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R-loops have both positive and negative impacts on chromosome functions. To identify toxic R-loops in the human genome, here, we map RNA:DNA hybrids, replication stress markers and DNA double-strand breaks (DSBs) in cells depleted for Topoisomerase I (Top1), an enzyme that relaxes DNA supercoiling and prevents R-loop formation. RNA:DNA hybrids are found at both promoters (TSS) and terminators (TTS) of highly expressed genes. In contrast, the phosphorylation of RPA by ATR is only detected at TTS, which are preferentially replicated in a head-on orientation relative to the direction of transcription. In Top1-depleted cells, DSBs also accumulate at TTS, leading to persistent checkpoint activation, spreading of γ-H2AX on chromatin and global replication fork slowdown. These data indicate that fork pausing at the TTS of highly expressed genes containing R-loops prevents head-on conflicts between replication and transcription and maintains genome integrity in a Top1-dependent manner.

Introduction: Drawing on the Unified Theory of Acceptance and Use of Technology 2 and the Diffusion of Innovation Theory, this article investigates the adoption of telemedicine services from a patient perspective in Germany, Spain, and the United States using a mixed-methods approach. Digital health technologies have the potential to improve access to care and to alleviate the burden on traditional health care systems and are becoming more integrated into everyday medicine. Therefore, understanding the factors that impact patients' intentions to use telemedicine is crucial to ensure successful development. Methods: Based on 1,200 surveys collected in Germany, Spain, and the United States, structural equation modeling (IBM SPSS Amos 24) is employed to test the hypotheses. The article also explores how age and gender moderate the proposed relationships. Results: Seven out of the 10 hypotheses (performance expectancy, hedonic motivation, habit, relative advantage, and perceived security) are found to be positive, direct, and statistically significant. Furthermore, findings suggest stronger effects for telemedicine usage intention for younger female users than their male counterparts. Discussion: With digital health technologies becoming more prevalent, the outcomes of this study can endorse the development of effective strategies to promote the adoption of telemedicine, ultimately improving access to care and contributing to the advancement of and modern health care. [ABSTRACT FROM AUTHOR]

At the core of the globalized Maker movement are the "Maker mindset" and imaginaries of a "new industrial revolution." Both embody elements of the Californian Ideology in an ongoing yet asymmetrical conversation between the U.S. organizational elite and local Makerspaces. This article explores these dynamics on the basis of a media ethnography carried out at four Makerspaces in Berlin and London. First, we will address the extent to which the Maker ideology provides a framing discourse for the establishment of local Makerspaces. We then look at casual references that are made about the Maker ideology. Finally, we reflect on how the Maker ideology is appropriated into the local realm. All this amounts to what we call local ambivalences toward the Maker ideology: The local spaces refer critically to the larger Maker movement, and it is precisely through this critique that parts of the Californian Ideology are embedded. [ABSTRACT FROM AUTHOR]

The Californian Ideology has been a buzzword for criticizing the tech industry in Silicon Valley for almost 30 years. But how exactly is this term to be understood? What is its historical context, and how does the Californian Ideology live on today? This introduction to the thematic issue approaches these questions by first reconstructing the genesis of Barbrook and Cameron's article, "The Californian Ideology," and the original discussion surrounding it. It then takes a closer look at the role of tech movements and pioneer communities: Both were not only an important context for the emergence of Californian Ideology but are also closely linked to its global spread. Finally, based on these clarifications, this introduction provides an overview of the articles in the thematic issue, focusing on their contribution to a discussion of ideological moments and subsequent imaginaries of possible digital futures. [ABSTRACT FROM AUTHOR]