Abstract / Das Wichtigste in KürzeDer Artikel greift die allgegenwärtigen Debatten zur „digitalen Transformation“ auf und möchte diese gesellschaftspolitisch einordnen. Ausgehend von den ...Veränderungen in Öffentlichkeit und Politik, Lebens- und Arbeitswelt sollen nicht nur bildungs- und sozialpolitische Herausforderungen markiert, sondern auch Fragen nach dem Wert Sozialer Arbeit in einer digitalen Gesellschaft diskutiert werden.
Digital transformation, a term introduced to talk about the various changes in business and society due to the increased usage of digital technologies, has recently gained much attention both in ...research and in practice. However, an analysis of 41 digital transformation frameworks following a developmental literature review shows that several areas can be expanded upon. We propose a novel framework that deals with the underrepresented areas by consolidating the various concepts found in the literature, explicitly including the role of society, highlighting the evolution over time, and including the drivers of digital transformation that we classified into 23 ‘digital transformation interactions’ across six categories. This novel perspective contributes to our macro-understanding of digital transformation and can be used as a lens for further research to generate fresh insights into unanswered research avenues. Ultimately, this paper can be the first step towards a unified understanding of digital transformation.
Sirtuin proteins regulate diverse cellular pathways that influence genomic stability, metabolism and ageing. SIRT7 is a mammalian sirtuin whose biochemical activity, molecular targets and ...physiological functions have been unclear. Here we show that SIRT7 is an NAD(+)-dependent H3K18Ac (acetylated lysine 18 of histone H3) deacetylase that stabilizes the transformed state of cancer cells. Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression. The spectrum of SIRT7 target genes is defined in part by its interaction with the cancer-associated E26 transformed specific (ETS) transcription factor ELK4, and comprises numerous genes with links to tumour suppression. Notably, selective hypoacetylation of H3K18Ac has been linked to oncogenic transformation, and in patients is associated with aggressive tumour phenotypes and poor prognosis. We find that deacetylation of H3K18Ac by SIRT7 is necessary for maintaining essential features of human cancer cells, including anchorage-independent growth and escape from contact inhibition. Moreover, SIRT7 is necessary for a global hypoacetylation of H3K18Ac associated with cellular transformation by the viral oncoprotein E1A. Finally, SIRT7 depletion markedly reduces the tumorigenicity of human cancer cell xenografts in mice. Together, our work establishes SIRT7 as a highly selective H3K18Ac deacetylase and demonstrates a pivotal role for SIRT7 in chromatin regulation, cellular transformation programs and tumour formation in vivo.
Hexavalent chromium Cr(VI) is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. ...Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promoter activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis.
•Luteolin inhibited Cr(VI)-induced oxidative stress.•Luteolin inhibited chronic Cr(VI)-induced malignant transformation.•Luteolin inhibited chronic Cr(VI)-induced inflammation.•Luteolin inhibited chronic Cr(VI)-induced angiogenesis.
A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an ...initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development
. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM
), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM
levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1β. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM
air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden.
A global medical crisis is unfolding as antibiotics lose effectiveness against a growing number of bacterial pathogens. Horizontal gene transfer (HGT) contributes significantly to the rapid spread of ...resistance, yet the transmission dynamics of genes that confer antibiotic resistance are poorly understood. Multiple mechanisms of HGT liberate genes from normal vertical inheritance. Conjugation by plasmids, transduction by bacteriophages, and natural transformation by extracellular DNA each allow genetic material to jump between strains and species. Thus, HGT adds an important dimension to infectious disease whereby an antibiotic resistance gene (ARG) can be the agent of an outbreak by transferring resistance to multiple unrelated pathogens. Here, we review the small number of cases where HGT has been detected in clinical environments. We discuss differences and synergies between the spread of plasmid-borne and chromosomal ARGs, with a special consideration of the difficulties of detecting transduction and transformation by routine genetic diagnostics. We highlight how 11 of the top 12 priority antibiotic-resistant pathogens are known or predicted to be naturally transformable, raising the possibility that this mechanism of HGT makes significant contributions to the spread of ARGs. HGT drives the evolution of untreatable “superbugs” by concentrating ARGs together in the same cell, thus HGT must be included in strategies to prevent the emergence of resistant organisms in hospitals and other clinical settings.
Quantitative traits analyzed in Genome‐Wide Association Studies (GWAS) are often nonnormally distributed. For such traits, association tests based on standard linear regression are subject to reduced ...power and inflated type I error in finite samples. Applying the rank‐based inverse normal transformation (INT) to nonnormally distributed traits has become common practice in GWAS. However, the different variations on INT‐based association testing have not been formally defined, and guidance is lacking on when to use which approach. In this paper, we formally define and systematically compare the direct (D‐INT) and indirect (I‐INT) INT‐based association tests. We discuss their assumptions, underlying generative models, and connections. We demonstrate that the relative powers of D‐INT and I‐INT depend on the underlying data generating process. Since neither approach is uniformly most powerful, we combine them into an adaptive omnibus test (O‐INT). O‐INT is robust to model misspecification, protects the type I error, and is well powered against a wide range of nonnormally distributed traits. Extensive simulations were conducted to examine the finite sample operating characteristics of these tests. Our results demonstrate that, for nonnormally distributed traits, INT‐based tests outperform the standard untransformed association test, both in terms of power and type I error rate control. We apply the proposed methods to GWAS of spirometry traits in the UK Biobank. O‐INT has been implemented in the R package RNOmni, which is available on CRAN.
Cancer metabolism: looking forward Martínez-Reyes, Inmaculada; Chandel, Navdeep S
Nature reviews. Cancer,
10/2021, Volume:
21, Issue:
10
Journal Article
Peer reviewed
Tumour initiation and progression requires the metabolic reprogramming of cancer cells. Cancer cells autonomously alter their flux through various metabolic pathways in order to meet the increased ...bioenergetic and biosynthetic demand as well as mitigate oxidative stress required for cancer cell proliferation and survival. Cancer driver mutations coupled with environmental nutrient availability control flux through these metabolic pathways. Metabolites, when aberrantly accumulated, can also promote tumorigenesis. The development and application of new technologies over the last few decades has not only revealed the heterogeneity and plasticity of tumours but also allowed us to uncover new metabolic pathways involved in supporting tumour growth. The tumour microenvironment (TME), which can be depleted of certain nutrients, forces cancer cells to adapt by inducing nutrient scavenging mechanisms to sustain cancer cell proliferation. There is growing appreciation that the metabolism of cell types other than cancer cells within the TME, including endothelial cells, fibroblasts and immune cells, can modulate tumour progression. Because metastases are a major cause of death of patients with cancer, efforts are underway to understand how metabolism is harnessed by metastatic cells. Additionally, there is a new interest in exploiting cancer genetic analysis for patient stratification and/or dietary interventions in combination with therapies that target metabolism. In this Perspective, we highlight these main themes that are currently under investigation in the context of in vivo tumour metabolism, specifically emphasizing questions that remain unanswered.
Filamentous fungi have been of great interest because of their excellent ability as cell factories to manufacture useful products for human beings. The development of genetic transformation ...techniques is a precondition that enables scientists to target and modify genes efficiently and may reveal the function of target genes. The method to deliver foreign nucleic acid into cells is the sticking point for fungal genome modification. Up to date, there are some general methods of genetic transformation for fungi, including protoplast-mediated transformation, Agrobacterium-mediated transformation, electroporation, biolistic method and shock-wave-mediated transformation. This article reviews basic protocols and principles of these transformation methods, as well as their advantages and disadvantages.
PurposeArtificial intelligence (AI) is one of the latest digital transformation (DT) technological trends the university library can use to provide library users with alternative educational ...services. AI can foster intelligent decisions for retrieving and sharing information for learning and research. However, extant literature confirms a low adoption rate by the university libraries in using AI to provide innovative alternative services, as this is missing in their strategic plan. The research develops (AI-LSICF) an artificial intelligence library services innovative conceptual framework to provide new insight into how AI technology can be used to deliver value-added innovative library services to achieve digital transformation. It will also encourage library and information professionals to adopt AI to complement effective service delivery.Design/methodology/approachThis study adopts a qualitative content analysis to investigate extant literature on how AI adoption fosters innovative services in various organisations. The study also used content analysis to generate possible solutions to aid AI service innovation and delivery in university libraries.FindingsThis study uses its findings to develop an Artificial Intelligence Library Services Innovative Conceptual Framework (AI-LSICF) by integrating AI applications and functions into the digital transformation framework elements and discussed using a service innovation framework.Research limitations/implicationsIn research, AI-LSICF helps increase an understanding of AI by presenting new insights into how the university library can leverage technology to actualise innovation in service provision to foster DT. This trail will be valuable to scholars and academics interested in addressing the application pathways of AI library service innovation, which is still under-explored in digital transformation.Practical implicationsIn practice, AI-LSICF could reform the information industry from its traditional brands into a more applied and resolutely customer-driven organisation. This reformation will awaken awareness of how librarians and information professionals can leverage technology to catch up with digital transformation in this age of the fourth industrial revolution.Social implicationsThe enlightenment of AI-LSICF will motivate library professionals to take advantage of AI's potential to enhance their current business model and achieve a unique competitive advantage within their community.Originality/valueAI-LSICF development serves as a revelation, motivating university libraries and information professionals to consider AI in their strategic plan to enable technology to support university education. This act will enable alternative service delivery in the face of unforeseen circumstances like technological disruption and the present global COVID-19 pandemic that requires non-physical interaction.
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