Recent Activities in the Center for Membrane Biosciences

poster abstractThe Center for Membrane Biosciences (CMB) is active in facilitating collaborative research among center members and other IUPUI community members. A number of seed grants have been made and the results from two will be presented. Recent major funding from the NSF supports a CMB-centered program that promotes intensive undergraduate research opportunities. Project 1: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the slow growth of fluid-filled cysts in the kidney tubules and liver bile ducts. We identified LPA (lysophosphatic acid) as a component of cyst fluid that stimulates secretory Cl- and compensatory water flux into cysts through binding of receptors on the basolateral membrane of renal cells. LPA concentrations measured in ADPKD cyst fluid and in normal serum are sufficient to maximally stimulate ion transport. Thus, cyst fluid seepage and/or leakage of vascular LPA into the interstitial space are capable of stimulating secretion from epithelial cells resulting in cyst enlargement. Project 2: Upon the recent acquisition of Center-supported high-resolution mass spectrometers at IUPUI, methods for the analysis of lipid and protein samples to support nascent research endeavors within the CMB are being developed. Identification and quantification of sphingolipids in biological samples as well as other lipidomic experiments will be presented. Project 3: The IUPUI URM Immersion in Interdisciplinary Research in Biological Signaling program targets underrepresented minorities in the biological sciences, and through early and sustained undergraduate research experiences that are intensely mentored at multiple levels, aims to increase the number of underrepresented minorities achieving graduate degrees in the Biological Sciences. The first cohort will begin research in the program during the summer of 2011 and are currently in the selection process

Determining value in health technology assessment: Stay the course or tack away?

The economic evaluation of new health technologies to assess whether the value of the expected health benefits warrants the proposed additional costs has become an essential step in making novel interventions available to patients. This assessment of value is problematic because there exists no natural means to measure it. One approach is to assume that society wishes to maximize aggregate health, measured in terms of quality-adjusted life-years (QALYs). Commonly, a single 'cost-effectiveness' threshold is used to gauge whether the intervention is sufficiently efficient in doing so. This approach has come under fire for failing to account for societal values that favor treating more severe illness and ensuring equal access to resources, regardless of pre-existing conditions or capacity to benefit. Alternatives involving expansion of the measure of benefit or adjusting the threshold have been proposed and some have advocated tacking away from the cost per QALY entirely to implement therapeutic area-specific efficiency frontiers, multicriteria decision analysis or other approaches that keep the dimensions of benefit distinct and value them separately. In this paper, each of these alternative courses is considered, based on the experiences of the authors, with a view to clarifying their implications

LIPIDOMIC PROFILING OF DICTYOSTELIUM DISCOIDEUM

Indiana University-Purdue University Indianapolis (IUPUI)The lipid profile of Dictyostelium discoideum, a cellular slime mold found evolutionarily between plants and animals, has never been clearly defined. To address this, the fatty acid content of vegetative cells was analyzed by gas chromatography-mass spectrometry of fatty acid methyl esters and their identities verified with synthesized authentic standards. The synthetic scheme developed to produce the unusual fatty acids found in D. discoideum was engineered to afford the labeling of compounds (2H) for use in feeding studies to elucidate the fatty acid elongation and desaturation pathways present in D. discoideum. After establishing the fatty acid profile and acyl metabolic pathway, an initial understanding the complex lipids present in D. discoideum, chiefly sphingolipids, was sought. Triple quadrupole and quadrupole time-of flight mass spectrometers equipped with electrospray ionization sources were used to identify these complex lipids

Lipidomic profiling of Dictyostelium discoideum

The lipid profile of Dictyostelium discoideum, a cellular slime mold found evolutionarily between plants and animals, has never been clearly defined. To address this, the fatty acid content of vegetative cells was analyzed by gas chromatography-mass spectrometry of fatty acid methyl esters and their identities verified with synthesized authentic standards. The synthetic scheme developed to produce the unusual fatty acids found in D. discoideum was engineered to afford the labeling of compounds (2H) for use in feeding studies to elucidate the fatty acid elongation and desaturation pathways present in D. discoideum. After establishing the fatty acid profile and acyl metabolic pathway, an initial understanding the complex lipids present in D. discoideum, chiefly sphingolipids, was sought. Triple quadrupole and quadrupole time-of flight mass spectrometers equipped with electrospray ionization sources were used to identify these complex lipids

Positioning Patronage: Lanyer's Salve Deus Rex Judæorum and the Countess of Cumberland in Time and Place

This article places the composition and publication of Aemilia Lanyer's Salve Deus Rex Judæorum within the context of particular periods in the life of Margaret Russell, Countess of Cumberland and her daughter, Anne Clifford, Countess of Dorset. Lanyer's use of mirroring, shared discourse, possible worlds and reconstruction of memory all relate to these periods and were designed to engage the interest of Russell and Clifford. Through the identification of the period of the women's stay in Cookham in 1604, Lanyer's poetic strategies – directly appealing to Russell – can be identified. Lanyer's decision to publish her verse collection in 1610 was also influenced by events in the lives of Russell and Clifford, thus providing insight into Lanyer's canny understanding of patronage in the period