Search

Sialic acids have a special place in vertebrate glycobiology, where they constitute the dominant terminal saccharides on many cell surface glycans. From early studies that identified sialoglycans as receptors for important pathogens and toxins to more recent discoveries of sialic acid-binding proteins essential for immune system (and other) functions in humans, sialic acids and sialoglycans have become cornerstones in understanding vertebrate glycobiology and pathology. During a remarkable 3-year period in the late 1950s, a newly minted postdoctoral fellow (Donald G. Comb) and his young mentor (Saul Roseman) made a surprising series of discoveries that put sialic acid research on sound chemical and biochemical footing. A detailed personal letter written by Dr. Roseman that describes this period of intense sialic acid discovery, complete with inserted figures, was given to one of us (Y.C.L.) several years later. The text and figures of this letter provide a look back at the enthusiasm, rigor and serendipity that led to their important findings through the eyes of one of the key figures in sialic acid research. [ABSTRACT FROM AUTHOR]

Introduction Indoxyl sulfate (IS) and p cresyl sulfate (PCS) are protein bound toxins which accumulate with chronic kidney disease. Haemodiafiltration (HDF) increases middle molecule clearances and has been suggested to increase IS and PCS clearance. We therefore wished to establish whether higher convective clearances with HDF would reduce IS and PCS concentrations. Methods We measured total plasma IS and PCS in a cohort of 138 CKD5d patients treated by On-line HDF (Ol-HDF), by high pressure liquid chromatography. Findings Mean patient age was 64.6 ± 16.5 years, 60.1% male, 57.3% diabetic, median dialysis vintage 25.9 months (12.4-62.0). The mean ICS concentration was 79.8 ± 56.4 umol/L and PCS 140.3 ± 101.8 umol/L. On multivariate analysis, IS was associated with serum albumin (β 4.31,P < 0.001), and negatively with residual renal function (β-4.1,P = 0.02) and vegetarian diet(β-28.3, P = 0.048) and PCS negatively with log C reactive protein (β-75.8, P < 0.001) and vegetarian diet (β-109, P = 0.001). Vegetarian patients had lower IS and PCS levels (median 41.5 (24.2-71.9) vs. 78.1 (49.5-107.5) and PCS (41.6 (14.2-178.3) vs. 127.3 (77.4-205.6) µmol/L, respectively, P < 0.05. Vegetarian patients had lower preOl-HDF serum urea, and phosphate (13.8 ±3.8 vs. 18.4 ± 5.2 mmol/L, and 1.33 ± 0.21 vs. 1.58 ± 0.45 mmol/L), and estimated urea nitrogen intake (1.25 ± 0.28 vs. 1.62 ± 0.5 g/kg/day), respectively, all P < 0.05. Discussion Plasma IS and PCS concentrations were not lower with Ol-HDF compared to previous studies in haemodialysis patients. However those eating a vegetarian diet had reduced IS and PCS concentrations. Although this could be due to differences in dietary protein intake, a vegetarian diet may also potentially reduce IS and PCS production by the intestinal microbiome. [ABSTRACT FROM AUTHOR]

Microcystis aeruginosa is a cyanobacterium that can cause harmful algal blooms (HABs) in freshwater bodies. In this study, the bacterium Raoultella sp. R11 was evaluated for its ability to control the growth of M. aeruginosa . Algal growth, denitrification activity, and toxin production were measured in the presence of various concentrations of Raoultella sp. R11. The algicidal effects of Raoultella sp. R11 were studied by measuring the zeta potential (surface charge), the activity of superoxide dismutase (SOD), and the concentrations of chlorophyll-a, dissolved organic matter, and microcystin-LR in algal cultures. The results suggested that chlorophyll-a removal, which indicates algal death, was correlated with the dose of Raoultella sp. R11. The zeta potential and denitrification activity decreased in the presence of bacteria in a dose-dependent manner. SOD activity was correlated with the inoculation dosage of Raoultella sp. R11. Using a 30% (v/v) dose of bacterial culture, the removal efficiency of chlorophyll-a was as high as 94.28% after 6 days. In addition, dissolved microbial metabolites and humic acid were detected in high quantities whereas low quantities of protein-like substances and fulvic acid were found. Furthermore, toxic microcystin-LR produced by the algae was eliminated at up to 92.21% efficiency. A high denitrification rate (1.57 mg NO 3 - -N L −1 h −1 ) and chlorophyll-a removal efficiency (73.12%) were observed within 6 days at an inoculation dosage of 20% (v/v) of bacterial culture. Our findings indicated that Raoultella sp. R11 has a high potential for applications in simultaneously controlling M. aeruginosa and facilitating denitrification in freshwater bodies. [ABSTRACT FROM AUTHOR]

Bacterial type I toxin–antitoxin systems consist of stable toxin-encoding mRNAs whose expression is counteracted by unstable RNA antitoxins. Accumulating evidence suggests that these players belong to broad regulatory networks influencing overall bacterial physiology. The majority of known transmembrane type I toxic peptides have conserved structural characteristics. However, recent studies demonstrated that their mechanisms of toxicity are diverse and complex. To better assess the current state of the art, type I toxins can be grouped into two classes according to their location and mechanisms of action: membrane-associated toxins acting by pore formation and/or by nucleoid condensation; and cytosolic toxins inducing nucleic acid cleavage. This classification will evolve as a result of future investigations. [ABSTRACT FROM AUTHOR]

Killer toxins secreted by some yeast strains are the proteins that kill sensitive cells of the same or related yeast genera. In recent years, many new yeast species have been found to be able to produce killer toxins against the pathogenic yeasts, especially Candida albicans. Some of the killer toxins have been purified and characterized, and the genes encoding the killer toxins have been cloned and characterized. Many new targets including different components of cell wall, plasma membrane, tRNA, DNA and others in the sensitive cells for the killer toxin action have been identified so that the new molecular mechanisms of action have been elucidated. However, it is still unknown how some of the newly discovered killer toxins kill the sensitive cells. Studies on the killer phenomenon in yeasts have provided valuable insights into a number of fundamental aspects of eukaryotic cell biology and interactions of different eukaryotic cells. Elucidation of the molecular mechanisms of their action will be helpful to develop the strategies to fight more and more harmful yeasts. [ABSTRACT FROM AUTHOR]

Progressive reduction in kidney function in patients following myocardial infarction ( MI) is associated with an increase in circulating uremic toxins levels leading to increased extracellular matrix deposition. We have recently reported that treatment with uremic toxin adsorbent AST-120 in rats with MI inhibits serum levels of uremic toxin indoxyl sulfate ( IS) and downregulates expression of cardiac profibrotic cytokine transforming growth factor beta ( TGF- β1). In this study, we examined the effect of uremic toxins post- MI on cardiac micro RNA-21 and micro RNA-29b expression, and also the regulation of target genes and matrix remodeling proteins involved in TGF β1 and angiotensin II signaling pathways. Sixteen weeks after MI, cardiac tissues were assessed for pathological and molecular changes. The percentage area of cardiac fibrosis was 4.67 ± 0.17 in vehicle-treated MI, 2.9 ± 0.26 in sham, and 3.32 ± 0.38 in AST-120-treated MI, group of rats. Compared to sham group, we found a twofold increase in the cardiac expression of micro RNA-21 and 0.5-fold decrease in micro RNA-29b in heart tissue from vehicle-treated MI. Treatment with AST-120 lowered serum IS levels and attenuated both, cardiac fibrosis and changes in expression of these micro RNAs observed after MI. We also found increased mRNA expression of angiotensin-converting enzyme ( ACE) and angiotensin receptor 1a (Agtr1a) in cardiac tissue collected from MI rats. Treatment with AST-120 attenuated both, expression of ACE and Agtr1a mRNA. Exposure of rat cardiac fibroblasts to IS upregulated angiotensin II signaling and altered the expression of both micro RNA-21 and micro RNA-29b. These results collectively suggest a clear role of IS in altering micro RNA-21 and micro RNA-29b in MI heart, via a mechanism involving angiotensin signaling pathway, which leads to cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Plant and microbial toxins are considered bioterrorism threat agents because of their extreme toxicity and/or ease of availability. Additionally, some of these toxins are increasingly responsible for accidental food poisonings. The current study utilized an ELISA-based protein antibody microarray for the multiplexed detection of ten biothreat toxins, botulinum neurotoxins (BoNT) A, B, C, D, E, F, ricin, shiga toxins 1 and 2 (Stx), and staphylococcus enterotoxin B (SEB), in buffer and complex biological matrices. The multiplexed assay displayed a sensitivity of 1.3 pg mL−1 (BoNT/A, BoNT/B, SEB, Stx-1 and Stx-2), 3.3 pg mL−1 (BoNT/C, BoNT/E, BoNT/F) and 8.2 pg mL−1 (BoNT/D, ricin). All assays demonstrated high accuracy (75–120 percent recovery) and reproducibility (most coefficients of variation <20%). Quantification curves for the ten toxins were also evaluated in clinical samples (serum, plasma, nasal fluid, saliva, stool, and urine) and environmental samples (apple juice, milk and baby food) with overall minimal matrix effects. The multiplex assays were highly specific, with little cross-reactivity observed between the selected toxin antibodies. The results demonstrate a multiplex microarray that improves current immunoassay sensitivity for biological warfare agents in buffer, clinical, and environmental samples. [ABSTRACT FROM AUTHOR]

Aggregatibacter actinomycetemcomitans is a common inhabitant of the upper aerodigestive tract of humans and non-human primates and is associated with disseminated infections, including lung and brain abscesses, pediatric infective endocarditis, and localized aggressive periodontitis. Aggregatibacter actinomycetemcomitans secretes a repeats-in-toxin protein, leukotoxin, which exclusively kills lymphocyte function-associated antigen-1-bearing cells. The toxin's pathological mechanism is not fully understood; however, experimental evidence indicates that it involves the association with and subsequent destabilization of the target cell's plasma membrane. We have long hypothesized that leukotoxin secondary structure is strongly correlated with membrane association and destabilization. In this study, we tested this hypothesis by analysing lipid-induced changes in leukotoxin conformation. Upon incubation of leukotoxin with lipids that favor leukotoxin-membrane association, we observed an increase in leukotoxin α-helical content that was not observed with lipids that favor membrane destabilization. The change in leukotoxin conformation after incubation with these lipids suggests that membrane binding and membrane destabilization have distinct secondary structural requirements, suggesting that they are independent events. These studies provide insight into the mechanism of cell damage that leads to disease progression by A. actinomycetemcomitans. [ABSTRACT FROM AUTHOR]

Venomous animals use their venoms as tools for defense or predation. These venoms are complex mixtures, mainly enriched of proteic toxins or peptides with several, and different, biological activities. In general, spider venom is rich in biologically active molecules that are useful in experimental protocols for pharmacology, biochemistry, cell biology and immunology, as well as putative tools for biotechnology and industries. Spider venoms have recently garnered much attention from several research groups worldwide. Brown spider (Loxosceles genus) venom is enriched in low molecular mass proteins (5-40 kDa). Although their venom is produced in minute volumes (a few microliters), and contain only tens of micrograms of protein, the use of techniques based on molecular biology and proteomic analysis has afforded rational projects in the area and permitted the discovery and identification of a great number of novel toxins. The brown spider phospholipase-D family is undoubtedly the most investigated and characterized, although other important toxins, such as low molecular mass insecticidal peptides, metalloproteases and hyaluronidases have also been identified and featured in literature. The molecular pathways of the action of these toxins have been reported and brought new insights in the field of biotechnology. Herein, we shall see how recent reports describing discoveries in the area of brown spider venom have expanded biotechnological uses of molecules identified in these venoms, with special emphasis on the construction of a cDNA library for venom glands, transcriptome analysis, proteomic projects, recombinant expression of different proteic toxins, and finally structural descriptions based on crystallography of toxins. [ABSTRACT FROM AUTHOR]

Purpose: Lead is environmental and/or occupational toxicant. It has been known to induce hematological disturbance during haematopoiesis. However, it has not well known whether it has effects on coagulation system or not. Therefore, we aimed to investigate how coagulation system is affected by the level of elevated blood lead. Material and Methods: Fifty-two occupational lead exposure patients applied with lead intoxication symptoms. Blood examples of patients were obtained for lead level, platelet count, in-vitro bleeding time, prothrombine time, partial thromboplastine time (aPTT), fibrinogen, thrombine time, protein C, protein S and antithrombine III. The patients are evaluated according to three groups as mild, moderate and severe. Results: Blood lead levels were mean 71,15±18,19μg/dl. Mean values results of primary and secondary hemostasis and physiological coagulation inhibitors tests were in normal ranges, except fibrinogen degree. Despite mean fibrinogen degree being under normal ranges, statistically significant difference between the groups was not detected. Mean aPTT and protein S degrees were in normal ranges, however, compared with the mild-toxicated group statistically important prolongment in aPTT and reducement in protein S degrees detected in moderate-toxicated group. Conclusion: As a result, although our results need suggestion by in vivo and in vitro studies, it is concluded that haemostatic parameters excluding fibrinogen were not effected by mild and moderate degree elevation of blood lead. [ABSTRACT FROM AUTHOR]

Abstract: 2,7-Dihydroxycadalene and lacinilene C, sesquiterpenoid phytoalexins that accumulate at infection sites during the hypersensitive resistant response of cotton foliage to Xanthomonas campestris pv. malvacearum, have light-dependent toxicity toward host cells, as well as toward the bacterial pathogen. Adaxial epidermal cells surrounding and sometimes covering infection sites turn red. The red cells exhibited 3–4-fold higher absorption at the photoactivating wavelengths of sunlight than nearby colorless epidermal cells. Red epidermal cells protected underlying palisade mesophyll cells from the toxic effects of 2,7-dihydroxycadalene plus sunlight, indicating a role for epidermal pigments in protecting living cells that surround infection sites from toxic effects of the plant’s own phytoalexins. A semi-quantitative survey of UV-absorbing substances extracted from epidermal strips from inoculated and mock-inoculated cotyledons indicated that the principal increase in capacity to absorb the photoactivating wavelengths was due to a red anthocyanin and a yellow flavonol, which were identified as cyanidin-3-O-β-glucoside and quercetin-3-O-β-glucoside, respectively. [Copyright &y& Elsevier]

We present an OR gate based on monoclonal antibodies for the simultaneous detection of multiple toxins in a single tube. To further simplify the operating procedure, the Boolean rule of simplification was used to guide the selection of a marker toxin among the natural toxin profiles. [ABSTRACT FROM AUTHOR]