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中国菌物学会2018年学术年会

作者：罗宏杨祝良 jonathan d.walton 中国科学院昆明植物研究所 Michigan State University

鹅膏（Amanita）中的剧毒种是对人类威胁最大的蘑菇,国外90%以上的蘑菇致死案例由其导致,在我国这一数字也高达80%。鹅膏环肽毒素虽然致死率极高,却在癌症治疗等方面具有重要医药价值,其生物合成机制可用于人工环肽库的构建。研究组近... 详细信息

鹅膏（Amanita）中的剧毒种是对人类威胁最大的蘑菇,国外90%以上的蘑菇致死案例由其导致,在我国这一数字也高达80%。鹅膏环肽毒素虽然致死率极高,却在癌症治疗等方面具有重要医药价值,其生物合成机制可用于人工环肽库的构建。研究组近期扩建了已有的鹅膏多基因组数据平台,通过高通量测序获得了9个产鹅膏环肽毒素的蘑菇基因组,包括6种外生菌根鹅膏,即黄盖鹅膏（A. subjunquillea）、淡红鹅膏（A. pallidorosea）、裂褶鹅膏（A. rimosa）、灰花纹鹅膏（A. fuliginea）、致命鹅膏（A. exitialis）和***,以及3种腐生剧毒环柄菇,即肉褐鳞环柄菇（Lepiota brunneoincarnata）、近肉红环柄菇（***）和L. venenata。通过整合研究组先前获得的剧毒蘑菇基因组,包括双孢鹅膏（A. bisporigera）、绿盖鹅膏（A. phalloides）和纹缘盔孢伞（Galerina marginata）,本研究大幅扩充了已有的多基因组平台,搭建了一个共计12个基因组、囊括共生与腐生、可用于各项鹅膏研究的多基因组平台。该平台目前支持了超过5项鹅膏基因组、功能基因与系统进化方面的研究。其中,最新的成果表明,该平台对研究基因和代谢途径进化非常奏效,研究组已经得到了鹅膏产毒代谢途径水平基因转移的重要证据,为全面深入地解析该途径的演化历史提供了坚实条件。这一平台也为比较基因组工作的开展创造了机会,通过对毒素区域的综合分析,一些同线性区域已经被找到;在功能研究中该平台也发挥了关键作用,比如黄素单核苷酸（FMO）的工作得以加速进行。综上,鹅膏多基因组平台正在多个领域呈现出显著的研究价值。

关键词：鹅膏环柄菇鹅膏环肽基因组比较基因组

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剧毒鹅膏环肽的生物合成

剧毒鹅膏环肽的生物合成

A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

中国菌物学会2016年学术年会

作者：罗宏 jonathan d.walton Heather Hallen-Adams 中国科学院昆明植物研究所 Michigan State University University of Nebraska-Lincoln

剧毒鹅膏（Amanita spp.）所含环肽毒素直接导致90%以上的蘑菇致死案例,其环肽合成基因具有重要医药价值。对鹅膏基因组、转录组和遗传生化的综合研究证明,鹅膏环肽生物合成途径为真菌中首个报道的核糖体环肽合成途径,前体基因（MSdIN... 详细信息

剧毒鹅膏（Amanita spp.）所含环肽毒素直接导致90%以上的蘑菇致死案例,其环肽合成基因具有重要医药价值。对鹅膏基因组、转录组和遗传生化的综合研究证明,鹅膏环肽生物合成途径为真菌中首个报道的核糖体环肽合成途径,前体基因（MSdIN家族）含保守区及高变区,以组合式方式合成环肽。前体肽通过脯氨酸寡肽酶的切割和大环化作用高效转化为环肽,并由后修饰基因逐步加工成为活性环肽。基因组数据表明,在产生α-鹅膏毒肽的纹缘盔孢伞（Galerina marginata）中,鹅膏环肽生物合成基因构成一个"非典型"基因簇。通过基因敲除等遗传学分析,研究进一步证明多个未知基因参与了鹅膏环肽的后修饰,目前已经初步明确了两个细胞色素（P450）参与了重要位点的羟基化,其中Gm P450A完成脯氨酸残基的羟基化,Gm P450B可能作用于异亮氨酸残基。此外,一个黄素单加氧酶（Flavin-containing monooxygenase）可能参与了架桥和/或磺化的反应。研究还确定了其它多个未知基因与鹅膏环肽生物合成相关,功能研究工作已经展开。综合目前的研究结果,大致确定鹅膏环肽合成需要10个以上基因的参与,这些基因形成一个基因簇,多数基因已经专化并在代谢途径中行使独特功能。本研究为清晰勾勒鹅膏环肽合成的整体轮廓并揭示其合成机理,为开发利用这些基因资源奠定了坚实基础。

关键词：鹅膏环肽生物合成基因组基因簇

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Neural Regeneration Research 2025年第4期20卷 1081-1082页

作者： John Mitrofanis jonathan Stone Michael R.Hamblin Pierre Magistretti Alim-Louis Benabid Glen Jeffery Fonds Clinatec UniversitéGrenoble AlpesGrenobleFrance School of Medical Science University of SydneySydneyAustralia Faculty of Health Sciences University of JohannesburgJohannesburgSouth Africa King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of Ophthalmology University College LondonLondonUK

Neurons are notoriously vulnerable cell *** the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper *** most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell *** challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological *** interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical *** this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective *** are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

关键词： protective dosage distress

Wilson's disease in two siblings from Ecuador:Two case reports

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World Journal of Clinical Cases 2025年第3期13卷 50-60页

作者： Enrique Carrera jonathan Alvarado Martina Astudillo Galo Pillajo department of Gastroenterology and Hepatology Hospital de Especialidades Eugenio EspejoQuito 170136PichinchaEcuador Faculty of Medicine Pontificia Universidad Catolica del EcuadorQuito 170143PichinchaEcuador department of Radiology Hospital de Especialidades Eugenio EspejoQuito 170136PichinchaEcuador

BACKGROUNd Wilson's disease(Wd)is a rare metabolic disorder of copper accumulation in organs such as liver,brain,and *** and treatments are challenging in settings,where advanced diagnostic tests are unavailable,copper chelating agents are frequently scarce,healthcare professionals lack disease awareness,and medical follow-ups are *** diagnoses and treatments help prevent complications,improve patients’quality of life,and ensure a normal life *** clinical presentations and outcomes of Wd can vary within a single *** SUMMARY We present the cases of two siblings(19 and 27 years)from a consanguineous family in rural Ecuador,diagnosed as having Wd during a family *** male patient,diagnosed at age 19 after his brother’s death from acute liver failure,presented with compensated cirrhosis,neurological symptoms,and bilateral Kayser-Fleischer *** developed progressive neurological deterioration during an irregular treatment with d-penicillamine due to medication *** condition improved upon switching to trientine tetrahydrochloride,and his neurological symptoms improved over an 8-year period of *** female patient,diagnosed at age 10,exhibited only biochemical *** treatment history was similar;however,she remained asymptomatic without disease progression over the same follow-up *** discuss the potential influence of epigenetic mechanisms and modifier genes on the various phenotypes,emphasizing the need for research in these areas to optimize therapeutic *** Our patients’medical histories show how early diagnosis and treatment can prevent disease progression;and,how suboptimal treatments impact disease outcomes.

关键词： Wilson disease Kayser-Fleischer rings Copper chelator d-penicillamine Trientine tetrahydrochloride Case report

High-resolution geological maps of central London, UK： Comparisons with the London Underground

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Geoscience Frontiers 2016年第2期7卷 273-286页

作者： jonathan d. Paul department of Earth Sciences Bullard Laboratories University of Cambridge Madingley Rise Cambridge CB3 0EZ UK

This study presents new thickness maps of post-Cretaceous sedimentary strata beneath central London. 〉1100 borehole records were analysed. London Clay is thickest in the west; thicker deposits extend as a narrow finger along the axis of the London Basin. More minor variations are probably governed by periglacial erosion and faulting. A shallow anticline in the Chalk in north-central London has resulted in a pronounced thinning of succeeding strata. These results are compared to the position of London Underground railway tunnels. Although tunnels have been bored through the upper levels of London Clay where thick, some tunnels and stations are positioned within the underlying, more lithologically variable, Lower London Tertiary deposits. Although less complex than other geological models of the London Basin, this technique is more objective and uses a higher density of borehole data. The high resolution of the resulting maps emphasises the power of modelling an expansive dataset in a rigorous but simnle fashion.

关键词： London London Underground London Clay Lambeth Group Chalk Tunnelling Boreholes

Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez daniel Refai Gerald R.Rodts Christian Mustroph david Gimbel jonathan Grossberg daniel L.Barrow Matthew F.Gary Ali M.Alawieh department of Neurosurgery Emory University School of MedicineAtlantaGAUSA department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

Hierarchical methodology to evaluate the quality of disparate axle load data sources for pavement design

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Journal of Traffic and Transportation Engineering(English Edition) 2022年第2期9卷 261-279页

作者： Steven Wood jonathan d.Regehr Transportation division City of WinnipegWinnipegMB R3B 1B9Canada department of Civil Engineering University of ManitobaMB R3T 5V6Canada

Axle load data are an essential input for pavement design,yet for most North American agencies,there is uncertainty about the quality of axle load data obtained from weigh-inmotion(WIM)systems,the applicability of these data for pavement design,and potential opportunities to integrate axle load data from disparate *** article presents a novel and practical methodology to evaluate the quality of axle load data from WIM systems and roadside weigh scales through a series of hierarchical analyses designed to test data *** applied using data from Manitoba,Canada,the methodology quantified the uncertainty of axle loads measured at the weigh scales and piezo-quartz WIM,concluding that both could be used for pavement design *** collected at piezo-polymer WIM sites exhibited poorer data validity;however,application of site-specific temperature correction factors significantly improved data validity at these *** article describes how other data quality dimensions,including spatial coverage,temporal coverage,and long-term data availability,could be considered when determining the suitability of disparate axle load data sources for pavement *** of the methodology enables a pragmatic evaluation of the quality and limitations of commonlyavailable axle load data,revealing uncertainties and data needs relevant for pavement design practice.

关键词： Road engineering Pavement design Axle load Weigh-in-motion data quality Truck traffic

Integration of three-dimensional continuum model and two-dimensional bonded block model for studying the damage process in a granite pillar at the Creighton Mine,Sudbury,Canada

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Journal of Rock Mechanics and Geotechnical Engineering 2021年第2期13卷 275-288页

作者： Sankhaneel Sinha Gabriel walton Geology and Geological Engineering Colorado School of MinesGoldenCO80401USA

Bonded blockmodel(BBM)has shownpotential in replicating rockmass behavior aswell as the rockesupport interactionmechanism,but their practical application is limited totwo dimensions due to the high associated computational *** allow for the use of BBM in simulating three-dimensional(3d)problems,this study proposes an integrated 3d continuumetwo-dimensional(2d)discontinuum approach,in context of rock pillars.A cross-section of a granite pillar was simulated using a BBM with a load path from a calibrated mine-scale FLAC^(3d)*** support as employed in the mine was also incorporated in different stages during the *** was calibrated by varying the input parameters until the displacements at six locations within the pillarmatchedthosemeasuredby amulti-point borehole extensometer(MPBX)inthe *** calibratedmodel was subsequently used to understand how the support and load path influenced the damage evolution in the *** shear component of the load pathwas found to have amajor effect on the severity and extent of the damaged *** the support density was increased in the model,the lateral displacements along the pillar walls were significantly suppressed in a somewhat unpredictable *** explained by the interaction between the supports and the damaged regions at the corners,which ultimately modified the stresses along the pillar *** amount of displacement reduction obtained by increasing the support density illustrates the potential of BBMto be used as a support design tool.

关键词： Bonded block model(BBM) Rock pillars Supports Continuum-discontinuum integration

On the calibration of a shear stress criterion for rock joints to represent the full stress-strain profile

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第2期16卷 379-392页

作者： Akram deiminiat jonathan d.Aubertin Yannic Ethier department of Construction Engineering École de Technologie Supérieure(ÉTS)MontréalCanada

Conventional numerical solutions developed to describe the geomechanical behavior of rock interfaces subjected to differential load emphasize peak and residual shear *** detailed analysis of preand post-peak shear stress-displacement behavior is central to various time-dependent and dynamic rock mechanic problems such as rockbursts and structural instabilities in highly stressed *** complete stress-displacement surface(CSdS)model was developed to describe analytically the pre-and post-peak behavior of rock interfaces under differential *** formulations of the CSdS model required extensive curve-fitting iterations which limited its practical applicability and transparent integration into engineering *** present work proposes modifications to the CSdS model aimed at developing a comprehensive and modern calibration protocol to describe the complete shear stressdisplacement behavior of rock interfaces under differential *** proposed update to the CSdS model incorporates the concept of mobilized shear strength to enhance the post-peak ***’s concepts of joint roughness coefficient(JRC)and joint compressive strength(JCS)are incorporated to facilitate empirical estimations for peak shear stress and normal closure ***/uniaxial compression test and direct shear test results are used to validate the updated model and exemplify the proposed calibration *** results illustrate that the revised model successfully predicts the post-peak and complete axial stressestrain and shear stressedisplacement curves for rock joints.

关键词： Full shear profile Post-peak shear behavior Rock joint Joint roughness coefficient(JRC) Axial stress-strain curve