Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7

Accumulating evidence supports the role of an aberrant transcriptome as a driver of metastatic potential. Deadenylation is a general regulatory node for post-transcriptional control by microRNAs and other determinants of RNA stability. Previously, we demonstrated that the CCR4-NOT scaffold component Cnot2 is an inherited metastasis susceptibility gene. In this study, using orthotopic metastasis assays and genetically engineered mouse models, we show that one of the enzymatic subunits of the CCR4-NOT complex, Cnot7, is also a metastasis modifying gene. We demonstrate that higher expression of Cnot7 drives tumor cell autonomous metastatic potential, which requires its deadenylase activity. Furthermore, metastasis promotion by CNOT7 is dependent on interaction with CNOT1 and TOB1. CNOT7 ribonucleoprotein-immunoprecipitation (RIP) and integrated transcriptome wide analyses reveal that CNOT7-regulated transcripts are enriched for a tripartite 3’UTR motif bound by RNA-binding proteins known to complex with CNOT7, TOB1, and CNOT1. Collectively, our data support a model of CNOT7, TOB1, CNOT1, and RNA-binding proteins collectively exerting post-transcriptional control on a metastasis suppressive transcriptional program to drive tumor cell metastasis

Macrocheles species (Acari: Macrochelidae) associated with human corpses in Europe

The biology of macrochelid mites might offer new venues for the interpretation of the environmental conditions surrounding human death and decomposition. Three human corpses, one from Sweden and two from Spain, have been analysed for the occurrence of Macrochelidae species. Macrocheles muscaedomesticae females were associated with a corpse that was found in a popular beach area of southeast Spain. Their arrival coincides with the occurrence of one of their major carrier species, the filth fly Fannia scalaris, the activity of which peaks during mid-summer. M. glaber specimens were collected from a corpse in a shallow grave in a forest in Sweden at the end of summer, concurrent with the arrival of beetles attracted by odours from the corpse. M. perglaber adults were sampled from a corpse found indoors in the rural surroundings of Granada city, Spain. The phoretic behaviour of this species is similar to that of M. glaber, but being more specific to Scarabaeidae and Geotrupidae dung beetles, most of which favour human faeces. M. muscaedomesticae is known from urban and rural areas and poultry farms; M. glaber from outdoors, particularly the countryside; while M. perglaber from outdoor, rural, and remote, potentially mountainous locations. M. muscaedomesticae and M. perglaber are reported for the first time from the Iberian Peninsula. This is the first record of M. perglaber from human remains

Macrocheles species (Acari: Macrochelidae) associated with human corpses in Europe

The biology of macrochelid mites might offer new venues for the interpretation of the environmental conditions surrounding human death and decomposition. Three human corpses, one from Sweden and two from Spain, have been analysed for the occurrence of Macrochelidae species. Macrocheles muscaedomesticae females were associated with a corpse that was found in a popular beach area of southeast Spain. Their arrival coincides with the occurrence of one of their major carrier species, the filth fly Fannia scalaris, the activity of which peaks during mid-summer. M. glaber specimens were collected from a corpse in a shallow grave in a forest in Sweden at the end of summer, concurrent with the arrival of beetles attracted by odours from the corpse. M. perglaber adults were sampled from a corpse found indoors in the rural surroundings of Granada city, Spain. The phoretic behaviour of this species is similar to that of M. glaber, but being more specific to Scarabaeidae and Geotrupidae dung beetles, most of which favour human faeces. M. muscaedomesticae is known from urban and rural areas and poultry farms; M. glaber from outdoors, particularly the countryside; while M. perglaber from outdoor, rural, and remote, potentially mountainous locations. M. muscaedomesticae and M. perglaber are reported for the first time from the Iberian Peninsula. This is the first record of M. perglaber from human remains

Risk-stratified approach to breast cancer screening in canada: Women’s knowledge of the legislative context and concerns about discrimination from genetic and other predictive health data

The success of risk-stratified approaches in improving population-based breast cancer screening programs depends in no small part on women’s buy-in. Fear of genetic discrimination (GD) could be a potential barrier to genetic testing uptake as part of risk assessment. Thus, the objective of this study was twofold. First, to evaluate Canadian women’s knowledge of the legislative context governing GD. Second, to assess their concerns about the possible use of breast cancer risk levels by insurance companies or employers. We use a cross-sectional survey of 4293 (age: 30–69) women, conducted in four Canadian provinces (Alberta, British Colombia, Ontario and Québec). Canadian women’s knowledge of the regulatory framework for GD is relatively limited, with some gaps and misconceptions noted. About a third (34.7%) of the participants had a lot of concerns about the use of their health information by employers or insurers; another third had some concerns (31.9%), while 20% had no concerns. There is a need to further educate and inform the Canadian public about GD and the legal protections that exist to prevent it. Enhanced knowledge could facilitate the implementation and uptake of risk prediction informed by genetic factors, such as the risk-stratified approach to breast cancer screening that includes risk levels

Roadmap on dynamics of molecules and clusters in the gas phase

This roadmap article highlights recent advances, challenges and future prospects in studies of the dynamics of molecules and clusters in the gas phase. It comprises nineteen contributions by scientists with leading expertise in complementary experimental and theoretical techniques to probe the dynamics on timescales spanning twenty order of magnitudes, from attoseconds to minutes and beyond, and for systems ranging in complexity from the smallest (diatomic) molecules to clusters and nanoparticles. Combining some of these techniques opens up new avenues to unravel hitherto unexplored reaction pathways and mechanisms, and to establish their significance in, e.g. radiotherapy and radiation damage on the nanoscale, astrophysics, astrochemistry and atmospheric science

Global, regional, and national prevalence of adult overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021

Background: Overweight and obesity is a global epidemic. Forecasting future trajectories of the epidemic is crucial for providing an evidence base for policy change. In this study, we examine the historical trends of the global, regional, and national prevalence of adult overweight and obesity from 1990 to 2021 and forecast the future trajectories to 2050. Methods: Leveraging established methodology from the Global Burden of Diseases, Injuries, and Risk Factors Study, we estimated the prevalence of overweight and obesity among individuals aged 25 years and older by age and sex for 204 countries and territories from 1990 to 2050. Retrospective and current prevalence trends were derived based on both self-reported and measured anthropometric data extracted from 1350 unique sources, which include survey microdata and reports, as well as published literature. Specific adjustment was applied to correct for self-report bias. Spatiotemporal Gaussian process regression models were used to synthesise data, leveraging both spatial and temporal correlation in epidemiological trends, to optimise the comparability of results across time and geographies. To generate forecast estimates, we used forecasts of the Socio-demographic Index and temporal correlation patterns presented as annualised rate of change to inform future trajectories. We considered a reference scenario assuming the continuation of historical trends. Findings: Rates of overweight and obesity increased at the global and regional levels, and in all nations, between 1990 and 2021. In 2021, an estimated 1·00 billion (95% uncertainty interval [UI] 0·989–1·01) adult males and 1·11 billion (1·10–1·12) adult females had overweight and obesity. China had the largest population of adults with overweight and obesity (402 million [397–407] individuals), followed by India (180 million [167–194]) and the USA (172 million [169–174]). The highest age-standardised prevalence of overweight and obesity was observed in countries in Oceania and north Africa and the Middle East, with many of these countries reporting prevalence of more than 80% in adults. Compared with 1990, the global prevalence of obesity had increased by 155·1% (149·8–160·3) in males and 104·9% (95% UI 100·9–108·8) in females. The most rapid rise in obesity prevalence was observed in the north Africa and the Middle East super-region, where age-standardised prevalence rates in males more than tripled and in females more than doubled. Assuming the continuation of historical trends, by 2050, we forecast that the total number of adults living with overweight and obesity will reach 3·80 billion (95% UI 3·39–4·04), over half of the likely global adult population at that time. While China, India, and the USA will continue to constitute a large proportion of the global population with overweight and obesity, the number in the sub-Saharan Africa super-region is forecasted to increase by 254·8% (234·4–269·5). In Nigeria specifically, the number of adults with overweight and obesity is forecasted to rise to 141 million (121–162) by 2050, making it the country with the fourth-largest population with overweight and obesity. Interpretation: No country to date has successfully curbed the rising rates of adult overweight and obesity. Without immediate and effective intervention, overweight and obesity will continue to increase globally. Particularly in Asia and Africa, driven by growing populations, the number of individuals with overweight and obesity is forecast to rise substantially. These regions will face a considerable increase in obesity-related disease burden. Merely acknowledging obesity as a global health issue would be negligent on the part of global health and public health practitioners; more aggressive and targeted measures are required to address this crisis, as obesity is one of the foremost avertible risks to health now and in the future and poses an unparalleled threat of premature disease and death at local, national, and global levels. Funding: Bill & Melinda Gates Foundation

Electroless nano zinc oxide–activate carbon composite supercapacitor electrode

An electroless deposition process was used to synthesize the nanostructured zinc oxide (ZnO)–activated carbon (AC) as supercapacitor. The composite oxide was studied by high resolution transmission electron microscopy (HRTEM), scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction analysis (XRD). The electrochemical performance of the nanocomposite was analyzed through cyclic voltammetry (CV) and AC impedance spectroscopy (EIS) in 0.1 M Na2SO4 as electrolyte. A specific capacitance 187 F g−1 at a scan rate of 5 mV s−1 was obtained using cyclic voltammetry (CV) and a nearly rectangular shaped CV curve was observed for the composite oxide. The supercapacitor was quite stable during charge–discharge cycling and exhibited constant capacitance during the long-term cycling. It also yielded a specific capacitance 171 F g−1 at 5 mA cm−2 with a high energy density of 21.9 Wh kg−1 and 4.2 kW kg−1 of power density. Due to unique structure of prepared ZnO–AC nanocomposite, it is a promising candidate for supercapacitor