1,721,034 research outputs found
MICAL flavoprotein monooxygenases: Structure, function and role in semaphorin signaling
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Axon guidance receptors: Endocytosis, trafficking and downstream signaling from endosomes
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Squaring the circle: The expression and function of axon guidance circular RNAs during neuronal development
No full textIn this thesis we investigated the expression and function of axon guidance circular RNAs (circRNAs) in the developing (mouse) brain. We tested and optimized various assays to measure, label and overexpress or knockdown axon guidance circRNAs using RNA-seq, RT-qPCR, Nanostring and (sm)(F)ISH to study the spatiotemporal expression of a selected group of axon guidance circRNAs and we adapted various manipulation tools to investigate their function in vitro and in vivo. Our major findings are that axon guidance circRNAs i) are conserved between human and mice, ii) are dynamically expressed throughout the mammalian brain over the course of development, iii) reveal expression peaks in the mouse cortex before birth, iv) show age-related accumulation, v) are expressed in excitatory cells, vi) have no expression in glia and vii) are upregulated after cellular activation. These findings increase our understanding on axon guidance circRNA expression and function, but further studies are necessary to elucidate the exact function(s) of each axon guidance circRNA in neuronal development and their role(s) in neurological disease
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
From Genes to Circuits: Molecular Regulation of Dopamine Neuron Development
No full textThe interaction of a myriad of molecular factors is necessary for proper development of mDA circuitry. Although significant progress has been made in uncovering the mechanisms involved in mDA neuron development, our understanding of the role played by specific classes of molecules (such as non-coding RNAs) is still incomplete. To extend existing knowledge, we examined the cellular aspects of mDA neuron development (chapter 1). Using this information, we identified relevant timepoints for a comprehensive transcriptomic profiling study of mouse mDA neurons and employed bioinformatics analysis to uncover patterns of lncRNA and circRNA expression during embryonic and postnatal development (chapter 1). We selected specific circRNA candidates for further functional investigation (chapter 2). Through in vitro and in vivo knockdown of a particular circRNA, we discovered several cellular and molecular changes in normal mDA neuron development.
Advances in sequencing techniques have facilitated the assessment of molecular profiles at the single-cell level in a more efficient and rapid manner. However, the definition of subtypes remains a subject of debate. Therefore, to gain a better understanding of the extent of mDA system heterogeneity, it is crucial to study cellular properties, such as morphology and electrophysiology. Consequently, we utilized intersectional mouse genetics to investigate different subsets of mDA neurons and their individual morphology (chapter 3).
The mDA system can be broadly categorized into the VTA and the SNc. These two regions receive and respond to distinct molecular signals that guide the neurons to their final positions after birth. In chapter 4, we made a novel discovery regarding a long-range mechanism that promotes cellular migration. Furthermore, we demonstrate the importance of the localization of other cell types (specifically, GABAergic neurons) for the proper placement of mDA neurons
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The multifunctional role of Semaphorin6A during brain development and disease: Moving forward with reverse signaling
No full textThe brain is a complex and versatile organ that undergoes various phases of development. This thesis focuses on the moment when neurons migrate from their birthplace to different brain areas and start to make connections with other cells to form neural circuits. During this phase, axon guidance molecules play an important role in establishing proper neural organization and connectivity. The principle of axon guidance is that growing axons and migrating cells rely on intermediate targets and guidance cues presented over short or long distances along their paths in order to establish neuronal connections. Growing axons extend their growth cones to scan the environment and respond to axon guidance cues that provide direction towards or away from specific regions. Semaphorins are axon guidance molecules that are well-known for their function as attractants or repellents. Although only a limited set of semaphorins has been identified, accumulating evidence indicates that distinct molecular mechanisms act to diversify the effects of semaphorins, making semaphorins multifunctional molecules that control a wide variety of cellular events. Chapter 2 comprises an extended introduction and description of general features and novel aspects of semaphorin function and signaling, including the role of their receptors; plexins and neuropilins. The focus is on the contribution of these molecules to the regulation of cell migration and the formation of neuronal connections. Semaphorin6A (Sema6A) is an example of a member of the semaphorin protein family that plays a key role in the nervous system, yet we know very little about its multifunctional role and diverse signaling mechanisms. In this thesis, the aim is to determine and specify these Sema6A signaling events during the development of the brain. Throughout the subsequent chapters of the thesis, three topics will be addressed: 1. Sema6A reverse signaling in vivo (Chapters 3 and 4) 2. Sema6A cis interaction and the specific structural domains involved in this interaction (Chapter 5) and 3. Novel functions of Sema6A in the diseased brain (Chapter 6).
This thesis provides an overview of recent developments in the field of axon guidance research focusing on semaphorins, including the role of their interactors; plexins and neuropilins (Chapter 2). Furthermore, it focuses on Sema6A, which is known to play important roles during the development of the nervous system. The overall aim of this thesis is to study the multifunctional character of Sema6A by selectively exploring functions of the intracellular domain (Chapter 3) and reverse signaling events (Chapter 4), interactors and regulators involved in Sema6A signaling pathways (Chapter 4), cis interaction domains (Chapter 5) and to specify novel roles during puberty onset and neuronal disease (Chapter 6). These previously unexplored functions help to understand the complexity of semaphorin signaling pathways and provide an extensive and in-depth overview of Sema6A signaling during brain development. The findings described in this thesis contribute to the knowledge of complex and dynamic cellular and molecular events that help to understand brain development and disorders
The Road Less Travelled: Exploring the profile and functions of non-coding RNAs in brain disease
No full textNearly 98 - 99% of the genome has little to no coding function and it is transcribed into non-coding RNAs (ncRNAs). These influence transcription, RNA processing and translation and include different sorts of molecules such as transfer RNAs (tRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs).
RNA metabolism is extremely relevant in the brain, as RNA is dynamically expressed and shows highly regulated temporal and spatial patterns, including tissue- and cell-type specificity. Research has shown that ncRNAs participate in several processes including brain development, synaptic plasticity, cell death, oxidative stress and epigenetic modifications. Importantly, their expression is often perturbed in tissues affected by neurological disorders (e.g. Alzheimer’s disease, Autism spectrum disorder, Huntington's disease, glioma) and accounts for an important layer of complexity when trying to dissect brain disease-mechanisms. Epilepsy is considered the most common chronic brain disease by affecting more than 50 million people globally. Currently, it is considered as a complex disorder likely resulting from the interplay between intrinsic (genetic) and extrinsic factors such as head trauma, infection episodes or brain tumours. Mesial temporal lobe epilepsy (mTLE) is a common form of focal epilepsy in which seizures originate from the amygdalo-hippocampal regions. An initial injury event (status epilepticus) is thought to trigger brain alterations (epileptogenesis, or ‘latent phase’) which will later develop into spontaneous seizures and, in some cases, hippocampal sclerosis. The initial treatment for the majority of epilepsy patients is based on antiepileptic drugs (AEDs). However, more than 30% of epilepsy patients continue to experience seizures despite AED treatment. This condition, known as ‘refractory epilepsy’, is present in 80% of mTLE patients. As a result, there is an urgent unmet need for innovative therapeutic approaches for treating refractory epilepsy. The pathological mechanisms leading to temporal lobe epilepsy (TLE) are not fully comprehended. The extensive use of animal models along with observations from human tissue have underlined important features. Common deregulated mechanisms include: neuronal loss, granule cell mossy fiber sprouting, activated astrocytes and microglia, decreased glutamine synthetase, down-regulation of ion channels and neurotransmitters, altered synaptic plasticity and dysfunction of the blood-brain barrier. These processes co-exist in the epileptic brain and ultimately lead to excitotoxicity and neuronal hyperexcitability. How altered ncRNA expression influences these processes remains elusive.
In this dissertation, we aimed to explore the profile and function of the non-coding transcriptome in the healthy and diseased brain. Individually, the chapters in this dissertation illustrate how different ncRNA classes may contribute to disease-related mechanisms. Together, they provide a framework to rethink novel therapeutic approaches for brain disease which remain untreatable or associated with poor treatment outcomes
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