Depolarization by transient receptor potential melastatin 4 in pancreatic alpha-cells regulates glucagon secretion

The Transient Receptor Potential Melastatin 4 protein (TRPM4) is a member of the TRP family of ion channels that is expressed in both electrically excitable and non-excitable cells. Functional studies revealed that TRPM4 significantly impacts Ca2+ signals in both immune and pancreatic β-cells, which is important for cellular processes such as hormone secretion. However, its role in glucagon secreting α-cells has not been reported. Type 2 Diabetes Mellitus is often associated with increased glucagon levels; yet, the exact mechanism controlling its secretion is not known. In pancreatic α-cells, an increase in intracellular Ca2+ concentration causes glucagon secretion. We hypothesize that TRPM4 is important for glucagon secretion in α-cells by controlling intracellular Ca2+ signals. In this study, we investigated TRPM4 expression in the α-cell lines INR1G9 (hamster) and αTC1-6 (mouse) and characterized the channel using the patch-clamp technique. By RT-PCR we identified TRPM4-transcripts in both cell lines examined. Furthermore, patch-clamp recordings with increasing intracellular Ca2+ concentrations resulted in a dose-dependent activation of TRPM4-like currents. The greatest depolarizing currents were obtained with 3μM Ca2+ concentration. The current-voltage relationship (I/V) resembled those previously described for TRPM4. In addition, we demonstrated the voltage dependency of the channel, where negative potentials inhibited and positive potentials increased channel activity. Finally, replacement of Na+ ions in the extracellular solution with N-methyl-D-glucamine significantly reduced the inward currents and caused a hyperpolarizing shift in the I/V, which affirms that the channel is Na+ permeable. These data demonstrate that TRPM4 is present and functional in pancreatic α-cells and suggest a potential role for the channel in glucagon secretion and glucose homeostasis. The role of TRPM4 in glucagon secretion was assessed using a stable TRPM4 knockdown αTC1-6 cell line. Calcium-imaging and glucagon secretion experiments revealed a relationship between the decreased intracellular Ca2+ concentration and glucagon secretion in TRPM4 knockdown cells compared to controls. These results indicate that depolarization by TRPM4 plays an important role in glucagon secretion and perhaps glucose homeostasis. Elucidation of the glucagon secretion pathway could lead to a treatment for hyperglucagonemia associated with Type 2 Diabetes

Enhanced performance and functionality of titanium dioxide papermaking pigments with controlled morphology and surface coating

Novel, tailored titanium dioxide pigments with controllable nanoscale morphological features were shown to significantly enhance the optical and strength properties of paper. The opacifying power of synthesized polycrystalline TiO2 particles in a cellulose matrix was found experimentally to be superior to that of a commercial rutile pigment, depending on the crystal structure of the synthesized particles. High aspect ratio polycrystalline rutile pigments composed of a linear linkage of several individual rutile crystals gave 6% more opacity than the commercial rutile pigment. Theoretical light scattering calculations using the T-Matrix Method showed the light scattering efficiency of linearly arranged polycrystalline rutile particles to depend on number and size of crystals composing the particle and confirmed the higher efficiency of the synthesized polycrystalline rutile pigments over commercial rutile. The opacifying power of hollow polycrystalline rutile particles was found experimentally to be superior to that of a commercial rutile pigment in a highly pressed bleached fiber matrix, depending on cavity size, while the opacifying power of silica-rutile titania core-shell particles was found comparable to commercial rutile at constant titania loading. The light scattering efficiency of titania core-shell particles was shown to be dependant on the light scattering efficiency of the core material. The overall particle shape and aspect ratio of titania core-shell and hollow nanoparticles were shown to be tunable by choosing an appropriate template and coating thickness in layer-by-layer or sol-gel templating synthesis. Inorganic-cellulose core-shell and hollow cellulose nanoparticles were prepared by self-encapsulation with regenerated cellulose via precipitation of cellulose in a polyacrylic acid hydrogel layer surrounding inorganic particle templates in 4-Methylmorpholine N-oxide (NMMO) monohydrate solution. This discrete encapsulation of inorganic pigments with a thin, uniform cellulose shell was found to increase the bondability improvement between the particles and a polysaccharide substrate. The crystallinity of several carbohydrate polymers was shown to significantly affect the bondability of encapsulated core-shell particles.Ph.D.Committee Chair: Yulin Deng; Committee Member: Arthur Ragauskas; Committee Member: Jeff Empie; Committee Member: Jeffery Hsieh; Committee Member: Preet Sing

The agroecologies of a southern community: The Tye River Valley of Virginia, 1730-1860

The farmers of piedmont Virginia\u27s Tye River Valley adapted agriculture to a commercial frontier during the eighteenth century. This \u27frontier agroecosystem\u27 optimized labor returns by exploiting the stored fertility of mature ecosystems at the expense of conservation, but proved vulnerable to population growth and soil exhaustion. Out-migration increased after the Revolution, and economic growth was stymied by limited capital and consumer formation. The frontier agroecosystem could not provide the reliable commercial returns needed to promote development or stable neighborhoods.;During the early 1800s, prominent planters demanded that Virginia farming be intensified---that land productivity be maximized, rather than labor productivity. This strategy, many claimed, would anchor farm families while promoting economic independence. Those among the Tye Valley\u27s ordinary farmers who practiced traditional intensification---increased land productivity through increased labor investment---found it led to declining labor productivity and lower profits, declining consumer opportunities, and diminished political influence. Practical planters turned to entrepreneurial intensification---enhancing per-acre productivity by importing improved seed, livestock, fertilizers, and machinery. This would also increase labor productivity. to attract the capital to purchase these imports, the Valley\u27s leaders had to abandon colonial for capitalist politics, and practice the natural resource conservation necessary to use farmland to insure investments. The self-sufficiency idealized by republican \u27high farmers\u27 was compromised.;Many Tye Valley farmers, however, resisted the dependence of capitalist agriculture through a republicanism that accepted lower living standards and curtailed opportunity in return for agrarian independence. Middle and lower class farmers pursued traditional intensification on their land while trying to maintain common access to \u27free\u27 resources left over from the frontier property system. They also resisted attempts by the district\u27s entrepreneurial planter-politicians to modernize Virginia\u27s political economy and force the state into a capitalist economy.;High crop prices during the 1850s, however, helped the Valley\u27s capitalist farmers reinvest profits in modernized cultivation. By 1860, they had gone far toward incorporating the landscape of the Tye River Valley into a capitalist agroecosystem. Popular resistance, however, slowed the development of capital needed for a full transformation. Valley farmers found entrepreneurial farming, elite republicanism, and traditional intensification in jeopardy in 1860

Internal Structure of Semelfactive Predicates in English

This thesis presents an analysis of the internal structure of semelfactive predicates. I propose that the lexical aspect class of semelfactives consists of three sub-categories: (i) semelfactive predicates with internal plurality, (ii) semelfactive predicates which are uni-directional and (iii) semelfactive predicates with plurality of participants. Based on these sub-categories, I further propose that the feature of instantaneity attributed to semelfactives (Smith 1997), should not be used, as semelfactives are in actuality not instantaneous events. Furthermore, I propose that an additional feature of atomicity, which distinguishes between events with plurality and those without, should be added to the binary features of lexical aspectual classes in order to mark a distinction between semelfactives and activities. In order to arrive at these proposals this thesis examines data collected from native English speakers across a range of predicates (including predicates which have been classified as semelfactives in the literature as well as predicates which have not been analyzed in the literature). A series of tests were applied to these predicates in order to determine their potential internal structure. This thesis has several implications. First, it provides a better understanding of the feature of single occurrence which is often attributed to semelfactives (Smith, 1997). Second, it provides a means of accounting for some variation within the class of semelfactives. It has implications for the relation between semelfactives and other lexical aspect classes. Finally, it provides a series of tests which can be used both on English predicates as well as cross-linguistically to examine the internal structure of semelfactives

Is it really all downhill after puberty?: The Critical Period Hypothesis in Second Language Acquisition - A review of the literature

The Critical Period Hypothesis in Second Language Acquisition posits that there is a critical period, early childhood until puberty, in which human beings must acquire a second language if they are going to achieve native-like attainment in that language. This thesis is a review of the current state of research in regards to the Critical Period Hypothesis in Second Language Acquisition. While evidence is provided to refute the Critical Period Hypothesis in the studies examined, a general age effect is found in the native-like attainment of a second language both in the acquisition of grammatical features and in the acquisition of phonological system. A look at how to relate these findings to foreign language education in the United States is begun by looking specifically at foreign language immersion programs in the United States and their effectiveness on native-like attainment and proficiency. There are currently 448 foreign language immersion programs in the U.S. with 45% of these programs being Spanish immersion and 22% being French immersion. Research shows that foreign language immersion programs are effective in helping children acquire a second language more effectively, specifically the early immersion programs, as well as acquire more metalinguistic awareness of languages than their monolingual counterparts

Effects of Video and Cognitive Imagery on Throwing Performance of Baseball Pitchers: A Single Subject Design

The purpose of this study was to examine the effects of a three week imagery and video imagery intervention program on throwing accuracy performance of individual baseball pitchers. A secondary purpose of this study was to investigate if differences in accuracy response existed in low verses high ability imagers. A sample of pitchers (n=30) were asked to take the Movement Imagery Questionnaire- Revised and participants were randomly selected from the highest and lowest twenty percent of the group. The participants were obtained from high school and college level teams within the southeastern Georgia region (n= 6). Following the first week of baseline measurements, two high ability and two low ability imagers took part in a three week video imagery and imagery intervention program. Two participants of each imagery ability, served as the control group and were asked only try their best during throwing accuracy measurements. Results showed that two participants demonstrated an increase in performance, while all participants expressed a desire to continue to use imagery for its various effects. Suggestions for future research and further insight are discussed