This paper extends research on how the background of independent directors may affect the way in which their companies disclose information about corporate social responsibility (CSR). Using a sample ...of 83 Spanish‐listed firms over the period 2009–2014, the findings of a random effects probit model suggest that, in addition to board independence, having independent directors with political backgrounds and diverse education has a positive impact on their firm's probability of issuing a CSR report following the standards of the Global Reporting Initiative.
By studying female directors and their typology, this paper contributes to the empirical evidence relating to board gender diversity and the disclosure of corporate social responsibility (CSR) ...information. An ordered random effect probit model was applied to a panel of Spanish non‐financial and non‐insurance listed firms over the 2009–2013 period. The analyses revealed that a higher percentage of women in boardrooms and in groups of outside and independent directors imply better CSR disclosure. These results hold for corporations with a critical mass of three women on the board and among outside directors.
What is the fate of the biofilm matrix? Muthami, Joy M.; Fernández‐García, Laura; Tomás, María ...
Environmental microbiology,
October 2022, 2022-10-00, 20221001, Letnik:
24, Številka:
10
Journal Article
The chimeric EWSR1::FLI1 transcription factor is the main oncogenic event in Ewing sarcoma. Recently, it has been proposed that EWSR1::FLI1 levels can fluctuate in Ewing sarcoma cells, giving rise to ...two cell populations. EWSR1::FLI1
cells present a migratory and invasive phenotype, while EWSR1::FLI1
cells are more proliferative. In this work, we described how the CD44 standard isoform (CD44s), a transmembrane protein involved in cell adhesion and migration, is overexpressed in the EWSR1::FLI1
phenotype. The functional characterization of CD44s (proliferation, clonogenicity, migration, and invasion ability) was performed in three doxycycline-inducible Ewing sarcoma cell models (A673, MHH-ES1, and CADO-ES1). As a result, CD44s expression reduced cell proliferation in all the cell lines tested without affecting clonogenicity. Additionally, CD44s increased cell migration in A673 and MHH-ES1, without effects in CADO-ES1. As hyaluronan is the main ligand of CD44s, its effect on migration ability was also assessed, showing that high molecular weight hyaluronic acid (HMW-HA) blocked cell migration while low molecular weight hyaluronic acid (LMW-HA) increased it. Invasion ability was correlated with CD44 expression in A673 and MHH-ES1 cell lines. CD44s, upregulated upon EWSR1::FLI1 knockdown, regulates cell migration and invasion in Ewing sarcoma cells.
Quorum sensing (QS) is a communication mechanism between bacteria that allows specific processes to be controlled, such as biofilm formation, virulence factor expression, production of secondary ...metabolites and stress adaptation mechanisms such as bacterial competition systems including secretion systems (SS). These SS have an important role in bacterial communication. SS are ubiquitous; they are present in both Gram-negative and Gram-positive bacteria and in
sp. To date, 8 types of SS have been described (T1SS, T2SS, T3SS, T4SS, T5SS, T6SS, T7SS, and T9SS). They have global functions such as the transport of proteases, lipases, adhesins, heme-binding proteins, and amidases, and specific functions such as the synthesis of proteins in host cells, adaptation to the environment, the secretion of effectors to establish an infectious niche, transfer, absorption and release of DNA, translocation of effector proteins or DNA and autotransporter secretion. All of these functions can contribute to virulence and pathogenesis. In this review, we describe the known types of SS and discuss the ones that have been shown to be regulated by QS. Due to the large amount of information about this topic in some pathogens, we focus mainly on
and
spp.
Objectives
To synthesise the experience of nursing students in their final years regarding high‐fidelity simulation in acute and critical care.
Background
For the complex and changing healthcare ...environment, new tools are required to help health students, educational staff and managers to design and present rewarding educational simulations. Due to the complexity and limited learning opportunities in real settings, high‐fidelity simulation enables students to acquire skills for the provision of acute and critical care in a controlled environment that closely imitates reality; however, the literature on students’ learning experiences with this education methodology is still limited.
Design
This study followed Noblit and Hare's interpretive meta‐ethnography, which was written and reviewed for reporting clarity against the EQUATOR checklist using the eMERGe.
Data sources
A comprehensive systematic search strategy was carried out in five databases: PubMed, Scopus, CINAHL, Web of Science and PsycINFO.
Review methods
Ten studies met the research objective and inclusion criteria.
Results
The metaphor ‘Cultivating learning in vitro’ and four themes were developed to describe the learning experiences of nursing students regarding high‐fidelity simulation in acute and critical care. The themes were as follows: Learning roots—Ways to learn during high‐fidelity simulation; Learning stimulants—Elements that favour learning; Learning impairments—Elements that hinder learning; and Learning flourishing—Results after high‐fidelity simulation.
Conclusions
Seeing, doing and reflecting constituted the main sources of learning. Students identified the stimulating and debilitating aspects of learning which could help in the design of simulation sessions and promote their incorporation into nursing curricula. Finally, ‘the flowering of the plant’ represents the learning outcomes developed in a controlled and safe environment.
Relevance to clinical practice
The results of this meta‐ethnography provide keys to promote change in teaching planning in relation to acute and critical care.
Ewing sarcoma is an aggressive bone cancer affecting children and young adults. The main molecular hallmark of Ewing sarcoma are chromosomal translocations that produce chimeric oncogenic ...transcription factors, the most frequent of which is the aberrant transcription factor EWSR1–FLI1. Because this is the principal oncogenic driver of Ewing sarcoma, its inactivation should be the best therapeutic strategy to block tumor growth. In this study, we genetically inactivated EWSR1–FLI1 using CRISPR-Cas9 technology in order to cause permanent gene inactivation. We found that gene editing at the exon 9 of FLI1 was able to block cell proliferation drastically and induce senescence massively in the well-studied Ewing sarcoma cell line A673. In comparison with an extensively used cellular model of EWSR1–FLI1 knockdown (A673/TR/shEF), genetic inactivation was more effective, particularly in its capability to block cell proliferation. In summary, genetic inactivation of EWSR1–FLI1 in A673 Ewing sarcoma cells blocks cell proliferation and induces a senescence phenotype that could be exploited therapeutically. Although efficient and specific in vivo CRISPR-Cas9 editing still presents many challenges today, our data suggest that complete inactivation of EWSR1–FLI1 at the cell level should be considered a therapeutic approach to develop in the future.
Pancreatic cancer stem cells (PaCSCs) drive pancreatic cancer tumorigenesis, chemoresistance and metastasis. While eliminating this subpopulation of cells would theoretically result in tumor ...eradication, PaCSCs are extremely plastic and can successfully adapt to targeted therapies. In this study, we demonstrate that PaCSCs increase expression of interferon-stimulated gene 15 (ISG15) and protein ISGylation, which are essential for maintaining their metabolic plasticity. CRISPR-mediated ISG15 genomic editing reduces overall ISGylation, impairing PaCSCs self-renewal and their in vivo tumorigenic capacity. At the molecular level, ISG15 loss results in decreased mitochondrial ISGylation concomitant with increased accumulation of dysfunctional mitochondria, reduced oxidative phosphorylation (OXPHOS) and impaired mitophagy. Importantly, disruption in mitochondrial metabolism affects PaCSC metabolic plasticity, making them susceptible to prolonged inhibition with metformin in vivo. Thus, ISGylation is critical for optimal and efficient OXPHOS by ensuring the recycling of dysfunctional mitochondria, and when absent, a dysregulation in mitophagy occurs that negatively impacts PaCSC stemness.
New therapeutic targets are revolutionizing colorectal cancer clinical management, opening new horizons in metastatic patients’ outcome. Polo Like Kinase1 (PLK1) inhibitors have high potential as ...antitumoral agents, however, the emergence of drug resistance is a major challenge for their use in clinical practice. Overcoming this challenge represents a hot topic in current drug discovery research.
BI2536-resistant colorectal cancer cell lines HT29R, RKOR, SW837R and HCT116R, were generated in vitro and validated by IG50 assays and xenografts models by the T/C ratio. Exons 1 and 2 of PLK1 gene were sequenced by Sanger method. AXL pathway, Epithelial-to-Mesenchymal transition (EMT) and Multidrug Resistance (MDR1) were studied by qPCR and western blot in resistant cells. Simvastatin as a re-sensitizer drug was tested in vitro and the drug combination strategies were validated in vitro and in vivo.
PLK1 gene mutation R136G was found for RKOR. AXL pathway trough TWIST1 transcription factor was identified as one of the mechanisms involved in HT29R, SW837R and HCT116R lines, inducing EMT and upregulation of MDR1. Simvastatin was able to impair the mechanisms activated by adaptive resistance and its combination with BI2536 re-sensitized resistant cells in vitro and in vivo.
Targeting the mevalonate pathway contributes to re-sensitizing BI2536-resistant cells in vitro and in vivo, raising as a new strategy for the clinical management of PLK1 inhibitors.
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