Seven-month-old infants detect symmetrical structures in multi-featured abstract visual patterns

The present study investigated 7-month-old infants' ability to perceive structural symmetry in mosaic-like abstract visual patterns. We examined infants' (n = 98) spontaneous looking behaviour to mosaic-like sequences with symmetrical and asymmetrical structures. Sequences were composed of square tiles from two categories that differed in their colour scheme and internal shape. We manipulated sequence length (3 or 5 tiles) and abstractness of the symmetry (token vs. category level). The 7-month-olds discriminated structurally symmetrical from asymmetrical mosaics in the first half of the test phase (first 8 trials). Sequence length, level of symmetry, or number of unique tiles per sequence did not significantly modulate infants' looking behaviour. These results suggest that very young infants detect differences in structural symmetry in multi-featured visual patterns.This work was supported by the Agence Nationale de la Recherche (ANR): Grant [SpeechCode—ANR-15-CE37-0009-01] to JG; the ANR's French Investissements d’Avenir – Labex EFL Program under Grant [ANR-10-LABX-0083] to JG; the European Research Council [Consolidator Grant 773202 ERC-2017-COG ‘BabyRhythm’] to JG; the Basque Foundation for Science Ikerbasque, to IdlCP; the Spanish Ministry of Science and Innovation [Grant nr. PID2019-105100RJ-I00] to IdlCP; the Austrian Science Fund [FWF Hertha Firnberg Grant T827-B27] to GWF and FWF DK Grant #W1262-B29] to WTF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Performance of Deaf Participants in an Abstract Visual Grammar Learning Task at Multiple Formal Levels: Evaluating the Auditory Scaffolding Hypothesis

Previous research has hypothesized that human sequential processing may be dependent upon hearing experience (the “auditory scaffolding hypothesis”), predicting that sequential rule learning abilities should be hindered by congenital deafness. To test this hypothesis, we compared deaf signer and hearing individuals’ ability to acquire rules of different computational complexity in a visual artificial grammar learning task using sequential stimuli. As a group, deaf participants succeeded at all levels of the task; Bayesian analysis indicates that they successfully acquired each of several target grammars at ascending levels of the formal language hierarchy. Overall, these results do not support the auditory scaffolding hypothesis. However, age- and education-matched hearing participants did outperform deaf participants in two out of three tested grammars. We suggest that this difference may be related to verbal recoding strategies in the two groups. Any verbal recoding strategies used by the deaf signers would be less effective because they would have to use the same visual channel required for the experimental task

Genetic targeting of NRXN2 in mice unveils role in excitatory cortical synapse function and social behaviors

Human genetics has identified rare copy number variations and deleterious mutations for all neurexin genes (NRXN1-3) in patients with neurodevelopmental diseases, and electrophysiological recordings in animal brains have shown that Nrxns are important for synaptic transmission. While several mouse models for Nrxn1α inactivation have previously been studied for behavioral changes, very little information is available for other variants. Here, we validate that mice lacking Nrxn2α exhibit behavioral abnormalities, characterized by social interaction deficits and increased anxiety-like behavior, which partially overlap, partially differ from Nrxn1α mutant behaviors. Using patch-clamp recordings in Nrxn2α knockout brains, we observe reduced spontaneous transmitter release at excitatory synapses in the neocortex. We also analyse at this cellular level a novel NRXN2 mouse model that carries a combined deletion of Nrxn2α and Nrxn2β. Electrophysiological analysis of this Nrxn2-mutant mouse shows surprisingly similar defects of excitatory release to Nrxn2α, indicating that the β-variant of Nrxn2 has no strong function in basic transmission at these synapses. Inhibitory transmission as well as synapse densities and ultrastructure remain unchanged in the neocortex of both models. Furthermore, at Nrxn2α and Nrxn2-mutant excitatory synapses we find an altered facilitation and N-methyl-D-aspartate receptor (NMDAR) function because NMDAR-dependent decay time and NMDAR-mediated responses are reduced. As Nrxn can indirectly be linked to NMDAR via neuroligin and PSD-95, the trans-synaptic nature of this complex may help to explain occurrence of presynaptic and postsynaptic effects. Since excitatory/inhibitory imbalances and impairment of NMDAR function are alledged to have a role in autism and schizophrenia, our results support the idea of a related pathomechanism in these disorders

Artificial Grammar Learning Capabilities in an Abstract Visual Task Match Requirements for Linguistic Syntax

Whether pattern-parsing mechanisms are specific to language or apply across multiple cognitive domains remains unresolved. Formal language theory provides a mathematical framework for classifying pattern-generating rule sets (or “grammars”) according to complexity. This framework applies to patterns at any level of complexity, stretching from simple sequences, to highly complex tree-like or net-like structures, to any Turing-computable set of strings. Here, we explored human pattern-processing capabilities in the visual domain by generating abstract visual sequences made up of abstract tiles differing in form and color. We constructed different sets of sequences, using artificial “grammars” (rule sets) at three key complexity levels. Because human linguistic syntax is classed as “mildly context-sensitive,” we specifically included a visual grammar at this complexity level. Acquisition of these three grammars was tested in an artificial grammar-learning paradigm: after exposure to a set of well-formed strings, participants were asked to discriminate novel grammatical patterns from non-grammatical patterns. Participants successfully acquired all three grammars after only minutes of exposure, correctly generalizing to novel stimuli and to novel stimulus lengths. A Bayesian analysis excluded multiple alternative hypotheses and shows that the success in rule acquisition applies both at the group level and for most participants analyzed individually. These experimental results demonstrate rapid pattern learning for abstract visual patterns, extending to the mildly context-sensitive level characterizing language. We suggest that a formal equivalence of processing at the mildly context sensitive level in the visual and linguistic domains implies that cognitive mechanisms with the computational power to process linguistic syntax are not specific to the domain of language, but extend to abstract visual patterns with no meaning

Accuracy Analysis of a Next-Generation Tissue Microarray on Various Soft Tissue Samples of Wistar Rats

This study aimed to investigate accuracy in different sectional planes of the TMA Grand Master (3DHISTECH) Workstation in various soft tissue samples collected from Wistar rats. A total of 108 animals were sacrificed and 963 tissue specimens collected from 12 soft-tissue types. A total of 3307 tissue cores were punched and transferred into 40 recipient TMA blocks. Digital image analysis was performed. Core loss showed a significant correlation with tissue type and was highest in skin tissue (p < 0.001), renal medulla and femoral artery, nerve, and vein bundle (p < 0.01). Overall, 231 of 3307 tissue cores (7.0%) were lost. Hit rate analysis was performed in 1852 punches. The target was hit completely, partially and missed totally by 89.4%, 7.2% and 2.2%. A total of 54.5% of punches had good accuracy with less than 200 µm deviation from the centre of the targeted region and 92.6% less than 500 µm. Accuracy decreases with greater sectional depth. In the deepest sectional plane of roughly 0.5 mm median depth, almost 90% of cores had a deviation below 500 µm. Recommendations for automated TMA creation are given in this article. The ngTMA®-method has proven accurate and reliable in different soft tissues, even in deeper sectional layers

Conceptual and Visual Features Contribute to Visual Memory for Natural Images

We examined the role of conceptual and visual similarity in a memory task for natural images. The important novelty of our approach was that visual similarity was determined using an algorithm [1] instead of being judged subjectively. This similarity index takes colours and spatial frequencies into account. For each target, four distractors were selected that were (1) conceptually and visually similar, (2) only conceptually similar, (3) only visually similar, or (4) neither conceptually nor visually similar to the target image. Participants viewed 219 images with the instruction to memorize them. Memory for a subset of these images was tested subsequently. In Experiment 1, participants performed a two-alternative forced choice recognition task and in Experiment 2, a yes/no-recognition task. In Experiment 3, testing occurred after a delay of one week. We analyzed the distribution of errors depending on distractor type. Performance was lowest when the distractor image was conceptually and visually similar to the target image, indicating that both factors matter in such a memory task. After delayed testing, these differences disappeared. Overall performance was high, indicating a large-capacity, detailed visual long-term memory

Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated with MYO5B Mutations

Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling.This research was funded by Jubiläumsfonds der Österreichischen Nationalbank, grant no.16678 (to A.R.J.), grant no. 18019 (to G.-F.V.) and Tiroler Wissenschaftsfonds, grant No. 0404/2386 (toG.-F.V.).info:eu-repo/semantics/publishedVersio

The p53 Tumor Suppressor Is Stabilized by Inhibitor of Growth 1 (ING1) by Blocking Polyubiquitination

The INhibitor of Growth tumor suppressors (ING1-ING5) affect aging, apoptosis, DNA repair and tumorigenesis. Plant homeodomains (PHD) of ING proteins bind histones in a methylation-sensitive manner to regulate chromatin structure. ING1 and ING2 contain a polybasic region (PBR) adjacent to their PHDs that binds stress-inducible phosphatidylinositol monophosphate (PtIn-MP) signaling lipids to activate these INGs. ING1 induces apoptosis independently of p53 but other studies suggest proapoptotic interdependence of ING1 and p53 leaving their functional relationship unclear. Here we identify a novel ubiquitin-binding domain (UBD) that overlaps with the PBR of ING1 and shows similarity to previously described UBDs involved in DNA damage responses. The ING1 UBD binds ubiquitin with high affinity (Kd∼100 nM) and ubiquitin competes with PtIn-MPs for ING1 binding. ING1 expression stabilized wild-type, but not mutant p53 in an MDM2-independent manner and knockdown of endogenous ING1 depressed p53 levels in a transcription-independent manner. ING1 stabilized unmodified and six multimonoubiquitinated forms of wild-type p53 that were also seen upon DNA damage, but not p53 mutants lacking the six known sites of ubiquitination. We also find that ING1 physically interacts with herpesvirus-associated ubiquitin-specific protease (HAUSP), a p53 and MDM2 deubiquitinase (DUB), and knockdown of HAUSP blocks the ability of ING1 to stabilize p53. These data link lipid stress signaling to ubiquitin-mediated proteasomal degradation through the PBR/UBD of ING1 and further indicate that ING1 stabilizes p53 by inhibiting polyubiquitination of multimonoubiquitinated forms via interaction with and colocalization of the HAUSP-deubiquitinase with p53