Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitrogen Addition and Arbuscular Mycorrhizal Fungi Beta Diversity: Patterns and Mechanisms

Global nitrogen eutrophication, which is disrupting the intimate plant–arbuscular mycorrhizal fungi (AMF) symbiosis, can alter the diversity and physiological functions of soil AMF greatly. However, shifts of beta diversity and the intrinsic patterns of AMF community dissimilarities in response to nitrogen addition remain unclear. Based on a 7-year nitrogen addition experiment in a Qinghai–Tibet Plateau alpine meadow, we detected the changes in soil AMF alpha diversity (richness and genus abundance) and the community composition beta diversity by partitioning the two components of Simpson and nestedness dissimilarities along (turnover) and within (variation) nitrogen addition treatments, and fitted with environmental factor dissimilarities. We found that nitrogen addition decreased AMF richness by decreasing the most dominant AMF genus of Glomus but increasing the abundance of the rare genera. The turnover of the AMF community overall beta diversity along the nitrogen addition gradients was induced by the increased nestedness dissimilarity, while the variation within treatments was explained by both increased Simpson and nestedness dissimilarities, which was significantly correlated with soil pH. Our study found both Simpson and nestedness dissimilarities worked on the AMF community dissimilarity after nitrogen addition and the significant variation within the same treatment, which would be important in the future for predicting global AMF or microbial diversity changes in response to nitrogen eutrophication.
Effect of Planting Density and K2O:N Ratio on the Yield, External Quality, and Traders' Perceived Shelf Life of Pineapple Fruits in Benin

Quality, shelf life, and yield of a pineapple fruit are the important attributes for the producers and customers in the pineapple value chain of Benin, whereas poor quality, short shelf life, and low yield are the main constraints. We quantified the effects of planting density and K2O:N fertilizer ratio on the pineapple yield, external quality, and perceived shelf life in four on-farm experiments with cv. Sugarloaf in Benin; two experiments were installed in the long rainy season and two in the short rainy season. A split-plot design was used with the planting density as the main factor at three levels: 54,000, 66,600, and 74,000 plants.ha−1. The K2O:N ratio was a subfactor with three levels: K2O:N = 0.35 (farmers' practice), K2O:N = 1, and K2O:N = 2. The results showed that both factors had no effect on the crop development variables (such as the number of functional leaves and D-leaf length) at the moment of flowering induction. The planting density had no effect on the total weight per fruit, infructescence weight, total fruit length, infructescence length, crown length, or the fruit shelf life as perceived by traders. The yield increased from 54.9–69.1 up to 90.1 t.ha−1 with an increase in the planting density. The yield increase was not at the expense of the fruit weight. Increased K2O:N ratio led to a higher fruit weight whereas the fruit length was not affected. The shelf life of fruits produced at a K2O:N ratio of 1 and as perceived by traders was 6 days longer than that of fruits produced at a ratio of 0.35 (farmers' practice). Based on these results, we suggest the fresh pineapple farmers in Benin to use a combination of 66,600 plants.ha−1 with a K-fertilization scheme based on a K2O:N ratio of 1 to meet the expectation of both producers and customers in terms of fruit yield and fruit quality.
Post-Diagnostic Beta Blocker Use and Prognosis of Ovarian Cancer: A Systematic Review and Meta-Analysis of 11 Cohort Studies With 20,274 Patients

Objectives Previous experimental studies have indicated that exposure to beta blocker provides protective effects against ovarian cancer (OC). However, findings from epidemiologic studies have still been controversial. Therefore, we carried out a meta-analysis to update and quantify the correlation between post-diagnostic beta blocker usage and OC prognosis. Methods The meta-analysis had been registered at PROSPEPO. The number of registration is CRD42020188806. A comprehensive search of available literatures in English prior to April 16, 2020, was conducted in PubMed, EMBASE, and the Web of Science databases. Random-effects models were used to calculate overall hazard ratios (HRs) and 95% confidence intervals (CIs). Publication bias assessments, and subgroup, sensitivity, and meta-regression analyses were also performed. Results Of the 637 initially identified articles, 11 retrospective cohort studies with 20,274 OC patients were included. The summary HRs did not reveal any statistically significant associations between post-diagnostic beta blocker use and OC prognosis characteristics, such as total mortality (HR = 1.08, 95% CI = 0.92–1.27, I2 = 76.5%, n = 9), cancer-specific mortality (HR = 1.22, 95% CI = 0.89–1.67, I2 = 88.1%, n=3), and progression-free survival (HR = 0.88, 95% CI = 0.75–1.05, I2 = 0, n = 4). No evidence of publication bias was observed in current analysis. In our subgroup analyses, the majority of results were consistent with the main findings. However, several positive correlations were detected in studies with ≥800 cases (HR = 1.20, 95% CI = 1.05–1.37), no immortal time bias (HR = 1.28, 95% CI = 1.10–1.49), and adjustment for comorbidity (HR = 1.20, 95% CI = 1.05–1.37). In the meta-regression analysis, no evidence of heterogeneity was detected in the subgroups according to study characteristics and confounding factors. Conclusions Post-diagnostic beta blocker use has no statistical correlation with OC prognosis. More prospective cohort studies are necessary to further verify our results. Systematic Review Registration Identifier (CRD42020188806).
De Novo Mutation in Non-Tyrosine Kinase Domain of ROS1 as a Potential Predictor of Immune Checkpoint Inhibitors in Melanoma

Purpose Despite the success of targeted therapy in c-ros oncogene 1 (ROS1)-rearranged cancers, especially non-small cell lung cancer (NSCLC), the clinical significance of ROS1 de novo mutation has not yet been understood. We sought to elucidate the predictive effect of ROS1 mutation for immune checkpoint inhibitor (ICI) therapy in melanoma. Methods The Cancer Genome Atlas [TCGA (n = 10967)] and Memorial Sloan Kettering Cancer Center [MSK (n = 10,945)] datasets, as well as two clinical cohorts of melanoma received ICI [CA209-038 (n = 73) and MEL-IPI (n = 110)], were included to explore the prevalence, prognostic effect, and immunotherapeutic predictive effect of ROS1 mutation in melanoma. Overall survival (OS) was defined as the primary outcome. Results Overall, melanoma accounted for the highest proportion of ROS1 mutation (~20%) which made up the majority (~95%) of the ROS1-alterated cases. Remarkably, ROS1 mutation yielded longer OS from ICI than the wild-type counterpart in the MSK melanoma population [hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.30–0.74], and two external melanoma cohorts (CA209-038: HR 0.42, 95% CI 0.20–0.89; MEL-IPI: HR 0.55, 95% CI 0.34–0.91), without affecting the prognosis of patients. Elevated tumor mutational burden and enrichment of DNA damage repair was observed in ROS1 mutated patients, providing an explanation for the favorable responses to ICI therapy. Precisely, ROS1 mutation in non-protein tyrosine kinase (PTK) domain but not PTK mutation was responsible for the immunotherapy-specific responses of the ROS1 mutated patients in melanoma. Conclusions Collectively, ROS1 mutation, specifically the non-PTK mutation, is a potential predictor of ICI therapy in melanoma, which is distinct from the well-established role of ROS1 rearrangement for targeted therapy in NSCLC.
Genome-Wide Profiling of WRKY Genes Involved in Benzylisoquinoline Alkaloid Biosynthesis in California Poppy (Eschscholzia californica)

Transcription factors of the WRKY family play pivotal roles in plant defense responses, including the biosynthesis of specialized metabolites. Based on the previous findings of WRKY proteins regulating benzylisoquinoline alkaloid (BIA) biosynthesis, such as CjWRKY1—a regulator of berberine biosynthesis in Coptis japonica—and PsWRKY1—a regulator of morphine biosynthesis in Papaver somniferum—we performed genome-wide characterization of the WRKY gene family in Eschscholzia californica (California poppy), which produces various BIAs. Fifty WRKY genes were identified by homology search and classified into three groups based on phylogenetic, gene structure, and conserved motif analyses. RNA sequencing showed that several EcWRKY genes transiently responded to methyl jasmonate, a known alkaloid inducer, and the expression patterns of these EcWRKY genes were rather similar to those of BIA biosynthetic enzyme genes. Furthermore, tissue expression profiling suggested the involvement of a few subgroup IIc EcWRKYs in the regulation of BIA biosynthesis. Transactivation analysis using luciferase reporter genes harboring the promoters of biosynthetic enzyme genes indicated little activity of subgroup IIc EcWRKYs, suggesting that the transcriptional network of BIA biosynthesis constitutes multiple members. Finally, we investigated the coexpression patterns of EcWRKYs with some transporter genes and discussed the diversified functions of WRKY genes based on a previous finding that CjWRKY1 overexpression in California poppy cells enhanced BIA secretion into the medium.
Glutamate Dehydrogenase Is Important for Ammonia Fixation and Amino Acid Homeostasis in Brain During Hyperammonemia

Impaired liver function may lead to hyperammonemia and risk for hepatic encephalopathy. In brain, detoxification of ammonia is mediated mainly by glutamine synthetase (GS) in astrocytes. This requires a continuous de novo synthesis of glutamate, likely involving the action of both pyruvate carboxylase (PC) and glutamate dehydrogenase (GDH). An increased PC activity upon ammonia exposure and the importance of PC activity for glutamine synthesis has previously been demonstrated while the importance of GDH for generation of glutamate as precursor for glutamine synthesis has received little attention. We therefore investigated the functional importance of GDH for brain metabolism during hyperammonemia. To this end, brain slices were acutely isolated from transgenic CNS-specific GDH null or litter mate control mice and incubated in aCSF containing [U-13C]glucose in the absence or presence of 1 or 5 mM ammonia. In another set of experiments, brain slices were incubated in aCSF containing 1 or 5 mM 15N-labeled NH4Cl and 5 mM unlabeled glucose. Tissue extracts were analyzed for isotopic labeling in metabolites and for total amounts of amino acids. As a novel finding, we reveal a central importance of GDH function for cerebral ammonia fixation and as a prerequisite for de novo synthesis of glutamate and glutamine during hyperammonemia. Moreover, we demonstrated an important role of the concerted action of GDH and alanine aminotransferase in hyperammonemia; the products alanine and α-ketoglutarate serve as an ammonia sink and as a substrate for ammonia fixation via GDH, respectively. The role of this mechanism in human hyperammonemic states remains to be studied.
p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition

Skeletal muscle, the most abundant tissue in the body, plays vital roles in locomotion and metabolism. Understanding the cellular processes that govern regulation of muscle mass and function represents an essential step in the development of therapeutic strategies for muscular disorders. Myostatin, a member of the TGF-β family, has been identified as a negative regulator of muscle development. Indeed, its inhibition induces an extensive skeletal muscle hypertrophy requiring the activation of Smad 1/5/8 and the Insulin/IGF-I signaling pathway, but whether other molecular mechanisms are involved in this process remains to be determined. Using transcriptomic data from various Myostatin inhibition models, we identified Pak1 as a potential mediator of Myostatin action on skeletal muscle mass. Our results show that muscle PAK1 levels are systematically increased in response to Myostatin inhibition, parallel to skeletal muscle mass, regardless of the Myostatin inhibition model. Using Pak1 knockout mice, we investigated the role of Pak1 in the skeletal muscle hypertrophy induced by different approaches of Myostatin inhibition. Our findings show that Pak1 deletion does not impede the skeletal muscle hypertrophy magnitude in response to Myostatin inhibition. Therefore, Pak1 is permissive for the skeletal muscle mass increase caused by Myostatin inhibition.
Phosphorylation and O-GlcNAcylation of the PHF-1 Epitope of Tau Protein Induce Local Conformational Changes of the C-Terminus and Modulate Tau Self-Assembly Into Fibrillar Aggregates

Phosphorylation of the neuronal microtubule-associated Tau protein plays a critical role in the aggregation process leading to the formation of insoluble intraneuronal fibrils within Alzheimer’s disease (AD) brains. In recent years, other posttranslational modifications (PTMs) have been highlighted in the regulation of Tau (dys)functions. Among these PTMs, the O-β-linked N-acetylglucosaminylation (O-GlcNAcylation) modulates Tau phosphorylation and aggregation. We here focus on the role of the PHF-1 phospho-epitope of Tau C-terminal domain that is hyperphosphorylated in AD (at pS396/pS404) and encompasses S400 as the major O-GlcNAc site of Tau while two additional O-GlcNAc sites were found in the extreme C-terminus at S412 and S413. Using high resolution NMR spectroscopy, we showed that the O-GlcNAc glycosylation reduces phosphorylation of PHF-1 epitope by GSK3β alone or after priming by CDK2/cyclin A. Furthermore, investigations of the impact of PTMs on local conformation performed in small peptides highlight the role of S404 phosphorylation in inducing helical propensity in the region downstream pS404 that is exacerbated by other phosphorylations of PHF-1 epitope at S396 and S400, or O-GlcNAcylation of S400. Finally, the role of phosphorylation and O-GlcNAcylation of PHF-1 epitope was probed in in-vitro fibrillization assays in which O-GlcNAcylation slows down the rate of fibrillar assembly while GSK3β phosphorylation stimulates aggregation counteracting the effect of glycosylation.
Chelating Agent Functionalized Substrates for the Formation of Thick Films via Electrophoretic Deposition

Incorporating nanoparticles into devices for a wide range of applications often requires the formation of thick films, which is particularly necessary for improving magnetic power storage, microwave properties, and sensor performance. One approach to assembling nanoparticles into films is the use of electrophoretic deposition (EPD). This work seeks to develop methods to increase film thickness and stability in EPD by increasing film-substrate interactions via functionalizing conductive substrates with various chelating agents. Here, we deposited iron oxide nanoparticles onto conductive substrates functionalized with three chelating agents with different functional moieties and differing chelating strengths. We show that increasing chelating strength can increase film-substrate interactions, resulting in thicker films when compared to traditional EPD. Results will also be presented on how the chelating strength relates to film formation as a function of deposition conditions. Yield for EPD is influenced by deposition conditions including applied electric field, particle concentration, and deposition time. This work shows that the functionalization of substrates with chelating agents that coordinate strongly with nanoparticles (phosphonic acid and dopamine) overcome parameters that traditionally hinder the deposition of thicker and more stable films, such as applied electric field and high particle concentration. We show that functionalizing substrates with chelating agents is a promising method to fabricate thick, stable films of nanoparticles deposited via EPD over a larger processing space by increasing film-substrate interactions.
Long-Term Effect of a Vaccine Targeting Endothelin-1 Receptor Type A in Pulmonary Arterial Hypertension

Background: Previously, we invented a therapeutic vaccine targeting the endothelin-A receptor (termed ETRQβ-002). ETRQβ-002 successfully prevented the remodeling of pulmonary arterioles (PAs) and right ventricle (RV) without significant immune-mediated damage in experimental pulmonary arterial hypertension (PAH) mice models. Objective: Here, we aim to further evaluate the long-term effects of ETRQβ-002. Methods: PAH mice model was induced by a combination of subcutaneous injection with Sugen5416 and chronic hypoxic conditions (10% O2). PAH mice were immunized with ETRQβ-002 at different time points, and the experiment lasted for 21 weeks. Hemodynamic, histological, and biochemical analyses were conducted to evaluate the long-term effects of ETRQβ-002. Results: We demonstrated that the titer of the specific antibody against ETR-002 could be maintained chronically after periodic booster immunization in PAH mice. Long-term reduction of right ventricular systolic pressure and amelioration of PA remodeling by ETRQβ-002 were confirmed. Moreover, we found that ETRQβ-002 also exerted antiproliferation, anti-inflammation, and antifibrosis effects in PA remodeling. Besides, ETRQβ-002 durably limited pathological RV hypertrophy and fibrosis. Finally, no immune-mediated damage was observed in hepatic or renal function or by pathology in liver and kidney during the long-term administration of ETRQβ-002. Conclusion: Our findings indicate that ETRQβ-002 provides long-term therapeutic effects in Sugen/hypoxia-induced PAH animals and offers a promising clinical prospect for PAH treatment.
Naturalistic Stimuli in Affective Neuroimaging: A Review

Naturalistic stimuli such as movies, music, and spoken and written stories elicit strong emotions and allow brain imaging of emotions in close-to-real-life conditions. Emotions are multi-component phenomena: relevant stimuli lead to automatic changes in multiple functional components including perception, physiology, behavior, and conscious experiences. Brain activity during naturalistic stimuli reflects all these changes, suggesting that parsing emotion-related processing during such complex stimulation is not a straightforward task. Here, I review affective neuroimaging studies that have employed naturalistic stimuli to study emotional processing, focusing especially on experienced emotions. I argue that to investigate emotions with naturalistic stimuli, we need to define and extract emotion features from both the stimulus and the observer.
Changes of Regional Neural Activity Homogeneity in Preclinical Alzheimer’s Disease: Compensation and Dysfunction

Introduction Subjective cognitive decline (SCD) is the preclinical stage of Alzheimer’s disease and may develop into amnestic mild cognitive impairment (aMCI). Finding suitable biomarkers is the key to accurately identifying SCD. Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies on SCD patients showed functional connectivity disorders. Our goal was to explore whether local neurological homogeneity changes in SCD patients, the relationship between these changes and cognitive function, and similarities of neurological homogeneity changes between SCD and aMCI patients. Materials and Methods 37 cases of the healthy control (HC) group, 39 cases of the SCD group, and 28 cases of the aMCI group were included. Participants underwent rs-fMRI examination and a set of neuropsychological test batteries. Regional homogeneity (ReHo) was calculated and compared between groups. ReHo values were extracted from meaningful regions in the SCD group, and the correlation between ReHo values with the performance of neuropsychological tests was analyzed. Results Our results showed significant changes in the ReHo among groups. In the SCD group compared with the HC group, part of the parietal lobe, frontal lobe, and occipital lobe showed decreased ReHo, and the temporal lobe, part of the parietal lobe and the frontal lobe showed increased ReHo. The increased area of ReHo was negatively correlated with the decreased area, and was related to decrease on multiple neuropsychological tests performance. Simultaneously, the changed areas of ReHo in SCD patients are similar to aMCI patients, while aMCI group’s neuropsychological test performance was significantly lower than that of the SCD group. Conclusion There are significant changes in local neurological homogeneity in SCD patients, and related to the decline of cognitive function. The increase of neurological homogeneity in the temporal lobe and adjacent area is negatively correlated with cognitive function, reflecting compensation for local neural damage. These changes in local neurological homogeneity in SCD patients are similar to aMCI patients, suggesting similar neuropathy in these two stages. However, the aMCI group’s cognitive function was significantly worse than that of the SCD group, suggesting that this compensation is limited. In summary, regional neural activity homogeneity may be a potential biomarker for identifying SCD and measuring the disease severity.
Criticality-Driven Evolution of Adaptable Morphologies of Voxel-Based Soft-Robots

The paradigm of voxel-based soft robots has allowed to shift the complexity from the control algorithm to the robot morphology itself. The bodies of voxel-based soft robots are extremely versatile and more adaptable than the one of traditional robots, since they consist of many simple components that can be freely assembled. Nonetheless, it is still not clear which are the factors responsible for the adaptability of the morphology, which we define as the ability to cope with tasks requiring different skills. In this work, we propose a task-agnostic approach for automatically designing adaptable soft robotic morphologies in simulation, based on the concept of criticality. Criticality is a property belonging to dynamical systems close to a phase transition between the ordered and the chaotic regime. Our hypotheses are that 1) morphologies can be optimized for exhibiting critical dynamics and 2) robots with those morphologies are not worse, on a set of different tasks, than robots with handcrafted morphologies. We introduce a measure of criticality in the context of voxel-based soft robots which is based on the concept of avalanche analysis, often used to assess criticality in biological and artificial neural networks. We let the robot morphologies evolve toward criticality by measuring how close is their avalanche distribution to a power law distribution. We then validate the impact of this approach on the actual adaptability by measuring the resulting robots performance on three different tasks designed to require different skills. The validation results confirm that criticality is indeed a good indicator for the adaptability of a soft robotic morphology, and therefore a promising approach for guiding the design of more adaptive voxel-based soft robots.