Recreational and occupational field exposure to freshwater cyanobacteria – a review of anecdotal and case reports, epidemiological studies and the challenges for epidemiologic assessment

Cyanobacteria are common inhabitants of freshwater lakes and reservoirs throughout the world. Under favourable conditions, certain cyanobacteria can dominate the phytoplankton within a waterbody and form nuisance blooms. Case reports and anecdotal references dating from 1949 describe a range of illnesses associated with recreational exposure to cyanobacteria: hay fever-like symptoms, pruritic skin rashes and gastro-intestinal symptoms are most frequently reported. Some papers give convincing descriptions of allergic reactions while others describe more serious acute illnesses, with symptoms such as severe headache, pneumonia, fever, myalgia, vertigo and blistering in the mouth. A coroner in the United States found that a teenage boy died as a result of accidentally ingesting a neurotoxic cyanotoxin from a golf course pond. This death is the first recorded human fatality attributed to recreational exposure to cyanobacteria, although uncertainties surround the forensic identification of the suspected cyanotoxin in this case. We systematically reviewed the literature on recreational exposure to freshwater cyanobacteria. Epidemiological data are limited, with six studies conducted since 1990. Statistically significant increases in symptoms were reported in individuals exposed to cyanobacteria compared to unexposed counterparts in two Australian cohort studies, though minor morbidity appeared to be the main finding. The four other small studies (three from the UK, one Australian) did not report any significant association. However, the potential for serious injury or death remains, as freshwater cyanobacteria under bloom conditions are capable of producing potent toxins that cause specific and severe dysfunction to hepatic or central nervous systems. The exposure route for these toxins is oral, from ingestion of recreational water, and possibly by inhalation. A range of freshwater microbial agents may cause acute conditions that present with features that resemble illnesses attributed to contact with cyanobacteria and, conversely, acute illness resulting from exposure to cyanobacteria or cyanotoxins in recreational waters could be misdiagnosed. Accurately assessing exposure to cyanobacteria in recreational waters is difficult and unreliable at present, as specific biomarkers are unavailable. However, diagnosis of cyanobacteria-related illness should be considered for individuals presenting with acute illness following freshwater contact if a description is given of a waterbody visibly affected by planktonic mass development

The Interactive Effects of Ammonia and Microcystin on Life-History Traits of the Cladoceran Daphnia magna: Synergistic or Antagonistic?

The occurrence of Microcystis blooms is a worldwide concern that has caused numerous adverse effects on water quality and lake ecology. Elevated ammonia and microcystin concentrations co-occur during the degradation of Microcystis blooms and are toxic to aquatic organisms; we studied the relative and combined effects of these on the life history of the model organism Daphnia magna. Ammonia and microcystin-LR treatments were: 0, 0.366, 0.581 mg L−1 and 0, 10, 30, 100 µg L−1, respectively. Experiments followed a fully factorial design. Incubations were 14 d and recorded the following life-history traits: number of moults, time to first batch of eggs, time to first clutch, size at first batch of eggs, size at first clutch, number of clutches per female, number of offspring per clutch, and total offspring per female. Both ammonia and microcystin were detrimental to most life-history traits. Interactive effects of the toxins occurred for five traits: the time to first batch of eggs appearing in the brood pouch, time to first clutch, size at first clutch, number of clutches, and total offspring per female. The interactive effects of ammonia and microcystin appeared to be synergistic on some parameters (e.g., time to first eggs) and antagonistic on others (e.g., total offspring per female). In conclusion, the released toxins during the degradation of Microcystis blooms would result, according to our data, in substantially negative effect on D. magna

Massive multiplication of genome and ribosomes in dormant cells (akinetes) of Aphanizomenon ovalisporum (Cyanobacteria)

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in The ISME Journal 6 (2012): 670–679, doi:10.1038/ismej.2011.128.Akinetes are dormancy cells commonly found among filamentous cyanobacteria, many of which are toxic and/or nuisance, bloom-forming species. Development of akinetes from vegetative cells is a process that involves morphological and biochemical modifications. Here we applied a single cell approach to quantify genome and ribosome content of akinetes and vegetative cells in Aphanizomenon ovalisporum (Cyanobacteria). Vegetative cells of A. ovalisporum were naturally polyploid and contained on average 8 genome copies per cell. However, the chromosomal content of akinetes increased up to 450 copies, with an average value of 119 genome copies per akinete, 15 fold higher that in vegetative cells. Based on fluorescence in situ hybridization with a probe targeting 16S rRNA and detection with confocal laser scanning microscopy we conclude that ribosomes accumulated in akinetes to a higher level than that found in vegetative cells. We further present evidence that this massive accumulation of nucleic acids in akinetes is likely supported by phosphate supplied from inorganic polyphosphate bodies that were abundantly present in vegetative cells, but notably absent from akinetes. These results are interpreted in the context of cellular investments for proliferation following long term dormancy, as the high nucleic acid content would provide the basis for extended survival, rapid resumption of metabolic activity and cell division upon germination.Supported by the Gruss Lipper Foundation research award (AS). This study was part of the Joint German-Israeli-Project (FKZ 02WT0985, WR803) funded by the German Ministry of Research and Technology (BMBF) and Israel Ministry of Science and Technology (MOST)

NSC23925, Identified in a High-Throughput Cell-Based Screen, Reverses Multidrug Resistance

Multidrug resistance (MDR) is a major factor which contributes to the failure of cancer chemotherapy, and numerous efforts have been attempted to overcome MDR. To date, none of these attempts have yielded a tolerable and effective therapy to reverse MDR; thus, identification of new agents would be useful both clinically and scientifically.To identify small molecule compounds that can reverse chemoresistance, we developed a 96-well plate high-throughput cell-based screening assay in a paclitaxel resistant ovarian cancer cell line. Coincubating cells with a sublethal concentration of paclitaxel in combination with each of 2,000 small molecule compounds from the National Cancer Institute Diversity Set Library, we identified a previously uncharacterized molecule, NSC23925, that inhibits Pgp1 and reverses MDR1 (Pgp1) but does not inhibit MRP or BCRP-mediated MDR. The cytotoxic activity of NSC23925 was further evaluated using a panel of cancer cell lines expressing Pgp1, MRP, and BCRP. We found that at a concentration of >10 microM NSC23925 moderately inhibits the proliferation of both sensitive and resistant cell lines with almost equal activity, but its inhibitory effect was not altered by co-incubation with the Pgp1 inhibitor, verapamil, suggesting that NSC23925 itself is not a substrate of Pgp1. Additionally, NSC23925 increases the intracellular accumulation of Pgp1 substrates: calcein AM, Rhodamine-123, paclitaxel, mitoxantrone, and doxorubicin. Interestingly, we further observed that, although NSC23925 directly inhibits the function of Pgp1 in a dose-dependent manner without altering the total expression level of Pgp1, NSC23925 actually stimulates ATPase activity of Pgp, a phenomenon seen in other Pgp inhibitors.The ability of NSC23925 to restore sensitivity to the cytotoxic effects of chemotherapy or to prevent resistance could significantly benefit cancer patients

Choosing a control intervention for a randomised clinical trial

BACKGROUND: Randomised controlled clinical trials are performed to resolve uncertainty concerning comparator interventions. Appropriate acknowledgment of uncertainty enables the concurrent achievement of two goals : the acquisition of valuable scientific knowledge and an optimum treatment choice for the patient-participant. The ethical recruitment of patients requires the presence of clinical equipoise. This involves the appropriate choice of a control intervention, particularly when unapproved drugs or innovative interventions are being evaluated. DISCUSSION: We argue that the choice of a control intervention should be supported by a systematic review of the relevant literature and, where necessary, solicitation of the informed beliefs of clinical experts through formal surveys and publication of the proposed trial's protocol. SUMMARY: When clinical equipoise is present, physicians may confidently propose trial enrollment to their eligible patients as an act of therapeutic beneficence

Signatures of a dissipative phase transition in photon correlation measurements

This work was supported by the Swiss National Science Foundation (SNSF) through the National Centre of Competence in Research - Quantum Science and Technology (NCCR QSIT). A.S., C.S., and S.H. acknowledge support by the State of Bavaria and the DFG within the Project Schn1376/3-1.Understanding and characterizing phase transitions in driven-dissipative systems constitutes a new frontier for many-body physics[1-8]. A generic feature of dissipative phase transitions is a vanishing gap in the Liouvillian spectrum [9], which leads to long-lived deviations from the steady state as the system is driven towards the transition. Here, we show that photon correlation measurements can be used to characterize the corresponding critical slowing down of non-equilibrium dynamics. We focus on the extensively studied phenomenon of optical bistability in GaAs cavity polaritons [10,11], which can be described as a first-order dissipative phase transition [12-14]. Increasing the excitation strength towards the bistable range results in an increasing photon-bunching signal along with a decay time that is prolonged by more than nine orders of magnitude as compared with that of single polaritons. In the limit of strong polariton interactions leading to pronounced quantum fluctuations, the mean-field bistability threshold is washed out. Nevertheless, the functional form with which the Liouvillian gap closes as the thermodynamic limit is approached provides a signature of the emerging dissipative phase transition. Our results establish photon correlation measurements as an invaluable tool for studying dynamical properties of dissipative phase transitions without requiring phase-sensitive interferometric measurements.PostprintPeer reviewe

Sensorimotor Experience Influences Recovery of Forelimb Abilities but Not Tissue Loss after Focal Cortical Compression in Adult Rats

Sensorimotor activity has been shown to play a key role in functional outcome after extensive brain damage. This study was aimed at assessing the influence of sensorimotor experience through subject-environment interactions on the time course of both lesion and gliosis volumes as well as on the recovery of forelimb sensorimotor abilities following focal cortical injury. The lesion consisted of a cortical compression targeting the forepaw representational area within the primary somatosensory cortex of adult rats. After the cortical lesion, rats were randomly subjected to various postlesion conditions: unilateral C5–C6 dorsal root transection depriving the contralateral cortex from forepaw somatosensory inputs, standard housing or an enriched environment promoting sensorimotor experience and social interactions. Behavioral tests were used to assess forelimb placement during locomotion, forelimb-use asymmetry, and forepaw tactile sensitivity. For each group, the time course of tissue loss was described and the gliosis volume over the first postoperative month was evaluated using an unbiased stereological method. Consistent with previous studies, recovery of behavioral abilities was found to depend on post-injury experience. Indeed, increased sensorimotor activity initiated early in an enriched environment induced a rapid and more complete behavioral recovery compared with standard housing. In contrast, severe deprivation of peripheral sensory inputs led to a delayed and only partial sensorimotor recovery. The dorsal rhizotomy was found to increase the perilesional gliosis in comparison to standard or enriched environments. These findings provide further evidence that early sensory experience has a beneficial influence on the onset and time course of functional recovery after focal brain injury

Cyanobacterial lipopolysaccharides and human health – a review

Cyanobacterial lipopolysaccharide/s (LPS) are frequently cited in the cyanobacteria literature as toxins responsible for a variety of heath effects in humans, from skin rashes to gastrointestinal, respiratory and allergic reactions. The attribution of toxic properties to cyanobacterial LPS dates from the 1970s, when it was thought that lipid A, the toxic moiety of LPS, was structurally and functionally conserved across all Gram-negative bacteria. However, more recent research has shown that this is not the case, and lipid A structures are now known to be very different, expressing properties ranging from LPS agonists, through weak endotoxicity to LPS antagonists. Although cyanobacterial LPS is widely cited as a putative toxin, most of the small number of formal research reports describe cyanobacterial LPS as weakly toxic compared to LPS from the Enterobacteriaceae. We systematically reviewed the literature on cyanobacterial LPS, and also examined the much lager body of literature relating to heterotrophic bacterial LPS and the atypical lipid A structures of some photosynthetic bacteria. While the literature on the biological activity of heterotrophic bacterial LPS is overwhelmingly large and therefore difficult to review for the purposes of exclusion, we were unable to find a convincing body of evidence to suggest that heterotrophic bacterial LPS, in the absence of other virulence factors, is responsible for acute gastrointestinal, dermatological or allergic reactions via natural exposure routes in humans. There is a danger that initial speculation about cyanobacterial LPS may evolve into orthodoxy without basis in research findings. No cyanobacterial lipid A structures have been described and published to date, so a recommendation is made that cyanobacteriologists should not continue to attribute such a diverse range of clinical symptoms to cyanobacterial LPS without research confirmation

Anti-cyanobacterial activity of Moringa oleifera seeds

Filtrates from crushed Moringa oleifera seeds were tested for their effects on growth and Photosystem II efficiency of the common bloom-forming cyanobacterium Microcystis aeruginosa. M. aeruginosa populations exhibited good growth in controls and treatments with 4- and 8-mg crushed Moringa seeds per liter, having similar growth rates of 0.50 (±0.01) per day. In exposures of 20- to 160-mg crushed Moringa seeds L−1, growth rates were negative and on average −0.23 (±0.05) .day−1. Presumably, in the higher doses of 20- to 160-mg crushed seeds per liter, the cyanobacteria died, which was supported by a rapid drop in the Photosystem II efficiency (ΦPSII), while the ΦPSII was high and unaffected in 0, 4, and 8 mg L−1. High-density populations of M. aeruginosa (chlorophyll-a concentrations of ∼270 µg L−1) were reduced to very low levels within 2 weeks of exposure to ≥80-mg crushed seeds per liter. At the highest dosage of 160 mg L−1, the ΦPSII dropped to zero rapidly and remained nil during the course of the experiment (14 days). Hence, under laboratory conditions, a complete wipeout of the bloom could be achieved. This is the first study that yielded evidence for cyanobactericidal activity of filtrate from crushed Moringa seeds, suggesting that Moringa seed extracts might have a potential as an effect-oriented measure lessening cyanobacterial nuisance