Phytochrome-interacting factors PIF4 and PIF5 directly regulate autophagy during leaf senescence in Arabidopsis.

During leaf senescence, autophagy plays a critical role by removing damaged cellular components and participating in nutrient remobilization to sink organs. However, how AUTOPHGAY (ATG) genes are regulated during natural leaf senescence remains largely unknown. In this study, we attempted to identify upstream transcriptional regulator(s) of ATGs and their molecular basis during leaf senescence in Arabidopsis through the combined analyses of promoter binding, autophagy flux, and genetic interactions.

Knockout of Dectin-1 does not modify disease onset or progression in a MATR3 S85C knock-in mouse model of ALS.

Microglia have been increasingly implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Dectin-1, encoded by the gene, is highly upregulated in a specific microglial response state called disease-associated microglia (DAM) in various neurodegenerative conditions. However, the role of Dectin-1 in ALS is undetermined.

MATR3's Role beyond the Nuclear Matrix: From Gene Regulation to Its Implications in Amyotrophic Lateral Sclerosis and Other Diseases.

Matrin-3 (MATR3) was initially discovered as a component of the nuclear matrix about thirty years ago. Since then, accumulating studies have provided evidence that MATR3 not only plays a structural role in the nucleus, but that it is also an active protein involved in regulating gene expression at multiple levels, including chromatin organization, DNA transcription, RNA metabolism, and protein translation in the nucleus and cytoplasm. Furthermore, MATR3 may play a critical role in various cellular processes, including DNA damage response, cell proliferation, differentiation, and survival.

Microglia and Astrocytes in Amyotrophic Lateral Sclerosis: Disease-Associated States, Pathological Roles, and Therapeutic Potential.

Microglial and astrocytic reactivity is a prominent feature of amyotrophic lateral sclerosis (ALS). Microglia and astrocytes have been increasingly appreciated to play pivotal roles in disease pathogenesis. These cells can adopt distinct states characterized by a specific molecular profile or function depending on the different contexts of development, health, aging, and disease.

Evidence of Metabolic Dysfunction in Amyotrophic Lateral Sclerosis (ALS) Patients and Animal Models.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons, leading to muscle weakness, paralysis, and eventual death. Research from the past few decades has appreciated that ALS is not only a disease of the motor neurons but also a disease that involves systemic metabolic dysfunction. This review will examine the foundational research of understanding metabolic dysfunction in ALS and provide an overview of past and current studies in ALS patients and animal models, spanning from full systems to various metabolic organs.

A Bivalent Inactivated Vaccine Prevents Enterovirus 71 and Coxsackievirus A16 Infections in the Mongolian Gerbil.

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease.

Dipolar Noise in Fluorinated Molecular Wires.

We demonstrate a strategy to directly map and quantify the effects of dipole formation on electrical transports and noises in the self-assembled monolayers (SAMs) of molecular wires. In this method, the SAM patterns of fluorinated molecules with dipole moments were prepared on conducting substrates, and a conducting probe in contact-mode atomic force microscopy was utilized to map currents and noises through the probe on the molecular patterns. The maps were analyzed to extract the characteristic parameters of dipolar noises in SAMs, and the results were compared with those of hydrogenated molecular patterns without dipole moments.

Selective Loss of MATR3 in Spinal Interneurons, Upper Motor Neurons and Hippocampal CA1 Neurons in a MATR3 S85C Knock-In Mouse Model of Amyotrophic Lateral Sclerosis.

The neuropathological hallmark of amyotrophic lateral sclerosis (ALS) is motor neuron degeneration in the spinal cord and cortex. Accumulating studies report that other neurons in the central nervous system (CNS) are also affected in ALS. Mutations in , which encodes a nuclear matrix protein involved in RNA splicing, have been linked to ALS.

Mapping the nanoscale effects of charge traps on electrical transport in grain structures of indium tin oxide thin films.

We report the mapping of the nanoscale effects of charge trap activities in the grain structures of an oxygen plasma-treated indium tin oxide (ITO) thin film. Here, a conducting Pt probe made direct contact with the surface of an ITO thin film and scanned the surface while measuring the maps of electrical currents and noises. The measured data were analyzed to obtain the maps of sheet conductance ( ) and charge trap density ( ) in the grain structures of the ITO thin film.

MATR3 F115C knock-in mice do not exhibit motor defects or neuropathological features of ALS.

The F115C mutation in the MATR3 gene has been linked to amyotrophic lateral sclerosis (ALS). To determine the pathogenicity of the F115C mutation and the mechanism by which this mutation causes ALS, we generated mice that harbor the F115C mutation in the endogenous murine Matr3 locus. Heterozygous or homozygous MATR3 F115C knock-in mice were viable and did not exhibit motor deficits up to 2 years of age.

Selective neuronal degeneration in MATR3 S85C knock-in mouse model of early-stage ALS.

A missense mutation, S85C, in the MATR3 gene is a genetic cause for amyotrophic lateral sclerosis (ALS). It is unclear how the S85C mutation affects MATR3 function and contributes to disease. Here, we develop a mouse model that harbors the S85C mutation in the endogenous Matr3 locus using the CRISPR/Cas9 system.

Knockdown of genes involved in axonal transport enhances the toxicity of human neuromuscular disease-linked MATR3 mutations in Drosophila.

Mutations in the nuclear matrix protein Matrin 3 (MATR3) have been identified in amyotrophic lateral sclerosis and myopathy. To investigate the mechanisms underlying MATR3 mutations in neuromuscular diseases and efficiently screen for modifiers of MATR3 toxicity, we generated transgenic MATR3 flies. Our findings indicate that expression of wild-type or mutant MATR3 in motor neurons reduces climbing ability and lifespan of flies, while their expression in indirect flight muscles (IFM) results in abnormal wing positioning and muscle degeneration.

Burden of Osteoporotic Fractures Using Disability-Adjusted Life Years in South Korea.

There is an increase in the number of patients with osteoporotic fractures due to the aging population in Korea. This study investigated the burden of osteoporotic fractures including hip, spine, and wrist fractures in the Korean population by estimating disability-adjusted life years (DALYs). The DALY for a given condition in a population captures years of life lost due to premature death and years of life lived with a disability and its severity and duration.

Zoledronic acid and skeletal-related events in patients with bone metastatic cancer or multiple myeloma.

Introduction: Investigations of ZA effectiveness using large, real-world databases are rare. We examined whether zoledronic acid (ZA) decreased the risk of skeletal-related events (SREs) among patients with bone metastases (BMs) from breast cancer (BC) or prostate cancer (PC), or multiple myeloma (MM) in routine clinical practice.

Materials And Methods: We conducted a propensity score-matched cohort study using the Korean National Health Insurance database.

Disability Weights for Osteoporosis and Osteoporotic Fractures in South Korea.

Background: Korea is expected to become an ultra-aged society, in which the elderly population will account for more than 20% of the total population, after 2025. Thus, the social costs due to osteoporotic fractures are expected to increase. Therefore, this study aimed to measure disability weights (DWs) of osteoporosis and osteoporotic fractures in Korea.

Incidence of skeletal-related events in patients with breast or prostate cancer-induced bone metastasis or multiple myeloma: A 12-year longitudinal nationwide healthcare database study.

Background: This study examined the incidence of skeletal-related events (SRE) among patients with breast cancer (BC)- or prostate cancer (PC)-induced bone metastasis or multiple myeloma (MM) based on a population-based, 12-year healthcare database.

Methods: Patients aged ≥18 years with bone metastasis from BC or PC or with MM between 2004 and 2015 were included. SRE was defined as pathologic fracture, spinal cord compression, radiation, or surgery to bone.

Health state utility values of osteoporotic fractures among Korean women.

: This study aimed to investigate health state utility values in eight health states related to osteoporosis and osteoporotic fractures using time trade-off (TTO) technique among postmenopausal Korean women.: Scenarios describing eight health states including osteoporosis and hip, vertebral, post-hip, post-vertebral, ankle, humerus, and wrist fractures were developed and presented to 500 female participants aged 45 to 59 years who were selected with probability proportionate to age group and region for this investigation. Each health states valuation was derived using the trade-off (TTO) technique.

RNA-Binding Proteins in Amyotrophic Lateral Sclerosis.

Significant research efforts are ongoing to elucidate the complex molecular mechanisms underlying amyotrophic lateral sclerosis (ALS), which may in turn pinpoint potential therapeutic targets for treatment. The ALS research field has evolved with recent discoveries of numerous genetic mutations in ALS patients, many of which are in genes encoding RNA binding proteins (RBPs), including TDP-43, FUS, ATXN2, TAF15, EWSR1, hnRNPA1, hnRNPA2/B1, MATR3 and TIA1. Accumulating evidence from studies on these ALS-linked RBPs suggests that dysregulation of RNA metabolism, cytoplasmic mislocalization of RBPs, dysfunction in stress granule dynamics of RBPs and increased propensity of mutant RBPs to aggregate may lead to ALS pathogenesis.

PAK1 regulates ATXN1 levels providing an opportunity to modify its toxicity in spinocerebellar ataxia type 1.

Spinocerebellar ataxia type 1 (SCA1) is caused by the expansion of a trinucleotide repeat that encodes a polyglutamine tract in ataxin-1 (ATXN1). The expanded polyglutamine in ATXN1 increases the protein's stability and results in its accumulation and toxicity. Previous studies have demonstrated that decreasing ATXN1 levels ameliorates SCA1 phenotypes and pathology in mouse models.

The Chromatin Modifier MSK1/2 Suppresses Endocrine Cell Fates during Mouse Pancreatic Development.

Type I diabetes is caused by loss of insulin-secreting beta cells. To identify novel, pharmacologically-targetable histone-modifying proteins that enhance beta cell production from pancreatic progenitors, we performed a screen for histone modifications induced by signal transduction pathways at key pancreatic genes. The screen led us to investigate the temporal dynamics of ser-28 phosphorylated histone H3 (H3S28ph) and its upstream kinases, MSK1 and MSK2 (MSK1/2).

TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau.

Several neurodegenerative diseases are driven by the toxic gain-of-function of specific proteins within the brain. Elevated levels of alpha-synuclein (α-Syn) appear to drive neurotoxicity in Parkinson's disease (PD); neuronal accumulation of tau is a hallmark of Alzheimer's disease (AD); and their increased levels cause neurodegeneration in humans and model organisms. Despite the clinical differences between AD and PD, several lines of evidence suggest that α-Syn and tau overlap pathologically.