Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast‐cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow‐cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions. SCCs display enhanced invasion and chemoresistance, suggesting their important role in tumor recurrence. SCCs also demonstrate increased lipid contents that are specifically metabolized under glucose‐deprived conditions. Fatty acid transport in SCCs is targetable by pharmacological inhibition or genomic deletion of FABP7, both of which sensitize SCCs to metabolic stress. Furthermore, FABP7 inhibition, whether alone or in combination with glycolysis inhibition, leads to overall increased survival. Our studies reveal the existence of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7‐related metabolic pathways is a viable therapeutic strategy.

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The overall objective of this study was to study the influence of induced estrus on body temperature, comparing 5 distinct intervals around induced estrus and to determine the diurnal pattern from 4 ± 1 d before to 4 ± 1 d after induced estrus. Sixteen estrous cycles of 9 postpartum dairy cows were synchronized with 2 injections of PGF(2α), 10 d apart. After the second PGF(2α) injection on d 10, temperature loggers were inserted into the vaginal cavity for a 12 ± 1-d period. Two days later, a third dose of PGF(2α) was injected to induce estrus. After confirmation of a corpus luteum, loggers were removed on d 5 ± 1. Observation of estrus, rectal palpation, and ultrasound scanning to determine ovulation were carried out every 4 ± 1h, beginning at 12h after the third PGF(2α) injection. Blood samples from the vena coccygea mediana were collected twice daily from d 11 to 12 and every 4 ± 1h after the third PGF(2α) injection until ovulation. Vaginal temperature was recorded every 5 min and averaged to hourly means for the following 5 periods: 1) 48 h preceding the third PGF(2α) injection, 2) from the third PGF(2α) injection to first signs of estrus, 3) estrus to ovulation, 4) a 4-h interval in which ovulation occurred, and 5) a 96-h post-ovulation period. High body temperatures (39.0 ± 0.5 °C) and low progesterone (P4) concentrations (<0.5 ng/mL) were observed during estrus, whereas low body temperatures were observed from PGF(2α) injection to estrus (38.6 ± 0.3 °C) and around ovulation (38.5 ± 0.2 °C), respectively. An association between body temperature and serum P4 concentrations did not exist. However, P4 concentrations on d 11 and 12 were high (5.0 ± 1.5 ng/mL) and decreased (0.9 ± 0.2 ng/mL) after ovulation. Diurnal temperature rhythms were similar before and after estrus. Vaginal temperature before estrus (d 11 and 12) was slightly (0.1 °C) higher compared with the post-ovulation period.

Early blight, caused by Alternaria solani, is an economically important foliar disease of potato in several production areas of the United States. Few potato cultivars possess resistance to early blight; therefore, the application of fungicides is the primary means of achieving disease control. Previous work in our laboratory reported resistance to the succinate dehydrogenase-inhibiting (SDHI) fungicide boscalid in this plant pathogen with a concomitant loss of disease control. Two phenotypes were detected, one in which A. solani isolates were moderately resistant to boscalid, the other in which isolates were highly resistant to the fungicide. Resistance in other fungal plant pathogens to SDHI fungicides is known to occur due to amino acid exchanges in the soluble subunit succinate dehydrogenase B (SdhB), C (SdhC), and D (SdhD) proteins. In this study, the AsSdhB, AsSdhC, and AsSdhD genes were analyzed and compared in sensitive (50% effective concentration [EC50] < 5 μg ml(-1)), moderately resistant (EC50 = 5.1 to 20 μg ml(-1)), highly resistant (EC50 = 20.1 to 100 μg ml(-1)), and very highly resistant (EC50 > 100 μg ml(-1)) A. solani isolates. In total, five mutations were detected, two in each of the AsSdhB and AsSdhD genes and one in the AsSdhC gene. The sequencing of AsSdhB elucidated point mutations cytosine (C) to thymine (T) at nucleotide 990 and adenine (A) to guanine (G) at nucleotide 991, leading to an exchange from histidine to tyrosine (H278Y) or arginine (H278R), respectively, at codon 278. The H278R exchange was detected in 4 of 10 A. solani isolates moderately resistant to boscalid, exhibiting EC50 values of 6 to 8 μg ml(-1). Further genetic analysis also confirmed this mutation in isolates with high and very high EC50 values for boscalid of 28 to 500 μg ml(-1). Subsequent sequencing of AsSdhC and AsSdhD genes confirmed the presence of additional mutations from A to G at nucleotide position 490 in AsSdhC and at nucleotide position 398 in the AsSdhD, conferring H134R and H133R exchanges in AsSdhC and AsSdhD, respectively. The H134R exchange in AsSdhC was observed in A. solani isolates with sensitive, moderate, highly resistant, and very highly resistant boscalid phenotypes, and the AsSdhD H133R exchange was observed in isolates with both moderate and very high EC50 value boscalid phenotypes. Detection and differentiation of point mutations in AsSdhB resulting in H278R and H278Y exchanges in the AsSdhB subunit were facilitated by the development of a mismatch amplification mutation assay. Detection of these two mutations in boscalid-resistant isolates, in addition to mutations in AsSdhC and AsSdhD resulting in an H134R and H133R exchange, respectively, was achieved by the development of a multiplex polymerase chain reaction to detect and differentiate the sensitive and resistant isolates based on the single-nucleotide polymorphisms present in all three genes. A single A. solani isolate with resistance to boscalid did not contain any of the above-mentioned exchanges but did contain a substitution of a...

Tan spot, caused by Pyrenophora tritici‐repentis, is an important disease of wheat (Triticum aestivum L.) worldwide. Pathogenic races of P. tritici‐repentis have been identified on the basis of their ability to induce tan necrosis and/or chlorosis symptoms on differential wheat genotypes. A group of isolates of P. tritici‐repentis collected from Arkansas did not fit into the current race classification system because they lack the ToxA gene. In this study, 535 spring wheat accessions were inoculated with a representative novel isolate (AR CrossB10) of P. tritici‐repentis from Arkansas. An association mapping approach and 832 polymorphic diversity array technology markers were used to identify quantitative trait loci (QTL) associated with resistance to the isolate AR CrossB10. Two models (QK1 and QK2) with the least mean square difference were selected among nine linear regression models tested, and 11 QTL involved in resistance to AR CrossB10 were identified, which are located on chromosomes 1A, 1D, 2B, 2D, 6A, and 7A. The results suggest that multiple disease resistance genes also are clustered around a few of the significant markers and will be useful for wheat breeding programs and for search of candidate genes.

The toxin sensitivity gene Tsn1 interacts with Ptr ToxA (ToxA), a host-selective toxin produced by the necrotrophic fungus Pyrenophora tritici-repentis. The molecular mechanisms associated with cell death in sensitive wheat cultivars following ToxA application are not well understood. To address this question, we used the Affymetrix GeneChip Wheat Genome Array to compare gene expression in a sensitive wheat cultivar possessing the Tsn1 gene with the insensitive wheat cv. Nec103, which lacks the Tsn1 gene. This analysis was performed at early timepoints after infiltration with ToxA (e.g., 0.5 to 12 h postinfiltration [hpi]); at this time, ToxA is known to internalize into mesophyll cells without visible cell death symptoms. Gene expression also was monitored at later timepoints (24 to 48 hpi), when ToxA causes extensive damage in cellular compartments and visible cell death. At both early and late timepoints, numerous defense-related genes were induced (2- to 197-fold increases) and included genes involved in the phenylpropanoid pathway, lignification, and the production of reactive oxygen species (ROS). Furthermore, a subset of host genes functioning in signal transduction, metabolism, and as transcription factors was induced as a consequence of the Tsn1-ToxA interaction. Nine genes known to be involved in the host defense response and signaling pathways were selected for analysis by quantitative real-time polymerase chain reaction, and the expression profiles of these genes confirmed the results obtained in microarray experiments. Histochemical analyses of a sensitive wheat cultivar showed that H(2)O(2) was present in leaves undergoing cell death, indicating that ROS signaling is a major event involved in ToxA-mediated cell death. The results suggest that recognition of ToxA via Tsn1 triggers transcriptional reprogramming events similar to those reported for avirulence-resistance gene interactions, and that host-derived genes play an important role in the modulation of susceptibility to P. tritici-repentis.

Tan spot (caused by Pyrenophora tritici‐repentis) and Stagonospora nodorum blotch (SNB), (caused by Phaeosphaeria nodorum) are destructive diseases of wheat (Triticum aestivum L.). The majority of currently grown wheat varieties are susceptible to both diseases, presumably because of high pathogenic variability occurring in these fungi or narrow genetic background for resistance in wheat varieties. Therefore, identifying new sources of tan spot and SNB resistance in wheat is imperative. A subset of 825 wheat accessions from the core collection of the National Small Grains Collection (NSGC) of the United States Department of Agriculture, National Plant Germplasm System (NPGS) was evaluated for resistance to tan spot and SNB at seedling stage in a growth chamber. On the basis of disease reactions, 88 wheat accessions exhibited resistance to both diseases. Data from the Germplasm Resources Information Network (GRIN) were examined for the 88 accessions to identify those that also have resistance to other key diseases and on this basis 28 accessions with multiple resistances were identified. The genetic relationship among the 88 accessions was assessed using resistance gene analog polymorphism (RGAP) primers. Wheat accessions with similar growth habit were grouped together despite differences in country of origin. Associations between agronomic traits and host resistance indicated that winter wheat habit in the studied collection was strongly associated with both SNB and tan spot resistance. This study identified genetically diverse wheat accessions with broad‐spectrum resistance that can be used in developing cultivars with high levels of resistance to multiple diseases in wheat breeding programs.

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