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Characterization of two α4/7-conotoxins,Mrl.1 and Lpl.4,as novel antagonists of nicotinic acetylcholine receptors

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Characterization of two α4/7-conotoxins,Mrl.1 and Lpl.4,as ...

第九届中国生物毒素学术研讨会

作者： Tanya Sanders Geoffrey Chew edward hawrot Department of Molecular Pharmacology.Physiology and Biotechnology Brown Medical SchoolProvidenceRhode Island 02912USA

＜正＞α-Conotoxins from cone snails are small disulfide-constrained peptides that act as potent and selective antagonists on specific subtypes of nicotinic acetylcholine receptors（nAChRs）.We recently identified two conopeptides in venom duct mRNA and muscle tissue genomic DNA from the South China Sea species,Mr1.1 from the molluscivorous Conus marmoreus and Lp1.4 from the vermivorous Conus *** have the typical 4/7-type framework characteristic of the subfamily ofα-conotoxins that act on neuronal-type *** two toxins were chemically synthesized and folded into the globular disulfide isomer through different oxidative approaches. Functional studies were carried out in oocytes expressing various nAChRs and with a rat model of inflammatory *** synthetic Mr1.1 primarily inhibited ACh-evoked currents reversibly in the ratα7 receptor,whereas Lp1.4 s unexpectedly a specific blocker of the mouse fetal muscleα1β1γδ*** the two toxins share low-affinity inhibition of nAChRs at high toxin concentrations,their unique receptor recognition profiles make them valuable tools for studying the toxin-receptor *** 1.1 was also shown to potently suppress the inflammatory response to pain in vivo,suggesting that it should be further investigated with respect to the molecular role of Mr1.1 in analgesia and its mechanism or therapeutic target for the treatment of pain.

关键词： Conus α4/7-conotoxins nicotinic acetylcholine receptors analgesia

Characterization of a novel alpha4/4-conotoxin,Qc1.2,from vermivorous Conus quercinus

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Characterization of a novel alpha4/4-conotoxin,Qc1.2,from ve...

第九届中国生物毒素学术研讨会

作者： Tanya Sanders Geoffrey Chew edward hawrot Department of Molecular Pharmacology Physiology and BiotechnologyBrown Medical SchoolProvidenceRhode Island 02912USA

＜正＞Theα4/4-conotoxin first identified in a vermivorous Conus speices, designated Qc1.2,was originally obtained by cDNA and genomic DNA cloning from Conus quercinus collected in the South China *** predicted mature toxin of Qc1.2 contains 14 amino acid residues with two disulfide bonds（Ⅰ-Ⅲ,Ⅱ-Ⅳconnectivity） in a native globular *** mature peptide of Qc1.2 is supposed to contain an N-terminal posttranslationally processed pyroglutamate residue and a free carboxyl *** peptide was chemically synthesized and refolded for further characterizing its function *** synthetic Qc1.2 has two interconvertible conformations in aqueous solution,which may due to the cis-trans isomerization of the two successive Pro residues in its first cysteine *** the Xenopus oocyte heterologous expression system,Qc1.2 was shown to selectively inhibit both rat neuronalα3β2 andα3β4 subtypes of nicotinic acetylcholine receptors with low potency.A block of approximately 63%and 37%of the ACh-evoked currents was observed,respectively,and the toxin dissociated rapidly from the *** to other characterizedα-conotoxin members,the unusual structural features in Qc1.2 that confer to its receptor recognition profile are addressed.

关键词： nicotinic acetylcholine receptor subtypes α4/4-conotoxins posttranslational modification Xenopus oocytes

Blast waveform tailoring using controlled venting in blast simulators and shock tubes

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Defence Technology（防务技术） 2024年第7期37卷 14-26页

作者： edward Chern Jinn Gan Alex Remennikov David Ritzel Faculty of Engineering and Information Sciences University of WollongongWollongongNSW2522Australia Dyn-FX Consulting Ltd 19 Laird Ave NorthAmherstburgONN9V 2T5Canada

A critical challenge of any blast simulation facility is in producing the widest possible pressure-impulse range for matching against equivalent high-explosive *** tubes and blast simulators are often constrained with the lack of effective ways to control blast wave profiles and as a result have a limited performance *** wave shaping techniques employed in some facilities are reviewed but often necessitate extensive geometric modifications,inadvertently cause flow anomalies,and/or are only applicable under very specific *** paper investigates controlled venting as an expedient way for waveforms to be tuned without requiring extensive modifications to the driver or existing geometry and could be widely applied by existing and future blast simulation and shock tube *** use of controlled venting is demonstrated experimentally using the Advanced Blast Simulator(shock tube)at the Australian National Facility of Physical Blast Simulation and via numerical flow simulations with Computational Fluid *** venting is determined as an effective method for mitigating the impact of re-reflected waves within the blast *** control method also allows for the adjustment of parameters such as tuning the peak overpressure,the positive phase duration,and modifying the magnitude of the negative phase and the secondary shock of the blast *** paper is concluded with an illustration of the potential expanded performance range of the Australian blast simulation facility when controlled venting for blast waveform tailoring as presented in this paper is applied.

关键词： Advanced blast simulator Shock wave propagation Far-field explosion Blast loads Blast waves Computational fluid dynamics

Characterization of two α4/7-conotoxins,Mrl.1 and Lpl.4,as novel antagonists of nicotinic acetylcholine receptors

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Characterization of two α4/7-conotoxins,Mrl.1 and Lpl.4,as ...

第九届中国生物毒素学术研讨会

作者：彭灿陈伟华 Tanya Sanders Geoffrey Chew edward hawrot 戚正武郭占云 Institute of Protein Research Tongji University Department of Molecular Pharmacology Physiology and BiotechnologyBrown Medical SchoolProvidence Institute of Biochemistry and Cell Biology Shanghai Institute for Biological SciencesChinese Academy of Sciences

＜正＞α-Conotoxins are small disulfide-constrained peptides that act as potent and selective antagonists on specific subtypes of nicotinic acetylcholine receptors（nAChRs）.We previously cloned twoα-conotoxins,Mr1.1 from the molluscivorous Conus marmoreus and Lp1.4 from the vermivorous Conus *** of them have the typical 4/7-type framework of the subfamily ofα-conotoxins that act on neuronal *** this work,we chemically synthesized the two toxins and characterized their functional *** synthetic Mr1.1 could primarily inhibit acetylcholine （ACh）-evoked currents reversibly in the oocyte-expressed ratα7 nAChR,whereas Lp1.4 was unexpectedly a specific blocker of the mouse fetal muscleα1β1γδreceptor. Although their inhibition affinities were relatively low,their unique receptor recognition profiles make them valuable tools for toxin-receptor interaction studies. Mr1.1 could also suppress the inflammatory response to pain in vivo,suggesting that it should be further investigated with respect to the molecular role of Mr1.1 in analgesia and its mechanism or therapeutic target for the treatment of pain.

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Reflections on Studying Huang Di Nei Jing in the West

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Chinese Medicine and Culture 2024年第1期7卷 72-76页

作者： edward Neal Apricot Grove Educational Services Portland 97213the United States of America Xinglin Institute for Early East Asian Medicine Portland 97213the United States of America

Huang Di Nei Jing(《黄帝内经》The Yellow Emperor’s Inner Classic) has been the source text of Chinese medicine knowledge and innovation for over two thousand years. Despite this key relevance, many of its ideas and practices have proven difficult to understand and implement fully into clinical practice. Cultural and language differences can be compounded with these challenges but may also present new opportunities for advancement and insight when studied by researchers outside of the originating culture. This article introduces the method of Classical-Text Archaeology and delves into the author’s two-decade journey of researching this text, with a discussion on cultural differences and issues of medical scholarship.

关键词： Huang Di Nei Jing Chinese medicine Nei Jing nature-based medicine Classical text research Global health Medical anthropology Classical-Text Archaeology

Identification and Characterization of New Framework 14 Conotoxins from Two Vermivorous Conus Species,as Novel Antagonists of Nicotinic Acetylcholine Receptors

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Identification and Characterization of New Framework 14 Cono...

第九届中国生物毒素学术研讨会

作者：彭灿叶铭宇汪燕芳邵晓霞袁多多 edward hawrot 戚正武王春光 Institute of Protein Research College of Life Sciences and TechnologyTongji University Department of Molecular Pharmacology Physiology and BiotechnologyBrown Medical School Providence Institute of Biochemistry and Cell Biology Shanghai Institute of Biological SciencesChinese Academy of SciencesGraduate School of the Chinese Academy of Sciences

As part of studies of the venom components present in Conus pulicarius and Conus tessulatus, two vermivorous Conus species collected from the South China Sea,we identified two new conotoxins,designated pu14a and ts14a,by cDNA cloning and peptide purification,respectively. The predicted mature toxin region of pu14a contains 19 amino acid(aa) residues with two disulfide bonds(1-3,2-4 connectivity) in a pattern of C(X)C(X)C(X)C(framework 14). However,the 69-amino acid pu14a precursor surprisingly exhibits an identical signal sequence to corresponding regions of previously characterizedα-conotoxins,revealing a new level of conotoxin diversity and a plausible evolution mechanism of Conus prepropeptide recombination. The peptide pu14a has very unique primary structure and intercysteine spacing pattern with its first loop rich in proline *** peptide was chemically synthesized to further characterize its *** synthetic pu14a induces a sleeping phenotype in mice,and it is also toxic to freshwater goldfish upon intramuscular *** the Xenopus oocyte heterologous expression system,pu14a(1μM) was shown to inhibit both rat neuronalα3β2-containing and mouse neuromuscularα1β1γδsubtypes of nicotinic acetylcholine receptors(nAChRs).It blocked the ACh-induced currents(51%anc 55%) in recombinantα3β2 andα6α3β2 nAChRs,respectively, and the toxin dissociated rapidly from the receptor.A block of approximately 82%of the ACh-evoked current was obtained inα1β1γδ,with a similar dissociation *** 20-aa polypeptide chain of ts14a with a 1-3/2-4 cysteine pairing shows high sequence similarity with pu14a,suggesting that it may also inhibit ***,pu14a is a defining member of a novel family of framework 14 conotoxins in the A gene superfamily.

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Areal Roughness of the Dorsal Nail Plate

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International Journal of Dermatology and Venereology 2024年第1期7卷 27-34页

作者： Brian Lee Beatty edward Li Adaeze Anaekwe Anatomy Department NYIT College of Osteopathic MedicineOld WestburyNY 11568USA United States National Museum Smithsonian InstitutionWashingtonDC 20560USA Division of Paleobiology Friends AcademyLocust ValleyNY 11560USA

Objective:Beau lines,onychorrhexis,and psoriatic lesions of the dorsal nail plate may be missed by photographic methods,indicating a need for surface texture measurement methods that are more quantitative,sensitive,and repeatable than visual inspection or *** conducted this study to evaluate the utility of surface texture measurements of cadaveric nails that can be associated with histopathological studies in the ***:The nail plates of 4 cadaveric right pollices and halluces were cleaned and molded,cast in clear epoxy,and scanned with a Sensofar S Neox optical profilometer.A one-way analysis of variance was performed to determine statistical significance of ***:Almost no differences were observed between the pollex and hallux scans and between the distal and proximal *** greatest differences were found between *** lower magnification(5×)is less sensitive than higher magnification(20×),the lower magnification represented and characterized more of the dorsal nail ***:The dorsal nail plate areal roughness has a measurable range of values that may serve as a starting point for evaluating pathological findings,particularly Beau lines and psoriatic *** sensitivity of these techniques may be especially valuable in the recognition of less severe states of these diseases that may enable the diagnosis of earlier stages of growth disruptions(Beau lines)or *** applications could be especially useful in investigations of the health of wildlife populations or vulnerable human populations with incomplete treatment records.

关键词： nail plate surface metrology areal roughness

α-神经毒素-受体相互作用的2D-NMR研究

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α-神经毒素-受体相互作用的2D-NMR研究

第七届全国波谱学学术会议

作者：宋国强 edward hawrot 中科院上海药物所 Dept.of Phamacology Yele Univ.U.S.A.

＜正＞α-bungarotoxin与nicotinic acetylcholine recepter（AChR）相互作用机理的研究,由于这些膜蛋白的分子太大,使得X-射线与NMR的研究变得相当困难.为此,合成了一系列多肽片段,其中由12个氨基酸组成的多肽片段（KHWVYYTCCPDT）,它...

＜正＞α-bungarotoxin与nicotinic acetylcholine recepter（AChR）相互作用机理的研究,由于这些膜蛋白的分子太大,使得X-射线与NMR的研究变得相当困难.为此,合成了一系列多肽片段,其中由12个氨基酸组成的多肽片段（KHWVYYTCCPDT）,它属受体中的活性作用部位,仍

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DEM analysis of the influence of stirrer design on die filling with forced powder feeding

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Particuology 2024年第5期88卷 107-115页

作者： Chao Zheng edward Yost Ariel R.Muliadi Nicolin Govender Ling Zhang Chuan-Yu Wu School of Chemistry and Chemical Engineering University of SurreyGuildfordGU2 7XHUnited Kingdom Small Molecule Pharmaceutics GenentechInc.One DNA WaySouth San FranciscoCA94080USA

Die filling is a critical stage during powder compaction,which can significantly affect the product quality and *** this paper,a forced feeder is introduced attempting to improve the filling performance of a lab-scale die filling *** die filling process is analysed with a graphics processing units(GPU)enhanced discrete element method(DEM).Various stirrer designs are assessed for a wide range of process settings(i.e.,stirrer speed,filling speed)to explore their influence on the die filling performance of free-flowing *** results show that die filing with the novel helical-ribbon(i.e.,type D)stirrer design exhibits the highest filling ratio,implying that it is the most robust stirrer design for the feeder configuration ***,die filling performance with the type D stirrer design is a function of the stirrer speed and the filling speed.A positive variation of filling ratio(ηf>0%)can be ensured over the whole range of filling speed by adjusting the stirrer speed(i.e.,increasing the stirrer speed).The approach used in this study can not only help understand how the stirrer design affects the die filling performance but also guide the optimization of feeder system and process settings.

关键词： Discrete element method Die filling Forced feeding Stirrer design GPU computing