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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

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

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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

(Super)paramagnetic nanoparticles as platform materials for environmental applications: From synthesis to demonstration

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Frontiers of Environmental Science & Engineering 2020年第5期14卷 15-23页

作者： Wenlu Li john d.Fortner department of Chemical and Environmental Engineering Yale UniversityNew HavenCT 06520USA

Over the past few decades,engineered,(super)paramagnetic nanoparticles have drawn extensive research attention for a broad range of applications based on their tunable size and shape,surface chemistries,and magnetic *** review summaries our recent work on the synthesis,surface modification,and environmental application of(super)paramagnetic *** utilizing high-temperature thermo-decomposition methods,first,we have broadly demonstrated the synthesis of highly monodispersed,(super)paramagnetic nanoparticles,via the pyrolysis of metal carboxylate salts in an organic *** uniform magnetic nanoparticles with various size,composition,and shape can be precisely tuned by controlled reaction parameters,such as the initial precursors,heating rate,final reaction temperature,reaction time,and the *** materials can be further rendered water stable via functionalization with surface mono/bi-layer coating structure using a series of tunable ionic/non-ionic ***,we have demonstrated platform potential of these materials for heavy metal ions sensing,sorption,and separation from the aqueous phase.

关键词： Superparamagnetic nanoparticles Surface functionalization Environmental sensing Heavy metal ion sorption

Computational Modeling of dual-Phase Ceramics with Finsler-Geometric Phase Field Mechanics

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Computer Modeling in Engineering & Sciences 2019年第8期120卷 333-350页

作者： john d.Clayton US ARL Impact Physics BranchAberdeen Proving GroundMD21005-5066USA

A theory invoking concepts from differential geometry of generalized Finsler space in conjunction with diffuse interface modeling is described and implemented in finite element(FE)simulations of dual-phase polycrystalline ceramic *** parameters accounting for fracture and other structural transformations,notably partial dislocation slip,twinning,or phase changes,are dimensionless entries of an internal state vector of generalized pseudo-Finsler *** investigated in computations are a boron carbide-titanium diboride(B4C-TiB2)composite and a diamond-silicon carbide(C-SiC)*** mechanisms-in addition to elasticity and cleavage fracture in grains of any phase-include restricted dislocation glide(TiB2 phase),deformation twinning(B4C and-SiC phases),and stress-induced amorphization(B4C phase).The metric tensor of generalized Finsler space is scaled conformally according to dilatation induced by cavitation or other fracture modes and densification induced by phase *** of pure shear consider various morphologies and lattice *** of microstructure on overall strength of each composite are *** B4C-TiB2,minor improvements in shear strength and ductility are observed with an increase in the second phase from 10 to 18%by volume,suggesting that residual stresses or larger-scale crack inhibition may be responsible for toughness gains reported *** diamond-SiC,a composite consisting of diamond crystals encapsulated in a nano-crystalline SiC matrix shows improved strength and ductility relative to a two-phase composite with isolated bulk SiC grains.

关键词： Micromechanics ceramic composites,Finsler space differential geometry phase field finite elements

RESIdENTIAL STORMWATER:METHOdS FOR dECREASING RUNOFF ANd INCREASING STORMWATER INFILTRATION

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Journal of Green Building 2012年第2期7卷 15-30页

作者： john R.Freeborn david J.Sample laurie J.Fox department of Horticulture Virginia Polytechnic Institute&State University department of Biological Systems Engineering Virginia Polytechnic Institute&State University department of Horticulture Hampton Roads Agricultural Research&Extension CenterVirginia Polytechnic Institute&State University

INTROdUCTION Humans and plants depend on an adequate supply of clean water for numerous reasons,from food production to sustaining terrestrial and aquatic *** average Virginia resident uses about 47 gallons(178 L)of fresh water daily(VdEQ 2008).While a majority of Virginians are provided water from a centralized,public utility,there are nearly two million Virginia residents who depend on well water as their main source(VdH 2008).Replenishing groundwater withdrawals depends on recharge(water moving from the surface to groundwater)from infiltration of precipitation through permeable surfaces in the environment;an important part of the hydrologic,or water,cycle(VdEQ 2010).Forests and grasslands provide much of the available recharge area due to their high capacities to infiltrate ***,the urbanization process is rapidly converting forested areas and grasslands to commercial,residential,or industrial *** conversion creates a significant increase in impervious surfaces such as concrete,asphalt,building roofs,and even compacted vegetated sites(*** 2003).Impervious surfaces decrease infiltration and groundwater *** also generate increases in stormwater runoff;defined as any precipitation from a rain or snow event that flows off of an impervious *** water runs off urban impervious surfaces,it picks up sediment,oils,debris,nutrients,chemicals,and *** runoff is then collected in a conveyance system,transported,and discharged to surface waters such as creeks and rivers;most of the time without any type of water quality treatment(*** 2003;Paul and Meyer 2001).In addition to carrying pollutants,the runoff is also typically warmer than the receiving surface *** increased volume and velocity of the stormwater runoff erodes soil and stream channels and can lead to stream“blow out.”Water quality is degraded and aquatic habitats are adversely altered(Meyer,et al.2005,Booth and Jackson 1997).due to the interc

关键词： residential stormwater management low impact development environmental site design permeable pavement rainwater harvesting rain gardens green roofs dry swales bioretention

Inverse analysis of laboratory data and observations for evaluation of backward erosion piping process

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Journal of Rock Mechanics and Geotechnical Engineering 2020年第5期12卷 1080-1092页

作者： Sige Peng john d.Rice School of Civil Engineering and Transportation South China University of TechnologyGuangzhou510640China department of Civil and Environmental Engineering Utah State UniversityLogan84322UTUSA

An inverse analysis procedure has been developed to interpret collected pore pressure data and observations during backward erosion piping(BEP)initiation and progression in sandy *** procedure has been applied to laboratory models designed to mimic the initiation and progression of BEP through a constricted vertical *** inverse analysis uses three-dimensional(3d)finite element method(FEM)to successively produce models of the hydraulic head regime surrounding progressive stages of BEP based on observations at the sample surface and pore pressure measurements obtained from the laboratory *** inverse analysis results in a series of 3d contour plots that represent the hydraulic-head regime at each stage of the BEP development,allowing for assessing the development of BEP mechanism as well as calculating the critical hydraulic conditions required for various BEP stages to initiate and *** of the results identified four significant stages of the piping process:(1)loosened zone initiation,(2)channel initiation and progression,(3)riser sand fluidization,and(4)loosened zone *** of the hydraulic head contour plots allows assessment of the critical hydraulic gradients needed to initiate and progress various components of the BEP development.

关键词： Backward erosion piping(BEP) Laboratory modeling Inverse analysis Finite element method(FEM) Soil loosening Critical gradient

Ileal inflammatory fibroid polyp causing chronic ileocolic intussusception and mimicking cecal carcinoma

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World Journal of Gastrointestinal Oncology 2009年第1期1卷 89-92页

作者： Naveen Gara john S Falzarano Whitney ML Limm Thomas S Namiki laurie KS Tom Uinversity of Hawaii Internal Medicine Residency Program

Inflammatory fibroid polyp(IFP) is a rare,idiopathic pseudotumorous lesion of the gastrointestinal *** mostly reported as solitary gastric lesions,multiple cases of small bowel IFPs are also *** is a documented cause of intussusception in *** the case reports of ileal inflammatory fibroid polyps with intussusception,an emergent presentation with small bowel obstruction has been most often *** we depict a case of ileal inflammatory fibroid polyp presenting with chronic intermittent ileocolic intussusception,anemia and weight loss with an endoscopic appearance mimicking necrotic cecal carcinoma.

关键词： Ileal polyp Colon cancer Endoscopy Intussusception Intussusception in elderly

Effect of p-d exchange with an itinerant carrier in a GaMnAs quantum dot

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Journal of Semiconductors 2013年第7期34卷 1-6页

作者： d.Lalitha A.john Peter department of Physics GTN College department of Physics Government Arts College

Hydrogenic acceptor binding energy as a function of dot radius in a GaMnAs/Ga_（0.6）Al_（0.4）As quantum dot is calculated including the exchange interaction of Mn alloy content with an itinerant *** are performed by varying its dot radius,for various Mn alloy contents in GaMnAs quantum dot within a single band effective mass approximation using variational *** spin polaronic energy of the acceptor impurity for different Mn^（2＋） is evaluated for different dot radii using a mean field theory in the presence of magnetic field *** magnetization is computed in the influence of magnetic field and the Mn *** effective g-factor of the valence band electron with the inclusion of effects of Mn ion impurities is found in the influence of the magnetic *** exchange coupling constant is calculated for various magnetic field *** results show that the p-d exchange interaction in the GaMnAs/Ga_（0.6）Al_（0.4）As quantum dot has a strong dependence on spatial confinement,effect of magnetic field strength and the Mn alloy *** results are in good agreement with the other investigators.

关键词： quantum dot acceptor diluted magnetic semiconductors

Role of nitric oxide in hepatic ischemia-reperfusion injury

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World Journal of Gastroenterology 2010年第48期16卷 6079-6086页

作者： Arunotai Siriussawakul Ahmed Zaky john d Lang department of Anesthesiology and Pain Medicine and the VA Puget Sound Healthcare System the University of Washington School of Medicine

Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic blood flow after a period of ischemia. decreased endogenous nitric oxide (NO) production resulting in capillary luminal narrowing is central in the pathogenesis of IRI. Exogenous NO has emerged as a potential therapy for IRI based on its role in decreasing oxidative stress,cytokine release,leukocyte endothelial-adhesion and hepatic apoptosis. This review will highlight the influence of endogenous NO on hepatic IRI,role of inhaled NO in ameliorating IRI,modes of delivery,donor drugs and potential side effects of exogenous NO.

关键词： Nitric oxide Liver Ischemia-reperfusion injury drug delivery