Occurrence of free glycans in salmonid serum.

Free N-glycans (FNGs) are oligosaccharides that are structurally related to N-linked glycans, and are widely found in nature. The mechanisms responsible for the formation and degradation of intracellular FNGs are well characterized in mammalian cells. More recent analysis in mammalian sera shows that there are various types of extracellular free glycans, including FNGs.

[Evolution of the Model Core Curriculum for Pharmacy Education and Issues Concerning the Six-year Pharmacy University Education Program].

The six-year pharmacy university education program that began in 2006 was guided by the Model Core Curriculum for Pharmacy Education which started as process-based education. It was first revised in 2013 and further revised in 2023 to provide outcome-based education. There remains a need to develop a consistent six-year curriculum spanning basic science to clinical pharmacy.

Development of new NGLY1 assay systems - toward developing an early screening method for NGLY1 deficiency.

Cytosolic peptide: N-glycanase (PNGase/NGLY1 in mammals) is an amidase (EC:3.5.1.

Sugar-mediated non-canonical ubiquitination impairs Nrf1/NFE2L1 activation.

Proteasome is essential for cell survival, and proteasome inhibition induces proteasomal gene transcription via the activated endoplasmic-reticulum-associated transcription factor nuclear factor erythroid 2-like 1 (Nrf1/NFE2L1). Nrf1 activation requires proteolytic cleavage by DDI2 and N-glycan removal by NGLY1. We previously showed that Nrf1 ubiquitination by SKP1-CUL1-F-box (SCF), an N-glycan-recognizing E3 ubiquitin ligase, impairs its activation, although the molecular mechanism remained elusive.

Intranasal oxytocin suppresses seizure-like behaviors in a mouse model of NGLY1 deficiency.

NGLY1 deficiency is a genetic disease caused by biallelic mutations of the Ngly1 gene. Although epileptic seizure is one of the most severe symptoms in patients with NGLY1 deficiency, preclinical studies have not been conducted due to the lack of animal models for epileptic seizures in NGLY1 deficiency. Here, we observed the behaviors of male and female Ngly1 mice by video monitoring and found that these mice exhibit spontaneous seizure-like behaviors.

ELISA-based highly sensitive assay system for the detection of endogenous NGLY1 activity.

Cytosolic peptide:N-glycanase (NGLY1, PNGase) is an enzyme that cleaves N-glycans from misfolded glycoproteins. In 2012, a human genetic disorder, NGLY1 deficiency, was first reported to be caused by mutations of the NGLY1 gene. Since then, there has been rapid progresses on NGLY1 biology, and gene therapy has been proposed as a promising therapeutic option for NGLY1 deficiency.

Development of a fluorescence and quencher-based FRET assay for detection of endogenous peptide:N-glycanase/NGLY1 activity.

Cytosolic peptide:N-glycanase (PNGase/NGLY1 in mammals) catalyzes deglycosylation of N-glycans on glycoproteins. A genetic disorder caused by mutations in the NGLY1 gene leads to NGLY1 deficiency with symptoms including motor deficits and neurological problems. Effective therapies have not been established, though, a recent study used the administration of an adeno-associated viral vector expressing human NGLY1 to dramatically rescue motor functions in young Ngly1 rats.

Excited state properties of 5-fluoro-4-thiouridine derivative.

The excited state properties of thionated 5-fluorouridine (2',3',5'-tri-O-acetyl-5-fluoro-4-thiouridine; ta5F4TUrd), synthesized with Lawesson's reagent, have been intensively investigated with nanosecond transient absorption spectroscopy, time-resolved thermal lensing, near-infrared emission, and quantum chemical calculation. The intrinsic triplet lifetime of ta5F4TUrd was determined to be μs in acetonitrile, and the formation quantum yield of the excited triplet state was as large as . The quenching rate constants of the triplet ta5F4TUrd by the dissolved oxygen molecule and by the self-quenching process were found to be nearly equal to the diffusion-controlled rate of acetonitrile.

Rat hepatocytes secrete free oligosaccharides.

We recently established a method for the isolation of serum-free oligosaccharides, and characterized various features of their structures. However, the precise mechanism for how these glycans are formed still remains unclarified. To further investigate the mechanism responsible for these serum glycans, here, we utilized rat primary hepatocytes to examine whether they are able to secrete free glycans.

Conformational preference of 2-(4-methoxyphenyl)ethanol studied by supersonic jet spectroscopy: Intramolecular OH/π interaction.

A π-type hydrogen bonding between the OH group and the π electron is a crucial factor for the conformational preference of the molecular structure with a flexible group. However, the information on the effect of the substituent on the OH/π interaction is insufficient. The laser-induced fluorescence (LIF) excitation, the dispersed fluorescence (DF), the IR-UV hole-burning, and the IR dip spectra of jet-cooled 2-(4-methoxyphenyl)ethanol were measured for the first time.

Large-scale cultivation of human iPS cells in bioreactor with reciprocal mixing.

A substantial number of human iPS cells (hiPSCs) is needed for cell therapy to be successful against various diseases. We previously reported on a bioreactor with reciprocal mixing that produces specific physical properties that differ from those of conventional bioreactors with rotary paddle stirring. Moreover, such reactors not only provide a homogeneous environment but also allow the control of spheroid size by changing the mixing speed.

A commentary on 'Patient-derived gene and protein expression signatures of NGLY1 deficiency'.

The cytosolic peptide:N-glycanase (PNGase; NGLY1 in human and PNG1 in budding yeast) is a deglycosylating enzyme widely conserved in eukaryotes. Initially, functional importance of this enzyme remained unknown as the png1Δ mutant in yeast did not exhibit any significant phenotypes. However, the discovery of NGLY1 deficiency, a rare genetic disorder with biallelic mutations in NGLY1 gene, prompted an intensification of research that has resulted in uncovering the significance of NGLY1 as well as the proteins under its influence that are involved in numerous cellular processes.

Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature.

Introduction: NGLY1-associated congenital disorder of deglycosylation (CDDG1: OMIM #615273) is a rare autosomal recessive disorder caused by a functional impairment of endoplasmic reticulum in degradation of glycoproteins. Neurocognitive dysfunctions have been documented in patients with CDDG1; however, deteriorating phenotypes of affected individuals remain elusive.

Case Presentation: A Japanese boy with delayed psychomotor development showed ataxic movements from age 5 years and myoclonic seizures from age 12 years.

Hydrolytic activity of yeast oligosaccharyltransferase is enhanced when misfolded proteins accumulate in the endoplasmic reticulum.

It is known that oligosaccharyltransferase (OST) has hydrolytic activity toward dolichol-linked oligosaccharides (DLO), which results in the formation of free N-glycans (FNGs), i.e. unconjugated oligosaccharides with structural features similar to N-glycans.

NGLY1: A fascinating, multifunctional molecule.

NGLY1, a cytoplasmic de-N-glycosylating enzyme is well conserved among eukaryotes. This enzyme has attracted considerable attention after mutations on the NGLY1 gene were found to cause a rare genetic disorder called NGLY1 deficiency. Recent explosive progress in NGLY1 research has revealed multi-functional aspects of this protein.

Amino acid editing of NFE2L1 by PNGase causes abnormal mobility on SDS-PAGE.

NFE2L1 (also known as NRF1) is a member of the nuclear erythroid 2-like family of transcription factors and is critical for counteracting various types of cellular stress such as oxidative, proteotoxic or metabolic stress. This unique transcription factor is also known to undergo changes, including post-translational modifications, limited proteolysis or translocation into the nucleus, before it exerts full transcriptional activity. As a result, there are various molecular forms with distinct sizes for this protein, while the precise nature of each form remains elusive.

Effects of Two Electron-Donating and/or -Withdrawing Substituents on Two-Photon Absorption for Diphenylacetylene Derivatives.

Two-photon absorption for diphenylacetylene (DPA) derivatives with two substituents (-OMe and/or -NO) at the 4,4'-position was investigated experimentally and theoretically. The two-photon absorption spectra and the two-photon absorption cross-sections σ for DPA derivatives were obtained by optical-probing photoacoustic spectroscopy (OPPAS). The simulated two-photon absorption spectra of the DPA derivatives, obtained with the time-dependent density functional theory within the Tamm-Dancoff approximation, agreed well with the experimental ones.

Relationship Between Cardiovascular Events and Serum Lipid and Plasma Fatty Acid Profile in Maintenance Hemodialysis Patients With Diabetic Mellitus.

Background/aim: Cardiovascular disease (CVD) is a frequent complication in hemodialysis (HD) patients, especially when the underlying disease is diabetes mellitus (DM). In this study, we investigated cardiovascular events and lipid and fatty acid profile in maintenance HD patients with diabetic kidney disease (DKD).

Patients And Methods: The subjects were 123 patients undergoing HD at Oyokyo Kidney Research Institute Hirosaki Hospital, who were considered to have DKD as the underlying cause of dialysis induction.

Synthesis of azafluoranthenes by iridium-catalyzed [2 + 2 + 2] cycloaddition and evaluation of their fluorescence properties.

We report a method for the synthesis of azafluoranthenes under neutral reaction conditions in a highly atom-economical manner by the iridium-catalyzed [2 + 2 + 2] cycloaddition of 1,8-dialkynylnaphthalenes with nitriles. A variety of nitriles react with methyl- or phenyl-substituted 1,8-dialkynylnaphthalenes to give a wide range of azafluoranthenes. Azafluoranthenes bearing an amino group show intense fluorescence at around 500 nm.

Mitotic phosphorylation inhibits the Golgi mannosidase MAN1A1.

N-glycans are processed mainly in the Golgi, and a well-organized Golgi structure is required for accurate glycosylation. However, during mitosis the Golgi undergoes severe fragmentation. The resulting trafficking block leads to an extended exposure of cargo molecules to Golgi enzymes.

Luminescence detection of peptide:-glycanase activity using engineered split inteins.

A split intein-based method has been developed to detect peptide:-glycanase (PNGase) activity in live cells. PNGase cleaves the linkage between '-diacetylchitobiose and the Asn side-chain of N-intein peptides and the products react rapidly with C-intein by protein trans-splicing to generate an active luciferase.

[Reviewing the Model Core Curriculum for Pharmacy Education and Fundamental Capacities to Become a Pharmacist with a 20-year Perspective on Human Resources Development].

The model core curriculum for pharmacy education (core curriculum) specifies the basics of 6-year pharmacy education. Pharmacy education is currently being provided based on the revised version of the core curriculum created in 2013 (revised core curriculum), with the aim of training pharmacists with the ability to fulfill social needs. The revised core curriculum also defines the "fundamental capacities to become a pharmacist" that should be acquired by the time of graduation.

TMEM2 expression is downregulated as bladder cancer invades the muscle layer.

Cell surface hyaluronidase transmembrane protein 2 (TMEM2), which also serves as a reportedly functions in malignancy of several solid tumors. However, TMEM2 involvement in bladder cancer (BCa) is unknown. Therefore, we investigate potential changes in expression of TMEM2 during BCa invasion and over the course of the epithelial mesenchymal transition (EMT).