Discovery of novel arylpyridine derivatives for motile ciliogenesis.

Motile cilia are crucial for maintaining healthy bodily functions by facilitating fluid transport and removing foreign substances or debris from the body. The dysfunction of motile cilia leads to ciliopathy. In particular, damage to the motile cilia of the airways can cause or worsen respiratory disease, making it an attractive target for therapeutic interventions.

Arcuate Nucleus of the Hypothalamus: Anatomy, Physiology, and Diseases.

The hypothalamus is part of the diencephalon and has several nuclei, one of which is the arcuate nucleus. The arcuate nucleus of hypothalamus (ARH) consists of neuroendocrine neurons and centrally-projecting neurons. The ARH is the center where the homeostasis of nutrition/metabolism and reproduction are maintained.

Biomineralized Nanoscavenger Abrogates Proinflammatory Macrophage Polarization and Induces Neutrophil Clearance through Reverse Migration during Gouty Arthritis.

The deposition of monosodium urate (MSU) crystals induces the overexpression of reactive oxygen species (ROS) and proinflammatory cytokines in residential macrophages, further promoting the infiltration of inflammatory leukocytes in the joints of gouty arthritis. Herein, a peroxidase-mimicking nanoscavenger was developed by forming manganese dioxide over albumin nanoparticles loaded with an anti-inflammatory drug, indomethacin (BIM), to block the secretion of ROS and COX2-induced proinflammatory cytokines in the MSU-induced gouty arthritis model. In the MSU-induced arthritis mouse model, the BIM nanoparticles alleviated joint swelling, which is attributed to the abrogation of ROS and inflammatory cytokine secretions from proinflammatory macrophages that induces neutrophil infiltration and fluid building up in the inflammation site.

Multidimensional Early Prediction Score for Drug-Resistant Epilepsy.

Background And Purpose: Achieving favorable postoperative outcomes in patients with drug-resistant epilepsy (DRE) requires early referrals for preoperative examinations. The purpose of this study was to investigate the possibility of a user-friendly early DRE prediction model that is easy for nonexperts to utilize.

Methods: A two-step genotype analysis was performed, by applying 1) whole-exome sequencing (WES) to the initial test set (=243) and 2) target sequencing to the validation set (=311).

A Rapid and Noninvasive Method That Extracts Polymerase Chain Reaction-Ready Genomic DNA from Adult Zebrafish.

Genotyping usually entails analysis of the products of polymerase chain reaction (PCR) carried out with genomic DNA (gDNA) as template, and is employed for validation of mutant or transgenic organisms. For genotyping of adult zebrafish, gDNA is often extracted from clipped caudal fin or skin mucus through either alkaline lysis using NaOH or proteinase K (PK) treatment. Further purification of the gDNA using ethanol precipitation was optional.

A Genotype-Phenotype Study of Multiple Hereditary Exostoses in Forty-Three Patients.

Multiple hereditary exostoses (MHE) is a rare autosomal dominant skeletal disorder with a variety of clinical manifestations. We aimed to evaluate the general clinical phenotypic severity of MHE using our own scoring system and analyzed the risk factors associated with severe clinical phenotypes. In this study, 43 patients from 30 families were analyzed.

A novel in-frame GFAP p.E138_L148del mutation in Type II Alexander disease with atypical phenotypes.

Alexander disease (AxD) is a neurodegenerative astrogliopathy caused by mutation in the glial fibrillary acidic protein (GFAP) gene. A 42-year-old Korean man presented with temporary gait disturbance and psychiatric regression after a minor head trauma in the absence of bulbar symptoms and signs. Magnetic resonance images of the brain and spinal cord showed significant atrophy of the medulla oblongata and the entire spinal cord as well as contrast-enhanced T2 hypointensity in the basal ganglia.

Transgenic fluorescent zebrafish lines that have revolutionized biomedical research.

Since its debut in the biomedical research fields in 1981, zebrafish have been used as a vertebrate model organism in more than 40,000 biomedical research studies. Especially useful are zebrafish lines expressing fluorescent proteins in a molecule, intracellular organelle, cell or tissue specific manner because they allow the visualization and tracking of molecules, intracellular organelles, cells or tissues of interest in real time and in vivo. In this review, we summarize representative transgenic fluorescent zebrafish lines that have revolutionized biomedical research on signal transduction, the craniofacial skeletal system, the hematopoietic system, the nervous system, the urogenital system, the digestive system and intracellular organelles.

Loss of splicing factor IK impairs normal skeletal muscle development.

Background: IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an ik knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo.

Fulminant Course of Neuromyelitis Optica in a Patient With Anti-MDA5 Antibody-Positive Dermatomyositis: A Case Report.

Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody is a myositis-specific marker detected in clinically amyopathic dermatomyositis (DM). DM with anti-MDA5 antibody can be accompanied by rapidly progressive interstitial lung disease (RP-ILD) and other autoimmune disorders. Until now, only one case of neuromyelitis optica (NMO) with anti-MDA5-positive DM has been reported worldwide, in which the patient achieved a favorable outcome with intensive immunotherapy.

Wnt-PLC-IP-Connexin-Ca axis maintains ependymal motile cilia in zebrafish spinal cord.

Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies.

ACOX3 Dysfunction as a Potential Cause of Recurrent Spontaneous Vasospasm of Internal Carotid Artery.

Recurrent spontaneous vasospasm of the extracranial internal carotid artery (RSV-eICA) is a rarely recognized cause of ischemic stroke in young adults. However, its pathophysiology remains largely unknown. Through whole-exome sequencing of the ACOX3 gene of two dizygotic Korean twin brothers affected by RSV-eICA, we identified two compound heterozygous missense variants c.

A zebrafish model of nondystrophic myotonia with sodium channelopathy.

Nondystrophic myotonias are disorders of Na (Na1.4 or SCN4A) and Cl (CLCN1) channels in skeletal muscles, and frequently show phenotype heterogeneity. The molecular mechanism underlying their pathophysiology and phenotype heterogeneity remains unclear.

Hyaluronan-Stabilized Redox-Sensitive Nanoassembly for Chemo-Gene Therapy and Dual T1/T2 MR Imaging in Drug-Resistant Breast Cancer Cells.

Tailoring combinatorial therapies along with real-time monitoring strategies has been the major focus of overcoming multidrug resistance in cancer. However, attempting to develop a multifunctional nanoplatform in a single construct leads to compromising therapeutic outcomes. Herein, we developed a simple, theranostic nanoassembly containing a hyaluronic acid-stabilized redox-sensitive (HART) polyethylenimine polyplex composed of a doxorubicin (DOX) intercalated Bcl-2 shRNA encoded plasmid along with a green-synthesized hausmannite (MnO) and hematite (FeO) nanoparticle (GMF).

Author Correction: Zebrafish as an animal model in epilepsy studies with multichannel EEG recordings.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

A 3D-Printed Sensor for Monitoring Biosignals in Small Animals.

Although additive manufacturing technologies, also known as 3D printing, were first introduced in the 1980s, they have recently gained remarkable popularity owing to decreased costs. 3D printing has already emerged as a viable technology in many industries; in particular, it is a good replacement for microfabrication technology. Microfabrication technology usually requires expensive clean room equipment and skilled engineers; however, 3D printing can reduce both cost and time dramatically.

Aggregation-prone GFAP mutation in Alexander disease validated using a zebrafish model.

Background: Alexander disease (AxD) is an astrogliopathy that predominantly affects the white matter of the central nervous system (CNS), and is caused by a mutation in the gene encoding the glial fibrillary acidic protein (GFAP), an intermediate filament primarily expressed in astrocytes and ependymal cells. The main pathologic feature of AxD is the presence of Rosenthal fibers (RFs), homogeneous eosinophilic inclusions found in astrocytes. Because of difficulties in procuring patient' CNS tissues and the presence of RFs in other pathologic conditions, there is a need to develop an in vivo assay that can determine whether a mutation in the GFAP results in aggregation and is thus disease-causing.

Functional validation of novel MKS3/TMEM67 mutations in COACH syndrome.

COACH syndrome is an autosomal recessive developmental disorder, a subtype of Joubert syndrome and related disorders, characterized by cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis. Although mutations in TMEM67 (transmembrane protein 67)/MKS3 (Meckel-Gruber syndrome, type 3) were reported to cause COACH syndrome, this causality has not verified by functional studies. In a 20-year-old Korean man, we found cerebellar ataxia, isolated elevation in serum γ-glutamyl transpeptidase (γ-GTP) activity, oligophrenia, the molar tooth sign (MTS) in the brain MR images and congenital hepatic fibrosis (CHF).

Zebrafish as an animal model in epilepsy studies with multichannel EEG recordings.

Despite recent interest in using zebrafish in human disease studies, sparked by their economics, fecundity, easy handling, and homologies to humans, the electrophysiological tools or methods for zebrafish are still inaccessible. Although zebrafish exhibit more significant larval-adult duality than any other animal, most electrophysiological studies using zebrafish are biased by using larvae these days. The results of larval studies not only differ from those conducted with adults but also are unable to delicately manage electroencephalographic montages due to their small size.