Incidence and levels of fumonisin contamination in Colombian corn and corn products

A survey was conducted to determine the levels of fumonisins B1 and B2 in corn and corn-based products available in Colombia for human and animal consumption. A total of 120 samples were analyzed by acetonitrile-water extraction, cleanup with a strong-anion-exchange column, and liquid chromatography with o-phthaldialdehyde-2-mercaptoethanol derivatization and fluorescence detection. The samples of corn and corn-based products for animal intake were taken at different feed manufacturing plants, whereas the samples used for human foods where purchased from local retail stores. The number of positive samples for fumonisin B1 was 20.0% higher in corn and corn-based products for animal intake (75.0%) than in corn and corn-based products for human consumption (55.0%). The levels of fumonisin B1 were also higher in corn and corn-based products for animal intake (mean = 694 μg/kg; range = 32–2964 μg/kg), than in corn and corn-based products for human intake (mean = 218 μg/kg; range = 24–2170 μg/ kg). The incidence and levels of fumonisin B2 were lower than those for fumonisin B1. Corn and corn-based products for animal consumption had an incidence of fumonisin B2 of 58.3%, with a mean value of 283 μg/kg, and a range of 44–987 μg/kg. The incidence of fumonisin B2 in corn-based products for human intake was 35.0%, with a mean value of 118 μg/kg and a range of 21–833 μg/kg. The highest incidence and levels of fumonisins were found in samples of hominy feed, with concentrations ranging from 86 to 2964 μg/kg fumonisin B1 and 57 to 987 μg/kg fumonisin B2.     

Relief influence on the spatial distribution of the Atlantic Forest cover on the Ibiúna Plateau, SP.

Several studies suggest that, on a large scale, relief conditions influence the Atlantic Forest cover. The aim of this work was to explore these relationships on a local scale, in Caucaia do Alto, on the Ibiúna Plateau. Within an area of about 78 km(2), the distribution of forest cover, divided into two successional stages, was associated with relief attribute data (slope, slope orientation and altitude). The mapping of the vegetation was based on the interpretation of stereoscopic pairs of aerial photographs, from April 2000, on a scale of 1:10,000, while the relief attributes were obtained by geoprocessing from digitalized topographic maps on a scale of 1:10,000. Statistical analyses, based on qui-square tests, revealed that there was a more extensive forest cover, irrespective of the successional stage, in steeper areas (>10 degrees) located at higher altitudes (>923 m), but no influence of the slope orientation. There was no sign of direct influence of relief on the forest cover through environmental gradients that might have contributed to the forest regeneration. Likewise, there was no evidence that these results could have been influenced by the distance from roads or urban areas or with respect to permanent preservation areas. Relief seems to influence the forest cover indirectly, since agricultural land use is preferably made in flatter and lower areas. These results suggest a general distribution pattern of the forest remnants, independent of the scale of study, on which relief indirectly has a strong influence, since it determines human occupation.     

Prevention of Influenza Virus-Induced Immunopathology by TGF-β Produced during Allergic Asthma

Asthma is believed to be a risk factor for influenza infection, however little experimental evidence exists to directly demonstrate the impact of asthma on susceptibility to influenza infection. Using a mouse model, we now report that asthmatic mice are actually significantly more resistant to a lethal influenza virus challenge. Notably, the observed increased resistance was not attributable to enhanced viral clearance, but instead, was due to reduced lung inflammation. Asthmatic mice exhibited a significantly reduced cytokine storm, as well as reduced total protein levels and cytotoxicity in the airways, indicators of decreased tissue injury. Further, asthmatic mice had significantly increased levels of TGF-β1 and the heightened resistance of asthmatic mice was abrogated in the absence of TGF-β receptor II. We conclude that a transient increase in TGF-β expression following acute asthma can induce protection against influenza-induced immunopathology.     

Do Parents Meet Adolescents’ Monitoring Standards? Examination of the Impact on Teen Risk Disclosure and Behaviors if They Don’t

In this study, we examined how adolescents compare monitoring efforts by their parents to those of a "good parent" standard and assessed the impact of these comparisons on adolescent self-disclosure and risk behavior and their perceptions of their parents'' monitoring knowledge. Survey responses from 519 adolescents (12–17 years) at baseline of a larger, longitudinal study examining parental monitoring and adolescent risk were examined. Adolescents’ “good parent comparisons” differed greatly by monitoring areas (e.g., telephone use, health, money); however, between 5.5% and 25.8% of adolescents believed their parents needed to monitor their activities more than they currently were monitoring. Alternatively, between 8.5% and 23.8% of adolescents believed their parents needed to monitor their activities less often. These perceptions significantly distinguished adolescents in terms of their level of disclosure, perceived monitoring knowledge, and risk involvement. Adolescents who viewed their parents as needing to monitor more were less likely to disclose information to their parents (p<.001), less likely to perceive their parents as having greater monitoring knowledge (p<.001), and more likely to be involved in a risk behaviors (p<.001) than adolescents who perceived their parents needed no change. Adolescent disclosure to a parent is a powerful predictor of adolescent risk and poor health outcomes. These findings demonstrate that adolescents'' comparisons of their parents'' monitoring efforts can predict differences in adolescent disclosure and future risk. Obtaining adolescent "good parent" comparisons may successfully identify intervention opportunities with the adolescent and parent by noting the areas of need and direction of monitoring improvement.     

Role of Maternal Dietary Peanut Exposure in Development of Food Allergy and Oral Tolerance

Background

The impact of maternal ingestion of peanut during pregnancy and lactation on an offspring’s risk for peanut allergy is under debate.

Objective

To investigate the influence of maternal dietary peanut exposure and breast milk on an offspring’s allergy risk.

Methods

Preconceptionally peanut-exposed C3H/HeJ females were either fed or not fed peanut during pregnancy and lactation. The offsprings’ responses to peanut sensitization or oral tolerance induction by feeding antigen prior to immunization were assessed. We also assessed the impact of immune murine milk on tolerance induction pre- or post-weaning. For antigen uptake studies, mice were gavaged with fluorescent peanut in the presence or absence of immune murine milk; Peyer’s patches were harvested for immunostaining.

Results

Preconceptional peanut exposure resulted in the production of varying levels of maternal antibodies in serum (and breast milk), which were transferred to the offspring. Despite this, maternal peanut exposure either preconceptionally or during pregnancy and lactation, when compared to no maternal exposure, had no impact on peanut allergy. When offspring were fed peanut directly, dose-dependent tolerance induction, unaltered by maternal feeding of peanut, was seen. Although peanut uptake into the gut-associated lymphoid tissues was enhanced by immune milk as compared to naïve milk, tolerance induction was not affected by the co-administration of immune milk either pre- or post-weaning.

Conclusion

Maternal peanut exposure during pregnancy and lactation has no impact on the development of peanut allergy in the offspring. Tolerance to peanut can be induced early, even pre-weaning, by giving moderate amounts of peanut directly to the infant, and this is neither enhanced nor impaired by concurrent exposure to immune milk.     

Probing ADAMTS13 Substrate Specificity using Phage Display

Von Willebrand factor (VWF) is a large, multimeric protein that regulates hemostasis by tethering platelets to the subendothelial matrix at sites of vascular damage. The procoagulant activity of plasma VWF correlates with the length of VWF multimers, which is proteolytically controlled by the metalloprotease ADAMTS13. To probe ADAMTS13 substrate specificity, we created phage display libraries containing randomly mutated residues of a minimal ADAMTS13 substrate fragment of VWF, termed VWF73. The libraries were screened for phage particles displaying VWF73 mutant peptides that were resistant to proteolysis by ADAMTS13. These peptides exhibited the greatest mutation frequency near the ADAMTS13 scissile residues. Kinetic assays using mutant and wild-type substrates demonstrated excellent agreement between rates of cleavage for mutant phage particles and the corresponding mutant peptides. Cleavage resistance of selected mutations was tested in vivo using hydrodynamic injection of corresponding full-length expression plasmids into VWF-deficient mice. These studies confirmed the resistance to cleavage resulting from select amino acid substitutions and uncovered evidence of alternate cleavage sites and recognition by other proteases in the circulation of ADAMTS13 deficient mice. Taken together, these studies demonstrate the key role of specific amino acids residues including P3-P2’ and P11’, for substrate specificity and emphasize the importance in flowing blood of other ADAMTS13–VWF exosite interactions outside of VWF73.     

Molecular Determinants of Cardiac Myocyte Performance as Conferred by Isoform-Specific TnI Residues

Troponin I (TnI) is the molecular switch of the sarcomere. Cardiac myocytes express two isoforms of TnI during development. The fetal heart expresses the slow skeletal TnI (ssTnI) isoform and shortly after birth ssTnI is completely and irreversibly replaced by the adult cardiac TnI (cTnI) isoform. These two isoforms have important functional differences; broadly, ssTnI is a positive inotrope, especially under acidic/hypoxic conditions, whereas cTnI facilitates faster relaxation performance. Evolutionary directed changes in cTnI sequence suggest cTnI evolved to favor relaxation performance in the mammalian heart. To investigate the mechanism, we focused on several notable TnI isoform and trans-species-specific residues located in TnI’s helix 4 using structure/function and molecular dynamics analyses. Gene transduction of adult cardiac myocytes by cTnIs with specific helix 4 ssTnI substitutions, Q157R/A164H/E166V/H173N (QAEH), and A164H/H173N (AH), were investigated. cTnI QAEH is similar in these four residues to ssTnI and nonmammalian chordate cTnIs, whereas cTnI AH is similar to fish cTnI in these four residues. In comparison to mammalian cTnI, cTnI QAEH and cTnI AH showed increased contractility and slowed relaxation, which functionally mimicked ssTnI expressing myocytes. cTnI QAEH molecular dynamics simulations demonstrated altered intermolecular interactions between TnI helix 4 and cTnC helix A, specifically revealing a new, to our knowledge, electrostatic interaction between R171of cTnI and E15 of cTnC, which structurally phenocopied the ssTnI conformation. Free energy perturbation calculation of cTnC Ca²⁺ binding for these conformations showed relative increased calcium binding for cTnI QAEH compared to cTnI. Taken together, to our knowledge, these new findings provide evidence that the evolutionary-directed coordinated acquisition of residues Q157, A164, E166, H173 facilitate enhanced relaxation performance in mammalian adult cardiac myocytes.     

Synthesis of 7-benzyl-5-(piperidin-1-yl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-1-ylamine and its analogs as bombesin receptor subtype-3 agonists

The original structure of a high-throughput screening hit obtained from an external vendor was revised based on multiple NMR studies. The active compound was re-synthesized via a novel route and its structure and biological activity as a BRS-3 agonist were unambiguously confirmed. Multi-gram quantities of the hit were prepared for pharmacokinetic and efficacy studies. The synthetic strategy allowed for the preparation of multiple analogs for SAR exploration.     

Variety matters: adaptive genetic diversity and parasite load in two mouse opossums from the Brazilian Atlantic forest

The adaptive potential of a species to a changing environment and in disease defence is primarily based on genetic variation. Immune genes, such as genes of the major histocompatibility complex (MHC), may thereby be of particular importance. In marsupials, however, there is very little knowledge about natural levels and functional importance of MHC polymorphism, despite their key role in the mammalian evolution. In a previous study, we discovered remarkable differences in the MHC class II diversity between two species of mouse opossums (Gracilinanus microtarsus, Marmosops incanus) from the Brazilian Atlantic forest, which is one of the most endangered hotspots for biodiversity conservation. Since the main forces in generating MHC diversity are assumed to be pathogens, we investigated in this study gastrointestinal parasite burden and functional associations between the individual MHC constitution and parasite load. We tested two contrasting scenarios, which might explain differences in MHC diversity between species. We predicted that a species with low MHC diversity would either be under relaxed selection pressure by low parasite diversity (‘Evolutionary equilibrium’ scenario), or there was a recent loss in MHC diversity leading to a lack of resistance alleles and increased parasite burden (‘Unbalanced situation’ scenario). In both species it became apparent that the MHC class II is functionally important in defence against gastrointestinal helminths, which was shown here for the first time in marsupials. On the population level, parasite diversity did not markedly differ between the two host species. However, we did observe considerable differences in the individual parasite load (parasite prevalence and infection intensity): while M. incanus revealed low MHC DAB diversity and high parasite load, G. microtarsus showed a tenfold higher population wide MHC DAB diversity and lower parasite burden. These results support the second scenario of an unbalanced situation.     

Foetal hepatocyte transplantation in a vascularized AV-Loop transplantation model in the rat

The use of foetal liver cells (FLC) in the context of hepatic tissue engineering might permit efficient in vitro expansion and cryopreservation in a cell bank. A prerequisite for successful application of bioartificial liver tissue is sufficient initial vascularization. In this study, we evaluated the transplantation of fibrin gel-immobilized FLC in a vascularized arterio-veno-venous (AV)-loop model. FLC were isolated from embryonic/foetal (ED 16) rat livers and were enriched by using magnetic cell sorting (MACS). After cryopreservation, FLC were labelled by pkh-26. Cells were transplanted in a fibrin matrix into a subcutaneous chamber containing a microsurgically created AV-loop in the femoral region of the recipient rat. The chambers were explanted after 14 days. Subcutaneous implants without an AV-loop and cell-free implants served as controls. Fluorescence microscopy of the constructs was used to identify pkh-26⁺- donor cells. Characterization was performed by RT-PCR and immunhistology (IH) for CK-18 and CD31. Transplantation of FLC using the AV-loop permitted a neo -tissue formation in the fibrin matrix. A high-density vascularization was observed in the AV-loop constructs as shown by CD31 IH. Viable foetal donor cells were detected which expressed CK-18. FLC can be successfully used for heterotopic transplantation. Fibrin matrix permits rapid blood vessel ingrowth from the AV-loop and supports engraftment of FLC. It is therefore an appropriate environment for hepatocyte transplantation in combination with microsurgical vascularization strategies. Transplantation of fibrin gel-immobilized FLC may be a promising approach for the development of highly vascularized in vivo tissue-engineering-based liver support systems.