Dendritic cells process synthetic long peptides better than whole protein,improving antigen presentation and T‐cell activation

The efficiency of antigen (Ag) processing by dendritic cells (DCs) is vital for the strength of the ensuing T‐cell responses. Previously, we and others have shown that in comparison to protein vaccines, vaccination with synthetic long peptides (SLPs) has shown more promising (pre‐)clinical results. Here, we studied the unknown mechanisms underlying the observed vaccine efficacy of SLPs. We report an in vitro processing analysis of SLPs for MHC class I and class II presentation by murine DCs and human monocyte‐derived DCs. Compared to protein, SLPs were rapidly and much more efficiently processed by DCs, resulting in an increased presentation to CD4⁺ and CD8⁺ T cells. The mechanism of access to MHC class I loading appeared to differ between the two forms of Ag. Whereas whole soluble protein Ag ended up largely in endolysosomes, SLPs were detected very rapidly outside the endolysosomes after internalization by DCs, followed by proteasome‐ and transporter associated with Ag processing‐dependent MHC class I presentation. Compared to the slower processing route taken by whole protein Ags, our results indicate that the efficient internalization of SLPs, accomplished by DCs but not by B or T cells and characterized by a different and faster intracellular routing, leads to enhanced CD8⁺ T‐cell activation.     

Interactions between the perception of age and ethnicity in faces: an event-related potential study

Face perception models propose that different facial attributes are processed by anatomically distinct neural pathways that partially overlap. Whether these attributes interact functionally is an open question. Our goal was to determine if there are interactions between age and ethnicity processing and, if so, at what temporal epoch these interactions are evident. We monitored event-related potentials on electroencephalography while subjects categorized faces by age or ethnicity in two conditions: a baseline in which the other of these two properties not being categorized was held constant and an interference condition in which it also varied, as modelled after the Garner interference paradigm. We found that, when participants were categorizing faces by age, variations in ethnicity increased the amplitude of the right face-selective N170 component. When subjects were categorizing faces by ethnicity, variations in age did not alter the N170. We concluded that there is an asymmetric pattern of influence between age and ethnicity on early face-specific stages of visual processing, which has parallels with behavioural evidence of asymmetric interactions between identity and expression processing of faces.     

Working memory and emotional interpretation bias in a sample of Syrian refugee adolescents

The number of adolescent refugees around the world has been continuously increasing over the past few years trying to escape war and terror, among other things. Such experience not only increases the risk for mental health problems including anxiety, depression, and post-traumatic stress disorder (PTSD), but also may have implications for socio-cognitive development. This study tested cognitive-affective processing in refugee adolescents who had escaped armed conflict in Syria and now resided in Istanbul, Turkey. Adolescents were split into a high trauma (n = 31, 12 girls, mean age = 11.70 years, SD = 1.15 years) and low trauma (n = 27, 14 girls, mean age = 11.07 years, SD = 1.39 years) symptom group using median split, and performed a working memory task with emotional distraction to assess cognitive control and a surprise faces task to assess emotional interpretation bias. The results indicated that high (vs. low) trauma symptom youth were ~ 20% worse correctly remembering the spatial location of a cue, although both groups performed at very low levels. However, this finding was not modulated by emotion. In addition, although all youths also had a ~ 20% bias toward interpreting ambiguous (surprise) faces as more negative, the high (vs. low) symptom youth were faster when allocating such a face to the positive (vs. negative) emotion category. The findings suggest the impact of war-related trauma on cognitive-affective processes essential to healthy development.

     

Learning to Synchronize: Midfrontal Theta Dynamics during Rule Switching

In recent years, several hierarchical extensions of well-known learning algorithms have been proposed. For example, when stimulus-action mappings vary across time or context, the brain may learn two or more stimulus-action mappings in separate modules, and additionally (at a hierarchically higher level) learn to appropriately switch between those modules. However, how the brain mechanistically coordinates neural communication to implement such hierarchical learning remains unknown. Therefore, the current study tests a recent computational model that proposed how midfrontal theta oscillations implement such hierarchical learning via the principle of binding by synchrony (Sync model). More specifically, the Sync model uses bursts at theta frequency to flexibly bind appropriate task modules by synchrony. The 64-channel EEG signal was recorded while 27 human subjects (female: 21, male: 6) performed a probabilistic reversal learning task. In line with the Sync model, postfeedback theta power showed a linear relationship with negative prediction errors, but not with positive prediction errors. This relationship was especially pronounced for subjects with better behavioral fit (measured via Akaike information criterion) of the Sync model. Also consistent with Sync model simulations, theta phase-coupling between midfrontal electrodes and temporoparietal electrodes was stronger after negative feedback. Our data suggest that the brain uses theta power and synchronization for flexibly switching between task rule modules, as is useful, for example, when multiple stimulus-action mappings must be retained and used.SIGNIFICANCE STATEMENT Everyday life requires flexibility in switching between several rules. A key question in understanding this ability is how the brain mechanistically coordinates such switches. The current study tests a recent computational framework (Sync model) that proposed how midfrontal theta oscillations coordinate activity in hierarchically lower task-related areas. In line with predictions of this Sync model, midfrontal theta power was stronger when rule switches were most likely (strong negative prediction error), especially in subjects who obtained a better model fit. Additionally, also theta phase connectivity between midfrontal and task-related areas was increased after negative feedback. Thus, the data provided support for the hypothesis that the brain uses theta power and synchronization for flexibly switching between rules.     

Detection of ectopic thyroid remnants: A serious diagnostic dilemma. When molecular biology and immunohistochemistry can solve the problem

The presence of ectopic thyroid tissue is a frequent diagnostic feedback related to a possible histogenetic abnormality or a result of post-surgical seeding. The important challenge is the diagnostic definition of its nature, which could lead to a different therapeutic approach. We describe a case with all the possible implications and differential diagnoses supported by the application of immunohistochemistry and BRAF-V600E molecular detection.     

A study of prevention and regression of cardiac hypertrophy with a prolactin inhibitor in a biological model of ventricular hypertrophy caused by aorto caval fistulae in rat

BackgroundThe possibility of decreasing or reverting left ventricular hypertrophy and, therefore, cardiac hypertrophy (CH) is an important medical issue. The aim of the present study was to evaluate these two possibilities with a 3-week daily dose of captopril, losartan, or bromocriptine in a preventive or corrective model.MethodsAfter aorto caval fistulae (ACF) surgery on adult male Wistar rats to induce CH, animals were assigned to the preventive protocol (drug treatment began immediately after surgery) or corrective protocol (hypertrophy was allowed to develop before drug treatment). After treatments, isoproterenol was administered to half of the animals to further induce CH. The groups included the passive control, the sham-operated animals, those with ACF surgery but without drug treatment, and the 3-week treatments with captopril, losartan, or the low or high dose of bromocriptine.ResultsThree treatments, with captopril, losartan, or the high dose of bromocriptine, significantly impeded/reverted an increase in CH-related parameters in the preventive/corrective model compared to the surgically treated group without drug treatment. The same effect was found after isoproterenol administration. The present results show an avoidance/reversion of CH with these three treatments. Better results were found with the angiotensin converting enzyme inhibitor (captopril) than with the prolactin inhibitor (bromocriptine).ConclusionsTreatments with captopril, losartan, and the high dose of bromocriptine were effective in preventing/reversing the manifestation of CH in the preventive/corrective rat models. Further studies are needed to identify the initial mediator, the key component, and the molecular events involved in the pathogenesis of CH.     

Autosomal Recessive Spinocerebellar Ataxia 7 (SCAR7) is Caused by Variants in TPP1, The Gene Involved in Classic Late‐Infantile Neuronal Ceroid Lipofuscinosis 2 Disease (CLN2 Disease)

Spinocerebellar ataxias are phenotypically, neuropathologically, and genetically heterogeneous. The locus of autosomal recessive spinocerebellar ataxia type 7 (SCAR7) was previously linked to chromosome band 11p15. We have identified TPP1 as the causative gene for SCAR7 by exome sequencing. A missense and a splice site variant in TPP1, cosegregating with the disease, were found in a previously described SCAR7 family and also in another patient with a SCAR7 phenotype. TPP1, encoding the tripeptidyl‐peptidase 1 enzyme, is known as the causative gene for late infantile neuronal ceroid lipofuscinosis disease 2 (CLN2 disease). CLN2 disease is characterized by epilepsy, loss of vision, ataxia, and a rapidly progressive course, leading to early death. SCAR7 patients showed ataxia and low activity of tripeptidyl‐peptidase 1, but no ophthalmologic abnormalities or epilepsy. Also, the slowly progressive evolution of the disease until old age and absence of ultra structural curvilinear profiles is different from the known CLN2 phenotypes. Our findings now expand the phenotypes related to TPP1‐variants to SCAR7. In spite of the limited sample size and measurements, a putative genotype–phenotype correlation may be drawn: we hypothesize that loss of function variants abolishing TPP1 enzyme activity lead to CLN2 disease, whereas variants that diminish TPP1 enzyme activity lead to SCAR7.