scholarly journals Reverse complementary matches simultaneously promote both back-splicing and exon-skipping

2021 ◽  
Author(s):  
Dong Cao
Keyword(s):  
Large Scale ◽  
Exon Skipping ◽  
Circular Rnas ◽  
Branch Points ◽  
C Elegans ◽  
Neuronal Genes ◽  
Almost All ◽  
First Time ◽  
The Brain

Abstract Background: Circular RNAs (circRNAs) play diverse roles in different biological and physiological environments and are always expressed in a tissue-specific manner. Especially, circRNAs are enriched in the brain tissues of almost all investigated species, including humans, mice, Drosophila, etc. Although circRNAs were found in C. elegans, the neuron-specific circRNA data is not available yet. Exon-skipping is found to be correlated to circRNA formation, but the mechanisms that link them together are not clear.Results: Here, through large-scale neuron isolation from the first larval (L1) stage of C. elegans followed by RNA sequencing with ribosomal RNA depletion, the first neuronal circRNA data in C. elegans were obtained. Hundreds of novel circRNAs were annotated with high accuracy. circRNAs were highly expressed in the neurons of C. elegans and were positively correlated to the levels of their cognate linear mRNAs. Disruption of RCMs in circRNA flanking introns effectively abolished circRNA formation. In the zip-2 gene, deletion of either upstream or downstream RCMs almost eliminated the production of both the circular and the skipped transcript. Interestingly, the 13-nt RCM in zip-2 is highly conserved across five nematode ortholog genes, which show conserved exon-skipping patterns. Finally, through in vivo one-by-one mutagenesis of all the splicing sites and branch points required for exon-skipping and back-splicing in the zip-2 gene, I showed that back-splicing still happened without exon-skipping, and vice versa.Conclusions: For the first time, total RNA obtained from sorted neurons is increased to hundreds of nanograms. circRNAs highly expressed in the neurons of C. elegans are likely derived from neuronal genes. RCMs are abundant in circRNA flanking introns, and RCM-deletion is an efficient way to knockout circRNAs. More importantly, these RCMs are not only required for back-splicing but also promote the skipping of exon(s) to be circularized. Finally, RCMs in circRNA flanking introns can directly promote both exon-skipping and back-splicing, providing a new explanation for the correlation between them.

scholarly journals Reverse complementary matches simultaneously promote both back-splicing and exon-skipping

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Dong Cao
Keyword(s):  
Ribosomal Rna ◽  
Large Scale ◽  
Exon Skipping ◽  
Circular Rnas ◽  
Branch Points ◽  
C Elegans ◽  
Almost All ◽  
The Brain ◽  
Rna Depletion

Abstract Background Circular RNAs (circRNAs) play diverse roles in different biological and physiological environments and are always expressed in a tissue-specific manner. Especially, circRNAs are enriched in the brain tissues of almost all investigated species, including humans, mice, Drosophila, etc. Although circRNAs were found in C. elegans, the neuron-specific circRNA data is not available yet. Exon-skipping is found to be correlated to circRNA formation, but the mechanisms that link them together are not clear. Results Here, through large-scale neuron isolation from the first larval (L1) stage of C. elegans followed by RNA sequencing with ribosomal RNA depletion, the neuronal circRNA data in C. elegans were obtained. Hundreds of novel circRNAs were annotated with high accuracy. circRNAs were highly expressed in the neurons of C. elegans and were positively correlated to the levels of their cognate linear mRNAs. Disruption of reverse complementary match (RCM) sequences in circRNA flanking introns effectively abolished circRNA formation. In the zip-2 gene, deletion of either upstream or downstream RCMs almost eliminated the production of both the circular and the skipped transcript. Interestingly, the 13-nt RCM in zip-2 is highly conserved across five nematode ortholog genes, which show conserved exon-skipping patterns. Finally, through in vivo one-by-one mutagenesis of all the splicing sites and branch points required for exon-skipping and back-splicing in the zip-2 gene, I showed that back-splicing still happened without exon-skipping, and vice versa. Conclusions Through protocol optimization, total RNA obtained from sorted neurons is increased to hundreds of nanograms. circRNAs highly expressed in the neurons of C. elegans are more likely to be derived from genes also highly expressed in the neurons. RCMs are abundant in circRNA flanking introns, and RCM-deletion is an efficient way to knockout circRNAs. More importantly, these RCMs are not only required for back-splicing but also promote the skipping of exon(s) to be circularized. Finally, RCMs in circRNA flanking introns can directly promote both exon-skipping and back-splicing, providing a new explanation for the correlation between them.

scholarly journals Reverse complementary matches simultaneously promote both back-splicing and exon-skipping

2021 ◽  
Author(s):  
Dong Cao
Keyword(s):  
Larval Stage ◽  
Large Scale ◽  
Exon Skipping ◽  
The Other ◽  
Circular Rnas ◽  
Branch Points ◽  
Rna Seq ◽  
C Elegans ◽  
Neuronal Genes ◽  
Whole Transcriptome

Circular RNAs (circRNAs) play diverse roles in different biological and physiological environments. Understanding circRNA expression profile and how circRNAs are regulated help make better use of them. Here, using large-scale neuron isolation from the first larval stage (L1) of Caenorhabditis elegans (C. elegans) followed by whole-transcriptome RNA sequencing (RNA-seq), we provide the first neuronal circRNA data in C. elegans. We show that circRNAs are highly expressed in the neurons of C. elegans and are preferably derived from neuronal genes. More importantly, reverse complementary matches (RCMs) in circRNA-flanking introns are not only required for back-splicing but also promote the skipping of exon(s) to be circularized. Finally, through one-by-one mutagenesis of all the splicing sites and branch points required for exon-skipping and back-splicing, we show that exon-skipping is not absolutely required for back-splicing, neither the other way. Instead, the coupled exon-skipping and back-splicing are happening at the same time and the two pathways work together to regulate the levels of the circular and the skipped transcripts.

Implantable neural interfaces

2018 ◽  
Author(s):  
Stefano Vassanelli
Keyword(s):  
Brain Function ◽  
Large Scale ◽  
Ionic Channels ◽  
Patch Clamp Technique ◽  
Advantages And Disadvantages ◽  
Optogenetic Stimulation ◽  
Physical Interfaces ◽  
The Brain

Establishing direct communication with the brain through physical interfaces is a fundamental strategy to investigate brain function. Starting with the patch-clamp technique in the seventies, neuroscience has moved from detailed characterization of ionic channels to the analysis of single neurons and, more recently, microcircuits in brain neuronal networks. Development of new biohybrid probes with electrodes for recording and stimulating neurons in the living animal is a natural consequence of this trend. The recent introduction of optogenetic stimulation and advanced high-resolution large-scale electrical recording approaches demonstrates this need. Brain implants for real-time neurophysiology are also opening new avenues for neuroprosthetics to restore brain function after injury or in neurological disorders. This chapter provides an overview on existing and emergent neurophysiology technologies with particular focus on those intended to interface neuronal microcircuits in vivo. Chemical, electrical, and optogenetic-based interfaces are presented, with an analysis of advantages and disadvantages of the different technical approaches.

What Has Direct Cortical and Subcortical Electrostimulation Taught Us about Neurolinguistics?

2019 ◽  
pp. 185-211
Author(s):  
Hugues Duffau
Keyword(s):  
White Matter ◽  
Large Scale ◽  
Functional Neuroimaging ◽  
Great Accuracy ◽  
Subcortical White Matter ◽  
Cerebral Lesions ◽  
Physiological Basis ◽  
Postoperative Mri ◽  
The Brain

Investigating the neural and physiological basis of language is one of the most important challenges in neurosciences. Direct electrical stimulation (DES), usually performed in awake patients during surgery for cerebral lesions, is a reliable tool for detecting both cortical and subcortical (white matter and deep grey nuclei) regions crucial for cognitive functions, especially language. DES transiently interacts locally with a small cortical or axonal site, but also nonlocally, as the focal perturbation will disrupt the entire subnetwork sustaining a given function. Thus, in contrast to functional neuroimaging, DES represents a unique opportunity to identify with great accuracy and reproducibility, in vivo in humans, the structures that are actually indispensable to the function, by inducing a transient virtual lesion based on the inhibition of a subcircuit lasting a few seconds. Currently, this is the sole technique that is able to directly investigate the functional role of white matter tracts in humans. Thus, combining transient disturbances elicited by DES with the anatomical data provided by pre- and postoperative MRI enables to achieve reliable anatomo-functional correlations, supporting a network organization of the brain, and leading to the reappraisal of models of language representation. Finally, combining serial peri-operative functional neuroimaging and online intraoperative DES allows the study of mechanisms underlying neuroplasticity. This chapter critically reviews the basic principles of DES, its advantages and limitations, and what DES can reveal about the neural foundations of language, that is, the large-scale distribution of language areas in the brain, their connectivity, and their ability to reorganize.

Bistability of somatic pattern memories: stochastic outcomes in bioelectric circuits underlying regeneration

2021 ◽  
Vol 376 (1821) ◽  
pp. 20190765 ◽  
Author(s):  
Giovanni Pezzulo ◽  
Joshua LaPalme ◽  
Fallon Durant ◽  
Michael Levin
Keyword(s):  
Large Scale ◽  
Computational Models ◽  
State Of The Art ◽  
Memory Representation ◽  
Theme Issue ◽  
Evolutionary Innovation ◽  
New Interpretation ◽  
The Brain

Nervous systems’ computational abilities are an evolutionary innovation, specializing and speed-optimizing ancient biophysical dynamics. Bioelectric signalling originated in cells' communication with the outside world and with each other, enabling cooperation towards adaptive construction and repair of multicellular bodies. Here, we review the emerging field of developmental bioelectricity, which links the field of basal cognition to state-of-the-art questions in regenerative medicine, synthetic bioengineering and even artificial intelligence. One of the predictions of this view is that regeneration and regulative development can restore correct large-scale anatomies from diverse starting states because, like the brain, they exploit bioelectric encoding of distributed goal states—in this case, pattern memories. We propose a new interpretation of recent stochastic regenerative phenotypes in planaria, by appealing to computational models of memory representation and processing in the brain. Moreover, we discuss novel findings showing that bioelectric changes induced in planaria can be stored in tissue for over a week, thus revealing that somatic bioelectric circuits in vivo can implement a long-term, re-writable memory medium. A consideration of the mechanisms, evolution and functionality of basal cognition makes novel predictions and provides an integrative perspective on the evolution, physiology and biomedicine of information processing in vivo . This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens’.

The expression, lamin-dependent localization and RNAi depletion phenotype for emerin inC. elegans

2002 ◽  
Vol 115 (5) ◽  
pp. 923-929 ◽  
Author(s):  
Yosef Gruenbaum ◽  
Kenneth K. Lee ◽  
Jun Liu ◽  
Merav Cohen ◽  
Katherine L. Wilson
Keyword(s):  
Nuclear Envelope ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Growth Conditions ◽  
Rnai Phenotype ◽  
Lamin B ◽  
C Elegans ◽  
Nuclear Lamins ◽  
First Time

Emerin belongs to the LEM-domain family of nuclear membrane proteins, which are conserved in metazoans from C. elegans to humans. Loss of emerin in humans causes the X-linked form of Emery-Dreifuss muscular dystrophy(EDMD), but the disease mechanism is not understood. We have begun to address the function of emerin in C. elegans, a genetically tractable nematode. The emerin gene (emr-1) is conserved in C. elegans. We detect Ce-emerin protein in the nuclear envelopes of all cell types except sperm, and find that Ce-emerin co-immunoprecipitates with Ce-lamin from embryo lysates. We show for the first time in any organism that nuclear lamins are essential for the nuclear envelope localization of emerin during early development. We further show that four other types of nuclear envelope proteins, including fellow LEM-domain protein Ce-MAN1, as well as Ce-lamin, UNC-84 and nucleoporins do not depend on Ce-emerin for their localization. This result suggests that emerin is not essential to organize or localize the only lamin (B-type) expressed in C. elegans. We also analyzed the RNAi phenotype resulting from the loss of emerin function in C. elegans under laboratory growth conditions, and found no detectable phenotype throughout development. We propose that C. elegans is an appropriate system in which to study the molecular mechanisms of emerin function in vivo.

scholarly journals Caenorhabditis elegans, a Host to Investigate the Probiotic Properties of Beneficial Microorganisms

2020 ◽  
Vol 7 ◽  
Author(s):  
Cyril Poupet ◽  
Christophe Chassard ◽  
Adrien Nivoliez ◽  
Stéphanie Bornes
Keyword(s):  
Caenorhabditis Elegans ◽  
High Throughput Screening ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Probiotic Properties ◽  
C Elegans ◽  
Probiotic Potential ◽  
Challenges And Opportunities ◽  
Future Challenges

Caenorhabditis elegans, a non-parasitic nematode emerges as a relevant and powerful candidate as an in vivo model for microorganisms-microorganisms and microorganisms-host interactions studies. Experiments have demonstrated the probiotic potential of bacteria since they can provide to the worm a longer lifespan, an increased resistance to pathogens and to oxidative or heat stresses. Probiotics are used to prevent or treat microbiota dysbiosis and associated pathologies but the molecular mechanisms underlying their capacities are still unknown. Beyond safety and healthy aspects of probiotics, C. elegans represents a powerful way to design large-scale studies to explore transkingdom interactions and to solve questioning about the molecular aspect of these interactions. Future challenges and opportunities would be to validate C. elegans as an in vivo tool for high-throughput screening of microorganisms for their potential probiotic use on human health and to enlarge the panels of microorganisms studied as well as the human diseases investigated.

scholarly journals THE ROLE OF TECTONICS IN THE FORMATION OF SMALL WATER OBJECTS

2018 ◽  
Author(s):  
Е.В. Кюль ◽  
Л.И. Канкулова
Keyword(s):  
Large Scale ◽  
Practical Importance ◽  
Water Bodies ◽  
Small Water ◽  
Fault Type ◽  
Aquifer Systems ◽  
Tectonic Disturbances ◽  
Almost All ◽  
First Time ◽  
Small Water Bodies

В статье приведены результаты площадной оценки распределения малых водных объектов на территории КБР. При инвентаризации описаны 83 объекта, 75 из которых составляют родники. Практически все они приурочены к таким типам водоносных систем, как трещинно-жильные воды и воды зон тектонических нарушений. Прослеживается чёткая взаимосвязь между разрывными тектоническими нарушениями, оползневыми массивами и родниками трещинно-тектонического (разломного) типа. Масштабные работы по данной проблеме исследований на территории КБР проводятся впервые и имеют достаточно большое практическое значение. В дальнейшем, при определении рационального использования малых водных объектов в хозяйственных целях необходимо проведение комплекса специализированных (гидрохимических, экологических и др.) исследований. The article presents the results of an area assessment of the distribution of small water bodies in the KBR. The inventory describes 83 objects, 75 of which are springs. Almost all of them are confined to such types of aquifer systems as fractured-vein water and water zones of tectonic disturbances. The correlation between the discontinuous tectonic faults, landslides arrays and education of the springs are fracture-tectonic(fault) type. Large – scale work on this problem of research on the territory of the KBR is carried out for the first time and are of great practical importance. Further, in determining the rational use of small water bodies for economic purposes it is necessary to conduct complex specialized investigations (hydrochemical, environmental, etc.).

scholarly journals Neurons expressing pathological Tau protein trigger dramatic changes in microglial morphology and dynamics

2019 ◽  
Author(s):  
Rahma Hassan-Abdi ◽  
Alexandre Brenet ◽  
Mohamed Bennis ◽  
Constantin Yanicostas ◽  
Nadia Soussi-Yanicostas
Keyword(s):  
Morphological Changes ◽  
Pathological Process ◽  
Wild Type ◽  
Zebrafish Model ◽  
Genetic Ablation ◽  
Microglial Morphology ◽  
First Time ◽  
The Brain ◽  
Heterogeneous Class

AbstractMicroglial cells, the resident macrophages of the brain, are important players in the pathological process of numerous neurodegenerative disorders, including tauopathies, a heterogeneous class of diseases characterized by intraneuronal Tau aggregates. However, microglia response in Tau pathologies remains poorly understood. Here we exploit a genetic zebrafish model of tauopathy, combined with live microglia imaging, to investigate the behaviour of microglia in vivo in the disease context. Results show that while microglia were almost immobile and displayed long and highly dynamic branches in a wild-type context, in presence of diseased neurons cells became highly mobile and displayed morphological changes, with highly mobile cell bodies together with fewer and shorter processes. We also imaged, for the first time to our knowledge, the phagocytosis of apoptotic tauopathic neurons by microglia in vivo and observed that microglia engulfed about as twice materials as in controls. Finally, genetic ablation of microglia in zebrafish tauopathy model significantly increased Tau hyperphosphorylation, suggesting that microglia provide neuroprotection to diseased neurons. Our findings demonstrate for the first time the dynamics of microglia in contact with tauopathic neurons in vivo and open perspectives for the real-time study of microglia in many neuronal diseases.

scholarly journals A Review on Forest Fire Detection Techniques: A Decadal Perspective

2018 ◽  
Vol 7 (3.12) ◽  
pp. 1312 ◽  
Author(s):  
Vinay Chowdary ◽  
Mukul Kumar Gupta ◽  
Rajesh Singh
Keyword(s):  
Forest Fire ◽  
Forest Fires ◽  
Large Scale ◽  
Early Stage ◽  
Fire Detection ◽  
Great Loss ◽  
Detection Techniques ◽  
Almost All ◽  
Vegetation Loss ◽  
First Time

Forest fire disasters have always been mankind’s constant and inconvenient companion since time immemorial. In the recent past years, managing crisis for example a large scale fire has become a very difficult and challenging task. Things that are common in most of the forest fire that occur at large scale are loss of life (human or animal), loss of vegetation, loss of flora and fauna, and communication failure (if any). Apart from causing a great loss to valuable natural resources of nature forest fire pose a greater risk not only to life of human being but also to the inhabitant’s such as wild life living in the forest. As per National Fire Danger Rating System (NFDRS), if a fire is detected within 6 minutes of its occurrence then it can be easily disposed-off before it turns into a large scale fire. For this a network that can detect fire at a very early stage is required. There are numerous techniques to detect the occurrence of forest fire and this article is dedicated towards reviewing detection techniques present in the literature. This work will give a bird’s eye view of the technologies used in automatic detection of forest fires and reviews almost all the detection techniques available in the literature. To the best of our knowledge this is the first time that almost all the techniques available in the literature are reviewed and considering almost all the parameters.

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