Effects of in vitro Brevetoxin Exposure on Apoptosis and Cellular Metabolism in a Leukemic T Cell Line (Jurkat)

Harmful algal blooms (HABs) of the toxic dinoflagellate, Karenia brevis, produce red tide toxins, or brevetoxins. Significant health effects associated with red tide toxin exposure have been reported in sea life and in humans, with brevetoxins documented within immune cells from many species. The objective of this research was to investigate potential immunotoxic effects of brevetoxins using a leukemic T cell line (Jurkat) as an in vitro model system. Viability, cell proliferation, and apoptosis assays were conducted using brevetoxin congeners PbTx-2, PbTx-3, and PbTx-6. The effects of in vitro brevetoxin exposure on cell viability and cellular metabolism or proliferation were determined using trypan blue and MTT (1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan), respectively. Using MTT, cellular metabolic activity was decreased in Jurkat cells exposed to 5 – 10 μg/ml PbTx-2 or PbTx-6. After 3 h, no significant effects on cell viability were observed with any toxin congener in concentrations up to 10 μg/ml. Viability decreased dramatically after 24 h in cells treated with PbTx-2 or -6. Apoptosis, as measured by caspase-3 activity, was significantly increased in cells exposed to PbTx-2 or PbTx-6. In summary, brevetoxin congeners varied in effects on Jurkat cells, with PbTx-2 and PbTx-6 eliciting greater cellular effects compared to PbTx-3

Acacia trees on the cultural landscapes of the Red Sea Hills

This paper examines interactions between five pastoral nomadic culture groups of the Egyptian and Sudanese Red Sea Hills and the acacia trees Acacia tortilis (Forssk.) Hayne subsp. tortilis and subsp. raddiana growing in their arid environments. A. tortilis is described as a keystone species both ecologically and culturally: the trees play such critical roles in ecosystems and social groups that their removal would greatly impact both systems. Interviews in the field with the Semitic, Arabic-speaking Ma‘aza and Ababda, and the Cushitic, Beja, Bidhaawyeet-speaking Bishaari, Amar Ar and Hadandawa nomads probed the cultural and ecological contexts of acacias in pastoral nomadism, revealing deep insight into traditional ecological knowledge and traditional perceptions and uses of the trees. The paper describes how this knowledge guides pastoral decision-making, with acacias as a particularly critical component of the pastoral livelihood in both normal and stressful circumstances. A. tortilis is the most important reliable vegetation resource for nomads while also providing fuel and other useful products, ecosystem services for people and animals, and increased biodiversity by providing diverse microhabitats and resources for other species. We describe aspects of kinship, territorial organization, spiritual beliefs and tribal law underlying the significance of trees on the cultural landscape. We discuss environmental and economic challenges to human/tree relationships and to pastoral livelihoods. We challenge views of nomads as agents of ecological destruction, and propose maintenance and restoration of traditional pastoralism as viable alternatives in dryland development.publishedVersio

Space Station Engineering Design Issues

Space Station Freedom topics addressed include: general design issues; issues related to utilization and operations; issues related to systems requirements and design; and management issues relevant to design

Phylogeny and palaeoecology of Polyommatus blue butterflies show Beringia was a climate-regulated gateway to the New World

Transcontinental dispersals by organisms usually represent improbable events that constitute a major challenge for biogeographers. By integrating molecular phylogeny, historical biogeography and palaeoecology, we test a bold hypothesis proposed by Vladimir Nabokov regarding the origin of Neotropical Polyommatus blue butterflies, and show that Beringia has served as a biological corridor for the dispersal of these insects from Asia into the New World. We present a novel method to estimate ancestral temperature tolerances using distribution range limits of extant organisms, and find that climatic conditions in Beringia acted as a decisive filter in determining which taxa crossed into the New World during five separate invasions over the past 11 Myr. Our results reveal a marked effect of the Miocene–Pleistocene global cooling, and demonstrate that palaeoclimatic conditions left a strong signal on the ecology of present-day taxa in the New World. The phylogenetic conservatism in thermal tolerances that we have identified may permit the reconstruction of the palaeoecology of ancestral organisms, especially mobile taxa that can easily escape from hostile environments rather than adapt to them

Characterization of Marine Aerosol for Assessment of Human Exposure to Brevetoxins

Red tides in the Gulf of Mexico are commonly formed by the fish-killing dinoflagellate Karenia brevis, which produces nine potent polyether brevetoxins (PbTxs). Brevetoxins can be transferred from water to air in wind-powered white-capped waves. Inhalation exposure to marine aerosol containing brevetoxins causes respiratory symptoms. We describe detailed characterization of aerosols during an epidemiologic study of occupational exposure to Florida red tide aerosol in terms of its concentration, toxin profile, and particle size distribution. This information is essential in understanding its source, assessing exposure to people, and estimating dose of inhaled aerosols. Environmental sampling confirmed the presence of brevetoxins in water and air during a red tide exposure period (September 2001) and lack of significant toxin levels in the water and air during an unexposed period May 2002). Water samples collected during a red tide bloom in 2001 showed moderate-to-high concentrations of K. brevis cells and PbTxs. The daily mean PbTx concentration in water samples ranged from 8 to 28 μg/L from 7 to 11 September 2001; the daily mean PbTx concentration in air samples ranged from 1.3 to 27 ng/m(3). The daily aerosol concentration on the beach can be related to PbTx concentration in water, wind speed, and wind direction. Personal samples confirmed human exposure to red tide aerosols. The particle size distribution showed a mean aerodynamic diameter in the size range of 6–12 μm, with deposits mainly in the upper airways. The deposition pattern correlated with the observed increase of upper airway symptoms in healthy lifeguards during the exposure periods

Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.

Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD

Acquisition of a Distributed Computation and Immersive Visualization Environment for Complex Systems - Scientific Applications on Arrays of Multiprocessors (SCAAMP)

NSF Award ID: CDA-9601632 9/15/1996-8/31/199

Intratumoral Delivery of Plasmid Interleukin-12 Via Electroporation Leads to Regression of Injected and Non-Injected Tumors in Merkel Cell Carcinoma

Purpose: Interleukin-12 (IL12) promotes adaptive type I immunity and has demonstrated antitumor efficacy, but systemic administration leads to severe adverse events (AE), including death. This pilot trial investigated safety, efficacy, and immunologic activity of intratumoral delivery of IL12 plasmid DNA (tavo) via in vivo electroporation (i.t.-tavo-EP) in patients with Merkel cell carcinoma (MCC), an aggressive virus-associated skin cancer. Experimental Design: Fifteen patients with MCC with superficial injectable tumor(s) received i.t.-tavo-EP on days 1, 5, and 8 of each cycle. Patients with locoregional MCC (cohort A, N = 3) received one cycle before definitive surgery in week 4. Patients with metastatic MCC (cohort B, N = 12) received up to four cycles total, administered at least 6 weeks apart. Serial tumor and blood samples were collected. Results: All patients successfully completed at least one cycle with transient, mild (grades 1 and 2) AEs and without significant systemic toxicity. Sustained (day 22) intratumoral expression of IL12 protein was observed along with local inflammation and increased tumor-specific CD8+ T-cell infiltration, which led to systemic immunologic and clinical responses. The overall response rate was 25% (3/12) in cohort B, with 2 patients experiencing durable clinical benefit (16 and 55+ months, respectively). Two cohort A patients (1 with pathologic complete remission) were recurrence-free at 44+ and 75+ months. Conclusions: I.t.-tavo-EP was safe and feasible without systemic toxicity. Sustained local expression of IL12 protein and local inflammation led to systemic immune responses and clinically meaningful benefit in some patients. Gene electrotransfer, specifically i.t.-tavo-EP, warrants further investigation for immunotherapy of cancer