeper age-related decrease in the burst rate. Out of all the signal features of the sensorimotor activity, only burst rate was associated with increased severity of bradykinesia. Our study shows that general non-oscillatory features (broadband PSD slope and offset) of the sensorimotor signals are related to disease state and oscillatory burst rate scales with symptom severity in PD.
Task modulation of spatiotemporal dynamics in semantic brain networks: an EEG/MEG study
Authors: Rahimi Setareh , Farahibozorg Seyedeh-Rezvan , Jackson Rebecca , Hauk Olaf 
Published: June 2021

AbstractHow does brain activity in distributed semantic brain networks evolve over time, and how do these regions interact to retrieve the meaning of words? We compared spatiotemporal brain dynamics between visual lexical and semantic decision tasks (LD and SD), analysing whole-cortex evoked responses and spectral functional connectivity (coherence) in source-estimated electroencephalography and magnetoencephalography (EEG and MEG) recordings. Our evoked analysis revealed generally larger activation for SD compared to LD, starting in primary visual area (PVA) and angular gyrus (AG), followed by left posterior temporal cortex (PTC) and left anterior temporal lobe (ATL). The earliest activation effects in ATL were significantly left-lateralised. Our functional connectivity results showed significant connectivity between left and right ATLs and PTC and right ATL in an early time window, as well as between left ATL and IFG in a later time window. The connectivity of AG was comparatively sparse. We quantified the limited spatial resolution of our source estimates via a leakage index for careful interpretation of our results. Our findings suggest that semantic task demands modulate visual and attentional processes early-on, followed by modulation of multimodal semantic information retrieval in ATLs and then control regions (PTC and IFG) in order to extract task-relevant semantic features for response selection. Whilst our evoked analysis suggests a dominance of left ATL for semantic processing, our functional connectivity analysis also revealed significant involvement of right ATL in the more demanding semantic task. Our findings demonstrate the complementarity of evoked and functional connectivity analysis, as well as the importance of dynamic information for both types of analyses.HighlightsSemantic task demands affect activity and connectivity at different processing stagesEarliest task modulations occurred in posterior visual brain regionsATL, PTC and IFG effects reflect task-relevant retrieval of multimodal informationATL effects left-lateralised for activation but bilateral for functional connectivityDynamic evoked and connectivity data are essential to study semantic networks
Whole genome sequencing elucidates the species-wide diversity and evolution of fungicide resistance in the early blight pathogen Alternaria solani
Authors: Einspanier Severin , Susanto Tamara , Metz Nicole , Wolters Pieter J. , Vleeshouwers Vivianne G.A.A. , Lankinen Åsa , Liljeroth Erland , Landschoot Sofie , Ivanović Žarko , Hückelhoven Ralph , Hausladen Hans , Stam Remco 
Published: June 2021

AbstractEarly blight of potato is caused by the fungal pathogen Alternaria solani and is an increasing problem worldwide. The primary strategy to control the disease is applying fungicides such as succinate dehydrogenase inhibitors (SDHI). SDHI-resistant strains, showing reduced sensitivity to treatments, appeared in Germany in 2013, five years after the introduction of SDHIs. Two primary mutations in the Sdh complex (SdhB-H278Y and SdhC-H134R) have been frequently found throughout Europe. How these resistances arose and spread, and whether they are linked to other genomic features, remains unknown.We performed whole-genome sequencing for A. solani isolates from potato fields across Europe (Germany, Sweden, Belgium, and Serbia) to better understand the pathogen’s genetic diversity in general and understand the development and spread of the genetic mutations that lead to SDHI resistance. We used ancestry analysis and phylogenetics to determine the genetic background of 48 isolates. The isolates can be grouped into 7 genotypes. These genotypes do not show a geographical pattern but appear spread throughout Europe. The Sdh mutations appear in different genetic backgrounds, suggesting they arose independently, and the observed admixtures might indicate a higher adaptive potential in the fungus than previously thought.Our research gives insights into the genetic diversity of A. solani on a genome level. The mixed occurrence of different genotypes and apparent admixture in the populations indicate higher genomic complexity than anticipated. The conclusion that SDHI tolerance arose multiple times independently has important implications for future fungicide resistance management strategies. These should not solely focus on preventing the spread of isolates between locations but also on limiting population size and the selective pressure posed by fungicides in a given field to avoid the rise of new mutations in other genetic backgrounds.
Analysis of the leaf metabolome in Arabidopsis thaliana mutation accumulation lines reveals association of pleiotropy and fitness consequences
Authors: Kreutzmann Sydney , Pompa Elizabeth , Nguyen Nhan D. , Tilahun Liya , Rutter Matthew T. , Weng Mao-Lun , Fenster Charles B. , Olson-Manning Carrie F. 
Published: June 2021

ABSTRACTUnderstanding the mechanisms by which mutations affect fitness and the distribution of mutational effects are central goals in evolutionary biology. Mutation accumulation (MA) lines have long been an important tool for understanding the effect of new mutations on fitness, phenotypic variation, and mutational parameters. However, there is a clear gap in predicting the effect of specific new mutations to their effects on fitness. Here, we complete gene ontology analysis and metabolomics experiments on Arabidopsis thaliana MA lines to determine how spontaneous mutations directly affect global metabolic output in lines that have measured fitness consequences. For these analyses, we compared three lines with relative fitness consistently higher than the unmutated progenitor and three lines with lower relative fitness as measured in four different field trials. In a gene ontology analysis, we find that the high fitness lines were significantly enriched in mutations in or near genes with transcription regulator activity. We also find that although they do not have an average difference in the number of mutations, low fitness lines have significantly more metabolic subpathways disrupted than high fitness lines. Taken together, these results suggest that the effect of a new mutation on fitness depends less on the specific metabolic pathways disrupted and more on the pleiotropic effects of those mutations, and that organisms can explore a considerable amount of physiological space with only a few mutations.Significance StatementAs the source of all genetic variation, new mutations are crucial for understanding how organisms adapt to their environment. However, the ways in which new mutations affect the range of metabolic reactions that occur in the cell is unknown. With a combination of gene functional analyses and measurement of the small molecules that drive cellular function and physiology, we find that mutations associated with high fitness are disproportionately found in or near proteins-coding genes that regulate the specific timing and location of gene expression and are less disruptive of cellular physiology.
High-throughput screening of aqueous two-phase systems for polyphenol extraction fromA. nodosum: a green chemistry approach
Authors: Olivares-Molina Alex , Parker Brenda 
Published: June 2021

AbstractBrown macroalgae are an attractive third-generation feedstock of natural products, in order to design green chemistry-compliant processes and reduce the use of organic solvents in bioactive product extraction, aqueous two-phase systems (ATPS) was applied. This research aimed to develop a high-throughput screening (HTS) to recover polyphenols fromAscophyllum nodosumusing ATPS. In total, 384 different 2-phase systems were assessed using an automated liquid-handling system to evaluate polyphenol recovery using a model system of phloroglucinol to establish an optimal 2-phase system for polyphenol partitioning. Various ratios of PEG:potassium phosphate solutions were explored to evaluate partitioning of polyphenols via a scale-down approach. Scale-down selected system showed a recovery of phloroglucinol of 62.9±12.0%, this system was used for scale-up trials. Scale-up studies confirmed that the HTS method was able to recover polyphenols with a 54.8±14.2% in the phloroglucinol model system. When the optimised ATPS system was tested with a polyphenol extract, 93.62±8.24% recovery was observed. When ATPS was applied to a fucoidan and alginate biorefinery residue, 88.40±4.59% polyphenol was recovered. These findings confirm that ATPS is a valuable addition to the bioprocess toolkit for sustainable extraction of natural products from macroalgae in a multiproduct biorefinery approach.Practical applicationSelection of the best concentrations of phase-forming components and recovery conditions for the application of aqueous two-phase systems in an industrial setup has been proved to be laborious and cumbersome. This paper presents an automated platform to rapidly assess several ATPS to recover polyphenols from brown macroalgae and a subsequent confirmation with the scale-up of the potential candidates and contrasted with two case studies. This methodology allows a quick screening for the best aqueous two-phase system and can be expanded to recover high-value products from other types of macroalgae or microalgae.
Systems Genetics of Single Nucleotide Polymorphisms at the Drosophila Obp56h Locus
Authors: Mokashi Sneha S. , Shankar Vijay , Johnstun Joel A. , Huang Wen , Mackay Trudy F. C. , Anholt Robert R. H. 
Published: June 2021

AbstractVariation in quantitative traits arises from naturally segregating alleles with environmentally sensitive effects, but how individual variants in single genes affect the genotype-phenotype map and molecular phenotypes is not understood. We used CRISPR/Cas9 germline gene editing to generate naturally occurring variants with different site classes and allele frequencies in the Drosophila melanogaster Obp56h gene in a common genetic background. Single base pair changes caused large allele-specific and sexually dimorphic effects on the mean and micro-environmental variance for multiple fitness-related traits and in the Obp56h co-regulated transcriptome. However, these alleles were not associated with quantitative traits in the Drosophila Genetic Reference Panel, suggesting that the small allelic effects observed in genome wide association studies may be an artifact of averaging variable context-dependent allelic effects over multiple genetic backgrounds. Thus, the traditional infinitesimal additive model does not reflect the underlying biology of quantitative traits.
An Efficient Coalescent Epoch Model for Bayesian Phylogenetic Inference
Authors: Bouckaert Remco R. 
Published: June 2021

AbstractWe present a two headed approach called Bayesian Integrated Coalescent Epoch PlotS (BICEPS) for efficient inference of coalescent epoch models. Firstly, we integrate out population size parameters and secondly we introduce a set of more powerful Markov chain Monte Carlo (MCMC) proposals for flexing and stretching trees. Even though population sizes are integrated out and not explicitly sampled through MCMC, we are still able to generate samples from the population size posteriors. This allows demographic reconstruction through time and estimating the timing and magnitude of population bottlenecks and full population histories. Altogether, BICEPS can be considered a more muscular version of the popular Bayesian skyline model.We demonstrate its power and correctness by a well calibrated simulation study. Furthermore, we demonstrate with an application to SARS-CoV-2 genomic data that some analyses that have trouble converging with the traditional Bayesian skyline prior and standard MCMC proposals can do well with the BICEPS approach.BICEPS is available as open source package for BEAST 2 under GPL license and has a user friendly graphical user interface. Bayesian phylogenetics, coalescent model, BEAST 2, BICEPS
Using diffusion MRI data acquired with ultra-high gradients to improve tractography in routine-quality data
Authors: Maffei C. , Lee C. , Planich M. , Ramprasad M. , Ravi N. , Trainor D. , Urban Z. , Kim M. , Jones R.J. , Henin A. , Hofmann S.G. , Pizzagalli D.A. , Auerbach R.P. , Gabrieli J.D.E. , Whitfield-Gabrieli S. , Greve D.N. , Haber S.N. , Yendiki A. 
Published: June 2021

AbstractThe development of scanners with ultra-high gradients, spearheaded by the Human Connectome Project, has led to dramatic improvements in the spatial, angular, and diffusion resolution that is feasible for in vivo diffusion MRI acquisitions. The improved quality of the data can be exploited to achieve higher accuracy in the inference of both microstructural and macrostructural anatomy. However, such high-quality data can only be acquired on a handful of Connectom MRI scanners worldwide, while remaining prohibitive in clinical settings because of the constraints imposed by hardware and scanning time. In this study, we first update the classical protocols for tractography-based, manual annotation of major white-matter pathways, to adapt them to the much greater volume and variability of the streamlines that can be produced from today’s state-of-the-art diffusion MRI data. We then use these protocols to annotate 42 major pathways manually in data from a Connectom scanner. Finally, we show that, when we use these manually annotated pathways as training data for global probabilistic tractography with anatomical neighborhood priors, we can perform highly accurate, automated reconstruction of the same pathways in much lower-quality, more widely available diffusion MRI data. The outcomes of this work include both a new, comprehensive atlas of WM pathways from Connectom data, and an updated version of our tractography toolbox, TRActs Constrained by UnderLying Anatomy (TRACULA), which is trained on data from this atlas. Both the atlas and TRACULA are distributed publicly as part of FreeSurfer. We present the first comprehensive comparison of TRACULA to the more conventional, multi-region-of-interest approach to automated tractography, and the first demonstration of training TRACULA on high-quality, Connectom data to benefit studies that use more modest acquisition protocols.
Comprehensive analysis of full-length transcripts reveal aberrations of splicing variants in liver cancer
Authors: Kiyose Hiroki , Nakagawa Hidewaki , Ono Atsushi , Aikata Hiroshi , Ueno Masaki , Hayami Shinya , Yamaue Hiroki , Chayama Kazuaki , Shimada Mihoko , Wong Jing Hao , Fujimoto Akihiro 
Published: June 2021

AbstractGenes generate various transcripts by alternative splicing, and these transcripts can have diverse functions. However, in most transcriptome studies, short-reads sequencing technologies (next-generation sequencers) have been used and full-length transcripts have not been observed directly. Although long-reads sequencing technologies would enable us to sequence full-length transcripts, analysis of the data is a difficult task. In the present study, we developed an analysis pipeline named SPLICE to analyze full-length cDNA sequences. Using this method, we analyzed cDNA sequences from 42 pairs of hepatocellular carcinoma (HCC) and matched non-cancerous liver with Oxford Nanopore technology. Our analysis detected 46,663 transcripts from the protein-coding genes in the HCCs and the matched non-cancerous livers, of which 5,366 (11.5 %) were novel. Comparison of expression levels identified 9,933 differentially expressed transcripts (DETs) in 4,744 genes. Importantly, 746 genes with DET were not found by the gene-level analysis. We also identified novel exons derived from transposable elements (TEs). In the analysis of transcripts from hepatitis B virus (HBV), HBx-human TE fusions were found to be overexpressed in the HCCs. Furthermore, fusion gene detection showed novel recurrent fusion events. These results suggest that long-reads sequencing technologies allow us to analyze full-length transcripts, and show the importance of splicing variants in carcinogenesis.
Information redundancy across spatial scales modulates early visual cortical processing
Authors: Petras Kirsten , ten Oever Sanne , Dalal Sarang S. , Goffaux Valerie 
Published: June 2021

AbstractVisual images contain redundant information across spatial scales where low spatial frequency contrast is informative towards the location and likely content of high spatial frequency detail. Previous research suggests that the visual system makes use of those redundancies to facilitate efficient processing. In this framework, a fast, initial analysis of low-spatial frequency (LSF) information guides the slower and later processing of high spatial frequency (HSF) detail. Here, we used multivariate classification as well as time-frequency analysis of MEG responses to the viewing of intact and phase scrambled images of human faces to demonstrate that the availability of redundant LSF information, as found in broadband intact images, correlates with a reduction in HSF representational dominance in both early and higher-level visual areas as well as a reduction of gamma-band power in early visual cortex. Our results indicate that the cross spatial frequency information redundancy that can be found in all natural images might be a driving factor in the efficient integration of fine image details.
Structural analysis of the C. elegans dauer larval anterior sensilla by Focused Ion Beam-Scanning Electron Microscopy
Authors: Britz Sebastian , Markert Sebastian Matthias , Witvliet Daniel , Steyer Anna Maria , Tröger Sarah , Mulcahy Ben , Kollmannsberger Philip , Schwab Yannick , Zhen Mei , Stigloher Christian 
Published: June 2021

AbstractAt the end of the first larval stage, the nematode Caenorhabditis elegans developing in harsh environmental conditions is able to choose an alternative developmental path called the dauer diapause. Dauer larvae exhibit different physiology and behaviors from non-dauer larvae. Using focused ion beam scanning electron microscopy (FIB-SEM), we volumetrically reconstructed the anterior sensory apparatus of C. elegans dauer larvae with unprecedented precision. We provide a detailed description of some neurons, focusing on structural details that were unknown or unresolved by previously published studies. They include: 1) dauer-specific branches of the IL2 sensory neurons project into the periphery of anterior sensilla and motor or putative sensory neurons at the sub-lateral cords; 2) ciliated endings of URX sensory neurons are supported by both ILso and AMso socket cells near the amphid openings; 3) variability in amphid sensory dendrites among dauers; 4) somatic RIP interneurons maintain their projection into the pharyngeal nervous system. Our results support the notion that dauer larvae structurally expand their sensory system to facilitate searching for more favorable environments.
Rapid determination of the wide dynamic range of SARS-CoV-2 Spike T cell responses in whole blood of vaccinated and naturally infected
Authors: Tan Anthony T , Lim Joey Ming Er , Le Bert Nina , Kunasegaran Kamini , Chia Adeline , Qui Martin Daniel Co , Tan Nicole , Chia Wan Ni , de Alwis Ruklanthi , Ying Ding , Ooi Eng Eong , Wang Lin-Fa , Chen Mark I-Cheng , Young Barnaby , Hsu Li Yang , Low Jenny GH , Lye David Chien , Bertoletti Antonio 
Published: June 2021

AbstractBackgroundAntibodies and T cells cooperate to control virus infections. The definition of the correlates of protection necessary to manage the COVID-19 pandemic, require both immune parameters but the complexity of traditional tests limits virus-specific T cell measurements.MethodsWe test the sensitivity and performance of a simple and rapid SARS-CoV-2 Spike-specific T cell test based on stimulation of whole blood with peptides covering the SARS-CoV-2 Spike protein followed by cytokine (IFN-γ, IL-2) measurement in different cohorts including BNT162b2 vaccinated (n=112; 201 samples), convalescent asymptomatic (n=62; 62 samples) and symptomatic (n=68; 115 samples) COVID-19 patients and SARS-CoV-1 convalescent individuals (n=12; 12 samples).ResultsThe sensitivity of the rapid cytokine whole blood test equates traditional methods of T cell analysis (ELISPOT, Activation Induced Markers). Utilizing this test we observed that Spike-specific T cells in vaccinated preferentially target the S2 region of Spike and that their mean magnitude is similar between them and SARS-CoV-2 convalescents at 3 months after vaccine or virus priming respectively. However, a wide heterogeneity of Spike-specific T cell magnitude characterizes the individual responses irrespective of the time of analysis. No correlation between neutralizing antibody levels and Spike-specific T cell magnitude were found.ConclusionsRapid measurement of cytokine production in whole blood after peptide activation revealed a wide dynamic range of Spike-specific T cell response after vaccination that cannot be predicted from neutralizing antibody quantities. Both Spike-specific humoral and cellular immunity should be tested after vaccination to define the correlates of protection necessary to evaluate current vaccine strategies.