Publications by authors named "Eric Chiles"

Rising sea surface temperatures are increasingly causing breakdown in the nutritional relationship between corals and algal endosymbionts (Symbiodiniaceae), threatening the basis of coral reef ecosystems and highlighting the critical role of coral reproduction in reef maintenance. The effects of thermal stress on metabolic exchange (i.e.

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Changes in an organism's environment, genome, or gene expression patterns can lead to changes in its metabolism. The metabolic phenotype can be under selection and contributes to adaptation. However, the networked and convoluted nature of an organism's metabolism makes relating mutations, metabolic changes, and effects on fitness challenging.

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Changes in an organism's environment, genome, or gene expression patterns can lead to changes in its metabolism. The metabolic phenotype can be under selection and contributes to adaptation. However, the networked and convoluted nature of an organism's metabolism makes relating mutations, metabolic changes, and effects on fitness challenging.

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Unlabelled: T-cell acute lymphoblastic leukemia (T-ALL) is a NOTCH1-driven disease in need of novel therapies. Here, we identify a NOTCH1-SIRT1-KAT7 link as a therapeutic vulnerability in T-ALL, in which the histone deacetylase SIRT1 is overexpressed downstream of a NOTCH1-bound enhancer. SIRT1 loss impaired leukemia generation, whereas SIRT1 overexpression accelerated leukemia and conferred resistance to NOTCH1 inhibition in a deacetylase-dependent manner.

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Coral bleaching, precipitated by the expulsion of the algal symbionts that provide colonies with fixed carbon is a global threat to reef survival. To protect corals from anthropogenic stress, portable tools are needed to detect and diagnose stress syndromes and assess population health prior to extensive bleaching. Here, medical grade Urinalysis strips, used to detect an array of disease markers in humans, were tested on the lab stressed Hawaiian coral species, Montipora capitata (stress resistant) and Pocillopora acuta (stress sensitive), as well as samples from nature that also included Porites compressa.

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Dietary fructose, especially in the context of a high-fat western diet, has been linked to type 2 diabetes. Although the effect of fructose on liver metabolism has been extensively studied, a significant portion of the fructose is first metabolized in the small intestine. Here, we report that dietary fat enhances intestinal fructose metabolism, which releases glycerate into the blood.

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Article Synopsis
  • Corals are essential for diverse reef ecosystems and are threatened by warming oceans, so the study investigates the thermal stress response of Hawaiian rice coral during a spawning event.
  • Researchers analyzed transcriptomic and polar metabolomic data over 5 weeks to identify thermal stress-related genes and metabolites, aiming to understand gene-metabolite interactions and their potential as markers of stress.
  • Findings showed that thermal stress affects various biological functions in corals, expanding gene co-expression networks and leading to suppressed metabolite transport as the coral approaches bleaching.
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NAD is an essential coenzyme for all living cells. NAD concentrations decline with age, but whether this reflects impaired production or accelerated consumption remains unclear. We employed isotope tracing and mass spectrometry to probe age-related changes in NAD metabolism across tissues.

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The brush border is comprised of microvilli surface protrusions on the apical surface of epithelia. This specialized structure greatly increases absorptive surface area and plays crucial roles in human health. However, transcriptional regulatory networks controlling brush border genes are not fully understood.

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  • T-cell acute lymphoblastic leukemia (T-ALL) is a serious blood cancer with high relapse rates despite improved chemotherapy.
  • Researchers explored a new compound, MB1-47, that disrupts mitochondrial function and shows promising anti-cancer effects by hindering cell growth and nucleotide synthesis in T-ALL cells.
  • MB1-47 not only activated important cellular energy regulators but also improved survival rates in mouse models of T-ALL, indicating potential as a new treatment approach with fewer side effects.
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  • Understanding how coral holobionts react to environmental changes is vital for effective conservation, especially in the context of coral bleaching caused by thermal stress.
  • Using untargeted metabolite profiling, researchers studied the physiological responses of coral species to heat stress with the aim of finding early markers for bleaching.
  • The study identified specific co-regulated dipeptides that vary between symbiotic and aposymbiotic populations of the sea anemone Aiptasia, indicating their potential as diagnostic markers for thermal stress in wild corals.
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A large proportion of the complexity and redundancy of LC-MS metabolomics data comes from adduct formation. To reduce such redundancy, many tools have been developed to recognize and annotate adduct ions. These tools rely on predefined adduct lists that are generated empirically from reversed-phase LC-MS studies.

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  • The study explores how transcription factors HNF4A and HNF4G regulate metabolism and the functioning of intestinal stem cells (ISCs) in mice.
  • The researchers used specific transgenic mouse lines to analyze the impact of fatty acid absorption and metabolism on the expression of stem cell markers.
  • They found that fatty acid oxidation (FAO) is crucial for ISC renewal, and while individually knocking out HNF4A or HNF4G didn't affect ISCs, their combined knockout led to significant declines in ISC function.
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  • Glutamine helps fuel cancer cell metabolism by converting to α-ketoglutarate (aKG), which supports the tricarboxylic acid (TCA) cycle necessary for energy production.
  • In pancreatic ductal carcinoma (PDAC) cells, restoring aKG can aid survival when glutamine is low, but this process requires the enzyme glutamate ammonia ligase (GLUL), which synthesizes glutamine.
  • Elevated levels of GLUL in PDAC samples suggest its crucial role in tumor growth, as disabling GLUL can hinder tumor development in models of pancreatic cancer.
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Gluconeogenesis (GNG) is production of glucose from endogenous carbon sources. Although it is a commonly studied pathway, particularly in disease, there is a lack of consensus about substrate preference. Moreover, primary hepatocytes are the current gold standard for liver studies, but no direct comparison of substrate preference at physiological fasting concentrations has been performed.

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Glucose and glycerol are important circulating metabolites. Due to poor ionization and/or ion suppression, the liquid chromatography-mass spectrometry (LC-MS) detection of glucose and glycerol presents challenges. Here, we propose an efficient LC-MS method of quantitative glucose and glycerol detection via enzymatic derivatization to glucose-6-phosphate and sn-glycerol-3-phosphate, respectively.

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