Background Autistic perception encompasses both inferior and superior performance on different types of visuospatial tasks. Influential neurocognitive models relevant to atypical perception (i.e., ...weak central coherence, enhanced perceptual functioning) can, to differing degrees, account for these findings. However, the neural underpinnings mediating atypical visuospatial autistic perception have yet to be elucidated. Methods In the present study, we used a lateral masking paradigm to assess the functional integrity of lateral interactions mediating visuospatial information processing within early visual areas of autistic ( n = 18) and nonautistic ( n = 15) observers. Detection thresholds were measured for centrally presented Gabor targets flanked collinearly at different distances (experiment 1) and flanked orthogonally at different contrasts (experiment 2). Results Autistic and nonautistic groups showed increased target sensitivity when the distance between collinear targets and flankers was small (3 lambda) but not large (6 lambda). However, the effect of small-distance facilitation was significantly greater for the autistic group. In addition, we observed a group-specific effect of contrast: in the autistic group, target sensitivity was enhanced by low flanker contrasts of both 5% and 10% luminance difference, whereas for the nonautistic group, this effect occurred at 10% contrast only. Conclusions These findings support the idea that atypical visuospatial perception in autism may originate from altered lateral connectivity within primary visual areas, differentially affecting perception at the earliest levels of feature extraction.
Autistics demonstrate superior performances on several visuo-spatial tasks where local or detailed information processing is advantageous. Altered spatial filtering properties at an early level of ...visuo-spatial analysis may be a plausible perceptual origin for such detailed perception in Autism Spectrum Disorder. In this study, contrast sensitivity for both luminance and texture-defined vertically-oriented sine-wave gratings were measured across a range of spatial frequencies (0.5, 1, 2, 4 & 8 cpd) for autistics and non-autistic participants. Contrast sensitivity functions and peak frequency ratios were plotted and compared across groups. Results demonstrated that autistic participants were more sensitivity to luminance-defined, high spatial frequency gratings (8 cpd). A group difference in peak distribution was also observed as 35% of autistic participants manifested peak sensitivity for luminance-defined gratings of 4 cpd, compared to only 7% for the comparison group. These findings support that locally-biased perception in Autism Spectrum Disorder originates, at least in part, from differences in response properties of early spatial mechanisms favouring detailed spatial information processing.
Although autism presents a unique perceptual phenotype defined in part by atypical (often enhanced) analysis of spatial information, few biologically plausible hypotheses have been advanced to ...explain its neural underpinnings. One plausible explanation is functional but altered lateral connectivity mediating early or local mechanisms selectively responsive to different stimulus attributes, including spatial frequency and contrast. The goal of the present study was first to assess far visual acuity in autism using Landolt-C optotypes defined by different local stimulus attributes. Second, we investigated whether acuity is differentially affected in autism when target optotypes are simultaneously presented with flanking stimuli at different distances. This typical detrimental "crowding effect" of flanking stimuli on target optotype discrimination is attributed to lateral inhibitory interaction of neurons encoding for visual properties of distracters close to the target. Results failed to demonstrate a between-group difference in acuity to Landolt-C optotypes, whether defined by luminance- or texture-contrast. However, the expected crowding effect at one gap-size opening distance was evidenced for the control group only; a small effect was observed for the autism group at two gap-size opening. These results suggest that although far visual acuity is unremarkable in autism, altered local lateral connectivity within early perceptual areas underlying spatial information processing in autism is atypical. Altered local lateral connectivity in autism might originate from an imbalance in excitatory/inhibitory neural signaling, resulting in changes regarding elementary feature extraction and subsequent downstream visual integration and visuo-spatial analysis. This notion is discussed within the context of characteristic lower- and higher-level perceptual processing in autism.
Hemispheric dominance has been behaviourally documented for the local (left hemisphere, LH) or global (right hemisphere, RH) processing of hierarchical letters. However, Fink et al. (1997) indicated ...that stimulus category modulates this hemispheric asymmetry. The purpose of this study was to investigate the influence of the category (letters versus objects) on hemispheric specialisation for global and local processing using a visual half-field presentation in a task where participants ignored whether the target appeared at the global or local level. In Experiment 1 we replicated the classic hemispheric asymmetry for global/local processing of hierarchical letters. In Experiment 2, which consisted of hierarchical object processing, a RH dominance for the local level was observed. In Experiment 3 a within-participant design was used where anticipation about the stimulus category was precluded, resulting in the classic RH and LH specialisations for global and local processing for both letter-based and object-based stimuli. Taken together, these results suggest that the highly demanding local processing stage engages one hemisphere more than the other, according to the lateralisation of cerebral networks specialised for stimulus category. In addition, the direction of lateralisation for the local level was also modulated by the predictability of the stimulus category.
The global level of hierarchical stimuli (Navon's stimuli) is typically processed quicker and better than the local level; further differential hemispheric dominance is described for local (left ...hemisphere, LH) and global (right hemisphere, RH) processing. However, neuroimaging and behavioral data indicate that stimulus category (letter or object) could modulate the hemispheric asymmetry for the local level processing. Besides, when the targets are unpredictably displayed at the global or local level, the participant has to switch between levels, and the magnitude of the switch cost increases with the number of repeated-level trials preceding the switch. The hemispheric asymmetries associated with level switching is an unresolved issue. LH areas may be involved in carrying over the target level information in case of level repetition. These areas may also largely participate in the processing of level-changed trials. Here we hypothesized that RH areas underly the inhibitory mechanism performed on the irrelevant level, as one of the components of the level switching process. In an experiment using a within-subject design, hierarchical stimuli were briefly presented either to the right or to the left visual field. 32 adults were instructed to identify the target at the global or local level. We assessed a possible RH dominance for the non-target level inhibition by varying the attentional demands through the manipulation of level repetitions (two or gour repeated-level trials before the switch). The behavioral data confirmed a LH specialization only for the local level processing of letter-based stimuli, and detrimental effect of increased level repetitions before a switch. Further, data provides evidence for a RH advantage in inhibiting the non-target level. Taken together, the data supports the notion of the existence of multiple mechanisms underlying level-switch effects.
Peptide drugs and biologics provide opportunities for treatments of many diseases. However, due to their poor stability and permeability in the gastrointestinal tract, the oral bioavailability of ...peptide drugs is negligible. Nanoparticle formulations have been proposed to circumvent these hurdles, but systemic exposure of orally administered peptide drugs has remained elusive. In this study, we investigated the absorption mechanisms of four insulin-loaded arginine-rich nanoparticles displaying differing composition and surface characteristics, developed within the pan-European consortium TRANS-INT. The transport mechanisms and major barriers to nanoparticle permeability were investigated in freshly isolated human jejunal tissue. Cytokine release profiles and standard toxicity markers indicated that the nanoparticles were nontoxic. Three out of four nanoparticles displayed pronounced binding to the mucus layer and did not reach the epithelium. One nanoparticle composed of a mucus inert shell and cell-penetrating octarginine (ENCP), showed significant uptake by the intestinal epithelium corresponding to 28 ± 9% of the administered nanoparticle dose, as determined by super-resolution microscopy. Only a small fraction of nanoparticles taken up by epithelia went on to be transcytosed via a dynamin-dependent process. In situ studies in intact rat jejunal loops confirmed the results from human tissue regarding mucus binding, epithelial uptake, and negligible insulin bioavailability. In conclusion, while none of the four arginine-rich nanoparticles supported systemic insulin delivery, ENCP displayed a consistently high uptake along the intestinal villi. It is proposed that ENCP should be further investigated for local delivery of therapeutics to the intestinal mucosa.
PIWI-interacting RNAs (piRNAs) silence transposons to maintain genome integrity in animal germ lines. piRNAs are classified as primary and secondary piRNAs, depending on their biogenesis machinery. ...Primary piRNAs are processed from long non-coding RNA precursors transcribed from piRNA clusters in the genome through the primary processing pathway. Although the existence of a ribonuclease participating in this pathway has been predicted, its molecular identity remained unknown. Here we show that Zucchini (Zuc), a mitochondrial phospholipase D (PLD) superfamily member, is an endoribonuclease essential for primary piRNA biogenesis. We solved the crystal structure of Drosophila melanogaster Zuc (DmZuc) at 1.75 Å resolution. The structure revealed that DmZuc has a positively charged, narrow catalytic groove at the dimer interface, which could accommodate a single-stranded, but not a double-stranded, RNA. DmZuc and the mouse homologue MmZuc (also known as Pld6 and MitoPLD) showed endoribonuclease activity for single-stranded RNAs in vitro. The RNA cleavage products bear a 5'-monophosphate group, a hallmark of mature piRNAs. Mutational analyses revealed that the conserved active-site residues of DmZuc are critical for the ribonuclease activity in vitro, and for piRNA maturation and transposon silencing in vivo. We propose a model for piRNA biogenesis in animal germ lines, in which the Zuc endoribonuclease has a key role in primary piRNA maturation.
PurposeEntrepreneurship education scholarship has been recently challenged to look at what goes on inside the entrepreneurship classroom to assess what students are really learning. Relying on the ...construction and analysis of a 3-h long set of learning activities on responsible entrepreneurship, this paper focuses on the activities conducted and what students have learned, based on Bloom's revised taxonomy of educational objectives.Design/methodology/approachThis paper builds on a pre-/post-intervention assessment around a set of learning activities with 151 undergraduate students. Before and after the class, students were asked to produce a definition of responsible entrepreneurship. They were also asked to reflect on what had changed from the beginning.FindingsAnalysis of students' pre/post definitions shows a standardization of their conceptions of responsible entrepreneurship. This result confirms that the learning objective of this class was met. Nevertheless, applying Bloom's revised taxonomy to students' reflections allows for more nuanced interpretation. The analysis indeed revealed that some students manifest relatively superficial learning while other shows a deeper ability to reflect on the concept.Originality/valueFirst, this paper contributes to the entrepreneurship education literature by showing the relevance of using Bloom's revised taxonomy for both teaching and research purposes. Second, it presents a set of innovative learning activities on responsible entrepreneurship that could be easily reproduced in other educational contexts. Third, it shows the importance of asking students what they learned and what has changed for them through class activities.