Swimming impairment and acetylcholinesterase inhibition in zebrafish exposed to copper or chlorpyrifos separately,or as mixtures

Pesticides such as chlorpyrifos (CPF) and metals such as copper can impair swimming behavior in fish. However, the impact to swimming behavior from exposure to mixtures of neurotoxicants has received little attention. In the current study, we analyzed spontaneous swimming rates of adult zebrafish (Danio rerio) to investigate in vivo mixture interactions involving two chemical classes. Zebrafish were exposed to the neurotoxicants copper chloride (CuCl, 0.1 μM, 0.25 μM, 0.6 μM, or 6.3, 16, 40 ppb), chlorpyrifos (CPF, 0.1 μM, 0.25 μM, 0.6 μM, or 35, 88, 220 ppb) and binary mixtures for 24 h to better understand the effects of Cu on CPF neurotoxicity. Exposure to CPF increased the number of animals undergoing freeze responses (an anti-predator behavior) and, at the highest CPF dose (0.6 μM), elicited a decrease in zebrafish swimming rates. Interestingly, the addition of Cu caused a reduction in the number of zebrafish in the CPF exposure groups undergoing freeze responses. There was no evidence of additive or synergistic toxicity between Cu and CPF. Although muscle AChE activity was significantly reduced by CPF, there was a relatively poor relationship among muscle AChE concentrations and swimming behavior, suggesting non-muscle AChE mechanisms in the loss of swimming behavior. In summary, we have observed a modulating effect of Cu on CPF swimming impairment that appears to involve both AChE and non-AChE mechanisms. Our study supports the utility of zebrafish in understanding chemical mixture interactions and neurobehavioral injury.     

Short rotation coppice culture of willows and poplars as energy crops on metal contaminated agricultural soils

Phytoremediation, more precisely phytoextraction, has been placed forward as an environmental friendly remediation technique, that can gradually reduce increased soil metal concentrations, in particular the bioavailable fractions. The aim of this study was to investigate the possibilities of growing willows and poplars under short rotation coppice (SRC) on an acid, poor, sandy metal contaminated soil, to combine in this way soil remediation by phytoextraction on one hand, and production of biomass for energy purposes on the other. Above ground biomass productivities were low for poplars to moderate for willows, which was not surprising, taking into account the soil conditions that are not very favorable for growth of these trees. Calculated phytoextraction efficiency was much longer for poplars than these for willows. We calculated that for phytoextraction in this particular case it would take at least 36 years to reach the legal threshold values for cadmium, but in combination with production of feedstock for bioenergy processes, this type of land use can offer an alternative income for local farmers. Based on the data of the first growing cycle, for this particular case, SRC of willows should be recommended.     

Structural transition in peptide nanotubes

Phase transitions in organic and inorganic materials are well-studied classical phenomena, where a change in the crystal space group symmetry induces a wide variation of physical properties, permitted by the crystalline symmetry in each phase. Here we observe a conformational induced transition in bioinspired peptide nanotubes (PNTs). We found that the PNTs change their original molecular assembly from a linear peptide conformation to a cyclic one, followed by a change of the nanocrystalline structure from a noncentrosymmetric hexagonal space group to a centrosymmetric orthorhombic space group. The observed transition is irreversible and induces a profound variation in the PNTs properties, from the microscopic to the macroscopic level. In this context, we follow the unique changes in the molecular, morphological, piezoelectric, second harmonic generation, and wettability properties of the PNTs.     

Video-Assisted Implantation of a Left Ventricular Lead and Intrathoracic Tunneling to a Right-Sided CRT-D Device

We describe two cases in which a biventricular implantable cardioverter defibrillator for cardiac resynchronization therapy had to be placed on the right side due to unsuitability of the left subclavian vein. Endocardial implantation of a left ventricular lead through the coronary sinus was previously attempted but was unsuccessful. Implantation of the epicardial left ventricular pacing lead was performed through video-assisted thoracic surgery on the left side. The connector end of the left ventricular pacing lead was tunnelized through the anterior mediastinum into the right pleural space. The right-sided pocket was then opened. A tunnel was created from the pocket to the thoracic wall, and the pleural space was entered over the second rib. The lead was retrieved from the right pleural space and connected with the Cardiac resynchronization therapy-device (CRT-D). Both procedures and postoperative periods were uneventful. Intrathoracic left-to-right tunneling of an epicardial left ventricular lead by video-assisted thoracic surgery is feasible and safe. It provides an alternative to subcutaneous tunneling.     

The genetic basis for 3-ADON and 15-ADON trichothecene chemotypes in Fusarium

Certain Fusarium species cause head blight of wheat and other small grains worldwide and produce trichothecene mycotoxins. These mycotoxins can induce toxicoses in animals and humans and can contribute to the ability of some fusaria to cause plant disease. Production of the trichothecene 3-acetyldeoxynivalenol (3-ADON) versus 15-acetyldeoxynivalenol (15-ADON) is an important phenotypic difference within and among some Fusarium species. However, until now, the genetic basis for this difference in chemotype has not been identified. Here, we identified consistent DNA sequence differences in the coding region of the trichothecene biosynthetic gene TRI8 in 3-ADON and 15-ADON strains. Functional analyses of the TRI8 enzyme (Tri8) in F. graminearum, the predominant cause of wheat head blight in North America and Europe, revealed that Tri8 from 3-ADON strains catalyzes deacetylation of the trichothecene biosynthetic intermediate 3,15-diacetyldeoxynivalenol at carbon 15 to yield 3-ADON, whereas Tri8 from 15-ADON strains catalyzes deacetylation of 3,15-diacetyldeoxynivalenol at carbon 3 to yield 15-ADON. Fusarium strains that produce the trichothecene nivalenol have a Tri8 that functions like that in 15-ADON strains. TRI3, which encodes a trichothecene carbon 15 acetyltransferase, was found to be functional in all three chemotypes. Together, our data indicate that differential activity of Tri8 determines the 3-ADON and 15-ADON chemotypes in Fusarium.     

A polymorphism in the splice donor site of ZNF419 results in the novel renal cell carcinoma-associated minor histocompatibility antigen ZAPHIR

Nonmyeloablative allogeneic stem cell transplantation (SCT) can induce remission in patients with renal cell carcinoma (RCC), but this graft-versus-tumor (GVT) effect is often accompanied by graft-versus-host disease (GVHD). Here, we evaluated minor histocompatibility antigen (MiHA)-specific T cell responses in two patients with metastatic RCC who were treated with reduced-intensity conditioning SCT followed by donor lymphocyte infusion (DLI). One patient had stable disease and emergence of SMCY.A2-specific CD8+ T cells was observed after DLI with the potential of targeting SMCY-expressing RCC tumor cells. The second patient experienced partial regression of lung metastases from whom we isolated a MiHA-specific CTL clone with the capability of targeting RCC cell lines. Whole genome association scanning revealed that this CTL recognizes a novel HLA-B7-restricted MiHA, designated ZAPHIR, resulting from a polymorphism in the splice donor site of the ZNF419 gene. Tetramer analysis showed that emergence of ZAPHIR-specific CD8+ T cells in peripheral blood occurred in the absence of GVHD. Furthermore, the expression of ZAPHIR in solid tumor cell lines indicates the involvement of ZAPHIR-specific CD8+ T cell responses in selective GVT immunity. These findings illustrate that the ZNF419-encoded MiHA ZAPHIR is an attractive target for specific immunotherapy after allogeneic SCT.     

MHC mismatch inhibits neurogenesis and neuron maturation in stem cell allografts

Background

The role of histocompatibility and immune recognition in stem cell transplant therapy has been controversial, with many reports arguing that undifferentiated stem cells are protected from immune recognition due to the absence of major histocompatibility complex (MHC) markers. This argument is even more persuasive in transplantation into the central nervous system (CNS) where the graft rejection response is minimal.

Methodology/Principal Findings

In this study, we evaluate graft survival and neuron production in perfectly matched vs. strongly mismatched neural stem cells transplanted into the hippocampus in mice. Although allogeneic cells survive, we observe that MHC-mismatch decreases surviving cell numbers and strongly inhibits the differentiation and retention of graft-derived as well as endogenously produced new neurons. Immune suppression with cyclosporine-A did not improve outcome but non-steroidal anti-inflammatory drugs, indomethacin or rosiglitazone, were able to restore allogeneic neuron production, integration and retention to the level of syngeneic grafts.

Conclusions/Significance

These results suggest an important but unsuspected role for innate, rather than adaptive, immunity in the survival and function of MHC-mismatched cellular grafts in the CNS.     

Event-related potential correlates of performance-monitoring in a lateralized time-estimation task

Performance-monitoring as a key function of cognitive control covers a wide range of diverse processes to enable goal directed behavior and to avoid maladjustments. Several event-related brain potentials (ERP) are associated with performance-monitoring, but their conceptual background differs. For example, the feedback-related negativity (FRN) is associated with unexpected performance feedback and might serve as a teaching signal for adaptational processes, whereas the error-related negativity (ERN) is associated with error commission and subsequent behavioral adaptation. The N2 is visible in the EEG when the participant successfully inhibits a response following a cue and thereby adapts to a given stop-signal. Here, we present an innovative paradigm to concurrently study these different performance-monitoring-related ERPs. In 24 participants a tactile time-estimation task interspersed with infrequent stop-signal trials reliably elicited all three ERPs. Sensory input and motor output were completely lateralized, in order to estimate any hemispheric processing preferences for the different aspects of performance monitoring associated with these ERPs. In accordance with the literature our data suggest augmented inhibitory capabilities in the right hemisphere given that stop-trial performance was significantly better with left- as compared to right-hand stop-signals. In line with this, the N2 scalp distribution was generally shifted to the right in addition to an ipsilateral shift in relation to the response hand. Other than that, task lateralization affected neither behavior related to error and feedback processing nor ERN or FRN. Comparing the ERP topographies using the Global Map Dissimilarity index, a large topographic overlap was found between all considered components.With an evenly distributed set of trials and a split-half reliability for all ERP components ≥.85 the task is well suited to efficiently study N2, ERN, and FRN concurrently which might prove useful for group comparisons, especially in clinical populations.