bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying dynamic facial expressions under naturalistic conditions
Authors: Jeganathan Jayson , Campbell Megan , Hyett Matthew , Parker Gordon , Breakspear Michael 
Published: May 2022

AbstractFacial affect is expressed dynamically – a giggle, grimace, or an agitated frown. However, the characterization of human affect has relied almost exclusively on static images. This approach cannot capture the nuances of human communication or support the naturalistic assessment of affective disorders. Using the latest in machine vision and systems modelling, we studied dynamic facial expressions of people viewing emotionally salient film clips. We found that the apparent complexity of dynamic facial expressions can be captured by a small number of simple spatiotemporal states - composites of distinct facial actions, each expressed with a unique spectral fingerprint. Sequential expression of these states is common across individuals viewing the same film stimuli but varies in those with the melancholic subtype of major depressive disorder. This approach provides a platform for translational research, capturing dynamic facial expressions under naturalistic conditions and enabling new quantitative tools for the study of affective disorders and related mental illnesses.
Beyond the Euclidean brain: inferring non-Euclidean latent trajectories from spike trains
Authors: Jensen Kristopher T. , Liu David , Kao Ta-Chu , Lengyel Máté , Hennequin Guillaume 
Published: May 2022

AbstractNeuroscience faces a growing need for scalable data analysis methods that reduce the dimensionality of population recordings yet retain key aspects of the computation or behaviour. To extract interpretable latent trajectories from neural data, it is critical to embrace the inherent topology of the features of interest: head direction evolves on a ring or torus, 3D body rotations on the special orthogonal group, and navigation is best described in the intrinsic coordinates of the environment. Accordingly, we recently proposed the manifold Gaussian process latent variable model (mGPLVM) to simultaneously infer latent representations on non-Euclidean manifolds and how neurons are tuned to these representations. This probabilistic method generalizes previous Euclidean models and allows principled selection between candidate latent topologies. While powerful, mGPLVM makes two unjustified approximations that limit its practical applicability to neural datasets. First, consecutive latent states are assumed independent a priori, whereas behaviour is continuous in time. Second, its Gaussian noise model is inappropriate for positive integer spike counts. Previous work in Euclidean LVMs such as GPFA has shown significant improvements in performance when modeling such features appropriately (Jensen et al., 2021). Here, we extend mGPLVM by incorporating temporally continuous priors over latent states and flexible count-based noise models. This improves inference on synthetic data, avoiding negative spike count predictions and discontinuous jumps in latent trajectories. On real data, we also mitigate these pathologies while improving model fit compared to the original mGPLVM formulation. In summary, our extended mGPLVM provides a widely applicable tool for inferring (non-)Euclidean neural representations from large-scale, heterogeneous population recordings. We provide an efficient implementation in python, relying on recent advances in approximate inference to e.g. fit 10,000 time bins of recording for 100 neurons in five minutes on a single GPU.
Mitotic chromosome condensation resets chromatin to maintain transcriptional homeostasis
Authors: Ramos-Alonso Lucía , Holland Petter , Le Gras Stéphanie , Zhao Xu , Jost Bernard , Bjørås Magnar , Barral Yves , Enserink Jorrit M. , Chymkowitch Pierre 
Published: May 2022

AbstractMitotic entry correlates with the condensation of the chromosomes, remodeling of histone modifications, exclusion of transcription factors from DNA and the broad downregulation of transcription. However, whether mitotic condensation influences transcription in the subsequent interphase is unknown. Here, we show that preventing one chromosome to condense during mitosis causes it to fail resetting transcription. Rather it diverted the transcription machinery and underwent unscheduled initiation of gene expression. This caused the activation of inducible transcriptional programs, such as the GAL genes, even in absence of the relevant stimuli. Strikingly, aberrant gene expression persisted into the next interphase. Thus, our study identifies the maintenance of transcriptional homeostasis as an unexpected and yet unexplored function of mitotic chromosome condensation.One-Sentence SummaryMitotic chromatin condensation resets the transcriptome to protect cells from transcriptional drifting after anaphase.
A lysine residue from an extracellular turret switches the ion preference in a Cav3 T-Type channel
Authors: Guan W. , Orellana K. G. , Stephens R.F. , Zhorov B. , Spafford J.D 
Published: May 2022

AbstractA dominant sodium influx is mediated by a lysine residue in a novel extracellular loop of T-type Cav3 channels. Here we expressed calcium- and sodium-permeable splice variants which have exons 12b and 12a, respectively, as well as mutated channels containing exons Lys-12a-Ala and Ala-12b-Lys. We demonstrate that the mutant channels render high sodium permeability and calcium selectivity, respectively. Modelling illustrate that the pore lysine is salt-bridged to an aspartate residue immediately C-terminal to the second-domain glutamate of the selectivity-filter. We propose that a calcium ion chelated between the aspartate and the selectivity-filter glutamate is knocked-out by the incoming calcium ion in the process of calcium permeation, but sodium ions are repelled. The aspartate is neutralized by the lysine residue in the sodium-permeant variant, allowing for sodium permeation through the selectivity filter ring of four acidic residues akin to the prokaryotic sodium channels with four glutamates in the selectivity filter.
Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases
Authors: Nutma Erik , Fancy Nurun , Weinert Maria , Marzin Manuel C. , Tsartsalis Stergios , Muirhead Robert C.J. , Falk Irene , de Bruin Joy , Hollaus David , Pieterman Robin , Anink Jasper , Story David , Chandran Siddharthan , Tang Jiabin , Trolese Maria C. , Saito Takashi , Saido Takaomi C. , Wiltshire Katie , Beltran-Lobo Paula , Philips Alexandra , Antel Jack , Healy Luke , Moore Craig S. , Bendotti Caterina , Aronica Eleonora , Radulescu Carola I. , Barnes Samuel J. , Hampton David W. , van der Valk Paul , Jacobson Steven , Matthews Paul M. , Amor Sandra , Owen David R. 
Published: May 2022

AbstractMicroglial activation plays central roles in neuro-inflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells is unique to a subset of species within the Muroidea superfamily of rodents. We show that TSPO is mechanistically linked to classical pro-inflammatory myeloid cell function in rodents but not humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO PET reflects density of inflammatory cells rather than activation state.
Membrane-associated shortened Trk receptors promote neuroprotection and robust axon regeneration without ligands
Authors: Nishijima Euido , Honda Sari , Kitamura Yuta , Namekata Kazuhiko , Kimura Atsuko , Guo Xiaoli , Azuchi Yuriko , Harada Chikako , Murakami Akira , Matsuda Akira , Nakano Tadashi , Parada Luis F. , Harada Takayuki 
Published: May 2022

AbstractActivation of neurotrophic factor signaling is a promising therapy for neurodegeneration. However, limited availability of both ligands and receptors permits only transient activation. In this study, we conquered this problem by inventing a new system that forces membrane localization of the intracellular domain of neurotrophin receptor TrkB, which results in constitutive activation without ligands. Our new system overcomes the small size limitation of the genome packaging in adeno-associated virus and allows high expression of the transgene. Single gene therapy using the modified form of TrkB enhances neuroprotection in mose models of glaucoma, and stimulates robust axon regeneration after optic nerve injury. Our system may be also applicable to other trophic factor signaling and lead to a significant advance in the field of gene therapy for neurodegenerative disorders.
Pain management after dental extractions – non-opioid combination analgesics minimize opioid use for acute dental pain
Authors: Huang Qirong , Rasubala Linda , Gracely Richard , Khan Junad , Eliav Eli , Ren Yanfang 
Published: May 2022

AbstractObjectiveTo evaluate long-term changes in pain management strategies and assess the outcomes of opioids and non-opioid combination analgesics after dental extractions.MethodsThis is a cross-sectional study of patients who received dental extractions and analgesic prescriptions in a large dental urgent care center in two 12-month periods: January 2012 to December 2012 (Year-2012) and March 2021 to February 2022 (Year-2022). Data extracted from electronic records include type of dental extractions, analgesics prescribed, and follow-up visits. The primary outcome was failure rate measured by the proportions of patients who returned to the clinic for management of pain after receiving dental extractions and analgesic prescriptions.ResultsA total of 3,357 patients in Year-2012 and 3,785 patients in Year-2022 received analgesic prescriptions in conjunction with dental extractions. Combination analgesics were significantly higher in Year-2022 (62.5%) than in Year-2012 (34.9%) (RR=1.79, 95% CI 1.70-1.89. p<0.0001). Combinations analgesics were almost exclusively opioids and 1,166 patients, or 34.7%, received opioids in Year-2012, compared to none received opioids, 49.4% received ibuprofen/ acetaminophen and 13.1% received gabapentin combinations in Year-2022. After surgical extractions, a majority were prescribed opioids (52.4%), followed by ibuprofen (46.2%) in Year-2012. In contrast, a majority received ibuprofen/acetaminophen (56.2%) or gabapentin combinations (17.3%) in Year-2022. Ibuprofen/acetaminophen had a failure rate (2.2%) lower than gabapentin combinations (4.4%) (RR=0.50, 95%CI 0.31-0.83. p=0.01), or opioid combinations (21.4%) (RR=0.10, 95%CI 0.08-0.14. p<0.0001). Failure rate for gabapentin combinations was lower than opioids (RR=0.21, 95%CI 0.14-0.31. p<0.0001).Conclusions and RelevanceThis study showed a paradigm shift from opioids and single medication analgesics to non-opioids and combination analgesics with ibuprofen, acetaminophen and gabapentin as components in prescribing for pain after dental extractions, which presents an opportunity to minimize or eliminate our reliance on opioids for dental pain.
Academic dependency: the influence of the prevailing international biomedical research agenda on Argentina’s CONICET
Authors: García Carrillo M. , Testoni F. , Gagnon M. A. , Rikap C. , Blaustein M. 
Published: May 2022

AbstractBackgroundPrevious research within the field of health and biomedical sciences (HBMS) reported that its prevailing research agenda is determined by leading academic institutions and big pharma companies, prioritizing the exploration of novel pharmacological interventions over research on the socio-environmental determinants of disease. Unlike previous studies, which have relied primarily on qualitative analyses, the aim of this investigation is to quantitatively explore if that prevailing international research agenda influences research in semi-peripheral countries and to which extent.MethodsWe used the Web of Science database and the CorText platform to proxy the HBMS research agenda of a prestigious research institution from Latin America: Argentina’s National Research Council (CONICET). We conducted a bibliometric and lexical analysis of 16,309 HBMS scientific articles whereby CONICET was among the authors’ affiliations. The content of CONICET’s agenda was depicted through co-occurrence network maps of the most prevalent multi-terms found in titles, keywords, and abstracts. We compared our findings with previous reports on the international HBMS research agenda.ResultsIn line with the results previously reported for the prevailing international agenda, we found that multi-terms linked to molecular biology and cancer research hegemonize CONICET’s HBMS research agenda, whereas multi-terms connecting HBMS research with socio-environmental cues are marginal. However, we also found differences with the international agenda: CONICET’s HBMS agenda shows a marginal presence of multi-terms linked to translational medicine, while multi-terms associated with categories such as pathogens, plant research, agrobiotechnology, and food industry are more represented than in the prevailing agenda.ConclusionsIn line with the academic dependency theory, CONICET’s HBMS research agenda shares topics, priorities, and methodologies with the prevailing HBMS international research agenda. However, CONICET’s HBMS research agenda is internally heterogeneous, appearing to be mostly driven by a combination of elements that not only reflect academic dependency but also economic dependency.
Systematic functional annotation workflow for insects
Authors: Bono Hidemasa , Sakamoto Takuma , Kasukawa Takeya , Tabunoki Hiroko 
Published: May 2022

AbstractNext generation sequencing has revolutionized entomological study, rendering it possible to analyze the genomes and transcriptomes of non-model insects. However, use of this technology is often limited to obtaining nucleotide sequences of target or related genes, with many of the acquired sequences remaining unused because other available sequences are not sufficiently annotated. To address this issue, we have developed a functional annotation workflow for transcriptome-sequenced insects to determine transcript descriptions, which represents a significant improvement over the previous method (functional annotation pipeline for insects). The developed workflow attempts to annotate not only the protein sequences obtained from transcriptome analysis but also the ncRNA sequences obtained simultaneously. In addition, the workflow integrates the expression level information obtained from transcriptome sequencing for application as functional annotation information. Using the workflow, functional annotation was performed on the sequences obtained from transcriptome sequencing of stick insect (Entoria okinawaensis) and silkworm (Bombyx mori), yielding richer functional annotation information than that obtained in our previous study. The improved workflow allows more comprehensive exploitation of transcriptome data and is applicable to other insects because the workflow has been openly developed on GitHub.Simple SummaryThe function of all genes encoded in the genome should be studied for genome editing. The genome editing technology can speeds up insect research for functional analysis of genes. Our knowledge about the functional information of genes is still incomplete currently while genome sequencing of an organism can be completed. The functional information has been annotated based solely on the information that has been obtained from the result of previous biological research. However, this information will be important in determining the target genes for genome editing. In particular, it is very important that this information is in machine-readable form because computer programs mainly parse this information for the understanding of biological systems. In this paper, we describe a workflow-based method for annotating gene functions in insects that make use of transcribed sequence information as well as reference genome and protein sequence databases. Using the developed workflow, we annotated functional information of Japanese stick insect and silkworm, including gene expression as well as sequence analysis. The functional annotation information obtained by the workflow will greatly expand the possibilities of entomological research using genome editing.
Accounting for within-species variation in continuous trait evolution on a phylogenetic network
Authors: Teo Benjamin , Rose Jeffrey P. , Bastide Paul , Ané Cécile 
Published: May 2022

ABSTRACTWithin-species trait variation may be the result of genetic variation, environmental variation or measurement error for example. In phylogenetic comparative studies, failing to account for within-species variation has many adverse effects, such as increased error in testing hypotheses about evolutionary correlations, biased estimates of evolutionary rates, and inaccurate inference of the mode of evolution. These adverse effects were demonstrated in studies that considered a tree-like underlying phylogeny. Comparative methods on phylogenetic networks are still in their infancy. The impact of within-species variation on network-based methods has not been studied. Here, we introduce a phylogenetic linear model in which the phylogeny can be a network, to account for within-species variation in the continuous response trait assuming equal within-species variances across species. We show how inference based on the individual values can be reduced to a problem using species-level summaries, even when the within-species variance is estimated. Our method performs well under various simulation settings, and is robust when within-species variances are unequal across species. When phenotypic (within-species) correlations differ from evolutionary (between-species) correlations, estimates of evolutionary coefficients are pulled towards the phenotypic coefficients, for all methods we tested. Also, evolutionary rates are either underestimated or overestimated, depending on the mismatch between phenotypic and evolutionary relationships. We applied our method to morphological and geographical data fromPolemonium. We find a strong negative correlation of leaflet size with elevation, despite a positive correlation within species. Our method can explore the role of gene flow in trait evolution, by comparing the fit of a network to that of a tree. We find marginal evidence for leaflet size being affected by gene flow, and support for previous observations on the challenges of using individual continuous traits to infer inheritance weights at reticulations. Our method is freely available in theJuliapackagePhyloNetworks.
Cell-free Tumor Methylome Analysis of Small Cell Lung Cancer Patients Identifies Subgroups with Prognostic Associations
Authors: Haq Sami Ul , Schmid Sabine , Aparnathi Mansi K. , Hueniken Katrina , Zhan Luna Jia , Sacdalan Danielle , Li Janice J.N. , Meti Nicholas , Patel Devalben , Cheng Dangxiao , Philip Vivek , Tsao Ming S. , Cabanero Michael , de Carvalho Daniel , Liu Geoffrey , Bratman Scott V. , Lok Benjamin H. 
Published: May 2022

AbstractIntroductionSmall cell lung cancer (SCLC) is a highly aggressive type of cancer with a high risk of recurrence. The SCLC methylome may yield biologic insight but is understudied due to difficulty in acquiring primary patient tissue. Here, we comprehensively profile the SCLC methylome using cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq).MethodscfDNA was extracted from plasma samples collected from 74 SCLC patients prior to initiation of first-line treatment and from 20 non-cancer smoker participants. Genomic DNA (gDNA) was also extracted from paired peripheral blood leukocytes from the 74 SCLC patients and 7 accompanying circulating-tumour-cell patient-derived xenografts (CDX). cfDNA and gDNA were used as input for cfMeDIP-seq. We developed PeRIpheral blood leukocyte MEthylation (PRIME) subtraction as an algorithm to improve tumour specificity of cell-free methylome.ResultsSCLC total plasma cfDNA methylation profiles obtained using cfMeDIP-seq are representative of CDX tumour methylation. SCLC cfDNA methylation is distinct from non-cancer plasma. Using PRIME and k-means consensus clustering, we identified two SCLC methylome clusters with prognostic associations. These clusters had methylated biological pathways related to axon guidance, neuroactive ligand−receptor interaction, pluripotency of stem cells, and were differentially methylated at long noncoding RNA, LINEs, SINEs, retrotransposons, and other repeats features.ConclusionsWe have comprehensively profiled the SCLC methylome using cfMeDIP-seq in a large patient cohort and identified methylome clusters with prognostic associations. Our work demonstrates the potential of liquid biopsies in examining SCLC biology encoded in the methylome.
Differential effect of Fas activation on spinal muscular atrophy motoneuron death and induction of axonal growth
Authors: Benlefki Salim , Younes Richard , Challuau Désiré , Bernard-Marissal Nathalie , Hilaire Cécile , Scamps Frédérique , Bowerman Melissa , Kothary Rashmi , Schneider Bernard L , Raoul Cédric 
Published: May 2022

AbstractAmyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are the most common motoneuron diseases affecting adults and infants, respectively. ALS and SMA are both characterized by the selective degeneration of motoneurons. Although different in their genetic etiology, growing evidence indicate that they share molecular and cellular pathogenic signatures that constitute potential common therapeutic targets. We previously described a motoneuron-specific death pathway elicited by the Fas death receptor, whereby vulnerable ALS motoneurons show an exacerbated sensitivity to Fas activation. However, the mechanisms that drive the loss of SMA motoneurons remains poorly understood. Here, we describe an in vitro model of SMA-associated degeneration using primary motoneurons derived from Smn2B/- SMA mice and show that Fas activation selectively triggers death of the proximal motoneurons. Fas-induced death of SMA motoneurons has the molecular signature of the motoneuron-selective Fas death pathway that requires activation of p38 kinase, caspase-8, -9 and -3 as well as upregulation of collapsin response mediator protein 4 (CRMP4). In addition, Rho Kinase (ROCK) is required for Fas recruitment. Remarkably, we found that exogenous activation of Fas also promotes axonal elongation in both wildtype and SMA motoneurons. Axon outgrowth of motoneurons promoted by Fas requires the activity of ERK, ROCK and caspases. This work defines a dual role of Fas signaling in motoneurons that can elicit distinct responses from cell death to axonal growth.