bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compulsive drinking is associated with neural activity patterns reflecting diminished behavioral control and enhanced seeking representations in dorsal medial prefrontal cortex
Authors: Timme Nicholas M. , Ma Baofeng , Linsenbardt David , Cornwell Ethan , Galbari Taylor , Lapish Christopher 
Published: March 2021

AbstractDrinking despite negative consequences (compulsive drinking) is a central contributor to high-risk alcohol intake and is associated with poor treatment outcomes in humans. We used a rodent model of compulsive drinking to examine the role played by dorsal medial prefrontal cortex (dmPFC), a brain region involved in maladaptive decision-making in addiction, in this clinically critical phenomenon. We developed novel advances in principal component and change point analyses to dissect neural population representations of specific decision-making variables. Compulsive subjects showed weakened representations of behavioral control signals that relate to drinking within a trial, but strengthened session-wide seeking state representations that were associated with drinking engagement at the start of each drinking opportunity. Finally, chemogenetic-based excitation of dmPFC prevented escalation of compulsive drinking. Collectively, these data indicate that compulsive drinking is associated with alterations in dmPFC neural activity that underlie diminished behavioral control and enhanced seeking.
The salmon louse genome: copepod features and parasitic adaptations
Authors: Skern-Mauritzen Rasmus , Malde Ketil , Eichner Christiane , Dondrup Michael , Furmanek Tomasz , Besnier Francois , Komisarczuk Anna Zofia , Nuhn Michael , Dalvin Sussie , Edvardsen Rolf B. , Klages Sven , Huettel Bruno , Stueber Kurt , Grotmol Sindre , Karlsbakk Egil , Kersey Paul , Leong Jong S. , Glover Kevin A. , Reinhardt Richard , Lien Sigbjørn , Jonassen Inge , Koop Ben F. , Nilsen Frank 
Published: March 2021

AbstractCopepods encompass a range of ecological roles from parasites to phytoplankton grazers linking primary producers to higher trophic levels. Despite these important roles, copepod genome assemblies are scarce.Lepeophtheirus salmonisis an economically and ecologically important ectoparasitic copepod. We present the 695.4 MbpL. salmonisgenome assembly containing ≈60% repetitive regions and 13081 annotated protein-coding genes. The genome comprises 14 autosomes and a ZZ-ZW sex chromosome system. Assembly assessment identified 92.4% of the expected arthropod genes. Transcriptomics validated annotation and revealed a marked shift in gene expression after host attachment, including downregulation of genes related to circadian rhythm coinciding with abandoning diurnal migration. The genome shows evolutionary signatures including loss of peroxisomes, numerous FNII domains, and an incomplete heme homeostasis pathway suggesting heme proteins to be obtained from the host. Despite large capacity to develop resistance against chemical treatmentsL. salmonisexhibits low numbers of many genes involved in detoxification.
Responding kinetic of B-cell receptor repertoire to the Toll-like receptor 7/8 stimulation in non-human primates
Authors: Wang Shiyu , Mandl Judith , Feinberg Mark , Citron Michael , Saksena Nitin K. , Luo Lihua , Li Zida , Zhu Yonggang , Li Tao , Nie Chao , Zhang Xiuqing , Liu Ya , Liu Xiao , Wang I-Ming , Zhang Wei 
Published: March 2021

AbstractTLR7 and 8 regulate B cell immunity, but the precise details of the mechanism are still unclear. Here, we studied the kinetics of both heavy and light chains (IgKL) of B-cell receptor (BCR) repertoire responding to the TLR7/8 stimulation in two geniuses of non-human primates (NHPs), African green monkeys (AGMs) and rhesus macaques (RMs). We evaluated the activation of lymphocytes by flow cytometry, and studied characteristics of BCR repertoire in terms of gene usage, repertoire diversity, and the number of lineages. Although AGMs had a weaker activation than RMs, and a different responding kinetic, both AGMs and RMs presented an increased IgKL repertoire diversity and lineages expansion. It suggested that the responding time rather than initiation of TLR7/8-induced IgKL repertoire response related to B cell activation. Expanded IgKL lineages with frequency from 0.001% to 1% had an elevated mutation rate and expanded IgH lineages used more IgA/G/E, suggesting that the TLR7/8 stimulation expanded low-frequent but high-mutated lineages. Besides, most of expanded IgKL lineages were λ isotype. In conclusion, TLR7/8 selectively expands IgKL lineages with a high mutation rate, low frequency, and λ isotype. The selective effect of TLR7/8 on BCR repertoire allows TLR7/8 agonists to be adjuvant for selectively accelerating antibody maturation.
Personalized sleep-wake patterns aligned with circadian rhythm relieve daytime sleepiness
Authors: Hong Jaehyoung , Choi Su Jung , Park Se Ho , Hong Hyukpyo , Booth Victoria , Joo Eun Yeon , Kim Jae Kyoung 
Published: March 2021

SummaryShift workers and many other groups experience irregular sleep-wake patterns. This can induce excessive daytime sleepiness that decreases productivity and elevates the risk of accidents. However, the degree of daytime sleepiness is not correlated with standard sleep parameters like total sleep time, suggesting other factors are involved. Here, we analyze real-world sleep-wake patterns of shift workers measured by wearables with a newly developed user-friendly computational package that simulates homeostatic sleep pressure – the physiological need for sleep – and the circadian rhythm. This reveals that shift workers who align sleep-wake patterns with their circadian rhythm have lower daytime sleepiness, even if they sleep less. The alignment, quantified by a new parameter, circadian sleep sufficiency, can be increased by dynamically adjusting daily sleep durations according to varying bedtimes. Our computational package provides flexible and personalized real-time sleep-wake patterns for individuals to reduce their daytime sleepiness and could be used with wearable devices to develop smart alarms.
Codependency and mutual exclusivity for gene community detection from sparse single-cell transcriptome data
Authors: Nakajima Natsu , Hayashi Tomoatsu , Fujiki Katsunori , Shirahige Katsuhiko , Akiyama Tetsu , Akutsu Tatsuya , Nakato Ryuichiro 
Published: March 2021

AbstractSingle-cell RNA-seq (scRNA-seq) can be used to characterize cellular heterogeneity in thousands of cells. The reconstruction of a gene network based on coexpression patterns is a fundamental task in scRNA-seq analyses, and the mutual exclusivity of gene expression can be critical for understanding such heterogeneity. Here, we propose an approach for detecting communities from a genetic network constructed on the basis of coexpression properties. The community-based comparison of multiple coexpression networks enables the identification of functionally related gene clusters that cannot be fully captured through differential gene expression-based analysis. We also developed a novel metric referred to as the exclusively expressed index (EEI) that identifies mutually exclusive gene pairs from sparse scRNA-seq data. EEI quantifies and ranks the exclusive expression levels of all gene pairs from binary expression patterns while maintaining robustness against a low sequencing depth. We applied our methods to glioblastoma scRNA-seq data and found that gene communities were partially conserved after serum stimulation despite a considerable number of differentially expressed genes. We also demonstrate that the identification of mutually exclusive gene sets with EEI can improve the sensitivity of capturing cellular heterogeneity. Our methods complement existing approaches and provide new biological insights, even for a large, sparse dataset, in the single-cell analysis field.
The formal demography of kinship III: Kinship dynamics with time-varying demographic rates
Authors: Caswell Hal , Song Xi 
Published: March 2021

AbstractBackgroundKinship models generally assume time-invariant demographic rates, and compute the kinship structures implied by those rates. It is important to compute the consequences of time variation in demographic rates for kinship stuctures.ObjectivesOur goal is to develop a matrix model for the dynamics of kinship networks subject to arbitrary temporal variation in survival, fertility, and population structure.MethodsWe develop a system of equations for the dynamics of the age structure of each type of kin of a Focal individual. The matrices describing survival and fertility vary with time. The initial conditions in the time-invariant model are replaced with a set of boundary conditions for initial time and initial age.ResultsThe time-varying model maintains the network structure of the time-invariant model. In addition to the results of the time-invariant model, it provides kinship structures by period, cohort, and age. It applies equally to historical sequences of past rates and to projections of future rates. As an illustration, we analyze the kinship structure of Sweden from 1891 to 2120.ContributionThe time-varying kinship model makes it possible to analyze the consequences of changing demographic rates, in the past or the future. It is easily computable, requires no simulations, and is readily extended to include additional, more distant relatives in the kinship network. The method can also be used to show the growth of families, lineages, and dynasties in populations across time and place and between social groups.
Response inhibition in premotor cortex corresponds to a complex reshuffle of the mesoscopic information network
Authors: Bardella Giampiero , Giuffrida Valentina , Giarrocco Franco , Brunamonti Emiliano , Pani Pierpaolo , Ferraina Stefano 
Published: March 2021

ABSTRACTRecent studies have explored functional and effective neural networks in animal models; however, the dynamics of information propagation among functional modules under cognitive control remain largely unknown. Here, we addressed the issue using Transfer Entropy and graph theory methods on mesoscopic neural activities recorded in the dorsal premotor cortex of rhesus monkeys. We focused our study on the decision time of a Stop-signal task, looking for patterns in the network configuration that could influence motor plan maturation when the Stop signal is provided. When comparing trials with successful inhibition to those with generated movement, the nodes of the network resulted organized into four clusters, hierarchically arranged, and distinctly involved in information transfer. Interestingly, the hierarchies and the strength of information transmission between clusters varied throughout the task, distinguishing between generated movements and canceled ones and corresponding to measurable levels of network complexity. Our results suggest a putative mechanism for motor inhibition in premotor cortex: a topological reshuffle of the information exchanged among ensembles of neurons.AUTHOR SUMMARYIn this study, we investigated the dynamics of information transfer among functionally identified neural modules during cognitive motor control. Our focus was on mesoscopic neural activities in the dorsal premotor cortex of rhesus monkeys engaged in a Stop-signal task. Leveraging multivariate Transfer Entropy and graph theory, we uncovered insights on how behavioral control shapes the topology of information transmission in a local brain network. Task phases modulated the strength and hierarchy of information exchange between modules, revealing the nuanced interplay between neural populations during generated and canceled movements. Notably, during successful inhibition, the network displayed a distinctive configuration, unveiling a novel mechanism for motor inhibition in the premotor cortex: a topological reshuffle of information among neuronal ensembles.
Broccoli sprout Sulforaphane affected hemodynamics and aorta myogenic spontaneous rhythmic contraction in sanitized water uptake mice
Authors: Li Linmei , Gao Lingfeng , Wang Ting , He Tong , Li Jiaxing , Suwardi Rifqah Kurnia , Xu Xuan , Wang Yang 
Published: March 2021

AbstractDrinking seawater erodes water source will lead to hemodynamic changes in cardiovascular system. The erosion affected vascular biomechanics further interrupt the blood supply in arterial network. In this study, we investigated the carotid arterial hemodynamics in salinity water fed mice, and the relative spontaneous contraction of aorta preparation. The biological effect of Broccoli sprout Sulforaphane was assessed in intake hemodynamic changes.Kunmingmice were randomly divided into seawater feeding group, seawater + Sulforaphane group, freshwater feeding group, fresh water + Sulforaphane group. After 4 weeks of feeding, the pressure waveforms of common carotid artery were analyzedin vivo. The enhanced common carotid arterial pressures were calculated according to the breakpoint of systolic pressure rising phase. The ejection time was calculated according to the dicrotic notch.In vitro, the isolated aorta biomechanical features were tested on a micro stepping platform. The passive tension and relative myogenic spontaneous contraction were evaluated. The results indicated that in salinity water fed mice heart rate, ejection period were significantly accelerated. The systolic pressure breakpoint of the ascending phase was significantly increased; however, the central aortic pressure augment index was decreased.In vitrostudy, the isolated aorta preparations indicated remarkable myogenic spontaneous contraction in salinity water fed mice. The spontaneous contraction indicated a significant cycle pattern, the waveform cluster changes regularly in one cycle, maximal amplitude of myogenic autonomic contraction increased significantly. Spontaneous contraction became more active, however cycle duration shortened. In biological effect of Broccoli sprout supplement, Sulforaphane was effective in reducing the heart rate, prolonging ejection period, improving systolic pressure and pulse pressure amplitude in salinity water fed mice. We concluded that long-term salinity water uptake can form a new hypertension model in mice, which can affect the changes of carotid artery hemodynamics and local blood supply. The Broccoli sprout Sulforaphane can improve the high systolic blood pressure and ejection period of artery, and its mechanism needs further study.
Insights into the drivers of radiating diversification in biodiversity hotspots usingSaussurea(Asteraceae) as a case
Authors: Zhang Xu , Landis Jacob B. , Sun Yanxia , Zhang Huajie , Feng Tao , Lin Nan , Tiamiyu Bashir B. , Huang Xianhan , Deng Tao , Wang Hengchang , Sun Hang 
Published: March 2021

AbstractThe Qinghai-Tibet Plateau (QTP) encompasses areas with a remarkably high degree of biodiversity, harboring exceptional species-rich radiations. How these radiations formed by interacting with geology, climate and ecology remains seldom examined.We investigate the roles of abiotic (environmental) and biotic (species-intrinsic) factors in driving radiating diversification ofSaussurea(Asteraceae) by deploying a number of time-dependent, paleoenvironment-dependent and trait-dependent models, as well as ecological distribution data.We show that three main clades ofSaussureabegin to diversify in the Miocene almost simultaneously, with increasing diversification rates toward the present and negative dependence to paleotemperature. Acceleration in diversification rates are correlated with adaptive traits, as well climate lability, niche breadth and species range.We conclude that fluctuation of paleoclimate along with complex QTP environments provided opportunities for increased diversification rates ofSaussureawith diverse adaptive traits, highlighting the importance of combinations of clade-specific traits and ecological niches in driving rapid radiation.
The role of ventromedial prefrontal cortex in reward valuation and future thinking during intertemporal choice
Authors: Ciaramelli Elisa , De Luca Flavia , Kwan Donna , Mok Jenkin , Bianconi Francesca , Knyagnytska Violetta , Craver Carl , Green Leonard , Myerson Joel , Rosenbaum R. Shayna 
Published: March 2021

AbstractIntertemporal choices require trade-offs between short-term and long-term outcomes. Ventromedial prefrontal cortex (vmPFC) damage causes steep discounting of future rewards (delay discounting; DD) and impoverished episodic future thinking (EFT). The role of vmPFC in reward valuation, EFT, and their interaction during intertemporal choice is still unclear. Here, twelve patients with lesions to vmPFC and forty-one healthy controls chose between smaller-immediate and larger-delayed hypothetical monetary rewards while we manipulated reward magnitude and the availability of EFT cues. In the EFT condition, participants imagined personal events to occur at the delays associated with the larger-delayed rewards. We found that DD was steeper in vmPFC patients compared to controls, and not modulated by reward magnitude. However, EFT cues downregulated DD in vmPFC patients as well as controls. These findings indicate that vmPFC integrity is critical for the valuation of (future) rewards, but not to instill EFT in intertemporal choice.
Powering electronic implants by high frequency volume conduction: in human validation
Authors: Minguillon Jesus , Tudela-Pi Marc , Becerra-Fajardo Laura , Perera-Bel Enric , del-Ama Antonio J. , Gil-Agudo Ángel , Megía-García Álvaro , García-Moreno Aracelys , Ivorra Antoni 
Published: March 2021

AbstractWireless power transfer (WPT) is frequently used as an alternative to batteries to accomplish miniaturization in electronic medical implants (eMIs). However, established WPT methods require bulky parts within the implant or cumbersome external systems, hindering minimally invasive deployments and the development of networks of eMIs. As an alternative, we propose a WPT approach based on volume conduction of high frequency (HF) current bursts. These currents are applied through external textile electrodes and are collected by the eMIs through two electrodes at their opposite ends. This approach avoids bulky components to obtain power, making it possible to develop implants with a flexible threadlike conformation. In here we study in humans if HF (6.78 MHz) current bursts complying with safety standards and applied through two textile electrodes strapped around a limb can provide substantial powers from pairs of implanted electrodes. Time averaged electric powers obtained from needle electrodes (diameter = 0.4 mm, length = 3 mm, separation = 30 mm) inserted into arms and lower legs of five healthy participants were 5.9 ± 0.7 mW and 2.4 ± 0.3 mW respectively. We also report a procedure to characterize the coupling between the external system and the implants using two-port impedance models generated from medical images. The results demonstrate for the first time in humans that innocuous and imperceptible HF current bursts that flow through the tissues by volume conduction can be used to wirelessly power threadlike eMIs, overcoming the limitations of existing WPT methods in terms of minimal invasiveness and usability.
α-lipoic acid has the potential to normalize copper metabolism, which is dysregulated in Alzheimer’s disease
Authors: Metsla Kristel , Kirss Sigrid , Laks Katrina , Sildnik Gertrud , Palgi Mari , Palumaa Teele , Tõugu Vello , Palumaa Peep 
Published: March 2021

AbstractAlzheimer’s disease (AD) is an age-dependent progressive neurodegenerative disorder and the most common cause of dementia. The treatment and prevention of AD present immense yet unmet needs. One of the hallmarks of AD is the formation of extracellular amyloid plaques in the brain, composed of amyloid-beta (Aβ) peptides. Multiple amyloid-targeting drug candidates have recently failed in clinical trials, which creates the necessity to focus also on alternative therapeutic strategies. One factor contributing to the development of AD is dysregulated copper metabolism, reflected in the intracellular copper deficit and excess extracellular copper levels. In the current study, we follow the widely accepted hypothesis that the normalization of copper metabolism leads to the prevention or slowing of the disease and searched for new copper-regulating ligands. We demonstrate that the natural intracellular copper chelator, α-lipoic acid (LA) translocates copper from extracellular to intracellular space in a SH-SY5Y-based neuronal cell model, and is thus suitable to alleviate the intracellular copper deficit characteristic of AD neurons. Furthermore, we show that supplementation with LA protects theDrosophila melanogastermodel of AD from developing AD phenotype, reflecting in decreased locomotor activity. Collectively, these results provide evidence that LA has the potential to normalize copper metabolism in AD and supports the hypothesis that LA supplementation may serve as a promising cost-effective method for the prevention and/or treatment of AD.Significance statementAlzheimer’s disease (AD) is a major biomedical concern that requires novel effective prevention and treatment approaches. An early determinant of AD pathology is dysregulated copper metabolism, which initiates the amyloid cascade, induces oxidative stress and impairs the functioning of cellular copper proteins, all contributing to the development of neurodegeneration. We suggest that the natural copper chelator α-lipoic acid (LA) can normalize impaired copper metabolism in AD. We demonstrate that LA promotes the influx of copper into SH-SY5Y cells in a dose-dependent manner. Moreover, we show that LA alleviates the disease phenotype in a Drosophila melanogaster model of AD. Together with previously published data, these results support the hypothesis that LA has the potential for the prevention and treatment of AD.
Tissue environment, not ontogeny, defines intestinal intraepithelial T lymphocytes
Authors: Brenes Alejandro , Vandereyken Maud , James Olivia J. , Hukelmann Jens , Spinelli Laura , Lamond Angus I. , Swamy Mahima 
Published: March 2021

AbstractTissue-resident intestinal intraepithelial T lymphocytes (T-IEL) patrol the gut and have important roles in regulating intestinal homeostasis. T-IEL include both induced T-IEL, derived from systemic antigen-experienced lymphocytes, and natural IEL, which are developmentally targeted to the intestine. While the processes driving T-IEL development have been elucidated, the precise roles of the different subsets and the processes driving activation and regulation of these cells remain unclear. To gain functional insights into these enigmatic cells, we used high-resolution, quantitative mass spectrometry to investigate the proteomic landscape of the main T-IEL populations in the gut. Comparing the proteomes of induced T-IEL and natural T-IEL subsets, with naive CD8+T cells from lymph nodes exposes the dominant effect of the gut environment over ontogeny on T-IEL phenotypes. Analyses of protein copy numbers of >7000 proteins in T-IEL reveal skewing of the cell surface repertoire towards epithelial interactions and checkpoint receptors; strong suppression of the metabolic machinery indicating a high energy barrier to functional activation; and changes in T cell antigen receptor signalling pathways reminiscent of chronically activated T cells. These novel findings illustrate how multiple input signals need to be integrated to regulate T-IEL function.