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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt damien d.Pearse W.dalton dietrich Allan d.Levi james d.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FdA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

Culprits or consequences:Understanding the metabolic dysregulation of muscle in diabetes

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World Journal of Biological Chemistry 2021年第5期12卷 70-86页

作者： Colleen L O'Reilly Selina Uranga james d.fluckey Health and Kinesiology Texas A&M UniversityTX 77843United States

The prevalence of type 2 diabetes(T2d)continues to rise despite the amount of research dedicated to finding the culprits of this debilitating *** muscle is arguably the most important contributor to glucose disposal making it a clear target in insulin resistance and T2d *** skeletal muscle there is a clear link to metabolic dysregulation during the progression of T2d but the determination of culprits vs consequences of the disease has been *** evidence in skeletal muscle implicates influential cross talk between a key anabolic regulatory protein,the mammalian target of rapamycin(mTOR)and its associated complexes(mTORC1 and mTORC2),and the well-described canonical signaling for insulin-stimulated glucose *** new understanding of cellular signaling crosstalk has blurred the lines of what is a culprit and what is a consequence with regard to insulin ***,we briefly review the most recent understanding of insulin signaling in skeletal muscle,and how anabolic responses favoring anabolism directly impact cellular glucose *** review highlights key cross-over interactions between protein and glucose regulatory pathways and the implications this may have for the design of new therapeutic targets for the control of glucoregulatory function in skeletal muscle.

关键词： Insulin resistance Skeletal muscle Mammalian target of rapamycin Glucose uptake Glucose regulation Insulin signaling

Light controlled imaging probes for intracellular target recognition： photochromism as a tool to enhance sensing precision

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Science China Chemistry 2017年第12期60卷 1563-1564页

作者： Tony d. james department of Chemistry University of BathBath BA2 7AYUK

Chemosensors and imaging probes have been the focus of significant research interest over the past few decades. In part due to ease of preparation and simplicity in manipulation, fluorescent probes have been extensive... 详细信息

关键词： Light controlled imaging probes for intracellular target recognition photochromism enhance sensing precision

Promises and paradoxes of regulatory T cells in inflammatory bowel disease

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World Journal of Gastroenterology 2015年第40期21卷 11236-11245页

作者： james d LordJ Translational Program Benaroya Research Institute at Virginia Mason Mailstop

Since their discovery two decades ago,Cd4+Cd25+Foxp3+ regulatory T cells(Tregs) have become the subject of intense investigation by immunologists. Unlike other T cells,which promote an immune response,Tregs actively inhibit inflammation when activated by their cognate antigen,thus raising hope that these cells could be engineered into a highly targeted,antigenspecific,immunosuppressant therapy. Although Tregs represent less than 10% of circulating Cd4+T cells,they have been shown to play an essential role in preventing or limiting inflammation in a variety of animal models and human diseases. In particular,spontaneous intestinal inflammation has been shown to occur in the absence of Tregs,suggesting that there may be a Treg defect central to the pathogenesis of human inflammatory bowel disease(IBd). However,over the past decade,multiple groups have reported no qualitative or quantitative deficits in Tregs from the intestines and blood of IBd patients to explain why these cells fail to regulate inflammation in Crohn's disease and ulcerative colitis. In this review,we will discuss the history of Tregs,what is known about them in IBd,and what progress and obstacles have been seen with efforts to employ them for therapeutic benefit.

关键词： Foxp3 Regulatory T cells Crohn’s disease Th17 Ulce

A new direction for Alzheimer's research

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Neural Regeneration Research 2018年第2期13卷 190-193页

作者： james d.Weinstein Marshall University School of Medicine Medical Center

despite decades of research, at present there is no curative therapy for Alzheimer＇s disease. Changes in the way new drugs are tested appear to be necessary. Three changes are presented here and will be discussed. The first change is that Alzheimer＇s disease must be considered a disease of four major pathological processes, not one. The four processes are： 1） vascular hy- poperfusion of the brain with associated mitochondrial dysfunction, 2） destructive protein inclusions, 3） uncontrolled oxidative stress, and 4） proinflammatory immune processes second- ary to microglial and astrocytic dysfunction in the brain. The second change recommended is to alter the standard cognitive measurement tools used to quantify mental decline in test patients. Specifically the dementia Severity Rating Scale （dSRS） should supersede Mini-Mental State Examination （MMSE） and other popular tests, and a measurement scale developed in research should be used to produce a linear and non-irregular baseline. Finally, accepting the concept that four etiologies cause Alzheimer＇s disease leads to the last necessary change, that new thera- pies must be employed directed against all four causes, likely as a combination. There are drugs ready to be employed in such a combinations which are available and used clinically for other purposes so can be used ＂offlabel＂ and one such combination is suggested.

关键词： Alzheimer's disease etiologies combination therapy cognitive testing failed research off-label use dementia Severity Rating Scale

design of soft magnetic materials

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npj Computational Materials 2022年第1期8卷 17-26页

作者： Ananya Renuka Balakrishna Richard d.james Aerospace and Mechanical Engineering University of Southern CaliforniaLos AngelesCA90089USA Aerospace and Engineering Mechanics University of MinnesotaMinneapolisMN55455USA

We present a strategy for the design of ferromagnetic materials with exceptionally low magnetic hysteresis,quantified by *** this strategy,we use a micromagnetic algorithm that we have developed in previous research and which has been validated by its success in solving the“Permalloy Problem”—the well-known difficulty of predicting the composition 78.5%Ni of the lowest coercivity in the Fe–Ni system—and by the insight it provides into the“Coercivity Paradox”of ***,the design strategy predicts that cubic materials with large saturation magnetization ms and large magnetocrystalline anisotropy constant κ_(1) will have low coercivity on the order of that of Permalloy,as long as the magnetostriction constantsλ_(100),λ_(111)are tuned to special *** explicit prediction for a cubic material with low coercivity is the dimensionless number(c_(11)−c_(12))λ_(100)^(2)/(2_(κ_(1)))=81 for〈100〉easy *** results would seem to have broad potential application,especially to magnetic materials of interest in energy research.

关键词： magnetic cubic exceptional

Biodiversity of Arbuscular Mycorrhizal (AM) fungi in mangroves of Goa in West India

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Journal of Forestry Research 2013年第3期24卷 515-523页

作者： james d'Souza Bernard Felinov Rodrigues department of Botany Goa UniversityGoa 403 206 India

Seventeen mangrove species of eight families at seven river- ine and fringe habitats in Goa West India were surveyed for Arbuscular Mycorrhizal （AM） fungal diversity. Sixteen species were found to be mycorrhizal and one species showed no AM fungal colonization. AM root colonization was recorded at all seven sites and ranged from 6%-77%. Maximum root colonization was recorded in Excoecaria agal- locha （77%） and minimum colonization in Avicennia marina （6%）. Paris-type colonization was predominant at all sites. Auxiliary cells were recorded in roots of Acanthus ilicifolius, Ceriops tagal and Sonneretia alba. AM fungal root colonization and spore density varied by plant species and site. Site average spore density ranged from 1.84 spores.g^-1 to 0.54 spores.g-1 of soil. In total, 28 AM fungal species of five genera, viz. Glomus, Acaulospora, Scutellospora, Gigaspora and Entrophospora, were recovered. Glomus was the dominant genus, three species of which were sporocarpic forms. Maximum site species richness （SR） ranged from 16 to 5. Species richness was maximum in A. ilicifolius where seven species of three genera were recovered. Based on relative abun- dance （RA） and isolation frequency （IF）, two common species, viz. G. intraradices and A. laevis, were recovered from all seven sites.

关键词： Glomus intraradices root colonization Paris type sporedensity rhizosphcre

Special issue on “Molecular Sensors and Molecular Logic Gates”

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Frontiers of Chemical Science and Engineering 2022年第1期16卷 1-3页

作者： Luling Wu Tony d.james department of Chemistry University of BathBath BA27AYUK

This issue of Frontiers of Chemical Science and Engineering highlights recent progress toward fluorescent probes that was originally conceived to coincide with 7th Conference on Molecular Sensors and Molecular Logic Gates(MSMLG 2020)to celebrate the career of Seiji Shinkai and hosted by Anthony Czarnik at the University of Nevada in ***,that meeting was cancelled due to the pandemic associated with ***,this collection of research and review papers will now serve as an introduction to MSMLG 2022 which will be in dublin,Ireland on 7–10 June 2022,where Thorfinnur Gunnlaugsson will be the local *** collection of papers contained in this special issue covers in vitro and in vivo applications and illustrates the potential for practical sensing and imaging of disease-related species.

关键词： Sensors Logic Molecular

Addressing nonresponse bias in forest inventory change estimation using response homogeneity classifications

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Forest Ecosystems 2023年第1期10卷 125-131页

作者： james A.Westfall Mark d.Nelson U.S.Forest Service Northern Research StationYorkPAUSA U.S.Forest Service Northern Research StationSt.PaulMNUSA

Estimating amounts of change in forest resources over time is a key function of most national forest inventories(NFI). As this information is used broadly for many management and policy purposes, it is imperative that accurate estimations are made from the survey sample. Robust sampling designs are often used to help ensure representation of the population, but often the full sample is unrealized due to hazardous conditions or possibly lack of land access permission. Potentially, bias may be imparted to the sample if the nonresponse is nonrandom with respect to forest characteristics, which becomes more difficult to assess for change estimation methods that require measurements of the same sample plots at two points in time, i.e., remeasurement. To examine potential nonresponse bias in change estimates, two synthetic populations were constructed: 1) a typical NFI population consisting of both forest and nonforest plots, and 2) a population that mimics a large catastrophic disturbance event within a forested population. Comparisons of estimates under various nonresponse scenarios were made using a standard implementation of post-stratified estimation as well as an alternative approach that groups plots having similar response probabilities(response homogeneity). When using the post-stratified estimators, the amount of change was overestimated for the NFI population and was underestimated for the disturbance population, whereas the response homogeneity approach produced nearly unbiased estimates under the assumption of equal response probability within groups. These outcomes suggest that formal strategies may be needed to obtain accurate change estimates in the presence of nonrandom nonresponse.

关键词： disturbance Post-stratification Land use conversion Sample bias