Actin filament content in platelets—A sensitive index of cellular reactivity

Blood platelets have the capacity to participate in a number of physiological as well as pathological processes within the circulation. In order to evaluate their cellular reactivity a number of platelet function tests have been developed. The mainin vitro function tests are assessment of aggregation and adhesion, secretion, arachidonate metabolism, coagulant activities and the characterization of surface membrane glycoproteins (Day and Rao, 1986). Here we measure alterations of the G-/F-actin equilibrium of platelets. High F-actin values of unstimulated platelets indicate a hyperreactivity of the cell as examined in platelets from diabetics. Determination of the actin filament content in platelets can be considered as a new sensitive function test.     

Aggregation of Leslie matrix models with application to ten diverse animal species

Some grouping is necessary when constructing a Leslie matrix model because it involves discretizing a continuous process of births and deaths. The level of grouping is determined by the number of age classes and frequency of sampling. It is largely unknown what is lost or gained by using fewer age classes, and I address this question using aggregation theory. I derive an aggregator for a Leslie matrix model using weighted least squares, determine what properties an aggregated matrix inherits from the original matrix, evaluate aggregation error, and measure the influence of aggregation on asymptotic and transient behaviors. To gauge transient dynamics, I employ reactivity of the standardized Leslie matrix. I apply the aggregator to 10 Leslie models developed for animal populations drawn from a diverse set of species. Several properties are inherited by the aggregated matrix: (a) it is a Leslie matrix; (b) it is irreducible whenever the original matrix is irreducible; (c) it is primitive whenever the original matrix is primitive; and (d) its stable population growth rate and stable age distribution are consistent with those of the original matrix if the least squares weights are equal to the original stable age distribution. In the application, depending on the population modeled, when the least squares weights do not follow the stable age distribution, the stable population growth rate of the aggregated matrix may or may not be approximately consistent with that of the original matrix. Transient behavior is lost with high aggregation.     

Adaptive Evolution Targets a piRNA Precursor Transcription Network

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Intrinsic reactivity of uric acid with dioxygen: Towards the elucidation of the catalytic mechanism of urate oxidase

Urate oxidase catalyzes the transformation of uric acid in 5-hydroxyisourate, an unstable compound which is latter decomposed into allantoïn. Crystallographic data have shown that urate oxidase binds a dianion urate species deprotonated in N3 and N7, while kinetics experiments have highlighted the existence of several intermediates during catalysis. We have employed a quantum mechanical approach to analyze why urate oxidase is selective for one particular dianion and to explore all possible reaction pathways for the oxidation of one uric acid species by molecular dioxygen in presence of water. Our results indicate the urate dianion deprotonated in N3 and N7 is among all urate species that can coexist in solution it is the compound which will lose the most easiestly one electron in presence of molecular dioxygen. In addition, the transformation of this dianion in 5-hydroxyisourate is thermodynamically the most favorable reaction. Finally, several reaction pathways can be drawn, each starting with the spontaneous transfer of one electron from the urate dianion to molecular dioxygen. During that period, the existence of a 5-hydroperoxyisourate intermediate, which has been proposed elsewhere, does not seem mandatory.     

Cardiovascular Response to Interpersonal Provocation and Mental Arithmetic among High and Low Hostile Young Adult Males

To examine the relation between hostility and cardiovascular reactivity to stress, 42 undergraduate men were categorized into high and low hostile groups based on responses to the Cook Medley Hostility Scale. Participants engaged in two laboratory tasks: a Cognitive Task (mental arithmetic) and a Social Task (confrontation role-play). Cardiovascular measures of heart rate and blood pressure were obtained throughout rest and task periods and participants provided ratings of state anger and forgiveness following task completion. Results revealed that low hostile participants exhibited greater systolic blood pressure (SBP) responses to both tasks than high hostile participants (p < .05), but no significant group differences were observed for heart rate or diastolic blood pressure. High hostile men reported greater state anger during resting conditions and less forgiveness following completion of tasks than low-hostile counterparts, but neither of these findings moderated the relation between hostility and SBP reactivity. Higher ratings of forgiveness were associated with lower SBP reactivity. These findings show that hostility is not always associated with exaggerated cardiovascular reactivity to stress, and the influence of various moderating factors should be considered in elucidating this relation.     

Structural insights into the half-of-sites reactivity in homodimeric and homotetrameric metalloenzymes

Half-of-sites reactivity in many homodimeric and homotetrameric metalloenzymes has been known for half a century, yet its benefit remains poorly understood. A recently reported cryo-electron microscopy structure has given some clues on the less optimized reactivity of Escherichia coli ribonucleotide reductase with an asymmetric association of α2β2 subunits during catalysis. Moreover, nonequivalence of enzyme active sites has been reported in many other enzymes, possibly as a means of regulation. They are often induced by substrate binding or caused by a critical component introduced from a neighboring subunit in response to substrate loadings, such as in prostaglandin endoperoxide H synthase, cytidine triphosphate synthase, glyoxalase, tryptophan dioxygenase, and several decarboxylases or dehydrogenases. Overall, half-of-sites reactivity is likely not an act of wasting resources but rather a method devised in nature to accommodate catalytic or regulatory needs.     

Engineered AAVs for non-invasive gene delivery to rodent and non-human primate nervous systems

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Synthesis of chiral building blocks for organic synthesis via lipase-catalyzed reaction: New method of enhancing enzymatic reaction enantioselectivity

The optically active building blocks for organic synthesis: tertiary carbinols, antitumor lignan, liquid crystals, 1,3-diene and biscyclopropyl compounds were synthesized through lipase-catalyzed reaction. This paper discusses ways in which organic chemists can expand the applicability of lipase-catalyzed reactions for use in designing a synthetic strategy. Several excellent examples are described in which lipase-catalyzed reactions were involved as the key steps. Because lipase-catalyzed reactions often offer insufficient enantioselectivity, a new method to enhance the enantioselectivity of a lipase-catalyzed reaction was demonstrated. Thiacrown ether technology was typically used to synthesize new optically active ,-difluoro-γ-lactone.     

Enhanced expansion of the thymic CD8+ cell subset as a potential mechanism for the generation of enhanced antitumor cytotoxicity by thymocytes from low-dose melphalan-treated MOPC-315 tumor bearers

Summary We have previously shown that thymocytes from low-dose melphalan (l-phenylalanine mustard)-treated MOPC-315-tumor-bearing mice (melphalan TuB) are able to generate an enhanced level of anti-MOPC-315 cytotoxicity, as compared to thymocytes from untreated MOPC-315-tumor-bearing mice or thymocytes from untreated or low-dose melphalan-treated normal mice, upon in vitro stimulation with MOPC-315 tumor cells in the presence of a low concentration of recombinant interleukin-2 (rIL-2). Here we show that the generation of enhanced anti-MOPC-315 cytotoxicity by melphalan TuB thymocytes depends on the ability of the thymocytes to proliferate. In addition, the ability of melphalan TuB thymocytes to generate an enhanced level of anti-MOPC-315 cytotoxicity correlated with their ability to proliferate more readily than thymocytes from untreated tumor-bearing mice and thymocytes from untreated or melphalan-treated normal mice in response to stimulation with MOPC-315 tumor cells plus a low concentration of rIL-2. Moreover, although fresh melphalan TuB thymocytes do not contain a higher percentage of phenotypically mature cells (i.e., CD4^–/CD8⁺ or CD4⁺/CD8^–) than do thymocytes from normal mice or untreated tumor-bearing mice, after a 5-day culture with both MOPC-315 tumor cells and a low concentration of rIL-2, cultures of thymocytes from melphalan TuB contained a much higher percentage of CD4^–/CD8⁺ (but not CD4⁺/CD8^–) cells than did cultures of thymocytes from the other two sources. Since CD4^–/CD8⁺ cells were previously shown to be responsible for the exertion of antitumor cytotoxicity by thymocytes stimulated with MOPC-315 in vitro, our results indicate that the enhanced antitumor cytotoxicity exerted by melphalan TuB thymocytes following in vitro stimulation with MOPC-315 tumor cells in the presence of a low concentration of rIL-2 is due, at least in part, to an expansion of the pool of CD4^–/CD8⁺ effector cells.Supported by research grant CA-35 761 from the National Cancer InstituteIn partial fulfillment of the requirements for the Doctor of Philosophy degreeSupported by career development award CA-01 350 from the National Cancer Institute