The gut microbiota has recently been recognized to play a role in the pathogenesis of autoimmune liver disease (AILD), mainly primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). This study aimed to analyze and compare the composition of the oral microbiota of 56 patients with AILD and 15 healthy controls (HCs) and to evaluate its association with salivary immunological biomarkers and gut microbiota. The subjects included 39 patients with PBC and 17 patients with AIH diagnosed at our hospital. The control population comprised 15 matched HCs. Salivary and fecal samples were collected for analysis of the microbiome by terminal restriction fragment length polymorphism of 16S rDNA. Correlations between immunological biomarkers measured by Bio-Plex assay (Bio-Rad) and the oral microbiomes of patients with PBC and AIH were assessed. Patients with AIH showed a significant increase in Veillonella with a concurrent decrease in Streptococcus in the oral microbiota compared with the HCs. Patients with PBC showed significant increases in Eubacterium and Veillonella and a significant decrease in Fusobacterium in the oral microbiota compared with the HCs. Immunological biomarker analysis showed elevated levels of inflammatory cytokines (IL-1β, IFN-γ, TNF-α, IL-8) and immunoglobulin A in the saliva of patients with AILD. The relative abundance of Veillonella was positively correlated with the levels of IL-1β, IL-8 and immunoglobulin A in saliva and the relative abundance of Lactobacillales in feces. Dysbiosis of the oral microbiota is associated with inflammatory responses and reflects changes in the gut microbiota of patients with AILD. Dysbiosis may play an important role in the pathogenesis of AILD.

Snail, also called Snai1, is a key regulator of EMT. Snail plays crucial roles in cancer progression, including resistance to anti-tumor drugs and invasion by various cancer cells. Slug, also known as Snai2, is also involved in the aggravation of certain tumors. In this study, we examined the roles of Slug in human oral squamous cell carcinoma (OSCC) cells. Slug is highly expressed in these cells, and Slug siRNA effectively represses anti-tumor drug resistance and invasive properties. In addition, transforming growth factor (TGF)-β upregulates the expression of Snail and Slug and promotes resistance to anti-tumor drugs in OSCC cells. Surprisingly, Slug siRNA appears to upregulate Snail expression considerably in OSCC cells. Snail siRNA also appears to upregulate Slug expression. Thus, either Slug or Snail siRNA alone partially mitigates malignant phenotypes in the presence of TGF-β, whereas both Slug and Snail siRNAs together dramatically suppress them. Therefore, Slug and Snail in tandem, but not alone, are potential therapeutic targets for nucleic acid medicines to treat oral cancer.

We employ a time-dependent Hurst analysis to identify EEG signals that differentiate between healthy controls and combat-related PTSD subjects. The Hurst exponents, calculated using a rescaled range analysis, demonstrate a significant differential response between healthy and PTSD samples which may lead to diagnostic applications. To overcome the non-stationarity of EEG data, we apply an appropriate window length wherein the EEG data displays stationary behavior. We then use the Hurst exponents for each channel as hypothesis test statistics to identify differences between PTSD cases and controls. Our study included a cohort of 12 subjects with half healthy controls. The Hurst exponent of the PTSD subjects is found to be significantly smaller than the healthy controls in channel F3. Our results indicate that F3 may be a useful channel for diagnostic applications of Hurst exponents in distinguishing PTSD and healthy subjects.

Bone substitutes are frequently used in clinical practice but often exhibit limited osteoinductivity. We hypothesized that unfocused shockwaves enhance the osteoinductivity of bone substitutes and improve osteointegration and angiogenesis. Three different bone substitutes, namely porous tricalcium phosphate, porous hydroxyapatite and porous titanium alloy, were implanted in a critical size (i.e. 6-mm) femoral defect in rats. The femora were treated twice with 1500 shockwaves at 2 and 4 weeks after surgery and compared with non-treated controls. The net volume of de novo bone in the defect was measured by microCT-scanning during 11-weeks follow-up. Bone ingrowth and angiogenesis in the bone substitutes was examined at 5 and 11 weeks using histology. It was shown that hydroxyapatite and titanium both had an increase of bone ingrowth with more bone in the shockwave group compared to the control group, whereas resorption was seen in tricalcium phosphate bone substitutes over time and this was insensitive to shockwave treatment. In conclusion, hydroxyapatite and titanium bone substitutes favour from shockwave treatment, whereas tricalcium phosphate does not. This study shows that osteoinduction and osteointegration of bone substitutes can be influenced with unfocused shockwave therapy, but among other factors depend on the type of bone substitute, likely reflecting its mechanical and biological properties.

Most false negative findings in DWI of ischemic stroke are in patients with minor deficits clinically localized to the brainstem. Our goal was to evaluate the benefit of a thin-sliced sagittal DWI in addition to conventional axial DWI at 1.5T for the detection of brainstem infarctions.

Establishment of a beneficial microbiota profile for piglets as early in life as possible is important as it will impact their future health. In the current study, we hypothesized that resistant starch (RS) provided in the maternal diet during gestation and lactation will be fermented in their hindgut, which would favourably modify their milk and/or gut microbiota composition and that it would in turn affect piglets' microbiota profile and their absorptive and immune abilities.

Optogenetics offers a unique method to regulate the activity of select neural circuits. However, the electrophysiological consequences of targeted optogenetic manipulation upon the entire circuit remain poorly understood. Analysis of the sensory-CNS-motor circuit in Drosophila larvae expressing eHpHR and ChR2-XXL revealed unexpected patterns of excitability. Optical stimulation of motor neurons targeted to express eNpHR resulted in inhibition followed by excitation of body wall contraction with repetitive stimulation in intact larvae. In situ preparations with direct electrophysiological measures showed an increased responsiveness to excitatory synaptic activity induced by sensory stimulation within a functional neural circuit. To ensure proper function of eNpHR and ChR2-XXL they were expressed in body wall muscle and direct electrophysiological measurements were obtained. Under eNpHR induced hyperpolarization the muscle remained excitable with increased amplitude of excitatory postsynaptic synaptic potentials. Theoretical models to explain the observations are presented. This study aids in increasing the understanding of the varied possible influences with light activated proteins within intact neural circuits.

Symptoms of orthostatic intolerance (OI) are common in Chronic Fatigue Syndrome (CFS) and similar disorders. These symptoms may relate to individual differences in intracranial compliance and cerebral blood perfusion. The present study used phase-contrast, quantitative flow magnetic resonance imaging (MRI) to determine intracranial compliance based on arterial inflow, venous outflow and cerebrospinal fluid flow along the spinal canal into and out of the cranial cavity. Flow-sensitive Alternating Inversion Recovery (FAIR) Arterial Spin Labelling was used to measure cerebral blood perfusion at rest. Forty patients with CFS and 10 age and gender matched controls were scanned. Severity of symptoms of OI was determined from self-report using the Autonomic Symptom Profile. CFS patients reported significantly higher levels of OI (p < .001). Within the patient group, higher severity of OI symptoms were associated with lower intracranial compliance (r = -.346, p = .033) and higher resting perfusion (r = .337, p = .038). In both groups intracranial compliance was negatively correlated with cerebral perfusion. There were no significant differences between the groups in intracranial compliance or perfusion. In patients with CFS, low intracranial compliance and high resting cerebral perfusion appear to be associated with an increased severity of symptoms of OI. This may signify alterations in the ability of the cerebral vasculature to cope with changes to systemic blood pressure due to orthostatic stress, but this may not be specific to CFS.

Hypoglycin A (HGA) toxicity, following ingestion of material from certain plants, is linked to an acquired multiple acyl-CoA dehydrogenase deficiency known as atypical myopathy, a commonly fatal form of equine rhabdomyolysis seen worldwide. Whilst some plants are known to contain this toxin, little is known about its function or the mechanisms that lead to varied HGA concentrations between plants. Consequently, reliable tools to detect this amino acid in plant samples are needed. Analytical methods for HGA detection have previously been validated for the food industry, however, these techniques rely on chemical derivatisation to obtain accurate results at low HGA concentrations. In this work, we describe and validate a novel method, without need for chemical derivatisation (accuracy = 84-94%; precision = 3-16%; reproducibility = 3-6%; mean linear range R2 = 0.999). The current limit of quantitation for HGA in plant material was halved (from 1μg/g in previous studies) to 0.5μg/g. The method was tested in Acer pseudoplatanus material and other tree and plant species. We confirm that A. pseudoplatanus is most likely the only source of HGA in trees found within European pastures.

fMRI provides spatial resolution that is unmatched by non-invasive neuroimaging techniques. Its temporal dynamics however are typically neglected due to the sluggishness of the hemodynamic signal.

The serotonin receptor 2C (5HT2C) is an important drug target to treat obesity and depression. Its pre-mRNA undergoes alternative splicing, encoding a short RNA1 isoform that is localized intracellularly and a full-length isoform (RNA2) that can reach the cell membrane. These splicing isoforms are deregulated in Prader-Willi syndrome (PWS), due to the loss of a trans-acting regulatory RNA, SNORD115. Here we show that the 5HT2C mRNA is expressed in the posterior pituitary, suggesting that 5HT2C mRNA is generated in the hypothalamus and subsequently conveyed by axonal transport. In the pituitary, the ratio of 5HT2C isoforms is regulated by feeding, and can be manipulated using a splice-site changing oligonucleotide injected into the blood. The pituitary expression of the 5HT2C mRNA may constitute a previously unknown mechanism whereby serotonin in the circulation or drugs targeting the 5HT2C might induce side-effects. Finally, the deregulation of 5HT2C splicing isoforms in PWS could contribute to the known hormonal imbalances.

Panicle architecture is an important component of agronomic trait in rice, which is also a key ingredient that could influence yield and quality of rice. In the panicle growth and development process, there are a series of complicated molecular and cellular events which are regulated by many interlinking genes. In this study, to explore the potential mechanism and identify genes and pathways involved in the formation of rice panicle, we compared the transcriptional profile of rice panicles (NIL-GW8 and NIL-gw8Amol) at three different stages of panicle development: In5 (formation of higher-order branches), In6 (differentiation of glumes) and In7 (differentiation of floral organs). A range of 40.5 to 54.1 million clean reads was aligned to 31,209 genes in our RNA-Seq analysis. In addition, we investigated transcriptomic changes between the two rice lines during different stages. A total of 726, 1121 and 2584 differentially expressed genes (DEGs) were identified at stages 1, 2 and 3, respectively. Based on an impact analysis of the DEGs, we hypothesize that MADS-box gene family, cytochrome P450 (CYP) and pentatricopeptide repeat (PPR) protein and various transcription factors may be involved in regulation of panicle development. Further, we also explored the functional properties of DEGs by gene ontology analysis, and the results showed that different numbers of DEGs genes were associated with 53 GO groups. In KEGG pathway enrichment analysis, many DEGs related to biosynthesis of secondary metabolites and plant hormone signal transduction, suggesting their important roles during panicle development. This study provides the first examination of changes in gene expression between different panicle development stages in rice. Our results of transcriptomic characterization provide important information to elucidate the complex molecular and cellular events about the panicle formation in rice or other cereal crops. Also, the findings will be helpful for the further identification of the genes related to panicle development.

We utilized a spectral and network analysis technique with an integrated support vector classification algorithm for the automated detection of cognitive capacity using resting state electroencephalogram (EEG) signals.

α-Synucleinopathy in the brain is the neuropathological hallmark of Parkinson's disease (PD). However, the functional impact of α-synucleinopathy in the enteric nervous system remains unknown. We aim to evaluate the association between gastrointestinal (GI) dysfunction and α-synuclein (αSYN) pathology in the stomach and colon of PD patients and controls, as well as to investigate the association between the αSYN pathology in GI tract and future PD risk.

To determine the prevalence and clinical findings of benign thyroid nodules and cancer in Korean pediatric patients with thyroid nodules.

The objective of our study was to determine the epidemiological, laboratory, and serological characteristics of patients with chronic hepatitis B virus (HBV) infection and normal transaminases. The study also aimed to evaluate liver damage by measuring the liver fibrosis (LF) grade and to identify possible factors associated with the presence of fibrosis.

Vascular-targeted therapies exhibit radiosensitizing effects by remodeling tumor vasculature, thus facilitating the increased oxygenation of the remaining tumor tissue. To examine these phenomena, the effects of antiendoglin gene therapy alone and in combination with irradiation were monitored for 5 consecutive days on a murine mammary adenocarcinoma (TS/A) tumor model growing in a dorsal window chamber. The vascularization of the tumors was assessed by the determination of the tumor vascular area and by measurement of tumor perfusion by using laser Doppler flowmetry to provide insight into intratumoral gene electrotransfer effects. The changes in the vascular area after this specific therapy correlated with laser Doppler measurements, indicating that either of the methods can be used to demonstrate the induced changes in the vascularization and perfusion of tumors. Gene electrotransfer with an endothelial-specific promoter resulted in a vascular-targeted effect on tumor vasculature within the first 24 hours and did not restore within 5 days. The combination with the irradiation did not result in a more pronounced vascular effect, and irradiation alone only abrogated the formation of new vessels and prevented an increase in the tumor perfusion over time. The results indicate that tumors grown in a dorsal window chamber facilitate intravital measurements of the vascularization of tumors and blood perfusion, enabling the monitoring of the antiangiogenic or vascular disruptive effects of different therapies.

Hybridization and polyploidization are regarded as the major driving forces in plant speciation, diversification, and ecological adaptation. Our knowledge regarding the mechanisms of duplicated-gene regulation following genomic merging or doubling is primarily derived from plants and is sparse for vertebrates.

Bivalent chromatin domains consisting of the activating histone 3 lysine 4 trimethylation (H3K4me3) and repressive histone 3 lysine 27 trimethylation (H3K27me3) histone modifications are enriched at developmental genes that are repressed in embryonic stem cells but active during differentiation. However, it is unknown whether another repressive histone modification, histone 4 lysine 20 trimethylation (H4K20me3), co-localizes with activating histone marks in ES cells.

Cyclic vomiting syndrome (CVS) is characterized by repeated, stereotypical vomiting episodes. It is possibly associated with mitochondrial DNA (mtDNA) variants. We examined the phenotype, disease burden, treatment and performed mtDNA analysis in pediatric CVS.