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With the global COVID-19 pandemic, governments from many countries in the world implemented various restrictions to prevent the SARS-Cov-2 virus's spread, including social distancing measures, quarantine, in-home lockdown, and the closure of services and public spaces. This led to an in-creased use of social media platforms to make people feel more connected, but also to maintain physical activity while self-isolating. Concerns about physical appearance and the desire to keep or reach a muscular and toned ideal body, might have further reinforced the engagement in fitness-related social media activities, like sharing progresses in training achievements or following more fitness contents on popular profiles. To better understand the underlying relation among these factors, the present study investigates 729 responses to the Exercise Addiction Inventory (EAI), the Appearance Anxiety Inventory (AAI), the Self-Compassion Scale (SCS) and their association to social media usage and compares the results cross-culturally in five countries (Spain, Lithuania, United Kingdom, Japan, and Hungary). Findings highlight significant differences between males and females, espe-cially in regard to the time spent online (U = 477.5, p = 0.036). Greater levels of appearance anxiety were associated with the exposure to fitness-related contents on social media. These results strongly confirm the previously highlighted association between fitspiration media and body image anxiety predominantly in females. Clinical implications and future considerations in terms of prevention and treatment in a situation of global emergency are also discussed. Published version This publication is based upon work from the European Network for Problematic Usage of the Internet, supported by COST (European Cooperation in Science and Technology; CA16207). This research was also supported by Fundaç ̃ao para a Ciˆencia e Tecnologia (FCT) through R&D Units funding (UIDB/05210/2020). ZD’s contribution was supported by the Hungarian National Research, Development, and Innovation Office (KKP126835; K134807; ELTE Thematic Excellence Programme, 2020; KP2020-IKA-05). HF’s contribution was supported by “Grant-in-Aid” by the Smoking Research Foundation.

Background Attentional impairments are associated with attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Previous evidence suggests both commonalities and differences in the nature of attention deficits between these disorders. This study aimed to investigate the neural correlates of ADHD and ASD traits in healthy individuals, focusing on the functional connectivity (FC) of the large-scale brain networks (LSBN) subserving attentional functions. Methods The participants were 61 healthy individuals (30 males; age, 21.9 ± 1.9 years). The Adult ADHD Self-Report Scale (ASRS) and Autism-Spectrum Quotient (AQ) were administered as indicators of ADHD and ASD traits, respectively. Performance in the continuous performance test (CPT) was used as a behavioural measure of sustained attentional function. Functional magnetic resonance imaging scans were performed during the resting state (Rest) and during the auditory oddball task (Odd). Regions of interest (ROI)-to-ROI analyses (FDR

Problematic internet use (PIU) is increasingly recognized as a mental health concern, particularly among adolescents. The resting-state functional connectivity (rsFC) of the triple-network model has been described inconsistently in PIU. Using resting-state fMRI (rsFMRI) and hypothesizing a lower rsFC between default mode (DMN) and central executive networks (CEN) but a higher rsFC within the salience network (SN), this study scrutinized the neural substrates of PIU adolescents. A total of 30 adolescents with PIU and 30 control subjects underwent rsFMRI. The severity of PIU was evaluated by the Internet Addiction Test. Additionally, personality traits as well as emotional and behavioral problems were evaluated by the Temperament and Character Inventory (TCI) and the Strength and Difficulties Questionnaire (SDQ), respectively. Focusing on the DMN, SN, and CEN, we compared rsFC values between PIU and the control. Subsequently, within the combined group of subjects, TCI and SDQ correlation and mediation effects were investigated. Higher rsFC values of the left lateral prefrontal cortex (LPFC(L)) with the left anterior insula (aIns(L)) were observed for PIU than for the control, while rsFCs of the LPFC(L) with the medial PFC (MPFC), LPFC(L), as well as with the right lateral parietal cortex (LP(R)) were lower for PIU. Among these significant group differences, the rsFC between the LPFC(L) and MPFC was mediated by emotional symptoms (standardized β = −0.12, 95% CI −0.29, −0.0052). The dysfunctional attention switching and incentive salience regulated by the SN were implicated as being a neural correlate of PIU, and this relationship would in part be explained by the emotional dysregulation associated with PIU in adolescents.

Tissue stem cells are vital for organ homeostasis and regeneration owing to their ability to self-renew and differentiate into the various cell types that constitute organ tissue. These stem cells are formed during complex and dynamic organ development, necessitating spatial-temporal coordination of morphogenetic events and cell fate specification during this process. In recent years, technological advances have enabled the tracing of the cellular dynamics, states, and lineages of individual cells over time in relation to tissue morphological changes. These dynamic data have not only revealed the origin of tissue stem cells in various organs but have also led to an understanding of the molecular, cellular, and biophysical bases of tissue stem cell formation. Herein, we summarize recent findings on the developmental origin of tissue stem cells in the hair follicles, intestines, brain, skeletal muscles, and hematopoietic system, and further discuss how stem cell fate specification is coordinated with tissue topology.

Tissue stem cells are generated from a population of embryonic progenitors through organ-specific morphogenetic events1,2. Although tissue stem cells are central to organ homeostasis and regeneration, it remains unclear how they are induced during development, mainly because of the lack of markers that exclusively label prospective stem cells. Here we combine marker-independent long-term 3D live imaging and single-cell transcriptomics to capture a dynamic lineage progression and transcriptome changes in the entire epithelium of the mouse hair follicle as it develops. We found that the precursors of different epithelial lineages were aligned in a 2D concentric manner in the basal layer of the hair placode. Each concentric ring acquired unique transcriptomes and extended to form longitudinally aligned, 3D cylindrical compartments. Prospective bulge stem cells were derived from the peripheral ring of the placode basal layer, but not from suprabasal cells (as was previously suggested3). The fate of placode cells is determined by the cell position, rather than by the orientation of cell division. We also identified 13 gene clusters: the ensemble expression dynamics of these clusters drew the entire transcriptional landscape of epithelial lineage diversification, consistent with cell lineage data. Combining these findings with previous work on the development of appendages in insects4,5, we describe the ‘telescope model’, a generalized model for the development of ectodermal organs in which 2D concentric zones in the placode telescope out to form 3D longitudinally aligned cylindrical compartments. Live imaging and single-cell transcriptomics of mouse hair follicles reveal their development from 2D concentric zones in the placode to 3D longitudinal compartments, one of which is a stem cell compartment.

Although striatal dopamine neurotransmission is believed to be functionally linked to the formation of the corticostriatal network, there has been little evidence for this regulatory process in the human brain and its disruptions in neuropsychiatric disorders. Here, we aimed to investigate associations of striatal dopamine transporter (DAT) and D2 receptor availabilities with gray matter (GM) volumes in healthy humans. Positron emission tomography images of D2 receptor (n = 34) and DAT (n = 17) captured with the specific radioligands [11C]raclopride and [18F]FE‐PE2I, respectively, were acquired along with T1‐weighted magnetic resonance imaging data in our previous studies, and were re‐analyzed in this work. We quantified the binding potentials (BP ND) of these radioligands in the limbic, executive, and sensorimotor functional subregions of the striatum. Correlations between the radioligand BP ND and regional GM volume were then examined by voxel‐based morphometry. In line with the functional and anatomical connectivity, [11C]raclopride BP ND in the limbic striatum was positively correlated with volumes of the uncal/parahippocampal gyrus and adjacent temporal areas. Similarly, we found positive correlations between the BP ND of this radioligand in the executive striatum and volumes of the prefrontal cortices and their adjacent areas as well as between the BP ND in the sensorimotor striatum and volumes of the somatosensory and supplementary motor areas. By contrast, no significant correlation was found between [18F]FE‐PE2I BP ND and regional GM volumes. Our results suggest unique structural and functional corticostriatal associations involving D2 receptor in healthy humans, which might be partially independent of the nigrostriatal pathway reflected by striatal DAT., This is the first study to investigate the relationship between regional gray matter volumes and availabilities of both dopamine D2 receptor and transporter in the striatum of healthy adults, by using our previous magnetic resonance imaging and positron emission tomography datasets. We have demonstrated positive correlations between dopamine D2/3 receptor radioligand BP ND in the functional subregions of the striatum and the gray matter (GM) volumes of regions that could be functionally and anatomically connected to each of these striatal subdomains. Meanwhile, no marked correlations were observed between dopamine transporter radioligand BP ND and regional GM volumes.

Although striatal dopamine neurotransmission is believed to be functionally linked to the formation of the corticostriatal network, there has been little evidence for this regulatory process in the human brain and its disruptions in neuropsychiatric disorders. Here, we aimed to investigate associations of striatal dopamine transporter (DAT) and D2 receptor availabilities with gray matter (GM) volumes in healthy humans. Positron emission tomography images of D2 receptor (n = 34) and DAT (n = 17) captured with the specific radioligands [11C]raclopride and [18F]FE-PE2I, respectively, were acquired along with T1-weighted magnetic resonance imaging data in our previous studies, and were re-analyzed in this work. We quantified the binding potentials (BPND) of these radioligands in the limbic, executive, and sensorimotor functional subregions of the striatum. Correlations between the radioligand BPND and regional GM volume were then examined by voxel-based morphometry. In line with the functional and anatomical connectivity, [11C]raclopride BPND in the limbic striatum was positively correlated with volumes of the uncal/parahippocampal gyrus and adjacent temporal areas. Similarly, we found positive correlations between the BPND of this radioligand in the executive striatum and volumes of the prefrontal cortices and their adjacent areas as well as between the BPND in the sensorimotor striatum and volumes of the somatosensory and supplementary motor areas. By contrast, no significant correlation was found between [18F]FE-PE2I BPND and regional GM volumes. Our results suggest unique structural and functional corticostriatal associations involving D2 receptor in healthy humans, which might be partially independent of the nigrostriatal pathway reflected by striatal DAT.

著者人数: 12名, 形態: カラー図版あり, Number of authors: 12, Physical characteristics: Original contains color illustrations, Accepted: 2021-10-19, 資料番号: PA2220050000

This cross-sectional study aimed to explore specific online behaviours and their association with a range of underlying psychological and other behavioural factors during the COVID-19 pandemic. Eight countries (Italy, Spain, the United Kingdom, Lithuania, Portugal, Japan, Hungary, and Brazil) participated in an international investigation involving 2223 participants (M = 33 years old; SD = 11), 70% of whom were females. Participants were surveyed for specific type of Internet use severity, appearance anxiety, self-compassion, and image and use of performance-enhancing drugs (IPEDs). Results were compared cross-culturally. The mean time spent online was 5 h (SD = ±3) of daily browsing during the pandemic. The most commonly performed activities included social networking, streaming, and general surfing. A strong association between these online behaviours and appearance anxiety, self-compassion, and IPEDs use was found after adjustment for possible confounders, with higher scores being associated with specific online activities. Significant cross-cultural differences also emerged in terms of the amount of time spent online during the initial stages of the COVID-19 pandemic.

Resilience is a dynamic process that enables organisms to cope with demanding environments. Resting-state functional MRI (fMRI) studies have demonstrated a negative correlation between resilience and functional connectivities (FCs) within the default mode network (DMN). Considering the on-demand recruitment process of resilience, dynamic changes in FCs during cognitive load increases may reflect essential aspects of resilience. We compared DMN FC changes in resting and task states and their association with resilience. Eighty-nine healthy volunteers completed the Connor–Davidson Resilience Scale (CD-RISC) and an fMRI with an auditory oddball task. The fMRI time series was divided into resting and task periods. We focused on FC changes between the latter half of the resting period and the former half of the task phase (switching), and between the former and latter half of the task phase (sustaining). FCs within the ventral DMN significantly increased during “switching” and decreased during “sustaining”. For FCs between the retrosplenial/posterior cingulate and the parahippocampal cortex, increased FC during switching was negatively correlated with CD-RISC scores. In individuals with higher resilience, ventral DMN connectivities were more stable and homeostatic in the face of cognitive demand. The dynamic profile of DMN FCs may represent a novel biomarker of resilience.

Inter-tissue interaction is fundamental to multicellularity. Although the basement membrane (BM) is located at tissue interfaces, its mode of action in inter-tissue interactions remains poorly understood, mainly because the molecular and structural details of the BM at distinct inter-tissue interfaces remain unclear. By combining quantitative transcriptomics and immunohistochemistry, we systematically identify the cellular origin, molecular identity and tissue distribution of extracellular matrix molecules in mouse hair follicles, and reveal that BM composition and architecture are exquisitely specialized for distinct inter-tissue interactions, including epithelial–fibroblast, epithelial–muscle and epithelial–nerve interactions. The epithelial–fibroblast interface, namely, hair germ–dermal papilla interface, makes asymmetrically organized side-specific heterogeneity in the BM, defined by the newly characterized interface, hook and mesh BMs. One component of these BMs, laminin α5, is required for hair cycle regulation and hair germ–dermal papilla anchoring. Our study highlights the significance of BM heterogeneity in distinct inter-tissue interactions.

Dopamine supersensitivity psychosis (DSP) frequently arises with long-term antipsychotic treatment and accounts for a significant proportion of treatment-resistant schizophrenia. The mechanism underlying DSP is thought to be a compensatory increase in dopamine receptor density in the striatum caused by long-term antipsychotic treatment. Previous animal studies have reported that antipsychotics increase serotonin 5-HT2A receptor density in the striatum and that 5-HT2A receptor blockers suppress dopamine-sensitive psychomotor activity, which may be linked to the pathophysiology of DSP. In this paper, we describe a patient who was hospitalised with treatment-resistant schizophrenia. Following treatment with high-dose antipsychotic polypharmacy for 10 weeks, the patient experienced worsening of psychotic and extrapyramidal symptoms. The patient was then started on second-generation antipsychotic asenapine while other antipsychotics were tapered off, resulting in improvement of these symptoms. Retrospectively, we presumed that the high-dose antipsychotic polypharmacy caused DSP, which was effectively treated by the potent 5-HT2A receptor antagonism of asenapine.

Blood vessels induce epidermal proliferating clusters in the vicinity of activating stem cells to populate expanding skin., Stem cell (SC) proliferation and differentiation organize tissue homeostasis. However, how SCs regulate coordinate tissue scaling in dynamic organs remain unknown. Here, we delineate SC regulations in dynamic skin. We found that interfollicular epidermal SCs (IFESCs) shape basal epidermal proliferating clusters (EPCs) in expanding abdominal epidermis of pregnant mice and proliferating plantar epidermis. EPCs consist of IFESC-derived Tbx3+–basal cells (Tbx3+-BCs) and their neighboring cells where Adam8–extracellular signal–regulated kinase signaling is activated. Clonal lineage tracing revealed that Tbx3+-BC clones emerge in the abdominal epidermis during pregnancy, followed by differentiation after parturition. In the plantar epidermis, Tbx3+-BCs are sustained as long-lived SCs to maintain EPCs invariably. We showed that Tbx3+-BCs are vasculature-dependent IFESCs and identified mechanical stretch as an external cue for the vasculature-driven EPC formation. Our results uncover vasculature-mediated IFESC regulations, which explain how the epidermis adjusts its size in orchestration with dermal constituents in dynamic skin.

With the development of digital technology, media multitasking behaviour, which is using two or more media simultaneously, has become more commonplace. There are two opposing hypotheses of media multitasking with regard to its impact on attention. One hypothesis claims that media multitasking can strengthen attention control, and the other claims heavy media multitaskers are less able to focus on relevant tasks in the presence of distractors. A total of 103 healthy subjects took part in this study. We measured the Media Multitasking Index (MMI) and subjects performed the continuous performance test. Resting state and oddball task functional MRI were conducted to analyse functional connectivity in the dorsal attention network, and the degree centrality (DC) was calculated using graph theory analysis. We found that the DCs in the dorsal attention network were higher during resting state than during the oddball task. Furthermore, the DCs during the task were positively correlated with the MMI. These results indicated that the DC reduction from resting state to the oddball task in high media multitaskers was attenuated compared with low media multitaskers. This study not only reveals more about the neurophysiology of media multitasking, but could also indicate brain biomarkers of media multitasking behaviour.

Background Lithium carbonate is widely used as a first-line therapeutic agent for the depressive and manic phases of bipolar disorder. Although limb tremors and hypothyroidism are well-known side effects of lithium carbonate, other rare adverse reactions can also occur. Case presentation A 53-year-old Japanese woman diagnosed with lithium intoxication developed dysgeusia and glossalgia during treatment with lithium carbonate. She also showed symptoms of a swaying gait, finger tremors, and dysarthria. All of these symptoms subsided when her blood lithium concentration was reduced to a level below that which induces intoxication. Conclusions We present a rare case of lithium carbonate–induced dysgeusia accompanied by glossalgia. Early detection of these symptoms is important in clinical settings because they can be overlooked until patients lose their appetite, which severely impairs their quality of life.

BackgroundPrevious studies have demonstrated that individuals with autism spectrum disorder (ASD) exhibit dysfunction in the three attention systems (i.e., alerting, orienting, and executive control) as well as atypical relationships among these systems. Additionally, other studies have reported that individuals with subclinical but high levels of autistic traits show similar attentional tendencies to those observed in ASD. Based on these findings, it was hypothesized that autistic traits would affect the functions and relationships of the three attention systems in a general population. Resting-state functional magnetic resonance imaging (fMRI) was performed in 119 healthy adults to investigate relationships between autistic traits and within- and between-system functional connectivity (FC) among the three attention systems. Twenty-six regions of interest that were defined as components of the three attention systems by a previous task-based fMRI study were examined in terms of within- and between-system FC. We assessed autistic traits using the Autism-Spectrum Quotient.ResultsCorrelational analyses revealed that autistic traits were significantly correlated with between-system FC, but not with within-system FC.ConclusionsOur results imply that a high autistic trait level, even when subclinical, is associated with the way the three attention systems interact.

Background: It is generally known that analyses of gene expression at single-cell resolution and spatial location of genes will reveal insights into the regulation of gene expression. Although transcriptome-wide single-cell gene expression analyses with genetic spatial information are not yet feasible, many bioinformaticians and biologists are trying to understand and predict gene expression levels using genetic spatial information of genes by implementing statistical regression models. An accurate prediction of gene expression is an important step for transcriptome-wide association studies which constructs a more biologically meaningful relationship between genes and diseases. In this sense, prediction analysis of using pseudo-temporal gene expression patterns (PTGEPs) based on trajectory inference analysis can provide important implications on the single cell RNA-sequencing (scRNA-seq) data analysis associated with the genetic spatial information. Accurate Trajectory inference (TI) analysis, also known as a pseudotime analysis, in a single-cell RNA-sequencing (scRNA-seq) data analysis has been widely used to explore a cellular dynamic process such as the cell differentiation by computationally ordering cells along the trajectory based on the similarities in their gene expression patterns. These TI methods help to understand the stochastic biological process by comparing pseudo-temporal gene expression patterns (PTGEPs), known as a differential expression (DE) analysis. However, the autocorrelation between the genetic spatial information and pseudo-temporal gene expression patterns (PTGEPs) as well as predicting PTGEP using spatial variables have not been well studied. Methods: We implement a trajectory inference analysis in order to identify the pseudo-temporal gene expression patterns (PTGEPs) for single cell RNA-sequencing (scRNA-seq) data. In here, each PTGEP is obtained as a functional form in which we treat as functional response in spatial functional regression model. For a predictor, we propose a new concept of genetic spatial information, it pseudo-location by incorporating the chromosome number and molecular starting position of genes. Then we applied and compared several types of functional response regression models to evaluate the prediction performance, including standard function-on-scalar regression model, penalized flexible functional regression model, and Bayes function-on-scalar regression model. We calculate and compared the squared correlation, R_i^2, for each gene under each model to evaluate the prediction performance. Results: We applied these spatial functional regression model and other function-on-scalar regression models to scRNA-seq data sets including Trapnell2014, Kumar2014, and Shekhar2016. To see the robustness of the prediction performance, we also increase the total number of genes for regression analysis from 1,000 to 3,000, and 10,000. Almost 30% of genes can be predicted for each model and for each data set . By comparing the predictive genes (R_i^2 > 0.1) and higher predictive genes (R_i^2 > 0.3), we found that spatial functional regression model using pseudo-location is able to provide the better prediction performance compared to other standard functional regression models.

Inter-tissue interaction is fundamental to multicellularity. Although the basement membrane (BM) is located at tissue interfaces, its mode of action in inter-tissue interactions remains poorly understood, mainly because the molecular and structural details of the BM at distinct inter-tissue interfaces remain unclear. By combining quantitative transcriptomics and immunohistochemistry, we systematically identify the cellular origin, molecular identity and tissue distribution of extracellular matrix molecules in mouse hair follicles, and reveal that BM composition and architecture are exquisitely specialized for distinct inter-tissue interactions, including epidermal–fibroblast, epidermal–muscle and epidermal–nerve interactions. The epidermal–fibroblast interface, namely, hair germ–dermal papilla interface, makes asymmetrically organized side-specific heterogeneity in BM, defined by the newly characterized interface, hook and mesh BMs. One component of these BMs, laminin α5, is required for the topological and functional integrity of hair germ–dermal papilla interactions. Our study highlights the significance of BM heterogeneity in distinct inter-tissue interactions.

Tissue stem cells are generated from a population of embryonic progenitors through organ-specific morphogenetic events

BackgroundIn single-cell RNA-sequencing (scRNA-seq) data analysis, a number of statistical tools in multivariate data analysis (MDA) have been developed to help analyze the gene expression data. This MDA approach is typically focused on examining discrete genomic units of genes that ignores the dependency between the data components. In this paper, we propose a functional data analysis (FDA) approach on scRNA-seq data whereby we consider each cell as a single function. To avoid a large number of dropouts (zero or zero-closed values) and reduce the high dimensionality of the data, we first perform a principal component analysis (PCA) and assign PCs to be the amplitude of the function. Then we use the index of PCs directly from PCA for the phase components. This approach allows us to apply FDA clustering methods to scRNA-seq data analysis.ResultsTo demonstrate the robustness of our method, we apply several existing FDA clustering algorithms to the gene expression data to improve the accuracy of the classification of the cell types against the conventional clustering methods in MDA. As a result, the FDA clustering algorithms achieve superior accuracy on simulated data as well as real data such as human and mouse scRNA-seq data.ConclusionsThis new statistical technique enhances the classification performance and ultimately improves the understanding of stochastic biological processes. This new framework provides an essentially different scRNA-seq data analytical approach, which can complement conventional MDA methods. It can be truly effective when current MDA methods cannot detect or uncover the hidden functional nature of the gene expression dynamics.

Japanese martial arts, Budo, have been reported to improve cognitive function, especially attention. However, the underlying neural mechanisms of the effect of Budo on attention processing has not yet been investigated. Kendo, a type of fencing using bamboo swords, is one of the most popular forms of Budo worldwide. We investigated the difference in functional connectivity (FC) between Kendo players (KPs) and non-KPs (NKPs) during an attention-related auditory oddball paradigm and during rest. The analyses focused on the brain network related to “motivation.” Resting-state functional magnetic resonance imaging (rs-fMRI) and task-based fMRI using the oddball paradigm were performed in healthy male volunteers (14 KPs and 11 NKPs). Group differences in FC were tested using CONN-software within the motivation network, which consisted of 22 brain regions defined by a previous response-conflict task-based fMRI study with a reward cue. Daily general physical activities were assessed using the International Physical Activity Questionnaire (IPAQ). We also investigated the impact of major confounders, namely, smoking habits, alcohol consumption, IPAQ score, body mass index (BMI), and reaction time (RT) in the oddball paradigm. Resting-state fMRI revealed that KPs had a significantly lower FC than NKPs between the right nucleus accumbens and right frontal eye field (FEF) within the motivation network. Conversely, KPs exhibited a significantly higher FC than NKPs between the left intraparietal sulcus (IPS) and the left precentral gyrus (PCG) within the network during the auditory oddball paradigm [statistical thresholds, False Discovery Rate (FDR) < 0.05]. These results remained significant after controlling for major covariates. Our results suggest that attenuated motivation network integrity at rest together with enhanced motivation network integrity during attentional demands might underlie the instantaneous concentration abilities of KPs.

Over the past decade, multiple stem cell compartments have been identified within the epidermis. These stem cell pools have different transcriptional properties, proliferative modes and anatomical locations, and they maintain distinct epidermal compartments. The importance of this stem cell heterogeneity and compartmentalization has been understood as a key feature in epidermal homeostasis. However, recent studies have revealed that these heterogeneous stem cells themselves act as a niche for neighboring cells, thereby establishing spatially and temporally patterned epidermal-dermal functional units. These studies provide a new perspective for interpreting the biological significance of stem cell heterogeneity and compartmentalization beyond their role in epidermal maintenance.