1,720,975 research outputs found
Crucial role of protein oligomerization in the pathogenesis of Alzheimer's and Parkinson's diseases
No full textMisfolding and aggregation of the proteins amyloid-, tau and alpha-synuclein is the predominant pathology underlying the neurodegenerative disorders, Alzheimer's and Parkinson's disease. While end stage insoluble products of aggregation have been well characterised in human and animal models of disease, accumulating evidence from biophysical, cellular and invivo studies has shown that soluble intermediates of aggregation, or oligomers, may be the key species that mediate toxicity and underlie seeding and spreading in disease. Here, we review the process of protein misfolding, and the intrinsic and extrinsic processes that cause the native states of the key aggregating proteins to undergo conformational change to form oligomers and ultimately fibrils. We discuss the structural features of the key toxic intermediate, and describe the putative mechanisms by which oligomers may cause cell toxicity. Finally, we explore the potential therapeutic approaches raised by the oligomer hypothesis in neurodegenerative disease.
A simple assessment model to quantifying the dynamic hippocampal neurogenic process in the adult mammalian brain
No full textAdult hippocampal neurogenesis is a highly dynamic process in which new cells are born, but only some of which survive. Of late it has become clear that these surviving newborn neurons have functional roles, most notably in certain forms of memory. Conventional methods to look at adult neurogenesis are based on the quantification of the number of newly born neurons using a simple cell counting methodology. However, this type of approach fails to capture the dynamic aspects of the neurogenic process, where neural proliferation, death and differentiation take place continuously and simultaneously. In this paper, we propose a simple mathematical approach to better understand the adult neurogenic process in the hippocampus which in turn will allow for a better analysis of this process in disease states and following drug therapies. (c) 2015 Wiley Periodicals, Inc.
The Fabry disease-associated lipid Lyso-Gb3 enhances voltage-gated calcium currents in sensory neurons and causes pain
No full textFabry disease is an X-linked lysosomal storage disorder characterised by accumulation of glycosphingolipids, and accompanied by clinical manifestations, such as cardiac disorders, renal failure, pain and peripheral neuropathy. Globotriaosylsphingosine (lyso-Gb3), a deacylated form of globotriaosylceramide (Gb3), has emerged as a marker of Fabry disease. We investigated the link between Gb3, lyso-Gb3 and pain. Plantar administration of lyso-Gb3 or Gb3 caused mechanical allodynia in healthy mice. In vitro application of 100nM lyso-Gb3 caused uptake of extracellular calcium in 10% of sensory neurons expressing nociceptor markers, rising to 40% of neurons at 1μM, a concentration that may occur in Fabry disease patients. Peak current densities of voltage-dependent Ca(2+) channels were substantially enhanced by application of 1μM lyso-Gb3. These studies suggest a direct role for lyso-Gb3 in the sensitisation of peripheral nociceptive neurons that may provide an opportunity for therapeutic intervention in the treatment of Fabry disease-associated pain
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
인체유래 신경세포의 비표지 이미지를 이용한 인공지능 기반 파킨슨병 하위 유형 분류
No full text학위논문(석사) - 한국과학기술원 : 뇌인지과학과, 2025.2,[iv, 37 p. :]Parkinson’s Disease (PD) is a complex and heterogeneous neurodegenerative disorder that poses significant challenges for personalized medicine due to its diverse pathological mechanisms and predominantly idiopathic nature. Current treatment approaches fail to address the underlying mechanisms of the disease, partly due to the lack of robust systems for identifying patient-specific mechanisms. In this study, we propose a machine learning-based classifier for PD subtypes, leveraging in vitro cellular models and a label-free imaging technique. By introducing chemically induced perturbations in healthy cortical neurons, we generated reproducible and versatile models of key PD pathological features, including mitochondrial dysfunction, lysosomal dysfunction, and protein aggregation. The transformer-based model achieved an exceptional classification accuracy of 96% during training with these chemical models. Furthermore, validation using patient-derived neurons carrying the SNCA triplication mutation underscores its translational relevance and potential for real-world applications. We establish a powerful drug screening paradigm that enables highly efficient, patient-specific therapeutic development by distinguishing the cellular and molecular underpinnings of the disease in individual patients.한국과학기술원 :뇌인지과학과
신경전구세포를 활용한 인체 유래 뇌 오가노이드 개발 및 파킨슨병 모델링
No full text학위논문(석사) - 한국과학기술원 : 뇌인지과학과, 2025.2,[iv, 58 p. :]Human induced pluripotent stem cell (hiPSC)-derived brain organoids are emerging as a promising tool for overcoming the limitations of 2D neuronal models. However, existing organoid models face challenges in achieving precise differentiation of specific brain regions and replicating disease-relevant phenotypes. In this study, we developed an optimized protocol for generating brain organoids starting from neural progenitor cells (NPCs). The generated organoids demonstrated clear regional specificity and characteristic neuronal activity patterns. Additionally, we established both patient-derived and chemically induced models to investigate Parkinson’s Disease (PD) pathology. In the chemically induced model, mitochondrial dysfunction and disease-related molecular pathway alterations were observed. The patient-derived organoids exhibited disease-specific phenotypes, including slower growth rates, reduced viability, and alpha-synuclein aggregation. These findings demonstrate the potential of NPC-based brain organoids as a model for studying the pathological mechanisms of PD and other human-specific neurological disorders.한국과학기술원 :뇌인지과학과
Variations on the Author
Get PDF“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
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe 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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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