Humic acid-coated goethite nanoparticles (HA-GoeNPs) have been recently proposed as an effective reagent for the in situ nanoremediation of contaminated aquifers. However, the effective dosage of ...these particles has been studied only at laboratory scale to date. This study investigates the possibility of using HA-GoeNPs in remediation of real field sites by mimicking the injection and transport of HA-GoeNPs under realistic conditions. To this purpose, a three-dimensional (3D) transport experiment was conducted in a large-scale container representing a heterogeneous unconfined aquifer. Monitoring data, including particle size distribution, total iron (Fetot) content and turbidity measurements, revealed a good subsurface mobility of the HA-GoeNP suspension, especially within the higher permeability zones. A radius of influence of 2 m was achieved, proving that HA-GoeNPs delivery is feasible for aquifer restoration. A flow and transport model of the container was built using the numerical code Micro and Nanoparticle transport Model in 3D geometries (MNM3D) to predict the particle behavior during the experiment. The agreement between modeling and experimental results validated the capability of the model to reproduce the HA-GoeNP transport in a 3D heterogeneous aquifer. Such result confirms MNM3D as a valuable tool to support the design of field-scale applications of goethite-based nanoremediation.
: Antibodies, specific to murine DEC205, can be used to target antigens to dendritic cells. The immunodominant domain of human type XVII collagen, hNC16A, was fused to this antibody (DEC‐hNC16A) and ...was administered as expression plasmid by gene gun transfection with the aim of inducing tolerance to human type XVII collagen in a skin transplantation model. Mice transfected with DEC‐hNC16A were challenged with skin grafts from transgenic mice engineered to express human type XVII collagen. Graft survival was either prolonged or grafts were accepted infinitely (33% and 16%, respectively) upon treatment with DEC‐hNC16A while 100% of grafts were rejected in untreated controls. Graft acceptance was associated with the absence of a CD4+ infiltrate and a dense CD8+ T‐cell infiltrate and was not strictly dependent on antibody production. Our results show that DEC‐hNC16A targets dendritic cells in vivo leading to prolonged survival of transgenic skin grafts. This indicates that DEC205‐targeting may be used for the induction of tolerance to skin antigens, which would increase the chances of successful skin gene therapy of epidermolysis bullosa patients.
Light-scatter artefacts are a methodological problem in testing residual visual capacities (RVCs), for instance blindsight, in patients with homonymous visual field defects (HVFDs). The term ...light-scatter artefact describes the phenomenon that light from targets directed towards the HVFD can stray into the sighted visual field. This might enable an observer to respond correctly to information directed at her blind field despite the fact that she is unable to process that information in the blind field itself. In this manuscript, we present a review of the relevance of light-scatter in visual neuroscience, discuss factors that influence the impact of light-scatter and evaluate means to test for light-scatter artefacts. Furthermore, we present findings from an empirical study that was aimed at developing tests for RVCs that are free of light-scatter artefacts. Previous studies on light scatter only used small sample sizes and equipment that is no longer in use. Hence, their results cannot be generalized to future experiments making it necessary to run laborious light-scatter tests for every new study on RVCs. To avoid this, we hereby start a pool of stimuli and paradigms which demonstrably do not elicit light-scatter artefacts. To this end, we investigated 21 healthy young participants in three frequently used RVC-paradigms: (1) temporal 2AFC task, (2) movement direction discrimination, and (3) redundant target paradigm. For each paradigm, we applied the blind-spot method. But first, we had to establish that our testing paradigm was sufficiently sensitive to detect light-scatter artefacts. For this, we used conditions that are known to produce strong light scatter and a paradigm that is very sensitive to such effects. Specifically, we presented white targets on a black background in a dark room. The stimuli were presented to observers’ blind spot. To check for light-scatter artefacts, we used a target-detection task in a temporal 2AFC format. We obtained clear light-scatter artefacts. Participants produced reliably above-chance detection performance under these conditions. The other two luminance conditions, measured in an illuminated room, did not produce light-scatter artefacts. Accuracy in the temporal 2AFC task was at chance level for white targets on a grey background at the blind-spot position. Additionally, black targets on a grey background avoided light-scatter artefacts in all three RVC-paradigms. In future, researchers can apply these stimulus and illumination conditions when using one of the three above paradigms in their studies. Using these conditions, they will be able to avoid light-scatter artefacts without having to perform their own blind-spot tests.
The redundant target effect (RTE) is the well-known effect whereby a single target is detected faster when a second, redundant target is presented simultaneously. The RTE was shown in different ...experimental designs and applied in various clinical contexts. However, there are also studies showing non-effects or effects in the opposite direction. Our meta-analysis aims to investigate the replicability of the RTE. Herein, we focused on the clinical context within which the RTE has been applied most often and for which it gained particular prominence: The research on blindsight and other forms of residual vision in patients with damage to the neuronal visual system. The application of the RTE in clinical contexts assumes that whenever vision is present, an RTE will be found. Put differently, the RTE as a tool to uncover residual vision presumes that the RTE is a consistent feature of vision in the healthy population. We found a significant summary effect size of the RTE in healthy participants. The effect size depended on certain experimental features: task type, target configuration in the redundant condition, and how reaction times were computed in the single condition. A specific feature combination is typically used in blindsight research. Analyzing studies with this feature combination revealed a significant summary effect size in healthy participants predicting positive RTEs for future studies. A power-analysis revealed a required sample size of 14 participants to obtain an RTE with high reliability. However, the required sample size is rarely reached in blindsight research. Rather, blindsight research is mostly based on single-case studies. In summary, the RTE is a robust effect on group level but does not occur in every single individual. This means failure to obtain an RTE in a single patient should not be interpreted as evidence for the absence of residual vision in this patient.
HAX1 was originally described as HS1‐associated protein with a suggested function in receptor‐mediated apoptotic and proliferative responses of lymphoid cells. Recent publications refer to a complex ...and multifunctional role of this protein. To investigate the in vivo function of HAX1 (HS1‐associated protein X1) in B cells, we generated a Hax1‐deficient mouse strain. Targeted deletion of Hax1 resulted in premature death around the age of 12 wk accompanied by a severe reduction of lymphocytes in spleen, thymus and bone marrow. In the bone marrow, all B‐cell populations were lost comparably. In the spleen, B220⁺ cells were reduced by almost 70%. However, as investigated by adoptive transfer experiments, this impairment is not exclusively B‐cell intrinsic and we hypothesize that a HAX1‐deficient environment cannot sufficiently provide the essential factors for proper lymphocyte development, trafficking and survival. Hax1⁻/⁻ B cells show a significantly reduced expression of CXCR4, which might have an influence on the observed defects in B‐cell development.
Spatial neglect is a debilitating neurological disorder marked by reduced exploration of contralesional space. We developed an intervention in which eye movements to and within one half of a search ...display were reduced over the course of several hundred trials. The aim of this study was to determine whether this intervention had an effect on the deployment of attention of healthy participants as a first step towards application in patients. The participants carried out a visual search task during which the stimuli in one half of the search display were removed whenever the participants made eye movements towards it. The stimuli in the other half were unaffected by eye movements. Indeed, this led to a steady relative decrease in fixations within the affected half over the course of the intervention. In five experiments, the performance in different spatial attention paradigms was measured before and after this intervention. In two visual search paradigms (feature and conjunction search), exploration of the affected half decreased compared to the unaffected half. In a Posner task with exogenous cues, a partial effect of the intervention was found. However, an attempt at replicating this effect was not successful. The fifth experiment showed that performance in a line bisection paradigm was not significantly influenced by the intervention. To conclude, the intervention showed the potential to influence the behavior of healthy participants in overt attentional exploration tasks.
•We introduce a new intervention intended for the treatment of spatial neglect.•It is based on the gaze-contingent, side-specific removal of stimuli.•In healthy participants, it caused changes in the visual exploration pattern.•It changed where participants started a visual search and where they fixated.•The training effects transferred to a different search task.
The classical allergic reaction starts seconds or minutes after Ag contact and is committed by Abs produced by a special subset of B lymphocytes. These Abs belong to the IgE subclass and are ...responsible for Type I hyperreactivity reactions. Treatment of allergic diseases with humanized anti-IgE Abs leads primarily to a decrease of serum IgE levels. As a consequence, the number of high-affinity IgE receptors on mast cells and basophils decreases, leading to a lower excitability of the effector cells. The biological mechanism behind anti-IgE therapy remains partly speculative; however, it is likely that these Abs also interact with membrane IgE (mIgE) on B cells and possibly interfere with IgE production. In the present work, we raised a mouse mAb directed exclusively against the extracellular membrane-proximal domain of mIgE. The interaction between the monoclonal anti-mIgE Ab and mIgE induces receptor-mediated apoptosis in vitro. Passive immunization experiments lead to a block of newly synthesized specific IgEs during a parallel application of recombinant Bet v1a, the major birch pollen allergen. The decrease of allergen-specific serum IgE might be related to tolerance-inducing mechanisms stopping mIgE-displaying B cells in their proliferation and differentiation.
Hematopoietic progenitor kinase 1 (HPK1) is a Ste20-related serine/threonine kinase activated by a range of environmental stimuli including genotoxic stress, growth factors, inflammatory cytokines ...and antigen receptor triggering. Being inducibly recruited to membrane-proximal signalling scaffolds to regulate NFAT, AP-1 and NFkappaB-mediated gene transcription in T-cells, the function of HPK1 in B-cells to date remains rather ill-defined.
By using two loss of function models, we show that HPK1 displays a novel function in regulating B-cell integrin activity. Wehi 231 lymphoma cells lacking HPK1 after shRNA mediated knockdown exhibit increased basic activation levels of Ras-related protein 1 (Rap1), accompanied by a severe lymphocyte function-associated antigen-1 (LFA-1) dependent homotypic aggregation and increased adhesion to intercellular adhesion molecule 1 (ICAM-1). The observed phenotype of enhanced integrin activity is caused downstream of Src, by a signalling module independent of PI3K and PLC, involving HPK1, SKAP55 homologue (SKAP-HOM) and Rap1-GTP-interacting adaptor molecule (RIAM). This alters actin dynamics and renders focal adhesion kinase (FAK) constitutively phosphorylated. Bone marrow and splenic B-cell development of HPK1(-/-) mice are largely unaffected, except age-related tendencies for increased splenic cellularity and BCR downregulation. In addition, naïve splenic knockout B-cells appear hyperresponsive to a range of stimuli applied ex vivo as recently demonstrated by others for T-cells.
We therefore conclude that HPK1 exhibits a dual function in B-cells by negatively regulating integrin activity and controlling cellular activation, which makes it an interesting candidate to study in pathological settings like autoimmunity and cancer.
Submicron-scale milled zerovalent iron (milled ZVI) particles produced by grinding macroscopic raw materials could provide a cost-effective alternative to nanoscale zerovalent iron (nZVI) particles ...for in situ degradation of chlorinated aliphatic hydrocarbons in groundwater. However, the aggregation and settling of bare milled ZVI particles from suspension presents a significant obstacle to their in situ application for groundwater remediation. In our investigations we reduced the rapid aggregation and settling rate of bare milled ZVI particles from suspension by stabilization with a “green” agar agar polymer. The transport potential of stabilized milled ZVI particle suspensions in a diverse array of natural heterogeneous porous media was evaluated in a series of well-controlled laboratory column experiments. The impact of agar agar on trichloroethene (TCE) removal by milled ZVI particles was assessed in laboratory-scale batch reactors. The use of agar agar significantly enhanced the transport of milled ZVI particles in all of the investigated porous media. Reactivity tests showed that the agar agar-stabilized milled ZVI particles were reactive towards TCE, but that their reactivity was an order of magnitude less than that of bare, non-stabilized milled ZVI particles. Our results suggest that milled ZVI particles could be used as an alternative to nZVI particles as their potential for emplacement into contaminated zone, their reactivity, and expected longevity are beneficial for in situ groundwater remediation.
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•Rapid aggregation and sedimentation were observed in bare milled ZVI particles.•Agar agar improved the stability of milled ZVI particle suspensions.•Agar agar enhanced the transport of milled ZVI particles in heterogeneous sands.•Agar agar reduced the reactivity of milled ZVI particles towards TCE.
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