Extracellular cracking and content removal of benthic diatoms by intertidal foraminifera

Abstrac

xCT-Driven Expression of GPX4 Determines Sensitivity of Breast Cancer Cells to Ferroptosis Inducers

Inducers of ferroptosis such as the glutathione depleting agent Erastin and the GPX4 inhibitor Rsl-3 are being actively explored as potential therapeutics in various cancers, but the factors that determine their sensitivity are poorly understood. Here, we show that expression levels of both subunits of the cystine/glutamate antiporter xCT determine the expression of GPX4 in breast cancer, and that upregulation of the xCT/selenocysteine biosynthesis/GPX4 production axis paradoxically renders the cancer cells more sensitive to certain types of ferroptotic stimuli. We find that GPX4 is strongly upregulated in a subset of breast cancer tissues compared to matched normal samples, and that this is tightly correlated with the increased expression of the xCT subunits SLC7A11 and SLC3A2. Erastin depletes levels of the antioxidant selenoproteins GPX4 and GPX1 in breast cancer cells by inhibiting xCT-dependent extracellular reduction which is required for selenium uptake and selenocysteine biosynthesis. Unexpectedly, while breast cancer cells are resistant compared to nontransformed cells against oxidative stress inducing drugs, at the same time they are hypersensitive to lipid peroxidation and ferroptosis induced by Erastin or Rsl-3, indicating that they are \u27addicted\u27 to the xCT/GPX4 axis. Our findings provide a strategic basis for targeting the anti-ferroptotic machinery of breast cancer cells depending on their xCT status, which can be further explored

Modulating carbohydrate–protein interactions through glycoengineering of monoclonal antibodies to impact cancer physiology

Diverse glycans on proteins help impact cell and organism physiology along with drug activity. Since many protein-based biotherapeutics are glycosylated and these glycans have biological activity, there is a desire to engineer glycosylation for recombinant protein-based biotherapeutics. Engineered glycosylation can impact the recombinant protein efficacy and also influence many cell pathways by first changing glycan-protein interactions and consequently modulating disease physiologies. However, its complexity is enormous. Due to recent advances in glycoengineering, modulating protein-glycan interactions become more amenable to therapeutic approaches. Here, we discuss how engineered glycans contribute to therapeutic monoclonal antibodies (mAbs) in the treatment of cancers, how these glycoengineered therapeutic mAbs affect the transformed phenotypes and downstream cell pathways, and how systems biology can help in the next generation mAb glycoengineering process by aiding in data analysis and guiding engineering efforts to tailor mAb glycan and ultimately drug efficacy, safety and affordability

My Road Ahead study protocol: a randomised controlled trial of an online psychological intervention for men following treatment for localised prostate cancer

BACKGROUND There is a need for psychosocial interventions for men with prostate cancer to promote adaptive coping with the challenges and distress associated with diagnosis, treatment and recovery. In addition, interventions are needed that help to overcome barriers to psychosocial treatment such as limited face-to-face psychosocial support services, a shortage of adequately trained professionals, geographical distance, perceived and personal stigma and a preference for consumer-centric and self-directed learning. My Road Ahead is an online cognitive behaviour therapy (CBT) intervention for prostate cancer. This protocol describes a randomised controlled trial (RCT) that will evaluate the efficacy of this online intervention alone, the intervention in combination with a moderated online forum, and the moderated online forum alone. METHODS/DESIGN This study utilises a RCT design with three groups receiving: 1) the 6-module My Road Ahead intervention alone; 2) the My Road Ahead intervention plus a moderated online forum; and 3) the moderated online forum alone. It is expected that 150 men with localised prostate cancer will be recruited into the RCT. Online measures will assess men's psychological distress as well as sexual and relationship adjustment at baseline, post-intervention, 3 month follow-up and 6 month follow-up. The study is being conducted in Australia and participants will be recruited from April 2012 to Feb 2014. The primary aim of this study is to evaluate the efficacy of My Road Ahead in reducing psychological distress. DISCUSSION To our knowledge, My Road Ahead is the first self-directed online psychological intervention developed for men who have been treated for localised prostate cancer. The RCT will assess the efficacy of this intervention in improving psychological well-being, sexual satisfaction, relationship satisfaction and overall quality of life. If successful, this intervention could provide much needed support to men receiving treatment for localised prostate cancer in a highly accessible manner. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry Identifier: ACTRN12611000278932.The authors would like to acknowledge the funding partners involved in this study; the Prostate Cancer Foundation of Australia (PCFA), beyondblue: the National Depression and Anxiety Initiative with funding support from Movember Foundation

Investigation of the Thomson scattering-ECE discrepancy in ICRF heated plasmas at Alcator C-Mod

This paper reports on new experiments at Alcator C-Mod that were performed in order to investigate the long-standing, unresolved discrepancy between Thomson scattering (TS) and electron cyclotron emission (ECE) measurements of electron temperature in high temperature tokamak plasmas. Ion cyclotron range of frequency (ICRF) heating is used to produce high temperature conditions where the type of TS-ECE discrepancy observed in the past at JET and TFTR should become observable. At Alcator C-Mod, plasmas with Te(0) up to 8 keV are obtained using ion cyclotron resonance heating (ICRH), ICRF mode conversion heating and a combination of the two heating methods in order to explore the hypothesis that the presence of ICRH-generated fast ions may be related to the discrepancy. In all high temperature cases, the TS and ECE measurements of electron temperature agree to within experimental uncertainties. We find no evidence for the type of discrepancy reported at JET and TFTR. These results show that the TS-ECE discrepancy does not depend on high temperatures alone and also that the presence of ICRH-generated fast ions is insufficient to cause the TS-ECE discrepancy.United States. Dept. of Energy (DE-FC02-99ER54512

Phosphorus in the landscape: diffuse sources to surface waters. Land and Water Resources Research and Development Corporation. Occasional Paper 16/98

The National Eutrophication Management Program (NEMP) and Environment Australia convened a workshop to develop a coherent overview of the sources and transport of diffuse phosphorus in Australian catchments based on the latest knowledge. The Land and Water Resources Research and Development Corporation (LWRRDC) and the Murray–Darling Basin Commission (MDBC) jointly fund NEMP. A select group of scientists attended the workshop and developed a coherent statement about phosphorus sources and transport in Australian catchments. The group did not extend this statement to include recommended management practices. This paper reports the findings from the workshop. State governments have developed algal and nutrient management strategies in response to concerns about the frequency and severity of algal blooms, including cyanobacterial blooms, in Australian rivers and estuaries. There is an emphasis on phosphorus management, particularly in rural environments, now that nutrients are recognised as fundamental drivers of algal growth. Best management practices (BMPs) were developed for these strategies on the basis of the limited scientific evidence that was available at the time. The absence of a significant body of Australian information meant that there was a reliance on overseas research findings to develop such BMPs. A number of research projects have been completed in recent years on the sources and transport of nutrients in Australian catchments that challenge the Northern Hemisphere model of nutrient behaviour and will have implications for future development of BMPs. Principal conclusions 1. The studies presented in the workshop demonstrate that control of phosphorus entering surface waters must start with land management that minimises accelerated erosion and overland flow of water potentially rich in phosphorus. Heavily grazed lands, irrigation areas and intensive animal and horticultural industries are at risk, especially at the onset of rainy seasons and during periods of high rain intensity. 2. The transport of phosphorus from diffuse sources in landscapes can occur in both dissolved and particulate form. This can be due to different mobilisation and delivery mechanisms operating in different environments. Phosphorus mobilisation and delivery 1. Diffuse sources of phosphorus are the dominant component in most Australian catchments. Episodic rainfall is responsible for the bulk of phosphorus loss from the landscape. The mechanisms vary with each catchment. 2. Particulate phosphorus is carried by overland flow, resulting from run-off and erosion. In high to medium rainfall environments most is carried as filterable reactive phosphorus of less than 0.45 microns. Although most of the coarser materials from high parts of the landscape are deposited before they reach a watercourse, the particles ultimately carried into drainage lines are phosphorus-enriched by processes of sorting and filtration. 3. In river systems studied in the Murray–Darling Basin river sediments that originate from gully erosion and stream-bank collapse of readily dispersible soils carry most of the diffuse-source phosphorus. It is very likely that most of the phosphorus on these sediments is ‘native’ phosphorus coming from subsoils. 2 Phosphorus in the landscape: diffuse sources to surface waters Although the major episodes of gully formation occurred several decades ago, inputs of sediments and phosphorus from these sources continue at a high rate. Reduced input rates can best be achieved by targeting the gullies themselves and stabilising them by conservation works—particularly in small headwater catchments. 4. In larger dry-land catchments, fertiliser phosphorus is generally not an important component of phosphorus loss/export, although it may be locally significant. 5. Local soil, vegetation, terrain and climate conditions dictate whether surface erosion is the dominant source of phosphorus into a watercourse. To describe phosphorus exports from a specific landscape by surface erosion requires local studies. However, guidelines can be developed for management purposes to identify and minimise sources of phosphorus carried by overland flow. 6. Potential sources of diffuse phosphorus run-off occur wherever fertilisers are applied to soils that are already wet at the surface, or that may become wet by seasonally emerging groundwater. The magnitude of the loss will be greater if the application occurs on bare soils, or if it is next to a waterbody. 7. Dissolved phosphorus (from fertilisers and other sources) is readily mobilised and transported directly where the soil has both little ability to bind the phosphorus and a high leaching rate, as occurs in sandy regions of high rainfall around the continent. Phosphorus-laden water then travels via overland or shallow sub-surface flow to surface waterbodies quite quickly, unless other processes impede the movement. If the dissolved phosphorus moves via deep groundwater the time scales for its reappearance in surface water are generally large. 8. Dissolved phosphorus may also enter tributary waterbodies in headwater catchments via shortcircuit pathways, such as macropores, but this is only likely to be important over distances of hundreds of metres. However, these sub-surface pathways may reduce the effectiveness of local management practices that do not take them into account. 9. Large amounts of dissolved phosphorus are also being produced from irrigated dairy pastures (and possibly from other irrigation enterprises also). There is little or no sub-surface movement because soils are generally high in clay and flat. Phosphorus-laden water is pumped or drained across the land surface to channels. The time scale of dissolved phosphorus movement is comparable with the time with which the water itself moves. Once within drainage channels and streambeds the dissolved phosphorus fraction may be partially re-adsorbed onto particulates. 10. Large quantities of dissolved phosphorus are found in surface waters next to areas where animal excreta or over-fertilised market gardens give rise to phosphorus in surface wastewater that flows directly into waterways. These situations are most likely to arise in catchments that contain mixtures of horticultural, dairying, hobby-farming and similar land uses. Where farm dams are abundant a significant fraction of this phosphorus will not enter streams but will be retarded or retained in the landscape

Effect of the Planet Health Intervention on Eating Disorder Symptoms in Massachusetts Middle Schools, 2005–2008

Introduction: The Planet Health obesity prevention curriculum has prevented purging and abuse of diet pills (disordered weight control behavior [DWCB]) in middle-school girls in randomized trials, but the effects of Planet Health on DWCB when implemented by schools under dissemination conditions are not known. Methods: Massachusetts Department of Public Health and Blue Cross Blue Shield of Massachusetts disseminated Planet Health as part of the 3-year, Healthy Choices obesity prevention program in middle schools. We conducted an evaluation in 45 schools from fall 2005 to spring 2008. We gathered data from school staff to quantify intervention activities, and we gathered anonymous cross-sectional survey data from students on DWCB at baseline and Year 3 follow-up (n = 16,369). Multivariate logistic analyses with generalized estimating equations examined the effect of intervention activities on odds of students reporting DWCB at follow-up. Results: Students in schools reaching a high number of youth with Planet Health lessons on reducing television viewing had lower odds of DWCB at follow-up (odds ratio [OR], 0.80 per 100 lesson-exposures; 95% confidence interval [CI], 0.74–0.85). In addition, reduced odds of DWCB at follow-up were found in schools with active staff teamwork (OR, 0.76; 95% CI, 0.66–0.86) and the presence of programs addressing television viewing goals with staff (OR, 0.38; 95% CI, 0.28–0.53). Conclusion: Combined evidence from efficacy and effectiveness trials and now from dissemination research indicates that appropriately designed obesity prevention programs can achieve DWCB prevention on a large scale

Effect of the planet health intervention on eating disorder symptoms in Massachusetts middle schools, 2005-2008

INTRODUCTION: The Planet Health obesity prevention curriculum has prevented purging and abuse of diet pills (disordered weight control behavior [DWCB]) in middle-school girls in randomized trials, but the effects of Planet Health on DWCB when implemented by schools under dissemination conditions are not known. METHODS: Massachusetts Department of Public Health and Blue Cross Blue Shield of Massachusetts disseminated Planet Health as part of the 3-year, Healthy Choices obesity prevention program in middle schools. We conducted an evaluation in 45 schools from fall 2005 to spring 2008. We gathered data from school staff to quantify intervention activities, and we gathered anonymous cross-sectional survey data from students on DWCB at baseline and Year 3 follow-up (n = 16,369). Multivariate logistic analyses with generalized estimating equations examined the effect of intervention activities on odds of students reporting DWCB at follow-up. RESULTS: Students in schools reaching a high number of youth with Planet Health lessons on reducing television viewing had lower odds of DWCB at follow-up (odds ratio [OR], 0.80 per 100 lesson-exposures; 95% confidence interval [CI], 0.74-0.85). In addition, reduced odds of DWCB at follow-up were found in schools with active staff teamwork (OR, 0.76; 95% CI, 0.66-0.86) and the presence of programs addressing television viewing goals with staff (OR, 0.38; 95% CI, 0.28-0.53). CONCLUSION: Combined evidence from efficacy and effectiveness trials and now from dissemination research indicates that appropriately designed obesity prevention programs can achieve DWCB prevention on a large scale

Financial Burden and Mental Health Among LGBTQIA+ Adolescent and Young Adult Cancer Survivors During the COVID-19 Pandemic

Background In the United States, the cost of cancer treatment can lead to severe financial burden for cancer survivors. The economic impacts of the COVID-19 pandemic compound cancer survivors’ financial challenges. Financial burden may be particularly challenging for lesbian, gay, bisexual, transgender, queer, intersex, asexual and other sexual and gender minority (LGBTQIA+) survivors. LGBTQIA+ survivors who are adolescent and young adults (AYA) may face elevated financial burden due to multiple, intersecting identities. Methods An explanatory sequential mixed methods design was applied, beginning with a survey of AYA cancer survivors in the Mountain West region of the United States. Survey measures included demographics, COVID-19 impacts, the COmprehensive Score for financial Toxicity (COST), Perceived Stress Scale-4 (PSS-4), and PROMIS anxiety and depression scales. Two-way t-tests were used to analyze differences in outcomes between LGBTQIA+ and non-LGBTQIA+ AYAs. All LGBTQIA+ survey participants were invited to complete an interview, and those who agreed participated in descriptive interviews about financial burden due to cancer, COVID-19, and LGBTQIA+ identity. Interviews were audio recorded, transcribed, and analyzed using Dedoose. Results Survey participants (N=325) were LGBTQIA+ (n=29, 8.9%), primarily female (n= 197, 60.6%), non-Hispanic White (n= 267, 82.2%), and received treatment during COVID-19 (n= 174, 54.0%). LGBTQIA+ interview participants (n=9, 100%) identified as a sexual minority and (n=2, 22.2%) identified as a gender minority. Most were non-Hispanic White (n=6, 66.7%) and had received treatment during COVID-19 (n=7, 77.8%). Statistical analyses revealed that LGBTQIA+ AYAs reported significantly worse COST scores than non-LGBTQIA+ AYAs (p=0.002). LGBTQIA+ AYAs also reported significantly higher PSS-4 (p=0.001), PROMIS anxiety (p=0.002) and depression scores (p<0.001) than non-LGBTQIA+ AYAs, reflecting worse mental health outcomes. High costs of cancer treatment and employment disruptions due to COVID-19 contributed to substantial financial stress, which exacerbated existing mental health challenges and introduced new ones. Conclusions LGBTQIA+ AYA survivors reported substantial financial burden and psychological distress exacerbated by cancer, the COVID-19 pandemic, and LGBTQIA+ stigma. Given their multiple intersecting identities and potential for marginalization, LGBTQIA+ AYA survivors deserve prioritization in research to reduce financial burden and poor mental health