A gene regulatory network combining Pax3/7, Sox10 and Mitf generates diverse pigment cell types in medaka and zebrafish.

Neural crest cells generate numerous derivatives, including pigment cells, and are a model for studying how fate specification from multipotent progenitors is controlled. In mammals, the core gene regulatory network for melanocytes (their only pigment cell type) contains three transcription factors, Sox10, Pax3 and Mitf, with the latter considered a master regulator of melanocyte development. In teleosts, which have three to four pigment cell types (melanophores, iridophores and xanthophores, plus leucophores e.

Helix-Stabilized Cell-Penetrating Peptides for Delivery of Antisense Morpholino Oligomers: Relationships among Helicity, Cellular Uptake, and Antisense Activity.

The secondary structures of cell-penetrating peptides (CPPs) influence their properties including their cell-membrane permeability, tolerability to proteases, and intracellular distribution. Herein, we developed helix-stabilized arginine-rich peptides containing α,α-disubstituted α-amino acids and their conjugates with antisense phosphorodiamidate morpholino oligomers (PMOs), to investigate the relationships among the helicity of the peptides, cellular uptake, and antisense activity of the peptide-conjugated PMOs. We demonstrated that helical CPPs can efficiently deliver the conjugated PMO into cells compared with nonhelical CPPs and that their antisense activities are synergistically enhanced in the presence of an endosomolytic reagent or an endosomal escape domain peptide.

Ring-opening fluorination of bicyclic azaarenes.

We have discovered a ring-opening fluorination of bicyclic azaarenes. Upon treatment of bicyclic azaarenes such as pyrazolo[1,5-]pyridines with electrophilic fluorinating agents, fluorination of the aromatic ring is followed by a ring-opening reaction. Although this overall transformation can be classified as an electrophilic fluorination of an aromatic ring, it is a novel type of fluorination that results in construction of tertiary carbon-fluorine bonds.

Identification of 2,6-Disubstituted 3-Imidazo[4,5-]pyridines as Therapeutic Agents for Dysferlinopathies through Phenotypic Screening on Patient-Derived Induced Pluripotent Stem Cells.

Dysferlinopathies, which are muscular diseases caused by mutations in the dysferlin gene, remain serious medical problems due to the lack of therapeutic agents. Herein, we report the design, synthesis, and structure-activity relationships of a 2,6-disubstituted 3-imidazo[4,5-]pyridine series, which was identified from the phenotypic screening of chemicals that increase the level of dysferlin in myocytes differentiated from patient-derived induced pluripotent stem cells (iPSCs). Optimization studies with cell-based phenotypic assay led to the identification of a highly potent compound, , with dysferlin elevation effects at double-digit nanomolar concentrations.

Distinct interactions of Sox5 and Sox10 in fate specification of pigment cells in medaka and zebrafish.

Mechanisms generating diverse cell types from multipotent progenitors are fundamental for normal development. Pigment cells are derived from multipotent neural crest cells and their diversity in teleosts provides an excellent model for studying mechanisms controlling fate specification of distinct cell types. Zebrafish have three types of pigment cells (melanocytes, iridophores and xanthophores) while medaka have four (three shared with zebrafish, plus leucophores), raising questions about how conserved mechanisms of fate specification of each pigment cell type are in these fish.

A Synthetic Route to Sodium α-Aminoalkanesulfinates and Their Application in the Generation of α-Aminoalkyl Radicals for Radical Addition Reactions.

The synthesis of sodium α-aminoalkanesulfinates and their synthetic utility as α-aminoalkyl radical precursors are reported. A variety of α-aminoalkanesulfinates were readily obtained from the reaction between the anions of N-Boc-protected alkylamines and 1,4-diazabicyclo[2.2.

Role of Neurokinin 3 Receptor Signaling in Oral Squamous Cell Carcinoma.

Background/aim: The neurokinin 3 receptor (NK-3R) is differentially expressed in the central nervous system including cases of human oral squamous cell carcinoma. However, the role of NK-3R signaling in oral squamous cell carcinoma is not well known.

Materials And Methods: NK-3R expression in surgically resected oral squamous cell carcinoma was examined immunohistochemically and the strength of the expression was quantified.

Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC.

Tachykinin Receptor 3 Distribution in Human Oral Squamous Cell Carcinoma.

Background: Tachykinin 3 (TAC3) and its preferred tachykinin receptor 3 (TACR3) that are prominently detected in the central nervous system, play significant roles in physiological development and specifically in the human reproductive system. The roles of TAC3/TACR3 in oral squamous cell carcinoma are unknown.

Materials And Methods: We examined the expression pattern of TAC3/TACR3 in clinically-resected oral squamous cell carcinoma samples using immunohistochemistry and immunofluorescence analysis.

The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction.

Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction.

Expression pattern of sonic hedgehog signaling and calcitonin gene-related peptide in the socket healing process after tooth extraction.

Sonic Hedgehog (SHH), a neural development inducer, plays a significant role in the bone healing process. Calcitonin gene-related peptide (CGRP), a neuropeptide marker of sensory nerves, has been demonstrated to affect bone formation. The roles of SHH signaling and CGRP-positive sensory nerves in the alveolar bone formation process have been unknown.

Epilepsies after Pocket Monster seizures.

Background: We conducted a 5-year follow-up study in patients with a seizure induced by animated cartoon "Pocket Monster."

Methods: A recurrence of seizures was observed in 25 of 91 patients with a Pocket Monster seizure. The patients were divided into two groups: Epilepsy group of 12 patients with a history of epilepsy and Nonepilepsy group of 13 patients without a history of epilepsy.

A follow-up survey on seizures induced by animated cartoon TV program "Pocket Monster".

Purpose: To identify the short-term outcome of patients who had seizures while watching an animated cartoon TV program, "Pocket Monster," on December 16, 1997.

Methods: One and three years after the incident, questionnaires were sent to physicians of each patient about seizure recurrence, EEGs, and medication.

Results: Among 103 patients in whom epileptic seizures occurred during the TV program and information on the outcomes was available, 25 (24%) patients had a history of unprovoked seizures before the incident (Epilepsy Group), and 78 (76%) did not (Non-Epilepsy Group).

Prognostic value of positron emission tomography in cryptogenic West syndrome.

The relationship between positron emission tomography (PET) findings and developmental or seizure outcome was examined in 17 infants (11 males, six females; mean age at onset of spasms 7 months, range 3 to 26 months) with newly diagnosed cryptogenic West syndrome. The predictive value of PET in these infants was assessed. PET was performed in the infants at the onset of spasms and 3 months after initial therapy using 18F-labelled 2-deoxy-2-fluoro-D-glucose.