Genome-Wide Analysis Identifies NURR1-Controlled Network of New Synapse Formation and Cell Cycle Arrest in Human Neural Stem Cells.

Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas.

Effects of test item disclosure on medical licensing examination.

In 2012, the National Health Personnel Licensing Examination Board of Korea decided to publicly disclose all test items and answers to satisfy the test takers' right to know and enhance the transparency of tests administered by the government. This study investigated the effects of item disclosure on the medical licensing examination (MLE), examining test taker performance, psychometric characteristics, and factors affecting pass rates. This paper analyzed examinee performance data (n = 20,455) from 41 medical schools who took the MLE before (2009-2011) and after (2012-2014) the item disclosure policy (5548 total items).

Decreased serotonin2C receptor responses in male patients with schizophrenia.

Serotonin (5-HT)2C receptors in brain affect psychosis, reward, substance abuse, anxiety, other behaviors, appetite, body temperature, and other physiological measures. They also have been implicated in antipsychotic drug efficacy and side effects. We previously reported that the hyperthermia following administration of MK-212, a predominantly 5-HT(2C) receptor agonist, was diminished in a small sample of patients with schizophrenia (SCH), suggesting decreased 5-HT(2C) receptor responsiveness.

TIMP-1 modulates chemotaxis of human neural stem cells through CD63 and integrin signalling.

We recently reported that hNSCs (human neural stem cells) have the interesting characteristic of migration towards an intracranial glioma. However, the molecules and mechanisms responsible for tumour tropism are unclear. In the present study, we used microarray and proteomics analyses to identify a novel chemoattractant molecule, TIMP-1 (tissue inhibitor of metalloproteinase-1), secreted from human brain tumour tissues.

Nurr1 represses tyrosine hydroxylase expression via SIRT1 in human neural stem cells.

Nurr1 is an orphan nuclear receptor best known for its essential role in the development and maintenance of midbrain dopaminergic (DA) neurons. During DA neurogenesis, Nurr1 directly targets human tyrosine hydroxylase (hTH). Here we investigated this targeting to identify the molecular mechanisms by which Nurr1 regulates DA neurogenesis.

Integrative analysis of congenital muscular torticollis: from gene expression to clinical significance.

Background: Congenital muscular torticollis (CMT) is characterized by thickening and/or tightness of the unilateral sternocleidomastoid muscle (SCM), ending up with torticollis. Our aim was to identify differentially expressed genes (DEGs) and novel protein interaction network modules of CMT, and to discover the relationship between gene expressions and clinical severity of CMT.

Results: Twenty-eight sternocleidomastoid muscles (SCMs) from 23 subjects with CMT and 5 SCMs without CMT were allocated for microarray, MRI, or immunohistochemical studies.

The effects of the Trendelenburg position and intrathoracic pressure on the subclavian cross-sectional area and distance from the subclavian vein to pleura in anesthetized patients.

Background: The effects of maneuvers to increase intrathoracic pressure and of Trendelenburg position on the cross-sectional area (CSA) of the subclavian vein (SCV) and the relationship between the SCV and adjacent structures have not been investigated.

Methods: In ultrasonography-guided SCV catheterization (N = 30), the CSA of the SCV and the distance between the SCV and pleura (DSCV-pleura) were determined during 10-second airway opening, and 10-second positive inspiratory hold with 20 cm H2O in the supine position (S-0, and S-20) and the 10° Trendelenburg position (T-0, and T-20). In addition to a statistical significance of P < 0.

Transgenic mice expressing yellow fluorescent protein under control of the human tyrosine hydroxylase promoter.

Pathogenesis of Parkinson's disease and related catecholaminergic neurological disorders is closely associated with changes in the levels of tyrosine hydroxylase (TH). Therefore, investigation of the regulation of the TH gene system should assist in understanding the pathomechanisms involved in these neurological disorders. To identify regulatory domains that direct human TH expression in the central nervous system (CNS), we generated two transgenic mouse lines in which enhanced yellow fluorescent protein (EYFP) is expressed under the control of either 3.

Spectral entropy for assessing the depth of propofol sedation.

Background: For patients in the intensive care unit (ICU) or under monitored anesthetic care (MAC), the precise monitoring of sedation depth facilitates the optimization of dosage and prevents adverse complications from underor over-sedation. For this purpose, conventional subjective sedation scales, such as the Observer's Assessment of Alertness/Sedation (OAA/S) or the Ramsay scale, have been widely utilized. Current procedures frequently disturb the patient's comfort and compromise the already well-established sedation.

Expression of tyrosine hydroxylase is epigenetically regulated in neural stem cells.

Tyrosine hydroxylase (TH) is the first and rate-limiting enzyme in the biosynthesis of catecholamines, and its expression is regulated in a developmental stage- and cell type-specific manner. Our previous work suggested that the genetic elements responsible for cell type-specific expression of TH were in the repressor region of the TH promoter between -2187 and -1232 bp. To investigate the molecular mechanisms underlying the specificity of TH expression, the DNA methylation patterns of the CpG islands in the repressor region of the TH promoter were examined in human neural stem cells (NSCs) and dopaminergic neuron-like cells.

Identification of gliotropic factors that induce human stem cell migration to malignant tumor.

Neural stem cells are mobile, are attracted to regions of brain damage, and can migrate a considerable distance to reach a glioma site. However, the molecular basis of the progression of gliotropism to malignant gliomas remains poorly understood. With the use of clinically and histologically assessed glioma cells, we have assessed their protein and gene profiles via proteomics and microarray approaches, and have identified candidate genes from human glioma tissues.

Meningitis after a combined spinal epidural anesthesia: A case report.

The incidence of post-dural puncture meningitis is very low. A 44-year-old patient developed a fever (38degrees C, headache, neck stiffness, nausea, and vomiting after combined spinal epidural (CSE) anesthesia and surgery for closed reduction and internal fixation (CRIF) with intramedullary (IM) nailing, tibia, Rt. With a preliminary diagnosis of bacterial meningitis, empiric broad spectrum antimicrobial treatment was immediately started after cerebrospinal fluid (CSF) sampling.

Migration of human neural stem cells toward an intracranial glioma.

Many in vivo and in vitro studies have demonstrated the targeted migration of neural stem cells (NSC) to infiltrating brain tumors, including malignant glioma, highlighting a potential therapeutic approach. However, there is not enough information to apply this approach to clinical therapy. The most important things in stem cell therapy for brain tumors involve selecting the appropriate neural progenitor type and optimizing the efficiency of the cell engraftment.

Regulation of human tyrosine hydroxylase gene by neuron-restrictive silencer factor.

Tyrosine hydroxylase (TH), the biosynthetic enzyme of catecholamine, is synthesized specifically in catecholaminergic neurons. Thus, it is possible that neuronal cell type-specific expression of this gene is coordinately regulated. One of the neuron-specific transcription regulators, neuron-restrictive silencer factor (NRSF)/repressor element 1 (RE1) silencing transcription factor (REST), represses the expression of neuronal genes in non-neuronal cells.

Thrombin induces suppressor of cytokine signaling 3 expression in brain microglia via protein kinase Cdelta activation.

Microglia (brain macrophages) are activated upon brain damage. In this study, we demonstrated that thrombin, a pro-inflammatory stimulator of microglia, induced expression of suppressors of cytokine signaling (SOCS) in microglia. RT-PCR analysis and Northern blot analysis showed that thrombin induced SOCS3 mRNA expression.

Cloning and cell type-specific regulation of the human tyrosine hydroxylase gene promoter.

Tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis, is predominantly expressed in several cell groups within the brain, including the dopaminergic (DA) neurons of the substantia nigra and ventral tegmental area, and the noradrenergic neurons of the locus coeruleus. To investigate the regulation of cell type-specific TH expression, we cloned and sequenced a 5.5kb fragment of human genomic DNA immediately 5(') of the TH coding region.

Sonic hedgehog and FGF8 collaborate to induce dopaminergic phenotypes in the Nurr1-overexpressing neural stem cell.

Neural stem cells are self-renewing cells capable of differentiating into all neural lineage cells in vivo and in vitro. In the present study, coordinated induction of midbrain dopaminergic phenotypes in an immortalized multipotent neural stem cell line can be achieved by both overexpression of nuclear receptor Nurr1, and fibroblast growth factor-8 (FGF-8), and sonic hedgehog (Shh) signals. Nurr1 overexpression induces neuronal differentiation and confers competence to respond to extrinsic signals such as Shh and FGF-8 that induce dopaminergic fate in a mouse neural stem cell line.

Intracellular trafficking and metabolic turnover of yeast prepro-alpha-factor-SRIF precursors in GH3 cells.

Chimeric genes coding for prepro region of yeast alpha-factor and anglerfish SRIF were expressed in rat GH3 cells to determine whether yeast signals could regulate hormone processing in mammalian cells. We report that nascent hybrid polypeptides were efficiently targeted to ER, where cleavage of signal peptides and core glycosylation occurred, and were localized mainly in Golgi. These data indicate that prepro region of yeast alpha-factor functions in sorting molecules to secretory pathway in mammalian cells.

Overexpression of midbrain-specific transcription factor Nurr1 modifies susceptibility of mouse neural stem cells to neurotoxins.

Nurr1 is a member of the nuclear receptor superfamily of transcription factors that is highly expressed in midbrain dopaminergic (DA) neurons, the cells primarily lost in human Parkinson's disease (PD), and in Nurr1-null mice selective agenesis of midbrain DA neurons is found. To investigate possible correlation between the expression of Nurr1 gene and neurotoxin-induced cell death of DA neurons, a neural stem cell line (NSC, A3) and Nurr1-overexpressing NSC (A3.Nurr1) were exposed to DA neurotoxins 6-hydroxydopamine (6-OHDA) and methyl phenylpyridinium (MPP(+)).

Evidence of a novel dipeptidyl aminopeptidase in mammalian GH(3) cells: new insights into the processing of peptide hormone precursors.

We investigated whether yeast signals could regulate hormone processing in mammalian cells. Chmeric genes coding for the prepro region of yeast alpha-factor and the functional hormone region of anglerfish somatostatin was expressed in rat pituitary GH(3) cells. The nascent prepro-alpha-factor-somatostatin peptides disappeared from cells with a half-life of 30 min, and about 20% of unprocessed precursors remained intracellular after a 2 h chase period.

Hrp3, a chromodomain helicase/ATPase DNA binding protein, is required for heterochromatin silencing in fission yeast.

Hrp3, a paralog of Hrp1, is a novel member of the CHD1 (chromo-helicase/ATPase-DNA binding 1) protein family of Schizosaccharomyces pombe. Although it has been considered that CHD1 proteins are required for chromatin modifications in transcriptional regulations, little is known about their roles in vivo. In this study, we examined the effects of Hrp3 on heterochromatin silencing using several S.