Anti-allergic effect of Cyclopia (honeybush) extracts via anti-degranulation activity in a murine allergy model for inhaled antigen.

The anti-allergic effects of extracts prepared from two species of honeybush, Cyclopia genistoides and Cyclopia subternata, were demonstrated in vivo in a murine allergy model for inhaled antigen induced with ovalbumin (OVA) inhalation to mimic pollen allergy. Intake of the extracts increased the production of OVA-specific immunoglobulin (Ig) E (IgE), IgG1, and IgG2a antibodies in serum and significantly suppressed anaphylactic reaction-induced body temperature decline. Moreover, the extracts significantly inhibited antigen-antibody-induced degranulation in RBL-2H3 cells. They also inhibited body temperature decline when the allergic mice were given them after antigen sensitization, indicating that anti-degranulation activity is the major mechanism underlying the anti-allergic effect of Cyclopia extracts. Despite their qualitative and quantitative differences in phenolic composition, the two extracts exhibited similar effects, suggesting that several active compounds might be involved in the activity. Therefore, oral administration of either Cyclopia extract potentially exerts a systemic anti-allergic effect, supporting the increased consumption of honeybush tea for general wellness and improved quality of life.

Simulation of the optical system in the GroundBIRD telescope.

GroundBIRD is a ground-based telescope for measuring the polarization of cosmic microwave background radiation, and it is soon to be operational at the Teide Observatory. The GroundBIRD telescope employs Mizuguchi-Dragone dual reflectors and 161 kinetic inductance detectors coupled with single polarization antennas as photon detectors. We present the results of our optical simulation on the pointing direction, stray light response, and influence of the blackbody radiation from the baffle. We also find that the power of the baffle radiation incident on the detectors is reduced by 99.95% when corrugated feed horns are coupled to the detectors.

Transcriptionally linked simultaneous overexpression of P450 genes for broad-spectrum herbicide resistance.

Broad-spectrum herbicide resistance (BSHR), often linked to weeds with metabolism-based herbicide resistance, poses a threat to food production. Past studies have revealed that overexpression of catalytically promiscuous enzymes explains BSHR in some weeds; however, the mechanism of BSHR expression remains poorly understood. Here, we investigated the molecular basis of high-level resistance to diclofop-methyl in BSHR late watergrass (Echinochloa phyllopogon) found in the United States, which cannot be solely explained by the overexpression of promiscuous cytochrome P450 monooxygenases CYP81A12/21. The BSHR late watergrass line rapidly produced 2 distinct hydroxylated diclofop acids, only 1 of which was the major metabolite produced by CYP81A12/21. RNA-seq and subsequent reverse transcription quantitative PCR (RT-qPCR)-based segregation screening identified the transcriptionally linked overexpression of a gene, CYP709C69, with CYP81A12/21 in the BSHR line. The gene conferred diclofop-methyl resistance in plants and produced another hydroxylated diclofop acid in yeast (Saccharomyces cerevisiae). Unlike CYP81A12/21, CYP709C69 showed no other herbicide-metabolizing function except for a presumed clomazone-activating function. The overexpression of the 3 herbicide-metabolizing genes was also identified in another BSHR late watergrass in Japan, suggesting a convergence of BSHR evolution at the molecular level. Synteny analysis of the P450 genes implied that they are located at mutually independent loci, which supports the idea that a single trans-element regulates the 3 genes. We propose that transcriptionally linked simultaneous overexpression of herbicide-metabolizing genes enhances and broadens the metabolic resistance in weeds. The convergence of the complex mechanism in BSHR late watergrass from 2 countries suggests that BSHR evolved through co-opting a conserved gene regulatory system in late watergrass.

Analysis of spontaneous speech in Parkinson's disease by natural language processing.

INTRODUCTION: Patients with Parkinson's disease (PD) encounter a variety of speech-related problems, including dysarthria and language disorders. To elucidate the pathophysiological mechanisms for linguistic alteration in PD, we compared the utterance of patients and that of healthy controls (HC) using automated morphological analysis tools. METHODS: We enrolled 53 PD patients with normal cognitive function and 53 HC, and assessed their spontaneous speech using natural language processing. Machine learning algorithms were used to identify the characteristics of spontaneous conversation in each group. Thirty-seven features focused on part-of-speech and syntactic complexity were used in this analysis. A support-vector machine (SVM) model was trained with ten-fold cross-validation. RESULTS: PD patients were found to speak less morphemes on one sentence than the HC group. Compared to HC, the speech of PD patients had a higher rate of verbs, case particles (dispersion), and verb utterances, and a lower rate of common noun utterances, proper noun utterances, and filler utterances. Using these conversational changes, the respective discrimination rates for PD or HC were more than 80%. CONCLUSIONS: Our results demonstrate the potential of natural language processing for linguistic analysis and diagnosis of PD.

Clinico-imaging features of subjects at risk of Lewy body disease in NaT-PROBE baseline analysis.

Individuals with prodromal symptoms of Lewy body disease (LBD), such as rapid eye movement sleep behavior disorder (RBD), often showed imaging defects similar to patients with Parkinson's disease and dementia with Lewy bodies. We examined dopamine transporter (DaT) single-photon-emission computed tomography (SPECT) and metaiodobenzylguanidine (MIBG) scintigraphy in 69 high-risk subjects with ≥2 prodromal symptoms (dysautonomia, hyposmia, and probable RBD) and 32 low-risk subjects without prodromal symptoms, whom were identified through a questionnaire survey of health checkup examinees. The high-risk subjects had significantly worse scores on Stroop test, line orientation test, and the Odor Stick Identification Test for Japanese than the low-risk subjects. The prevalence of abnormalities on DaT-SPECT was higher in the high-risk group than in the low-risk group (24.6% vs. 6.3%, p = 0.030). A decreased uptake on DaT-SPECT was associated with motor impairment, and MIBG scintigraphy defects were associated with hyposmia. The simultaneous evaluation of DaT-SPECT and MIBG scintigraphy may capture a wide range of individuals with prodromal LBD.

Functional improvements in ß-conglycinin by edible bioconjugation with carboxymethyl dextran.

ß-Conglycinin was conjugated with carboxymethyl dextran (CMD) by the Maillard reaction to improve its function. The ß-conglycinin-CMD conjugate was purified by dialysis. Conjugation was confirmed by SDS-PAGE with CBB and PAS staining. Composition of the ß-conglycinin-CMD was ß-conglycinin:CMD = 1:2.7 (molar ratio) which was confirmed by BCA method and phenol sulfuric acid method. Solubility of ß-conglycinin in the range of pH 2.0-7.0 was much improved by conjugation with CMD. Emulsifying property of ß-conglycinin at pH 7 and in presence of salt was improved by conjugation with CMD. Immunogenicity of ß-conglycinin was reduced by conjugation with CMD. Conjugation method performed in this study was considered to be valuable in that it can be used in food processing.

Functional improvements in ß-conglycinin by preparing edible bioconjugates with ε-polylysine and dextran.

ß-Conglycinin was conjugated with ε-polylysine (PL) by means of microbial transglutaminase (MTGase) to improve its function. The ß-conglycinin-PL conjugate was purified by dialysis. Composition of the ß-conglycinin-PL was ß-conglycinin:PL = 1:18 (molar ratio) which was confirmed by amino acid analysis. The ß-conglycinin-PL was further conjugated with dextran (Dex) by the Maillard reaction. The ß-conglycinin-PL-Dex conjugate was purified by dialysis. Conjugation was confirmed by SDS-PAGE and PAS staining. Composition of the ß-conglycinin-PL-Dex was ß-conglycinin-PL:Dex = 1:41 (molar ratio) which was confirmed by UV spectra measurement and phenol sulfuric acid method. Solubility of ß-conglycinin in the acidic range was much improved by conjugation with PL and further improved by further conjugation with Dex. Emulsifying property of ß-conglycinin in acidic pH range was much improved by conjugation with PL and Dex. Immunogenicity of ß-conglycinin was decreased by conjugation with PL and Dex.

Reduced immunogenicity and endowed antimicrobial activity in ß-lactoglobulin by preparing edible bioconjugate.

ß-lactoglobulin (BLG) and ε-polylysine (PL) were bound by using microbial transglutaminase. Dextran (Dex) was further conjugated to the BLG-PL conjugate by the Maillard reaction. Confirmation of conjugation was carried out by SDS-PAGE. From the results of isoelectric focusing, it was revealed that the isoelectric point of the BLG-PL conjugate was shifted to the basic side as compared with native BLG. Immunogenicity of BLG in BALB/c mice was lowered by conjugation with PL and further lowered by conjugation with Dex. By conjugation with PL and PL-Dex, antibacterial activity against Staphylococcus aureus was endowed to BLG. Because the conjugation method in this study is a safe method, it is valuable in that it can be applicable to food processing.

Site-specific glycosylation and single amino acid substitution dramatically reduced the immunogenicity of ß-lactoglobulin.

To reduce the immunogenicity of ß-lactoglobulin (BLG), we prepared recombinant BLG which has both site-specific glycosylation and single amino acid substitution (D28N/P126A), and expressed it in the methylotrophic yeast Pichia pastoris by fusion of the cDNA to the sequence coding for the α-factor signal peptide from Saccharomyces cerevisiae. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that the D28N/P126A was conjugated with a ∼4 kDa high-mannose chain. D28N/P126A retained ∼61% of the retinol-binding activity of BLG. Structural analyses by circular dichroism (CD) spectra, intrinsic fluorescence, and Enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies indicated that the surface structure of BLG was slightly changed by using protein engineering techniques, but D28N/P126A was covered by high-mannose chains and substituted amino acid without substantial disruption of native conformation. Antibody responses to the D28N/P126A considerably reduced in C57BL/6 mice. We conclude that inducing both site-specific glycosylation and single amino acid substitution simultaneously is an effective method to reduce the immunogenicity of BLG.

Reduced immunogenicity of ß-lactoglobulin by single amino acid substitution.

To reduce the immunogenicity of ß-lactoglobulin (BLG), we prepared single amino acid substituted recombinant BLG mutants (BLG/P126A, BLG/V128D and BLG/D129A) in the methylotrophic yeast Pichia Pastris by fusion of the cDNA to the sequence coding for the α-factor signal peptide from Saccharomyces cerevisiae. Isoelectric points of single amino acid substituted BLGs were lower than that of native BLG. CD spectra indicated that the secondary structure of BLG had maintained native structure in single amino acid substituted BLGs. Fluorescence studies indicated that the conformation around Trp had not changed in single amino acid substituted BLGs. Anti-BLG antibody response was evaluated after immunization to C57BL/6 mice. Antibody response was reduced after immunization with BLG/P126A, BLG/V128D and BLG/D129A. And novel immunogenicity was not observed in the experiments. T cell proliferative response was evaluated in C57BL/6 mice, and it was clarified that BLG mutants also showed low response. Methods employed in this study was considered to be very effective to reduce immunogenicity of BLG.

Effects of MAO-B inhibitors on non-motor symptoms and quality of life in Parkinson's disease: A systematic review.

Non-motor symptoms (NMS) are common among patients with Parkinson's disease and reduce patients' quality of life (QOL). However, there remain considerable unmet needs for NMS management. Three monoamine oxidase B inhibitors (MAO-BIs), selegiline, rasagiline, and safinamide, have become commercially available in many countries. Although an increasing number of studies have reported potential beneficial effects of MAO-BIs on QOL and NMS, there has been no consensus. Thus, the primary objective of this study was to provide an up-to-date systematic review of the QOL and NMS outcomes from the available clinical studies of MAO-BIs. We conducted a literature search using the PubMed, Scopus, and Cochrane Library databases in November 2021. We identified 60 publications relevant to this topic. Overall, rasagiline and safinamide had more published evidence on QOL and NMS changes compared with selegiline. This was likely impacted by selegiline being introduced many years prior to the field embarking on the study of NMS. The impact of MAO-BIs on QOL was inconsistent across studies, and this was unlikely to be clinically meaningful. MAO-BIs may potentially improve depression, sleep disturbances, and pain. In contrast, cognitive and olfactory dysfunctions are likely unresponsive to MAO-BIs. Given the paucity of evidence and controlled, long-term studies, the effects of MAO-BIs on fatigue, autonomic dysfunctions, apathy, and ICD remain unclear. The effects of MAO-BIs on static and fluctuating NMS have never been investigated systematically. More high-quality studies will be needed and should enable clinicians to provide personalized medicine based on a non-motor symptom profile.

Suppressive effect of the deep placement of lime nitrogen on N2O emissions in a soybean field.

Deep placement of slow-release nitrogen (N) fertilizers improves the growth and yield of soybean with a high N use efficiency. This study examined the effectiveness of deep placement of lime nitrogen (LN) in reducing N2O emissions in a soybean field and compared it with conventional fertilization. Before sowing soybeans, the starter N fertilizer (16 kg-N ha-1 ammonium sulfate) was mixed in the surface soil and the following four treatments were installed: the control with only the starter N (CT), conventional top-dressing of 60 kg-N ha-1 coated urea (CV), deep placement (20 cm depth) of 100 kg-N ha-1 urea (DU), and deep placement (20 cm depth) of 100 kg-N ha-1 LN (DL). The seasonal patterns of N2O emission rates measured using the closed chamber method differed among the treatments: in CT, N2O emissions were relatively low; in CV, N2O emissions derived from the top-dressed coated urea were observed from 91 days after sowing; in DU and DL, deeply-placed N was converted to N2O in the early growth stages. The cumulative N2O emissions in DL (1.8 kg-N ha-1) during the soybean cultivation period were significantly lower than those in DU (3.1 kg-N ha-1) and CV (2.8 kg-N ha-1), and slightly higher than CT (1.2 kg-N ha-1). The magnitude of N2O emissions was significantly lower in DL than DU, indicating that the choice of N fertilizer is important to reduce N2O emissions. Focusing on N2O emissions per unit coarse grain yield of soybeans, the value in DL was 0.45 g-N kg-1, which was significantly lower than 0.74 g-N kg-1 in CV. In conclusion, the deep placement of LN has the potential to be a sustainable farming method that can promote yields and reduce N2O emissions in soybean cultivation for high yield with N fertilization.

Instability of speech in Parkinson disease patients with subthalamic nucleus deep brain stimulation.

INTRODUCTION: The impact of deep brain stimulation (DBS) on speech rhythm and its mechanism remains unclear. We investigated speech rhythm characteristics of patients with Parkinson's disease (PD) treated with subthalamic nucleus (STN) DBS to understand the underlying pathophysiology better. METHODS: We enrolled a total of 105 participants and evaluated speech rhythm performances among patients with PD who had undergone STN-DBS (the PD-DBS group), patients with PD treated only with medication (the PD-Med group), patients with cerebellar ataxia (the CA group), and healthy controls (the HC group). Each participant was asked to repeat the syllable/pa/at a comfortable self-chosen steady pace. A widely-used software (the Motor Speech Profile) program performed an acoustic analysis. RESULTS: Compared to the PD-Med and HC groups, speech rate instability (DDKjit) was significantly higher in the PD-DBS and CA groups (p < 0.01). However, after DBS was turned off, the DDKjit of the PD-DBS group improved to a level comparable to that of the PD-Med and HC groups. In contrast to the significantly higher variability of speech volume (DDKcvi) in the CA group, the PD-DBS group showed similar DDKcvi to the PD-Med and HC groups. CONCLUSIONS: STN-DBS affects the speech rate stability of patients with PD. Speech rhythm disorders caused by STN-DBS were phenotypically similar to that in CA in terms of interval variability but different regarding amplitude variability. Further studies are warranted to elucidate the underlying pathophysiology of speech rhythm disorders in PD patients treated with DBS.

Preparation of hypoallergenic ovalbumin by high-temperature water treatment.

The high-temperature water treatment is one of the methods used to reduce the molecular weight of proteins. In this study, in order to establish a practical method for preparing hypoallergenic materials using the high-temperature water treatment, we investigated the effects of processing temperature on the antigenicity and allergenicity of a food allergen. Additionally, the foaming ability of the samples was also evaluated as a function desired in the food industry. We used ovalbumin as a model allergen. As a result, although there was no significant difference among the samples treated with different processing temperatures, all the antigens treated with high-temperature water showed a decrease in antigenicity and allergenicity. In addition, when ovalbumin was treated at a temperature of 130 °C or higher, there was a significant improvement in foaming properties. These findings indicate that high-temperature water treatment is a potential strategy for preparing practical hypoallergenic materials.

The Simons Observatory: metamaterial microwave absorber and its cryogenic applications.

Controlling stray light at millimeter wavelengths requires special optical design and selection of absorptive materials that should be compatible with cryogenic operating environments. While a wide selection of absorptive materials exists, these typically exhibit high indices of refraction and reflect/scatter a significant fraction of light before absorption. For many lower index materials such as commercial microwave absorbers, their applications in cryogenic environments are challenging. In this paper, we present a new tool to control stray light: metamaterial microwave absorber tiles. These tiles comprise an outer metamaterial layer that approximates a lossy gradient index anti-reflection coating. They are fabricated via injection molding commercially available carbon-loaded polyurethane (25% by mass). The injection molding technology enables mass production at low cost. The design of these tiles is presented, along with thermal tests to 1 K. Room temperature optical measurements verify their control of reflectance to less than 1% up to 65∘ angles of incidence, and control of wide angle scattering below 0.01%. The dielectric properties of the bulk carbon-loaded material used in the tiles is also measured at different temperatures, confirming that the material maintains similar dielectric properties down to 3 K.

The wide-ranging clinical and genetic features in Japanese families with valosin-containing protein proteinopathy.

Mutations in the valosin-containing protein (VCP) gene are known to cause various neurodegenerative disorders. Here, we report 8 Japanese patients [6 men, 2 women; median age at onset: 49.5 (range, 35-58) years] from 5 unrelated families with VCP missense mutations. Although 7 of 8 patients were diagnosed with either inclusion body myopathy or amyotrophic lateral sclerosis, 1 patient showed demyelinating polyneuropathy, which was confirmed by longitudinal nerve conduction studies. Sural nerve biopsy of the patient revealed intranuclear ubiquitin staining in Schwann cells. Three known pathogenic VCP mutations (p.Arg191Gln, p.Arg155Cys, and p.Ile126Phe) were detected. A novel mutation, c.293 A>T (p.Asp98Val), was also identified in a patient with amyotrophic lateral sclerosis and frontotemporal dementia. This mutation was predicted to be "deleterious" or "disease causing" using in silico mutation analyses. In conclusion, demyelinating polyneuropathy may be a novel phenotype caused by VCP mutations. The p.Asp98Val mutation was found to be a novel pathogenic mutation of VCP proteinopathy. We believe our cases represent a wide clinical spectrum of VCP mutations.

Aggravation of Food Allergy by Skin Sensitization via Systemic Th2 Enhancement.

BACKGROUND: Recently, the relationship between antigen contact via skin (skin sensitization) and the development of food allergies has gained increasing attention. However, few studies have examined the effects of skin sensitization on healthy skin. OBJECTIVE: To examine the effect of sensitization in healthy skin on IgE and cytokine production during food allergy development. METHODS: The effect of skin sensitization on food allergy was evaluated using DO11.10 mice whose T cells express ovalbumin (OVA)-specific T-cell receptors. OVA was applied to the back skin of mice dehaired by various methods, and then food allergy was induced by providing them with an OVA-containing diet. OVA-specific IgE production in the sera and decreases in body temperature due to anaphylactic reaction were measured as indicators of food allergy. In addition, IL-4 production and proliferation of splenocytes were measured in mice with food allergy after skin sensitization. RESULTS: Skin sensitization in healthy skin increased IgE production and exacerbated anaphylactic symptoms induced by ingesting the antigen. Moreover, skin sensitization enhanced IL-4 production from splenocytes during the onset of food allergy. In contrast, oral tolerance was induced even after establishing skin sensitization. CONCLUSION: Skin sensitization temporarily exacerbated food allergy by enhancing systemic Th2 responses. These findings will help identify the mechanisms involved in food allergy and help develop treatments.

Longitudinal analysis of premotor anthropometric and serological markers of Parkinson's disease.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder in which nonmotor symptoms, such as constipation and hyposmia, precede the onset of motor symptoms by 20 years. The aim of this study was to identify biomarkers at the premotor stage of PD. We assessed the differences in longitudinal changes in anthropometric and serological indices obtained from health check-up data before and after the onset of motor symptoms between male and female PD patients and healthy subjects. We enrolled 22 male and 23 female PD patients and 60 male and 60 female healthy controls. A mixed-effects model was used to estimate the trajectory of each clinical marker over the years before and after motor symptoms onset in the PD subjects, which were then compared with the trajectories of the healthy controls. The results showed a premotor blood pressure increase in female PD patients and premotor decreases in haematocrit, total cholesterol and low-density lipoprotein cholesterol in the male patients. Our results indicated that blood pressure, haematocrit and serum cholesterol levels are potential premotor markers of PD. Additionally, the changes in anthropometric and serological indices before PD motor symptoms onset were sex specific.

Subjects at risk of Parkinson's disease in health checkup examinees: cross-sectional analysis of baseline data of the NaT-PROBE study.

INTRODUCTION: The present study aimed to survey the prevalence of prodromal symptoms of Parkinson's disease (PD) in Japanese health checkup examinees, for identifying at-risk subjects. METHODS: We conducted a questionnaire survey of annual health checkup examinees without neurological symptoms using the following self-reported questionnaires: Japanese version of the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA-AUT); Self-administered Odor Question (SAOQ); REM Sleep Behavior Disorder Screening Scale (RBDSQ); Beck Depression Inventory-Second Edition (BDI-II); Epworth Sleepiness Scale (ESS); and Physical Activity Scale for the Elderly (PASE). The presence of prodromal symptoms was determined using the 90th percentile threshold of each questionnaire. Subjects ≥ 50 years of age with ≥ 2 core prodromal symptoms (dysautonomia, hyposmia, and RBD), were classified as at risk. RESULTS: Between March 2017 and March 2018, 4,953 participants sufficiently answered the questionnaires. Among 2,726 subjects ≥ 50 years of age, 155 were classified as at risk. These subjects had worse values of BDI-II (12.0 ± 8.3 vs. 4.4 ± 3.8, p < 0.001) and ESS (9.6 ± 5.0 vs. 6.3 ± 3.2, p < 0.001), in addition to SCOPA-AUT, SAOQ, and RBDSQ. Male at-risk subjects showed lower values of hemoglobin (14.8 ± 1.3 vs. 15.0 ± 1.1, p = 0.032) and low density lipoprotein cholesterol (114.5 ± 30.3 vs. 123.0 ± 28.9, p = 0.004) than the examinees reporting no prodromal symptoms. CONCLUSION: Approximately 6% of the population aged 50 years or older was at risk for PD. Male at-risk subjects had mild hematological and metabolic changes relevant to PD.