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In September 2007, reports of respiratory irritation and fish kills were received by the Florida Fish and Wildlife Conservation Commission (FWC) from the Jacksonville, Florida area. Water samples collected in this area indicated a bloom of Karenia brevis, the dinoflagellate that produces brevetoxin, which can cause neurotoxic shellfish poisoning. For the next four months, K. brevis was found along approximately 400 km of coastal and Intracoastal waterways from Jacksonville to Jupiter Inlet. This event represents the longest and most extensive red tide the east coast of Florida has experienced and the first time Karenia species other than K. brevis have been reported in this area. This extensive red tide influenced commercial and recreational shellfish harvesting activities along Florida's east coast. Fourteen shellfish harvesting areas (SHAs) were monitored weekly during this event and 10 SHAs were closed for an average of 53 days due to this red tide. The length of SHA closure was dependent on the shellfish species present. Interagency cooperation in monitoring this K. brevis bloom was successful in mitigating any human health impacts. Kernel density estimation was used to create geographic extent maps to help extrapolate discreet sample data points into 5 km^sup 2^ radius values for better visualization of the bloom.

Potent marine neurotoxins known as brevetoxins are produced by the 'red tide' dinoflagellate Karenia brevis. They kill large numbers of fish and cause illness in humans who ingest toxic filter-feeding shellfish or inhale toxic aerosols. The toxins are also suspected of having been involved in events in which many manatees and dolphins died, but this has usually not been verified owing to limited confirmation of toxin exposure, unexplained intoxication mechanisms and complicating pathologies. Here we show that fish and seagrass can accumulate high concentrations of brevetoxins and that these have acted as toxin vectors during recent deaths of dolphins and manatees, respectively. Our results challenge claims that the deleterious effects of a brevetoxin on fish (ichthyotoxicity) preclude its accumulation in live fish, and they reveal a new vector mechanism for brevetoxin spread through food webs that poses a threat to upper trophic levels.

Background: From January 2002 to May 2004, 28 puffer fish poisoning (PFP) cases in Florida, New Jersey, Virginia, and New York were linked to the Indian River Lagoon (IRL) in Florida. Saxitoxins (STXs) of unknown source were first identified in fillet remnants from a New Jersey PFP case in 2002. Methods: We used the standard mouse bioassay (MBA), receptor binding assay (RBA), mouse neuroblastoma cytotoxicity assay (MNCA), Ridascreen ELISA, MIST Alert assay, HPLC, and liquid chromatography-mass spectrometry (LC-MS) to determine the presence of STX, decarbamoyl STX (dc-STX), and N-sulfocarbamoyl (B1) toxin in puffer fish tissues, clonal cultures, and natural bloom samples of Pyrodinium bahamense from the IRL. Results: We found STXs in 516 IRL southern (Sphoeroides nephelus), checkered (Sphoeroides testudineus), and bandtail (Sphoeroides spengleri) puffer fish. During 36 months of monitoring, we detected STXs in skin, muscle, and viscera, with concentrations up to 22,104 ug STX equivalents (eq)/100 g tissue (action level, 80 µg STX eq/100 g tissue) in ovaries. Puffer fish tissues, clonal cultures, and natural bloom samples of P. bahamense from the IRL tested toxic in the MBA, RBA, MNCA, Ridascreen ELISA, and MIST Alert assay and positive for STX, dc-STX, and B1 toxin by HPLC and LC-MS. Skin mucus of IRL southern puffer fish captive for 1-year was highly toxic compared to Florida Gulf coast puffer fish. Therefore, we confirm puffer fish to be a hazardous reservoir of STXs in Florida's marine waters and implicate the dinoflagellate P. bahamense as the putative toxin source. Conclusions: Associated with fatal paralytic shellfish poisoning (PSP) in the Pacific but not known to be toxic in the western Atlantic, P. bahamense is an emerging public health threat. We propose characterizing this food poisoning syndrome as saxitoxin puffer fish poisoning (SPFP) to distinguish it from PFP, which is traditionally associated with tetrodotoxin, and from PSP caused by STXs in shellfish.

In September 2007, reports of respiratory irritation and fish kills were received by the Florida Fish and Wildlife Conservation Commission (FWC) from the Jacksonville, Florida area. Water samples collected in this area indicated a bloom of Karenia brevis, the dinoflagellate that produces brevetoxin, which can cause neurotoxic shellfish poisoning. For the next four months, K. brevis was found along approximately 400 km of coastal and Intracoastal waterways from Jacksonville to Jupiter Inlet. This event represents the longest and most extensive red tide the east coast of Florida has experienced and the first time Karenia species other than K. brevis have been reported in this area. This extensive red tide influenced commercial and recreational shellfish harvesting activities along Florida's east coast. Fourteen shellfish harvesting areas (SHAs) were monitored weekly during this event and 10 SHAs were closed for an average of 53 days due to this red tide. The length of SHA closure was dependent on the shellfish species present. Interagency cooperation in monitoring this K. brevis bloom was successful in mitigating any human health impacts. Kernel density estimation was used to create geographic extent maps to help extrapolate discreet sample data points into $5km^2$ radius values for better visualization of the bloom.

Unexpected brevetoxin vectors may account for deaths long after or remote from an algal bloom. Red alert A string of recent reports have claimed that the deaths of groups of dolphins and manatees off the Florida coast have been caused by red tides (toxic algal blooms). It has been hard to verify the true cause of these deaths. But the discovery that algal toxins accumulate in fish and seagrass, food for dolphins and manatees, respectively, suggests that the red tides are indeed to blame. Potent marine neurotoxins known as brevetoxins are produced by the ‘red tide’ dinoflagellate Karenia brevis . They kill large numbers of fish and cause illness in humans who ingest toxic filter-feeding shellfish or inhale toxic aerosols 1 . The toxins are also suspected of having been involved in events in which many manatees and dolphins died, but this has usually not been verified owing to limited confirmation of toxin exposure, unexplained intoxication mechanisms and complicating pathologies 2 , 3 , 4 . Here we show that fish and seagrass can accumulate high concentrations of brevetoxins and that these have acted as toxin vectors during recent deaths of dolphins and manatees, respectively. Our results challenge claims that the deleterious effects of a brevetoxin on fish (ichthyotoxicity) preclude its accumulation in live fish, and they reveal a new vector mechanism for brevetoxin spread through food webs that poses a threat to upper trophic levels.

In human airways diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), host defense is compromised and airways inflammation and infection often result. Mucus clearance and trapping of inhaled pathogens constitute key elements of host defense. Clearance rates are governed by mucus viscous and elastic moduli at physiological driving frequencies, whereas transport of trapped pathogens in mucus layers is governed by diffusivity. There is a clear need for simple and effective clinical biomarkers of airways disease that correlate with these properties. We tested the hypothesis that mucus solids concentration, indexed as weight percent solids (wt%), is such a biomarker. Passive microbead rheology was employed to determine both diffusive and viscoelastic properties of mucus harvested from human bronchial epithelial (HBE) cultures. Guided by sputum from healthy (1.5-2.5 wt%) and diseased (COPD, CF; 5 wt%) subjects, mucus samples were generated in vitro to mimic in vivo physiology, including intermediate range wt% to represent disease progression. Analyses of microbead datasets showed mucus diffusive properties and viscoelastic moduli scale robustly with wt%. Importantly, prominent changes in both biophysical properties arose at ∼4 wt%, consistent with a gel transition (from a more viscous-dominated solution to a more elastic-dominated gel). These findings have significant implications for: (1) penetration of cilia into the mucus layer and effectiveness of mucus transport; and (2) diffusion vs. immobilization of micro-scale particles relevant to mucus barrier properties. These data provide compelling evidence for mucus solids concentration as a baseline clinical biomarker of mucus barrier and clearance functions.

Effective treatment for glioblastoma (GBM) is limited by the presence of the blood–brain barrier (BBB) and rapid resistance to single agent therapies. To address these issues, we developed a transferrin-functionalized nanoparticle (Tf-NP) that can deliver dual combination therapies. Using intravital imaging, we show the ability of Tf-NPs to traverse intact BBB in mice as well as achieve direct tumor binding in two intracranial orthotopic models of GBM. Treatment of tumor-bearing mice with Tf-NPs loaded with temozolomide and the bromodomain inhibitor JQ1 leads to increased DNA damage and apoptosis that correlates with a 1.5- to 2-fold decrease in tumor burden and corresponding increase in survival compared to equivalent free-drug dosing. Immunocompetent mice treated with Tf-NP-loaded drugs also show protection from the effects of systemic drug toxicity, demonstrating the preclinical potential of this nanoscale platform to deliver novel combination therapies to gliomas and other central nervous system tumors. The blood-brain barrier often limits effective delivery  of treatments for glioblastoma . In this study, the authors develop transferrin-functionalized nanoparticles able to traverse the intact blood-brain barrier and deliver combination temozolomide and bromodomain inhibitor therapy to  glioma-bearing mice.

Every night across the world’s oceans, numerous marine animals arrive at the surface of the ocean to feed on plankton after an upward migration of hundreds of metres. Just before sunrise, this migration is reversed and the animals return to their daytime residence in the dark mesopelagic zone (at a depth of 200–1,000 m). This daily excursion, referred to as diel vertical migration (DVM), is thought of primarily as an adaptation to avoid visual predators in the sunlit surface layer 1 , 2 and was first recorded using ship-net hauls nearly 200 years ago 3 . Nowadays, DVMs are routinely recorded by ship-mounted acoustic systems (for example, acoustic Doppler current profilers). These data show that night-time arrival and departure times are highly conserved across ocean regions 4 and that daytime descent depths increase with water clarity 4 , 5 , indicating that animals have faster swimming speeds in clearer waters 4 . However, after decades of acoustic measurements, vast ocean areas remain unsampled and places for which data are available typically provide information for only a few months, resulting in an incomplete understanding of DVMs. Addressing this issue is important, because DVMs have a crucial role in global ocean biogeochemistry. Night-time feeding at the surface and daytime metabolism of this food at depth provide an efficient pathway for carbon and nutrient export 6 – 8 . Here we use observations from a satellite-mounted light-detection-and-ranging (lidar) instrument to describe global distributions of an optical signal from DVM animals that arrive in the surface ocean at night. Our findings reveal that these animals generally constitute a greater fraction of total plankton abundance in the clear subtropical gyres, consistent with the idea that the avoidance of visual predators is an important life strategy in these regions. Total DVM biomass, on the other hand, is higher in more productive regions in which the availability of food is increased. Furthermore, the 10-year satellite record reveals significant temporal trends in DVM biomass and correlated variations in DVM biomass and surface productivity. These results provide a detailed view of DVM activities globally and a path for refining the quantification of their biogeochemical importance. Satellite-derived analysis of daily vertical migrations of ocean animals shows that the relative abundance and total biomass of these animals differ between different regions globally, depending on the availability of food and necessity to avoid predators.