Insights into the Structural Basis of Amyloid Resistance Provided by Cryo-EM Structures of AApoAII Amyloid Fibrils.

Amyloid resistance is the inability or the reduced susceptibility of an organism to develop amyloidosis. In this study we have analysed the molecular basis of the resistance to systemic AApoAII amyloidosis, which arises from the formation of amyloid fibrils from apolipoprotein A-II (ApoA-II). The disease affects humans and animals, including SAMR1C mice that express the C allele of ApoA-II protein, whereas other mouse strains are resistant to development of amyloidosis due to the expression of other ApoA-II alleles, such as ApoA-IIF.

BALB.NCT- is a unique mouse model of hereditary coproporphyria.

In humans, mutations in the coproporphyrinogen oxidase () gene can result in hereditary coproporphyria (HCP), characterized by high levels of coproporphyrin excretion in the urine and feces, as well as acute neurovisceral and chronic cutaneous manifestations. Appropriate animal models for comprehending the precise pathogenesis mechanism of HCP have not been reported that show similarities in terms of gene mutation, reduced CPOX activity, excess coproporphyrin accumulation, and clinical symptoms. As previously discovered, the BALB.

Renal Function in Aged C57BL/6J Mice Is Impaired by Deposition of Age-Related Apolipoprotein A-II Amyloid Independent of Kidney Aging.

Spontaneous and age-related amyloidosis has been reported in C57BL/6J mice. However, the biochemical characteristics of age-related amyloidosis remain unclear. Herein, the age-related prevalence of amyloidosis, the types of amyloid fibril proteins, and the effects of amyloid deposition were investigated in renal function in C57BL/6J mice.

Macrophages in the reticuloendothelial system inhibit early induction stages of mouse apolipoprotein A-II amyloidosis.

Amyloidosis refers to a group of degenerative diseases that are characterized by the deposition of misfolded protein fibrils in various organs. Deposited amyloid may be removed by a phagocyte-dependent innate immune system; however, the precise mechanisms during disease progression remain unclear. We herein investigated the properties of macrophages that contribute to amyloid degradation and disease progression using inducible apolipoprotein A-II amyloidosis model mice.

Exercise suppresses mouse systemic AApoAII amyloidosis through enhancement of the p38 MAPK signaling pathway.

Exercise interventions are beneficial for reducing the risk of age-related diseases, including amyloidosis, but the underlying molecular links remain unclear. Here, we investigated the protective role of interval exercise training in a mouse model of age-related systemic apolipoprotein A-II amyloidosis (AApoAII) and identified potential mechanisms. Mice subjected to 16 weeks of exercise showed improved whole-body physiologic functions and exhibited substantial inhibition of amyloidosis, particularly in the liver and spleen.

Polygenic control of the wavy coat of the NCT mouse: involvement of an intracisternal A particle insertional mutation of the protease, serine 53 (Prss53) gene, and a modifier gene.

The Nakano cataract mouse (NCT) manifests a wavy coat for their first hair as a genetic trait. In this study, we explored the molecular genetic basis of the wavy coat. We revealed by crossing experiments that the wavy coat is controlled by a major gene on chromosome 7 of NCT, homozygosity of which is a prerequisite for developing the wavy coat, and by a gene on chromosome 9 with a minor effect to reinforce the manifestation of the trait.

Involvement of increased endoplasmic reticulum stress in the development of cataracts in BALB.NCT-Cpox mice.

The BALB.NCT-Cpox is a mutant mouse model for hereditary cataracts. We previously uncovered that the primary cause of the cataracts of BALB.

Glavonoid-rich oil supplementation reduces stearoyl-coenzyme A desaturase 1 expression and improves systemic metabolism in diabetic, obese KK-A mice.

Aims: Glavonoid-rich oil (GRO) derived from ethanol extraction of licorice (Glycyrrhiza glabra Linne) root has been reported to have beneficial effects on health. In this study, we aimed to determine the effect of long-term administration of GRO on metabolic disorders and to elucidate the molecular mechanism.

Main Methods: Female obese, type 2 diabetic KK-A mice were fed diets supplemented with 0.

Development of diagnostic antibodies against immunoglobulin heavy chain variable region for heavy chain amyloidosis (AH amyloidosis).

It is difficult to diagnose immunoglobulin heavy chain amyloidosis (AH amyloidosis) without proteomic analysis due to no useful diagnostic antibodies. The aim of this study was to develop diagnostic antibodies available to immunohistochemistry and immunoblotting. Two rabbit anti-heavy chain variable region antibodies were generated and evaluated in immunohistochemical studies performed on 11 AH amyloidosis patients and 64 patients with other systemic amyloidoses.

Curcumin promotes AApoAII amyloidosis and peroxisome proliferation in mice by activating the PPARα signaling pathway.

Curcumin is a polyphenol compound that exhibits multiple physiological activities. To elucidate the mechanisms by which curcumin affects systemic amyloidosis, we investigated amyloid deposition and molecular changes in a mouse model of amyloid apolipoprotein A-II (AApoAII) amyloidosis, in which mice were fed a curcumin-supplemented diet. Curcumin supplementation for 12 weeks significantly increased AApoAII amyloid deposition relative to controls, especially in the liver and spleen.

Dialysis-related amyloidosis associated with a novel β-microglobulin variant.

Till date, there had been no reported case of dialysis-related amyloidosis (DRA) associated with a β-microglobulin variant. We report here a 41-year-old haemodialysis patient with systemic amyloidosis, exhibiting macroglossia and swelling salivary glands, uncommon clinical manifestations for DRA. Molecular analysis showed that the patient had a new variant of β-microglobulin (V27M).

Weaker prepulse exerts stronger suppression of a change-detecting neural circuit.

Change-N1 peaking 90-180 ms after changes in a sound feature of a continuous sound is clearly attenuated by a preceding change stimulus (called a "prepulse"). Here, we investigated the effects of a preceding decrease in sound pressure on the degree of inhibition of the subsequent Change-N1 amplitude. Using 100-Hz click train sounds, we obtained Change-N1s from 11 healthy volunteers.

Recognition on trigger condition of autonomous emergency braking system.

Introduction: Automobiles carrying an autonomous emergency braking system (AEBS) are currently prevailing. While the reduction of traffic accidents is expected because of the widespread use of the system, concerns as regards many drivers using the system without proper understanding of the trigger conditions (TCs) have arisen. This research aims to grasp the degree of recognition of the AEBS TCs by a driver with a vehicle equipped with the system.

Suppression of Mouse AApoAII Amyloidosis Progression by Daily Supplementation with Oxidative Stress Inhibitors.

Amyloidosis is a group of diseases characterized by protein misfolding and aggregation to form amyloid fibrils and subsequent deposition within various tissues. Previous studies have indicated that amyloidosis is often associated with oxidative stress. However, it is not clear whether oxidative stress is involved in the progression of amyloidosis.

[The senescence-accelerated mouse as a model for geriatrics and aging biology].

Rapid expansion of aged population is predicted worldwide. To cope with problems expected from this situation and extend the period of active and healthy life of people as much as possible, it is important to elucidate not only the biological mechanisms of "aging", but also the etiology of various "age-related diseases". To attain this goal, extensive studies using excellent animal models are indispensable.

Coenzyme Q10 Prevents Senescence and Dysfunction Caused by Oxidative Stress in Vascular Endothelial Cells.

Oxidative damage in endothelial cells is proposed to play an important role in endothelial dysfunction and atherogenesis. We previously reported that the reduced form of coenzyme Q10 (CoQH) effectively inhibits oxidative stress and decelerates senescence in senescence-accelerated mice. Here, we treated human umbilical vein endothelial cells (HUVECs) with HO and investigated the protective effect of CoQH against senescence, oxidative damage, and reduction in cellular functions.

Apolipoprotein A-II induces acute-phase response associated AA amyloidosis in mice through conformational changes of plasma lipoprotein structure.

During acute-phase response (APR), there is a dramatic increase in serum amyloid A (SAA) in plasma high density lipoproteins (HDL). Elevated SAA leads to reactive AA amyloidosis in animals and humans. Herein, we employed apolipoprotein A-II (ApoA-II) deficient (Apoa2 ) and transgenic (Apoa2Tg) mice to investigate the potential roles of ApoA-II in lipoprotein particle formation and progression of AA amyloidosis during APR.

Amyloidosis-inducing activity of blood cells in mouse AApoAII amyloidosis.

Mouse senile amyloidosis is a disorder in which apolipoprotein A-II (APOA2) deposits as amyloid fibrils (AApoAII) in many organs. We previously reported that AApoAII amyloidosis can be transmitted by feces, milk, saliva and muscle originating from mice with amyloid deposition. In this study, the ability of blood components to transmit amyloidosis was evaluated in our model system.

Comprehensive proteomic profiles of mouse AApoAII amyloid fibrils provide insights into the involvement of lipoproteins in the pathology of amyloidosis.

Unlabelled: Amyloidosis is a disorder characterized by extracellular fibrillar deposits of misfolded proteins. The amyloid deposits commonly contain several non-fibrillar proteins as amyloid-associated proteins, but their roles in amyloidosis pathology are still unknown. In mouse senile amyloidosis, apolipoprotein A-II (ApoA-II) forms extracellular amyloid fibril (AApoAII) deposits with other proteins (AApoAII-associated proteins) in many organs.

Coenzyme Q10 Improves Lipid Metabolism and Ameliorates Obesity by Regulating CaMKII-Mediated PDE4 Inhibition.

Our recent studies revealed that supplementation with the reduced form of coenzyme Q10 (CoQH) inhibits oxidative stress and slows the process of aging in senescence-accelerated mice. CoQH inhibits adipocyte differentiation and regulates lipid metabolism. In the present study, we show that dietary supplementation with CoQH significantly reduced white adipose tissue content and improved the function of brown adipose tissue by regulating expression of lipid metabolism-related factors in KKAy mice, a model of obesity and type 2 diabetes.