scholarly journals Brain Cytoplasmic RNAs in Neurons: From Biosynthesis to Function

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 313
Author(s):  
Younghoon Lee ◽  
Hee-Seung Lee ◽  
Meehyein Kim ◽  
Heegwon Shin
Keyword(s):  
Brain Function ◽  
Signal Transmission ◽  
Therapeutic Agents ◽  
Brain Diseases ◽  
Specific Expression ◽  
Control Of Gene Expression ◽  
Active Research ◽  
High Level ◽  
Important Basis ◽  
Cytoplasmic Rnas

Flexibility in signal transmission is essential for high-level brain function. This flexibility is achieved through strict spatial and temporal control of gene expression in neurons. Given the key regulatory roles of a variety of noncoding RNAs (ncRNAs) in neurons, studying neuron-specific ncRNAs provides an important basis for understanding molecular principles of brain function. This approach will have wide use in understanding the pathogenesis of brain diseases and in the development of therapeutic agents in the future. Brain cytoplasmic RNAs (BC RNAs) are a leading paradigm for research on neuronal ncRNAs. Since the first confirmation of brain-specific expression of BC RNAs in 1982, their investigation has been an area of active research. In this review, we summarize key studies on the characteristics and functions of BC RNAs in neurons.

scholarly journals Post-transcriptional mechanisms distinguish human and chimp forebrain progenitor cells

2019 ◽  
Author(s):  
Daniela A Grassi ◽  
Per Ludvik Brattås ◽  
Jeovanis G Valdés ◽  
Melinda Rezeli ◽  
Marie E Jönsson ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Transcriptional Control ◽  
Neural Progenitor Cells ◽  
Specific Expression ◽  
Control Of Gene Expression ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms ◽  
Species Specific ◽  
High Level ◽  
Rna Levels

AbstractThe forebrain has expanded in size and complexity during hominoid evolution. The contribution of post-transcriptional control of gene expression to this process is unclear. Using in-depth proteomics in combination with bulk and single-cell RNA sequencing, we analyzed protein and RNA levels of almost 5,000 genes in human and chimpanzee forebrain neural progenitor cells. We found that species differences in protein expression level was often independent of RNA levels, and more frequent than transcriptomic differences. Low-abundant proteins were more likely to show species-specific expression levels, while proteins expressed at a high level appeared to have evolved under stricter constraints. Our study implicates a previously unappreciated broad and important role for post-transcriptional regulatory mechanisms in the evolution of the human forebrain.

Language and Aging

2019 ◽  
pp. 294-316
Author(s):  
Jonathan E. Peelle
Keyword(s):  
Language Processing ◽  
Brain Function ◽  
Neural Systems ◽  
Language Abilities ◽  
Physiological Mechanisms ◽  
Cognitive Changes ◽  
Older Adulthood ◽  
Neural Organization ◽  
Age Related ◽  
High Level

Language processing in older adulthood is a model of balance between preservation and decline. Despite widespread changes to physiological mechanisms supporting perception and cognition, older adults’ language abilities are frequently well preserved. At the same time, the neural systems engaged to achieve this high level of success change, and individual differences in neural organization appear to differentiate between more and less successful performers. This chapter reviews anatomical and cognitive changes that occur in aging and popular frameworks for age-related changes in brain function, followed by an examination of how these principles play out in the context of language comprehension and production.

scholarly journals Cortical response to naturalistic stimuli is largely predictable with deep neural networks

2021 ◽  
Vol 7 (22) ◽  
pp. eabe7547
Author(s):  
Meenakshi Khosla ◽  
Gia H. Ngo ◽  
Keith Jamison ◽  
Amy Kuceyeski ◽  
Mert R. Sabuncu
Keyword(s):  
Brain Function ◽  
Deep Neural Networks ◽  
Neural Responses ◽  
Dynamic Interactions ◽  
Hierarchical Processing ◽  
Human Connectome Project ◽  
Neural Information ◽  
Neural Information Processing ◽  
Visual Interactions ◽  
High Level

Naturalistic stimuli, such as movies, activate a substantial portion of the human brain, invoking a response shared across individuals. Encoding models that predict neural responses to arbitrary stimuli can be very useful for studying brain function. However, existing models focus on limited aspects of naturalistic stimuli, ignoring the dynamic interactions of modalities in this inherently context-rich paradigm. Using movie-watching data from the Human Connectome Project, we build group-level models of neural activity that incorporate several inductive biases about neural information processing, including hierarchical processing, temporal assimilation, and auditory-visual interactions. We demonstrate how incorporating these biases leads to remarkable prediction performance across large areas of the cortex, beyond the sensory-specific cortices into multisensory sites and frontal cortex. Furthermore, we illustrate that encoding models learn high-level concepts that generalize to task-bound paradigms. Together, our findings underscore the potential of encoding models as powerful tools for studying brain function in ecologically valid conditions.

A challenge for historical research: Making data FAIR using a collaborative ontology management environment (OntoME)

Semantic Web ◽  
2020 ◽  
pp. 1-16
Author(s):  
Francesco Beretta
Keyword(s):  
Semantic Analysis ◽  
Historical Research ◽  
Data Modelling ◽  
Fine Grained ◽  
Fair Principles ◽  
Active Research ◽  
New Research ◽  
High Level ◽  
Conceptual Data ◽  
Ontology Management

This paper addresses the issue of interoperability of data generated by historical research and heritage institutions in order to make them re-usable for new research agendas according to the FAIR principles. After introducing the symogih.org project’s ontology, it proposes a description of the essential aspects of the process of historical knowledge production. It then develops an epistemological and semantic analysis of conceptual data modelling applied to factual historical information, based on the foundational ontologies Constructive Descriptions and Situations and DOLCE, and discusses the reasons for adopting the CIDOC CRM as a core ontology for the field of historical research, but extending it with some relevant, missing high-level classes. Finally, it shows how collaborative data modelling carried out in the ontology management environment OntoME makes it possible to elaborate a communal fine-grained and adaptive ontology of the domain, provided an active research community engages in this process. With this in mind, the Data for history consortium was founded in 2017 and promotes the adoption of a shared conceptualization in the field of historical research.

scholarly journals The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice [published erratum appears in Blood 1995 Apr 1;85(7):1983]

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 319-329 ◽  
Author(s):  
S Dziennis ◽  
RA Van Etten ◽  
HL Pahl ◽  
DL Morris ◽  
TL Rothstein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mice ◽  
Transgene Expression ◽  
Heterologous Gene Expression ◽  
Myeloid Cells ◽  
Reporter Genes ◽  
Regulatory Elements ◽  
Specific Expression ◽  
High Level

Abstract CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells.

Addiction and schizophrenia

2000 ◽  
Vol 15 (2) ◽  
pp. 115-122 ◽  
Author(s):  
P. Batel
Keyword(s):  
Epidemiologic Studies ◽  
Self Medication ◽  
Addictive Disorders ◽  
Co Morbidity ◽  
Dependency Type ◽  
Active Research ◽  
Social Environmental ◽  
High Level ◽  
Environmental Hypothesis ◽  
High Degree

SummaryEpidemiologic studies in the general population and those based on the clinical assessment of schizophrenic populations have revealed a high degree of overlap between schizophrenia and addictive disorders. The abuse of psychoactive substances (including alcohol) throughout life is so frequent (50%) that the possibility of a specific link inevitably arises. Various hypotheses have been suggested to explain the high co-morbidity between schizophrenia and addiction: 1) The social-environmental hypothesis has been developed but studies have provided poor evidence to validate it. 2) The possible shared biological vulnerability between schizophrenia and addictions led researchers to explore common genetic determinants and study the involvement of the dopaminergic and opioid systems in the aetiology of both schizophrenia and the abuse of and dependence on psychoactive drugs. 3) Finally, the theory of self-medication suggests that schizophrenics may be attempting to counter the deficit linked to their disorders by using the substances they take or their dependency-type behaviour to cope with their emotional problems. The clinical profile of schizophrenic addicts does seem to display some distinctive features, such as the high level of depressive co-morbidity, very high nicotine and alcohol dependence, with a very poor prognosis. These patients are difficult to manage; the possibility of pharmacologic interactions between the substances they are taking and neuroleptic medication calls for prudence, and their compliance is also poor. Addictive disorders in schizophrenics are currently a topic of active research intended to lead to identifying specific treatments. The early identification of addictive disorders in schizophrenics should make it possible to limit their development and improve the prognosis.

scholarly journals The brain timewise: how timing shapes and supports brain function

2015 ◽  
Vol 370 (1668) ◽  
pp. 20140170 ◽  
Author(s):  
Riitta Hari ◽  
Lauri Parkkonen
Keyword(s):  
Human Brain ◽  
Brain Imaging ◽  
Brain Function ◽  
Temporal Dynamics ◽  
Generative Models ◽  
Network Activity ◽  
Brain Diseases ◽  
Specific Information ◽  
Non Invasive ◽  
The Brain

We discuss the importance of timing in brain function: how temporal dynamics of the world has left its traces in the brain during evolution and how we can monitor the dynamics of the human brain with non-invasive measurements. Accurate timing is important for the interplay of neurons, neuronal circuitries, brain areas and human individuals. In the human brain, multiple temporal integration windows are hierarchically organized, with temporal scales ranging from microseconds to tens and hundreds of milliseconds for perceptual, motor and cognitive functions, and up to minutes, hours and even months for hormonal and mood changes. Accurate timing is impaired in several brain diseases. From the current repertoire of non-invasive brain imaging methods, only magnetoencephalography (MEG) and scalp electroencephalography (EEG) provide millisecond time-resolution; our focus in this paper is on MEG. Since the introduction of high-density whole-scalp MEG/EEG coverage in the 1990s, the instrumentation has not changed drastically; yet, novel data analyses are advancing the field rapidly by shifting the focus from the mere pinpointing of activity hotspots to seeking stimulus- or task-specific information and to characterizing functional networks. During the next decades, we can expect increased spatial resolution and accuracy of the time-resolved brain imaging and better understanding of brain function, especially its temporal constraints, with the development of novel instrumentation and finer-grained, physiologically inspired generative models of local and network activity. Merging both spatial and temporal information with increasing accuracy and carrying out recordings in naturalistic conditions, including social interaction, will bring much new information about human brain function.

scholarly journals Role of Methylation in the Induced and Spontaneous Expression of the Avian Endogenous Virusev-1: DNA Structure and Gene Products

1982 ◽  
Vol 2 (6) ◽  
pp. 638-652 ◽  
Author(s):  
Kathleen F. Conklin ◽  
John M. Coffin ◽  
Harriet L. Robinson ◽  
Mark Groudine ◽  
Robert Eisenman
Keyword(s):  
Dna Methylation ◽  
Strong Support ◽  
Reverse Transcriptase Activity ◽  
Structural Defects ◽  
Long Terminal Repeats ◽  
Control Of Gene Expression ◽  
Rna Molecules ◽  
Hypersensitive Sites ◽  
High Level

The endogenous avian provirusev-1 is widespread in white leghorn chickens. Although it has no major structural defects,ev-1 has not been associated with any phenotype and is ordinarily expressed at a very low level. In this report, we describe a chicken embryo (Number 1836) cell culture containing bothev-1 andev-6 which spontaneously expressed theev-1 provirus. This culture released a high level of noninfectious virions containing a full complement of virion structural (gag) proteins but devoid of reverse transcriptase activity or antigen. These virions contained 70S RNA closely related to the genome of Rous-associated virus type 0, but identifiable as theev-1 genome by oligonucleotide mapping. A fraction of the RNA molecules in the 70S complex were unusual in that they were polyadenylated 100 to 200 nucleotides downstream of the usual polyadenylation site. Eight sibling embryo cultures did not share this unusual phenotype with 1836, indicating that it was not inherited. However, an identical phenotype was inducible in the sibling cultures by treatment with 5-azacytidine, an inhibitor of DNA methylation, and the induced expression was stable for more than 10 generations. Analysis of chromatin structure and DNA methylation of theev-1 provirus in 1836 cells revealed the presence (in a fraction of the proviruses) of both DNase I hypersensitive sites in the long terminal repeats and ingagand a pattern of cleavage sites for methyl-sensitive restriction endonuclease not found in a nonexpressing sibling. These results lend strong support to the role of DNA methylation in the control of gene expression. Additionally, they explain the lack of phenotype associated withev-1 as due to a combination of its low expression and defectiveness inpolandenv.

Activation of octamer-containing promoters by either octamer-binding transcription factor 1 (OTF-1) or OTF-2 and requirement of an additional B-cell-specific component for optimal transcription of immunoglobulin promoters

1990 ◽  
Vol 10 (12) ◽  
pp. 6204-6215
Author(s):  
A Pierani ◽  
A Heguy ◽  
H Fujii ◽  
R G Roeder
Keyword(s):  
B Cell ◽  
Regulatory Element ◽  
Immunoglobulin Gene ◽  
Mobility Shift ◽  
Specific Expression ◽  
Tissue Specific ◽  
Activation Domains ◽  
Cell Extracts ◽  
Octamer Motif ◽  
High Level

Several distinct octamer-binding transcription factors (OTFs) interact with the sequence ATTTGCAT (the octamer motif), which acts as a transcription regulatory element for a variety of differentially controlled genes. The ubiquitous OTF-1 plays a role in expression of the cell cycle-regulated histone H2b gene as well as several other genes, while the tissue-specific OTF-2 has been implicated in the tissue-specific expression of immunoglobulin genes. In an attempt to understand the apparent transcriptional selectivity of these factors, we have investigated the physical and functional characteristics of OTF-1 purified from HeLa cells and both OTF-1 and OTF-2 purified from B cells. High-resolution footprinting and mobility shift-competition assays indicated that these factors were virtually indistinguishable in binding affinities and DNA-protein contacts on either the H2b or an immunoglobulin light-chain (kappa) promoter. In addition, each of the purified factors showed an equivalent intrinsic capacity to activate transcription from either immunoglobulin promoters (kappa and heavy chain) or the H2b promoter in OTF-depleted HeLa and B-cell extracts. However, with OTF-depleted HeLa extracts, neither factor could restore immunoglobulin gene transcription to the relatively high level observed in unfractionated B-cell extracts. Restoration of full immunoglobulin gene activity appears to require an additional B-cell regulatory component which interacts with the OTFs. The additional B-cell factor could act either by facilitating interaction of OTF activation domains with components of the general transcriptional machinery or by contributing a novel activation domain.

Insights into Enhancer RNAs: Biogenesis and Emerging Role in Brain Diseases

2021 ◽  
pp. 107385842110468
Author(s):  
Yuxin Shen ◽  
Zhengyi Huang ◽  
Ruiqing Yang ◽  
Yunlong Chen ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Small Proportion ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Histone Mark ◽  
Brain Diseases ◽  
Enhancer Activity ◽  
Cis Acting ◽  
High Level ◽  
Classification Function

Enhancers are cis-acting elements that control the transcription of target genes and are transcribed into a class of noncoding RNAs (ncRNAs) termed enhancer RNAs (eRNAs). eRNAs have shorter half-lives than mRNAs and long noncoding RNAs; however, the frequency of transcription of eRNAs is close to that of mRNAs. eRNA expression is associated with a high level of histone mark H3K27ac and a low level of H3K27me3. Although eRNAs only account for a small proportion of ncRNAs, their functions are important. eRNAs can not only increase enhancer activity by promoting the formation of enhancer-promoter loops but also regulate transcriptional activation. Increasing numbers of studies have found that eRNAs play an important role in the occurrence and development of brain diseases; however, further research into eRNAs is required. This review discusses the concept, characteristics, classification, function, and potential roles of eRNAs in brain diseases.

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