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Axonal regeneration and sprouting as a potential therapeutic target for nervous system disorders

Neural Regeneration Research 2021年第10期16卷 1901-1910页

作者： katherine L.Marshall Mohamed H.Farah Department of Neurology at Johns Hopkins school of Medicine BaltimoreMDUSA

Nervous system disorders are prevalent health issues that will only continue to increase in frequency as the population ***-back axonopathy is a hallmark of many neurologic diseases and leads to axonal disconnection from their targets,which in turn leads to functional *** the course of many of neurologic diseases,axons can regenerate or sprout in an attempt to reconnect with the target and restore synapse *** amyotrophic lateral sclerosis(ALs),distal motor axons retract from neuromuscular junctions early in the disease-course before significant motor neuron *** is evidence of compensatory motor axon sprouting and reinnervation of neuromuscular junctions in ALs that is usually quickly overtaken by the disease *** drugs that enhance compensatory sprouting and encourage reinnervation may slow symptom progression and retain muscle function for a longer period of time in ALs and in other diseases that exhibit dying-back *** remain many outstanding questions as to the impact of distinct disease-causing mutations on axonal outgrowth and regeneration,especially in regards to motor neurons derived from patient induced pluripotent stem *** microfluidic chambers are powerful tools for studying the distal axons of human induced pluripotent stem cells-derived motor neurons,and have recently been used to demonstrate striking regeneration defects in human motor neurons harboring ALs disease-causing *** the human neuromuscular circuit with human induced pluripotent stem cells-derived motor neurons will be critical for developing drugs that enhance axonal regeneration,sprouting,and reinnervation of neuromuscular *** this review we will discuss compensatory axonal sprouting as a potential therapeutic target for ALs,and the use of compartmentalized microfluidic devices to find drugs that enhance regeneration and axonal sprouting of motor axons.

关键词： amyotrophic lateral sclerosis axonal regeneration dying-back axonopathy in vitro neuromuscular junction iPsC-derived motor neurons microfluidic device motor axon sprouting

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Dexamethasone-Inducible Green Fluorescent Protein Gene Expression in Transgenic Plant Cells

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Genomics, Proteomics & Bioinformatics 2004年第1期2卷 15-23页

作者： Hilary Collver katherine Kinken Department of Biology Howell Science ComplexEast Carolina UniversityGreenvNC 27858-4353USA.Department of BiologyHowell Science ComplexEast Carolina UniversityGreenvNC 27858-4353USA.

Genomic research has made a large number of sequences of novel genes orexpressed sequence tags available. To investigate functions of these genes, a system for conditionalcontrol of gene expression would be a useful tool. Inducible trans-gene expression that uses greenfluorescent protein gene (gfp) as a reporter gene has been investigated in transgenic cell lines ofcotton (COT; Gossypium hirsutum L.), Fraser fir [FRA; Abies fraseri (Pursh) Poir], Nordmann fir(NOR; Abies nord-manniana Lk.), and rice (RIC; Oryza sativa L. cv. Radon). Transgenic cell lineswere used to test the function of the chemical inducer dexamethasone. Inducible transgene expressionwas observed with fluorescence and confocal microscopy, and was confirmed by northern blotanalyses. Dexamethasone at 5 mg/L induced gfp expression to the nearly highest level 48 h aftertreatment in COT, FRA, NOR, and RIC. Dexamethasone at 10 mg/L inhibited the growth of transgeniccells in FRA and NOR, but not COT and RIC. These results demonstrated that concentrations of inducerfor optimum inducible gene expression system varied among transgenic cell lines. The inducible geneexpression system described here was very effective and could be valuable in evaluating thefunction of novel gene.

关键词： inducible gene expression confocal microscopy transcriptional activatorGVG fluorescence microscopy

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Circulating tumor cells(CTCs)in breast cancer:a diagnostic tool for prognosis and molecular analysis

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Chinese Journal of Cancer Research 2012年第4期24卷 388-398页

作者： Xiaoshen Dong R.katherine Alpaugh Massimo Cristofanilli Department of surgical Oncology First Affiliated HospitalChina Medical University Fox Chase Cancer Center 333 Cottman AvePhiladelphia

Metastatic breast cancer （MBC） is characterized by a combination of tumor growth, proliferation and metastatic progression and is typically managed with palliative intent. The benefit of standard systemic therapies is relatively limited and the disease is considered incurable suggesting the need to investigate the biological drivers of the various phases of the metastatic process in order to improve the selection of molecularly driven therapies. The detection, enumeration and molecular analysis of circulating tumor cells （CTCs） provide an intriguing opportunity to advance this knowledge. CTCs enumerated by the Food and Drugs Administration-cleared CellsearchTM system are an independent prognostic factor of progression- free survival （PFs） and overall survival （Os） in MBC patients. several published papers demonstrated the poor prognosis for MBC patients that presented basal CTC count _〉5 in 7.5 mL of blood. Therefore, the enumeration of CTCs during treatment for MBC provides a tool with the ability to predict progression of disease earlier than standard timing of anatomical assessment using conventional radiological tests. During the metastatic process cancer cells exhibit morphological and phenotypic plasticity undergoing epithelial- mesenchymal transition （EMT）. This important phenomenon is associated with down regulation of epithelial marker （e.g., EpCAM） with potential limitations in the applicability of current CTCs enrichment methods. such observations translated in a number of investigations aimed at improving our capabilities to enumerate and perform molecular characterization of CTCs. Theoretically, the phenotypic analysis of CTCs can represent a ＂liquid＂ biopsy of breast tumor that is able to identify a new potential target against the metastatic disease and advance the development and monitoring of personalized therapies.

关键词： Circulating tumor cells (CTCs) metastatic breast cancer (MBC) epithelial-mesenchymal transition(EMT) cancer stem cells

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Implementing a multispecies size-spectrum model in a datapoor ecosystem

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Acta Oceanologica sinica 2016年第4期35卷 63-73页

作者： ZHANG Chongliang CHEN Yong THOMPsON katherine REN Yiping College of Fisheries Ocean University of China school of Marine sciences University of Maine

Multispecies ecological models have been used for predicting the effects of fishing activity and evaluating the performance of management strategies. size-spectrum models are one type of physiologically-structured ecological model that provide a feasible approach to describing fish communities in terms of individual dietary variation and ontogenetic niche shift. Despite the potential of ecological models in improving our understanding of ecosystems, their application is usually limited for data-poor fisheries. As a first step in implementing ecosystem-based fisheries management（EBFM）, this study built a size-spectrum model for the fish community in the Haizhou Bay, China. We describe data collection procedures and model parameterization to facilitate the implementation of such size-spectrum models for future studies of data-poor ecosystems. The effects of fishing on the ecosystem were exemplified with a range of fishing effort and were monitored with a set of ecological indicators. Total community biomass, biodiversity index, W-statistic, LFI（Large fish index）, Mean W（mean body weight） and slope（slope of community size spectra） showed a strong non-linear pattern in response to fishing pressure, and largest fishing effort did not generate the most drastic responses in certain scenarios. We emphasize the value and feasibility of developing size-spectrum models to capture ecological dynamics and suggest limitations as well as potential for model improvement. This study aims to promote a wide use of this type of model in support of EBFM.

关键词： size-spectrum model trophic interaction data-poor model parameterization Haizhou Bay

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Wild bee distribution near forested landscapes is dependent on successional state

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Forest Ecosystems 2020年第2期7卷 159-171页

作者： katherine A.Odanaka sandra M.Rehan Department of Biological sciences University of New HampshireDurhamNHUSA Department of Biology York UniversityTorontoONCanada

Background:Forested landscapes are valuable sources of ecosystem services especially in areas dedicated to intense agricultural *** from forest margin is known to influence the wild bee community in the landscape surrounding forested *** little is known regarding how bee communities distribute themselves in landscapes that exhibit different forest successional ***:We examined how land use type and distance from the forest edge affect the abundance and richness of the wild bee community across four forest successional *** were collected in sites representing four stages of forest succession and analyzed using generalized linear mixed models with negative binomial ***:Wild bee diversity is reduced in forested environments that maintain dense stands of trees and high canopy ***,distance from the forest edge was an important factor determining wild bee distribution in successional stages adjacent to forest ***,we found that bees maintain high specificity for distinct successional states and ***:Our results demonstrate how different successional stages can harbor different bee species and highlight the ability of microhabitats to act as reservoirs of bee diversity in and around forest ***,we found that maximizing successional patchiness across forested landscapes increases the amount of available habitat that can support a diverse suite of bees with different nesting biologies and behaviors.

关键词： Pollinator Forest margin Bee habitat Nesting biology Wild bees

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Alcohol,inflammation,and gut-liver-brain interactions in tissue damage and disease development

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World Journal of Gastroenterology 2010年第11期16卷 1304-1313页

作者： H Joe Wang samir Zakhari M katherine Jung Division of Metabolism and Health Effects National Institute on Alcohol Abuse and Alcoholism National Institutes of Health

Chronic inflammation is often associated with alcoholrelated medical conditions. The key inducer of such inflammation, and also the best understood, is gut microflora-derived lipopolysaccharide (LPs). Alcohol can significantly increase the translocation of LPs from the gut. In healthy individuals, the adverse effects of LPs are kept in check by the actions and interactions of multiple organs. The liver plays a central role in detoxifying LPs and producing a balanced cytokine milieu. The central nervous system contributes to anti-inflammatory regulation through neuroimmunoendocrine actions. Chronic alcohol use impairs not only gut and liver functions, but also multi-organ interactions, leading to persistent systemic inflammation and ultimately, to organ damage. The study of these interactions may provide potential new targets for therapeutic intervention.

关键词： Chronic alcohol use Chronic inflammation Li- popolysaccharides Pro-inflammatory and anti-inflammatory cytokines Kupffer cells Monocytes Tumor necrosis factor α Interleukin-10 Neuroendocrine Hypothalamo-pituitary-adrenal axis Glucocorticoid

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Regulation of macrophage activation in the liver after acute injury: Role of the fibrinolytic system

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World Journal of Gastroenterology 2020年第16期26卷 1879-1887页

作者： katherine Roth Jenna strickland Bryan L Copple Department of Pharmacology and Toxicology Institute for Integrative ToxicologyMichigan State UniversityEast LansingMI 48824United States

The liver functions,in part,to prevent exposure of the body to potentially harmful substances ingested in the *** it is highly efficient at accomplishing this,it is frequently prone to liver injury due to the biotransformation of xenobiotics into toxic *** counter this injury,the liver has evolved a unique capacity to rapidly and efficiently repair *** resolution of acute liver injury relies on hepatic macrophage populations that orchestrate the reparative *** injury,Kupffer cells,the resident macrophages of the liver,become activated and secrete proinflammatory *** cytokines recruit other immune cells,including monocyte-derived macrophages,to the liver where they contribute to the repair ***-derived macrophages traffic into the necrotic foci where they rapidly phagocytose dead cell *** with this process,these cells change phenotype from a proinflammatory macrophage to a prorestorative macrophage that produce pro-mitogenic growth factors and antiinflammatory *** this process triggers resolution of inflammation,and along with proliferation of other hepatic cells,restores the liver architecture and *** the mechanisms regulating specific macrophage functions during repair remain to be elucidated,recent studies indicate a key role for the fibrinolytic system in coordinating macrophage function during *** this review,we will highlight the function and role of hepatic macrophages in repair after acute liver injury,and will discuss the role of the fibrinolytic enzyme,plasmin,in regulation of these various processes.

关键词： Macrophage Plasmin Acetaminophen Liver injury Liver repair

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Long-term modifications of blood pressure in normotensive and spontane-ously hypertensive rats by gene delivery of rAAV-mediated cytochrome P450 arachidonic acid hydroxylase

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Cell Research 2005年第9期 42-49页

作者： katherine CIANFLONE Montreal Mike Rosenbloom Laboratory for Cardiovascular Research Canada McGill University Health Center Quebec H3A 1A1

Arachidonic acid cytochrome P-450 (CYP) hydroxylase 4A isoforms, including 4A1, 4A2, 4A3 and 4A8 in the rat kidney, catalyze arachidonic acid to produce 19/20-Hydroxyeicosatetraenoic acids (20-HETE), a biologically active metabolite, which plays an important role in the regulation of blood pressure. However, controversial results have been reported regarding the exact role of 20-HETE on blood pressure. In the present study, we used recombinant adeno- associated viral vector (rAAV) to deliver CYP 4A1 cDNA and antisense 4A1 cDNA into sprague-Dawley (sD) rats and spontaneously hypertensive rats (sHR), respectively, to investigate the effects of long-term modifications of blood pressure and the potential for gene therapy of hypertension. The mean systolic pressure increased by 14.2±2.5 mm Hg in rAAV·4A1-treated sD rats and decreased by 13.7±2.2 mm Hg in rAAV·anti4A1-treated sHR rats 5 weeks after the injection compared with controls and these changes in blood pressure were maintained until the experiments ended at 24 weeks. In 4A1 treated animals CYP4A was overexpressed in various tissues, but preferentially in the kidney at both mRNA and protein levels. In anti-4A1-treated sHR, CYP4A mRNA in various tissues was probed, especially in kidneys, but 4A1 protein expression was almost completely inhibited. These results suggest that arachidonic acid CYP hydroxy- lases contribute not only to the maintenance of normal blood pressure but also to the development of hypertension. rAAV-mediated anti4A administration strategy has the potential to be used as targeted gene therapy in human hyperten- sion by blocking expression of CYP 4A in kidneys.

关键词： Arachidonic acid cytochrome P450 4A1 hypertension recombinant adeno-associated virus 20- Hydroxyeicosatetraenoic acids spontaneously hypertensive rats.

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Challenges in elucidating cholangiocarcinoma etiology

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Hepatobiliary surgery and Nutrition 2020年第4期9卷 537-539页

作者： sarah s.Jackson Andrea A.Florio katherine A.McGlynn Jessica L.Petrick Division of Cancer Epidemiology and Genetics National Cancer InstituteNIHDHHSBethesdaMDUSA slone Epidemiology Center Boston UniversityBostonMAUSA

Cholangiocarcinomas(CCAs)are rare tumors that originate from cholangiocytes in the bile ducts and are classified as intra-or extrahepatic(ICC or ECC).ICCs account for 10–12%of liver cancers,while ECCs account for approximately one-third of biliary tract cancers(1).Incidence rates of CCA are geographically variable,with the highest rates in ***,even in the highest incidence country(south Korea)the rates are only 2.8 and 2.2 per 100,000 person-years for ICC and ECC,respectively(2).Incidence rates of both ICC and ECC have been increasing in most countries globally,which potentially indicates a changing etiology(2).

关键词： etiology Incidence dating

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Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

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International Journal of Oral science 2013年第3期5卷 130-140页

作者： Carol L Fischer katherine s Walters David R Drake Deborah V Dawson Derek R Blanchette Kim A Brogden Philip W Wertz Dows Institute for Dental Research College of Dentistry The University of Iowa Central Microscopy Research Facility College of Dentistry The University of Iowa Department of Endodontics College of Dentistry The University of Iowa Department of Pediatric Dentistry College of Dentistry The University of Iowa Department of Periodontics College of Dentistry The University of Iowa Department of Oral Pathology Radiology & Medicine College of Dentistry The University of Iowa

Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria;however,little is known about their spectrum of antimicrobial activity or mechanisms of action against oral *** this study,we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis,an important colonizer of the oral cavity implicated in *** inhibitory concentrations,minimal bactericidal concentrations,and kill kinetics revealed variable,but potent,activity of oral mucosal and salivary lipids against ***,indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria,although specific components of bacterial membranes are also likely *** micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma *** information,coupled with the association of treatment lipids with *** lipids revealed via thin layer chromatography,suggests that the plasma membrane is a likely target of lipid antibacterial *** a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique *** stress response,including proteins important in fatty acid biosynthesis,metabolism and energy production,protein processing,cell adhesion and *** or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.

关键词： antimicrobial lipid fatty acid Porphyromonasgingivalis sphingoid base sphingolipid ultrastructure

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