Neurocognitive approaches to developmental disorders of numerical and mathematical cognition: The perils of neglecting the role of development

Rationale: The highly conserved NOTCH (neurogenic locus notch homolog protein) signaling pathway functions as a key cell–cell interaction mechanism controlling cell fate and tissue patterning, whereas its dysregulation is implicated in a variety of developmental disorders and cancers. The pivotal role of endothelial NOTCH in regulation of angiogenesis is widely appreciated; however, little is known about what controls its signal transduction. Our previous study indicated the potential role of post-translational SUMO (small ubiquitin-like modifier) modification (SUMOylation) in vascular disorders. Objective: The aim of this study was to investigate the role of SUMOylation in endothelial NOTCH signaling and angiogenesis. Methods and Results: Endothelial SENP1 (sentrin-specific protease 1) deletion, in newly generated endothelial SENP1 (the major protease of the SUMO system)–deficient mice, significantly delayed retinal vascularization by maintaining prolonged NOTCH1 signaling, as confirmed in cultured endothelial cells. An in vitro SUMOylation assay and immunoprecipitation revealed that when SENP1 associated with N1ICD (NOTCH1 intracellular domain), it functions as a deSUMOylase of N1ICD SUMOylation on conserved lysines. Immunoblot and immunoprecipitation analyses and dual-luciferase assays of natural and SUMO-conjugated/nonconjugated NOTCH1 forms demonstrated that SUMO conjugation facilitated NOTCH1 cleavage. This released N1ICD from the membrane and stabilized it for translocation to the nucleus where it functions as a cotranscriptional factor. Functionally, SENP1-mediated NOTCH1 deSUMOylation was required for NOTCH signal activation in response to DLL4 (Delta-like 4) stimulation. This in turn suppressed VEGF (vascular endothelial growth factor) receptor signaling and angiogenesis, as evidenced by immunoblotted signaling molecules and in vitro angiogenesis assays. Conclusions: These results establish reversible NOTCH1 SUMOylation as a regulatory mechanism in coordinating endothelial angiogenic signaling; SENP1 acts as a critical intrinsic mediator of this process. These findings may apply to NOTCH-regulated biological events in nonvascular tissues and provide a novel therapeutic strategy for vascular diseases and tumors.

Download Full-text

An abundance of developmental anomalies and abnormalities in Pleistocene people

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1814989115 ◽

2018 ◽

Vol 115 (47) ◽

pp. 11941-11946 ◽

Cited By ~ 22

Author(s):

Erik Trinkaus

Keyword(s):

Fossil Record ◽

Elevated Level ◽

Developmental Disorders ◽

Upper Paleolithic ◽

Developmental Changes ◽

Single Factor ◽

Developmental Abnormalities ◽

Low Probability ◽

Developmental Variants

Diverse developmental abnormalities and anomalous features are evident in the PleistoceneHomofossil record, varying from minor but rare dental, vertebral, and carpal variants to exceptional systemic disorders. There are currently 75 documented anomalies or abnormalities from 66 individuals, spanning the Pleistocene but primarily from the Late Pleistocene Middle and Upper Paleolithic with their more complete skeletal remains. The expected probabilities of finding these variants or developmental disorders vary from <5% to <0.0001%, based on either recent human incidences or relevant Pleistocene sample distributions. Given the modest sample sizes available for the skeletal or dental elements in question, especially if the samples are appropriately limited in time and geography, the cumulative multiplicative probability of finding these developmental changes is vanishingly small. These data raise questions regarding social survival abilities, differing mortuary treatments of the biologically unusual, the role of ubiquitous stress among these Pleistocene foragers, and their levels of consanguinity. No single factor sufficiently accounts for the elevated level of these developmental variants or the low probability of finding them in the available paleontological record.

Download Full-text

The Role of Musical Development in Early Language Acquisition

The Oxford Handbook of Music and the Brain ◽

10.1093/oxfordhb/9780198804123.013.23 ◽

2018 ◽

pp. 565-591

Author(s):

Anthony Brandt ◽

L. Robert Slevc ◽

Molly Gebrian

Keyword(s):

Language Acquisition ◽

Cultural Transmission ◽

Developmental Disorders ◽

Native Language ◽

Current Understanding ◽

Early Language ◽

Music And Language ◽

Language And Music ◽

Infant Brain

Language and music are readily distinguished by adults, but there is growing evidence that infants first experience speech as a special type of music. By listening to the phonemic inventory and prosodic patterns of their caregivers’ speech, infants learn how their native language is composed, later bootstrapping referential meaning onto this musical framework. Our current understanding of infants’ sensitivities to the musical features of speech, the co-development of musical and linguistic abilities, and shared developmental disorders, supports the view that music and language are deeply entangled in the infant brain and modularity emerges over the course of development. This early entanglement of music and language is crucial to the cultural transmission of language and children’s ability to learn any of the world’s tongues.

Download Full-text

KNOWLEDGE AND THE ROLE OF CADRES IN THE IMPLEMENTATION OF EARLY DETECTION OF TODDLERS DEVELOPMENT USING KPSP

Jurnal Kesehatan Poltekkes Ternate ◽

10.32763/juke.v10i1.32 ◽

2017 ◽

Vol 10 (1) ◽

pp. 22

Author(s):

Nuryanin Yani ◽

Ayesha H.N, Nurwening T.W.

Keyword(s):

Early Detection ◽

Developmental Disorders ◽

Early Childhood Development ◽

Childhood Development ◽

Rank Test ◽

Cross Sectional ◽

Independent Variable ◽

Relationship Of

Introduction: The development of toddlers is noteworthy considering the population size is large enough. Early detection is an important development with KPSP carried out in an effort to facilitate early detection of developmental disorders that can be given early intervention and referral early in children, in the end the quality of a child's development may be optimal. Trained cadres have the authority to monitor the development of children with KPSP Method: cross sectional analytic approach. Population health cadres in the district Lembeyan with Random sampling techniques with independent variable knowledge and skills of cadres, the role of cadres in the implementation of early detection of early childhood development using KPSP as the dependent variable. Results: Correlation between knowledge and the role of cadres in the implementation of early detection of toddlers development using KPSP analyzed using Spearman Rank test with the results of 0565, while the role and the skills to 0.485 correlation value. Conclusion: there is a relationship of knowledge to the role of cadres and there is a relationship between skill to the role of cadres in the implementation of early detection of toddler development using KPSP. It is hoped the clinic routinely provide refresher material on monitoring developments and increasing the number of screening kit (infrastructure for monitoring developments).

Download Full-text

Preparation for Independent Life of People with ASD and Other Developmental Disorders in The Autonomous Noncommercial Organization «Adain Lo» (ANO «Adain Lo»).

Autism and Developmental Disorders ◽

10.17759/autdd.2018160105 ◽

2018 ◽

Vol 16 (1) ◽

pp. 29-35

Author(s):

A.A. Ginsburg ◽

M.E. Gitshabash ◽

Ya.L. Ivanova

Keyword(s):

Developmental Disorders ◽

Autism Spectrum ◽

Adults With Autism ◽

Saint Petersburg ◽

Independent Life ◽

Spectrum Disorders ◽

Self Service ◽

Role Of Parents ◽

Commercial Organization

The problems of preparation of children and adults with autism spectrum disorders and other developmental disabilities for independent life, modern ways of development of their independence are considered. The role of parents in this process and parent-specialist interaction are stressed. The techniques of tutor support, parents and other specialists are described. Presented techniques are realized in autonomous non-commercial organization «Adain Lo» (Saint-Petersburg) and aimed for maintenance of independent life, self-service, game, communication and education of people with special needs.

Download Full-text

Cognitive robots in the development and rehabilitation of children with developmental disorders

Bio-Algorithms and Med-Systems ◽

10.1515/bams-2016-0010 ◽

2016 ◽

Vol 12 (3) ◽

Cited By ~ 1

Author(s):

Tomasz Komendziński ◽

Emilia Mikołajewska ◽

Dariusz Mikołajewski ◽

Joanna Dreszer ◽

Bibianna Bałaj

Keyword(s):

Developmental Disorders ◽

Interdisciplinary Approach ◽

Higher Order ◽

Symbol Manipulation ◽

Knowledge And Skills ◽

Future Role ◽

Group Activities ◽

Sensorimotor Knowledge ◽

Cognitive Robots

AbstractCognitive robots constitute a highly interdisciplinary approach to the issue of therapy of children with developmental disorders. Cognitive robots become more popular, especially in action and language integration areas, joining the experience of psychologists, neuroscientists, philosophers, and even engineers. The concept of a robot as a cognitive companion for humans may be very useful. The interaction between humans and cognitive robots may be a mediator of movement patterns, learning behaviors from demonstrations, group activities, and social behaviors, as far as higher-order concepts such as symbol manipulation capabilities, words acquisition, and sensorimotor knowledge organization. Moreover there is an occupation to check many theories, such as transferring the knowledge and skills between humans and robots. Although several robotic solutions for children have been proposed the diffusion of aforementioned ideas is still limited. The review summarizes the current and future role of cognitive robots in the development and rehabilitation of children with developmental disorders.

Download Full-text

Contribution of retrotransposition to developmental disorders

Nature Communications ◽

10.1038/s41467-019-12520-y ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 10

Author(s):

Eugene J. Gardner ◽

Elena Prigmore ◽

Giuseppe Gallone ◽

Petr Danecek ◽

Kaitlin E. Samocha ◽

...

Keyword(s):

Developmental Disorders ◽

De Novo ◽

Purifying Selection ◽

Selective Constraint ◽

Protein Coding ◽

Genome Wide ◽

De Novo Gene ◽

The Impact ◽

Transcribed Sequences

Abstract Mobile genetic Elements (MEs) are segments of DNA which can copy themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. Here we identify RT-derived events in 9738 exome sequenced trios with DD-affected probands. We ascertain 9 de novo MEs, 4 of which are likely causative of the patient’s symptoms (0.04%), as well as 2 de novo gene retroduplications. Beyond identifying likely diagnostic RT events, we estimate genome-wide germline ME mutation rate and selective constraint and demonstrate that coding RT events have signatures of purifying selection equivalent to those of truncating mutations. Overall, our analysis represents a comprehensive interrogation of the impact of retrotransposition on protein coding genes and a framework for future evolutionary and disease studies.

Download Full-text

Exploring the role of family in enhancing the well-being of patients with developmental disorders

Journal of Services Marketing ◽

10.1108/jsm-12-2018-0365 ◽

2019 ◽

Vol 33 (6) ◽

pp. 721-734 ◽

Cited By ~ 2

Author(s):

Paula Lam ◽

Constanza Bianchi

Keyword(s):

Family Relationships ◽

Personal Growth ◽

Developmental Disorders ◽

Qualitative Methodology ◽

Family Members ◽

Well Being ◽

Service Research ◽

Content Type ◽

Therapy Services

Purpose The purpose of this paper is to investigate how family members co-create value and improve the well-being of patients with chronic developmental disorders, such as Asperger syndrome (AS) that undertake permanent therapy services. Design/methodology/approach Qualitative methodology is used to identify family value co-creation activities and well-being outcomes. Extensive interviews with family members and professional therapists of AS patients were conducted as the main data collection method. Findings Drawing from previous conceptualizations of value co-creation activities in health contexts, the findings of this study identify the specific value co-creation activities held by family members that influence the different dimensions of well-being for AS patients and their families: co-learning, combining therapies, changing ways of doing things, connecting, co-operation and co-production, managing daily life, motivating, protecting, regulating and establishing roles. The findings also reveal improvements in the following dimensions of patient well-being: autonomy, self-acceptance, purpose in life, positive relationships with others, control of the environment and personal growth. In addition, value co-creation activities also improve family relationships at home and the well-being of patient family members. Originality/value This study contributes to the services literature and addresses a gap in transformative service research by exploring the value co-creation activities of family members for improving well-being outcomes of patients with chronic developmental disorders. People with chronic developmental disorders engage in permanent therapy services and tend to have below-average well-being scores, which also extends to their family members.

Download Full-text