The effect of a citrus-derived flavonoid, hesperetin, on the automaticity and contraction of isolated guinea pig myocardium was examined. Hesperetin inhibited the rate of ectopic action potential firing of the pulmonary vein myocardium; the slope of the diastolic depolarization was decreased with minimum change in the action potential waveform. The effect was dependent on the concentration; the EC value for firing rate was 56.
View Article and Find Full Text PDFThe effects of enhanced late I, a persistent component of the Na channel current, on the intracellular ion dynamics and the automaticity of the pulmonary vein cardiomyocytes were studied with fluorescent microscopy. Anemonia viridis toxin II (ATX- II), an enhancer of late I, caused increases in the basal Na and Ca concentrations, increases in the number of Ca sparks and Ca waves, and the generation of repetitive Ca transients. These phenomena were inhibited by eleclazine, a blocker of the late I; SEA0400, an inhibitor of the Na/Ca exchanger (NCX); H89, a protein kinase A (PKA) inhibitor; and KN-93, a Ca/calmodulin-dependent protein kinase II (CaMKII) inhibitor.
View Article and Find Full Text PDFMicrotubule affinity-regulating kinase 2 (MARK2) is a Ser/Thr protein kinase that regulates cell polarity and immune responses. Here, we report that Orf9b, one of the accessory proteins encoded in the SARS-CoV-2 genome, increases MARK2 activity via interaction with the autoinhibitory KAI domain. We found that co-expression of Orf9b enhances the kinase activity of MARK2 in HEK293 cells.
View Article and Find Full Text PDFAccumulation of abnormally phosphorylated tau proteins is linked to various neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia. Microtubule affinity-regulating kinase 4 (MARK4) has been genetically and pathologically associated with Alzheimer's disease and reported to enhance tau phosphorylation and toxicity in and mouse traumatic brain-injury models but not in mammalian tauopathy models. To investigate the role of MARK4 in tau-mediated neuropathology, we crossed P301S tauopathy model (PS19) and knockout mice.
View Article and Find Full Text PDFAccumulation of abnormally phosphorylated tau and its aggregation constitute a significant hallmark of Alzheimer's disease (AD). Tau phosphorylation at Ser262 and Ser356 in the KXGS motifs of microtubule-binding repeats plays a critical role in its physiological function and AD disease progression. Major tau kinases to phosphorylate tau at Ser262 and Ser356 belong to the Microtubule Affinity Regulating Kinase family (MARK1-4), which are considered one of the major contributors to tau abnormalities in AD.
View Article and Find Full Text PDFIn strawberry production, western flower thrips (WFT) and two-spotted spider mites (TSSM) inflict feeding damage and reduce the yield. Biological control for these pests often includes phytoseiid predatory mites and entomopathogenic fungi. The hemipteran family Nabidae have been reported as prominent predators in open-field strawberry.
View Article and Find Full Text PDFDuring the novel coronavirus outbreak and vaccine development, antibody production garnered major focus as the primary immunogenic response. However, cellular immunity's recent demonstration of comparable or greater significance in controlling infection demands the re-evaluation of the importance of T-cell immunity in SARS-CoV-2 infection. Here, we developed a novel assay, the ex vivo activation of genes in leukocytes (EAGL), which employs short-term whole blood stimulation with the LeukoComplete™ system, to measure ex vivo SARS-CoV-2-specific T cell responses (cellular immunity).
View Article and Find Full Text PDFAbnormal activation of microtubule affinity-regulating kinase 4 (MARK4) and its phosphorylation of the microtubule-associated protein tau are believed to play a role in the pathogenesis of Alzheimer's disease, and MARK4 inhibition can be a strategy to develop disease-modifying therapy. Here we report the development of a membrane-permeable peptide that inhibits MARK4 activity in an allosteric manner. The SARS-CoV-2-derived protein Orf9b inhibited MARK4-mediated tau phosphorylation in primary neurons and Drosophila.
View Article and Find Full Text PDFWe report on the development of a versatile and accurate bioanalytical method for bevacizumab using a pretreatment method combining affinity purification with anti-idiotypic DNA aptamers and centrifugal ultrafiltration concentration, followed by liquid chromatography (LC)-fluorescence analysis. An affinity purification method using Sepharose beads as an affinity support removed immunoglobulin G and a large amount of coexisting substances in the serum sample. Purified bevacizumab was separated as a single peak by conventional LC and detected fluorometrically, showing good linearity (R = 0.
View Article and Find Full Text PDFComplex I (CI) deficiency in mitochondrial oxidative phosphorylation (OXPHOS) is the most common cause of mitochondrial diseases, and limited evidence-based treatment options exist. Although CI provides the most electrons to OXPHOS, complex II (CII) is another entry point of electrons. Enhancement of this pathway may compensate for a loss of CI; however, the effects of boosting CII activity on CI deficiency are unclear at the animal level.
View Article and Find Full Text PDFKey Clinical Message: Bile duct metastasis of breast cancer is rare. It often causes obstructive jaundice which makes the patient interrupt state of treatment. Endoscopic drainage for obstructive jaundice is effective and less invasive treatment option also in this case.
View Article and Find Full Text PDFTherapeutic monoclonal antibodies (mAbs) are currently the most effective medicines for a wide range of diseases. Therefore, it is expected that easy and rapid measurement of mAbs will be required to improve their efficacy. Here, we report an anti-idiotype aptamer-based electrochemical sensor for a humanized therapeutic antibody, bevacizumab, based on square wave voltammetry (SWV).
View Article and Find Full Text PDFA 38-year-old man was taken to hospital with generalized clonic seizure. Brain magnetic resonance imaging (MRI) showed multiple ring-enhancing lesions centered in the left frontoparietal lobe. A histopathological examination of a brain biopsy sample revealed granulomatous lesions with caseous necrosis.
View Article and Find Full Text PDFThe effect of blocking the persistent component of the sodium channel current (late I) on the automatic activity of the isolated guinea pig pulmonary vein myocardium was examined. NCC-3902 blocked late I, but did not affect other major ion channel currents stably expressed in cell lines. In isolated pulmonary vein cardiomyocytes, NCC-3902 blocked the late I induced by a ramp depolarizing voltage clamp pulse similar to that of the pacemaker depolarization observed in the pulmonary vein myocardium.
View Article and Find Full Text PDFMicrotubule (MT) dynamics are modulated through the coordinated action of various MT-associated proteins (MAPs). However, the regulatory mechanisms underlying MT dynamics remain unclear. We show that the MAP7 family protein Map7D2 stabilizes MTs to control cell motility and neurite outgrowth.
View Article and Find Full Text PDFA generalist predatory mite, Anystis baccarum (L.), was evaluated as a biological control agent against western flower thrips (WFT), Frankliniella occidentalis (Pergande). Laboratory assays showed A.
View Article and Find Full Text PDFTherapeutic monoclonal antibodies (mAbs) are successful biomedicines; however, evaluation of their pharmacokinetics and pharmacodynamics demands highly specific discrimination from human immunoglobulin G naturally present in the blood. Here, we developed a novel anti-idiotype aptamer (termed A14#1) with extraordinary specificity against the anti-vascular endothelial growth factor therapeutic mAb, bevacizumab. Structural analysis of the antibody-aptamer complex showed that several bases of A14#1 recognized only the complementarity determining region (CDR) of bevacizumab, thereby contributing to its extraordinary specificity.
View Article and Find Full Text PDFDeclines in mitochondrial functions are associated with aging. The combination of 5-aminolevulinic acid (5-ALA) and sodium ferrous citrate (SFC) improves mitochondrial functions in cultured cells. In this study, we investigated the effects of dietary supplementation with 5-ALA and SFC (5-ALA/SFC) on the healthspan and life span of Drosophila melanogaster.
View Article and Find Full Text PDFLemur tail kinase 1 (LMTK1), previously called apoptosis-associated tyrosine kinase (AATYK), is an endosomal Ser/Thr kinase. We recently reported that LMTK1 regulates axon outgrowth, dendrite arborization and spine formation via Rab11-mediated vesicle transport. Rab11, a small GTPase regulating recycling endosome trafficking, is shown to be associated with late-onset Alzheimer's disease (LOAD).
View Article and Find Full Text PDFA generalist predatory mite, (L.), has been identified as a key predator of small, soft-bodied pest species in various agroecosystems around the world. The foxglove aphid (Keltenbach) is a new problematic pest in Canadian greenhouses.
View Article and Find Full Text PDFAccumulation of microtubule-associated tau protein is thought to cause neuron loss in a group of neurodegenerative diseases called tauopathies. In diseased brains, tau molecules adopt pathological structures that propagate into insoluble forms with disease-specific patterns. Several types of posttranslational modifications in tau are known to modulate its aggregation propensity in vitro, but their influence on tau accumulation and toxicity at the whole-organism level has not been fully elucidated.
View Article and Find Full Text PDFA 66-year-old man presented with worsening dyspnea. A colonoscopy revealed an elevated lesion at the rectosigmoid junction. The biopsy specimen and bone marrow aspiration demonstrated adenocarcinoma, leading to a diagnosis of disseminated carcinomatosis of the bone marrow.
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