754 research outputs found

    The Role Of The Glucocorticoids And Insulin In The Regulation Of Hepatic Glucose-6-Phosphate Dehydrogenase

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    The objective of my research project was to examine how insulin and the glucocorticoids, alone, and in combination, regulate hepatic glucose-6-phosphate dehydrogenase (G6PD) at the level of functional mRNA coding for G6PD. The model system I utilized for these studies was primary cultures of adult rat liver parenchymal cells. These cells were maintained in a serum-free and chemically defined medium so that direct effects of added hormones on the hepatocytes could be ascertained. Dexamethasone (Dex), a synthetic glucocorticoid, when added alone did not have an effect on G6PD activity. Insulin caused about a 1.6-fold increase in enzyme activity, and when Dex and insulin were present together, Dex acted in a permissive manner to amplify the insulin stimulation of G6PD (2.5-fold increase). These effects on enzyme activity were paralleled by increases in the relative rate of G6PD synthesis. Upon measurement of the levels of functional mRNA coding for G6PD it was observed that Dex by itself stimulated G6PD mRNA levels 4-fold while insulin treatment resulted in a 2-fold increase. When Dex and insulin were added together G6PD mRNA levels were increased in an additive fashion (an approximate 7-fold stimulation). The results of my studies suggest that glucocorticoid exerts its regulation on G6PD at the pretranslational level by modulating levels of mRNA coding for G6PD, however, this mRNA is not expressed unless insulin has also been added. Thus insulin would appear to regulate G6PD at the pretranslational level (as evidenced by insulin treatment alone) and possibly at the translational or posttranscriptional level (as evidenced by combined Dex and insulin treatment). More definitive conclusions as to the exact nature of the pretranslational regulation being exerted by Dex and insulin, i.e., whether this represents authentic regulation of gene transcription as opposed to regulation of posttranscriptional events such as mRNA processing, transport of mRNA to the cytoplasm, or stabilization of cytoplasmic mRNA must await the availability of a cDNA probe specific for rat liver glucose-6-phosphate dehydrogenase

    Mass Spectrometry Imaging of Neurotransmitters

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    Mass spectrometry imaging (MSI) is a powerful analytical method for the simultaneous analysis of hundreds of compounds within a biological sample. Despite the broad applicability of this technique, there is a critical need for advancements in methods for small molecule detection. Some molecular classes of small molecules are more difficult than others to ionize, e.g., neurotransmitters (NTs). The chemical structure of NTs (i.e., primary, secondary, and tertiary amines) affects ionization and has been a noted difficulty in the literature. In order to achieve detection of NTs using MSI, strategies must focus on either changing the chemistry of target molecules to aid in detection or focus on new methods of ionization. Additionally, even with new strategies, the issues of delocalization, chemical background noise, and ability to achieve high throughput (HTP) must be considered. This chapter will explore previous and up-and-coming techniques for maximizing the detection of NTs

    sylvae parvae: poems

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    The following is a collection of original poetry, supplemented by a critical introduction tracing biographical, literary, and theoretical influences. The critical introduction takes the form of a series of loosely connected notes. The poems are divided into two major sections. I begin by discussing the difficulties involved in writing an overarching introduction to a collection which was never intended to be a cohesive whole, that is to say, a group of individual poems rather than a themed collection or sequence. I examine some of the influences on my work, including other poets and authors. These poets do not fall into strictly defined schools or chronological periods. Rather, I find that certain poets throughout history pay attention in greater or lesser detail to the spaces around words (potential meanings) and the system that is constructed in a given poem. I align myself, therefore, not with particular schools or eras, but with writing styles. I also discuss some of the theories that come into play in my work. Most often these resemble postmodernism, yet I tend to draw on metaphors from science or philosophy rather than literary theorists themselves, who are often needlessly obtuse. Lastly, I look at autobiographical influences that have shaped my writing. I complete my introduction with a detailed discussion of two poems and how these various elements are visible therein, and a few comments on the title of the thesis. The first section of poetry is titled "Lyrics & Observations." As can be gleaned from this title, the poetry is primarily lyric, though alternating between formal and informal in structure. Additionally, most of the lyric poems I write tend to make observations on life, leaving any moral unspoken or open-ended. The second section of poetry, on the other hand, is titled "Narratives & Lessons" and tends towards poetry with an overt message. These poems represent a selected output of the last year. Some of the poems may have begun their lives before I began my studies at Texas A&M University, but almost all have been revised since that point, reflecting my continuing growth and change as a writer

    Size-selected 2, 5, and 10 nm gold nanoparticles for laser desorption/ionization mass spectrometry

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    The analytical utility of gold nanoparticles (AuNPs) for laser desorption/ionization mass spectrometry (LDI-MS) is examined here. An evaluation of the parameters that affect desorption/ionization show that careful treatments of AuNPs is needed, as subtle changes in the solution environment can result in subsequent changes in the mass spectra. A thorough evaluation of the parameters that affect desorption/ionization of peptides is presented here, and these parameters include: (i) AuNP-to-analyte ratio, (ii) AuNP size, (iii) solvent, (iv) AuNP surface composition, (v) pH and buffer effects, (vi) amino acid sequence, and (vii) additives such as fructose or glycerol. Specifically, controlling the AuNP-to-analyte ratio, pH, peptide composition, and AuNP size are important parameters for ionization. Additionally, effects of passivating the AuNP surface with halides or oxyanions was investigated. The presence of NaF, NaCl, NaBr, and NH4X (X = F, Cl, Br, I) were shown to not significantly affect analyte ion abundances, whereas addition of NaI strongly suppressed analyte ion yields. Further physical characterization of the NPs showed that etching had occurred, which suggests that the surface chemistry of the NPs is important for desorption/ionization. Throughout these investigations, questions remain as to what the internal energies of peptides are after the desorption/ionization event, and how energy is deposited. Peptide ion fragmentation is examined under different solution conditions to evaluate the relative internal energies of peptides, and the fragmentation pattern examined for insight into fragmentation mechanisms. The data suggest that radical species are important for fragmentation of peptides when using AuNPs. However, it is likely that multiple processes are actually directing the fragmentation. Finally, based on the data presented in this dissertation, a thermal desorption mechanism of pre-formed ions is proposed. This fundamental research is intended to lay foundations for optimizing the use of nanoparticles in routine LDI-MS analysis as well as giving insight into nanoparticle ionization mechanisms. Since very little work has been done in this area, this dissertation investigates, in detail, many of the subtle characteristics that affect desorption/ionization of biomolecules when using NPs

    The RNA-binding protein, ZFP36L2, influences ovulation and oocyte maturation

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    ZFP36L2 protein destabilizes AU-rich element-containing transcripts and has been implicated in female fertility. In the C57BL/6NTac mouse, a mutation in Zfp36l2 that results in the decreased expression of a form of ZFP36L2 in which the 29 N-terminal amino acid residues have been deleted, ΔN-ZFP36L2, leads to fertilized eggs that arrest at the two-cell stage. Interestingly, homozygous ΔN-Zfp36l2 females in the C57BL/6NTac strain release 40% fewer eggs than the WT littermates (Ramos et al., 2004), suggesting an additional defect in ovulation and/or oocyte maturation. Curiously, the same ΔN-Zfp36l2 mutation into the SV129 strain resulted in anovulation, prompting us to investigate a potential problem in ovulation and oocyte maturation. Remarkably, only 20% of ΔN-Zfp36l2 oocytes in the 129S6/SvEvTac strain matured ex vivo, suggesting a defect on the oocyte meiotic maturation process. Treatment of ΔN-Zfp36l2 oocytes with a PKA inhibitor partially rescued the meiotic arrested oocytes. Furthermore, cAMP levels were increased in ΔN-Zfp36l2 oocytes, linking the cAMP/PKA pathway and ΔN-Zfp36l2 with meiotic arrest. Since ovulation and oocyte maturation are both triggered by LHR signaling, the downstream pathway was investigated. Adenylyl cyclase activity was increased in ΔN-Zfp36l2 ovaries only upon LH stimulation. Moreover, we discovered that ZFP36L2 interacts with the 3′UTR of LHR mRNA and that decreased expression levels of Zfp36l2 correlates with higher levels of LHR mRNA in synchronized ovaries. Furthermore, overexpression of ZFP36L2 decreases the endogenous expression of LHR mRNA in a cell line. Therefore, we propose that lack of the physiological down regulation of LHR mRNA levels by ZFP36L2 in the ovaries is associated with anovulation and oocyte meiotic arrest.Fil: Ball, Christopher B.. University of North Carolina; Estados UnidosFil: Rodriguez, Karina F.. National Institutes of Health; Estados UnidosFil: Stumpo, Deborah J.. National Institutes of Health; Estados UnidosFil: Ribeiro Neto, Fernando. National Institutes of Health; Estados UnidosFil: Korach, Kenneth S.. National Institutes of Health; Estados UnidosFil: Blackshear, Perry J.. University of Duke; Estados Unidos. National Institutes of Health; Estados UnidosFil: Birnbaumer, Lutz. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ramos, Silvia B. V.. University of North Carolina; Estados Unido

    Reconciling Parker Solar Probe observations and magnetohydrodynamic theory

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    The Parker Solar Probe mission provides a unique opportunity to characterize several features of the solar wind at different heliocentric distances. Recent findings have shown a transition in the inertial range spectral and scaling properties around 0.4-0.5 au when moving away from the Sun. Here we provide, for the first time, how to reconcile these observational results on the radial evolution of the magnetic and velocity field fluctuations with two scenarios drawn from the magnetohydrodynamic theory. The observed breakdown is the result of the radial evolution of magnetic field fluctuations and plasma thermal expansion affecting the distribution between magnetic and velocity fluctuations. The two scenarios point towards an evolving nature of the coupling between fields that can be also reconciled with Kraichnan and Kolmogorov pictures of turbulence. Our findings have important implications for turbulence studies and modeling approaches.Comment: 9 pages, 4 figure

    ZFP36L1 (zinc finger protein 36, C3H type-like 1)

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    Review on ZFP36L1 (zinc finger protein 36, C3H type-like 1), with data on DNA, on the protein encoded, and where the gene is implicated

    Regímenes competitivos sectoriales, productividad y competitividad internacional

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    Incluye BibliografíaResumen A partir de estadísticas de producción y empleo, por una parte, y de competitividad revelada" internacional, por otra, el estudio examina el impacto que sobre distintos países de América Latina y el Caribe han tenido las reformas pro-competitivas de años recientes. Se muestra cómo se han ido perfilando en la región dos grandes "modelos dominantes": el de las industrias procesadoras de recursos naturales, en los países del Cono Sur de la región, y el de la "maquila" -electrónica y del vestuario- en México y varios países más pequeños de América Central. El trabajo muestra, además, cómo dicho proceso de cambio en el patrón de especialización productiva y competitividad internacional ha estado asociado a fenómenos de entrada y salida de firmas de y a los mercados, de absorción y expulsión ocupacional, de cambios en las "fuentes" de progreso tecnológico y, finalmente, de sustentabilidad de las cuentas externas de cada economía. El trabajo concluye con una breve discusión sobre políticas posibles de desarrollo productivo y competencia destinadas a mejorar la productividad y competitividad internacional de las economías de la región.
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