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Search Results: 1 - 10 of 215188 matches for " Deborah L. Johnson "
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PNRC is a unique nuclear receptor coactivator that stimulates RNA polymerase III-dependent transcription
Dujin Zhou, Shuping Zhong, Jing-Jing Ye, Keith M Quach, Deborah L Johnson, Shiuan Chen
Journal of Molecular Signaling , 2007, DOI: 10.1186/1750-2187-2-5
Abstract: RNA pol III/RPC39 fragments were repeatedly identified as PNRC-interacting partners in two independent screenings. The interaction between these RPC39 fragments and PNRC was further confirmed in the independent yeast two-hybrid assays. The association of endogenous PNRC and RPC39 in MCF7 cells was demonstrated by co-immunoprecipitation. Furthermore, ChIP analysis detected co-recruitment of PNRC and RPC39 to tRNA and U6 RNA promoters. The biological consequence of the interaction between PNRC and RPC39 was further studied. Overexpression of PNRC, either by transient or stable transfection, increased RNA pol III-dependent transcription in MCF7 cells, while a decrease in transcription in MCF7 cells treated with PNRC/siRNA was observed.Here, we demonstrate that human PNRC stimulates RNA pol III transcription through its interaction with the subunit RPC39 of RNA pol III.PNRC is a unique coactivator that has profound effects on many aspects of cellular function by directly influencing both RNA pol II- and RNA pol III-dependent transcription.Nuclear receptors are ligand-dependent transcription factors that regulate the expression of various genes by binding to the specific hormone-responsive elements located in the target gene promoters, thus playing essential roles in development, differentiation, cell proliferation, and metabolism. For the past few years, a great deal of progress has been made in understanding the mechanisms by which the nuclear receptors regulate gene transcription. The function of nuclear receptors can be regulated by a number of factors including ligand binding, DNA binding, interaction with other members in the family, interaction with basal transcription factors, and interaction with coactivators and corepressors. Most of these coactivators of nuclear receptors have molecular weights of ~160 kDa and interact with the liganded nuclear receptors using a short hydrophobic motif called NR-box or LXXLL-motif [1].Our studies to elucidate the mechanisms th
Maf1 Is a Novel Target of PTEN and PI3K Signaling That Negatively Regulates Oncogenesis and Lipid Metabolism
Beth M. Palian equal contributor,Aarti D. Rohira equal contributor,Sandra A. S. Johnson equal contributor,Lina He,Ni Zheng,Louis Dubeau,Bangyan L. Stiles,Deborah L. Johnson
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004789
Abstract: Maf1 was initially identified as a transcriptional repressor of RNA pol III-transcribed genes, yet little is known about its other potential target genes or its biological function. Here, we show that Maf1 is a key downstream target of PTEN that drives both its tumor suppressor and metabolic functions. Maf1 expression is diminished with loss of PTEN in both mouse models and human cancers. Consistent with its role as a tumor suppressor, Maf1 reduces anchorage-independent growth and tumor formation in mice. PTEN-mediated changes in Maf1 expression are mediated by PTEN acting on PI3K/AKT/FoxO1 signaling, revealing a new pathway that regulates RNA pol III-dependent genes. This regulatory event is biologically relevant as diet-induced PI3K activation reduces Maf1 expression in mouse liver. We further identify lipogenic enzymes as a new class of Maf1-regulated genes whereby Maf1 occupancy at the FASN promoter opposes SREBP1c-mediated transcription activation. Consistent with these findings, Maf1 inhibits intracellular lipid accumulation and increasing Maf1 expression in mouse liver abrogates diet-mediated induction of lipogenic enzymes and triglycerides. Together, these results establish a new biological role for Maf1 as a downstream effector of PTEN/PI3K signaling and reveal that Maf1 is a key element by which this pathway co-regulates lipid metabolism and oncogenesis.
A Heuristic Text Analytic Approach for Classifying Research Articles  [PDF]
Steven Walczak, Deborah L. Kellogg
Intelligent Information Management (IIM) , 2015, DOI: 10.4236/iim.2015.71002
Abstract: Classification of research articles is fundamental to analyze and understand research literature. Underlying concepts from both text analytics and concept mining form a foundation for the development of a quantitative heuristic methodology, the Scale of Theoretical and Applied Research (STAR), for classifying research. STAR demonstrates how concept mining may be used to classify research with respect to its theoretical and applied emphases. This research reports on evaluating the STAR heuristic classifier using the Business Analytics domain, by classifying 774 Business Analytics articles from 23 journals. The results indicate that STAR effectively evaluates overall article content of journals to be consistent with the expert opinion of journal editors with regard to the research type disposition of the respective journals.
Pretest probability assessment derived from attribute matching
Jeffrey A Kline, Charles L Johnson, Charles V Pollack, Deborah B Diercks, Judd E Hollander, Craig D Newgard, J Lee Garvey
BMC Medical Informatics and Decision Making , 2005, DOI: 10.1186/1472-6947-5-26
Abstract: Eight clinical variables (attributes) were chosen by classification and regression tree analysis of a prospectively collected reference database of 14,796 emergency department (ED) patients evaluated for possible ACS. For attribute matching, a computer program identifies patients within the database who have the exact profile defined by clinician input of the eight attributes. The novel method was compared with the LRE for ability to produce PTP estimation <2% in a validation set of 8,120 patients evaluated for possible ACS and did not have ST segment elevation on ECG. 1,061 patients were excluded prior to validation analysis because of ST-segment elevation (713), missing data (77) or being lost to follow-up (271).In the validation set, attribute matching produced 267 unique PTP estimates [median PTP value 6%, 1st–3rd quartile 1–10%] compared with the LRE, which produced 96 unique PTP estimates [median 24%, 1st–3rd quartile 10–30%]. The areas under the receiver operating characteristic curves were 0.74 (95% CI 0.65 to 0.82) for the attribute matching curve and 0.68 (95% CI 0.62 to 0.77) for LRE.The attribute matching system categorized 1,670 (24%, 95% CI = 23–25%) patients as having a PTP < 2.0%; 28 developed ACS (1.7% 95% CI = 1.1–2.4%). The LRE categorized 244 (4%, 95% CI = 3–4%) with PTP < 2.0%; four developed ACS (1.6%, 95% CI = 0.4–4.1%).Attribute matching estimated a very low PTP for ACS in a significantly larger proportion of ED patients compared with a validated LRE.Despite its importance, pretest probability assessment remains a relatively imprecise and inferential process, sometimes referred to as the "doctor's best guess" [1,2]. Previous authors have broadly defined pretest probability as the clinician's estimate of the probability of disease from the patient's words, physical findings, risk factors, and exposures, rendered prior to knowledge of objective test results [3,4]. Presently, the most widely recognized quantitative method of determining pretest
The Brine Shrimp's Butterfly Stroke
Brennan Johnson,Deborah Garrity,Lakshmi Prasad Dasi
Physics , 2011,
Abstract: We investigate the fluid dynamics of brine shrimp larvae swimming in this gallery of fluid motion video. Time resolved particle image velocimetry was performed using nano-particles as seeding material to measure the time dependent velocity and vorticity fields. The Reynolds number of the flow was roughly 8 and the Womerseley number (ratio of periodic forcing to viscous forcing) was about 5. Vorticity dynamics reveals the formation of a vortex ring structure at the tip of each arm at the beginning of the power stroke. This two vortex system evolves dramatically with time as the stroke progresses. The outer circulation is noted to weaken while the inner circulation strengthens over the power stroke. The gaining strength of the inner vortex correlates with the acceleration and forward movement of the larvae.
Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: a decade of the PREDICT-HD study
Jane S. Paulsen,Jeffrey D. Long,Hans J. Johnson,Elizabeth H. Aylward,Christopher A. Ross,Janet K. Williams,Martha A. Nance,Holly J. Westervelt,Deborah L. Harrington,H. Jeremy Bockholt,Elizabeth A. McCusker,Peter K. Panegyres
Frontiers in Aging Neuroscience , 2014, DOI: 10.3389/fnagi.2014.00078
Abstract: There is growing consensus that intervention and treatment of Huntington disease (HD) should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. Neurobiological predictors of Huntington’s disease is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest HD and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease 7–12 years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease.
The epithelium in idiopathic pulmonary fibrosis: breaking the barrier
Deborah L. Clarke
Frontiers in Pharmacology , 2014, DOI: 10.3389/fphar.2013.00173
Abstract: Idiopathic pulmonary fibrosis is a progressive disease of unknown etiology characterized by a dysregulated wound healing response that leads to fatal accumulation of fibroblasts and extracellular matrix (ECM) in the lung, which compromises tissue architecture and lung function capacity. Injury to type II alveolar epithelial cells is thought to be the key event for the initiation of the disease, and so far both genetic factors, such as mutations in telomerase and MUC5B genes as well as environmental components, like cigarette smoking, exposure to asbestos and viral infections have been implicated as potential initiating triggers. The injured epithelium then enters a state of senescence-associated secretory phenotype whereby it produces both pro-inflammatory and pro-fibrotic factors that contribute to the wound healing process in the lung. Immune cells, like macrophages and neutrophils as well as activated myofibroblasts then perpetuate this cascade of epithelial cell apoptosis and proliferation by release of pro-fibrotic transforming growth factor beta and continuous deposition of ECM stiffens the basement membrane, altogether having a deleterious impact on epithelial cell function. In this review, we describe the role of the epithelium as both a physical and immunological barrier between environment and self in the homeostatic versus diseased lung and explore the potential mechanisms of epithelial cell injury and the impact of loss of epithelial cell permeability and function on cytokine production, inflammation, and myofibroblast activation in the fibrotic lung.
Mycobacterium tuberculosis Specific CD8+ T Cells Rapidly Decline with Antituberculosis Treatment
Melissa R. Nyendak, Byung Park, Megan D. Null, Joy Baseke, Gwendolyn Swarbrick, Harriet Mayanja-Kizza, Mary Nsereko, Denise F. Johnson, Phineas Gitta, Alphonse Okwera, Stefan Goldberg, Lorna Bozeman, John L. Johnson, W. Henry Boom, Deborah A. Lewinsohn, David M. Lewinsohn, for the Tuberculosis Research Unit and the Tuberculosis Trials Consortium
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081564
Abstract: Rationale Biomarkers associated with response to therapy in tuberculosis could have broad clinical utility. We postulated that the frequency of Mycobacterium tuberculosis (Mtb) specific CD8+ T cells, by virtue of detecting intracellular infection, could be a surrogate marker of response to therapy and would decrease during effective antituberculosis treatment. Objectives: We sought to determine the relationship of Mtb specific CD4+ T cells and CD8+ T cells with duration of antituberculosis treatment. Materials and Methods We performed a prospective cohort study, enrolling between June 2008 and August 2010, of HIV-uninfected Ugandan adults (n = 50) with acid-fast bacillus smear-positive, culture confirmed pulmonary TB at the onset of antituberculosis treatment and the Mtb specific CD4+ and CD8+ T cell responses to ESAT-6 and CFP-10 were measured by IFN-γ ELISPOT at enrollment, week 8 and 24. Results There was a significant difference in the Mtb specific CD8+ T response, but not the CD4+ T cell response, over 24 weeks of antituberculosis treatment (p<0.0001), with an early difference observed at 8 weeks of therapy (p = 0.023). At 24 weeks, the estimated Mtb specific CD8+ T cell response decreased by 58%. In contrast, there was no significant difference in the Mtb specific CD4+ T cell during the treatment. The Mtb specific CD4+ T cell response, but not the CD8+ response, was negatively impacted by the body mass index. Conclusions Our data provide evidence that the Mtb specific CD8+ T cell response declines with antituberculosis treatment and could be a surrogate marker of response to therapy. Additional research is needed to determine if the Mtb specific CD8+ T cell response can detect early treatment failure, relapse, or to predict disease progression.
The Effects of Vestibular Rehabilitation after Bilateral Superior Semicircular Canal Dehiscence: A Case Report  [PDF]
Connor L. Naccarato, Kristen M. Johnson
International Journal of Clinical Medicine (IJCM) , 2017, DOI: 10.4236/ijcm.2017.86042
Abstract: Background and Purpose: Despite the strong body of evidence for vestibular rehabilitation, research is lacking for effective clinical management of patients with superior semicircular canal dehiscence (SSCD) and endolymphatic hydrops (EH). The purpose of this case report is to describe the effects of physical therapy in the treatment of a patient diagnosed with bilateral SSCD. Case Description: The patient was a 56-year-old woman with a long-standing otologic history involving bilateral SSCD and EH. The patient’s body structure and function impairments include constant headaches, dizziness with head rotation and eye movements, sensitivity to sounds and lights, and instability during gait. Her activity limitations include lower extremity dressing, driving, and playing her flute. Her participation restrictions include taking part in social gatherings, going to church, driving longer than 30 minutes, playing with her dogs, and teaching flute lessons. Interventions: Specific interventions included vestibular habituation and adaptation exercises, balance and gait training, and patient education. Physical therapy services were provided for approximately 11 weeks with a frequency of two times per week. Outcomes: After eleven weeks of physical therapy, the patient made improvements on the Lower Extremity Functional Scale (43/80 to 52/80), the Dynamic Gait Index (19/24 to 24/24), the Dizziness Handicap Inventory (86/100 to 68/100), and the Sharpened Romberg (2 seconds to >30 seconds). The patient improved in all her activity limitations and participation restrictions. She was able to play her flute for 20-minute intervals, play with her dogs, partake in social gatherings, and drive for 5 hours without symptoms. The patient had plans to pursue surgical intervention within the next year. Discussion: For a patient with a complex otologic history and a current diagnosis of bilateral SSCD, vestibular rehabilitation was an effective management option. The information from this case can be used to guide the effective treatment of similar patients diagnosed with vestibular dysfunction.
Variability of Serum Concentration of Calcium, Phosphate and Parathyroid Hormone Depending on Time of Blood Draw for Patients on Nocturnal Home Hemodialysis  [PDF]
Nasim Shahbazi, Pierre A. Brown, Ayub Akbari, Deborah L. Zimmerman
Open Journal of Nephrology (OJNeph) , 2012, DOI: 10.4236/ojneph.2012.24011
Abstract: Background: Guidelines for patients treated with conventional hemodialysis patients have been written for target serum levels for calcium (Ca), phosphate (PO4) and intact parathyroid hormone (iPTH). No guidelines exist for nocturnal home hemodialysis (NHHD) patients for target values or timing of the blood sample draw. We undertook a prospective cohort study to examine the variability in pre, post and clinic (post-post) serum values for Ca, PO4, and iPTH in NHHD patients to determine if timing of blood draw could affect clinical decisions. Methods: Twenty prevalent NHHD patients collected blood pre and post their usual NHHD session with an additional blood sample drawn in clinic (post-post). Median and interquartile range of pre, post and clinic (post-post) values of iPTH, PO4 and Ca were calculated and compared with Freidman/Wilcoxon test. Serum concentrations were also categorized according to Canadian Society of Nephrology (CSN) guidelines target values for pre and clinic (post-post) samples. The proportion of patients that would be categorized differently by clinic (post-post) samples was determined. Results: There was a significant difference between pre-serum values compared to post and clinic (post-post) values. Overall, iPTH, PO4 and Ca values would be misclassified in 25%, 70% and 50% respectively if blood was drawn at the clinic visit (post-post) compared to pre-HD as per CSN guidelines. Conclusions: Although no specific guideline has been written for NHHD patients, to ensure consistency of management compared to in-centre HD patients, lab values should be drawn pre-HD until clinical evidence suggests that the recommendations should be different for NHHD.
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