Miracle-dz/UniFAR-FTUs huggingface dataset:
Cutaneous Melanoma: Mutational Status and Potential Links to Tertiary Lymphoid Structure Formation

Recent advances in immunotherapy have enabled rapid evolution of novel interventional approaches designed to reinvigorate and expand patient immune responses against cancer. An emerging approach in cancer immunology involves the conditional induction of tertiary lymphoid structures (TLS), which are non-encapsulated ectopic lymphoid structures forming at sites of chronic, pathologic inflammation. Cutaneous melanoma (CM), a highly-immunogenic form of solid cancer, continues to rise in both incidence and mortality rate, with recent reports supporting a positive correlation between the presence of TLS in melanoma and beneficial treatment outcomes amongst advanced-stage patients. In this context, TLS in CM are postulated to serve as dynamic centers for the initiation of robust anti-tumor responses within affected regions of active disease. Given their potential importance to patient outcome, significant effort has been recently devoted to gaining a better understanding of TLS neogenesis and the influence these lymphoid organs exert within the tumor microenvironment. Here, we briefly review TLS structure, function, and response to treatment in the setting of CM. To uncover potential tumor-intrinsic mechanisms that regulate TLS formation, we have taken the novel perspective of evaluating TLS induction in melanomas impacted by common driver mutations in BRAF, PTEN, NRAS, KIT, PRDM1, and MITF. Through analysis of The Cancer Genome Atlas (TCGA), we show expression of DNA repair proteins (DRPs) including BRCA1, PAXIP, ERCC1, ERCC2, ERCC3, MSH2, and PMS2 to be negatively correlated with expression of pro-TLS genes, suggesting DRP loss may favor TLS development in support of improved patient outcome and patient response to interventional immunotherapy.
Visual Modulation of Human Responses to Support Surface Translation

Vision is known to improve human postural responses to external perturbations. This study investigates the role of vision for the responses to continuous pseudorandom support surface translations in the body sagittal plane in three visual conditions: with the eyes closed (EC), in stroboscopic illumination (EO/SI; only visual position information) and with eyes open in continuous illumination (EO/CI; position and velocity information) with the room as static visual scene (or the interior of a moving cabin, in some of the trials). In the frequency spectrum of the translation stimulus we distinguished on the basis of the response patterns between a low-frequency, mid-frequency, and high-frequency range (LFR: 0.0165-0.14 Hz; MFR: 0.15–0.57 Hz; HFR: 0.58–2.46 Hz). With EC, subjects’ mean sway response gain was very low in the LFR. On average it increased with EO/SI (although not to a significant degree p = 0.078) and more so with EO/CI (p < 10−6). In contrast, the average gain in the MFR decreased from EC to EO/SI (although not to a significant degree, p = 0.548) and further to EO/CI (p = 0.0002). In the HFR, all three visual conditions produced, similarly, high gain levels. A single inverted pendulum (SIP) model controlling center of mass (COM) balancing about the ankle joints formally described the EC response as being strongly shaped by a resonance phenomenon arising primarily from the control’s proprioceptive feedback loop. The effect of adding visual information in these simulations lies in a reduction of the resonance, similar as in the experiments. Extending the model to a double inverted pendulum (DIP) suggested in addition a biomechanical damping effective from trunk sway in the hip joints on the resonance.
Biochar’s Leacheates Affect the Abscisic Acid Pathway in Rice Seedlings Under Low Temperature

Organic molecules of biochar’s leacheates are known to increase the cold resistance of rice seedlings. Yet, it remains unclear whether the organic molecules of biochar leacheates can interact with the abscisic acid (ABA) signaling pathway associated with low temperature. This study used experiments and bioinformatics (molecular docking) to determine which of the organic molecules of biochar’s leacheates could influence the ABA signaling pathway. Specifically, we investigated whether these molecules affected ABA, a plant hormone linked to cold resistance. The contents of endogenous ABA and its precursor carotenoids were determined under low-temperature stress (10°C) and treatment with different concentrations of biochar leacheates. With increased leacheate concentrations, the endogenous ABA and carotenoid contents also increased, as did the expression of ABA- and cold-related genes. When rice seedlings were instead treated with exogenous ABA, it also affected the above-measured indexes; hence, we surmised that certain water-soluble organic molecules of biochar could exert a similar effect as ABA. We first used gas chromatography/mass spectrometry (GC/MS) to identify the organic molecules in the biochar extract, and then we used molecular docking software Autodock to show how they interact. We found that the molecule (1R, 2R, 4S)-2-(6-chloropyridin-3-yl)-7-azabicyclo(2.2.1)heptane was simplified, as Cyah could dock with the ABA receptor protein OsPYL2 in rice, which shows Cyah in biochar is probably an analog of ABA, with a similar function. Based on these results, we conclude that organic molecules of biochar’s leacheates could enter into rice plants and interact with ABA-related proteins to affect the ABA signaling pathway, thereby improving the cold stress resistance of plants.
The Impacts of Age and Sex in a Mouse Model of Childhood Narcolepsy

Narcolepsy is a sleep disorder caused by selective death of the orexin neurons that often begins in childhood. Orexin neuron loss disinhibits REM sleep during the active period and produces cataplexy, episodes of paralysis during wakefulness. Cataplexy is often worse when narcolepsy develops in children compared to adults, but the reason for this difference remains unknown. We used orexin-tTA; TetO DTA mice to model narcolepsy at different ages. When doxycycline is removed from the diet, the orexin neurons of these mice express diphtheria toxin A and die within 2–3 weeks. We removed doxycycline at 4 weeks (young-onset) or 14 weeks (adult-onset) of age in male and female mice. We implanted electroencephalography (EEG) and electromyography (EMG) electrodes for sleep recordings two weeks later and then recorded EEG/EMG/video for 24 h at 3 and 13 weeks after removal of doxycycline. Age-matched controls had access to doxycycline diet for the entire experiment. Three weeks after doxycycline removal, both young-onset and adult-onset mice developed severe cataplexy and the sleep-wake fragmentation characteristic of narcolepsy. Cataplexy and maintenance of wake were no worse in young-onset compared to adult-onset mice, but female mice had more bouts of cataplexy than males. Orexin neuron loss was similarly rapid in both young- and adult-onset mice. As age of orexin neuron loss does not impact the severity of narcolepsy symptoms in mice, the worse symptoms in children with narcolepsy may be due to more rapid orexin neuron loss than in adults.
Pb Toxicity on Gut Physiology and Microbiota

Lead (Pb) is a toxic heavy metal, having profound threats to the global population. Multiple organs such as kidney, and liver, as well as nervous, hematologic, and reproductive systems, are commonly considered the targets of Pb toxicity. Increasing researches reported that the effects of Pb on gastrointestinal tracts are equally intensive, especially on intestinal microbiota. This review summarized Pb toxicity on gut physiology and microbiota in different animal models and in humans, of which the alterations may further have effects on other organs in host. To be more specific, Pb can impair gut barrier and increase gut permeability, which make inflammatory cytokines, immunologic factors, as well as microbial metabolites such as bile acids (BA) and short-chain fatty acids (SCFAs) enter the enterohepatic circulation easily, and finally induce multiple systematic lesion. In addition, we emphasized that probiotic treatment may be one of the feasible and effective strategies for preventing Pb toxicity.
Identification and Validation of a Stromal EMT Related LncRNA Signature as a Potential Marker to Predict Bladder Cancer Outcome

Bladder cancer (BLCA) has become one of the most common malignant tumors in the genitourinary system. BLCA is one of the tumors considered suitable for immunotherapy because of the large proportion of immune cells in TME. Epithelial to mesenchymal transition (EMT) is closely related to tumor immunity through its crosstalk with immune cells. A recent study validated that EMT-related genes were mainly expressed by stromal cells and could influence immunotherapy responsiveness. Stromal EMT-related gene signature was also demonstrated to affect the prognosis of multiple tumors, including BLCA. To further explore the prognostic roles of stromal components, we performed a comprehensive analysis of LncRNAs closely associated with stromal EMT-related genes in the TCGA BLCA cohort. We identified a signature including five stromal EMT gene-related LncRNAs that showed significant prognostic value for BLCA patients. By the CIBERSORT and MCP-COUNTER algorithm, we found the signature was markedly correlated with infiltrated immune cells and stromal components of the tumor microenvironment, which may further influence patient’s responsiveness to immune checkpoint blockade therapy. Through immunohistochemical analysis, we confirmed the correlation of the signature with macrophages M2 and CAFs. Meanwhile, key genes related to these LncRNAs, including VIM, MMP2, were also differentially expressed in the stromal components concerning the signature. Our research confirmed the prognostic and immune-associated role of stromal EMT-related LncRNAs. Meantime, we further confirmed that EMT-related genes were mainly expressed in stromal components. Targeting these LncRNAs as well as their related stromal EMT genes may provide potential therapeutic targets for BLCA immunotherapy and precision medicine.
Simultaneous Ablation of the Catalytic AMPK α-Subunit SNF1 and Mitochondrial Matrix Protease CLPP Results in Pronounced Lifespan Extension

Organismic aging is known to be controlled by genetic and environmental traits. Pathways involved in the control of cellular metabolism play a crucial role. Previously, we identified a role of PaCLPP, a mitochondrial matrix protease, in the control of the mitochondrial energy metabolism, aging, and lifespan of the fungal aging model Podospora anserina. Most surprisingly, we made the counterintuitive observation that the ablation of this component of the mitochondrial quality control network leads to lifespan extension. In the current study, we investigated the role of energy metabolism of P. anserina. An age-dependent metabolome analysis of the wild type and a PaClpP deletion strain verified differences and changes of various metabolites in cultures of the PaClpP mutant and the wild type. Based on these data, we generated and analyzed a PaSnf1 deletion mutant and a ΔPaSnf1/ΔPaClpP double mutant. In both mutants PaSNF1, the catalytic α-subunit of AMP-activated protein kinase (AMPK) is ablated. PaSNF1 was found to be required for the development of fruiting bodies and ascospores and the progeny of sexual reproduction of this ascomycete and impact mitochondrial dynamics and autophagy. Most interestingly, while the single PaSnf1 deletion mutant is characterized by a slight lifespan increase, simultaneous deletion of PaSnf1 and PaClpP leads to a pronounced lifespan extension. This synergistic effect is strongly reinforced in the presence of the mating-type “minus”-linked allele of the rmp1 gene. Compared to the wild type, culture temperature of 35°C instead of the standard laboratory temperature of 27°C leads to a short-lived phenotype of the ΔPaSnf1/ΔPaClpP double mutant. Overall, our study provides novel evidence for complex interactions of different molecular pathways involved in mitochondrial quality control, gene expression, and energy metabolism in the control of organismic aging.
Cell Wall Polysaccharide Composition of Grafted ‘Liberty’ Watermelon With Reduced Incidence of Hollow Heart Defect

Grafting watermelon scions to interspecific squash hybrids has been found to increase fruit firmness. Triploid (seedless) watermelon are prone to hollow heart (HH), an internal fruit disorder characterized by a crack in the placental tissue expanding to a cavity. Although watermelon with lower tissue firmness tend to have a higher HH incidence, associated differences in cell wall polysaccharide composition are unknown. Grafting “Liberty” watermelon to “Carnivor” (interspecific hybrid rootstock, C. moschata × C. maxima) reduced HH 39% and increased tissue firmness by 3 N. Fruit with and without severe HH from both grafted and non-grafted plants were analyzed to determine differences in cell wall polysaccharides associated with grafting and HH. Alcohol insoluble residues (AIR) were sequentially extracted from placental tissue to yield water soluble (WSF), carbonate soluble (CSF), alkali soluble (ASF), or unextractable (UNX) pectic fractions. The CSF was lower in fruit with HH (24.5%) compared to those without HH (27.1%). AIRs were also reduced, hydrolyzed, and acetylated for GC-MS analysis of monosaccharide composition, and a portion of each AIR was methylated prior to hydrolysis and acetylation to produce partially methylated alditol acetates for polysaccharide linkage assembly. No differences in degree of methylation or galacturonic and glucuronic acid concentrations were found. Glucose and galactose were in highest abundance at 75.9 and 82.4 μg⋅mg–1 AIR, respectively, followed by xylose and arabinose (29.3 and 22.0 μg⋅mg–1). Mannose was higher in fruit with HH (p < 0.05) and xylose was highest in fruit from grafted plants (p < 0.05). Mannose is primarily found in heteromannan and rhamnogalacturonan I side chains, while xylose is found in xylogalacturonan or heteroxylan. In watermelon, 34 carbohydrate linkages were identified with galactose, glucose, and arabinose linkages in highest abundance. This represents the most comprehensive polysaccharide linkage analysis to date for watermelon, including the identification of several new linkages. However, total pectin and cell wall composition data could not explain the increased tissue firmness observed in fruit from grafted plants. Nonetheless, grafting onto the interspecific hybrid rootstock decreased the incidence of HH and can be a useful method for growers using HH susceptible cultivars.
Navigated Transcranial Magnetic Stimulation Motor Mapping Usefulness in the Surgical Management of Patients Affected by Brain Tumors in Eloquent Areas: A Systematic Review and Meta-Analysis

Background: The surgical strategy for brain glioma has changed, shifting from tumor debulking to a more careful tumor dissection with the aim of a gross-total resection, extended beyond the contrast-enhancement MRI, including the hyperintensity on FLAIR MR images and defined as supratotal resection. It is possible to pursue this goal thanks to the refinement of several technological tools for pre and intraoperative planning including intraoperative neurophysiological monitoring (IONM), cortico-subcortical mapping, functional MRI (fMRI), navigated transcranial magnetic stimulation (nTMS), intraoperative CT or MRI (iCT, iMR), and intraoperative contrast-enhanced ultrasound. This systematic review provides an overview of the state of the art techniques in the application of nTMS and nTMS-based DTI-FT during brain tumor surgery. Materials and Methods: A systematic literature review was performed according to the PRISMA statement. The authors searched the PubMed and Scopus databases until July 2020 for published articles with the following Mesh terms: (Brain surgery OR surgery OR craniotomy) AND (brain mapping OR functional planning) AND (TMS OR transcranial magnetic stimulation OR rTMS OR repetitive transcranial stimulation). We only included studies regarding motor mapping in craniotomy for brain tumors, which reported data about CTS sparing. Results: A total of 335 published studies were identified through the PubMed and Scopus databases. After a detailed examination of these studies, 325 were excluded from our review because of a lack of data object in this search. TMS reported an accuracy range of 0.4–14.8 mm between the APB hotspot (n1/4 8) in nTMS and DES from the DES spot; nTMS influenced the surgical indications in 34.3–68.5%. Conclusion: We found that nTMS can be defined as a safe and non-invasive technique and in association with DES, fMRI, and IONM, improves brain mapping and the extent of resection favoring a better postoperative outcome.
Acceptance of Diversity as a Building Block of Social Cohesion: Individual and Structural Determinants

High levels of social cohesion have been shown to be beneficial both for social entities and for their residents. It is therefore not surprising that scholars from several disciplines investigate which factors contribute to or hamper social cohesion at various societal levels. In recent years, the question of how individuals deal with the increasing diversity of their neighborhoods and society as a whole has become of particular interest when examining cohesion. The present study takes this a step further by combining sociological and psychological approaches in investigating whether the group-level acceptance of diversity, a core feature of cohesive societies, is related to prevailing mentalities of individuals once the social structure of a community is accounted for. We hypothesize that after controlling for individual sociodemographic and for structural variables, three individual characteristics play an important role for the level of acceptance of diversity in a given entity. We propose that individual intergroup anxiety (IGA) acts as a motor of the rejection of diversity whereas individual empathy should act as a safeguard. Furthermore, we propose that right-leaning political orientation (PO) has a negative influence on the acceptance of diversity. This study is based on a large, representative sample of the German general population (N1 = 2,869). To draw comparisons among different social entities, the sample was divided by federal states (N2 = 16). Data were analyzed by using a two-step approach for analyzing group-level outcomes in multilevel models. The analyses confirmed our hypothesis that intergroup anxiety at the individual level hampers the acceptance of diversity in a given sociopolitical entity. Furthermore, we found that intergroup anxiety is impacted by the economic situation in a federal state (measured per capita gross domestic product), as economic weakness intensified the fear of others. Surprisingly, neither empathy nor political orientation played a role for the acceptance of diversity. Implications for future research on social cohesion as well as for the work of policy makers are discussed.
Molecular Diversity and Distribution of Arbuscular Mycorrhizal Fungi at Different Elevations in Mt. Taibai of Qinling Mountain

Arbuscular mycorrhizal fungi (AMFs) play a vital role in ecosystems, especially in ecosystem variability, diversity, and function. Understanding the AMF diversity, distribution, and their driver at different altitudinal gradients is a benefit for understanding the ecological function of AMF in mountain ecosystems. In this study, we explored the AMF molecular diversity and their distribution from 660 to 3,500 m a.s. l. in Mount Taibai of Qinling Mountains based on high-throughput sequencing technology. A total of 702 operational taxonomic units (OTUs) in 103 species of AMF are isolated from soil samples, which belong to 18 identified and 1 unidentified genus in 10 families. The fungi in the genus of Glomus is the most dominant, with the occurrence frequency of 100% and the relative abundance of 42.268% and 33.048% on the species and OTU level, respectively. The AMF colonization in root could be simulated by a cubic function with the change of altitudes with the peak and trough at a.s. l. 1,170 and 2,850 m, respectively. Further, AMF diversity indices including Sob, Shannon diversity, and Pielou evenness also showed the same cubic function change trends with increasing altitude at OTU and species levels. However, the average values of diversity indices at OTU level are always higher than these at the species level. Based on the OTU level, the highest and lowest values of Shannon and Pielou indices are observed at the altitudes of 1,400 and 2,800 m, respectively. The pattern of AMF community distribution in Mt. Taibai is driven by altitude with the characteristics of more abundance in the medium- to low-altitude than high-altitude areas. In general, abundant AMF molecular diversity and species exit in different elevations of Mt. Taibai, which indicate gradient changes with elevations.
Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy

Glioblastoma (GBM) is the most common and devastating primary cancer of the central nervous system in adults. High grade gliomas are able to modify and respond to the brain microenvironment. When GBM tumors infiltrate the Subventricular zone (SVZ) they have a more aggressive clinical presentation than SVZ-distal tumors. We suggest that cerebrospinal fluid (CSF) contact contributes to enhance GBM malignant characteristics in these tumors. We evaluated the impact of human CSF on GBM, performing a transcriptome analysis on human primary GBM cells exposed to CSF to measure changes in gene expression profile and their clinical relevance on disease outcome. In addition we evaluated the proliferation and migration changes of CSF-exposed GBM cells in vitro and in vivo. CSF induced transcriptomic changes in pathways promoting cell malignancy, such as apoptosis, survival, cell motility, angiogenesis, inflammation, and glucose metabolism. A genetic signature extracted from the identified transcriptional changes in response to CSF proved to be predictive of GBM patient survival using the TCGA database. Furthermore, CSF induced an increase in viability, proliferation rate, and self-renewing capacity, as well as the migratory capabilities of GBM cells in vitro. In vivo, GBM cells co-injected with human CSF generated larger and more proliferative tumors compared to controls. Taken together, these results provide direct evidence that CSF is a key player in determining tumor growth and invasion through the activation of complex gene expression patterns characteristic of a malignant phenotype. These findings have diagnostic and therapeutic implications for GBM patients. The changes induced by CSF contact might play a role in the increased malignancy of SVZ-proximal GBM.