237 research outputs found
NRF2 activation restores disease related metabolic deficiencies in olfactory neurosphere-derived cells from patients with sporadic Parkinson's Disease
Get PDFExtent: 14p.Background: Without appropriate cellular models the etiology of idiopathic Parkinson’s disease remains unknown. We recently reported a novel patient-derived cellular model generated from biopsies of the olfactory mucosa (termed olfactory neurosphere-derived (hONS) cells) which express functional and genetic differences in a disease-specific manner. Transcriptomic analysis of Patient and Control hONS cells identified the NRF2 transcription factor signalling pathway as the most differentially expressed in Parkinson’s disease. Results: We tested the robustness of our initial findings by including additional cell lines and confirmed that hONS cells from Patients had 20% reductions in reduced glutathione levels and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium, inner salt] metabolism compared to cultures from healthy Control donors. We also confirmed that Patient hONS cells are in a state of oxidative stress due to higher production of H2O2 than Control cultures. siRNA-mediated ablation of NRF2 in Control donor cells decreased both total glutathione content and MTS metabolism to levels detected in cells from Parkinson’s Disease patients. Conversely, and more importantly, we showed that activation of the NRF2 pathway in Parkinson’s disease hONS cultures restored glutathione levels and MTS metabolism to Control levels. Paradoxically, transcriptomic analysis after NRF2 pathway activation revealed an increased number of differentially expressed mRNAs within the NRF2 pathway in L-SUL treated Patient-derived hONS cells compared to L-SUL treated Controls, even though their metabolism was restored to normal. We also identified differential expression of the PI3K/AKT signalling pathway, but only post-treatment. Conclusions: Our results confirmed NRF2 as a potential therapeutic target for Parkinson’s disease and provided the first demonstration that NRF2 function was inducible in Patient-derived cells from donors with uniquely varied genetic backgrounds. However, our results also demonstrated that the response of PD patient-derived cells was not co-ordinated in the same way as in Control cells. This may be an important factor when developing new therapeutics.Anthony L. Cook, Alejandra M. Vitale, Sugandha Ravishankar, Nicholas Matigian, Greg T. Sutherland, Jiangou Shan, Ratneswary Sutharsan, Chris Perry, Peter A. Silburn, George D. Mellick, Murray L. Whitelaw, Christine A. Wells, Alan Mackay-Sim and Stephen A. Woo
Racism Reflected in Colour Blind Novel (1968) by Catherine Cookson: Critical Race Theory
Get PDFThis research is the study of racism reflected in Colour Blind novel (1968) by Catherine Cookson viewed from critical race theory. The purpose of this research is to analyze the racism reflected in Colour Blind novel (1968) by Catherine Cookson based on critical race theory. Method of data collection is conducted by analyzing and interpreting descriptively while the techniques of data analysis is a descriptive technique. The results of this research are: 1) The researcher finds the indicators of racism in Colour Blind as seen from critical race theory by Richard Delgado and Jean Stefancic (2001). 2) The researcher describes the racism happened in the novel Colour Blind. 3) The author takes the issue "racism" because in that year discrimination is an unfair treatment that usually happens by the majority groups towards minority groups that lead to racism in society
The first Australian palynologist: Isabel Clifton Cookson (1893–1973) and her scientific work
Get PDFIsabel Clifton Cookson (1893–1973) of Melbourne, Australia, was one of that country’s first professional woman scientists. She is remembered as one of the most eminent palaeontologists of the twentieth century and had a distinguished research career of 58 years, authoring or co-authoring 93 scientific publications. Isabel worked with great distinction on modern and fossil plants, and pioneered palynology in Australia. She was a consumate taxonomist and described, or jointly described, a prodigious total of 110 genera, 557 species and 32 subspecific taxa of palynomorphs and plants. Cookson was a trained biologist and initially worked as a botanist during the 1920s. At the same time she became interested in fossil plants and then, Mesozoic–Cenozoic terrestrial (1940s–1950s) and aquatic (1950s–1970s) palynomorphs. Cookson’s research into the late Silurian–Early Devonian plants of Australia and Europe, particularly the Baragwanathia flora, between the 1920s and the 1940s was highly influential in the field of early plant evolution. The fossil plant genus Cooksonia was named for Isabel in 1937 by her principal mentor in palaeobotany, Professor William H. Lang. From the 1940s Cookson focussed on Cenozoic floras and, with her students, elucidated floral affinities by comparative analyses of micromorphology, anatomy and in situ pollen/spores between fossil and extant taxa. This led to an interest in pre-Quaternary and Quaternary terrestrial pollen and spores; hence Isabel was the first palynologist in Australia. Her work on Paleogene and Neogene pollen and spores during the 1940s and 1950s provided incontrovertible evidence of the former widespread distribution of many important elements of Southern Hemisphere floras. During the early 1950s, while approaching her 60th year, Isabel turned her attention to marine palynomorphs. She worked with great distinction with Georges Deflandre and Alfred Eisenack, and also as a sole author, on acritarchs, dinoflagellate cysts and prasinophytes from the Jurassic to Quaternary of Australia and Papua New Guinea. She also co-authored papers on aquatic palynomorphs with Lucy M. Cranwell, Norman F. Hughes and Svein B. Manum. Isabel Cookson laid out the taxonomic basis for the study of Australasian Mesozoic and Cenozoic marine palynofloras by establishing, or jointly establishing, 76 genera and 386 species of marine microplankton. Her studies throughout her career, although especially in marine palynology, concentrated largely on taxonomy. However, she was one of the first palynologists to demonstrate the utility of dinoflagellate cysts for relative age dating and correlation in geological exploration
Racism Reflected in Colour Blind Novel (1968) By Catherine Cookson: Critical Race Theory
No full textThis study discusses the Racism that is reflected in the Novel colour blind (1968) by Catherine Cookson area: critical race theory. Racism systems encompass economic, political, social, and cultural actions, as well believe that institutionalizes and perpetuate an unequal distribution of privileges, resources, and power between white people and people of Color. Racism involves white people and black people. People do discriminate towards white people or another people who have black skin because of their skin; The purpose of this research was to analyze the racism reflected in color blind (1968) Novel by Catherine Cookson area based on critical race theory. Method of data collection is done with documentation and analyzing using Critical Race Theory while the technique of data analysis is a descriptive technique. The main data in this research is character, punctuation, words, phrases, sentences, paragraphs/discourse in novel colour blind. The results of this research are; 1) Indicator lines using critical race theory by Delgado and Stefancic (2001: 101). In the community, 2) describes the racism occur in the novel color blind. Racism already existed long before the main character Rose Angela was born. 3) Reveals the reason why the author in the work of colour blind novel specifically addresses racism color blind published in 1968
Socio-economic inequality in small area use of elective total hip replacement in the English NHS in 1991 and 2001
Get PDFInternational evidence suggests that there are substantial socio-economic inequalities in the delivery of specialist health services, even in the UK and other high-income countries with publicly funded health systems (Goddard and Smith 2001, Dixon et al. 2003, Van Doorslaer, Koolman and Jones 2004, Van Doorslaer et al. 2000). Studies of total hip replacement in the English NHS have yielded particularly striking examples, given that hip replacement is such a common, effective and longestablished health technology. Administrative data show that people living in deprived areas are less likely to receive hip replacement (Chaturvedi and Ben-Shlomo 1995, Dixon et al. 2004) while survey data suggest they may be more likely to need it (Milner et al. 2004). However, previous studies have not examined change in inequality over time. This paper presents evidence on the change in socio-economic inequality in small area use of elective total hip replacement in the English NHS, comparing 1991 with 2001. This was a period of important large-scale health care reform in England, involving at least two significant reforms that might potentially have influenced socio-economic inequality in health care delivery: (1) the introduction and subsequent abolition of the Conservative “internal market” 1991-7, and (2) the introduction in 1995 of a revised NHS resource allocation formula designed to reduce geographical inequalities in health care delivery. Two datasets, for 1991 and 2001, were assembled from routine NHS data sources: Hospital Episode Statistics (HES) on hospital utilisation in England and the corresponding decennial National Censuses in 1991 and 2001. Both datasets contain information on over 8,000 electoral wards in England (over 95% of the total). To improve comparability, a common geography of frozen 1991 wards was adopted. The Townsend deprivation score was employed as an indicator of socio-economic status. Inequality was analysed in two ways. First, for comparability with previous small area studies of hip replacement, by using simple range measures based on indirectly age-sex standardised utilisation ratios (SURs) by deprivation quintile groups. Second, using concentration indices of deprivationrelated inequality in use based on indirectly age-sex standardised utilisation ratios for each individual small area. Each SUR is the observed use divided by the expected use, if each age and sex group in the study population had the same rates of use as the national population.
Studies of activation and toxicity in cultured astrocytes
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Law and Finance Matter: Lessons from Externally Imposed Courts
Get PDFThis paper provides novel evidence on the real and financial market effects of legal institutions. Our analysis exploits persistent and externally imposed differences in court enforcement that arose when the U.S. Congress assigned state courts to adjudicate contracts on a subset of Native American reservations. Using area-specific data on small business lending, we find that reservations assigned to state courts, which enforce contracts more predictably than tribal courts, have stronger credit markets. Moreover, the law-driven component of credit market development is associated with significantly higher per capita income, with stronger effects in sectors that depend more on external financing.This is a pre-copyedited, author-produced version of an article accepted for publication in The Review of Financial Studies, following peer review. The version of record Law and Finance Matter: Lessons from Externally Imposed Courts James R. Brown J. Anthony Cookson Rawley Z. Heimer; Volume 30, Issue 3, 1 March 2017, Pages 1019–1051. is available online at: DOI: 10.1093/rfs/hhw030. Posted with permission.</p
Courting Economic Development
Get PDFWe show that court enforcement uncertainty hinders economic development using sharp variation in judiciaries across Native American reservations in the United States. Congressional legislation passed in 1953 assigned state courts the authority to resolve civil disputes on a subset of reservations, while tribal courts retained authority on unaffected reservations. Although affected and unaffected reservations had similar economic conditions when the law passed, reservations under state courts experienced significantly greater long-run growth. When we examine the distribution of incomes across reservations, the average difference in development is due to the lower incomes of the most impoverished reservations with tribal courts. We show that the relative under-development of reservations with tribal courts is driven by reservations with the most uncertainty in court enforcement.This is a pre-copyedited, author-produced PDF of an article accepted for publication in The World Bank Economic Review following peer review. The version of record Courting Economic Development (with T. Cookson and R. Heimer). 2017. World Bank Economic Review, Papers and Proceedings of the 26th Annual Bank Conference on Development Economics, 30 (Supplement_1), S176-S187. is available online at: DOI: 10.1093/wber/lhw027. Posted with permission.</p
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