12 research outputs found
Dual-image-based reversible data hiding scheme with integrity verification using exploiting modification direction
Abstract(#br)In this paper, a novel dual-image-based reversible data hiding scheme using exploiting modification direction (EMD) is proposed. This scheme embeds two 5-base secret digits into each pixel pair of the cover image simultaneously according to the EMD matrix to generate two stego-pixel pairs. By shifting these stego-pixel pairs to the appropriate locations in some cases, two meaningful shadows are produced. The secret data can be extracted accurately, and the cover image can be reconstructed completely in the data extraction and the image reconstruction procedure, respectively. Experimental results show that our scheme outperforms the comparative methods in terms of image quality and embedding ratio. Pixel-value differencing (PVD) histogram analysis reveals that our scheme..
Orchestration of the neural stem cell fate by NRF2 and TAZ
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 11-10-2019Neurogenesis is a multiple step process that must be tightly regulated or otherwise results in
pathological events. Therefore, a deep characterization of the molecular mechanisms that control the
biology of neural stem/progenitor cells (NSPCs) will provide a better understanding of the role of
neurogenic niches and new therapeutic strategies for neurodegenerative diseases and brain tumours.
In this thesis we have analyzed the regulation of NSCs fate by the transcription factor Nuclear
factor (erythroid-derived 2)-like 2 (NRF2), which is considered a master regulator of cellular
homeostasis, and the Transcriptional co-activator with PDZ-binding motif (TAZ), a major effector of the
Hippo pathway. NRF2 controls the expression of a wide battery of cytoprotective genes that have a
tremendous impact on physiological responses such as inflammation, senescence or metabolism.
However, its relevance in neurogenesis is just starting to be unveiled. On the other hand, TAZ is a major
effector of the Hippo pathway, which plays a key role in tissue homeostasis and organ size control by
regulating tissue-specific stem cells. However, the implication of TAZ in neurogenesis has not been
analyzed.
In this study, we have identified NRF2 as a regulator of hippocampal NSCs self-renewal and
differentiation. We show that genetic manipulation of NRF2 results in the modulation of NSPCs
differentiation and proliferation capacity. To assess the functional relevance of NRF2 in neurogenesis
under pathological conditions, we analyzed the impact of NRF2 deficiency in neurogenesis of the
subgranular zone (SGZ) of the hippocampus in a mouse model of Alzheimer´s Disease (AD). We found
that NRF2 deficiency results in an accelerated loss of NSCs, loss of synaptic plasticity measured as long
term potentiation (LTP) and impaired the execution of cognitive tasks.
At the molecular level, we have identified NRF2 enhancer sequences, termed Antioxidant
Response Elements (AREs), in the promoter region of the TAZ coding gene. Consequently, we show that
genetic and pharmacological manipulation of NRF2 results in the modulation of TAZ gene expression in
NSPCs. These findings open a new window to understand the molecular mechanisms underlying NRF2
function in stemness.
We have also established a novel role of TAZ as repressor of neuronal differentiation, based on
the transcriptional repression of SOX2 and the basic helix-loop-helix (bHLH) factors ASCL1,
NEUROG2 and NEUROD1. Data mining of The Cancer Genome Atlas showed a negative correlation
between TAZ and the expression of these proneurogenic factors in lower grade gliomas and
glioblastomas. We found that TAZ favours glioblastoma CSCs tumorigenic capacity and that genetic
modulation of TAZ in these cells inversely correlated with proneurogenic genes expression. Due to the
relevance of these proneurogenic factors in the ablation of glioblastoma cancer stem cells (CSCs), this
novel TAZ/proneurogenic factors axis may have important implications in the development of this type
of brain tumours.
The characterization of molecular mechanism governing NSPCs fate provides new insights to
harness these cells for brain repair. Overall, this thesis describes a novel role of NRF2 and TAZ in the
control of neural stem cell fate, suggesting a new strategy to combat brain pathology
LIPIcs, Volume 251, ITCS 2023, Complete Volume
LIPIcs, Volume 251, ITCS 2023, Complete Volum
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The ALS-Linked Gene TDP-43 Regulates Expression through a Novel Mechanism of 3' UTR-Mediated Promoter cis-Regulation
The TAR DNA-binding protein (TDP-43) is a heterogeneous nuclear ribonucleprotein that is involved in multiple stages of RNA processing. Mutations in the TDP-43 gene and mislocalization of TDP-43 protein have been implicated in a growing number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here, we show that TDP-43 negatively regulates innate immune gene expression in response to RNA virus sensing. Perturbation of TDP-43 protein expression leads to an increase in antiviral gene expression in a variety of human and mouse cells. Crosslinked RNA immunoprecipitation (CLIP) experiments revealed that TDP-43 binds to type I interferon (IFN) and interferon stimulated gene (ISGs) transcripts. Using massively parallel 3’ UTR reporter assays coupled with high throughput sequencing (MPRA-seq), we identified polyadenylation signal sequences in the 3' UTRs of innate immune genes to be specifically regulated by TDP-43. Surprisingly, IFN and ISG mRNA decay rates are faster in TDP-43-perturbed cells. Using a metabolic labeling approach to measure nascent transcript generation, we found that perturbation of TDP-43 expression leads to an increase in antiviral gene transcription rates. Additionally, RNA polymerase II (pol II) chromatin immunoprecipitation (ChIP) confirmed that there is greater pol II occupancy on innate immune genes when TDP-43 is depleted. Although TDP-43 perturbation has no effect on an isolated promoter reporter, we found that TDP-43 inhibits promoter activity when the 3' UTR sequence is inserted downstream of the promoter element, suggesting a novel mechanism of 3' UTR-mediated promoter cis-regulation
Fungal Pigments 2021
New edition of the reprint Fungal pigments: Chapters titles: PART 1. Investigation on various chemical classes of fungal pigments: Genomic Analysis and Assessment of Melanin Synthesis in Amorphotheca resinae by Jeong-Joo Oh et al.; Fungal Melanins and Applications in Healthcare, Bioremediation and Industry by Ellie Rose Mattoon et al.; Recent Findings in Azaphilone Pigments by Lúcia P. S. Pimenta et al.; Characterization of a Biofilm Bioreactor Designed for the Single-Step Production of Aerial Conidia and Oosporein by Beauveria bassiana PQ2 by Héctor Raziel Lara-Juache et al.; PART 2. Molecular characterization: Molecular Characterization of Fungal Pigments by Miriam S. Valenzuela-Gloria et al.; PART 3. Biological properties: Seven New Cytotoxic and Antimicrobial Xanthoquinodins from Jugulospora vestita by Lulu Shao et al.; PART 4. Toxicity assessment and safety evaluation of fungal pigments: Safety Evaluation of Fungal Pigments for Food Applications by Rajendran Poorniammal et al.; Preliminary Examination of the Toxicity of Spalting Fungal Pigments: A Comparison between Extraction Methods by Badria H. Almurshidi et al.; PART 5. Use of by-products or waste for industrial production of fungal pigments: Production of Bio-Based Pigments from Food Processing Industry By-Products Using Aspergillus carbonarius by Ezgi Bezirhan Arikan et al.; PART 6. Prospective aspects and brainstorming: Does Structural Color Exist in True Fungi? by Juliet Brodie et al.; Fungal Biomarkers Stability in Mars Regolith Analogues after Simulated Space and Mars-like Conditions by Alessia Cassaro et al
Biofunctional hydrogels based on elastin-like recombinamers as extracellular matrix analogues
Uno de los objetivos principales de esta tesis consiste en la formación de hidrogeles mediante un proceso citocompatible que permita encapsular células dentro de dichos geles en el momento de su formación y que simulen las propiedades de las matrices extracelulares naturales para su utilización en ingeniería de tejidos. Dichos hidrogeles se obtendrán utilizando Polímeros Recombinantes tipo Elastina (ELRs) por presentar unas excelentes propiedades de partida como son su elevada biocompatibilidad o la posibilidad de incorporar diferentes bioactividades entre otras. Tambien Se quiere desarrollar un sistema fractal de formación de nanogeles mediante tecnología click sin cobre, y comprobar la influencia de la temperatura en dicha fractalidad durante el proceso de formación de estos geles. Se pretende evaluar y caracterizar, mediante el estudio de las dimensiones así como de las propiedades microreológicas y eléctricas, las estructuras formadas para tener un mejor conocimiento de su validez como sistemas de dosificación de fármacos. Por otro lado, se investigará la capacidad de estos hidrogeles para ser utilizados como recubrimiento de distintos materiales como poliestireno, vidrio y titanio mediante la tecnología “capa a capa” (layer by layer); siendo el titanio de especial interés debido a su creciente utilización como implante en procesos quirúrgicos. Se pretende obtener un sistema de formación de capas rápido, reproducible y escalable. Además dicho recubrimiento debe ser totalmente citocompatible y que nos permita incluir diferentes agentes terapéuticos que puedan ser de interés en futuras aplicaciones tanto en ingeniería de tejidos como en dosificación de fármacos. Por último, otro objetivo fundamental de la tesis consistió en demostrar la eficacia de los hidrogeles formados por ELRs y obtenidos mediante tecnología click sin cobre, como “scaffolds” en ingeniería de tejidos y más concretamente en el tratamiento de enfermedades cardiovasculares. Las características, tanto mecánicas como biológicas, de estos hidrogeles podrían convertirlos en biomateriales especialmente útiles en el tratamiento de ciertas afecciones del sistema circulatorio.Departamento de Química AnalíticaDoctorado en Arquitectur
RNA, the Epicenter of Genetic Information
The origin story and emergence of molecular biology is muddled. The early triumphs in bacterial genetics and the complexity of animal and plant genomes complicate an intricate history. This book documents the many advances, as well as the prejudices and founder fallacies. It highlights the premature relegation of RNA to simply an intermediate between gene and protein, the underestimation of the amount of information required to program the development of multicellular organisms, and the dawning realization that RNA is the cornerstone of cell biology, development, brain function and probably evolution itself. Key personalities, their hubris as well as prescient predictions are richly illustrated with quotes, archival material, photographs, diagrams and references to bring the people, ideas and discoveries to life, from the conceptual cradles of molecular biology to the current revolution in the understanding of genetic information. Key Features Documents the confused early history of DNA, RNA and proteins - a transformative history of molecular biology like no other. Integrates the influences of biochemistry and genetics on the landscape of molecular biology. Chronicles the important discoveries, preconceptions and misconceptions that retarded or misdirected progress. Highlights major pioneers and contributors to molecular biology, with a focus on RNA and noncoding DNA. Summarizes the mounting evidence for the central roles of non-protein-coding RNA in cell and developmental biology. Provides a thought-provoking retrospective and forward-looking perspective for advanced students and professional researchers