Heterodimeric Ciliary Dynein f/I1 Adopts a Distinctive Structure, Providing Insight Into the Autoinhibitory Mechanism Common to the Dynein Family.

Dyneins are huge motor protein complexes that are essential for cell motility, cell division, and intracellular transport. Dyneins are classified into three major subfamilies, namely cytoplasmic, intraflagellar-transport (IFT), and ciliary dyneins, based on their intracellular localization and functions. Recently, several near-atomic resolution structures have been reported for cytoplasmic/IFT dyneins.

Land Use Change Consistently Reduces α- But Not β- and γ-Diversity of Bees.

Land use change threatens global biodiversity and compromises ecosystem functions, including pollination and food production. Reduced taxonomic α-diversity is often reported under land use change, yet the impacts could be different at larger spatial scales (i.e.

Initiation of Psychotropic Drugs in Spouses of Patients With Early-Onset Alzheimer's Disease: A Matched Cohort Study.

Objectives: The diagnosis of early-onset Alzheimer's disease (EOAD) can cause emotional stress not only to the patients themselves but also to their spouses. This study aimed to evaluate the risk of psychiatric disorders in spouses of EOAD patients, using psychotropic drug initiation as a surrogate indicator.

Methods: A cohort study was conducted using a Japanese claims database, with spouses of EOAD patients (exposed spouses) matched with spouses of non-EOAD individuals (reference spouses) up to a 1:10 ratio.

Recent advances in biomarkers for senescence: Bridging basic research to clinic.

In this review, we review the current status of biomarkers for aging and possible perspectives on anti-aging or rejuvenation from the standpoint of biomarkers. Aging is observed in all cells and organs, and we focused on research into senescence in the skin, musculoskeletal system, immune system, and cardiovascular system. Commonly used biomarkers include SA-βgal, cell-cycle markers, senescence-associated secretory phenotype (SASP) factors, damage-associated molecular patterns (DAMPs), and DNA-damage-related markers.

Target Identification of Marine Natural Product Odoamide: Odoamide Induces Apoptotic Cell Death by Targeting ATPase Na+/K+ Transporting Subunit Alpha 1 (ATP1A1).

Marine natural products show a large variety of unique chemical structures and potent biological activities. Elucidating the target molecule and the mechanism of action is an essential and challenging step in drug development starting with a natural product. Odoamide, a member of aurilide-family isolated from Okinawan marine cyanobacterium, has been known to exhibit highly potent cytotoxicity against various cancer cell lines.

Cough and sputum symptoms reduce physical activity in patients with NTM pulmonary disease.

Although physical activity is an important outcome in patients with chronic respiratory disease, it has not been characterised in those with non-tuberculous mycobacterial pulmonary disease (NTM-PD). This study aimed to evaluate physical activity and its associated factors in patients with NTM-PD.This prospective observational study measured daily step counts using an accelerometer to assess physical activity (steps per day).

Spatially ordered recruitment of fast muscles in accordance with movement strengths in larval zebrafish.

In vertebrates, skeletal muscle comprises fast and slow fibers. Slow and fast muscle cells in fish are spatially segregated; slow muscle cells are located only in a superficial region, and comprise a small fraction of the total muscle cell mass. Slow muscles support low-speed, low-force movements, while fast muscles are responsible for high-speed, high-force movements.

Analysis and prediction of subarachnoid hemorrhage burden in global, China, and Japan.

Background: Subarachnoid hemorrhage (SAH) remains a serious public health problem worldwide, especially in economically developed regions/countries. This study intends to thoroughly analyze the incidence, mortality, and disability-adjusted life years (DALYs) rate of SAH at the global, regional, and national levels. This study focused on the differences in SAH incidence between China and Japan from 1990 to 2019, and projected global, Chinese, and Japanese SAH incidence rates until 2030.

Cerebrovascular stenosis related to tyrosine kinase inhibitor for chronic myeloid leukemia: two illustrative cases.

Background: Tyrosine kinase inhibitors (TKIs) improve prognosis in chronic myeloid leukemia (CML). Nilotinib and ponatinib, second- and third-generation TKIs, respectively, have been reported to cause adverse vascular occlusive events such as myocardial infarction and peripheral arterial disease. However, little is known about the risk of cerebral infarction associated with severe cerebrovascular stenosis, which is a late complication of TKIs.

PNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism.

Hepatocellular carcinoma (HCC) necessitates innovative prognostic biomarkers and therapeutic targets. By investigating PNMA1 in HCC via the TCGA and GEO databases and our clinical data, we found that its overexpression is associated with worse survival. The relevance of PNMA1 extends to immune factors such as M1 macrophages, CD8 T cells, and immune checkpoints.

Increased acute-phase reaction after the transoral endoscopic thyroidectomy vestibular approach (TOEVA) compared with minimally invasive video-assisted thyroidectomy (MIVAT) for unilateral thyroidectomy.

Purposes: We analyzed the acute-phase response in unilateral thyroidectomy by comparing the transoral endoscopic thyroidectomy vestibular approach (TOEVA) with the minimally invasive video-assisted thyroidectomy (MIVAT).

Methods: Patients were randomly assigned to undergo either TOEVA or MIVAT, after we obtained their written informed consent to participate in this study. Blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-1β (IL-1β), IL-6 and tumor necrosis factor (TNF-) were measured before surgery and then 4, 24, and 48 h after surgery.

Development of the membrane ceiling method for in vitro spermatogenesis.

Spermatogenesis is one of the most complex processes of cell differentiation and its failure is a major cause of male infertility. Therefore, a proper model that recapitulates spermatogenesis in vitro has been long sought out for basic and clinical research. Testis organ culture using the gas-liquid interphase method has been shown to support spermatogenesis in mice and rats.

Complement classical and alternative pathway activation contributes to diabetic kidney disease progression: a glomerular proteomics on kidney biopsies.

Increasing evidence points toward an essential role for complement activation in the pathogenesis of diabetic kidney disease (DKD). However, the precise molecular mechanisms remain unclear, and the pathway predominantly contributing to complement activation in DKD is of particular interest. In this study, the glomerular proteome, especially the profiles of the complement proteins, was analyzed in kidney biopsies from 40 DKD patients and 10 normal controls using laser microdissection-assisted liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS).

Spatiotemporal patterns in active four-state Potts models.

Many types of spatiotemporal patterns have been observed under nonequilibrium conditions. Cycling through four or more states can provide specific dynamics, such as the spatial coexistence of multiple phases. However, transient dynamics have only been studied by previous theoretical models, since absorbing transition into a uniform phase covered by a single state occurs in the long-time limit.

A modeling study to define guidelines for antigen screening in schools and workplaces to mitigate COVID-19 outbreaks.

Background: In-person interaction offers invaluable benefits to people. To guarantee safe in-person activities during a COVID-19 outbreak, effective identification of infectious individuals is essential. In this study, we aim to analyze the impact of screening with antigen tests in schools and workplaces on identifying COVID-19 infections.

The influence of increasing color variety on numerosity estimation and counting.

Previous research has suggested that numerosity estimation and counting are closely related to distributed and focused attention, respectively (Chong & Evans, WIREs Cognitive Science, 2(6), 634-638, 2011). Given the critical role of color in guiding attention, this study investigated its effects on numerosity processing by manipulating both color variety (single color, medium variety, high variety) and spatial arrangement (clustered, random). Results from the estimation task revealed that high color variety led to a perceptual bias towards larger quantities, regardless of whether colors were clustered or randomly arranged.

Human Epidermal Growth Factor Receptor 2 Positive Advanced Gastric or Esophagogastric Adenocarcinoma: Reflecting on the Past to Gain a New Insights.

Purpose Of Review: Human epidermal growth factor receptor 2 (HER2) is a critical target in advanced gastric cancer (AGC). This review highlights the current treatment landscape, lessons learned from past clinical trials, and prospects for future treatment strategies for HER2-positive AGC.

Recent Findings: Trastuzumab had been the standard treatment for HER2-positive AGC for a decade, and subsequently, trastuzumab deruxtecan, an antibody-drug conjugate (ADC), emerged with an impressive response.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

Blood DNA virome associates with autoimmune diseases and COVID-19.

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).