g., to study their numerical competence or categorical perception, to further elucidate how nonhuman animals learn and perceive the world.The well-being of the public during the 2019 coronavirus (COVID-19) pandemic is deeply rooted in institutional trust in the government’s risk communication effort. The objective of this study was to examine the psychological pathway through which public trust in the government is associated with mental and physical well-being. We collected cross-sectional data from 501 participants aged ≥18 years using an online panel. Public trust in the government was assessed as our exposure variable. We screened for psychological distress by combining the Patient Health Questionnaire and the General Anxiety Disorder scale. Physical well-being was examined using self-rated health. We further assessed the roles of risk perceptions. The author conducted a one-way analysis of variance (ANOVA), Pearson’s correlations, multivariable regressions, and mediation analyses (using the Preachers and Hayes’ approach). Participants were 55.29% female, 67.86% Caucasian/white with a mean age of 32.44 ± 11.94 years. Public trust in the government regarding COVID-19 was negatively correlated with psychological distress (r = -0.20; p less then 0.001) and positively associated with physical well-being (r = 0.13; p less then 0.001). After adjusting for sociodemographic and socioeconomic factors, public trust remained negatively associated with psychological distress (β = -0.19; 95% confidence intervals, [CI] -0.30, -0.09) and positively associated with physical well-being (β = 0.26; 95% CI [0.16, -0.37]). Perceived self-efficacy to practice COVID-19 protective behavior partially mediated the relationship between public trust and psychological distress (13.07%); and physical well-being (28.02%). Perceived self-efficacy to protect self against COVID-19 infection can serve as a psychological pathway through which public trust may be associated with mental and physical health.There is increasing effort to characterize the soundscapes around us so that we can design more compelling and immersive experiences. This review paper focuses on the challenges and opportunities around sound perception, with a particular focus on spatial sound perception in a virtual reality (VR) cityscape. We review how research on temporal aspects has recently been extended to evaluating spatial factors when designing soundscapes. In particular, we discuss key findings on the human capability of localizing and distinguishing spatial sound cues for different technical setups. We highlight studies carried out in both real-world and virtual reality settings to evaluate spatial sound perception. We conclude this review by highlighting the opportunities offered by VR technology and the remaining open questions for virtual soundscape designers, especially with the advances in spatial sound stimulation.Frailty is an age-related dynamic status, characterized by a reduced resistance to stressors due to the cumulative decline of multiple physiological systems. Several researches have highlighted a relationship between physical frailty and cognitive decline; however, the role of specific cognitive domains has not been deeply clarified yet. Current studies have hypothesized that physical frailty and neuropsychological deficits may share systemic inflammation and increased oxidative stress in different neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. However, the role of the executive dysfunction should be investigated in a more detailed way using a multidimensional approach. With this aim, we conducted a review of the literature on the few experimental articles published to discuss the existence of a relationship between frailty and cognitive impairment in neurocognitive disorders, particularly focusing on the domain of executive dysfunction. The data suggest that physical frailty and cognitive decline, especially executive dysfunction, are two aspects strongly linked in mild and major neurocognitive disorders due to Alzheimer’s and Parkinson’s disease. In light of this, a new framework linking aging, cognitive decline, and neurodegenerative diseases is needed. In order to analyze the effects that aging processes have on neural decline and neurocognitive disease, and to identify relevant groups of users and patients, future longitudinal studies should adopt a multidimensional approach, in the field of primary prevention and in the continuum from mild to major neurocognitive disorder.Recently, leadership literature has faced the challenge of dealing with a growing pervasive diffusion of information and communication technologies that are deeply changing relationships among workers. Consequently, leadership is continuing to develop through the support of these technologies. This emerging phenomenon has been labeled e-leadership, and it has been studied with the objective of understanding the differences it exhibits from traditional leadership. Our research seeks to examine whether enterprises, which use leadership as an important „tool” to manage workers as effectively as possible, are conscious of this evolution, whether their behavior is supportive of the related needs, and how they are organizing themselves to face the problems and opportunities arising in this new context. The present study involved 15 Italian companies. Through in-depth interviews based on face-to-face meetings using a semi-structured questionnaire with enterprises’ representatives, we explored the extent of these chaeem now to be the main path to managing the present situation and the aftermath it inevitably will have. Despite this research being carried out before such an event has happened, we believe that its results may further enrich the current lively debate.Many organizations encourage their employees to participate in charitable activities as part of their corporate social responsibility strategies. As a result, there has been an increased research interest in employee volunteering behavior. However, while previous research on employee volunteering decisions has focused on both individual-level and organizational-level factors, there has been less focus on peer involvement and volunteer cause proximity. To go some way to filling this research area, this paper conducted two studies to examine the possible effects of colleague participation, colleague position and public cause proximity on employee volunteering intentions. Study 1 found that colleague participation and public cause proximity had significant effects on employee volunteering, and Study 2 found that power distance played a moderating role in the relationship between colleague position and employee volunteering. This study contributes to theoretical research on employee volunteering and provides some information to assist firms retain engaged volunteers.Cognitive dissonance has been studied for more than 60 years and many insightful findings have come from this research. However, some important theoretical and methodological issues are yet to be resolved, particularly regarding dissonance reduction. In this paper, we place dissonance theory in the larger framework of appraisal theories of emotion, emotion regulation, and coping. The basic premise of dissonance theory is that people experience negative affect (to varying degrees) following the detection of cognitive conflict. The individual will be motivated to alleviate these emotional reactions and could do so by reducing dissonance in some manner. We argue that detection of dissonance will follow the same principles as when people interpret any other stimuli as emotionally significant. Thus, appraisal theory of emotion, which argues that emotions are generated via the cognitive evaluation of surrounding stimuli, should be applicable to the dissonance-detection process. In short, we argue that dissonance-reduction strategies (attitude change, trivialization, denial of responsibility, etc.) can be understood as emotion-regulation strategies. We further argue that this perspective contributes to reconciling fragmented (and sometimes contrary) viewpoints present in the literature on dissonance reduction. In addition to proposing the general model of dissonance reduction, we illustrate at the hand of empirical data how research on dissonance reduction can be performed without relying on experimental paradigms that focus on a specific reduction strategy.Background Due to the aging society the number of informal caregivers is growing. Most informal caregivers are women working as nurses within a health organization (also labeled as double-duty caregiver) and they have a high risk of developing mental and physical exhaustion. Until now little research attention has been paid to the expectations and needs of double duty caregivers and the role of self-management in managing private-work balance. Objective The overall aim of this study was to investigate the expectations and needs of double duty caregivers in Netherlands, and to examine the meaning of self-management in managing work-life balance. Method Different research methods have been applied in this exploratory study. Firstly, a scoping review has been conducted on the topics self-management and sustainable employability of double-duty caregivers using the search engines CINAHL, MEDLINE, PubMed, and Google Scholar. Furthermore, a qualitative study has been conducted through focus groups with double duty cnd employability levels across time. Health care organizations and the double duty caregiver often wait too long to act instead of taking more preventive measures. Furthermore, community care organizations should dialog with double duty caregivers about their wishes concerning the division of caring tasks. This finding calls for special attention, with long-term solutions at both macro (health-care level), organizational (meso-level), and employee level (micro level).Epidemiological studies have shown that environmental green space contributes to the reduction of psychosis incidence in the population. Clarifying the psychological and neuro-functional mechanisms underlying the risk-decreasing effects of green surroundings could help optimize preventive environmental interventions. This perspective article specifically aims to open a new window on the link between environmental green space and psychosis by considering its core psychopathological features. Psychotic disorders, such as schizophrenia, are essentially characterized by self-disturbances. The psychological structure of the self has been described as a multidimensional phenomenon that emerges from the reciprocal interaction with the environment through intrinsic and extrinsic self-processes. The intrinsic self refers to the experience of mental activity and environmental information as inherently related to one’s own person, which involves self-referential processing, self-reflection, memory, interoception, and emotional evaluation. The extrinsic self refers to sensorimotor interactions with the environment and the sense of agency, that is, the experience of being the source of one’s own actions and the multisensory consequences thereof. In psychosis, anomalous self-processing has been related to a functional fragmentation of intrinsic and extrinsic self-processes and related brain networks. Moreover, evidence from cognitive neuroscience suggests that green space could have beneficial effects on self-related processing. Based on the literature, it could be hypothesized that self-processing is involved in mediating the beneficial effects of green space for psychosis. Considering the multidimensionality of the self, it is proposed that urban green space design aimed at improving mental health ideally impacts the complexity of self-facets and thus restores the individual’s self.This article presents the pedagogical paradigm of reflexive interaction and its application in the field of technology-enhanced learning and children’s musical creativity. The main feature of reflexive interaction is the repetition-variation mechanism something is repeated and varied during the interaction, through a continual process of imitation and variation. In the context of the MIROR project (EU-ICT Project), we exploited the educational potential of the reflexive interaction paradigm and implemented the MIROR platform, an educational device consisting of a set of softwares that implement the reflexive paradigm not only in music improvisation (as was the case for the first interactive reflexive system), but also in the field of music composition and dance. The platform was conceived as a tool to stimulate and develop musical and motor creativity in children, although it can also be used to teach a specific musical instrument. The hypothesis of the MIROR project was that reflexive interaction sustains and promotes the learning and creative expression processes of music and movement. This initial hypothesis, which stemmed mainly from the pilot study in which we observed children who were interacting with the first prototype of the interactive reflexive musical system, was subjected to a series of empirical studies conducted within the MIROR project, and was theoretically defined in order to lay down the foundations of the reflexive interaction paradigm and its pedagogical implications. This article summarizes the state-of-the-art of the project and brings together, in a comprehensive overview, the theoretical framework, the pedagogical concepts, the empirical studies, and the description of the MIROR platform, with the aim to reflect on the results achieved so far and point out the contribution of the reflexive perspective to the field of children’s instrumental learning and creativity.Background Long-term pharmacological maintenance therapy is often essential among people with bipolar disorder to reduce the need for inpatient care. Sex-specific responses to maintenance therapies are expected but remain largely unknown. Here, we examined for sex-specific associations between common maintenance therapies for bipolar disorder with inpatient rehospitalizations following patients’ index discharges during 2006-2014. Methods Population-based data on maintenance therapies and rehospitalizations were extracted from Swedish national registries. We adopted the within-individual design to compare the time on- vs. off- maintenance therapy for males and females, respectively. Extended stratified Cox proportional hazards regression models were employed to quantify the rate of rehospitalization as a function of common maintenance drugs and other important time-varying control variables. Results Our primary analysis included 22,681 bipolar disorder rehospitalizations by 6,400 males and 9,588 (60.0%) females over an observation time of 62,813 person-years. The time spent on- vs. off- maintenance lithium, lamotrigine, quetiapine, or olanzapine was statistically significant upon adjustment among either sex for reducing the rate of bipolar rehospitalizations. Adjusted sex-specific statistically significant associations were also observed. Among females, the time on- (vs. off-) long-acting injectable risperidone reduced the rate of bipolar rehospitalizations by 73% (56-84%), carbamazepine by 44% (18-62%), aripiprazole by 29% (13-42%), and valproate by 23% (11-33%); whereas among males, ziprasidone by 65% (41-79%). Conclusion The effectiveness of most maintenance therapies is generally comparable and uniform among both males and females. Despite some statistically significant sex-specific associations, estimates for each drug were fairly consistent between sexes.The COVID-19 pandemic is likely to have affected the psychological well-being and mental health of many people. Data on prevalence rates of mental health problems are needed for mental health service planning. Psychological well-being and prevalence of clinically significant mental distress were measured in a large sample from Wales 11-16 weeks into lockdown and compared to population-based data collected in 2019 before the COVID-19 pandemic. Data were collected using an online survey disseminated across Wales and open to adults (age 16+) from 9th June to 13th July 2020. Psychological well-being was indexed via the Warwick-Edinburgh Mental Well-being Scale, and psychological distress was indexed via the K10. Data from 12,989 people who took part in this study were compared to that from April 2018 – March 2019, gathered by the National Survey for Wales (N = 11,922). Well-being showed a large decrease from 2019 levels. Clinically significant psychological distress was found in around 50% of the population (men = 47.4%, women = 58.6%), with around 20% showing „severe” effects (men = 17.0%, women = 20.9%) a 3-4-fold increase in prevalence. Most affected were young people, women, and those in deprived areas. By June-July 2020 the COVID-19 pandemic had dramatic effects on the mental health of people living in Wales (and by implication those in the UK and beyond). The effects are larger than previous reports. This probably reflects that the current data were taken deeper into the lockdown period than previous evaluations. Mental health services need to prepare for this wave of mental health problems with an emphasis on younger adults, women, and in areas of greater deprivation.The aim of the study is to describe the clinical characteristics and outcomes of a series of older patients consecutively admitted into a non-ICU ward due to SARS-CoV-2 infection (14, males 11), developing delirium. Hypokinetic delirium with lethargy and confusion was observed in 43% of cases (6/14 patients). A total of eight patients exhibited hyperkinetic delirium and 50% of these patients (4/8) died. The overall mortality rate was 71% (10/14 patients). Among the four survivors we observed two different clinical patterns two patients exhibited dementia and no ARDS (acute respiratory distress syndrome), while the remaining two patients exhibited ARDS and no dementia. The observed different clinical patterns of delirium (hypokinetic delirium; hyperkinetic delirium with or without dementia; hyperkinetic delirium with or without ARDS) identified patients with different prognosis we believe these observations may have an impact on the management of older subjects with delirium due to COVID-19.As the frequency of cannabis use by 14-16-year-olds increases, it becomes increasingly important to understand the effect of cannabis on the developing central nervous system. Using mice as a model system, we treated adolescent (28 day old) C57BL6/J mice of both sexes for 3 weeks with 3 mg/kg tetrahydrocannabinol (THC). Starting a week after the last treatment, several cognitive behaviors were analyzed. Mice treated with THC as adolescents acquired proficiency in a working memory task more slowly than vehicle-treated mice. Working memory recall in both sexes of THC-treated mice was also deficient during increasing cognitive load compared to vehicle-treated mice. Our adolescent THC treatment did not strongly affect social preference, anxiety behaviors, or decision-making behaviors on the elevated T maze task. In summary, under the conditions of this study, adolescent THC treatment of mice markedly affected the establishment, and persistence of working memory, while having little effect on decision-making, social preference or anxiety behaviors. This study provides further support that adolescent THC affects specific behavioral domains.Objectives To date, there is no reliable instrument which could be used to assess problematic Internet use (PIU) in Lithuania. The nine-item Problematic Internet Use Questionnaire (PIUQ-9) previously validated in multiple countries, could be a potential tool for measuring PIU severity. The main objective of the present study was to explore the psychometric properties of the Lithuanian version of the questionnaire. Methods A total of 272 students (17% men, mean age 27 ± 9 years) completed the PIUQ-9, the Patient Health Questionnaire (PHQ) and answered questions about the impairment of daily functioning caused by PIU in an online survey. Results A confirmatory factor analysis indicated that a bi-factor model with one general factor „general problem” and two-specific factors „obsession” and „neglect + control disorder” fitted the data well. The presence of a strong global factor was supported by the common variance index in the bi-factor model indicating that the „general problem” factor explained 67.7% of common variance. The multiple indicators multiple causes (MIMIC) model showed that psychiatric symptoms (β = 0.25) had a moderate, while impairment due to PIU (β = 0.41) had a moderate-to-strong direct effect on the factor „general problem” supporting the construct validity of the scale. Conclusion The Lithuanian version of the PIUQ-9 has appropriate psychometric properties to be used in measuring PIU severity in student samples.Background Treatment of borderline personality disorder (BPD) in publicly funded mental health services generally use approaches based on medical interventions and generic case management. Specific psychological therapies developed for BPD may be more effective but have rarely been evaluated in routine clinical practice. Aim To examine the effectiveness of Mentalization Based Treatment (MBT) in adults with an established diagnosis of BPD under the care of a publicly funded Mental Health Service (MHS), on rates of non-suicidal self-harm (NSSH) and attempted suicide (SA). Methods A randomized, controlled trial (RCT) comparing 18 months of MBT with Enhanced Therapeutic Case Management (ETCM), a form of Structured Clinical Case Management (ICTRP ACTRN12612000951853). Participants were adults recruited from a patient population under the care of a publicly funded mental health service (MHS) with a confirmed diagnosis of BPD. The primary outcome measures were the incidence of non-suicidal self-harm or suicide attempt over 18 months of treatment. Results 72 participants (71 females, 1 male) were randomized to MBT (n = 38) or ETCM (n = 34). Both groups showed a significant reduction in the overall incident rate of SA and NSSH. Between groups, SA rates were higher in the MBT group and conversely NSSH rates were higher in the ECTM group. Conclusions The introduction of a structured service that delivered a structured psychotherapy (MBT) and an effective case management approach (ETCM) both resulted in a reduction in SA and NSSH. The differences in improvements found between groups within this study setting will require further research.Functional gastrointestinal disorders (FGID), such as functional dyspepsia (FD) and irritable bowel syndrome (IBS) are characterized by chronic abdominal symptoms in the absence of an organic, metabolic or systemic cause that readily explains these complaints. Their pathophysiology is still not fully elucidated and animal models have been of great value to improve the understanding of the complex biological mechanisms. Over the last decades, many animal models have been developed to further unravel FGID pathophysiology and test drug efficacy. In the first part of this review, we focus on stress-related models, starting with the different perinatal stress models, including the stress of the dam, followed by a discussion on neonatal stress such as the maternal separation model. We also describe the most commonly used stress models in adult animals which brought valuable insights on the brain-gut axis in stress-related disorders. In the second part, we focus more on models studying peripheral, i.e., gastrointestinal, mechanisms, either induced by an infection or another inflammatory trigger. In this section, we also introduce more recent models developed around food-related metabolic disorders or food hypersensitivity and allergy. Finally, we introduce models mimicking FGID as a secondary effect of medical interventions and spontaneous models sharing characteristics of GI and anxiety-related disorders. The latter are powerful models for brain-gut axis dysfunction and bring new insights about FGID and their comorbidities such as anxiety and depression.Background Kinesiology taping (KT) is well known measure for preventing musculoskeletal injuries. Our study aims to explore the actual effects of KT on healthy participants’ knee proprioception and quadriceps performance within 1 h. Methods A total of 35 healthy male amateur runners were recruited in our study. Four taping sequences were randomly allocated to four different weeks, namely, no taping, placebo taping, KT with tension, and KT with no tension. A CON-TREX isokinetic dynamometer was used in assessing the participants’ knee proprioception and muscle strength of knee extension and flexion at 60°/s. The electromyography (EMG) signals of medial oblique muscle and vastus lateralis were collected using Myon EMG system synchronously. Two-way repeated measures ANOVA was used in exploring the difference between taping and time effects, and the significance was set to alpha less then 0.05. Results Significant interaction effect was found between the taping groups and time effect [F (3.32) = 2.389, p = 0.029, η2 = 0.050] in the peak torque during the concentric contraction of quadriceps. No significant interaction and no significant differences between groups and time effects in knee proprioception and muscle activation. Conclusion The effect of KT seems insufficiently large to impose a positive effect on healthy people within short periods. Health participants may not necessarily use KT to increase muscle activation and proprioception of knee.Extensive evidence from epidemiologic, genetic, and clinical intervention studies has indisputably shown that elevated low-density lipoprotein cholesterol (LDL-C) concentrations play a central role in the pathophysiology of atherosclerotic cardiovascular disease. Apart from LDL-C, also triglycerides independently modulate cardiovascular risk. Reduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma LDL-C, but it is also associated with a reduction in triglyceride levels potentially through modulation of the expression of free fatty acid transporters. Preclinical data indicate that PCSK9 is up-regulated in the ischaemic heart and decreasing PCSK9 expression impacts on infarct size, post infarct inflammation and remodeling as well as cardiac dysfunction following ischaemia/reperfusion. Clinical data support that notion in that PCSK9 inhibition is associated with reductions in the incidence of myocardial infarction, stroke, and coronary revascularization and an improvement of endothelial function in subjects with increased cardiovascular risk. The aim of the current review is to summarize the current knowledge on the importance of free fatty acid metabolism on myocardial ischaemia/reperfusion injury and to provide an update on recent evidence on the role of hyperlipidemia and PCSK9 in myocardial infarction and cardioprotection.Store-operated calcium entry (SOCE) plays a pivotal role in skeletal muscle physiology as, when impaired, the muscle is prone to early fatigue and the development of different myopathies. A chronic mode of slow SOCE activation is carried by stromal interaction molecule 1 (STIM1) and calcium-release activated channel 1 (ORAI1) proteins. A phasic mode of fast SOCE (pSOCE) occurs upon single muscle twitches in synchrony with excitation-contraction coupling, presumably activated by a local and transient depletion at the terminal cisternae of the sarcoplasmic reticulum Ca2+-stores. Both SOCE mechanisms are poorly understood. In particular, pSOCE has not been described in detail because the conditions required for its detection in mouse skeletal muscle have not been established to date. Here we report the first measurements of pSOCE in mouse extensor digitorum longus muscle fibers using electrical field stimulation (EFS) in a skinned fiber preparation. We show moderate voluntary wheel running to be a prerequisite to render muscle fibers reasonably susceptible for EFS, and thereby define an experimental paradigm to measure pSOCE in mouse muscle. Continuous monitoring of the physical activity of mice housed in cages equipped with running wheels revealed an optimal training period of 5-6 days, whereby best responsiveness to EFS negatively correlated with running distance and speed. A comparison of pSOCE kinetic data in mouse with those previously derived from rat muscle demonstrated very similar properties and suggests the existence and similar function of pSOCE across mammalian species. The new technique presented herein enables future experiments with genetically modified mouse models to define the molecular entities, presumably STIM1 and ORAI1, and the physiological role of pSOCE in health and under conditions of disease.Utilizing single-cell sequencing, recent studies were able to analyze at a greater resolution the heterogeneity of the vasculature and its complex composition in different tissues. Differing subpopulations have been detected, distinguishable only by their transcriptome. Designed to provide further insight into the heterogeneity of the functional vascular tissue, endothelial cells have been the main target of those studies. This review aims to present a synopsis of the variability of the different vascular beds, their endothelial variety, and the supporting cells that allow the vessels to serve their various purposes. Firstly, we are going to chart vascular tissue heterogeneity on a cellular level, describing endothelial diversity as well as stromal microenvironmental variety and interaction in a physiological setting. Secondly, we will summarize the current knowledge of pathological vessel formation in the context of cancer. Conventional anti-tumor therapeutic targets as well as anti-angiogenetic therapy is frequently limited by poor response of the tumor tissue. Reasons for moderate response and resistance to treatment can be found through different drivers of angiogenesis, different mechanisms of blood supply, but also in poorly understood tissue diversity. Based on this, we are comparing how pathologies alter the normal structure of vascular tissues highlighting the involved mechanisms. Lastly, illustrating the concept above, we will focus on the hepatic microenvironment, an organ of frequent metastatic spreading (e.g., from colorectal, breast, and lung cancers). We will address how the hepatic vasculature usually develops and subsequently we will describe how common liver metastases vary in their vasculature and the way they supply themselves (e.g., angiogenesis versus vessel co-option).Blood brain barrier (BBB) damage is an important pathophysiological feature of ischemic stroke which significantly contributes to development of severe brain injury and therefore is an interesting target for therapeutic intervention. A popular permanent occlusion model to study long term recovery following stroke is the photothrombotic model, which so far has not been anatomically characterized for BBB leakage beyond the acute phase. Here, we observed enhanced BBB permeability over a time course of 3 weeks in peri-infarct and core regions of the ischemic cortex. Slight increases in BBB permeability could also be seen in the contralesional cortex, hippocampus and the cerebellum at different time points, regions where lesion-induced degeneration of pathways is prominent. Severe damage of tight and adherens junctions and loss of pericytes was observed within the peri-infarct region. Overall, the photothrombotic stroke model reproduces a variety of features observed in human stroke and thus, represents a suitable model to study BBB damage and therapeutic approaches interfering with this process.Cold climates represent one of the major environmental challenges that anatomically modern humans faced during their dispersal out of Africa. The related adaptive traits have been achieved by modulation of thermogenesis and thermoregulation processes where nuclear (nuc) and mitochondrial (mt) genes play a major role. In human populations, mitonuclear genetic interactions are the result of both the peculiar genetic history of each human group and the different environments they have long occupied. This study aims to investigate mitonuclear genetic interactions by considering all the mitochondrial genes and 28 nuclear genes involved in brown adipose tissue metabolism, which have been previously hypothesized to be crucial for cold adaptation. For this purpose, we focused on three human populations (i.e., Finnish, British, and Central Italian people) of European ancestry from different biogeographical and climatic areas, and we used a machine learning approach to identify relevant nucDNA-mtDNA interactions that characterized each population. The obtained results are twofold (i) at the methodological level, we demonstrated that a machine learning approach is able to detect patterns of genetic structure among human groups from different latitudes both at single genes and by considering combinations of mtDNA and nucDNA loci; (ii) at the biological level, the analysis identified population-specific nuclear genes and variants that likely play a relevant biological role in association with a mitochondrial gene (such as the „obesity gene” FTO in Finnish people). Further studies are needed to fully elucidate the evolutionary dynamics (e.g., migration, admixture, and/or local adaptation) that shaped these nucDNA-mtDNA interactions and their functional role.Mitochondria are key determinants of cellular health. However, the functional role of mitochondria varies from cell to cell depending on the relative demands for energy distribution, metabolite biosynthesis, and/or signaling. In order to support the specific needs of different cell types, mitochondrial functional capacity can be optimized in part by modulating mitochondrial structure across several different spatial scales. Here we discuss the functional implications of altering mitochondrial structure with an emphasis on the physiological trade-offs associated with different mitochondrial configurations. Within a mitochondrion, increasing the amount of cristae in the inner membrane improves capacity for energy conversion and free radical-mediated signaling but may come at the expense of matrix space where enzymes critical for metabolite biosynthesis and signaling reside. Electrically isolating individual cristae could provide a protective mechanism to limit the spread of dysfunction within a mitochondrion buable for contact sites with other organelles as well as for metabolite exchange with cytosol. Though the precise mechanisms guiding the coordinated multi-scale mitochondrial configurations observed in different cell types have yet to be elucidated, it is clear that mitochondrial structure is tailored at every level to optimize mitochondrial function to meet specific cellular demands.IDH1 mutations occur in about 20-30% of gliomas and are a promising target for the treatment of cancer. In the present study, the performance of aIDH1R132H was verified via glide-docking-based virtual screening. On the basis of the two crystal structures (5TQH and 6B0Z) with the best discriminating ability to identify IDH1R132H inhibitors from a decoy set, a docking-based virtual screening strategy was employed for identifying new IDH1R132H inhibitors. In the end, 57 structurally diverse compounds were reserved and evaluated through experimental tests, and 10 of them showed substantial activity in targeting IDH1R132H (IC50 less then 50 μM). Molecular docking technology showed that L806-0255, V015-1671, and AQ-714/41674992 could bind to the binding pocket composed of hydrophobic residues. These findings indicate that L806-0255, V015-1671, and AQ-714/41674992 have the potential as lead compounds for the treatment of IDH1-mutated gliomas through further optimization.Ethanol-induced gastric mucosal injury is a common gastrointestinal disorder. Polysaccharides separated from herbs have been shown to be effective for ethanol-induced gastric mucosal injury, but whether the polysaccharides from Dendrobium officinale Kimura & Migo leaves (LDOP-1) protected mucosa from ethanol-induced injury remains unknown. Thus, the present study carried out gastric mucosal protection and the mechanism of LDOP-1 in vivo and vitro. The chemical composition of LDOP-1 was a heteropolysaccharide comprising mannose, galacturonic acid, glucose, galactose, and arabinose at a molar ratio of 2.01.10.70.50.4. Pharmacological results showed that LDOP-1 significantly reduced gastric mucosal injury score and pathological injury, improved antioxidant capacity, reduced the level of reactive oxygen species, and reversed the apoptosis of GES-1 in vivo and vitro. Research showed that LDOP-1 pretreatment upregulated the expression level of p-AMPK, LC3β, HO-1, and Beclin-1; downregulated the expression level of p-mTOR and p62; and reversed the expression level of caspase3, Bax, and Bcl-2. This study was the first to demonstrate that LDOP-1 could protect against ethanol-induced gastric mucosal injury via the AMPK/mTOR signaling pathway in vitro and vivo.Background Intrinsically organized large-scale brain networks and their interactions support complex cognitive function. Investigations suggest that the default network (DN) is the earliest disrupted network and that the frontoparietal control network (FPCN) and dorsal attention network (DAN) are subsequently impaired in Alzheimer’s disease (AD). These large-scale networks comprise different subsystems (DN medial temporal lobe (MTL), dorsomedial prefrontal cortex (DM) subsystems and a Core; FPCN FPCNA and FPCNB). Our previous research has indicated that different DN subsystems are not equally damaged in AD. However, changes in the patterns of interactions among these large-scale network subsystems and the underlying cause of the alterations in AD remain unclear. We hypothesized that disrupted DN subsystems cause specific impairments in inter-system interactions and a higher regulatory burden for the FPCNA. Method To test this hypothesis, Granger causality analysis (GCA) was performed to explore effective funcms and FPCN subsystems/DAN decreased. Critically, the correlation values of the decreased bidirectional IFS between the DN subsystems and FPCNA diminished. Additionally, the Core and DM play pivotal roles in disordered temporal co-evolution. Furthermore, the FPCNA showed enhanced regulation of the Core. Finally, the MTL subsystem and Core were effective at discriminating patients from controls. Conclusion The predominantly disrupted DN subsystems caused impaired inter-system interactions and created a higher regulatory burden for the FPCNA.In robotic radiosurgery, motion tracking is crucial for accurate treatment planning of tumor inside the thoracic or abdominal cavity. Currently, motion characterization for respiration tracking mainly focuses on markers that are placed on the surface of human chest. Nevertheless, limited markers are not capable of expressing the comprehensive motion feature of the human chest and abdomen. In this paper, we proposed a method of respiratory motion characterization based on the voxel modeling of the thoracoabdominal torso. Point cloud data from depth cameras were used to achieve three-dimensional modeling of the chest and abdomen surface during respiration, and a dimensionality reduction algorithm was proposed to extract respiratory features from the established voxel model. Finally, experimental results including the accuracy of voxel model and correlation coefficient were compared to validate the feasibility of the proposed method, which provides enhanced accuracy of target motion correlation than traditional methods that utilized external markers.Our understanding of the neurofunctional mechanisms of speech production and their pathologies is still incomplete. In this paper, a comprehensive model of speech production based on the Neural Engineering Framework (NEF) is presented. This model is able to activate sensorimotor plans based on cognitive-functional processes (i.e., generation of the intention of an utterance, selection of words and syntactic frames, generation of the phonological form and motor plan; feedforward mechanism). Since the generation of different states of the utterance are tied to different levels in the speech production hierarchy, it is shown that different forms of speech errors as well as speech disorders can arise at different levels in the production hierarchy or are linked to different levels and different modules in the speech production model. In addition, the influence of the inner feedback mechanisms on normal as well as on disordered speech is examined in terms of the model. The model uses a small number of core concepts provided by the NEF, and we show that these are sufficient to create this neurobiologically detailed model of the complex process of speech production in a manner that is, we believe, clear, efficient, and understandable.Numerous studies find that creativity is not only associated with low effort and flexible processes but also associated with high effort and persistent processes especially when defensive behavior is induced by negative emotions. The important role of self-esteem is to buffer negative emotions, and individuals with low self-esteem are prone to instigating various forms of defensive behaviors. Thus, we thought that the relationships between trait creativity and executive control brain networks might be modulated by self-esteem. The resting-state electroencephalogram (RS-EEG) microstates can be divided into four classical types (MS1, MS2, MS3, and MS4), which can reflect the brain networks as well as their dynamic characteristic. Thus, the Williams Creative Tendency Scale (WCTS) and Rosenberg Self-esteem Scale (RSES) were used to investigate the modulating role of self-esteem on the relationships between trait creativity and the RS-EEG microstates. As our results showed, self-esteem consistently modulated the relationships between creativity and the duration and contribution of MS2 related to visual or imagery processing, the occurrence of MS3 related to cingulo-opercular networks, and transitions between MS2 and MS4, which were related to frontoparietal control networks. Based on these results, we thought that trait creativity was related to the executive control of bottom-up processing for individuals with low self-esteem, while the bottom-up information from vision or visual imagery might be related to trait creativity for individuals with high self-esteem.Detecting changes in the environment is fundamental for our survival. According to predictive coding theory, detecting these irregularities relies both on incoming sensory information and our top-down prior expectations (or internal generative models) about the world. Prediction errors (PEs), detectable in event-related potentials (ERPs), occur when there is a mismatch between the sensory input and our internal model (i.e., a surprise event). Many changes occurring in our environment are irrelevant for survival and may remain unseen. Such changes, even if subtle, can nevertheless be detected by the brain without emerging into consciousness. What remains unclear is how these changes are processed in the brain at the network level. Here, we used a visual oddball paradigm in which participants engaged in a central letter task during electroencephalographic (EEG) recordings while presented with task-irrelevant high- or low-coherence background, random-dot motion. Critically, once in a while, the direction of the dots changed. After the EEG session, we confirmed that changes in motion direction at high- and low-coherence were visible and invisible, respectively, using psychophysical measurements. ERP analyses revealed that changes in motion direction elicited PE regardless of the visibility, but with distinct spatiotemporal patterns. To understand these responses, we applied dynamic causal modeling (DCM) to the EEG data. Bayesian Model Averaging showed visible PE relied on a release from adaptation (repetition suppression) within bilateral MT+, whereas invisible PE relied on adaptation at bilateral V1 (and left MT+). Furthermore, while feedforward upregulation was present for invisible PE, the visible change PE also included downregulation of feedback between right MT+ to V1. Our findings reveal a complex interplay of modulation in the generative network models underlying visible and invisible motion changes.Olfaction plays an important role in the evaluation, motivation, and palatability of food. The chemical identity of odorants is coded by a spatial combination of activated glomeruli in the olfactory bulb, which is referred to as the odor map. However, the functional roles of the olfactory cortex, a collective region that receives axonal projections from the olfactory bulb, and higher olfactory centers in odor-guided eating behaviors are yet to be elucidated. The olfactory tubercle (OT) is a component of the ventral striatum and forms a node within the mesolimbic dopaminergic pathway. Recent studies have revealed the anatomical domain structures of the OT and their functions in distinct odor-guided motivated behaviors. Another component of the ventral striatum, the nucleus accumbens, is well known for its involvement in motivation and hedonic responses for foods, which raises the possibility of functional similarities between the OT and nucleus accumbens in eating. This review first summarizes recent findings on the domain- and neuronal subtype-specific roles of the OT in odor-guided motivated behaviors and then proposes a model for the regulation of eating behaviors by the OT.Neurons have been long regarded as the basic functional cells of the brain, whereas astrocytes and microglia have been regarded only as elements of support. However, proper intercommunication among neurons-astrocytes-microglia is of fundamental importance for the functional organization of the brain. Perturbation in the regulation of brain energy metabolism not only in neurons but also in astrocytes and microglia may be one of the pathophysiological mechanisms of neurodegeneration, especially in hypoxia/ischemia. Glial activation has long been considered detrimental for survival of neurons, but recently it appears that glial responses to an insult are not equal but vary in different brain areas. In this review, we first take into consideration the modifications of the vascular unit of the glymphatic system and glial metabolism in hypoxic conditions. Using the method of triple-labeling fluorescent immunohistochemistry coupled with confocal microscopy (TIC), we recently studied the interplay among neurons, astrus and interconnected hippocampal areas, demonstrate that glial response to the same hypoxic insult is not equal but varies significantly. Understanding the differences of glial reactivity is of great interest to explain the differential susceptibility of hippocampal areas to hypoxia/ischemia. Further studies may evidence the differential reactivity of glia in different brain areas, explaining the higher or lower sensitivity of these areas to different insults and whether glia may represent a target for future therapeutic interventions.Maternal exposure to the valproate short-chain fatty acid (SCFA) during pregnancy is known to possibly induce autism spectrum disorders (ASDs) in the offspring. By contrast, case studies have evidenced positive outcomes of this anticonvulsant drug in children with severe autism. Interestingly, the same paradoxical pattern applies to the IL-17a inflammatory cytokine involved in the immune system regulation. Such joint apparent contradictions can be overcome by pointing out that, among their respective signaling pathways, valproate and IL-17a share an enhancement of the „type A monoamine oxidase” (MAOA) enzyme carried by the X chromosome. In the Guided Propagation (GP) model of autism, such enzymatic rise triggers a prenatal epigenetic downregulation, which, without possible X-inactivation, and when coinciding with genetic expression variants of other brain enzymes, results in the delayed onset of autistic symptoms. The underlying imbalance of synaptic monoamines, serotonin in the first place, would reflect a mismatch between the environment to which the brain metabolism was prepared during gestation and the postnatal actual surroundings. Following a prenatal exposure to molecules that significantly elicit the MAOA gene expression, a daily treatment with the same metabolic impact would tend to recreate the fetal environment and contribute to rebalance monoamines, thus allowing proper neural circuits to gradually develop, provided behavioral re-education. Given the multifaceted other players than MAOA that are involved in the regulation of serotonin levels, potential compensatory effects are surveyed, which may underlie the autism heterogeneity. This explanatory framework opens up prospects regarding autism prevention and treatment, strikingly in line with current advances along the gut microbiome-brain axis.Selective negative allosteric modulators (NAMs), targeting α5 subunit-containing GABAA receptors (GABAARs) as potential therapeutic targets for disorders associated with cognitive deficits, including Alzheimer’s disease (AD), continually fail clinical trials. We investigated whether this was due to the change in the expression of α5 GABAARs, consequently altering synaptic function during AD pathogenesis. Using medicinal chemistry and computational modeling, we developed aqueous soluble hybrids of 6,6-dimethyl-3-(2-hydroxyethyl) thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophene-4(5H)-one, that demonstrated selective binding and high negative allosteric modulation, specifically for the α5 GABAAR subtypes in constructed HEK293 stable cell-lines. Using a knock-in mouse model of AD (APPNL-F/NL-F), which expresses a mutant form of human amyloid-β (Aβ), we performed immunofluorescence studies combined with electrophysiological whole-cell recordings to investigate the effects of our key molecule, α5-SOP002 in the hippocampal CA1 region. In aged APPNL-F/NL-F mice, selective preservation of α5 GABAARs was observed in, calretinin- (CR), cholecystokinin- (CCK), somatostatin- (SST) expressing interneurons, and pyramidal cells. Previously, we reported that CR dis-inhibitory interneurons, specialized in regulating other interneurons displayed abnormally high levels of synaptic inhibition in the APPNL-F/NL-F mouse model, here we show that this excessive inhibition was „normalized” to control values with bath-applied α5-SOP002 (1 μM). However, α5-SOP002, further impaired inhibition onto CCK and pyramidal cells that were already largely compromised by exhibiting a deficit of inhibition in the AD model. In summary, using a multi-disciplinary approach, we show that exposure to α5 GABAAR NAMs may further compromise aberrant synapses in AD. We, therefore, suggest that the α5 GABAAR is not a suitable therapeutic target for the treatment of AD or other cognitive deficits due to the widespread neuronal-networks that use α5 GABAARs.