PI3Kδ and primary immunodeficiencies.

Primary immunodeficiencies are inherited disorders of the immune system, often caused by the mutation of genes required for lymphocyte development and activation. Recently, several studies have identified gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (which encodes p110δ) and PIK3R1 (which encodes p85α) that cause a combined immunodeficiency syndrome, referred to as activated PI3Kδ syndrome (APDS; also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (PASLI)). Paradoxically, both loss-of-function and gain-of-function mutations that affect these genes lead to immunosuppression, albeit via different mechanisms. Here, we review the roles of PI3Kδ in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3Kδ gleaned from these patients, as well as implications of these findings for clinical therapy

Achieving Education for Sustainable Development (ESD) in Early Childhood Education Through Critical Reflection in Transformative Learning

The central role of education in creating a more sustainable future has been already recognized by educators and policy-makers alike. This chapter argues that this can only be truly achieved through the efforts of teachers in implementing an “education of a different kind,” a general educational shift that seeks to encompass a converging transformation of the priorities and mindsets of education professionals. In this regard, the professional preparation of teachers, as the leading actors in shaping children’s learning processes, and their continuous professional development are vital considerations for Education for Sustainable Development (ESD) to be successfully achieved. Linking transformative learning and ESD has emerged as a distinct and useful pedagogy because they both support the process of critically examining habits of mind, then revising these habits and acting upon the revised point of view. This study aims to describe and evaluate the potential of transformative learning in innovating mainstream education toward sustainability by focusing on the role of critical reflection in a capacity building research project realized in Turkey. The data was gathered from 24 early childhood educators using a mixed-method research design involving learning diaries, a learning activities survey, and follow-up interviews. This chapter identified content, context, and application method of the in-service training as factors that have contributed to the reflective practices of the participants. In addition, presenting the implications regarding the individual differences in how learners engage in critical reflection practices, this research offers a framework for a content- and process-based approach derived from Mezirow’s conception of critical reflection

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission