bluuebunny/crossref_metadata_2025_split huggingface dataset:
Swallowing-related neural oscillation: An intracranial EEG study
Authors: Hashimoto Hiroaki , Takahashi Kazutaka , Kameda Seiji , Yoshida Fumiaki , Maezawa Hitoshi , Oshino Satoru , Tani Naoki , Khoo Hui Ming , Yanagisawa Takufumi , Yoshimine Toshiki , Kishima Haruhiko , Hirata Masayuki 
Published: December 2020

AbstractSwallowing is a unique movement due to the indispensable orchestration of voluntary and involuntary movement. The transition from voluntary to involuntary swallowing is executed on the order of milliseconds. We hypothesized that its neural mechanism is revealed by high frequency cortical activities. Eight epileptic participants fitted with intracranial electrodes over the orofacial cortex were asked to swallow a water bolus, and cortical oscillatory changes, including high γ band (75–150 Hz) and β band (13–30 Hz) were investigated at the time of mouth-opening, water-injection, and swallowing. High γ power increases associated with mouth-opening were observed in the ventrolateral prefrontal cortex with water-injection in the lateral central sulcus and with swallowing in the region along the Sylvian fissure. Mouth-opening induced a β power decrease, which continued until the completion of swallowing. The high γ burst activity was focal and specific to swallowing, however, the β activities were extensive and not specific to swallowing. At the boundary time between voluntary and involuntary swallowing, swallowing-related high γ power achieved the peak, and subsequently, the power decreased. We demonstrated three distinct activities related to mouth-opening, water-injection, and swallowing induced at different timings, using high γ activities. The peak of high γ power related to swallowing suggests that during voluntary swallowing phases, the cortex is the main driving force for swallowing rather than the brain stem.
Dynamic larval dispersal can mediate the response of marine metapopulations to multiple climate change impacts
Authors: Bani Ridouan , Marleau Justin , Fortin Marie-Josée , Daigle Rémi M. , Guichard Frédéric 
Published: December 2020

AbstractClimate change is having multiple impacts on marine species characterized by sedentary adult and pelagic larval phases, from increasing adult mortality to changes in larval duration and ocean currents. Recent studies have shown impacts of climate change on species persistence through direct effects on individual survival and development, but few have considered the indirect effects mediated by ocean currents and species traits such as pelagic larval duration. We used a density-dependent and stochastic metapopulation model to predict how changes in adult mortality and dynamic connectivity can affect marine metapopulation stability. We analyzed our model with connectivity data simulated from a biophysical ocean model of the northeast Pacific coast forced under current (1998-2007) and future (2068-2077) climate scenarios in combination with scenarios of increasing adult mortality and decreasing larval duration. Our results predict that changes of ocean currents and larval duration mediated by climate change interact in complex and opposing directions to shape local mortality and metapopulation connectivity with synergistic effects on regional metapopulation stability: while species with short larval duration are most sensitive to temperature-driven reduction in larval duration, the response of species with longer larval duration are mostly mediated by changes in both the mean and variance of larval connectivity driven by ocean currents. Our results emphasize the importance of considering the spatiotemporal structure of connectivity in order to predict how the multiple effects of climate change will impact marine populations.
Shaping sustainable harvest boundaries for marine populations despite estimation bias
Authors: Goto Daisuke , Devine Jennifer A. , Umar Ibrahim , Fischer Simon H. , De Oliveira José A. A. , Howell Daniel , Jardim Ernesto , Mosqueira Iago , Ono Kotaro 
Published: December 2020

AbstractBiased estimates of population status are a pervasive conservation problem. This problem has plagued assessments of commercial exploitation of marine species and can threaten the sustainability of both populations and fisheries. We develop a computer-intensive approach to minimize adverse effects of persistent estimation bias in assessments by optimizing operational harvest measures (harvest control rules) with closed-loop simulation of resource–management feedback systems: management strategy evaluation. Using saithe (Pollachius virens), a bottom-water, apex predator in the North Sea, as a real-world case study, we illustrate the approach by first diagnosing robustness of the existing harvest control rule and then optimizing it through propagation of biases (overestimated stock abundance and underestimated fishing pressure) along with select process and observation uncertainties. Analyses showed that severe biases lead to overly optimistic catch limits and then progressively magnify the amplitude of catch fluctuation, thereby posing unacceptably high overharvest risks. Consistent performance of management strategies to conserve the resource can be achieved by developing more robust control rules. These rules explicitly account for estimation bias through a computational grid search for a set of control parameters (threshold abundance that triggers management action,Btrigger, and target exploitation rate,Ftarget) that maximize yield while keeping stock abundance above a precautionary level. When the biases become too severe, optimized control parameters– for saithe, raisingBtriggerand loweringFtarget–would safeguard against overharvest risk (<3.5% probability of stock depletion) and provide short-term stability in catch limit (<20% year-to-year variation), thereby minimizing disruption to fishing communities. The precautionary approach to fine-tuning adaptive risk management through management strategy evaluation offers a powerful tool to better shape sustainable harvest boundaries for exploited resource populations when estimation bias persists. By explicitly accounting for emergent sources of uncertainty our proposed approach ensures effective conservation and sustainable exploitation of living marine resources even under profound uncertainty.Open Research StatementData sets and code utilized for this research are available on Figshare. DOI:https://doi.org/10.6084/m9.figshare.13281266
Pollinators mediate floral microbial diversity and network under agrochemical disturbance
Authors: Wei Na , Russell Avery L. , Jarrett Abigail R. , Ashman Tia-Lynn 
Published: December 2020

AbstractHow pollinators mediate microbiome assembly in the anthosphere is a major unresolved question of theoretical and applied importance in the face of anthropogenic disturbance. We addressed this question by linking visitation of diverse pollinator functional groups (bees, wasps, flies, butterflies, beetles, true bugs and other taxa) to the key properties of floral microbiome (microbial α- and β-diversity and microbial network) under agrochemical disturbance, using a field experiment of bactericide and fungicide treatments on cultivated strawberries that differ in flower abundance. Structural equation modeling was used to link agrochemical disturbance and flower abundance to pollinator visitation to floral microbiome properties. Our results revealed that (1) pollinator visitation influenced the α- and β-diversity and network centrality of floral microbiome, with different pollinator functional groups affecting different microbiome properties; (2) flower abundance influenced floral microbiome both directly by governing the source pool of microbes and indirectly by enhancing pollinator visitation; and (3) agrochemical disturbance affected floral microbiome primarily directly by fungicide, and less so indirectly via pollinator visitation. These findings improve the mechanistic understanding of floral microbiome assembly, and may be generalizable to many other plants that are visited by diverse insect pollinators in natural and managed ecosystems.
More from less: Genome skimming for nuclear markers for animal phylogenomics, a case study using decapod crustaceans
Authors: Tan Mun Hua , Gan Han Ming , Bracken-Grissom Heather , Chan Tin-Yam , Grandjean Frederic , Austin Christopher M. 
Published: December 2020

AbstractLow coverage genome sequencing is rapid and cost-effective for recovering complete mitochondrial genomes for animal phylogenomics. The recovery of high copy number nuclear genes, including histone H3, 18S and 28S ribosomal RNAs, is also possible using this approach. In this study, we explore the potential of the genome skimming (GS) to recover additional nuclear genes from shallow sequencing projects. Using anin silicobaited approach, we recover three additional core histone genes (H2A, H2B and H4) from our existing collection of low coverage decapod crustacean dataset (99 species, 69 genera, 38 families, 10 infraorders). Phylogenetic analyses based on various combinations of mitochondrial and nuclear genes for the entire decapod dataset and 40 species of crayfish (Infraorder Astacidea) found that the evolutionary rates for different classes of genes varied widely. The highlight being a very high level of congruence found between trees from the six nuclear genes and those derived from the mitogenome sequences for freshwater crayfish. These findings indicate that nuclear genes recovered from the same genome skimming datasets designed to obtain mitogenomes can be used to support more robust and comprehensive phylogenetic analyses. Further, a search for additional intron-less nuclear genes identified several high copy number genes across the decapod dataset and recovery of NaK, PEPCK and GAPDH gene fragments is possible at slightly elevated coverage, suggesting the potential and utility of GS in recovering even more nuclear genetic information for phylogenetic studies from these inexpensive and increasingly abundant datasets.
Personalise Dose Regimen of Vitamin D3 Using Physiologically-Based Pharmacokinetic Modelling
Authors: Huang Zhonghui , You Tao 
Published: December 2020

AbstractBackground and AimVitamin D3 (i.e. cholecalciferol) produces an active metabolite 25-hydroxyvitamin D3 (i.e. 25(OH)D3) to promote intestinal calcium absorption. Given high population heterogeneity in 25(OH)D3 plasma concentration profiles, vitamin D3 dose regimen needs to be personalised. The objective of this study is to establish a model that accurately predicts 25(OH)D3 pharmacokinetics (PK) on an individual level to enable selection of an appropriate dose regimen for anyone.MethodsPlasma or serum concentrations of Vitamin D3 and 25(OH)D3 from different trials were compiled together. We then developed a series of Physiologically-Based Pharmacokinetic (PBPK) models for vitamin D3 and 25(OH)D3 in a stepwise manner to select the best model to optimally recapitulate the 10μg and 100μg daily dose data. Each arm of the clinical trials was simulated individually. Model predictions were qualified with PK data at other doses.ResultsFrom data exploration, we observed an interesting phenomenon: the increase in plasma 25(OH)D3 after repeat dosing was negatively correlated with 25(OH)D3 baseline levels. Our final model assumes a first-order vitamin D3 absorption, linear vitamin D3 elimination and a non-linear 25(OH)D3 elimination which is described with an Emax function. This model offers a simple explanation to the apparent paradox: the negative correlation might arise from the non-linear 25(OH)D3 elimination process. The model was also able to accurately predict plasma 25(OH)D3 after repeat dosing at daily doses other than 10μg and 100μg, which was reassuring.ConclusionsWe developed a PBPK model to recapitulate PK of plasma vitamin D3 and 25(OH)D3. A personalised vitamin D3 supplementation protocol requires measurement of 25(OH)D3 baseline levels. This should be tested in the clinics for each individual.
Proof of concept study to develop a novel connectivity-based electric-field modelling approach for individualized targeting of transcranial magnetic stimulation treatment
Authors: Balderston Nicholas L , Beer Joanne C , Seok Darsol , Makhoul Walid , Deng Zhi-De , Girelli Tommaso , Teferi Marta , Smyk Nathan , Jaskir Marc , Oathes Desmond J , Sheline Yvette I 
Published: December 2020

AbstractBackgroundResting state functional connectivity (rsFC) offers promise for individualizing stimulation targets for transcranial magnetic stimulation (TMS) treatments. However current targeting approaches do not account for non-focal TMS effects or large-scale connectivity patterns. To overcome these limitations, we propose a novel targeting optimization approach that combines whole-brain rsFC and electric-field (e-field) modelling to identify single-subject, symptom-specific TMS targets.MethodsIn this proof of concept study, we recruited 91 anxious misery (AM) patients and 25 controls. We measured depression symptoms (MADRS/HAMD) and recorded rsFC. We used a PCA regression to predict symptoms from rsFC and estimate the parameter vector, for input into our e-field augmented model. We modeled 17 left dlPFC and 7 M1 sites using 24 equally spaced coil orientations. We computed single-subject predicted ΔMADRS/HAMD scores for each site/orientation using the e-field augmented model, which comprises a linear combination of the following elementwise products 1) the estimated connectivity/symptom coefficients, 2) a vectorized e-field model for site/orientation, 3) the pre-treatment rsFC matrix, scaled by a proportionality constant.ResultsIn AM patients, our pre-stimulation connectivity-based model predicted a significant decrease depression for sites near BA46, but not M1 for coil orientations perpendicular to the cortical gyrus. In control subjects, no site/orientation combination showed a significant predicted change.DiscussionThese results corroborate previous work suggesting the efficacy of left dlPFC stimulation for depression treatment, and predict better outcomes with individualized targeting. They also suggest that our novel connectivity-based e-field modelling approach may effectively identify potential TMS treatment responders and individualize TMS targeting to maximize the therapeutic impact.
Post release immune responses of Tasmanian devils vaccinated with an experimental devil facial tumour disease vaccine
Authors: Pye Ruth , Darby Jocelyn , Flies Andrew , Fox Samantha , Carver Scott , Elmer Jodie , Swift Kate , Hogg Carolyn , Pemberton David , Woods Gregory , Lyons A. Bruce 
Published: December 2020

ABSTRACTDisease is increasingly becoming a driver of wildlife population declines and extinction risk. Vaccines have been one of the most successful health interventions in human history, but few have been tested for mitigating wildlife disease. The transmissible cancer, devil facial tumour disease (DFTD), triggered the Tasmanian devil’s (Sarcophilus harrisii) inclusion on the international endangered species list. Development of a protective DFTD vaccine would provide a valuable management approach for conservation of the species. In 2016, 33 devils from a DFTD-free insurance population were given an experimental DFTD vaccination prior to their release on the north coast of Tasmania. The release site was already home to an incumbent population of devils, including some individuals with DFTD. To determine the efficacy of the vaccination protocol and the longevity of the response it induced, six trapping trips took place at the site over the 2.5 years following release. Eight of the 33 vaccinated devils were re-trapped, and six of those developed DFTD within the monitoring period. Despite the apparent lack of protection provided by the vaccine for the re-trapped devils, we observed several signs of immune activation not usually found in unvaccinated devils. Firstly, sera collected from the eight devils showed that anti-DFTD antibodies persisted for up to two years post vaccination. Secondly, tumour infiltrating lymphocytes were found in three out of four biopsies collected from vaccinated devils which contrasts with the “immune deserts” typical of DFT’s; only one out of twenty incumbent devils with DFTD trapped during the same period had a tumour biopsy exhibiting immune cell infiltrate. Thirdly, immunohistochemical analysis of tumour biopsies from the vaccinated devils identified the functional immune molecules associated with antigen presenting cells (MHC-II) and T cells (CD3), and the immune checkpoint molecule PD-1, all associated with anti-tumour immunity in other species. These results correlate with our previous study on captive devils in which a prophylactic vaccine primed the devil immune system and, following DFTD challenge and tumour growth, immunotherapy induced complete tumour regressions. The field trial results presented here provide further evidence that the devil immune system can be primed to recognise DFTD cells, but additional immune manipulation could be needed for complete protection or induction of tumour regressions.
The new generation hDHODH inhibitor MEDS433 hinders thein vitroreplication of SARS-CoV-2
Authors: Calistri Arianna , Luganini Anna , Conciatori Valeria , Vecchio Claudia Del , Sainas Stefano , Boschi Donatella , Lolli Marco Lucio , Gribaudo Giorgio , Parolin Cristina 
Published: December 2020

AbstractIdentification and development of effective drugs active against SARS-CoV-2 are urgently needed. Here, we report on the anti-SARS-CoV-2 activity of MEDS433, a novel inhibitor of human dihydroorotate dehydrogenase (hDHODH), a key cellular enzyme of thede novopyrimidines biosynthesis. MEDS433 inhibitsin vitrovirus replication in the low nanomolar range, and through a mechanism that stems from its ability to block hDHODH activity. MEDS433 thus represents an attractive candidate to develop novel anti-SARS-CoV-2 agents.
Global transcriptomics reveals specialized roles for splicing regulatory proteins in the macrophage innate immune response
Authors: West KO , Wagner AR , Scott HM , Vail KJ , Carter KE , Watson RO , Patrick KL 
Published: December 2020

ABSTRACTPathogen sensing via pattern recognition receptors triggers massive reprogramming of macro-phage gene expression. While the signaling cascades and transcription factors that activate these responses are well-known, the role of post-transcriptional RNA processing in modulating innate immune gene expression remains understudied. Recent phosphoproteomics analyses revealed that members of the SR and hnRNP families of splicing regulatory proteins are dynamically post-translationally modified in infected macrophages. To begin to test if these splicing factors play a privileged role in controlling the innate immune transcriptome, we analyzed steady state gene expression and alternatively spliced isoform production in ten SR/hnRNP knockdown RAW 264.7 macrophage cell lines following infection with the bacterial pathogenSalmonella entericaserovar Typhimurium (Salmonella). We identified thousands of transcripts whose abundance was increased or decreased by SR/hnRNP knockdown in macrophages. We observed that different SR/hnRNPs control the expression of distinct gene regulons in uninfected andSalmonella-infected macrophages, with several key innate immune genes (Nos2, Mx1, Il1a) relying on multiple SR/hnRNPs to maintain proper induction and/or repression. Knockdown of SR/hnRNPs promoted differential isoform usage (DIU) for a number of key immune sensors and signaling molecules and many of these splicing changes were again, distinct in uninfected andSalmonella-infected macrophages. Finally, after observing a surprising degree of similarity between the DEGs and DIUs in hnRNP K and U knockdown macrophages, we found that these cells are better able to restrict vesicular stomatitis virus replication than control cells, supporting a role for these hnRNPs in controlling infection outcomes in macrophagesex vivo. Based on these findings, we conclude that many innate immune genes have evolved to rely on one or more splicing regulatory factors to ensure the proper timing and magnitude of their induction, bolstering a model wherein pre-mRNA splicing is a critical regulatory node in the innate immune response.
Variation in insect herbivore communities on individual plants reveals phylogenetic signal in uncertainty of attack in Brassicaceae
Authors: Mertens Daan , Bouwmeester Klaas , Poelman Erik H. 
Published: December 2020

AbstractAs a result of co-evolution between plants and herbivores, related plants often interact with similar communities of herbivores. On individual plants, typically only a subset of interactions is realized. The stochasticity of realized interactions leads to uncertainty of attack on individual plants and is likely to determine adaptiveness of plant defence strategies. Here, we show that across 12 plant species in two phylogenetic lineages of the Brassicaceae, variation in realized herbivore communities reveals a phylogenetic signal in the uncertainty of attack on individual plants. Individual plants of Brassicaceae Lineage II were attacked by a larger number of herbivore species from a larger species pool, resulting in a higher uncertainty of realized antagonistic interactions compared to plants in Lineage I. We argue that uncertainty of attack in terms of realized interactions on individual plants is ecologically relevant and must therefore be considered in the evolution of plant defences.
A Potential Role for Aminoacylation in Primordial RNA Copying Chemistry
Authors: Radakovic Aleksandar , Wright Tom H. , Lelyveld Victor S. , Szostak Jack W. 
Published: December 2020

ABSTRACTAminoacylated tRNAs are the substrates for ribosomal protein synthesis in all branches of life, implying an ancient origin for aminoacylation chemistry. In the 1970s, Orgel and colleagues reported potentially prebiotic routes to aminoacylated nucleotides and their RNA templated condensation to form amino acid bridged dinucleotides. However, it is unclear whether such reactions would have aided or impeded nonenzymatic RNA replication. Determining whether aminoacylated RNAs could have been advantageous in evolution prior to the emergence of protein synthesis remains a key challenge. We therefore tested the ability of aminoacylated RNA to participate in both templated primer extension and ligation reactions. We find that at low magnesium concentrations that favor fatty acid-based protocells, these reactions proceed orders of magnitude more rapidly than when initiated from the cis-diol of unmodified RNA. We further demonstrate that amino acid bridged RNAs can act as templates in a subsequent round of copying. Our results suggest that aminoacylation facilitated nonenzymatic RNA replication, thus outlining a potentially primordial functional link between aminoacylation chemistry and RNA replication.Abstract Figure