Atypical neural responding to hearing one’s own name in adults with ASD

Diminished responding to hearing one's own name is one of the earliest and strongest predictors of autism spectrum disorder (ASD). Here, we studied, for the first time, the neural correlates of hearing one's own name in ASD. Based on existing research, we hypothesized enhancement of late parietal positive activity specifically for the own name in neurotypicals, and for this effect to be reduced in adults with ASD. Source localization analyses were conducted to estimate group differences in brain regions underlying this effect. Twenty-one adults with ASD, and 21 age-and gender-matched neurotypicals were presented with 3 categories of names (own name, close other, unknown other) as task-irrelevant deviant stimuli in an auditory oddball paradigm while electroencephalogram was recorded. As expected, late parietal positivity was observed specifically for own names in neurotypicals, indicating enhanced attention to the own name. This preferential effect was absent in the ASD group. This group difference was associated with diminished activation in the right temporoparietal junction (rTPJ) in adults with ASD. Further, a familiarity effect was found for N1 amplitude, with larger amplitudes for familiar names (own name and close other). However, groups did not differ for this effect. These findings provide evidence of atypical neural responding to hearing one's own name in adults with ASD, suggesting a deficit in self-other distinction associated with rTPJ dysfunction

The interplay between serine proteases and caspase-1 regulates the autophagy-mediated secretion of Interleukin-1 beta in human neutrophils

Neutrophils play major roles against bacteria and fungi infections not only due to their microbicide properties but also because they release mediators like Interleukin-1 beta (IL-1β) that contribute to orchestrate the inflammatory response. This cytokine is a leaderless protein synthesized in the cytoplasm as a precursor (pro-IL-1β) that is proteolytically processed to its active isoform and released from human neutrophils by secretory autophagy. In most myeloid cells, pro-IL-1β is processed by caspase-1 upon inflammasome activation. Here we employed neutrophils from both healthy donors and patients with a gain-of-function (GOF) NLRP3-mutation to dissect IL-1β processing in these cells. We found that although caspase-1 is required for IL-1β secretion, it undergoes rapid inactivation, and instead, neutrophil serine proteases play a key role in pro-IL-1β processing. Our findings bring to light distinctive features of the regulation of caspase-1 activity in human neutrophils and reveal new molecular mechanisms that control human neutrophil IL-1β secretion.Fil: Keitelman, Irene Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Shiromizu, Carolina Maiumi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Zgajnar, Nadia Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Danielián, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Jancic, Carolina Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Fuentes, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Yancoski, Judith. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Vera Aguilar, Douglas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Rosso, David Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Goris, Verónica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Buda, Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Katsicas, María Martha. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Galigniana, Mario D.. Universidad de Buenos Aires; ArgentinaFil: Galletti, Jeremías Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Sabbione, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Trevani, Analía Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Assessment of Global Ocean Biogeochemistry Models for Ocean Carbon Sink Estimates in RECCAP2 and Recommendations for Future Studies

The ocean is a major carbon sink and takes up 25%–30% of the anthropogenically emitted CO2. A state-of-the-art method to quantify this sink are global ocean biogeochemistry models (GOBMs), but their simulated CO2 uptake differs between models and is systematically lower than estimates based on statistical methods using surface ocean pCO2 and interior ocean measurements. Here, we provide an in-depth evaluation of ocean carbon sink estimates from 1980 to 2018 from a GOBM ensemble. As sources of inter-model differences and ensemble-mean biases our study identifies (a) the model setup, such as the length of the spin-up, the starting date of the simulation, and carbon fluxes from rivers and into sediments, (b) the simulated ocean circulation, such as Atlantic Meridional Overturning Circulation and Southern Ocean mode and intermediate water formation, and (c) the simulated oceanic buffer capacity. Our analysis suggests that a late starting date and biases in the ocean circulation cause a too low anthropogenic CO2 uptake across the GOBM ensemble. Surface ocean biogeochemistry biases might also cause simulated anthropogenic fluxes to be too low, but the current setup prevents a robust assessment. For simulations of the ocean carbon sink, we recommend in the short-term to (a) start simulations at a common date before the industrialization and the associated atmospheric CO2 increase, (b) conduct a sufficiently long spin-up such that the GOBMs reach steady-state, and (c) provide key metrics for circulation, biogeochemistry, and the land-ocean interface. In the long-term, we recommend improving the representation of these metrics in the GOBMs

Autistic traits in the general population do not correlate with a preference for associative information

Background: Associations and regularities in our environment can foster expectations and thereby help create a perceptually predictable world (e.g., a knife next to a plate predicts with high certainty a fork on the other side). Based on several observations, it has been suggested that individuals with autism spectrum disorder (ASD) have an above average tendency to prefer well-organized information or structured environments. Surprisingly, however, this tendency has not yet been tested under controlled experimental conditions. Method: A recent study suggested that neurotypical adults prefer associative information, regardless of their semantic content. Therefore, in this study, we examined the relation of this preference bias to the scores of 123 neurotypical adults on questionnaires that measure autistic traits, known to co-vary with typical autism spectrum characteristics. Participants were presented with different configurations of meaningless abstract shapes. Some shapes were always presented in the exact same fixed configuration, and other shapes were always presented in different random configurations. In an unannounced subsequent evaluation task, participants were required to indicate which shapes they preferred. Results: We replicate the observation that people exhibit a general preference for shapes that were presented in fixed configurations. However, there were no correlations between autistic traits and this general preference. Conclusions: Our findings suggest the preference for associative information in ASD might be less general than first thought, or restricted to more complex (social) situations or other levels of information processing. We outline specific guidelines for future systematic investigations into the hypothesized increased preference for associative information in ASD

Autistic traits are related to worse performance in a volatile reward learning task despite adaptive learning rates

Recent theories propose that autism is characterized by an impairment in determining when to learn and when not. We investigated this by estimating learning rate in environments varying in volatility and uncertainty. Specifically, we correlated autistic traits (in 163 neurotypical participants) with modelled learning behaviour during probabilistic reward learning under the following three conditions: a Stationary Low Noise condition with stable reward contingencies, a Volatile condition with changing reward contingencies and a Stationary High Noise condition where reward probabilities for all options were 60%, resulting in an uncertain, noisy environment. Consistent with earlier findings, we found less optimal decision-making in the Volatile condition for participants with more autistic traits. However, we observed no correlations between underlying adjustments in learning rates and autistic traits, suggesting no impairment in updating learning rates in response to volatile versus noisy environments. Exploratory analyses indicated that impaired performance in the Volatile condition in participants with more autistic traits, was specific to trials with reward contingencies opposite to those initially learned, suggesting a primacy bias. We conclude that performance in volatile environments is lower in participants with more autistic traits, but this cannot be unambiguously attributed to difficulties with adjusting learning rates. Lay abstract Recent theories propose that autism is characterized by an impairment in determining when to learn and when not. Here, we investigated this hypothesis by estimating learning rates (i.e. the speed with which one learns) in three different environments that differed in rule stability and uncertainty. We found that neurotypical participants with more autistic traits performed worse in a volatile environment (with unstable rules), as they chose less often for the most rewarding option. Exploratory analyses indicated that performance was specifically worse when reward rules were opposite to those initially learned for participants with more autistic traits. However, there were no differences in the adjustment of learning rates between participants with more versus less autistic traits. Together, these results suggest that performance in volatile environments is lower in participants with more autistic traits, but that this performance difference cannot be unambiguously explained by an impairment in adjusting learning rates

The relation between preference for predictability and autistic traits

A common idea about individuals with autism spectrum disorder (ASD) is that they have an above-average preference for predictability and sameness. However, surprisingly little research has gone toward this core symptom, and some studies suggest the preference for predictability in ASD might be less general than commonly assumed. Here, we investigated this important symptom of ASD using three different paradigms, which allowed us to measure preference for predictability under well-controlled experimental conditions. Specifically, we used a dimensional approach by investigating correlations between autistic traits (as measured with the Autism-Spectrum Quotient and Social Responsiveness Scale in a neurotypical population) and the scores on three different tasks. The "music preference" task assessed preferences for tone sequences that varied in predictability. The "perceptual fluency" task required participants to evaluate stimuli that were preceded by a similar versus dissimilar subliminally presented prime. The "gambling" task presented four decks of cards that had equal outcome probabilities but varied in predictability. We observed positive correlations between autistic traits and a preference for predictability in both the music preference and perceptual fluency task. We did not find our hypothesized correlation with gambling behavior but did observe a post hoc correlation showing that participants with more autistic traits were faster to choose the predictable deck. Together, these findings show that a relation between autistic traits and preference for predictability can be observed in a standardized lab environment, and should be considered an important first step toward a better, more mechanistic understanding of insistence on sameness in ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary A core symptom of autism spectrum disorder (ASD) is a strong preference for predictability, but little research has gone toward it. We show that neurotypical adults with more autistic traits have stronger preferences for predictable tunes, evaluate images that can be predicted as more beautiful, and are faster in choosing a gambling option resulting in predictable reward. These results offer the first important evidence that insistence on sameness in ASD can be studied in controlled lab settings