Miracle-dz/UniFAR-FTUs huggingface dataset:
TCF3 Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cells by Targeting PODXL

Spermatogonial stem cells (SSCs) are the initial cells for the spermatogenesis. Although much progress has been made on uncovering a number of modulators for the SSC fate decisions in rodents, the genes mediating human SSCs remain largely unclear. Here we report, for the first time, that TCF3, a member of the basic helix-loop-helix family of transcriptional modulator proteins, can stimulate proliferation and suppress the apoptosis of human SSCs through targeting podocalyxin-like protein (PODXL). TCF3 was expressed primarily in GFRA1-positive spermatogonia, and EGF (epidermal growth factor) elevated TCF3 expression level. Notably, TCF3 enhanced the growth and DNA synthesis of human SSCs, whereas it repressed the apoptosis of human SSCs. RNA sequencing and chromatin immunoprecipitation (ChIP) assays revealed that TCF3 protein regulated the transcription of several genes, including WNT2B, TGFB3, CCN4, MEGF6, and PODXL, while PODXL silencing compromised the stem cell activity of SSCs. Moreover, the level of TCF3 protein was remarkably lower in patients with spermatogenesis failure when compared to individuals with obstructive azoospermia with normal spermatogenesis. Collectively, these results implicate that TCF3 modulates human SSC proliferation and apoptosis through PODXL. This study is of great significance since it would provide a novel molecular mechanism underlying the fate determinations of human SSCs and it could offer new targets for gene therapy of male infertility.
A Regional, Honey Bee-Centered Approach Is Needed to Incentivize Grower Adoption of Bee-Friendly Practices in the Almond Industry

Managed and wild bee populations contribute over $15 billion in pollination services to US agriculture, yet both are declining or becoming increasingly vulnerable to parasites and disease. The loss of healthy and diverse forage is a key driver in bee declines, so incentivizing land managers to adopt diversified bee-friendly management practices such as forage plantings and reduced pesticide use can directly increase food security, pollinator health, and farmer adaptive capacity. To better understand what might incentivize growers to adopt bee-friendly practices, we conducted a survey of California almond growers, whose orchards are entirely dependent on bee pollination and draw nearly 88% of US bee colonies each February to pollinate almond bloom. We asked 329 respondents across all major almond growing regions of CA about their adoption rate and incentives for planting cover crops, pollinator habitat, and practicing the recommended and legally required bee-friendly best management practices, as well as their interest in bee-friendly certification programs. Using a model selection framework, we evaluated which geographic, social, operational, and pollination-service related factors were predictive of bee-friendly practice adoption. We found that no single factor was a statistically significant predictor of adoption across all models, suggesting there is no silver bullet determining bee-friendly practice adoption. However, we discovered that region and concerns about future pollination services consistently emerged as important factors related to all the practices we investigated, except the adoption of legally required BMPs. These findings suggest that a regionally flexible pollinator conservation strategy focused on supporting honey bee colonies might have the highest likelihood of grower participation and adoption.
Temporal Behavioral Parameters of On-Going Gaze Encounters in a Virtual Environment

To navigate the social world, humans heavily rely on gaze for non-verbal communication as it conveys information in a highly dynamic and complex, yet concise manner: For instance, humans utilize gaze effortlessly to direct and infer the attention of a possible interaction partner. Many traditional paradigms in social gaze research though rely on static ways of assessing gaze interaction, e.g., by using images or prerecorded videos as stimulus material. Emerging gaze contingent paradigms, in which algorithmically controlled virtual characters can respond flexibly to the gaze behavior of humans, provide high ecological validity. Ideally, these are based on models of human behavior which allow for precise, parameterized characterization of behavior, and should include variable interactive settings and different communicative states of the interacting agents. The present study provides a complete definition and empirical description of a behavioral parameter space of human gaze behavior in extended gaze encounters. To this end, we (i) modeled a shared 2D virtual environment on a computer screen in which a human could interact via gaze with an agent and simultaneously presented objects to create instances of joint attention and (ii) determined quantitatively the free model parameters (temporal and probabilistic) of behavior within this environment to provide a first complete, detailed description of the behavioral parameter space governing joint attention. This knowledge is essential to enable the modeling of interacting agents with a high degree of ecological validity, be it for cognitive studies or applications in human-robot interaction.
Molecular Subtypes of Oral Squamous Cell Carcinoma Based on Immunosuppression Genes Using a Deep Learning Approach

Background: The mechanisms through which immunosuppressed patients bear increased risk and worse survival in oral squamous cell carcinoma (OSCC) are unclear. Here, we used deep learning to investigate the genetic mechanisms underlying immunosuppression in the survival of OSCC patients, especially from the aspect of various survival-related subtypes. Materials and methods: OSCC samples data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and OSCC-related genetic datasets with survival data in the National Center for Biotechnology Information (NCBI). Immunosuppression genes (ISGs) were obtained from the HisgAtlas and DisGeNET databases. Survival analyses were performed to identify the ISGs with significant prognostic values in OSCC. A deep learning (DL)-based model was established for robustly differentiating the survival subpopulations of OSCC samples. In order to understand the characteristics of the different survival-risk subtypes of OSCC samples, differential expression analysis and functional enrichment analysis were performed. Results: A total of 317 OSCC samples were divided into one inferring cohort (TCGA) and four confirmation cohorts (ICGC set, GSE41613, GSE42743, and GSE75538). Eleven ISGs (i.e., BGLAP, CALCA, CTLA4, CXCL8, FGFR3, HPRT1, IL22, ORMDL3, TLR3, SPHK1, and INHBB) showed prognostic value in OSCC. The DL-based model provided two optimal subgroups of TCGA-OSCC samples with significant differences (p = 4.91E-22) and good model fitness [concordance index (C-index) = 0.77]. The DL model was validated by using four external confirmation cohorts: ICGC cohort (n = 40, C-index = 0.39), GSE41613 dataset (n = 97, C-index = 0.86), GSE42743 dataset (n = 71, C-index = 0.87), and GSE75538 dataset (n = 14, C-index = 0.48). Importantly, subtype Sub1 demonstrated a lower probability of survival and thus a more aggressive nature compared with subtype Sub2. ISGs in subtype Sub1 were enriched in the tumor-infiltrating immune cells-related pathways and cancer progression-related pathways, while those in subtype Sub2 were enriched in the metabolism-related pathways. Conclusion: The two survival subtypes of OSCC identified by deep learning can benefit clinical practitioners to divide immunocompromised patients with oral cancer into two subpopulations and give them target drugs and thus might be helpful for improving the survival of these patients and providing novel therapeutic strategies in the precision medicine area.
Mindsets and Neural Mechanisms of Automatic Reactions to Negative Feedback in Mathematics in Elementary School Students

Neuroscientific research regarding mindsets is so far scarce, especially among children. Moreover, even though research indicates the importance of domain specificity of mindsets, this has not yet been investigated in neuroscientific studies regarding implicit beliefs. The purpose of this study was to examine general intelligence and math ability mindsets and their relations to automatic reactions to negative feedback in mathematics in the Finnish elementary school context. For this, event-related potentials of 97 elementary school students were measured during the completion of an age-appropriate math task, where the participants received performance-relevant feedback throughout the task. Higher growth mindset was marginally associated with a larger P300 response and significantly associated with a smaller later peaking negative-going waveform. Moreover, with the domain-specific experimental setting, we found a higher growth mindset regarding math ability, but not general intelligence, to be associated with these brain responses elicited by negative feedback regarding errors in math. This suggests that it might be important to address domain-specific and even academic-domain-specific beliefs in addition to general mindsets in research and practice.
Update on the Crosstalk Between Adipose Tissue and Mineral Balance in General Population and Chronic Kidney Disease

Adipose tissue is nowadays considered as a major endocrine organ, which apart from controlling lipid metabolism, displays a significant role in energy expenditure, food intake and in the regulation of various systemic physiological processes. Adipose derived pro-inflammatory cytokines and adipokines, particularly leptin and adiponectin, provide inter-communication of adipose tissue with various metabolic pathways, ultimately resulting in a complex network of interconnected organ systems. Recent clinical and experimental research has been focused on exploring the direct interaction between adipokine profile and elements of mineral metabolism, including parathormone (PTH), fibroblast growth factor-23 (FGF23) and calcitriol. The emerging crosstalk between adipose tissue and calcium and phosphorus homeostasis suggests that metabolic disorders from one system may directly affect the other and vice versa. It is current knowledge that fat metabolism disturbance, commonly encountered in obese individuals, influences the expression of calciotriopic hormones in general population, while various clinical trials attempting to successfully achieve body fat loss by modulating mineral profile have been published. In chronic kidney disease (CKD) state, there is an increasing evidence suggesting that mineral disorders, influence adipose tissue and linked endocrine function. On the contrary, the impact of disturbed fat metabolism on CKD related mineral disorders has been also evocated in clinical studies. Recognizing the pathogenetic mechanisms of communication between adipose tissue and mineral balance is critical for understanding the effects of metabolic perturbations from the one system to the other and for identifying possible therapeutic targets in case of disrupted homeostasis in one of the two connected systems. To that end, this review aims to enlighten the recent advances regarding the interplay between mineral metabolism, fat mass and adipokine profile, based on in vitro, in vivo and clinical studies, in general population and in the course of CKD.
Tryptophan and Its Metabolites in Lung Cancer: Basic Functions and Clinical Significance

Lung cancer is the most lethal malignancy worldwide. Recently, it has been recognized that metabolic reprogramming is a complex and multifaceted factor, contributing to the process of lung cancer. Tryptophan (Try) is an essential amino acid, and Try and its metabolites can regulate the progression of lung cancer. Here, we review the pleiotropic functions of the Try metabolic pathway, its metabolites, and key enzymes in the pathogenic process of lung cancer, including modulating the tumor environment, promoting immune suppression, and drug resistance. We summarize the recent advance in therapeutic drugs targeting the Try metabolism and kynurenine pathway and their clinical trials.
Inoculation With Ectomycorrhizal Fungi and Dark Septate Endophytes Contributes to the Resistance of Pinus spp. to Pine Wilt Disease

Pine wilt disease (PWD) is a deadly disease to pines (Pinus spp.) worldwide. The occurrence of PWD can reduce the relative abundance of root ectomycorrhizal fungi (ECMF) and dark septate endophytes (DSE). However, the effects of exogenous ECMF/DSE inoculation on the rhizosphere microbial community structure of Pinus tabulaeformis infected by pine wood nematode (PWN) is little known. Here, we tested how ECMF/DSE may improve resistance to PWD by quantifying microbial carbon biomass and soil enzymatic activity among different treatments at 6 and 9 months after PWN infection. Denaturing gradient gel electrophoresis (DGGE) was used to study the microbial community structure at 3, 6, and 9 months after PWN infection in the rhizosphere of P. tabulaeformis seedlings inoculated with ECMF/DSE. The results showed that exogenous ECMF/DSE inoculation reduced the disease severity caused by PWN infection. After PWN infection, the rhizosphere microbial carbon of seedlings inoculated with Amanita vaginata, Suillus bovinus, Gaeumannomyces cylindrosporus, and Paraphoma chrysanthemicola was 38.16, 49.67, 42.11, and 96.05% higher than that of the control group, respectively. Inoculation of ECMF/DSE inhibited the decrease of rhizosphere microbial biomass caused by PWN infection. The richness and diversity of P. tabulaeformis rhizosphere fungi at 9 months were reduced by PWN infection but partially recovered by the exogenous fungi (ECMF/DSE) inoculation except for P. chrysanthemicola, which indicates a role of ECMF/DSE in maintaining stability of the microbial community. Inoculation with ECMF/DSE increased the beneficial bacterial (Thauera sp., Mesorhizobium sp., etc.) and fungal groups (Tomentella ellisii, Wilcoxina mikolae, etc.) of in the rhizosphere. In summary, exogenous ECMF/DSE inoculation could increase P. tabulaeformis resistance to PWD probably by improving the rhizosphere microenvironment.
CUX1 Facilitates the Development of Oncogenic Properties Via Activating Wnt/β-Catenin Signaling Pathway in Glioma

Background: Homeobox cut like 1 (CUX1), which often presents aberrated expression in many cancer cells, exerts a crucial role in tumorigenesis. Evidence describing CUX1 in gliomagenesis is scarce, and the effects of CUX1 on the Wnt/β-catenin pathway have not been reported. Our study aimed to explore the biological functions and molecular mechanisms involved in CUX1 activity in glioma. Methods: Datasets for bioinformatics analysis were obtained from the GEO, TCGA, CGGA, GTEX and CCLE databases. qRT-PCR, western blotting (WB), and immunohistochemistry (IHC) assays were used to investigate the expression patterns of CUX1 among glioma and brain tissues. CUX1 knockdown and overexpression vectors were transfected into glioma cell lines, the CCK-8, clone formation assay, wound healing, Transwell assay, and flow cytometry were performed to detect changes in cell viability, invasiveness, and the cell cycle. WB and immunofluorescence (IF) assays were used to explore changes in cell cycle-related and Wnt/β-catenin signaling protein levels. Results: Overexpression of CUX1 was identified in glioma tissues, and especially in glioblastoma (GBM), when compared to normal controls and correlated with poor prognosis. In comparison with untreated cells, TJ905 glioma cells overexpressing CUX1 showed higher proliferation and invasion abilities and S phase cell-cycle arrest, while the knockdown of CUX1 suppressed cell invasive ability and induced G1 phase arrest. Active Wnt/β-catenin signaling was enriched and clustered in a CUX1-associated GSEA/GSVA analysis. IF and WB assays indicated that CUX1 regulated the distribution of Axin2/β-catenin in glioma cells and regulated the expression of proteins downstream of the Wnt/β-catenin signaling pathway, suggesting that CUX1 served as an upstream positive regulator of the Wnt/β-catenin pathway. Finally, the knockdown of Axin2 or β-catenin could reverse the tumor-promoting effects caused by CUX1 overexpression, suggesting that CUX1 induced gliomagenesis and malignant phenotype by activating the Wnt/β-catenin signaling pathway. Conclusion: Our data suggested that the transcription factor CUX1 could be a novel therapeutic target for glioma with gene therapy.
Depression-, Anxiety-, and Anger and Cognitive Functions: Findings From a Longitudinal Prospective Study

Background: Determinants of changes in cognitive function during aging are not well-understood. We aimed to estimate the effects of depression-, anxiety- and anger symptoms on cognition and on cognition changes, especially on changes in episodic memory (EM) and executive functioning (EF). Methods: We analyze data from the Mid-Life in the Midlife in the United States Biomarker study at two time points including n = 710 women, and n = 542 men (1996/1997) at the first assessment and n = 669 women, and n = 514 men at the second assessment (2013/2014). To assess cognition we used the Brief Test of Adult Cognition (BTACT). To measure depression-, anxiety- and anger symptoms we used the Mood and Anxiety Symptom Questionnaire (MASQ), the Center for Epidemiologic Studies Depression Scale (CES-D) and the State-Trait Anger Expression Inventory (STAXI). We used repeated models analyses to explore changes in cognition, and repeated measures linear mixed-effects models to investigate depression, anxiety and anger effects on cognition. All analyses were adjusted for potential confounders (cognition at baseline, age, education, income). Results: At the first assessment, women had significantly better episodic memory functioning than men; men in the oldest age group had significant better executive functioning. At the second assessment, more education, and white ethnicity were associated with less negative changes on episodic memory and executive functioning. Depression- and anger symptoms were associated with declines in episodic memory among women; anxiety symptoms were associated with declines in episodic memory and executive functioning in both gender in men (EF: β: −0.02, (95% CI: −0.03, −0.01; EM: β −0.02 (−0.02, 95% CI: −0.03, −0.01) and in women (EF: β −0.01, 95% CI: −0.02, −0.0004; EM: β −0.013, 95% CI: −0.03, −0.001). Conclusions: Depression-, anxiety- and anger symptoms were associated with changes in episodic memory and executive functioning. Further longitudinal studies are critical in populations in more countries to better understand the impact of depression, anxiety and anger symptoms on cognition changes.
Progress With Livestock Welfare in Extensive Production Systems: Lessons From Australia

The extensive livestock production industries are vital to the national economy of Australia. Continuing improvements to extensively-raised livestock welfare is desirable, necessary and in some situations mandatory, if the social license for animal sourced food and fiber production is to continue sustainably. However, meeting increasingly high welfare standards is challenging. The changing climate in this millennium, has seen the occurrence of two of the most severe drought periods on record in Australia, resulting in complex welfare issues arising from unforeseen disease, trade and environmental catastrophes. The onset of the first drought coincided with an uncontrolled epidemic of ovine paratuberculosis. It ended just prior to a temporary ban on live export of tropical cattle to Indonesia that induced a major market failure and led to severe morbidity and mortality on some beef properties. The second drought period progressed in severity and culminated in the most extreme bushfires recorded, causing unprecedented levels of mortality, morbidity and suffering in farmed animals and wildlife. Temperature extremes have also caused periodic heat-associated or cold-induced hyopthermia losses, requiring increased vigilance and careful management to reduce both temperature-induced stress during transport and the high ovine peri-parturient losses traditionally observed in extensive sheep farming. Several issues remain controversial, including surgical mulesing of wool sheep to manage flystrike, and the continuing live export trade of sheep and cattle. However, in reviewing the increasingly complex welfare challenges for the extensive livestock population industries that are export trade dependent and remain vulnerable to welfare activism, it appears progress has been made. These include development of prescribed livestock welfare Standards and Guidelines and the introduction of the Exporter Supply Chain Assurance System (ESCAS) to address export concerns. Further, the sheep mulesing crisis led to improved producer welfare attitudes and practices, including pain management during aversive husbandry procedures that is now occurring globally. Finally, innovations in animal welfare surveillance and assessment, are additional encouraging signs that suggest improving change management of extensive farm animal welfare is occurring that provides lessons well-beyond Australian shores.
Clinical Implications of IL-32, IL-34 and IL-37 in Atherosclerosis: Speculative Role in Cardiovascular Manifestations of COVID-19

Atherosclerosis, which is a primary cause of cardiovascular disease (CVD) deaths around the world, is a chronic inflammatory disease that is characterised by the accumulation of lipid plaques in the arterial wall, triggering inflammation that is regulated by cytokines/chemokines that mediate innate and adaptive immunity. This review focuses on IL-32, -34 and -37 in the stable vs. unstable plaques from atherosclerotic patients. Dysregulation of the novel cytokines IL-32, -34 and -37 has been discovered in atherosclerotic plaques. IL-32 and -34 are pro-atherogenic and associated with an unstable plaque phenotype; whereas IL-37 is anti-atherogenic and maintains plaque stability. It is speculated that these cytokines may contribute to the explanation for the increased occurrence of atherosclerotic plaque rupture seen in patients with COVID-19 infection. Understanding the roles of these cytokines in atherogenesis may provide future therapeutic perspectives, both in the management of unstable plaque and acute coronary syndrome, and may contribute to our understanding of the COVID-19 cytokine storm.
Ablation of Survivin in T Cells Attenuates Acute Allograft Rejection after Murine Heterotopic Heart Transplantation by Inducing Apoptosis

Although studies in oncology have well explored the pharmacological effects of Birc5, little is known about its role in allogeneic T-cell responses. Therefore, the present study used a mouse model of acute heart allograft rejection to investigate the protective effect and mechanism of conditional knockout of Birc5 in T cells. Survivin (encoded by Birc5) was up-regulated in T cells activated in vivo and in vitro. Deletion of Birc5 in T cells attenuated acute heart allograft rejection by reducing the ratio of effector to naive T cells and Th1 to Tregs. In addition, deletion of Birc5 had no noticeable effect on proliferation but on apoptosis and the secretion of IFN-γ. The results revealed a significant increase in the percentage of Annexin V positive CD4+ T cells in the Birc5-/- group, compared to the WT. Moreover, there was significant increase in early apoptotic alloreactive T cells in Birc5 -/- mice and this was partly mediated by caspase-3. Furthermore, treatment with YM155 inhibited acute heart allograft rejection in vivo and increased T-cell apoptosis in healthy human PBMCs in vitro. The results highlight a potential therapeutic target for the prevention and treatment of acute transplant rejection.