bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seeing social: A neural signature for conscious perception of social interactions
Authors: Varrier Rekha S. , Finn Emily S. 
Published: May 2022

AbstractPercepts of ambiguous information are subjective and depend on observers’ traits and mental states. Social information is some of the most ambiguous content we encounter in our daily lives, yet in experimental contexts, percepts of social interactions—i.e., whether an interaction is present and if so, the nature of that interaction—are often dichotomized as correct or incorrect based on experimenter-assigned labels. Here, we investigated the behavioral and neural correlates of conscious social perception using a large dataset in which neurotypical individuals viewed animations of geometric shapes during fMRI and indicated whether they perceived a social interaction or random motion. Critically, rather than experimenter-assigned labels, we used observers’ own reports of “Social” or “Non-social” to classify percepts and characterize brain activity, including leveraging a particularly ambiguous animation perceived as “Social” by some observers but “Non-social” by others to control for visual input. Observers were biased toward perceiving information as social (versus non-social), and activity across much of the brain was higher during animations ultimately perceived as social. Using “Unsure” reports, we identified several regions that responded parametrically to perceived socialness. Neural responses to social versus nonsocial content diverged early both in time and in the cortical hierarchy. Lastly, individuals with higher internalizing trait scores showed both a higher response bias towards social and an inverse relationship with activity in default-mode and limbic regions while scanning for social information. Findings underscore the subjective nature of social perception and the importance of using observer reports to study percepts of social interactions.Significance StatementSimple animations involving two or more geometric shapes have been used as a gold standard to understand social cognition and impairments thereof. Yet experimenter-assigned labels of what is social versus non-social are frequently used as a ground truth, despite the fact that percepts of such ambiguous social stimuli are highly subjective. Here, we used behavioral and fMRI data from a large sample of neurotypical individuals to show that participants’ responses reveal subtle behavioral biases, help us study neural responses to social content more precisely, and covary with internalizing trait scores. Our findings underscore the subjective nature of social perception and the importance of considering observer reports in studying its behavioral and neural dynamics.
Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases
Authors: Altay Melek Firat , Kumar Senthil T. , Burtscher Johannes , Jagannath Somanath , Strand Catherine , Miki Yasuo , Parkkinen Laura , Holton Janice L. , Lashuel Hilal A. 
Published: May 2022

ABSTRACTThe abnormal aggregation and accumulation of alpha-synuclein (aSyn) in the brain is a defining hallmark of synucleinopathies. Different aSyn conformations and post-translationally modified forms accumulate in pathological inclusions and vary in abundance across synucleinopathies. Relying on antibodies that have not been assessed for their ability to capture the diversity of aSyn species may not provide an accurate estimation of aSyn pathology in human brains or disease models. To address this challenge, we developed and characterised an expanded antibody panel that targets different sequences and post-translational modifications along the length of aSyn and recognises all three aSyn conformations (monomeric, oligomeric, fibrillar). Next, we profiled aSyn pathology across sporadic and familial Lewy body diseases (LBDs) and reveal heterogeneously modified aSyn pathologies rich in Serine 129 phosphorylation but also in Tyrosine 39 nitration and N- and C-terminal tyrosine phosphorylations, scattered to neurons and glia. We also show that aSyn may become hyperphosphorylated during the aggregation and inclusion maturation processes in neuronal and animal models of aSyn aggregation and spreading. The antibody validation pipeline we describe here paves the way for more systematic investigations of aSyn pathological diversity in the human brain and peripheral tissues, and in cellular and animal models of synucleinopathies.
Lighting Up Mechanosensation: dyeing to see PIEZO2
Authors: Villarino Nicholas W. , Dubin Adrienne E. , Patapoutian Ardem , Marshall Kara L. 
Published: May 2022

SUMMARYSensory neurons gather information about mechanical forces from both the environment and internal organs to regulate physiology. PIEZO2 is a mechanosensory ion channel critical for touch, proprioception and bladder stretch sensation, yet its broad expression in sensory neurons and elsewhere suggests it may have undiscovered physiological roles. To fully understand mechanosensory physiology, we must know where and when PIEZO2-expressing neurons detect force. The fluorescent styryl dye FM 1-43 was shown to permeate several ion channels in cell culture and label sensory neurons. Surprisingly, we find that the vast majority of FM 1-43 somatosensory neuron labeling in vivo is dependent on PIEZO2-activity within nerve endings. We illustrate the potential of FM 1-43 by using it to identify novel Piezo2-expressing urethral neurons that are engaged by urination. These data reveal that FM 1-43 is a functional probe for mechanosensitivity via PIEZO2 activation in vivo and will facilitate the characterization of known and novel mechanosensory processes.
The encoding of touch by somatotopically aligned dorsal column subdivisions
Authors: Turecek Josef , Lehnert Brendan P. , Ginty David D. 
Published: May 2022

ABSTRACTThe somatosensory system decodes a range of tactile stimuli to generate a coherent sense of touch. Discriminative touch of the body depends on signals conveyed from peripheral mechanoreceptors to the brain via the spinal cord dorsal column and its brainstem target the dorsal column nuclei (DCN)1, 2. Models of somatosensation emphasize that fast-conducting low- threshold mechanoreceptors (LTMRs) innervating the skin drive the DCN3, 4. However, post- synaptic dorsal column neurons (PSDCs) within the spinal cord dorsal horn also collect mechanoreceptor signals and form a second major input to the DCN5–7. The significance of PSDCs and their contributions to the coding of touch have remained unclear since their discovery. Here, we show that direct LTMR inputs to the DCN convey vibrotactile stimuli with high temporal precision, whereas PSDCs primarily encode touch onset and the intensity of sustained contact into the high force range. LTMR and PSDC signals topographically re-align in the DCN to preserve precise spatial detail. Different DCN neuron subtypes have specialized responses that are generated by unique combinations of LTMR and PSDC inputs. Thus, LTMR and PSDC subdivisions of the dorsal column encode different tactile features and differentially converge in the DCN to generate unique ascending sensory processing streams.
ICAT: A Novel Algorithm to Robustly Identify Cell States Following Perturbations in Single Cell Transcriptomes
Authors: Hawkins Dakota Y. , Zuch Daniel T. , Huth James , Rodriguez-Sastre Nahomie , McCutcheon Kelley R. , Glick Abigail , Lion Alexandra T. , Thomas Christopher F. , Descoteaux Abigail E. , Johnson W. Evan , Bradham Cynthia A. 
Published: May 2022

AbstractMotivationThe detection of distinct cellular identities is central to the analysis of single-cell RNA sequencing experiments. However, in perturbation experiments, current methods typically fail to correctly match cell states between conditions or erroneously remove population substructure. Here we present the novel, unsupervised algorithm ICAT that employs self-supervised feature weighting and control-guided clustering to accurately resolve cell states across heterogeneous conditions.ResultsUsing simulated and real datasets, we show ICAT is superior in identifying and resolving cell states compared to current integration workflows. While requiring no a priori knowledge of extant cell states or discriminatory marker genes, ICAT is robust to low signal strength, high perturbation severity, and disparate cell type proportions. We empirically validate ICAT in a developmental model and find that only ICAT identifies a perturbation-unique cellular response. Taken together, our results demonstrate that ICAT offers a significant improvement in defining cellular responses to perturbation in single-cell RNA sequencing data.Availability and implementationhttps://github.com/BradhamLab/icatSupplemental Methods, Tables and Figures are available online.
Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress
Authors: Naama Maria , Telpaz Shahar , Awad Aya , Ben-Simon Shira , Harshuk-Shabso Sarina , Modilevsky Sonia , Rubin Elad , Sawaed Jasmin , Zelik Lilach , Zigdon Mor , Fadida Nofar , Turjeman Sondra , Werbner Michal , Wongkuna Supapit , Schroeder Bjoern O , Nyska Abraham , Nuriel-Ohayon Meital , Bel Shai 
Published: May 2022

SummaryColonic goblet cells are specialized epithelial cells that secrete mucus to form a barrier between the host and its microbiota, thus preventing bacterial invasion and inflammation. How goblet cells control the amount of mucus they secrete is unclear. We found that constitutive activation of autophagy in mice via Beclin 1 led to production of a thicker and less penetrable mucus layer by reducing endoplasmic reticulum (ER) stress. Accordingly, inhibiting Beclin 1-induced autophagy via Bcl-2 impaired mucus secretion. Furthermore, alleviating intestinal ER stress with a bile acid, or activating the unfolded protein response (UPR) pharmacologically via eIF2α phosphorylation, led to excessive mucus production. Over-production of mucus altered the gut microbiome, with expansion of mucus-utilizing bacteria, and protected from intestinal inflammation. Thus, ER stress is a cell-intrinsic switch that limits mucus secretion, while autophagy maintains proper mucus secretion and intestinal homeostasis by relieving ER stress.
Kinematics of individual muscle units in natural contractions measured in vivo using ultrafast ultrasound
Authors: Lubel Emma , Sgambato Bruno Grandi , Barsakcioglu Deren Y. , Ibáñez Jaime , Tang Meng-Xing , Farina Dario 
Published: May 2022

AbstractObjectiveThe study of human neuromechanical control at the motor unit (MU) level has predominantly focussed on electrical activity and force generation, whilst the link between these, the muscle deformation, has not been widely studied. An important example of this is excitation-contraction coupling (E-C coupling) – the process by which electrical excitation is converted into contraction in the muscle fibres. Despite this being a clear marker for progression of certain diseases, it cannot be measured in vivo in natural contractions. To address this, we analyse the kinematics of muscle units in natural contractions.ApproachWe combine high density surface electromyography (HDsEMG) and ultrafast ultrasound (US) recordings of a mildly contracted muscle (tibialis anterior) to measure the deformation of the muscular tissue caused by individual MU twitches (decomposed from the HDsEMG). With a novel analysis on the US images we identified, with high spatio-temporal precision, the velocity maps associated with single muscle unit movements. From the individual MU profiles obtained from the velocity maps the region of movement, the duration of the mechanical twitch, the total and active contraction times, and the activation time (equivalent to E-C coupling) were computed.Main resultsThe E-C coupling was 3.8 ± 3.0 ms (n = 390), providing the first measurement of this value in for single MUs in non-stimulated contractions. Furthermore, the experimental measures provided the first evidence of single muscle unit twisting during voluntary contractions and showed the presence of MUs with territories with multiple distinct split regions across the muscle region.SignificanceWe show that the combined use of HDsEMG and ultrafast US can allow for the study of kinematics of individual MU twitches, including measurement of the excitation-contraction coupling time under natural neural control conditions. These measurements and characterisations open new avenues for study of neuromechanics in healthy and pathological conditions.
An essential experimental control for functional connectivity mapping with optogenetics
Authors: Tadres David , Shiozaki Hiroshi M. , Tastekin Ibrahim , Stern David L. , Louis Matthieu 
Published: May 2022

AbstractTo establish functional connectivity between two candidate neurons that might form a circuit element, a common approach is to activate an optogenetic tool such as Chrimson in the candidate pre-synaptic neuron and monitor fluorescence of the calcium-sensitive indicator GCaMP in a candidate post-synaptic neuron. While performing such experiments, we found that low levels of leaky Chrimson expression can lead to strong artifactual GCaMP signals in presumptive postsynaptic neurons even when Chrimson is not intentionally expressed in any particular neurons. Withholding all-trans retinal, the chromophore required as a co-factor for Chrimson response to light, eliminates GCaMP signal but does not provide an experimental control for leaky Chrimson expression. Leaky Chrimson expression appears to be an inherent feature of current Chrimson transgenes, since artifactual connectivity was detected with Chrimson transgenes integrated into three different genomic locations (two insertions tested in larvae; a third insertion tested in the adult fly). These false-positive signals may complicate the interpretation of functional connectivity experiments. We illustrate how a no-Gal4 negative control improves interpretability of functional connectivity assays. We also propose a simple but effective procedure to identify experimental conditions that minimize potentially incorrect interpretations caused by leaky Chrimson expression.
50 shades of greenbeard: Robust evolution of altruism based on similarity of complex phenotypes
Authors: Båvik Linnéa M , Mehta Rohan S , Weissman Daniel B 
Published: May 2022

AbstractWe study the evolution of altruistic behavior under a model where individuals choose to cooperate by comparing a set of continuous phenotype tags. Individuals play a donation game and only donate to other individuals that are sufficiently similar to themselves in a multidimensional phenotype space. We find the generic maintenance of robust altruism when phenotypes are multidimensional. Selection for altruism is driven by the coevolution of individual strategy and phenotype; altruism levels shape the distribution of individuals in phenotype space. Low donation rates induce a phenotype distribution that renders the population vulnerable to the invasion of altruists, whereas high donation rates prime a population for cheater invasion, resulting in cyclic dynamics that maintain substantial levels of altruism. Altruism is therefore robust to invasion by cheaters in the long term in this model. Furthermore, the shape of the phenotype distribution in high phenotype dimension—which is potentially more biologically relevant than low phenotype dimension—allows altruists to better resist the invasion by cheaters, and as a result the amount of donation increases with increasing phenotype dimension. We also generalize previous results in the regime of weak selection to two competing strategies in continuous phenotype space, and show that success under weak selection is crucial to success under strong selection in our model. Our results support the viability of a simple similarity-based mechanism for altruism in a well-mixed population.
Leucine-Rich Repeat Kinase 2 limits dopamine D1 receptor signaling in striatum and biases against heavy persistent alcohol drinking
Authors: da Silva e Silva Daniel , Matsui Aya , Murray Erin M. , Mamais Adamantios , Shaw Marlisa , Ron Dorit , Cookson Mark R. , Alvarez Veronica A. 
Published: May 2022

AbstractThe transition from hedonic alcohol drinking to problematic drinking is a hallmark of alcohol use disorder that occurs only in a subset of drinkers. This transition is known to require long-lasting changes in the synaptic drive and the activity of striatal neurons expressing dopamine D1 receptor (D1R). The molecular mechanisms that generate vulnerability in some individuals to undergo the transition are less understood. Here, we report that the Parkinson’s-related protein leucine-rich repeat kinase 2 (LRRK2) modulates striatal D1R function to affect the behavioral response to alcohol and the likelihood that mice transition to heavy, persistent alcohol drinking. Deletion of theLrrk2gene specifically from D1R-expressing neurons potentiates D1R signaling at the cellular and synaptic level, enhancing alcohol-related behaviors and drinking. Mice with cell-specific deletion ofLrrk2are more prone to heavy alcohol drinking and consumption is insensitive to punishment. These findings identify a novel role for LRRK2 function in the striatum in promoting resilience against heavy and persistent alcohol drinking.
High frequency DBS-like optogenetic stimulation of nucleus accumbens dopamine D2 receptor-containing neurons attenuates cocaine reinstatement in male rats
Authors: Swinford-Jackson Sarah E. , Huffman Phillip J. , Knouse Melissa C. , Thomas Arthur S. , Mankame Sharvari , Worobey Samantha J. , Sarmiento Mateo , Coleman Ayanna , Pierce R. Christopher 
Published: May 2022

AbstractBackgroundPrevious work indicated that deep brain stimulation (DBS) of the nucleus accumbens shell in male rats attenuated reinstatement of cocaine seeking, an animal model of craving. However, the potential differential impact of DBS on specific populations of neurons to drive the suppression of cocaine seeking is unknown. Medium spiny neurons in the nucleus accumbens are differentiated by expression of dopamine D1 receptors (D1DRs) or D2DRs, activation of which promotes or inhibits cocaine-related behaviors, respectively. The advent of transgenic rat lines expressing Cre recombinase selectively in D1DR-containing or D2DR-containing neurons, when coupled with Cre-dependent virally mediated gene transfer of channelrhodopsin (ChR2), enabled mimicry of DBS in a selective subpopulation of neurons during complex tasks.HypothesisWe tested the hypothesis that high frequency DBS-like optogenetic stimulation of D1DR-containing neurons in the accumbens shell would potentiate, whereas stimulation of D2DR-containing neurons in the accumbens shell would attenuate, cocaine-primed reinstatement of cocaine seeking.ResultsResults indicated that high frequency, DBS-like optogenetic stimulation of D2DR-containing neurons attenuated reinstatement of cocaine seeking in male rats, whereas DBS-like optogenetic stimulation of D1DR-containing neurons did not alter cocaine-primed reinstatement. Surprisingly, DBS-like optogenetic stimulation did not alter reinstatement of cocaine seeking in female rats. In rats which only expressed eYFP, intra-accumbens optogenetic stimulation did not alter cocaine reinstatement relative to sham stimulation, indicating that the effect of DBS-like stimulation to attenuate cocaine reinstatement is mediated specifically by ChR2 rather than consequent to prolonged light delivery.ConclusionsThese results suggest that DBS of the accumbens attenuates cocaine-primed reinstatement in male rats through the selective manipulation of D2DR-containing neurons.
The dynseq genome browser track enables visualization of context-specific, dynamic DNA sequence features at single nucleotide resolution
Authors: Nair Surag , Barrett Arjun , Li Daofeng , Raney Brian J , Lee Brian T , Kerpedjiev Peter , Ramalingam Vivekanandan , Pampari Anusri , Lekschas Fritz , Wang Ting , Haeussler Maximilian , Kundaje Anshul 
Published: May 2022

AbstractWe introduce the dynseq genome browser track, which displays DNA nucleotide characters scaled by user-specified, base-resolution scores provided in the BigWig file format. The dynseq track enables visualization of context-specific, informative genomic sequence features. We demonstrate its utility in three popular genome browsers for interpreting cis-regulatory sequence syntax and regulatory variant interpretation by visualizing nucleotide importance scores derived from machine learning models of regulatory DNA trained on protein-DNA binding and chromatin accessibility experiments.
A proton pump enhancing photosynthesis links phagocytosis to marine algae symbiogenesis
Authors: Yee Daniel P. , Samo Ty J. , Abbriano Raffaela M. , Shimasaki Bethany , Vernet Maria , Mayali Xavier , Weber Peter K. , Mitchell B. Greg , Hildebrand Mark , Tresguerres Martin 
Published: May 2022

SummaryDiatoms, dinoflagellates, and coccolithophorids are the dominant groups of marine eukaryotic phytoplankton collectively responsible for the majority of primary production in the ocean1. These phytoplankton contain additional intracellular membranes around their chloroplasts derived from ancestral engulfment of red microalgae by unicellular heterotrophic eukaryotes that led to secondary endosymbiosis2. This symbiogenesis hypothesis for the origin of modern secondary endosymbiotic phytoplankton is supported by a wealth of palaeontologic, morphologic, and genomic evidence3–6. However, the selectable evolutionary advantage of these membranes and the physiological significance for extant phytoplankton are unknown. We report that the proton-pumping enzyme V-type H+-ATPase (VHA), ubiquitously used in eukaryotic intercellular digestion, is localized around the chloroplasts of centric diatoms and that VHA-activity significantly enhances photosynthesis over a wide range of oceanic irradiances. Similar results in pennate diatoms, dinoflagellates, and coccolithophorids, but not green or red microalgae, imply a mechanism resulting from the co-option of phagocytic VHA activity into a carbon concentrating mechanism that is common to secondary endosymbiotic phytoplankton. Furthermore, analogous VHA-dependent mechanisms in extant photosymbiotic marine invertebrates7–9 provide functional evidence for an adaptive advantage throughout the transition from endosymbiosis to symbiogenesis. Our results suggest that VHA-dependent enhancement of photosynthesis contributes at least 7% of primary production in the ocean, providing an example of a symbiosis-derived evolutionary innovation with global environmental implications.
Clavis: an open and versatile identification key format
Authors: Koch Wouter , Elven Hallvard , Finstad Anders G. 
Published: May 2022

AbstractThe skills and knowledge needed to recognize and classify taxa are becoming increasingly scarce in the scientific community. At the same time, it is clear that these skills are strongly needed in biodiversity monitoring for management and conservation, especially when carried out by citizen scientists. Formalizing the required knowledge in the form of digital identification keys is one way of making such knowledge more available for professional and amateur observers of biodiversity. In this paper we describe Clavis, an open and versatile data format for capturing the knowledge required for taxon identification through digital keys, allowing for a level of detail beyond that of any current key format. We present the format independently from any particular implementation, as our aim is for Clavis to serve as a basis for interoperable tools and interfaces serving different needs and actors.