The Oxidative Status and Na +/K + -ATPase Activity in Obsessive-Compulsive Disorder: A Case Control Study

Background: Oxidative stress is involved in pathogenesis of some psychiatric disorders. To examine the role of oxidative stress in the etiopathogenesis of obsessive-compulsive disorder (OCD), we aimed to determine oxidative stress indices, including MDA levels in serum and red blood cells (RBC) membrane, total antioxidant capacity (TAC), serum glutathione (GSH) levels, serum antioxidant vitamins (A and E) and Na+/K+-ATPase activity in patients with the mentioned disorder vs. healthy controls.Method: 39 OCD patients diagnosed based on Diagnostic and Statistical Manual of Mental Disorders (DSM-V), and 39 volunteers’ healthy subjects were included in this study. MDA levels in serum and RBC membrane were measured using fluorimetric method. Serum TAC level, serum GSH level and Na+/K+-ATPase activity were also measured using spectrophotometric methods. Serum levels of vitamins were calculated by Reversed-phase high-performance liquid chromatography (RP-HPLC).Result: There was a significantly higher MDA level in serum (p<0.0001) and RBC membrane (p=0.002) of OCD patients compared with those in controls. A significant reduction in vitamin A (p=0.024) and vitamin E (p=0.001) levels was found in OCD patients vs. controls. There was significantly lower activity of erythrocyte membrane Na+-K+ ATPase in RBC membrane of OCD patients vs. controls (p<0.0001).Conclusion: Our findings indicate significantly higher levels MDA in both serum and RBC membrane, lower levels of serum vitamin A and E, and lower activity of membrane Na+-K+ ATPase in OCD patients compared to controls. These suggest an imbalance between oxidant and antioxidant factors in OCD patients that might play a fundamental role in the etiopathogenesis of OCD.

A Gradient Harmonic Grammar Account of Nasals in Extended Phonological Words

The article aims at contributing to the long-standing research on the prosodic organization of linguistic elements and the criteria used for identifying prosodic structures. Our focus is on final coronal nasals in function words in Greek and the variability in their patterns of realization before lexical words. Certain nasals coalesce before stops and delete before fricatives, whereas others do not. We propose that this split in the behavior of nasals does not pertain to item-specific prosody because the relevant strings are uniformly prosodified into an extended phonological word (Itô & Mester 2007, 2009). It rather stems from the contrastive activity level of nasals in underlying forms in the spirit of Smolensky & Goldrick’s (2016) Gradient Symbolic Representations; nasals with lower activity coalesce and delete in the respective phonological environments, whereas those with higher activity do not. We show that the proposed analysis captures certain gradient effects that alternative analyses cannot account for.

Accelerometer-Derived Patterns of Physical Activity and Incident Frailty

Low physical activity (PA) is a common phenotype of frailty, but whether disengagement of daily lifestyle PA signals impending frailty remains unexplored. Using STURDY (Study to Understand Fall Reduction and Vitamin D in You) data from 499 robust/prefrail adults (mean age=76 + 5 years; 42% women), we examined whether accelerometer patterns (activity counts/day, active minutes/day, and activity fragmentation) were prospectively associated with incident frailty over 2 years of follow-up; 48 (10%) participants developed frailty. In Discrete-Cox hazard models adjusted for demographics, medical conditions, and device wear days, every 30 min/day higher baseline active time, 100,000 more activity counts/day, and 1% lower activity fragmentation was associated with a 13% (p=0.003), 10% (p=0.001), and 8% (p&lt;0.001) lower risk of frailty, respectively. Our results show that both reduced amounts and fragmented patterns of daily PA captured from accelerometry are associated with phenotypic frailty and might signal frailty onset.

Alleviation of Postharvest Chilling Injury of Carambola Fruit by γ-aminobutyric Acid: Physiological, Biochemical, and Structural Characterization

Chilling injury is a physiological disorder affecting the quality of carambola fruit. In the present study, the effect of exogenous γ-aminobutyric acid (GABA) on CI development in carambola fruit during storage at 4°C for 15 days was investigated. The results showed that 2.5-mM GABA reduced CI index, maintained pericarp lightness, and decreased the electrolyte leakage (EL) and malondialdehyde content (MDA) while increased the superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) enzyme activities. Endogenous GABA content was significantly higher in the treated fruit than in the control fruit during the whole storage. Besides, the treatment promoted the accumulation of proline and ascorbic acid (AsA) under chilling stress. Compared to the control, GABA-treated fruit exhibited a higher activity of phenylalanine ammonia-lyase (PAL) and total phenolic compounds, and a lower activity of polyphenol oxidase (PPO). In addition, the Safranin O/fast green staining revealed via microscopic images that the GABA treatment reduced the cell walls degradation of carambola fruit. Moreover, the results displayed a lower activity of phospholipase D (PLD) and lipoxygenase (LOX) enzymes, which coincided with a higher content of oleic acid (C18:1), linoleic acid (C18:2n6), and α-linolenic acid (C18:3n3) after 15 days of treatment, leading to the maintenance of the integrity and prevention of the membrane of the rapid softening of carambola fruit. The findings of the present work showed particularly new insights into the crosstalk between GABA and fatty acids. GABA might preserve the pericarp of carambola fruit by increasing the content of the unsaturated fatty acid (UFA) γ-linolenic acid and reducing the saturated fatty acid (SFA) such as caproic acid (C6:0), caprylic acid (C8:0), myristic acid (C14:0), and palmitic acid (C16:0) progressively. GABA can be used as an appropriate postharvest technology for improving the quality of carambola fruit during low-temperature storage.

Cross-neutralizing activity against SARS-CoV-2 variants in COVID-19 patients: Comparison of four waves of the pandemic in Japan

Background In March 2021, Japan is facing a 4th wave of SARS-CoV-2 infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but is not firmly established. Methods We investigated the neutralizing potency of 81 COVID-19 patients' sera from the 1st–4th waves of pandemic against SARS-CoV-2 D614G, B.1.1.7, P.1, and B.1.351 variants using their authentic viruses. Results Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the 4th wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The sera-neutralizing activity in less-severe patients was lower than that of more-severe patients for all variants. Conclusions The cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351. The high neutralizing activity specific for B.1.1.7 in the 4th wave suggests that the mutations in the virus might cause conformational change of its spike protein, which affects immune recognition for D614G. Our results indicate that individuals who recover from COVID-19 could be protected from the severity caused by infection with newly emerging variants.

Cross-neutralizing activity against SARS-CoV-2 variants in COVID-19 patients: Comparison of four waves of the pandemic in Japan

In March 2021, Japan is facing a 4th wave of SARS-CoV-2 infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but is not firmly established. We investigated the neutralizing potency of 81 COVID-19 patients' sera from 4 waves of pandemic against SARS-CoV-2 variants using their authentic viruses. Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the 4th wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351.

Genome editing in animals with minimal PAM CRISPR-Cas9 enzymes

The requirement for Cas nucleases to recognize a specific PAM is a major restriction for genome editing. SpCas9 variants SpG and SpRY, recognizing NGN and NRN PAM, respectively, have contributed to increase the number of editable genomic sites in cell cultures and plants. However, their use has not been demonstrated in animals. We have characterized and optimized the activity of SpG and SpRY in zebrafish and C. elegans. Delivered as mRNA-gRNA or ribonucleoprotein (RNP) complexes, SpG and SpRY were able to induce mutations in vivo, albeit at a lower rate than SpCas9 in equivalent formulations. This lower activity was overcome by optimizing mRNA-gRNA or RNP concentration, leading to efficient mutagenesis at regions inaccessible to SpCas9. We also found that the CRISPRscan algorithm can predict SpG and SpRY activity in vivo. Finally, we applied SpG and SpRY to generate knock-ins by homology-directed repair. Altogether, our results expand the CRISPR-Cas targeting genomic landscape in animals.

Applying time series analyses on continuous accelerometry data—A clinical example in older adults with and without cognitive impairment

Introduction Many clinical studies reporting accelerometry data use sum score measures such as percentage of time spent in moderate to vigorous activity which do not provide insight into differences in activity patterns over 24 hours, and thus do not adequately depict circadian activity patterns. Here, we present an improved functional data analysis approach to model activity patterns and circadian rhythms from accelerometer data. As a use case, we demonstrated its application in patients with mild cognitive impairment (MCI) and age-matched healthy older volunteers (HOV). Methods Data of two studies were pooled for this analysis. Following baseline cognitive assessment participants were provided with accelerometers for seven consecutive days. A function on scalar regression (FoSR) approach was used to analyze 24 hours accelerometer data. Results Information on 48 HOV (mean age 65 SD 6 years) and 18 patients with MCI (mean age 70, SD 8 years) were available for this analysis. MCI patients displayed slightly lower activity in the morning hours (minimum relative activity at 6:05 am: -41.3%, 95% CI -64.7 to -2.5%, p = 0.031) and in the evening (minimum relative activity at 21:40 am: -48.4%, 95% CI -68.5 to 15.4%, p = 0.001) as compared to HOV after adjusting for age and sex. Discussion Using a novel approach of FoSR, we found timeframes with lower activity levels in MCI patients compared to HOV which were not evident if sum scores of amount of activity were used, possibly indicating that changes in circadian rhythmicity in neurodegenerative disease are detectable using easy-to-administer accelerometry. Clinical trials Effects of Brain Stimulation During Nocturnal Sleep on Memory Consolidation in Patients With Mild Cognitive Impairments, ClinicalTrial.gov identifier: NCT01782391. Effects of Brain Stimulation During a Daytime Nap on Memory Consolidation in Patients With Mild Cognitive Impairment, ClinicalTrial.gov identifier: NCT01782365.

Tandem UGT71B5s Catalyze Lignan Glycosylation in Isatis indigotica With Substrates Promiscuity

Lignans are a class of chemicals formed by the combination of two molecules of phenylpropanoids with promising nutritional and pharmacological activities. Lignans glucosides, which are converted from aglycones catalyzed by uridine diphosphate (UDP) glycosyltransferases (UGTs), have abundant bioactivities. In the present study, two UGTs from Isatis indigotica Fort., namely IiUGT71B5a and IiUGT71B5b, were characterized to catalyze the glycosylation of lignans with promiscuities toward various sugar acceptors and sugar donors, and pinoresinol was the preferred substrate. IiUGT71B5a was capable of efficiently producing both pinoresinol monoglycoside and diglycoside. However, IiUGT71B5b only produced monoglycoside, and exhibited considerably lower activity than IiUGT71B5a. Substrate screening indicated that ditetrahydrofuran is the essential structural characteristic for sugar acceptors. The transcription of IiUGT71B5s was highly consistent with the spatial distribution of pinoresinol glucosides, suggesting that IiUGT71B5s may play biological roles in the modification of pinoresinol in I. indigotica roots. This study not only provides insights into lignan biosynthesis, but also elucidates the functional diversity of the UGT family.