scholarly journals Neurobiological Insights into Twice Exceptionality: Circuits, Cells, and Molecules

2021 ◽  
Author(s):  
Benjamin A. Kelvington ◽  
Thomas Nickl-Jockschat ◽  
Ted Abel
Keyword(s):  
Molecular Mechanisms ◽  
Neural Circuits ◽  
Genetic Alterations ◽  
Synaptic Function ◽  
Neural Signals ◽  
Twice Exceptional ◽  
Nervous System Function ◽  
Pedagogical Research ◽  
Regulated Gene Expression ◽  
Exceptional Learners

Twice-exceptional learners face a unique set of challenges arising from the intersection of extraordinary talent and disability. Neurobiology research has the capacity to complement pedagogical research and provide support for twice-exceptional learners. Very few studies have attempted to specifically address the neurobiological underpinnings of twice-exceptionality. However, neurobiologists have built a broad base of knowledge in nervous system function spanning from the level of neural circuits to the molecular basis of behavior. It is known that distinct neural circuits mediate different neural functions, which suggests that 2e learning may result from enhancement in one circuit and disruption in another. Neural circuits are known to adapt and change in response to experience, a cellular process known as neuroplasticity. Plasticity is controlled by a bidirectional connection between the synapse, where neural signals are received, and the nucleus, where regulated gene expression can return to alter synaptic function. Complex molecular mechanisms compose this connection in distinct neural circuits, and genetic alterations in these mechanisms are associated with both memory enhancements and psychiatric disorder. Understanding the consequences of these changes at the molecular, cellular, and circuit levels will provide critical insights into the neurobiological bases of twice-exceptional learning.

Glial Cells in the Auditory Brainstem

2018 ◽  
pp. 680-706
Author(s):  
Giedre Milinkeviciute ◽  
Karina S. Cramer
Keyword(s):  
Nervous System ◽  
Glial Cells ◽  
Sound Localization ◽  
Auditory Brainstem ◽  
Synaptic Function ◽  
System Function ◽  
Auditory Neurons ◽  
System P ◽  
The Central Nervous System ◽  
Nervous System Function

The auditory brainstem carries out sound localization functions that require an extraordinary degree of precision. While many of the specializations needed for these functions reside in auditory neurons, additional adaptations are made possible by the functions of glial cells. Astrocytes, once thought to have mainly a supporting role in nervous system function, are now known to participate in synaptic function. In the auditory brainstem, they contribute to development of specialized synapses and to mature synaptic function. Oligodendrocytes play critical roles in regulating timing in sound localization circuitry. Microglia enter the central nervous system early in development, and also have important functions in the auditory system’s response to injury. This chapter highlights the unique functions of these non-neuronal cells in the auditory system.

scholarly journals Aerobic Exercise Induces Alternative Splicing of Neurexins in Frontal Cortex

2021 ◽  
Vol 6 (2) ◽  
pp. 48
Author(s):  
Elisa Innocenzi ◽  
Ida Cariati ◽  
Emanuela De Domenico ◽  
Erika Tiberi ◽  
Giovanna D’Arcangelo ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Aerobic Exercise ◽  
Frontal Cortex ◽  
Molecular Mechanisms ◽  
Splice Variants ◽  
Brain Regions ◽  
Synaptic Function ◽  
Molecular Changes ◽  
Beneficial Effects ◽  
The Impact

Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and NRXN3) have been identified, each encoding for α and β neurexins, from two independent promoters. Moreover, each Nrxns gene (1–3) has several alternative exons and produces many splice variants that bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength, and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We showed that exercise promoted Nrxns1–3 AS at splice site 4 (SS4) both in α and β isoforms, inducing a switch from exon-excluded isoforms (SS4−) to exon-included isoforms (SS4+) in FC but not in hippocampus. Additionally, we showed that the same AE program enhanced the expression level of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show molecular changes.

scholarly journals Widespread alteration of protein autoinhibition in human cancers

2018 ◽  
Author(s):  
Ashwani Jha ◽  
Jennifer M. Bui ◽  
Dokyun Na ◽  
Jörg Gsponer
Keyword(s):  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Signal Propagation ◽  
Genetic Alterations ◽  
Missense Mutations ◽  
Pathway Activation ◽  
Tumorigenic Potential ◽  
Significant Enrichment ◽  
Cancer Types ◽  
Cancer Drivers

ABSTRACTAutoinhibition is a prevalent allosteric regulatory mechanism in signaling proteins as it prevents spurious pathway activation and primes for signal propagation only under appropriate inputs. Altered functioning of inhibitory allosteric switches underlies the tumorigenic potential of numerous cancer drivers. However, whether protein autoinhibition is altered generically in cancer cells remains elusive. Here, we reveal that cancer-associated missense mutations and fusion breakpoints are found with significant enrichment within inhibitory allosteric switches across all cancer types, which in the case of the fusion breakpoints is specific to cancer and not present in other diseases. Recurrently disrupted or mutated allosteric switches identify established and new cancer drivers. Cancer-specific mutations in allosteric switches are associated with distinct changes in signaling, and suggest molecular mechanisms for altered protein regulation, which in the case of ASK1, DAPK2 and EIF4G1 were supported by biophysical simulations. Our results demonstrate that autoinhibition-modulating genetic alterations are positively selected for by cancer cells, and that their study provides valuable insights into molecular mechanisms of cancer misregulation.

scholarly journals Identification of Neuronal Pentraxins as Synaptic Binding Partners of C1q and the Involvement of NP1 in Synaptic Pruning in Adult Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Réka Á. Kovács ◽  
Henrietta Vadászi ◽  
Éva Bulyáki ◽  
György Török ◽  
Vilmos Tóth ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Potential Interaction ◽  
Synaptic Function ◽  
Classical Pathway ◽  
Microglial Phagocytosis ◽  
Classical Complement Pathway ◽  
Adult Mice ◽  
Synaptic Pruning

Elements of the immune system particularly that of innate immunity, play important roles beyond their traditional tasks in host defense, including manifold roles in the nervous system. Complement-mediated synaptic pruning is essential in the developing and healthy functioning brain and becomes aberrant in neurodegenerative disorders. C1q, component of the classical complement pathway, plays a central role in tagging synapses for elimination; however, the underlying molecular mechanisms and interaction partners are mostly unknown. Neuronal pentraxins (NPs) are involved in synapse formation and plasticity, moreover, NP1 contributes to cell death and neurodegeneration under adverse conditions. Here, we investigated the potential interaction between C1q and NPs, and its role in microglial phagocytosis of synapses in adult mice. We verified in vitro that NPs interact with C1q, as well as activate the complement system. Flow cytometry, immunostaining and co-immunoprecipitation showed that synapse-bound C1q colocalizes and interacts with NPs. High-resolution confocal microscopy revealed that microglia-surrounded C1q-tagged synapses are NP1 positive. We have also observed the synaptic occurrence of C4 suggesting that activation of the classical pathway cannot be ruled out in synaptic plasticity in healthy adult animals. In summary, our results indicate that NPs play a regulatory role in the synaptic function of C1q. Whether this role can be intensified upon pathological conditions, such as in Alzheimer’s disease, is to be disclosed.

Understanding Twice-Exceptional Learners

2021 ◽  
Author(s):  
C. Matthew Fugate ◽  
Wendy A. Behrens ◽  
Cecelia Boswell
Keyword(s):  
Twice Exceptional ◽  
Exceptional Learners

crooked legs encodes a family of zinc finger proteins required for leg morphogenesis and ecdysone-regulated gene expression during Drosophila metamorphosis

Development ◽  
1998 ◽  
Vol 125 (9) ◽  
pp. 1733-1745 ◽  
Author(s):  
P.P. D'Avino ◽  
C.S. Thummel
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Genetic Locus ◽  
Regulatory Genes ◽  
Protein Isoforms ◽  
Sequence Motif ◽  
Specific Effects ◽  
Insect Metamorphosis ◽  
Adult Head ◽  
Regulated Gene Expression

Drosophila imaginal discs undergo extensive pattern formation during larval development, resulting in each cell acquiring a specific adult fate. The final manifestation of this pattern into adult structures is dependent on pulses of the steroid hormone ecdysone during metamorphosis, which trigger disc eversion, elongation and differentiation. We have defined genetic criteria that allow us to screen for ecdysone-inducible regulatory genes that are required for this transformation from patterned disc to adult structure. We describe here the first genetic locus isolated using these criteria: crooked legs (crol). crol mutants die during pupal development with defects in adult head eversion and leg morphogenesis. The crol gene is induced by ecdysone during the onset of metamorphosis and encodes at least three protein isoforms that contain 12–18 C2H2 zinc fingers. Consistent with this sequence motif, crol mutations have stage-specific effects on ecdysone-regulated gene expression. The EcR ecdysone receptor, and the BR-C, E74 and E75 early regulatory genes, are submaximally induced in crol mutants in response to the prepupal ecdysone pulse. These changes in gene activity are consistent with the crol lethal phenotypes and provide a basis for understanding the molecular mechanisms of crol action. The genetic criteria described here provide a new direction for identifying regulators of adult tissue development during insect metamorphosis.

Twice-Exceptional Learners and RtI

2021 ◽  
pp. 229-251
Author(s):  
Cheryll M. Adams ◽  
Nina Yssel ◽  
Heidi Anwiler
Keyword(s):  
Twice Exceptional ◽  
Exceptional Learners

Twice-Exceptional Learners

2021 ◽  
pp. 17-35
Author(s):  
Stuart N. Omdal ◽  
Lois Baldwin ◽  
Daphne Pereles
Keyword(s):  
Twice Exceptional ◽  
Exceptional Learners

scholarly journals Integrative Transcriptome and Proteome Analyses Provide New Insights Into the Interaction Between Live Borrelia burgdorferi and Frontal Cortex Explants of the Rhesus Brain

2020 ◽  
Vol 79 (5) ◽  
pp. 518-529 ◽  
Author(s):  
Zhe Ding ◽  
Luyun Sun ◽  
Yunfeng Bi ◽  
Yu Zhang ◽  
Peng Yue ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Frontal Cortex ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Binding Activity ◽  
Synaptic Function ◽  
Integrated Omics ◽  
Disease Associated Genes ◽  
Lyme Spirochete

Abstract Borrelia burgdorferi (Bb), which is neurotropic, can attack the central nervous system (CNS), leading to the development of various neurologic symptoms. The pathogenesis of Lyme neuroborreliosis (LNB) remains poorly understood. Presently, there is a lack of knowledge of the changes in mRNA and proteins in the CNS following early disseminated Lyme disease. Explants from the frontal cortex of 3 rhesus brains were incubated with medium alone or with medium containing live Bb for 6, 12, or 24 hours. Then, we analyzed identified mRNA and proteins in the frontal cortex tissues, allowing for an in-depth view of the transcriptome and proteome for a macroscopic and unbiased understanding of early disseminated Lyme disease in the brain. Through bioinformatics analysis, a complex network of enriched pathways that were mobilized during the progression of Lyme spirochete infection was described. Furthermore, based on the analysis of omics data, translational regulation, glycosaminoglycan/proteoglycan-binding activity in colonization and dissemination to tissues, disease-associated genes, and synaptic function were enriched, which potentially play a role in pathogenesis during the interaction between frontal cortex tissues and spirochetes. These integrated omics results provide unbiased and comprehensive information for the further understanding of the molecular mechanisms of LNB.

scholarly journals Bullying and the Unique Experiences of Twice Exceptional Learners: Student Perspective Narratives

2018 ◽  
Vol 42 (1) ◽  
pp. 19-35 ◽  
Author(s):  
Michelle Ronksley-Pavia ◽  
Peter Grootenboer ◽  
Donna Pendergast
Keyword(s):  
Gifted Students ◽  
Student Perspective ◽  
Exceptional Children ◽  
Twice Exceptional ◽  
Social Settings ◽  
Being Bullied ◽  
Recommendations For Practice ◽  
Bullying Experiences ◽  
Emotional Effects ◽  
Exceptional Learners

Bullying is known to be prevalent across social settings for children, particularly, for those who have disability and intermittently gifted students. What remains relatively underresearched is the phenomenon of bullying in the lives of twice-exceptional children. This article presents findings about the bullying experiences of eight twice-exceptional children aged 9 to 16 years from a study that explored the lived experiences of these children. Their narratives describe the pervasiveness of bullying. The six themes which emerged from the data about bullying experiences were (a) bullying by peers, (b) bullying by teachers, (c) teachers’ and adults’ responses to bullying, (d) social isolation and bullying, (e) the emotional effects of being bullied, and (f) protective factors. The contribution to the field of twice-exceptionality along with the children’s experiences and consequences of being bullied are discussed. This article concludes with recommendations for practice and further research.

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