bluuebunny/crossref_metadata_2025_split huggingface dataset:
A specific relationship between musical sophistication and auditory working memory
Authors: Lad Meher , Billig Alexander J. , Kumar Sukhbinder , Griffiths Timothy D. 
Published: July 2021

AbstractMusical engagement may be associated with better listening skills, such as the perception of and working memory for notes, in addition to the appreciation of musical rules. The nature and extent of this association is controversial. In this study we assessed the relationship between musical engagement and both sound perception and working memory.We developed a task to measure auditory perception and working memory for sound using a behavioural measure for both, precision. We measured the correlation between these tasks and musical sophistication based on a validated measure (the Goldsmiths Musical Sophistication Index) that can be applied to populations of both musicians and non-musicians. The data show that musical sophistication accounts for 21% of the variance in the precision of working memory for frequency in an analysis that accounts for age and non-verbal intelligence. Musical sophistication was not significantly associated with the precision of working memory for amplitude modulation rate or with the precision of perception of either acoustic feature.The work supports a specific association between musical sophistication and working memory for sound frequency.
Critical genetic program forDrosophilaimaginal disc regeneration revealed by single-cell analysis
Authors: Worley Melanie I. , Everetts Nicholas J. , Yasutomi Riku , Yosef Nir , Hariharan Iswar K. 
Published: July 2021

AbstractWhether regeneration is primarily accomplished by re-activating gene regulatory networks used previously during development or by activating novel regeneration-specific transcriptional programs remains a longstanding question. Currently, most genes implicated in regeneration also function during development. Using single-cell transcriptomics in regeneratingDrosophilawing discs, we identified two regeneration-specific cell populations within the blastema. They are each composed of cells that upregulate multiple genes encoding secreted proteins that promote regeneration. In this regenerative secretory zone, the transcription factor Ets21C controls the expression of multiple regenerationpromoting genes. While eliminatingEts21Cfunction has no discernible effect on development, it severely compromises regeneration. This Ets21C-dependent gene regulatory network is also activated in blastema-like cells in tumorous discs, suggesting that pro-regenerative mechanisms can be co-opted by tumors to promote aberrant growth.
Knock-in tagging in zebrafish facilitated by insertion into non-coding regions
Authors: Levic Daniel S. , Yamaguchi Naoya , Wang Siyao , Knaut Holger , Bagnat Michel 
Published: July 2021

AbstractZebrafish provide an excellent model for in vivo cell biology studies due to their amenability to live imaging. Protein visualization in zebrafish has traditionally relied on overexpression of fluorescently tagged proteins from heterologous promoters, making it difficult to recapitulate endogenous expression patterns and protein function. One way to circumvent this problem is to tag the proteins by modifying their endogenous genomic loci. Such an approach is not widely available to zebrafish researchers due to inefficient homologous recombination and the error-prone nature of targeted integration in zebrafish. Here, we report a simple approach for tagging proteins in zebrafish on their N- or C termini with fluorescent markers by inserting PCR-generated donor amplicons into non-coding regions of the corresponding genes. Using this approach, we generated endogenously tagged alleles for several genes critical for epithelial biology and organ development including the tight junction components ZO-1 and Cldn15la, the trafficking effector Rab11a, and the ECM receptor β1 integrin. Our approach facilitates the generation of knock-in lines in zebrafish, opening the way for accurate quantitative imaging studies.Summary statementGeneration of endogenously tagged stable zebrafish knock-in lines is simplified by the integration of fluorescent protein cassettes with mRNA splicing elements into non-coding regions of genes.
An Empirical Bayes Approach to Estimating Dynamic Models of Co-Regulated Gene Expression
Authors: Venkatraman Sara , Basu Sumanta , Clark Andrew G. , Delbare Sofie , Lee Myung Hee , Wells Martin T. 
Published: July 2021

AbstractTime-course gene expression datasets provide insight into the dynamics of complex biological processes, such as immune response and organ development. It is of interest to identify genes with similar temporal expression patterns because such genes are often biologically related. However, this task is challenging due to the high dimensionality of these datasets and the nonlinearity of gene expression time dynamics. We propose an empirical Bayes approach to estimating ordinary differential equation (ODE) models of gene expression, from which we derive a similarity metric between genes called the Bayesian lead-lag R2 (LLR2). Importantly, the calculation of the LLR2 leverages biological databases that document known interactions amongst genes; this information is automatically used to define informative prior distributions on the ODE model’s parameters. As a result, the LLR2 is a biologically-informed metric that can be used to identify clusters or networks of functionally-related genes with co-moving or time-delayed expression patterns. We then derive data-driven shrinkage parameters from Stein’s unbiased risk estimate that optimally balance the ODE model’s fit to both data and external biological information. Using real gene expression data, we demonstrate that our methodology allows us to recover interpretable gene clusters and sparse networks. These results reveal new insights about the dynamics of biological systems.
Persistent autism-relevant phenotype produced by in utero and lactational exposure of female mice to the commercial PBDE mixture, DE-71
Authors: Kozlova Elena V. , Valdez Matthew C. , Denys Maximillian E. , Bishay Anthony E. , Krum Julia M. , Rabbani Kayhon M. , Carrillo Valeria , Gonzalez Gwendolyn M. , Lampel Gregory , Tran Jasmin D. , Vazquez Brigitte M. , Anchondo Laura M. , Uddin Syed A. , Huffman Nicole M. , Monarrez Eduardo , Olomi Duraan S. , Chinthirla Bhuvaneswari D. , Hartman Richard E. , Rao Kodavanti Prasada S. , Chompre Gladys , Phillips Allison L. , Stapleton Heather M. , Henkelmann Bernhard , Schramm Karl-Werner , Curras-Collazo Margarita C. 
Published: July 2021

AbstractPolybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display altered short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks.
Photoredox-catalyzed decarboxylative C-terminal differentiation for bulk and single molecule proteomics
Authors: Zhang Le , Floyd Brendan M. , Chilamari Maheshwerreddy , Mapes James , Swaminathan Jagannath , Bloom Steven , Marcotte Edward M. , Anslyn Eric V. 
Published: July 2021

AbstractMethods for the selective labeling of biogenic functional groups on peptides are being developed and used in the workflow of both current and emerging proteomics technologies, such as single-molecule fluorosequencing. To achieve successful labeling with any one method requires that the peptide fragments contain the functional group for which the labeling chemistry is designed. In practice, only two functional groups are present on every peptide fragment regardless of the protein cleavage site, namely, an N-terminal amine and a C-terminal carboxylic acid. Developing a global-labeling technology, therefore, requires one to specifically target the N- and/or C-terminus of peptides. In this work, we showcase the first successful application of photocatalyzed C-terminal decarboxylative-alkylation for peptide mass-spectrometry and single molecule protein sequencing, that can be broadly applied to any proteome. We demonstrate that peptides in complex mixtures generated from enzymatic digests from bovine serum albumin, as well as protein mixtures from yeast and human cell extracts, can be site-specifically labeled at their C-terminal residue with a Michael acceptor. Using two distinct analytical approaches, we characterize C-terminal labeling efficiencies of greater than 50% across complete proteomes and document the proclivity of various C-terminal amino acid residues for decarboxylative-labeling, showing histidine and tryptophan to be the most disfavored. Finally, we combine C-terminal decarboxylative labeling with an orthogonal carboxylic acid labeling technology in tandem, to establish a new platform for fluorosequencing.
Lipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues
Authors: Atherton Elaina , Brown Sophie , Papiez Emily , Restrepo Maria I. , Borton David A. 
Published: July 2021

AbstractThree-dimensional (3D) neural microtissues are a powerful in vitro paradigm for studying brain development and disease under controlled conditions, while maintaining many key attributes of the in vivo environment. Here, we used primary cortical microtissues to study the effects of neuroinflammation on neural microcircuits. We demonstrated the use of a genetically encoded calcium indicator combined with a novel live-imaging platform to record spontaneous calcium transients in microtissues from day 14-34 in vitro. We implemented graph theory analysis of calcium activity to characterize underlying functional connectivity and community structure of microcircuits, which are capable of capturing subtle changes in network dynamics during early diseases states. We found that microtissues cultured for 34 days displayed functional remodeling of microcircuits and that community structure strengthened over time. Lipopolysaccharide, a neuroinflammatory agent, significantly increased functional connectivity and disrupted community structure 5-9 days after exposure. These microcircuit-level changes have broad implications for the role of neuroinflammation in functional dysregulation of neural networks.
Luminance and contrast of images in the THINGS database
Authors: Harrison William J 
Published: July 2021

AbstractThe THINGS database is a freely available stimulus set that has the potential to facilitate the generation of theory that bridges multiple areas within cognitive neuroscience. The database consists of 26,107 high quality digital photos that are sorted into 1,854 concepts. While a valuable resource, relatively few technical details relevant to the design of studies in cognitive neuroscience have been described. We present an analysis of two key low-level properties of THINGS images, luminance and luminance contrast. These image statistics are known to influence common physiological and neural correlates of perceptual and cognitive processes. In general, we found that the distributions of luminance and contrast are in close agreement with the statistics of natural images reported previously. However, we found that image concepts are separable in their luminance and contrast: we show that luminance and contrast alone are sufficient to classify images into their concepts with above chance accuracy. We describe how these factors may confound studies using the THINGS images, and suggest simple controls that can be implemented a priori or post-hoc. We discuss the importance of using such natural images as stimuli in psychological research.
caliPER: A software for blood-free parametric Patlak mapping using PET/MRI input function
Authors: Dassanayake Praveen , Cui Lumeng , Finger Elizabeth , Kewin Matthew , Hadaway Jennifer , Soddu Andrea , Jakoby Bjoern , Zuehlsdorf Sven , Lawrence Keith S St , Moran Gerald , Anazodo Udunna C 
Published: July 2021

AbstractRoutine clinical use of absolute PET quantification techniques is limited by the need for serial arterial blood sampling for input function and more importantly by the lack of automated pharmacokinetic analysis tools that can be readily implemented in clinic with minimal effort. PET/MRI provides the ability for absolute quantification of PET probes without the need for serial arterial blood sampling using image-derived input functions (IDIFs). Here we introduce caliPER, a modular and scalable software for simplified pharmacokinetic modelling of PET probes with irreversible uptake or binding based on PET/MR IDIFs and Patlak Plot analysis. caliPER generates regional values or parametric maps of net influx rate (Ki) using reconstructed dynamic PET images and anatomical MRI aligned to PET for IDIF vessel delineation. We evaluated the performance of caliPER for blood-free region-based and pixel-wise Patlak analyses of [18F] FDG by comparing caliPER IDIF to serial arterial blood input functions and its application in imaging brain glucose hypometabolism in Frontotemporal dementia. IDIFs corrected for partial volume errors including spill-out and spill-in effects were similar to arterial blood input functions with a general bias of around 6-8%, even for arteries <5 mm. The Ki and cerebral metabolic rate of glucose estimated using caliPER IDIF were similar to estimates using arterial blood sampling (<2%) and within limits of whole brain values reported in literature. Overall, caliPER is a promising tool for irreversible PET tracer quantification and can simplify the ability to perform parametric analysis in clinical settings without the need for blood sampling.HighlightscaliPER is an adaptable image processing software for extracting image-derived input functions and generating parametric maps of irreversible PET tracer uptake.Anatomical (T1-weighted/T2-weighted/time-of-flight angiography) MRI carefully aligned to PET provides a robust approach for delineation of vessels on PET, eliminating the need for serial blood sampling for input functions.Application of caliPER in modelling glucose uptake in patients with Frontotemporal dementia, demonstrates the feasibility of absolute quantification of cerebral metabolic rate of glucose in clinical populations.
The mitochondrial Na+/Ca2+exchanger, NCLX, mediates PDE2 dependent neuronal survival and learning
Authors: Rozenfeld Maya , Azoulay Ivana Savic , Ben Kasus Nissim Tsipi , Stavsky Alexandra , Hershfinkel Michal , Kofman Ora , Sekler Israel 
Published: July 2021

AbstractImpaired phosphodiesterase (PDE) function and mitochondrial Ca2+- [Ca2+]m signaling leads to cardiac failure, ischemic damage and dysfunctional learning and memory. Yet, a causative link between these pathways is unknown. Here, we fluorescently monitored [Ca2+]m transients in hippocampal neurons evoked by caffeine followed by depolarization. [Ca2+]m efflux was apparent in WT but diminished in neurons deficient in the mitochondrial Na+/Ca2+exchanger NCLX. Surprisingly, neuronal depolarization-induced Ca2+transients alone failed to evoke strong [Ca2+]m efflux in WT neurons. Caffeine is also a PDE inhibitor. Pretreatment with the PDE2 inhibitor Bay 60-7550 rescued [Ca2+]m efflux triggered by neuronal depolarization. Inhibition of PDE2 acted by diminishing the Ca2+dependent reduction of mitochondrial cAMP, thereby promoting NCLX phosphorylation. Selective PDE2 inhibition also enhanced [Ca2+]m efflux triggered by neuromodulators. We found that protection of neurons against excitotoxic insults, conferred by PDE2 inhibition, was diminished in NCLX KO neurons, thus is NCLX dependent. Finally, administration of Bay 60-7550 enhanced new object recognition learning in WT but not in NCLX KO mice. Our results identify a long-sought link between PDE and [Ca2+]m signaling thereby providing new therapeutic targets.
Instrumental aversion coding in the basolateral amygdala and its reversion by a benzodiazepine
Authors: Jean-Richard-dit-Bressel Philip , Tran Jenny , Didachos Angelos , McNally Gavan P. 
Published: July 2021

AbstractPunishment involves learning the relationship between actions and their adverse consequences. Both the acquisition and expression of punishment learning depend on the basolateral amygdala (BLA), but how BLA supports punishment remains poorly understood. To address this, we measured calcium (Ca2+) transients in BLA principal neurons during punishment. Male rats were trained to press two individually presented levers for food; when one of these levers also yielded aversive footshock, responding on this punished lever decreased relative to the other, unpunished lever. In rats with the Ca2+indicator GCaMP6f targeted to BLA principal neurons, we observed excitatory activity transients to the footshock punisher and inhibitory transients to lever-presses. Critically, as rats learned punishment, activity around the punished response transformed from inhibitory to excitatory and similarity analyses showed that these punished lever-press transients resembled BLA transients to the punisher itself. Systemically administered benzodiazepine (midazolam) selectively alleviated punishment. Moreover, the degree to which midazolam alleviated punishment was associated with how much punished response-related BLA transients reverted to their pre-punishment state. Together, these findings show that punishment learning is supported by aversion-coding of instrumental responses in the BLA and that the anti-punishment effects of benzodiazepines are associated with a reversion of this aversion coding.
Long-distance migration was associated with increased prevalence of post-traumatic stress disorder in Syrian refugees
Authors: Eiset Andreas Halgreen , Aoun Michaelangelo P. , Stougaard Monica , Gottlieb Annemarie Graa , Haddad Ramzi S. , Frydenberg Morten , Naja Wadih J. 
Published: July 2021

AbstractBackgroundRefugees are forced migrants but there is a large variation in the distance that refugees cover and there is a paucity in the evidence of how this may affect refugees’ health and health care needs. We investigated the association between long-distance migration and post-traumatic stress disorder (PTSD), a serious psychiatric disorder associated with deteriorating mental and somatic health.MethodsIncluded from 2016-2019 were 712 adult Syrian refugees and asylum seekers in Lebanon and Denmark arrived up to 12 months prior. PTSD was assessed using the Harvard Trauma Questionnaire and the estimate of association was obtained by multiply imputing missing data and adjusting for confounding by propensity score-weighting with covariates age, sex, socioeconomic status, trauma experience and WHO-5-score, reporting the bootstrap 95-percentile confidence interval (95% CI). Additionally, a number of sensitivity analyses were performed.ResultsAfter multiply imputing missing data and propensity score-weighted adjustment for confounding, migration to Denmark instead of Lebanon was associated with an increase in PTSD prevalence of 9 percentage point (95% CI [-1; 19] percentage point).DiscussionWe found that long-distance migration was associated with an increase in the prevalence of PTSD suggesting that long-distance migration may be a factor to consider when assessing refugees’ and asylum seekers’ health. Practitioners should consider “long-distance migration” in refugee health screenings and in particular when assessing the risk of post-traumatic stress disorder. Future research should be designed to ultimately lead to studies of relevant interventions to lower the risk of post-traumatic stress disorder in refugees.
Genome-wide polygenic risk score method for diabetic kidney disease in patients with type 2 diabetes
Authors: Vy Ha My T. , Dellepiane Sergio , Chaudhary Kumardeep , Blair Alexander , Glicksberg Benjamin S , Coca Steven G , Chan Lili , He John Cijiang , Do Ron , Nadkarni Girish N 
Published: July 2021

ABSTRACTDiabetic kidney disease (DKD) is considered partially hereditary, but the genetic factors underlying disease remain largely unknown. A key barrier to our understanding stems from its heterogeneity, and likely polygenic etiology. Proteinuric and non-proteinuric DKD are two sub-classes of DKD, defined by high urinary albumin-to-creatinine ratio (UACR) and low creatinine estimated glomerular filtration rate (eGFR). Prior genome-wide association studies (GWAS) have identified multiple loci associated with eGFR and UACR. We aimed to combine summary statistics from previous GWAS’ for eGFR and UACR in one prediction model and associate it with DKD prevalence. We then tested this using genetic data from 18,841 individuals diagnosed with type 2 diabetes in UK Biobank. We computed two genome-wide polygenic risk scores (GPS) aggregating effects of common variants associated with the two measurements, eGFR and UACR. We show that including both GPS’ in a single model confers significant improvement in comparison with the single GPS model generated from GWAS summary statistics for DKD. We also find in replication analysis in 5,389 individuals in the multi-ethnic BioMe Biobank, that although the combined model had consistent direction of association, the lowest performance was in individuals with recent African ancestry. In summary, we show that joint modeling of polygenic associations of eGFR and UACR is more significantly associated with DKD than individual modeling as well as a GPS comprised of only DKD summary statistics and may be used to gain insights into biology and progression. However, efforts should be made to develop and validate polygenic approaches in diverse populations.