144 research outputs found

    Chronicles of Oklahoma

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    Article describes the establishment and history of Murray State College in the Chickasaw Nation, including its historical context, physical layout of buildings, and student population

    Cross-species chemogenomic profiling reveals evolutionarily conserved drug mode of action

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    Chemogenomic screens were performed in both budding and fission yeasts, allowing for a cross-species comparison of drug–gene interaction networks.Drug–module interactions were more conserved than individual drug–gene interactions.Combination of data from both species can improve drug–module predictions and helps identify a compound's mode of action

    A Forward Chemical Screen in Zebrafish Identifies a Retinoic Acid Derivative with Receptor Specificity

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    Background: Retinoids regulate key developmental pathways throughout life, and have potential uses for differentiation therapy. It should be possible to identify novel retinoids by coupling new chemical reactions with screens using the zebrafish embryonic model. Principal Findings: We synthesized novel retinoid analogues and derivatives by amide coupling, obtaining 80–92% yields. A small library of these compounds was screened for bioactivity in living zebrafish embryos. We found that several structurally related compounds significantly affect development. Distinct phenotypes are generated depending on time of exposure, and we characterize one compound (BT10) that produces specific cardiovascular defects when added 1 day post fertilization. When compared to retinoic acid (ATRA), BT10 shows similar but not identical changes in the expression pattern of embryonic genes that are known targets of the retinoid pathway. Reporter assays determined that BT10 interacts with all three RAR receptor sub-types, but has no activity for RXR receptors, at all concentrations tested. Conclusions: Our screen has identified a novel retinoid with specificity for retinoid receptors. This lead compound may be useful for manipulating components of retinoid signaling networks, and may be further derivatized for enhanced activity

    Effects of long-term moderate exercise and increase in number of daily steps on serum lipids in women: randomised controlled trial [ISRCTN21921919]

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    BACKGROUND: This study was designed to evaluate the effects of a 24-month period of moderate exercise on serum lipids in menopausal women. METHODS: The subjects (40–60 y) were randomly divided into an exercise group (n = 14) and a control group (n = 13). The women in the exercise group were asked to participate in a 90-minute physical education class once a week and to record their daily steps as measured by a pedometer for 24 months. RESULTS: Mean of daily steps was significantly higher in the exercise group from about 6,800 to over 8,500 steps (P < 0.01). In the control group, the number of daily steps ranged from 5,700 to 6,800 steps throughout the follow-up period. A significant interaction between the exercise group and the control group in the changes og total cholesterol (TC), high-density lipoprotein cholesterol (HDLC) and TC : HDLC ratio could be observed (P < 0.05). By multiple regression analysis, the number of daily steps was related to HDLC and TC : HDLC levels after 24 months, and the changes in TC and HDLC concentrations. CONCLUSIONS: These results suggest that daily exercise as well as increasing the number of daily steps can improve the profile of serum lipids

    Chemical genetics strategies for identification of molecular targets

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    Chemical genetics is an emerging field that can be used to study the interactions of chemical compounds, including natural products, with proteins. Usually, the identification of molecular targets is the starting point for studying a drug’s mechanism of action and this has been a crucial step in understanding many biological processes. While a great variety of target identification methods have been developed over the last several years, there are still many bioactive compounds whose target proteins have not yet been revealed because no routine protocols can be adopted. This review contains information concerning the most relevant principles of chemical genetics with special emphasis on the different genomic and proteomic approaches used in forward chemical genetics to identify the molecular targets of the bioactive compounds, the advantages and disadvantages of each and a detailed list of successful examples of molecular targets identified with these approaches

    Diagnosis and management of chronic myeloid leukemia: a survey of American and European practice patterns.

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    BACKGROUND: The success of imatinib therapy for chronic myeloid leukemia (CML) has brought new challenges; these include optimizing disease monitoring, imatinib resistance, and use of novel, more potent tyrosine kinase inhibitors. Thus, there is a need to establish new best practices for CML management in the post-imatinib era. METHODS: An internet-based questionnaire, consisting of 26 multiple choice questions, was developed to assess hematologists' and oncologists' self-reported treatment strategies for CML. RESULTS: Between November 2005 and January 2006, 956 eligible physicians responded to the survey; 727 from the US and 229 from Europe. Most US respondents (60%) practiced in the community setting, whereas European respondents were primarily academic (44%) and hospital-based (40%). Physicians' responses were generally in line with current recommendations, although differences were identified. Confusion existed among respondents over optimal timing of treatment decisions, with a notable proportion of physicians focusing on a single timepoint rather than consistent monitoring, as currently advocated. Some respondents were unaware of new molecular monitoring techniques, when to monitor for BCR-ABL mutations (and the impact on treatment decisions), and the benefit of new tyrosine kinase inhibitors. CONCLUSIONS: Responses to the survey suggest that treatment practices in some areas of CML management are not in line with current recommendations. Identified areas of need should be targeted in future educational activities for the CML community. (c) 2007 American Cancer Society
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