bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained pupil responses are modulated by predictability of auditory sequences
Authors: Milne Alice , Zhao Sijia , Tampakaki Christina , Bury Gabriela , Chait Maria 
Published: November 2020

AbstractThe brain is highly sensitive to auditory regularities and exploits the predictable order of sounds in many situations, from parsing complex auditory scenes, to the acquisition of language. To understand the impact of stimulus predictability on perception, it is important to determine how the detection of predictable structure influences processing and attention. Here we use pupillometry to gain insight into the effect of sensory regularity on arousal. Pupillometry is a commonly used measure of salience and processing effort, with more perceptually salient or perceptually demanding stimuli consistently associated with larger pupil diameters.In two experiments we tracked human listeners’ pupil dynamics while they listened to sequences of 50ms tone pips of different frequencies. The order of the tone pips was either random, contained deterministic (fully predictable) regularities (experiment 1, n = 18, 11 female) or had a probabilistic regularity structure (experiment 2, n = 20, 17 female). The sequences were rapid, preventing conscious tracking of sequence structure thus allowing us to focus on the automatic extraction of different types of regularities. We hypothesized that if regularity facilitates processing by reducing processing demands, a smaller pupil diameter would be seen in response to regular relative to random patterns. Conversely, if regularity is associated with heightened arousal and attention (i.e. engages processing resources) the opposite pattern would be expected. In both experiments we observed a smaller sustained (tonic) pupil diameter for regular compared with random sequences, consistent with the former hypothesis and confirming that predictability facilitates sequence processing.Significance statementThe brain is highly sensitive to auditory regularities. To appreciate the impact that detecting predictability has on perception, we need to better understand how a predictable structure influences processing and attention. We recorded listeners’ pupil responses to sequences of tones that followed either a predictable or unpredictable pattern, as the pupil can be used to implicitly tap into these different cognitive processes. We found that the pupil showed a smaller sustained diameter to predictable sequences, indicating that predictability eased processing rather than boosted attention. The findings suggest that the pupil response can be used to study the automatic extraction of regularities, and that the effects are most consistent with predictability helping the listener to efficiently process upcoming sounds.
LongTron: Automated Analysis of Long Read Spliced Alignment Accuracy
Authors: Wilks Christopher , Schatz Michael C. 
Published: November 2020

AbstractMotivationLong read sequencing has increased the accuracy and completeness of assemblies of various organisms’ genomes in recent months. Similarly, spliced alignments of long read RNA sequencing hold the promise of delivering much longer transcripts of existing and novel isoforms in known genes without the need for error-prone transcript assemblies from short reads. However, low coverage and high-error rates potentially hamper the widespread adoption of long-read spliced alignments in annotation updates and isoform-level expression quantifications.ResultsAddressing these issues, we first develop a simulation of error modes for both Oxford Nanopore and PacBio CCS spliced-alignments. Based on this we train a Random Forest classifier to assign new long-read alignments to one of two error categories, a novel category, or label them as non-error. We use this classifier to label reads from the spliced-alignments of the popular aligner minimap2, run on three long read sequencing datasets, including NA12878 from Oxford Nanopore and PacBio CCS, as well as a PacBio SKBR3 cancer cell line. Finally, we compare the intron chains of the three long read alignments against individual splice sites, short read assemblies, and the output from the FLAIR pipeline on the same samples.Our results demonstrate a substantial lack of precision in determining exact splice sites for long reads during alignment on both platforms while showing some benefit from postprocessing. This work motivates the need for both better aligners and additional post-alignment processing to adjust incorrectly called putative splice-sites and clarify novel transcripts support.Availability and implementationSource code for the random forest implemented in python is available athttps://github.com/schatzlab/LongTronunder the MIT license. The modified version of GffCompare used to construct Table 3 and related is here:https://github.com/ChristopherWilks/gffcompare/releases/tag/0.11.2LTSupplementary InformationSupplementary notes and figures are available online.
The unfolded protein response links tumor aneuploidy to local immune dysregulation
Authors: Xian Su , Searles Stephen , Sahani Paras , Waller T. Cameron , Jepsen Kristen , Carter Hannah , Zanetti Maurizio 
Published: November 2020

AbstractAneuploidy is a chromosomal abnormality associated with poor prognosis in many cancer types. Here we tested the hypothesis that the unfolded protein response (UPR) links mechanistically aneuploidy and local immune dysregulation. Using a single somatic copy-number alteration (SCNA) score inclusive of whole-chromosome, arm and focal chromosome alterations in a pan-cancer analysis of 9,375 samples in The Cancer Genome Atlas (TCGA) database, we found an inverse correlation with a cytotoxicity (CYT) score across disease stages. Co-expression patterns of UPR genes changed substantially between SCNAlowand SCNAhighgroups. Pathway activity scores showed increased activity by multiple branches of the UPR in response to aneuploidy. The PERK branch showed the strongest association with a reduced CYT score. The conditioned medium of aneuploid cells transmitted XBP1 splicing and caused IL-6 and Arginase1 transcription in receiver bone marrow-derived macrophages. We propose the UPR as a mechanistic link between aneuploidy and immune dysregulation in the tumor microenvironment.Statement of SignificanceAneuploidy accumulates over the life of a tumor and is associated with poor prognosis. Tumor progression is also associated with a progressive immune dysregulation. To explain these complex and concurrent disorders we tested the hypothesis that the unfolded protein could represent the link between aneuploidy and a dysregulation of local immunity favoring tumor progression.
Distributed Representation of Taste Quality by Second-Order Gustatory Neurons inDrosophila
Authors: Snell Nathaniel J. , Fisher John D. , Hartmann Griffin G. , Talay Mustafa , Barnea Gilad 
Published: November 2020

SUMMARYSweet and bitter compounds excite different sensory cells and drive opposing behaviors. It is commonly thought that the neural circuits linking taste sensation to behavior conform to a labeled-line architecture, but inDrosophila, evidence for labeled lines beyond first-order neurons is lacking. To address this, we devisedtrans-Tango(activity), a strategy for calcium imaging of second-order gustatory projection neurons based ontrans-Tango, a genetic transsynaptic tracing technique. We found distinct projection neuron populations that respond to sweet and bitter tastants. However, the bitter-responsive population was also activated by water alone. We further discovered that bitter tastants evoke activity upon both stimulus onset and offset. Bitter offset responses are exhibited by both first- and second-order gustatory neurons, but these responses are distributed among multiple types of projection neurons in the second order. These findings suggest a more complex coding scheme for gustatory information than can be explained by a labeled line model.
ASCL1 represses a latent osteogenic program in small cell lung cancer in multiple cells of origin
Authors: Olsen Rachelle R. , Kastner David W. , Ireland Abbie S. , Groves Sarah M. , Pozo Karine , Whitney Christopher P. , Guthrie Matthew R. , Wait Sarah J. , Soltero Danny , Witt Benjamin L. , Quaranta Vito , Johnson Jane E. , Oliver Trudy G. 
Published: November 2020

AbstractASCL1 is a neuroendocrine-lineage-specific oncogenic driver of small cell lung cancer (SCLC), highly expressed in a significant fraction of tumors. However, ~25% of human SCLC are ASCL1-low and associated with low-neuroendocrine fate and high MYC expression. Using genetically-engineered mouse models (GEMMs), we show that alterations inRb1/Trp53/Mycin the mouse lung induce an ASCL1+state of SCLC in multiple cells of origin. Genetic depletion of ASCL1 in MYC-driven SCLC dramatically inhibits tumor initiation and progression to the NEUROD1+subtype of SCLC. Surprisingly, ASCL1 loss converts tumors to a SOX9+mesenchymal/neural-crest-stem-like state that can differentiate into RUNX2+bone tumors. ASCL1 represses SOX9 expression, as well as WNT and NOTCH developmental pathways, consistent with human gene expression data. Together, SCLC demonstrates remarkable cell fate plasticity with ASCL1 repressing the emergence of non-endodermal stem-like fates that have the capacity for bone differentiation.
Structure of the RPAP3:TRBP interaction reveals an involvement of the HSP90/R2TP chaperone complex in dsRNA pathways
Authors: Abel Yoann , Charron Christophe , Bourguignon-Igel Valérie , Quinternet Marc , Chagot Marie-Eve , Verheggen Céline , Branlant Christiane , Bertrand Edouard , Manival Xavier , Charpentier Bruno , Rederstorff Mathieu 
Published: November 2020

ABSTRACTMicroRNAs silence mRNAs by guiding the RISC complex. RISC assembly requires cleavage of pre-miRNAs by Dicer, assisted by TRBP or PACT, and the transfer of miRNAs to AGO proteins. The R2TP complex is an HSP90 cochaperone involved in the assembly of ribonucleoprotein particles. Here, we show that the R2TP component RPAP3 binds TRBP but not PACT. Specifically, the RPAP3-TPR1 domain interacts with the TRBP-dsRBD3 and the 1.5 Å resolution crystal structure of this complex is presented. We identify key residues involved in the interaction and show that binding of TRBP to RPAP3 or Dicer is mutually exclusive. In contrast, RPAP3 can simultaneously bind TRBP and HSP90. Interestingly, AGOs and Dicer are sensitive to HSP90 inhibition and TRBP becomes sensitive in absence of RPAP3. These data indicate that the HSP90/R2TP chaperone is an important cofactor of proteins involved in dsRNA pathways.
Genetically-identified cell types in avian pallium mirror core principles of excitatory and inhibitory neurons in mammalian cortex
Authors: Spool Jeremy A. , Macedo-Lima Matheus , Scarpa Garrett , Morohashi Yuichi , Yazaki-Sugiyama Yoko , Remage-Healey Luke 
Published: November 2020

AbstractIn vertebrates, advanced cognitive abilities are associated with a highly developed telencephalic pallium. In mammals, the six-layered neocortex of the pallium is composed of excitatory neurons and inhibitory interneurons, organized across layers into microcircuits. These organizational principles are proposed to support efficient, high-level information processing. Comparative perspectives across vertebrates provide a lens to understand what common features of pallium are important for complex cognition. For non-mammalian vertebrates that exhibit complex cognitive abilities, such as birds, the physiology of identified pallial cell types and their circuit organization are largely unresolved. Using viral tools to target excitatory vs. inhibitory neurons in the zebra finch auditory association pallium, we systematically tested predictions derived from mammalian neocortex. We identify two segregated neuronal populations that exhibit profound physiological and computational similarities with mammalian excitatory and inhibitory neocortical cells. Specifically, despite dissimilarities in gross architecture, avian association pallium exhibits neocortex-typical coding principles, and inhibitory-dependent cortical synchrony, gamma oscillations, and local suppression. Our findings suggest parallel evolution of physiological and network roles for pallial cell types in amniotes with substantially divergent pallial organization.
Swimming, fast and slow: strategy and survival of bacterial predators in response to chemical cues
Authors: Carlson M , Seyler S L , Pressé S 
Published: November 2020

ABSTRACTBdellovibrio bacteriovorusis a predatory bacterium that preys upon gram-negative bacteria. As such,B. bacteriovorushas the potential to control antibiotic-resistant pathogens and biofilm populations. To survive and reproduce,B. bacteriovorusmust locate and infect a host cell. However, in the temporary absence of prey, it is largely unknown howB. bacteriovorusmodulate their motility patterns in response to physical or chemical environmental cues to optimize their energy expenditure. To investigateB. bacteriovorus’predation strategy, we track and quantify their motion by measuring speed distributions and velocity autocorrelations as a function of starvation time. An initial unimodal speed distribution, relaxing to that expected for pure diffusion at long times, may be expected. Instead, we observe a complex, non-Brownian, search strategy as evidenced by distinctly bimodal speed distributions. That is, for an increasing amount of time over whichB. bacteriovorusis starved, we observe a progressive re-weighting from a fast mode to a slow mode in the speed distribution obtained over consecutive frames. By contrast to its predator,B. bacteriovorus’prey,Escherichia coliexhibits almost immediate decrease to a speed expected from passive diffusion following resuspension from rich to poor media. Distributions of trajectory-averaged speeds forB. bacteriovorusare largely unimodal, indicating nontrivialswitchingbetween fast and slow swimming modes within individual observed trajectories rather than there being distinct fast and slow populations. We also find thatB. bacteriovorus’slow speed mode is not merely caused by the diffusion of inviable bacteria as subsequent spiking experiments show that bacteria can be resuscitated and bimodality restored. Indeed, starvedB. bacteriovorusmay modulate the frequency and duration of active swimming as a means of balancing energy consumption and procurement. Our results are evidence of a nontrivial predation strategy, which contrasts with the comparatively simple search pattern of its prey, in response to environmental cues.SIGNIFICANCEBdellovibrio bacteriovorusis a predatory bacterium that is poised to help control gram-negative bacterial populations in environmental and clinical settings. In order to locate its prey in solution,B. bacteriovorusmust expend energy in order to fight hydrodynamic drag. This raises the question as to howB. bacteriovorusshould expend its energy reserves in the absence of chemical cues from its prey. Here, we show thatB. bacteriovorusadapts its motility to minimize energy expenditure (due to fighting drag in swimming) upon prolonged starvation by exploiting two modes of motility. This is in sharp contrast to its prey,E. coli, which shows little active motility under starvation conditions.
Impact of conscious awareness on pupillary response to faces
Authors: Yang Yung-Hao , Liao Hsin-I , Furukawa Shigeto 
Published: November 2020

AbstractPupillary response reflects not only ambient light changes but also top-down factors. Nevertheless, it remains inconclusive whether the conscious awareness modulates the pupillary response. We investigated pupillary responses to faces under different conscious conditions using continuous flash suppression (CFS). In Experiment 1 and 2, we used a breaking-CFS procedure in which participants had to detect the face from suppression. Results showed that the pupil constricted more to upright faces than to inverted faces before the face was detected, suggesting that pupillary responses reflect face processing entering consciousness. In Experiment 3 and 4, we used a fixed duration-CFS procedure with both objective performance and subjective reports. Different pupillary responses were observed only when the participant was aware of the face. These findings imply that the conscious awareness is critical for modulating autonomic neural circuits of the pupillary function. The corresponding pupillary responses may reflect dynamic processes underlying conscious awareness.
Chirality-dependent anti-inflammatory effect of glutathione after spinal cord injury
Authors: Kim Seong Jun , Ko Wan-Kyu , Han Gong Ho , Lee Daye , Lee Yuhan , Sheen Seung Hun , Hong Je Beom , Sohn Seil 
Published: November 2020

AbstractNeuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared to that in L-GSH-treated rats (***p< 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared to those outcomes in L-GSH-treated rats (**p< 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial scar via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared to L-GSH (***p< 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (***p< 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases.
Neurons in the dorso-central division of zebrafish pallium respond to change in visual numerosity
Authors: Messina Andrea , Potrich Davide , Schiona Ilaria , Sovrano Valeria Anna , Fraser Scott E. , Brennan Caroline H. , Vallortigara Giorgio 
Published: November 2020

AbstractNon-symbolic number cognition based on an approximate sense of magnitude has been documented in zebrafish. Here we investigated for the first time its neural bases. Zebrafish were habituated to a set of three or nine small dots associated with food reward. During habituation trials, the dots changed in their individual size, position and density maintaining their numerousness and overall surface area. In the dishabituation test, zebrafish faced a change (i) in number (from three to nine or vice versa with the same overall surface), (ii) in shape (with the same overall surface and number), or (iii) in size (with the same shape and number); in a control group (iv) zebrafish faced the same familiar stimuli as during the habituation. Using qPCR to measure modulation of the expression of the immediate early genes c-fos and egr-1 and in-situ hybridization to count egr1-positive cells we found a specific and selective activation of the caudal part of the dorso-central (Dc) division of the zebrafish pallium upon change in numerosity. As pallial regions are implicated in number cognition in mammals and birds, these findings support the existence of an evolutionarily conserved mechanism for approximate magnitude and provide an avenue for exploring the underlying molecular correlates.
Water-mediated interactions determine helix formation of peptides in open nanotubes
Authors: Suvlu Dylan , Thirumalai D. , Rasaiah Jayendran C. 
Published: November 2020

AbstractWater-mediated interactions (WMIs) play diverse roles in molecular biology. They are particularly relevant in geometrically confined spaces such as the interior of the chaperonin, at the interface between ligands and their binding partners, and in the ribosome tunnel. Inspired in part by the geometry of the ribosome tunnel, we consider confinement effects on the stability of peptides. We describe results from replica exchange molecular dynamics simulations of a system containing a 23-alanine or 23-serine polypeptide confined to non-polar and polar nanotubes in the gas phase and when open to a water reservoir. We quantify the effect of water in determining the preferred conformational states of these polypeptides by calculating the difference in the solvation free energy for the helix and coil states in the open nanotube in the two phases. Our simulations reveal several possibilities. We find that nanoscopic confinement preferentially stabilizes the helical state of polypeptides with hydrophobic side chains, which is explained by the entropic stabilization mechanism proposed on the basis of polymer physics. Polypeptide chains with hydrophilic side chains can adopt helical structures within nanotubes, but helix formation is sensitive to the nature of the nanotube due to WMIs. We elaborate on the potential implications of our findings to the stability of peptides in the ribosome tunnel.
N-Terminus ofDrosophila MelanogasterMSL1 Is Critical for Dosage Compensation
Authors: Babosha Valentin , Klimenko Natalia , Revel-Muroz Anastasia , Tikhonova Evgeniya , Georgiev Pavel , Maksimenko Oksana 
Published: November 2020

AbstractThe male-specific lethal complex (MSL), which consists of five proteins and two non-coding roX RNAs, is involved in the transcriptional enhancement of X-linked genes to compensate for the sex chromosome monosomy inDrosophilaXY males compared with XX females. The MSL1 and MSL2 proteins form the heterotetrameric core of MSL complex and are critical for the specific recruitment of the complex to the high-affinity “entry” sites (HAS) on the X chromosome. In this study, we demonstrated that the N-terminal region of MSL1 is critical for stability and functions of MSL1. Amino acid deletions and substitutions in the N-terminal region of MSL1 strongly affect both the interaction with roX2 RNA and the MSL complex binding to HAS on the X chromosome. In particular, substitution of the conserved N-terminal amino-acids 3-7 in MSL1 (MSL1GS) affects male viability similar to the inactivation of genes encoding roX RNAs. In addition, MSL1GSbinds to promoters such as MSL1WTbut does not co-bind with MSL2 and MSL3 to X chromosomal HAS. However, overexpression of MSL2 partially restores the dosage compensation. Thus, the interaction of MSL1 with roX RNA is critical for the efficient assembly of the MSL complex on HAS of the male X chromosome.