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Aquatic ecosystems play an important role in global methane cycling and many field studies have reported methane supersaturation in the oxic surface mixed layer (SML) of the ocean and in the epilimnion of lakes. The origin of methane formed under oxic condition is hotly debated and several pathways have recently been offered to explain the “methane paradox.” In this context, stable isotope measurements have been applied to constrain methane sources in supersaturated oxygenated waters. Here we present stable carbon isotope signatures for six widespread marine phytoplankton species, three haptophyte algae and three cyanobacteria, incubated under laboratory conditions. The observed isotopic patterns implicate that methane formed by phytoplankton might be clearly distinguished from methane produced by methanogenic archaea. Comparing results from phytoplankton experiments with isotopic data from field measurements, suggests that algal and cyanobacterial populations may contribute substantially to methane formation observed in the SML of oceans and lakes. Plain Language Summary Methane plays an important role in atmospheric chemistry and physics as it contributes to global warming and to the destruction of ozone in the stratosphere. Knowing the sources and sinks of methane in the environment is a prerequisite for understanding the global atmospheric methane cycle but also to better predict future climate change. Measurements of the stable carbon isotope composition of carbon—the ratio between the heavy and light stable isotope of carbon—help to identify methane sources in the environment and to distinguish them from other formation processes. We identified the carbon isotope fingerprint of methane released from phytoplankton including algal and cyanobacterial species. The observed isotope signature improves our understanding of methane cycling in the surface layers of aquatic environments helping us to better estimate methane emissions to the atmosphere. Key Points Stable carbon isotope values of methane emitted from six phytoplankton cultures incubated in the laboratory Isotope fractionation between methane source signature and biomass of widespread algal and cyanobacterial species Isotopic patterns of methane released by phytoplankton may be clearly distinguished from methane formed by methanogenic archaea

The lipophilic electron-transport cofactor rhodoquinone (RQ) facilitates anaerobic metabolism in a variety of bacteria and selected eukaryotic organisms in hypoxic environments. We have shown that an intact rquA gene in Rhodospirillum rubrum is required for RQ production and efficient growth of the bacterium under anoxic conditions. While the explicit details of RQ biosynthesis have yet to be fully delineated, ubiquinone (Q) is a required precursor to RQ in R. rubrum, and the RquA gene product is homologous to a class I methyltransferase. In order to identify any additional requirements for RQ biosynthesis or factors influencing RQ production in R. rubrum, we performed transcriptome analysis to identify differentially expressed genes in anoxic, illuminated R. rubrum cultures, compared with those aerobically grown in the dark. To further select target genes, we employed a bioinformatics approach to assess the likelihood that a given differentially expressed gene under anoxic conditions may also have a direct role in RQ production or regulation of its levels in vivo. Having thus compiled a list of candidate genes, nine were chosen for further study by generation of knockout strains. RQ and Q levels were quantified using liquid chromatography-mass spectrometry, and rquA gene expression was measured using the real-time quantitative polymerase chain reaction. In one case, Q and RQ levels were decreased relative to wild type; in another case, the opposite effect was observed. These results comport with the crucial roles of rquA and Q in RQ biosynthesis, and reveal the existence of potential modulators of RQ levels in R. rubrum.

Despite evidence that precision medicine (PM) results in improved patient care, the broad adoption and implementation has been challenging across the United States (US). To better understand the perceived barriers associated with PM adoption, a quantitative survey was conducted across five stakeholders including medical oncologists, surgeons, lab directors, payers, and patients. The results of the survey reveal that stakeholders are often not aligned on the perceived challenges with PM awareness, education and reimbursement, with there being stark contrast in viewpoints particularly between clinicians, payers, and patients. The output of this study aims to help raise the awareness that misalignment on the challenges to PM adoption is contributing to broader lack of implementation that ultimately impacts patients. With better understanding of stakeholder viewpoints, we can help alleviate the challenges by focusing on multi-disciplinary education and awareness to ultimately improve patient outcomes.

Vitamin D deficiency is a common problem worldwide. In particular, it is an issue in the Northern Hemisphere where UVB radiation does not penetrate the atmosphere as readily. There is a correlation between vitamin D deficiency and colorectal cancer incidence and mortality. Furthermore, there is strong evidence that cancer of the ascending (right side) colon is different from cancer of the descending (left side) colon in terms of prognosis, tumor differentiation, and polyp type, as well as at the molecular level. Right-side tumors have elevated Wnt signaling and are more likely to relapse, whereas left-side tumors have reduced expression of tumor suppressor genes. This study seeks to understand both the proteomic and metabolomic changes resulting from treatment of the active metabolite of vitamin D, calcitriol, in right-sided and left-sided colon cancer. Our results show that left-sided colon cancer treated with calcitriol has a substantially greater number of changes in both the proteome and the metabolome than right-sided colon cancer. We found that calcitriol treatment in both right-sided and left-sided colon cancer causes a downregulation of ribosomal protein L37 and protein S100A10. Both of these proteins are heavily involved in tumorigenesis, suggesting a possible mechanism for the correlation between low vitamin D levels and colon cancer.

Lifestyle optimizations are implementable changes that can have an impact on health and disease. Nutrition is a lifestyle optimization that has been shown to be of great importance in cancer initiation, progression, and metastasis. Dozens of clinical trials are currently in progress that focus on the nutritional modifications that cancer patients can make prior to and during medical care that increase the efficacy of treatment. In this review, we discuss various nutritional inventions for cancer patients and the analytical approaches to characterize the downstream molecular effects. We first begin by briefly explaining the many different forms of nutritional intervention currently being used in cancer treatment as well as their motivating biology. The forms of nutrient modulation described in this review include calorie restriction, the different practices of fasting, and carbohydrate restriction. The review then shifts to explain how proteomics is used to determine biomarkers of cancer and how it can be utilized in the future to determine the metabolic phenotype of a tumor, and inform physicians if nutritional intervention should be recommended for a cancer patient. Nutrigenomics aims to understand the relationship of nutrients and gene expression and can be used to understand the downstream molecular effects of nutrition restriction, partially through proteomic analysis. Proteomics is just beginning to be used as cancer diagnostic and predictive tools. However, these approaches have not been used to their full potential to understand nutritional intervention in cancer.

Background and aims While predictors of survival in older people have been examined in depth in a large number of studies, a literature search revealed no cross-national comparative prospective cohort studies on this issue. This study investigated survival and its predictors from age 75 to 85 among three local Nordic populations using survival data on national cohorts as background information. Methods The data were derived from national registers and from samples of 75-year old living in Denmark, Sweden, and Finland. The subjects were invited to take part in interviews and examinations focusing on different domains of health, functional capacity, and physical and social activities. Results The proportion of survivors to age 75 was markedly smaller among the Finnish men and women than Danish or Swedish subjects. In the local population no marked differences in survival from age 75 to 85 were observed between the groups of men, while women survived longer than men and longer in Göteborg than in Glostrup or Jyväskylä. Univariate models revealed 12 predictors of survival. In the multivariate models, the significant predictors among men related to physical fitness, whereas among women they pertained to social activities and morbidity. Conclusions Despite great differences in the proportions of survivors to age 75, and excepting the survival advantage of women, only minor differences were present in the subjects’ further survival to age 85. In the univariate analyses, many of the factors predictive of survival from age 75 to 85 were the same in the examined populations, whereas in the multivariate analyses differences between the sexes emerged.

Current United States Preventive Services Task Force (USPSTF) recommendations include routine screening for breast, cervical, colorectal, and lung cancer; however, two out of every three cancer cases occur in other indications, leading to diagnoses in advanced stages of the disease and a higher likelihood of mortality. Blood-based multi-cancer early detection (MCED) tests can impact cancer screening and early detection by monitoring for multiple different cancer types at once, including indications where screening is not performed routinely today. We conducted a survey amongst healthcare providers (HCPs), payers, and patients within the U.S. health system to understand the current utilization of cancer screening tests and the anticipated barriers to widespread adoption of blood-based MCED tests. The results indicated that the community favors the adoption of blood-based MCED tests and that there is broad agreement on the value proposition. Despite this recognition, the survey highlighted that there is limited use today due to the perceived lack of clinical accuracy and utility data, high out-of-pocket patient costs, and lack of payer coverage. To overcome the hurdles for future widespread adoption of blood-based MCED tests, increased investment in data generation, education, and implementation of logistical support for HCPs will be critical.

This study analyses the risk of coronary heart disease (CHD) associated with food intake patterns. A cohort study with follow-up in 1996 for first admission to hospital for a CHD diagnosis or death caused by CHD (280 cases). Three food patterns were identified from a food frequency questionnaire: (1) a predefined healthy food index; (2) a prudent diet (reflecting frequent intakes of wholemeal cereals, fruit and vegetables); and (3) a Western food pattern (reflecting frequent intakes of meat products, butter and white bread) derived by factor analysis. Both factor scores had a mean of zero and a standard deviation of 1. Copenhagen County, Denmark. A random sample of 7316 adults participated in health examinations conducted either in 1982-1984, 1987, or 1991-1992. The healthy food index and the Western pattern were not associated with CHD. The prudent pattern was associated with a decreased risk of CHD (Hazard ratio (HR per score unit increase)=0.85; 95% confidence intervals (CI), 0.75, 0.96), but the association vanished (HR=1.06; 95% CI, 0.93, 1.21) after controlling for confounding. Body mass index (BMI) modified the effect of the prudent and the Western patterns on CHD risk, suggesting an inverse association between both patterns and CHD in persons with low BMI, while the risk of CHD seemed to be positively related to the prudent and the Western pattern in those with high BMIs. This study showed no association between dietary patterns and CHD risk, but suggests that BMI modifies the relation between diet and CHD risk.

Short-term glucose starvation prior to chemotherapy has the potential to preferentially weaken cancer cells, making them more likely to succumb to treatment, while protecting normal cells. In this study, we used 3D cell cultures of colorectal cancer and assessed the effects of short-term glucose starvation and chemotherapy compared to treatment of either individually. We evaluated both phenotypic changes and protein expression levels. Our findings indicate that the combined treatment results in more significant phenotypic responses, including decreased cell viability and clonogenicity. These phenotypic responses can be explained by the decreased expression of LDHA and 14-3-3 family proteins, which were found only in the combined treatment groups. This study indicates that short-term glucose starvation has the potential to increase the efficacy of current cancer treatment regimes. Graphical Abstract ᅟ

Methane (CH4) is the most abundant organic compound in the atmosphere and is emitted from many biotic and abiotic sources. Recent studies have shown that CH4 production occurs under aerobic conditions in eukaryotes, such as plants, animals, algae, and saprotrophic fungi. Saprotrophic fungi play an important role in nutrient recycling in terrestrial ecosystems via the decomposition of plant litter. Although CH4 production by saprotrophic fungi has been reported, no data on the stable carbon isotope values of the emitted CH4 (δ13C-CH4 values) are currently available. In this study, we measured the δ13C values of CH4 and carbon dioxide (δ13C-CO2 values) emitted by two saprotrophic fungi, Pleurotus sapidus (oyster mushroom) and Laetiporus sulphureus (sulphur shelf), cultivated on three different substrates, pine wood (Pinus sylvestris), grass (mixture of Lolium perenne, Poa pratensis, and Festuca rubra), and corn (Zea mays), which reflect both C3 and C4 plants with distinguished bulk δ13C values. Applying Keeling plots, we found that the δ13C source values of CH4 emitted from fungi cover a wide range from −40 to −69 mUr depending on the growth substrate and fungal species. Whilst little apparent carbon isotopic fractionation (in the range from −0.3 to 4.6 mUr) was calculated for the δ13C values of CO2 released from P. sapidus and L. sulphureus relative to the bulk δ13C values of the growth substrates, much larger carbon isotopic fractionations (ranging from −22 to −42 mUr) were observed for the formation of CH4. Although the two fungal species showed similar δ13CH4 source values when grown on pine wood, δ13CH4 source values differed substantially between the two fungal species when they were grown on grass or corn. We found that the source values of δ13CH4 emitted by saprotrophic fungi are highly dependent on the fungal species and the metabolized substrate. The source values of δ13CH4 cover a broad range and overlap with values reported for methanogenic archaea, the thermogenic degradation of organic matter, and other eukaryotes.