![[PukiWiki]](image/pukiwiki.png "[PukiWiki]")
Human dental pulp cells (hDPCs) possess the capacity to differentiate into odontoblast-like cells in response to exogenous stimuli. Histone methylation is one of the most robust epigenetic marks and is essential for the regulation of multiple cellular processes. Previous studies have shown that histone methyltransferases (HMTs) and histone demethylases (HDMs) are crucial for the osteogenic differentiation of human bone marrow, adipose tissue, and tooth tissue. However, little is known about the role of histone methylation in hDPC differentiation. Here, the expression levels of HMTs and HDMs were profiled in hDPCs undergoing odontogenic induction. Among several differentially expressed enzymes, HDM KDM5A demonstrated significantly enhanced expression during cytodifferentiation. Furthermore, KDM5A expression increased during early passages and in a time-dependent manner during odontogenic induction. Using a shRNA-expressing lentivirus, KDM5A was knocked down in hDPCs. KDM5A depletion resulted in greater alkaline phosphatase activity and more mineral deposition formation. Meanwhile, the expression levels of the odontogenic markers DMP1, DSPP, OSX, and OCN were increased by KDM5A knockdown. As a histone demethylase specific for tri- and dimethylated histone H3 at lysine 4 (H3K4me3/me2), KDM5A deficiency led to a significant increment in total H3K4me3 levels, whereas no significant difference was found for H3K4 me2. H3K4me3 levels on the promoters of the odontogenic markers increased after KDM5A knockdown in hDPCs. These results demonstrated that KDM5A is present in hDPCs and inhibits the odontogenic differentiation potentiality of hDPCs by removing H3K4me3 from specific gene promoters, suggesting that KDM5A-dependent histone demethylation may play an important role in reparative dentinogenesis.When making decisions, people naturally ask two implicit questions how soon can I make a decision, and how certain am I? In perception, people's confidence (how certain?) shows a non-monotonic relationship with response-time (how soon?), such that choice confidence can either increase or decrease with response-time. While a fronto-parietal network has been implicated as a neural substrate that binds choice confidence and action (e.g., response-time), the dynamic interplay between choice behaviors within such a network has not been clarified. Here we show that frontal event-related potentials (ERPs) reflect choice confidence prior to a decision. https://www.selleckchem.com/products/homoharringtonine.html Specifically, we report a second positive peak of the stimulus-locked frontal ERP at ~500ms that scales with confidence but not stimulus level, while the centro-parietal ERP amplitude covaries inversely with response-time. This frontal ERP component occurs before the response, which helps explain the inverse relationship between choice confidence and response-time (i.e., higher confidence for shorter response-time) when choice accuracy is emphasized over speed. Our findings provide the first early neural representation of confidence, consistent with the temporal precedence for its causal role in the current decision-making task - "I decided earlier because I am confident".Brain stimulation approaches are important to gain causal mechanistic insights into the relevance of functional brain regions and/or neurophysiological systems for human cognitive functions. In recent years, transcutaneous vagus nerve stimulation (tVNS) has attracted considerable popularity. It is a noninvasive brain stimulation technique based on the stimulation of the vagus nerve. The stimulation of this nerve activates subcortical nuclei, such as the locus coeruleus and the nucleus of the solitary tract, and from there, the activation propagates to the cortex. Since tVNS is a novel stimulation technique, this literature review outlines a brief historical background of tVNS, before detailing underlying neurophysiological mechanisms of action, stimulation parameters, cognitive effects of tVNS on healthy humans, and, lastly, current challenges and future directions of tVNS research in cognitive functions. Although more research is needed, we conclude that tVNS, by increasing noradrenaline (NA) and gamma-aminobutyric acid (GABA) levels, affects NA and GABA-related cognitive performance. The review provides detailed background information how to use tVNS as a neuromodulatory tool in cognitive neuroscience and outlines important future leads of research on tVNS.Since effective immunotherapeutic agents such as immune checkpoint blockade to treat cancer have emerged, the need for reliable preclinical cancer models that can evaluate and discover such drugs became stronger than ever before. The traditional preclinical cancer model using a cancer cell line has several limitations to recapitulate intra-tumor heterogeneity and in-vivo tumor activity including interactions between tumor-microenvironment. In this review, we will go over various preclinical cancer models recently discovered including patient-derived xenografts, humanized mice, organoids, organotypic-tumor spheroids, and organ-on-a-chip models. Moreover, we will discuss the future directions of preclinical cancer research.Recent studies put forward the idea that stimulus-evoked gamma-band oscillations (GBOs; 30-100 Hz) play a specific role in nociception. So far, evidence for the specificity of GBOs for nociception, their possible involvement in nociceptive sensory discriminatory abilities and knowledge regarding their cortical sources is just starting to grow. To address these questions, we used electroencephalography (EEG) to record brain activity evoked by phasic nociceptive laser stimuli and tactile stimuli applied at different intensities to the right hand and foot of 12 healthy volunteers. The EEG was analyzed in the time domain to extract phase-locked event-related brain potentials (ERPs), and in three regions of interest in the time-frequency domain (delta/theta, 40 Hz gamma, 70 Hz gamma) to extract stimulus-evoked changes in the magnitude of non-phase locked brain oscillations. Both nociceptive and tactile stimuli, matched with respect to subjective intensity, elicited phase locked ERPs of increasing amplitude with increasing stimulus intensity. In contrast, only nociceptive stimuli elicited a significant enhancement of GBOs (65-85 Hz, 150-230 ms after stimulus onset), whose magnitude encoded stimulus intensity, whereas tactile stimuli led to a GBO decrease. Following nociceptive hand stimulation, the topographical distribution of GBOs was maximal at contralateral electrode C3, whereas maximum activity following foot stimulation was recorded at the midline electrode Cz, compatible with generation of GBOs in the representations of the hand and foot of the primary sensorimotor cortex, respectively. The differential behavior of high frequency GBOs and low frequency 40 Hz GBOs is indicating different functional roles and regions in sensory processing.Endophytism is one of the widely explored phenomena related to orchids and fungi. Endophytic fungi assist plants by supplementing nutrient acquisition, and synthesis of plant growth regulators. Vanda cristata is an epiphytic orchid that has a great diversity of endophytic fungi. Endophytic fungi were isolated from roots, stems, and leaves of V.Vanda cristata and identified by both morphological and molecular study. Furthermore, the isolated endophytic fungi were subjected to auxin synthesis, phosphate solubilization, ammonia synthesis, and elicitor growth test for understanding their growth-promoting effect in a qualitative and quantitative manner. Altogether, 12 different endophytic fungi were isolated from roots, stems, and leaves of V. cristata of which most species belonged to Ascomycota. Unidentified II fungi were found to be most effective for auxin synthesis and phosphate solubilization while Agaricus bisporous and Mycolepto discus were most effective for ammonia synthesis. We have tested the plant growth-promoting activity of the twelve isolated endophytic fungi on Cymbidium aloifolium protocorms (12 weeks old). All the endophytic fungi showed growth-promoting activity. Plant growth of Cymbidium aloifolium was found higher on the MS medium supplemented with all fungal elicitors. Fungal elicitor CVS4, however, showed the highest plant growth-promoting activity toward C. aloifolium.The role of olfactory receptor (Olfr)-78 in carotid body (CB) response to hypoxia was examined. BL6 mice with global deletion of Olfr78 manifested an impaired hypoxic ventilatory response (HVR), a hallmark of the CB chemo sensory reflex, CB sensory nerve activity, and reduced [Ca2+]i response of glomus cells to hypoxia (pO2 ~40 mmHg). In contrast, severe hypoxia (pO2 ~10 mmHg) which depressed breathing and produced a very weak CB sensory nerve excitation but robust elevation of [Ca2+]i in Olfr78 null glomus cells. CB sensory nerve excitation evoked by Olfr78 ligands, lactate, propionate, acetate and butyrate were unaffected in mutant mice and were smaller than that evoked by hypoxia (pO2 ~40mmHg). Similar results were obtained in Olfr78 null mice on a JAX genetic background. These results demonstrate a role for Olfr78 in CB responses to a wide range of hypoxia but not severe hypoxia, and do not require either lactate or any other short-chain fatty acids.Proliferation of dental pulp stem cells (DPSCs) is crucial in tooth development and damage repairing, also includes its therapy application for tissue engineering. MicroRNAs (miRNAs) are key players in biological processes of DPSCs, and transcriptional co-activator with PDZ-binding motif (TAZ) also plays important roles in cell proliferation and differentiation, however, the roles of miR-584 and TAZ in DPSCs are not known. We found up-regulated miR-584 expression and down-regulated TAZ expression levels in aging dental pulp tissue compare to those in young dental pulp tissue. In proliferating DPSCs we demonstrated the decreased miR-584 expression and increased TAZ expression. miR-584 mimics suppressed DPSCs proliferation and migration, and significantly reduced TAZ production, whereas miR-584 inhibition exerted the converse effects. Knocking down of the TAZ in DPSCs had a similar effect as overexpression of miR-584. Furthermore, luciferase reporter assay demonstrated that miR-584 could directly bind to the TAZ mRNA 3'UTR to repress its translation. Overexpression of TAZ can partly rescue miR-584 mimic-mediated the inhibition of proliferation. Additionally, miR-584 inhibited cell proliferation and downregulated expression of cell cycle proteins by AKT signaling pathway. Together, we identified that miR-584 may be a key regulator in the proliferation of DPSCs by regulating TAZ expression via AKT signaling pathway. It would be a promising biomarker and therapeutic target for pulp disease.PURPOSE The purpose of this study was to assess the effectiveness of periarticular multidrug infiltration (PMDI) and compare it with that of epidural catheter use. METHODS Fifty-eight patients (58 joints) who underwent total knee arthroplasty were included in this single-center, prospective, parallel, randomized, controlled trial. Preoperatively, patients were randomly categorized into the PMDI and epidural catheter groups. We evaluated postoperative pain (visual analog scale (VAS) and narcotic consumption), functional outcomes (range of motion (ROM) of knee flexion, the day patients could perform the straight-leg raising (SLR) test, and day of starting cane use), and laboratory data (white blood cell (WBC) and C-reactive protein (CRP)). RESULTS There was no significant difference in the VAS score, ROM of knee flexion, the day patients could do SLR, and the day of starting cane use between the PMDI and epidural catheter groups. However, the PMDI group could perform SLR on a postoperative day (POD) 1 (p less then 0.
