Lloydhalberg3011

Background Omics technologies have been widely applied in toxicology studies to investigate the effects of different substances on exposed biological systems. A classical toxicogenomic study consists in testing the effects of a compound at different dose levels and different time points. The main challenge consists in identifying the gene alteration patterns that are correlated to doses and time points. The majority of existing methods for toxicogenomics data analysis allow the study of the molecular alteration after the exposure (or treatment) at each time point individually. However, this kind of analysis cannot identify dynamic (time-dependent) events of dose responsiveness. Results We propose TinderMIX, an approach that simultaneously models the effects of time and dose on the transcriptome to investigate the course of molecular alterations exerted in response to the exposure. Starting from gene log fold-change, TinderMIX fits different integrated time and dose models to each gene, selects the optimal one, and computes its time and dose effect map; then a user-selected threshold is applied to identify the responsive area on each map and verify whether the gene shows a dynamic (time-dependent) and dose-dependent response; eventually, responsive genes are labelled according to the integrated time and dose point of departure. Conclusions To showcase the TinderMIX method, we analysed 2 drugs from the Open TG-GATEs dataset, namely, cyclosporin A and thioacetamide. We first identified the dynamic dose-dependent mechanism of action of each drug and compared them. Our analysis highlights that different time- and dose-integrated point of departure recapitulates the toxicity potential of the compounds as well as their dynamic dose-dependent mechanism of action.The dendritic cell (DC) is recognized as a vital mediator of anti-tumor immunity. More recent studies have also demonstrated the important role of DCs in the generation of effective responses to checkpoint inhibitor immunotherapy. Metabolic programming of DCs dictates their functionality and can determine which DCs become immunostimulatory versus those that develop a tolerized phenotype capable of actively suppressing effector T-cell responses to cancers. As a result, there is great interest in understanding what mechanisms have evolved in cancers to alter these metabolic pathways, thereby allowing for their continued progression and metastasis. The therapeutic strategies developed to reverse these processes of DC tolerization in the tumor microenvironment represent promising candidates for future testing in combination immunotherapy clinical trials.Historically, the wheat stem sawfly, Cephus cinctus Norton was a pest in spring wheat-growing regions of the northern Great Plains. However, in the 1980s, it was found infesting winter wheat fields in Montana. Infestations were first detected in western Nebraska in the 1990s, and have since spread throughout the Nebraska Panhandle. Larval damage occurs from stem-mining, but stem girdling that results in lodged stems that are not harvested results in the greatest yield losses. The biology and phenology of the wheat stem sawfly are well described in the northern portion of its range, but they are lacking in Colorado, southeast Wyoming, and Nebraska. In this study, the phenology and dispersal of the wheat stem sawfly in Nebraska winter wheat fields is described using sweep net and larval sampling. During this 2-yr study, adult activity began on May 23 and ended on June 21. Adult sex ratios were 2.32 males per female in 2014 and 0.46 males per female in 2015. Both sexes demonstrated an edge effect within the wheat fields, with greater densities near the field edge. The edge effect was stronger for male wheat stem sawfly than females. Wheat stem sawfly larval density also had an edge effect, regardless of the density of female wheat stem sawfly present. This information will be useful for developing management plans for the wheat stem sawfly in Nebraska and neighboring regions.Insects are ecotothermic organisms. Their development, survival, reproduction as well as distribution and abundance are affected by temperature. Heat shock protein (HSP) gene expression is closely associated with temperature variation and influences the adaptation of organisms to adverse environments. The beetle Agasicles hygrophila has successfully been used for biological control of the invasive plant alligator weed (Alternanthera philoxeroides). As A. hygrophila populations are substantially inhibited by high temperatures in the summer, increasing global temperatures may limit the efficacy of this control agent. We previously established that A. hygrophila eggs have low tolerance to heat and this factored into the decreased numbers of A. hygrophila beetles at temperatures of 37.5°C and above. Bak protein Here, we identified 26 HSP genes in A. hygrophila and examined the relationship between the transcript levels of these genes and heat tolerance. The temperature at which the expression of these 21 HSP genes peaked (Tpeak) was 37.5°C, which is in line with the limit of the high temperatures that A. hygrophila eggs tolerate. Therefore, we speculate that the Tpeak of HSP gene expression in eggs indicates the upper limit of temperatures that A. hygrophila eggs tolerate. This study identifies HSP genes as potential robust biomarkers and emphasizes that determining species' heat tolerance in their natural habitats remains an important consideration for biocontrol. HSP gene expression data provide information about a species' heat tolerance and may be used to predict its geographical distribution.'There's antimony, arsenic, aluminum, selenium, and hydrogen, and oxygen, and nitrogen and rhenium'-so begins 'The Elements' song (https//www.youtube.com/watch?v=AcS3NOQnsQM), whereby Tom Lehrer (Fig. 1) assiduously deconstructed the many painstaking decades of research effort by scores of scientists in assembling the Periodic Table as primarily based upon the atomic numbers of the elements. Lehrer instead opted for his imaginative rhyme, with its musical meter purloined from the patter song of Major General Stanley ("I am the Very Model of a Modern Major General') as in the Gilbert and Sullivan's operetta 'The Pirates of Penzance'. By some coincidence, however, three of the four named in the first stanza are Group 15 and 16 elements with which I have considerable microbiological research experience. Only one is missing (tellurium). Hence, by futzing with Lehrer's 'libretto' to suit my own needs for this issue of FEMS, I would pose the following introductory re-rearrangement 'There's antimony, arsenic, selenium, tellurium, and cadmium, and chromium, and calcium and curium'.