bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metacommunity analyses show increase in ecological specialisation throughout the Ediacaran
Authors: Eden Rebecca , Manica Andrea , Mitchell Emily G. 
Published: May 2021

AbstractThe first animals appear during the late Ediacaran (572 – 541 Ma); an initial diversity increase was followed by a drop, interpreted as catastrophic mass extinction. We investigate the processes underlying these changes using the “Elements of Metacommunity Structure” framework. The oldest metacommunity was characterized by taxa with wide environmental tolerances, and limited specialisation and inter-taxa interactions. Structuring increased in the middle metacommunity, with groups of taxa sharing synchronous responses to environmental gradients, aggregating into distinct communities. This pattern strengthened in the youngest metacommunity, with communities showing strong environmental segregation and depth structure. Thus, metacommunity structure increased in complexity, with increased specialisation and resulting competitive exclusion, not a catastrophic environmental disaster, leading to diversity loss in the terminal Ediacaran, revealing that the complex eco-evolutionary dynamics associated with Cambrian diversification were established in the Ediacaran.
Unsupervised learning for robust working memory
Authors: Gu Jintao , Lim Sukbin 
Published: May 2021

AbstractWorking memory is a core component of critical cognitive functions such as planning and decision-making. Persistent activity that lasts long after the stimulus offset has been considered a neural substrate for working memory. Attractor dynamics based on network interactions can successfully reproduce such persistent activity. However, it suffers from a fine-tuning of network connectivity, in particular, to form continuous attractors suggested for working memory encoding analog signals. Here, we investigate whether a specific form of synaptic plasticity rules can mitigate such tuning problems in two representative working memory models, namely, rate-coded and location-coded persistent activity. We consider two prominent types of plasticity rules, differential plasticity targeting the slip of instant neural activity and homeostatic plasticity regularizing the long-term average of activity, both of which have been proposed to fine-tune the weights in an unsupervised manner. Consistent with the findings of previous works, differential plasticity alone was enough to recover a graded-level persistent activity with less sensitivity to learning parameters. However, for the maintenance of spatially structured persistent activity, differential plasticity could recover persistent activity, but its pattern can be irregular for different stimulus locations. On the other hand, homeostatic plasticity shows a robust recovery of smooth spatial patterns under particular types of synaptic perturbations, such as perturbations in incoming synapses onto the entire or local populations, while it was not effective against perturbations in outgoing synapses from local populations. Instead, combining it with differential plasticity recovers location-coded persistent activity for a broader range of perturbations, suggesting compensation between two plasticity rules.Author SummaryWhile external error and reward signals are essential for supervised and reinforcement learning, they are not always available. For example, when an animal holds a piece of information in mind for a short delay period in the absence of the original stimulus, it cannot generate an error signal by comparing its memory representation with the stimulus. Thus, it might be helpful to utilize an internal signal to guide learning. Here, we investigate the role of unsupervised learning for working memory maintenance, which acts during the delay period without external inputs. We consider two prominent classes of learning rules, namely, differential plasticity, which targets the slip of instant neural activity, and homeostatic plasticity, which regularizes the long-term average of activity. The two learning rules have been proposed to fine-tune the synaptic weights without external teaching signals. Here, by comparing their performance under various types of network perturbations, we reveal the conditions under which each rule can be effective and suggest possible synergy between them.
Cortical Oscillatory Dysrhythmias in Visual Snow Syndrome: A MEG Study
Authors: Hepschke Jenny L. , Seymour Robert A , He Wei , Etchell Andrew , Sowman Paul F , Fraser Clare L 
Published: May 2021

AbstractVisual Snow (VS) refers to the persistent visual experience of static in the whole visual field of both eyes. It is often reported by patients with migraine and co-occurs with conditions like tinnitus and tremor. The underlying pathophysiology of the condition is poorly understood. Previously we hypothesised, that VSS may be characterised by disruptions to rhythmical activity within the visual system1.To test this, data from 18 patients diagnosed with visual snow syndrome (VSS), and 16 matched controls, were acquired using Magnetoencephalography (MEG). Participants were presented with visual grating stimuli, known to elicit decreases in alpha-band (8-13Hz) power and increases in gamma-band power (40-70Hz).Data were mapped to source-space using a beamformer. Across both groups, decreased alpha power and increased gamma power localised to early visual cortex. Data from primary visual cortex (V1) were compared between groups. No differences were found in either alpha or gamma peak frequency or the magnitude of alpha power, p>.05. However, compared with controls, our VSS cohort displayed significantly increased V1 gamma power, p=.035. This new electromagnetic finding concurs with previous fMRI and PET findings suggesting that in VSS, the visual cortex is hyper-excitable. The coupling of alpha-phase to gamma amplitude (i.e., phase-amplitude coupling, PAC) within V1 was also quantified. Compared with controls, the VSS group had significantly reduced alpha-gamma PAC, p<.05, indicating a potential excitation-inhibition imbalance in VSS, as well as a potential disruption to top-down “noise-cancellation” mechanisms.Overall, these results suggest that rhythmical brain activity in primary visual cortex is both hyperexcitable and disorganised in VSS, consistent with visual snow being a condition of thalamocortical dysrhythmia.
Toughening mechanisms for the attachment of architectured materials: The mechanics of the tendon enthesis
Authors: Golman Mikhail , Abraham Adam C. , Kurtaliaj Iden , Marshall Brittany P. , Hu Yizhong Jenny , Schwartz Andrea G. , Guo X. Edward , Birman Victor , Thurner Philipp J. , Genin Guy M. , Thomopoulos Stavros 
Published: May 2021

AbstractArchitectured materials offer tailored mechanical properties but are limited in engineering applications due to challenges in maintaining toughness across their attachments. The enthesis connects tendon and bone, two vastly different architectured materials, and exhibits toughness across a wide range of loadings. Understanding the mechanisms by which this is achieved could inform the development of engineered attachments. Integrating experiments, simulations, and novel imaging that enabled simultaneous observation of mineralized and unmineralized tissues, we identified putative mechanisms of enthesis toughening in a mouse model and then manipulated these mechanisms viain vivocontrol of mineralization and architecture. Imaging uncovered a fibrous architecture within the enthesis that controls trade-offs between strength and toughness.In vivomodels of pathology revealed architectural adaptations that optimize these trade-offs through cross-scale mechanisms including nanoscale protein denaturation, milliscale load-sharing, and macroscale energy absorption. Results suggest strategies for optimizing architecture for tough bimaterial attachments in medicine and engineering.TeaserThe architecture of the tendon-to-bone attachment is designed for toughness.
Rat sensitivity to multipoint statistics is predicted by efficient coding of natural scenes
Authors: Caramellino Riccardo , Piasini Eugenio , Buccellato Andrea , Carboncino Anna , Balasubramanian Vijay , Zoccolan Davide 
Published: May 2021

AbstractEfficient processing of sensory data requires adapting the neuronal encoding strategy to the statistics of natural stimuli. Previously, in Hermundstad et al. 2014, we showed that local multipoint correlation patterns that are most variable in natural images are also the most perceptually salient for human observers, in a way that is compatible with the efficient coding principle. Understanding the neuronal mechanisms underlying such adaptation to image statistics will require performing invasive experiments that are impossible in humans. Therefore, it is important to understand whether a similar phenomenon can be detected in animal species that allow for powerful experimental manipulations, such as rodents. Here we selected four image statistics (from single- to four-point correlations) and trained four groups of rats to discriminate between white noise patterns and binary textures containing variable intensity levels of one of such statistics. We interpreted the resulting psychometric data with an ideal observer model, finding a sharp decrease in sensitivity from 2- to 4-point correlations and a further decrease from 4- to 3-point. This ranking fully reproduces the trend we previously observed in humans, thus extending a direct demonstration of efficient coding to a species where neuronal and developmental processes can be interrogated and causally manipulated.
Dissociation in basolateral and central amygdala effective connectivity predicts the stability of emotion-related impulsivity in adolescents with borderline personality symptoms: a resting-state fMRI study
Authors: Hall Nathan T. , Hallquist Michael N. 
Published: May 2021

AbstractBackgroundBorderline personality disorder (BPD) is associated with altered activity in the prefrontal cortex (PFC) and amygdala, yet no studies have examined fronto-limbic circuitry in borderline adolescents. Here, we examined the contribution of fronto-limbic connectivity to the longitudinal stability of emotion-related impulsivity (ERI), a key feature of BPD, in symptomatic adolescents and young adults.MethodsWe compared resting-state effective connectivity (EC) in 82 adolescents and emerging adults with and without clinically significant borderline symptoms (n BPD = 40, ages 13-30). Group-specific directed networks were estimated amongst fronto-limbic nodes including PFC, ventral striatum (VS), central amygdala (CeN), and basolateral amygdala (BLA). We calculated directed centrality metrics and examined if these values were associated with initial levels and rates of change in ERI symptoms over a one-year follow-up using latent growth curve models (LGCMs).ResultsIn the healthy group, ventromedial prefrontal cortex (vmPFC) and dorsal ACC had a directed influence on CeN and VS respectively. In the borderline group bilateral BLA had a directed influence on CeN, whereas in the healthy group CeN influenced BLA. LGCMs revealed that in borderline adolescents, ERI remained stable across follow-ups. Further, higher output of R CeN in controls was associated with stronger within-person decreases in ERI.ConclusionsFunctional inputs from BLA and vmPFC appear to play competing roles in influencing CeN activity. In borderline adolescents BLA may predominate over CeN activity, while in controls the ability of CeN to conversely influence BLA activity is associated with more rapid reductions in ERI.
An Atlas of Cortical Arealization Identifies Dynamic Molecular Signatures
Authors: Bhaduri Aparna , Sandoval-Espinosa Carmen , Otero-Garcia Marcos , Oh Irene , Yin Raymund , Eze Ugomma C. , Nowakowski Tomasz J. , Kriegstein Arnold R. 
Published: May 2021

AbstractThe human brain is subdivided into distinct anatomical structures. The neocortex, one of these structures, enables higher-order sensory, associative, and cognitive functions, and in turn encompasses dozens of distinct specialized cortical areas. Early morphogenetic gradients are known to establish an early blueprint for the specification of brain regions and cortical areas. Furthermore, recent studies have uncovered distinct transcriptomic signatures between opposing poles of the developing neocortex1. However, how early, broad developmental patterns result in finer and more discrete spatial differences across the adult human brain remains poorly understood2. Here, we use single-cell RNA-sequencing to profile ten major brain structures and six neocortical areas during peak neurogenesis and early gliogenesis. Our data reveal that distinct cell subtypes are predominantly brain-structure specific. Within the neocortex, we find that even early in the second trimester, a large number of genes are differentially expressed across distinct cortical areas in all cell types, including radial glia, the neural progenitors of the cortex. However, the abundance of areal transcriptomic signatures increases as radial glia differentiate into intermediate progenitor cells and ultimately give rise to excitatory neurons. Using an automated, multiplexed single-molecule fluorescentin situhybridization (smFISH) approach, we validated the expression pattern of area-specific neuronal genes and also discover that laminar gene expression patterns are highly dynamic across cortical regions. Together, our data suggest that early cortical areal patterning is defined by strong, mutually exclusive frontal and occipital gene expression signatures, with resulting gradients giving rise to the specification of areas between these two poles throughout successive developmental timepoints.
“Δ133p53α Protects Human Astrocytes from Amyloid-Beta Induced Senescence and Neurotoxicity”
Authors: Ungerleider Kyra , Lissa Delphine , Beck Jessica A. , Horikawa Izumi , Harris Curtis C. 
Published: May 2021

ABSTRACTCellular senescence is an important contributor to aging and age-related diseases such as Alzheimer’s disease (AD). Senescent cells are characterized by a durable cell proliferation arrest and the acquisition of a proinflammatory senescence-associated secretory phenotype (SASP), which participates in the progression of neurodegenerative disorders. Clearance of senescent glial cells in an AD mouse model prevented cognitive decline suggesting pharmacological agents targeting cellular senescence might provide novel therapeutic approaches for AD. Δ133p53α, a natural protein isoform of p53, was previously shown to be a negative regulator of cellular senescence in primary human astrocyte, with clinical implications from its diminished expression in brain tissues from AD patients. Here we show that treatment of proliferating human astrocytes with amyloid-beta oligomers (Aβ), an endogenous pathogenic agent of AD, results in reduced expression of Δ133p53α, as well as induces the cells to become senescent and express proinflammatory SASP cytokines such as IL-6, IL-1β and TNFα. Our data suggest that Aβ-induced astrocyte cellular senescence is associated with accelerated DNA damage, and upregulation of full-length p53 and its senescence-inducing target gene p21WAF1. We also show that exogenously enhanced expression of Δ133p53α rescues human astrocytes from Aβ-induced cellular senescence and SASP through both protection from DNA damage and dominantnegative inhibition of full-length p53, leading to inhibition of Aβ-induced, astrocyte-mediated neurotoxicity. The results presented here demonstrate that Δ133p53α manipulation could modulate cellular senescence in the context of AD, possibly opening new therapeutic avenues.HIGHLIGHTSAβ diminishes the expression of the p53 isoform Δ133p53α, and induces cellular senescence, SASP, and DNA damage in human astrocytes.Δ133p53α protects human astrocytes from Aβ-induced DNA damage and cellular senescence.Δ133p53α prevents astrocyte-mediated neurotoxicity to neuro-progenitor cells.
An Open–Access Simultaneous Electrocardiogram and Phonocardiogram Database
Authors: Kazemnejad Arsalan , Gordany Peiman , Sameni Reza 
Published: May 2021

AbstractThe electro-phono-cardiogram (EPHNOGRAM) project focused on the development of low-cost and low-power devices for recording simultaneous electrocardiogram (ECG) and phonocardiogram (PCG) data, with auxiliary channels for capturing environmental audio noise, which could be used for PCG quality enhancement through signal processing. The current database, recorded by version 2.1 of the developed hardware, has been acquired from 24 healthy adults aged between 23 and 29 (average: 25.4 ± 1.9 years) in 30 min stress-test sessions during resting, walking, running and biking conditions, using indoor fitness center equipment. The dataset also contains several 30 s sample records acquired during rest conditions. This data is useful for simultaneous multi-modal analysis of ECG and PCG. It provides interesting insights into the inter-relationship between the mechanical and electrical mechanisms of the heart, under rest and physical activity. The database is provided online on PhysioNet.
Correcting for Body Size Variation in Morphometric Analysis
Authors: Chan Kin Onn , Lee Grismer L. 
Published: May 2021

ABSTRACTUsing an allometric growth model to correct for body size variation has been known for many decades to be superior to several other widely used methods such as ratios, analysis of covariance, principal components analysis, and residual analysis. However, this technique remains relatively obscure and rarely applied. We optimize the implementation of this method through a newly developed and easy-to-use R package GroupStruct and use empirical datasets to test its relative efficacy compared to several commonly used methods. Our results demonstrate the superiority of the allometric method and highlights the negative impacts of applying improper body size correction methods.
Subcellular localization of PKA catalytic subunits provides a basis for their distinct functions in the retina
Authors: Roa Jinae N. , Ma Yuliang , Mikulski Zbigniew , Xu Qianlan , Ilouz Ronit , Taylor Susan S. , Skowronska-Krawczyk Dorota 
Published: May 2021

AbstractPKA signaling is essential for numerous processes but the subcellular localization of specific PKA isoforms has yet to be explored comprehensively in tissues. Expression of the Cβ protein, in particular, has not been mapped previously at the tissue level. In this study we used retina as a window into PKA signaling in the brain and characterized localization of PKA Cα, Cβ, RIIα, and RIIβ subunits. Each subunit presented a distinct localization pattern. Cα and Cβ were localized in all tissue layers, while RIIα and RIIβ were enriched in the photoreceptor cells in contrast to the cell body and retinal portion of retinal ganglion cells. Only Cα was observed in photoreceptor outer segments and the cilia transition zone, while Cβ was localized primarily to mitochondria and was especially prominent in the ellipsoid of the cone cells. In contrast to Cα, Cβ also never colocalized with RIIα or RIIβ. Using BaseScope technology to track expression of the Cβ isoforms we find that Cβ4 and Cβ4ab are prominently expressed and, therefore, likely code for mitochondrial-Cβ proteins. Our data indicates that PKA subunits are functionally nonredundant in the retina and suggesting that Cβ might be important for mitochondrial-associated neurodegenerative diseases previously linked to PKA dysfunction.
Higher concentrations of bacterial enveloped virus Phi6 can protect the virus from environmental decay
Authors: Bangiyev Ronald , Chudaev Maxim , Schaffner Donald W. , Goldman Emanuel 
Published: May 2021

ABSTRACTPhage Phi6 is an enveloped virus considered as a possible non-pathogenic surrogate for SARS-CoV-2 and other viral pathogens in transmission studies. Higher input amounts of bacteriophage Phi6 are shown to delay and protect the phage from environmental decay, both when the phage are dried in plastic tubes, and when they are stored in saline solution at 4°C. When bacteriophage Phi6 are placed in LB (Luria-Bertani) growth medium prior to placement on the plastic surface, viral recovery is not influenced by the starting concentration. The protection is reflected in longer half-lives of the phage at higher concentrations compared to lower. Because experiments supporting the possibility of fomite transmission of SARS-CoV-2 and other viruses rely upon survival of infectious virus following inoculation of various surfaces, high initial amounts of input virus on a surface may generate artificially inflated survival times compared to realistic lower levels of virus that a subject would normally encounter. This is not only because there are extra half-lives to go through at the higher concentrations, but also because the half-lives themselves are extended at the higher virus concentrations. It is important to design surface drying experiments for pathogens with realistic levels of input virus, and to consider the role of the carrier and matrix if the results are to be clinically relevant.IMPORTANCEDuring the COVID-19 pandemic, a lot of attention has been paid to the environmental decay of SARS-CoV-2 due to proposed transmission of the virus via fomites. However, published experiments have commenced with very high virus titer inoculums, an experimental design not representative of real-life conditions. The study described here evaluated the impact of initial virus titer on environmental decay of an enveloped virus, using a non-pathogenic surrogate for SARS-CoV-2, enveloped bacteriophage Phi6. We establish that higher concentrations of virus can protect the virus from environmental decay, depending on conditions. This has important implications for stability studies of SARS-CoV-2 and other viruses. Our results point to a limitation in the fundamental methodology that has been used to attribute fomite transmission for almost all respiratory viruses.
Prophylactic inhibition of colonization by Streptococcus pneumoniae with the secondary bile acid metabolite deoxycholic acid
Authors: Vidal Jorge E. , Wier Meagan N. , Angulo-Zamudio Uriel , McDevitt Erin , Jop Vidal Ana G. , Alibayov Babek , Scasny Anna , Wong Sandy M. , Akerley Brian J. , McDaniel Larry S. 
Published: May 2021

AbstractStreptococcus pneumoniae (Spn) colonizes the nasopharynx of children and the elderly but also kills millions worldwide yearly. The secondary bile acid metabolite, deoxycholic acid (DoC), affects the viability of human pathogens but also plays multiple roles in host physiology. We assessed in vitro the antimicrobial activity of DoC and investigated its potential to eradicate Spn colonization using an ex vivo model of human nasopharyngeal colonization and an in vivo mouse model of colonization. At a physiological concentration DoC (0.5 mg/ml; 1.27 mM) killed all tested Spn strains (N=48) two h post-inoculation. The ex-vivo model of nasopharyngeal colonization showed that DoC eradicated colonization by Spn strains as soon as 10 min post-exposure. The mechanism of action did not involve activation of autolysis since the autolysis-defective double mutants ΔlytAΔlytC and ΔspxBΔlctO were as susceptible to DoC as was the wild-type (WT). Oral streptococcal species (N=20), however, were not susceptible to DoC (0.5 mg/ml). Unlike trimethoprim, whose spontaneous resistance frequency (srF) for TIGR4 or EF3030 was ≥1×10−9, no spontaneous resistance was observed with DoC (srF≥1×10−12). Finally, the efficacy of DoC to eradicate Spn colonization was assessed in vivo using a topical route via intranasal (i.n.) administration and as a prophylactic treatment. Mice challenged with Spn EF3030 carried a median of 4.05×105 cfu/ml four days post-inoculation compared to 6.67×104 cfu/ml for mice treated with DoC. Mice in the prophylactic group had a ∼99% reduction of the pneumococcal density (median, 2.61 ×103 cfu/ml). Thus, DoC, an endogenous human bile salt, has therapeutic potential against Spn.