From developmental neuroscience to policy:A novel framework based on participatory research

Insights from developmental neuroscience are not always translated to actionable policy decisions. In this review, we explore the potential of bridging the gap between developmental neuroscience and policy through youth participatory research approaches. As the current generation of adolescents lives in an increasingly complex and rapidly changing society, their lived experiences are crucial for both research and policy. Moreover, their active involvement holds significant promise, given their heightened creativity and need to contribute. We therefore advocate for a transdisciplinary framework that fosters collaboration between developmental scientists, adolescents, and policy makers in addressing complex societal challenges. We highlight the added value of adolescents' lived experiences in relation to two pressing societal issues affecting adolescents’ mental health: performance pressure and social inequality. By integrating firsthand lived experiences with insights from developmental neuroscience, we provide a foundation for progress in informed policy decisions.</p

Genetic basis of hyperlysinemia

Background: Hyperlysinemia is an autosomal recessive inborn error of L-lysine degradation. To date only one causal mutation in the AASS gene encoding aminoadipic semialdehyde synthase has been reported. We aimed to better define the genetic basis of hyperlysinemia. Methods. We collected the clinical, biochemical and molecular data in a cohort of 8 hyperlysinemia patients with distinct neurological features. Results: We found novel causal mutations in AASS in all affected individuals, including 4 missense mutations, 2 deletions and 1 duplication. In two patients originating from one family, the hyperlysinemia was caused by a contiguous gene deletion syndrome affecting AASS and PTPRZ1. Conclusions: Hyperlysinemia is caused by mutations in AASS. As hyperlysinemia is generally considered a benign metabolic variant, the more severe neurological disease course in two patients with a contiguous deletion syndrome may be explained by the additional loss of PTPRZ1. Our findings illustrate the importance of detailed biochemical and genetic studies in any hyperlysinemia patient

Development of a genotyping microarray for Usher syndrome

BACKGROUND: Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons. METHODS: To improve DNA diagnostics for patients with Usher syndrome, we developed a genotyping microarray based on the arrayed primer extension (APEX) method. Allele-specific oligonucleotides corresponding to all 298 Usher syndrome-associated sequence variants known to date, 76 of which are novel, were arrayed. RESULTS: Approximately half of these variants were validated using original patient DNAs, which yielded an accuracy of >98%. The efficiency of the Usher genotyping microarray was tested using DNAs from 370 unrelated European and American patients with Usher syndrome. Sequence variants were identified in 64/140 (46%) patients with Usher syndrome type I, 45/189 (24%) patients with Usher syndrome type II, 6/21 (29%) patients with Usher syndrome type III and 6/20 (30%) patients with atypical Usher syndrome. The chip also identified two novel sequence variants, c.400C>T (p.R134X) in PCDH15 and c.1606T>C (p.C536S) in USH2A. CONCLUSION: The Usher genotyping microarray is a versatile and affordable screening tool for Usher syndrome. Its efficiency will improve with the addition of novel sequence variants with minimal extra costs, making it a very useful first-pass screening tool

Insights of ion mobility spectrometry and its application on food safety and authenticity: A review

Ion mobility spectrometry (IMS) is gaining importance in the field of food safety and authenticity in recent years due to its main potential to overcome the challenges that arise from the complexity of food matrices. For many years, IMS has been used as a stand-alone analytical detector due to its quick response, high sensitivity, and portability, and stand-alone applications in food analysis have been explored in recent years. At the same time, IMS hyphenation to mass spectrometry (MS) techniques, usually combined with liquid or gas chromatography (LC/GC), provides an additional dimension to separate isobaric compounds and thus improves method selectivity. Besides, with such ion mobility – mass spectrometry (IM−MS) methods, background noise decreases, increasing method sensitivity, and it provides complementary information to mass spectra and retention time with the collision cross section (CCS). The development of CCS databases within the food safety field would even permit the identification of compounds in non-targeted approaches. Furthermore, it would increase the confidence of control laboratories when determining a sample as non-compliant. Therefore, the number of applications by IMS on food safety and authenticity has increased remarkably in recent years. This review provides the general insights of IMS with the current state and recent approaches for its performance improvement and a general outlook of its applicability in food safety and authenticity

Positive and Negative Risk-Taking in Adolescence and Early Adulthood: A Citizen Science Study During the COVID-19 Pandemic

Sensation seeking is an important underlying factor of both positive and negative forms of risk-taking during adolescence and early adulthood. However, macro-factors such as the global COVID-19 pandemic may influence sensation seeking opportunities and risk-taking behaviors that are considered negative and positive. Therefore, the primary aim of this study was to examine the associations between sensation seeking and behaviors that are considered positive or negative forms of risk-taking during the Covid-19 pandemic in a sample of adolescents and early adults (N = 660, Mage = 22.91, SD = 3.14). Using citizen science methods, negative risk-taking was defined as taking unaccepted risks, such as falsifying vaccination reports or deliberately contracting COVID-19. Positive risk-taking was defined as taking socially accepted risks, such as balancing between the risk to infect elderly people and the need to socialize with peers. Results showed that participants with higher levels of sensation seeking took more positive and negative COVID-19 related risks. An additional finding was that sensation seeking was positively associated with the need to contribute to society. This indicates that during adolescence and early adulthood, sensation seeking may be a driving factor for both positive (i.e., socially accepted) and negative (i.e., socially unaccepted) risk-taking in the context of a high-stake global pandemic, arguing against a one-direction negative relation between sensation seeking and risk-taking

Bidirectional Effects between Parenting and Aggressive Child Behavior in the Context of a Preventive Intervention

Over time, developmental theories and empirical studies have gradually started to adopt a bidirectional viewpoint. The area of intervention research is, however, lagging behind in this respect. This longitudinal study examined whether bidirectional associations between (changes in) parenting and (changes in) aggressive child behavior over time differed in three conditions: a child intervention condition, a child + parent intervention condition and a control condition. Participants were 267 children (74 % boys, 26 % girls) with elevated levels of aggression, their mothers and their teachers. Reactive aggression, proactive aggression and perceived parenting were measured at four measurement times from pretest to one-year after intervention termination. Results showed that associations between aggressive child behavior and perceived parenting are different in an intervention context, compared to a general developmental context. Aggressive behavior and perceived parenting were unrelated over time for children who did not receive an intervention. In an intervention context, however, decreases in aggressive child behavior were related to increases in perceived positive parenting and decreases in perceived overreactivity. These findings underscore the importance of addressing child-driven processes in interventions aimed at children, but also in interventions aimed at both children and their parents

A cognitive versus behavioral approach to emotion regulation training for externalizing behavior problems in adolescence: Study protocol of a randomized controlled trial

Background Interventions for adolescents with externalizing behavior problems are generally found to be only moderately effective, and treatment responsiveness is variable. Therefore, this study aims to increase intervention effectiveness by examining effective approaches to train emotion regulation, which is considered to be a crucial mechanism involved in the development of externalizing behavior problems. Specifically, we aim to disentangle a cognitive and behavioral approach to emotion regulation training. Methods A randomized controlled parallel-group study with two arms will be used. Participants are adolescents between 12 and 16 years old, with elevated levels of externalizing behavior problems. Participants will be randomly assigned to either the control condition or the intervention condition. Participants in the intervention condition receive both a cognitive and behavioral emotion regulation module, but in different sequences. Primary outcome measures are emotion regulation skills, emotion regulation strategies, and externalizing behavior problems. Questionnaires will be completed at pre-test, in-between modules, and post-test. Moreover, intensive longitudinal data is collected, as adolescents will complete weekly and daily measures. Discussion Gaining insight into which approaches to emotion regulation training are more effective, and for whom, is important because it may lead to the adaptation of effective intervention programs for adolescents with externalizing behavior problems. Eventually, this could lead to individually tailored evidence-based interventions

Processing of mutant N-acetyl-alpha-glucosaminidase in mucopolysaccharidosis type IIIB fibroblasts cultured at low temperature

Background: The autosomal recessive, neurodegenerative disorder mucopolysaccharidosis type IIIB (MPSIIIB) is caused by a deficiency of the lysosomal enzyme N-acetyl-alpha-glucosaminidase (NAGLU), resulting in accumulation of heparan sulfate. The disease spectrum comprises a severe, rapidly progressing (RP) phenotype and a more attenuated, slowly progressing (SP) phenotype. Previous studies showed significantly higher NAGLU activity in sldn fibroblasts of SP patients when cultured at 30 degrees C which may be relevant for development of novel therapeutic strategies. Here we report on the processes involved in this phenomenon. Methods: Fibroblasts from controls, one RP patient (homozygous for the p.R297* mutation) and three SP MPSIIIB patients (homozygous for the mutation p.S612G or p.R643C, or compound heterozygous for the mutations p.A72_G79dup8 and p.R565Q) were cultured at temperatures ranging from 37 degrees C to 27 degrees C and harvested at different time points to assess NAGLU activity, mRNA and protein levels, and NAGLU glycosylation. Intracellular localization of wild-type and mutant mCherry-tagged NAGLU was analyzed by immunofluorescence. Results: In control fibroblasts NAGLU was present is a 85 kDa precursor and a 82 kDa mature form. In SP patients' fibroblasts cultured at 37 degrees C, only the 85 kDa form was detected. Culturing at lower temperatures resulted in higher NAGLU mRNA levels, increased levels of both precursor and mature NAGLU protein and improved processing. The formation of mature NAGLU corresponded with higher NAGLU activity levels. Conclusion: We show that the NAGLU protein consists of a precursor and a mature form and that in SP MPSIIIB patients' fibroblasts only the precursor protein is present at 37 degrees C. Culturing at lower temperatures resulted in the formation of the mature, enzymatically active form, due to higher mRNA levels and improved processing. (C) 2017 Elsevier Inc. All rights reserve