2,678 research outputs found
Computational techniques to interpret the neural code underlying complex cognitive processes
Advances in large-scale neural recording technology have significantly improved the
capacity to further elucidate the neural code underlying complex cognitive processes.
This thesis aimed to investigate two research questions in rodent models. First, what
is the role of the hippocampus in memory and specifically what is the underlying
neural code that contributes to spatial memory and navigational decision-making.
Second, how is social cognition represented in the medial prefrontal cortex at the
level of individual neurons. To start, the thesis begins by investigating memory and
social cognition in the context of healthy and diseased states that use non-invasive
methods (i.e. fMRI and animal behavioural studies). The main body of the thesis
then shifts to developing our fundamental understanding of the neural mechanisms
underpinning these cognitive processes by applying computational techniques to ana lyse stable large-scale neural recordings. To achieve this, tailored calcium imaging
and behaviour preprocessing computational pipelines were developed and optimised
for use in social interaction and spatial navigation experimental analysis. In parallel,
a review was conducted on methods for multivariate/neural population analysis. A
comparison of multiple neural manifold learning (NML) algorithms identified that non linear algorithms such as UMAP are more adaptable across datasets of varying noise
and behavioural complexity. Furthermore, the review visualises how NML can be
applied to disease states in the brain and introduces the secondary analyses that
can be used to enhance or characterise a neural manifold. Lastly, the preprocessing
and analytical pipelines were combined to investigate the neural mechanisms in volved in social cognition and spatial memory. The social cognition study explored
how neural firing in the medial Prefrontal cortex changed as a function of the social
dominance paradigm, the "Tube Test". The univariate analysis identified an ensemble
of behavioural-tuned neurons that fire preferentially during specific behaviours such
as "pushing" or "retreating" for the animal’s own behaviour and/or the competitor’s
behaviour. Furthermore, in dominant animals, the neural population exhibited greater
average firing than that of subordinate animals. Next, to investigate spatial memory,
a spatial recency task was used, where rats learnt to navigate towards one of three
reward locations and then recall the rewarded location of the session. During the
task, over 1000 neurons were recorded from the hippocampal CA1 region for five rats
over multiple sessions. Multivariate analysis revealed that the sequence of neurons encoding an animal’s spatial position leading up to a rewarded location was also active
in the decision period before the animal navigates to the rewarded location. The result
posits that prospective replay of neural sequences in the hippocampal CA1 region
could provide a mechanism by which decision-making is supported
Displacement and the Humanities: Manifestos from the Ancient to the Present
This is the final version. Available on open access from MDPI via the DOI in this recordThis is a reprint of articles from the Special Issue published online in the open access journal Humanities (ISSN 2076-0787) (available at: https://www.mdpi.com/journal/humanities/special_issues/Manifestos Ancient Present)This volume brings together the work of practitioners, communities, artists and other researchers from multiple disciplines. Seeking to provoke a discourse around displacement within and beyond the field of Humanities, it positions historical cases and debates, some reaching into the ancient past, within diverse geo-chronological contexts and current world urgencies. In adopting an innovative dialogic structure, between practitioners on the ground - from architects and urban planners to artists - and academics working across subject areas, the volume is a proposition to: remap priorities for current research agendas; open up disciplines, critically analysing their approaches; address the socio-political responsibilities that we have as scholars and practitioners; and provide an alternative site of discourse for contemporary concerns about displacement. Ultimately, this volume aims to provoke future work and collaborations - hence, manifestos - not only in the historical and literary fields, but wider research concerned with human mobility and the challenges confronting people who are out of place of rights, protection and belonging
Genetically engineered hydrogels based on elastin-like recombinamers for cardiovascular applications
Tissue engineering and regenerative medicine (TERM) is a prominent field of research that aims to repair or replace damaged tissues or organs, by the development of scaffolds with essential features, such as biocompatibility and functionality. Nowadays, recombinant polypeptides arise as promising candidates due to their tunability at the genetic level, affording exquisite control over the final physico-chemical properties and bioactivities. In particular, elastin-like recombinamers (ELRs) are genetically engineered polypeptides based on the repetition of the pentapeptide Val-Pro-Gly-X-Gly, found in the hydrophobic domains of tropoelastin, where X can be any amino acid except L-proline. These, ELRs exhibit a reversible phase transition in aqueous environments and their recombinant nature allows the inclusion of specific epitopes, such as cell adhesion, proteolytic sequences, and biologically active molecules such as growth factors. Interestingly, they can be chemically modified to obtain covalently cross-linked hydrogels through orthogonal and cytocompatible “click chemistry” reactions.
The first chapter of this thesis is dedicated to the spatiotemporal control of angiogenesis, which has been proven essential for the correct integration and long-term stability of the implant. To this end, we designed a three-dimensional (3D) model consisting of a coaxial binary ELR tubular construct that displays proteolytic sequences with fast and slow cleavage kinetics towards the urokinase plasminogen activator protease on its inner and outer part respectively. The ELRs further included the universal cell-adhesion domain (RGD) and a VEGF-mimetic tethered peptide (QK) to induce angiogenesis. In vitro studies evidenced the effect of the QK peptide on endothelial cell extension and anastomosis. The subcutaneous implantation of the 3D models in mice showed a guided cell infiltration and capillary formation in the pre-designed spatiotemporal arrangement of the construct. Furthermore, the ELR hydrogels induced a mild macrophage response that resolved over time, supporting the potential integration of the resorbable scaffold within the host tissue.
The second chapter study the preferential guidance of angiogenesis and neurogenesis in a spatiotemporal manner. In particular, we designed a 3D model ELR scaffold comprising two internal cylinders, with the pro-angiogenic peptide (QK) in one of them, and the neuronal cell adhesive peptide (IKVAV) in the vicinal one, both covalently tethered. In addition, these cylinders contain proteolytic sequences with fast cleavage kinetics towards the urokinase plasminogen activator enzyme and RGD cell adhesive domains. On the other hand, the outer part displays a slow-resorbable or non-protease-sensitive ELR hydrogel. In vitro studies demonstrated the effect of IKVAV epitope on neurite extension. The subcutaneous implantation of the 3D model ELR constructs in mice showed a guided cell infiltration accompanied by preferential angiogenesis or innervation on the respective QK and IKVAV containing cylinders, with a faster integration within the host tissue for the slow-resorbable scaffold.
The third chapter describes the development of a ready-to-use bi-leaflet transcatheter venous valve for the treatment of chronic venous insufficiency (CVI), a leading worldwide vascular disease. For this purpose, we combined (i) ELRs, (ii) a textile mesh reinforcement and (iii) a bioabsorbable magnesium stent. Burst strength analysis demonstrated mechanical properties suitable for vascular pressures, whereas equibiaxial analysis confirmed the anisotropic performance equivalent to the native saphenous vein valves. In vitro studies identified the non-thrombogenic, minimal hemolysis and self-endothelialization properties endowed by the ELR hydrogel. The hydrodynamic testing under pulsatile conditions revealed minimal regurgitation (< 10%) and pressure drop (< 5 mmHg) in accordance with values stated for functional venous valves, and no stagnation points. Furthermore, in vitro simulated transcatheter delivery showed the ability to withstand the implantation procedure.
In summary, the thesis presented herein provide new insights in the design and development of novel ELR-forming hydrogels to be used in tissue engineering and regenerative medicine applications.La ingeniería de tejidos y la medicina regenerativa (TERM) es un campo de investigación cuyo objetivo es reparar o reemplazar tejidos u órganos dañados, mediante el desarrollo de andamios biocompatibiles y funcionalizados. Hoy en día, los polipéptidos recombinantes, permiten un control exquisito sobre las propiedades fisicoquímicas y bioactividades. En particular, los elastin-like recombinamers (ELRs) son polipéptidos modificados genéticamente basados en la repetición del pentapéptido Val-Pro-Gly-X-Gly, que se encuentra en los dominios hidrófobos de la tropoelastina, donde X puede ser cualquier aminoácido excepto L-prolina. Estos ELR exhiben una transición de fase reversible en medios acuosos y su naturaleza recombinante permite la inclusión de epítopos específicos, como la adhesión celular, secuencias proteolíticas y moléculas bioactivas como factores de crecimiento. Curiosamente, pueden modificarse químicamente para obtener hidrogeles entrecruzados covalentemente a través de reacciones de "química de clic" ortogonales y citocompatibles.
El primer capítulo está dedicado al control espaciotemporal de la angiogénesis, la cual es fundamental para la correcta integración y estabilidad del implante. Para ello, diseñamos un modelo tridimensional (3D) que consiste en una construcción binaria coaxial de hidrogeles de ELR, que lleva secuencias proteolíticas con cinética de escisión rápida y lenta sensibles a la proteasa del activador del plasminógeno tipo uroquinasa (uPA) en su parte interna y externa respectivamente, y un péptido mimético de VEGF (QK) anclado para inducir la angiogénesis. Los estudios in vitro evidenciaron el efecto del péptido QK sobre la extensión y anastomosis de las células endoteliales. La implantación subcutánea del modelo 3D en ratones mostró una infiltración celular guiada. Además, los hidrogeles ELR indujeron una respuesta leve de macrófagos que se resolvió con el tiempo, lo que respalda la integración de estos andamios reabsorbibles.
El segundo capítulo estudia la orientación preferencial de la angiogénesis y la neurogénesis de manera espaciotemporal. En particular, diseñamos un modelo 3D de ELR que comprende dos cilindros internos, con el péptido proangiogénico (QK) en uno de ellos, y el péptido adhesivo de células neuronales (IKVAV) en el vecinal, ambos unidos covalentemente. Además, estos cilindros contienen secuencias proteolíticas con una cinética de escisión rápida frente a la enzima uPa y los dominios adhesivos RGD. Por otro lado, la parte exterior presenta un hidrogel ELR de reabsorción lenta o no sensible a las proteasas. Los estudios in vitro demostraron el efecto del epítopo IKVAV sobre la extensión de axones. La implantación subcutánea de las construcciones en ratones mostró una infiltración celular guiada acompañada de angiogénesis o inervación preferencial en los respectivos, con una integración más rápida dentro del tejido hospedador para el andamio con reabsorción lenta.
El tercer capítulo describe el desarrollo de una válvula venosa transcatéter biválvula lista para usar para el tratamiento de la insuficiencia venosa crónica (IVC), una enfermedad vascular predominante en todo el mundo. Para ello, combinamos (i) ELR, (ii) un refuerzo de malla textil y (iii) un stent de magnesio bioabsorbible. El análisis de resistencia a rotura demostró propiedades mecánicas adecuadas para las presiones vasculares, mientras que el análisis equibiaxial confirmó el rendimiento anisotrópico equivalente a las válvulas de vena safena nativa. Los estudios in vitro identificaron las propiedades no trombogénicas, de hemólisis mínima y de autoendotelización que otorga el hidrogel ELR. Las pruebas hidrodinámicas en condiciones pulsátiles revelaron regurgitación mínima (< 10 %) y caída de presión (< 5 mmHg) de acuerdo con los valores establecidos para válvulas venosas funcionales y sin puntos de estancamiento. Además, el suministro transcatéter simulado in vitro mostró la capacidad de soportar el procedimiento de implantación.
En resumen, la tesis presentada proporciona nuevos conocimientos en el diseño y desarrollo de nuevos hidrogeles ELR para su uso en ingeniería de tejidos y medicina regenerativa.Escuela de DoctoradoDoctorado en Físic
Recommended from our members
Policy options for food system transformation in Africa and the role of science, technology and innovation
As recognized by the Science, Technology and Innovation Strategy for Africa – 2024 (STISA-2024), science, technology and innovation (STI) offer many opportunities for addressing the main constraints to embracing transformation in Africa, while important lessons can be learned from successful interventions, including policy and institutional innovations, from those African countries that have already made significant progress towards food system transformation. This chapter identifies opportunities for African countries and the region to take proactive steps to harness the potential of the food and agriculture sector so as to ensure future food and nutrition security by applying STI solutions and by drawing on transformational policy and institutional innovations across the continent. Potential game-changing solutions and innovations for food system transformation serving people and ecology apply to (a) raising production efficiency and restoring and sustainably managing degraded resources; (b) finding innovation in the storage, processing and packaging of foods; (c) improving human nutrition and health; (d) addressing equity and vulnerability at the community and ecosystem levels; and (e) establishing preparedness and accountability systems. To be effective in these areas will require institutional coordination; clear, food safety and health-conscious regulatory environments; greater and timely access to information; and transparent monitoring and accountability systems
A new contextual and comprehensive application of the UTAUT2 model post - COVID-19 pandemic in higher education
This study examines tertiary students' behavioural intention
to resume face-to-face mode of study, post-COVID-19. A modified UTAUT2 model of nine factors and a moderator
is used to investigate the impact of these factors on developing country's tertiary students' behavioural intention. The influence of these students' behavioural intention on se behaviour is also examined. Using a quantitative research approach, data were gathered from 419 students at a regional university using convenience sampling technique. Data were analysed to test and validate the proposed model using covariance-based structural equation modelling. The study's findings reveal significant positive relationships between social influence, hedonic motivation, facilitating conditions, commitment, behavioural intention and use behaviour. However, it did not find performance expectancy, effort expectancy, price value, trust and comfortability, reporting any significant positive influence on behavioural intentions. Additionally, the moderating analysis shows that COVID-19 fear did not moderate or strengthen the association between behavioural intentions and use behaviour, given the insignificant interaction effect of COVID-19 fear. This study provides novelty in the contextual application of the modified UTAUT2 model, post-COVID-19. The addition of three additional constructs (trust, commitment and comfortability) has further improved the predictive power of the model. Lastly, the new construct that emerged in recent literature, COVID-19 fear, has been tested for the first time within the UTAUT2 model as a moderator between behavioural intentions and use behaviour. In terms of practical implications, this study first adds to the current literature on higher education, after the COVID-19 situation,being useful to education scholars. Second, it also offers specific suggestions to educational institutions and policymakers who fund universities. Such suggestions include: involving students' families in orientation and open day events, featuring family and friend support in promotional activities, upgrading facilities, including more teaching and learning sessions with team-based assessments, encouraging comfortable interactions and continuously practising COVID-19 safety protocols
- …