scholarly journals Spine impairment in mice high-expressing neuregulin 1 due to LIMK1 activation

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Peng Chen ◽  
Hongyang Jing ◽  
Mingtao Xiong ◽  
Qian Zhang ◽  
Dong Lin ◽  
...  
Keyword(s):  
Neural Development ◽  
Protein Level ◽  
Brain Regions ◽  
Postmortem Brain ◽  
Pathophysiological Mechanism ◽  
Brain Disorders ◽  
Spine Density ◽  
Genes Encoding ◽  
High Level ◽  
And Function

AbstractThe genes encoding for neuregulin1 (NRG1), a growth factor, and its receptor ErbB4 are both risk factors of major depression disorder and schizophrenia (SZ). They have been implicated in neural development and synaptic plasticity. However, exactly how NRG1 variations lead to SZ remains unclear. Indeed, NRG1 levels are increased in postmortem brain tissues of patients with brain disorders. Here, we studied the effects of high-level NRG1 on dendritic spine development and function. We showed that spine density in the prefrontal cortex and hippocampus was reduced in mice (ctoNrg1) that overexpressed NRG1 in neurons. The frequency of miniature excitatory postsynaptic currents (mEPSCs) was reduced in both brain regions of ctoNrg1 mice. High expression of NRG1 activated LIMK1 and increased cofilin phosphorylation in postsynaptic densities. Spine reduction was attenuated by inhibiting LIMK1 or blocking the NRG1–LIMK1 interaction, or by restoring NRG1 protein level. These results indicate that a normal NRG1 protein level is necessary for spine homeostasis and suggest a pathophysiological mechanism of abnormal spines in relevant brain disorders.

scholarly journals Decoupling of brain function from structure reveals regional behavioral specialization in humans

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Maria Giulia Preti ◽  
Dimitri Van De Ville
Keyword(s):  
Brain Function ◽  
Brain Activity ◽  
Surrogate Data ◽  
Brain Regions ◽  
Sensory Function ◽  
Strongly Coupled ◽  
Neuronal Populations ◽  
High Level ◽  
And Function ◽  
Spatially Varying

Abstract The brain is an assembly of neuronal populations interconnected by structural pathways. Brain activity is expressed on and constrained by this substrate. Therefore, statistical dependencies between functional signals in directly connected areas can be expected higher. However, the degree to which brain function is bound by the underlying wiring diagram remains a complex question that has been only partially answered. Here, we introduce the structural-decoupling index to quantify the coupling strength between structure and function, and we reveal a macroscale gradient from brain regions more strongly coupled, to regions more strongly decoupled, than expected by realistic surrogate data. This gradient spans behavioral domains from lower-level sensory function to high-level cognitive ones and shows for the first time that the strength of structure-function coupling is spatially varying in line with evidence derived from other modalities, such as functional connectivity, gene expression, microstructural properties and temporal hierarchy.

Mutation of genes controlling mRNA metabolism and protein synthesis predisposes to neurodevelopmental disorders

2015 ◽  
Vol 43 (6) ◽  
pp. 1259-1265 ◽  
Author(s):  
Francesca Sartor ◽  
Jihan Anderson ◽  
Colin McCaig ◽  
Zosia Miedzybrodzka ◽  
Berndt Müller
Keyword(s):  
Neural Development ◽  
Neurodevelopmental Disorders ◽  
Nuclear Export ◽  
Mrna Splicing ◽  
Mrna Metabolism ◽  
Aberrant Gene Expression ◽  
Genes Encoding ◽  
And Function ◽  
Aberrant Gene ◽  
New Strategies

Brain development is a tightly controlled process that depends upon differentiation and function of neurons to allow for the formation of functional neural networks. Mutation of genes encoding structural proteins is well recognized as causal for neurodevelopmental disorders (NDDs). Recent studies have shown that aberrant gene expression can also lead to disorders of neural development. Here we summarize recent evidence implicating in the aetiology of NDDs mutation of factors acting at the level of mRNA splicing, mRNA nuclear export, translation and mRNA degradation. This highlights the importance of these fundamental processes for human health and affords new strategies and targets for therapeutic intervention.

scholarly journals Cadherins in early neural development

2021 ◽  
Author(s):  
Karolina Punovuori ◽  
Mattias Malaguti ◽  
Sally Lowell
Keyword(s):  
Adhesion Molecules ◽  
Cell Fate ◽  
Neural Development ◽  
Ex Vivo ◽  
Directed Differentiation ◽  
Culture Dish ◽  
Cell Identity ◽  
Cell Fate Decisions ◽  
Neural Tissues ◽  
And Function

AbstractDuring early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why are differentiation and adhesion so tightly linked? It is now over 60 years since Conrad Waddington noted the remarkable "Constancy of the Wild Type” (Waddington in Nature 183: 1654–1655, 1959) yet we still do not fully understand the mechanisms that make development so reproducible. Conversely, we do not understand why directed differentiation of cells in a dish is sometimes unpredictable and difficult to control. It has long been suggested that cells make decisions as 'local cooperatives' rather than as individuals (Gurdon in Nature 336: 772–774, 1988; Lander in Cell 144: 955–969, 2011). Given that the cadherin family of adhesion molecules can simultaneously influence morphogenesis and signalling, it is tempting to speculate that they may help coordinate cell fate decisions between neighbouring cells in the embryo to ensure fidelity of patterning, and that the uncoupling of these processes in a culture dish might underlie some of the problems with controlling cell fate decisions ex-vivo. Here we review the expression and function of cadherins during early neural development and discuss how and why they might modulate signalling and differentiation as neural tissues are formed.

scholarly journals Arabidopsis Genes Essential for Seedling Viability: Isolation of Insertional Mutants and Molecular Cloning

Genetics ◽  
2001 ◽  
Vol 159 (4) ◽  
pp. 1765-1778
Author(s):  
Gregory J Budziszewski ◽  
Sharon Potter Lewis ◽  
Lyn Wegrich Glover ◽  
Jennifer Reineke ◽  
Gary Jones ◽  
...  
Keyword(s):  
Large Scale ◽  
Protein Translocation ◽  
Gene Families ◽  
Mutant Phenotype ◽  
Lethal Mutant ◽  
A Genome ◽  
Genes Encoding ◽  
High Level ◽  
Mutant Lines ◽  
Genome Scale

Abstract We have undertaken a large-scale genetic screen to identify genes with a seedling-lethal mutant phenotype. From screening ~38,000 insertional mutant lines, we identified >500 seedling-lethal mutants, completed cosegregation analysis of the insertion and the lethal phenotype for >200 mutants, molecularly characterized 54 mutants, and provided a detailed description for 22 of them. Most of the seedling-lethal mutants seem to affect chloroplast function because they display altered pigmentation and affect genes encoding proteins predicted to have chloroplast localization. Although a high level of functional redundancy in Arabidopsis might be expected because 65% of genes are members of gene families, we found that 41% of the essential genes found in this study are members of Arabidopsis gene families. In addition, we isolated several interesting classes of mutants and genes. We found three mutants in the recently discovered nonmevalonate isoprenoid biosynthetic pathway and mutants disrupting genes similar to Tic40 and tatC, which are likely to be involved in chloroplast protein translocation. Finally, we directly compared T-DNA and Ac/Ds transposon mutagenesis methods in Arabidopsis on a genome scale. In each population, we found only about one-third of the insertion mutations cosegregated with a mutant phenotype.

L2 acquisition of the bei passive in Mandarin Chinese: A constructionist approach

2020 ◽  
Vol 9 (2) ◽  
pp. 169-198
Author(s):  
Chen Chen ◽  
Feng-hsi Liu
Keyword(s):  
Mandarin Chinese ◽  
Choice Task ◽  
L2 Acquisition ◽  
Low Level ◽  
Passive Construction ◽  
Form And Function ◽  
L2 Learners ◽  
Constructionist Approach ◽  
High Level ◽  
And Function

Abstract A major claim in the constructionist approach to language acquisition is that grammar is learned by pairings of form and function. In this study we test this claim by examining how L2 learners of Mandarin Chinese acquire the bei passive construction, a construction that is associated with the meaning of adversity. Our goal is to find out whether L2 learners make the association between the passive and adversity. Participants performed a sentence choice task under four conditions: an adversative context with an adversative verb, an adversative context with a neutral verb, a neutral context with a neutral verb and a positive context with a neutral verb. In each context participants were asked to select either the bei passive construction or its active counterpart. We found that high-level learners consistently chose the bei passive significantly more in adversative contexts than in non-adversative contexts regardless of the connotations of the verbs, while low-level learners made the distinction half of the time. In addition, while low-level learners did not yet associate adversity with the form of the construction, high-level learners did. We conclude that L2 learners do learn the bei passive construction as a form-meaning pair. The constructionist approach is supported.

Compressed sensorimotor-to-transmodal hierarchical organization in schizophrenia

2021 ◽  
pp. 1-14
Author(s):  
Debo Dong ◽  
Dezhong Yao ◽  
Yulin Wang ◽  
Seok-Jun Hong ◽  
Sarah Genon ◽  
...  
Keyword(s):  
Sensory Information ◽  
Resting State Fmri ◽  
Brain Regions ◽  
High Order ◽  
Hierarchical Organization ◽  
System Level ◽  
Integrative System ◽  
Sensorimotor Region ◽  
Cortical Hierarchy ◽  
High Level

Abstract Background Schizophrenia has been primarily conceptualized as a disorder of high-order cognitive functions with deficits in executive brain regions. Yet due to the increasing reports of early sensory processing deficit, recent models focus more on the developmental effects of impaired sensory process on high-order functions. The present study examined whether this pathological interaction relates to an overarching system-level imbalance, specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. Methods We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state fMRI to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients v. 122 controls). Results We demonstrated compression of the cortical hierarchy organization in schizophrenia, with a prominent compression from the sensorimotor region and a less prominent compression from the frontal−parietal region, resulting in a diminished separation between sensory and fronto-parietal cognitive systems. Further analyses suggested reduced differentiation related to atypical functional connectome transition from unimodal to transmodal brain areas. Specifically, we found hypo-connectivity within unimodal regions and hyper-connectivity between unimodal regions and fronto-parietal and ventral attention regions along the classical sensation-to-cognition continuum (voxel-level corrected, p < 0.05). Conclusions The compression of cortical hierarchy organization represents a novel and integrative system-level substrate underlying the pathological interaction of early sensory and cognitive function in schizophrenia. This abnormal cortical hierarchy organization suggests cascading impairments from the disruption of the somatosensory−motor system and inefficient integration of bottom-up sensory information with attentional demands and executive control processes partially account for high-level cognitive deficits characteristic of schizophrenia.

scholarly journals A High-Quality Grapevine Downy Mildew Genome Assembly Reveals Rapidly Evolving and Lineage-Specific Putative Host Adaptation Genes

2019 ◽  
Vol 11 (3) ◽  
pp. 954-969 ◽  
Author(s):  
Yann Dussert ◽  
Isabelle D Mazet ◽  
Carole Couture ◽  
Jérôme Gouzy ◽  
Marie-Christine Piron ◽  
...  
Keyword(s):  
Downy Mildew ◽  
Genome Assembly ◽  
Population Genomics ◽  
Plasmopara Viticola ◽  
Plant Diseases ◽  
Host Specialization ◽  
Grapevine Downy Mildew ◽  
Downy Mildews ◽  
Genes Encoding ◽  
High Level

Abstract Downy mildews are obligate biotrophic oomycete pathogens that cause devastating plant diseases on economically important crops. Plasmopara viticola is the causal agent of grapevine downy mildew, a major disease in vineyards worldwide. We sequenced the genome of Pl. viticola with PacBio long reads and obtained a new 92.94 Mb assembly with high contiguity (359 scaffolds for a N50 of 706.5 kb) due to a better resolution of repeat regions. This assembly presented a high level of gene completeness, recovering 1,592 genes encoding secreted proteins involved in plant–pathogen interactions. Plasmopara viticola had a two-speed genome architecture, with secreted protein-encoding genes preferentially located in gene-sparse, repeat-rich regions and evolving rapidly, as indicated by pairwise dN/dS values. We also used short reads to assemble the genome of Plasmopara muralis, a closely related species infecting grape ivy (Parthenocissus tricuspidata). The lineage-specific proteins identified by comparative genomics analysis included a large proportion of RxLR cytoplasmic effectors and, more generally, genes with high dN/dS values. We identified 270 candidate genes under positive selection, including several genes encoding transporters and components of the RNA machinery potentially involved in host specialization. Finally, the Pl. viticola genome assembly generated here will allow the development of robust population genomics approaches for investigating the mechanisms involved in adaptation to biotic and abiotic selective pressures in this species.

A Family of Genes Clustered at the Triplo-lethal Locus of Drosophila melanogaster Has an Unusual Evolutionary History and Significant Synteny With Anopheles gambiae

Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 613-621 ◽  
Author(s):  
Douglas R Dorer ◽  
Jamie A Rudnick ◽  
Etsuko N Moriyama ◽  
Alan C Christensen
Keyword(s):  
Phylogenetic Analysis ◽  
Drosophila Melanogaster ◽  
Anopheles Gambiae ◽  
Evolutionary History ◽  
Codon Bias ◽  
Good Target ◽  
The Family ◽  
Genes Encoding ◽  
And Function ◽  
Gambiae Genome

Abstract Within the unique Triplo-lethal region (Tpl) of the Drosophila melanogaster genome we have found a cluster of 20 genes encoding a novel family of proteins. This family is also present in the Anopheles gambiae genome and displays remarkable synteny and sequence conservation with the Drosophila cluster. The family is also present in the sequenced genome of D. pseudoobscura, and homologs have been found in Aedes aegypti mosquitoes and in four other insect orders, but it is not present in the sequenced genome of any noninsect species. Phylogenetic analysis suggests that the cluster evolved prior to the divergence of Drosophila and Anopheles (250 MYA) and has been highly conserved since. The ratio of synonymous to nonsynonymous substitutions and the high codon bias suggest that there has been selection on this family both for expression level and function. We hypothesize that this gene family is Tpl, name it the Osiris family, and consider possible functions. We also predict that this family of proteins, due to the unique dosage sensitivity and the lack of homologs in noninsect species, would be a good target for genetic engineering or novel insecticides.

scholarly journals Comparison of Activation in the Prefrontal Cortex of Native Speakers of Mandarin by Ability of Japanese as a Second Language Using a Novel Speaking Task

Healthcare ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 412
Author(s):  
Li Cong ◽  
Hideki Miyaguchi ◽  
Chinami Ishizuki
Keyword(s):  
Second Language ◽  
Prefrontal Cortex ◽  
Cognitive Load ◽  
Near Infrared ◽  
Native Speakers ◽  
Brain Activation ◽  
Brain Regions ◽  
Strong Inhibition ◽  
Functional Near Infrared Spectroscopy ◽  
High Level

Evidence shows that second language (L2) learning affects cognitive function. Here in this work, we compared brain activation in native speakers of Mandarin (L1) who speak Japanese (L2) between and within two groups (high and low L2 ability) to determine the effect of L2 ability in L1 and L2 speaking tasks, and to map brain regions involved in both tasks. The brain activation during task performance was determined using prefrontal cortex blood flow as a proxy, measured by functional near-infrared spectroscopy (fNIRS). People with low L2 ability showed much more brain activation when speaking L2 than when speaking L1. People with high L2 ability showed high-level brain activation when speaking either L2 or L1. Almost the same high-level brain activation was observed in both ability groups when speaking L2. The high level of activation in people with high L2 ability when speaking either L2 or L1 suggested strong inhibition of the non-spoken language. A wider area of brain activation in people with low compared with high L2 ability when speaking L2 is considered to be attributed to the cognitive load involved in code-switching L1 to L2 with strong inhibition of L1 and the cognitive load involved in using L2.

scholarly journals Induction of the Maize GapC4 Promoter in Transgenic Potato under Anaerobiosis and in Erwinia carotovora-Inoculated Tuber Tissue

1999 ◽  
Vol 12 (3) ◽  
pp. 182-188 ◽  
Author(s):  
Lorenz Bülow ◽  
Uwe Köhler ◽  
Rüdiger Cerff ◽  
Reinhard Hehl ◽  
Klaus Düring
Keyword(s):  
Experimental System ◽  
Erwinia Carotovora ◽  
Transgenic Potato ◽  
Intact Tissue ◽  
Induction Pattern ◽  
Pectolytic Enzymes ◽  
Genes Encoding ◽  
Live Bacteria ◽  
Foreign Genes ◽  
High Level

The induction pattern of the GapC4 promoter from maize in transgenic potato has been analyzed by fusion to the β-glucuronidase (gus) gene. Under anaerobic conditions this promoter confers high level expression not only in leaves, stems, and roots but also in tubers. After inoculation of potato tuber disks with Erwinia carotovora subsp. atroseptica, β-glucuronidase (GUS) activity could be detected in macerated tissue as well as in surrounding intact tissue. In mock controls no induction was detected, ruling out any induction due to an overall limitation in oxygen in the experimental system. In addition, it could be proven that no diffusion of GUS protein from macerated into intact tissue occurred. The promoter was shown to be aerobically induced even in the absence of live bacteria by incubation with purified Erwinia spp. pectolytic enzymes alone. Therefore, promoter induction seems to be mediated by a mobile factor instead of by limitation in oxygen. These results demonstrate that the maize GapC4 promoter is suitable for directing foreign genes encoding antibacterial proteins in transgenic potato.

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