Loss of Sfpq Causes Long-Gene Transcriptopathy in the Brain.

Genes specifically expressed in neurons contain members with extended long introns. Longer genes present a problem with respect to fulfilment of gene length transcription, and evidence suggests that dysregulation of long genes is a mechanism underlying neurodegenerative and psychiatric disorders. Here, we report the discovery that RNA-binding protein Sfpq is a critical factor for maintaining transcriptional elongation of long genes.

Acrolein as a Major Volatile in the Early Stages of Fish Oil TAG Oxidation.

Fish oil rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is known to have an unpleasant smell, even at low oxidation levels. Therefore, it is highly important to know the major volatiles formed during the early stages of fish oil oxidation. Comparative study with solid-phase microextraction (SPME) and static headspace (SHS) methods showed that 2-propenal (acrolein) was formed as the major volatile from the beginning of fish oil triacylglycerol (TAG) oxidation.

Development of a Caco-2 Cell Line Carrying the Human Intestine-Type CES Expression Profile as a Promising Tool for Ester-Containing Drug Permeability Studies.

Carboxylesterase 2 (CES2), which is a member of the serine hydrolase superfamily, is primarily expressed in the human small intestine, where it plays an important role in the metabolism of ester-containing drugs. Therefore, to facilitate continued progress in ester-containing drug development, it is crucial to evaluate how CES2-mediated hydrolysis influences its intestinal permeability characteristics. Human colon carcinoma Caco-2 cells have long been widely used in drug permeability studies as an enterocyte model.

Comparison Between the Pouch-Perineum Distance in Neonates With a Low-Type Anorectal Malformation With and Without an Opened Fistula: Pitfall of Measuring the Pouch-Perineum Distance on Sonography.

Objective: An anorectal malformation (ARM) in neonates requires urgent surgery, with the type of surgery being dependent on the type of malformation (low, intermediate, or high). Distal rectal pouch and perineum (pouch-perineum) distance is reported to be useful for differentiating the type of ARM; however, the impact of an opened fistula on pouch-perineum distance is not well known. The purpose of this study was to evaluate the difference in pouch-perineum distance between neonates with a low-type ARM with and without an opened fistula.

Molecular characterization and polymorphisms of butyrylcholinesterase in cynomolgus macaques.

Background: Butyrylcholinesterase (BChE), an enzyme essential for drug metabolism, has been investigated as antidotes against organophosphorus nerve agents, and the efficacy and safety have been studied in cynomolgus macaques. BChE polymorphisms partly account for variable BChE activities among individuals in humans, but have not been investigated in cynomolgus macaques.

Methods: Molecular characterization was carried out by analyzing primary sequence, gene, tissue expression, and genetic variants.

Chemical synthesis of an indomethacin ester prodrug and its metabolic activation by human carboxylesterase 1.

It is necessary to consider the affinity of prodrugs for metabolic enzymes for efficient activation of the prodrugs in the body. Although many prodrugs have been synthesized with consideration of these chemical properties, there has been little study on the design of a structure with consideration of biological properties such as substrate recognition ability of metabolic enzymes. In this report, chemical synthesis and evaluation of indomethacin prodrugs metabolically activated by human carboxylesterase 1 (hCES1) are described.

Detection and identification of furan fatty acids from fish lipids by high-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry.

Using high-performance liquid chromatography coupled to high-resolution electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC/ESI-Q-TOF-MS), we have developed a new method for detection and identification of furan fatty acids (F-acids), which are widely distributed in living organisms and foods as minor lipid components and are known to have antioxidant and anti-inflammatory effects. For this purpose, total fatty acids prepared from the testis lipids of Japanese chum salmon (Oncorhynchus keta) were examined without any concentration or isolation of F-acids. In negative ESI mode, F-acids gave a prominent [M-H] ion, by which individual F-acids could be detected and identified.

Combinatory use of distinct single-cell RNA-seq analytical platforms reveals the heterogeneous transcriptome response.

Single-cell RNA-seq is a powerful tool for revealing heterogeneity in cancer cells. However, each of the current single-cell RNA-seq platforms has inherent advantages and disadvantages. Here, we show that combining the different single-cell RNA-seq platforms can be an effective approach to obtaining complete information about expression differences and a sufficient cellular population to understand transcriptional heterogeneity in cancers.

Results of a Treat-and-Eextend Regimen of Intravitreal Ranibizumab Injection for Macular Edema due to Branch Retinal Vein Occlusion.

To investigate the effectiveness of a treat-and-extend regimen (TAE) of intravitreal ranibizumab injections (IVR) for macular edema (ME) due to branch retinal vein occlusion (BRVO). We retrospectively examined 35 eyes of 35 patients with ME due to BRVO who underwent TAE for 1 year. Patients whose treatment interval extended to 12 weeks were switched to a pro re nata regimen (PRN; TAE to PRN group), while TAE was continued for patients whose treatment interval was less than 12 weeks (continued TAE group).

Obtaining high-quality draft genomes from uncultured microbes by cleaning and co-assembly of single-cell amplified genomes.

Single-cell genomics is a straightforward approach to obtain genomes from uncultured microbes. However, sequence reads from a single-cell amplified genome (SAG) contain significant bias and chimeric sequences. Here, we describe Cleaning and Co-assembly of a Single-Cell Amplified Genome (ccSAG), a novel analytical workflow to obtain composite single-cell genomes with elimination of sequence errors.

Analysis of carboxylesterase 2 transcript variants in cynomolgus macaque liver.

Carboxylesterase (CES) is important for the detoxification of a wide range of drugs and xenobiotics. In this study, the hepatic level of CES2 mRNA was examined in cynomolgus macaques used widely in preclinical studies for drug metabolism. Three CES2 mRNAs were present in cynomolgus macaque liver.

Assessment of Lamellar Macular Hole and Macular Pseudohole With a Combination of En Face and Radial B-scan Optical Coherence Tomography Imaging.

Purpose: To investigate lamellar macular hole (LMH) and macular pseudohole (MPH) using a combination of en face and radial B-scan OCT.

Design: Retrospective observational case series.

Methods: Setting: Institutional study.

Effective Prevention of Oxidative Deterioration of Fish Oil: Focus on Flavor Deterioration.

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), both abundant in fish oil, are known to have significant biochemical and physiological effects primarily linked to the improvement of human health, especially cardiovascular and brain health. However, the incorporation of fish oil into foods and beverages is often challenging, as fish oil is very easily oxidized and can cause undesirable flavors. This review discusses this rapid formation of the fishy and metallic off-flavors, focusing especially on an early stage of fish oil oxidation.

Comparative Analysis of Chrysanthemum Stunt Viroid Accumulation and Movement in Two Chrysanthemum () Cultivars with Differential Susceptibility to the Viroid Infection.

Chrysanthemum stunt viroid (CSVd) was inoculated into two chrysanthemum () cultivars, the CSVd-susceptible cultivar Piato and the CSVd-resistant cultivar Mari Kazaguruma. For CSVd inoculation, grafting and -mediated inoculation were used. In grafting experiments, CSVd was detectable in Mari Kazaguruma after grafting onto infected Piato, but after removal of infected rootstocks, CSVd could not be detected in the uppermost leaves.

Factors affecting foveal avascular zone in healthy eyes: An examination using swept-source optical coherence tomography angiography.

Objective: To examine factors affecting foveal avascular zone (FAZ) area in healthy eyes using swept-source optical coherence tomography angiography (OCTA).

Methods: This prospective, cross-sectional study included 144 eyes of 144 individuals (77 women, 67 men) with a best corrected visual acuity of at least 20/20 and no history of ocular disorders. The area of the superficial FAZ was assessed using OCTA.

Monophosphorylation by deoxycytidine kinase affects apparent cellular uptake of decitabine in HCT116 colon cancer cells.

Decitabine (DAC), a nucleoside-related DNA methylation inhibitor, is taken up into cancer cells via equilibrative nucleoside transporter 1 (ENT1), and is then monophosphorylated by deoxycytidine kinase (dCK). In the present study, we examined the contribution of dCK to the uptake of DAC in HCT116 colon cancer cells. Irinotecan and etoposide inhibited the uptake of [H]-uridine and [H]-DAC at 10 s and 5 min, while cytarabine and gemcitabine only inhibited that of [H]-DAC at 5 min.

Distance Between the Distal Rectal Pouch and Perineum in Neonates of Low-Birth Weight With Imperforate Anus.

This study was to evaluate the correlation between birth weight and the distance between distal rectal pouch and perineum (P-P distance) and to determine a cutoff value for P-P distance to diagnose low-type imperforate anus in neonates with low-birth weight (LBW).We included 15 neonates with LBW (mean weight, 2012 ± 470 g; range, 906-2452 g) and imperforate anus (surgically confirmed: 11 low type and 3/1 intermediate/high type), who underwent ultrasonography on the day after birth. Type of imperforate anus was defined based on the International Classification of Anorectal Anomalies.

Histogen Layers Contributing to Adventitious Bud Formation Are Determined by their Cell Division Activities.

is propagated by adventitious buds in horticulture, and periclinal chimeral cultivars are usually difficult to propagate. However, some periclinal chimeral cultivars can be propagated with adventitious buds, and the mechanism of which has been unknown. Striped flower cultivars "Kaname," "Concord," and "Monique" were used to investigate what causes flower color separation in adventitious shoot-derived plants by tissue culture.

Post-transcriptional silencing of chalcone synthase is involved in phenotypic lability in petals and leaves of bicolor dahlia (Dahlia variabilis) 'Yuino'.

Post-transcriptional gene silencing (PTGS) of a chalcone synthase ( DvCHS2 ) occurred in the white part of bicolor petals and flavonoid-poor leaves; however, it did not in red petals and flavonoid-rich leaves. Petal color lability is a prominent feature of bicolor dahlia cultivars, and causes plants to produce not only original bicolor petals with colored bases and pure white tips, but also frequently single-colored petals without white tips. In this study, we analysed the molecular mechanisms that are associated with petal color lability using the red-white bicolor cultivar 'Yuino'.

Different Schedule-Dependent Effects of Epigenetic Modifiers on Cytotoxicity by Anticancer Drugs in Colorectal Cancer Cells.

Limited information is currently available on how to apply epigenetic modifiers to current colorectal cancer (CRC) chemotherapy. The purpose of this study is to clarify the schedule-dependent effects of combined treatment with conventional anticancer drugs and epigenetic modifiers in human CRC cells. Cytotoxicity in 4 CRC cell lines (SW480, HT29, SW48, and HCT116) was measured using the WST-8 assay.

Docosapentaenoic Acid (22:5n-3) Downregulates mRNA Expression of Pro-inflammatory Factors in LPS-activated Murine Macrophage Like RAW264.7 Cells.

Docosapentaenoic acid (22:5n-3, n-3 DPA) is a n-3 polyunsaturated fatty acid (PUFA) found in fish oil, and has been reported to have health benefits. This study investigated conversion of n-3 DPA, and examined the anti-inflammatory effects of n-3 DPA on activated macrophages. Murine macrophage-like RAW264.

PARI Regulates Stalled Replication Fork Processing To Maintain Genome Stability upon Replication Stress in Mice.

DNA replication is frequently perturbed by intrinsic, as well as extrinsic, genotoxic stress. At damaged forks, DNA replication and repair activities require proper coordination to maintain genome integrity. We show here that PARI antirecombinase plays an essential role in modulating the initial response to replication stress in mice.

Progranulin haploinsufficiency reduces amyloid beta deposition in Alzheimer's disease model mice.

Granulin (Grn) mutations were identified in familial frontotemporal lobar degeneration (FTLD) patients with TAR DNA-binding protein of 43 kd (TDP-43) pathology. Grn transcript haploinsufficiency is proposed as a disease mechanism that leads to the loss of functional progranulin (PGRN) protein. Thus, these mutations are strongly involved in FTLD pathogenesis.

Retinal sensitivity after displacement of submacular hemorrhage due to polypoidal choroidal vasculopathy: effectiveness and safety of subretinal tissue plasminogen activator.

Purpose: To investigate the effectiveness of displacement of submacular hemorrhage (SMH) caused by polypoidal choroidal vasculopathy (PCV) by assessing retinal sensitivity using microperimetry.

Methods: We retrospectively reviewed the medical records of 11 consecutive PCV patients with SMH. All patients underwent vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-air exchange, followed by antivascular endothelial growth factor therapy using a pro re nata regimen.