Accounting for the preference for literal meanings in autism spectrum conditions

Pragmatic difficulties are considered a hallmark of autism spectrum conditions (ASC), but remain poorly understood. We discuss and evaluate existing hypotheses regarding the literalism of ASC individuals, that is, their tendency for literal interpretations of non-literal communicative intentions. We present evidence that reveals a developmental stage at which neurotypical children also have a tendency for literalism and suggest an explanation for such behaviour that links it to other behavioural, rule-following, patterns typical of that age. We discuss evidence showing that strict adherence to rules is also widespread in ASC, and suggest that literalism might be linked to such rule-following behaviour.This paper is part of a project that has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant agreement No. 853211). Funding for this research was also supported by Agencia Estatal de Investigación, Spain grant number: PGC2018-093464-B-I00; by the Basque Government, grant number: IT1396-19; and by the University of the Basque Country (UPV/EHU), grant numbers: GIU18/221 and US20/03

Autistic camouflaging across the spectrum

Camouflaging may be characterized as a set of actions and strategies more or less consciously adopted by some autistic people to navigate the neurotypical social world. Despite the increased interest that this phenomenon has garnered, its nature remains elusive and in need of conceptual clarification. In this paper, we aim to put forward an inclusive view of camouflaging that does justice to its complexity while also reflecting the heterogeneity of autism as a condition. First, we offer an overview of the main characterizations of camouflaging. This overview shows that current characterizations fail to paint a cohesive picture, and that different accounts emphasize different aspects of the phenomenon. Second, we explore the analogy between camouflaging and passing, which we take to be illuminating to describe some forms of camouflaging, while probably obscuring the study of others. Third, we extend the discussion about camouflaging to currently understudied groups across the autistic spectrum – i.e., children, and adults with linguistic and/or intellectual disabilities. We argue that camouflaging in such groups may differ from what the current literature describes as typical instances of camouflaging. We conclude by revisiting the nature of camouflaging in light of such understudied groups, and we offer some suggestions on how to move research forward.We are grateful to Elena Castroviejo, Inge-Marie Eigsti, Marta Jorba, and Teresa Roversi for their valuable feedback on earlier versions of this paper. Conversations with Itziar Arbina and Oiane Musitu from the Landaberde Daycare Center were important in the development of our ideas concerning camouflaging in adults with verbal and intellectual difficulties. Earlier versions of this material were discussed at the Philosophy of Psychiatry Work in Progress at Lancaster University and at Lindy Lab seminars at the University of the Basque Country (UPV/EHU). We would also like to thank two anonymous referees of this journal for their constructive, encouraging, and engaging suggestions throughout the revision process

El blason mas excelso de España, Santiago el Mayor : sermon, que en la solemnidad celebrada por el Real Consejo de las Ordenes... en la Iglesia de Comendadoras de Santiago el dia primero de agosto

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-2010Sign. : []2, A-D4, E

A highly efficient organogenesis protocol based on zeatin riboside for in vitro regeneration of eggplant

[EN] Background Efficient organogenesis induction in eggplant (Solanum melongena L.) is required for multiple in vitro culture applications. In this work, we aimed at developing a universal protocol for efficient in vitro regeneration of eggplant mainly based on the use of zeatin riboside (ZR). We evaluated the effect of seven combinations of ZR with indoleacetic acid (IAA) for organogenic regeneration in five genetically diverse S. melongena and one S. insanum L. accessions using two photoperiod conditions. In addition, the effect of six different concentrations of indolebutyric acid (IBA) in order to promote rooting was assessed to facilitate subsequent acclimatization of plants. The ploidy level of regenerated plants was studied. Results In a first experiment with accessions MEL1 and MEL3, significant (p < 0.05) differences were observed for the four factors evaluated for organogenesis from cotyledon, hypocotyl and leaf explants, with the best results obtained (9 and 11 shoots for MEL1 and MEL3, respectively) using cotyledon tissue, 16 h light / 8 h dark photoperiod conditions, and medium E6 (2 mg/L of ZR and 0 mg/L of IAA). The best combination of conditions was tested in the other four accessions and confirmed its high regeneration efficiency per explant when using both cotyledon and hypocotyl tissues. The best rooting media was R2 (1 mg/L IBA). The analysis of ploidy level revealed that between 25 and 50% of the regenerated plantlets were tetraploid. Conclusions An efficient protocol for organogenesis of both cultivated and wild accessions of eggplant, based on the use of ZR, is proposed. The universal protocol developed may be useful for fostering in vitro culture applications in eggplant requiring regeneration of plants and, in addition, allows developing tetraploid plants without the need of antimitotic chemicals.This research was funded by the Spanish Ministerio de Ciencia, Innovacion y Universidades, Agencia Estatal de Investigacion and Fondo Europeo de Desarrollo Regional (grant RTI-2018-094592-B-100 from MCIU/AEI/FEDER, UE) and by Universitat Politecnica de Valencia. The Spanish Ministerio de Educacion, Cultura y Deporte funded a predoctoral fellowship granted to Edgar Garcia-Fortea (FPU17/02389). The Generalitat Valenciana and Fondo Social Europeo funded a post-doctoral fellowship granted to Mariola Plazas (APOSTD/2018/014). The Japan Society for the Promotion of Science funded a post-doctoral fellowship granted to Pietro Gramazio (FY 2019 Postdoctoral Fellowship for Research in Japan [Standard]). 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Expanding the genetic spectrum of TUBB1-related thrombocytopenia

β1-Tubulin plays a major role in proplatelet formation and platelet shape maintenance, and pathogenic variants in TUBB1 lead to thrombocytopenia and platelet anisocytosis (TUBB1-RT). To date, the reported number of pedigrees with TUBB1-RT and of rare TUBB1 variants with experimental demonstration of pathogenicity is limited. Here, we report 9 unrelated families presenting with thrombocytopenia carrying 6 β1-tubulin variants, p.Cys12LeufsTer12, p.Thr107Pro, p.Gln423*, p.Arg359Trp, p.Gly109Glu, and p.Gly269Asp, the last of which novel. Segregation studies showed incomplete penetrance of these variants for platelet traits. Indeed, most carriers showed macrothrombocytopenia, some only increased platelet size, and a minority had no abnormalities. Moreover, only homozygous carriers of the p.Gly109Glu variant displayed macrothrombocytopenia, highlighting the importance of allele burden in the phenotypic expression of TUBB1-RT. The p.Arg359Trp, p.Gly269Asp, and p.Gly109Glu variants deranged β1-tubulin incorporation into the microtubular marginal ring in platelets but had a negligible effect on platelet activation, secretion, or spreading, suggesting that β1-tubulin is dispensable for these processes. Transfection of TUBB1 missense variants in CHO cells altered β1-tubulin incorporation into the microtubular network. In addition, TUBB1 variants markedly impaired proplatelet formation from peripheral blood CD34+ cell-derived megakaryocytes. Our study, using in vitro modeling, molecular characterization, and clinical investigations provides a deeper insight into the pathogenicity of rare TUBB1 variants. These novel data expand the genetic spectrum of TUBB1-RT and highlight a remarkable heterogeneity in its clinical presentation, indicating that allelic burden or combination with other genetic or environmental factors modulate the phenotypic impact of rare TUBB1 variants.This work was partially supported by grants from Instituto de Salud Carlos III (ISCIII) and Feder (PI17/01311, PI17/01966, PI20/00926 and CB15/00055), Fundacion Séneca (19873/ GERM/15), Gerencia Regional de Salud (GRS 2061A/19 and 1647/A/17), Fundacion Mutua Madrile´ña (AP172142019), and ~ Sociedad Espanola de Trombosis y Hemostasia (Premio L ~ opez Borrasca 2019 and Ayuda a Grupos de Trabajo en Patologıa Hemorragica). The authors’ research on inherited platelet disorders is conducted in accordance with the aims of the Functional and Molecular Characterization of Patients with Inherited Platelet Disorders Project, from Grupo Espanol de Alteraciones Plaqueta- ~ rias Congenitas, which is supported by the Spanish Society of Thrombosis and Haemostasis. V.P.-B. has a predoctoral contract from CIBERER. L.B. was supported by a fellowship from Fondazione Umberto Veronesi. M.E.d.l.M.-B. holds a postdoctoral fellowship from the University of Murcia. A.M.-Q. holds a predoctoral grant from the Junta de Castilla y Leon

Introducing high-throughput sequencing into mainstream genetic diagnosis practice in inherited platelet disorders

Inherited platelet disorders are a heterogeneous group of rare diseases, caused by inherited defects in platelet production and/or function. Their genetic diagnosis would benefit clinical care, prognosis and preventative treatments. Until recently, this diagnosis has usually been performed via Sanger sequencing of a limited number of candidate genes. High-throughput sequencing is revolutionizing the genetic diagnosis of diseases, including bleeding disorders. We have designed a novel high-throughput sequencing platform to investigate the unknown molecular pathology in a cohort of 82 patients with inherited platelet disorders. Thirty-four (41.5%) patients presented with a phenotype strongly indicative of a particular type of platelet disorder. The other patients had clinical bleeding indicative of platelet dysfunction, but with no identifiable features. The high-throughput sequencing test enabled a molecular diagnosis in 70% of these patients. This sensitivity increased to 90% among patients suspected of having a defined platelet disorder. We found 57 different candidate variants in 28 genes, of which 70% had not previously been described. Following consensus guidelines, we qualified 68.4% and 26.3% of the candidate variants as being pathogenic and likely pathogenic, respectively. In addition to establishing definitive diagnoses of well-known inherited platelet disorders, high-throughput sequencing also identified rarer disorders such as sitosterolemia, filamin and actinin deficiencies, and G protein-coupled receptor defects. This included disease-causing variants in DIAPH1 (n=2) and RASGRP2 (n=3). Our study reinforces the feasibility of introducing high-throughput sequencing technology into the mainstream laboratory for the genetic diagnostic practice in inherited platelet disorders.This study was supported by research grants from the Gerencia Regional de Salud (GRS 1370/A/16), ISCIII & Feder (PI14/01956), CIBERER CB15/00055, Fundación Séneca (19873/GERM/15) and Sociedad Española de Trombosis y Hemostasia (SETH). SPW holds a British Heart Foundation chair.Peer Reviewe