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Leishmania tarentolae: an alternative approach to the production of monoclonal antibodies to treat emerging viral infections

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Infectious diseases of Poverty 2015年第1期4卷 83-87页

作者： joshua d Jones division of Virology Department of PathologyUniversity of CambridgeTennis Court RoadCambridge CB21QPUK

Background:Monoclonal antibody therapy has an important role to play as a post-exposure prophylactic and therapeutic for the treatment of viral infections,including emerging *** example,several patients of the present Ebola virus outbreak in West Africa were treated with ZMapp,a cocktail of three monoclonal antibodies which are expressed in Nicotiana ***:The majority of monoclonal antibodies in clinical use are expressed in mammalian cell lines which offer native folding and glycosylation of the expressed *** antibody expression in vegetal systems offers advantages over expression in mammalian cell lines,including improved potential for scale up and reduced *** this paper,I highlight the advantages of an upcoming protozoal system for the expression of recombinant antibody *** tarentolae offers a robust,economical expression of proteins with mammalian glycosylation patterns expressed in stable cell lines and grown in suspension *** advantages of this system make it particularly suited for use in developing ***:Given the potential importance of monoclonal antibody therapy in the containment of emerging viral infections,novel and alternative strategies to improve production must be explored.

关键词： Antibody Ebola Emerging Expression Infection Leishmania Monoclonal Therapy

Modeling Alzheimer's disease:considerations for a better translational and replicable mouse model

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Neural Regeneration Research 2022年第11期17卷 2448-2449页

作者： joshua d.Cho Mu Yang Ismael Santa-Maria Taub Institute for Research on Alzheimer's disease and the Aging Brain Department of Pathology&Cell BiologyColumbia University The Mouse NeuroBehavior Core.Institute for Genomic Medicine Columbia University

Alzheimer's disease (Ad) mouse models have proven to be an invaluable tool for deepening our understanding of disease mechanisms and for developing ***,one common frustration is the lack of replicability in behavioral *** we have discussed in our recent publication (Cho et al.,2021),in the htau mouse model,the cognitive impairment reported in the original study has not been consistently replicated by different labs over the past *** variability in behavioral findings seems to exist in many,if not all,Ad mouse models that have been behaviorally evaluated.

关键词： Alzheimer tau

An epigenetic perspective on the failing heart and pluripotent-derived-cardiomyocytes for cell replacement therapy

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Frontiers in Biology 2015年第1期10卷 11-27页

作者： joshua d. TOMPKINS Arthur d. RIGGS department of diabetes and Metabolic disease Research Beckman Research Institute/City of Hope National Medical Center 1500 E DuarteRoad Duarte CA 91010 USA

As life expectancy rises, the prevalence of heart failure is steadily increasing, while donors for organ transplantation remain in short supply （Zwi-dantsis and Gepstein, 2012）. Indeed, myocardial infarction represents the foremost cause of death within industrialized nations （Henning, 2011） and further, approximately 1% of all newborns harbor a congenital heart defect. Although medical interventions allow 〉 80% of those with cardiac defects to survive to adulthood, there are often extreme emotional and financial burdens that accompany such congenital anomalies, and many individuals will remain at a heightened risk for myocardial infarction throughout the remainder of their lives （Verheugt et al., 2010; Amianto et al., 2011）. In this review, we will discuss the nature of the failing heart and strategies for repair from an epigenetic standpoint. Significant focus will reside on pluripotent-to-cardiomyocyte differentiation for cell replacement, epigenetic mechanisms of cardiomyocyte differentiation, epigenetic ＂memories,＂ and epigenetic control of cardiomyocyte cell fate toward translational utility.

关键词： heart failure pluripotent cardiomyocytes epigenetics dNA methylation lncRNA

Geographic patterns of plant-herbivore interactions are driven by soil fertility

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Journal of Plant Ecology 2019年第4期12卷 653-661页

作者： joshua S.Lynn Jason d.Fridley department of Biology Syracuse UniversitySyracuseNY 13244USA department of Biology University of New MexicoAlbuquerqueNM 87131USA

Aims Geographic patterns of the intensity of plant herbivory in relation to climate factors have garnered little general support and appear to be species ***,plant-herbivore interactions are also driven by resource availability,such as soil nutrient content,and it remains unclear whether broad-scale variation in soil factors is reflected in herbivore consumption rates across species’***,we know little of how intraspecific variation in tissue quality associates with edaphic and climatic factors,and how this variation controls herbivore *** resource availability hypothesis(RAH)predicts that plant individuals growing in low-resource environments will have lower leaf nutritional quality and more constitutive defenses,which will result in lower rates of leaf *** We collected leaves from the old-field dominant species,Solidago altissima L.,from 20 sites across 10 degrees of latitude in the Eastern USA to determine the percentage leaf area consumed by insect *** obtained soil and climate data for each site,as well as plant functional and defensive traits,including specific leaf area(SLA),leaf carbon:nitrogen(C:N),and trichome *** Findings Although we found no significant latitudinal trend of leaf consump-tion rate,there was strong evidence that leaf herbivory decreased with leaf C:N and trichome density,which themselves decreased with soil N,supporting our hypothesis that the RAH applies for intraspecific variation across spatial ***,high precipitation seasonality and soil nitrogen predicted decreased *** results suggest that spatial variation in herbivory can be driven by factors other than herbivore communities and climatic gradients,and that bottom-up processes,where plant traits and soil fertility control leaf consumption,must be incorporated into spatial predictions of herbivory.

关键词： biogeography bottom-up controls old fields plant-insect interactions plant functional and defense traits

Probing Electrocatalytic CO_(2) Reduction at Individual Cu Nanostructures via Optically Targeted Electrochemical Cell Microscopy

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Journal of Analysis and Testing 2019年第2期3卷 140-149页

作者： joshua d.Walmsley joshua W.Hill Partha Saha Caleb M.Hill department of Chemistry University of WyomingLaramieWY 82071USA

Optically targeted electrochemical cell microscopy(OTECCM)was applied to measure electrocatalytic rates at individual Cu nanoparticles(NPs)under electrolyte conditions relevant to CO_(2) *** electrocatalytic responses from individual NPs were found to exhibit a wide variation in behavior,with significant NP-to-NP variations in the magnitude of electrocata-lytic currents and necessary overpotentials being *** of these quantities with metrics of NP size suggest no significant variations in the inherent electrocatalytic activity of the NPs with *** element simulations of diffusion in this system demonstrate the observed diffusion-limited currents are significantly smaller than expected,attributable to the presence of a significant amount of residual ligand on the surface of the Cu NPs,which were prepared via an organic phase *** results presented here further demonstrate the promise of techniques which employ correlated optical and electrochemical measurements,such as OTECCM,for studying electrocatalysis at individual NPs.

关键词： Electrochemistry Electrochemical microscopy Nanoparticles CO_(2)reduction

Common genetic variants in the TP53 pathway and their impact on cancer

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Journal of Molecular Cell Biology 2019年第7期11卷 578-585页

作者： Thibaut Barnoud joshua L.d.Parris Maureen E.Murphy Program in Molecular and Cellular Oncogenesis The Wistar InstitutePhiladelphiaPA 19104USA Cell and Molecular Biology Program Perelman School of Medicine at the University of PennsylvaniaPhiladelphiaPA 19104USA

The TP53 gene is well known to be the most frequently mutated gene in human *** addition to mutations,there are > 20 different coding region single-nucleotide polymorphisms (SNPs) in the TP53 gene,as well as SNPs in MdM2,the negative regulator of *** of these SNPs are known to alter p53 pathway *** makes p53 rather unique among cancer-critical genes,*** coding regions of other cancer-critical genes like Ha-Ras,RB,and PI3KCA do not have non-synonymous coding region SNPs that alter their function in *** next frontier in p53 biology will consist of probing which of these coding region SNPs are moderately or strongly pathogenic and whether they influence cancer risk and the efficacy of cancer *** challenge after that will consist of determining whether we can tailor chemotherapy to correct the defects for each ofthese *** we review the SNPs in TP53 and MdM2 that show the most significant impact on cancer and other *** also propose avenues for how this information can be used to better inform personalized medicine approaches to cancer and other diseases.

关键词： p53 Pro47Ser Pro72Arg PAS MdM2 SNP309

Estimation of the density of neural,glial,and endothelial lineage cells in the adult mouse dentate gyrus

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Neural Regeneration Research 2022年第6期17卷 1286-1292页

作者： joshua d.Rieskamp Patricia Sarchet Bryon M.Smith Elizabeth d.Kirby Neuroscience Graduate Program The Ohio State UniversityColumbusOHUSA department of Psychology The Ohio State UniversityColumbusOHUSA department of Neuroscience The Ohio State UniversityColumbusOHUSA Chronic Brain Injury Program The Ohio State UniversityColumbusOHUSA

The dentate gyrus subregion of the mammalian hippocampus is an adult neural stem cell niche and site of lifelong *** regarding the role of adult-born neuron synaptic integration in hippocampal circuit function are framed by robust estimations of adultborn versus pre/perinatally-born neuron *** contrast,the non-neurogenic functions of adult neural stem cells and their immediate progeny,such as secretion of bioactive growth factors and expression of extracellular matrix-modifying proteins,lack similar framing due to few estimates of their number versus other prominent secretory ***,we apply immunohistochemical methods to estimate cell density of neural stem/progenitor cells versus other major classes of glial and endothelial cell types that are potentially secretory in the dentate gyrus of adult *** the cell types quantified,we found that GFAP^(+)SOX2^(+)stellate astrocytes were the most numerous,followed by Cd31^(+)endothelia,GFAP-SOX2^(+)intermediate progenitors,Olig2^(+)oligodendrocytes,Iba1+microglia,and GFAP^(+)SOX2^(+)radial glia-like neural stem *** did not observe any significant sex differences in density of any cell ***,neural stem/progenitor cells were present at a similar density as several cell types known to have potent functional roles via their *** findings may be useful for refining hypotheses regarding the contributions of these cell types to regulating hippocampal function and their potential therapeutic *** experimental protocols were approved by the Ohio State University Institutional Animal Care and Use Committee(protocol#2016A00000068)on July 14,2016.

关键词： adult neurogenesis dentate gyrus endothelia glia hippocampus neural stem cell secretome stereology

Structural health monitoring of bridges in the State of Connecticut

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Earthquake Engineering and Engineering Vibration 2008年第4期7卷 427-437页

作者： Chengyin Liu joshua Olund Alan Cardini Paul d＇Attilio Eric Feldblum John deWolf SP-SELLS Inc. Briarcliff Manor NY 10510 USA department of Civil and Environmental Engineering University of Connecticut 261 Glenbrook Rd Unit 2037 Storrs CT06269 USA dMJM Harris Boston MA 02110 USA Connecticut department of Transportation 280 West Street Rocky Hill CT 06067 USA

A joint effort between the Connecticut department of Transportation and the University of Connecticut has been underway for more than 20 years to utilize various structural monitoring approaches to assess different bridges in Connecticut. This has been done to determine the performance of existing bridges, refine techniques needed to evaluate different bridge components, and develop approaches that can be used to provide a continuous status of a bridge＇s structural integrity. This paper briefly introduces the background of these studies, with emphasis on recent research and the development of structural health monitoring concepts. This paper presents the results from three different bridge types： a post-tensioned curved concrete box girder bridge, a curved steel box-girder bridge, and a steel multi-girder bridge. The structural health monitoring approaches to be discussed have been successfully tested using field data collected during multi-year monitoring periods, and are based on vibrations, rotations and strains. The goal has been to develop cost-effective strategies to provide critical information needed to manage the State of Connecticut＇s bridge infrastructure.

关键词： structural integrity structural health monitoring field data vibrations

How well does XAd resin extraction recover halogenated disinfection byproducts for comprehensive identification and toxicity testing?

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Journal of Environmental Sciences 2022年第7期34卷 264-275页

作者： Xiaobin Liao joshua M.Allen Caroline O.Granger Susan d.Richardson department of Chemistry and Biochemistry University of South CarolinaColumbiaSouth Carolina 29208USA Institute of Municipal and Environmental Engineering College of Civil EngineeringHuaqiao UniversityFujian 361021China Currently at LanzaTech 535 Commerce DriveSopertonGeorgia 30457USA

Halogenated disinfection byproducts(dBPs) are an unintended consequence of drinking water disinfection, and can have significant toxicity. XAd resins are commonly used to extract and enrich trace levels of dBPs for comprehensive, nontarget identification of dBPs and also for in vitro toxicity studies. However, XAd resin recoveries for complete classes of halogenated dBPs have not been evaluated, particularly for low, environmentally relevant levels(ng/L to low μg/L). Thus, it is not known whether levels of dBPs or the toxicity of drinking water might be underestimated. In this study, dAX-8/XAd-2 layered resins were evaluated, considering both adsorption and elution from the resins, for extracting 66 dBPs from water. Results demonstrate that among the 7 classes of dBPs investigated, trihalomethanes(THMs), including iodo-THMs, were the most efficiently adsorbed, with recovery of most THMs ranging from 50%-96%, followed by halonitromethanes(40%-90%). The adsorption ability of XAd resins for haloacetonitriles, haloacetamides, and haloacetaldehydes was highly dependent on the individual species. The adsorption capacity of XAd resins for haloacetic acids was lower(5%-48%), even after adjusting to p H 1 before extraction. Recovery efficiency for most dBPs was comparable with their adsorption, as most were eluted effectively from XAd resins by ethyl acetate. dBP polarity and molecular weight were the two most important factors that determine their recovery. Recovery of trichloromethane, iodoacetic acid, chloro-and iodo-acetonitrile, and chloroacetamide were among the lowest, which could lead to underestimation of toxicity, particularly for iodoacetic acid and iodo-acetonitrile, which are highly toxic.

关键词： XAd resins disinfection byproducts dBPs Recovery Toxicity