Miracle-dz/UniFAR-FTUs huggingface dataset:
FER Regulated by miR-206 Promotes Hepatocellular Carcinoma Progression via NF-κB Signaling

Objectives Feline sarcoma-related protein (FER) is known to play a critical regulatory role in several carcinomas. However, the exact biological function of FER in hepatocellular carcinoma (HCC) still needs to be investigated. The primary objective of this research was to investigate the unknown function and molecular mechanisms of FER in HCC. Materials and Methods The expression level of FER in HCC tissue samples and cells was examined by RT-qPCR, immunohistochemistry and western blot. Cellular and animal experiments were used to explore the effect of FER on the proliferative and metastatic capacities of HCC cells. The crosstalk between FER and NF-κB signaling was explored by western blot. The upstream factors that regulate FER were evaluated through dual-luciferase experiments and western blot assays. Results FER was overexpressed in HCC specimens and HCC cell lines. FER expression levels were positively associated with unfavorable clinicopathological characteristics. The higher the expression of FER was, the worse the overall survival of HCC patients was. The results of loss-of-function and gain-of-function experiments indicated that knockdown of FER decreased, while overexpression of FER increased, the proliferation, invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, we found that FER activated the NF-κB signaling pathway and stimulated epithelial-to-mesenchymal transition (EMT). We also found that FER was directly regulated by miR-206, and the downregulation of miR-206 was associated with proliferation and metastatic progression in HCC. Conclusions The present research was the first to reveal that a decrease in miR-206 levels results in an increase in FER expression in HCC, leading to enhanced cell growth and metastatic abilities via activation of the NF-κB signaling pathway.
Becoming Team Members: Identifying Interaction Patterns of Mutual Adaptation for Human-Robot Co-Learning

Becoming a well-functioning team requires continuous collaborative learning by all team members. This is called co-learning, conceptualized in this paper as comprising two alternating iterative stages: partners adapting their behavior to the task and to each other (co-adaptation), and partners sustaining successful behavior through communication. This paper focuses on the first stage in human-robot teams, aiming at a method for the identification of recurring behaviors that indicate co-learning. Studying this requires a task context that allows for behavioral adaptation to emerge from the interactions between human and robot. We address the requirements for conducting research into co-adaptation by a human-robot team, and designed a simplified computer simulation of an urban search and rescue task accordingly. A human participant and a virtual robot were instructed to discover how to collaboratively free victims from the rubbles of an earthquake. The virtual robot was designed to be able to real-time learn which actions best contributed to good team performance. The interactions between human participants and robots were recorded. The observations revealed patterns of interaction used by human and robot in order to adapt their behavior to the task and to one another. Results therefore show that our task environment enables us to study co-learning, and suggest that more participant adaptation improved robot learning and thus team level learning. The identified interaction patterns can emerge in similar task contexts, forming a first description and analysis method for co-learning. Moreover, the identification of interaction patterns support awareness among team members, providing the foundation for human-robot communication about the co-adaptation (i.e., the second stage of co-learning). Future research will focus on these human-robot communication processes for co-learning.
How Action Shapes Body Ownership Momentarily and Throughout the Lifespan

Objects which a human agent controls by efferent activities (such as real or virtual tools) can be perceived by the agent as belonging to his or her body. This suggests that what an agent counts as “body” is plastic, depending on what she or he controls. Yet there are possible limitations for such momentary plasticity. One of these limitations is that sensations stemming from the body (e.g., proprioception) and sensations stemming from objects outside the body (e.g., vision) are not integrated if they do not sufficiently “match”. What “matches” and what does not is conceivably determined by long–term experience with the perceptual changes that body movements typically produce. Children have accumulated less sensorimotor experience than adults have. Consequently, they express higher flexibility to integrate body-internal and body-external signals, independent of their “match” as suggested by rubber hand illusion studies. However, children’s motor performance in tool use is more affected by mismatching body-internal and body-external action effects than that of adults, possibly because of less developed means to overcome such mismatches. We review research on perception-action interactions, multisensory integration, and developmental psychology to build bridges between these research fields. By doing so, we account for the flexibility of the sense of body ownership for actively controlled events and its development through ontogeny. This gives us the opportunity to validate the suggested mechanisms for generating ownership by investigating their effects in still developing and incomplete stages in children. We suggest testable predictions for future studies investigating both body ownership and motor skills throughout the lifespan.
Identification of Potential Signatures and Their Functions for Acute Lymphoblastic Leukemia: A Study Based on the Cancer Genome Atlas

Objective Acute lymphoblastic leukemia (ALL) is a malignant disease most commonly diagnosed in adolescents and young adults. This study aimed to explore potential signatures and their functions for ALL. Methods Differentially expressed mRNAs (DEmRNAs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified for ALL from The Cancer Genome Atlas (TCGA) and normal control from Genotype-Tissue Expression (GTEx). DElncRNA–microRNA (miRNA) and miRNA–DEmRNA pairs were predicted using online databases. Then, a competing endogenous RNA (ceRNA) network was constructed. Functional enrichment analysis of DEmRNAs in the ceRNA network was performed. Protein–protein interaction (PPI) network was then constructed. Hub genes were identified. DElncRNAs in the ceRNA network were validated using Real-time qPCR. Results A total of 2,903 up- and 3,228 downregulated mRNAs and 469 up- and 286 downregulated lncRNAs were identified for ALL. A ceRNA network was constructed for ALL, consisting of 845 lncRNA-miRNA and 395 miRNA–mRNA pairs. These DEmRNAs in the ceRNA network were mainly enriched in ALL-related biological processes and pathways. Ten hub genes were identified, including SMAD3, SMAD7, SMAD5, ZFYVE9, FKBP1A, FZD6, FZD7, LRP6, WNT1, and SFRP1. According to Real-time qPCR, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were significantly upregulated in ALL bone marrow samples compared to normal samples. Conclusion Our results showed the lncRNA expression profiles and constructed ceRNA network in ALL. Furthermore, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were identified. These results could provide a novel insight into the study of ALL.
Altered Effective Connectivity of Children and Young Adults With Unilateral Amblyopia: A Resting-State Functional Magnetic Resonance Imaging Study

The altered functional connectivity (FC) in amblyopia has been investigated by many studies, but the specific causality of brain connectivity needs to be explored further to understand the brain activity of amblyopia. We investigated whether the effective connectivity (EC) of children and young adults with amblyopia was altered. The subjects included 16 children and young adults with left eye amblyopia and 17 healthy controls (HCs). The abnormalities between the left/right primary visual cortex (PVC) and the other brain regions were investigated in a voxel-wise manner using the Granger causality analysis (GCA). According to the EC results in the HCs and the distribution of visual pathways, 12 regions of interest (ROIs) were selected to construct an EC network. The alteration of the EC network of the children and young adults with amblyopia was analyzed. In the voxel-wise manner analysis, amblyopia showed significantly decreased EC between the left/right of the PVC and the left middle frontal gyrus/left inferior frontal gyrus compared with the HCs. In the EC network analysis, compared with the HCs, amblyopia showed significantly decreased EC from the left calcarine fissure, posterior cingulate gyrus, left lingual gyrus, right lingual gyrus, and right fusiform gyrus to the right calcarine fissure. Amblyopia also showed significantly decreased EC from the right inferior frontal gyrus and right lingual gyrus to the left superior temporal gyrus compared with the HCs in the EC network analysis. The results may indicate that amblyopia altered the visual feedforward and feedback pathway, and amblyopia may have a greater relevance with the feedback pathway than the feedforward pathway. Amblyopia may also correlate with the feedforward of the third visual pathway.
Determinants of Persistent Patterns of Pepino Mosaic Virus Mixed Infections

Pepino mosaic virus (PepMV) has become a pandemic virus in tomato crops, causing important economic losses worldwide. In Spain, isolates of the EU and CH2 strains co-circulate, with PepMV-EU predominantly found in mixed infections. Simultaneous in planta mixed infections result in an asymmetric antagonism against PepMV-CH2, but the outcome of over-infections has never been tested. PepMV-EU and PepMV-CH2 time-lagged inoculations were performed, and viral accumulation was measured 10 days after challenge inoculation. PepMV-EU had a protective effect over PepMV-CH2; in contrast, the accumulation of PepMV-EU increased in plants pre-inoculated with PepMV-CH2 as compared to single infections. We also studied the effect of the type of infection on viral transmission. Independently of the nature of the infection (single or mixed), we observed a strong positive correlation between virus accumulation in the source plant and transmission, excluding mixed infection effects different than modulating viral accumulation. Finally, in order to determine the genetic variability of PepMV strains in single and mixed infections, a 430 nucleotide region was RT-PCR amplified from samples from a serial passages experiment and deep-sequenced. No significant differences were found in the number of nucleotide substitutions between single and mixed infections for PepMV-EU; in contrast, significant differences were found for PepMV-CH2, which was more variable in single than in mixed infections. Comparing PepMV-EU with PepMV-CH2, a higher nucleotide diversity was found for PepMV-CH2. Collectively, our data strongly suggest that PepMV mixed infections can impact the virus epidemiology by modulating in planta virus strain accumulation and diversification.
Impaired SNF2L Chromatin Remodeling Prolongs Accessibility at Promoters Enriched for Fos/Jun Binding Sites and Delays Granule Neuron Differentiation

Chromatin remodeling proteins utilize the energy from ATP hydrolysis to mobilize nucleosomes often creating accessibility for transcription factors within gene regulatory elements. Aberrant chromatin remodeling has diverse effects on neuroprogenitor homeostasis altering progenitor competence, proliferation, survival, or cell fate. Previous work has shown that inactivation of the ISWI genes, Smarca5 (encoding Snf2h) and Smarca1 (encoding Snf2l) have dramatic effects on brain development. Smarca5 conditional knockout mice have reduced progenitor expansion and severe forebrain hypoplasia, with a similar effect on the postnatal growth of the cerebellum. In contrast, Smarca1 mutants exhibited enlarged forebrains with delayed progenitor differentiation and increased neuronal output. Here, we utilized cerebellar granule neuron precursor (GNP) cultures from Smarca1 mutant mice (Ex6DEL) to explore the requirement for Snf2l on progenitor homeostasis. The Ex6DEL GNPs showed delayed differentiation upon plating that was not attributed to changes in the Sonic Hedgehog pathway but was associated with overexpression of numerous positive effectors of proliferation, including targets of Wnt activation. Transcriptome analysis identified increased expression of Fosb and Fosl2 while ATACseq experiments identified a large increase in chromatin accessibility at promoters many enriched for Fos/Jun binding sites. Nonetheless, the elevated proliferation index was transient and the Ex6DEL cultures initiated differentiation with a high concordance in gene expression changes to the wild type cultures. Genes specific to Ex6DEL differentiation were associated with an increased activation of the ERK signaling pathway. Taken together, this data provides the first indication of how Smarca1 mutations alter progenitor cell homeostasis and contribute to changes in brain size.
Experiences and Perspectives of Traditional Bullying and Cyberbullying Among Adolescents in Mainland China-Implications for Policy

The prevalence of traditional bullying and cyberbullying is high among Chinese adolescents. The aims of this study are to explore: (1) characteristics of children who are targets or perpetrators of traditional bullying or cyberbullying; (2) causes of bullying in middle school; (3) reactions and coping strategies of bullying victims; and (4) impacts of bullying on victims' psychosocial well-being. Students were selected based on the findings of previous quantitative research at schools in Zhejiang, Henan, and Chongqing. Snowball sampling led to identification of more informants. Semi-structured interviews were conducted with students involved in traditional bullying and cyberbullying as perpetrators, victims, and bystanders. Forty-one students aged 12–16 years (21 boys and 20 girls) from 16 schools in three provinces participated. Data collection and analysis followed a grounded theory approach. Among these students traditional bullying was much more common than cyberbullying, but there was a large overlap between the two types. The results informed a conceptual framework which identified the main causes of bullying in these settings: these included lack of education about bullying, inadequate classroom and dormitory management, and teachers' failure to recognize and punish bullying. Children with specific characteristics (such as being unattractive or low-achieving), were more likely to be bullied. Most victims lacked support of parents and teachers even when requested, leading to poor psychosocial well-being, difficulties with socialization, and poor academic performance. Our findings suggest that schools need to address bullying culture, through multi-faceted locally-appropriate approaches, based on zero tolerance. It is crucial to ensure that students, teachers and parents recognize the importance of such interventions.
Searching for Function: Reconstructing Adaptive Niche Changes Using Geochemical and Morphological Data in Planktonic Foraminifera

Dead species remain dead. The diversity record of life is littered with examples of declines and radiations, yet no species has ever re-evolved following its true extinction. In contrast, functional traits can transcend diversity declines, often develop iteratively and are taxon-free allowing application across taxa, environments and time. Planktonic foraminifera have an unrivaled, near continuous fossil record for the past 200 million years making them a perfect test organism to understand trait changes through time, but the functional role of morphology in determining habitat occupation has been questioned. Here, we use single specimen stable isotopes to reconstruct the water depth habitat of individual planktonic foraminifera in the genus Subbotina alongside morphological measurements of the tests to understand trait changes through the Middle Eocene Climatic Optimum [MECO: ∼40 Myr ago (mega annum, Ma)]. The MECO is a geologically transient global warming interval that marks the beginning of widespread biotic reorganizations in marine organisms spanning a size spectrum from diatoms to whales. In contrast to other planktonic foraminiferal genera, the subbotinids flourished through this interval despite multiple climatic perturbations superimposed on a changing background climate. Through coupled trait and geochemical analysis, we show that Subbotina survival through this climatically dynamic interval was aided by trait plasticity and a wider ecological niche than previously thought for a subthermocline dwelling genus supporting a generalist life strategy. We also show how individually resolved oxygen isotopes can track shifts in depth occupancy through climatic upheaval. During and following the MECO, temperature changes were substantial in the thermocline and subthermocline in comparison to the muted responses of the surface ocean. In our post-MECO samples, we observe restoration of planktonic foraminifera depth stratification. Despite these changing temperatures and occupied depths, we do not detect a contemporaneous morphological response implying that readily available traits such as test size and shape do not have a clear functional role in this generalist genus. Modern imaging measurement technologies offer a promising route to gather more informative morphological traits for functional analysis, rather than the traditional candidates that are most easily measured.
Using Dynamics of Eye Movements, Speech Articulation and Brain Activity to Predict and Track mTBI Screening Outcomes

Repeated subconcussive blows to the head during sports or other contact activities may have a cumulative and long lasting effect on cognitive functioning. Unobtrusive measurement and tracking of cognitive functioning is needed to enable preventative interventions for people at elevated risk of concussive injury. The focus of the present study is to investigate the potential for using passive measurements of fine motor movements (smooth pursuit eye tracking and read speech) and resting state brain activity (measured using fMRI) to complement existing diagnostic tools, such as the Immediate Post-concussion Assessment and Cognitive Testing (ImPACT), that are used for this purpose. Thirty-one high school American football and soccer athletes were tracked through the course of a sports season. Hypotheses were that (1) measures of complexity of fine motor coordination and of resting state brain activity are predictive of cognitive functioning measured by the ImPACT test, and (2) within-subject changes in these measures over the course of a sports season are predictive of changes in ImPACT scores. The first principal component of the six ImPACT composite scores was used as a latent factor that represents cognitive functioning. This latent factor was positively correlated with four of the ImPACT composites: verbal memory, visual memory, visual motor speed and reaction speed. Strong correlations, ranging between r = 0.26 and r = 0.49, were found between this latent factor and complexity features derived from each sensor modality. Based on a regression model, the complexity features were combined across sensor modalities and used to predict the latent factor on out-of-sample subjects. The predictions correlated with the true latent factor with r = 0.71. Within-subject changes over time were predicted with r = 0.34. These results indicate the potential to predict cognitive performance from passive monitoring of fine motor movements and brain activity, offering initial support for future application in detection of performance deficits associated with subconcussive events.
Novel Scalable and Simplified System to Generate Microglia-Containing Cerebral Organoids From Human Induced Pluripotent Stem Cells

Human cerebral organoid (CO) is a three-dimensional (3D) cell culture system that recapitulates the developing human brain. While CO has proved an invaluable tool for studying neurological disorders in a more clinically relevant matter, there have still been several shortcomings including CO variability and reproducibility as well as lack of or underrepresentation of certain cell types typically found in the brain. As the technology to generate COs has continued to improve, more efficient and streamlined protocols have addressed some of these issues. Here we present a novel scalable and simplified system to generate microglia-containing CO (MCO). We characterize the cell types and dynamic development of MCOs and validate that these MCOs harbor microglia, astrocytes, neurons, and neural stem/progenitor cells, maturing in a manner that reflects human brain development. We introduce a novel technique for the generation of embryoid bodies (EBs) directly from induced pluripotent stem cells (iPSCs) that involves simplified steps of transitioning directly from 3D cultures as well as orbital shaking culture in a standard 6-well culture plate. This allows for the generation of MCOs with an easy-to-use system that is affordable and accessible by any general lab.
Assessment of Epigenetic and Phenotypic Variation in Populus nigra Regenerated via Sequential Regeneration

Somatic variation has been demonstrated in tissue culture regenerated plants of many species. In the genus Populus, phenotypic variation caused by changes in 5-methylcytosine within the plant genome have been reported. To date, the phenotypic and epigenetic stability of plants regenerated from sequential regeneration has not been tested in trees. In this study, we detected DNA methylation of CCGG sites in regenerated plants of five generations in Populus nigra using methylation-sensitive amplified polymorphisms, and evaluated their growth performance and physiological traits. About 10.86–26.80% of CCGG sites in the regenerated plant genome were demethylated and 5.50–8.45% were methylated, resulting in significantly lower DNA methylation levels among all regenerated plants than among donor plants. We detected a significant difference in methylation levels between first regeneration regenerated plants (G1) and those of the other four generations (G2–G5); there were no significant differences among the four later generations. Therefore, the dramatic decrease in DNA methylation levels occurred only in the first and second poplar regenerations; levels then stabilized later in the regeneration process, indicating that two regeneration events were sufficient to change the methylation statuses of almost all CCGG sites sensitive to regeneration. Differences in growth and physiological traits were observed between regenerated plants and donor plants, but were significant only among plants of certain generations. Significant correlations were detected between methylation level and transpiration rate, net photosynthetic rate, peroxidase activity, and instant water utilization efficiency, indicating the involvement of epigenetic regulation in this unpredictable phenotypic variation.