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The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score was developed to establish a simple, standardized scoring system for researchers to quantify adherence to the 2018 WCRF/AICR Cancer Prevention Recommendations and assess its impact on cancer risk and other health-related outcomes. The aim of this commentary is to clarify potential points of ambiguity in its application, focusing on aspects related to specific sub-score components (physical activity, fast foods, alcohol, and sugar sweetened drinks), how to address different data needs due to varied data collection instruments, and future exploratory score approaches. [https://www.selleckchem.com/products/LY335979.html this website] Overall, we encourage researchers to utilize the standardized Score to enhance comparability across populations and countries. Researchers who may adapt or augment the 2018 WCRF/AICR Score are strongly encouraged to provide detailed descriptions of their methods to promote transparency and reproducibility. Copyright ©2020, American Association for Cancer Research.BACKGROUND The key characteristics (KCs) of human carcinogens provide a uniform approach to evaluating mechanistic evidence in cancer hazard identification. Refinements to the approach were requested by organizations and individuals applying the KCs. METHODS We assembled an expert committee with knowledge of carcinogenesis and experience in applying the KCs in cancer hazard identification. We leveraged this expertise and an examination of the literature to more clearly describe each KC; identify current and emerging assays and in vivo biomarkers that can be used to measure them; and, make recommendations for future assay development. RESULTS We found that the KCs are clearly distinct from the Hallmarks of Cancer, that interrelationships among the KCs can be leveraged to strengthen the KC approach (and an understanding of environmental carcinogenesis), and that the KC approach is applicable to the systematic evaluation of a broad range of potential cancer hazards in vivo and in vitro. We identified gaps in coverage of the KCs by current assays. CONCLUSION Future efforts should expand the breadth, specificity and sensitivity of validated assays and biomarkers that can measure the 10 KCs. IMPACT Refinement of the KC approach will enhance and accelerate carcinogen identification, a first step in cancer prevention. Copyright ©2020, American Association for Cancer Research.Crop improvement is crucial to ensuring global food security under climate change, and hence there is a pressing need for phenotypic observations that are both high throughput and improve mechanistic understanding of plant responses to environmental cues and limitations. In this study, chlorophyll a fluorescence light response curves and gas-exchange observations are combined to test the photosynthetic response to moderate drought in four genotypes of Brassica rapa. The quantum yield of photosystem II (øPSII) is here analyzed as an exponential decline under changing light intensity and soil moisture. Both the maximum øPSII (αPSII) and the rate of øPSII decline across a large range of light intensities (0-1000 μmol photons m-2 s-1) (βPSII) are negatively affected by drought. We introduce an alternative photosynthesis model (βPSII model) incorporating parameters from rapid fluorescence response curves. Specifically, the model uses βPSII as an input for estimating the photosynthetic electron transport rate (ETR), which agrees well with two existing photosynthesis models (Farquhar-von Caemmerer-Berry and Yin). The βPSII model represents a major improvement in photosynthesis modeling through the integration of high-throughput fluorescence phenotyping data, resulting in gained parameters of high mechanistic value. copyright, serif 2020 American Society of Plant Biologists. All rights reserved.Plants have evolved effective strategies to defend themselves against pathogen invasion. Starting from the plasma membrane with the recognition of microbe-associated molecular patterns (MAMPs) via pattern recognition receptors, internal cellular signaling pathways are induced to ultimately fend off the attack. Phospholipase D (PLD) hydrolyzes membrane phospholipids to produce phosphatidic acid (PA), which has been proposed to play a second messenger role in immunity. The Arabidopsis (Arabidopsis thaliana) PLD family consists of 12 members and for some a specific function in resistance towards a subset of pathogens has been shown. We demonstrate here that Arabidopsis PLDγ1, but not its close homologs PLDγ2 and PLDγ3, is specifically involved in plant immunity. Genetic inactivation of PLDγ1 resulted in increased resistance towards the virulent bacterium Pseudomonas syringae pv. tomato DC3000 and the necrotrophic fungus Botrytis cinerea. As pldγ1 mutant plants responded with elevated levels of reactive oxygen species to MAMP-treatment, a negative regulatory function for this PLD isoform is proposed. Importantly, PA levels in pldγ1 mutants were not affected compared to stressed wild-type plants, suggesting that alterations in PA levels are not likely the cause for the enhanced immunity in the pldγ1 line. Instead, the plasma-membrane-attached PLDγ1 protein colocalized and associated with the BAK1-INTERACTING RECEPTOR-LIKE KINASES BIR2 and BIR3, which are known negative regulators of pattern-triggered immunity. Moreover, complex formation of PLDγ1 and BIR2 was further promoted upon MAMP-treatment. Hence, we propose that PLDγ1 acts as a negative regulator of plant immune responses in complex with immunity-related proteins BIR2 and BIR3. copyright, serif 2020 American Society of Plant Biologists. All rights reserved.The goal of this Brief Review is to highlight literature that demonstrates how cytokines made by T lymphocytes impact the gastric epithelium, especially during Helicobacter pylori infection. These cytokines effect many of the diverse functions of the epithelium and the epithelium's interactions with H. pylori The focal point of this Brief Review will be on how T cell cytokines impact antimicrobial function and barrier function and how T cell cytokines influence the development and progression of cancer. Furthermore, the modulation of epithelial-derived chemokines by H. pylori infection will be discussed. Copyright © 2020 by The American Association of Immunologists, Inc.The continued existence of diseases of poverty is one of the great medical moral dilemmas of the 21st century. That this group of largely either preventable or treatable diseases still plagues a great many of the world's poorest citizens is a challenging problem to address. This paper examines diseases of poverty not by looking at the pathogenic diseases themselves but by looking at the 'diseases' of society that lead to the prevalence of such morbidity. 'Diseases' such as lack of infrastructure, lack of nutrition, lack of education, lack of funding and lack of socioeconomic stability. By addressing each of these, in turn, this paper looks to stimulate thought on how society can approach and prevent diseases of poverty in the future. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.The interface between humanitarianism, development and peacebuilding is increasingly congested. Western foreign policies have shifted towards pro-active stabilisation agendae and so Civil-Military Relationships (CMRel) will inevitably be more frequent. Debate is hampered by lack of a common language or clear, mutually understood operational contexts to define such relationships. Often it may be easier to simply assume that military co-operation attempts are solely to 'win hearts and minds', rather than attempt to navigate the morass of different acronyms. In healthcare, such relationships are common and more complex - partly as health is seen as both an easy entry point for diplomacy and so is a priority for militaries, and because health is so critical to apolitical humanitarian responses. This paper identifies the characteristics of commonly described kinds of CMRel, and then derives a typology that describe them in functional groups as they apply to healthcare-related contexts (although it is likely to be mployer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Despite considerable progress, development of glucose-responsive insulins (GRI) still largely depends on empirical knowledge and tedious experimentation - especially on rodents. To assist the rational design and clinical translation of the therapeutic, we present a Pharmacokinetic Algorithm Mapping GRI Efficacies in Rodents and Humans (PAMERAH), built upon our previous human model. PAMERAH constitutes a framework for predicting the therapeutic efficacy of a GRI candidate from its user-specified mechanism of action, kinetics, and dosage, which we show is accurate when checked against data from experiments and literature. Results from simulated glucose clamps also agree quantitatively with recent GRI publications. We demonstrate that the model can be used to explore the vast number of permutations constituting the GRI parameter space, and thereby identify the optimal design ranges that yield desired performance. A design guide aside, PAMERAH more importantly can facilitate GRI's clinical translation by connecting each candidate's efficacies in rats, mice, and humans. The resultant mapping helps find GRIs which appear promising in rodents but underperform in humans (i.e. false-positives). Conversely, it also allows for the discovery of optimal human GRI dynamics not captured by experiments on a rodent population (false-negatives). We condense such information onto a translatability grid as a straightforward, visual guide for GRI development. © 2020 by the American Diabetes Association.Amylin, a pancreatic hormone and neuropeptide, acts principally in the hindbrain to decrease food intake and has been recently shown to act as a neurotrophic factor to control the development of AP→NTS and ARC→PVN axonal fiber outgrowth. Amylin is also able to activate ERK signaling specifically in POMC neurons independently of leptin. To investigate the physiological role of amylin signaling in POMC neurons, the core component of the amylin receptor, calcitonin receptor (CTR) was depleted from POMC neurons using an inducible mouse model. The loss of CTR in POMC neurons leads to increased body weight gain, increased adiposity, and glucose intolerance in male knockout mice, characterized by decreased energy expenditure (EE) and decreased expression of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). Furthermore, a decreased spontaneous locomotor activity and absent thermogenic reaction to the application of the amylin receptor agonist were observed in male and female mice. Together, these results show a significant physiological impact of amylin/calcitonin signaling in CTR-POMC neurons on energy metabolism and demonstrate the need for sex-specific approaches in obesity research and potentially treatment. © 2020 by the American Diabetes Association.PURPOSE Pheochromocytomas and paragangliomas (PCPGs) are usually benign neuroendocrine tumors. However, PCPGs with mutations in the succinate dehydrogenase B subunit (SDHB) have a poor prognosis and frequently develop metastatic lesions. SDHB-mutated PCPGs exhibit dysregulation in oxygen metabolic pathways, including pseudohypoxia and formation of reactive oxygen species (ROS), suggesting that targeting redox balance pathway could be a potential therapeutic approach. EXPERIMENTAL DESIGN We studied the genetic alterations of Cluster I PCPGs compared to Cluster II PCPGs, which usually present as benign tumors. By targeting the signature molecular pathway, we investigated the therapeutic effect of ascorbic acid on PCPGs using in vitro and in vivo models. RESULTS By investigating PCPG cells with low SDHB levels, we show that pseudohypoxia resulted in elevated expression of iron transport proteins, including transferrin (TF), transferrin receptor 2 (TFR2) and the divalent metal transporter 1 (SLC11A2; DMT1), leading to iron accumulation.