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Secondary metastases, accounting for 90 % of cancer-related deaths, pose a formidable challenge in cancer treatment, with bone being a prevalent site. Importantly, tumours may relapse, often in the skeleton even after successful eradication of the primary tumour, indicating that tumour cells may lay dormant within bone for extended periods of time. This review summarises recent findings in the mechanisms underlying tumour cell dormancy and the role of bone cells in this process. Hematopoietic stem cell (HSC) niches in bone provide a model for understanding regulatory microenvironments. Dormant tumour cells have been shown to exploit similar niches, with evidence suggesting interactions with osteoblast-lineage cells and other stromal cells via CXCL12-CXCR4, integrins, and TAM receptor signalling, especially through GAS6-AXL, led to dormancy, with exit of dormancy potentially regulated by osteoclastic bone resorption and neuronal signalling. A comprehensive understanding of dormant tumour cell niches and their regulatory mechanisms is essential for developing targeted therapies, a critical step towards eradicating metastatic tumours and stopping disease relapse.
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Osteocytes are master regulators of the skeleton. We mapped the transcriptome of osteocytes from different skeletal sites, across age and sexes in mice to reveal genes and molecular programs that control this complex cellular-network. We define an osteocyte transcriptome signature of 1239 genes that distinguishes osteocytes from other cells. 77% have no previously known role in the skeleton and are enriched for genes regulating neuronal network formation, suggesting this programme is important in osteocyte communication. We evaluated 19 skeletal parameters in 733 knockout mouse lines and reveal 26 osteocyte transcriptome signature genes that control bone structure and function. We showed osteocyte transcriptome signature genes are enriched for human orthologs that cause monogenic skeletal disorders (P = 2.4 × 10-22) and are associated with the polygenic diseases osteoporosis (P = 1.8 × 10-13) and osteoarthritis (P = 1.6 × 10-7). Thus, we reveal the molecular landscape that regulates osteocyte network formation and function and establish the importance of osteocytes in human skeletal disease.
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Enfermedades Óseas/genética , Homeostasis , Osteocitos/metabolismo , Transcriptoma , Factores de Edad , Animales , Enfermedades Óseas/metabolismo , Huesos/metabolismo , Biología Computacional , Femenino , Humanos , Masculino , Ratones , Ratones Noqueados , Osteocitos/citología , Osteoporosis/genética , Análisis de Secuencia de ARN , Factores SexualesRESUMEN
Following the 1986 Chornobyl accident, an area approaching 5000 km2 surrounding the nuclear plant was abandoned, creating the Chornobyl exclusion zone (CEZ). Although this area likely contains the most radioactive terrestrial ecosystem on earth, the absence of humans and associated activities for nearly 35 years since the accident has resulted in increases in wildlife numbers. Both the Belarussian and Ukrainian components of the CEZ are now designated as nature reserves; together they form one of Europe's largest protected areas and have been described as an iconic example of rewilding. Forests and former agricultural land (now scrub) dominate the CEZ and wildfires are an annual event. In April 2020, the CEZ suffered its most widespread fires to date when greater than 800 km2 of the 2600 km2 Ukrainian portion of the CEZ was burnt. Large-scale fires in the CEZ have implications for wildlife, as they do elsewhere, but they also pose additional radioecological and radiological protection questions. We discuss the implications of wildfires in the CEZ, considering effects on wildlife and changes in radionuclide mobility. We also demonstrate that the risk to firefighters and the wider public from the inhalation of radionuclides in smoke resulting from fires in the CEZ is likely to be low. However, further experimental and modeling work to evaluate potential doses to firefighters from inhaled radioactive particles would be valuable, not least for reassurance purposes. Integr Environ Assess Manag 2021;17:1141-1150 © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
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Accidente Nuclear de Chernóbil , Incendios Forestales , Ecosistema , Bosques , Humanos , PlantasRESUMEN
The noctuid Helicoverpa armigera (Hübner) is a major insect pest of chickpea Cicer arietinum L., pigeonpea Cajanus cajan (L.) Millsp., peanut Arachis hypogaea L., and cotton Gossypium spp., and host plant resistance is an important component for managing this pest in different crops. Because of variations in insect density and staggered flowering of the test material, it is difficult to identify cultivars with stable resistance to H. armigera across seasons and locations. To overcome these problems, we standardized the detached leaf assay to screen for resistance to this pest in chickpea, pigeonpea, peanut, and cotton under uniform insect pressure under laboratory conditions. Terminal branch (three to four fully expanded leaves) of chickpea, first fully expanded leaf of cotton, trifoliate of pigeonpea, or quadrifoliate of peanut, embedded in 3% agar-agar in a plastic cup/jar of appropriate size (250-500-ml capacity) infested with 10-20 neonate larvae can be used to screen for resistance to H. armigera. This technique keeps the leaves in a turgid condition for approximately 1 wk. The experiments can be terminated when the larvae have caused > 80% leaf damage in the susceptible check or when differences in leaf feeding between the resistant and susceptible checks are maximum. Detached leaf assay can be used as a rapid screening technique to evaluate germplasm, segregating breeding materials, and mapping populations for resistance to H. armigera in a short span of time with minimal cost, and under uniform insect infestation. It also provides useful information on antibiosis component of resistance to the target insect pest.
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Lepidópteros/fisiología , Control Biológico de Vectores , Hojas de la Planta , Plantas/genética , Animales , Arachis/genética , Cajanus/genética , Cicer/genética , Ingestión de Alimentos , Genotipo , Gossypium/genética , Plantas Modificadas Genéticamente , Densidad de PoblaciónRESUMEN
This study tests a whole-lake experiment to reduce the bioaccumulation of radiocaesium (137Cs) in fish in lakes contaminated by the Chernobyl accident. In many lakes in the Chernobyl contaminated areas, radiocaesium activity concentrations in fish are still significantly higher (up to 100 times in some species) than acceptable limits for human consumption. Estimates of the long-term rate of decline of 137Cs in fish in these regions, in the absence of countermeasures, show that radioactivity in fish in some lakes may remain above acceptable consumption limits for a further 50-100 years from the present date. In February 1998 we applied 15 t of potassium chloride to Lake Svyatoe, Kostiukovichy. The addition of potassium chloride fertilizer to the lake resulted in a decrease in activity concentration of 137Cs to approximately 40% of pre-countermeasure values in a number of different fish species. In contrast to Lake Svyatoe, 137Cs activity concentrations in fish from four control lakes showed no systematic decrease over the study period. Simplified models for transfers of 137Cs in lakes successfully 'blind' predicted the changes in 137Cs in water and fish resulting from this major alteration of the potassium concentration of the lake. The experiment represents the first test of a predictive model for the dynamics of radiocaesium in response to a major perturbation in potassium (its major competitor ion) in a whole lake ecosystem.