bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning to be on time: temporal coordination of neural dynamics by activity-dependent myelination
Authors: Talidou Afroditi , Frankland Paul W. , Mabbott Donald , Lefebvre Jérémie 
Published: August 2021

AbstractActivity-dependent myelination is the mechanism by which myelin changes as a function of neural activity, and plays a fundamental role in brain plasticity. Mediated by structural changes in glia, activity-dependent myelination regulates axonal conduction velocity. It remains unclear how neural activity impacts myelination to orchestrate the timing of neural signaling. We developed a model of spiking neurons enhanced with neuron-glia feedback. Inspired by experimental data and use-dependent synaptic plasticity, we introduced a learning rule, called the Activity-Dependent Myelination (ADM) rule, by which conduction velocity scales with firing rates. We found that the ADM rule implements a homeostatic control mechanism that promotes and preserves synchronization. ADM-mediated plasticity was found to optimize synchrony by compensating for variability in axonal lengths by scaling conduction velocity in an axon-specific way. This property was maintained even when the network structure is altered. We further explored how external stimuli interact with the ADM rule to trigger bidirectional and reversible changes in conduction delays. These results highlight the role played by activity-dependent myelination in synchronous neural communication and brain plasticity.
Micromechanical Characterisation of 3D Bioprinted neural cell models using Brillouin Microscopy
Authors: Rad Maryam Alsadat , Mahmodi Hadi , Filipe Elysse C. , Cox Thomas R. , Kabakova Irina , Tipper Joanne L. 
Published: August 2021

AbstractBiofabrication of artificial 3D in vitro neural cell models that closely mimic the central nervous system (CNS) is an emerging field of research with applications from fundamental biology to regenerative medicine, and far reaching benefits for the economy, healthcare and the ethical use of animals. The micromechanical properties of such models are an important factor dictating the success of modelling outcomes in relation to accurate reproduction of the processes in native tissues. Characterising the micromechanical properties of such models non-destructively and over a prolonged span of time, however, are key challenges. Brillouin microscopy (BM) could provide a solution to this problem since this technology is non-invasive, label-free and is capable of microscale 3D imaging. In this work, the viscoelasticity of 3D bioprinted neural cell models consisting of NG 108-15 neuronal cells and GelMA hydrogels of various concentrations were investigated using BM. We demonstrate changes in the micro- and macro-scale mechanical properties of these models over a 7 day period, in which the hydrogel component of the model are found to soften as the cells grow, multiply and form stiffer spheroid-type structures. These findings signify the necessity to resolve in microscopic detail the mechanics of in vitro 3D tissue models and suggest Brillouin microscopy to be a suitable technology to bridge this gap.
Working memory capacity of crows and monkeys arises from similar neuronal computations
Authors: Hahn Lukas Alexander , Balakhonov Dmitry , Fongaro Erica , Nieder Andreas , Rose Jonas 
Published: August 2021

AbstractComplex cognition relies on flexible working memory, which is severely limited in its capacity. The neuronal computations underlying these capacity limits have been extensively studied in humans and in monkeys, resulting in competing theoretical models. We probed the working memory capacity of crows (Corvus corone) in a change detection task, developed for monkeys (Macaca mulatta), while we performed extracellular recordings of the prefrontal-like area nidopallium caudolaterale. We found that neuronal encoding and maintenance of information were affected by item load, in a way that is virtually identical to results obtained from monkey prefrontal cortex. Contemporary neurophysiological models of working memory employ divisive normalization as an important mechanism that may result in the capacity limitation. As these models are usually conceptualized and tested in an exclusively mammalian context, it remains unclear if they fully capture a general concept of working memory or if they are restricted to the mammalian neocortex. Here we report that carrion crows and macaque monkeys share divisive normalization as a neuronal computation that is in line with mammalian models. This indicates that computational models of working memory developed in the mammalian cortex can also apply to non-cortical associative brain regions of birds.
Visual recognition of social signals by a tecto-thalamic neural circuit
Authors: Kappel Johannes M. , Slangewal Katja , Förster Dominique , Shainer Inbal , Svara Fabian , Januszewski Michal , Sherman Shachar , Baier Herwig , Larsch Johannes 
Published: August 2021

AbstractSocial affiliation emerges from individual-level behavioral rules that are driven by conspecific signals1–5. Long-distance attraction and short-distance repulsion, for example, are rules that jointly set a preferred inter-animal distance in swarms6–8. However, little is known about their perceptual mechanisms and executive neuronal circuits3. Here we trace the neuronal response to self-like biological motion9,10(BM), a visual trigger for affiliation in developing zebrafish2,11. Unbiased activity mapping and targeted volumetric two-photon calcium imaging revealed 19 activity hotspots distributed throughout the brain and clustered BM-tuned neurons in a multimodal, socially activated nucleus of the dorsal thalamus (DT). Individual DT neurons encode fish-like local acceleration but are insensitive to global or continuous motion. Electron microscopic reconstruction of DT neurons revealed synaptic input from the optic tectum (TeO/superior colliculus) and projections into nodes of the conserved social behavior network12,13. Chemogenetic ablation of the TeO selectively disrupted DT responses to BM and social attraction without affecting short-distance repulsion. Together, we discovered a tecto-thalamic pathway that drives a core network for social affiliation. Our findings provide an example of visual social processing, and dissociate neuronal control of attraction from repulsion during affiliation, thus revealing neural underpinnings of collective behavior.
Age-associated Senescent - T Cell Signaling Promotes Type 3 Immunity that Inhibits Regenerative Response
Authors: Han Jin , Cherry Christopher , Mejias Joscelyn C. , Ruta Anna , Maestas David R. , Peña Alexis N. , Nguyen Helen Hieu , Yang Brenda , Gray-Gaillard Elise , Rutkowski Natalie , Krishnan Kavita , Tam Ada J. , Fertig Elana J. , Housseau Franck , Ganguly Sudipto , Moore Erika M. , Pardoll Drew M. , Elisseeff Jennifer H. 
Published: August 2021

AbstractAging is associated with immunological changes that compromise response to infections and vaccines, exacerbate inflammatory diseases and could potentially mitigate tissue repair. Even so, age-related changes to the immune response to tissue damage and regenerative medicine therapies remain unknown. Here, we characterized how aging induces senescence and immunological changes that inhibit tissue repair and therapeutic response to a clinical regenerative biological scaffold derived from extracellular matrix. Tissue signatures of inflammation and interleukin (IL)-17 signaling increased with injury and treatment in aged animals, and computational analysis uncovered age-associated senescent-T cell communication that promotes type 3 immunity in T cells. Local inhibition of type 3 immune activation using IL17-neutralizing antibodies improved healing and restored therapeutic response to the regenerative biomaterial, promoting muscle repair in older animals. These results provide insights into tissue immune dysregulation that occurs with aging that can be targeted to rejuvenate repair.
Effects of climate warming on the pine processionary moth at the southern edge of its range: a retrospective analysis on egg survival in Tunisia
Authors: Bourougaaoui Asma , Robinet Christelle , Ben Jamaa Mohamed L. , Laparie Mathieu 
Published: August 2021

AbstractIn recent years, ectotherm species have largely been impacted by extreme climate events, essentially heatwaves. In Tunisia, the pine processionary moth (PPM),Thaumetopoea pityocampa, is a highly damaging pine defoliator, which typically lays eggs in summer. Its geographical range is expanding northwards in Europe while retracting from South Tunisia where summer temperatures can reach extremely high values. In this study, we aimed at exploring the effects of climate change on this species at its southern range edge. We investigated variations of fecundity and causes of egg mortality over time using historical and contemporary collections of egg masses from different Tunisian sites to seek relationships with regional climate change over three decades (1990-2019). Our results suggest negative effects of summer heat on egg survival, reflected in a decrease of hatching rate down to 0% in one site during a heatwave. Such a high hatching failure was found to result from both high egg sterility (our results did not allow distinguishing impeded mating success from failed egg maturation or early death of the embryo) and increased abortion of more developed embryos, but little effects of parasitism rate, thereby suggesting vulnerability to heat during embryonic development. We also observed decreasing female fecundity (i.e., number of eggs laid per female) in regions where data were available both in the 1990s and the 2010s, which was associated with a decrease in parasitism rate, while the climatic variability increased. This study investigated direct hatching failure in nature that may be related to the magnitude of warming in summer. Previous studies have confirmed the thermal sensitivity of early instars of the PPM to temperatures observed in the present work, including one population from South Tunisia. However, further work is required to evaluate the relative importance of warming summers among populations because the risk of heat stress depends on the phenology of sensitive instars, and populations from the warmest areas may not necessarily be the most vulnerable to climate change if they already evolved phenological heat avoidance. In addition to heat-induced mortality, the ultimate fitness of individuals that survive challenging heat stresses during early developmental stages should also be explored to determine potential carry-over effects on subsequent life stages.
Mechanical intercellular communication via matrix-borne cell force transmission during vascular network formation
Authors: Davidson Christopher D. , DePalma Samuel J. , Wang William Y. , Kamen Jordan L. , Jayco Danica Kristen P. , Baker Brendon M. 
Published: August 2021

ABSTRACTIntercellular communication is critical to the development and homeostatic function of all tissues. Previous work has shown that cells can communicate mechanically via transmission of cell-generated forces through their surrounding extracellular matrix, but this process is not well understood. Here, we utilized synthetic, electrospun fibrous matrices in conjunction with a microfabrication-based cell patterning approach to examine mechanical intercellular communication (MIC) between endothelial cells (ECs) during the assembly of microvascular networks. We found that cell force-mediated matrix displacements in deformable fibrous matrices underly directional migration of neighboring ECs towards each other prior to the formation of stable cell-cell connections. We also identified a critical role for intracellular calcium signaling mediated by focal adhesion kinase and TRPV4 during MIC that extends to multicellular assembly of vessel-like networks in 3D fibrin hydrogels. The results presented here are critical to the design of biomaterials that support cellular self-assembly for tissue engineering applications.
Features of peptide fragmentation spectra in single cell proteomics
Authors: Boekweg Hannah , Van Der Watt Daisha , Truong Thy , Guise Amanda J , Plowey Edward D , Kelly Ryan T , Payne Samuel H 
Published: August 2021

AbstractThe goal of proteomics is to identify and quantify the complete set of proteins in a biological sample. Single cell proteomics specializes in identification and quantitation of proteins for individual cells, often used to elucidate cellular heterogeneity. The significant reduction in ions introduced into the mass spectrometer for single cell samples could impact the features of MS2 fragmentation spectra. As all peptide identification software tools have been developed on spectra from bulk samples and the associated ion rich spectra, the potential for spectral features to change is of great interest. We characterize the differences between single cell spectra and bulk spectra by examining three fundamental spectral features that are likely to affect peptide identification performance. All features show significant changes in single cell spectra, including loss of annotated fragment ions, blurring signal and background peaks due to diminishing ion intensity and distinct fragmentation pattern compared to bulk spectra. As each of these features is a foundational part of peptide identification algorithms, it is critical to adjust algorithms to compensate for these losses.
An Endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells
Authors: Broadbent Lindsay , Bamford Connor G.G. , Campos Guillermo Lopez , Manzoor Sheerien , Courtney David , Ali Ahlam , Touzelet Olivier , McCaughey Conall , Mills Ken , Power Ultan F. 
Published: August 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the coronavirus disease-19 (COVID-19) pandemic, was identified in late 2019 and went on to cause over 3.3 million deaths in 15 months. To date, targeted antiviral interventions against COVID-19 are limited. The spectrum of SARS-CoV-2 infection ranges from asymptomatic to fatal disease. However, the reasons for varying outcomes to SARS-CoV-2 infection are yet to be elucidated. Here we show that an endogenously activated interferon lambda (IFNλ) pathway leads to resistance against SARS-CoV-2 infection. Using a well-differentiated primary nasal epithelial cell (WD-PNEC) model from multiple adult donors, we discovered that susceptibility to SARS-CoV-2 infection, but not respiratory syncytial virus (RSV) infection, varied. One of four donors was resistant to SARS-CoV-2 infection. High baseline IFNλ expression levels and associated interferon stimulated genes correlated with resistance to SARS-CoV-2 infection. Inhibition of the JAK/STAT pathway in WD-PNECs with high endogenous IFNλ secretion resulted in higher SARS-CoV-2 titres. Conversely, prophylactic IFNλ treatment of WD-PNECs susceptible to infection resulted in reduced viral titres. An endogenously activated IFNλ response, possibly due to genetic differences, may be one explanation for the differences in susceptibility to SARS-CoV-2 infection in humans. Importantly, our work supports the continued exploration of IFNλ as a potential pharmaceutical against SARS-CoV-2 infection.
Accuracy of multiple sequence alignment methods in the reconstruction of transposable element families
Authors: Hubley Robert , Wheeler Travis J. , Smit Arian F.A. 
Published: August 2021

AbstractThe construction of a high-quality multiple sequence alignment (MSA) from copies of a transposable element (TE) is a critical step in the characterization of a new TE family. Most studies of MSA accuracy have been conducted on protein or RNA sequence families where structural features and strong signals of selection may assist with alignment. Less attention has been given to the quality of sequence alignments involving neutrally evolving DNA sequences such as those resulting from TE replication. Such alignments play an important role in understanding and representing TE family history. Transposable element sequences are challenging to align due to their wide divergence ranges, fragmentation, and predominantly-neutral mutation patterns. To gain insight into the effects of these properties on MSA accuracy, we developed a simulator of TE sequence evolution, and used it to generate a benchmark with which we evaluated the MSA predictions produced by several popular aligners, along with Refiner, a method we developed in the context of our RepeatModeler software. We find that MAFFT and Refiner generally outperform other aligners for low to medium divergence simulated sequences, while Refiner is uniquely effective when tasked with aligning high-divergent and fragmented instances of a family. As a result, consensus sequences derived from Refiner-based MSAs are more similar to the true consensus.
Intracellular glycosyl hydrolase PslG shapes bacterial cell fate, signaling, and the biofilm development of Pseudomonas aeruginosa
Authors: Zhang Jingchao , Wu Huijun , Wang Di , Zhang Chenxi , Zhao Kun , Ma Luyan Z. 
Published: August 2021

AbstractBiofilm formation is one of most important causes leading to persistent infections. Exopolysaccharides are usually a main component of biofilm matrix. Genes encoding for glycosyl hydrolases are often found in gene clusters that are involved in the exopolysaccharide synthesis. It remains elusive about the functions of intracellular glycosyl hydrolase and why a polysaccharide synthesis gene cluster requires a glycosyl hydrolase. Here we systematically studied the role of intracellular PslG, a glycosyl hydrolase that is co-transcribed with 15 psl genes, which is responsible for the synthesis of exopolysaccharide Psl (ePsl), a key biofilm matrix polysaccharide in opportunistic pathogen Pseudomonas aeruginosa. We showed that lacking of PslG in this opportunistic pathogen alters the signaling function and structure of ePsl, changes the relative level of cyclic-di-GMP within daughter cells during cell division and shapes the localization of ePsl on bacterial periphery, thus results in long chains of bacterial cells, fast-forming and compact biofilm microcolonies. Our results reveal the important roles of intracellular PslG on the cell fate and biofilm development.
Selection for seed size has indirectly shaped specialized metabolite abundance in oat (Avena sativaL.)
Authors: Brzozowski Lauren J. , Hu Haixiao , Campbell Malachy T. , Broeckling Corey D. , Caffe-Treml Melanie , Gutiérrez Lucía , Smith Kevin P. , Sorrells Mark E. , Gore Michael A. , Jannink Jean-Luc 
Published: August 2021

SummaryPlant breeding strategies to optimize metabolite profiles are necessary to develop health-promoting food crops. In oats (Avena sativaL.), seed metabolites are of interest for their antioxidant properties and their agronomic role in mitigating disease severity, yet have not been a direct target of selection in breeding. In a diverse oat germplasm panel spanning a century of breeding, we investigated the degree of variation of these specialized metabolites and how it has been molded by selection for other traits, like yield components. We also ask if these patterns of variation persist in modern breeding pools. Integrating genomic, transcriptomic, metabolomic and phenotypic analyses for three types of seed specialized metabolites – avenanthramides, avenacins, and avenacosides – we found reduced genetic variation in modern germplasm compared to diverse germplasm, in part due to increased seed size associated with more intensive breeding. Specifically, we found that abundance of avenanthramides increases with seed size, but additional variation is attributable to expression of biosynthetic enzymes, but avenacoside abundance decreases with seed size and plant breeding intensity. Overall, we show that increased seed size associated with plant breeding has uneven effects on the seed metabolome, and broadly contributes to understanding how selection shapes plant specialized metabolism.
Emerging harmful algal blooms caused by distinct seasonal assemblages of the toxic diatomPseudo-nitzschiain Narragansett Bay, RI, USA
Authors: Sterling Alexa R. , Kirk Riley D. , Bertin Matthew J. , Rynearson Tatiana A. , Borkman David G. , Caponi Marissa C. , Carney Jessica , Hubbard Katherine A. , King Meagan A. , Maranda Lucie , McDermith Emily J. , Santos Nina R. , Strock Jacob P. , Tully Erin M. , Vaverka Samantha B. , Wilson Patrick D. , Jenkins Bethany D. 
Published: August 2021

AbstractThe diatomPseudo-nitzschiaproduces the neurotoxin domoic acid (DA) that bioaccumulates in shellfish, causing illness in humans and marine animals upon ingestion. In 2017, high levels of DA in shellfish meat closed shellfish harvest in Narragansett Bay (NBay), Rhode Island for the first time in history, although abundantPseudo-nitzschiahave been observed for over 50 years. What caused these events is unknown: whether an environmental factor altered endemicPseudo-nitzschiaphysiology or new DA-producing strain(s) were introduced. To investigate, we conducted weekly sampling from 2017-2019 to compare with 2016 precautionary closure and 2017 closure samples. Particulate DA was quantified by highly sensitive LC-MS/MS and correlated with environmental metadata.Pseudo-nitzschiawere identified using high-throughput rDNA sequencing, yielding a detailed understanding of distinct seasonal multi-species assemblages. Low DA was detected throughout 2017-2019, except in recurring peaks in the fall and early summer. Fall DA peaks contained toxigenic species (P. pungensvar.pungens, P. multiseries, P. calliantha,andP. subpacifica) as well as a novelP. americanataxon. Fewer species were present during summer DA peaks including toxigenicP. multiseries, P. plurisecta,andP. delicatissima.Most 2017 closure samples containedP. australis.Our data showedP. australisas infrequent but particularly concerning. RecurringPseudo-nitzschiaassemblages were driven by seasonal temperature changes and DA correlated with low dissolved inorganic nitrogen. Thus, the NBay closures were likely caused by resident assemblages dependent on nutrient status as well as the episodic introductions of species that may be a result of oceanographic and climactic shifts.
svaRetro and svaNUMT: Modular packages for annotation of retrotransposed transcripts and nuclear integration of mitochondrial DNA in genome sequencing data
Authors: Dong Ruining , Cameron Daniel , Bedo Justin , Papenfuss Anthony T 
Published: August 2021

AbstractBackgroundThe biological significance of structural variation is now more widely recognized. However, due to the lack of available tools for downstream analysis, including processing and annotating, interpretation of structural variant calls remains a challenge.FindingsHere we present svaRetro and svaNUMT, R packages that provide functions for annotating novel genomic events such as non-reference retro-copied transcripts and nuclear integration of mitochondrial DNA. We evaluate the performance of these packages to detect events using simulations and public benchmarking datasets, and annotate processed transcripts in a public structural variant database.ConclusionssvaRetro and svaNUMT provide efficient, modular tools for downstream identification and annotation of structural variant calls.