Detection of Substrate Phosphorylation of LRRK2 in Tissues and Cultured Cells.

Recent studies revealed that leucine-rich repeat kinase 2 (LRRK2) phosphorylates several Rab proteins under physiological conditions. Mutations linked with familial Parkinson's disease cause an abnormal increase in the Rab phosphorylation, which has not been elucidated in an in vitro kinase assays where artificial peptide substrates are often used. Here, we provide protocols for detecting the LRRK2 activity in tissues and cultured cells using Rab phosphorylation as a readout.

Toxoplasma gondii Matrix Antigen 1 Is a Secreted Immunomodulatory Effector.

Our studies on novel cyst wall proteins serendipitously led us to the discovery that cyst wall and vacuolar matrix protein MAG1, first identified a quarter of a century ago, functions as a secreted immunomodulatory effector. MAG1 is a dense granular protein that is found in the parasitophorous vacuolar matrix in tachyzoite vacuoles and the cyst wall and matrix in bradyzoite vacuoles. In the current study, we demonstrated that MAG1 is secreted beyond the parasitophorous vacuole into the host cytosol in both tachyzoites and bradyzoites.

Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer's disease mouse model.

Conjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer's disease (AD) remain to be elucidated.

Autopsy of a case of rheumatoid arthritis with severe bicytopoenia due to gelatinous transformation of the bone marrow.

We present the case of an elderly female patient with rheumatoid arthritis (RA) treated with methotrexate. She was referred to our hospital with severe malaise. She was emaciated and had massive pleural effusion that induced atelectasis.

Regulation of vascular permeability in cancer metastasis.

Enhancement of vascular permeability is indispensable for cancer metastasis. Weakened endothelial barrier function enhances vascular permeability. Circulating tumor cells moving in the microvasculature tend to invade into stromal tissue at the location where vascular permeability is enhanced.

Patellar resurfacing has minimal impact on in vitro tibiofemoral kinematics during deep knee flexion in total knee arthroplasty.

Background: While patellar resurfacing can affect patellofemoral kinematics, the effect on tibiofemoral kinematics is unknown. We hypothesized that patellar resurfacing would affect tibiofemoral kinematics during deep knee flexion due to biomechanical alteration of the extensor mechanism.

Methods: We performed cruciate-retaining TKA in fresh-frozen human cadaveric knees (N = 5) and recorded fluoroscopic kinematics during deep knee flexion before and after the patellar resurfacing.

Impact of Perihematomal Edema on Infectious Complications after Spontaneous Intracerebral Hemorrhage.

Objective: Intracerebral hematoma involves two mechanisms leading to brain injury: the mechanical disruption of adjacent brain tissue by the hematoma and delayed neurological injury. Delayed neurological injury involves perihematomal edema (PHE) formation. Infectious complications following intracerebral hemorrhage (ICH) are a significant contributor to post-ICH recovery.

Role of the β-Catenin/REG Iα Axis in the Proliferation of Sessile Serrated Adenoma/Polyps Associated with .

Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma-carcinoma sequence, details of SSA/P tumorigenesis still remain unclear. () is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between and the β-catenin/REG Iα axis in SSA/Ps and their involvement in the proliferation of these lesions.

Morphological features of the nasal cavities of hawksbill, olive ridley, and black sea turtles: Comparative studies with green, loggerhead and leatherback sea turtles.

We analyzed the internal structure of the nasal cavities of hawksbill, olive ridley and black sea turtles from computed tomography images. The nasal cavities of all three species consisted of a vestibule, nasopharyngeal duct and cavum nasi proprium that included anterodorsal, posterodorsal and anteroventral diverticula, and a small posteroventral salience formed by a fossa of the wall. These findings were similar to those of green and loggerhead sea turtles (Cheloniidae), but differed from those of leatherback sea turtles (Dermochelyidae).

The higher patient-reported outcome measure group had smaller external rotation of the femur in bicruciate-stabilized total knee arthroplasty.

Purpose: The hypothesis of this study was that the kinematics of patients with higher patient-reported outcome measures (PROMs) differ from those of patients with lower PROMs after bicruciate-stabilized total knee arthroplasty (BCS-TKA).

Methods: A total of 32 patients with severe knee osteoarthritis were examined 11.2 ± 3.

Photo-oxygenation by a biocompatible catalyst reduces amyloid-β levels in Alzheimer's disease mice.

Amyloid formation and the deposition of the amyloid-β peptide are hallmarks of Alzheimer's disease pathogenesis. Immunotherapies using anti-amyloid-β antibodies have been highlighted as a promising approach for the prevention and treatment of Alzheimer's disease by enhancing microglial clearance of amyloid-β peptide. However, the efficiency of antibody delivery into the brain is limited, and therefore an alternative strategy to facilitate the clearance of brain amyloid is needed.

Analysis of ADAM12-Mediated Ephrin-A1 Cleavage and Its Biological Functions.

Accumulating evidence indicates that an elevated ephrin-A1 expression is positively correlated with a worse prognosis in some cancers such as colon and liver cancer. The detailed mechanism of an elevated ephrin-A1 expression in a worse prognosis still remains to be fully elucidated. We previously reported that ADAM12-cleaved ephrin-A1 enhanced lung vascular permeability and thereby induced lung metastasis.

Effect of Instruction on Preventing Delayed Bleeding after Colorectal Polypectomy and Endoscopic Mucosal Resection.

Background: The frequency of delayed bleeding after colorectal polypectomy has been reported as 0.6-2.8%.

Butyrate Alleviates Cytokine-Induced Barrier Dysfunction by Modifying Claudin-2 Levels.

Gastrointestinal (GI) disorders such as celiac disease and inflammatory bowel disease are attributed to intestinal barrier disruption. Imbalance of cytokines has been reported in the intestinal epithelium of patients with GI disorders. Short-chain fatty acids (SCFAs), derived from the fermentation of dietary fiber in the intestine, have been reported to benefit the intestinal barrier.

Catalytic photooxygenation degrades brain Aβ in vivo.

Protein degradation induced by small molecules by recruiting endogenous protein degradation systems, such as ubiquitin-proteasome systems, to disease-related proteins is an emerging concept to inhibit the function of undruggable proteins. Protein targets without reliable ligands and/or existing outside the cells where ubiquitin-proteasome systems do not exist, however, are beyond the scope of currently available protein degradation strategies. Here, we disclose photooxygenation catalyst that permeates the blood-brain barrier and selectively and directly degrades an extracellular Alzheimer's disease-related undruggable protein, amyloid-β protein (Aβ).

A Novel Gene Cluster Is Involved in the Degradation of Lignin-Derived Monoaromatics in Thermus oshimai JL-2.

A novel gene cluster involved in the degradation of lignin-derived monoaromatics such as -hydroxybenzoate, vanillate, and ferulate has been identified in the thermophilic nitrate reducer JL-2. Based on conserved domain analyses and metabolic pathway mapping, the cluster was classified into upper- and peripheral-pathway operons. The upper-pathway genes, responsible for the degradation of -hydroxybenzoate and vanillate, are located on a 0.

Sequential conformational changes in transmembrane domains of presenilin 1 in Aβ42 downregulation.

Alzheimer disease (AD) is the most common neurodegenerative disease worldwide. AD is pathologically characterized by the deposition of senile plaques in the brain, which are composed of an amyloid-β peptide (Aβ) that is produced through the multistep cleavage of amyloid precursor protein (APP) by γ-secretase. γ-Secretase is a membrane protein complex, which includes its catalytic subunit presenilin 1 (PS1).

In vivo kinematics and cruciate ligament forces in bicruciate-retaining total knee arthroplasty.

We analyzed the effects of bicruciate-retaining total knee arthroplasty (BCR-TKA) on knee kinematics and cruciate ligament forces. Patients (N = 15) with osteoarthritis (OA) and an intact anterior cruciate ligament (ACL) underwent magnetic resonance imaging and single-plane fluoroscopy to measure tibiofemoral kinematics during two deep knee bend activities before and after BCR-TKA: (1) weight-bearing squat; (2) non-weight-bearing cross-legged sitting. Forces in ligament bundles were calculated using VivoSim.

In vivo kinematics of a newly updated posterior-stabilised mobile-bearing total knee arthroplasty in weight-bearing and non-weight-bearing high-flexion activities.

Background: The purpose of this study was to clarify the in vivo kinematics of a newly updated posterior-stabilised (PS) mobile-bearing total knee arthroplasty during high-flexion activities in weight-bearing (WB) and non-weight-bearing (NWB) conditions. The hypothesis was that the kinematics would differ between the WB and NWB conditions, and the kinematics would be affected by the WB condition.

Methods: The kinematics of 19 knees were investigated under fluoroscopy during squatting (WB) and active-assisted knee flexion (NWB) with two- and three-dimensional registration technique.

Flexible and Accurate Substrate Processing with Distinct Presenilin/γ-Secretases in Human Cortical Neurons.

Mutations in the genes (, ) have been linked to the majority of familial Alzheimer's disease (AD). Although great efforts have been made to investigate pathogenic mutations, which ultimately cause an increase in the toxic form of β-amyloid (Aβ), the intrinsic physiological functions of PS in human neurons remain to be determined. In this study, to investigate the physiological roles of PS in human neurons, we generated conditional knock-out (KO) induced pluripotent stem cells (iPSCs), in which PS1 can be selectively abrogated under Cre transduction with or without additional KO.

A first, naturally occurring substitution at the second pyrethroid receptor of voltage-gated sodium channel of Aedes aegypti.

Background: Aedes aegypti is a remarkably effective mosquito vector of epidemiologically important arboviral diseases including dengue fever, yellow fever and Zika. The present spread of resistance against pyrethroids, the primary insecticides used for mosquito control, in global populations of this species is of great concern. The voltage-gated sodium channel (VGSC) in the nervous system is the known target site of pyrethroids in insects.

Iris-like eye closure of the fine-patterned pufferfish, Takifugu flavipterus.

Unlike many tetrapods and elasmobranchs, eye-closing ability is absent in bony fishes, with the single-known exception of the family Tetraodontidae. We observed the eye-closing response of the tetraodontid fine-patterned puffer, Takifugu flavipterus, which provides the first detailed data on the kinematics and mechanism of this ability in this family. During eye-closing behavior, the skin around the eye converges toward the center of the iris.

Seeded assembly in vitro does not replicate the structures of α-synuclein filaments from multiple system atrophy.

The propagation of conformational strains by templated seeding is central to the prion concept. Seeded assembly of α-synuclein into filaments is believed to underlie the prion-like spreading of protein inclusions in a number of human neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We previously determined the atomic structures of α-synuclein filaments from the putamen of five individuals with MSA.