SREBP1 regulates mitochondrial metabolism in oncogenic KRAS expressing NSCLC [preprint]

Cancer cells require extensive metabolic reprogramming in order to provide the bioenergetics and macromolecular precursors needed to sustain a malignant phenotype. Mutant KRAS is a driver oncogene that is well known for its ability to regulate the ERK and PI3K signaling pathways. However, it is now appreciated that KRAS can promote tumor growth via upregulation of anabolic metabolism. We recently showed that oncogenic KRAS promotes a gene expression program of de novo lipogenesis in non-small cell lung cancer (NSCLC). To define the mechanism(s) responsible, we focused on the lipogenic transcription factor SREBP1. We observed that KRAS increases SREBP1 expression and genetic knockdown of SREBP1 significantly inhibited cell proliferation of mutant KRAS-expressing cells. Unexpectedly, lipogenesis was not significantly altered in cells subject to SREBP1 knockdown. Carbon tracing metabolic studies showed a significant decrease in oxidative phosphorylation and RNA-seq data revealed a significant decrease in mitochondrial encoded subunits of the electron transport chain (ETC). Taken together, these data support a novel role, distinct from lipogenesis, of SREBP1 on mitochondrial function in mutant KRAS NSCLC

Prediction of IBD based on population history for fine gene mapping

A novel multiple regression method (RM) is developed to predict identity-by-descent probabilities at a locus L (IBDL), among individuals without pedigree, given information on surrounding markers and population history. These IBDL probabilities are a function of the increase in linkage disequilibrium (LD) generated by drift in a homogeneous population over generations. Three parameters are sufficient to describe population history: effective population size (Ne), number of generations since foundation (T), and marker allele frequencies among founders (p). IBDL are used in a simulation study to map a quantitative trait locus (QTL) via variance component estimation. RM is compared to a coalescent method (CM) in terms of power and robustness of QTL detection. Differences between RM and CM are small but significant. For example, RM is more powerful than CM in dioecious populations, but not in monoecious populations. Moreover, RM is more robust than CM when marker phases are unknown or when there is complete LD among founders or Ne is wrong, and less robust when p is wrong. CM utilises all marker haplotype information, whereas RM utilises information contained in each individual marker and all possible marker pairs but not in higher order interactions. RM consists of a family of models encompassing four different population structures, and two ways of using marker information, which contrasts with the single model that must cater for all possible evolutionary scenarios in CM

Behaviour of the additive finite locus model

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Micro-optical Tandem Luminescent Solar Concentrators

Traditional concentrating photovoltaic (CPV) systems utilize multijunction cells to minimize thermalization losses, but cannot efficiently capture diffuse sunlight, which contributes to a high levelized cost of energy (LCOE) and limits their use to geographical regions with high direct sunlight insolation. Luminescent solar concentrators (LSCs) harness light generated by luminophores embedded in a light-trapping waveguide to concentrate light onto smaller cells. LSCs can absorb both direct and diffuse sunlight, and thus can operate as flat plate receivers at a fixed tilt and with a conventional module form factor. However, current LSCs experience significant power loss through parasitic luminophore absorption and incomplete light trapping by the optical waveguide. Here we introduce a tandem LSC device architecture that overcomes both of these limitations, consisting of a PLMA polymer layer with embedded CdSe/CdS quantum dot (QD) luminophores and InGaP micro-cells, which serve as a high bandgap absorber on top of a conventional Si photovoltaic. We experimentally synthesize CdSe/CdS QDs with exceptionally high quantum-yield (99%) and ultra-narrowband emission optimally matched to fabricated III-V InGaP micro-cells. Using a Monte Carlo ray-tracing model, we show the radiative limit power conversion efficiency for a module with these components to be 30.8% diffuse sunlight conditions. These results indicate that a tandem LSC-on-Si architecture could significantly improve upon the efficiency of a conventional Si photovoltaic module with simple and straightforward alterations of the module lamination steps of a Si photovoltaic manufacturing process, with promise for widespread module deployment across diverse geographical regions and energy markets

Anaerobic Digestion in a Flooded Densified Leachbed

A document discusses the adaptation of a patented biomass-digesting process, denoted sequential batch anaerobic composting (SEBAC), to recycling of wastes aboard a spacecraft. In SEBAC, high-solids-content biomass wastes are converted into methane, carbon dioxide, and compost

Oxygen transfer rate model for cell-free and predictive D.O. control in intensified bioreactor processes

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Cyanobacteria and their secondary metabolites in three freshwater reservoirs in the United Kingdom

Background Bloom-forming cyanobacteria occur globally in aquatic environments. They produce diverse bioactive metabolites, some of which are known to be toxic. The most studied cyanobacterial toxins are microcystins, anatoxin, and cylindrospermopsin, yet more than 2000 bioactive metabolites have been identified to date. Data on the occurrence of cyanopeptides other than microcystins in surface waters are sparse. Results We used a high-performance liquid chromatography-high-resolution mass spectrometry/tandem mass spectrometry (HPLC-HRMS/MS) method to analyse cyanotoxin and cyanopeptide profiles in raw drinking water collected from three freshwater reservoirs in the United Kingdom. A total of 8 cyanopeptides were identified and quantified using reference standards. A further 20 cyanopeptides were identified based on a suspect-screening procedure, with class-equivalent quantification. Samples from Ingbirchworth reservoir showed the highest total cyanopeptide concentrations, reaching 5.8, 61, and 0.8 µg/L in August, September, and October, respectively. Several classes of cyanopeptides were identified with anabaenopeptins, cyanopeptolins, and microcystins dominating in September with 37%, 36%, and 26%, respectively. Samples from Tophill Low reservoir reached 2.4 µg/L in September, but remained below 0.2 µg/L in other months. Samples from Embsay reservoir did not exceed 0.1 µg/L. At Ingbirchworth and Tophill Low, the maximum chlorophyll-a concentrations of 37 µg/L and 22 µg/L, respectively, and cyanobacterial count of 6 × 10 cells/mL were observed at, or a few days after, peak cyanopeptide concentrations. These values exceed the World Health Organization's guideline levels for relatively low probability of adverse health effects, which are defined as 10 µg/L chlorophyll-a and 2 × 10 cells/mL. Conclusions This data is the first to present concentrations of anabaenopeptins, cyanopeptolins, aeruginosins, and microginins, along with icrocystins, in U.K. reservoirs. A better understanding of those cyanopeptides that are abundant in drinking water reservoirs can inform future monitoring and studies on abatement efficiency during water treatment

Crocodylian head width allometry and phylogenetic prediction of body size in extinct crocodyliforms

Body size and body-size shifts broadly impact life-history parameters of all animals, which has made accurate body-size estimates for extinct taxa an important component of understanding their paleobiology. Among extinct crocodylians and their precursors (e.g., suchians), several methods have been developed to predict body size from suites of hard-tissue proxies. Nevertheless, many have limited applications due to the disparity of some major suchian groups and biases in the fossil record. Here, we test the utility of head width (HW) as a broadly applicable body-size estimator in living and fossil suchians. We use a dataset of sexually mature male and female individuals