133 research outputs found

    The full repertoire of Drosophila gustatory receptors for detecting an aversive compound.

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    The ability to detect toxic compounds in foods is essential for animal survival. However, the minimal subunit composition of gustatory receptors required for sensing aversive chemicals in Drosophila is unknown. Here we report that three gustatory receptors, GR8a, GR66a and GR98b function together in the detection of L-canavanine, a plant-derived insecticide. Ectopic co-expression of Gr8a and Gr98b in Gr66a-expressing, bitter-sensing gustatory receptor neurons (GRNs) confers responsiveness to L-canavanine. Furthermore, misexpression of all three Grs enables salt- or sweet-sensing GRNs to respond to L-canavanine. Introduction of these Grs in sweet-sensing GRNs switches L-canavanine from an aversive to an attractive compound. Co-expression of GR8a, GR66a and GR98b in Drosophila S2 cells induces an L-canavanine-activated nonselective cation conductance. We conclude that three GRs collaborate to produce a functional L-canavanine receptor. Thus, our results clarify the full set of GRs underlying the detection of a toxic tastant that drives avoidance behaviour in an insect

    Design and Evaluation of Passive Shoulder Joint Tracking Module for Upper-Limb Rehabilitation Robots

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    As the number of people suffering from shoulder movement disabilities increases, there is a rising demand for shoulder rehabilitation. The natural motion of the shoulder joint [glenohumeral (GH) joint] includes not only three-degrees-of-freedom (DOF) rotation but also three-DOF translation of the joint center due to simultaneous motion of the shoulder girdle. If the motion of the shoulder girdle is restricted, then the arm cannot be raised above a certain posture. This paper presents a passive shoulder joint tracking device that allows three-DOF translation of the shoulder joint while compensating for gravity. The single-DOF vertical tracker with a constant-force spring compensates for the gross weight of the user's arm, the upper limb rehabilitation device, and the tracker itself while allowing vertical tracking motion. The two-DOF horizontal tracker consists of two linear guides arranged perpendicular to each other. The tracker freely follows the shoulder joint in the horizontal plane. The effect of using the passive shoulder joint tracking device was evaluated by means of experiments by combining two popular commercial upper limb rehabilitation apparatuses with the proposed tracker. Nineteen subjects (8 healthy persons and 11 patients with shoulder impairments) participated in the evaluation study. The movement of the GH joint and the interactive force between the subject and the commercial rehabilitation device were analyzed when subjects made the following shoulder movements: flexion/extension and abduction/adduction. The improved tracker allowed a greater range of motion and reduced interaction. The tracker can be combined with existing commercial rehabilitation devices for more natural shoulder movement during rehabilitation tasks

    A Microchip for High-throughput Axon Growth Drug Screening

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    It has been recently known that not only the presence of inhibitory molecules associated with myelin but also the reduced growth capability of the axons limit mature central nervous system (CNS) axonal regeneration after injury. Conventional axon growth studies are typically conducted using multi-well cell culture plates that are very difficult to use for investigating localized effects of drugs and limited to low throughput. Unfortunately, there is currently no other in vitro tool that allows investigating localized axonal responses to biomolecules in high-throughput for screening potential drugs that might promote axonal growth. We have developed a compartmentalized neuron culture platform enabling localized biomolecular treatments in parallel to axons that are physically and fluidically isolated from their neuronal somata. The 24 axon compartments in the developed platform are designed to perform four sets of six different localized biomolecular treatments simultaneously on a single device. In addition, the novel microfluidic configuration allows culture medium of 24 axon compartments to be replenished altogether by a single aspiration process, making high-throughput drug screening a reality

    ZnO nanoparticle growth on single-walled carbon nanotubes by atomic laye r deposition and a consequent lifetime elongation of nanotube field emission emission

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    ZnO nanoparticles were grown on single-walled carbon nanotubes (SWNTs) by atomic layer deposition using diethylzinc (DEZ) and water. The athors discuss that, because of chemical inertness of nanotubes to DEZ and water molecules, such nanoparticles are not likely to grow on the wall of clean and perfect nanotubes. Rather, the growth of ZnO nanoparticles should be attributed to imperfection of nanotubes, such as defects and carbonaceous impurities. Lifetime of field emission from SWNTs with the ZnO nanoparticles is 2.5 times longer than that from the as-grown nanotubes. It is thought that the protection of the defects or impurities by ZnO nanoparticles mainly contributed to the improvement of the field emission lifetime from SWNTs.open262

    Clinical and Echocardiographic Findings of Newly Diagnosed Acute Decompensated Heart Failure in Elderly Patients

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    PURPOSE: Elderly patients (pts) (EPs; ≥ 65 years old) with newly diagnosed-acute decompensated heart failure (ND-ADHF) have not yet been studied. The aim of the present study was to investigate clinical characteristics, including echocardiographic findings and prognosis, for EPs with ND-ADHF and to compare those with non-elderly pts (NEPs). MATERIALS AND METHODS: We retrospectively investigated 256 pts (144 males, 63.0 ± 14.8 years old) who were admitted to our hospital between January 2005 and March 2009 with ND-ADHF. Clinical characteristics and echocardiographic parameters were analyzed in EPs (n = 135, 58 males) and NEPs (n = 121, 86 males). RESULTS: In intergroup comparison, female gender, diabetes mellitus, previous stroke and hypertension were more common in EPs. Body mass index (22.3 ± 4.5 vs. 24.0 ± 4.4 kg/m(2)), estimated glomerular filtration rate (54.8 ± 24.3 vs. 69.2 ± 30.7 mL/min/m(2)), C-reactive protein (28.5 ± 46.9 vs. 7.6 ± 11.6 mg/dL), hemoglobin (12.3 ± 2.1 vs. 13.6 ± 2.3 g/dL) and N-terminal pro-brain natriuretic peptide level (10,538.2 ± 10,942.3 vs. 6,771.0 ± 8,964.7 pg/mL) were significantly different (p < 0.05 for all). Early mitral inflow velocity to early diastolic mitral annular velocity (E/E') was significantly higher in EPs than in NEPs (21.2 ± 9.4 vs. 18.0 ± 8.9, p < 0.05). During follow-up (44.7 ± 14.5 months), there were no significant differences in in-hospital mortality, re-hospitalization and cardiovascular mortality between EPs and NEPs (p = NS for all). CONCLUSION: EPs with ND-ADHF have different clinical characteristics and higher LV filling pressure when compared with NEPs. However, the clinical outcomes for NEPs with ND-ADHF are not necessarily more favorable than those for EPs.ope

    Nlrp3, Csf3, and Edn1 in Macrophage Response to Saturated Fatty Acids and Modified Low-Density Lipoprotein

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    Background and Objectives: The relationship between metabolic stress, inflammation, and cardiovascular disease is being studied steadily. The aim of this study was to evaluate the effect of palmitate (PA) and minimally modified low-density lipoprotein (mmLDL) on macrophages and to identify the associated pathways. Methods: J774 macrophages were incubated with PA or mmLDL and lipopolysaccharide (LPS). Secretion of inflammatory chemokines and the expression of corresponding genes were determined. The phosphorylation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase was also assessed. RNA sequencing of macrophages was performed to identify the genes regulated by PA or mmLDL. Some of the genes regulated by the 2 agents were validated by knocking down the cells using small interfering RNA. Results: PA or mmLDL promoted the secretion of interleukin (IL)-6 and IL-1 beta in LPS-stimulated macrophages, and this was accompanied by higher phosphorylation of ERK. RNA sequencing revealed dozens of genes that were regulated in this process, such as Csf3and Edn1, which were affected by PA and mmLDL, respectively. These agents also increased NIrp3 expression. The effect of Csf3 or Edn1 silencing on inflammation was modest, whereas toll-like receptor (TLR) 4 inhibition reduced a large proportion of macrophage activation. Conclusions: We demonstrated that the proinflammatory milieu with high levels of PA or mmLDL promoted macrophage activation and the expression of associated genes such as NIrp3, 613, and Edn1. Although the TLR4 pathway appeared to be most relevant, additional role of other genes in this process provided insights regarding the potential targets for intervention.11Nsciescopu

    Risk of newly developed atrial fibrillation by alcohol consumption differs according to genetic predisposition to alcohol metabolism: a large-scale cohort study with UK Biobank

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    Background The predictive relationship between mild-to-moderate alcohol consumption and the risk of incident atrial fibrillation (AF) remains controversial. Objective We investigated whether the relationship between alcohol consumption and the risk of incident AF could be associated with the genetic predisposition to alcohol metabolism. Methods A total of 399,329 subjects with genetic data from the UK Biobank database, enrolled between 2006 and 2010, were identified and followed for incident AF until 2021. Genetic predisposition to alcohol metabolism was stratified according to the polygenic risk score (PRS) tertiles. Alcohol consumption was categorized as non-drinkers, mild-to-moderate drinkers (< 30 g/day), and heavy drinkers (≥ 30 g/day). Results During the follow-up (median 12.2 years), 19,237 cases of AF occurred. When stratified by PRS tertiles, there was a significant relationship between genetic predisposition to alcohol metabolism and actual alcohol consumption habits (P < 0.001). Mild-to-moderate drinkers showed a decreased risk of AF (HR 0.96, 95% CI 0.92–0.99), and heavy drinkers showed an increased risk of AF (HR 1.06, 95% CI 1.02–1.10) compared to non-drinkers. When stratified according to PRS tertiles for genetic predisposition to alcohol metabolism, mild-to-moderate drinkers had equivalent AF risks, and heavy drinkers showed increased AF risk in the low PRS tertile group. However, mild-to-moderate drinkers had decreased AF risks and heavy drinkers showed similar risks of AF in the middle/high PRS tertile groups. Conclusions Differential associations between alcohol consumption habits and incident AF across genetic predisposition to alcohol metabolism were observed; individuals with genetic predisposition to low alcohol metabolism were more susceptible to AF.This work was supported by grant no. 04-2022-2260 from the SNUH Research Fund

    Change in the diagnosis of inflammatory bowel disease: a hospital-based cohort study from Korea

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    Background/AimsAccurately diagnosing inflammatory bowel disease (IBD) remains a challenge, but is crucial for providing proper management for affected patients. The aim of the present study was to evaluate the frequency of change in diagnosis in Korean patients who were referred to our institution with a diagnosis of IBD.MethodsWe enrolled 1,444 patients diagnosed with ulcerative colitis (UC) and 1,452 diagnosed with Crohn's disease (CD), who had been referred to the Asan Medical Center between January 2010 and December 2014. These patients were assessed and subsequently classified as having UC, CD, indeterminate colitis, possible IBD, or non-IBD.ResultsDuring a median follow-up of 15.9 months, 400 of the 2,896 patients (13.8%) analyzed in this study experienced a change in diagnosis. A change in diagnosis from UC to CD, or vice-versa, was made in 24 of 1,444 patients (1.7%) and 23 of 1,452 patients (1.6%), respectively. A change to a non-IBD diagnosis was the most common modification; 7.5% (108 of 1444) and 12.7% (184 of 1452) of the patients with a referral diagnosis of UC and CD, respectively, were reclassified as having non-IBD. Among the 292 patients who were ultimately determined not to have IBD, 135 (55 UC and 80 CD cases) had received IBD-related medication.ConclusionsThere are diagnostic uncertainties and difficulties in relation to IBD. Therefore, precise assessment and systematic follow-up are essential in the management of this condition
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