7,500 research outputs found
Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico
Valve replacement remains as the standard therapeutic option for aortic
stenosis patients, aiming at abolishing pressure overload and triggering
myocardial reverse remodeling. However, despite the instant hemodynamic
benefit, not all patients show complete regression of myocardial hypertrophy,
being at higher risk for adverse outcomes, such as heart failure. The current
comprehension of the biological mechanisms underlying an incomplete reverse
remodeling is far from complete. Furthermore, definitive prognostic tools and
ancillary therapies to improve the outcome of the patients undergoing valve
replacement are missing. To help abridge these gaps, a combined myocardial
(phospho)proteomics and pericardial fluid proteomics approach was followed,
taking advantage of human biopsies and pericardial fluid collected during
surgery and whose origin anticipated a wealth of molecular information
contained therein.
From over 1800 and 750 proteins identified, respectively, in the myocardium
and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated
proteins were detected. Gene annotation and pathway enrichment analyses,
together with discriminant analysis, are compatible with a scenario of increased
pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by
complement activity and other extrinsic factors, such as death receptor
activators), acute-phase response, immune system activation and fibrosis.
Specific validation of some targets through immunoblot techniques and
correlation with clinical data pointed to complement C3 β chain, Muscle Ring
Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation
regulated kinase 1A (DYRK1A) as potential markers of an incomplete
response. In addition, kinase prediction from phosphoproteome data suggests
that the modulation of casein kinase 2, the family of IκB kinases, glycogen
synthase kinase 3 and DYRK1A may help improve the outcome of patients
undergoing valve replacement. Particularly, functional studies with DYRK1A+/-
cardiomyocytes show that this kinase may be an important target to treat
cardiac dysfunction, provided that mutant cells presented a different response
to stretch and reduced ability to develop force (active tension).
This study opens many avenues in post-aortic valve replacement reverse
remodeling research. In the future, gain-of-function and/or loss-of-function
studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic
targets. Besides, clinical studies in larger cohorts will bring definitive proof of
complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de
referência para doentes com estenose aórtica e visa a eliminação da
sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica.
Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes
apresentam regressão completa da hipertrofia do miocárdio, ficando com maior
risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os
mecanismos biológicos subjacentes a uma remodelagem reversa incompleta
ainda não são claros. Além disso, não dispomos de ferramentas de
prognóstico definitivos nem de terapias auxiliares para melhorar a condição
dos pacientes indicados para substituição da válvula. Para ajudar a resolver
estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica
para a caracterização, respetivamente, do miocárdio e do líquido pericárdico
foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em
ambiente cirúrgico.
Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio
e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90
proteínas desreguladas foram detetadas. As análises de anotação de genes,
de enriquecimento de vias celulares e discriminativa corroboram um cenário de
aumento da expressão de genes pro-hipertróficos e de síntese proteica, um
sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular
(potencialmente acelerada pela atividade do complemento e por outros fatores
extrínsecos que ativam death receptors), com ativação da resposta de fase
aguda e do sistema imune, assim como da fibrose.
A validação de alguns alvos específicos através de immunoblot e correlação
com dados clínicos apontou para a cadeia β do complemento C3, a Muscle
Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation
regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta
incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma,
sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a
glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição
dos pacientes indicados para intervenção. Em particular, a avaliação funcional
de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo
importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes
responderam de forma diferente ao estiramento e mostraram uma menor
capacidade para desenvolver força (tensão ativa).
Este estudo levanta várias hipóteses na investigação da remodelagem reversa.
No futuro, estudos de ganho e/ou perda de função realizados em
cardiomiócitos isolados ou em modelos animais de banding-debanding da
aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos
encontrados. Além disso, estudos clínicos em coortes de maior dimensão
trarão conclusões definitivas quanto ao valor de prognóstico do complemento
C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin
School-based interventions to increase physical activity and reduce cardiometabolic risk in children
Post-Millennial Queer Sensibility: Collaborative Authorship as Disidentification in Queer Intertextual Commodities
This dissertation is examining LGBTQ+ audiences and creatives collaborating in the creation of new media texts like web shows, podcasts, and video games. The study focuses on three main objects or media texts: Carmilla (web series), Welcome to Night Vale (podcast), and Undertale (video game). These texts are transmedia objects or intertextual commodities. I argue that by using queer gestures of collaborative authorship that reaches out to the audience for canonical contribution create an emerging queer production culture that disidentifies with capitalism even as it negotiates capitalistic structures. The post-millennial queer sensibility is a constellation of aesthetics, self-representation, alternative financing, and interactivity that prioritizes community, trust, and authenticity using new technologies for co-creation.
Within my study, there are four key tactics or queer gestures being explored: remediation, radical ambiguity and multi-forms as queer aesthetics, audience self-representation, alternative financing like micropatronage & licensed fan-made merchandise, and interactivity as performance. The goal of this project is to better understand the changing conceptions of authorship/ownership, canon/fanon (official text/fan created extensions), and community/capitalism in queer subcultures as an indicator of the potential change in more mainstream cultural attitudes. The project takes into consideration a variety of intersecting identities including gender, race, class, and of course sexual orientation in its analysis. By examining the legal discourse around collaborative authorship, the real-life production practices, and audience-creator interactions and attitudes, this study provides insight into how media creatives work with audiences to co-create self-representative media, the motivations, and rewards for creative, audiences, and owners. This study aims to contribute towards a fuller understanding of queer production cultures and audience reception of these media texts, of which there is relatively little academic information. Specifically, the study mines for insights into the changing attitudes towards authorship, ownership, and collaboration within queer indie media projects, especially as these objects are relying on the self-representation of both audiences and creatives in the formation of the text
Um modelo para suporte automatizado ao reconhecimento, extração, personalização e reconstrução de gráficos estáticos
Data charts are widely used in our daily lives, being present in regular media,
such as newspapers, magazines, web pages, books, and many others. A well constructed
data chart leads to an intuitive understanding of its underlying data
and in the same way, when data charts have wrong design choices, a redesign
of these representations might be needed. However, in most cases, these
charts are shown as a static image, which means that the original data are not
usually available. Therefore, automatic methods could be applied to extract the
underlying data from the chart images to allow these changes. The task of
recognizing charts and extracting data from them is complex, largely due to the
variety of chart types and their visual characteristics.
Computer Vision techniques for image classification and object detection are
widely used for the problem of recognizing charts, but only in images without
any disturbance. Other features in real-world images that can make this task
difficult are not present in most literature works, like photo distortions, noise,
alignment, etc. Two computer vision techniques that can assist this task and
have been little explored in this context are perspective detection and
correction. These methods transform a distorted and noisy chart in a clear
chart, with its type ready for data extraction or other uses. The task of
reconstructing data is straightforward, as long the data is available the
visualization can be reconstructed, but the scenario of reconstructing it on the
same context is complex.
Using a Visualization Grammar for this scenario is a key component, as these
grammars usually have extensions for interaction, chart layers, and multiple
views without requiring extra development effort.
This work presents a model for automated support for custom recognition, and
reconstruction of charts in images. The model automatically performs the
process steps, such as reverse engineering, turning a static chart back into its
data table for later reconstruction, while allowing the user to make modifications
in case of uncertainties. This work also features a model-based architecture
along with prototypes for various use cases. Validation is performed step by
step, with methods inspired by the literature. This work features three use
cases providing proof of concept and validation of the model.
The first use case features usage of chart recognition methods focused on
documents in the real-world, the second use case focus on vocalization of
charts, using a visualization grammar to reconstruct a chart in audio format,
and the third use case presents an Augmented Reality application that
recognizes and reconstructs charts in the same context (a piece of paper)
overlaying the new chart and interaction widgets. The results showed that with
slight changes, chart recognition and reconstruction methods are now ready for
real-world charts, when taking time, accuracy and precision into consideration.Os gráficos de dados são amplamente utilizados na nossa vida diária, estando
presentes nos meios de comunicação regulares, tais como jornais, revistas,
páginas web, livros, e muitos outros. Um gráfico bem construído leva a uma
compreensão intuitiva dos seus dados inerentes e da mesma forma, quando
os gráficos de dados têm escolhas de conceção erradas, poderá ser
necessário um redesenho destas representações. Contudo, na maioria dos
casos, estes gráficos são mostrados como uma imagem estática, o que
significa que os dados originais não estão normalmente disponíveis. Portanto,
poderiam ser aplicados métodos automáticos para extrair os dados inerentes
das imagens dos gráficos, a fim de permitir estas alterações. A tarefa de
reconhecer os gráficos e extrair dados dos mesmos é complexa, em grande
parte devido à variedade de tipos de gráficos e às suas características visuais.
As técnicas de Visão Computacional para classificação de imagens e deteção
de objetos são amplamente utilizadas para o problema de reconhecimento de
gráficos, mas apenas em imagens sem qualquer ruído. Outras características
das imagens do mundo real que podem dificultar esta tarefa não estão
presentes na maioria das obras literárias, como distorções fotográficas, ruído,
alinhamento, etc. Duas técnicas de visão computacional que podem ajudar
nesta tarefa e que têm sido pouco exploradas neste contexto são a deteção e
correção da perspetiva. Estes métodos transformam um gráfico distorcido e
ruidoso em um gráfico limpo, com o seu tipo pronto para extração de dados
ou outras utilizações. A tarefa de reconstrução de dados é simples, desde que
os dados estejam disponíveis a visualização pode ser reconstruída, mas o
cenário de reconstrução no mesmo contexto é complexo.
A utilização de uma Gramática de Visualização para este cenário é um
componente chave, uma vez que estas gramáticas têm normalmente
extensões para interação, camadas de gráficos, e visões múltiplas sem exigir
um esforço extra de desenvolvimento.
Este trabalho apresenta um modelo de suporte automatizado para o
reconhecimento personalizado, e reconstrução de gráficos em imagens
estáticas. O modelo executa automaticamente as etapas do processo, tais
como engenharia inversa, transformando um gráfico estático novamente na
sua tabela de dados para posterior reconstrução, ao mesmo tempo que
permite ao utilizador fazer modificações em caso de incertezas. Este trabalho
também apresenta uma arquitetura baseada em modelos, juntamente com
protótipos para vários casos de utilização. A validação é efetuada passo a
passo, com métodos inspirados na literatura. Este trabalho apresenta três
casos de uso, fornecendo prova de conceito e validação do modelo.
O primeiro caso de uso apresenta a utilização de métodos de reconhecimento
de gráficos focando em documentos no mundo real, o segundo caso de uso
centra-se na vocalização de gráficos, utilizando uma gramática de visualização
para reconstruir um gráfico em formato áudio, e o terceiro caso de uso
apresenta uma aplicação de Realidade Aumentada que reconhece e reconstrói
gráficos no mesmo contexto (um pedaço de papel) sobrepondo os novos
gráficos e widgets de interação. Os resultados mostraram que com pequenas
alterações, os métodos de reconhecimento e reconstrução dos gráficos estão
agora prontos para os gráficos do mundo real, tendo em consideração o
tempo, a acurácia e a precisão.Programa Doutoral em Engenharia Informátic
Investigating the mechanism of human beta defensin-2-mediated protection of skin barrier in vitro
The human skin barrier is a biological imperative. Chronic inflammatory skin diseases, such as Atopic Dermatitis (AD), are characterised by a reduction in skin barrier function and an increased number of secondary infections. Staphyloccocus aureus (S. aureus) has an increased presence on AD lesional skin and contributes significantly to AD pathology. It was previously demonstrated that the damage induced by a virulence factor of S. aureus, V8 protease, which causes further breakdown in skin barrier function, can be reduced by induction of human β- defensin (HBD)2 (by IL-1β) or exogenous HBD2 application. Induction of this defensin is impaired in AD skin. This thesis examines the mechanism of HBD2-mediated barrier protection in vitro; demonstrating that in this system, HBD2 was not providing protection through direct protease inhibition, nor was it altering keratinocyte proliferation or migration, or exhibiting specific localisation within the monolayer. Proteomics data demonstrated that HBD2 did not induce expression of known antiproteases but suggested that HBD2 stimulation may function by modulating expression of extracellular matrix proteins, specifically collagen- IVα2 and Laminin-β-1. Alternative pathways of protection initiated by IL-1β and TNFα stimulation were also investigated, as well as their influence over generalised wound healing. Finally, novel 3D human skin epidermal models were used to better recapitulate the structure of human epidermis and examine alterations to skin barrier function in a more physiological system. These data validate the barrier-protective properties of HBD2 and extended our knowledge of the consequences of exposure to this peptide in this context
SYSTEMS METHODS FOR ANALYSIS OF HETEROGENEOUS GLIOBLASTOMA DATASETS TOWARDS ELUCIDATION OF INTER-TUMOURAL RESISTANCE PATHWAYS AND NEW THERAPEUTIC TARGETS
In this PhD thesis is described an endeavour to compile litterature about Glioblastoma key molecular mechanisms into a directed network followin Disease Maps standards, analyse its topology and compare results with quantitative analysis of multi-omics datasets in order to investigate Glioblastoma resistance mechanisms. The work also integrated implementation of Data Management good practices and procedures
Cis-Regulation of Gremlin1 Expression during Mouse Limb Bud Development and its Diversification during Vertebrate Evolution
Embryonic development and organogenesis rely on tightly controlled gene expression, which is achieved by cis-regulatory modules (CRMs) interacting with distinct transcription factors (TFs) that control spatio-temporal and tissue-specific gene expression. During organogenesis, gene regulatory networks (GRNs) with selfregulatory feedback properties coordinately control growth and patterning and provide systemic robustness against genetic and/or environmental perturbations. During limb bud development, various interlinked GRNs control outgrowth and patterning along all three limb axes. A paradigm network is the epithelial-mesenchymal (e-m) SHH/GREM1/AER-FGF feedback signaling system which controls limb bud outgrowth and digit patterning. The BMP antagonist GREMLIN1 (GREM1) is central to this e-m interactions as its antagonism of BMP activity is essential to maintain both AER-Fgf and Shh expression. In turn, SHH signaling upregulates Grem1 expression, which results in establishment of a self-regulatory signaling network. One previous study provided evidence that several CRMs could regulate Grem1 expression during limb bud development. However, the cis-regulatory logics underlying the spatio-temporal regulation of the Grem1 expression dynamics remained obscure. From an evolutionary point of view, diversification of CRMs can result in diversification of gene regulation which can drive the establishment of morphological novelties and adaptions. This was evidenced by the observed differences in Grem1 expression in different species that correlates with the evolutionary plasticity of tetrapod digit patterning. Hence, a better understanding of spatio-temporal regulation of the Grem1 expression dynamics and underlying cis-regulatory logic is of interest from both adevelopmental and an evolutionary perspective.
Recently, multiple candidate CRMs have been identified that might be functionally relevant for Grem1 expression during mouse limb bud development. For my PhD project, I genetically analyzed which of these CRMs are involved in the regulation of the spatial-temporal Grem1 expression dynamics in limb buds. Therefore, we generated various single and compound CRM mutant alleles using CRISPR/Cas9. Our CRMs allelic series revealed a complex Grem1 cis-regulation among a minimum of six CRMs, where a subset of CRMs regulates Grem1 transcript levels in an additive manner. Surprisingly, phenotypic robustness depends not on threshold transcript levels but the spatial integrity of the Grem1 expression domain. In particular, interactions among five CRMs control the characteristic asymmetrical and posteriorly biased Grem1 expression in mouse limb buds. Our results provide an example of how multiple seemingly redundant limb-specific CRMs provide phenotypical robustness by cooperative/synergistic regulation of the spatial Grem1 expression dynamics.
Three CRMs are conserved along the phylogeny of extant vertebrates with paired appendages. Of those, the activities of two CRMs recapitulate the major spatiotemporal aspects of Grem1 expression in mouse limb buds. In order to study their functions in species-specific regulation of Grem1 expression and their functional diversification in tetrapods, I tested the orthologous of both CRMs from representative species using LacZ reporter assays in transgenic mice, in comparison to the endogenous Grem1 expression in limb buds of the species of origin. Surprisingly, the activities of CRM orthologues display high evolutionary plasticity, which correlates better with the Grem1 expression pattern in limb buds of the species of origin than its mouse orthologue. This differential responsiveness to the GRNs in mouse suggests that TF binding site alterations in CRMs could underlie the spatial diversification of Grem1 in limb buds during tetrapod evolution.
While the fish fin and tetrapod limb share some homologies of proximal bones, the autopod is a neomorphic feature of tetrapods. The Grem1 requirement for digit patterning and conserved expression in fin buds prompted us to assess the enhancer activity of fish CRM orthologues in transgenic mice. Surprisingly, all tested fish CRMs are active in the mouse autopod primordia providing strong evidence that Grem1 CRMs are active in fin buds and that they predate the fin-to-limb transition. Our results corroborate increasing evidence that CRMs governing autopodial gene expression have been co-opted during the emergence of tetrapod autopod.
Furthermore, as part of a collaboration with Dr. S. Jhanwar, I contributed to the study of shared and species-specific epigenomic and genomic variations during mouse and chicken limb bud development. In this analysis, Dr. S. Jhanwar identified putative enhancers that show higher chicken-specific sequence turnover rates in comparison to their mouse orthologues, which defines them as so-called chicken accelerated regions (CARs). Here, I analyzed the CAR activities in comparison to their mouse orthologues by transgenic LacZ reporter assays, which was complemented by analysis of the endogenous gene expression in limb buds of both species. This analysis indicates that diversified activity of CARs and their mouse orthologues could be linked to the differential gene expression patterns in limb buds of both species
The Role of the Metabolome in the Development of Gestational Diabetes Mellitus in High-Risk Minority Women: A Causal Investigation
Gestational Diabetes Mellitus (GDM) is the most common pregnancy complication worldwide. However, GDM prevalence is substantially lower in white Europeans (WEs) compared to other ethnicities, especially South Asians (SAs) who experience the highest risk. Globally, healthy diet promotion is the mainstay in GDM prevention, however current guidelines are predominantly based on evidence from WEs. Furthermore, metabolic factors responsible for the disparities in prevalence are unknown but may offer guidance for improved prevention and management.
This project aimed to (i) assess the association between diet and GDM across ethnic groups, (ii) determine if distinct metabolic profiles characterise GDM in SAs and WEs, and (iii) evaluate the presence of ethnic-specific causal associations between metabolites and gestational dysglycemia. Aims (ii) and (iii) utilised data from the Born in Bradford cohort (mean gestational age 26.1 weeks).
First, through a systematic review of observational and randomised studies, pre-pregnancy diet was found to associate with GDM in WEs, but not in Asians. Secondly, the multivariate analyses of metabolites identified 7 metabolites that were characteristic of GDM in both ethnicities, with an additional 6 characteristic in WEs only. Finally, through Mendelian Randomisation (MR) analyses, 14 metabolites associated with pregnancy dysglycemia in WEs and 11 in SAs. No metabolites were identified in both ethnicities. Cholesterols and fatty acids were the most commonly identified classes identified in WEs and SAs, respectively.
This project demonstrated (i) inconsistencies in the association between diet and GDM across ethnicities (ii) distinct metabolic profiles that associate with GDM in WEs and SAs and offers and supports the need for ethnic-specific manage GDM management strategies. In high-risk SAs, fatty acids may be the most important predictors of GDM. Future work should evaluate the role of pre-pregnancy fatty acid intake in GDM development in SAs to aid in the development of culturally tailored dietary interventions
Chinese Benteng Women’s Participation in Local Development Affairs in Indonesia: Appropriate means for struggle and a pathway to claim citizen’ right?
It had been more than two decades passing by aftermath the devastating Asia’s Financial Crisis in 1997, subsequently followed by Suharto’s step down from his presidential throne which he occupied for more than three decades. The financial turmoil turned to a political disaster furthermore has led to massive looting that severely impacted Indonesians of Chinese descendant, including unresolved mystery of the most atrocious sexual violation against women and covert killings of students and democracy activists in this country. Since then, precisely aftermath May 1998, which publicly known as “Reformasi”1, Indonesia underwent political reform that eventually corresponded positively to its macroeconomic growth. Twenty years later, in 2018, Indonesia captured worldwide attention because it has successfully hosted two internationally renowned events, namely the Asian Games 2018 – the most prestigious sport events in Asia – conducted in Jakarta and Palembang; and the IMF/World Bank Annual Meeting 2018 in Bali. Particularly in the IMF/World Bank Annual Meeting, this event has significantly elevated Indonesia’s credibility and international prestige in the global economic powerplay as one of the nations with promising growth and openness. However, the narrative about poverty and inequality, including increasing racial tension, religious conservatism, and sexual violation against women are superseded by friendly climate for foreign investment and eventually excessive glorification of the nation’s economic growth. By portraying the image of promising new economic power, as rhetorically promised by President Joko Widodo during his presidential terms, Indonesia has swept the growing inequality in this highly stratified society that historically compounded with religious and racial tension under the carpet of digital economy.Arte y Humanidade
Investigating PAX6 and SOX2 dynamic interactions at the single molecule level in live cells
The abundance of transcription factor (TF) molecules in the nuclei of
eukaryotic cells are in the range of thousands. However, the functional binding
sites of most TFs lie in the range of hundreds. This suggests that there is a
surplus of the number of molecules for many TFs, relative to their binding sites
at any given time. Nevertheless, precise TF levels are instrumental for normal
development and maintenance, with haploinsufficiency (namely lowering the
dosage of a TF by half) being a hallmark of many TF-related human
developmental disorders. Qualitative methods assessing TF binding such as
chromatin immunoprecipitation, provide static information, from fixed cell
populations and so fail to provide insight into TF dynamic behaviour. Live-cell
imaging methodologies such as Fluorescence Correlation Spectroscopy
(FCS) offer the ability to measure kinetics of binding to chromatin, protein-protein interactions, absolute concentrations of molecules and the underlying
cell-to-cell variability.
SOX2 and PAX6 TFs exhibit haploinsufficiency in humans. Heterozygous point
mutations, deletions or insertions in these genes can lead to a plethora of
abnormal ocular developmental disorders (e.g. coloboma, aniridia,
microphthalmia, anopthalmia). SOX2 encodes a high-mobility group (HMG)
domain-containing TF, essential for maintaining self-renewal of embryonic
stem cells and is expressed in proliferating central nervous system (CNS)
progenitors. PAX6 contains two DNA binding domains; a PAIRED domain (PD)
and a homeodomain (HD). Both DNA binding domains present in PAX6 (PD
and HD) can function either jointly, or separately, to regulate a plethora of
genes implicated in the development and maintenance of the CNS, the eye
and the pancreas. Despite existing genetic and phenotypic evidence, it
remains unclear how PAX6 and SOX2 influence each other at the molecular
level and how sensitive their stoichiometry is during ocular development.
In this thesis I investigated the dynamic interplay between PAX6/SOX2 and
chromatin in live cells, at the molecular level. I compared wild-type protein
function with pathogenic missense variants using advanced fluorescence
microscopy techniques and assessed how these mutations quantitatively and
qualitatively affected molecular behaviour. My results showed that both SOX2
and PAX6 pathogenic missense mutants display differential subnuclear
localisation, as well as altered protein-protein and protein-chromatin
interactions, linking molecular diffusion to pathogenic phenotype in humans.
More importantly, I identified a novel role of SOX2 in stabilising PAX6-
chromatin complexes in live cells, providing further insight into the complex
and dynamic relation of PAX6 and SOX2 in ocular tissue specification,
maintenance and development
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