Agave Negatively Regulates Yap And Taz Transcriptionally And Post Translationally In Osteosarcoma Cell Lines

Osteosarcoma (OS) is the most aggressive type of primary solid tumor that develops in bone. Whilst conventional chemotherapy can improve survival rates, the outcome for patients with metastatic or recurrent OS remains poor, so novel treatment agents and strategies are required. Previously published works indicate that Agave exhibits anticancer properties. In the present study, anticancer effects of Agave leaf extract were investigated in the OS cells, discovering that Agave inhibits cell growth and cell migration, and sensitizes OS cells to cisplatin (CDDP), to overcome chemoresistance. Agave’s mechanisms of action include an initial process in which Agave induces YAP/TAZ oncogenic protein degradation, followed by a secondary event whereby Agave inhibits YAP/TAZ transcription through NF-κB p65:p50 heterodimers deregulation. Winner of the Competition “Prize for PhD Thesis 2020” arranged by Sapienza University Press.

Microtubules are essential cellular constituents of eukaryotes formed by tubulin subunits. This book is a collection of medicinal chemistry research projects that utilizes microtubules as drug targets for human diseases of global health impact. The main chapters (2 – 4) include an in-depth description of different synthetic and biological approaches to characterize the therapeutic potential of novel synthetic molecules for cancer, Alzheimer’s disease, and neglected tropical diseases. This book also includes three short chapters (5 – 7) of additional collaborative projects focused on varied drug discovery topics, including SAR studies of new lead compounds targeting carbonic anhydrase enzymes, FAAH and TRPV1, and novel bioisosteres of the carboxylic acid functional group.

Carbapenems resistant Enterobacteriaceae infections are increasing worldwide representing an emerging public health problem. The application of phylogenetic and phylodynamic analyses to bacterial whole genome sequencing (WGS) data have become essential in epidemiological surveillance of MDR pathogens to discern outbreak from non-outbreak strains in both community and hospital settings. In this study, K. pneumoniae strains circulating within different wards of university hospital were collected and WGS applied. Moreover a microbiological surveillance on duedonoscopes was performed to evaluate their reprocessing. The aim was to infer the origin and the spread of K. pneumoniae nosocomial strains and to clarify the epidemiological transmission as so as the eventual reservoir in the hospital setting supporting the epidemiological surveillance and infections control strategies. Winner of the Competition “Prize for PhD Thesis 2020” arranged by Sapienza University Press.

The LIU program at CERN is of paramount importance at international level. The program foresees a significant upgrade of the LHC injector chain to increase the luminosity of the LHC beam by a factor of ten after 2024, when the HL-LHC era will start. This thesis deals with longitudinal beam dynamics studies for two LHC injectors (PSB and SPS), the main goal being the analysis of beam instabilities in the HL-LHC scenario.

Despite being the leading paradigm in computer vision, deep neural networks are inherently limited by the visual and semantic information contained in their training set. In this thesis, we aim to design deep models operating with previously unseen visual domains and semantic concepts. We first describe different solutions for generalizing to new visual domains, applying variants of normalization layers to multiple challenging settings e.g. where new domain data is not available but arrives online or is described by metadata. In the second part, we incorporate new semantic concepts into pretrained deep models. We propose specific solutions for different problems such as multi-task/incremental learning and open-world recognition. Finally, we merge the two challenges: given images of multiple domains and categories, can we recognize unseen concepts in unseen domains? We propose an approach that is the first, promising step, towards solving this problem. Winner of the Competition “Prize for PhD Thesis 2020” arranged by Sapienza University Press.

This edited volume is the first to propose new readings of Italian and transnational female-authored texts through the lens of Trauma Studies. Illuminating a space that has so far been left in the shadows, Trauma Narratives in Italian and Transnational Women’s Writing provides new insights into how the trope of trauma shapes the narrative, temporal and linguistic dimension of these works. The various contributions delineate a landscape of female-authored Italian and transnational trauma narratives and their complex textual negotiation of suffering and pathos, from the twentieth century to the present day. These zones of trauma engender a new aesthetics and a new reading of history and cultural memory as an articulation of female creativity and resistance against a dominant cultural and social order.

Nonalcoholic fatty liver disease (NAFLD) is known as the hepatic manifestation of the metabolic syndrome, and while most patients develop simple steatosis, up to one-third can develop nonalcoholic steatohepatitis (NASH). NASH is a chronic inflammatory condition of the liver that can further progress to fibrosis and cirrhosis, which may eventually lead to liver failure and death. While we have increased our mechanistic knowledge regarding the pathogenesis of NASH within the last decade, treatment options are still limited and liver biopsies have remained the gold standard for diagnosis. To achieve major clinical breakthroughs for NASH patients, it is not sufficient to use a single animal model, since each model has specific limitations. Furthermore, we should rely more on alternative models such as organ-on-a-chip, which will enable us to explore unknown aspects of disease pathogenesis much faster and serve as clinically relevant surrogates for murine models. Another important direction for the improvement of patient health is to pay more attention to extrahepatic, organ-specific and systemic effects, which are associated with NASH. The articles in this Special Issue include an up-to-date overview of the rapidly developing technologies, novel targets for intervention and insights in the field in NASH. Additionally, these articles describe the major challenges in the field, strategies to overcome them and suggestions for future directions. To improve patient's outcome, clinicians, as well as scientists with biomedical, nutrition, physics and mathematics backgrounds, should join forces. Although challenges remain, the future of the field seems promising as these novel technologies and developments are expected to lead to progress in NASH.

Structural and Functional Analysis of Extracts in Plants collects 1 editorial, 3 reviews, and 26 research articles reporting recent research findings which cover several aspects of plant-derived bioactive compounds, to correlate extraction techniques with the chemical composition of extracts and their bioactivity for identifying molecules that might be used as active substances in a wide variety of areas.This book is a valuable resource for members of the scientific community wishing to further explore plants and the therapeutic applications of their bioactive compounds. It will appeal to scholars, teachers and scientists involved in plant product research, and facilitate the development of innovative new drugs.