bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding Age-specific Changes in Brain Functional Connectivity Using a Sliding-window Based Clustering Method
Authors: Zhang Aiying , Pagliaccio David , Marsh Rachel , Lee Seonjoo 
Published: September 2022

AbstractFunctional magnetic resonance imaging (fMRI) permits detailed study of human brain function. Understanding the age-specific development of neural circuits in the typically developing brain may help us generate new hypotheses for developmental psychopathologies. Functional connectivity (FC), defined as the statistical associations between two brain regions, has been widely used in estimating functional networks from fMRI data. Previous research has shown that the evolution of FC does not follow a linear trend, particularly from childhood to young adulthood. Thus, this work aims to detect the nuanced FC changes with age from the non-linear curves and identify age-period-specific FC development patterns. We proposed a sliding-window based clustering approach to identify refined age interval of FC development. We used resting-state fMRI (rs-fMRI) data from the human connectome project-development (HCP-D), which recruited children, adolescents, and young adults aged from 5 to 21 years. Our analyses revealed different developmental patterns of resting-state FC by sex. In general, females matured earlier than males, but males had a faster development rate during age 100 -120 months. We identified four developmental phases: network construction in late childhood, segregation and integration construction in adolescence, network pruning in young adulthood, and a unique phase in males -- U-shape development. In addition, we investigated the sex effect on the slopes of FC-age correlation. Males had higher slopes during late childhood and young adulthood. These results inform trajectories of normal FC development, information that can in the future be used to pinpoint when development might go awry in neurodevelopmental disorders.HighlightPropose a novel sliding-window-based framework to identify refined age intervals of functional connectivity (FC) development.Identify four developmental phases: network construction in late childhood, segregation and integration in adolescence, network pruning in young adulthood, and a unique phase in males -- U-shape development.Characterize the representative FC pattern for each developmental phase based on global network statistics, modular connectivity, and hub ROIs.Reveal sex differences in developmental timing, rate, and patterns of resting-state FC.
Characterising stationary and dynamic effective connectivity changes in the motor network during and after tDCS
Authors: Calzolari Sara , Jalali Roya , Fernández-Espejo Davinia 
Published: September 2022

AbstractThe exact mechanisms behind the effects of transcranial direct current stimulation (tDCS) at a network level are still poorly understood, with most studies to date focusing on local (cortical) effects and changes in motor-evoked potentials or BOLD signal. Here, we explored stationary and dynamic effective connectivity across the motor network at rest in two experiments where we applied tDCS over the primary motor cortex (M1-tDCS) or the cerebellum (cb-tDCS) respectively. Two cohorts of healthy volunteers (n = 21 and n = 22) received anodal, cathodal, and sham tDCS sessions (counterbalanced) during 20 minutes of resting-state functional magnetic resonance imaging (fMRI). We used spectral Dynamic Causal Modelling (DCM) and hierarchical Parametrical Empirical Bayes (PEB) to analyse data after (compared to a pre-tDCS baseline) and during stimulation. We also implemented a novel dynamic (sliding windows) DCM/PEB approach to model the nature of network reorganisation across time. In both experiments we found widespread effects of tDCS that extended beyond the targeted area and modulated effective connectivity between cortex, thalamus, and cerebellum. These changes were characterised by unique nonlinear temporal fingerprints across connections and polarities. Our results challenged the classic notion of anodal and cathodal tDCS as excitatory and inhibitory respectively, as well as the idea of a cumulative effect of tDCS over time. Instead, they described a rich set of changes with specific spatial and temporal patterns. Our work provides a starting point for advancing our understanding of network-level tDCS effects and optimise its cognitive and clinical applications.
Wild red deer (Cervus elaphus) do not play a role as vectors or reservoirs of SARS-CoV-2 in northeastern Poland
Authors: Krupińska Martyna , Borkowski Jakub , Goll Aleksander , Nowicka Joanna , Baranowicz Karolina , Bourret Vincent , Strandin Tomas , Mäki Sanna , Kant Ravi , Sironen Tarja , Grzybek Maciej 
Published: September 2022

AbstractSeveral studies reported a high prevalence of SARS-CoV-2 among white-tailed deer in North America. Monitoring cervids in all regions to better understand SARS-CoV-2 infection and circulation in other deer populations has been urged. To evaluate deer exposure to SARS-CoV-2 in Poland, we sampled 90 reed deer individuals shot by hunters in five hunting districts in northeastern Poland. Serum and nasopharyngeal swabs were collected, and then the Immunofluorescent Assay (IFA) to detect anti-SARS-CoV-2 antibodies was performed as well as real-time PCR with reverse transcription for direct virus detection. No positive samples were detected. There is no evidence of spillover of SARS-CoV-2 from the human to deer population in Poland.
Intrinsic neural timescales in the temporal lobe support an auditory processing hierarchy
Authors: Cusinato Riccardo , Alnes Sigurd L. , van Maren Ellen , Boccalaro Ida , Ledergerber Debora , Adamantidis Antoine , Imbach Lukas L. , Schindler Kaspar , Baud Maxime O. , Tzovara Athina 
Published: September 2022

AbstractDuring rest, intrinsic neural dynamics manifest at multiple timescales, which progressively increase along visual and somatosensory hierarchies. Theoretically, intrinsic timescales are thought to facilitate processing of external stimuli at multiple stages. However, direct links between timescales at rest and sensory processing, as well as translation to the auditory system are lacking. Here, we used intracranial electroencephalography in humans to show that in the auditory network, intrinsic neural timescales progressively increase, while the spectral slope flattens, from temporal to entorhinal cortex, hippocampus, and amygdala. Within the neocortex, intrinsic timescales exhibit spatial gradients that follow the temporal lobe anatomy. Crucially, intrinsic timescales at rest can explain the latency of auditory responses: as intrinsic timescales increase, so do the single-electrode response onset and peak latencies. Our results suggest that the human auditory network exhibits a repertoire of intrinsic neural dynamics, which manifest in cortical gradients with millimeter resolution and may provide a variety of temporal windows to support auditory processing.
Effect of Nonlinear Hyperelastic Property of Arterial Tissues on the Pulse Wave Velocity based on the Unified-Fiber-Distribution (UFD) Model
Authors: Dong Hai , Liu Minliang , Woodall Julia , Leshnower Bradley , Gleason Rudolph L. 
Published: September 2022

AbstractPulse wave velocity (PWV) is a key, independent risk factor for future cardiovascular events. The Moens-Korteweg equation describes the relation between PWV and the stiffness of arterial tissue with an assumption of isotopic linear elastic property of the arterial wall. However, the arterial tissue exhibits highly nonlinear and anisotropic mechanical behaviors. There is a limited study regarding the effect of arterial nonlinear and anisotropic properties on the PWV. In this study, we investigated the impact of the arterial nonlinear hyperelastic properties on the PWV, based on our recently developed unified-fiber-distribution (UFD) model. The UFD model considers the fibers (embedded in the matrix of the tissue) as a unified distribution, which expects to be more physically consistent with the real fiber distribution than existing models that separate the fiber distribution into two/several fiber families. With the UFD model, we fitted the measured relation between the PWV and blood pressure which obtained a good accuracy. We also modeled the aging effect on the PWV based on observations that the stiffening of arterial tissue increases with aging, and the results agree well with experimental data. In addition, we did parameter studies on the dependence of the PWV on the arterial properties of fiber initial stiffness, fiber distribution, and matrix stiffness. The results indicate the PWV increases with increasing overall fiber component in the circumferential direction. The dependences of the PWV on the fiber initial stiffness, and matrix stiffness are not monotonic and change with different blood pressure. The results of this study could provide new insights into arterial property changes and disease information from the clinical measured PWV data.
Iterative immunostaining combined with expansion microscopy and image processing reveals nanoscopic network organization of nuclear lamina
Authors: Mäntylä Elina , Montonen Toni , Azzari Lucio , Mattola Salla , Hannula Markus , Vihinen-Ranta Maija , Hyttinen Jari , Vippola Minnamari , Foi Alessandro , Nymark Soile , Ihalainen Teemu O. 
Published: September 2022

AbstractInvestigation of nuclear lamina architecture relies on super-resolved microscopy. However, epitope accessibility, labeling density, and detection precision of individual molecules pose challenges within the molecularly crowded nucleus. We developed iterative indirect immunofluorescence (IT–IF) staining approach combined with expansion microscopy (ExM) and structured illumination microscopy to improve super-resolution microscopy of subnuclear nanostructures like lamins. We prove that ExM is applicable in analyzing highly compacted nuclear multiprotein complexes such as viral capsids and provide technical improvements to ExM method including 3D-printed gel casting equipment. We show that in comparison to conventional immunostaining, IT-IF results in a higher signal-to-background –ratio and a mean fluorescence intensity by improving the labeling density. Moreover, we present a signal processing pipeline for noise estimation, denoising, and deblurring to aid in quantitative image analyses and provide this platform for the microscopy imaging community. Finally, we show the potential of signal-resolved IT–IF in quantitative super-resolution ExM imaging of nuclear lamina and reveal nanoscopic details of the lamin network organization - a prerequisite for studying intranuclear structural co-regulation of cell function and fate. (Words: 175)
The Developmental Profile of Visual Cortex Astrocytes
Authors: Watanabe Airi , Guo Connie , Sjöström Per Jesper 
Published: September 2022

SUMMARYThough once thought of as passive support cells for neurons, it is now clear that astrocytes signal via calcium (Ca2+) to trigger gliotransmission that impacts surrounding neurons and synapses. We therefore investigated how astrocytes in layer-5 (L5) mouse visual cortex mature electrophysiologically and morphologically over postnatal days (P) 3 – 30 and how these relate to changes in spontaneous Ca2+ events. Across this age range, resting membrane potential increased, and input resistance decreased. Astrocytes also revealed different membrane responses to voltage steps: notably, membrane responses became more passive with age. Two-photon (2p) imaging of dye-loaded patched cells and confocal imaging revealed that gap-junction coupling increased starting around P7. Morphological reconstructions revealed increased branch density but also shorter branches after P20, suggesting that astrocyte branches may get pruned as dense tiling is established. Finally, we visualized spontaneous Ca2+ transients with 2p microscopy and found that Ca2+ events decorrelated, became more frequent as well as briefer with age. As astrocytes mature, spontaneous Ca2+ activity thus changes from relatively cell-wide, synchronous waves to local transients. Several astrocyte properties were stably mature from ~P15 onwards, although morphology continued to develop further. Our findings provide a descriptive foundation of astrocyte maturation, useful for the study of astrocytic impact on visual cortex critical period plasticity.
Pollen contamination and mating structure in maritime pine (Pinus pinasterAit.) clonal seed orchards revealed by SNP markers
Authors: Bouffier Laurent , Debille Sandrine , Alazard Pierre , Raffin Annie , Pastuszka Patrick , Trontin Jean-François 
Published: September 2022

AbstractMaritime pine (Pinus pinasterAit.) is a major forest tree species in south-western Europe. In France, an advanced breeding program for this conifer species has been underway since the early 1960s. Open-pollinated seed orchards currently supply more than 90% of maritime pine seedlings for plantation forestry. However, pollen contamination and mating structure have been poorly studied in such seed orchards whereas they could impact genetic gains and diversity. We analyzed these features in three maritime pine clonal seed orchards. We addressed biological (tree genotype, age, flowering phenology) and environmental factors (vicinity with external pollen sources, orchard structure, soil type, climatic conditions) that are expected to determine the genetic composition of seed lots. Genetic analyses were based on an optimized set of 60 SNP markers and performed on 2,552 seedlings with Cervus software (likelihood inference methodology).Pollen contamination rates were highly variable between seed lots (from 20 to 96%), with a mean value of 50%. Interpretative factors included the distance between the seed orchard and external pollen sources, rain during the pollination period, seed orchard age, soil conditions and seed parent identity. All parental genotypes from the seed orchards contributed to the offspring as pollen parents, but differences in paternal reproductive success were detected. Finally, the overall self-fertilization rate was estimated at 5.4%, with considerable variability between genotypes (from 0% to 26%). These findings are useful to formulate recommendations for seed orchard management (seed orchard location, soil and climate optimal conditions, minimum age for commercial seed lots harvesting) and for identifying new research perspectives (exploring links between pollen contamination and climatic data, genetic control of flowering traits).
A Multivariate Approach to Understanding the Genetic Overlap between Externalizing Phenotypes and Substance Use Disorders
Authors: Poore Holly E. , Hatoum Alexander , Mallard Travis T. , Sanchez-Roige Sandra , Waldman Irwin D. , Palmer Abraham A. , Harden K. Paige , Barr Peter B. , Dick Danielle M. 
Published: September 2022

AbstractSubstance use disorders (SUDs) are phenotypically and genetically correlated with each other and with other psychological traits characterized by behavioral undercontrol, termed externalizing phenotypes. In this study, we used Genomic Structural Equation Modeling to explore the shared genetic architecture among six externalizing phenotypes and four SUDs used in two previous multivariate GWAS of an externalizing and an addiction risk factor, respectively. Using a preregistered set of criteria, we first evaluated the performance of five confirmatory factor analytic models, including a common factor model, alternative parameterizations of two-factor structures, and a bifactor model. We used a combination of model fit, factor reliability, and model characteristics to adjudicate among the models. We next explored the genetic correlations between factors identified in these models and other relevant psychological traits. We found that a common factor model, in which all externalizing phenotypes and SUDs were influenced by a single dimension of genetic risk best characterized the relationships among our phenotypes. Although two two-factor models also performed well, we found that the factors in those models were very highly correlated with each other (rgS > .87) and similarly genetically correlated with external criteria, suggesting they did not represent meaningfully distinct dimensions. Results from this study can be used to inform future efforts to characterize genetic liability for broad externalizing as well as specific externalizing phenotypes.
Permittivity-Based Microparticle Classification by the Integration of Impedance Cytometry and Microwave Resonators
Authors: Tefek Uzay , Sari Burak , Hanay Mehmet S. 
Published: September 2022

AbstractPermittivity of microscopic particles can be used as a classification parameter for applications in materials and environmental sciences. However, directly measuring the permittivity of individual microparticles has proven to be challenging due to the convoluting effect of particle size on capacitive signals. To overcome this challenge, we built a sensing platform to independently obtain both the geometric and electric size of a particle, by combining impedance cytometry and microwave resonant sensing in a microfluidic chip. This way the microwave signal, which contains both permittivity and size effects, can be normalized by the size information provided by impedance cytometry to yield an intensive parameter that depends only on permittivity. The technique allowed us to differentiate between polystyrene and soda lime glass microparticles — below 22 microns in diameter— with more than 94% accuracy, despite their similar sizes and electrical characteristics. The technique offers a potential route for targeted applications such as environmental monitoring of microplastic pollution or quality control in pharmaceutical industry.
YAP/TAZ inactivation with simvastatin attenuates glucocorticoid-induced human trabecular meshwork cell dysfunction
Authors: Yoo Hannah , Singh Ayushi , Li Haiyan , Strat Ana N. , Bagué Tyler , Ganapathy Preethi S. , Herberg Samuel 
Published: September 2022

AbstractPurposeImpairment of the trabecular meshwork (TM) is the principal cause of increased outflow resistance in the glaucomatous eye. Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ) are emerging as potential mediators of TM cell/tissue dysfunction. Furthermore, YAP/TAZ activity was recently found to be controlled by the mevalonate pathway in non-ocular cells. Clinically-used statins block the mevalonate cascade and were shown to improve TM cell pathobiology; yet, the link to YAP/TAZ signaling was not investigated. In this study, we hypothesized that YAP/TAZ inactivation with simvastatin attenuates glucocorticoid-induced human TM (HTM) cell dysfunction.MethodsPrimary HTM cells were seeded atop or encapsulated within bioengineered extracellular matrix (ECM) hydrogels. Dexamethasone was used to induce a pathologic phenotype in HTM cells in the absence or presence of simvastatin. Changes in YAP/TAZ activity, actin cytoskeletal organization, phospho-myosin light chain levels, hydrogel contraction/stiffness, and fibronectin deposition were assessed.ResultsSimvastatin potently blocked pathologic YAP/TAZ nuclear localization/activity, actin stress fiber formation, and myosin light chain phosphorylation in HTM cells. Importantly, simvastatin co-treatment significantly attenuated dexamethasone-induced ECM contraction/stiffening and extracellular fibronectin deposition. Sequential treatment was similarly effective but did not match clinically-used Rho kinase inhibition.ConclusionsYAP/TAZ inactivation with simvastatin attenuates HTM cell pathobiology in a tissue-mimetic ECM microenvironment. Our data may help explain the association of statin use with a reduced risk of developing glaucoma via indirect YAP/TAZ inhibition as a proposed regulatory mechanism.
Genome-wide co-essentiality analysis inMycobacterium tuberculosisreveals an itaconate defense enzyme module
Authors: Jinich Adrian , Nazia Sakila Z. , Tellez Andrea V. , Wu Amy M. , Almada-Monter Ricardo , Smith Clare M. , Rhee Kyu 
Published: September 2022

AbstractGenome-wide random mutagenesis screens using transposon sequencing (TnSeq) have been a cornerstone of functional genetics inMycobacterium tuberculosis(Mtb), helping to define gene essentiality across a wide range of experimental conditions. Here, we harness a recently compiled TnSeq database to identify pairwise correlations of gene essentiality profiles (i.e. co-essentiality analysis) across theMtbgenome and reveal clusters of genes with similar function. We describe selected modules identified by our pipeline, review the literature supporting their associations, and propose hypotheses about novel associations. We focus on a cluster of seven enzymes for experimental validation, characterizing it as an enzymatic arsenal that helpsMtbcounter the toxic effects of itaconate, a host-derived antibacterial compound. We extend the use of these correlations to enable prediction of protein complexes by designing a virtual screen that ranks potentially interacting heterodimers from co-essential protein pairs. We envision co-essentiality analysis will help accelerate gene functional discovery in this important human pathogen.
Substrate stiffness engineered to replicate disease conditions influence senescence and fibrotic responses in primary lung fibroblasts
Authors: Blokland Kaj E.C. , Nizamoglu Mehmet , Habibie Habibie , Borghuis Theo , Schuliga Michael , Melgert Barbro N. , Knight Darryl A. , Brandsma Corry-Anke , Pouwels Simon D. , Burgess Janette K. 
Published: September 2022

AbstractIn idiopathic pulmonary fibrosis (IPF) there is excessive ECM deposition, increased stiffness and ultimately destruction of lung parenchyma. IPF presents mainly in the elderly, implying that senescence, a hallmark of ageing, contributes to disease progression. Several studies have reported that IPF is characterised by increased senescence and accumulating evidence suggests that structural changes, such as increased stiffness may contribute to senescence. This study therefore investigated if increased tissue stiffness could modulate markers of senescence and/or fibrosis in primary lung fibroblasts. Using hydrogels representing healthy and fibrotic stiffnesses, we cultured primary fibroblasts from non-diseased lung tissue on top of these hydrogels for up to seven days before assessing senescence and fibrosis markers. Fibroblasts cultured on stiff (±15kPa) hydrogels showed higher Yes-associated protein-1 (YAP) nuclear translocation compared to soft hydrogels. When looking at senescence-associated proteins we also found higher secretion of receptor activator of nuclear factor kappa-B ligand (RANKL) but no change in transforming growth factor-β1 (TGF-β1) or connective tissue growth factor (CTGF) expression and higher decorin protein deposition on stiff matrices. With respect to genes associated with fibrosis, fibroblasts on stiff hydrogels compared to soft had higher expression of smooth muscle alpha (α)-2 actin (ACTA2), collagen (COL) 1A1andfibulin-1(Fbln1) and higher Fbln1 protein deposition after seven days. Our results show that exposure of lung fibroblasts to fibrotic stiffness activates genes and secreted factors that are part of fibrotic responses and part of the senescence-associated secretory profile (SASP). This overlap may contribute to the creation of a feedback loop whereby fibroblasts create a perpetuating cycle reinforcing disease progression in IPF.