scholarly journals Cognitive Domains Function Complementation by NTNG Gene Paralogs

2015 ◽  
Author(s):  
Pavel Prosselkov ◽  
Denis Polygalov ◽  
Qi Zhang ◽  
Thomas J. McHugh ◽  
Shigeyoshi Itohara
Keyword(s):  
Gene Duplication ◽  
Protein Structures ◽  
Cognitive Disorders ◽  
Autism Spectrum ◽  
Function Concept ◽  
Cognitive Domains ◽  
Intellectual Quotient ◽  
Brain Transcriptome ◽  
Accelerated Evolution ◽  
Identical Gene

ABSTRACTGene duplication was proposed by S.Ohno (1) as a key mechanism of a novel gene function evolution. A pair of gene paralogs, NTNG1 and NTNG2, sharing identical gene and protein structures and encoding similar proteins, forms a functional complement subfunctionalising (SF) within cognitive domains and forming cognitive endophenotypes, as detected by Intellectual Quotient (IQ) tests (2). Both NTNG paralogs are associated with autism spectrum disorder (ASD), bipolar disorder (BD) and schizophrenia (SCZ), with unique nonoverlapping segregation among the other 15 cognitive disorders (CD), emphasizing an evolutionary gain-dependent link between advanced cognitive functions and concomitant neurocognitive pathologies. Complementary expression and human brain transcriptome composition of the paralogs explains the observed phenomena of their functional complementarity. The lowest identity among NTNGs is found in a middle of encoded by them proteins designated as uknown (Ukd) domain. NTNG1 contains anthropoid-specific constrained regions, and both genes contain non-coding conserved sequences underwent accelerated evolution in human. NTNG paralogs SF perturbates “structure drives function” concept at protein and gene levels. The paralogs function diversification forms a so-called “Cognitive Complement (CC)”, a product of gene duplication and subsequent cognitive subfunction bifurcation among the NTNG gene duplicates.

scholarly journals Comprehensive Profiling of Gene Expression in the Cerebral Cortex and Striatum of BTBRTF/ArtRbrc Mice Compared to C57BL/6J Mice

2020 ◽  
Vol 14 ◽  
Author(s):  
Shota Mizuno ◽  
Jun-na Hirota ◽  
Chiaki Ishii ◽  
Hirohide Iwasaki ◽  
Yoshitake Sano ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Synaptic Transmission ◽  
Mouse Strain ◽  
Translational Regulation ◽  
Interaction Analysis ◽  
Autism Spectrum ◽  
Pcr Analysis ◽  
Chromatin Regulation ◽  
Brain Transcriptome ◽  
Rna Interaction

Mouse line BTBR T+ Iptr3tf/J (hereafter referred as to BTBR/J) is a mouse strain that shows lower sociability compared to the C57BL/6J mouse strain (B6) and thus is often utilized as a model for autism spectrum disorder (ASD). In this study, we utilized another subline, BTBRTF/ArtRbrc (hereafter referred as to BTBR/R), and analyzed the associated brain transcriptome compared to B6 mice using microarray analysis, quantitative RT-PCR analysis, various bioinformatics analyses, and in situ hybridization. We focused on the cerebral cortex and the striatum, both of which are thought to be brain circuits associated with ASD symptoms. The transcriptome profiling identified 1,280 differentially expressed genes (DEGs; 974 downregulated and 306 upregulated genes, including 498 non-coding RNAs [ncRNAs]) in BTBR/R mice compared to B6 mice. Among these DEGs, 53 genes were consistent with ASD-related genes already established. Gene Ontology (GO) enrichment analysis highlighted 78 annotations (GO terms) including DNA/chromatin regulation, transcriptional/translational regulation, intercellular signaling, metabolism, immune signaling, and neurotransmitter/synaptic transmission-related terms. RNA interaction analysis revealed novel RNA–RNA networks, including 227 ASD-related genes. Weighted correlation network analysis highlighted 10 enriched modules including DNA/chromatin regulation, neurotransmitter/synaptic transmission, and transcriptional/translational regulation. Finally, the behavioral analyses showed that, compared to B6 mice, BTBR/R mice have mild but significant deficits in social novelty recognition and repetitive behavior. In addition, the BTBR/R data were comprehensively compared with those reported in the previous studies of human subjects with ASD as well as ASD animal models, including BTBR/J mice. Our results allow us to propose potentially important genes, ncRNAs, and RNA interactions. Analysis of the altered brain transcriptome data of the BTBR/R and BTBR/J sublines can contribute to the understanding of the genetic underpinnings of autism susceptibility.

HIV-associated cognitive disorders in perinatally infected children and adolescents: a novel composite cognitive domains score

AIDS Care ◽  
2018 ◽  
Vol 30 (sup1) ◽  
pp. 8-16 ◽  
Author(s):  
Nicole J. Phillips ◽  
Jacqueline Hoare ◽  
Dan J. Stein ◽  
Landon Myer ◽  
Heather J. Zar ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Cognitive Disorders ◽  
Cognitive Domains ◽  
Perinatally Infected

scholarly journals Mutations in neuroligin-3 in male mice impact behavioral flexibility but not relational memory in a touchscreen test of visual transitive inference

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Rebecca H. C. Norris ◽  
Leonid Churilov ◽  
Anthony J. Hannan ◽  
Jess Nithianantharajah
Keyword(s):  
Neurodevelopmental Disorders ◽  
Reaction Times ◽  
Gene Mutations ◽  
Behavioral Flexibility ◽  
Cognitive Disorders ◽  
Autism Spectrum ◽  
Transitive Inference ◽  
Relational Memory ◽  
Response Latencies ◽  
Inference Test

AbstractCognitive dysfunction including disrupted behavioral flexibility is central to neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). A cognitive measure that assesses relational memory, and the ability to flexibly assimilate and transfer learned information is transitive inference. Transitive inference is highly conserved across vertebrates and disrupted in cognitive disorders. Here, we examined how mutations in the synaptic cell-adhesion molecule neuroligin-3 (Nlgn3) that have been documented in ASD impact relational memory and behavioral flexibility. We first refined a rodent touchscreen assay to measure visual transitive inference, then assessed two mouse models of Nlgn3 dysfunction (Nlgn3−/y and Nlgn3R451C). Deep analysis of touchscreen behavioral data at a trial level established we could measure trajectories in flexible responding and changes in processing speed as cognitive load increased. We show that gene mutations in Nlgn3 do not disrupt relational memory, but significantly impact flexible responding. Our study presents the first analysis of reaction times in a rodent transitive inference test, highlighting response latencies from the touchscreen system are useful indicators of processing demands or decision-making processes. These findings expand our understanding of how dysfunction of key components of synaptic signaling complexes impact distinct cognitive processes disrupted in neurodevelopmental disorders, and advance our approaches for dissecting rodent behavioral assays to provide greater insights into clinically relevant cognitive symptoms.

scholarly journals Prediction and Characterization of RXLR Effectors in Pythium Species

2019 ◽  
Author(s):  
Gan Ai ◽  
Kun Yang ◽  
Yuee Tian ◽  
Wenwu Ye ◽  
Hai Zhu ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Plant Pathogens ◽  
Genome Rearrangement ◽  
Common Ancestor ◽  
De Novo ◽  
Protein Structures ◽  
Plant Diseases ◽  
Biocontrol Agents ◽  
Ecological Niches ◽  
Rxlr Effectors

AbstractBeing widely existed in oomycetes, the RXLR effector features conserved RXLR-dEER motifs in its N terminal. Every known Phytophthora or Hyaloperonospora pathogen harbors hundreds of RXLRs. In Pythium species, however, none of the RXLR effectors has been characterized yet. Here, we developed a stringent method for de novo identification of RXLRs and characterized 359 putative RXLR effectors from nine tested Pythium species. Phylogenetic analysis revealed a single superfamily formed by all oomycetous RXLRs, suggesting they descent from a common ancestor. RXLR effectors from Pythium and Phytophthora species exhibited similar sequence features, protein structures and genome locations. In particular, the mosquito biological agent P. guiyangense contains a significantly larger RXLR repertoire than the other eight Pythium species examined, which may result from gene duplication and genome rearrangement events as indicated by synteny analysis. Expression pattern analysis of RXLR-encoding genes in the plant pathogen P. ultimum detected transcripts from the vast majority of predicted RXLRs with some of them being induced at infection stages. One such RXLRs showed necrosis-inducing activity. Furthermore, all predicted RXLRs were cloned from two biocontrol agents P. oligandrum and P. periplocum. Three of them were found to encode effectors inducing defense response in Nicotiana benthamiana. Taken together, our findings represent the first complete synopsis of Pythium RXLR effectors, which provides critical clues on their evolutionary patterns as well as the mechanisms of their interactions with diverse hosts.Author summaryPathogens from the Pythium genus are widespread across multiple ecological niches. Most of them are soilborne plant pathogens whereas others cause infectious diseases in mammals. Some Pythium species can be used as biocontrol agents for plant diseases or mosquito management. Despite that phylogenetically close oomycete pathogens secrete RXLR effectors to enable infection, no RXLR protein was previously characterized in any Pythium species. Here we developed a stringent method to predict Pythium RXLR effectors and compared them with known RXLRs from other species. All oomycetous RXLRs form a huge superfamily, which indicates they may share a common ancestor. Our sequence analysis results suggest that the expansion of RXLR repertoire results from gene duplication and genome recombination events. We further demonstrated that most predicted Pythium RXLRs can be transcribed and some of them encode effectors exhibiting pathogenic or defense-inducing activities. This work expands our understanding of RXLR evolution in oomycetes in general, and provides novel insights into the molecular interactions between Pythium pathogens and their diverse hosts.

Considerations for Translational Research in the Study of Adult Cognitive Disorders

2019 ◽  
pp. 827-851
Author(s):  
Erich S. Franz ◽  
Sarah E. Chancellor ◽  
Lee E. Goldstein
Keyword(s):  
Health Care ◽  
Animal Models ◽  
Translational Research ◽  
Human Subjects ◽  
Cognitive Disorders ◽  
Health Care Outcomes ◽  
Cognitive Domains ◽  
Complex Interactions ◽  
Disease Mechanisms ◽  
Care Outcomes

Adult cognitive disorders exact a staggering burden on worldwide health care, with the need for efficacious and accessible treatments growing every day. The ability to probe questions relevant to normal or aberrant cognition in humans makes animal models indispensable tools in translational research. The use of animal models enables detailed investigation of complex interactions between genes, environment, and cognition that would be difficult or impossible in human subjects or populations. However, special consideration must be given to create specific, translatable models of human cognitive disorders. First, a model must prove statistically reliable, reproducible, and valid. Successful translational research requires thoughtful consideration and careful deployment of reliable, well-chosen animal models that are appropriately matched to their experimental purpose. In addition, to ensure specificity of a model to one disorder, it is prudent to focus on clusters of clinical features and disease-specific phenotypes in addition to environmental and genetic risk factors. Many neurological disorders share symptomatic elements in common, which drives the necessity for relevant cognitive domains to the disease in question to be carefully considered and replicated. Thoughtfully created animal models facilitate translational research aimed at understanding disease mechanisms and developing effective diagnostics, therapeutics, and preventive strategies to achieve better health care outcomes for people affected by cognitive disorders.

scholarly journals The influence of circadian rhythms and aerobic glycolysis in autism spectrum disorder

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexandre Vallée ◽  
Yves Lecarpentier ◽  
Rémy Guillevin ◽  
Jean-Noël Vallée
Keyword(s):  
Autism Spectrum Disorder ◽  
Circadian Rhythms ◽  
Aerobic Glycolysis ◽  
Cognitive Disorders ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Metabolic Reprogramming ◽  
Main Role ◽  
Circadian Expression ◽  
Canonical Wnt

AbstractIntellectual abilities and their clinical presentations are extremely heterogeneous in autism spectrum disorder (ASD). The main causes of ASD remain unclear. ASD is frequently associated with sleep disorders. Biologic rhythms are complex systems interacting with the environment and controlling several physiological pathways, including brain development and behavioral processes. Recent findings have shown that the deregulation of the core clock neurodevelopmental signaling is correlated with ASD clinical presentation. One of the main pathways involved in developmental cognitive disorders is the canonical WNT/β-catenin pathway. Circadian clocks have a main role in some tissues by driving circadian expression of genes involved in physiologic and metabolic functions. In ASD, the increase of the canonical WNT/β-catenin pathway is enhancing by the dysregulation of circadian rhythms. ASD progression is associated with a major metabolic reprogramming, initiated by aberrant WNT/β-catenin pathway, the aerobic glycolysis. This review focuses on the interest of circadian rhythms dysregulation in metabolic reprogramming in ASD through the aberrant upregulation of the canonical WNT/β-catenin pathway.

scholarly journals Reduced Cardiorespiratory Capacity in Children with Autism Spectrum Disorders

2018 ◽  
Vol 7 (10) ◽  
pp. 361 ◽  
Author(s):  
Véronique-Aurélie Bricout ◽  
Marion Pace ◽  
Léa Dumortier ◽  
Flavie Baillieul ◽  
Anne Favre-Juvin ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cardiorespiratory Fitness ◽  
Muscular Strength ◽  
Motor Impairment ◽  
Autism Spectrum ◽  
Activity Levels ◽  
Intellectual Quotient ◽  
Explosive Power ◽  
Spectrum Disorders ◽  
The Difference

Background—Children with autistic spectrum disorders (ASDs) are frequently hampered by motor impairment. It limits them from regularly practicing physical activities and results in a lower physical fitness even though low cardiorespiratory fitness is one of the most important predictors of all-cause mortality. This study aimed to investigate the cardiorespiratory fitness of boys with ASD compared to typically developed children. Methods—forty male children participated. Twenty were control children (CONT—10.0 ± 1.6 years) and 20 were ASD children (ASD—10.7 ± 1.2 years; intellectual quotient > 70). All participants completed an incremental exercise test on a treadmill. An evaluation of motor characteristics by three tests was conducted (muscular strength; explosive power; flexibility). Assessments of daily physical activity were obtained by questionnaires (PAQ-C) and by actigraphy. Results—in the ASD group, aerobic capacity values (VO2peak), effort duration and maximal speed were significantly lower compared to CONT (p < 0.05). Flexibility, explosive power and muscular strength were significantly lower in ASD compared to CONT (p < 0.05). Similarities between all children were observed for physical activity evaluation by actigraphy and with the PAQ-C. Conclusions—children with ASD had lower cardiorespiratory fitness than CONT despite similar physical activity levels. Our results suggested that the difference may be due to motor discrepancies.

Normative Data for the Spanish Version of the Addenbrooke's Cognitive Examination III

2016 ◽  
Vol 41 (5-6) ◽  
pp. 243-250 ◽  
Author(s):  
Jordi A. Matías-Guiu ◽  
Ramón Fernández-Bobadilla ◽  
Aníbal Fernández-Oliveira ◽  
María Valles-Salgado ◽  
Teresa Rognoni ◽  
...  
Keyword(s):  
Normative Data ◽  
Cognitive Disorders ◽  
Demographic Factors ◽  
Spanish Version ◽  
Cognitive Test ◽  
Test Results ◽  
Cognitive Domains ◽  
Visuospatial Skills ◽  
And Gender ◽  
Addenbrooke’S Cognitive Examination

Background: Addenbrooke's Cognitive Examination III (ACE-III) is a cognitive test that has been validated for the diagnosis of cognitive disorders. The aim of this study was to provide normative data for the ACE-III for age, education and gender. Methods: The Spanish version of the ACE-III was administered to a group of 273 healthy subjects in a multicenter study in Spain. Correlation and determination coefficients for age, education and gender were estimated. The overlapping interval strategy and linear regression analyses were used to provide adjusted norms for demographic factors and to explore the potential influence of these factors in the performance of the test. Results: Age and education correlated significantly with the total score and with all the domains. Gender correlated only with the domains of attention and visuospatial skills. Norms for the total score and for cognitive domains (attention, memory, fluency, language, and visuospatial skills) are provided. Conclusion: This study confirms the influence of demographic factors (especially age and education) on the performance in the ACE-III and provides normative data for the Spanish version of the ACE-III.

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