68 research outputs found
Azaspiracid Shellfish Poisoning: A Review on the Chemistry, Ecology, and Toxicology with an Emphasis on Human Health Impacts
Azaspiracids (AZA) are polyether marine toxins that accumulate in various shellfish species and have been associated with severe gastrointestinal human intoxications since 1995. This toxin class has since been reported from several countries, including Morocco and much of western Europe. A regulatory limit of 160 μg AZA/kg whole shellfish flesh was established by the EU in order to protect human health; however, in some cases, AZA concentrations far exceed the action level. Herein we discuss recent advances on the chemistry of various AZA analogs, review the ecology of AZAs, including the putative progenitor algal species, collectively interpret the in vitro and in vivo data on the toxicology of AZAs relating to human health issues, and outline the European legislature associated with AZAs
Field applications of the second-generation Environmental Sample Processor (ESP) for remote detection of harmful algae: 2006-2007
We assess the application of the second-generation Environmental Sample Processor (ESP) for the detection of harmful algal bloom (HAB) species in field and laboratory settings using two molecular probe techniques: a sandwich hybridization assay (SHA) and fluorescent in situ hybridization (FISH). During spring 2006, the first time this new instrument was deployed, the ESP successfully automated application of DNA probe arrays for various HAB species and other planktonic taxa, but non-specific background binding on the SHA probe array support made results interpretation problematic. Following 2006, the DNA array support membrane that we were using was replaced with a different membrane, and the SHA chemistry was adjusted. The sensitivity and dynamic range of these modifications were assessed using 96-well plate and ESP array SHA formats for several HAB species found commonly in Monterey Bay over a range of concentrations; responses were significantly correlated (p < 0.01). Modified arrays were deployed in 2007. Compared to 2006, probe arrays showed improved signal:noise, and remote detection of various HAB species was demonstrated. We confirmed that the ESP and affiliated assays can detect HAB populations at levels below those posing human health concerns, and results can be related to prevailing environmental conditions in near real-time
Marine Algal Toxin Azaspiracid Is an Open-State Blocker of hERG Potassium Channels
Azaspiracids (AZA) are polyether marine dinoflagellate toxins that accumulate in shellfish and represent an emerging human health risk. Although human exposure is primarily manifested by severe and protracted diarrhea, this toxin class has been shown to be highly cytotoxic, a teratogen to developing fish, and a possible carcinogen in mice. Until now, AZA's molecular target(s) has not yet been determined. Using three independent methods (voltage clamp, channel binding assay, and thallium flux assay), we have for the first time demonstrated that AZA1, AZA2, and AZA3 each bind to and block the hERG (human ether-à-go-go related gene) potassium channel heterologously expressed in HEK-293 mammalian cells. Inhibition of K+ current for each AZA analogue was concentration-dependent (IC50 value range: 0.64 - 0.84 μM). The mechanism of hERG channel inhibition by AZA1 was investigated further in Xenopus oocytes where it was shown to be an open state-dependent blocker and, using mutant channels, to interact with F656 but not with Y652 within the S6 transmembrane domain that forms the channel's central pore. AZA1, AZA2, and AZA3 were each shown to inhibit [3H]dofetilide binding to the hERG channel and thallium ion flux through the channel (IC50 value range: 2.1 – 6.6 μM). AZA1 did not block K+ current of the closely related EAG1 channel. Collectively, these data suggest that the AZAs physically block the K+ conductance pathway of hERG1 channels by occluding the cytoplasmic mouth of the open pore. Although the concentrations necessary to block hERG channels are relatively high, AZA-induced blockage may prove to contribute to the toxicological properties of the AZAs
Diversity and toxicity of Pseudo-nitzschia species in Monterey Bay : perspectives from targeted and adaptive sampling
Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Harmful Algae 78 (2018): 129-141, doi:10.1016/j.hal.2018.08.006.Monterey Bay, California experiences near-annual blooms of Pseudo-nitzschia that can
affect marine animal health and the economy, including impacts to tourism and
commercial/recreational fisheries. One species in particular, P. australis, has been
implicated in the most toxic of events, however other species within the genus can
contribute to widespread variability in community structure and associated toxicity across
years. Current monitoring methods are limited in their spatial coverage as well as their
ability to capture the full suite of species present, thereby hindering understanding of
HAB events and limiting predictive accuracy. An integrated deployment of multiple in
situ platforms, some with autonomous adaptive sampling capabilities, occurred during
two divergent bloom years in the bay, and uncovered detailed aspects of population and
toxicity dynamics. A bloom in 2013 was characterized by spatial differences in Pseudo39
nitzschia populations, with the low-toxin producer P. fraudulenta dominating the inshore
community and toxic P. australis dominating the offshore community. An exceptionally
toxic bloom in 2015 developed as a diverse Pseudo-nitzschia community abruptly
transitioned into a bloom of highly toxic P. australis within the time frame of a week.
Increases in cell density and proliferation coincided with strong upwelling of nutrients.
High toxicity was driven by silicate limitation of the dense bloom. This temporal shift in
species composition mirrored the shift observed further north in the California Current
System off Oregon and Washington. The broad scope of sampling and unique platform
capabilities employed during these studies revealed important patterns in bloom
formation and persistence for Pseudo-nitzschia. Results underscore the benefit of
expanded biological observing capabilities and targeted sampling methods to capture
more comprehensive spatial and temporal scales for studying and predicting future
events.This work was
supported by the National Oceanic and Atmospheric Administration
(NA11NOS4780055, NA11NOS4780056, NA11NOS4780030) and a fellowship to H.
Bowers from the Packard Foundation
Striking the Right Balance of Intermolecular Coupling for High-Efficiency Singlet Fission
Singlet fission is a process that splits collective excitations, or excitons, into two with unity efficiency. This exciton splitting process, unique to molecular photophysics, has the potential to considerably improve the efficiency of optoelectronic devices through more efficient light harvesting. While the first step of singlet fission has been characterized in great detail, subsequent steps critical to achieving overall highly-efficient singlet-to-triplet conversion are only just beginning to become well understood. One of the most elementary suggestions, which has yet to be tested, is that an appropriately balanced coupling is necessary to ensure overall highly efficient singlet fission; that is, the coupling needs to be strong enough so that the first step is fast and efficient, yet weak enough to ensure the independent behavior of the resultant triplets. In this work, we show how high overall singlet-to-triplet conversion efficiencies can be achieved in singlet fission by ensuring that the triplets comprising the triplet pair behave as independently as possible. We show that side chain sterics govern local packing in amorphous pentacene derivative nanoparticles, and that this in turn controls both the rate at which triplet pairs form and the rate at which they decay. We show how compact side chains and stronger couplings promote a triplet pair that effectively couples to the ground state, whereas bulkier side chains promote a triplet pair that appears more like two independent and long-lived triplet excitations. Our results show that the triplet pair is not emissive, that its decay is best viewed as internal conversion rather than triplet–triplet annihilation, and perhaps most critically that, in contrast to a number of recent suggestions, the triplets comprising the initially formed triplet pair cannot be considered independently. This work represents a significant step toward better understanding intermediates in singlet fission, and how molecular packing and couplings govern overall triplet yields
The state of the Martian climate
60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
AZASPIRACIDS – Toxicological Evaluation, Test Methods and Identifcation of the Source Organisms (ASTOX II)
Since the Irish monitoring program was set up in 2001 azaspiracids (AZAs) have been detected in shellfish above the regulatory limit every year with the exception of 2004. The south west coast of Ireland is especially prone to the onsets of AZA events. Over this period a number of poisoning incidents associated with this toxin group have occurred, all related to Irish shellfish. In 2003 the Marine Institute was awarded funding for a research project named ASTOX. This project was very successful in producing a range of reference materials (RMs, which are essential for accurate detection and monitoring, and which up to this point were unavailable. The project also examined the toxicity of AZAs, primarily using in vitro cell assays but some in vivo studies were also performed. The overall aims of the ASTOX 2 project were to strengthen knowledge on the causative organism and toxicity of AZAs. The project aims were grouped into three areas: ecology, chemical support and toxicology.Marine Institute Marine Research Sub Programme (NDP 2007 - 2013), co financed under the European Regional Development Fund
Cardiac Complications in Patients with Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Observational Studies
Vicente Corrales-Medina and colleagues report estimates of the risk of cardiac complications among patients with community-acquired pneumonia from a systematic review and meta-analysis
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Global solutions to regional problems : collecting global expertise to address the problem of harmful cyanobacterial blooms. A Lake Erie case study
In early August 2014, the municipality of Toledo, OH (USA) issued a ‘do not drink’ advisory on their water supply directly affecting over 400,000 residential customers and hundreds of businesses (Wilson, 2014). This order was attributable to levels of microcystin, a potent liver toxin, which rose to 2.5 μg L⁻¹ in finished drinking water. The Toledo crisis afforded an opportunity to bring together scientists from around the world to share ideas regarding factors that contribute to bloom formation and toxigenicity, bloom and toxin detection as well as prevention and remediation of bloom events. These discussions took place at an NSF- and NOAA-sponsored workshop at Bowling Green State University on April 13 and 14, 2015. In all, more than 100 attendees from six countries and 15 US states gathered together to share their perspectives. The purpose of this review is to present the consensus summary of these issues that emerged from discussions at the Workshop. As additional reports in this special issue provide detailed reviews on many major CHAB species, this paper focuses on the general themes common to all blooms, such as bloom detection, modeling, nutrient loading, and strategies to reduce nutrients.This is the publisher’s final pdf. The published article is copyrighted by Elsevier and can be found at: http://www.journals.elsevier.com/harmful-algae/Keywords: Nitrogen, CHAB, Phosphorus, Microcystin, Cyanobacteria, Lake Eri
Vitamin A and Retinoid Derivatives for Lung Cancer: A Systematic Review and Meta Analysis
Despite reported antiproliferative activity of vitamin A and its common use for cancer, there is no comprehensive synthesis of its safety and efficacy in lung cancers. To address this issue we conducted a systematic review of the safety and efficacy of vitamin A for the treatment and prevention of lung cancers.Two independent reviewers searched six electronic databases from inception to July 2009 for clinical, observational, and preclinical evidence pertaining to the safety and efficacy of vitamin A and related retinoids for lung cancers. 248 studies were included for full review and analysis. Five RCTs assessed treatment of lung cancers, three assessed primary prevention, and three looked at secondary prevention of lung cancers. Five surrogate studies, 26 phase I/II, 32 observational, and 67 preclinical studies were also included. 107 studies were included for interactions between vitamin A and chemo- or radiation-therapy. Although some studies demonstrated benefits, there was insufficient evidence overall to support the use of vitamin A or related retinoids for the treatment or prevention of lung cancers. Retinyl palmitate combined with beta carotene increased risk of lung cancer in smokers in the large CARET trial. Pooling of three studies pertaining to treatment and three studies on secondary prevention revealed no significant effects on response rate, second primary tumor, recurrence, 5-year survival, and mortality. There was a small improvement in event free survival associated with vitamin A compared to controls, RR 1.24 (95% CI 1.13-1.35). The synthetic rexinoid bexarotene increased survival significantly among a subset of patients in two RCTs (p<0.014, <0.087).There is a lack of evidence to support the use of naturally occurring retinoids for the treatment and prevention of lung cancers. The rexinoid bexarotene may hold promise for use among a subset of patients, and deserves further study
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