University of Hawaii at Manoa

About: University of Hawaii at Manoa is a education organization based out in Honolulu, Hawaii, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 13693 authors who have published 25161 publications receiving 1023924 citations.

FUdR induction of the X chromosome fragile site: evidence for the mechanism of folic acid and thymidine inhibition.

Abstract: Experiments designed to illuminate the mechanism by which folic acid and thymidine inhibit expression of the Xq28 fragile site in human lymphocytes are described. The fragile site is induced by 5-fluorodeoxyuridine (FUdR), a potent inhibitor of thymidylate synthetase, in the presence of otherwise inhibiting concentrations of folic acid but not in the presence of thymidine. These results indicate that the fragile site is expressed because of depletion of deoxythymidine monophosphate (dTMP) available for DNA synthesis.

Regional Patterns of Sea Surface Temperature Change: A Source of Uncertainty in Future Projections of Precipitation and Atmospheric Circulation*

Abstract: Precipitation change in response to global warming has profound impacts on environment for life but is highly uncertain. Effects of sea surface temperature (SST) warming on the response of rainfall and atmospheric overturning circulation are investigated using Coupled Model Intercomparison Project simulations. The SST warming is decomposed into a spatially uniform SST increase (SUSI) and deviations from it. The SST pattern effect is found to be important in explaining both the multimodel ensemble mean distribution and intermodel variability of rainfall change over tropical oceans. In the ensemble mean, the annual rainfall change follows a “warmer-get-wetter” pattern, increasing where the SST warming exceeds the tropical mean, and vice versa. Two SST patterns stand out both in the ensemble mean and intermodel variability: an equatorial peak anchoring a local precipitation increase and a meridional dipole mode with increased rainfall and weakened trade winds over the warmer hemisphere. These two mod...

Quantitative analysis of trace element abundances in glasses and minerals: a comparison of laser ablation inductively coupled plasma mass spectrometry, solution inductively coupled plasma mass spectrometry, proton microprobe and electron microprobe data

Abstract: Many geological, environmental and industrial applications can be enhanced through integrated microbeam and bulk geochemical determinations of major and trace element concentrations. Advantages ofin situ microanalysis include minimal sample preparation, low blanks, information about the spatial distribution of compositional characteristics and the ability to avoid microscopic inclusions of foreign material. In this paper we compare trace element data obtained by laser ablation ICP-MS, solution ICP-MS, electron microprobe analysis and proton microprobe analysis for a variety of silicate glasses and minerals. New determinations for 36 trace elements in BCR-2G, a microbeam glass standard, are presented. Results obtained by the various microbeam and solution methods agree well for concentrations ranging over several orders of magnitude. Replicate analyses of BCR-2G demonstrate an analytical precision of 2–8% relative (1σ) for all elements by laser ablation ICP-MS and ≤3% by solution ICP-MS, except for Li (5%). These data emphasize the utility of laser ablation ICP-MS as a quantitative microbeam technique capable of rapid, precise determinations of sub-ppm trace element abundances in a variety of targets.

Nitrated alpha-synuclein-activated microglial profiling for Parkinson's disease.

Abstract: Microglial neuroinflammatory processes play a primary role in dopaminergic neurodegeneration for Parkinson's disease (PD). This can occur, in part, by modulation of glial function following activation by soluble or insoluble modified alpha-synuclein (alpha-syn), a chief component of Lewy bodies that is released from affected dopaminergic neurons. alpha-Syn is nitrated during oxidative stress responses and in its aggregated form, induces inflammatory microglial functions. Elucidation of these microglial function changes in PD could lead to new insights into disease mechanisms. To this end, PD-associated inflammation was modeled by stimulation of microglia with aggregated and nitrated alpha-syn. These activated microglia were ameboid in morphology and elicited dopaminergic neurotoxicity. A profile of nitrated, aggregated alpha-syn-stimulated microglia was generated using combinations of genomic (microarrays) and proteomic (liquid chromatography-tandem mass spectrometry, differential gel electrophoresis, and protein array) assays. Genomic studies revealed a substantive role for nuclear factor-kappa B transcriptional activation. Qualitative changes in the microglial proteome showed robust increases in inflammatory, redox, enzyme, and cytoskeletal proteins supporting the genomic tests. Autopsy brain tissue acquired from substantia nigra and basal ganglia of PD patients demonstrated that parallel nuclear factor-kappa B-related inflammatory processes were, in part, active during human disease. Taken together, the transcriptome and proteome of nitrated alpha-syn activated microglia, shown herein, provide new potential insights into disease mechanisms.

A recombinant baculovirus 42-kilodalton C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 protects Aotus monkeys against malaria.

Abstract: The immunogenicity and protective efficacy of baculovirus recombinant polypeptide based on the Plasmodium falciparum merozoite surface protein 1 (MSP-1) has been evaluated in Aotus lemurinus griseimembra monkeys. The MSP-1-based polypeptide, BVp42, corresponds to the 42-kDa C-terminal processing fragment of the precursor molecule. Immunization of Aotus monkeys with BVp42 in complete Freund's adjuvant resulted in high antibody titers against the immunogen as well as parasite MSP-1. Fine specificity studies indicated that major epitopes recognized by these antibodies localize to conserved determinants of the 19-kDa C-terminal fragment derived from cleavage of the 42-kDa processing fragment. Effective priming of MSP-1-specific T cells was also demonstrated in lymphocyte proliferation assays. All three Aotus monkeys immunized with BVp42 in complete Freund's adjuvant showed evidence of protection of protection against blood-stage challenge with P. falciparum. Two animals were completely protected, with only one parasite being detected in thick blood films on a single days after injection. The third animal had a modified course of infection, controlling its parasite infection to levels below detection by thick blood smears for an extended period in comparison with adjuvant control animals. All vaccinated, protected Aotus monkeys produced antibodies which inhibited in vitro parasite growth, indicating that this assay may be a useful correlate of protective immunity and that immunity induced by BVp42 immunization is mediated, at least in part, by a direct effect of antibodies against the MSP-1 C-terminal region. The high level of protection obtained in these studies supports further development of BVp42 as a candidate malaria vaccine.