Mechanisms of growth inhibition of primary prostate epithelial cells following gamma irradiation or photodynamic therapy including senscence, necrosis, and autophagy, but not apoptosis

In comparison to more differentiated cells, prostate cancer stem-like cells are radioresistant, which could explain radio-recurrent prostate cancer. Improvement of radiotherapeutic efficacy may therefore require combination therapy. We have investigated the consequences of treating primary prostate epithelial cells with gamma irradiation and photodynamic therapy (PDT), both of which act through production of reactive oxygen species (ROS). Primary prostate epithelial cells were cultured from patient samples of benign prostatic hyperplasia and prostate cancer prior to treatment with PDT or gamma irradiation. Cell viability was measured using MTT and alamar blue assay, and cell recovery by colony-forming assays. Immunofluorescence of gamma-H2AX foci was used to quantify DNA damage, and autophagy and apoptosis were assessed using Western blots. Necrosis and senescence were measured by propidium iodide staining and beta-galactosidase staining, respectively. Both PDT and gamma irradiation reduced the colony-forming ability of primary prostate epithelial cells. PDT reduced the viability of all types of cells in the cultures, including stem-like cells and more differentiated cells. PDT induced necrosis and autophagy, whereas gamma irradiation induced senescence, but neither treatment induced apoptosis. PDT and gamma irradiation therefore inhibit cell growth by different mechanisms. We suggest these treatments would be suitable for use in combination as sequential treatments against prostate cancer

Modelling of microstructural evolution in multi-layered overlay coatings

Functionally graded, multi-layered coatings are designed to provide corrosion protection over a range of operating conditions typically found in industrial gas turbines. A model incorporating diffusion, equilibrium thermodynamics and oxidation has been developed to simulate the microstructural evolution within a multi-layered coating system. The phase and concentration profiles predicted by the model have been compared with an experimental multi-layered system containing an Al-rich outer layer, a Cr-enriched middle layer and an MCrAlY-type inner layer deposited on a superalloy substrate. The concentration distribution and many microstructural features observed experimentally can be predicted by the model. The model is expected to be useful for assessing the microstructural evolution of multilayer coated systems which can be potentially used on industrial gas turbine aerofoils

Functional Characterization of the Chlamydomonas reinhardtii ERG3 Ortholog, a Gene Involved in the Biosynthesis of Ergosterol

The predominant sterol in the membranes of the alga Chlamydomonas reinhardtii is ergosterol, which is commonly found in the membranes of fungi, but is rarely found in higher plants. Higher plants and fungi synthesize sterols by different pathways, with plants producing cycloartenol as a precursor to end-product sterols, while non-photosynthesizing organisms like yeast and humans produce lanosterol as a precursor. Analysis of the C. reinhardtii genome sequence reveals that this algae is also likely to synthesize sterols using a pathway resembling the higher plant pathway, indicating that its sterols are synthesized somewhat differently than in fungi. The work presented here seeks to establish experimental evidence to support the annotated molecular function of one of the sterol biosynthetic genes in the Chlamydomonas genome.A gene with homology to the yeast sterol C-5 desaturase, ERG3, is present in the Chlamydomonas genome. To test whether the ERG3 ortholog of C. reinhardtii encodes a sterol C-5 desaturase, Saccharomyces cerevisiae ERG3 knockout strains were created and complemented with a plasmid expressing the Chlamydomonas ERG3. Expression of C. reinhardtii ERG3 cDNA in erg3 null yeast was able to restore ergosterol biosynthesis and reverse phenotypes associated with lack of ERG3 function.Complementation of the yeast erg3 null phenotypes strongly suggests that the gene annotated as ERG3 in C. reinhardtii functions as a sterol C-5 desaturase

Trade unions and the challenge of fostering solidarities in an era of financialisation

This articles re-examines evidence that trade unions in the UK have struggled to renew themselves despite considerable investment of time and effort. It argues that financialisation in the realms of capital accumulation, organisational decision making and everyday life has introduced new barriers to building the solidarities within and between groups of workers that would be necessary to develop a stronger response to the catastrophic effects on labour of financialisation in general, and the financial crisis specifically. The crisis highlighted the weaknesses of trade unions as institutions of economic and industrial democracy, but has also given some opportunities to establish narratives of solidarity in spaces and platforms created within a financialised context

Preventive antibiotic treatment of calves: emergence of dysbiosis causing propagation of obese state-associated and mobile multidrug resistance-carrying bacteria

In agriculture, antibiotics are used for the treatment and prevention of livestock disease. Antibiotics perturb the bacterial gut composition but the extent of these changes and potential consequences for animal and human health is still debated. Six calves were housed in a controlled environment. Three animals received an injection of the antibiotic florfenicol (Nuflor), and three received no treatment. Faecal samples were collected at 0, 3 and 7 days, and bacterial communities were profiled to assess the impact of a therapy on the gut microbiota. Phylogenetic analysis (16S‐rDNA) established that at day 7, antibiotic‐treated microbiota showed a 10‐fold increase in facultative anaerobic Escherichia spp, a signature of imbalanced microbiota, dysbiosis. The antibiotic resistome showed a high background of antibiotic resistance genes, which did not significantly change in response to florfenicol. However, the maintenance of Escherichia coli plasmid‐encoded quinolone, oqxB and propagation of mcr‐2, and colistin resistance genes were observed and confirmed by Sanger sequencing. The microbiota of treated animals was enriched with energy harvesting bacteria, common to obese microbial communities. We propose that antibiotic treatment of healthy animals leads to unbalanced, disease‐ and obese‐related microbiota that promotes growth of E. coli carrying resistance genes on mobile elements, potentially increasing the risk of transmission of antibiotic resistant bacteria to humans

Age of Barrier Canyon-style rock art constrained by cross-cutting relations and luminescence dating techniques

Rock art compels interest from both researchers and a broader public, inspiring many hypotheses about its cultural origin and meaning, but it is notoriously difficult to date numerically. Barrier Canyon-style (BCS) pictographs of the Colorado Plateau are among the most debated examples; hypotheses about its age span the entire Holocene epoch and previous attempts at direct radiocarbon dating have failed. We provide multiple age constraints through the use of cross-cutting relations and new and broadly applicable approaches in optically stimulated luminescence dating at the Great Gallery panel, the type section of BCS art in Canyonlands National Park, southeastern Utah. Alluvial chronostratigraphy constrains the burial and exhumation of the alcove containing the panel, and limits are also set by our related research dating both a rockfall that removed some figures and the rock’s exposure duration before that time. Results provide a maximum possible age, a minimum age, and an exposure time window for the creation of the Great Gallery panel, respectively. The only prior hypothesis not disproven is a late Archaic origin for BCS rock art, although our age result of A.D. ∼1–1100 coincides better with the transition to and rise of the subsequent Fremont culture. This chronology is for the type locality only, and variability in the age of other sites is likely. Nevertheless, results suggest that BCS rock art represents an artistic tradition that spanned cultures and the transition from foraging to farming in the region. Archaeology is focused upon material records, contextualized in time. Rock art is a record with the potential to provide unique insight into the dynamics and evolution of culture, but it generally lacks stratigraphic or chronologic context. Interpretation of the origin and meaning of rock art is indirect at best, or simply speculative. In the case of some pictographs, pigments may include or have enough accessory carbon for accelerator mass spectrometry (AMS) radiocarbon dating (1⇓⇓–4). In other special situations, such as caves, minimum age constraints have been obtained by various techniques of dating material that overlies or entombs rock art (5⇓–7). However, most rock art remains undatable and researchers rely upon stylistic comparison and indirect associations with artifacts at nearby sites (8, 9). The case in point for this study is arguably the most compelling and debated rock art in the United States—the Barrier Canyon style (BCS) of the Colorado Plateau. Previous attempts to derive an absolute chronology have failed and its age remains unknown, with widely ranging hypotheses that have remained untested until now. The continued development of dating techniques offers new possibilities for hypothesis testing. The optically stimulated luminescence (OSL) signals from mineral grains make it possible to date the deposition of most sediment that is exposed to a few seconds of full sunlight before burial, and its use in the earth and cultural sciences has greatly increased (10, 11). Among the latest applications of OSL are techniques dating the outer surfaces of rock clasts that have become shielded from light, including those with archaeological context (12⇓⇓–15). Recent work has furthermore used the “bleaching” profile of decreasing luminescence signal toward the surface of rock to estimate exposure time to sunlight (16, 17). Using these dating tools, we can constrain the age of rock art and gain new insight into past cultures and landscapes. Here, we synthesize results from three approaches to dating the type section of BCS art, the Great Gallery in Canyonlands National Park of southeastern Utah. Through dating the full alluvial stratigraphy and a rockfall event that both have incontrovertible cross-cutting relations with the rock art, and then by determining the exposure duration of a painted rock surface, we greatly narrow the window of time when the rock art was created. These approaches do not require direct sampling of rock art and have strong potential for application to other archaeological and surface processes research. Although our results are only for the type section of BCS art, and chronological variability should be expected for the style across the region, they suggest that BCS art coincides with the transition to agriculture in the northern Colorado Plateau and may not have been limited to a specific archaeological culture