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Ticks are obligate haematophagous arthropods that feed on vertebrate blood containing high levels of iron. The host-derived iron reacts to oxygen in the tick's body, and then high levels of reactive oxygen species, including hydrogen peroxide (H2O2), may be generated. High levels of H2O2 cause oxidative stress to aerobic organisms. Therefore, antioxidant responses are necessary to control H2O2. We focused on peroxiredoxins (Prxs), H2O2-scavenging enzymes. The sequence of Haemaphysalis longicornis 2-Cys Prx (HlPrx2) was identified from fat body cDNA libraries of this tick and recombinant HlPrx2 was then pre- pared using Escherichia coli. By comparison with the 2-Cys Prxs of other organisms, we found two conserved cysteines in HlPrx2, Cys51 and Cys172. We examined the antioxidant activity of HlPrx2 and mutant proteins produced by a single base substitution, converting one or both of these cysteines into serines. The assays revealed that proteins containing Cys51 showed antioxidant activity when H2O2 was removed. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and size-exclusion chromatography demonstrated that only the wild-type HlPrx2 formed homodimers and that all of the proteins that we made had a high molecular weight peak. These results indicate that both Cys51 and Cys172 are essential for the dimerization of HlPrx2, whereas only the Cys51 residue is necessary for antioxidant activity. [ABSTRACT FROM AUTHOR]

Resting-state functional connectivity (FC) is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. For instance, studies in pre-clinical AD subjects have shown increases of cerebral spinal fluid soluble platelet-derived growth factor receptor-β (CSF sPDGFRβ, a marker of BBB breakdown) but have not demonstrated if this vascular impairment affects neuronal dysfunction. It's possible that increased levels of sPDGFRβ in the CSF may correlate with impaired FC in metabolically demanding brain regions (i.e. Default Mode Network, DMN). Our study aimed to investigate the relationship between these two markers in older individuals that were cognitively normal and had cognitive impairment. Eighty-nine older adults without dementia from the University of Southern California were selected from a larger cohort. Region of interest (ROI) to ROI analyses were conducted using DMN seed regions. Linear regression models measured significant associations between BOLD FC strength among seed-target regions and sPDGFRβ values, while covarying for age and sex. Comparison of a composite ROI created by averaging FC values between seed and all target regions among cognitively normal and impaired individuals was also examined. Using CSF sPDGFRβ as a biomarker of BBB breakdown, we report that increased breakdown correlated with decreased functional connectivity in DMN areas, specifically the PCC, and while the hippocampus exhibited an interaction effect using CDR score, this was an exploratory analysis that we feel can lead to further research. Ultimately, we found that BBB breakdown, as measured by CSF sPDGFRβ, is associated with neural networks, and decreased functional connections., (© 2024. The Author(s).)

[Purpose] This study aimed to examine falls among older adults in Japanese households and determine the risk associated with each fall location. [Participants and Methods] This study included 99 participants (249 fall events) who received daycare rehabilitation at a nursing care facility. Data on fall circumstances were collected from the medical records and accident reports. The analyzed variables included age, medical status, level of care required, fall history, location, and mode of transportation during the falls. [Results] Falls occurred most commonly in bedrooms. Falls at an entrance were associated with no assistive device (OR: 1.76, 95% CI: 1.06-1.80) and 1 history of falls (OR: 1.22, 95% CI: 1.03-3.10). Risk factors for falls in bedrooms included Parkinson's disease (OR: 1.83, 95% CI: 1.11-1.87), orthopedic disease (OR: 1.11, 95% CI: 1.15-3.43), and cane walking (OR: 1.08, 95% CI: 1.33-4.13). Falls in a hallway were associated with no assistive device (OR: 1.75, 95% CI: 1.15-1.91). [Conclusion] Bedrooms and hallways in Japanese households were identified as locations with a high risk of falls. The unique architectural and cultural features of Japanese homes may contribute to this risk. Rehabilitation programs should consider individual fall histories, medical conditions, and differences in mobility., Competing Interests: There are no conflicts of interest to disclose in this study., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

[Purpose] The aim in this study was to evaluate the impact of caregiver understanding of their ability to perform activities of daily living (ADLs), movement abilities, diseases, and attitudes on the prevalence of occupational low back pain. [Participants and Methods] A cross-sectional survey was conducted of caregivers of older adults living in residential care facilities. Of the 150 questionnaires distributed, 71 were valid. The survey collected data on demographics, low back pain status using a numerical rating scale, and familiarity with ten ADLs and five diseases (stroke, rheumatoid arthritis, fractures, Parkinson's disease, and dementia). [Results] In this study, 52% of the participants reported lower back pain. Significant factors included an understanding of repositioning in ADLs, familiarity with stroke and rheumatoid arthritis, and attitudes toward using patients' residual functions. Participants with limited knowledge of repositioning and stroke, a better understanding of rheumatoid arthritis, and those who did not consider residual function were more prone to lower back pain. [Conclusion] Our findings highlight the importance of enhancing caregiver education on ADL movements and disease specifics, particularly stroke and rheumatoid arthritis, and promoting the use of patients' residual capabilities. Improved training and information sharing among caregivers may reduce the risk of occupational low back pain., Competing Interests: There are no conflicts of interest to disclose in this study., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

[Purpose] This study investigated whether pre-season HAGOS (Japanese Copenhagen Hip and Groin Outcome Scores) and eccentric muscle strength of the hip muscles predict in-season groin pain incidences in high school soccer players. [Participants and Methods] This study had a cohort design. The participants were male high school players under 18 years playing in the Japan Soccer League, which is an elite-level soccer league of that age category in Japan. The HAGOS and the strength of hip abductor and adductor muscles in eccentric contraction were measured before the season, and hip and groin pain incidences were recorded during the season. Multiple logistic regression analysis was performed to investigate the factors derived from the pre-season HAGOS and hip muscle strength tests, presumably pertaining to the development of in-season groin pain. [Results] The eccentric adductor muscle strength of the dominant leg and the HAGOS were selected as factors associated with groin pain during the season. [Conclusion] Low pre-season HAGOS and weak dominant-leg eccentric adductor muscle strength were suggested as factors to predict in-season groin pain occurrence in male high school soccer players., Competing Interests: The authors declare that they have no funding or competing interests., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Gentians ( Gentiana spp.) as floriculture crops are constantly exposed to several fungal and viral pathogens in the field. Among the fungal diseases afflicting gentian production, gentian sclerotial flower blight caused by Ciborinia gentianae incurs economic losses, as it affects flowers before and after harvest. Currently, preventive measures for this disease are limited, and no resistant cultivars have been reported. This is partly because of the lack of a reliable infection system that could promote research on this plant-fungus interaction. In this study, Gentiana plant tissue culture material was inoculated with C. gentianae culture filtrate. We successfully demonstrated non-ascospore-mediated infection of C. gentianae . Inoculation of individual hyphal structures present in the culture filtrate suggested that sclerotial primordia are the main agents of this infection. Interestingly, our results indicated that primary infection of C. gentianae occurs in petals rather than leaves, which enables systemic infection and therefore mirrors the fungus's infection strategy observed in the field. Moreover, we showed that (i) non-ascospore hyphal structures can also cause disease in flowers grown in the field, and (ii) ascosporic infection can also be observed using the in vitro system, opening possibilities for both practical and basic research aimed to combat gentian sclerotial flower blight disease., Competing Interests: The author(s) declare no conflict of interest.

During the perinatal period, the immune system sets the threshold to select either response or tolerance to environmental Ags, which leads to the potential to provide a lifetime of protection and health. B-1a B cells have been demonstrated to develop during this perinatal time window, showing a unique and restricted BCR repertoire, and these cells play a major role in natural Ab secretion and immune regulation. In the current study, we developed a highly efficient temporally controllable RAG2-based lymphoid lineage cell labeling and tracking system and applied this system to understand the biological properties and contribution of B-1a cells generated at distinct developmental periods to the adult B-1a compartments. This approach revealed that B-1a cells with a history of RAG2 expression during the embryonic and neonatal periods dominate the adult B-1a compartment, including those in the bone marrow (BM), peritoneal cavity, and spleen. Moreover, the BCR repertoire of B-1a cells with a history of RAG2 expression during the embryonic period was restricted, becoming gradually more diverse during the neonatal period, and then heterogeneous at the adult stage. Furthermore, more than half of plasmablasts/plasma cells in the adult BM had embryonic and neonatal RAG2 expression histories. Moreover, BCR analysis revealed a high relatedness between BM plasmablasts/plasma cells and B-1a cells derived from embryonic and neonatal periods, suggesting that these cell types have a common origin. Taken together, these findings define, under native hematopoietic conditions, the importance in adulthood of B-1a cells generated during the perinatal period., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Filamentous plant pathogens deliver effector proteins into host cells to suppress host defence responses and manipulate metabolic processes to support colonization. Understanding the evolution and molecular function of these effectors provides knowledge about pathogenesis and can suggest novel strategies to reduce damage caused by pathogens. However, effector proteins are highly variable, share weak sequence similarity and, although they can be grouped according to their structure, only a few structurally conserved effector families have been functionally characterized to date. Here, we demonstrate that Zinc-finger fold (ZiF) secreted proteins form a functionally diverse effector family in the blast fungus Magnaporthe oryzae. This family relies on the Zinc-finger motif for protein stability and is ubiquitously present in blast fungus lineages infecting 13 different host species, forming different effector tribes. Homologs of the canonical ZiF effector, AVR-Pii, from rice infecting isolates are present in multiple M. oryzae lineages. Wheat infecting strains of the fungus also possess an AVR-Pii like allele that binds host Exo70 proteins and activates the immune receptor Pii. Furthermore, ZiF tribes may vary in the proteins they bind to, indicating functional diversification and an intricate effector/host interactome. Altogether, we uncovered a new effector family with a common protein fold that has functionally diversified in lineages of M. oryzae. This work expands our understanding of the diversity of M. oryzae effectors, the molecular basis of plant pathogenesis and may ultimately facilitate the development of new sources for pathogen resistance., Competing Interests: SK receives funding from Industry on NLR biology., (Copyright: © 2024 Concepcion et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We previously reported that brain atrophy was more severe and progressed more rapidly in patients with end-stage kidney disease on peritoneal dialysis (PD) than those with non-dialysis-dependent chronic kidney disease. However, it remains unknown whether there is a difference between patients on PD and hemodialysis (HD). In total, 73 PD and 34 HD patients who underwent brain magnetic resonance imaging (MRI) were recruited for a cross-sectional analysis. Among them, 42 PD and 25 HD patients who underwent a second brain MRI after 2 years were recruited for a longitudinal analysis. T1-weighted MRI images were analyzed. Total gray matter volume (GMV), total white matter volume, and cerebrospinal fluid volume were segmented, and each volume was quantified using statistical parametric mapping software. The ratio of GMV (GMR) was calculated by dividing GMV by intracranial volume, to adjust for variations in head size. We compared GMR between PD and HD patients in the cross-sectional analysis and the annual change in GMR (AC-GMR) in the longitudinal analysis. In the cross-sectional analysis, age- and sex-adjusted GMR was significantly lower in PD than HD patients [least square mean (LSM): 39.2% vs. 40.0%, P = 0.018]. AC-GMR was significantly greater in PD than HD patients and this difference remained significant even after adjustment for potential confounding factors (LSM: -0.68 vs. -0.28 percentage-points/year, P = 0.011). In conclusion, the present study demonstrated a more rapid progression of brain atrophy in PD patients compared with HD patients. We demonstrated that decline in GMR progressed significantly more rapidly in PD than HD patients independent of potential confounding factors. GMR gray matter volume ratio, HD hemodialysis, PD peritoneal dialysis., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Introduction: QT interval prolongation is a risk factor for fatal arrhythmias and other cardiovascular complications. QT interval prolongation in patients on hemodialysis (HD) is not well understood. Hypocalcemia is a suspected, but poorly verified etiology in these patients, and the association between serum phosphorus levels and QT interval prolongation is unknown. We sought to determine the prevalence of QT interval prolongation in patients on HD and to verify the association between predialysis serum calcium (Ca) and phosphate (P) levels and QT interval prolongation., Methods: A cross-sectional study was conducted on adult patients on maintenance HD who were enrolled in the Japanese Society for Dialysis Therapy and Renal Data Registry 2019. After assessing patient characteristics, linear regression analysis was performed with predialysis serum Ca and P levels as exposures and a rate-corrected QT (QTc) interval as the outcome., Results: A total of 204,530 patients were analyzed with a mean QTc of 451.2 (standard deviation, 36.9) ms. After multivariable analysis, estimated change in QTc (coefficients; 95% confidence interval) per 1 mg/dl increase in serum Ca and P was -2.02 (-3.00 to -1.04) and 5.50 (3.92-7.09), respectively. In the restricted cubic spline curve, estimated change in QTc increased with lower values of serum Ca. The correlation between serum P and QTc showed a U-shaped curve., Conclusion: Decreased serum Ca levels and decreased and increased serum P levels may be associated with QT interval prolongation in patients on maintenance HD., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Plant nucleotide-binding leucine-rich repeat (NLRs) immune receptors directly or indirectly recognize pathogen-secreted effector molecules to initiate plant defense. Recognition of multiple pathogens by a single NLR is rare and usually occurs via monitoring for changes to host proteins; few characterized NLRs have been shown to recognize multiple effectors. The barley (Hordeum vulgare) NLR gene Mildew locus a (Mla) has undergone functional diversification, and the proteins encoded by different Mla alleles recognize host-adapted isolates of barley powdery mildew (Blumeria graminis f. sp. hordei [Bgh]). Here, we show that Mla3 also confers resistance to the rice blast fungus Magnaporthe oryzae in a dosage-dependent manner. Using a forward genetic screen, we discovered that the recognized effector from M. oryzae is Pathogenicity toward Weeping Lovegrass 2 (Pwl2), a host range determinant factor that prevents M. oryzae from infecting weeping lovegrass (Eragrostis curvula). Mla3 has therefore convergently evolved the capacity to recognize effectors from diverse pathogens., Competing Interests: Conflict of interest statement. None declared., (Published by Oxford University Press on behalf of American Society of Plant Biologists 2023.)

Diabetic nephropathy (DN) is a major complication of diabetes. Nonalcoholic fatty liver disease (NAFLD) is common in diabetes, and liver fibrosis is a prognostic risk factor for NAFLD. The interaction between DN and liver fibrosis in NAFLD remains unclear. In 189 patients with DN and NAFLD who received an education course about diabetic nephropathy, liver fibrosis was evaluated using the fibrosis-4 (FIB-4) index. The association between the outcome of DN and changes in liver fibrosis was examined. The FIB-4 index was maintained at the baseline level in patients with improved DN, while it was increased in other patients. The ΔFIB-4 index was positively correlated with changes in albuminuria and proteinuria (ρ = 0.22, p = 0.004). In a multivariate analysis, changes in albuminuria and proteinuria were associated with the ΔFIB-4 index ( p = 0.002). Patients with a progressive FIB-4 index category from baseline to 5 years showed a lower event-free survival rate after 5 years than patients with an improved FIB-4 index category ( p = 0.037). The outcome of DN is associated with changes in liver fibrosis in patients with diabetes, NAFLD and DN. Developing a preventive and therapeutic approach for these conditions is required.