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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

The influence of abiotic and spatial variables on woody and herbaceous species abundances in a woodland-grassland system in the Eastern Terai of India

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Journal of Plant Ecology 2022年第1期15卷 155-167页

作者： Dhritiman Das Subham Banerjee john Lehmkuhl Jagdish Krishnaswamy robert john Academy of Conservation Science and Sustainability Studies Ashoka Trust for Research in Ecology and the Environment(ATREE)Royal EnclaveSriramapuraJakkur PostBangalore 560064India Manipal Academy of Higher Education Manipal 576104KarnatakaIndia Pygmy Hog Conservation Programme Durrell Wildlife Conservation TrustLes Augres ManorLa Profonde RueTrinityJersey JE35BPChannel Islands Department of Biological Sciences Indian Institute of Science Education and ResearchKolkataRoom 214Research ComplexMohanpur 741246West BengalIndia USDA Forest Service Pacific Northwest Research StationWenatcheeWA 98801USA

The environmental factors that influence tree-grass abundances in tropical savanna and grasslands are not well understood,particularly for woodland-grassland mosaics in humid *** studied the effects of abiotic and spatial variables on woody and herbaceous species distributions in a Terai ecosystem of northeastern *** evaluated the importance of climatic and non-climatic factors that maintain variable tree-grass ratios across the landscape,and also accounted for spatial connectivity and *** measured species abundances of woody and herbaceous plant species in 134 plots with each 30 m×30 m in a 519 km^(2)protected Terai habitat,and derived several climatic and non-climatic environmental *** constructed variables based on different models of spatial connectivity among sites,to test their influence on species *** then used redundancy analyses and variation partitioning to quantify the importance of environmental variables and spatial structure on variation in tree-grass *** found that environmental variables including rainfall,fire,water stress,topography and soil nutrients had statistically significant effects on species abundance and tree-grass *** structure was significant,and the best spatial model was an inverse distance-weighted model with linkage extending to 23.5 km,indicating weak dispersal *** 21%of the variation in species abundance was explained by the selected environmental and spatial *** results indicate that dynamic plant communities in which spatial-temporal variation in environmental factors may drive stochasticity in species distribution and abundance,thus dominantly influencing on the vegetation mosaic.

关键词： woodland-grassland Eastern Terai Manas National Park variation partitioning ground fires spatial connectivity

Classification of Soybean Pubescence from Multispectral Aerial Imagery

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Plant Phenomics 2021年第1期3卷 156-166页

作者： robert W.Bruce Istvan Rajcan john Sulik Department of Plant Agriculture University of GuelphGuelphONCanada

The accurate determination of soybean pubescence is essential for plant breeding programs and cultivar ***,soybean pubescence is classified visually,which is a labor-intensive and time-consuming ***,the three classes of phenotypes(tawny,light tawny,and gray)may be difficult to visually distinguish,especially the light tawny class where misclassification with tawny frequently *** objectives of this study were to solve both the throughput and accuracy issues in the plant breeding workflow,develop a set of indices for distinguishing pubescence classes,and test a machine learning(ML)classification approach.A principal component analysis(PCA)on hyperspectral soybean plot data identified clusters related to pubescence classes,while a Jeffries-Matusita distance analysis indicated that all bands were important for pubescence class *** images from 2018,2019,and 2020 were analyzed in this study.A 60-plot test(2019)of genotypes with known pubescence was used as reference data,while whole-field images from 2018,2019,and 2020 were used to examine the broad applicability of the classification *** indices,a red/blue ratio and blue normalized difference vegetation index(blue NDVI),were effective at differentiating tawny and gray pubescence types in high-resolution imagery.A ML approach using a support vector machine(SVM)radial basis function(RBF)classifier was able to differentiate the gray and tawny types(83.1%accuracy and kappa=0:740 on a pixel basis)on images where reference training data was *** tested indices and ML model did not generalize across years to imagery that did not contain the reference training panel,indicating limitations of using aerial imagery for pubescence classification in some environmental ***-throughput classification of gray and tawny pubescence types is possible using aerial imagery,but light tawny soybeans remain difficult to classify and may require training da

关键词： indices spectral consuming

Identification of isopeptidase activity in the midgut of insects： Purification, properties and nutritional ecology of a Hofmannophila pseudospretella （Lepidoptera： Oecophoridae） larval enzyme

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Insect Science 2010年第4期17卷 325-334页

作者： robert M. Simpson john T. Christeller Plant and Food Research Institute Tennant Drive Palmerston North 4474 Private Bag 11 030 New Zealand

A γ-glutamyl transpeptidase （isopeptidase） has been purified 580-fold to homogeneity from the midgut of keratinophagous larvae of Hofmannophila pseudospretella. The enzyme is a single polypeptide of molecular mass 80 kDa. The enzyme was identified by its hydrolytic activity against the synthetic substrate, γ-glutamyl-AMC, its molecular mass and inhibition profile compared to other γ-glutamyl transpeptidases. The enzyme is low or absent from most other insect digestive systems apart from other keratinophagous lepidopteran larvae and predatory carabids. While isopepfide bonds are present in high levels of the proteins in the diet of keratinophages, their presence in the diet of predatory beetles has not been established.

关键词： γ-glutamyl transpeptidase Hofmannophila pseudospretella isopeptidase,keratinophagous nutritional ecology

A Couple Nagging Interpretive Difficulties in Zhuangzi Studies vis-à-vis William James on the Ethics and Psychology of Belief

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Frontiers of Philosophy in China 2019年第4期14卷 593-611页

作者： john robert Williams Department of Philosophy National University of SingaporeSingapore 117570Singapore

The present article addresses two lingering questions in the interpretation of the Zhuangzi莊子—(a)How can one reconcile the scepticism of the Zhuangzi with its positive project(s)?and(b)Who can become a sagely person?The questions are addressed with reference to aspects of William James’accounts of the ethics and psychology of belief.

关键词： Zhuangzi William James scepticism ethics of belief psychology of belief sagely person

Phase Field Models Versus Parametric Front Tracking Methods: Are They Accurate and Computationally Efficient?

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Communications in Computational Physics 2014年第2期15卷 506-555页

作者： john W.Barrett Harald Garcke robert Nurnberg Department of Mathematics Imperial College LondonLondonSW72AZUK. Fakultat fur Mathematik Universitat Regensburg93040 RegensburgGermany

We critically compare the practicality and accuracy of numerical approximations of phase field models and sharp interface models of *** we focus on Stefan problems,and their quasi-static variants,with applications to crystal *** approaches with a high mesh quality for the parametric approximations of the resulting free boundary problems and new stable discretizations of the anisotropic phase field system are taken into account in a comparison involving benchmark problems based on exact solutions of the free boundary problem.

关键词： Phase field models parametric sharp interface methods Stefan problem anisotropy solidification crystal growth numerical simulations benchmark problems.

Interactive Image Enhancement by Fuzzy Relaxation

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International Journal of Automation and computing 2007年第3期4卷 229-235页

作者： Shang-Ming Zhou john Q.Can Li-Da Xu robert john School of Computing De Montfort UniversityLeicester LE1 9BHUK Department of Computer Science University of EssexColchester CO3 4SQUK Department of Information Technology and Decision Sciences Old Dominion UniversityNorfolk VA23529-0218USA

In this paper, an interactive image enhancement （HE） technique based on fuzzy relaxation is presented, which allows the user to select different intensity levels for enhancement and intermit the enhancement process according to his/her preference in applications. First, based on an analysis of the convergence of a fuzzy relaxation algorithm for image contrast enhancement, an improved version of this algorithm, which is called FuzzIIE Method 1, is suggested by deriving a relationship between the convergence regions and the parameters in the transformations defined in the algorithm. Then a method called FuzzIIE Method 2 is introduced by using a different fuzzy relaxation function, in which there is no need to re-select the parameter values for interactive image enhancement. Experimental results are presented demonstrating the enhancement capabilities of the proposed methods under different conditions.

关键词： Interactive image enhancement fuzzy relaxation fuzzy set crossover point convergence.

Palladium Nanoparticles Loaded on Carbon Modified TiO_2 Nanobelts for Enhanced Methanol Electrooxidation

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Nano-Micro Letters 2013年第3期5卷 202-212页

作者： robert Liang Anming Hu john Persic Y.Norman Zhou Centre for Advanced Materials Joining Department of Mechanical and Mechatronics Engineering University of Waterloo 200 University Waterloo Institute for Nanotechnology University of Waterloo 200 University Microbonds Inc.

Carbon modified TiO_2 nanobelts(TiO_2-C) were synthesized using a hydrothermal growth method,as a support material for palladium(Pd) nanoparticles(Pd/TiO_2-C) to improve the electrocatalytic performance for methanol electrooxidation by comparison to Pd nanoparticles on bare TiO_2 nanobelts(Pd/TiO_2)and activated carbon(Pd/AC). Cyclic voltammetry characterization was conducted with respect to saturated calomel electrode(SCE) in an alkaline methanol solution, and the results indicate that the specific activity of Pd/TiO_2-C is 2.2 times that of Pd/AC and 1.5 times that of Pd/TiO_2. Chronoamperometry results revealed that the TiO_2-C support was comparable in stability to activated carbon, but possesses an enhanced current density for methanol oxidation at a potential of -0.2 V vs. SCE. The current study demonstrates the potential of Pd nanoparticle loaded on hierarchical TiO_2-C nanobelts for electrocatalytic applications such as fuel cells and batteries.

关键词： Titanium oxide nanobelts Carbon-modification Fuel cell Methanol electrooxidation Palladium nanoparticles Electrocatalysts

Mechanical behavior predictions of additively manufactured microstructures using functional Gaussian process surrogates

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npj Computational Materials 2021年第1期7卷 720-730页

作者： robert Saunders Celia Butler john Michopoulos Dimitris Lagoudas Alaa Elwany Amit Bagchi US Naval Research Laboratory WashingtonDCUSA Texas A&M University College StationTXUSA Synopsys Northern Europe Ltd ExeterUK University of Exeter ExeterUK

Relational linkages connecting process,structure,and properties are some of the most sought after goals in additive manufacturing(AM).This is desired especially because the microstructural grain morphologies of AM components can be vastly different than their conventionally manufactured ***,data collection at the microscale is ***,this work describes and demonstrates a methodology to link microstructure morphology to mechanical properties using functional Gaussian process surrogate models in a directed graphical network capable of achieving near real-time property predictions with single digit error magnitudes when predicting full stress–strain histories of a given *** methodology is presented and demonstrated using computationally generated microstructures and results from crystal plasticity simulations on those *** surrogate model uses grain-level microstructural descriptors rather than whole microstructure descriptors so that properties of new,arbitrary microstructures can be *** developed network has the potential to scale to predict mechanical properties of grain structures that would be infeasible to simulate using finite element methods.

关键词： grain microstructure additive