Linear Ballistic Accumulator Modeling of Attentional Bias Modification Revealed Disturbed Evidence Accumulation of Negative Information by Explicit Instruction

In recent years, several attentional bias modification (ABM) studies have been conducted. Previous studies have suggested that explicit instruction (i.e., informing participants of the contingency of stimuli) enhances the effect of ABM. However, the specific working mechanism has not been identified. This is partly because reaction time (RT) data are typically reduced to an attention bias score, which is a mere difference of RT between experimental and control conditions. This data reduction causes a loss of information, as RT reflects various cognitive processes at play while making a response or decision. To overcome this issue, the present study applied linear ballistic accumulator (LBA) modeling to the outcomes (RT measures) of explicitly guided (compared to standard) ABM. This computational modeling approach allowed us to dissociate RTs into distinct components that can be relevant for attentional bias, such as efficiency of information processing or prior knowledge of the task;this provides an understanding of the mechanism of action underlying explicitly guided ABM. The analyzed data were RT-observed in the dot-probe task, which was administered before and after 3-days of ABM training. Our main focus was on the changes in LBA components that would be induced by the training. Additionally, we analyzed in-session performances over the 3 days of training. The LBA analysis revealed a significant reduction in processing efficiency (i.e., drift rate) in the congruent condition, where the target probe is presented in the same location as a negative stimulus. This explains the reduction in the overall attentional bias score, suggesting that explicit ABM suppresses processing of negative stimuli. Moreover, the results suggest that explicitly guided ABM may influence prior knowledge of the target location in the training task and make participants prepared to respond to the task. These findings highlight the usefulness of LBA-based analysis to explore the underlying cognitive mechanisms in ABM, and indeed our analyses revealed the differences between the explicit and the standard ABM that could not be identified by traditional RT analysis or attentional bias scores

Ablation of Myeloid Cell MRP8 Ameliorates Nephrotoxic Serum-induced Glomerulonephritis by Affecting Macrophage Characterization through Intraglomerular Crosstalk

Toll-like receptor 4 (TLR4) and one of its endogenous ligands myeloid-related protein 8 (MRP8 or S100A8), especially expressed in macrophages, play an important role in diabetic nephropathy and autoimmune disorders. However, detailed mechanisms and consequence of MRP8 expression remain unknown, partly due to embryonic lethality of MRP8 knockout mice. In this study, Myeloid lineage cell-specific MRP8 knockout mice were generated, and nephrotoxic serum-induced glomerulonephritis was developed. Mice with conditional ablation of MRP8 gene in myeloid cells exhibited less severe histological damage, proteinuria and inflammatory changes compared to control mice. Mechanism of MRP8 upregulation was investigated using cultured cells. Co-culture of macrophages with mesangial cells or mesangial cell-conditioned media, but not with proximal tubules, markedly upregulated MRP8 gene expression and inflammatory M1 phenotype in macrophages, which was attenuated in MRP8-deleted bone marrow-derived macrophages. Effects of MRP8 deletion was further studied in the context of macrophage-inducible C-type lectin (Mincle), which is critically involved in maintenance of M1 phenotype of macrophages. MRP8 ablation in myeloid cells suppressed the induction of Mincle expression on macrophages in glomerulonephritis. Thus, we propose that intraglomerular crosstalk between mesangial cells and macrophages plays a role in inflammatory changes in glomerulonephritis, and MRP8-dependent Mincle expression in macrophage may be involved in the process

Explicitly Guided Attentional Bias Modification Promotes Attentional Disengagement From Negative Stimuli

Previous studies have shown that attentional bias modification (ABM) is effective in reducing negative attentional biases. However, the mechanisms underlying how ABM effectively reduces negative attentional biases are still unclear. In the present study, we conducted an ABM procedure that included a 3-day training session with a sample of nonclinical participants (N = 40) to investigate the effect of ABM on emotional and nonemotional attentional biases. Participants completed a modified dot-probe task with 2 different instructions (explicit or standard) during the training; their attentional biases were tested before and after the training. Only participants trained with explicit instructions showed a reduction in negative attentional biases in dot-probe task and an improvement in attentional disengagement from negative stimuli in gap-overlap task. On the other hand, attention toward nonemotional stimuli was only marginally improved by training with both explicit and standard instructions. These results indicate that explicit instructions may promote ABM training.status: publishe

Retinal ferroptosis as a critical mechanism for the induction of retinochoroiditis during ocular toxoplasmosis

Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer 57Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT

Assay for Hepatitis B Core-related Antigen Identify Patients With High Viral Load: Systematic Review and Meta-analysis of Individual Participant Data

International audienceScale-up of tests and treatments is needed to eliminate hepatitis B virus (HBV) infection from resource-limited countries. However, access to nucleic acid tests that quantify HBV DNA, to determine treatment eligibility, is severely limited. We performed a systematic review and meta-analysis to assess the performance of the hepatitis B core-related antigen (HBcrAg) immunoassay, a low-cost (less than $15/assay) alternative to the nucleic acid test, to identify highly viremic patients, infected with any HBV genotype

Critical Role of Heparin Binding Domains of Ameloblastin for Dental Epithelium Cell Adhesion and Ameloblastoma Proliferation*

AMBN (ameloblastin) is an enamel matrix protein that regulates cell adhesion, proliferation, and differentiation of ameloblasts. In AMBN-deficient mice, ameloblasts are detached from the enamel matrix, continue to proliferate, and form a multiple cell layer; often, odontogenic tumors develop in the maxilla with age. However, the mechanism of AMBN functions in these biological processes remains unclear. By using recombinant AMBN proteins, we found that AMBN had heparin binding domains at the C-terminal half and that these domains were critical for AMBN binding to dental epithelial cells. Overexpression of full-length AMBN protein inhibited proliferation of human ameloblastoma AM-1 cells, but overexpression of heparin binding domain-deficient AMBN protein had no inhibitory effect. In full-length AMBN-overexpressing AM-1 cells, the expression of Msx2, which is involved in the dental epithelial progenitor phenotype, was decreased, whereas the expression of cell proliferation inhibitors p21 and p27 was increased. We also found that the expression of enamelin, a marker of differentiated ameloblasts, was induced, suggesting that AMBN promotes odontogenic tumor differentiation. Thus, our results suggest that AMBN promotes cell binding through the heparin binding sites and plays an important role in preventing odontogenic tumor development by suppressing cell proliferation and maintaining differentiation phenotype through Msx2, p21, and p27