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1.
Int J Mol Sci ; 25(5)2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38473789

ABSTRACT

In the adult mammalian brain, neurons are produced from neural stem cells (NSCs) residing in two niches-the subventricular zone (SVZ), which forms the lining of the lateral ventricles, and the subgranular zone in the hippocampus. Epigenetic mechanisms contribute to maintaining distinct cell fates by suppressing gene expression that is required for deciding alternate cell fates. Several histone deacetylase (HDAC) inhibitors can affect adult neurogenesis in vivo. However, data regarding the role of specific HDACs in cell fate decisions remain limited. Herein, we demonstrate that HDAC8 participates in the regulation of the proliferation and differentiation of NSCs/neural progenitor cells (NPCs) in the adult mouse SVZ. Specific knockout of Hdac8 in NSCs/NPCs inhibited proliferation and neural differentiation. Treatment with the selective HDAC8 inhibitor PCI-34051 reduced the neurosphere size in cultures from the SVZ of adult mice. Further transcriptional datasets revealed that HDAC8 inhibition in adult SVZ cells disturbs biological processes, transcription factor networks, and key regulatory pathways. HDAC8 inhibition in adult SVZ neurospheres upregulated the cytokine-mediated signaling and downregulated the cell cycle pathway. In conclusion, HDAC8 participates in the regulation of in vivo proliferation and differentiation of NSCs/NPCs in the adult SVZ, which provides insights into the underlying molecular mechanisms.


Subject(s)
Adult Stem Cells , Neural Stem Cells , Percutaneous Coronary Intervention , Animals , Mice , Lateral Ventricles , Histone Deacetylase Inhibitors , Cell Proliferation , Mammals
2.
Osteoporos Int ; 35(3): 469-494, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38228807

ABSTRACT

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.


Subject(s)
Hip Fractures , Osteoporotic Fractures , Male , Humans , Female , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/etiology , Prospective Studies , Risk Assessment , Cohort Studies , Risk Factors , Bone Density , Hip Fractures/etiology , Hip Fractures/complications
3.
ACS Infect Dis ; 9(11): 2226-2251, 2023 11 10.
Article in English | MEDLINE | ID: mdl-37850869

ABSTRACT

The latest RNA genomic mutation of SARS-CoV-2 virus, termed the Omicron variant, has generated a stream of highly contagious and antibody-resistant strains, which in turn led to classifying Omicron as a variant of concern. We systematically collected Raman spectra from six Omicron subvariants available in Japan (i.e., BA.1.18, BA.2, BA.4, BA.5, XE, and BA.2.75) and applied machine-learning algorithms to decrypt their structural characteristics at the molecular scale. Unique Raman fingerprints of sulfur-containing amino acid rotamers, RNA purines and pyrimidines, tyrosine phenol ring configurations, and secondary protein structures clearly differentiated the six Omicron subvariants. These spectral characteristics, which were linked to infectiousness, transmissibility, and propensity for immune evasion, revealed evolutionary motifs to be compared with the outputs of genomic studies. The availability of a Raman "metabolomic snapshot", which was then translated into a barcode to enable a prompt subvariant identification, opened the way to rationalize in real-time SARS-CoV-2 activity and variability. As a proof of concept, we applied the Raman barcode procedure to a nasal swab sample retrieved from a SARS-CoV-2 patient and identified its Omicron subvariant by coupling a commercially available magnetic bead technology with our newly developed Raman analyses.


Subject(s)
COVID-19 , Humans , SARS-CoV-2/genetics , Spectrum Analysis, Raman , RNA
4.
Sci Rep ; 13(1): 17420, 2023 10 13.
Article in English | MEDLINE | ID: mdl-37833453

ABSTRACT

A variety of easy-to-use commercial bioelectrical impedance appliances are available. The aim of this study was to examine the usefulness of a commercially available body composition meter using bioelectrical impedance analysis (BIA) by comparing its measurement results with those obtained from dual-energy X-ray absorptiometry (DXA). The participants were 443 children aged from 10 to 14 years (226 boys and 217 girls). Fat mass, fat-free mass, lean body mass, percentage of body fat, and bone mineral contents were evaluated for all participants using BIA and DXA. The agreement in the anthropometric data obtained from both devices was analyzed using correlation analysis, intraclass correlation coefficient (ICC), Lin's concordance correlation coefficient (CCC), Bland-Altman plots, and ordinary least products regression analysis. Equivalence between both devices was tested by two one-sided t-test. All measured indicators showed strong linear correlations between the two measurement systems (r, 0.853-1.000). Fat mass, fat-free mass, and lean body mass showed absolute concordance (ICC, 0.902-0.972; Lin's CCC, 0.902-0.972). BIA overestimated bone mineral content (62.7-66.5%) and underestimated percentage of body fat (- 8.9 to - 0.8%), lean body mass (- 3.5 to - 1.8%), and body mass (- 0.8 to - 0.5%). For fat mass and fat-free mass, the overestimate or underestimate varied according to the sex and statistical analysis test. Bland-Altman analysis and ordinary least products analysis showed fixed bias and proportional bias in all indicators. Results according to quartiles of body mass index showed poor agreement for fat mass and percentage of body fat in both boys and girls in the lowest body mass index quartile. The present results revealed strong linear correlations between BIA and DXA, which confirmed the validity of the present single-frequency BIA-derived parameters. Our results suggest that BIA cannot provide the exact same values as DXA for some body composition parameters, but that performance is sufficient for longitudinal use within an individual for daily health management and monitoring.


Subject(s)
Breast Neoplasms , Precancerous Conditions , Male , Female , Humans , Child , Adolescent , Absorptiometry, Photon/methods , Electric Impedance , Body Composition , Adipose Tissue/diagnostic imaging , Anthropometry , Body Mass Index
5.
Commun Biol ; 6(1): 665, 2023 06 23.
Article in English | MEDLINE | ID: mdl-37353538

ABSTRACT

Cellular senescence, a state of irreversible cell-cycle arrest caused by a variety of cellular stresses, is critically involved in age-related tissue dysfunction in various organs. However, the features of cells in the central nervous system that undergo senescence and their role in neural impairment are not well understood as yet. Here, through comprehensive investigations utilising single-cell transcriptome analysis and various mouse models, we show that microglia, particularly in the white matter, undergo cellular senescence in the brain and spinal cord during ageing and in disease models involving demyelination. Microglial senescence is predominantly detected in disease-associated microglia, which appear in ageing and neurodegenerative diseases. We also find that commensal bacteria promote the accumulation of senescent microglia and disease-associated microglia during ageing. Furthermore, knockout of p16INK4a, a key senescence inducer, ameliorates the neuroinflammatory phenotype in damaged spinal cords in mice. These results advance our understanding of the role of cellular senescence in the central nervous system and open up possibilities for the treatment of age-related neural disorders.


Subject(s)
Microglia , White Matter , Mice , Animals , Aging/physiology , Cellular Senescence/physiology , Phenotype
6.
Article in English | MEDLINE | ID: mdl-37183008

ABSTRACT

BACKGROUND: Central obesity as measured by waist-to-hip circumference ratio (WHR) has been reported to be associated with renal hemodynamics and function. However, the adipose component of WHR, which is a composite measure of fat mass and fat-free mass, is small, particularly in nonobese subjects. Trunk-to-peripheral fat ratio as measured using dual-energy absorptiometry (DXA) is a more precise method for evaluating central fat distribution than WHR. The present study investigated the cross-sectional association between DXA-measured trunk-to-peripheral fat ratio and estimated glomerular filtration rate (eGFR) in community-dwelling elderly Japanese men. METHODS: Participants were 575 men aged ≥65 years at the time of the baseline survey of the second Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study. Trunk-to-appendicular fat ratio (TAR) was calculated as trunk fat divided by appendicular fat (sum of arm and leg fat), and trunk-to-leg fat ratio (TLR) as trunk fat divided by leg fat. RESULTS: eGFR values significantly decreased from the lowest to the highest quintile of TAR/TLR. After adjusting for potential confounding factors including whole-body fat, the highest quintile of both TAR and TLR showed statistically significant odds ratios for the risk of eGFR <60 ml/min/1.73 m2, relative to the lowest quintile. In addition, a significant decreasing trend was observed for eGFR values from the lowest to the highest quintile of TAR/TLR after adjusting for confounding factors including whole-body fat. CONCLUSION: Elderly men with a large trunk-to-peripheral fat ratio tended to have a lower eGFR. This association occurred independently of that between whole-body fat and eGFR.


Subject(s)
East Asian People , Osteoporosis , Risk Factors , Aged , Humans , Male , Absorptiometry, Photon/methods , Body Mass Index , Cohort Studies , Cross-Sectional Studies , Kidney/physiology , Obesity , Osteoporosis/epidemiology , Osteoporosis/etiology , Adiposity
7.
Genet Med ; 25(7): 100861, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37087635

ABSTRACT

PURPOSE: This study aimed to establish variants in CBX1, encoding heterochromatin protein 1ß (HP1ß), as a cause of a novel syndromic neurodevelopmental disorder. METHODS: Patients with CBX1 variants were identified, and clinician researchers were connected using GeneMatcher and physician referrals. Clinical histories were collected from each patient. To investigate the pathogenicity of identified variants, we performed in vitro cellular assays and neurobehavioral and cytological analyses of neuronal cells obtained from newly generated Cbx1 mutant mouse lines. RESULTS: In 3 unrelated individuals with developmental delay, hypotonia, and autistic features, we identified heterozygous de novo variants in CBX1. The identified variants were in the chromodomain, the functional domain of HP1ß, which mediates interactions with chromatin. Cbx1 chromodomain mutant mice displayed increased latency-to-peak response, suggesting the possibility of synaptic delay or myelination deficits. Cytological and chromatin immunoprecipitation experiments confirmed the reduction of mutant HP1ß binding to heterochromatin, whereas HP1ß interactome analysis demonstrated that the majority of HP1ß-interacting proteins remained unchanged between the wild-type and mutant HP1ß. CONCLUSION: These collective findings confirm the role of CBX1 in developmental disabilities through the disruption of HP1ß chromatin binding during neurocognitive development. Because HP1ß forms homodimers and heterodimers, mutant HP1ß likely sequesters wild-type HP1ß and other HP1 proteins, exerting dominant-negative effects.


Subject(s)
Chromobox Protein Homolog 5 , Heterochromatin , Animals , Mice , Chromatin/genetics , Chromosomal Proteins, Non-Histone/genetics , Histones/genetics , Histones/metabolism
8.
Front Endocrinol (Lausanne) ; 14: 1120801, 2023.
Article in English | MEDLINE | ID: mdl-36777357

ABSTRACT

Chronic kidney disease (CKD) prevalence is increasing worldwide, and reducing the number of patients with CKD is of utmost importance. The environment during the fetal, perinatal, and early childhood stages may influence CKD development (developmental origins of health and disease). Under conditions of maternal malnutrition, the glomerular number of infants reduces, and the risk of developing CKD may increase. Nephron progenitor cells and ureteric buds interact with each other to form glomeruli at the tip of the ureteric bud. Thus, the number of glomeruli is determined by the number of ureteric bud branches, which are reportedly decreased due to maternal malnutrition, in turn reducing the glomerular number. Four possible mechanisms can explain the low glomerular number resulting from maternal malnutrition: 1) suppression of c-Ret expression, 2) suppression of nephron formation by renin-angiotensin-aldosterone system inhibition, 3) exposure to excess glucocorticoids, and 4) promotion of apoptosis. Additionally, nephron formation does not continue after birth in humans. Therefore, a low glomerular number at birth is a lifelong burden on the glomeruli and increases the risk of developing CKD. Therefore, it is important to maintain the glomerular number at birth. Accurate glomerular counts are essential for conducting studies on the glomerular number. The dissector/fractionator method is the gold standard; however, it can only be performed at some institutions. Recently, methods have been developed to measure the glomerular number by combining computed tomography and pathological examination and measure the glomerular count using magnetic resonance imaging. Models of decreased and increased glomerular numbers have been developed. Moreover, research regarding the causes of decreased glomerular number and its relationship with development of lifestyle-related diseases and renal dysfunction has significantly progressed, furthering our understanding of the importance of glomerular number.


Subject(s)
Malnutrition , Renal Insufficiency, Chronic , Child, Preschool , Infant, Newborn , Pregnancy , Female , Humans , Kidney Glomerulus/pathology , Nephrons/pathology , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/pathology , Glucocorticoids
9.
PLoS One ; 18(2): e0281414, 2023.
Article in English | MEDLINE | ID: mdl-36827398

ABSTRACT

Gangliosides, sialic acid-containing glycosphingolipids, are widely involved in regulations of signal transductions to control cellular functions. It has been suggested that GM3, the simplest structure among gangliosides, is involved in insulin resistance, whereas it remains unclear whether insulin signaling diminished by GM3 actually aggravates the pathological conditions in metabolic disorders. Moreover, the functional roles of gangliosides in the regulation of insulin signaling have not yet been fully elucidated in liver or hepatocytes despite that it is one of the major insulin-sensitive organs. To understand physiological roles of GM3 in metabolic homeostasis in liver, we conducted a high fat diet (HFD) loading experiment using double knockout (DKO) mice of GM2/GD2 synthase and GD3 synthase, which lack all gangliosides except GM3, as well as wild-type (WT) mice. DKO mice were strikingly resistant to HFD-induced hepatosteatosis, and hepatic lipogenesis-related molecules including insulin signaling components were down-regulated in HFD-fed DKO. Furthermore, we established primary hepatocyte cultures from DKO and WT mice, and examined their responses to insulin in vitro. Following insulin stimulation, DKO hepatocytes expressing GM3 showed attenuated expression and/or activations in the downstream components compared with WT hepatocytes expressing GM2. While insulin stimulation induced lipogenic proteins in hepatocytes from both genotypes, their expression levels were lower in DKO than in WT hepatocytes after insulin treatment. All our findings suggest that the modified gangliosides, i.e., a shift to GM3 from GM2, might exert a suppressive effect on lipogenesis by attenuating insulin signaling at least in mouse hepatocytes, which might result in protection of HFD-induced hepatosteatosis.


Subject(s)
G(M3) Ganglioside , Insulin Resistance , Mice , Animals , Insulin/metabolism , Diet, High-Fat , Signal Transduction , Gangliosides/metabolism , Insulin, Regular, Human , G(M2) Ganglioside
10.
Clin J Sport Med ; 33(2): 172-178, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36633593

ABSTRACT

OBJECTIVE: To estimate the ratio of menstrual abnormalities, infertility, and other problems related to pregnancy and childbirth in former long-distance runners. We hypothesized that the female athlete triad during an athletic career affects future fertility and childbearing in former athletes. DESIGN: Cross-sectional study. SETTING: Participants of the All Japan University Women's Ekiden. PARTICIPANTS: Female former athletes who competed at national level were asked to complete the questionnaire; 137 valid responses were obtained. INDEPENDENT VARIABLES: Age at menarche and at the onset of pregnancy, history of amenorrhea and gynecological disorders, and lowest body mass index (BMI) during their athletic career. MAIN OUTCOME MEASURES: Menstrual status, history of pregnancy and childbirth, any related infertility treatment and problems, and history of stress fractures. RESULTS: The mean age at menarche was 13.3 ± 2.2 (range, 10-25) years. Five athletes (3.6%) had primary amenorrhea. Eleven of the 137 participants (8.0%) required treatment for infertility. Sixty participants had 121 pregnancies, of which 5 were yet to deliver during the survey. Fifteen of 116 pregnancies (12.9%) ended in miscarriage, induced abortion, or stillbirth. Logistic regression analysis showed that the factors related to "infertility treatment" were age at the onset of pregnancy ( P = 0.047) and higher BMI during their athletic career ( P = 0.032; odds ratio, 2.19). CONCLUSIONS: The main factor influencing infertility was an older age at the time of pregnancy, similar to that observed in the general population. Amenorrhea or being underweight during their athletic career was not associated with problems related to conception and childbirth.


Subject(s)
Infertility , Sports , Pregnancy , Female , Humans , Child , Adolescent , Young Adult , Adult , Amenorrhea , Cross-Sectional Studies , Sports/physiology , Body Mass Index
11.
PLoS One ; 17(11): e0277153, 2022.
Article in English | MEDLINE | ID: mdl-36342917

ABSTRACT

Previous studies have suggested that change-related cortical responses are phenomena similar to the onset response and could be applied to the loudness dependence of auditory evoked potential (LDAEP) paradigm. In the present study, we examined the relationship between LDAEP and the change-related response using electroencephalography findings in 50 healthy subjects. There were five conditions (55, 65, 75, 85, and 95 dB) for LDAEP and five similar conditions (abrupt sound pressure increase from 70 to 75, 80, 85, 90, and 95 dB) for the change-related response. Both the onset and abrupt sound pressure increase evoked a triphasic response with peaks at approximately 50 (P50), 100 (N100), and 200 (P200) ms. We calculated the peak-to-peak amplitudes for P50/N100 and N100/P200. Medians and slopes for P50/N100 and N100/P200 amplitudes were calculated and compared between the two measures. Results revealed a significant correlation for both the slope and median for P50/N100 (r = 0.36, 0.37, p = 1.0 × 10-2, 7.9 × 10-3), N100/P200 (r = 0.40, 0.34, p = 4.0 × 10-3, 1.6 × 10-2), and P50/N100/P200 (r = 0.36, 0.35, p = 1.0 × 10-2, 1.3 × 10-2). These results suggested that the change-related response and LDAEP shared generation mechanisms at least partially.


Subject(s)
Electroencephalography , Evoked Potentials, Auditory , Humans , Evoked Potentials, Auditory/physiology , Acoustic Stimulation/methods
12.
Environ Sci Technol ; 56(23): 17375-17384, 2022 12 06.
Article in English | MEDLINE | ID: mdl-36399796

ABSTRACT

The crucial role of healthy soil in achieving sustainable food production and environment is increasingly recognized, as is the importance of proper assessment of soil quality. We introduce a new framework, open soil index (OSI), which integrally evaluates soil health of agricultural fields and provides recommendation for farming practices. The OSI is an open-source modular framework in which soil properties, functions, indicators and scores, and management advice are linked hierarchically. Soil health is evaluated with respect to sustainable crop production but can be extended to other ecosystem functions. The OSI leverages the existing knowledge base of agronomic research and routine laboratory data, enabling its application with limited cost. The OSI is a generic framework that can be adopted for specific regions with specific objectives. As a proof of concept, the OSI is implemented for all (>700,000) Dutch agricultural fields and illustrated with 11 pairs ("good" and "poor") of local fields and 32 fields where soil quality and crop yield have been monitored. The OSI produced reasonable evaluation for most pairs when soil physical functions were refined with on-site soil visual assessment. The soil functions are sufficiently independent and yet together reflect complex multidimensionality of soil quality. The framework can facilitate designing sustainable soil management programs by bridging regional targets to field-level actions.


Subject(s)
Ecosystem , Soil , Agriculture
13.
J Photochem Photobiol B ; 236: 112584, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36272337

ABSTRACT

Fluorescence-spectral microscope observations of photosynthetic organisms at cryogenic temperatures have the ability to spectrally resolve the two photosystems (PSs) and thus provide a powerful tool to elucidate the functional analysis of photosynthesis in vivo. In the present study, a measurement channel of the fluorescence lifetime at 680 nm was added to the cryo-microscope system previously developed by the authors. This provides access to information on the functional state of the light-harvesting system in living cells during regulation by a mechanism called state transitions. The observations of state1-locked and state2-locked Chlamydomonas cells at 80 K enabled us to identify a component showing rapidly decaying fluorescence with a lifetime of ca. 3 ps and emitting at around 676 nm. The component was assigned to the light-harvesting complex II (LHCII) that is isolated from both PSs and in a quenched state, probably due to the formation of aggregates. Simultaneous spectral observations revealed the accumulation of this free LHCII in the photosystem I (PSI)-enriched region within each state2-locked cell. To the best of our knowledge, this is the first in-vivo observation which suggests the localization of the quenched LHCII aggregates.


Subject(s)
Chlamydomonas reinhardtii , Chlamydomonas , Photosystem I Protein Complex/metabolism , Chlamydomonas/metabolism , Photosystem II Protein Complex/metabolism , Chlamydomonas reinhardtii/metabolism , Light-Harvesting Protein Complexes/metabolism , Photosynthesis
14.
J Diabetes Investig ; 13(12): 2081-2090, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36047430

ABSTRACT

AIMS/INTRODUCTION: The aim of this study was to develop a scale to evaluate disease stigma in patients with lifestyle-related chronic non-communicable diseases (LCNCDs), which we named the Kanden Institute Stigma Scale (KISS), and to consider its possible clinical application for patients with diabetes. MATERIALS AND METHODS: An initial 90 questions were drafted and categorized into six subscales according to the manifestations of stigma. The final version of the KISS was developed as a 24-item questionnaire comprising four items for each subscale. RESULTS: A total of 539 outpatients including 452 patients with diabetes and 87 patients without diabetes were recruited. Construct validity was confirmed by assessing the correlation with previously established measures. Confirmatory factor analysis showed the KISS to have good model fitness (adjusted goodness-of-fit index = 0.856). Test-retest reproducibility analysis showed that the intraclass coefficient of the first and a second KISS was 0.843 (P < 0.001), indicating excellent reproducibility. The KISS showed higher scores for patients with diabetes than for patients without diabetes (12.23 ± 0.49 vs 5.76 ± 0.73, P < 0.05). The KISS score was significantly higher in type 1 and type 2 diabetes patients taking insulin therapy than in type 2 diabetes patients not taking insulin (P < 0.05). CONCLUSION: The KISS is a validated and reliable questionnaire for assessment of stigma among patients with diabetes as well as other lifestyle-related chronic non-communicable diseases, and might contribute to identifying and rectifying diabetes stigma, as well promoting awareness among health care professionals of this very consequential health problem.


Subject(s)
Diabetes Mellitus, Type 2 , Insulins , Noncommunicable Diseases , Humans , Psychometrics , Reproducibility of Results , Surveys and Questionnaires
15.
Proc Natl Acad Sci U S A ; 119(37): e2122032119, 2022 09 13.
Article in English | MEDLINE | ID: mdl-36067315

ABSTRACT

Photosynthetic organisms have developed a regulation mechanism called state transition (ST) to rapidly adjust the excitation balance between the two photosystems by light-harvesting complex II (LHCII) movement. Though many researchers have assumed coupling of the dynamic transformations of the thylakoid membrane with ST, evidence of that remains elusive. To clarify the above-mentioned coupling in a model organism Chlamydomonas, here we used two advanced microscope techniques, the excitation-spectral microscope (ESM) developed recently by us and the superresolution imaging based on structured-illumination microscopy (SIM). The ESM observation revealed ST-dependent spectral changes upon repeated ST inductions. Surprisingly, it clarified a less significant ST occurrence in the region surrounding the pyrenoid, which is a subcellular compartment specialized for the carbon-fixation reaction, than that in the other domains. Further, we found a species dependence of this phenomenon: 137c strain showed the significant intracellular inhomogeneity of ST occurrence, whereas 4A+ strain hardly did. On the other hand, the SIM observation resolved partially irreversible fine thylakoid transformations caused by the ST-inducing illumination. This fine, irreversible thylakoid transformation was also observed in the STT7 kinase-lacking mutant. This result revealed that the fine thylakoid transformation is not induced solely by the LHCII phosphorylation, suggesting the highly susceptible nature of the thylakoid ultrastructure to the photosynthetic light reactions.


Subject(s)
Chlamydomonas , Light-Harvesting Protein Complexes , Photosystem II Protein Complex , Thylakoids , Chlamydomonas/enzymology , Chlamydomonas/radiation effects , Light , Light-Harvesting Protein Complexes/chemistry , Phosphorylation , Photosynthesis/physiology , Photosystem II Protein Complex/chemistry , Thylakoids/enzymology , Thylakoids/radiation effects
16.
Article in English | MEDLINE | ID: mdl-36141775

ABSTRACT

(1) Background: Injuries to the upper limbs during wood splitting can affect social and economic life. We aimed to describe the clinical information concerning these injuries in Japan. (2) Methods: We identified patients from our patient database from April 2015-November 2021 and extracted data from their medical records, which includes age, gender, occupation, month, time and location of the injury, diagnosis, duration of hospitalization, ICU admission, treatment interventions including surgery, outcome, and medical costs. (3) Result: Seventeen cases were identified. Most of the patients were male (n = 15), with median age being 68 years old. Regarding the patients' backgrounds, six were apple farmers and three were unemployed. Injuries to the index finger was most common (n = 9), followed by injuries to the thumb in five cases (n = 5). Most of the incidents occurred at home or on the patient's farm estate. No injuries were due to incidents at work. (4) Conclusion: The wood splitter-related injuries required long-term treatment and frequently damaged the thumb, a functionally important digit. All the injuries were sustained during non-occupational use of a wood splitter. Therefore, we suggest that safety training should be provided to prevent traumatic injuries when these products are being sold.


Subject(s)
Farmers , Wood , Aged , Farms , Female , Hospitalization , Humans , Male , Upper Extremity
17.
Neuron ; 110(18): 2902-2915, 2022 09 21.
Article in English | MEDLINE | ID: mdl-35777365

ABSTRACT

Chromatin is organized into multiscale three-dimensional structures, including chromosome territories, A/B compartments, topologically associating domains, and chromatin loops. This hierarchically organized genomic architecture regulates gene transcription, which, in turn, is essential for various biological processes during brain development and adult plasticity. Here, we review different aspects of spatial genome organization and their functions in regulating gene expression in the nervous system, as well as their dysregulation in brain disorders. We also highlight new technologies to probe and manipulate chromatin architecture and discuss how investigating spatial genome organization can lead to a better understanding of the nervous system and associated disorders.


Subject(s)
Chromatin , Genome , Chromatin/genetics , Nervous System
18.
ACS Infect Dis ; 8(8): 1563-1581, 2022 08 12.
Article in English | MEDLINE | ID: mdl-35819780

ABSTRACT

Raman spectroscopy uncovered molecular scale markers of the viral structure of the SARS-CoV-2 Delta variant and related viral inactivation mechanisms at the biological interface with silicon nitride (Si3N4) bioceramics. A comparison of Raman spectra collected on the TY11-927 variant (lineage B.1.617.2; simply referred to as the Delta variant henceforth) with those of the JPN/TY/WK-521 variant (lineage B.1.617.1; referred to as the Kappa variant or simply as the Japanese isolate henceforth) revealed the occurrence of key mutations of the spike receptor together with profound structural differences in the molecular structure/symmetry of sulfur-containing amino acid and altered hydrophobic interactions of the tyrosine residue. Additionally, different vibrational fractions of RNA purines and pyrimidines and dissimilar protein secondary structures were also recorded. Despite mutations, hydrolytic reactions at the surface of silicon nitride (Si3N4) bioceramics induced instantaneous inactivation of the Delta variant at the same rate as that of the Kappa variant. Contact between virions and micrometric Si3N4 particles yielded post-translational deimination of arginine spike residues, methionine sulfoxidation, tyrosine nitration, and oxidation of RNA purines to form formamidopyrimidines. Si3N4 bioceramics proved to be a safe and effective inorganic compound for instantaneous environmental sanitation.


Subject(s)
COVID-19 , Spectrum Analysis, Raman , Ceramics/chemistry , Ceramics/pharmacology , Humans , Purines , RNA , SARS-CoV-2/genetics , Silicon Compounds , Tyrosine
19.
Article in English | MEDLINE | ID: mdl-35662999

ABSTRACT

Background: This study aimed to compare the clinical outcomes and patient reported outcome measurement scales (PROMs) between hamstring tendon (HT) or bone-patellar tendon-bone (BTB) grafts in each primary and revision anterior cruciate ligament (ACL) reconstruction. Additionally, the clinical outcomes and PROMs between primary and revision surgeries were compared. Methods: A total of 150 patients (109 primary and 41 revision ACL reconstructions) were enrolled and followed up for an average of 3.9 years (2 years minimum). Knee injury and osteoarthritis outcome scores (KOOS) were examined as PROMs. Side-to-side differences of anterior knee laxity were assessed using KT-1000 and were recorded at the final follow-up. After categorizing patients into HT and BTB reconstruction groups, regression analysis was performed to determine the relationship between revision surgery and changes in KOOS. Results: In patients who underwent primary surgery, there was no significant difference in side-to-side differences of anterior laxity and KOOS between HT and BTB grafts. In those who underwent revision surgery, BTB grafts had a higher KOOS for activities of daily living (ADL) than HT grafts (p = 0.032). Comparing primary and revision surgeries, postoperative side-to-side differences of anterior laxity in the revision group were significantly larger than those in the primary group (p = 0.001). The KOOS for sports after overall revision reconstruction was significantly lower than that after primary reconstruction (p = 0.026). Comparing the KOOS after dividing all patients into HT and BTB reconstruction groups, in the HT reconstruction group, postoperative KOOS results were not different in any subscale from BTB grafts. In contrast, the KOOS for sports (p = 0.008) and QOL (p = 0.039) were significantly lower in revision surgery than in primary surgery. Furthermore, regression analysis including multiple confounders in the HT reconstruction group showed revision surgery using HT graft was correlated with worsened KOOS for symptoms (p = 0.012) and sports (p = 0.010). Revision surgery using BTB graft was not correlated with decreased KOOS. Conclusions: There were no differences between the clinical outcome and KOOS in primary and revision surgery, except for ADL scores following revision ACL reconstruction using BTB graft. Side-to-side difference of anterior laxity and KOOS for sports following revision ACL reconstruction were inferior to those following primary ACL reconstruction.Furthermore, revision ACL reconstruction using HT grafts were correlated with low scores in KOOS for symptoms and sports, while there was no difference of anterior laxity between BTB and HT grafts in revision surgery.

20.
J Physiol Anthropol ; 41(1): 21, 2022 May 10.
Article in English | MEDLINE | ID: mdl-35538562

ABSTRACT

BACKGROUND: In Japan, height and weight measurements, taken for all children at birth and 1.5- and 3-year health checks, are recorded in the Mother and Child Health (MCH) Handbook, as required by the law. The present population-based retrospective cohort study aimed to evaluate the diagnostic performance of height and weight records in the Handbook for predicting excessive adiposity in adolescents. METHODS: The source population consisted of 8th grade students (800 students aged 14 years) registered at two public junior high schools. Of these, we excluded students who were born at a gestational age < 37 weeks or > 42 weeks. The present analyses included 435 participants who provided complete information. Body mass index (BMI) was calculated using height and weight records. Body fat mass at 14 years of age was measured by dual-energy X-ray absorptiometry (DXA). Diagnostic performance of BMI calculated from the MCH Handbook records to discriminate between the presence and absence of excessive adiposity at 14 years of age was evaluated using receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC) was used to quantify the diagnostic accuracy of BMI. RESULTS: With regard to the prediction of excessive fat at 14 years of age, AUCs and 95% confidence intervals for BMI at 1.5 and 3 years of age were greater than 0.5. Meanwhile, the AUC of BMI at birth was not significantly greater than 0.5. CONCLUSION: The present study findings indicate that BMI values calculated using MCH Handbook data have potential ability to distinguish between the presence and absence of excessive fat at 14 years of age.


Subject(s)
Adipose Tissue , Obesity , Absorptiometry, Photon , Adolescent , Body Mass Index , Body Weight , Child , Child, Preschool , Cohort Studies , Humans , Infant , Infant, Newborn , Obesity/epidemiology , Retrospective Studies
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