2,729 research outputs found

    Development of variable and robust brain wiring patterns in the fly visual system

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    Precise generation of synapse-specific neuronal connections are crucial for establishing a robust and functional brain. Neuronal wiring patterns emerge from proper spatiotemporal regulation of axon branching and synapse formation during development. Several neuropsychiatric and neurodevelopmental disorders exhibit defects in neuronal wiring owing to synapse loss and/or dys-regulated axon branching. Despite decades of research, how the two inter-dependent cellular processes: axon branching and synaptogenesis are coupled locally in the presynaptic arborizations is still unclear. In my doctoral work, I investigated the possible role of EGF receptor (EGFR) activity in coregulating axon branching and synapse formation in a spatiotemporally restricted fashion, locally in the medulla innervating Dorsal Cluster Neuron (M- DCN)/LC14 axon terminals. In this work I have explored how genetically encoded EGFR randomly recycles in the axon branch terminals, thus creating an asymmetric, non-deterministic distribution pattern. Asymmetric EGFR activity in the branches acts as a permissive signal for axon branch pruning. I observed that the M-DCN branches which stochastically becomes EGFR ‘+’ during development are synaptogenic, which means they can recruit synaptic machineries like Syd1 and Bruchpilot (Brp). My work showed that EGFR activity has a dual role in establishing proper M-DCN wiring; first in regulating primary branch consolidation possibly via actin regulation prior to synaptogenesis. Later in maintaining/protecting the levels of late Active Zone (AZ) protein Brp in the presynaptic branches by suppressing basal autophagy level during synaptogenesis. When M-DCNs lack optimal EGFR activity, the basal autophagy level increases resulting in loss of Brp marked synapses which is causal to increased exploratory branches and post-synaptic target loss. Lack of EGFR activity affects the M-DCN wiring pattern that makes adult flies more active and behave like obsessive compulsive in object fixation assay. In the second part of my doctoral work, I have asked how non-genetic factors like developmental temperature affects adult brain wiring. To test that, I increased or decreased rearing temperature which is known to inversely affect pupal developmental rate. We asked if all the noisy cellular processes of neuronal assembly: filopodial dynamics, axon branching, synapse formation and postsynaptic connections scale up or down accordingly. I observed that indeed all the cellular processes slow down at lower developmental temperature and vice versa, which changes the DCN wiring pattern accordingly. Interestingly, behavior of flies adapts to their developmental temperature, performing best at the temperature they have been raised at. This shows that optimal brain function is an adaptation of robust brain wiring patterns which are specified by noisy developmental processes. In conclusion, my doctoral work helps us better understand the developmental regulation of axon branching and synapse formation for establishing precise brain wiring pattern. We need all the cell intrinsic developmental processes to be highly regulated in space and time. It is infact a combinatorial effect of such stochastic processes and external factors that contribute to the final outcome, a functional and robust adult brain

    LIPIcs, Volume 251, ITCS 2023, Complete Volume

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    LIPIcs, Volume 251, ITCS 2023, Complete Volum

    The Individual And Their World

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    Examining The Roles of Histone Methyltransferases in Heterochromatin Formation

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    The eukaryotic genome is meticulously stored inside the cell to control gene expression, protect the genome integrity, and facilitate cell division. The storage of genome is often achieved through epigenetic modifications. These modifications divide the genome into euchromatin and heterochromatin, each associated with gene expression and gene repression, respectively. Epigenetic modifications are often covalent modifications onto histone proteins or methylated DNA. On their own, some modifications can alter chromatin states, but most require specific epigenetic machinery that often termed epigenetic reader proteins. The epigenetic reader protein recognizes a specific epigenetic modification to alter chromatin states. For heterochromatin, these modifications often require heterochromatin protein 1 (HP1) to function. Heterochromatin represents a highly condensed form of chromatin that is often devoid of any transcriptional activities. Trimethylation of histone 3 lysine 9 (H3K9me3) and the presence of HP1 are the hallmarks and core players in heterochromatin formation. H3K9me3 recruits HP1, which when bound, can serve as a scaffold protein for more heterochromatin machinery. One key group of proteins HP1 recruits are the histone methyltransferases, the enzymes that catalyze the methylation of H3K9. The recruitment of HP1 often results in more H3K9me3 modifications, which can induce a positive feedback loop that results in a heterochromatin state. This group of histone methyltransferases all belong to the SET-domain family of proteins and demonstrate overlapping roles in heterochromatin formation. The redundancy within this group of enzymes calls for a better understanding in differentiating individual H3K9 methyltransferases. Does the redundancy suggest overlap in functionality or individual methyltransferases contribute to heterochromatin formation differently. The central hypothesis for this project is that different H3K9 methyltransferases can have different impacts on heterochromatin formation. By combining CiA-Oct4 cell line and Molecular biosystem, we have studied the intricacy of heterochromatin formation. Our SETDB1 knockdown cell lines show that SETDB1 contributes heavily to heterochromatin formation. SETDB1 knockdown cell lines have also shown reductions in H3K9me3 accumulation and impaired heterochromatin formation kinetics.Doctor of Philosoph

    A study of the inter-relationship of identity and urban heritage in Chiang Mai Old City, Thailand

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    The urban heritage identity of historical cities has received growing attention due to the weakening of their urban identity. For this reason, urban identity has been identified as a preliminary study of this research. Forty years ago, many researchers attempted to explain a broader understanding of urban heritage identity, which is relevant to human factors that affect urban, place, and built environment relationships. This involved the three interrelated concepts of identity: distinctiveness; urban heritage; and place attachment. These establish a balance between people and their identification with places. Urban heritage identity is associated a place's physicality and heritage attributes that reflect socio-cultural values. It can be concluded that urban heritage identity becomes significant through concepts of environmental psychology. Distinctiveness theory, as a part of identity theory, has been used in this study to describe the genuine perception of local participants and is a fundamental part of defining place identity. Furthermore, the definition of place attachment has been used to explain the relationship of distinct places on time of residence, frequency of use, emotional, physical, social, and activities. The study also explores Chiang Mai Old City’s built environment, which especially analyses the façade and streetscape characteristics that reflect the city's socio-cultural value. The research concludes with suggestions for preserving the city's urban heritage characteristics. Chiang Mai Old City has unprecedented diversity and cultural dynamics related to its intangible and tangible urban heritage. Moreover, the city is in the critical stage of being nominated as a new World Heritage Site by UNESCO, with the city's distinctiveness and place attachment being significant in supporting further heritage management strategies. The research mainly focuses on how local people interpret and understand the urban heritage identity of Chiang Mai Old City. This has been achieved through surveys of four hundred participants living in the Old City, two-way focus groups with five participants in each group, in-depth interviews with twenty-five participants, and ten architects drawing suggestions for further built environment management strategies. The results are described through seven aspects that explore the distinctiveness and place attachment theories of Chiang Mai Old City. The findings can be described in seven aspects: historical value; cultural activities; a particular character; landmark; identity; community; and everyday life. The results reveal that there are five distinct places in the city: Pra Singha Temple; Chedi Luang Temple; Three Kings monument square; Tha-Pare gate square; and Chiang Mai Old City's Moat. The results can also be used to develop an assessment indicator for defining the distinctiveness of other historic cities through the engagement of local people. The study repeatedly employs distinct places to describe in-place attachment theory. The results reveal positivity, emotion, and the spiritual anchor of place attached to local people in social engagement, explicitly divulging the rootedness of religion, culture, and community activities through the length of time. All five distinct places have an inseparable ability to display tangible heritage value and such a positive emotion to places is crucial in contributing to urban heritage characteristics. Moreover, the time or length of residency is a vital aspect to people’s perception of the city's distinctiveness; however, the value of the physical setting itself can increase the sense of belonging of newcomers.This research used a mixed methods approach in defining place identity process and socio-cultural values in distinctive streetscapes scenes in the city. This study strongly believes that the findings demonstrate that local people can help to develop the management of the city. The results presented suggest that the heritage value of streetscapes is related to historical attributes, natural objects, people, and cultural events in the scenes that explain the meanings ascribed to places associated with social and cultural values. The built environment characteristics and heritage value can be assumed from human experience. The study can be a new perspective for local authorities, urban designers, and heritage teams to determine whether projects will strengthen the existing urban heritage identity. Most importantly, this research has revealed new perspectives on urban heritage identity and practical study methods whilst also contributing to management strategies. In addition, continuing research into urban heritage identity will significantly improve knowledge development, practical support, and collaboration with local people and architects to establish and maintain cherished distinct places and living environments for urban residents

    An “other” experience of videogames: analyzing the connections between videogames and the lived experience of chronic pain

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    In this dissertation I argue for the connections between the lived experience of chronic pain and videogames, exploring what interacts with and influences them. To answer this, I draw on cripistemology as I engage in autoethnography, close-reading and close-gameplay, restorying, mixed methods design, formal interviews, surveys, and inductive coding. I further argue for pushing back against the unhelpful binaries that define the “human” and a false idea of “universal” experience or ability, instead pointing to the intersectionality that better reflects the biopolitics of disability, including both debility and capacity. I engage with these methods in three specific projects that consider additional sub-questions to further tease out why videogames disability, chronic pain, game design, lived experience, human centered design, embodiment in video games have impacted me so deeply and how this ties to my identity as a disabled woman. I further offer this dissertation to highlight the growing research of lived experience and disability in the field of game studies, providing empirical data that offers a foundational look of how I as a member of the chronic pain community think and feel about videogames, as well as how a small portion of the chronic pain community discusses videogames and the range of experiences this encompasses. In doing so, I unpack and argue on the relationship that exists between chronic pain and videogames, and further articulate why this matters. In Chapter 1 I provide necessary history and information regarding my research to better articulate the findings as presented in the following chapters. In Chapter 2, I analyze my connection to Animal Crossing: New Leaf (AC:NL) (Nintendo EAD, 2012) and explore opportunities about genre and mechanics as reflections of my own daily lived experience with chronic pain, especially including my experience in a 2014 pain rehabilitation program. Through this process, I define the “slice of life” genre and argue that AC:NL is exemplary of its markers. In Chapter 3 I provide a deep reading and analysis of Nintendo’s GameCube release Chibi-Robo! (Skip Ltd. et al., 2005) to “restory” the titular main character to have chronic pain like my own. Through the lens of debility and capacitation machines, I map these ideas onto the biopsychosocial model to organize a thorough analysis of his restoried identity. In modding the game’s narrative to reflect a lived experience of chronic pain like my own, I interweave fanfiction with deep reading and deep gameplay to unpack what representation I am looking for in videogames both narratively and mechanically. In this I further argue how this practice can be used to inform future game design. Finally, in Chapter 4, I interview members of the chronic pain community to understand their perspective on the connections between their lived experience with chronic pain and videogames, as well as how additional factors of their identity impact those experiences. For this I engage in a mixed methods design to conduct a survey and formal interviews to offer foundational work on how the chronic pain community interacts with videogames. I offer this project to intersect current research in chronic pain and videogames (and its related technology) that focuses on games as tools for “curing” pain, and argue the importance of considering what embodiment people with chronic pain already have in videogames instead. Ultimately, I argue for the necessity to complicate current design practices in human centered design (HCD) and game design. To do so, I highlight the lived experience of Othered identities to combat misguided notions of “universal” intent. In this, I analyze the inherent connections between videogames and disability, in this case chronic pain, through embodiment and lived experience. I center in on how my experience of chronic pain has impacted the way in which I engage and think about with videogames, and further, how my experiences align with that of the chronic pain community

    Economic and Social Consequences of the COVID-19 Pandemic in Energy Sector

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    The purpose of the Special Issue was to collect the results of research and experience on the consequences of the COVID-19 pandemic for the energy sector and the energy market, broadly understood, that were visible after a year. In particular, the impact of COVID-19 on the energy sector in the EU, including Poland, and the US was examined. The topics concerned various issues, e.g., the situation of energy companies, including those listed on the stock exchange, mining companies, and those dealing with renewable energy. The topics related to the development of electromobility, managerial competences, energy expenditure of local government units, sustainable development of energy, and energy poverty during a pandemic were also discussed

    Economic diversity In contemporary Timor-Leste

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    Economic Diversity in Contemporary Timor-Leste analyses various economic dynamics in past and present Timor-Leste. Comprising 14 research chapters, the volume brings to the fore: 1) local, community-based economic values and arrangements; 2) community-based entanglements with a market-driven economy; 3) the colonial and postcolonial governance praxis through which a market-driven economy has permeated the country, and 4) the creative and place-based ways through which local people have responded to these transformations. The collection challenges hegemonic, market-driven analyses which characterise Timor-Leste’s economy as weak, deformed and homogenised and demonstrates the myriad of socially embedded ways through which Timor-Leste’s economy is diverse, richly complex and continually brought into being. To frame the analysis of these complex economic dynamics in Timor-Leste, the collection’s introduction develops the concept of economic ecologies: the assemblages of institutions and their localised and historical relationships mobilised for reproducing collective life, both in its material and immaterial aspects
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