Miracle-dz/UniFAR-FTUs huggingface dataset:
A bidirectional switch in the Shank3 phosphorylation state biases synapses toward up- or downscaling

Homeostatic synaptic plasticity requires widespread remodeling of synaptic signaling and scaffolding networks, but the role of posttranslational modifications in this process has not been systematically studied. Using deepscale, quantitative analysis of the phosphoproteome in mouse neocortical neurons, we found wide-spread and temporally complex changes during synaptic scaling up and down. We observed 424 bidirectionally modulated phosphosites that were strongly enriched for synapse-associated proteins, including S1539 in the ASD-associated synaptic scaffold protein Shank3. Using a parallel proteomic analysis performed on Shank3 isolated from rat neocortical neurons by immunoaffinity, we identified two sites that were hypo-phosphorylated during scaling up and hyper-phosphorylated during scaling down: one (rat S1615) that corresponded to S1539 in mouse, and a second highly conserved site, rat S1586. The phosphorylation status of these sites modified the synaptic localization of Shank3 during scaling protocols, and dephosphorylation of these sites via PP2A activity was essential for the maintenance of synaptic scaling up. Finally, phosphomimetic mutations at these sites prevented scaling up but not down, while phosphodeficient mutations prevented scaling down but not up. Thus, an activity-dependent switch between hypo- and hyperphosphorylation at S1586/ S1615 of Shank3 enables scaling up or down, respectively. Collectively our data show that activity-dependent phosphoproteome dynamics are important for the functional reconfiguration of synaptic scaffolds, and can bias synapses toward upward or downward homeostatic plasticity.
CHD8 regulates gut epithelial cell function and affects autism-related behaviours through the gut-brain axis

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by early onset deficits in social behavior and repetitive behavior. Chromodomain helicase DNA binding protein (CHD8) is one of the genes with the strongest association to autism. Alongside with the core symptoms of ASD, individuals with ASD are reported to have gastrointestinal (GI) problems, and a majority of individuals with CHD8 mutations display GI problems. However, the relationship between autism related genes, such as CHD8, gastrointestinal function, and autism related behaviours are yet very unclear. In the current study, we found that mice haploinsufficient for CHD8 have leaky gut, a dysregulated transcriptome in gut epithelial cells, decreased gut tuft cells and goblet cells, and an increase in microbial load. Specific deletion of CHD8 in gut epithelial cells induced an increase in anxiety-related behaviours in, a phenotype that is often observed in autism and full body knockdown of CHD8, in addition to decreased tuft cells. In addition, antibiotic treatment of CHD8 haploinsufficient mice attenuates sociability deficits. Therefore, the current study determines a pathway for autism-related GI deficits, and how these deficits may play a direct role in the development of autism-related behaviours.
Enzymes degraded under high light maintain proteostasis by transcriptional regulation in Arabidopsis

Photo-inhibitory high light stress in Arabidopsis leads to increases in markers of protein degradation and transcriptional upregulation of proteases and proteolytic machinery, but proteostasis is largely maintained. We find significant increases in the in vivo degradation rate for specific molecular chaperones, nitrate reductase, glyceraldehyde-3 phosphate dehydrogenase, and phosphoglycerate kinase and other plastid, mitochondrial, peroxisomal, and cytosolic enzymes involved in redox shuttles. Coupled analysis of protein degradation rates, mRNA levels, and protein abundance reveal that 57% of the nuclear-encoded enzymes with higher degradation rates also had high light-induced transcriptional responses to maintain proteostasis. In contrast, plastid-encoded proteins with enhanced degradation rates showed decreased transcript abundances and must maintain protein abundance by other processes. This analysis reveals a light-induced transcriptional program for nuclear-encoded genes, beyond the regulation of PSII D1 subunit and the function of PSII, to replace key protein degradation targets in plants and ensure proteostasis under high light stress.
Sex chromosomes, sex ratios and sex gaps in longevity in plants

In animals, males and females can display markedly different longevity (also called sex gap in longevity, SGLs). Recent work has revealed that sex chromosomes contribute to establishing these SGLs. X-hemizygosity and toxicity of the Y chromosomes are two mechanisms that have been suggested to reduce male longevity (Z-hemizygosity and W toxicity in females in ZW systems). In plants, SGLs are known to exist but the role of sex chromosomes remains to be established. Here, by using adult sex ratio as a proxy for measuring SGLs, we explored the relationship between sex chromosome and SGLs across 43 plant species. Based on the knowledge recently accumulated in animals, we specifically asked whether: (i) species with XY systems tend to have female-biased sex ratios (reduced male longevity) and species with ZW ones tend to have male-biased sex ratios (reduced female longevity), and (ii) this patterns was stronger in heteromorphic systems compared to homomorphic ones. Our results tend to support these predictions although we lack statistical power because of a small number of ZW systems and the absence of any heteromorphic ZW system in the dataset. We discuss the implications of these findings, which we hope will stimulate further research on sex-differences in lifespan and ageing across plants.
An Information Theoretic Framework for Protein Activity Measurement

Nonparametric analytical Rank-based Enrichment Analysis (NaRnEA) is a novel gene set analysis method which leverages an analytical null model derived under the Principle of Maximum Entropy. NaRnEA critically improves over two widely used methods – Gene Set Enrichment Analysis (GSEA) and analytical Rank-based Enrichment Analysis (aREA) – as shown by differential activity measurement of ~2,500 transcriptional regulatory proteins across three cohorts in The Cancer Genome Atlas (TCGA) based on the enrichment of their transcriptional targets in differentially expressed genes. Phenotype-matched proteomic data from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) was used to evaluate measurement accuracy. We show that the sample-shuffling empirical null models leveraged by GSEA and aREA are overly conservative, a shortcoming that is critically addressed by NaRnEA’s optimal analytical null model.
Oral and Injected Tamoxifen Alter Adult Hippocampal Neurogenesis in Female and Male Mice

Visual Abstract Inducible Cre recombinase facilitates temporal control of genetic recombination in numerous transgenic model systems, a feature which has made it a popular tool for adult neurogenesis studies. One of the most common forms of inducible Cre, CreERT2, requires activation by the selective estrogen receptor modulator tamoxifen (TAM) to initiate recombination of LoxP-flanked sequences. To date, most studies deliver TAM via intraperitoneal injection. But the introduction of TAM-infused commercial chows has recently expanded the possible modes of TAM delivery. Despite the widespread use of TAM-inducible genetic models in adult neurogenesis research, the comparative efficiency and off-target effects of TAM administration protocols is surprisingly infrequently studied. Here, we compare a standard, 5 d TAM injection regimen with voluntary consumption of TAM-infused chow. First, we used adult NestinCreERT2;Rosa-LoxP-STOP-LoxP-EYFP reporter mice to show that two weeks of TAM chow and 5 d of injections led to LoxP recombination in a similar phenotypic population of neural stem and progenitor cells (NSPCs) in the adult dentate gyrus. However, TAM chow resulted in substantially less overall recombination than injections. TAM administration also altered adult neurogenesis, but in different ways depending on administration route: TAM injection disrupted neural progenitor cell proliferation three weeks after TAM, whereas TAM chow increased neuronal differentiation of cells generated during the diet period. These findings provide guidance for selection of TAM administration route and appropriate controls in adult neurogenesis studies using TAM-inducible Cre mice. They also highlight the need for better understanding of off-target effects of TAM in other neurologic processes and organ systems.
Germination Characteristics Is More Associated With Phylogeny-Related Traits of Species in a Salinized Grassland of Northeastern China

Knowing the determinants of seed germination helps us understand plant adaptive strategies to the environment and predict population and community regeneration under climate change. However, multiple factors, including plant and seed traits that influence germination and their relative importance, have received little attention. Here, seed germination experiments were conducted on newly collected seeds for 89 herbaceous species from salinized Songnen grassland. We tested the effects of multiple phylogeny-related plant traits and seed morphological and physiological traits on germination percentage and initial germination time and their relative contribution to shaping germination variation. We found that biennials had higher germination percentages and rates than annuals and perennials. Species with brown seeds had higher germination percentages than those with yellow and black seeds. Eudicots germinated faster than monocots, and seeds with morphophysiological dormancy required more time to initiate germination than those with other kinds of dormancy. Phylogeny-related factors explained more of the variation in germination than seed traits. Seed mass and volume of the large-seeded, but not small-seeded group species were positively correlated with germination percentage. Our findings provide important information for understanding germination variation across species and local adaptation for species in the salinized Songnen grassland.
Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells

Along with direct anticancer activity, curcumin hinders the onset of chemoresistance. Among many, high glucose condition is a key driving factor for chemoresistance. However, the ability of curcumin remains unexplored against high glucose-induced chemoresistance. Moreover, chemoresistance is major hindrance in effective clinical management of liver cancer. Using hepatic carcinoma HepG2 cells, the present investigation demonstrates that high glucose induces chemoresistance, which is averted by the simultaneous presence of curcumin. Curcumin obviated the hyperglycemia-induced modulations like elevated glucose consumption, lactate production, and extracellular acidification, and diminished nitric oxide and reactive oxygen species (ROS) production. Modulated molecular regulators are suggested to play a crucial role as curcumin pretreatment also prevented the onset of chemoresistance by high glucose. High glucose instigated suppression in the intracellular accumulation of anticancer drug doxorubicin and drug-induced chromatin compactness along with declined expression of drug efflux pump MDR-1 and transcription factors and signal transducers governing the survival, aggressiveness, and apoptotic cell death (p53, HIF-1α, mTOR, MYC, STAT3). Curcumin alleviated the suppression of drug retention and nuclear condensation along with hindering the high glucose-induced alterations in transcription factors and signal transducers. High glucose-driven resistance in cancer cells was associated with elevated expression of metabolic enzymes HKII, PFK1, GAPDH, PKM2, LDH-A, IDH3A, and FASN. Metabolite transporters and receptors (GLUT-1, MCT-1, MCT-4, and HCAR-1) were also found upregulated in high glucose exposed HepG2 cells. Curcumin inhibited the elevated expression of these enzymes, transporters, and receptors in cancer cells. Curcumin also uplifted the SDH expression, which was inhibited in high glucose condition. Taken together, the findings of the present investigation first time demonstrate the ability of curcumin against high glucose-induced chemoresistance, along with its molecular mechanism. This will have implication in therapeutic management of malignancies in diabetic conditions.
Case Report: Autologous Bone Marrow Derived Intrathecal Stem Cell Transplant for Autistic Children - A Report of Four Cases and Literature Review

Despite steadily growing numbers of children diagnosed with autism spectrum disorders (ASD), causative treatment is unavailable. Recently, biological cell therapies involving pluripotent cells have raised hopes towards sustained beneficial outcome. We herein report data of four children diagnosed with ASD, who were treated with autologous, bone marrow (BM)-derived, intrathecally and simultaneously intravenously applied, point-of-care stem cell transplant (SCT). The three boys and one girl received the diagnosis at ages between 2–4 years. The decision to perform the procedure was preceded by limited beneficiary impact of conventional symptom-based, psychological and pharmacological interventions. At ages of 4–14 years the children received their SCT, no immediate or late adverse events were reported. Disappearance of symptoms were observed by the parents during the following year and consequently improved Autism Treatment Evaluation Checklist (ATEC) scores were reported. The SCT procedure, in trained hands, can be a safe and promising treatment option in children with ASD, responding in a non-satisfactory manner to conventional treatments. It is postulated that SCT may, among others, assert its positive effect by counteracting a cerebral inflammatory autoimmune process which in turn supports the responsiveness to behavioral and pharmacological interventions. Our results in this small group are encouraging, but certainly need further investigation in larger cohorts.
Wettability of liquid caesium iodine and boron oxide on yttria-stabilized zirconia

ABSTRACT During the Fukushima Daiichi Nuclear Power Plant accident occurred in 2011, volatile fission products (FPs) such as Cs and I had released and caused environmental contamination and public exposure, respectively. However, the release mechanism of these FPs from fuels under the accident is still not completely understood. In recent years, we have focused on the wettability of liquid FPs against solid fuels, because the interface between the fuel surface and the FPs becomes the migration pathway, which might have large influences on the release behaviour of the FPs. Here, we studied the wettability of liquid CsI and B2O3 on yttria-stabilized zirconia (YSZ) solid surface by the sessile drop test, where YSZ is a simulated material of the fuel. It was revealed that liquid CsI exhibited extremely high wettability against the YSZ surface with the contact angle of nearly zero. This high wettability may act to suppress the FPs release. Furthermore, it was confirmed that the crystal orientation and surface roughness of the YSZ solids have large influences on the wettability of liquid B2O3. The present results contribute for deep understanding of the release behaviour of the volatile FPs from fuels.
A Learn-to-Rank Approach for Predicting Road Cycling Race Outcomes

Professional road cycling is a very competitive sport, and many factors influence the outcome of the race. These factors can be internal (e.g., psychological preparedness, physiological profile of the rider, and the preparedness or fitness of the rider) or external (e.g., the weather or strategy of the team) to the rider, or even completely unpredictable (e.g., crashes or mechanical failure). This variety makes perfectly predicting the outcome of a certain race an impossible task and the sport even more interesting. Nonetheless, before each race, journalists, ex-pro cyclists, websites and cycling fans try to predict the possible top 3, 5, or 10 riders. In this article, we use easily accessible data on road cycling from the past 20 years and the Machine Learning technique Learn-to-Rank (LtR) to predict the top 10 contenders for 1-day road cycling races. We accomplish this by mapping a relevancy weight to the finishing place in the first 10 positions. We assess the performance of this approach on 2018, 2019, and 2021 editions of six spring classic 1-day races. In the end, we compare the output of the framework with a mass fan prediction on the Normalized Discounted Cumulative Gain (NDCG) metric and the number of correct top 10 guesses. We found that our model, on average, has slightly higher performance on both metrics than the mass fan prediction. We also analyze which variables of our model have the most influence on the prediction of each race. This approach can give interesting insights to fans before a race but can also be helpful to sports coaches to predict how a rider might perform compared to other riders outside of the team.
Mining of a Clinical Database: The Interpretation of Intense Serial Procalcitonin in the Prediction for Bloodstream Infection

Background: Procalcitonin (PCT) is a promising biomarker for predicting infection. Bloodstream infection (BSI) is usually a deteriorating stage of sepsis. The purpose of this study was to explore the predictive value of intense serial PCT assays for BSI in the intensive care unit (ICU). Methods: This study was a retrospective study based on a clinical database. We analyzed the data of critically ill patients from February 2016 to May 2020. The patients who received PCT assays and blood cultures (BCs) were classified into four groups according to the BCs: (i) BC negative, (ii) bacteria positive, (iii) fungi-positive, and (iv) combined-positive, and the patients with bacteremia were further subdivided into Gram+ and Gram– bacteremia. Results: The database included 11,219 patients. There were 3,593 patients who met the criteria for the analysis. The PCT concentration differed significantly across BC groups (p < 0.0001). The fluctuation of PCT significantly increased in the BC positive groups (p < 0.0001). According to the receiver operating characteristic (ROC), the optimum cutoff of the fluctuation of PCT was around 8 ng/ml for predicting BSI. Conclusion: Our study indicated that the fluctuation of PCT could be an indicator for screening BSI, but less accurate for Gram-positive infections. With a fluctuation of PCT less than 8 ng/ml, BSI should not be a rational cause for sepsis exacerbating.
Assessment of Childbirth-Related PTSD: Psychometric Properties of the German Version of the City Birth Trauma Scale

Background: About 3–4% of women in community samples suffer from childbirth-related posttraumatic stress disorder (PTSD). Surprisingly, the recently developed City Birth Trauma Scale (City BiTS) was the first diagnostic tool for childbirth-related PTSD covering DSM-5 criteria for PTSD. Since no questionnaire on childbirth-related PTSD is available in German, we aimed to validate a German translation of the City BiTS and to provide information on its psychometric properties. Methods: A community sample of 1,072 mothers completed an online survey, which included questions on sociodemographic and obstetric characteristics, the German version of the City BiTS, the Impact of Event Scale-Revised (IES-R), the PTSD Checklist for DSM-5 (PCL-5), Edinburgh Postnatal Depression Scale (EPDS), and the anxiety subscale of the Depression, Anxiety, and Stress Scale (DASS-Anxiety). Results: Exploratory factor analysis (EFA) on a random split-half sample confirmed the previously reported two-factorial structure of the City BiTS. The factors “Childbirth-related symptoms” and “General symptoms” explained about 53%, 52% of variance. Internal consistency was good to excellent for the subscales and the total scale (Cronbach's Alpha = 0.89−0.92). In a confirmatory factor analysis (CFA) in the holdout sample the two-factorial solution reached the best model fit out of three models. Correlation analyses showed convergent validity of the City BiTS (total scale and subscales) with the IES-R and PCL-5 and divergent validity with the EPDS and the DASS-Anxiety. Limitations: Data were acquired in a community sample and prevalence rates might not be representative for mothers of high-risk groups, e.g., after preterm birth. Conclusions: The German version of the City BiTS is the first German questionnaire which allows to assess symptoms of childbirth-related PTSD according to DSM-5 criteria. Besides an improvement in clinical routine it will help to make data on prevalence of childbirth-related PTSD internationally comparable. In addition, this work provides a basis to assess childbirth-related PTSD in studies conducted with a longitudinal study design or in high-risk samples.
Strong Genetic Structure Observed in Primulina danxiaensis, a Small Herb Endemic to Mount Danxia With Extremely Small Populations

Danxia landform occurring sporadically in southern China is a unique type of petrographic geomorphology. It has nurtured about 400 rare or threatened plant and animal species, whose diversity, endemism, and conservation have called increasing scientific and public attentions. Among them, Primulina danxiaensis (W. B. Liao, S. S. Lin, and R. J. Shen) W. B. Liao and K. F. Chung is a tiny perennial grass species recorded only in Mount Danxia, a natural World Heritage Site as part of China’s Danxia. In this study, restriction site-associated DNA sequencing (RAD-seq) was performed to investigate genetic diversity among these 12 populations of P. danxiaensis. A total of 432,041 variant sites were detected in 84,779 loci across 94 samples. The expected heterozygosity (H E ) ranged from 0.017 to 0.139. Bottleneck signals were detected in most populations, Tajima’s D tests showed that most loci could be under recent positive selection, and one of the six positively selected loci identified by BayeScan was annotated as tRNAGlu, which may contribute to the species’ adaptation to shady environment. STRUCTURE analysis and phylogenetic tree showed that the 12 populations of P. danxiaensis could be divided into four gene pools (clades) corresponding to their geographic locations, and significant correlation was observed between genetic and geographic distances. Our study demonstrated that P. danxiaensis maintained a middle level of genetic diversity and strong population structure; geographic distance could be an important factor limiting gene flow among populations of P. danxiaensis, which were only sporadically recorded in Mount Danxia.