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Secretion systems play a crucial role in microbe-microbe or host-microbe interactions. Among these systems, the extracellular contractile injection system (eCIS) is a unique bacterial and archaeal extracellular secretion system that injects protein toxins into target organisms. However, the specific proteins that eCISs inject into target cells and their functions remain largely unknown. Here, we developed a machine learning classifier to identify eCIS-associated toxins (EATs). The classifier combines genetic and biochemical features to identify EATs. We also developed a score for the eCIS N-terminal signal peptide to predict EAT loading. Using the classifier we classified 2,194 genes from 950 genomes as putative EATs. We validated four new EATs, EAT14-17, showing toxicity in bacterial and eukaryotic cells, and identified residues of their respective active sites that are critical for toxicity. Finally, we show that EAT14 inhibits mitogenic signaling in human cells. Our study provides insights into the diversity and functions of EATs and demonstrates machine learning capability of identifying novel toxins. The toxins can be employed in various applications dependently or independently of eCIS. Synopsis: Toxins delivered by the extracellular contractile injection system (eCIS) of 950 microbial genomes were identified using XGBoost classifier algorithm, four of which were experimentally confirmed and functionally characterized. eCIS is a poorly studied microbial toxin delivery system encoded by many environmental microbes. The first algorithm for predicting eCIS-associated toxins (EATs) was developed using genomic and biochemical features, and was used to identify ~2,200 EATs from 950 genomes. Features characterizing the N terminal signal peptide of EATs were identified and combined into a signal peptide score. Four new EATs genes (EAT14-17) were experimentally validated as being toxins, and critical EAT residues within the predicted catalytic sites were identified. EAT14 inhibits SRE-dependent mitogenic signaling in HEK293T cells. Toxins delivered by the extracellular contractile injection system (eCIS) of 950 microbial genomes were identified using XGBoost classifier algorithm, four of which were experimentally confirmed and functionally characterized. [ABSTRACT FROM AUTHOR]

Zeugodacus cucurbitae (Coquillett) (Diptera: Tephritidae) is a serious agro‐economic pest of cucurbits around the world. Management of tephritid fruit flies is till date mainly dependent on the use of chemical pesticides. In a rising concern about environment quality and rapid development of resistance in insect pests, biological control of insect pests is being contemplated, and in response, research approaches are constantly evolving. Various naturally occurring control agents of melon fruit fly such as parasitoids, bacteria, fungi and nematodes have potential in the management of Z. cucurbitae. Many parasitoids including Psyttalia fletcheri, Fopius arisanus, Dirhinus giffardii and Spalangia endius are known to attack various life stages of Z. cucurbitae. Although parasitoids are being principally exploited for control of Z. cucurbitae, various other entomopathogens such as fungi (Beauveria bassiana, Paecilomyces fumosoroseus, Metarhizium anisopliae), bacteria (Bacillus thuringiensis), nematodes (Heterorhabditis indica, Steinernema feltiae) and microbial toxins/products (spinosad, avermectin) are being investigated or used for biological control. The development of farming methodologies with greater credence on ecosystem services such as biological control of Z. cucurbitae will increase sustainability of agroecosystems. This review provides a concise compilation of these biological control agents along with their effectiveness and will help researchers in designing various integrated pest management strategies against Z. cucurbitae that involve biological control agents. [ABSTRACT FROM AUTHOR]

Foodborne pathogens and microbial toxins are the main causes of foodborne illness. However, trace pathogens and toxins in foods are difficult to detect. Thus, techniques for their rapid and sensitive identification and quantification are urgently needed. Phages can specifically recognize and adhere to certain species of microbes or toxins due to molecular complementation between capsid proteins of phages and receptors on the host cell wall or toxins, and thus they have been successfully developed into a detection platform for pathogens and toxins. This review presents an update on phage‐based luminescent detection technologies as well as their working principles and characteristics. Based on phage display techniques of temperate phages, reporter gene detection assays have been designed to sensitively detect trace pathogens by luminous intensity. By the host‐specific lytic effects of virulent phages, enzyme‐catalyzed chemiluminescent detection technologies for pathogens have been exploited. Notably, these phage‐based luminescent detection technologies can discriminate viable versus dead microbes. Further, highly selective and sensitive immune‐based assays have been developed to detect trace toxins qualitatively and quantitatively via antibody analogs displayed by phages, such as phage‐ELISA (enzyme‐linked immunosorbent assay) and phage‐IPCR (immuno‐polymerase chain reaction). This literature research may lead to novel and innocuous phage‐based rapid detection technologies to ensure food safety. [ABSTRACT FROM AUTHOR]

The human microbiome is essential for the correct functioning of many host physiological processes, including metabolic regulation and immune responses. Increasing evidence indicates that the microbiome may also influence cancer development, progression, and the response to therapy. Although most studies have focused on the effect of the gut microbiome, many other organs such as the skin, vagina, and lungs harbor their own microbiomes that are different from the gut. Tumor development has been associated with dysbiosis not only in the gut but also in the tissue from which the tumor originated. Furthermore, the intratumoral microbiota has a distinct signature in each tumor type. Here, we review the mechanisms by which the organ-specific microbiome can contribute to carcinogenesis: release of toxins that cause DNA damage and barrier failure; alteration of immune responses to create a local inflammatory or immunosuppressive environment; and regulation of nutrient levels in the tumor microenvironment through metabolite production and consumption. Solving the puzzle of how the microbiome influences the carcinogenesis process and treatment response requires an understanding of the two ways the microbiome can interact with cancer cells and the tumor microenvironment: through systemic effects exerted by the gut microbiota and local effects of the intratumoral microbiota. [ABSTRACT FROM AUTHOR]

The 2021 Annual Review Issue of The Journal of Pathology contains 14 invited reviews on current research areas of particular importance in pathology. The subjects included here reflect the broad range of interests covered by the journal, including both basic and applied research fields but always with the aim of improving our understanding of human disease. This year, our reviews encompass the huge impact of the COVID‐19 pandemic, the development and application of biomarkers for immune checkpoint inhibitors, recent advances in multiplexing antigen/nucleic acid detection in situ, the use of genomics to aid drug discovery, organoid methodologies in research, the microbiome in cancer, the role of macrophage‐stroma interactions in fibrosis, and TGF‐β as a driver of fibrosis in multiple pathologies. Other reviews revisit the p53 field and its lack of clinical impact to date, dissect the genetics of mitochondrial diseases, summarise the cells of origin and genetics of sarcomagenesis, provide new data on the role of TRIM28 in tumour predisposition, review our current understanding of cancer stem cell niches, and the function and regulation of p63. The reviews are authored by experts in their field from academia and industry, and provide comprehensive updates of the chosen areas, in which there has been considerable recent progress. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Cystic fibrosis transmembrane conductance regulator (CFTR) is an unusual ABC transporter. It acts as an anion‐selective channel that drives osmotic fluid transport across many epithelia. In the gut, CFTR is crucial for maintaining fluid and acid‐base homeostasis, and its activity is tightly controlled by multiple neuro‐endocrine factors. However, microbial toxins can disrupt this intricate control mechanism and trigger protracted activation of CFTR. This results in the massive faecal water loss, metabolic acidosis and dehydration that characterize secretory diarrhoeas, a major cause of malnutrition and death of children under 5 years of age. Compounds that inhibit CFTR could improve emergency treatment of diarrhoeal disease. Drawing on recent structural and functional insight, we discuss how existing CFTR inhibitors function at the molecular and cellular level. We compare their mechanisms of action to those of inhibitors of related ABC transporters, revealing some unexpected features of drug action on CFTR. Although challenges remain, especially relating to the practical effectiveness of currently available CFTR inhibitors, we discuss how recent technological advances might help develop therapies to better address this important global health need. [ABSTRACT FROM AUTHOR]

Background: Screening for Clostridioides difficile (CD) colonization can be performed using molecular testing to identify the presence of microbial DNA of the toxin gene. Colonization rates for hospitalized patients are as high as 20% and may be considerably higher in solid organ transplant (SOT) recipients. Treatment for CD should be based on clinical disease and not colonization, yet clinicians may misinterpret a positive CD screen resulting in overtreatment. Objectives: The objective of this analysis is to determine how often positive CD screens resulted in inappropriate treatment with oral vancomycin. Methods: Clostridioides difficile screens were performed using the Xpert C difficile assay (Cepheid), a nucleic acid amplification testing method utilizing polymerase chain reaction (PCR), on peri‐rectal swabs for newly admitted patients. This was a single‐center cohort study of adult patients with CD screens hospitalized between July 2015 and November 2018. The primary outcome was the rate of inappropriate oral vancomycin treatment in all patients and in SOT recipients, defined as therapy in the absence of diarrhea. Results: Of the 47 076 total CD screens reviewed, 1,921 were positive. In the SOT cohort, 58 of 329 screens were positive (4.1% vs 17.9%, P <.01). Of all patients with a positive CD screen, 20.1% (386/1921) were treated with oral vancomycin within 48 hours of swab collection. In the SOT cohort, 39.6% (23/58) with positive CD screens were treated with oral vancomycin within 48 hours. Of the SOT patients who received oral vancomycin, 39% (9/23) did not have true CD infection. Conclusion: Solid organ transplant recipients were more likely to have CD colonization detected by peri‐rectal screening than the general inpatient population. SOT and non‐SOT patients were treated with oral vancomycin at similar rates in response to the positive screen. Nearly half of the oral vancomycin use in SOT recipients was likely overtreatment, but this finding is limited by the low number of patients in this cohort. [ABSTRACT FROM AUTHOR]

Challenges to ensiling are coming from a wide spectrum. Faster harvest rates are making it more difficult to achieve target silage densities. Larger harvest equipment is increasing soil compaction and rural road issues. Older silos are too small and are overfilled, creating safety issues, or temporary piles are placed on bare ground permitting soil contamination. Mycotoxins and other pathogens in silages are still a problem. Global warming may affect the forage crops grown and crop characteristics as well as rates of silage fermentation and aerobic deterioration. Silage as an input to bio‐refineries has an unclear future. Silage analysis is challenged by sampling and knowing what components truly predict nutritional value. The future holds many opportunities for both ensiling and silage research. Robotic harvesting will release more labour for silo packing, and there are opportunities to develop tools to estimate silage density during filling. Total mixed ration silages should allow more by‐products in rations. The development of novel silage additives to improve silage hygiene or increase nutrient availability appears promising. Predicting the onset of aerobic deterioration with quick tests for lactate‐assimilating yeasts or silage temperatures seems possible. Metabolomics and metabonomics, in addition to the microbiome tools in development, put us at the cusp of being able to see which microorganisms are active in the silo and rumen and what compounds of significance they are producing. This could lead to many advances in silage quality including reduced microbial toxins, better hygiene and improved utilization by livestock. [ABSTRACT FROM AUTHOR]

Summary: Theabrownins (TB) are polymeric phenolic compounds associated with the multiple bioactivities of Pu‐erh tea, a post‐fermented Chinese dark tea. High‐TB instant Pu‐erh tea was produced via a novel submerged fermentation (SF) using Aspergillus tubingensis and compared with samples produced commercially via the conventional solid‐state fermentation (SSF). Viable microorganisms and microbial toxins, especially aflatoxins B1, G1, B2, G2, cyclopiazonic acid, fumonisins B1, B2, B3 and ochratoxin A, were below the detection limit in all samples. Fewer microbial metabolites were found in SF instant tea compared with the SSF teas. Based on an adult consuming 1 g of instant Pu‐erh tea daily, the dietary intake of investigated elements was below the safe limits recommended by various authorities. Tasters viewed the instant tea infusions as very mild, smooth, mellow and full. This suggested that submerged fermentation using A. tubingensis offers a speedy and safe alternative to commercial production of instant Pu‐erh tea. [ABSTRACT FROM AUTHOR]

When abruptly exposed to toxic levels of hexavalent uranium, the extremely thermoacidophilic archaeon Metallosphaera prunae, originally isolated from an abandoned uranium mine, ceased to grow, and concomitantly exhibited heightened levels of cytosolic ribonuclease activity that corresponded to substantial degradation of cellular RNA. The M. prunae transcriptome during 'uranium-shock' implicated VapC toxins as possible causative agents of the observed RNA degradation. Identifiable VapC toxins and PIN-domain proteins encoded in the M. prunae genome were produced and characterized, three of which (VapC4, VapC7, VapC8) substantially degraded M. prunae rRNA in vitro. RNA cleavage specificity for these VapCs mapped to motifs within M. prunae rRNA. Furthermore, based on frequency of cleavage sequences, putative target mRNAs for these VapCs were identified; these were closely associated with translation, transcription, and replication. It is interesting to note that Metallosphaera sedula, a member of the same genus and which has a nearly identical genome sequence but not isolated from a uranium-rich biotope, showed no evidence of dormancy when exposed to this metal. M. prunae utilizes VapC toxins for post-transcriptional regulation under uranium stress to enter a cellular dormant state, thereby providing an adaptive response to what would otherwise be a deleterious environmental perturbation. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON, also known as vomitoxin) is a common mycotoxin found worldwide, especially in contaminated food. DON is toxic to a variety of cells and tissues in humans. Three kinds of conjugated products (DON-3-glucuronide, DON-15-glucuronide and DON-7-glucuronide) can be found as major metabolites in human urine. Females and males show different patterns of exposure levels, and human exposure to DON also shows some geographical differences because of different DON levels in cereal-based foods, food intake habits and UDP-glucuronosyltransferase expression. Specifically, the C12, 13-deepoxy metabolite was found predominantly in French adults but was rarely detected in UK adults. However, a cohort of Spanish individuals demonstrated even lower DON levels than the levels in the UK populations, whereas a very high DON exposure level was detected in South Africa and Linxian, China. Recent publications have further indicated that DON could be detected in the urine of pregnant women from different countries, which suggests that there is a potential risk to both mothers and foetuses. Additionally, phytochemicals have been shown to be less toxic to cells and laboratory animals in research studies and may also be used as food additives for reducing the toxic effects of DON. In this review, we provide global information on DON metabolism, human exposure and gender differences in humans. Also, control strategies for this mycotoxin are discussed. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The synthesis of partially hydrolyzed fumonisins (PHFB1 and PHFB2) and hydrolyzed fumonisins (HFB1 and HFB2) by chemical hydrolysis of pure fumonisins (FB1 and FB2) is reported together with the isolation and characterization by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Two structural isomers of partially hydrolyzed forms of FB1 and FB2 were identified, namely PHFB1a and PHFB1b and PHFB2a and PHFB2b. Reaction yields were 21% for PHFB1 (sum of the two isomers), 52% for HFB1, 31% for PHFB2 (sum of the two isomers) and 30% for HFB2. Purity of each isolated compound was >98%. An LC-HRMS method for the simultaneous determination of fumonisins and their partially and totally hydrolyzed derivatives was applied to 24 naturally contaminated samples of maize and maize-based products. The majority of samples (18 out of 24) were contaminated with fumonisins B1 and B2. Fumonisins co-occurred with both partially hydrolyzed and hydrolyzed fumonisins in four nixtamalized samples (three masa flours and one tortilla chips). Co-occurrence of fumonisins with partially hydrolyzed fumonisins was also recorded in one sample of maize kernels and four samples of maize-based products (i.e. maize meal, cous-cous, corn-cakes and cornflakes). Mycotoxins levels ranged from 60 to 5700 µg/kg for fumonisins (sum of FB1 and FB2), from 10 to 210 µg/kg for partially hydrolyzed fumonisins (sum of PHFB1 and PHFB2) and from 30 to 200 µg/kg for hydrolyzed fumonisins (sum of HFB1 and HFB2). This is the first report of the isolation of PHFB2 and the co-occurrence of FB1, FB2, PHFB1, PHFB2, HFB1 and HFB2 in maize products. Considering the growing use of nixtamalized and maize-based products, the monitoring of fumonisins and their partially and totally hydrolyzed forms in these products may represent an important contributing factor in evaluating the relevant human risk exposure. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND Specific screening methods for complex food matrices are needed that enable unambiguous and sensitive detection of bio threat agents ( BTAs) such as Bacillus anthracis spores and microbial toxins (e.g. staphylococcal enterotoxin B ( SEB) and clostridial botulinum neurotoxins ( BoNTs)). The present study describes an image-based 96-well Meso Scale Discovery ( MSD) electrochemiluminescence ( ECL) assay for simultaneous detection of BTAs in dairy milk products. RESULTS The limit of detection of this ECL assay is 40 pg mL−1 for BoNT/A complex, 10 pg mL−1 for SEB and 40 000 CFU mL−1 for Bacillus anthracis spores in dairy milk products. The ECL assay was successfully applied to screen type A Clostridium botulinum outbreak strains. CONCLUSION The results of the study indicate that this ECL assay is very sensitive, rapid (<6 h) and multiplex in nature. The ECL assay has potential for use as an in vitro screening method for BTAs over other comparable immunoassays. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Micro-organisms are known to degrade a wide range of toxic substances. How the environment shapes microbial communities in polluted ecosystems and thus influences degradation capabilities is not yet fully understood. In this study, we investigated microbial communities in a highly complex environment: the capillary fringe and subjacent sediments in a hydrocarbon-contaminated aquifer. Sixty sediment sections were analysed using terminal restriction fragment length polymorphism ( T-RFLP) fingerprinting, cloning and sequencing of bacterial and archaeal 16 S rRNA genes, complemented by chemical analyses of petroleum hydrocarbons, methane, oxygen and alternative terminal electron acceptors. Multivariate statistics revealed concentrations of contaminants and the position of the water table as significant factors shaping the microbial community composition. Micro-organisms with highest T-RFLP abundances were related to sulphate reducers belonging to the genus Desulfosporosinus, fermenting bacteria of the genera Sedimentibacter and Smithella, and aerobic hydrocarbon degraders of the genus Acidovorax. Furthermore, the acetoclastic methanogens Methanosaeta, and hydrogenotrophic methanogens Methanocella and Methanoregula were detected. Whereas sulphate and sulphate reducers prevail at the contamination source, the detection of methane, fermenting bacteria and methanogenic archaea further downstream points towards syntrophic hydrocarbon degradation. [ABSTRACT FROM AUTHOR]

SUMMARY Tadpoles of Rana grylio were raised as edible frogs in fishponds of Guanqiao in Wuhan City, Hubei, China, during cyanobacterial blooms from June to October. The dominant cyanobacterial species was Microcystis, which was found to be lethally toxic by intraperitoneal (i.p.) mouse bioassay. Little is known about the effect of tadpoles on toxic cyanobacterial blooms. To evaluate the potential of the tadpoles to graze on cyanobacterial blooms, the tadpoles were fed on Microcystis collected from the field in the laboratory. The Microcystis cells decreased from 1.19 × 107 cells mL−1 to 3.23 × 106 cells mL−1, with a sharp reduction of 73% of the initial Microcystis population observed in the first 24 h after introduction of the tadpoles. The ponds containing tadpoles had a markedly lower density of Microcystis than those lacking tadpoles. Tadpoles exposed to either cultured Microcystis aeruginosa (NIES-90, 2.768 µg microcystins mg-1 dw-1) cells or lysed M. aeruginosa cells grew well, however, indicating that they were unaffected by Microcystis toxins. We found a significant increase in tadpole body weight after feeding on either field Microcystis or cultured M. aeruginosa. The mean increase in individual body weight was 20 mg day−1 when fed on Microcystis from the pond, and 7 mg day−1 when fed on M. aeruginosa from culture. Our study strongly suggested that there is a direct trophic relationship between R. grylio tadpoles and toxic Microcystis blooms and they possess the potential to graze on toxic Microcystis. The results imply that R. grylio tadpoles may play an important ecological role in reducing toxic cyanobacterial blooms caused by Microcystis. [ABSTRACT FROM AUTHOR]

Summary Carboxy-terminus of merozoite surface protein-1 (MSP-119) is the major protein on the surface of the plasmodial merozoite that acts as one of the most important blood-stage vaccine candidates. The present investigation was designed to evaluate the immune responses when either two recombinant antigens (rPvMSP-119 + rPfMSP-119) or two plasmid constructs (pcDNA3.1 hygro-PvMSP-119 + pcDNA3.1 hygro-PfMSP-119) were administered in combination at a single site in mice by using different immunization strategies (protein/protein, DNA/DNA and DNA/protein) at weeks 0, 5 and 8. All mice were monitored for the level of MSP-119-specific antibody for up to 40 weeks. The inclusion of both recombinant antigens in a vaccine mixture could not inhibit induction of antibodies to the other antigen when the two recombinant antigens were combined in immunization formulation. Interestingly, antisera from immunized mice with either recombinant antigen failed to cross-react with heterologous antigen. Moreover, the results of this study showed that co-immunization with both antigens at a single site generated a substantial PvMSP-119- and PfMSP-119-specific antibody responses and also IFN-γ cytokine production (Th1 response) in DNA/protein prime-boost immunization strategies. The increased humoral response to PvMSP-119 and PfMSP-119 lasted nearly a year after immunization. Therefore, the results of this study are encouraging for the development of multi-species malaria vaccine based on MSP-119 antigen. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

The second in this series of clinical reviews on neurological diseases in ruminant livestock in Australia examines toxic disorders associated with plant and microbial toxins as well as the neurological effects of vitamin and mineral deficiencies. The aim of these reviews is to assist in the surveillance of neurological diseases, especially the transmissible spongiform encephalopathies. [ABSTRACT FROM AUTHOR]

ADP-ribosylation of host cell proteins is a common mode of cell intoxication by pathogenic bacterial toxins. Antibodies induced by immunization with inactivated ADP-ribosylating toxins provide efficient protection in case of some secreted toxins, e.g., diphtheria and pertussis toxins. However, other ADP-ribosylating toxins, such as Salmonella SpvB toxin, are secreted directly from the Salmonella-containing vacuole into the cytosol of target cells via the SPI-2 encoded bacterial type III secretion system, and thus are inaccessible to conventional antibodies. Small-molecule ADP-ribosylation inhibitors are fraught with potential side effects caused by inhibition of endogenous ADP-ribosyltransferases. Here, we report the development of a single-domain antibody from an immunized llama that blocks the capacity of SpvB to ADP-ribosylate actin at a molar ratio of 1:1. The single-domain antibody, when expressed as an intrabody, effectively protected cells from the cytotoxic activity of a translocation-competent chimeric C2IN-C/SpvB toxin. Transfected cells were also protected against cytoskeletal alterations induced by wild-type SpvB-expressing strains of Salmonella. This proof of principle paves the way for developing new antidotes against intracellular toxins. [ABSTRACT FROM AUTHOR]

Streptococci secrete a large number of exoproteins including virulence-associated toxins and enzymes. To construct a reliable database of streptococcal exoproteins, we integrated the results that were derived from two approaches: LC-based shotgun proteomic analysis and 2-D PAGE-based proteomic analysis. We identified 74 and 82 proteins by LC-based and gel-based analysis, respectively. Forty-five proteins were identified by both methods. In addition, two proteins, one identified by both methods and the other only by LC-based shotgun analysis, were newly annotated. We therefore found the importance of combinational analysis by the two methods for the construction of a more reliable database. [ABSTRACT FROM AUTHOR]

Microbiological populations in natural and engineered systems may experience multiple exposures to chemical stressors, which may affect system functions. The impact of such exposures on the metabolism of a population of Pseudomonas aeruginosa was studied using respirometry. Two serial exposures to low concentrations of 2,4-dinitrophenol (DNP), pentachlorophenol (PCP), or N-ethyl maleimide (NEM) did not affect metabolism beyond that expected for a single exposure. However, at higher concentrations, three exposures to DNP led to a combination of metabolic stress and resilience in the population. At a low DNP concentration of 400 mg/L, multiple exposures led to increased stress but indicated no development of resilience. At a high DNP concentration of 1,200 mg/L, no biological activity was observed, indicating that the population did not survive the exposure. At intermediate concentrations of 800 and 900 mg/L DNP, stress was observed, but it was found to decrease after multiple exposures. This, combined with the observation that the size of the population decreased, indicated that resilience in the population had developed because of elimination of the weaker organisms in the population. In contrast, the lack of resilience at the lower DNP concentration was attributed to the survival of the strong as well as weak members, lowering the resilience of the population as a whole. The development of resilience within a window of stressor concentrations is an important finding with implications for predicting the performance of biotreatment processes and biosensor technologies and for interpreting ecotoxicity risk assessments. Environ. Toxicol. Chem. 2010;29:2161-2168. © 2010 SETAC [ABSTRACT FROM AUTHOR]

Cytolethal distending toxins (CDTs) are proteins produced and secreted by facultative pathogenic strains of Gram-negative bacteria with potentially genotoxic effects. Mammalian cells exposed to CDTs undergo cell type-dependent cell-cycle arrest or apoptosis; however, the cell fate responses to such intoxication are mechanistically incompletely understood. Here we show that both normal and cancer cells (BJ, IMR-90 and WI-38 fibroblasts, HeLa and U2-OS cell lines) that survive the acute phase of intoxication by Haemophilus ducreyi CDT possess the hallmarks of cellular senescence. This characteristic phenotype included persistently activated DNA damage signalling (detected as 53BP1/γH2AX+ foci), enhanced senescence-associated β-galactosidase activity, expansion of promyelocytic leukaemia nuclear compartments and induced expression of several cytokines (especially interleukins IL-6, IL-8 and IL-24), overall features shared by cells undergoing replicative or premature cellular senescence. We conclude that analogous to oncogenic, oxidative and replicative stresses, bacterial intoxication represents another pathophysiological stimulus that induces premature senescence, an intrinsic cellular response that may mechanistically underlie the ‘distended’ morphology evoked by CDTs. Finally, the activation of the two anticancer barriers, apoptosis and cellular senescence, together with evidence of chromosomal aberrations (micronucleation) reported here, support the emerging genotoxic and potentially oncogenic effects of this group of bacterial toxins, and warrant further investigation of their role(s) in human disease. [ABSTRACT FROM AUTHOR]

Mycotoxin toxicity occurs at very low concentrations, therefore sensitive and reliable methods for their detection are required. Consequently, sampling and analysis of mycotoxins is of critical importance because failure to achieve a suitable verified analysis can lead to unacceptable consignments being accepted or satisfactory shipments unnecessarily rejected. The general mycotoxin analyses carried out in laboratories are still based on physicochemical methods, which are continually improved. Further research in mycotoxin analysis has been established in such techniques as screening methods with TLC, GC, HPLC, and LC–MS. In some areas of mycotoxin method development, immunoaffinity columns and multifunctional columns are good choices as cleanup methods. They are appropriate to displace conventional liquid–liquid partitioning or column chromatography cleanup. On the other hand, the need for rapid yes/no decisions for exported or imported products has led to a number of new screening methods, mainly, rapid and easy-to-use test kits based on immuno-analytical principles. In view of the fact that analytical methods for detecting mycotoxins have become more prevalent, sensitive, and specific, surveillance of foods for mycotoxin contamination has become more commonplace. Reliability of methods and well-defined performance characteristics are essential for method validation. This article covers some of the latest activities and progress in qualitative and quantitative mycotoxin analysis. [ABSTRACT FROM AUTHOR]

Toxin–antitoxin (TA) systems on the chromosomes of free-living bacteria appear to facilitate cell survival during intervals of stress by inducing a state of reversible growth arrest. However, upon prolonged stress, TA toxin action leads to cell death. They have been implicated in several clinically important phenomena – bacterial persistence during antibiotic treatment, biofilm formation and bacterial pathogenesis – and serve as attractive new antibiotic targets for pathogens. We determined the mode of action of the YafQ toxin of the DinJ–YafQ TA system. YafQ expression resulted in inhibition of translation, but not transcription or replication. Purified YafQ exhibited robust ribonuclease activity in vitro that was specifically blocked by the addition of DinJ. However, YafQ associated with ribosomes in vivo and facilitated rapid mRNA degradation near the 5′ end via cleavage at AAA lysine codons followed by a G or A. YafQ(H87Q) mutants lost toxicity and cleavage activity but retained ribosome association. Finally, LexA bound to the dinJ–yafQ palindrome and triggered module transcription after DNA damage. YafQ function is distinct from other TA toxins: it associates with the ribosome through the 50S subunit and mediates sequence-specific and frame-dependent mRNA cleavage at 5′AAA – G/A3′ sequences leading to rapid decay possibly facilitated by the mRNA degradosome. [ABSTRACT FROM AUTHOR]

Spore formation is a common process in the developmental cycle of fungi. In the yeast Saccharomyces cerevisiae, Ime2 is a key protein kinase for the meiotic cell cycle, which precedes ascospore formation. Here, we analysed the IME2-related imeB gene of the filamentous ascomycete Aspergillus nidulans. imeB deletion strains are retarded in growth and overproduce fertile sexual fruiting bodies in the presence of light, which normally represses sexual development. imeB mutants also display abnormal differentiation of sexual Hülle cells in submerged cultures. Increased sexual development of imeB mutants is dependent on VeA, a component of the heterotrimeric velvet complex. A combined deletion of imeB with the phytochrome fphA, a red light receptor, results in a complete loss of light response, suggesting that ImeB and FphA cooperate in light-mediated inhibition of sexual development. Furthermore, we found that imeB mutants fail to produce the mycotoxin sterigmatocystin, an aflatoxin precursor, and show that ImeB is needed for expression of the sterigmatocystin gene cluster. ImeB contains a TXY motif conserved in mitogen-activated protein kinases. This sequence element is essential for ImeB function. We conclude that ImeB is a mitogen-activated protein kinase-related protein kinase required for the co-ordinated control of light-dependent development with mycotoxin production. [ABSTRACT FROM AUTHOR]

The article discusses the impact of insecticide treatments on Ostrinia nubialis, as well as their influence on the mycotoxin contamination of corn kernels. A study on the European corn borer (ECB) O. nubialis from 2000 to 2006 revealed that, except for 2003, the insecticide had a significant effect on ECB incidence. It was also observed that damage to corn kernels were reduced. Moreover, mycotoxin was reportedly reduced by an average of 68%. It is concluded that insecticide treatment of the second ECB generation can enhance the production of kernels with low fumonisin content.

Pseudomonas fluorescens CHA0 and the related strain Pf-5 are well-characterized representatives of rhizosphere bacteria that have the capacity to protect crop plants from fungal root diseases, mainly by releasing a variety of exoproducts that are toxic to plant pathogenic fungi. Here, we report that the two plant-beneficial pseudomonads also exhibit potent insecticidal activity. Anti-insect activity is linked to a novel genomic locus encoding a large protein toxin termed Fit (for P. luorescens nsecticidal oxin) that is related to the insect toxin Mcf ( akes aterpillars loppy) of the entomopathogen Photorhabdus luminescens, a mutualist of insect-invading nematodes. When injected into the haemocoel, even low doses of P. fluorescens CHA0 or Pf-5 killed larvae of the tobacco hornworm Manduca sexta and the greater wax moth Galleria mellonella. In contrast, mutants of CHA0 or Pf-5 with deletions in the Fit toxin gene were significantly less virulent to the larvae. When expressed from an inducible promoter in a non-toxic Escherichia coli host, the Fit toxin gene was sufficient to render the bacterium toxic to both insect hosts. Our findings establish the Fit gene products of P. fluorescens CHA0 and Pf-5 as potent insect toxins that define previously unappreciated anti-insect properties of these plant-colonizing bacteria. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the effect of zearalenone (zen) and α-zearalenol (α-zen) on the sperm of a boar. Zen, a Fusarium mycotoxin-produced food in cereals and grains, is known to greatly affect pigs. The determination of zen and α-zen is associated with the effect of the genetic material on pig husbandry. The study makes use of four boar semens which zen and α-zen concentration were applied to the samples. A positive result was derived in boar spermatozoa on the aspect of motility, viability and the binding ability of zona.

The article focuses on the methodological research on measuring three airborne mycotoxins and subsequent quantification of the mycotoxin production rate and physical aerosol characteristics. The exposure of individuals to mycotoxins in indoor environments employed as the standard method consists of screening and identifying the toxinogenic strains is presented. The researchers demonstrated that the amount of aerosolized mycotoxins was not proportional to that present on moldy materials. It also shows that the aerosolized mycotoxins could be transported in the alveolar fraction. Moreover, researchers have shown that the entry of mycotoxins into the respiratory tract can cause severe allergies or nonspecific symptoms including headaches, sore throat, and alopecia.

The article presents a study which examines the insecticidal activity of destruxin, a mycotoxin from Metarhizium anisopliae against Spodoptera litura larval stages. The cyclodepsipeptide destruxin was administered by topical application, ingestion and a combination of two in an attempt to minimize the mycotoxin dose for efficient management of the insect pest Spodoptera litura. According to the study, the quantitative differences between destruxins from low- and high-virulence strains of M. anisopliae are in accordance with its presumed role in virulence.

The target lipid model (TLM) was applied to literature data from 10 microbial toxicity assays to provide a quantitative effects assessment framework for wastewater treatment plant organisms. For the nonpolar organic chemicals considered, linear relationships between the logarithm of the median effect concentrations (EC50) and log(KOW) conformed to the TLM for all endpoints with the exception of nitrification inhibition. Additional experimental data for the nitrification inhibition endpoint were generated for 16 narcotic chemicals using a procedure that allowed testing of volatile substances. Results obtained from the present study demonstrated that the nitrification inhibition endpoint was not adequately described by the TLM consistent with previous literature data. Acute to chronic ratios (ACRs) defined as the ratio of the EC50 to the 10% effect concentration (EC10) were available for two of the endpoints investigated and ranged from 1.1 to 2.3 for the Tetrahymena growth assay and from 2.4 to 24.1 for the nitrification inhibition endpoint. No inhibitory effects for any of the microbial endpoints investigated were observed for compounds with log(KOW) >5. The critical target lipid body burdens (C*L ) were calculated for the nine microbial toxicity endpoints conforming C*L to the TLM and ranged from 252 to 2,250 μmol/g octanol. The Microtox® light inhibition (C*L = 252 μmol/g octanol) and C*L Tetrahymena pyriformis growth (C*L = 254 μmol/g octanol) assays were found to be the most sensitive endpoints. The predicted C*L no-effect concentration (PNEC) derived using the HC5 (hazardous concentration to 5% of test organisms) statistical extrapolation procedure was calculated using TLM parameters for substances with log(KOW) from 0 to 5. Results from this analysis demonstrate PNECs for narcotic compounds are protective of wastewater organisms excluding nitrifying bacteria. Further model improvement is needed if protection of nitrifying bacteria in wastewater treatment systems is required. [ABSTRACT FROM AUTHOR]

Aspergillus flavus is an opportunistic pathogen of crops. It is important because it produces aflatoxin as a secondary metabolite in the seeds of a number of crops both before and after harvest. Aflatoxin is a potent carcinogen that is highly regulated in most countries. In the field, aflatoxin is associated with drought-stressed oilseed crops including maize, peanut, cottonseed and tree nuts. Under the right conditions, the fungus will grow and produce aflatoxin in almost any stored crop seed. In storage, aflatoxin can be controlled by maintaining available moisture at levels below that which will support growth of A. flavus. A number of field control measures are being utilized or explored, including: modification of cultural practices; development of resistant crops through molecular and proteomic techniques; competitive exclusion using strains that do not produce aflatoxin; and development of field treatments that would block aflatoxin production. Taxonomy: Aspergillus flavus Link (teleomorph unknown) kingdom Fungi, phyllum Ascomycota, order Eurotiales, class Eurotiomycetes, family Trichocomaceae, genus Aspergillus, species flavus. Host range: Aspergillus flavus has a broad host range as an opportunistic pathogen/saprobe. It is an extremely common soil fungus. The major concern with this fungus in agriculture is that it produces highly carcinogenic toxins called aflatoxins which are a health hazard to animals. In the field, A. flavus is predominantly a problem in the oilseed crops maize, peanuts, cottonseed and tree nuts. Under improper storage conditions, A. flavus is capable of growing and forming aflatoxin in almost any crop seed. It also is a pathogen of animals and insects. In humans it is predominantly an opportunistic pathogen of immunosuppressed patients. Useful websites: , , plantpathology.tamu.edu/aflatoxin, [ABSTRACT FROM AUTHOR]

Fusarium head blight is a major concern for wheat production worldwide. The fungi that cause the disease may infect head tissues from flowering to late stages of kernel development, but a better understanding of the influence of the time of infection on grain weight reduction and mycotoxin accumulation resulting from the infection process is needed. We investigated the influence of wheat reproductive stage at the time of inoculation on disease and grain quality parameters, especially production of deoxynivalenol (DON) in mature grains. Heads of Norm wheat were spray inoculated with a macroconidial suspension of a DON-producing isolate of Fusarium graminearum at each of six reproductive stages from flowering to hard dough. Plants were incubated in a mist chamber for 48 h and then moved to the greenhouse until maturity. Norm wheat was susceptible at all stages inoculated but the highest grain weight reduction and DON accumulation occurred in plants inoculated past flowering to late milk stages. However, high incidences of kernel infection and significant levels of DON accumulation resulted from inoculations as late as the hard dough stage, even though there was no corresponding reduction in grain weight compared to non-inoculated plants. The occurrence of commercially significant levels of DON in plump, high-yielding wheat may result from infections that occur during favourable environments well after the flowering stages. Late infection and DON production should therefore be a future research focus for wheat breeding and integrated management of FHB and an important consideration for grading systems that employ the presence of visibly damaged kernels as a means of estimating DON content of wheat. [ABSTRACT FROM AUTHOR]

Twenty-seven preharvest maize ears affected by Fusarium poae rot (disease score 36–100%) were selected in 1998 and 1999 in Poland and examined for the occurrence of toxic hexadepsipeptides: beauvericin (BEA), enniatin A, enniatin B and enniatin B1. The identification of F. poae was confirmed by sequence analysis of variable internal transcribed spacer regions and compared with NCBI gene bank DNA sequences. Chemical analyses were performed by HPLC-MS. In 27 ears infected by F. poae were detected: BEA (trace to 46 μg/g) in 18 samples, enniatin A (trace to 37 μg/g) in nine samples, enniatin B (trace to 47 μg/g) in 15 samples and enniatin B1 (trace to 25 μg/g) in 12 samples. When 20 strains of F. poae isolated from these samples were cultured on rice, all produced BEA (1.9–75 μg/g), three enniatin A (1.8–2 μg/g), 12 enniatin B (1.1–5.1 μg/g) and eight enniatin B1 (1.2–5.2 μg/g). Occurrence and quantification of enniatin A, enniatin B and enniatin B1 and their co-occurrence with BEA in maize kernels is reported for the first time. [ABSTRACT FROM AUTHOR]

The occurrence of mycotoxins in agricultural commodities is a major health concern for livestock, humans, and the environment. Barley and subsequently malt quality is of fundamental importance to obtain good quality beer. Classical methods of analysis often require tedious, laborious, and expensive processes. Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) instrumentation enables highly sensitive and fast analysis and/or detection using a very small sample. The possibilities of MALDI-TOF MS for he identification and/or detection of trichothecene mycotoxins (deoxynivalenol (DON) and nivalenol (NIV), respectively) in barley malt were examined, and it was found that almost all classical MALDI matrices failed to ionize the compounds being studied. This detailed study of the ionization conditions and the search for unconventional matrices led to the discovery of suitable MALDI matrices, which enable ionization of trichothecene mycotoxins. These were: fine powdered synthetic diamond, sodium azide, or hydrazine hydrate. It is possible to detect 8.5 × 10-12 mol (2.5 ng) of deoxynivalenol or 64 × 10-12 mol (20 ng) of nivalenol in just 1 μL of barley malt extract (equivalent to 600 μg of DON in 1 kg of barley malt). The procedure developed enables fast determination of DON and NIV in barley, malt, or similar products. [ABSTRACT FROM AUTHOR]

The entomopathogen Bacillus sphaericus is an important tool for the vector control of Culex sp., and its effectiveness has been validated in field trials. The appearance of resistance to this bacterium, however, remains a threat to its use, and attempts have been made to understand the resistance mechanisms. Previous work showed that the resistance to B. sphaericus in a Culex quinquefasciatus colony is associated with the absence of the ≈ 60-kDa binary toxin receptor in larvae midgut microvilli. Here, the gene encoding the C. quinquefasciatus toxin receptor, Cqm1, was cloned and sequenced from a susceptible colony. The deduced amino-acid sequence confirmed its identity as an α-glucosidase, and analysis of the corresponding gene sequence from resistant larvae implicated a 19-nucleotide deletion as the basis for resistance. This deletion changes the ORF and originates a premature stop codon, which prevents the synthesis of the full-length Cqm1. Expression of the truncated protein, however, was not detected when whole larvae extracts were probed with antibodies raised against an N-terminal 45-kDa recombinant fragment of Cqm1. It seems that the premature stop codon directs the mutated cqm1 to the nonsense-mediated decay pathway of mRNA degradation. In-gel assays confirmed that a single α-glucosidase protein is missing from the resistant colony. Further in vitro affinity assays showed that the recombinant fragment binds to the toxin, and mapped the binding site to the N-terminus of the receptor. [ABSTRACT FROM AUTHOR]

The Institute of Food Technologists has issued this Scientific Status Summary to update readers on the science of fungal toxins. [ABSTRACT FROM AUTHOR]

Receptor-mediated internalization to the endoplasmic reticulum (ER) and subsequent retro-translocation to the cytosol are essential sequential processes required for the intoxication of mammalian cells by Pseudomonas exotoxin A (PEx). The toxin binds the α2-macroglobulin receptor/low-density lipoprotein receptor-related protein. Here, we show that in HeLa cells, PEx recruits a proportion of this receptor to detergent-resistant microdomains (DRMs). Uptake of receptor-bound PEx involves transport steps both directly from early endosomes to the trans-Golgi network (TGN) independently of Rab9 function and from late endosomes to the TGN in a Rab9-dependent manner. Furthermore, treatments that simultaneously perturb both Arf1-dependent and Rab6-dependent retrograde pathways show that PEx can use multiple routes to reach the ER. The Rab6-dependent route has only been described previously for cargo with lipid-sorting signals. These findings suggest that partial localization of PEx within DRM permits a choice of trafficking routes consistent with a model that DRM-associated toxins reach the ER on a lipid-dependent sorting pathway whilst non-DRM-associated PEx exploits the previously characterized KDEL receptor-mediated uptake pathway. Thus, unexpectedly, an ER-directed toxin with a proteinaceous receptor shows promiscuity in its intracellular trafficking pathways, exploiting routes controlled by both lipid- and protein-sorting signals. [ABSTRACT FROM AUTHOR]

Various studies have documented the associations between mold exposure and effects on health. Mycotoxins, which occur in spores and mold fragments, can be involved in processes that have pathological effects, such as adynamia of the immune system, recurrent infections of the respiratory tract, or asthma. Using Tetrahymena pyriformis, a single-cell organism well established as a suitable model for human respiratory epithelium-cell functionalities, we investigated dose-response relationships of the mycotoxins gliotoxin and penicillic acid. Our study focused on the viability (cell count, MIT assay), energy levels (adenosine-5′-triphosphate content), energy-providing processes (MIT reduction per cell), and cell respiration (oxygen consumption). Both mycotoxins acted as cytotoxins in a dose-dependent manner. Gliotoxin had a stronger inhibitory effect (EC50 0.38 μM) than did penicillic acid (EC50 343.19 μM). The energy-providing processes were not inhibited or were only weakly inhibited under the influence of gliotoxin, whereas penicillic acid caused stimulation of the physiological parameters. Summarizing the results, it is clear that the two investigated mycotoxins must have different modes of action. They are not only different in the strength of their toxic effects but also in a variety of physiological aspects. In addition, T pyriformis showed differences in its ability to overcome the negative effects of particular mycotoxin exposures. [ABSTRACT FROM AUTHOR]

Secreted, hormone-like lipogenic molecules, called oxylipins, mediate the balance of asexual to sexual spore ratio in Aspergillus nidulans. Oxylipin production in this fungus is dependent on developmental regulation of three conserved fatty acid oxygenases, PpoA, PpoB and PpoC. Here, we show that in addition to altering spore ratios, loss of ppo genes affect natural product biosynthesis and seed colonization. ΔppoA;ΔppoC and ΔppoA;ΔppoB;ΔppoC mutants were unable to produce the mycotoxin sterigmatocystin (ST) in vitro or in planta but in contrast overproduced the antibiotic penicillin (PN). These findings were correlated with decreased expression of genes involved in ST biosynthesis and increased expression of a PN biosynthetic gene, thus suggesting that oxylipin species regulate secondary metabolites at the transcriptional level. Additionally, the ΔppoA;ΔppoC and the ΔppoA;ΔppoB;ΔppoC mutants were defective in colonization of peanut seeds as reflected by a decrease in conidiation and production of the seed degradative enzyme lipase. These results indicate that oxylipin production is important for host colonization and mycotoxin production and may provide a promising target for future control strategies. [ABSTRACT FROM AUTHOR]

Microcystin, a hepatotoxin that represents a serious health risk for humans and livestock, is produced by the bloom-forming cyanobacterium Microcystis aeruginosa in freshwater bodies worldwide. Here we describe the discovery of a lectin, microvirin (MVN), in M. aeruginosa PCC7806 that shares 33% identity with the potent anti-HIV protein cyanovirin-N from Nostoc ellipsosporum. Carbohydrate microarrays were employed to demonstrate the high specificity of the protein for high-mannose structures containing α(1→2) linked mannose residues. Lectin binding analyses and phenotypic characterizations of MVN-deficient mutants suggest that MVN is involved in cell–cell recognition and cell–cell attachment of Microcystis. A binding partner of MVN was identified in the lipopolysaccharide fraction of M. aeruginosa PCC7806. MVN is differentially expressed in mutants lacking the hepatotoxin microcystin. Additionally, MVN-deficient mutants contain much lower amounts of microcystin than the wild-type cells. We discuss a possible functional correlation between microcystin and the lectin and possible implications on Microcystis morphotype formation. This study provides the first experimental evidence that microcystins may have an impact on Microcystis colony formation that is highly important for the competitive advantage of Microcystis over other phytoplankton species. [ABSTRACT FROM AUTHOR]

Vibrio choleraecytolysin (VCC) is an oligomerizing pore-forming toxin that is related to cytolysins of many other Gram-negative organisms. VCC contains six cysteine residues, of which two were found to be present in free sulphydryl form. The positions of two intramolecular disulphide bonds were mapped, and one was shown to be essential for correct folding of protoxin. Mutations were created in which the two free cysteines were deleted, so that single cysteine substitution mutants could be generated for site-specific labelling. Employment of polarity-sensitive fluorophores identified amino acid side-chains that formed part of the pore-forming domain of VCC. The sequence commenced at residue 311, and was deduced to form aβ-barrel in the assembled oligomer with the subsequent odd-numbered residues facing the lipid bilayer and even-numbered residues facing the lumen. Pro328/Lys329 were tentatively identified as the position at which the sequence turns back into the membrane and where the antiparallelβ-strand commences. This was deduced from fluorimetric analyses combined with experiments in which the pore was reversibly occluded by derivatization of sulphydryl groups with a bulky moiety. Our data support computer-based predictions that the membrane-permeabilizing amino acid sequence of VCC is homologous to theβ-barrel-forming sequence of staphylococcal cytolysins and identify theβ-barrel as a membrane-perforating structure that is highly conserved in evolution. [ABSTRACT FROM AUTHOR]

The role of cytochrome P450 activity in the nephrotoxicity of chlorotrifluoroethylene (CTFE) and 1,1-dichloro-2,2-difluoroethylene (DCDFE) was investigated in the male rat. Hepatic cytochrome P450 1A1 and principally P450 2B1[sol ]2 were induced by -naphthoflavone and phenobarbital, respectively. Nephrotoxicity was evaluated by investigating urine biochemical parameters, kidney histochemistry and histopathological modifications.Both CTFE and DCDFE induce severe nephrotoxicity in rats after 4 h of exposure to 200 and 100 ppm, respectively. Compared with controls, activity levels of ?-glutamyltranspeptidase (?GT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and N-acetyl--d-glucosaminidase (NAG) in 24-h urine were increased similarly, but urinary excretion of glucose, proteins and 2-microglobulin (2-m) and serum urea and creatinine levels were increased. Histopathological and histochemical examinations of kidney sections of CTFE- and DCDFE-exposed rats revealed cellular necrosis and tubular lesions 24 h after exposure.-Naphthoflavone-pretreated rats were afforded some protection against the nephrotoxicity of CTFE and DCDFE. Phenobarbital did not modify DCDFE nephrotoxicity but afforded some protection against CTFE nephrotoxicity. In conclusion, CTFE and DCDFE are strong nephrotoxins. Cytochrome P450 1A1 is implicated in CTFE and DCDFE metabolism and one or several cytochromes induced by phenobarbital are implicated in CTFE metabolism. The P450 cytochromes involved in CTFE and DCDFE metabolism probably constitute detoxication metabolic pathways. The nephrotoxicity of CTFE and DCDFE is therefore subordinated to the cytochrome P450 activity involved in their metabolism. Copyright 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In this study, the reduction of patulin content in apple juice concentrates during 6 months of storage at 22 and 30C was investigated. Results demonstrated that reduction in patulin content was dependent on the storage temperature and time. Patulin reductions after 1 month of storage at 22 and 30C were in the ranges of 45–64% and 66–86%, respectively. Levels of patulin were below detectable limits after 4 months of storage at 22 and 30C. [ABSTRACT FROM AUTHOR]

Background: There is a large amount of data on surgical root coverage procedures for the treatment of gingival recessions but no controlled clinical trials on the behavior of marginal gingiva following non-surgical therapy. The aim of our study was to compare in terms of root coverage two different modalities of root surface treatment, root planing and polishing versus polishing alone, over a 12-month period. Methods: The study was conducted in a split mouth design. Twenty-four non-smoking patients (14 females and 10 males, mean age 25.17 ± 4.03 years) with high levels of oral hygiene (full-mouth plaque score <20%) and with two bilateral Class I buccal recessions up to 2 mm deep were selected for the study. In each patient one recession was randomly assigned to the test group and the contra-lateral one to the control group. In the test group the exposed root surface was gently debrided and polished with mini curets and mini rubber cups, while the control group was polished only. The root surface instrumentation was repeated twice a month during the first 2 months and at 2-month intervals over the next 10 months. Clinical measurements were taken at baseline and 12 months post therapy. Results: At baseline the mean recession depth in the test group was 1.64 ± 0.37 mm and in the control sites 1.43 ± 0.42 mm. which decreased at 12 months to 0.78 ± 0.60 mm and to 1.34 ± 0.45 mm, respectively. The difference between the two groups was significant (P <0.0001). No significant differences were observed in keratinized tissue width and probing depth improvements. Conclusions: The removal of microbial toxins from the exposed root surfaces by polishing prevents further progression of gingival recession; the reduction of root convexity by scaling and root planing promotes the coronal shift of the gingival margin. [ABSTRACT FROM AUTHOR]

Discusses the modulation of "CD59-like" protein in naegleria fowleri amebae by bacteria. Expression of "CD59-like" protein in response to bacteria and bacterial toxins by Western immunoblot analysis; Use of electron microscopy on the examination of the co-cultures of amebae and bacteria; Role of the "CD59-like" protein in response to bacterial predators and bacterial toxins.

Botulinum toxin has rapidly gained wide acceptance as a treatment for focal spasticity, and is becoming more readily available. Early studies established its effectiveness, but many issues are still open for discussion. After a brief review of the historical and scientific development of botulinum toxin as a clinical tool and an outline of previous work in the field, some important questions are discussed in the light of more recent trials. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is the main mycotoxin that has been detected in coffee. The occurrence of OTA in coffee beans can be because of environmental conditions and/or processing conditions. Three coffee processes were evaluated (wet, mechanical and dry processes), at different stages from harvesting to storage, and fungi producing OTA were enumerated and identified. The frequency of potential OTA-producing fungi and their ability to produce OTA was also studied. By direct plating, the levels of contamination found in the coffee processes were 80, 72 and 92%, respectively, for parchment and dry cherry coffee and 20, 34 and 15% for green coffee. Aspergillus ochraceus isolated from the three processes accounted for 6.6, 8.3 and 3.3%, and Aspergillus niger for 15, 13 and 25% of the strains isolated, respectively. The toxigenic potential of five A. ochraceus and two A. niger strains was tested in FDA medium and coffee medium using the HPLC technique. There was no difference between the processes studied in terms of isolation and occurrence of ochratoxigenic fungi. [ABSTRACT FROM AUTHOR]