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Studies of face perception in primates elucidate the psychological and neural mechanisms that support this critical and complex ability. Recent progress in characterizing face perception across species, for example in insects and reptiles, has highlighted the ubiquity over phylogeny of this key ability for social interactions and survival. Here, we review the competence in face perception across species and the types of computation that support this behavior. We conclude that the computational complexity of face perception evinced by a species is not related to phylogenetic status and is, instead, largely a product of environmental context and social and adaptive pressures. Integrating findings across evolutionary data permits the derivation of computational principles that shed further light on primate face perception.

Human brain mapping 43(1), 37-55 (2022). doi:10.1002/hbm.25029 special issue: "Special Issue: The ENIGMA Consortium: the first 10 years / Issue Edited by: P.M. Thompson, N. Jahanshad, L. Schmaal, J.A. Turner, A. Winkler, S.I. Thomopoulos, G.F. Egan, P. Kochunov", Published by Wiley-Liss, New York, NY

Despite our differences, there is much about the natural visual world that most observers perceive in common. Across adults, approximately 30% of the brain is activated in a consistent fashion while viewing naturalistic input. At what stage of development is this consistency of neural profile across individuals present? Here, we focused specifically on whether this mature profile is present in adolescence, a key developmental period that bridges childhood and adulthood, and in which new cognitive and social challenges are at play. We acquired fMRI data evoked by a movie shown twice to younger (9–14 years old) and older adolescents (15–19 years old) and to adults, and conducted three key analyses. First, we characterized the consistency of the neural response within individuals (across separate runs of the movie), then within individuals of the same age group, and, last, between age groups. The neural consistency within individuals was similar across age groups with reliable activation in largely overlapping but slightly different cortical regions. In contrast, somewhat differing regions exhibited higher within-age correlations in both groups of adolescents than in the adults. Last, across the whole cortex, we identified regions evincing different patterns of maturation across age. Together, these findings provide a fine-grained characterization of functional neural development in adolescence and uncover signatures of widespread change in cortical coherence that supports the emerging mature stereotypical responses to naturalistic stimuli. These results also offer a more nuanced account of development that obeys neither a rigid linear progression nor a large qualitative change over time.

The right and left cerebral hemispheres are important for face and word recognition, respectively—a specialization that emerges over human development. The question is whether this bilateral distribution is necessary or whether a single hemisphere, be it left or right, can support both face and word recognition. Here, face and word recognition accuracy in patients (median age 16.7 y) with a single hemisphere following childhood hemispherectomy was compared against matched typical controls. In experiment 1, participants viewed stimuli in central vision. Across both face and word tasks, accuracy of both left and right hemispherectomy patients, while significantly lower than controls' accuracy, averaged above 80% and did not differ from each other. To compare patients' single hemisphere more directly to one hemisphere of controls, in experiment 2, participants viewed stimuli in one visual field to constrain initial processing chiefly to a single (contralateral) hemisphere. Whereas controls had higher word accuracy when words were presented to the right than to the left visual field, there was no field/hemispheric difference for faces. In contrast, left and right hemispherectomy patients, again, showed comparable performance to one another on both face and word recognition, albeit significantly lower than controls. Altogether, the findings indicate that a single developing hemisphere, either left or right, may be sufficiently plastic for comparable representation of faces and words. However, perhaps due to increased competition or “neural crowding,” constraining cortical representations to one hemisphere may collectively hamper face and word recognition, relative to that observed in typical development with two hemispheres.

A rich behavioral literature has shown that human object recognition is supported by a representation of shape that is tolerant to variations in an object's appearance. Such 'global' shape representations are achieved by describing objects via the spatial arrangement of their local features, or structure, rather than by the appearance of the features themselves. However, accumulating evidence suggests that the ventral visual pathway - the primary substrate underlying object recognition - may not represent global shape. Instead, ventral representations may be better described as a basis set of local image features. We suggest that this evidence forces a reevaluation of the role of the ventral pathway in object perception and posits a broader network for shape perception that encompasses contributions from the dorsal pathway.

In March 2020, the SARS-CoV-2 virus outbreak was declared as a world pandemic by the World Health Organization (WHO). The only measures for controlling the outbreak are testing and isolation of infected cases. Molecular real-time polymerase chain reaction (PCR) assays are very sensitive but require highly equipped laboratories and well-trained personnel. In this study, a rapid point-of-need detection method was developed to detect the RNA-dependent RNA polymerase (RdRP), envelope protein (E), and nucleocapsid protein (N) genes of SARS-CoV-2 based on the reverse transcription recombinase polymerase amplification (RT-RPA) assay. RdRP, E, and N RT-RPA assays required approximately 15 min to amplify 2, 15, and 15 RNA molecules of molecular standard/reaction, respectively. RdRP and E RT-RPA assays detected SARS-CoV-1 and 2 genomic RNA, whereas the N RT-RPA assay identified only SARS-CoV-2 RNA. All established assays did not cross-react with nucleic acids of other respiratory pathogens. The RT-RPA assay's clinical sensitivity and specificity in comparison to real-time RT-PCR (n = 36) were 94 and 100% for RdRP; 65 and 77% for E; and 83 and 94% for the N RT-RPA assay. The assays were deployed to the field, where the RdRP RT-RPA assays confirmed to produce the most accurate results in three different laboratories in Africa (n = 89). The RPA assays were run in a mobile suitcase laboratory to facilitate the deployment at point of need. The assays can contribute to speed up the control measures as well as assist in the detection of COVID-19 cases in low-resource settings.

Cytokines orchestrate responses to pathogens and in inflammatory processes, but they also play an important role in cancer by shaping the expression levels of cytokine response genes. Here, we conducted a large profiling study comparing miRNome and mRNA transcriptome data generated following different cytokine stimulations. Transcriptomic responses to STAT1- (IFNγ, IL-27) and STAT3-activating cytokines (IL6, OSM) were systematically compared in nine cancerous and non-neoplastic cell lines of different tissue origins (skin, liver and colon). The largest variation in our datasets was seen between cell lines of the three different tissues rather than stimuli. Notably, the variability in miRNome datasets was a lot more pronounced than in mRNA data. Our data also revealed that cells of skin, liver and colon tissues respond very differently to cytokines and that the cell signaling networks activated or silenced in response to STAT1- or STAT3-activating cytokines are specific to the tissue and the type of cytokine. However, globally, STAT1-activating cytokines had stronger effects than STAT3-inducing cytokines with most significant responses in liver cells, showing more genes upregulated and with higher fold change. A more detailed analysis of gene regulations upon cytokine stimulation in these cells provided insights into STAT1- versus STAT3-driven processes in hepatocarcinogenesis. Finally, independent component analysis revealed interconnected transcriptional networks distinct between cancer cells and their healthy counterparts.

Rationale: The PTH1R (PTH [parathyroid hormone]/PTHrP [PTH-related protein] receptor) is expressed in vascular smooth muscle (VSM) and increased VSM PTH1R signaling mitigates diet-induced arteriosclerosis in LDLR −/− mice. Objective: To study the impact of VSM PTH1R deficiency, we generated mice SM22-Cre:PTH1R(fl/fl);LDLR −/− mice (PTH1R-VKO) and Cre-negative controls. Methods and Results: Immunofluorescence and Western blot confirmed PTH1R expression in arterial VSM that was reduced by Cre-mediated knockout. PTH1R-VKO cohorts exhibited increased aortic collagen accumulation in vivo, and VSM cultures from PTH1R-VKO mice elaborated more collagen (2.5-fold; P =0.01) with elevated Col3a1 and Col1a1 expression. To better understand these profibrotic responses, we performed mass spectrometry on nuclear proteins extracted from Cre-negative controls and PTH1R-VKO VSM. PTH1R deficiency reduced Gata6 but upregulated the MADS (MCM1, Agamous, Deficiens, and Srf DNA-binding domain)-box transcriptional co-regulator, Mkl-1 (megakaryoblastic leukemia [translocation] 1). Co-transfection assays ( Col3a1 promoter-luciferase reporter) confirmed PTH1R-mediated inhibition and Mkl-1-mediated activation of Col3a1 transcription. Regulation mapped to a conserved hybrid CT(A/T) 6 GG MADS-box cognate in the Col3a1 promoter. Mutations of C/G in this motif markedly reduced Col3a1 transcriptional regulation by PTH1R and Mkl-1. Upregulation of Col3a1 and Col1a1 in PTH1R-VKO VSM was inhibited by small interfering RNA targeting Mkl1 and by treatment with the Mkl-1 antagonist CCG1423 or the Rock (Rho-associated coiled-coil containing protein kinase)-2 inhibitor KD025. Chromatin precipitation demonstrated that VSM PTH1R deficiency increased Mkl-1 binding to Col3a1 and Col1a1 , but not TNF , promoters. Proteomic studies of plasma extracellular vesicles and VSM from PTH1R-VKO mice identified C1r (complement component 1, r) and C1s (complement component 1, s), complement proteins involved in vascular collagen metabolism, as potential biomarkers. VSM C1r protein and C1r message were increased with PTH1R deficiency, mediated by Mkl-1-dependent transcription and inhibited by CCG1423 or KD025. Conclusions: PTH1R signaling restricts collagen production in the VSM lineage, in part, via Mkl-1 regulatory circuits that control collagen gene transcription. Strategies that maintain homeostatic VSM PTH1R signaling, as reflected in extracellular vesicle biomarkers of VSM PTH1R/Mkl-1 action, may help mitigate arteriosclerosis and vascular fibrosis.

Introduction: Myeloid malignancies are caused by uncontrolled proliferation of neoplastic cells and lack of mature hematopoietic cells. Beside intrinsic genetic and epigenetic alterations within the neoplastic population, abnormal function of the bone marrow stroma promotes the neoplastic process. To overcome the supportive action of the microenvironment, recent research focuses on the development of targeted therapies, inhibiting the interaction of malignant cells and niche cells. Areas covered: This review covers regulatory networks and potential druggable pathways within the hematopoietic stem cell niche. Recent insights into the cell-to-cell interactions in the bone marrow microenvironment are presented. We performed literature searches using PubMed Database from 2000 to the present. Expert opinion: Future therapy of myeloid malignancies must focus on targeted, personalized treatment addressing specific alterations within the malignant and the supporting niche cells. This includes treatments to overcome resistance mechanisms against chemotherapeutic agents mediated by supporting microenvironment. Novel techniques employing sequencing approaches, Crisp/Cas9, or transgenic mouse models are required to elucidate specific interactions between components of the bone marrow niche to identify new therapeutic targets.

Collagen VI is a ubiquitous heterotrimeric protein of the extracellular matrix (ECM) that plays an essential role in the proper maintenance of skeletal muscle. Mutations in collagen VI lead to a spectrum of congenital myopathies, from the mild Bethlem myopathy to the severe Ullrich congenital muscular dystrophy. Collagen VI contains only a short triple helix and consists primarily of von Willebrand factor type A (VWA) domains, protein–protein interaction modules found in a range of ECM proteins. Disease-causing mutations occur commonly in the VWA domains, and the second VWA domain of the α3 chain, the N2 domain, harbors several such mutations. Here, we investigate structure-function relationships of the N2 mutations to shed light on their possible myopathy mechanisms. We determined the X-ray crystal structure of N2, combined with monitoring secretion efficiency in cell culture of selected N2 single-domain mutants, finding that mutations located within the central core of the domain severely affect secretion efficiency. In longer α3 chain constructs, spanning N6-N3, small-angle X-ray scattering demonstrates that the tandem VWA array has a modular architecture and samples multiple conformations in solution. Single-particle EM confirmed the presence of multiple conformations. Structural adaptability appears intrinsic to the VWA domain region of collagen VI α3 and has implications for binding interactions and modulating stiffness within the ECM.

Subtyping of the most common non-small cell lung cancer (NSCLC) tumor types adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) is still a challenge in the clinical routine and a correct diagnosis is crucial for an adequate therapy selection. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has shown potential for NSCLC subtyping but is subject to strong technical variability and has only been applied to tissue samples assembled in tissue microarrays (TMAs). To our knowledge, a successful transfer of a classifier from TMAs to whole sections, which are generated in the standard clinical routine, has not been presented in the literature as of yet. We introduce a classification algorithm using extensive preprocessing and a classifier (either a neural network or a linear discriminant analysis (LDA)) to robustly classify whole sections of ADC and SqCC lung tissue. The classifiers were trained on TMAs and validated and tested on whole sections. Vital for a successful application on whole sections is the extensive preprocessing and the use of whole sections for hyperparameter selection. The classification system with the neural network/LDA results in 99.0%/98.3% test accuracy on spectra level and 100.0%/100.0% test accuracy on whole section level, respectively, and, therefore, provides a powerful tool to support the pathologist's decision making process. The presented method is a step further towards a clinical application of MALDI MSI and artificial intelligence for subtyping of NSCLC tissue sections.

Contains fulltext : 251394.pdf (Publisher’s version ) (Open Access) Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.

Background: Epstein-Barr virus (EBV) is an oncogenic virus found in about 95% of endemic Burkitt lymphoma (BL) cases. In latently infected cells, EBV DNA is mostly maintained in episomal form, but it can also be integrated into the host genome, or both forms can coexist in the infected cells. Methods: In this study, we mapped the chromosomal integration sites of EBV (EBV-IS) into the genome of 21 EBV+ BL cell lines (BL-CL) using metaphase fluorescence in situ hybridization (FISH). The data were used to investigate the EBV-IS distribution pattern in BL-CL, its relation to the genome instability, and to assess its association to common fragile sites and episomes. Results: We detected a total of 459 EBV-IS integrated into multiple genome localizations with a preference for gene-poor chromosomes. We did not observe any preferential affinity of EBV to integrate into common and rare fragile sites or enrichment of EBV-IS at the chromosomal breakpoints of the BL-CL analyzed here, as other DNA viruses do. Conclusions: We identified a non-random integration pattern into 13 cytobands, of which eight overlap with the EBV-IS in EBV-transformed lymphoblastoid cell lines and with a preference for gene- and CpGs-poor G-positive cytobands. Moreover, it has been demonstrated that the episomal form of EBV interacts in a non-random manner with gene-poor and AT-rich regions in EBV+ cell lines, which may explain the observed affinity for G-positive cytobands in the EBV integration process. Our results provide new insights into the patterns of EBV integration in BL-CL at the chromosomal level, revealing an unexpected connection between the episomal and integrated forms of EBV.

Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen's d = -0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.

Although there is mounting evidence that input from the dorsal visual pathway is crucial for object processes in the ventral pathway, the specific functional contributions of dorsal cortex to these processes remain poorly understood. Here, we hypothesized that dorsal cortex computes the spatial relations among an object’s parts – a processes crucial for forming global shape percepts – and transmits this information to the ventral pathway to support object categorization. Using fMRI with human participants (females and males), we discovered regions in the intraparietal sulcus (IPS) that were selectively involved in computing object-centered part relations. These regions exhibited task-dependent functional and effective connectivity with ventral cortex, and were distinct from other dorsal regions, such as those representing allocentric relations, 3D shape, and tools. In a subsequent experiment, we found that the multivariate response of posterior IPS, defined on the basis of part-relations, could be used to decode object category at levels comparable to ventral object regions. Moreover, mediation and multivariate effective connectivity analyses further suggested that IPS may account for representations of part relations in the ventral pathway. Together, our results highlight specific contributions of the dorsal visual pathway to object recognition. We suggest that dorsal cortex is a crucial source of input to the ventral pathway and may support the ability to categorize objects on the basis of global shape.Significance StatementHumans categorize novel objects rapidly and effortlessly. Such categorization is achieved by representing an object’s global shape structure, that is, the relations among object parts. Yet, despite their importance, it is unclear how part relations are represented neurally. Here, we hypothesized that object-centered part relations may be computed by the dorsal visual pathway, which is typically implicated in visuospatial processing. Using fMRI, we identified regions selective for the part relations in dorsal cortex. We found that these regions can support object categorization, and even mediate representations of part relations in the ventral pathway, the region typically thought to support object categorization. Together, these findings shed light on the broader network of brain regions that support object categorization.

Background: According to the WHO, the COVID-19 pandemic could have a negative impact on the mental health of individuals, such as an exacerbation of existing difficulties. Individuals with ADHD may be specifically challenged by the pandemic. Aims: To provide a systematic review of evidence regarding the COVID-19’s impact on mental health of individuals with ADHD during the COVID-19 lockdown. Methods: This registered review (PROSPERO ID CRD42021238770) adhered to Prisma guidelines. Systematic searches in electronic databases PubMed and PsycINFO were carried out. A total of 12 studies covering 3,028 subjects were included. Results: COVID-19 pandemic is associated with increased ADHD symptoms and psychological difficulties. Some studies reported that individuals experienced positive outcomes. The methodological quality of the studies was low to moderate. Conclusion: COVID-19 can affect the mental health of individuals with ADHD negatively, although methodological limitations should be considered. Further research should generate knowledge about long-term effects impact of the pandemic and about appropriate support.

ObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.MethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures).ResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.ConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.

Studies of the emergence of shape representations in childhood have focused primarily on the ventral visual pathway. Importantly, however, there is increasing evidence that, in adults, the dorsal pathway also represents shape-based information. These dorsal representations follow a gradient with more posterior regions being more shape-sensitive than anterior regions and with representational similarity in some posterior regions that is equivalent to that observed in some ventral regions. To explore the emergence and nature of dorsal shape representations in development, we acquired both fMRI BOLD signals and behavioral data in children (aged 8–10 years) using a parametric image scrambling paradigm. Children exhibited adult-like large-scale organization of shape processing along both ventral and dorsal pathways. Also, as in adults, the activation profiles of children's posterior dorsal and ventral regions were correlated with recognition performance, reflecting a possible contribution of these signals to perception. There were age-related changes, however, with children being more affected by the distortion of shape information than adults, both behaviorally and neurally. These findings reveal that shape-processing mechanisms along both dorsal and ventral pathways are subject to a protracted developmental trajectory.

Visual object recognition is performed effortlessly by humans notwithstanding the fact that it requires a series of complex computations, which are, as yet, not well understood. Here, we tested a novel account of the representations used for visual recognition and their neural correlates using fMRI. The rationale is based on previous research showing that a set of representations, termed “minimal recognizable configurations” (MIRCs), which are computationally derived and have unique psychophysical characteristics, serve as the building blocks of object recognition. We contrasted the BOLD responses elicited by MIRC images, derived from different categories (faces, objects, and places), sub-MIRCs, which are visually similar to MIRCs, but, instead, result in poor recognition and scrambled, unrecognizable images. Stimuli were presented in blocks, and participants indicated yes/no recognition for each image. We confirmed that MIRCs elicited higher recognition performance compared to sub-MIRCs for all three categories. Whereas fMRI activation in early visual cortex for both MIRCs and sub-MIRCs of each category did not differ from that elicited by scrambled images, high-level visual regions exhibited overall greater activation for MIRCs compared to sub-MIRCs or scrambled images. Moreover, MIRCs and sub-MIRCs from each category elicited enhanced activation in corresponding category-selective regions including fusiform face area and occipital face area (faces), lateral occipital cortex (objects), and parahippocampal place area and transverse occipital sulcus (places). These findings reveal the psychological and neural relevance of MIRCs and enable us to make progress in developing a more complete account of object recognition.

Objective Individuals with migraine exhibit heightened sensitivity to visual input that continues beyond their migraine episodes. However, the contribution of color to visual sensitivity, and how it relates to neural activity, has largely been unexplored in these individuals. Background Previously, it has been shown that, in non-migraine individuals, patterns with greater chromaticity separation evoked greater cortical activity, regardless of hue, even when colors were isoluminant. Therefore, to investigate whether individuals with migraine experienced increased visual sensitivity, we compared the behavioral and neural responses to chromatic patterns of increasing separation in migraine and non-migraine individuals. Methods Seventeen individuals with migraine (12 with aura) and 18 headache-free controls viewed pairs of colored horizontal grating patterns that varied in chromaticity separation. Color pairs were either blue-green, red-green, or red-blue. Participants rated the discomfort of the gratings and electroencephalogram was recorded simultaneously. Results Both groups showed increased discomfort ratings and larger N1/N2 event-related potentials (ERPs) with greater chromaticity separation, which is consistent with increased cortical excitability. However, individuals with migraine rated gratings as being disproportionately uncomfortable and exhibited greater effects of chromaticity separation in ERP amplitude across occipital and parietal electrodes. Ratings of discomfort and ERPs were smaller in response to the blue-green color pairs than the red-green and red-blue gratings, but this was to an equivalent degree across the 2 groups. Conclusions Together, these findings indicate that greater chromaticity separation increases neural excitation, and that this effect is heightened in migraine, consistent with the theory that hyper-excitability of the visual system is a key signature of migraine.

The consequences of cortical resection, a treatment for humans with pharmaco-resistant epilepsy, provide a unique opportunity to advance our understanding of the nature and extent of cortical (re)organization. Despite the importance of visual processing in daily life, the neural and perceptual sequellae of occipitotemporal resections remain largely unexplored. Using psychophysical and fMRI investigations, we compared the neural and visuoperceptual profiles of 10 children or adolescents following unilateral cortical resections and their age- and gender-matched controls. Dramatically, with the exception of two individuals, both of whom had relatively greater cortical alterations, all patients showed normal perceptual performance on tasks of intermediate- and high-level vision, including face and object recognition. Consistently, again with the exception of the same two individuals, both univariate and multivariate fMRI analyses revealed normal selectivity and representational structure of category-selective regions. Furthermore, the spatial organization of category-selective regions obeyed the typical medial-to-lateral topographic organization albeit unilaterally in the structurally preserved hemisphere rather than bilaterally. These findings offer novel insights into the malleability of cortex in the pediatric population and suggest that, although experience may be necessary for the emergence of neural category-selectivity, this emergence is not necessarily contingent on the integrity of particular cortical structures. SIGNIFICANCE STATEMENT One approach to reduce seizure activity in patients with pharmaco-resistant epilepsy involves the resection of the epileptogenic focus. The impact of these resections on the perceptual behaviors and organization of visual cortex remain largely unexplored. Here, we characterized the visuoperceptual and neural profiles of ventral visual cortex in a relatively large sample of post-resection pediatric patients. Two major findings emerged. First, most patients exhibited preserved visuoperceptual performance across a wide-range of visual behaviors. Second, normal topography, magnitude, and representational structure of category-selective organization were uncovered in the spared hemisphere. These comprehensive imaging and behavioral investigations uncovered novel evidence concerning the neural representations and visual functions in children who have undergone cortical resection, and have implications for cortical plasticity more generally.

Although shape perception is primarily considered a function of the ventral visual pathway, previous research has shown that both dorsal and ventral pathways represent shape information. Here, we examine whether the shape-selective electrophysiological signals observed in dorsal cortex are a product of the connectivity to ventral cortex or are independently computed. We conducted multiple EEG studies in which we manipulated the input parameters of the stimuli so as to bias processing to either the dorsal or ventral visual pathway. Participants viewed displays of common objects with shape information parametrically degraded across five levels. We measured shape sensitivity by regressing the amplitude of the evoked signal against the degree of stimulus scrambling. Experiment 1, which included grayscale versions of the stimuli, served as a benchmark establishing the temporal pattern of shape processing during typical object perception. These stimuli evoked broad and sustained patterns of shape sensitivity beginning as early as 50 msec after stimulus onset. In Experiments 2 and 3, we calibrated the stimuli such that visual information was delivered primarily through parvocellular inputs, which mainly project to the ventral pathway, or through koniocellular inputs, which mainly project to the dorsal pathway. In the second and third experiments, shape sensitivity was observed, but in distinct spatio-temporal configurations from each other and from that elicited by grayscale inputs. Of particular interest, in the koniocellular condition, shape selectivity emerged earlier than in the parvocellular condition. These findings support the conclusion of distinct dorsal pathway computations of object shape, independent from the ventral pathway.

© 2018 Elsevier Inc. Vision for action and vision for perception both rely on shape representations derived within the visual system. Whether the same psychological and neural mechanisms underlie both forms of behavior remains hotly contested, and whether this arrangement is equivalent in adults and children is controversial as well. To address these outstanding questions, we used an established psychophysical heuristic, Weber's law, which, in adults, has typically been observed for perceptual judgment tasks but not for actions such as grasping. We examined whether this perception–action dissociation in Weber's law was present in childhood as it is in adulthood and whether it was modulated by stimulus complexity. Two major results emerged. First, although adults evinced visuomotor behavior that violated Weber's law, young children (4.5–6.5 years) adhered to Weber's law when they grasped complex objects (“Efron” blocks), which varied along both the graspable and non-graspable dimensions to maintain a constant surface area, but not when they grasped simple objects, which varied only along the graspable dimension. Second, adherence to Weber's law was found across all ages in the context of a perceptual task. Together, these findings suggest that, in early childhood, visuomotor representations are modulated by perceptual representations, particularly when a refined description of object shape is needed.

This paper discusses otorhinolaryngological symptoms associated with functional disorders of the upper cervical spine. Hints aimed to avoid misdiagnoses of cross-organ otorhinolaryngological symptoms as phobic or psychogenic disorders are presented. Clinically relevant neuroanatomical convergence of the upper cervical spine (occiput to C3) is fundamental for the interpretation of functional otorhinolaryngological symptoms. Based thereon, evidence for the most common cervical differential diagnoses of dizziness, tinnitus, dysphagia, and craniomandibular dysfunction is presented separately. The corresponding therapeutic options and their contraindications are discussed in the concluding chapter. The importance of interdisciplinary cooperation in related fields is emphasized.

Congenital prosopagnosia (CP), a life-long impairment in face processing that occurs in the absence of any apparent brain damage, provides a unique model in which to explore the psychological and neural bases of normal face processing. The goal of this review is to offer a theoretical and conceptual framework that may account for the underlying cognitive and neural deficits in CP. This framework may also provide a novel perspective in which to reconcile some conflicting results that permits the expansion of the research in this field in new directions. The crux of this framework lies in linking the known behavioral and neural underpinnings of face processing and their impairments in CP to a model incorporating grid cell–like activity in the entorhinal cortex. Moreover, it stresses the involvement of active, spatial scanning of the environment with eye movements and implicates their critical role in face encoding and recognition. To begin with, we describe the main behavioral and neural characteristics of CP, and then lay down the building blocks of our proposed model, referring to the existing literature supporting this new framework. We then propose testable predictions and conclude with open questions for future research stemming from this model.

The human cortical visual system consists of two major pathways, a ventral pathway which subserves perception and a dorsal pathway which primarily subserves visuomotor control. Previous studies have found that children with cortical resections of the ventral visual pathway retain largely normal visuoperceptual abilities. Whether visually guided actions, supported by computations carried out by the dorsal pathway, follow a similar pattern of preservation remains unknown. To address this question, we examined visuoperceptual and visuomotor behaviors in a pediatric patient, TC, who underwent a cortical resection that included portions of the left ventral and dorsal pathways. We collected kinematic data when TC used her right and left hands to perceptually estimate the width of blocks that varied in width and length, and, separately, to grasp the same blocks. TC’s perceptual estimation performance was comparable to that of controls, independent of the hand used. In contrast, relative to controls, she showed reduced visuomotor sensitivity to object shape and this was more evident when she grasped the objects with her contralesional right hand. These results provide novel evidence for a striking difference in the competence of the two visual pathways to cortical injuries acquired in childhood.

Modern cancer therapies increased the survival rates of acute myeloid leukemia (AML) patients tremendously. However, the complexity of the disease and the identification of new targets require the adaptation of treatment protocols to reduce side effects and increase benefit for the patients. One key regulator of leukemogenesis and chemotherapy resistance in AML is the Hedgehog (HH) signaling pathway. It is deregulated in numerous cancer entities and inhibition of its downstream transcription factors GLI translates into anti-leukemic effects. One major regulator of GLI is BRD4, a BET family member with epigenetic functions. We investigated the effect of ZEN-3365, a novel BRD4 inhibitor, on AML cells in regard to the HH pathway. We show that ZEN-3365 alone or in combination with GANT-61 reduced GLI promoter activity, cell proliferation and colony formation in AML cell lines and primary cells. Our findings strongly support the evaluation of the BRD4 inhibitor ZEN-3365 as a new therapeutic option in AML.

Despite the relative successes in the surgical treatment of pharmacoresistant epilepsy, there is rather little research on the neural (re)organization that potentially subserves behavioral compensation. Here, we examined the post-surgical functional connectivity (FC) in children and adolescents who have undergone unilateral cortical resection and, yet, display remarkably normal behavior. Conventionally, FC has been investigated in terms of the mean correlation of the BOLD time courses extracted from different brain regions. Here, we demonstrated the value of segregating the voxel-wise relationships into mutually exclusive populations that were either positively or negatively correlated. While, relative to controls, the positive correlations were largely normal, negative correlations among networks were increased. Together, our results point to reorganization in the contralesional hemisphere, possibly suggesting competition for cortical territory due to the demand for representation of function. Conceivably, the ubiquitous negative correlations enable the differentiation of function in the reduced cortical volume following a unilateral resection.

The present article aims at describing a rare case of an RP patient who evolved with heart block and was successfully treated with corticoid pulse therapy, without the need for pacemaker insertion.A systematic research on relapsing polychondritis (RP) and heart block (HB) published in PubMed/MEDLINE, Web of Sciences, LILACS, and Scielo from 1966 to August 2020 was performed.It was found 10 studies on RP associated with HB, and we added a case. Most were male (7/10) with ages 30 to 66 years old. RP disease duration was 1 week-6 years. In most cases (7/10), the RP was active when the HB occurred. A complete HB was observed in 4/7, followed by type II degree block in 3/7, and one patient had a sinus node dysfunction. Most patients received glucocorticoids. A pacemaker was inserted in 4/9 cases. Good outcome was observed in 3/9 patients and mortality in 2/10.We report the first case of an RP patient who had a heart block and was successfully treated with methylprednisolone pulse therapy. The authors suggest that in these RP cases, an attempt with a glucocorticoid pulse therapy may be offered to treat the heart block and prevent the insertion of a pacemaker.

A rapid and cost-effective noninvasive tool to detect and characterize neural silences can be of important benefit in diagnosing and treating many disorders. We propose an algorithm, SilenceMap, for uncovering the absence of electrophysiological signals, or neural silences, using noninvasive scalp electroencephalography (EEG) signals. By accounting for the contributions of different sources to the power of the recorded signals, and using a hemispheric baseline approach and a convex spectral clustering framework, SilenceMap permits rapid detection and localization of regions of silence in the brain using a relatively small amount of EEG data. SilenceMap substantially outperformed existing source localization algorithms in estimating the center-of-mass of the silence for three pediatric cortical resection patients, using fewer than 3 minutes of EEG recordings (13, 2, and 11mm vs. 25, 62, and 53 mm), as well for 100 different simulated regions of silence based on a real human head model (12 ± 0.7 mm vs. 54 ± 2.2 mm). SilenceMap paves the way towards accessible early diagnosis and continuous monitoring of altered physiological properties of human cortical function., Chamanzar et al. demonstrate that an algorithm, ‘SilenceMap’, results in rapid detection and localization of neural silences using just a few minutes of noninvasive scalp electroencephalography (EEG) recording. SilenceMap vastly outperformed existing algorithms in accuracy of localizing silences in human participants with circumscribed cortical resections, indicating its potential use for the monitoring of cortical function and health.

In this case report, two boys were admitted to an eye department at a hospital in Denmark. They had been playing with a laser pointer, which had been bought abroad during a holiday. The laser was pointed directly into the eyes of both boys eyes, resulting in small retinal marks afterwards. The boys had visual discomfort and a feeling of missing some central vision. On an optical coherence tomography it was possible to capture a small retinal damage affecting the outer segment of the retina but without damage to Bruchs membrane. Both boys recovered from discomfort and were discharged from the department after a four month follow-up.

We recently argued that human unfamiliar face identity perception reflects substantial perceptual expertise, and that the advantage for familiar over unfamiliar face identity matching reflects a learned mapping between generic high-level perceptual features and a unique identity representation of each individual (Blauch, Behrmann and Plaut, 2020). Here we respond to two commentaries by Young and Burton (2020) and Yovel and Abudarham (2020), clarifying and elaborating our stance on various theoretical issues, and discussing topics for future research in human face recognition and the learning of perceptual representations.

Aberrant activation of the hedgehog (HH) pathway is observed in many neoplasms, including acute myeloid leukemia (AML). The glioma-associated oncogene homolog (GLI) transcription factors are the main downstream effectors of the HH signaling cascade and are responsible for the proliferation and maintenance of leukemic stem cells, which support chemotherapy resistance and leukemia relapse. Cytarabine (Ara-C)-resistant variants of AML cell lines were established through long-term cultivation with successively increasing Ara-C concentrations. Subsequently, differences in GLI expression were analyzed by RT-qPCR. GLI3 mRNA levels were detectable in parental Kasumi-1, OCI-AML3, and OCI-AML5 cells, whereas GLI3 expression was completely silenced in all resistant counterparts. Therefore, we generated GLI3-knockdown cell lines using small hairpin RNAs (shRNA) and evaluated their sensitivity to Ara-C in vitro. The knockdown of GLI3 partly abolished the effect of Ara-C on colony formation and induction of apoptosis, indicating that GLI3 downregulation results in Ara-C resistance. Moreover, we analyzed the expression of several genes involved in Ara-C metabolism and transport. Knockdown of GLI3 resulted in the upregulation of SAM and HD domain-containing protein 1 (SAMHD1), cytidine deaminase (CDA), and ATP-binding cassette C11 (ABCC11)/multidrug resistance-associated protein 8 (MRP8), each of which has been identified as a predictive marker for Ara-C response in acute myeloid leukemia. Our results demonstrate that GLI3 downregulation is a potential mechanism to induce chemotherapy resistance in AML.

Hypoxia is a common hallmark of solid tumors and is associated with aggressiveness, metastasis and poor outcome. Cancer cells under hypoxia undergo changes in metabolism and there is an intense crosstalk between cancer cells and cells from the tumor microenvironment. This crosstalk is facilitated by small extracellular vesicles (sEVs; diameter between 30 and 200 nm), including exosomes and microvesicles, which carry a cargo of proteins, mRNA, ncRNA and other biological molecules. Hypoxia is known to increase secretion of sEVs and has an impact on the composition of the cargo. This sEV-mediated crosstalk ultimately leads to various biological effects in the proximal tumor microenvironment but also at distant, future metastatic sites. In this review, we discuss the changes induced by hypoxia on sEV secretion and their cargo as well as their effects on the behavior and metabolism of cancer cells, the tumor microenvironment and metastatic events.

Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, such as hypersensitivity to environmental stimuli. Attentional engagement is known to be regulated by the locus coeruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether individuals with ASD exhibit a different profile of LC activity compared to typically developing controls under different attentional task demands. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses—an established inverse correlate for baseline LC activity—were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared to controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed only in response to task-relevant and not to task-irrelevant stimuli, providing confirmation that the group differences are specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD.Significance StatementIndividuals with autism spectrum disorder (ASD) exhibit atypical attentional behaviors, such as environmental hypersensitivity and atypical fixedness, but the neural mechanism underlying these behaviors remains elusive. One candidate mechanism is atypical locus coeruleus (LC) activity, as the LC has a critical role in attentional modulation. Elevated LC activity is associated with environmental exploration, while moderate LC activity is associated with focused attention on relevant stimuli. This study shows that, under tightly controlled conditions, task-evoked pupil responses—an LC activity proxy—are lower in individuals with ASD than in controls, but only in the presence of task-irrelevant stimuli. This suggests that individuals with ASD evince atypical modulation of LC activity in accordance with changes in attentional demands, offering a mechanistic account for attentional atypicalities in ASD.

Irrespective of whether one has substantial perceptual expertise for a class of stimuli, an observer invariably encounters novel exemplars from this class. To understand how novel exemplars are represented, we examined the extent to which previous experience with a category constrains the acquisition and nature of representation of subsequent exemplars from that category. Participants completed a perceptual training paradigm with either novel other-race faces (category of experience) or novel computer-generated objects (YUFOs) that included pairwise similarity ratings at the beginning, middle, and end of training, and a 20-d visual search training task on a subset of category exemplars. Analyses of pairwise similarity ratings revealed multiple dissociations between the representational spaces for those learning faces and those learning YUFOs. First, representational distance changes were more selective for faces than YUFOs; trained faces exhibited greater magnitude in representational distance change relative to untrained faces, whereas this trained–untrained distance change was much smaller for YUFOs. Second, there was a difference in where the representational distance changes were observed; for faces, representations that were closer together before training exhibited a greater distance change relative to those that were farther apart before training. For YUFOs, however, the distance changes occurred more uniformly across representational space. Last, there was a decrease in dimensionality of the representational space after training on YUFOs, but not after training on faces. Together, these findings demonstrate how previous category experience governs representational patterns of exemplar learning as well as the underlying dimensionality of the representational space.

Background The current outbreak of SARS-CoV-2 has spread to almost every country with more than 5 million confirmed cases and over 300,000 deaths as of May 26, 2020. Rapid first-line testing protocols are needed for outbreak control and surveillance. Methods We used computational and manual designs to generate a suitable set of reverse transcription recombinase polymerase amplification (RT-RPA) primer and exonuclease probe, internally quenched (exo-IQ), sequences targeting the SARS-CoV-2 N gene. RT-RPA sensitivity was determined by amplification of in vitro transcribed RNA standards. Assay selectivity was demonstrated with a selectivity panel of 32 nucleic acid samples derived from common respiratory viruses. To validate the assay against full-length SARS-CoV-2 RNA, total viral RNA derived from cell culture supernatant and 19 nasopharyngeal swab samples (8 positive and 11 negative for SARS-CoV-2) were screened. All results were compared to established RT-qPCR assays. Results The 95% detection probability of the RT-RPA assay was determined to be 7.74 (95% CI: 2.87–27.39) RNA copies per reaction. The assay showed no cross-reactivity to any other screened coronaviruses or respiratory viruses of clinical significance. The developed RT-RPA assay produced 100% diagnostic sensitivity and specificity when compared to RT-qPCR (n = 20). Conclusions With a run time of 15 to 20 minutes and first results being available in under 7 minutes for high RNA concentrations, the reported assay constitutes one of the fastest nucleic acid based detection methods for SARS-CoV-2 to date and may provide a simple-to-use alternative to RT-qPCR for first-line screening at the point of need.

Recent research has demonstrated that neural and behavioral data acquired in response to viewing face images can be used to reconstruct the images themselves. However, the theoretical implications, promises, and challenges of this direction of research remain unclear. Here, we evaluate the potential of this research for elucidating the visual representations underlying face recognition. Specifically, we outline complementary and converging accounts of the visual content, the representational structure, and the neural dynamics of face processing. We illustrate how this research addresses fundamental questions in the study of normal and impaired face recognition, and how image reconstruction provides a powerful framework for uncovering face representations, for unifying multiple types of empirical data, and for facilitating both theoretical and methodological progress.

Despite the similarity in structure, the hemispheres of the human brain have somewhat different functions. A traditional view of hemispheric organization asserts that there are independent and largely lateralized domain-specific regions in ventral occipitotemporal (VOTC), specialized for the recognition of distinct classes of objects. Here, we offer an alternative account of the organization of the hemispheres, with a specific focus on face and word recognition. This alternative account relies on three computational principles: distributed representations and knowledge, cooperation and competition between representations, and topography and proximity. The crux is that visual recognition results from a network of regions with graded functional specialization that is distributed across both hemispheres. Specifically, the claim is that face recognition, which is acquired relatively early in life, is processed by VOTC regions in both hemispheres. Once literacy is acquired, word recognition, which is co-lateralized with language areas, primarily engages the left VOTC and, consequently, face recognition is primarily, albeit not exclusively, mediated by the right VOTC. We review psychological and neural evidence from a range of studies conducted with normal and brain-damaged adults and children and consider findings which challenge this account. Last, we offer suggestions for future investigations whose findings may further refine this account.

The assessment of water quality is critical to implement preventive and emergency interventions aimed to limit/avoid environmental contamination and human exposure to toxic compounds. While established high-resolution techniques allow quantitative and qualitative determination of contaminants, their widespread application is not feasible due to cost, time, and need for trained personnel. In this context, the development of easy-to-implement approaches for preliminary detection of contaminants is of the utmost importance. Herein, a portable self-powered microbial electrochemical sensor enabling online monitoring of Cr(VI) is reported. The biosensor employs a bio-inspired redox mediating system to allow extracellular electron transfer between a bacterial isolate from chromium-contaminated environments and the electrode, providing a clear response to Cr(VI) presence. The biosensor shows good linearity (R

Interleukin-6 (IL-6)-type cytokines play important roles in liver (patho-)biology. For instance, they regulate the acute phase response to inflammatory signals and are involved in hepatocarcinogenesis. Much is known about the regulation of protein-coding genes by cytokines whereas their effects on the miRNome is less well understood. We performed a microarray screen to identify microRNAs (miRNAs) in human hepatocytes which are modulated by IL-6-type cytokines. Using samples of 2 donors, 27 and 68 miRNAs (out of 1,733) were found to be differentially expressed upon stimulation with hyper-IL-6 (HIL-6) for up to 72 h, with an overlap of 15 commonly regulated miRNAs. qPCR validation revealed that miR-146b-5p was also consistently up-regulated in hepatocytes derived from 2 other donors. Interestingly, miR-146b-5p (but not miR-146a-5p) was induced by IL-6-type cytokines (HIL-6 and OSM) in non-transformed liver-derived PH5CH8 and THLE2 cells and in Huh-7 hepatoma cells, but not in HepG2 or Hep3B hepatoma cells. We did not find evidence for a differential regulation of miR-146b-5p expression by promoter methylation, also when analyzing the TCGA data set on liver cancer samples. Inducible overexpression of miR-146b-5p in PH5CH8 cells followed by RNA-Seq analysis revealed effects on multiple mRNAs, including those encoding IRAK1 and TRAF6 crucial for Toll-like receptor signaling. Indeed, LPS-mediated signaling was attenuated upon overexpression of miR-146b-5p, suggesting a regulatory loop to modulate inflammatory signaling in hepatocytes. Further validation experiments suggest DNAJC6, MAGEE1, MPHOSPH6, PPP2R1B, SLC10A3, SNRNP27, and TIMM17B to be novel targets for miR-146b-5p (and miR-146a-5p). IL-6-type cytokines up-regulate miR-146b-5p expression in liver cells, an anti-inflammatory miRNA with multiple targets shared with miR-146a-5p.

In aortic vascular smooth muscle (VSM), the canonical Wnt receptor LRP6 inhibits protein arginine (Arg) methylation, a new component of noncanonical Wnt signaling that stimulates nuclear factor of activated T cells (viz. NFATc4). To better understand how methylation mediates these actions, MS was performed on VSM cell extracts from control and LRP6-deficient mice. LRP6-dependent Arg methylation was regulated on >500 proteins; only 21 exhibited increased monomethylation (MMA) with concomitant reductions in dimethylation. G3BP1, a known regulator of arteriosclerosis, exhibited a >30-fold increase in MMA in its C-terminal domain. Co-transfection studies confirm that G3BP1 (G3BP is Ras-GAP SH3 domain–binding protein) methylation is inhibited by LRP6 and that G3BP1 stimulates NFATc4 transcription. NFATc4 association with VSM osteopontin (OPN) and alkaline phosphatase (TNAP) chromatin was increased with LRP6 deficiency and reduced with G3BP1 deficiency. G3BP1 activation of NFATc4 mapped to G3BP1 domains supporting interactions with RIG-I (retinoic acid inducible gene I), a stimulus for mitochondrial antiviral signaling (MAVS) that drives cardiovascular calcification in humans when mutated in Singleton-Merten syndrome (SGMRT2). Gain-of-function SGMRT2/RIG-I mutants increased G3BP1 methylation and synergized with osteogenic transcription factors (Runx2 and NFATc4). A chemical antagonist of G3BP, C108 (C108 is 2-hydroxybenzoic acid, 2-[1-(2-hydroxyphenyl)ethylidene]hydrazide CAS 15533-09-2), down-regulated RIG-I–stimulated G3BP1 methylation, Wnt/NFAT signaling, VSM TNAP activity, and calcification. G3BP1 deficiency reduced RIG-I protein levels and VSM osteogenic programs. Like G3BP1 and RIG-I deficiency, MAVS deficiency reduced VSM osteogenic signals, including TNAP activity and Wnt5-dependent nuclear NFATc4 levels. Aortic calcium accumulation is decreased in MAVS-deficient LDLR(−/−) mice fed arteriosclerotic diets. The G3BP1/RIG-I/MAVS relay is a component of Wnt signaling. Targeting this relay may help mitigate arteriosclerosis.

Scientific research involves going beyond the well-trodden and well-tested ideas and theories that form the core of scientific knowledge. During the time scientists are working things out, some results will be right, and others will be wrong. Over time, the right results will emerge. Lisa Randall (Frank B. Baird, Jr. Professor of Science, Physics Department, Harvard University) We are grateful to all the commentators for the important and thoughtful comments raised in response to the Geskin and Behrmann (G & B) literature survey. The issues raised in the introduction to this Special Issue and in these commentaries not only address and challenge aspects of the G & B literature review, but contribute perspectives and extensions that go well beyond the scope of the review. As is evident from G & B and from the 13 commentaries, many aspects of congenital prosopagnosia (CP) remain controversial. Adopting the language of the quote above, the intention of the G & B survey, along with the commentaries and this response, is to establish a collaborative process from which the right results (and right theory) will emerge in time. We are grateful to the editor of this Special Issue, Dr. Brad Mahon, for his support and for facilitating this collaborative exchange in Cognitive Neuropsychology.

PCR inhibitors in clinical specimens negatively affect the sensitivity of diagnostic PCR and RT-PCR or may even cause false-negative results. To overcome PCR inhibition, increase the sensitivity of the assays and simplify the detection protocols, simple methods based on quantitative nested real-time PCR and RT-PCR were developed to detect exogenous DNA and RNA directly from large volumes of whole human blood (WHB). Thermus thermophilus (Tth) polymerase is resistant to several common PCR inhibitors and exhibits reverse transcriptase activity in the presence of manganese ions. In combination with optimized concentrations of magnesium ions and manganese ions, Tth polymerase enabled efficient detection of DNA and RNA from large volumes of WHB treated with various anticoagulants. The applicability of these methods was further demonstrated by examining WHB specimens collected from different healthy individuals and those stored under a variety of conditions. The detection limit of these methods was determined by detecting exogenous DNA, RNA, and bacteria spiked in WHB. To the best of our knowledge, direct RNA detection from large volumes of WHB has not been reported. The results of the developed methods can be obtained within 4 hours, making them possible for rapid and accurate detection of disease-causing agents from WHB.

Face perception is considered to be evolutionarily adaptive and conserved across species. While subcortical visual brain areas are implicated in face perception based on existing evidence from phylogenetic and ontogenetic studies, whether these subcortical structures contribute to more complex visual computations such as the holistic processing (HP) of faces in humans is unknown. To address this issue, we used a well-established marker of HP, the composite face effect (CFE), with a group of adult human observers, and presented two sequential faces in a trial monocularly or interocularly using a Wheatstone stereoscope. HP refers to the finding that two identical top (or bottom) halves of a face are judged to be different when their task-irrelevant bottom (or top) halves belong to different faces. Because humans process faces holistically, they are unable to ignore the information from the irrelevant half of the composite face, and this is true to an even greater extent when the two halves of the faces are aligned compared with when they are misaligned (‘Alignment effect’). The results revealed the HP effect and also uncovered the Alignment effect, a key marker of the CFE. The findings also indicated a monocular advantage, replicating the known subcortical contribution to face perception. There was, however, no statistically significant difference in the CFE when the images were presented in the monocular versus interocular conditions. These findings indicate that HP is not necessarily mediated by the subcortical visual pathway, and suggest that further investigation of cortical, rather than subcortical, structures might advance our understanding of HP and its role in face processing.

This study investigates the force required to reduce or “cinch” the tricuspid annulus under elevated right ventricular pressures, commonly seen in patients with pulmonary hypertension. Tricuspid regurgitation affects 1.6 million Americans. Approximately 43% of patients who undergo tricuspid valve repair to correct tricuspid regurgitation will develop residual pulmonary hypertension, putting them at risk for developing increased right ventricle pressures. Previous studies have quantified the forces required to cinch the tricuspid annulus by only pressurizing the right ventricle, leaving out forces from the pressurized left ventricle and septal wall unaccounted for. This study pressurized both left and right ventricles of 10 porcine hearts to their normal physiological pressures of 110 mmHg and 30 mmHg respectively, then increased right ventricular pressures to mimic moderate and severe pulmonary hypertension. A suture was anchored around the free wall of the tricuspid annulus with the free end attached to a force transducer. The force transducer was mounted on a slider system which pulled the suture at regular intervals. The cinching force on the tricuspid annulus was quantified with each annular reduction by simulating peak systole condition in both ventricles. The data was compared with only the right ventricle pressurized as previous studies did. There were significant differences in required cinching forces with each increase in right ventricular pressure and between trials that pressurized both ventricles versus only the right ventricle, suggesting adoption of this physiologically improved protocol. We also found with increased cinching of the tricuspid annulus, notable changes occur in the mitral annulus.