ACSL4-dependent ferroptosis does not represent a tumor-suppressive mechanism but ACSL4 rather promotes liver cancer progression

Ferroptosis is a novel type of programmed cell death that differs from apoptosis in that it involves iron-dependent peroxidation of membrane phospholipids. Its role in a variety of human disorders, including cancer has been hypothesized in recent years. While it may function as an endogenous tumor suppressor in a variety of cancers, its role during initiation and progression of liver cancer, particularly hepatocellular carcinoma (HCC), is yet unknown. Because HCC is most commonly found in chronically injured livers, we utilized two well-established mouse models of chronic injury-dependent HCC formation: Treatment with streptozotocin and high-fat diet as metabolic injury model, as well as treatment with diethylnitrosamine and carbon tetrachloride as toxic injury model. We used mice with hepatocyte-specific deletion of Acsl4, a key mediator of ferroptosis, to explore the significance of ferroptotic cell death in hepatocytes, the cell type of origin for HCC. Surprisingly, preventing ferroptotic cell death in hepatocytes by deleting Acsl4 does not increase the formation of HCC. Furthermore, Acsl4-deficient livers display less fibrosis and proliferation, especially in the HCC model of toxic damage. Intriguingly, in this model, the absence of ACSL4-dependent processes such as ferroptosis significantly slow down the growth of HCC. These findings suggest that during HCC formation in a chronically injured liver, ferroptotic cell death is not an endogenous tumor-suppressive mechanism. Instead, we find that ACSL4-dependent processes have an unanticipated cancer-promoting effect during HCC formation, which is most likely due to aggravated liver damage as demonstrated by increased hepatic fibrosis. Previous studies suggested that ferroptosis might have beneficial effects for patients during HCC therapy. As a result, during HCC progression and therapy, ferroptosis may have both cancer-promoting and cancer-inhibitory effects, respectively.Subject terms: Cancer models, Cancer genetics, Cell death     

Distribution of fitness effects of cross-species transformation reveals potential for fast adaptive evolution

Bacterial transformation, a common mechanism of horizontal gene transfer, can speed up adaptive evolution. How its costs and benefits depend on the growth environment is poorly understood. Here, we characterize the distributions of fitness effects (DFE) of transformation in different conditions and test whether they predict in which condition transformation is beneficial. To determine the DFEs, we generate hybrid libraries between the recipient Bacillus subtilis and different donor species and measure the selection coefficient of each hybrid strain. In complex medium, the donor Bacillus vallismortis confers larger fitness effects than the more closely related donor Bacillus spizizenii. For both donors, the DFEs show strong effect beneficial transfers, indicating potential for fast adaptive evolution. While some transfers of B. vallismortis DNA show pleiotropic effects, various transfers are beneficial only under a single growth condition, indicating that the recipient can benefit from a variety of donor genes to adapt to varying growth conditions. We scrutinize the predictive value of the DFEs by laboratory evolution under different growth conditions and show that the DFEs correctly predict the condition at which transformation confers a benefit. We conclude that transformation has a strong potential for speeding up adaptation to varying environments by profiting from a gene pool shared between closely related species.Subject terms: Molecular evolution, Bacterial genetics     

Functional and phylogenetic diversity of an agricultural matrix avifauna: The role of habitat heterogeneity in Afrotropical farmland

Varied strategies to alleviate the loss of farmland biodiversity have been tested, yet there is still insufficient evidence supporting their effectiveness, especially when considering phylogenetic and functional diversity alongside traditional taxonomic diversity metrics. This conservation challenge is accentuated in the Afrotropics by the rapid agricultural expansion and intensification for the production of cash crops and by a comparative lack of research. In this study, we assessed how farming practices influence avian phylogenetic and functional diversity. We conducted point‐count surveys to assess avian diversity in monocultures of tea and mixed crop farming systems surrounding the Nyungwe rainforest in south‐west Rwanda, allowing us to investigate the drivers of avian diversity at farm level. Species composition was found to be moderately different between farm types, with mixed crop farms supporting higher phylogenetic diversity than tea plantations. There were no significant seasonal differences in species composition, functional or phylogenetic diversity. Overall, functional diversity did not differ between farm types, but the dispersion of trophic‐related traits was significantly higher in mixed crop farms. Both functional and phylogenetic diversity were influenced by floristic diversity, vegetation height, tree number, and elevation to varying degrees. Our results also (i) highlight the role of farmland heterogeneity (e.g., crop species composition, height, and tree cover extent) in encouraging avian functional and phylogenetic diversity in the Afrotropics and (ii) indicate that the generally negative biodiversity impacts of monoculture agriculture can be partially alleviated by extensive agroforestry with an emphasis on indigenous tree species.     

Failla Memorial lecture. The future of heavy-ion science in biology and medicine

Interplanetary space contains fluxes of fast moving atomic nuclei. The distribution of these reflects the atomic composition of the universe, and such particles may pose limitations for space flight and for life in space. Over the past 50 years, since the invention of Ernest Lawrence's cyclotron, advances in accelerator technology have permitted the acceleration of charged nuclei to very high velocities. Currently, beams of any stable isotope species up to uranium are available at kinetic energies of several hundred MeV/nucleon at the Berkeley Bevalac. Recently, new areas of particle physics research relating to the mechanisms of spallation and fission have opened up for investigation, and it is now realistic to search for nuclear super-dense states that might be produced in heavy nuclear collisions. The heavy ions hold interest for a broad spectrum of research because of their effectiveness in producing a series of major lesions in DNA along single particle tracks and because of the Bragg depth ionization properties that allow the precise deposition of highly localized doses deep in the human body. Individual heavy ions can also interrupt the continuity of membraneous regions in cells. Heavy ions, when compared to low-LET radiation, have increased effectiveness for mammalian cell lethality, chromosome mutations, and cell transformation. The molecular mechanisms are not completely understood but appear to involve fragmentation and reintegration of DNA. Cells attempt to repair these lesions, and many of the deleterious effects are due to misrepair or misrejoining of DNA. Heavy ions do not require the presence of oxygen for producing their effects, and hypoxic cells in necrotic regions have nearly the same sensitivity as cells in well-oxygenated tissues. Heavy ions are effective in delaying or blocking the cell division process. Heavy ions are also strong enhancers of viral-induced cell transformation, a process that requires integration of foreign DNA. Some cell lines, known to be radioresistant to X rays, have exhibited greater sensitivity to heavy ions. These radiobiological properties, combined with the ability to deliver highly localized internal doses, make accelerated heavy ions potentially important radiotherapeutic tools. Other novel approaches include the utilization of radioactive heavy beams as instant tracers. Heavy-ion radiography and microscopy respond to delicate changes in tissue electron density. Dose localization with helium ions has achieved excellent results for pituitary tumors, tumors adjacent to the spinal cord, and ocular melanomas. We are working on adapting silicon- and neon-ion beams for controlled therapy studies.(ABSTRACT TRUNCATED AT 400 WORDS)     

Trachynema, a new genus in the Punctariaceae (Fucophyceae)

Two little known species of brown algae, Litosiphon mortensenii S. Lund and L. groenlandicus S. Lund, described from East Greenland have been compared with the type species of the genera Litosiphon Harv. and Asperococcus Lamour. They are distinguished from the genus Litosiphon by their basally sheathed hairs, hecatonematoid microthalli, mediate differentiation of embryospores, and lack of sympodial branching of the macrothallus. They are considered more primitive than Asperococcus by the absence of paraphyses and by the non-localized formation of reproductive structures. The new genus Trachynema is proposed to accommodate these plants; it finds a natural position in the Punctariaceae.     

Screening for carcinoma of the prostate by digital rectal examination in a randomly selected population.

OBJECTIVE--To study the acceptability, costs, psychosocial consequences, and organisation of screening for carcinoma of the prostate. DESIGN--A randomly selected population was personally invited for digital rectal examination by a urologist and a general practitioner. Further examinations were performed if induration was felt. Each man completed a questionnaire on his response to the examination. SETTING--General practices in the area of Norrköping. PATIENTS--1494 Men aged 50-69 randomly selected from a population of 9026. MAIN OUTCOME MEASURE--Prostates having a firm nodular consistency. RESULTS--Carcinoma of the prostate was suspected in 45 of 1163 patients examined; in 10 by the general practitioners, in 10 by the urologists, and in 25 by both. Forty four men had a fine needle aspiration biopsy, and carcinomas were found in 13 cases. Of these, one had been suspected by the general practitioner, four by urologists, and eight by both. The cost for each man was 11.60 pounds, and the cost for each case of carcinoma detected and treated by potentially curative methods was 2477 pounds. Of the 13 men with carcinoma, 10 underwent radical prostatectomy and one radiotherapy. One man had advanced disease and was given endocrine treatment, another was not treated. Only 193 men felt distress during the initial examination. Of the 44 men who had an aspiration biopsy, 25 experienced anxiety. CONCLUSIONS--Screening for carcinoma of the prostate by a urologist or a general practitioner using digital rectal examination is a cost effective method of early diagnosis. Whether such screening leads to prolonged survival, however, remains doubtful.