Introduction: This study aims to investigate how mother-adolescent relationships evolved before and during the COVID-19 pandemic and their correlation with pandemic-related stress and adolescents' psychological distress.
Methods: A longitudinal study involving 579 mother-adolescent dyads (junior high school students at Time 1; 50% male students) was conducted, with data collected before (October 2019) and during (October 2020) the pandemic in Japan. Both mothers and adolescents reported the perceived quality of their positive and conflictual relationships at each time point.
Nuclear clearance and cytoplasmic aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) are pathological hallmarks of amyotrophic lateral sclerosis (ALS) and its pathogenic mechanism is mediated by both loss-of-function and gain-of-toxicity of TDP-43. However, the role of TDP-43 gain-of-toxicity in oligodendrocytes remains unclear. To investigate the impact of excess TDP-43 on oligodendrocytes, we established transgenic mice overexpressing the ALS-linked mutant TDP-43 in oligodendrocytes through crossbreeding with Mbp-Cre mice.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis (ALS) selectively affects motor neurons. SOD1 is the first causative gene to be identified for ALS and accounts for at least 20% of the familial (fALS) and up to 4% of sporadic (sALS) cases globally with some geographical variability. The destabilisation of the SOD1 dimer is a key driving force in fALS and sALS.
View Article and Find Full Text PDFBackground: Neuroinflammation substantially contributes to the pathology of Alzheimer's disease (AD), the most common form of dementia. Studies have reported that nuclear factor erythroid 2-related factor 2 (Nrf2) attenuates neuroinflammation in the mouse models of neurodegenerative diseases, however, the detailed mechanism remains unclear.
Methods: The effects of dimethyl fumarate (DMF), a clinically used drug to activate the Nrf2 pathway, on neuroinflammation were analyzed in primary astrocytes and App (App-KI) mice.
Recent single-cell analyses have revealed the complexity of microglial heterogeneity in brain development, aging, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Disease-associated microglia (DAMs) have been identified in ALS mice model, but their role in ALS pathology remains unclear. The effect of genetic background variations on microglial heterogeneity and functions remains unknown.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2023
The organelle contact site of the endoplasmic reticulum and mitochondria, known as the mitochondria-associated membrane (MAM), is a multifunctional microdomain in cellular homeostasis. We previously reported that MAM disruption is a common pathological feature in amyotrophic lateral sclerosis (ALS); however, the precise role of MAM in ALS was uncovered. Here, we show that the MAM is essential for TANK-binding kinase 1 (TBK1) activation under proteostatic stress conditions.
View Article and Find Full Text PDFThe cytoplasmic aggregation of TAR DNA binding protein-43 (TDP-43), also known as TDP-43 pathology, is the pathological hallmark of amyotrophic lateral sclerosis (ALS). However, the mechanism underlying TDP-43 cytoplasmic mislocalization and subsequent aggregation remains unclear. Here, we show that TDP-43 dimerization/multimerization is impaired in the postmortem brains and spinal cords of patients with sporadic ALS and that N-terminal dimerization-deficient TDP-43 consists of pathological inclusion bodies in ALS motor neurons.
View Article and Find Full Text PDFPurpose: This study aimed to evaluate short-term outcomes at least 2 years after dome-shaped high tibial osteotomy (HTO) combined with all-inside anterior cruciate ligament reconstruction (ACL) in patients with persistent ACL insufficiency accompanied by pain due to varus deformity.
Methods: The study enrolled 19 knees of 18 patients. The mean age was 58.
Given the paucity of reports on all-inside reconstruction procedures via the transfemoral approach, we describe a minimally invasive, all-inside transfemoral technique that enables creating femoral and tibial sockets from the intra-articular cavity. Our transfemoral approach makes it possible to sequentially create femoral and tibial sockets using the same reamer bit, while a single drilling guide is set in place. Our custom socket drilling guide was designed to integrate with a tibial tunnel guide, which helped locate the tunnel exit at an anatomically acceptable location.
View Article and Find Full Text PDFLymphatic fluid drains from the liver via the periportal lymphatic, hepatic venous lymphatic, and superficial lymphatic systems. We performed a postmortem study to clarify the three-dimensional structure and flow dynamics of the human hepatic venous lymphatic system, as it still remains unclear. Livers were excised whole from three human cadavers, injected with India ink, and sliced into 1-cm sections from which veins were harvested.
View Article and Find Full Text PDFCanine degenerative myelopathy (DM), a fatal neurodegenerative disease in dogs, shares clinical and genetic features with amyotrophic lateral sclerosis, a human motor neuron disease. Mutations in the SOD1 gene encoding Cu/Zn superoxide dismutase (SOD1) cause canine DM and a subset of inherited human amyotrophic lateral sclerosis. The most frequent DM causative mutation is homozygous E40K mutation, which induces the aggregation of canine SOD1 but not of human SOD1.
View Article and Find Full Text PDFBackground: First successful human round spermatid injection (ROSI) was conducted by Tesarik et al. in 1996 for the sole treatment of nonobstructive azoospermic men whose most advanced spermatogenic cells were elongating round spermatids. Nine offsprings from ROSI were reported between 1996 and 2000.
View Article and Find Full Text PDFOrganelle contact sites are multifunctional platforms for maintaining cellular homeostasis. Alternations of the mitochondria-associated membranes (MAM), one of the organelle contact sites where the endoplasmic reticulum (ER) is tethered to the mitochondria, have been involved in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the detailed mechanisms through which MAM integrity is disrupted in ALS have not been fully elucidated.
View Article and Find Full Text PDFStructured Summary: Rationale: Nasal high-flow (NHF), a new method for respiratory management during procedural sedation, has greater advantages than conventional nasal therapy with oxygen. However, its clinical relevance for patients undergoing oral maxillofacial surgery and/or dental treatment remains uncertain and controversial, due to a paucity of studies. This scoping review compared and evaluated NHF and conventional nasal therapy with oxygen in patients undergoing oral maxillofacial surgery and/or dental treatment.
View Article and Find Full Text PDFBackground: Sperm DNA damage is a major cause of pre- and post-implantation embryonic loss in humans. However, the factors that control how and when such DNA damage occurs in human sperm are poorly understood.
Methods: Here, I review information relating to sperm DNA damage that can be obtained from the sperm chromosome assays described in the existing literature.
Kyphomelic dysplasia is a heterogeneous group of skeletal dysplasias characterized by severe bowing of the limbs associated with other variable findings, such as narrow thorax and abnormal facies. We searched for the genetic etiology of this disorder. Four individuals diagnosed with kyphomelic dysplasia were enrolled.
View Article and Find Full Text PDFDuring acetic acid fermentation, acetic acid bacteria face oxygen depletion stress caused by the vigorous oxidation of ethanol to acetic acid. However, the molecular mechanisms underlying the response to oxygen depletion stress remain largely unknown. Here, we focused on an oxygen-sensing FNR homolog, FnrG, in Komagataeibacter medellinensis.
View Article and Find Full Text PDFThe mitochondria-associated membrane (MAM) is a functional subdomain of the endoplasmic reticulum membrane that tethers to the mitochondrial outer membrane and is essential for cellular homeostasis. A defect in MAM is involved in various neurological diseases, including amyotrophic lateral sclerosis (ALS). Recently, we and others reported that MAM was disrupted in the models expressing several ALS-linked genes, including SOD1, SIGMAR1, VAPB, TARDBP, and FUS, suggesting that MAM disruption is deeply involved in the pathomechanism of ALS.
View Article and Find Full Text PDFBiochem Biophys Res Commun
June 2021
Involvement of the bone matrix protein osteocalcin (OC) in the development of learning and memory, and the prevention of anxiety-like behaviors in mice. However, the direct effects of OC on neurons are still unknown comparing to the mechanism how OC affects systemic energy expenditure and glucose homeostasis. In this study, we investigated the effect of OC on proliferation, differentiation, and survival of neurons using the rat pheochromocytoma cell line PC12.
View Article and Find Full Text PDFAim: Abdominoperineal resection is associated with poor prognosis in patients with advanced lower rectal cancer. This study aimed to analyse the functional lymphovascular network and tissue drainage in the anorectal region.
Methods: In this descriptive study, we performed microanatomical evaluations and intra-operative imaging analysis in a cadaver and patients with rectal cancer.
Microglia-mediated neuroinflammation has been implicated in the pathogenesis of Alzheimer's disease (AD). Although microglia in aging and neurodegenerative disease model mice show a loss of homeostatic phenotype and activation of disease-associated microglia (DAM), a correlation between those phenotypes and the degree of neuronal cell loss has not been clarified. In this study, we performed RNA sequencing of microglia isolated from three representative neurodegenerative mouse models, App with amyloid pathology, rTg4510 with tauopathy, and SOD1 with motor neuron disease by magnetic activated cell sorting.
View Article and Find Full Text PDFPurpose: Upper airway obstruction (UAO) and oxygen desaturation are risk factors for major complications of intravenous sedation (IVS) in pediatric dental patients. This study aimed to investigate the use of a nasal high-flow (NHF) system for the prevention of UAO and oxygen desaturation in pediatric dental patients under IVS.
Methods: The authors implemented a prospective randomized design.
Cytoplasmic inclusion of TAR DNA-binding protein 43 (TDP-43) is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and a subtype of frontotemporal lobar degeneration (FTLD). Recent studies have suggested that the formation of cytoplasmic TDP-43 aggregates is dependent on a liquid-liquid phase separation (LLPS) mechanism. However, it is unclear whether TDP-43 pathology is induced through a single intracellular mechanism such as LLPS.
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