Dengue is a pantropical mosquito-borne virus infecting SO to 100 million people a year. A group o... more Dengue is a pantropical mosquito-borne virus infecting SO to 100 million people a year. A group of four closely related serotypes, DENV -1 4, cause a wide spectrum of disease, from relatively mild dengue fever (DF) to the more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). All four serotypes have been expanding geographically, and now circulate hyperendemically in most tropical regions, such as Puerto Rico and the Caribbean. This study addresses the role ofvirus evolution in changing transmission dynamics in the Caribbean, expanding on initial studies on DENV2 and -4 to include DENY -1 and -3 over the same period using the envelope gene.
Learning and Reconciliation Through Indigenous Education in Oceania, 2022
Disenfranchisement of indigenous Pacific voices from STEM limits self-determination and the devel... more Disenfranchisement of indigenous Pacific voices from STEM limits self-determination and the development of Pacific-led solutions to regional challenges. To counteract this trend, Chaminade University's Inclusive Excellence program delivers culturally-sustaining STEM education focused on sense of belonging and family/community engagement. It seeks to authentically enculturate curriculum, pedagogy, and practice to privilege and separate Western and indigenous epistemologies and to provide deeply immersive non-academic support. This chapter discusses the imperatives for sustained, system-wide commitment to culture-based STEM education, theoretical and cultural frameworks guiding this paradigm, examples of IE program processes and practices, and a review of outcomes. Finally, next level challenges are considered: student experiences in structurally racist systems beyond the Pacific support bubble, tensions between providing opportunity and perpetuation of regional talent drains, and...
Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic) stimuli underlie the ... more Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic) stimuli underlie the pathology of physical urticarias. In vitro experiments suggest that mast cells respond directly to these stimuli, implying that a signaling mechanism couples functional responses to physical inputs in mast cells. We asked whether transient receptor potential (vanilloid) (TRPV) cation channels were present and functionally coupled to signaling pathways in mast cells, since expression of this channel subfamily confers sensitivity to thermal, osmotic, and pressure inputs. Transcripts for a range of TRPVs were detected in mast cells, and we report the expression, surface localization, and oligomerization of TRPV2 protein subunits in these cells. We describe the functional coupling of TRPV2 protein to calcium fluxes and proinflammatory degranulation events in mast cells. In addition, we describe a novel protein kinase A (PKA)–dependent signaling module, containing PKA and a putative A kinase ...
Secretory granules (SG) and lipid bodies (LB) are the primary organelles that mediate functional ... more Secretory granules (SG) and lipid bodies (LB) are the primary organelles that mediate functional responses in mast cells. SG contains histamine and matrix-active proteases, while LB are reservoirs of arachidonic acid and its metabolites, precursors for rapid synthesis of eicosanoids such as LTC. Both of these compartments can be dynamically or ontologically regulated, with metabolic and immunological stimuli altering lipid body content and granule numbers responding to contextual signals from tissue. We previously described that chronic or hyperinsulinemia expands the LB compartment with a concomitant loss of SG capacity, suggesting that this ratio is dynamically regulated. The objective of the current study is to determine if chronic insulin exposure initiates a transcriptional program that biases model mast cells towards a lipogenic state with accompanying loss of secretory granule biogenesis. We used a basophilic leukemic cell line with mucosal mast cell-like features as a model ...
Entomological protocols for aging blowfly (Diptera: Calliphoridae) larvae to estimate the time of... more Entomological protocols for aging blowfly (Diptera: Calliphoridae) larvae to estimate the time of colonization (TOC) are commonly used to assist in death investigations. While the methodologies for analyzing fly larvae differ, most rely on light microscopy, genetic analysis, or, more rarely, electron microscopy. This pilot study sought to improve resolution of larval stage in the forensically important blowfly Chrysomya rufifacies using high-content fluorescence microscopy and biochemical measures of developmental marker proteins. We established fixation and mounting protocols, defined a set of measurable morphometric criteria and captured developmental transitions of 2nd instar to 3rd instar using both fluorescence microscopy and anti-ecdysone receptor Western blot analysis. The data show that these instars can be distinguished on the basis of robust, nonbleaching, autofluorescence of larval posterior spiracles. High-content imaging techniques using confocal microscopy, combined wi...
Zika virus (ZIKV) is an emerging mosquito-borne pathogen. ZIKV infection is linked to the develop... more Zika virus (ZIKV) is an emerging mosquito-borne pathogen. ZIKV infection is linked to the development of severe fetal abnormalities that include spontaneous abortion, stillbirth, hydranencephaly, and microcephaly. ZIKV outbreaks have been recorded in the United States. We recently demonstrated the first congenital ZIKV infection in the United States. In this study, we investigated archived blood samples from six mothers who gave birth to babies with microcephaly and 12 mothers who gave birth to healthy babies in Hawaii between 2009 and 2012. We tested maternal blood for the presence of ZIKV IgM and IgG antibodies using commercially available human ZIKV IgM and IgG ELISA kits. Blood from one mother who delivered babies with microcephaly tested positive for ZIKV IgM antibody (16.6%) and blood from three mothers tested positive for ZIKV IgG antibody (50%). ZIKV showed a trend toward significance with microcephaly. ZIKV IgG antibody positive mothers were more likely to deliver babies wi...
Transcriptome and genome data from twenty stony coral species and a selection of reference bilate... more Transcriptome and genome data from twenty stony coral species and a selection of reference bilaterians were studied to elucidate coral evolutionary history. We identified genes that encode the proteins responsible for the precipitation and aggregation of the aragonite skeleton on which the organisms live, and revealed a network of environmental sensors that coordinate responses of the host animals to temperature, light, and pH. Furthermore, we describe a variety of stress-related pathways, including apoptotic pathways that allow the host animals to detoxify reactive oxygen and nitrogen species that are generated by their intracellular photosynthetic symbionts, and determine the fate of corals under environmental stress. Some of these genes arose through horizontal gene transfer and comprise at least 0.2% of the animal gene inventory. Our analysis elucidates the evolutionary strategies that have allowed symbiotic corals to adapt and thrive for hundreds of millions of years.
Methods are provided of treating cardiac hypertrophy and heart failure in a mammalian subject com... more Methods are provided of treating cardiac hypertrophy and heart failure in a mammalian subject comprising administering to the subject an anti-hypertrophic effective amount of an ion channel TRPV1 inhibitor. The methods include treatment of a symptom of cardiac hypertrophy in the subject comprises cardiac remodeling, cardiac fibrosis, apoptosis, hypertension, or heart failure
Dengue is a pantropical mosquito-borne virus infecting SO to 100 million people a year. A group o... more Dengue is a pantropical mosquito-borne virus infecting SO to 100 million people a year. A group of four closely related serotypes, DENV -1 4, cause a wide spectrum of disease, from relatively mild dengue fever (DF) to the more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). All four serotypes have been expanding geographically, and now circulate hyperendemically in most tropical regions, such as Puerto Rico and the Caribbean. This study addresses the role ofvirus evolution in changing transmission dynamics in the Caribbean, expanding on initial studies on DENV2 and -4 to include DENY -1 and -3 over the same period using the envelope gene.
Learning and Reconciliation Through Indigenous Education in Oceania, 2022
Disenfranchisement of indigenous Pacific voices from STEM limits self-determination and the devel... more Disenfranchisement of indigenous Pacific voices from STEM limits self-determination and the development of Pacific-led solutions to regional challenges. To counteract this trend, Chaminade University's Inclusive Excellence program delivers culturally-sustaining STEM education focused on sense of belonging and family/community engagement. It seeks to authentically enculturate curriculum, pedagogy, and practice to privilege and separate Western and indigenous epistemologies and to provide deeply immersive non-academic support. This chapter discusses the imperatives for sustained, system-wide commitment to culture-based STEM education, theoretical and cultural frameworks guiding this paradigm, examples of IE program processes and practices, and a review of outcomes. Finally, next level challenges are considered: student experiences in structurally racist systems beyond the Pacific support bubble, tensions between providing opportunity and perpetuation of regional talent drains, and...
Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic) stimuli underlie the ... more Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic) stimuli underlie the pathology of physical urticarias. In vitro experiments suggest that mast cells respond directly to these stimuli, implying that a signaling mechanism couples functional responses to physical inputs in mast cells. We asked whether transient receptor potential (vanilloid) (TRPV) cation channels were present and functionally coupled to signaling pathways in mast cells, since expression of this channel subfamily confers sensitivity to thermal, osmotic, and pressure inputs. Transcripts for a range of TRPVs were detected in mast cells, and we report the expression, surface localization, and oligomerization of TRPV2 protein subunits in these cells. We describe the functional coupling of TRPV2 protein to calcium fluxes and proinflammatory degranulation events in mast cells. In addition, we describe a novel protein kinase A (PKA)–dependent signaling module, containing PKA and a putative A kinase ...
Secretory granules (SG) and lipid bodies (LB) are the primary organelles that mediate functional ... more Secretory granules (SG) and lipid bodies (LB) are the primary organelles that mediate functional responses in mast cells. SG contains histamine and matrix-active proteases, while LB are reservoirs of arachidonic acid and its metabolites, precursors for rapid synthesis of eicosanoids such as LTC. Both of these compartments can be dynamically or ontologically regulated, with metabolic and immunological stimuli altering lipid body content and granule numbers responding to contextual signals from tissue. We previously described that chronic or hyperinsulinemia expands the LB compartment with a concomitant loss of SG capacity, suggesting that this ratio is dynamically regulated. The objective of the current study is to determine if chronic insulin exposure initiates a transcriptional program that biases model mast cells towards a lipogenic state with accompanying loss of secretory granule biogenesis. We used a basophilic leukemic cell line with mucosal mast cell-like features as a model ...
Entomological protocols for aging blowfly (Diptera: Calliphoridae) larvae to estimate the time of... more Entomological protocols for aging blowfly (Diptera: Calliphoridae) larvae to estimate the time of colonization (TOC) are commonly used to assist in death investigations. While the methodologies for analyzing fly larvae differ, most rely on light microscopy, genetic analysis, or, more rarely, electron microscopy. This pilot study sought to improve resolution of larval stage in the forensically important blowfly Chrysomya rufifacies using high-content fluorescence microscopy and biochemical measures of developmental marker proteins. We established fixation and mounting protocols, defined a set of measurable morphometric criteria and captured developmental transitions of 2nd instar to 3rd instar using both fluorescence microscopy and anti-ecdysone receptor Western blot analysis. The data show that these instars can be distinguished on the basis of robust, nonbleaching, autofluorescence of larval posterior spiracles. High-content imaging techniques using confocal microscopy, combined wi...
Zika virus (ZIKV) is an emerging mosquito-borne pathogen. ZIKV infection is linked to the develop... more Zika virus (ZIKV) is an emerging mosquito-borne pathogen. ZIKV infection is linked to the development of severe fetal abnormalities that include spontaneous abortion, stillbirth, hydranencephaly, and microcephaly. ZIKV outbreaks have been recorded in the United States. We recently demonstrated the first congenital ZIKV infection in the United States. In this study, we investigated archived blood samples from six mothers who gave birth to babies with microcephaly and 12 mothers who gave birth to healthy babies in Hawaii between 2009 and 2012. We tested maternal blood for the presence of ZIKV IgM and IgG antibodies using commercially available human ZIKV IgM and IgG ELISA kits. Blood from one mother who delivered babies with microcephaly tested positive for ZIKV IgM antibody (16.6%) and blood from three mothers tested positive for ZIKV IgG antibody (50%). ZIKV showed a trend toward significance with microcephaly. ZIKV IgG antibody positive mothers were more likely to deliver babies wi...
Transcriptome and genome data from twenty stony coral species and a selection of reference bilate... more Transcriptome and genome data from twenty stony coral species and a selection of reference bilaterians were studied to elucidate coral evolutionary history. We identified genes that encode the proteins responsible for the precipitation and aggregation of the aragonite skeleton on which the organisms live, and revealed a network of environmental sensors that coordinate responses of the host animals to temperature, light, and pH. Furthermore, we describe a variety of stress-related pathways, including apoptotic pathways that allow the host animals to detoxify reactive oxygen and nitrogen species that are generated by their intracellular photosynthetic symbionts, and determine the fate of corals under environmental stress. Some of these genes arose through horizontal gene transfer and comprise at least 0.2% of the animal gene inventory. Our analysis elucidates the evolutionary strategies that have allowed symbiotic corals to adapt and thrive for hundreds of millions of years.
Methods are provided of treating cardiac hypertrophy and heart failure in a mammalian subject com... more Methods are provided of treating cardiac hypertrophy and heart failure in a mammalian subject comprising administering to the subject an anti-hypertrophic effective amount of an ion channel TRPV1 inhibitor. The methods include treatment of a symptom of cardiac hypertrophy in the subject comprises cardiac remodeling, cardiac fibrosis, apoptosis, hypertension, or heart failure
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Papers by Alexander J Stokes