Human acidic fibroblast growth factor 1 (hFGF1) is a protein intricately involved in cell growth and tissue repair. In this study, we investigate the effect(s) of understanding the role of a conserved proline (P135), located in the heparin binding pocket, on the structure, stability, heparin binding affinity, and cell proliferation activity of hFGF1. Substitution of proline-135 with a positively charged lysine (P135K) resulted in partial destabilization of the protein; however, the overall structural integrity of the protein was maintained upon substitution of proline-135 with either a negative charge (P135E) or a polar amino acid (P135Q). Interestingly, upon heparin binding, an increase in thermal stability equivalent to that of wt-hFGF1 was observed when P135 was replaced with a positive (P135K) or a negative charge (P135E), or with a polar amino acid (P135Q). Surprisingly, introduction of negative charge in the heparin-binding pocket at position 135 (P135E) increased hFGF1's affinity for heparin by 3-fold, while the P135K mutation, did not alter the heparin-binding affinity. However, the enhanced heparin-binding affinity of mutant P135E did not translate to an increase in cell proliferation activity. Interestingly, the P135K and P135E double mutations, P135K/R136E and P135/R136E, reduced the heparin binding affinity by ∼3-fold. Furthermore, the cell proliferation activity was increased when the charge reversal mutation R136E was paired with both P135E (P135E/R136E) and P135K (P135K/R136E). Overall, the results of this study suggest that while heparin is useful for stabilizing hFGF1 on the cell surface, this interaction is not mandatory for activation of the FGF receptor.
According to the 2011 report developed by the Committee on Underrepresented Groups and the Expansion of the Science and Engineering Workforce Pipeline and the Committee on Science, Engineering, and Public Policy, "America is at a crossroads" in which greater national efforts to strengthen infrastructures of science must include the knowledge and talents of minority Americans. They believe inclusion of a variety of Americans will significantly enhance the sustainability of the nation, and at present such contributions are underrepresented in fields such as science and engineering. Concurrently, there is a lack of participation of minority groups in global health which inspired a partnership between the Consortium of Universities for Global Health and the Public Health Institute to develop the Global Health Engagement Initiative. Through this agreement, the collaborative has researched and produced data detailing the involvement of minority and underserved populations in global health academic programs and activities in universities and colleges across the United States and its Territories. The Initiative also specifically reached out to Minority-Serving Institutions to better understand the opportunities available to students through existing international programs as well as obstacles faced at individual and institutional levels that need to be addressed. This presentation will discuss these findings and offer recommendations for engagement of minorities in the field in global health.
Nomifensine is an isoquinoline antidepressant that inhibits the reuptake of dopamine at central synapses. It also inhibits norepinephrine reuptake but is only a weak inhibitor of 5-hydroxytryptamine. Open and controlled trials comparing nomifensine with placebo and other standard antidepressants have shown it to be an effective antidepressant in divided doses up to 200 mg/d. The full dosage range of 50–200 mg/d is well tolerated, and doses can be selected to suit patient disease, age, and therapeutic response. Minimal anticholinergic and sedative side effects and no impairment of psychomotor performance make nomifensine a suitable drug for use in a wide variety of ambulatory outpatients, including the elderly. A relative lack of cardiotoxicity and epileptogenic activity add to this profile; the safety of the drug, when taken in overdose, has been documented. However, the place of nomifensine in the treatment of depression, relative to other antidepressants, is still unclear.
the classroom, are dissected during 15 interactive workshops by 20 senior Medicine residents divided into 4 discussion teams. Evaluations (with 100% response rates) reflect their success in this setting: 5.7 mean, 6.0 median on a scale with 6¼outstanding. Voluntary (and therefore very selected) feedback about Cases posted on the CUGH website has been very positive. Going Forward: The cases may too closely reflect the clinical reality of district hospitals in rural Africa where "gold standards" are rare and diagnoses often uncertain. (Hopefully such presumed diagnoses do not detract from the pedagogical value of the discussions.) Funding: None.
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