bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘rbioacc’: an ‘R’-package to analyze toxicokinetic data
Authors: Ratier A. , Baudrot V. , Kaag M. , Siberchicot A. , Lopes C. , Charles S. 
Published: September 2021

Abstract‘rbioacc’ is an ‘R’-package dedicated to the analysis of experimental data collected from bioaccumulation tests during which organisms are exposed to a chemical (exposure phase) and then put into a clean media (depuration phase). Internal concentrations are regularly measured over time all along the experiment.‘rbioacc’ provides ready-to-use functions to visualize and fully analyze such data. Under a Bayesian framework, this package fits a generic one-compartment toxicokinetic (TK) model automatically built from the data. It provides TK parameter estimates (appropriate uptake and elimination rates) and bioaccumulation metrics (e.g., BCF, BSAF, BMF). All parameter estimates, bioaccumulation metrics as well as predictions of internal concentrations into organisms are delivered with their uncertainty.Bioaccumulation metrics are primarily provided in support of environmental risk assessment, in full compliance with regulatory requirements required to approve marketing applications of chemical substances.This paper gives brief worked examples of the use of ‘rbioacc’ from data collected through standard bioaccumulation tests, and publicly available within the scientific literature. These examples constitute step-by-step user-guides to analyze any new data set, uploaded in the right format.
Parkinson’s Disease-Associated, Sex-specific Changes in DNA Methylation at PARK7 (DJ-1), ATXN1, SLC17A6, NR4A2, and PTPRN2 in Cortical Neurons
Authors: Kochmanski Joseph , Kuhn Nathan C. , Bernstein Alison I. 
Published: September 2021

AbstractEvidence for epigenetic regulation playing a role in Parkinson’s disease (PD) is growing, particularly for DNA modifications. Approximately 90% of PD cases are due to a complex interaction between age, genes, and environmental factors, and epigenetic marks are thought to mediate the relationship between aging, genetics, the environment, and disease risk. To date, there are a small number of published genome-wide studies of DNA modifications in PD, but none accounted for cell-type or sex in their analyses. Given the hetereogeneity of bulk brain tissue samples and known sex differences in PD risk, progression, and severity, these are critical variables to account for. In this first genome-wide analysis of DNA methylation in an enriched neuronal population from PD post-mortem parietal cortex, we report sex-specific PD-associated methylation changes in PARK7 (DJ-1), SLC17A6 (VGLUT2), PTPRN2 (IA-2β), NR4A2 (NURR1), and other genes involved in developmental pathways, neurotransmitter packaging and release, and axon and neuron projection guidance.
Genome assembly and annotation of the tambaqui (Colossoma macropomum): an emblematic fish of the Amazon River basin
Authors: Hilsdorf Alexandre Wagner Silva , Uliano-Silva Marcela , Coutinho Luiz Lehmann , Montenegro Horácio , Almeida-Val Vera Maria Fonseca , Pinhal Danillo 
Published: September 2021

ABSTRACTColossoma macropomum known as “tambaqui” is the largest Characiformes fish in the Amazon River Basin and a leading species in Brazilian aquaculture and fisheries. Good quality meat and great adaptability to culture systems are some of its remarkable farming features. To support studies into the genetics and genomics of the tambaqui, we have produced the first high-quality genome for the species. We combined Illumina and PacBio sequencing technologies to generate a reference genome, assembled with 39X coverage of long reads and polished to a QV=36 with 130X coverage of short reads. The genome was assembled into 1,269 scaffolds to a total of 1,221,847,006 bases, with a scaffold N50 size of 40 Mb where 93% of all assembled bases were placed in the largest 54 scaffolds that corresponds to the diploid karyotype of the tambaqui. Furthermore, the NCBI Annotation Pipeline annotated genes, pseudogenes, and non-coding transcripts using the RefSeq database as evidence, guaranteeing a high-quality annotation. A Genome Data Viewer for the tambaqui was produced which benefits any groups interested in exploring unique genomic features of the species. The availability of a highly accurate genome assembly for tambaqui provides the foundation for novel insights about ecological and evolutionary facets and is a helpful resource for aquaculture purposes.
STRIDE: accurately decomposing and integrating spatial transcriptomics using single-cell RNA sequencing
Authors: Sun Dongqing , Liu Zhaoyang , Li Taiwen , Wu Qiu , Wang Chenfei 
Published: September 2021

AbstractThe recent advances in spatial transcriptomics have brought unprecedented opportunities to understand the cellular heterogeneity in the spatial context. However, the current limitations of spatial technologies hamper the exploration of cellular localizations and interactions at single-cell level. Here, we present spatial transcriptomics deconvolution by topic modeling (STRIDE), a computational method to decompose cell types from spatial mixtures by leveraging topic profiles trained from single-cell transcriptomics. STRIDE accurately estimated the cell-type proportions and showed balanced specificity and sensitivity compared to existing methods. We demonstrate STRIDE’s utility by applying it to different spatial platforms and biological systems. Deconvolution by STRIDE not only mapped rare cell types to spatial locations but also improved the identification of spatial localized genes and domains. Moreover, topics discovered by STRIDE were associated with cell-type-specific functions, and could be further used to integrate successive sections and reconstruct the three-dimensional architecture of tissues. Taken together, STRIDE is a versatile and extensible tool for integrated analysis of spatial and single-cell transcriptomics and is publicly available athttps://github.com/wanglabtongji/STRIDE.
Specialization of the photoreceptor transcriptome bySrrm3-dependent microexons is required for outer segment maintenance and vision
Authors: Ciampi Ludovica , Mantica Federica , Lopez-Blanch Laura , Rodríguez-Marin Cristina , Cianferoni Damiano , Zang Jingjing , Permanyer Jon , Jiménez-Delgado Senda , Bonnal Sophie , Miravet-Verde Samuel , Ruprecht Verena , Neuhauss Stephan C.F. , Banfi Sandro , Carrella Sabrina , Serrano Luis , Head Sarah A. , Irimia Manuel 
Published: September 2021

ABSTRACTRetinal photoreceptors differ in their transcriptomic profiles from other neuronal subtypes, likely as a reflection of their unique cellular morphology and function in the detection of light thorough the ciliary outer segment. We discovered a new layer of this molecular specialization by revealing that the vertebrate retina expresses the largest number of tissue-enriched microexons of all tissue types. A subset of these microexons is included exclusively in photoreceptor transcripts, particularly in genes involved in cilia biogenesis and in vesicle-mediated transport. This microexon program is regulated bySrrm3, a paralog of the neural microexon regulatorSrrm4. Despite both proteins positively regulate retina microexonsin vitro, onlySrrm3is highly expressed in mature photoreceptors and its deletion in zebrafish results in widespread downregulation of microexon inclusion, severe photoreceptor alterations and blindness. These results shed light into photoreceptor’s transcriptomic specialization and functionality, uncovering new cell type-specific roles forSrrm3and microexons with implication for retinal diseases.
Feasibility of Administering Human Pancreatic Cancer Chemotherapy in a Spontaneous Pancreatic Cancer Mouse Model
Authors: Delahoussaye Abagail M. , Jaoude Joseph Abi , Fujimoto Tara N. , Molkentine Jessica , Garcia Garcia Carolina J. , Gay Jason P. , Feng Ningping , Marszalek Joe , Taniguchi Cullen M. 
Published: September 2021

AbstractBackgroundBoth modified FOLFIRINOX (mFFX) and gemcitabine/nab-paclitaxel chemotherapy regimens have been shown to improve clinical outcomes in patients with pancreatic cancer, and are often used interchangeably as the standard of care. Preclinical studies often do not use these regimens, since administering these multiagent approaches can be difficult. In this study, we assessed the feasibility of administering these two chemotherapy regimens in spontaneous pancreatic tumors using KPC mice with the ultimate goal of advancing preclinical studies.MethodsKPC mice were created by breeding KrasLSL-G12D/+ to Trp53fl/fl;Ptf1αCre/+, resulting in KrasLSL-G12D/+;p53fl/+;Ptf1αCre/+ mice. At 14 weeks of age, mice were palpated for spontaneous tumor growth that was verified using ultrasounds. Mice with tumors under 15 mm in diameter were used. The mice were assigned to one of seven treatment regimens: 1 cycle of mFOLFIRINOX (FFX X1), 2 cycles of mFOLFIRINOX (FFX X2), 1 cycle of mFOLFIRINOX with 40Gy SBRT (FFX SBRT), 1 cycle of gemcitabine/nab-paclitaxel (GEM/AB X1), 2 cycles of gemcitabine/nab-paclitaxel (GEM/AB X2), 2 cycles of gemcitabine/nab-paclitaxel with 40Gy SBRT (GEM/AB SBRT), or no chemotherapy treatment (control).ResultsIn total, 92 mice were included. The median OS in the FFX X2 group was slightly longer that the median OS in the FFX X1 group (15 days vs 11 days, P=0.003). Mice in the GEM/AB X2 group had longer OS when compared to mice in the GEM/AB X1 group (33.5 vs 13 days, P=0.001). Mice treated with chemotherapy survived longer than untreated control animals (median OS: 6.5 days, P <0.001). Moreover, in mice treated with chemotherapy, mice that received 2 cycles of GEM/AB X2 had the longest survival, while the FFX X1 group had the poorest OS (P <0.001). Lastly, chemotherapy followed by consolidative SBRT trended towards increased local control and survival.ConclusionsWe demonstrate the utility and feasibility of clinicall relevant mFOLFIRINOX and gemcitabine/nab-paclitaxel in preclinical models of pancreatic cancer.
Malayan kraits (Bungarus candidus) show affinity to anthropogenic structures in a human dominated landscape
Authors: Hodges Cameron Wesley , Marshall Benjamin Michael , Hill Jacques George , Strine Colin Thomas 
Published: September 2021

AbstractAnimal movement can impact human-wildlife conflict through a variety of features: increased movement can lead to greater chance of encounter, remaining still can lead to greater or lesser detection, and activity can modulate their impact on humans. Here we assess the movement and space use of the highly venomous and medically important Malayan krait (Bungarus candidus) on a suburban university campus. We radio- tracked 14 kraits for an average of 114 days (min: 19, max: 218), with an average of 106 fixes (min: 21, max: 229). We assessed movement pathways and activity with dynamic Brownian Bridge Movement models, evaluated patterns of revisitation to identify site fidelity, and determined whether individuals selected for particular land-use types with Integrated Step Selection Functions. Most individuals displayed some level of attraction to buildings (n = 10) and natural areas (n = 12); we identified a similar unambiguous pattern of attraction to buildings and natural areas at the population level (of our sample). Snakes remained in shelter sites for long periods of time (max = 94 days) and revisited sites on average every 15.45 days. Over 50% of fixes were within human settlements and 37.1% were associated with buildings. We found generally seasonal patterns of activity, with higher activity in wet seasons (when classes are typically in session on campus), and lower activity in the hot season (when there are a number of short breaks causing students to leave campus). These results show frequent proximity between Malayan kraits and humans at Suranaree University of Technology, Thailand; thereby, suggesting a near constant potential for human- wildlife conflict. Despite the fact that no snakebites from this species occurred at the university during our study period, substantial education and awareness training should be considered to raise awareness to ensure continued coexistence on campus.
APIR: Aggregating Universal Proteomics Database Search Algorithms for Peptide Identification with FDR Control
Authors: Chen Yiling Elaine , Ge Xinzhou , Woyshner Kyla , McDermott MeiLu , Manousopoulou Antigoni , Ficarro Scott B. , Marto Jarrod A. , Li Kexin , Wang Leo David , Li Jingyi Jessica 
Published: September 2021

AbstractAdvances in mass spectrometry (MS) have enabled high-throughput analysis of proteomes in biological systems. The state-of-the-art MS data analysis relies on database search algorithms to quantify proteins by identifying peptide-spectrum matches (PSMs), which convert mass spectra to peptide sequences. Different database search algorithms use distinct search strategies and thus may identify unique PSMs. However, no existing approaches can aggregate all user-specified database search algorithms with a guaranteed increase in the number of identified peptides and control on the false discovery rate (FDR). To fill in this gap, we propose a statistical framework, Aggregation of Peptide Identification Results (APIR), that is universally compatible with all database search algorithms. Notably, under an FDR threshold, APIR is guaranteed to identify at least as many, if not more, peptides as individual database search algorithms do. Evaluation of APIR on a complex proteomics standard shows that APIR outpowers individual database search algorithms and empirically controls the FDR. Real data studies show that APIR can identify disease-related proteins and post-translational modifications missed by some individual database search algorithms. The APIR framework is easily extendable to aggregating discoveries made by multiple algorithms in other high-throughput biomedical data analysis, e.g., differential gene expression analysis on RNA sequencing data. The APIR R package is available athttps://github.com/yiling0210/APIR.
Vestibular CCK signaling drives motion-induced malaise
Authors: Machuca-Márquez Pablo , Sánchez-Benito Laura , Menardy Fabien , Urpi Andrea , Girona Mònica , Puighermanal Emma , Appiah Isabella , Palmiter Richard , Sanz Elisenda , Quintana Albert 
Published: September 2021

ABSTRACTTravel can induce motion sickness (MS) in susceptible individuals. MS is an evolutionary conserved mechanism caused by mismatches between motion-related sensory information and past visual and motion memory, triggering a malaise accompanied by hypolocomotion, hypothermia, hypophagia and nausea. Vestibular nuclei (VN) are critical for the processing of movement input from the inner ear. Motion-induced activation of VN neurons recapitulates MS-related signs. However, the genetic identity of VN neurons mediating MS- related autonomic and aversive responses remains unknown. Here, we identify a central role of cholecystokinin (CCK)-expressing VN neurons in motion-induced malaise. Moreover, we show that CCK VN inputs onto the parabrachial nucleus activateCalca- expressing neurons and are sufficient to establish avoidance to novel food, which is prevented by CCK-A receptor antagonism. These observations provide greater insight into the neurobiological regulation of MS by identifying the neural substrates of MS and providing potential targets for treatment.SIGNIFICANCE STATEMENTWe live in an age where travel is paramount. However, one of the most disabling conditions inherent to traveling is motion sickness (MS). While studies have underscored the role of the vestibular system in the development of MS, the neuronal populations involved in motion-induced malaise remain largely unknown.Here, we describe the vestibular pathways eliciting MS responses, and identify a key role for cholecystokinin (CCK)-expressing vestibular neurons. We reveal that a vestibulo-parabrachial (PBN) CCKergic projection is sufficient to induce conditioned taste aversion, likely through the activation of calcitonin gene-related peptide-expressing PBN neurons. Finally, we underscore the role of CCK-A receptor signaling as a novel druggable target to treat MS, providing novel insight on the neurobiological substrates of MS.
The Temporal Pattern of Spiking Activity of a Thalamic Neuron are Related to the Amplitude of the Cortical Local Field Potential
Authors: Tamura Hiroshi 
Published: September 2021

AbstractNeuron activity in the sensory cortices mainly depends on feedforward thalamic inputs. High-frequency activity of a thalamic input can be temporally integrated by a neuron in the sensory cortex and is likely to induce larger depolarization. However, feedforward inhibition (FFI) and depression of excitatory synaptic transmission in thalamocortical pathways attenuate depolarization induced by the latter part of high-frequency spiking activity and the temporal summation may not be effective. The spiking activity of a thalamic neuron in a specific temporal pattern may circumvent FFI and depression of excitatory synapses. The present study determined the relationship between the temporal pattern of spiking activity of a single thalamic neuron and the degree of cortical activation as well as that between the firing rate of spiking activity of a single thalamic neuron and the degree of cortical activation. Spiking activity of a thalamic neuron was recorded extracellularly from the lateral geniculate nucleus (LGN) in male Long-Evans rats. Degree of cortical activation was assessed by simultaneous recording of local field potential (LFP) from the visual cortex. A specific temporal pattern appearing in three consecutive spikes of an LGN neuron induced larger cortical LFP modulation than high-frequency spiking activity during a short period. These findings indicate that spiking activity of thalamic inputs is integrated by a synaptic mechanism sensitive to an input temporal pattern.Significance StatementSensory cortical activity depends on thalamic inputs. Despite the importance of thalamocortical transmission, how spiking activity of thalamic inputs is integrated by cortical neurons remains unclear. Feedforward inhibition and synaptic depression of excitatory transmission may not allow simple temporal summation of membrane potential induced by consecutive spiking activity of a thalamic neuron. A specific temporal pattern appearing in three consecutive spikes of a thalamic neuron induced larger cortical local field potential modulation than high-frequency spiking activity during a short period. The findings indicate the importance of the temporal pattern of spiking activity of a single thalamic neuron on cortical activation.
Humans reconfigure target and distractor processing to address distinct task demands
Authors: Ritz Harrison , Shenhav Amitai 
Published: September 2021

AbstractWhen faced with distraction, we can focus more on goal-relevant information (targets) or focus less goal-conflicting information (distractors). How people use cognitive control to distribute attention across targets and distractors remains unclear. To help address this question, we developed a parametric attentional control task that can index both target discriminability and distractor interference. We find that participants exert independent control over target and distractor processing. We measured control adjustments through the influence of incentives and previous conflict on target and distractor sensitivity, finding that these have dissociable influences on control. Whereas incentives preferentially led to target enhancement, conflict on the previous trial preferentially led to distractor suppression. These distinct drivers of control altered sensitivity to targets and distractors early in the trial, promptly followed by reactive reconfiguration towards task-appropriate feature sensitivity. Finally, we provide a process-level account of these findings by showing that these control adjustments are well-captured by an evidence accumulation model with attractor dynamics over feature weights. These results help establish a process-level account of control reconfiguration that provides new insights into how multivariate attentional signals are optimized to achieve task goals.
COVID-19 Vaccine Concerns about Safety, Effectiveness and Policies in the United States, Canada, Sweden, and Italy among Unvaccinated Individuals
Authors: Piltch-Loeb Rachael , Harriman Nigel , Healey Julia , Bonetti Marco , Toffolutti Veronica , Testa Marcia A , Su Max , Savoia Elena 
Published: September 2021

AbstractDespite the effectiveness of the COVID-19 vaccine, global vaccination distribution efforts have thus far had varying levels of success. Vaccine hesitancy remains a threat to vaccine uptake. This study has four objectives: 1) describe and compare vaccine hesitancy proportions by country; 2) categorize vaccine-related concerns; 3) rank vaccine-related concerns; and 4) compare vaccine-related concerns by country and hesitancy status in four countries- the United States, Canada, Sweden, and Italy. Using the Pollfish survey platform, we sampled 1000 respondents in Canada, Sweden, and Italy and 750 respondents in the United States between May 21-28, 2021. Results showed vaccine related concerns varied across three topical areas- vaccine safety and government control, vaccine effectiveness and population control, and freedom. For each thematic area, the top concern was statistically significantly different in each country and among the hesitant and non-hesitant subsamples within each county. Understanding the specific concerns among individuals when it comes to the COVID-19 vaccine can help to inform public communications and identify which, if any, salient narratives, are global.
Building a learnable universal coordinate system for single-cell atlas with a joint-VAE model
Authors: Gao Haoxiang , Hua Kui , Wei Lei , Wu Xinze , Chen Sijie , Yin Qijin , Jiang Rui , Zhang Xuegong 
Published: September 2021

AbstractA universal coordinate system that can ensemble the huge number of cells and capture their heterogeneities is of vital importance for constructing large-scale cell atlases as references for future molecular and cellular studies. Studies have shown that cells in complex organs exhibit multifaceted heterogeneities in their transcriptomic features at multiple resolutions. This nature of complexity makes it hard to design a fixed coordinate system through a combination of known features. It is desirable to build a learnable universal coordinate model that can capture major heterogeneities and serve as a controlled generative model for data argumentation. We developed UniCoord, a specially tuned joint-VAE model to represent single-cell transcriptomic data in a lower-dimensional latent space with high interpretability. Each latent dimension can represent either discrete or continuous feature, and either supervised by prior knowledge or unsupervised. The original transcriptomic profiles can be regenerated from the latent dimensions. The latent dimensions can be easily reconfigured to generate transcriptomic profiles of pseudo cells with desired properties. UniCoord can also be used as a pre-trained model to analyze new data with unseen cell types and thus can serve as a feasible framework for cell annotation and comparison. UniCoord provides a prototype for a learnable universal coordinate framework to enable better analysis and generation of cells with highly orchestrated functions and heterogeneities.