icroenvironment restores this malignant property of cancer cells during hormone therapy.Amplification and overexpression of the MYC oncogene in tumor cells, including ovarian cancer cells, correlates with poor responses to chemotherapy. As MYC is not directly targetable, we have analyzed molecular pathways downstream of MYC to identify potential therapeutic targets. Here we report that ovarian cancer cells overexpressing glutaminase (GLS), a target of MYC and a key enzyme in glutaminolysis, are intrinsically resistant to platinum-based chemotherapy and are enriched with intracellular antioxidant glutathione. Deprivation of glutamine by glutamine-withdrawal, GLS knockdown, or exposure to the GLS inhibitor CB-839 resulted in robust induction of reactive oxygen species in high GLS-expressing but not in low GLS-expressing ovarian cancer cells. Treatment with CB-839 rendered GLShigh cells vulnerable to the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, and prolonged survival in tumor-bearing mice. These findings suggest consideration of applying a combined therapy of GLS inhibitor and PARP inhibitor to treat chemoresistant ovarian cancers, especially those with high GLS expression. SIGNIFICANCE Targeting glutaminase disturbs redox homeostasis and nucleotide synthesis and causes replication stress in cancer cells, representing an exploitable vulnerability for the development of effective therapeutics. GRAPHICAL ABSTRACT http//cancerres.aacrjournals.org/content/canres/80/20/4514/F1.large.jpg.Six steers were used to study the effects of dietary supplementation with sodium sulfate (Na2SO4) on rumen fermentation, nutrient digestion, rumen microbiota, and plasma metabolites. The animals were fed a basal ration with Na2SO4 added at 0 g/day (sulfur [S] content of 0.115% dry matter [DM]), 20 g/day (S at 0.185% DM), or 40 g/day (S at 0.255% DM) in a replicate 3-by-3 Latin square design. The results indicated that supplementing with Na2SO4 increased the ruminal concentration of total volatile fatty acids, the molar proportions of acetate and butyrate, the ruminal concentrations of microbial protein, SO42--S, and S2--S, and the digestibility of fiber, while it decreased the molar proportion of propionate and the ruminal concentration of ammonia nitrogen. Supplementing with Na2SO4 increased the diversity and the richness of rumen microbiota and the relative abundances of the phylum Firmicutes and genera Ruminococcus 2, Rikenellaceae RC9 gut group, and Desulfovibrio, whereas it decreased the relative abundan through effects on the ruminal microbiome. The facts obtained from the present trial clarified the possible mechanisms of the positive effects of sulfur on rumen fermentation and nutrient utilization.Western Lake Erie (Laurentian Great Lakes) is prone to annual cyanobacterial harmful algal blooms (cHABs) dominated by Microcystis spp. that often yield microcystin toxin concentrations exceeding the federal EPA recreational contact advisory of 8 μg liter-1 In August 2014, microcystin levels were detected in finished drinking water above the World Health Organization 1.0 μg liter-1 threshold for consumption, leading to a 2-day disruption in the supply of drinking water for >400,000 residents of Toledo, Ohio (USA). Subsequent metatranscriptomic analysis of the 2014 bloom event provided evidence that release of toxin into the water supply was likely caused by cyanophage lysis that transformed a portion of the intracellular microcystin pool into the dissolved fraction, rendering it more difficult to eliminate during treatment. In August 2019, a similar increase in dissolved microcystins at the Toledo water intake was coincident with a viral lytic event caused by a phage consortium different in composition from we dominating Microcystis spp. are capable of producing microcystins. Detecting, characterizing, and quantifying the major cyanophages involved in lytic events will assist water treatment plant operators in making rapid decisions regarding the pool of microcystins entering the plant and the corresponding best practices to neutralize the toxin.Environmental nontuberculous mycobacteria (NTM), with the potential to cause opportunistic lung infections, can reside in soil. This might be particularly relevant in Hawai'i, a geographic hot spot for NTM infections and whose soil composition differs from many other areas of the world. Soil components are likely to contribute to NTM prevalence in certain niches as food sources or attachment scaffolds, but the particular types of soils, clays, and minerals that impact NTM growth are not well-defined. Hawai'i soil and chemically weathered rock (saprolite) samples were examined to characterize the microbiome and quantify 11 mineralogical features as well as soil pH. Machine learning methods were applied to identify important soil features influencing the presence of NTM. Next, these features were directly tested in vitro by incubating synthetic clays and minerals in the presence of Mycobacteroides abscessus and Mycobacterium chimaera isolates recovered from the Hawai'i environment, and changes in bacterial grow minerals that promote NTM growth in vitro Because Hawai'i is a hot spot for NTM and a unique geographic archipelago, we examined the composition of Hawai'i soil and identified individual clay, iron, and manganese minerals associated with NTM. Next, individual components were evaluated for their ability to directly modulate NTM growth in culture. In general, gibbsite and some manganese oxides were shown to decrease NTM, whereas iron-containing minerals were associated with higher NTM counts. These data provide new information to guide future analyses of soil-associated factors impacting persistence of these soil bacteria.Whole grains are generally low in nondigestible carbohydrates that are available for fermentation by the gut microbiota, or microbiota-accessible carbohydrates (MAC). However, there is potential to increase MAC in whole grains through food processing. Five processing methods boiling, extrusion, sourdough bread, unleavened bread, and yeast bread, were applied to whole wheat flour and then subjected to in vitro digestion followed by fermentation using fecal microbiomes from 10 subjects. The microbiomes separated into 2 groups those that showed high carbohydrate utilization (CU) and those that exhibited low CU. https://www.selleckchem.com/products/act001-dmamcl.html The former exhibited not only enhanced CU but also increased butyrate production (MAC, 31.1 ± 1.1% versus 19.3 ± 1.2%, P  less then  0.001; butyrate, 5.26 ± 0.26 mM versus 3.17 ± 0.27 mM, P  less then  0.001). Only the microbiomes in the high-CU group showed significant differences among processing methods extrusion and sourdough bread led to dichotomous results for MAC and short-chain fatty acid production, where extrusion resulted in high MAC but low butyrate production while sourdough bread resulted in low MAC but high butyrate production.