bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbially Driven Reversible Actuation and Color Changing Materials
Authors: Kuang Hui Yan , Bonanno Shanna , Chang Wei-Ting , Bower Duncan Q. , Pratt Violet M. , Zerkowski Jillian , Scaperdas Nicholas , Young Lindsey A. , Wilson Daniel J. , Deravi Leila F. , Joshi Neel S. 
Published: October 2023

AbstractA common feature of natural living systems that is underexplored in the field of engineered living materials (ELMs) is macroscale mechanical actuation, as driven by active cellular processes. Here we demonstrate an ELM whereinEscherichia colidrives the reversible swelling and de-swelling actuation of a pH-responsive hydrogel by producing or consuming acidic metabolites. We covalently incorporated a novel synthetic pH indicator dye into the hydrogel network that complements the hydrogel actuation with coordinated color change. Acid production or consumption is controlled by media composition and multiple hydrogel form factors are explored. This approach represents a new form of biologically driven actuation that could be compatible with a range of responsive hydrogel applications.
Vive la difference: why, how, and what trait combinations improve functional community ecology
Authors: Engler Alexandra , Fraser Dylan J. , Peres-Neto Pedro 
Published: October 2023

ABSTRACTAnalyses of functional trait variation across ecological communities offer valuable insights into the factors that influence and predict trait composition, deepening our understanding of community structure. These analyses also shed light on patterns of trait dispersion, including underdispersion and overdispersion, which are often linked to the mechanisms underlying community assembly. However, striking a balance between characterizing complex phenotypes through the integration of comprehensive set of traits while ensuring the preservation of the distinct signals of overdispersion and underdispersion can pose significant challenges. This is because some trait combinations can result in high functional dispersion or overdispersion, while others may lead to underdispersion within the same community. In this study, we provide a rationale for the importance of trait selection in community ecology and develop a framework that optimizes patterns of functional trait variation among communities. We explored the responses of six trait sets along large-scale environmental gradients, using ∼700 lake-fish communities in Ontario (Canada). We started by adopting the conventional approaches of combining all traits as well as leveraging prior knowledge in fish biology to group traits that are functionally related (Diet, Morphology, Temperature Preference). We contrasted these approaches with a novel computational method to select combinations of traits that maximise overdispersion and minimise underdispersion. We found that separating traits according to their functions or by their patterns revealed signals in communities that appeared random when all the traits were pooled together. Combining our computational approach with environmental models revealed that functional patterns could be very well explained by multiple environmental predictors (model R2 up to 0.7). Our study also outlines future selection procedures to further uncover more complex patterns of species associations based on their traits.
Integration of scHi-C and scRNA-seq data defines distinct 3D-regulated and biological-context dependent cell subpopulations
Authors: Zhou Yufan , Li Tian , Choppavarapu Lavanya , Jin Victor X. 
Published: October 2023

AbstractAn integration of 3D chromatin structure and gene expression at single-cell resolution has yet been demonstrated. Here, we develop a computational method, a multiomic data integration (MUDI) algorithm, which integrates scHi-C and scRNA-seq data to precisely define the 3D-regulated and biological-context dependent cell subpopulations or topologically integrated subpopulations (TISPs). We demonstrate its algorithmic utility on the publicly available and newly generated scHi-C and scRNA-seq data. We then test and apply MUDI in a breast cancer cell model system to demonstrate its biological-context dependent utility. We found the newly defined topologically conserved associating domain (CAD) is the characteristic single-cell 3D chromatin structure and better characterizes chromatin domains in single-cell resolution. We further identify 20 TISPs uniquely characterizing 3D-regulated breast cancer cellular states. We reveal two of TISPs are remarkably resemble to high cycling breast cancer persister cells and chromatin modifying enzymes might be functional regulators to drive the alteration of the 3D chromatin structures. Our comprehensive integration of scHi-C and scRNA-seq data in cancer cells at single-cell resolution provides mechanistic insights into 3D-regulated heterogeneity of developing drug-tolerant cancer cells.
Alveolar differentiation drives resistance to KRAS inhibition in lung adenocarcinoma
Authors: Li Zhuxuan , Zhuang Xueqian , Pan Chun-Hao , Yan Yan , Thummalapalli Rohit , Hallin Jill , Torborg Stefan , Singhal Anupriya , Chang Jason C. , Manchado Eusebio , Dow Lukas E. , Yaeger Rona , Christensen James G. , Lowe Scott W. , Rudin Charles M. , Joost Simon , Tammela Tuomas 
Published: October 2023

AbstractLung adenocarcinoma (LUAD), commonly driven byKRASmutations, is responsible for 7% of all cancer mortality. The first allele-specific KRAS inhibitors were recently approved in LUAD, but clinical benefit is limited by intrinsic and acquired resistance. LUAD predominantly arises from alveolar type 2 (AT2) cells, which function as facultative alveolar stem cells by self-renewing and replacing alveolar type 1 (AT1) cells. Using genetically engineered mouse models, patient-derived xenografts, and patient samples we found inhibition of KRAS promotes transition to a quiescent AT1-like cancer cell state in LUAD tumors. Similarly, suppressingKrasinduced AT1 differentiation of wild-type AT2 cells upon lung injury. The AT1-like LUAD cells exhibited high growth and differentiation potential upon treatment cessation, whereas ablation of the AT1-like cells robustly improved treatment response to KRAS inhibitors. Our results uncover an unexpected role for KRAS in promoting intra-tumoral heterogeneity and suggest targeting alveolar differentiation may augment KRAS-targeted therapies in LUAD.SignificanceTreatment resistance limits response to KRAS inhibitors in LUAD patients. We find LUAD residual disease following KRAS targeting is composed of AT1-like cancer cells with the capacity to reignite tumorigenesis. Targeting the AT1-like cells augments responses to KRAS inhibition, elucidating a therapeutic strategy to overcome resistance to KRAS-targeted therapy.
Identification of a convergent spinal neuron population that encodes itch
Authors: Sheahan Tayler D. , Warwick Charles A. , Cui Abby Y. , Baranger David A.A. , Perry Vijay J. , Smith Kelly M. , Manalo Allison P. , Nguyen Eileen K. , Koerber H. Richard , Ross Sarah E. 
Published: October 2023

SummaryItch is a protective sensation that drives scratching. Although specific cell types have been proposed to underlie itch, the neural circuit basis for itch remains unclear. Here, we used two-photon Ca2+imaging of the dorsal horn to visualize the neuronal populations that are activated by itch-inducing agents. We identify a convergent population of spinal neurons that is defined by the expression of GRPR. Moreover, we discover that itch is conveyed to the brain via GRPR-expressing spinal output neurons that target the lateral parabrachial nucleus. Further, we show that nalfurafine, a clinically effective kappa opioid receptor agonist, relieves itch by inhibiting GRPR spinoparabrachial neurons. Finally, we demonstrate that a subset of GRPR spinal neurons show persistent, cell-intrinsic Ca2+oscillations. These experiments provide the first population-level view of the spinal neurons that respond to pruritic stimuli, pinpoint the output neurons that convey itch to the brain, and identify the cellular target of kappa opioid receptor agonists for the inhibition of itch.In briefThrough population imaging, Sheahan et al. identify a network of neurons in the dorsal horn that is activated by pruritogens and find that kappa opioid receptor signaling inhibits itch through the selective inhibition of GRPR spinoparabrachial neurons.HighlightsItch-inducing agents drive activity in a common population of GRPR-expressing spinal interneuronsGRPR spinal projection neurons transmit itch from the spinal cord to the brainKappa opioids reduce itch through the inhibition of GRPR spinoparabrachial neuronsGRPR activation elicits persistent, intrinsic Ca2+oscillations
Synchrony in Networks of Type 2 Interneurons is More Robust to Noise with Hyperpolarizing Inhibition Compared to Shunting Inhibition in Both the Stochastic Population Oscillator and the Coupled Oscillator Regimes
Authors: Baravalle Roman , Canavier Carmen C. 
Published: October 2023

AbstractSynchronization in the gamma band (30-80 Hz) is mediated by PV+ inhibitory interneurons, and evidence is accumulating for the essential role of gamma oscillations in cognition. Oscillations can arise in inhibitory networks via synaptic interactions between individual oscillatory neurons (mean-driven) or via strong recurrent inhibition that destabilizes the stationary background firing rate in the fluctuation-driven balanced state, causing an oscillation in the population firing rate. Previous theoretical work focused on model neurons with Hodgkin’s type 1 excitability (integrators) connected by current-based synapses. Here we show that networks comprised of simple type 2 oscillators (resonators) exhibit a supercritical Hopf bifurcation between synchrony and asynchrony and a gradual transition via cycle skipping from coupled oscillators to stochastic population oscillator, as previously shown for type 1. We extended our analysis to homogeneous networks with conductance rather than current based synapses and found that networks with hyperpolarizing inhibitory synapses were more robust to noise than those with shunting synapses, both in the coupled oscillator and stochastic population oscillator regime. Assuming that reversal potentials are uniformly distributed between shunting and hyperpolarized values, as observed in one experimental study, converting synapses to purely hyperpolarizing favored synchrony in all cases, whereas conversion to purely shunting synapses made synchrony less robust except at very high conductance strengths. In mature neurons the synaptic reversal potential is controlled by chloride cotransporters that control the intracellular concentrations of chloride and bicarbonate ions, suggesting these transporters as a potential therapeutic target to enhance gamma synchrony and cognition.Significance StatementBrain rhythms in the gamma frequency band (30-80 Hz) depend on the activity of inhibitory interneurons and evidence for a causal role for gamma oscillations in cognitive functions is accumulating. Here we extend previous studies on synchronization mechanisms to interneurons that have an abrupt threshold frequency below which they cannot sustain firing. In addition to current based synapses, we examined inhibitory networks with conductance based synapses. We found that if the reversal potential for inhibition was below the average membrane potential (hyperpolarizing), synchrony was more robust to noise than if the reversal potential was very close to the average potential (shunting). These results have implications for therapies to ameliorate cognitive deficits.
Context dependent multisensory integration: Mechanosensation depends on luminance for robust performance
Authors: Sharma Varun P , Sponberg Simon 
Published: October 2023

AbstractMultisensory, goal-directed behaviors are ubiquitous and essential in animals across taxa. Individual sensory modalities may be significantly tuned by environmental context, and yet they must continue to combine and produce multisensory behaviors. This necessitates either behavioral robustness or goal-relevant adaptation in sensorimotor systems. In the case of hover-feeding hawkmoths of the speciesManduca sexta, proboscis mechanosensation and vision are known to combine linearly in tracking of moving flowers. This tracking behavior is affected by light-levels, and visual compensation is necessary for robust flower-tracking. Whether the mechanosensory response also adjusts to light-level, in order to produce linear combination across luminance contexts, is not known. We applied control theoretic analyses to study integration of mechanosensory and visual information in flower tracking hawkmoths in the context of high luminance. This was performed using a two-part robotic flower system. Under the conditions of high luminance, we verified the linear combination of mechanosensory and visual systems, and the complementary modulation of these systems. We show that both systems tune their frequency response with changing environmental light level,while keeping their combined error low at relevant frequencies. Thus, the animal adapts to changing conditions, across modalities, even when only one of the modalities (vision) is directly affected. This cross-talk between sensorimotor systems is constrained, and possibly driven, by performance requirements.
Sensory adaptation modulates coding and perceptual quality of odor mixtures
Authors: Pírez Nicolás , Gascue Federico Andrés , Locatelli Fernando Federico 
Published: October 2023

AbstractThe sensitivity of the sensory systems must be dynamic in order to allow animals to adjust their behavior based on experience to optimize detection of relevant information while ignoring stimuli with no predictive value. In this context, one of the main phenomena that modulate the olfactory system is sensory adaptation. It is usually defined as a decrease in the sensitivity or response to a stimulus after a sustained exposure to it. Adaptation may occur in brief intervals of time and depends on the immediate prior experience. Here, we investigate aspects of the function and neurobiology of sensory adaptation in olfaction using the honeybeeApis mellifera. By means of electroantennograms we set stimulation protocols that induced sensory adaptation. We show that activation patterns that encode mixtures of odorants in the antennal lobe are drastically altered after sensory adaptation, favoring the representation of stimuli that are present at sub-threshold concentrations. We investigate the effects that sensory adaptation has on the perception of odorant mixtures and show that adapting animals to one of the components of a binary mixture, reduces the appetitive learning of the adapted stimulus and enhances the detection and learning of the non-adapted stimulus in cases in which it would stay normally occluded. These results suggest that olfactory sensory adaptation is critical to allow detection of minor components present in complex mixtures, emphasizing its role as a fundamental mechanism to improve sensitivity to discrete stimuli.
Remyelination protects neurons from DLK-mediated neurodegeneration
Authors: Duncan Greg J. , Ingram Sam D , Emberley Katie , Hill Jo , Cordano Christian , Abdelhak Ahmed , McCane Michael , Jenks Jennifer E. , Jabassini Nora , Ananth Kirtana , Ferrara Skylar J. , Stedelin Brittany , Sivyer Benjamin , Aicher Sue A. , Scanlan Thomas , Watkins Trent A. , Mishra Anusha , Nelson Jonathan W. , Green Ari J. , Emery Ben 
Published: October 2023

AbstractChronic demyelination and oligodendrocyte loss deprive neurons of crucial support. It is the degeneration of neurons and their connections that drives progressive disability in demyelinating disease. However, whether chronic demyelination triggers neurodegeneration and how it may do so remain unclear. We characterize two genetic mouse models of inducible demyelination, one distinguished by effective remyelination and the other by remyelination failure and chronic demyelination. While both demyelinating lines feature axonal damage, mice with blocked remyelination have elevated neuronal apoptosis and altered microglial inflammation, whereas mice with efficient remyelination do not feature neuronal apoptosis and have improved functional recovery. Remyelination incapable mice show increased activation of kinases downstream of dual leucine zipper kinase (DLK) and phosphorylation of c-Jun in neuronal nuclei. Pharmacological inhibition or genetic disruption of DLK block c-Jun phosphorylation and the apoptosis of demyelinated neurons. Together, we demonstrate that remyelination is associated with neuroprotection and identify DLK inhibition as protective strategy for chronically demyelinated neurons.HighlightsCharacterization of a transgenic mouse model of demyelination without subsequent remyelinationRemyelination protects neurons from axon loss and neuronal apoptosisMAPK and c-Jun phosphorylation are increased in mice featuring remyelination failureDLK is necessary for the apoptosis of chronically demyelinated neurons
Incorporating extrinsic noise into mechanistic modelling of single-cell transcriptomics
Authors: Öcal Kaan 
Published: October 2023

AbstractA mechanistic understanding of single-cell transcriptomics data requires differentiating between intrinsic, extrinsic and technical noise, but an abundance of the latter often obscures underlying biological patterns. Accurately modelling such data in the presence of large cell-to-cell heterogeneity due to factors such as cell size and cell cycle stage is a challenging task. We propose a tractable, fully Bayesian framework for mechanistic modelling of single-cell RNA sequencing data in the presence of cellular heterogeneity. Applied to murine transcriptomics data, we show that cell-specific effects can significantly alter previously inferred dynamics of individual genes. Our implementation is statistically exact and readily extensible, and we demonstrate how it can be combined with Bayesian model selection to compare various models of gene expression and measurement noise.
A Syndrome of Joint Hypermobility, Autonomic Dysfunction, Gastrointestinal Dysfunction and Autoimmune markers (JAG-A): Clinical Associations and Response to Intravenous Immunoglobulin Therapy
Authors: Pasricha Pankaj J. , McKnight Megan , Villatoro Luisa , Barahona Guillermo , Brinker Jeffrey , Hui Ken , Polydefkis Michael , Burns Robert , McMahan Zsuzsanna H. , Gould Neda , Goodman Brent , Hentz Joseph , Treisman Glenn 
Published: October 2023

AbstractBackground and aimsWe examined autoimmunity markers (AIMs) in patients with unexplained gastrointestinal symptoms, their relationship to joint hypermobility/hypermobility spectrum disorder (JH/HSD) and the response to intravenous immunoglobulin (IVIG).MethodsThe study comprised of three cohorts, consisting of adolescent or adult patients with gastrointestinal symptoms affecting more than one region of the gut who underwent laboratory tests, whole gut transit studies, and autonomic testing. AIM positive patients were defined based on a diagnosis of known rheumatic disease with one positive seromarker of autoimmunity or at least two positive seromarkers. The three cohorts were (a) Retrospective (n = 300); (b) Prospective validation cohort (n =133); and (c) Patients with AIM (n=32) prospectively treated with IVIG and followed with standardized questionnaires.ResultsAIMs were found in 39% of the retrospective cohort, of which the majority had a known rheumatic disorder. In the prospective cohort AIMs were noted in 35% overall but the rate was much higher in patients with JH/HSD (49% versus 21%, p=0.001). Significantly more patients with AIMs had elevations of C-reactive protein and erythrocyte sedimentation rate along with trends in tilt table test and HLADQ8 positivity. IVIG treatment was associated with a significantly greater overall treatment effect than controls and robust improvement over baseline in pain, gastrointestinal and autonomic symptoms.ConclusionsAutoimmune markers and autonomic dysfunction are common in patients with unexplained gastrointestinal dysmotility, especially in those with joint hypermobility. IVIG treatment was associated with symptomatic improvement in both gastrointestinal and autonomic symptoms. These results need to be corroborated by randomized clinical trials of immunomodulators but suggest that an autoimmune etiology may be important to diagnose in such patients. Clinicaltrials.gov,NCT04859829
Non-obstetric risk factors for deformational plagiocephaly: A systematic review and meta-analysis
Authors: Hillyar Dr Christopher , Bishop Natalie , Bell-Davies Frances J , Ong Juling 
Published: October 2023

AbstractPlagiocephaly is defined as asymmetrical distortion of the skull resulting in an oblique trapezoid or parallelogram head shape. In the absence of skull growth restriction due to craniosynostosis, deformational plagiocephaly (DP) is caused by deformational forces acting on one side of the back of the head which distorts the normal symmetry of the skull. The aims of this systematic review and meta-analysis were to critically assess the evidence for non-obstetric risk factors for DP and to make evidence-based recommendations for reducing the prevalence of DP. A search of PubMed and Web of Science was performed covering 21 August 2010 to 21 August 2022. The searches yielded 159 articles, of which 18 articles were eligible for inclusion in this study. 43 non-obstetric factors were identified. Of these, a total of 17 factors were associated with DP. With the notable exceptions of maternal age, mechanical ventilation and tummy time, these associations were either supported by non-conflicting evidence or a meta-analysis that resolved conflicting evidence into a significant association. Thirteen factors had significant odds ratios that ranged from 1.10 (mechanical ventilation) to 7.15 (insufficient vitamin D intake). Of the five factors assessed by meta-analysis (male gender, reaching fewer motor milestones by six months of age, maternal education level, head position preference, sleeping position), only one (male gender) was associated with significant inter-study heterogeneity. No evidence of publication bias was detected. In summary, this study provides the most comprehensive meta-analytic assessment of non-obstetric factors associated with DP published to date. It provides 13 evidence-based recommendations which can be adopted by healthcare systems globally, to reduce the prevalence of DP and its impact on child development.