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Sesquiterpene lactones (SLs) such as parthenolide (PTL) and dehydroleucodine (DhL) selectively kill cancer cells without exerting normal tissue toxicity, potentially due to presence of α-methylene-γ-lactone (αMγL) fragment. We hypothesize that the addition of an azido group to the αMγL fragment of PTL or DhL further augments their anticancer properties as well as radiation sensitivity of cancer cells. Azido-SLs containing the azido group at the C14 methyl position of PTL (i.e., azido-melampomagnolide B, AzMMB) while preserving the mechanistically crucial exomethylene unit of αMγL fragment were also prepared. Sham-irradiated (i.e., unirradiated control) or irradiated human breast cancer cells (MCF7) were treated with different concentrations of azido-PTL (AzPTL) or azido-DhL (AzDhL) along with parental SLs. Proliferation rate of MCF7 cells were measured by MTT-assay, and their colony forming ability was determined by colony formation assay. Both AzPTL and AzDhL significantly suppress proliferation rate and colony forming ability of MCF-7 cells. AzPTL suppressed colony forming ability, not cellular proliferation, following irradiation to a greater extent than PTL at lower concentrations (5 and 10 μM). Electron spin resonance (ESR) studies were performed employing gamma-irradiated homogeneous supercooled aqueous solutions to investigate radical formation through addition of radiation-mediated prehydrated electrons to the azide group of AzPTL and AzDhL and to follow subsequent reactions of these radicals. In AzPTL, formation of a tertiary carbon-centered radical plausibly via a metastable aminyl radical was observed, whereas AzDhL produced both π-aminyl and α-azidoalkyl radicals. These radicals may contribute to the antitumor activities of AzPTL and AzDhL.

The disability, mortality and costs due to ionizing radiation (IR)-induced osteoporotic bone fractures are substantial and no effective therapy exists. Ionizing radiation increases cellular oxidative damage, causing an imbalance in bone turnover that is primarily driven via heightened activity of the bone-resorbing osteoclast. We demonstrate that rats exposed to sublethal levels of IR develop fragile, osteoporotic bone. At reactive surface sites, cerium ions have the ability to easily undergo redox cycling: drastically adjusting their electronic configurations and versatile catalytic activities. These properties make cerium oxide nanomaterials fascinating. We show that an engineered artificial nanozyme composed of cerium oxide, and designed to possess a higher fraction of trivalent (Ce3+) surface sites, mitigates the IR-induced loss in bone area, bone architecture, and strength. These investigations also demonstrate that our nanozyme furnishes several mechanistic avenues of protection and selectively targets highly damaging reactive oxygen species, protecting the rats against IR-induced DNA damage, cellular senescence, and elevated osteoclastic activity in vitro and in vivo. Further, we reveal that our nanozyme is a previously unreported key regulator of osteoclast formation derived from macrophages while also directly targeting bone progenitor cells, favoring new bone formation despite its exposure to harmful levels of IR in vitro. These findings open a new approach for the specific prevention of IR-induced bone loss using synthesis-mediated designer multifunctional nanomaterials.

Abstract Science advice for governments attracted great scrutiny during the COVID-19 pandemic, with the public spotlight on institutions and individual experts—putting science advice on the ‘Grand Stage’. A review of the academic literature identified transparency, a plurality of expertise, the science and policy ‘boundary’, and consensus whilst addressing uncertainty as key themes. The Scientific Advisory Group for Emergencies (SAGE) has been the primary provider of coordinated scientific and technical advice to the UK Government during emergencies since 2009. Using the first 89 of SAGE’s meeting minutes (study period: 22 January 2020–13 May 2021), the ‘metadata’ and linguistic choices are analysed to identify how SAGE’s role and protocols are communicated. This includes understanding which experts were regularly taking part in discussions, the role of scientific experts in the science advisory system and their influence on policy choices, and the degree of consensus and uncertainty within this group of experts—all of which relate to the degree of transparency with the public. In addition, a temporal analysis examines how these practices, such as linguistically marking uncertainty, developed over the period studied. Linguistic markers indexing certainty and uncertainty increased, demonstrating a commitment to precise and accurate communication of the science, including ambiguities and the unknown. However, self-references to SAGE decreased over the period studied. The study highlights how linguistic analysis can be a useful approach for developing an understanding of science communication practices and scientific ambiguity. By considering how SAGE presents to those outside the process, the research calls attention to what remains ‘behind the scenes’ and consequently limits the public’s understanding of SAGE’s role in the COVID-19 response.

Abstract Ecologists—especially those new to the field—are tasked with finding relevant literature matching their research interests and deciding upon a suitable venue for the publication of their work. To provide a roadmap for early career researchers to identify journals aligned with their interests, we analyzed major research themes found across the top 30 ecology journals and three high‐impact multi‐disciplinary journals (Nature, PNAS, and Science), utilizing an automated content analysis (ACA) of 84,841 article abstracts, titles, and author keywords published over the last four decades. Journals clustered into 10 distinct groups based on 46 research themes identified by ACA. We examined the frequency of ecological themes in each of these journal groups to identify the journals most associated with each theme. We found three themes (anthropogenic impacts, disease, and traits) that occurred at a high frequency in the high‐impact multi‐disciplinary journal group containing Nature, PNAS, and Science. Themes that increased in frequency over the last four decades, such as climate change, traits, anthropogenic, and cellular biology, were found more often in journals with higher impact factors, indicating that emerging research themes in ecology will likely become of interest to a broader readership over time. Our study provides a thematic review as a potential roadmap for junior ecologists to browse and publish journal articles.

Upon starvation or overcrowding, Caenorhabditis elegans interrupts its reproductive cycle and forms a specialised larva called dauer (enduring). This process is regulated by TGF-beta and insulin-signalling pathways and is connected with the control of life span through the insulin pathway components DAF-2 and DAF-16. We found that replacing cholesterol with its methylated metabolite lophenol induced worms to form dauer larvae in the presence of food and low population density. Our data indicate that methylated sterols do not actively induce the dauer formation but rather that the reproductive growth requires a cholesterol-derived hormone that cannot be produced from methylated sterols. Using the effect of lophenol on growth, we have partially purified activity, named gamravali, which promotes the reproduction. In addition, the effect of lophenol allowed us to determine the role of sterols during dauer larva formation and longevity. In the absence of gamravali, the nuclear hormone receptor DAF-12 is activated and thereby initiates the dauer formation program. Active DAF-12 triggers in neurons the nuclear import of DAF-16, a forkhead domain transcription factor that contributes to dauer differentiation. This hormonal control of DAF-16 activation is, however, independent of insulin signalling and has no influence on life span.

ABSTRACT Influenza epidemics cause numerous deaths and millions of hospitalizations each year. Because of the alarming emergence of resistance to anti-influenza drugs, there is a need to identify new naturally [...]