Identification and Characterization of a Dual-Acting Antinematodal Agent against the Pinewood Nematode, Bursaphelenchus xylophilus

The pinewood nematode (PWN), Bursaphelenchus xylophilus, is a mycophagous and phytophagous pathogen responsible for the current widespread epidemic of the pine wilt disease, which has become a major threat to pine forests throughout the world. Despite the availability of several preventive trunk-injection agents, no therapeutic trunk-injection agent for eradication of PWN currently exists. In the characterization of basic physiological properties of B. xylophilus YB-1 isolates, we established a high-throughput screening (HTS) method that identifies potential hits within approximately 7 h. Using this HTS method, we screened 206 compounds with known activities, mostly antifungal, for antinematodal activities and identified HWY-4213 (1-n-undecyl-2-[2-fluorphenyl] methyl-3,4-dihydro-6,7-dimethoxy-isoquinolinium chloride), a highly water-soluble protoberberine derivative, as a potent nematicidal and antifungal agent. When tested on 4 year-old pinewood seedlings that were infected with YB-1 isolates, HWY-4213 exhibited a potent therapeutic nematicidal activity. Further tests of screening 39 Caenorhabditis elegans mutants deficient in channel proteins and B. xylophilus sensitivity to Ca2+ channel blockers suggested that HWY-4213 targets the calcium channel proteins. Our study marks a technical breakthrough by developing a novel HTS method that leads to the discovery HWY-4213 as a dual-acting antinematodal and antifungal compound

Pulsed Electromagnetic Field Stimulates Cellular Proliferation in Human Intervertebral Disc Cells

∙The authors have no financial conflicts of interest. Purpose: The purpose of this study is to investigate the mechanism of cellular proliferation of electromagnetic field (EMF) on human intervertebral disc (IVD) cells. Materials and Methods: Human IVD cells were cultured three-dimensionally in alginate beads. EMF was exposed to IVD cells with 650 Ϊ, 1.8 millitesla magnetic flux density, 60 Hz sinusoidal wave. Cultures were divided into a control and EMF group. Cytotoxicity, DNA synthesis and proteoglycan synthesis were measured by MTT assay, [ 3 H]-thymidine, and [ 35 S]-sulfate incorporation. To detect phenotypical expression, reverse transcription-polymerase chain reactions (RT-PCR) were performed for aggrecan, collagen type I, and type II mRNA expression. To assess action mechanism of EMF, IVD cells were exposed to EMF with N G-Monomethyl-L-arginine (NMMA) and acetylsalicylic acid (ASA). Results: There was no cytotoxicity in IVD cells with the EMF group in MTT assay. Cellular proliferation was observed in the EMF group (p < 0.05). There was no difference in newl

Validation study of the Dinamap ProCare 200 upper arm blood pressure monitor in children and adolescents

PurposeTo validate the Dinamap ProCare 200 blood pressure (BP) monitor against a mercury sphygmomanometer in children 7 to 18 years old in accordance with the 2010 International Protocol of European Society of Hypertension (ESH-IP2) and the British Hypertension Society (BHS) protocol.MethodsForty-five children were recruited for the study. A validation procedure was performed following the protocol based on the ESH-IP2 and BHS protocols for children and adolescents. Each subject underwent 7 sequential BP measurements alternatively with a mercury sphygmomanometer and the test device by trained nurses. The results were analyzed according to the validation criteria of ESH-IP2.ResultsThe mean (±SD) difference in the absolute BP values between test device and mercury sphygmomanometer readings was 1.85±1.65 mmHg for systolic BP (SBP) and 4.41±3.53 mmHg for diastolic BP (DBP). These results fulfilled the Association for the Advancement of Medical Instrumentation criterion of a mean±SD below 5±8 mmHg for both SBP and DBP. The percentages of test device-observer mercury sphygmomanometer BP differences within 5, 10, and 15 mmHg were 96%, 100%, and 100% for SBP, and 69%, 92%, and 100% for DBP, respectively, in the part 1 analysis; both SBP and DBP passed the part 1 criteria. In the part 2 analysis, SBP passed the criteria but DBP failed.ConclusionAlthough the Dinamap ProCare 200 BP monitor failed an adapted ESH-IP2, SBP passed. When comparing BP readings measured by oscillometers and mercury sphygmomanometers, one has to consider the differences between them, particularly in DBP, because DBP can be underestimated

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Cuvette-Type LSPR Sensor for Highly Sensitive Detection of Melamine in Infant Formulas

The globalization of food distribution has made necessary to secure safe products to the general consumers through the rapid detection of harmful additives on the field. For this purpose, we developed a cuvette-type localized surface plasmon resonance (LSPR) sensor that can be easily used by consumers with conventional ultraviolet-visible light spectrophotometer for in-situ measurements. Gold nanoparticles were uniformly deposited on a transparent substrate via a self-assembly method to obtain a plasmonically active chip, and the chemical receptor p-nitroaniline (p-NA) was functionalized to stabilize the device sensitivity under external temperature and pH conditions. The fabricated chip was fixed onto a support and combined with a cuvette-type LSPR sensor. To evaluate the applicability of this sensor on the field, sensitivity and quantitative analysis experiments were conducted onto melamine as a model sample from harmful food additives. Under optimal reaction condition (2 mM p-NA for 20 min), we achieved an excellent detection limit (0.01 ppb) and a dynamic range allowing quantitative analysis over a wide concentration range (0.1–1000 ppb) from commercially available milk powder samples

Venous-predominant parenchymal arteriovenous malformation: a rare subtype with a venous drainage pattern mimicking developmental venous anomaly

OBJECT: Considerable confusion exists in the literature regarding the classification of cerebrovascular malformations and their clinical significance. One example is provided by the atypical developmental venous anomaly (DVA) with arteriovenous shunt, because it remains controversial whether these lesions should be classified as DVAs or as atypical cases of other subtypes of cerebrovascular malformations. The purpose of this study was to clarify the classification of these challenging vascular lesions in an effort to suggest an appropriate diagnosis and management strategy. METHODS: The authors present a series of 15 patients with intracranial vascular malformations that were angiographically classified as atypical DVAs with arteriovenous shunts. This type of vascular malformation shows a fine arterial blush without a distinct nidus and early filling of dilated medullary veins that drain these arterial components during the arterial phase on angiography. Those prominent medullary veins converge toward an enlarged main draining vein, which together form the caput medusae appearance of a typical DVA. RESULTS: Based on clinical, angiographic, surgical, and histological findings, the authors propose classifying these vascular malformations as a subtype of an arteriovenous malformation (AVM), rather than as a variant of DVA or as a combined vascular malformation. CONCLUSIONS: Correct recognition of this AVM subtype is required for its proper management, and its clinical behavior appears to follow that of a typical AVM. Gamma Knife radiosurgery appears to be a good alternative to resection, although long-term follow-up results require verification.This study was supported in part by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No. A06-0171-B51004-06N1-00040B)