Deacetylation of p53 induces autophagy by suppressing Bmf expression

Interferon γ (IFN-γ)–induced cell death is mediated by the BH3-only domain protein, Bik, in a p53-independent manner. However, the effect of IFN-γ on p53 and how this affects autophagy have not been reported. The present study demonstrates that IFN-γ down-regulated expression of the BH3 domain-only protein, Bmf, in human and mouse airway epithelial cells in a p53-dependent manner. p53 also suppressed Bmf expression in response to other cell death–stimulating agents, including ultraviolet radiation and histone deacetylase inhibitors. IFN-γ did not affect Bmf messenger RNA half-life but increased nuclear p53 levels and the interaction of p53 with the Bmf promoter. IFN-γ–induced interaction of HDAC1 and p53 resulted in the deacetylation of p53 and suppression of Bmf expression independent of p53’s proline-rich domain. Suppression of Bmf facilitated IFN-γ–induced autophagy by reducing the interaction of Beclin-1 and Bcl-2. Furthermore, autophagy was prominent in cultured bmf−/− but not in bmf+/+ cells. Collectively, these observations show that deacetylation of p53 suppresses Bmf expression and facilitates autophagy

Mastering the Hard Stuff: The History of College Concrete-Canoe Races and the Growth of Engineering Competition Culture

This article details the history of college engineering competitions, originating with student concrete-canoe racing in the 1970s, through today’s multi-million-dollar international multiplicity of challenges. Despite initial differences between engineering educators and industry supporters over the ultimate purpose of undergraduate competitions, these events thrived because they evolved to suit many needs of students, professors, schools, corporations, professional associations, and the engineering profession itself. The twenty-first-century proliferation of university-level competitions in turn encouraged a trickling-down of technical contests to elementary-age children and high schools, fostering the institutionalization of what might be called a competition culture in engineering

Bevacizumab for the Treatment of Recurrent Glioblastoma

Despite advances in upfront therapy, the prognosis in the great majority of patients with glioblastoma (GBM) is poor as almost all recur and result in disease-related death. Glioblastoma are highly vascularized cancers with elevated expression levels of vascular endothelial growth factor (VEGF), the dominant mediator of angiogenesis. A compelling biologic rationale, a need for improved therapy, and positive results from studies of bevacizumab in other cancers led to the evaluation of bevacizumab in the treatment of recurrent GBM. Bevacizumab, a humanized monoclonal antibody that targets VEGF, has been shown to improve patient outcomes in combination with chemotherapy (most commonly irinotecan) in recurrent GBM, and on the basis of positive results in two prospective phase 2 studies, bevacizumab was granted accelerated approval by the US Food and Drug Administration (FDA) as a single agent in recurrent GBM. Bevacizumab therapy is associated with manageable, class-specific toxicity as severe treatment-related adverse events are observed in only a minority of patients. With the goal of addressing questions and controversies regarding the optimal use of bevacizumab, the objective of this review is to provide a summary of the clinical efficacy and safety data of bevacizumab in patients with recurrent GBM, the practical issues surrounding the administration of bevacizumab, and ongoing investigations of bevacizumab in managing GBM

Nurture, nature and some very dubious social skills: An interpretative phenomenological analysis of talent identification practices in elite English youth soccer

This paper reports qualitative findings regarding the concepts and practices utilised in talent identification (TI) among professional coaches working in English youth soccer. Using interpretative phenomenological analysis, detailed interviews with seven such coaches are explored, with a view to elucidating the links between understanding, practice, experience and professional context. Findings reveal three superordinate themes, relating to (1) a primarily ‘nurtured’ and trainable understanding of the broad concept of talent itself, (2) an ostensibly contradictory model of semi-static player psychology, and (3) a highly selective mechanism for separating evidence for ‘mental strength’ and ‘social skills’. It is contended that these findings underscore a case for more thorough interrogation of the real worlds inhabited by coaches, such that ideas about ‘good practice’ in TI might be more effectively reconciled with grounded knowledge of the practical everyday necessities of being a coach

History of spinal neurosurgery and spine societies

Historically, spine and spinal cord surgery have been an integral part of neurosurgery. It was always a part of the neurosurgery education and practically a significant part of neurosurgeons’ daily work. However, spine societies have mostly been pioneered by orthopedic spine surgeons. It’s only in the last 4 decades that neurosurgeons are also forming spine societies. The term “Neurospine” becomes more popular and used by many authors, institutions during the last decades, although it is not widely used in North America. There are specific reasons for its popularity: (1) It is like a combination of neurosurgery and spine surgery. Neurosurgeons widely prefer to use it. (2) It has a sense inside to remind patients that the spine is with neurological structures. “Neurospine Surgery” is also used in the sense of a combination of “neuroscience” and “spine”. There are at least 2 journals with this theme, i.e., “Neurospine” and “Journal of Neurosurgery Spine.” [1] In this paper, a brief history of spine surgery and spine-related societies is discussed. We aimed to create a global summary of neuro spine with spinal neurosurgeons’ perspectives from other parts of the world and comment on the world's current condition

DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks

Maintaining chromatin integrity at the repetitive non-coding DNA sequences underlying centromeres is crucial to prevent replicative stress, DNA breaks and genomic instability. The concerted action of transcriptional repressors, chromatin remodelling complexes and epigenetic factors controls transcription and chromatin structure in these regions. The histone chaperone complex ATRX/DAXX is involved in the establishment and maintenance of centromeric chromatin through the deposition of the histone variant H3.3. ATRX and DAXX have also evolved mutually-independent functions in transcription and chromatin dynamics. Here, using paediatric glioma and pancreatic neuroendocrine tumor cell lines, we identify a novel ATRX-independent function for DAXX in promoting genome stability by preventing transcription-associated R-loop accumulation and DNA double-strand break formation at centromeres. This function of DAXX required its interaction with histone H3.3 but was independent of H3.3 deposition and did not reflect a role in the repression of centromeric transcription. DAXX depletion mobilized BRCA1 at centromeres, in line with BRCA1 role in counteracting centromeric R-loop accumulation. Our results provide novel insights into the mechanisms protecting the human genome from chromosomal instability, as well as potential perspectives in the treatment of cancers with DAXX alterations

On the need for rigorous welfare and methodological reporting for the live capture of large carnivores: A response to de Araujo et al. (2021)

1.De Araujo et al. (Methods in Ecology and Evolution, 2021, https://doi.org/10.1111/2041-210X.13516) described the development and application of a wire foot snare trap for the capture of jaguars Panthera onca and cougars Puma concolor. Snares are a commonly used and effective means of studying large carnivores. However, the article presented insufficient information to replicate the work and inadequate consideration and description of animal welfare considerations, thereby risking the perpetuation of poor standards of reporting. 2.Appropriate animal welfare assessments are essential in studies that collect data from animals, especially those that use invasive techniques, and are key in assisting researchers to choose the most appropriate capture method. It is critical that authors detail all possible associated harms and benefits to support thorough review, including equipment composition, intervention processes, general body assessments, injuries (i.e. cause, type, severity) and post-release behaviour. We offer a detailed discussion of these shortcomings. 3.We also discuss broader but highly relevant issues, including the capture of non-target animals and the omission of key methodological details. The level of detail provided by authors should allow the method to be properly assessed and replicated, including those that improve trap selectivity and minimize or eliminate the capture of non-target animals. 4.Finally, we discuss the central role that journals must play in ensuring that published research conforms to ethical, animal welfare and reporting standards. Scientific studies are subject to ever-increasing scrutiny by peers and the public, making it more important than ever that standards are upheld and reviewed. 5. We conclude that the proposal of a new or refined method must be supported by substantial contextual discussion, a robust rationale and analyses and comprehensive documentation

Applications of electrified dust and dust devil electrodynamics to Martian atmospheric electricity

Atmospheric transport and suspension of dust frequently brings electrification, which may be substantial. Electric fields of 10 kVm-1 to 100 kVm-1 have been observed at the surface beneath suspended dust in the terrestrial atmosphere, and some electrification has been observed to persist in dust at levels to 5 km, as well as in volcanic plumes. The interaction between individual particles which causes the electrification is incompletely understood, and multiple processes are thought to be acting. A variation in particle charge with particle size, and the effect of gravitational separation explains to, some extent, the charge structures observed in terrestrial dust storms. More extensive flow-based modelling demonstrates that bulk electric fields in excess of 10 kV m-1 can be obtained rapidly (in less than 10 s) from rotating dust systems (dust devils) and that terrestrial breakdown fields can be obtained. Modelled profiles of electrical conductivity in the Martian atmosphere suggest the possibility of dust electrification, and dust devils have been suggested as a mechanism of charge separation able to maintain current flow between one region of the atmosphere and another, through a global circuit. Fundamental new understanding of Martian atmospheric electricity will result from the ExoMars mission, which carries the DREAMS (Dust characterization, Risk Assessment, and Environment Analyser on the Martian Surface)-MicroARES (Atmospheric Radiation and Electricity Sensor) instrumentation to Mars in 2016 for the first in situ measurements

Playing with the Rules of the Game: Social Innovation for Urban Transformation

Innovation is perhaps the buzzword in local economic development policy. Associated narrowly with neoliberal ideas, conventional notions of innovation—like its capitalocentric counterparts, enterprise and entrepreneurialism—may promise higher productivity, global competitiveness and technological progress but do not fundamentally change the ‘rules of the game’. In contrast, an emerging field reimagines social innovation as disruptive change in social relations and institutional configurations. This article explores the conceptual and political differences within this pre‐paradigmatic field, and argues for a more transformative understanding of social innovation. Building on the work of David Graeber, I mobilize the novel constructs of ‘play’ and ‘games’ to advance our understanding of the contradictory process of institutionalizing social innovation for urban transformation. This is illustrated through a case study of Liverpool, where diverse approaches to innovation are employed in attempts to resolve longstanding socio‐economic problems. Dominant market‐ and state‐led economic development policies—likened to a ‘regeneration game’—are contrasted with more experimental, creative, democratic and potentially more effective forms of social innovation, seeking urban change through playing with the rules of the game. I conclude by considering how the play–game dialectic illuminates and reframes the way transformative social innovation might be cultivated by urban policy, the contradictions this entails, and possible ways forward

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe