High Levels Of Toxins Research Articles

Transcription factor cap n collar C regulates multiple cytochrome P450 genes conferring adaptation to potato plant allelochemicals and resistance to imidacloprid in Leptinotarsa decemlineata (Say)

Colorado potato beetle (CPB), Leptinotarsa decemlineata is a notorious pest of potato. Co-evolution with Solanaceae plants containing high levels of toxins (glycoalkaloids) helped this insect to develop an efficient detoxification system and resist almost every chemical insecticide introduced for its control. Even though the cross-resistance between plant allelochemicals and insecticides is well acknowledged, the underlying molecular mechanisms are not understood. Here, we investigated the molecular mechanisms involved in detoxification of potato plant allelochemicals and imidacloprid resistance in the field-collected CPB. Our results showed that the imidacloprid-resistant beetles employ metabolic detoxification of both potato plant allelochemicals and imidacloprid by upregulation of common cytochrome P450 genes. RNAi aided knockdown identified four cytochromes P450 genes (CYP6BJa/b, CYP6BJ1v1, CYP9Z25, and CYP9Z29) that are required for defense against both natural and synthetic chemicals. These P450 genes are regulated by the xenobiotic transcription factors Cap n Collar C, CncC and muscle aponeurosis fibromatosis, Maf. Studies on the CYP9Z25 promoter using the luciferase reporter assay identified two binding sites (i.e. GCAGAAT and GTACTGA) for CncC and Maf. Overall, these data showed that CPB employs the metabolic resistance mediated through xenobiotic transcription factors CncC and Maf to regulate multiple P450 genes and detoxify both imidacloprid and potato plant allelochemicals.

A P-Glycoprotein Is Linked to Resistance to the Bacillus thuringiensis Cry3Aa Toxin in a Leaf Beetle.

Chrysomela tremula is a polyvoltine oligophagous leaf beetle responsible for massive attacks on poplar trees. This beetle is an important model for understanding mechanisms of resistance to Bacillus thuringiensis (Bt) insecticidal toxins, because a resistant C. tremula strain has been found that can survive and reproduce on transgenic poplar trees expressing high levels of the Cry3Aa Bt toxin. Resistance to Cry3Aa in this strain is recessive and is controlled by a single autosomal locus. We used a larval midgut transcriptome for C. tremula to search for candidate resistance genes. We discovered a mutation in an ABC protein, member of the B subfamily homologous to P-glycoprotein, which is genetically linked to Cry3Aa resistance in C. tremula. Cultured insect cells heterologously expressing this ABC protein swell and lyse when incubated with Cry3Aa toxin. In light of previous findings in Lepidoptera implicating A subfamily ABC proteins as receptors for Cry2A toxins and C subfamily proteins as receptors for Cry1A and Cry1C toxins, this result suggests that ABC proteins may be targets of insecticidal three-domain Bt toxins in Coleoptera as well.

Love-iathan, the meat-whale and hidden people: ordering Faroese pilot whaling

A key question in any environmental dispute is the nature of what is under discussion. 'Cosmopolitics' – political battles over the form of reality – are a feature of many environmental clashes. This article focuses on one such clash: during the summer of 2014, grindadráp – the iconic practice of driving pilot whales for meat – was the big news item in the Faroe Islands. More accurately, a conservation campaign by the controversial group Sea Shepherd Conservation Society (SSCS), Operation Grindstop 2014, garnered most attention. Aiming to stop or at least disrupt the 'barbaric' and 'sadistic' grindadráp, SSCS were involved in several confrontations with Faroese authorities and publicly engaged with Faroese pro-whaling advocates in several discussions that were seemingly fruitless. Based on 3 months fieldwork during the campaign, this article describes a 'political ontology' of Grindstop 2014. What emerged was a 'hybrid' born of a clash between two fundamentally dissonant systems of ordering, which structured and were reinforced by various practices, both discursive and material. Activists on both sides were engaged in a cosmopolitical struggle to decisively enact their orderings, creating alternative stories of whales, Faroese whaling, the ocean environment and modernity. The aim is to understand what happened when these orderings met. This article argues that throughout the summer these two orderings moved apart, consequently hiding the diversity of opinion and discussion within Faroese society around grindadráp. As such, alternative orderings of grindadráp were suppressed, notably those voiced by Faroese activists arguing that the practice should cease because of the high levels of toxins in pilot whale meat.Key words: Faroe Islands, whaling, political ontology, cosmopolitics

Evidence of freshwater algal toxins in marine shellfish: Implications for human and aquatic health

The occurrence of freshwater harmful algal bloom toxins impacting the coastal ocean is an emerging threat, and the potential for invertebrate prey items to concentrate toxin and cause harm to human and wildlife consumers is not yet fully recognized. We examined toxin uptake and release in marine mussels for both particulate and dissolved phases of the hepatotoxin microcystin, produced by the freshwater cyanobacterial genus Microcystis. We also extended our experimental investigation of particulate toxin to include oysters (Crassostrea sp.) grown commercially for aquaculture. California mussels (Mytilus californianus) and oysters were exposed to Microcystis and microcystin toxin for 24h at varying concentrations, and then were placed in constantly flowing seawater and sampled through time simulating riverine flushing events to the coastal ocean. Mussels exposed to particulate microcystin purged the toxin slowly, with toxin detectable for at least 8 weeks post-exposure and maximum toxin of 39.11ng/g after exposure to 26.65μg/L microcystins. Dissolved toxin was also taken up by California mussels, with maximum concentrations of 20.74ng/g after exposure to 7.74μg/L microcystin, but was purged more rapidly. Oysters also took up particulate toxin but purged it more quickly than mussels. Additionally, naturally occurring marine mussels collected from San Francisco Bay tested positive for high levels of microcystin toxin. These results suggest that ephemeral discharge of Microcystis or microcystin to estuaries and the coastal ocean accumulate in higher trophic levels for weeks to months following exposure.

Post-invasion events after infection with Staphylococcus aureus are strongly dependent on both the host cell type and the infecting S. aureus strain

Host cell invasion is a major feature of Staphylococcus aureus and contributes to infection development. The intracellular metabolically active bacteria can induce host cell activation and death but they can also persist for long time periods. In this study a comparative analysis was performed of different well-characterized S. aureus strains in their interaction with a variety of host cell types. Staphylococcus aureus (strains 6850, USA300, LS1, SH1000, Cowan1) invasion was compared in different human cell types (epithelial and endothelial cells, keratinocytes, fibroblasts, osteoblasts). The number of intracellular bacteria was determined, cell inflammation was investigated, as well as cell death and phagosomal escape of bacteria. To explain strain-dependent differences in the secretome, a proteomic approach was used. Barrier cells took up high amounts of bacteria and were killed by aggressive strains. These strains expressed high levels of toxins, and possessed the ability to escape from phagolysosomes. Osteoblasts and keratinocytes ingested less bacteria, and were not killed, even though the primary osteoblasts were strongly activated by S. aureus. In all cell types S. aureus was able to persist. Strong differences in uptake, cytotoxicity, and inflammatory response were observed between primary cells and their corresponding cell lines, demonstrating that cell lines reflect only partially the functions and physiology of primary cells. This study provides a contribution for a better understanding of the pathomechanisms of S. aureus infections. The proteomic data provide important basic knowledge on strains commonly used in the analysis of S. aureus-host cell interaction.

The influence of plant defensive chemicals, diet composition, and winter severity on the nutritional condition of a free‐ranging, generalist herbivore

When consuming plants, herbivores must deal with both low nutritional quality from cell wall constituents and potentially toxic plant secondary metabolites, which are often inversely related. Herbivores that consume a highly nutritious, but chemically defended plant, may consume high levels of toxins that require energy for detoxification. Alternatively, herbivores may avoid consuming high levels of toxins by consuming a diverse diet that may be lower in overall nutritional quality. In this study, we assessed the relationship among nutritional restriction, detoxification and diet diversity in a free‐ranging wild herbivore. We collected urine deposited in the snow (hereafter, snow‐urine) and feces by free‐ranging moose Alces americanus, a generalist browser, during winter. We used the ratio of urinary urea nitrogen to creatinine (UN:C), measured in snow‐urine samples, as an indicator of nutritional restriction, and the ratio of glucuronic acid to creatinine (GA:C), as an indicator of investment in detoxification. We used microhistology to determine diet composition from fecal pellets. GA:C and UN:C were positively associated, suggesting that nutritional condition tends to be worse for individuals investing more in detoxification. We found, after accounting for the influence of winter severity, diet diversity and UN:C to be negatively related, suggesting that increasingly diverse diets were associated with improved nutritional condition. Overall, the most important predictor of UN:C was winter severity and proportion of diet comprised of balsam fir Abies balsamea. Physiological indicators of nutritional restriction tended to be worse during severe winters and among individuals that had consumed more balsam fir. These results highlight complex relationships among environmental conditions, foraging decisions, and costs of detoxification that can influence nutritional condition of herbivores.

Multiannual trend of microcystin production in the toxic cyanobacterium Planktothrix rubescens in Lake Garda (Italy)

ABSTRACTMassive developments (blooms) of cyanobacteria represent a major concern in many natural and artificial waterbodies, because of the high levels of toxins that can be released into water. Microcystins, potent hepatotoxins, represent the most frequent toxins produced by cyanobacteria. The determination of the microcystins’ profile in waterbodies is important for determining the real toxic potential. We have investigated the evolution of the microcystins’ profile of Lake Garda (Italy) from both a qualitative and a quantitative point of view over a period of five years. We have also analysed possible correlations between toxin profile and selected environmental parameters. We found that a demethylated microcystin variant (RRdm) was always dominant but showing a cyclic trend, alternating periods in which it represented the only variant, and periods in which other variants were present (LRdm, HtyrRdm, RR, and LR). These changes are probably due to changes in chemotypes composition inside the resident Planktothrix rubescens population and do not seem to be exclusively linked to the considered environmental variables. Total microcystin concentrations were always low (in the ng L−1 scale), and showed typical peaks in the metalimnetic layer during summer–autumn time of each year.

Increased toxin expression in a Clostridium difficile mfd mutant.

BackgroundThe symptoms of Clostridium difficile infection are mediated primarily by two toxins, TcdA and TcdB, the expression of which is governed by a multitude of factors including nutrient availability, growth phase and cell stress. Several global regulators have been implicated in the regulation of toxin expression, such as CcpA and CodY.ResultsDuring attempts to insertionally inactivate a putative secondary cell wall polysaccharide synthesis gene, we obtained several mutants containing off-target insertions. One mutant displayed an unusual branched colony morphology and was investigated further. Marker recovery revealed an insertion in mfd, a gene encoding a transcription-coupled repair factor. The mfd mutant exhibited pleiotropic effects, in particular increased expression of both toxin A and B (TcdA and TcdB) compared to the parental strain. Western blotting and cellular cytotoxicity assays revealed increased expression across all time points over a 24 h period, with inactivation of mfd resulting in at least a 10 fold increase in cell cytotoxicity. qRT-PCR demonstrated the upregulation of both toxins occurred on a transcriptional level. All effects of the mfd mutation were complemented by a plasmid-encoded copy of mfd, showing the effects are not due to polar effects of the intron insertion or to second site mutations.ConclusionsThis study adds Mfd to the repertoire of factors involved in regulation of toxin expression in Clostridium difficile. Mfd is known to remove RNA polymerase molecules from transcriptional sites where it has stalled due to repressor action, preventing transcriptional read through. The consistently high levels of toxin in the C. difficile mfd mutant indicate this process is inefficient leading to transcriptional de-repression.

Microbiota-Gut-Brain Axis: Yeast Species Isolated from Stool Samples of Children with Suspected or Diagnosed Autism Spectrum Disorders and In Vitro Susceptibility Against Nystatin and Fluconazole.

Autism spectrum disorder (ASD) is a general term for a group of complex neurodevelopmental disorders of brain development that limits a person's ability to function normally. Etiology has not been clearly defined up to date. However, gut microbiota and the bidirectional communication between the gastrointestinal tract and brain, the so-called microbiota-gut-brain axis, are hypothesized, which may be involved in the etiology of several mental disorders. Recent reports suggest that Candida, particularly Candida albicans, growth in intestines may cause lower absorption of carbohydrates and minerals and higher toxin levels which are thought to contribute autistic behaviors. The aim of this study was to identify the 3-year deposited yeasts isolated from stool samples of children with diagnosed or suspected ASD and to determine in vitro activity of nystatin and fluconazole against these isolates using Clinical Laboratory Standards Institute M27-A3 guidelines. A 17-year retrospective assessment was also done using our laboratory records. Among the species identified, intrinsically fluconazole-resistant Candida krusei (19.8 %) and Candida glabrata (14.8 %) with elevated MICs were remarkable. Overall, C. albicans (57.4 %) was the most commonly isolated species in 17 years. The species identification and/or antifungal susceptibility tests have to be performed using the strain isolated from stool sample, to select the appropriate antifungal agent, if antimycotic therapy is needed.

Draft Genome Sequences of Escherichia coli O157:H7 Strains Rafaela_II (Clade 8) and 7.1_Anguil (Clade 6) from Cattle in Argentina.

Escherichia coli O157:H7 is a major etiologic agent of diseases in humans that cause diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome. Here, we report the draft genome sequences of two strains isolated from cattle that had high levels of Shiga toxin 2 and high lethality in mice.

Pod and seed defensive coloration (camouflage and mimicry) in the genus Pisum

The small genusPisumis composed of two annual species,P.fulvumand the domesticated peaP.sativum. The domesticated pea has two main wild-type taxa:P.elatiusandP.humile. Members of the genusPisumare not well defended from herbivory by high levels of toxins like the seeds of many other legume species. We studied the color patterns in the pods and seeds of these three wild taxa (P.fulvum,P.elatiusandP.humile) in order to examine their potential for defensive coloration (camouflage and Batesian mimicry). All three taxa are polymorphic concerning pod and seed coloration. The mature pods of many individuals ofP.humileandP.elatiusmimic aposematic caterpillars, but some are plain green. The pods of some individuals ofP.elatiushave a zigzag or straight red marking along them that resembles the conspicuous dorsal markings of the local common venomous viper, potentially mimicking it. The pods of many individuals ofP.fulvumhave dark blotches that when compared to such patterns in animals, potentially function as camouflage. The seeds of all three species are camouflaged by either: (1) color matching with that of soil (especiallyP.fulvumandP.elatius), (2) disruptive coloration (especiallyP.humile), (3) variability in seed-coat color that may undermine the use of search images by visually oriented granivores that look for cryptic seeds (all taxa). The mature pods ofP.fulvumare also defended in many inflorescences by degenerated flowers that develop into sharp thorns. It seems that this species is still in the process of evolving this mechanical defense as the response to millennia of strong grazing pressure.

Effects of Uremic Toxins from the Gut Microbiota on Bone: A Brief Look at Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) frequently have mineral and bone disorders (CKD-MBD) that are caused by several mechanisms. Recent research has suggested that uremic toxins from the gut such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS) could also be involved in the development of bone disease in patients with CKD. IS and PCS are produced by microbiota in the gut, carried into the plasma bound to serum albumin, and are normally excreted into the urine. However, in patients with CKD, there is an accumulation of high levels of these uremic toxins. The exact mechanisms of action of uremic toxins in bone disease remain unclear. The purpose of this brief review is to discuss the link between uremic toxins (IS and PCS) and bone mineral disease in chronic kidney disease.

Quantitation of multiple mycotoxins and cyanogenic glucosides in cassava samples from Tanzania and Rwanda by an LC-MS/MS-based multi-toxin method

A multi-mycotoxin method based on liquid chromatography/tandem mass spectrometry (LC-MS/MS) was used for a mycotoxin survey in 627 samples of processed cassava collected from different districts across Tanzania and Rwanda after the method performance for this matrix had been determined. Matrix effects as well as extraction efficiencies were found to be similar to most other previously investigated matrices with the exception of distinct matrix effects in the negative ionisation mode for early eluting compounds. Limits of detection were far below the regulatory limits set in the European Union for other types of commodities. Relative standard deviations were generally lower than 10% as determined by replicates spiked on two concentration levels. The sample-to-sample variation of the apparent recoveries was determined for 15 individually spiked samples during three different analytical sequences. The related standard deviation was found to be lower than 15% for most of the investigated compounds, thus confirming the applicability of the method for quantitative analysis. The occurrence of regulated mycotoxins was lower than 10% (with the exception of zearalenone) and the related limits were exceeded only in few samples, which suggests that cassava is a comparatively safe commodity as regards mycotoxins. The most prevalent fungal metabolites were emodin, kojic acid, beauvericin, tryptophol, 3-nitropropionic acid, equisetin, alternariol methylether, monocerin, brevianamide F, tenuazonic acid, zearalenone, chrysophanol, monilifomin, enniatins, apicidin and macrosporin. The related concentrations exceeded 1 mg kg–1 only in few cases. However, extremely high levels of cyanogenic plant toxins, which had been previously added to the method, were observed in few samples, pointing out the need for improved post-harvest management to decrease the levels of these compounds.

Positive feedbacks between bottom-up and top-down controls promote the formation and toxicity of ecosystem disruptive algal blooms: A modeling study

Harmful algal blooms that disrupt and degrade ecosystems (ecosystem disruptive algal blooms, EDABs) are occurring with greater frequency and severity with eutrophication and other adverse anthropogenic alterations of coastal systems. EDAB events have been hypothesized to be caused by positive feedback interactions involving differential growth of competing algal species, low grazing mortality rates on EDAB species, and resulting decreases in nutrient inputs from grazer-mediated nutrient cycling as the EDAB event progresses. Here we develop a stoichiometric nutrient–phytoplankton–zooplankton (NPZ) model to test a conceptual positive feedback mechanism linked to increased cell toxicity and resultant decreases in grazing mortality rates in EDAB species under nutrient limitation of growth rate. As our model EDAB alga, we chose the slow-growing, toxic dinoflagellate Karenia brevis, whose toxin levels have been shown to increase with nutrient (nitrogen) limitation of specific growth rate. This species was competed with two high-nutrient adapted, faster-growing diatoms (Thalassiosira pseudonana and Thalassiosira weissflogii) using recently published data for relationships among nutrient (ammonium) concentration, carbon normalized ammonium uptake rates, cellular nitrogen:carbon (N:C) ratios, and specific growth rate. The model results support the proposed positive feedback mechanism for EDAB formation and toxicity. In all cases the toxic bloom was preceded by one or more pre-blooms of fast-growing diatoms, which drew dissolved nutrients to low growth rate-limiting levels, and stimulated the population growth of zooplankton grazers. Low specific grazing rates on the toxic, nutrient-limited EDAB species then promoted the population growth of this species, which further decreased grazing rates, grazing-linked nutrient recycling, nutrient concentrations, and algal specific growth rates. The nutrient limitation of growth rate further increased toxin concentrations in the EDAB algae, which further decreased grazing-linked nutrient recycling rates and nutrient concentrations, and caused an even greater nutrient limitation of growth rate and even higher toxin levels in the EDAB algae. This chain of interactions represented a positive feedback that resulted in the formation of a high-biomass toxic bloom, with low, nutrient-limited specific growth rates and associated high cellular C:N and toxin:C ratios. Together the elevated C:N and toxin:C ratios in the EDAB algae resulted in very high bloom toxicity. The positive feedbacks and resulting bloom formation and toxicity were increased by long water residence times, which increased the relative importance of grazing-linked nutrient recycling to the overall supply of limiting nutrient (N).

Detection of persistent microcystin toxins at the land–sea interface in Monterey Bay, California

Blooms of toxin-producing Microcystis aeruginosa occur regularly in freshwater systems throughout California, but until recently potential impacts in the coastal ocean have been largely ignored. Twenty-one sites in and around Monterey Bay were surveyed for evidence of microcystin toxin (2010–2011) at the land–sea interface. Following this initial survey four major watersheds in the Monterey Bay area were surveyed (2011–2013) for microcystin concentration, nutrients, alkalinity and water temperature to identify potential environmental factors correlated with the abundance of microcystin at the land–sea interface. During the first year microcystin was detected in 15 of 21 sites. Data from years two and three were analyzed by principal components analysis and mixed effects model. Results indicated that coastal nutrient loading (nitrate, phosphate silicate, ammonium, urea), were statistically significant predictors of the microcystin concentrations in the watersheds with clear evidence for seasonality at some sites. Microcystin was frequently at highest concentration in the autumn; however, at some locations high levels of toxin were measured during spring. Because this toxin has the ability to biomagnify and persist within food webs, elevated levels within the watershed may decrease potential for health and survival of wildlife and humans exposed to freshwater and marine waters. The widespread occurrence of microcystin at low to moderate levels throughout the year and throughout the sampled watersheds demonstrates the potential difficulty for management.

Staphylococcus aureus in vitro secretion of alpha toxin (hla) correlates with the affiliation to clonal complexes.

The alpha toxin of Staphylococcus aureus is a pore forming toxin that penetrates host cell membranes causing osmotic swelling, rupture, lysis and subsequently cell death. Haemolysin alpha is toxic to a wide range of different mammalian cells; i.e., neurotoxic, dermonecrotic, haemolytic, and it can cause lethality in a wide variety of animals. In this study, the in vitro alpha toxin production of 648 previously genotyped isolates of S. aureus was measured quantitatively using antibody microarrays. Isolates originated from medical and veterinary settings and were selected in order to represent diverse clonal complexes and defined clinical conditions. Generally, the production of alpha toxin in vitro is related to the clonal complex affiliation. For clonal complexes CC22, CC30, CC45, CC479, CC705 and others, invariably no alpha toxin production was noted under the given in vitro conditions, while others, such as CC1, CC5, CC8, CC15 or CC96 secreted variable or high levels of alpha toxin. There was no correlation between alpha toxin yield and clinical course of the disease, or between alpha toxin yield and host species.

Efficacy of surotomycin in an in vitro gut model of Clostridium difficile infection.

We investigated the efficacy of the cyclic lipopeptide surotomycin in treating clindamycin-induced Clostridium difficile infection (CDI) using an in vitro gut model. Two three-stage chemostat gut models were inoculated with human faeces, spiked with C. difficile spores (∼10(7) cfu/mL, PCR ribotype 027 or 001). Clindamycin (33.9 mg/L, four times daily for 7 days) was dosed to induce CDI. Following high-level toxin production, surotomycin (250 mg/L, twice daily for 7 days) was instilled. Microflora populations, C. difficile vegetative cells and spores, cytotoxin titres and antimicrobial levels (LC-MS/MS and bioassay) were determined. The emergence of C. difficile and enterococci with reduced susceptibility to surotomycin was monitored on breakpoint agar (4 × MIC). Counts of viable C. difficile were reduced to near the limit of detection on Days 1 and 3 of surotomycin instillation, and cytotoxin was undetectable on Days 3 and 4 of surotomycin instillation in the 027 and 001 models, respectively. Recurrence of vegetative growth and toxin production occurred 11 days (001 model) and 15 days (027 model) after surotomycin instillation had ceased, and remained for the duration of the experiment. Surotomycin instillation decreased populations of bifidobacteria, clostridia, enterococci and lactobacilli, but was sparing of Bacteroides fragilis group populations. All enumerated organisms had recovered to steady-state levels by 3 weeks post-surotomycin instillation. No evidence of the emergence of reduced susceptibility to surotomycin was observed. Surotomycin successfully reduced C. difficile vegetative cell counts and toxin levels in the gut model and was sparing of B. fragilis group populations. There was no evidence of decreased susceptibility to surotomycin during exposure or post-exposure.

Targeted Silencing of Anthrax Toxin Receptors Protects against Anthrax Toxins

Anthrax spores can be aerosolized and dispersed as a bioweapon. Current postexposure treatments are inadequate at later stages of infection, when high levels of anthrax toxins are present. Anthrax toxins enter cells via two identified anthrax toxin receptors: tumor endothelial marker 8 (TEM8) and capillary morphogenesis protein 2 (CMG2). We hypothesized that host cells would be protected from anthrax toxins if anthrax toxin receptor expression was effectively silenced using RNA interference (RNAi) technology. Thus, anthrax toxin receptors in mouse and human macrophages were silenced using targeted siRNAs or blocked with specific antibody prior to challenge with anthrax lethal toxin. Viability assays were used to assess protection in macrophages treated with specific siRNA or antibody as compared with untreated cells. Silencing CMG2 using targeted siRNAs provided almost complete protection against anthrax lethal toxin-induced cytotoxicity and death in murine and human macrophages. The same results were obtained by prebinding cells with specific antibody prior to treatment with anthrax lethal toxin. In addition, TEM8-targeted siRNAs also offered significant protection against lethal toxin in human macrophage-like cells. Furthermore, silencing CMG2, TEM8, or both receptors in combination was also protective against MEK2 cleavage by lethal toxin or adenylyl cyclase activity by edema toxin in human kidney cells. Thus, anthrax toxin receptor-targeted RNAi has the potential to be developed as a life-saving, postexposure therapy against anthrax.

Electronic Cigarettes May Be Gateway to Tobacco Smoking

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessElectronic Cigarettes May Be Gateway to Tobacco SmokingVabren WattsVabren WattsSearch for more papers by this authorPublished Online:14 Apr 2014https://doi.org/10.1176/appi.pn.2014.4b6AbstractThe popularity of electronic cigarettes may threaten the success of the decades-long battle against tobacco use in the United States.Marc Bruxelle/ShutterstockElectronic cigarettes (e-cigarettes) are marketed to help people quit smoking regular cigarettes and reduce addiction to nicotine, but a new study published March 14 in JAMA Pediatrics demonstrates that it may be doing the opposite in some adolescents.Researchers from the Center for Tobacco Control Research and Education at the University of California, San Francisco (UCSF), conducted the first published analysis of the relationship between e-cigarette use and conventional smoking among adolescents in the United States. “Despite claims that e-cigarettes are helping people quit smoking, we found that e-cigarettes were associated with more, not less, cigarette smoking among adolescents,” said Lauren Dutra, Sc.D., lead author and a postdoctoral fellow at UCSF. E-cigarettes are cigarette-like mechanical devices that vaporize a liquid form of nicotine without the smoky smell and high levels of toxins associated with conventional cigarette smoking, the authors noted. The devices are being aggressively promoted by tobacco manufacturers as a smoking-cessation aid and safer alternative to cigarettes. The advertisements can be seen on the Internet and even traditional media channels, which banned cigarette advertisements more than 40 years ago.“This is an exploding product on the market—being marketed to both adults and youth,” said Douglas Ziedonis, M.D., M.P.H., a substance abuse expert and chair of the Department of Psychiatry at the University of Massachusetts Medical School. “Flavors, such as cinnamon apple and strawberry, and the vibrant colors in which e-cigarettes are sold, make them appealing to children and teens.” Douglas Ziedonis, M.D., M.P.H., says that the scientific community is finally beginning to question the safety and long-term effects of electronic cigarettes.University of MassachusettsZiedonis told Psychiatric News that until recently, e-cigarettes—which are unregulated by the Food and Drug Administration—have received very minimal academic press. “The scientific community is beginning to become aware of e-cigarettes and ask a lot more questions about the harms or benefits of these products. Research is telling us that we need to treat e-cigarettes and other nicotine vapor products as we do cigarettes.”In the UCSF study, data were gathered from the nearly 40,000 middle-school and high-school youth who completed the National Tobacco Youth Survey in 2011 and 2012. Adolescents were surveyed on their tobacco use—including cigarettes, smokeless tobacco products, and emerging tobacco products—within the prior 30 days. The analysis showed that e-cigarette use among the students doubled within one year, from 3.1 percent to 6.5 percent. One troubling finding was that the use of e-cigarettes was associated with an increased risk of beginning to smoke conventional cigarettes. In addition, many of the e-cigarette users indicated that they were using regular cigarettes along with the new products.Ziedonis said that the study’s findings illustrate that once an individual begins using nicotine products and becomes addicted to nicotine, that person is likely to desire the “full range” of effects, which are provided by regular cigarette smoking. Jill Williams, M.D., director of the Division of Addiction Psychiatry at Rutgers University Robert Wood Johnson Medical School and an expert in nicotine addiction, told Psychiatric News that these findings are particularly concerning since the rates of conventional smoking have been declining to record lows over the last several years.Jill Williams, M.D., believes that physicians should be skeptical of defining electronic cigarettes as a smoking cessation aid, since these claims have not been approved by the Food and Drug Administration.Rutgers University Robert Wood Johnson Medical School“Behavioral health professionals, including psychiatrists, should do more to assess and treat their adolescent and adult patients for tobacco dependence, just as they would for any other substance use disorder,” said Williams, who emphasized that e-cigarettes should not be used as a cessation aid, since they have not been evaluated with the same level of rigor as evidence-based approaches to smoking cessation. “The exact chemical components of the vapor are largely unknown and can vary among devices and manufacturers. . . and we should remain skeptical” of their value in smoking-cessation programs. Williams stressed that if e-cigarettes continue to go unregulated, their growing popularity has the potential to undo decades of progress in reducing tobacco use by making smoking more attractive to youth and those with nicotine addiction.The UCSF study was funded by the National Cancer Institute. ■An abstract of “Electronic Cigarettes and Conventional Cigarette Use Among U.S. Adolescents” can be accessed here. ISSUES NewArchived

Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails.

Venomous animals are thought to inject the same combination of toxins for both predation and defence, presumably exploiting conserved target pharmacology across prey and predators. Remarkably, cone snails can rapidly switch between distinct venoms in response to predatory or defensive stimuli. Here, we show that the defence-evoked venom of Conus geographus contains high levels of paralytic toxins that potently block neuromuscular receptors, consistent with its lethal effects on humans. In contrast, C. geographus predation-evoked venom contains prey-specific toxins mostly inactive at human targets. Predation- and defence-evoked venoms originate from the distal and proximal regions of the venom duct, respectively, explaining how different stimuli can generate two distinct venoms. A specialized defensive envenomation strategy is widely evolved across worm, mollusk and fish-hunting cone snails. We propose that defensive toxins, originally evolved in ancestral worm-hunting cone snails to protect against cephalopod and fish predation, have been repurposed in predatory venoms to facilitate diversification to fish and mollusk diets.