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Novel approaches to combat chemoresistance against glioblastomas

Cancer Drug Resistance 2020年第4期3卷 686-698页

作者： Rheal A.Towner Michelle Zalles debra Saunders Nataliya Smith Advanced Magnetic Resonance Center Oklahoma Medical Research FoundationOklahoma CityOK 73104USA Oklahoma Center for Neuroscience University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA

The poor prognosis of glioblastoma multiforme(GBM)patients is in part due to resistance to current standard-of-care treatments including chemotherapy[predominantly temozolomide(TMZ;Temodar)],radiation therapy and an anti-angiogenic therapy[an antibody against the vascular endothelial growth factor(bevacizumab;Avastin)],resulting in recurrent *** recurrent GBM tumors are commonly resistant to either TMZ,radiation or bevacizumab,which contributes to the low survival rate for GBM *** review will focus on novel targets and therapeutic approaches that are currently being considered to combat GBM *** of these therapeutic options is a small molecule called OKlahoma Nitrone 007(OKN-007),which was discovered to inhibit the transforming growth factor β1 pathway,reduce TMZ-resistance and enhance ***-007 is currently an investigational new drug in clinical trials for both newly-diagnosed and recurrent GBM *** novel target is ELTD1(epidermal growth factor,latrophilin and seven transmembrane domain-containing protein 1;alternatively known as ADGRL4,Adhesion G protein-coupled receptor L4),which we used a monoclonal antibody against,where a therapy against it was found to inhibit Notch 1 in a pre-clinical GBM xenograft *** 1 is known to be associated with chemoresistance in *** potential therapeutic targets to combat GBM chemoresistance include the phosphoinositide 3-kinase pathway,nuclear factor-κB,the hepatocyte/scatter factor(c-MET),the epidermal growth factor receptor,and the tumor microenvironment.

关键词： Glioblastoma pre-clinical models OKlahoma Nitrone 007 transforming growth factor-β1 ELTD1 magnetic resonance imaging

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Tailoring minimalist self-assembling peptides for localized viral vector aene deliverv

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Nano Research 2016年第3期9卷 674-684页

作者： Alexandra L. Rodriguez Ting-Yi Wang Kiara F. Bruggeman Rui Li Richard J. Williams Clare L. parish David R. Nisbet Research School of Engineering The Australian National University Canberra ACT2601 Australia Florey Institute ofNeuroscience & Men tal Health The University of Melbourne Parkville VIC 3010 Australia Cen tre for Chemistry and Biotechnology Deakin University Waurn Ponds VIC 3217 Australia School of Aerospace Mechanical and Manufacturing Engineering and the Health Innovations Research Institute RMIT University Melbourne VIC 300 I Australia

Viral vector gene delivery is a promising technique for the therapeutic administra- tion of proteins to damaged tissue for the improvement of regeneration outcomes in various disease settings including brain and spinal cord injury, as well as autoimmune diseases. Though promising results have been demonstrated, limitations of viral vectors, including spread of the virus to distant sites, neutralization by the host immune system, and low transduction efficiencies have stimulated the investigation of biomaterials as gene delivery vehicles for improved protein expression at an injury site. Here, we show how N- fluorenylmethyloxycarbonyl （Fmoc） self-assembling peptide （SAP） hydrogels, designed for tissue-specific central nervous system （CNS） applications via incorporation of the laminin peptide sequence isoleucine-lysine-valine-alanine- valine （IKVAV）, are effective as biocompatible, localized viral vector gene delivery vehicles in vivo. Through the addition of a C-terminal lysine （K） residue, we show that increased electrostatic interactions, provided by the additional amine side chain, allow effective immobilization of lentiviral vector particles, thereby limiting their activity exclusively to the site of injection and enabling focal gene delivery in vivo in a tissue-specific manner. When the C-terminal lysine was absent, no difference was observed between the number of transfected cells, the volume of tissue transfected, or the transfection efficiency with and without the Fmoc-SAP. Importantly, immobilization of the virus only affected transfection cell number and volume, with no impact observed on transfection efficiency. This hydrogel allows the sustained and targeted delivery of growth factors post injury. We have established Fmoc-SAPs as a versatile platform for enhanced biomaterial design for a range of tissue engineering applications.

关键词： viral vectors gene therapy self-assembling peptides biomaterials

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Green tea extract:A potential cause of acute liver failure

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World Journal of Gastroenterology 2013年第31期19卷 5174-5177页

作者： Shreena S Patel Stacey Beer debra L Kearney Garrett Phillips Beth A Carter Department of Pediatrics Baylor College of Medicine Houston TX 77030 United States Division of Pediatric Gastroenterology Texas Children’s Hospital Houston TX 77030 United States Department of Pathology and Immunology Baylor College of Medicine Houston TX 77030 United States Division of Pediatric Gastroenterology Baylor College of Medicine Houston TX 77030 United States

The use of herbal products has increased significantly in recent *** these products are not subject to regulation by the Food and Drug Administration and are often used without supervision by a healthcare provider,the indication for and consumption of these supplements is quite ***,their use is generally regarded as safe and natural by the ***,there has been an increase in the number of reported adverse events occurring with the use of herbal *** present a case of acute impending liver failure in an adolescent male using a weightloss product containing green tea *** case adds to the growing concern surrounding the ingestion of green tea extract and serves to heighten healthcare provider awareness of a potential green tea extract *** the generally touted benefits of green tea as a whole,clinical concern regarding its use is emerging and has been linked to its concentration in multiple herbal ***,the suspected harmful compounds are those previously proposed to be advantageous for weight-loss,cancer remedy,and anti-inflammatory ***,we emphasize the need to be aware of not just green tea extract,but the importance of monitoring patient use of all dietary supplements and herbal products.

关键词： Green tea Plant extract Dietary supplements Liver failure Liver injury Hepatotoxicity

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Arabidopsis thaliana T-DNA Mutants Implicate GAUT Genes in the Biosynthesis of Pectin and Xylan in Cell Walls and Seed Testa

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Molecular Plant 2009年第5期2卷 1000-1014页

作者： Kerry H. Caffall Sivakumar Pattathil Sarah E. Phillips Michael G. Hahn debra Mohnen Department of Biochemistry and Molecular Biology University of Georgia Athens GA 30602 USA Complex Carbohydrate Research Center BioEnergy Science Center 315 Riverbend Road University of Georgia Athens GA 30602 USA Department of Plant Biology University of Georgia Athens GA 30602 USA

Galacturonosyltransferase 1 （GAUT1） is an α1,4-D-galacturonosyltransferase that transfers galacturonic acid from uridine 5＇-diphosphogalacturonic acid onto the pectic polysaccharide homogalacturonan （Sterling et al., 2006）. The 25-member Arabidopsis thaliana GAUT1-related gene family encodes 15 GAUT and 10 GAUT-like （GATL） proteins with, respectively, 56-84 and 42-53% amino acid sequence similarity to GAUT1. Previous phylogenetic analyses of AtGAUTs indicated three clades： A through C. A comparative phylogenetic analysis of the Arabidopsis, poplar and rice GAUT families has sub-classified the GAUTs into seven clades： clade A-1 （GAUTs 1 to 3）; A-2 （GAUT4）; A-3 （GAUTs 5 and 6）; A-4 （GAUT7）; B-1 （GAUTs 8 and 9）; B-2 （GAUTs 10 and 11）; and clade C （GAUTs 12 to 15）. The Arabidopsis GAUTs have a distribution comparable to the poplar orthologs, with the exception of GAUT2, which is absent in poplar. Rice, however, has no orthologs of GAUTs 2 and 12 and has multiple apparent orthologs of GAUTs 1, 4, and 7 compared with eitherArabidopsis or poplar. The cell wall glycosyl residue compositions of 26 homozygous T-DNA insertion mutants for 13 of 15 Arabidopsis GAUTgenes reveal significantly and reproducibly different cell walls in specific tissues of gaut mutants 6, 8, 9, 10, 11, 12, 13, and 14 from that of wild-type Arabidopsis walls. Pectin and xylan polysaccharides are affected by the loss of GAUT function, as demonstrated by the altered galacturonic acid, xylose, rhamnose, galactose, and arabinose composition of distinct gaut mutant walls. The wall glycosyl residue compositional phenotypes observed among the gaut mutants suggest that at least six different biosynthetic linkages in pectins and/or xylans are affected by the lesions in these GAUTgenes. Evidence is also presented to support a role for GAUT11 in seed mucilage expansion and in seed wall and mucilage composition.

关键词： Carbohydrate metabolism cell walls Arabidopsis biosynthesis mutant pectin mucilage

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Chinese nurses’ perceived impact of international educational experiences and cultural beliefs following a 1-year study abroad program: an exploratory study

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Frontiers of Nursing 2020年第1期7卷 23-29页

作者： debra MWolf Hui-Xin Wub Kathleen Spadaro Diane FHunker Nursing and Healthcare Informatics Chatham UniversityPittsburghPennsylvania 15232USA School of Nursing Davis&Elkins CollegeElkinsWest Virginia 26241USA School of Nursing Chatham UniversityPittsburghPennsylvania 15232USA

Objectives:To examine the perceived impact of international educational experiences and cultural beliefs before and after completing a 1-year Masters of Science in Nursing ***:An exploratory study was conducted among Chinese nurses studying abroad in a private medium-sized university in the United *** 27-item electronic pre-survey was administered within 1 week of starting the program and the post-survey was administered 1 year later at the completion of the ***:Majority of participants(n=25)were female,23–36 years of *** revealed that the perceived impact of international educational experiences assessed at the start of the program was similar to the perceived impact measured at the end of the 1-year program,suggesting that the students learned and experienced what they *** was a significant impact on cultural beliefs from the start of the program compared with the end of the program suggesting that a 1-year study abroad program does influence cultural ***:Understanding what is important to provide in a study abroad program and providing the educational experiences identified by students as impactful are avenues to help host universities best develop their *** suggested that the 1-year program can influence foreign students’cultural beliefs,yet the professional and personal impact of this change warrants further study.

关键词： international Chinese nurses cultural beliefs learning needs educational impact

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Mental Illness Education through Stories of Lived Experience: Validation Review of the DoNOHarm Framework

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International Journal of Mental Health Promotion 2021年第4期23卷 455-469页

作者： debra Rickwood Kerry Thomas Patricia M.Brown Heidi Prowse Faculty of Health University of CanberraCanberra2600Australia Mental Illness Education ACT Canberra2601Australia

The lived experience of people with mental illness is a powerful way to promote mental health literacy and reduce the stigma associated with mental ***,there is little guidance on how to do this *** Illness Education ACT is an Australian organisation that since 1993 has supported volunteer educators to share their individual stories of lived experience to school and community *** 2011,they developed the DoNOHarm Framework to assist volunteers to be able to talk about their experiences in a way that is safe for them and for their audience,a gap that they recognised in *** study reports a review of the Framework,considering the extent to which it is supported by the current literature and how it is being implemented and experienced by the volunteer *** research questions were addressed by a literature review and interviews with 14 volunteer educators and the staff that support *** review of published literature over the past 10 years showed strong evidence for three of the six principles of the Framework:Context and Purpose,Recovery Emphasis,and Safe *** the principle of Respectful and Inclusive Language is widely promoted in the mental healthfield,no recent studies investigated the benefits of this ***,there was no recent research into the two principles of Limits to Helping and Self *** interviews revealed strong support for the Frame-work among *** was seen to be effective to protect the safety of both presenter and audience,ensure the relevance of the presentation,give educators confidence in their message and delivery,convey a hopeful message,and make certain that presentations were engaging for the ***,this review shows that the DoNO-Harm Frameworkfills an important gap for mental health education,with a sound evidence base where there is published evidence available.

关键词： Mental illness education lived experience storytelling harm safety framework

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Combined immunohistochemical and retrograde tracing reveals little evidence of innervation of the rat dentate gyrus by midbrain dopamine neurons

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Frontiers in Biology 2016年第3期11卷 246-255页

作者： Charlotte M. Ermine Jordan L. Wright Clare L. parish Davor Stanic Lachlan H. Thompson The Florey Institute for Neuroscience and Mental Health The University of Melbourne Parkville Victoria 3010 Australia Current address Wolfson Institute for Biomedical Research University College London Gower Street London WC1E 6BT UK

Although the functional neuroanatomy of the midbrain dopamine （mDA） system has been well characterized, the literature regarding its capacity to innervate the hippocampal formation has been inconsistent. The lack of expression of definitive markers for dopaminergic fibers, such as the dopamine transporter, in the hippocampus has complicated studies in this area. Here we have used immunohistochemical techniques to characterize the tyrosine hydroxylase expressing fiber network in the rat hippocampus, combined with retrograde tracing from the dentate gyrus to assess the capacity for afferent innervation by mDA neurons. The results indicate that virtually all tyrosine hydroxylase fibers throughout the hippocampus are of a noradrenergic phenotype, while the overlying cortex contains both dopaminergic and noradrenergic fiber networks. Furthermore, retrograde tracing from the dentate gyrus robustly labels tyrosine hydroxylase-immunoreactive noradrenergic neurons in the locus coeruleus but not mDA neurons.

关键词： noradrenaline hippocampus connectivity DAT neurogenesis

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Conservation needs of amphibians in China: A review

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Science China(Life Sciences) 2007年第2期50卷 265-276页

作者： Michael Wai Neng LAU Simon N STUART Janice S CHANSON Neil A COX debra L FISCHMAN Kadoorie Farm and Botanic Garden Hong Kong China IUCN-SSC/CI-CABS Biodiversity Assessment Unit Center for Applied Biodiversity Science Conservation International Washing-ton DC 20036 USA GIS Laboratory Center for Applied Biodiversity Science Conservation International Washington DC 20036 USA

The conservation status of all the amphibians in China is analyzed,and the country is shown to be a global priority for conservation in comparison to many other countries of the *** Chinese regions are particularly rich in amphibian diversity:Hengduan,Nanling,and Wuyi ***-manders are more threatened than frogs and *** smaller families show a high propensity to become seriously threatened:Bombinatoridae,Cryptobranchidae,Hynobiidae and *** other parts of the world,stream-breeding,high-elevation forest amphibians have a much higher likeli-hood of being seriously *** loss,pollution,and over-harvesting are the most serious threats to Chinese ***-harvesting is a less pervasive threat than habitat loss,but it is more likely to drive a species into rapid *** conservation challenges are mentioned with recommendations for the highest priority research and conservation actions.

关键词： amphibians conservation status priority of the regions and animal group habitat preferences conservation challenge conservation recom-mendation

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The influence of habitat heterogeneity and latitude on gamma diversity of the Nearctic Simuliidae, a ubiquitous group of stream-dwelling insects

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Insect Science 2018年第4期25卷 712-720页

作者： John W. McCreadie Rachel H. Williams Sam Stutsman debra S. Finn Peter H. Adler Department of Biology University of South Alabama Mobile Alabama USA Department of Earth Sciences Biology University of South Alabama Mobile Alabama USA Department of Integrative Biology Oregon State University Corvallis Oregon USA Department of Plant and Environmental Sciences Clemson University Clemson South Carolina USA

Among the most prominent, large-scale patterns of species richness are the increases in richness with decreasing latitude and with increasing habitat heterogeneity. Using the stream-dwelling larval and pupal stages of North American black flies （Diptera： Simuliidae）, we address 3 broad questions about species richness：（i） Does a significant latitude-richness relationship exist？（ii） How does habitat heterogeneity influence gamma diversity？（iii） What is the sign （positive or negative） of the latitude-richness and the heterogeneity-richness relationships？ We found no evidence that habitat heterogeneity influences gamma diversity. The estimated peak species richness for black flies in North America was at 50-53°N, which also corresponds with peak generic richness. All plesiomorphic, extant lineages of the Simuliidae in the Western Hemisphere are found in cool mountainous environments of North America, suggesting that peak richness at 50-53°N might be a signature of this phylogenetic pattern and a reflection of underlying historical processes

关键词： aquatic insects biodiversity gamma richness North America Simuliidae streams

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Narrative Inquiry as a Research Methodology： Discovering Meaning From the Stories of Canadian Veterans Diagnosed With PTSD （Post-traumatic Stress Disorder）

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Psychology Research 2013年第10期3卷 547-562页

作者： debra Lynn Bastien Programme DISI Registered Nurses Professional Development Center New Brunswick Canada

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