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Search Results: 1 - 10 of 12043 matches for " Adrienne Henderson-Smith "
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SMG1 Identified as a Regulator of Parkinson’s Disease-Associated alpha-Synuclein through siRNA Screening
Adrienne Henderson-Smith, Donald Chow, Bessie Meechoovet, Meraj Aziz, Sandra A. Jacobson, Holly A. Shill, Marwan N. Sabbagh, John N. Caviness, Charles H. Adler, Erika D. Driver-Dunckley, Thomas G. Beach, Hongwei Yin, Travis Dunckley
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077711
Abstract: Synucleinopathies are a broad class of neurodegenerative disorders characterized by the presence of intracellular protein aggregates containing α-synuclein protein. The aggregated α-synuclein protein is hyperphosphorylated on serine 129 (S129) compared to the unaggregated form of the protein. While the precise functional consequences of S129 hyperphosphorylation are still being clarified, numerous in vitro and in vivo studies suggest that S129 phosphorylation is an early event in α-synuclein dysfunction and aggregation. Identifying the kinases and phosphatases that regulate this critical phosphorylation event may ultimately prove beneficial by allowing pharmacological mitigation of synuclein dysfunction and toxicity in Parkinson’s disease and other synucleinopathies. We report here the development of a high-content, fluorescence-based assay to quantitate levels of total and S129 phosphorylated α-synuclein protein. We have applied this assay to conduct high-throughput loss-of-function screens with siRNA libraries targeting 711 known and predicted human kinases and 206 phosphatases. Specifically, knockdown of the phosphatidylinositol 3-kinase related kinase SMG1 resulted in significant increases in the expression of pS129 phosphorylated α-synuclein (p-syn). Moreover, SMG1 protein levels were significantly reduced in brain regions with high p-syn levels in both dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD). These findings suggest that SMG1 may play an important role in increased α-synuclein pathology during the course of PDD, DLB, and possibly other synucleinopathies.
A Model-Based Analysis of Chemical and Temporal Patterns of Cuticular Hydrocarbons in Male Drosophila melanogaster
Clement Kent, Reza Azanchi, Ben Smith, Adrienne Chu, Joel Levine
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000962
Abstract: Drosophila Cuticular Hydrocarbons (CH) influence courtship behaviour, mating, aggregation, oviposition, and resistance to desiccation. We measured levels of 24 different CH compounds of individual male D. melanogaster hourly under a variety of environmental (LD/DD) conditions. Using a model-based analysis of CH variation, we developed an improved normalization method for CH data, and show that CH compounds have reproducible cyclic within-day temporal patterns of expression which differ between LD and DD conditions. Multivariate clustering of expression patterns identified 5 clusters of co-expressed compounds with common chemical characteristics. Turnover rate estimates suggest CH production may be a significant metabolic cost. Male cuticular hydrocarbon expression is a dynamic trait influenced by light and time of day; since abundant hydrocarbons affect male sexual behavior, males may present different pheromonal profiles at different times and under different conditions.
The use of CAM by women suffering from nausea and vomiting during pregnancy
Taras Hollyer, Heather Boon, Alexia Georgousis, Michael Smith, Adrienne Einarson
BMC Complementary and Alternative Medicine , 2002, DOI: 10.1186/1472-6882-2-5
Abstract: Women who called The Motherisk NVP helpline, were asked after the counseling session to complete a questionnaire, which included demographic data as well as information about their CAM use.Seventy women completed the questionnaire. 61% reported using CAM therapies, of which the three most popular were: ginger, vitamin B6 and acupressure. 21% of those who reported using CAM, had consulted CAM practitioners, 8% their physicians or pharmacists and 71% discussed the usage with family, friends and other allied health professionals. Women who did not use CAM stated they would probably use these modalities if there was more information about the safety in pregnancy.Pregnant women with NVP are mirroring the trend in the general population of the use of CAM. They are also using CAM therapies with little supervision from practitioners experienced in the use of these modalities.Nausea and vomiting during pregnancy (NVP) affects up to 80 % of all pregnant women, and has a significant impact on the quality of life of those who experience it [1,2]. The effects can range from mild nausea to more severe forms such as hyperemesis gravidarum, which is characterized by an intractable nausea and vomiting so severe that it can lead to hospitalization. Although only 0.3 to 3% of pregnant women are diagnosed with hyperemesis gravidarum[3], less severe forms of NVP exert a significant impact on the quality of life of those affected [1]. In one study, close to 50% of employed women reported reduced work efficiency due to NVP, with as many as 25–66% of women actually requiring time off work. Furthermore, almost 50% of women reported that their NVP negatively affected their relationship with their partner as well as having an adverse effect on their partner's day-to-day life [4].There are a number of effective options available for the alleviation of NVP, varying from non-pharmacological strategies such as diet and lifestyle changes to pharmacological treatments such as Diclectin? (doxylamine
Solar System constraints to general f(R) gravity
Takeshi Chiba,Tristan L. Smith,Adrienne L. Erickcek
Physics , 2006, DOI: 10.1103/PhysRevD.75.124014
Abstract: It has been proposed that cosmic acceleration or inflation can be driven by replacing the Einstein-Hilbert action of general relativity with a function f(R) of the Ricci scalar R. Such f(R) gravity theories have been shown to be equivalent to scalar-tensor theories of gravity that are incompatible with Solar System tests of general relativity, as long as the scalar field propagates over Solar System scales. Specifically, the PPN parameter in the equivalent scalar-tensor theory is gamma=1/2, which is far outside the range allowed by observations. In response to a flurry of papers that questioned the equivalence of f(R) theory to scalar-tensor theories, it was recently shown explicitly, without resorting to the scalar-tensor equivalence, that the vacuum field equations for 1/R gravity around a spherically symmetric mass also yield gamma= 1/2. Here we generalize this analysis to f(R) gravity and enumerate the conditions that, when satisfied by the function f(R), lead to the prediction that gamma=1/2.
Solar System tests DO rule out 1/R gravity
Adrienne L. Erickcek,Tristan L. Smith,Marc Kamionkowski
Physics , 2006, DOI: 10.1103/PhysRevD.74.121501
Abstract: Shortly after the addition of a 1/R term to the Einstein-Hilbert action was proposed as a solution to the cosmic-acceleration puzzle, Chiba showed that such a theory violates Solar System tests of gravity. A flurry of recent papers have called Chiba's result into question. They argue that the spherically-symmetric vacuum spacetime in this theory is the Schwarzschild-de Sitter solution, making this theory consistent with Solar System tests. We point out that although the Schwarzschild-de Sitter solution exists in this theory, it is not the unique spherically-symmetric vacuum solution, and it is not the solution that describes the spacetime in the Solar System. The solution that correctly matches onto the stellar-interior solution differs from Schwarzschild-de Sitter in a way consistent with Chiba's claims. Thus, 1/R gravity is ruled out by Solar System tests.
Pharmacy-based needle exchange in New Zealand: a review of services
Janie Sheridan, Charles Henderson, Nicola Greenhill, Andrew Smith
Harm Reduction Journal , 2005, DOI: 10.1186/1477-7517-2-10
Abstract: The study used a cross-sectional survey of all needle exchange pharmacies. Postal questionnaires were used with postal and telephone follow-up.A response rate of 88% was obtained overall. Pharmacists had been providing the service for a mean of 6 years. Pharmacies had given out an average of 130 injecting units, in a mean of 62 transactions to a mean of 17 clients in the 4 weeks prior to completing the questionnaire. The majority had not incurred problems such as violence or intoxicated clients in the last 12 months, although almost one third had experienced shoplifting which they associated with service provision. Training and improving return rates were identified as potential areas for further development.New Zealand needle exchange pharmacies are providing services to a number of clients. The majority of service providers had been involved for a number of years, indicating the problems incurred had not caused them to withdraw their services – findings which echo those from the UK. Further training and support, including an exploration of improving return rates may be needed in the future.During the 1980s with the advent of HIV and the realisation that the virus could be spread through shared, contaminated injecting equipment, a number of countries set up needle exchange programmes. These have been defined as services provided for the exchange of sterile injecting equipment for used injecting equipment, as a potential means of reducing the transmission of infectious diseases. They may operate as 'stand alone' agencies, from mobile outlets, in accident and emergency units at hospitals, from drug treatment services and from community pharmacies.Needle exchange services began to be offered in New Zealand in May 1987 [1]. Currently, New Zealand's needle exchange activities are enabled by the New Zealand Ministry of Health (MoH) contracting drug user groups, constituted as charitable trusts, to run individual needle exchanges as separate entities (known as dedicated e
Developing essential professional skills: a framework for teaching and learning about feedback
Penny Henderson, Anne C Ferguson-Smith, Martin H Johnson
BMC Medical Education , 2005, DOI: 10.1186/1472-6920-5-11
Abstract: We suggest that a single "teaching the skill of feedback" session provides superficial and ineffective learning in a medical culture that often uses feedback skills poorly or discourages feedback. Our experience suggests that both the skill and the underlying attitude informing its application must be addressed, and is best done so longitudinally and reiteratively using different forms of feedback delivery. These feedback learning opportunities include written and oral, peer to peer and cross-hierarchy, public and private, thereby addressing different cognitive processes and attitudinal difficulties.We conclude by asking whether it is possible to build a consensus approach to a framework for teaching and learning feedback skills?Notwithstanding many recent changes to the medical curriculum, medical teaching retains a strong apprentice-based element, in which experienced senior doctors pass on their knowledge and skills to students and juniors. The requirements of the profession demand both extensive acquisition of knowledge and a high level of specialist skill development. Multiple academic and qualification hurdles have to be surmounted and there is a highly structured promotion system. This hierarchy of skills and knowledge has consequences for the profession's ethos. First, juniors inevitably know and can do less than seniors. If ineffective or inadequate negative or positive feedback is given, juniors may either develop "false confidence" or become demoralised and fearful of making mistakes. This fear can easily lead to a culture of criticism or blame and so to defensiveness, closing down the junior's openness to learning. Either outcome can be ultimately dispiriting, especially in a highly stressful profession [1,2]. Second, the hierarchical nature of the profession discourages feedback from junior to senior doctors making for a uni-directional "them and us" educational and professional experience. The consequences for the profession of this difficulty in effec
Snail transcription factor negatively regulates maspin tumor suppressor in human prostate cancer cells
Neal Corey L,Henderson Veronica,Smith Bethany N,McKeithen Danielle
BMC Cancer , 2012, DOI: 10.1186/1471-2407-12-336
Abstract: Background Maspin, a putative tumor suppressor that is down-regulated in breast and prostate cancer, has been associated with decreased cell motility. Snail transcription factor is a zinc finger protein that is increased in breast cancer and is associated with increased tumor motility and invasion by induction of epithelial-mesenchymal transition (EMT). We investigated the molecular mechanisms by which Snail increases tumor motility and invasion utilizing prostate cancer cells. Methods Expression levels were analyzed by RT-PCR and western blot analyses. Cell motility and invasion assays were performed, while Snail regulation and binding to maspin promoter was analyzed by luciferase reporter and chromatin immunoprecipitation (ChIP) assays. Results Snail protein expression was higher in different prostate cancer cells lines as compared to normal prostate epithelial cells, which correlated inversely with maspin expression. Snail overexpression in 22Rv1 prostate cancer cells inhibited maspin expression and led to increased migration and invasion. Knockdown of Snail in DU145 and C4-2 cancer cells resulted in up-regulation of maspin expression, concomitant with decreased migration. Transfection of Snail into 22Rv1 or LNCaP cells inhibited maspin promoter activity, while stable knockdown of Snail in C4-2 cells increased promoter activity. ChIP analysis showed that Snail is recruited to the maspin promoter in 22Rv1 cells. Conclusions Overall, this is the first report showing that Snail can negatively regulate maspin expression by directly repressing maspin promoter activity, leading to increased cell migration and invasion. Therefore, therapeutic targeting of Snail may be useful to re-induce expression of maspin tumor suppressor and prevent prostate cancer tumor progression.
The Role of Library and Information Science Education in the Development of Community Health Information Services for People Living with HIV/AIDS: Perspectives of Directors and Managers of Public Libraries  [PDF]
Bharat Mehra, Adrienne Dessel
World Journal of AIDS (WJA) , 2011, DOI: 10.4236/wja.2011.13012
Abstract: This article identifies the role of library and information science (LIS) education in the development of community health information services for people living with HIV/AIDS (PLWHA). Preliminary findings are presented from semi- structured qualitative interviews that were conducted with eleven directors and managers of local branches in the Knox County Public Library (KCPL) System that is located in the East Tennessee region in the United States. Select feedback reported by research participants is summarized in the article about strategies in LIS education that can help local public librarians and others in their efforts to become more responsive information providers to PLWHA. Research findings help better understand the issues and concerns regarding the development of digital and non-digital health information services for PLWHA in local public library institutions.
Determinates That Influence Food Comsumption among Older Members of a Midwest Community  [PDF]
Deanna Pucciarelli, Adrienne Thomas
Food and Nutrition Sciences (FNS) , 2011, DOI: 10.4236/fns.2011.29136
Abstract: The goal of this study was to record Muncie, Indiana residents’ change in eating habits over time. Objectives: 1) Identify key determinants that influence a change in participants’ eating habits; 2) Analyze the data for convergent themes among participants and draw patterns; and 3) Compare patterns found in this study population with existing literature and/or accepted theories within the field. Hypotheses on changes in food patterns included: 1) Socio-economic status in the middle-class population maintained daily food production to remain inside the home; 2) Women working outside the home reduced labor hours allotted to home cooking; and 3) Social norms valued home cooking resulting in home prepared meals. Methods: The study used a cross-sectional, oral-history, interview format. The study sample consisted of 25 seniors (65y - 100y old) from a convenience sample taken from one, medium-sized, mid-western town, Muncie, Indiana. The study involved use of a semi-structured, questionnaire/interview script, (approved by Ball State University’s IRB committee). Results: Economics greatly influenced, and continues to influence, food consumption patterns for depression-era born adults. Women who grew up on home-only cooked meals, but entered the workforce adjusted traditional meals in favor of convenience. Implications: Health care providers trying to change dietary habits of older residents residing in the Midwest will need to consider foods and food preparatory methods introduced in childhood; these remained key components of the diet later in life and removing them may be met with resistance.
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