bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical intrinsic neural timescales in temporal lobe epilepsy
Authors: Xie Ke , Royer Jessica , Lariviere Sara , Rodriguez-Cruces Raul , Vos de Wael Reinder , Park Bo-yong , Auer Hans , Tavakol Shahin , DeKraker Jordan , Abdallah Chifaou , Caciagli Lorenzo , Bassett Dani S. , Bernasconi Andrea , Bernasconi Neda , Frauscher Birgit , Concha Luis , Bernhardt Boris C. 
Published: July 2022

AbstractObjectiveTemporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults. Here, we aimed to profile local neural function in TLE in vivo, building on prior evidence that has identified widespread structural alterations. Using multimodal MRI, we mapped intrinsic neural timescales (INT) at rest, examined associations to TLE-related structural compromise, and evaluated the clinical utility of INT.MethodsWe studied 46 TLE patients and 44 healthy controls from two independent sites, and mapped INT changes in patients relative to controls across hippocampal, subcortical, and neocortical regions. We examined region-specific associations to structural alterations and explored effects of age and epilepsy duration. A supervised machine learning paradigm assessed utility of INT for classifying patients-vs-controls and seizure focus lateralization.ResultsRelative to controls, TLE showed marked INT reductions across multiple regions bilaterally, indexing faster changing resting activity, with strongest effects in ipsilateral medial and lateral temporal regions, and sensorimotor cortices. Findings were consistent in each site and robust, albeit with reduced effect sizes, when correcting for structural alterations. TLE-related INT reductions increased with advancing disease duration, yet findings differed from aging effects seen in controls. Classifiers based on INT distinguished patients-vs-controls (balanced accuracy, 5-fold: 76±2.65%; cross-site, 72-83%) and lateralized the focus in TLE (balanced accuracy, 5-fold: 96±2.10%; cross-site, 95-97%) with high accuracies and generalization.ConclusionsOur findings robustly demonstrate atypical macroscale function in TLE in a topography that extends beyond mesiotemporal epicenters. INT measurements can assist in TLE diagnosis, seizure focus lateralization, and monitoring of disease progression, which suggests clinical utility.
Brachiopod and mollusc biomineralisation is a conserved process that was lost in the phoronid-bryozoan stem lineage
Authors: Wernström Joel Vikberg , Gąsiorowski Ludwik , Hejnol Andreas 
Published: July 2022

AbstractBackgroundBrachiopods and molluscs are lophotrochozoans with hard external shells which are often believed to have evolved convergently. While palaeontological data indicates that both groups are descended from biomineralising Cambrian ancestors, the closest relatives of brachiopods – phoronids and bryozoans – are mineralised to a much lower extent and are comparatively poorly represented in the Palaeozoic fossil record. Although brachiopod and mollusc shells are structurally analogous, genomic and proteomic evidence indicates that their formation involves a complement of conserved, orthologous genes. Here, we study a set of genes comprised of three homeodomain transcription factors, one signalling molecule and 6 structural proteins which are implicated in mollusc and brachiopod shell formation, search for their orthologs in transcriptomes or genomes of brachiopods, phoronids and bryozoans, and present expression patterns of 8 of the genes in postmetamorphic juveniles of the rhynchonelliform brachiopodTerebratalia transversa.ResultsTranscriptome and genome searches for the 10 target genes in the brachiopodsT. transversa, Lingula anatina, Novocrania anomala, the bryozoansBugula neritinaandMembranipora membranacea, and the phoronidsPhoronis australisandPhoronopsis harmeriresulted in the recovery of orthologs of the majority of the genes in all taxa. While the full complement of genes was present in all brachiopods with a single exception inL. anatina, a bloc of four genes could consistently not be retrieved from bryozoans and phoronids. The genesengrailed, distal-less, ferritin, perlucin, sp1andsp2were shown to be expressed in the biomineralising mantle margin ofT. transversajuveniles.ConclusionsThe gene expression patterns we recovered indicate that while mineralised shells in brachiopods and molluscs are structurally analogous, their formation builds on a homologous process that involves a conserved complement of orthologous genes. Losses of some of the genes related to biomineralisation in bryozoans and phoronids indicate that loss of the capacity to form mineralised structures occurred already in the phoronid-bryozoan stem group and supports the idea that mineralised skeletons evolved secondarily in some of the bryozoan subclades.
SiPLATZ12 transcript factor regulates multiple yield traits and salt tolerance in foxtail millet (Setaria italica)
Authors: Xiao Shenghui , Wan Yiman , Zhang Linlin , Tang Sha , Sui Yi , Bai Yichao , Wang Yan , Liu Miao , Fan Jiayin , Zhang Shizhong , Huang Jinguang , Yang Guodong , Yan Kang , Diao Xianmin , Zheng Chengchao , Wu Changai 
Published: July 2022

AbstractGrain yield and salt tolerance are critical for crop production. However, the genetic and biochemical basis underlying the trade-off of these characters remain poorly described in crops. We show here that SiPLATZ12 transcription factor positively regulates multiple elite yield traits at the expense of salt tolerance in foxtail millet. SiPLATZ12 overexpression increases seed size, panicle length, and stem diameter, while reduces plant height and salt tolerance of foxtail millet. A 9-bp insertion in the SiPLATZ12 promoter has significant effects on the different expression of SiPLATZ12, multiple yield traits, and salt tolerance between foxtail millet and its wild ancestor, green foxtail. Moreover, SiPLATZ12 upregulates the expression of genes involved in seed development, but repressing the transcription of most NHX, SOS, and CBL genes to regulate Na+, K+ and pH homeostasis. Therefore, our results uncover a domesticated site that could be used to improve grain yield and salt tolerance in foxtail millet.
Impacts and mechanisms of CO2 narcosis in bumble bees: Narcosis depends on dose, caste and mating status and is not induced by anoxia
Authors: Cressman Anna , Amsalem Etya 
Published: July 2022

AbstractCarbon dioxide (CO2) is commonly used to immobilize insects and to induce reproduction in bees. However, despite its wide use and potential off-target impacts, its underlying mechanisms are not fully understood. Here we used Bombus impatiens to examine whether CO2 impacts are mediated by anoxia and whether these mechanisms differ between female castes or following mating.We examined the behavior, physiology, and gene expression of workers, mated and virgin queens following exposure to anoxia, hypoxia, full and partial hypercapnia, and control. Hypercapnia and anoxia caused immobilization, but only hypercapnia resulted in behavioral, physiological, and molecular impacts in bees. Recovery from hypercapnia resulted in increased abdominal contractions and took longer in queens. Additionally, hypercapnia activated queens’-but inhibited workers’ ovaries in a dose-dependent manner and caused a depletion of fat-body lipids in both. All responses of hypercapnia were weaker following mating in queens. Analysis of gene expression related to hypoxia and hypercapnia supported the physiological findings in queens, demonstrating that the overall impacts of CO2, excluding virgin queen ovaries, were unique and were not induced by anoxia. This study contributes to our understanding of the impacts and the mechanistic basis of CO2 narcosis in insects and its impacts on bees’ physiology.
Aligning Model and Macaque Inferior Temporal Cortex Representations Improves Model-to-Human Behavioral Alignment and Adversarial Robustness
Authors: Dapello Joel , Kar Kohitij , Schrimpf Martin , Geary Robert , Ferguson Michael , Cox David D. , DiCarlo James J. 
Published: July 2022

AbstractWhile some state-of-the-art artificial neural network systems in computer vision are strikingly accurate models of the corresponding primate visual processing, there are still many discrepancies between these models and the behavior of primates on object recognition tasks. Many current models suffer from extreme sensitivity to adversarial attacks and often do not align well with the image-by-image behavioral error patterns observed in humans. Previous research has provided strong evidence that primate object recognition behavior can be very accurately predicted by neural population activity in the inferior temporal (IT) cortex, a brain area in the late stages of the visual processing hierarchy. Therefore, here we directly test whether making the late stage representations of models more similar to that of macaque IT produces new models that exhibit more robust, primate-like behavior. We conducted chronic, large-scale multi-electrode recordings across the IT cortex in six non-human primates (rhesus macaques). We then use these data to fine-tune (end-to-end) the model “IT” representations such that they are more aligned with the biological IT representations, while preserving accuracy on object recognition tasks. We generate a cohort of models with a range of IT similarity scores validated on held-out animals across two image sets with distinct statistics. Across a battery of optimization conditions, we observed a strong correlation between the models’ IT-likeness and alignment with human behavior, as well as an increase in its adversarial robustness. We further assessed the limitations of this approach and find that the improvements in behavioral alignment and adversarial robustness generalize across different image statistics, but not to object categories outside of those covered in our IT training set. Taken together, our results demonstrate that building models that are more aligned with the primate brain leads to more robust and human-like behavior, and call for larger neural data-sets to further augment these gains.
SARS-CoV-2 3CLpro mutations confer resistance to Paxlovid (nirmatrelvir/ritonavir) in a VSV-based, non-gain-of-function system
Authors: Heilmann Emmanuel , Costacurta Francesco , Volland Andre , von Laer Dorothee 
Published: July 2022

AbstractProtease inhibitors are among the most powerful antiviral drugs. A first protease inhibitor against the SARS-CoV-2 protease 3CLpro, Paxlovid (nirmatrelvir / ritonavir), has recently been authorized by the U.S. FDA for emergency use (EUA 105 Pfizer Paxlovid). To find resistant mutants against the protease-inhibitor-component of Paxlovid, nirmatrelvir, we engineered a chimeric Vesicular Stomatitis Virus (VSV). By replacing an intergenic region, which is essential for separate gene transcription, with 3CLpro, this chimeric VSV became dependent on the protease to process two of its genes. We then applied selective pressure with nirmatrelvir to induce mutations. The effect of those mutants was confirmed by re-introduction in the 3CLpro and testing with a recently developed cellular assay. Furthermore, we found that mutations predicted by our method already exist in SARS-CoV-2 sequence depositions in NCBI and GISAID data bases. These may represent emerging resistant virus variants or a natural heterogeneity in the susceptibility to nirmatrelvir.One-Sentence SummaryMutations of the main protease of SARS-CoV-2 result in resistance against licensed drugs such as Paxlovid (nirmatrelvir / ritonavir).Graphical abstract
Dissociable neuronal modules in the orbitofrontal cortex representing single and multi-attribute choice tasks
Authors: Xu Chengze , Ni Kuntan , Cai Xinying 
Published: July 2022

AbstractAn important component of biological intelligence lies in the capacity to learn and execute various cognitive tasks. This ability may be facilitated by a neural system comprising functionally dissociable neuronal modules. Within the orbitofrontal cortex (OFC) lies a neural circuit that supports economic decision-making across diverse contexts. To investigate the functional specialization of this circuit, we compared the neural activity of OFC neurons in rhesus monkeys during multi-attribute choice (MC) and single-attribute choice (SC) tasks. In MC, the monkeys made subjective tradeoffs between competing attributes, whereas in SC, choices were deterministic based on a single attribute’s value. Neuronally, in MC, OFC neurons primarily encoded offer value, chosen value, and choice in goods space. Upon transitioning from MC to SC, a significant portion of MC-modulated neurons disengaged, while a separate set of neurons emerged to encode SC-related variables in a spatial reference frame. Notably, we observed the clustering of value-encoding neurons in MC but not SC. In essence, our findings suggest that choice tasks involving different mental processes are represented by dissociable neuronal modules within the OFC.
Altered virome structrue and function characterization in Helicobacter pylori-driven colorectal carcinogenesis and H. pylori eradication
Authors: Luo Shiqi , Xue Jinling , Ru Jinlong , Mirzaei Mohammadali Khan , Ralser Anna , Mejías-Luque Raquel , Gerhard Markus , Deng Li 
Published: July 2022

AbstractThe understanding of gut virome and its role in Helicobacter pylori-driven colorectal cancer (CRC), as well as the long-term impact of H. pylori eradication via antibiotic treatment on it could contribute to better understanding the mechanisms of the disruption of gut bacteriome homeostasis involved in H. pylori-driven colorectal carcinogenesis and antibiotic therapy for H. pylori eradication. In the dynamic analysis of viral genome shotgun metagenomic of samples from lower gastrointestinal tract of the Apc+/1638N and C57BL/6 mice with H. pylori infection and eradication, stable viral abundance and replacement of bursted unique viral contigs in infected and uninfected Apc+/1638N mice were observed. Temperate phages, which encoding comprehensive microbial functional genes and targeting various susceptible hosts, were expanded extremely prior to cancer exacerbation. In addition, short-term antibiotic exposure for H. pylori eradication was able to alter the gut virome and thrive the antibiotic resistance genes (ARGs) in the viral genome for at least 6 months. Collectively, these results point toward a potential role of the altered, but dynamically balanced gut virome, characterized by the expanded temperate phages, in contributing to the H. pylori-driven CRC, and indicate that viral genome may act as ARG reservoir for the antibiotic resistance of bacteria after the antibiotics therapy to H. pylori eradication.
A novel hyper-parameter can increase the prediction accuracy in a single-step genetic evaluation
Authors: Neshat Mehdi , Lee Soohyun , Momin Md. Moksedul , Truong Buu , van der Werf Julius H. J. , Lee S. Hong 
Published: July 2022

AbstractThe H-matrix best linear unbiased prediction (HBLUP) method has been widely used in livestock breeding programs. It can integrate all information, including pedigree, genotypes, and phenotypes on both genotyped and non-genotyped individuals into one single evaluation that can provide reliable predictions of breeding values. The existing HBLUP method (e.g., that implemented in BLUPf90 software) requires hyper-parameters that should be adequately optimised as otherwise the genomic prediction accuracy may decrease. In this study, we assess the performance of HBLUP using various hyper-parameters such as blending, tuning and scale factor in simulated as well as real data on Hanwoo cattle. In both simulated and cattle data, we show that blending is not necessary, indicating that the prediction accuracy decreases when using a blending hyper-parameter < 1. The tuning process (adjusting genomic relationships accounting for base allele frequencies) improves prediction accuracy in the simulated data, confirming previous studies, although the improvement is not statistically significant in the Hanwoo cattle data. We also demonstrate that a scale factor, α, which determines the relationship between allele frequency and per-allele effect size, can improve the HBLUP accuracy in both simulated and real data. Our findings suggest that an optimal scale factor should be considered to increase the prediction accuracy, in addition to blending and tuning processes, when using HBLUP.Author SummaryDespite significant advancements in genotyping technologies, the capability to predict the phenotypes of complex traits is still limited. H-matrix best linear unbiased prediction (HBLUP) method has been used to tackle this limitation to demonstrate a promising prediction accuracy. However, the performance of HBLUP depends heavily on the optimisation of hyper-parameters (e.g. blending and tuning). In this study, we introduce a scale factor (α), as a new hyper-parameter in HBLUP, which accounts for the relationship between allele frequency and per-allele effect size. Using simulation and real data analysis, we investigate the impact of the hyper-parameters (blending, tuning, and scale factor) on the performance of HBLUP. In general, the blending process may not improve the prediction accuracy for simulation and cattle data although a marginally improved prediction accuracy is observed with a blending hyper-parameter = 0.86 for one of carcass traits in the cattle data. In contrast, the tuning process can increase the HBLUP accuracy particularly in simulated data. Furthermore, we observe that an optimal scale factor plays a significant role in improving the prediction accuracy in both simulated and real data, and the improvement is relatively large compared with blending and tuning processes. In this context, we propose considering the scale factor as a hyper-parameter to increase the predictive performance of HBLUP.
Tissue-specific regulation of gene expression via unproductive splicing
Authors: Mironov Alexey , Petrova Marina , Margasyuk Sergei , Vlasenok Maria , Mironov Andrei A. , Skvortsov Dmitry , Pervouchine Dmitri D. 
Published: July 2022

AbstractEukaryotic gene expression is regulated post-transcriptionally by a mechanism called unproductive splicing, in which mRNA is triggered to degradation by the nonsense-mediated decay (NMD) pathway as a result of regulated alternative splicing (AS). Only a few dozen unproductive splicing events (USEs) are currently documented, and many more remain to be identified. Here, we analyzed RNA-seq experiments from the Genotype-Tissue Expression (GTEx) Consortium to identify USEs, in which an increase in the NMD isoform splicing rate is accompanied by tissue-specific downregulation of the host gene. Further, to characterize RBPs that regulate USEs, we superimposed these results with RNA-binding protein (RBP) footprinting data and experiments on the response of the transcriptome to the perturbation of expression of a large panel of RBPs. Concordant tissue-specific changes between the expression of RBP and USE splicing rate revealed a high-confidence regulatory network including 27 tissue-specific USEs with strong evidence of RBP binding. Among them, we found previously unknown PTBP1-controlled events in the DCLK2 and IQGAP1 genes, for which we confirmed the regulatory effect using siRNA-knockdown experiments in the A549 cell line. In sum, we present a transcriptomic pipeline that allows the identification of tissue-specific USEs, potentially many more than we have reported here using stringent filters.
Contrasting patterns of single nucleotide polymorphisms and structural variations across multiple invasions
Authors: Stuart Katarina C. , Edwards Richard J. , Sherwin William B. , Rollins Lee A. 
Published: July 2022

AbstractAdaptive divergence is a fundamental process that shapes genetic diversity within and across species. Structural variants (SVs) are large-scale genetic differences (insertion, deletions, and rearrangements) within a species or population. SVs can cause important functional differences in the individual’s phenotype. Characterising SVs across invasive species will help fill knowledge gaps regarding how patterns of genetic diversity and genetic architecture shape rapid adaptation in response to new selection regimes. In this project we seek to understand patterns in genetic diversity within the globally invasive European starling,Sturnus vulgaris. We use whole genome sequencing of eight native United Kingdom (UK), eight invasive North America (NA), and 33 invasive Australian (AU) starlings to examine patterns in genome-wide SNPs and SVs between populations and within Australia. The findings of our research demonstrate that even within recently diverged lineages or populations, there may be high amounts of structural variation. Further, patterns of genetic diversity estimated from SVs do not necessarily reflect relative patterns from SNP data, either when considering patterns of diversity along the length of the organism’s chromosomes (owing to enrichment of SVs in sub telomeric repeat regions), or interpopulation diversity patterns (possibly a result of altered selection regimes or introduction history). Finally, we find that levels of balancing selection within the native range differ across SNP and SV of different classes and outlier classifications. Overall, our results demonstrate that the processes that shape allelic diversity within populations is complex and supports the need for further investigation of SVs across a range of taxa to better understand correlations between oft well studied SNP diversity and that of SVs.
Fifty years of reduction in sulphur deposition drives recovery in soil pH and plant communities
Authors: Seaton Fiona M. , Robinson David A. , Monteith Don , Lebron Inma , Bürkner Paul , Tomlinson Sam , Emmett Bridget A. , Smart Simon M. 
Published: July 2022

AbstractSulphur deposition through rainfall has led to species loss and ecosystem degradation globally, and across Europe huge reductions in sulphur emissions since the 1970s were expected to promote the recovery of acidified ecosystem. However, the rate and ecological impact of recovery from acidification in terrestrial ecosystems is still unclear as is the influence of management and climate, as to date there has been no long-term spatially extensive evaluation of these changes.Here we present data from thousands of sites across Great Britain surveyed repeatedly from 1978-2019 and assess change in soil pH and plant acidity preference (Ellenberg R) in response to atmospheric deposition of sulphur and nitrogen. We analyse change in grasslands managed for pasture, referred to as high-intensity habitats, and compare to semi-natural habitats comprising rough grassland, broadleaved woodland, bog and heathland, referred to as low-intensity habitats.Soil pH increased from 1978 to 2007 but then decreased between 2007 and 2019, resulting in a net increase of ~0.2 pH units in low-intensity habitats but no change in high-intensity habitats. The community average Ellenberg R increased in semi-natural habitats by ~0.2 units but remained stable in intensive grasslands.In semi-natural habitats, but not intensive grasslands, these changes in plant community composition were associated with the soil pH changes which were in turn linked to decreasing sulphur deposition and differences in rainfall.Nitrogen deposition, which was relatively stable over the survey period, showed no additional effect upon soil acidity once sulphur deposition was accounted for.Synthesis:Our results provide conclusive evidence that reductions in acid emissions are stimulating the gradual recovery of chronically acidified terrestrial ecosystems at a whole-country scale, while also suggesting this recovery is being compromised by changing climate and land management.