Incidence of anaphylactic reactions after propofol administration in dogs.

Propofol is an anesthetic agent suspended in an emulsion system that includes egg yolk lecithin and soybean oil, because of which, there is concern about the use of propofol in patients allergic to these substances. We examined the association between propofol administration and incidence of adverse events in dogs with allergy to egg yolk lecithin and soybean oil. On the basis of the findings of an allergen-specific immunoglobulin E (IgE) test, 14 dogs with high levels (high-IgE group) and 7 dogs with low levels (normal-IgE group) of IgE were selected.

Involvement of endoplasmic reticulum stress and neurite outgrowth in the model mice of autism spectrum disorder.

Neurodevelopmental disorders are congenital impairments, impeding the growth and development of the central nervous system. These disorders include autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder in Diagnostic and Statistical Manual of Mental Disorders-5. ASD is caused by a gene defect and chromosomal duplication.

Interactive Analysis of TX-1123 with Cyclo-oxygenase: Design of COX2 Selective TX Analogs.

Background: To date, two cyclo-oxygenase (COX) isoforms, COX1 and COX2, have been identified. In the present study, the COX-inhibitory activities of TX-1123 derivatives with the 2-hydroxyarylidene-4-cyclopentene-1,3-dione structure were examined, and the binding profiles of TX-1123 to COXs were analyzed using docking simulations.

Materials And Methods: X-Ray data on COX1 [protein data bank (PDB) ID=1PGG] and COX2 (PDB ID=3LN1) were used for molecular interactive simulations.

Easi-CRISPR: a robust method for one-step generation of mice carrying conditional and insertion alleles using long ssDNA donors and CRISPR ribonucleoproteins.

Background: Conditional knockout mice and transgenic mice expressing recombinases, reporters, and inducible transcriptional activators are key for many genetic studies and comprise over 90% of mouse models created. Conditional knockout mice are generated using labor-intensive methods of homologous recombination in embryonic stem cells and are available for only ~25% of all mouse genes. Transgenic mice generated by random genomic insertion approaches pose problems of unreliable expression, and thus there is a need for targeted-insertion models.

Activation of MMP-9 activity by acrolein in saliva from patients with primary Sjögren's syndrome and its mechanism.

We have recently reported that the altered recognition patterns of immunoglobulins due to acrolein conjugation are at least partially responsible for autoimmune diseases in patients with primary Sjögren's syndrome (pSS). In the current study, it was found that the specific activity (activity/ng protein) of metalloproteinase-9 (MMP-9) in saliva was elevated about 2.4-fold in pSS patients.

Virtual Clinical Studies to Examine the Probability Distribution of the AUC at Target Tissues Using Physiologically-Based Pharmacokinetic Modeling: Application to Analyses of the Effect of Genetic Polymorphism of Enzymes and Transporters on Irinotecan Induced Side Effects.

Purpose: To establish a physiologically-based pharmacokinetic (PBPK) model for analyzing the factors associated with side effects of irinotecan by using a computer-based virtual clinical study (VCS) because many controversial associations between various genetic polymorphisms and side effects of irinotecan have been reported.

Methods: To optimize biochemical parameters of irinotecan and its metabolites in the PBPK modeling, a Cluster Newton method was introduced. In the VCS, virtual patients were generated considering the inter-individual variability and genetic polymorphisms of enzymes and transporters.

Influenza A virus infection in Japanese wild boars (Sus scrofa leucomystax).

Serum samples were collected from 385 wild boars between 2010 and 2013 to examine the seroprevalence of influenza A virus (IAV) in Japan. Antibodies against IAV were identified using a commercial kit in 13 wild boars (3.4%).

Functional analysis of carboxylesterase in human induced pluripotent stem cell-derived enterocytes.

Human carboxylesterase (CES) is a key esterase involved in the metabolism and biotransformation of drugs. Hydrolysis activity in the human small intestine is predominantly mediated by CES2A1 rather than CES1A. In drug development studies, Caco-2 cells are commonly used as a model to predict drug absorption in the human small intestine.

Persistent Expression of Dopamine-Synthesizing Enzymes 15 Years After Gene Transfer in a Primate Model of Parkinson's Disease.

Restoring dopamine production in the putamen through gene therapy is a straightforward strategy for ameliorating motor symptoms for Parkinson's disease (PD). In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity-based primate model of PD, we previously showed the safety and efficacy of adeno-associated viral (AAV) vector-mediated gene delivery to the putamen of three dopamine-synthesizing enzymes (tyrosine hydroxylase [TH], aromatic l-amino acid decarboxylase [AADC], and guanosine triphosphate cyclohydrolase I [GCH]) up to 10 months postprocedure. Although three of four monkeys in this study have previously undergone postmortem analysis, one monkey was kept alive for 15 years after gene therapy to evaluate long-term effects.

Gene cassette knock-in in mammalian cells and zygotes by enhanced MMEJ.

Background: Although CRISPR/Cas enables one-step gene cassette knock-in, assembling targeting vectors containing long homology arms is a laborious process for high-throughput knock-in. We recently developed the CRISPR/Cas-based precise integration into the target chromosome (PITCh) system for a gene cassette knock-in without long homology arms mediated by microhomology-mediated end-joining.

Results: Here, we identified exonuclease 1 (Exo1) as an enhancer for PITCh in human cells.

Lgr4 Expression in Osteoblastic Cells Is Suppressed by Hydrogen Peroxide Treatment.

LGR4 is expressed in bone and has been shown to be involved in bone metabolism. Oxidative stress is one of the key issues in pathophysiology of osteoporosis. However, the link between Lgr4 and oxidative stress has not been known.

Correlation between brain damage, associated biomarkers, and medication in psychiatric inpatients: A cross-sectional study.

Background: We clarified the correlation between brain damage, associated biomarkers and medication in psychiatric patients, because patients with schizophrenia have an increased risk of stroke.

Methods: The cross-sectional study was performed from January 2013 to December 2015. Study participants were 96 hospitalized patients (41 men and 55 women) in the Department of Psychiatry at Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.

Nuclear and mitochondrial DNA analysis reveals that hybridization between Fasciola hepatica and Fasciola gigantica occurred in China.

The well-known pathogens of fasciolosis, Fasciola hepatica (Fh) and Fasciola Gigantica (Fg), possess abundant mature sperms in their seminal vesicles, and thus, they reproduce bisexually. On the other hand, aspermic Fasciola flukes reported from Asian countries, which have no sperm in their seminal vesicles, probably reproduce parthenogenetically. The aim of this study was to reveal the origin of aspermic Fasciola flukes.

Detection and Characterization of the Emerging Relapsing Fever Pathogen, Borrelia miyamotoi, from the Ixodes ricinus Tick in the Rural Trakya (Thrace) Region of Northwestern Turkey.

The hard tick-borne relapsing fever agent, Borrelia miyamotoi infection in Ixodes ricinus ticks sampled from Istanbul and the countryside of Kirklareli in northwestern Turkey, was examined by TaqMan-PCR targeting 16S rDNA, nested PCR targeting 16S rDNA, the flagellin gene (flaB), and the 16S and 23S rDNA intergenic spacer (IGS), and sequencing analyses of these amplicons. B. miyamotoi was detected in 1 out of 248 I.

Analysis of Macular Drusen and Blood Test Results in 945 Macaca fascicularis.

Age-dependent formation of macular drusen caused by the focal accumulation of extracellular deposits beneath the retinal pigment epithelium precede the development of age-related macular degeneration (AMD), one of the leading causes of blindness worldwide. It is established that inflammation contributes to the pathogenesis of drusen and AMD. However, development of a preemptive therapeutic strategy targeting macular drusen and AMD has been impeded by the lack of relevant animal models because most laboratory animals lack macula, an anatomic feature present only in humans and a subset of monkeys.

Molecular phylogeny of a genetically divergent hantavirus harbored by the Geoffroy's rousette (Rousettus amplexicaudatus), a frugivorous bat species in the Philippines.

The recent discovery of genetically distinct hantaviruses in multiple species of shrews and moles (order Eulipotyphla, families Soricidae and Talpidae) prompted a further exploration of their host diversification and geographic distribution by analyzing lung tissues from 376 fruit bats representing six genera (order Chiroptera, suborder Yinpterochiroptera, family Pteropodidae), collected in the Republic of the Philippines during 2008 to 2013. Hantavirus RNA was detected by RT-PCR in one of 15 Geoffroy's rousettes (Rousettus amplexicaudatus), captured in Quezon Memorial National Park on Luzon Island in 2009. Phylogenetic analyses of the S, M and L segments, using maximum-likelihood and Bayesian methods, showed that the newfound hantavirus, designated Quezon virus (QZNV), shared a common ancestry with hantaviruses hosted by insectivorous bats, in keeping with their evolutionary relationships and suggests that ancestral bats may have served as the early or original mammalian hosts of primordial hantaviruses.

Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2.

Proteoglycans (PGs), a family of glycosaminoglycan (GAG)-protein glycoconjugates, contribute to animal physiology through interactions between their glycan chains and growth factors, chemokines and adhesion molecules. However, it remains unclear how GAG structures are changed during the aging process. Here, we found that polyamine levels are correlated with the expression level of heparan sulfate (HS) in human skin.

Decrease in acrolein toxicity based on the decline of polyamine oxidases.

We have shown recently that acrolein is strongly involved in cell damage during brain infarction and chronic renal failure. To study the mechanism of acrolein detoxification, we tried to isolate Neuro2a cells with reduced sensitivity to acrolein toxicity (Neuro2a-ATD cells). In one cell line, Neuro2a-ATD1, the level of glutathione (GSH) was increased.

An Oral Aβ Vaccine Using a Recombinant Adeno-Associated Virus Vector in Aged Monkeys: Reduction in Plaque Amyloid and Increase in Aβ Oligomers.

With the objective to improve the amyloid-β (Aβ) targeting immunotherapy, we investigated the safety and efficacy of an oral vaccine with recombinant adeno-associated virus vector carrying a signal sequence and Aβ1-43 cDNA (rAAV/Aβ) in old non-human primates, 12 African green and 10 cynomolgus monkeys. The enteric-dissolving coated capsules containing rAAV/Aβ were orally administered once or twice, then monkeys' conditions were carefully observed with complete blood count and laboratory examinations of the sera. General conditions, food intake, water intake, stool conditions, body weight changes, and menstruation cycles were not significantly altered, and laboratory tests and pathological examinations of the systemic organs were unremarkable.

Genome-wide identification and gene expression profiling of ubiquitin ligases for endoplasmic reticulum protein degradation.

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a mechanism by which unfolded proteins that accumulate in the ER are transported to the cytosol for ubiquitin-proteasome-mediated degradation. Ubiquitin ligases (E3s) are a group of enzymes responsible for substrate selectivity and ubiquitin chain formation. The purpose of this study was to identify novel E3s involved in ERAD.

Effect of Spermidine Analogues on Cell Growth of Escherichia coli Polyamine Requiring Mutant MA261.

The effects of spermidine analogues [norspermidine (NSPD, 33), spermidine (SPD, 34), homospermidine (HSPD, 44) and aminopropylcadaverine (APCAD, 35)] on cell growth were studied using Escherichia coli polyamine-requiring mutant MA261. Cell growth was compared at 32°C, 37°C, and 42°C. All four analogues were taken up mainly by the PotABCD spermidine-preferential uptake system.

An Antitumor 2-Hydroxyarylidene-4-cyclopentene-1,3-Dione as a Protein Tyrosine Kinase Inhibitor: Interaction Between TX-1123 Derivatives and Src Kinase.

Background: Protein tyrosine kinases (PTKs) play major roles in signal transduction during cell proliferation and apoptosis. Tyrphostin AG17 was previously shown to be a potent tumor growth inhibitor, while AG17 induced apoptosis and inhibited activity of cyclin-dependent kinase 2. We herein describe the binding features of tyrphostin AG17 analogs, such as TX-1123, with Src kinase (Src-K).

[ER Stress-induced Aberrant Neuronal Maturation and Neurodevelopmental Disorders].

Neurodevelopmental disorders, which include autism spectrum disorder, are congenital impairments in the growth and development of the central nervous system. They are mainly accentuated during infancy and childhood. Autism spectrum disorder may be caused by environmental factors, genomic imprinting of chromosome 15q11-q13 regions, and gene defects such as those in genes encoding neurexin and neuroligin, which are involved in synaptogenesis and synaptic signaling.

Molecular mechanism underlying promiscuous polyamine recognition by spermidine acetyltransferase.

Spermidine acetyltransferase (SAT) from Escherichia coli, which catalyses the transfer of acetyl groups from acetyl-CoA to spermidine, is a key enzyme in controlling polyamine levels in prokaryotic cells. In this study, we determined the crystal structure of SAT in complex with spermidine (SPD) and CoA at 2.5Å resolution.