Miracle-dz/UniFAR-FTUs huggingface dataset:
Nexmifa Regulates Axon Morphogenesis in Motor Neurons in Zebrafish

Nexmif is mainly expressed in the central nervous system (CNS) and plays important roles in cell migration, cell to cell and cell-matrix adhesion, and maintains normal synaptic formation and function. Nevertheless, it is unclear how nexmif is linked to motor neuron morphogenesis. Here, we provided in situ hybridization evidence that nexmifa (zebrafish paralog) was localized to the brain and spinal cord and acted as a vital regulator of motor neuron morphogenesis. Nexmifa deficiency in zebrafish larvae generated abnormal primary motor neuron (PMN) development, including truncated Cap axons and decreased branches in Cap axons. Importantly, RNA-sequencing showed that nexmifa-depleted zebrafish embryos caused considerable CNS related gene expression alterations. Differentially expressed genes (DEGs) were mainly involved in axon guidance and several synaptic pathways, including glutamatergic, GABAergic, dopaminergic, cholinergic, and serotonergic synapse pathways, according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. In particular, when compared with other pathways, DEGs were highest (84) in the axon guidance pathway, according to Organismal Systems. Efna5b, bmpr2b, and sema6ba were decreased markedly in nexmifa-depleted zebrafish embryos. Moreover, both overexpression of efna5b mRNA and sema6ba mRNA could partially rescued motor neurons morphogenesis. These observations supported nexmifa as regulating axon morphogenesis of motor neurons in zebrafish. Taken together, nexmifa elicited crucial roles during motor neuron development by regulating the morphology of neuronal axons.
TLR2 Activation by Porphyromonas gingivalis Requires Both PPAD Activity and Fimbriae

Porphyromonas gingivalis, a keystone oral pathogen implicated in development and progression of periodontitis, may also contribute to the pathogenicity of diseases such as arthritis, atherosclerosis, and Alzheimer’s. P. gingivalis is a master manipulator of host immune responses due to production of a large variety of virulence factors. Among these, P. gingivalis peptidilarginine deiminase (PPAD), an enzyme unique to P. gingivalis, converts C-terminal Arg residues in bacterium- and host-derived proteins and peptides into citrulline. PPAD contributes to stimulation of proinflammatory responses in host cells and is essential for activation of the prostaglandin E2 (PGE2) synthesis pathway in gingival fibroblasts. Since P. gingivalis is recognized mainly by Toll-like receptor-2 (TLR2), we investigated the effects of PPAD activity on TLR2-dependent host cell responses to P. gingivalis, as well as to outer membrane vesicles (OMVs) and fimbriae produced by this organism. Using reporter cell lines, we found that PPAD activity was required for TLR2 activation by P. gingivalis cells and OMVs. We also found that fimbriae, an established TLR2 ligand, from wild-type ATCC 33277 (but not from its isogenic PPAD mutant) enhanced the proinflammatory responses of host cells. Furthermore, only fimbriae from wild-type ATCC 33277, but not from the PPAD-deficient strains, induced cytokine production and stimulated expression of genes within the PGE2 synthesis pathway in human gingival fibroblasts via activation of the NF-ĸB and MAP kinase-dependent signaling pathways. Analysis of ten clinical isolates revealed that type I FimA is preferable for TLR2 signaling enhancement. In conclusion, the data strongly suggest that both PPAD activity and fimbriae are important for TLR2-dependent cell responses to P. gingivalis infection.
Emerging Roles of Platelets in Allergic Asthma

Allergic asthma is a complex chronic inflammatory disease of the airways, driven by Th2 immune responses and characterized by eosinophilic pulmonary inflammation, airway hyperresponsiveness, excessive mucus production, and airway remodeling. Overwhelming evidence from studies in animal models and allergic asthmatic patients suggests that platelets are aberrantly activated and recruited to the lungs. It has been established that platelets can interact with other immune cells and secrete various biochemical mediators to promote allergic sensitization and airway inflammatory response, and platelet deficiency may alleviate the pathological features and symptoms of allergic asthma. However, the comprehensive roles of platelets in allergic asthma have not been fully clarified, leaving attempts to treat allergic asthma with antiplatelet agents questionable. In this review, we summarize the role of platelet activation and pulmonary accumulation in allergic asthma; emphasis is placed on the different interactions between platelets with crucial immune cell types and the contribution of platelet-derived mediators in this context. Furthermore, clinical antiplatelet approaches to treat allergic asthma are discussed. This review provides a clearer understanding of the roles of platelets in the pathogenesis of allergic asthma and could be informative in the development of novel strategies for the treatment of allergic asthma.
Invariance of the Trait Emotional Intelligence Construct Across Clinical Populations and Sociodemographic Variables

Recent research has shown that cultural, linguistic, and sociodemographic peculiarities influence the measurement of trait emotional intelligence (trait EI). Assessing trait EI in different populations fosters cross-cultural research and expands the construct’s nomological network. In mental health, the trait EI of clinical populations has been scarcely researched. Accordingly, the present study examined the relationship between trait EI and key sociodemographic variables on Trait Emotional Intelligence Questionnaire (TEIQue-SF) datasets with mental healthcare patients from three different Spanish-speaking countries. Collectively, these datasets comprised 528 participants, 23% from Chile (120), 28% from Peru (150), and 49% from Spain (258). The sociodemographic variables we used for trait EI comparisons were gender, age, educational level, civil status, and occupational status. Analyses involved Multigroup Exploratory Structural Equation Modelling (to test measurement invariance) and analysis of covariance (ANCOVA). Our results revealed significant between-country differences in trait EI across the studied sociodemographic variables and interactions between these variables. Measurement invariance across the datasets was attained up to the scalar level regarding gender and education (i.e., strong invariance), although analyses on age, civil status, and occupation displayed non-invariance. The resultant psychometric evidence supports the suitability of the TEIQue-SF for the accurate cross-cultural assessment of trait EI in mental health settings. It also highlights the importance of incorporating trait EI into extant psychotherapeutic frameworks to enhance non-pharmacological treatment efficacy.
A Dynamic Efficient Sensory Encoding Approach to Adaptive Tuning in Neural Models of Optic Flow Processing

This paper introduces a self-tuning mechanism for capturing rapid adaptation to changing visual stimuli by a population of neurons. Building upon the principles of efficient sensory encoding, we show how neural tuning curve parameters can be continually updated to optimally encode a time-varying distribution of recently detected stimulus values. We implemented this mechanism in a neural model that produces human-like estimates of self-motion direction (i.e., heading) based on optic flow. The parameters of speed-sensitive units were dynamically tuned in accordance with efficient sensory encoding such that the network remained sensitive as the distribution of optic flow speeds varied. In two simulation experiments, we found that model performance with dynamic tuning yielded more accurate, shorter latency heading estimates compared to the model with static tuning. We conclude that dynamic efficient sensory encoding offers a plausible approach for capturing adaptation to varying visual environments in biological visual systems and neural models alike.
Host Shift Speciation of the Ectomycorrhizal Genus Suillus (Suillineae, Boletales) and Biogeographic Comparison With Its Host Pinaceae

Suillus is a genus of ectomycorrhizal fungi associated almost exclusively with Pinaceae. Lack of sample collections in East Asia and unresolved basal phylogenetic relationships of the genus are the major obstacles for better understanding the Suillus evolution. A resolved phylogeny of Suillus representing global diversity was achieved by sequencing multiple nuclear ribosomal and protein coding genes and extensive samples collected in East Asia. Fungal fossils are extremely rare, and the Eocene ectomycorrhizal symbiosis (ECM) fossil of Pinus root has been widely used for calibration. This study explored an alternative calibration scenario of the ECM fossil for controversy. Ancestral host associations of Suillus were estimated by maximum likelihood and Bayesian Markov chain Monte Carlo (MCMC) analyses, inferred from current host information from root tips and field observation. Host shift speciation explains the diversification of Suillus major clades. The three basal subgenera of Suillus were inferred to be associated with Larix, and diverged in early Eocene or Upper Cretaceous. In the early Oligocene or Paleocene, subgenus Suillus diverged and switched host to Pinus subgenus Strobus, and then switched to subgenus Pinus four times. Suillus subgenus Douglasii switched host from Larix to Pseudotsuga in Oligocene or Eocene. Increased species diversity occurred in subgenus Suillus after it switched host to Pinus but no associated speciation rate shifts were detected. Ancestral biogeographic distributions of Suillus and Pinaceae were estimated under the Dispersal Extinction Cladogenesis (DEC) model. Ancestral distribution patterns of Suillus and Pinaceae are related but generally discordant. Dispersals between Eurasia and North America explain the prevalence of disjunct Suillus taxa.
Probing in vivo RNA Structure With Optimized DMS-MaPseq in Rice

RNA transcripts form various secondary and tertiary structures that have a wide range of regulatory functions. Several methods have been developed to profile in vivo RNA secondary structure in prokaryotes and eukaryotes. These methods, such as dimethyl sulfate (DMS) mutational profiling with high-throughput sequencing (DMS-MaPseq), couple small chemical-mediated RNA modifications with next-generation sequencing. DMS-MaPseq, a powerful method for genome-wide and target-specific RNA secondary structure profiling, has been applied in yeast, mammals, Drosophila, and Arabidopsis thaliana, but not in crops. Here, we used DMS-MaPseq to conduct a target-specific and genome-wide profile of in vivo RNA secondary structure in rice (Oryza sativa). The DMS treatment conditions were optimized for rice leaf and root tissues. To increase the sequencing depth and coverage of low-abundance transcripts in genome-wide DMS-MaPseq, we used streptavidin-biotin depletion to reduce the abundance of highly expressed chloroplast transcripts during library construction. The resulting target-specific and genome-wide rice DMS-MaPseq data were of high quality and reproducibility. Furthermore, we used DMS-MaPseq to profile the in vivo RNA secondary structure of an OsmiR399 target region located at 5′UTR of OsPHO2, which participates in rice phosphate homeostasis. An unfolded RNA structure downstream of miRNA target site was observed in predicted in vivo RNA secondary structure, reminiscence of the TAM (Target Adjacent nucleotide Motif) involved in mRNA structure-mediated regulation in miRNA cleavage. Our study optimized DMS-MaPseq for probing in vivo RNA secondary structure in rice, facilitating the study of RNA structure-mediated regulations in crops.
MiRKAT-MC: A Distance-Based Microbiome Kernel Association Test With Multi-Categorical Outcomes

Increasing evidence has elucidated that the microbiome plays a critical role in many human diseases. Apart from continuous and binary traits that measure the extent or presence of a disease, multi-categorical outcomes including variations/subtypes of a disease or ordinal levels of disease severity are commonly seen in clinical studies. On top of that, studies with clustered design (i.e., family-based and longitudinal studies) are popular alternatives to population-based ones as they are able to identify characteristics on both individual and population levels and to investigate the trajectory of traits of interest over time. However, existing methods for microbiome association analysis are inadequate to handle multi-categorical outcomes, neither independent nor clustered data. We propose a microbiome kernel association test with multi-categorical outcomes (MiRKAT-MC). Our method is versatile to deal with both nominal and ordinal outcomes for independent and clustered data. In addition, it incorporates multiple ecological distances to allow for different association patterns between outcomes and microbiome compositions to be incorporated. A computationally efficient pseudo-permutation strategy is used to evaluate the statistical significance. Comprehensive simulations show that MiRKAT-MC preserves the nominal type I error and increases statistical powers under various scenarios and data types. We also apply MiRKAT-MC to real data sets with nominal and ordinal outcomes to gain biological insights. MiRKAT-MC is easy to implement, and freely available via an R package at https://github.com/Zhiwen-Owen-Jiang/MiRKATMC with a Graphical User Interface through R Shinny also available.
Integrated Bioinformatics Algorithms and Experimental Validation to Explore Robust Biomarkers and Landscape of Immune Cell Infiltration in Dilated Cardiomyopathy

Background The etiology of dilated cardiomyopathy (DCM) is unclear. Bioinformatics algorithms may help to explore the underlying mechanisms. Therefore, we aimed to screen diagnostic biomarkers and identify the landscape of immune infiltration in DCM. Methods First, the CIBERSORT algorithm was used to excavate the proportion of immune-infiltration cells in DCM and normal myocardial tissues. Meanwhile, the Pearson analysis and principal component analysis (PCA) were used to identify immune heterogeneity in different tissues. The Wilcoxon test, LASSO regression, and machine learning method were conducted to identify the hub immune cells. In addition, the differentially expressed genes (DEGs) were screened by the limma package, and DEGs were analyzed for functional enrichment. In the protein–protein interaction (PPI) network, multiple algorithms were used to calculate the score of each DEG for screening the hub genes. Subsequently, external datasets were used to further validate the expression of hub genes, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy. Finally, we examined the expression of hub biomarkers in animal models. Results A total of 108 DEGs were screened, and these genes may be related to biological processes such as cytolysis, positive regulation of cytokine secretion, etc. Two types of hub immune cells [activated natural killer (NK) cells and eosinophils] and four hub genes (ASPN, CD163, IL10, and LUM) were identified in DCM myocardial tissues. CD163 was verified to have the capability to diagnose DCM with the most excellent specificity and sensitivity. It is worth mentioning that the combined CD163 and eosinophils may have better diagnostic efficacy. Moreover, the correlation analysis showed CD163 was negatively correlated with activated NK cells. Finally, the results of the mice model also indicated that CD163 might be involved in the occurrence of DCM. Conclusion ASPN, CD163, IL10, and LUM may have a potential predictive ability for DCM, and especially CD163 showed the most robust efficacy. Furthermore, activated NK cells and eosinophils may relate to the occurrence of DCM.
The Measurement Performance of the Parkinson's Disease Activities of Daily Living, Interference, and Dependence Instrument

Parkinson's disease is a neurodegenerative disease that can be associated with motor fluctuations that result in substantial negative impact to an individual's activities of daily living. Understanding the patient's perspective about the impact of Parkinson's disease therapies is an important part of drug development and shared treatment decision-making. The objective of this research was to examine the structure, scoring, internal consistency, test-retest reliability, and concurrent and known groups validity of the Parkinson's Disease Activities of Daily Living, Interference and Dependence (PD-AID) instrument, a new, patient-reported outcomes instrument, developed to assess the clinical benefit of Parkinson's disease treatment from the patient's perspective. This was a non-interventional study among persons with mild-to-moderate Parkinson's disease currently using and responding to L-Dopa. The structure of the measure was confirmed applying item response theory to data from baseline, supporting 4 candidate scores. Baseline Patient Global Impression of Severity ratings facilitated known-groups analysis. Data from all participants were used to estimate test-retest reliability. Concurrent validity was assessed using correlations with related measures. Participants (n = 94) were mean age 69 years (mean time since diagnosis 6.9 years); 34 experienced L-Dopa-related dyskinesia. Psychometric models supported 4 candidate scoring regimes for the PD-AID. All exhibited adequate reliability and validity characteristics and strong internal consistency. Correlations with reference measures were in the expected direction and range of magnitude. Analyses supported the PD-AID as fit-for-purpose, producing psychometrically sound scores. Further research to confirm the measurement properties of the PD-AID in an expanded sample and to establish thresholds for meaningful score changes is recommended.
Sex-Associated Differences in Neurovascular Dysfunction During Ischemic Stroke

Neurovascular units (NVUs) are basic functional units in the central nervous system and include neurons, astrocytes and vascular compartments. Ischemic stroke triggers not only neuronal damage, but also dissonance of intercellular crosstalk within the NVU. Stroke is sexually dimorphic, but the sex-associated differences involved in stroke-induced neurovascular dysfunction are studied in a limited extend. Preclinical studies have found that in rodent models of stroke, females have less neuronal loss, stronger repairing potential of astrocytes and more stable vascular conjunction; these properties are highly related to the cerebroprotective effects of female hormones. However, in humans, these research findings may be applicable only to premenopausal stroke patients. Women who have had a stroke usually have poorer outcomes compared to men, and because stoke is age-related, hormone replacement therapy for postmenopausal women may exacerbate stroke symptoms, which contradicts the findings of most preclinical studies. This stark contrast between clinical and laboratory findings suggests that understanding of neurovascular differences between the sexes is limited. Actually, apart from gonadal hormones, differences in neuroinflammation as well as genetics and epigenetics promote the sexual dimorphism of NVU functions. In this review, we summarize the confirmed sex-associated differences in NVUs during ischemic stroke and the possible contributing mechanisms. We also describe the gap between clinical and preclinical studies in terms of sexual dimorphism.
Correlation Among Body Composition Parameters and Long-Term Outcomes in Crohn's Disease After Anti-TNF Therapy

Background The impact of the body composition on the pathophysiology and clinical course of Crohn's disease (CD) has not been fully elucidated. Aims To reveal the correlations among body composition and long-term outcomes in CD after anti-TNF therapy. Methods Ninety-one patients who received anti-TNF therapy as their first biologic treatment were enrolled. The skeletal muscle index (SMI), visceral and subcutaneous fat area (VFA, SFA), and the ratio of the VFA to SFA (mesenteric fat index; MFI) at the 3rd lumbar level were measured using computed tomography (CT) imaging before the induction. The correlation among the body composition and outcomes were retrospectively analyzed. Results The 5-year cumulative secondary failure- and resection-free rates in patients with a low SMI (39.1% and 64.8%) were significantly lower than those with a high SMI (67.5% and 92.7%; p = 0.0071 and 0.0022, respectively). The 5-year cumulative secondary failure-free rate in the patients with low VF (45.0%) was significantly lower than that in those with high VF (77.6%; p = 0.016), and the 5-year cumulative resection-free rate in patients with a high MFI (68.9%) was significantly lower than that in those with a low MFI (83.0%; p = 0.031). Additionally, patients with low age and BMI had significantly lower cumulative secondary failure- and resection-free rates than those with high age and BMI (low age: 37.4% and 71.2%; high age: 70.7% and 88.9%; p = 0.0083 and 0.027, respectively) (low BMI: 27.2% and 64.8%; high BMI: 68.3% and 87.9%; p = 0.014 and 0.030, respectively), respectively. In the multivariate analyses, a low SMI was the only independent risk factor for secondary failure (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.04–4.44), while low age (HR 4.06, 95% CI 1.07–15.4), a low SMI (HR 4.19, 95% CI 1.01–17.3) and high MFI were risk factors for bowel resection (HR 4.31, 95% CI 1.36–13.7). Conclusion The skeletal muscle mass and ratio of visceral to subcutaneous fat were suggested to reflect the long-term clinical outcome and may be helpful as prognostic markers after anti-TNF therapy in CD.
Dissemination of Resistant Escherichia coli Among Wild Birds, Rodents, Flies, and Calves on Dairy Farms

Antimicrobial resistance (AMR) in bacteria in the livestock is a growing problem, partly due to inappropriate use of antimicrobial drugs. Antimicrobial use (AMU) occurs in Swedish dairy farming but is restricted to the treatment of sick animals based on prescription by a veterinary practitioner. Despite these strict rules, calves shedding antimicrobial resistant Enterobacteriaceae have been recorded both in dairy farms and in slaughterhouses. Yet, not much is known how these bacteria disseminate into the local environment around dairy farms. In this study, we collected samples from four animal sources (fecal samples from calves, birds and rodents, and whole flies) and two environmental sources (cow manure drains and manure pits). From the samples, Escherichia coli was isolated and antimicrobial susceptibility testing performed. A subset of isolates was whole genome sequenced to evaluate relatedness between sources and genomic determinants such as antimicrobial resistance genes (ARGs) and the presence of plasmids were assessed. We detected both ARGs, mobile genetic elements and low rates of AMR. In particular, we observed four potential instances of bacterial clonal sharing in two different animal sources. This demonstrates resistant E. coli dissemination potential within the dairy farm, between calves and scavenger animals (rodents and flies). AMR dissemination and the zoonotic AMR risk is generally low in countries with low and restricted AMU. However, we show that interspecies dissemination does occur, and in countries that have little to no AMU restrictions this risk could be under-estimated.