Aphid-Responsive Defense Networks in Hybrid Switchgrass

Aphid herbivory elicits plant defense-related networks that are influenced by host genetics. Plants of the upland switchgrass (Panicum virgatum) cultivar Summer can be a suitable host for greenbug aphids (Schizaphis graminum; GB), and yellow sugarcane aphids (Sipha flava, YSA), whereas the lowland cultivar Kanlow exhibited multi-species resistance that curtails aphid reproduction. However, stabilized hybrids of Summer (♀) x Kanlow (♂) (SxK) with improved agronomics can be damaged by both aphids. Here, hormone and metabolite analyses, coupled with RNA-Seq analysis of plant transcriptomes, were utilized to delineate defense networks induced by aphid feeding in SxK switchgrass and pinpoint plant transcription factors (TFs), such as WRKYs that potentially regulate these responses. Abscisic acid (ABA) levels were significantly higher in GB infested plants at 5 and 10 days after infestation (DAI). ABA levels were highest at 15DAI in YSA infested plants. Jasmonic acid levels were significantly elevated under GB infestation, while salicylic acid levels were signifi40cantly elevated only at 15 DAI in YSA infested plants. Similarly, levels of several metabolites were altered in common or specifically to each aphid. YSA infestation induced a significant enrichment of flavonoids consistent with an upregulation of many genes associated with flavonoid biosynthesis at 15DAI. Gene co-expression modules that responded singly to either aphid or in common to both aphids were differentiated and linked to specific TFs. Together, these data provide important clues into the interplay of metabolism and transcriptional remodeling accompanying defense responses to aphid herbivory in hybrid switchgrass

Transcriptional analysis of defense mechanisms in upland tetraploid switchgrass to greenbugs

Background: Aphid infestation of switchgrass (Panicum virgatum) has the potential to reduce yields and biomass quality. Although switchgrass-greenbug (Schizaphis graminum; GB) interactions have been studied at the whole plant level, little information is available on plant defense responses at the molecular level. Results: The global transcriptomic response of switchgrass cv Summer to GB was monitored by RNA-Seq in infested and control (uninfested) plants harvested at 5, 10, and 15 days after infestation (DAI). Differentially expressed genes (DEGs) in infested plants were analyzed relative to control uninfested plants at each time point. DEGs in GB-infested plants induced by 5-DAI included an upregulation of reactive burst oxidases and several cell wall receptors. Expression changes in genes linked to redox metabolism, cell wall structure, and hormone biosynthesis were also observed by 5- DAI. At 10-DAI, network analysis indicated a massive upregulation of defense-associated genes, including NAC, WRKY, and MYB classes of transcription factors and potential ancillary signaling molecules such as leucine aminopeptidases. Molecular evidence for loss of chloroplastic functions was also detected at this time point. Supporting these molecular changes, chlorophyll content was significantly decreased, and ROS levels were elevated in infested plants 10-DAI. Total peroxidase and laccase activities were elevated in infested plants at 10-DAI relative to control uninfested plants. The net result appeared to be a broad scale defensive response that led to an apparent reduction in C and N assimilation and a potential redirection of nutrients away from GB and towards the production of defensive compounds, such as pipecolic acid, chlorogenic acid, and trehalose by 10-DAI. By 15-DAI, evidence of recovery in primary metabolism was noted based on transcript abundances for genes associated with carbon, nitrogen, and nutrient assimilation. Conclusions: Extensive remodeling of the plant transcriptome and the production of ROS and several defensive metabolites in an upland switchgrass cultivar were observed in response to GB feeding. The early loss and apparent recovery in primary metabolism by 15-DAI would suggest that these transcriptional changes in later stages of GB infestation could underlie the recovery response categorized for this switchgrass cultivar. These results can be exploited to develop switchgrass lines with more durable resistance to GB and potentially other aphids

Analysis of two SMC HII Regions Considering Thermal Inhomogeneities: Implications for the Determinations of Extragalactic Chemical Abundances

We present long slit spectrophotometry considering the presence of thermal inhomogeneities (t^2) of two HII regions in the Small Magellanic Cloud (SMC): NGC 456 and NGC 460. Physical conditions and chemical abundances were determined for three positions in NGC 456 and one position in NGC 460, first under the assumption of uniform temperature and then allowing for the possibility of thermal inhomogeneities. We determined t^2 values based on three different methods: i) by comparing the temperature derived using oxygen forbidden lines with the temperature derived using helium recombination lines, ii) by comparing the abundances derived from oxygen forbidden lines with those derived from oxygen recombination lines, and iii) by comparing the abundances derived from ultraviolet carbon forbidden lines with those derived from optical carbon recombination lines. The first two methods averaged t^2=0.067+-0.013 for NGC 456 and t^2=0.036+-0.027 for NGC 460. These values of t^2 imply that when gaseous abundances are determined with collisionally excited lines they are underestimated by a factor of nearly 2. From these objects and others in the literature, we find that in order to account for thermal inhomogeneities and dust depletion, the O/H ratio in low metallicity HII regions should be corrected by 0.25-0.45 dex depending on the thermal structure of the nebula, or by 0.35 dex if such information is not available.Comment: Accepted for publication in The Astrophysical Journal. 41 pages in pre-print format. 3 figure

Prevalence of major depression in preschool children

The prevalence of preschool major depressive disorder (MDD) was studied in the community. The whole population of children between 3 and 6 years attending preschool nurseries in three areas (one urban, one rural and one suburban) in Spain (n = 1,427) were contacted. Selection was by a two-stage procedure. At stage I, the ESDM 3-6, a screening measure for preschool depression, was used to identify a sample for more intensive interviewing. Sensitivity and specificity of the cut-off point of the ESDM 3–6 had been previously tested in a pilot study (n = 229). During the first stage, 222 preschool children (15.6%) were found to be probable depressives, because they scored 27 or more, the cut-off used. At stage II, the children were interviewed and diagnosed by the consensus of two clinicians, blind to the ESDM 3-6 results. DSM-IV diagnostic criteria were used to define caseness. A total of 16 children (1.12%) met the MDD criteria. The prevalence by areas was urban 0.87%, rural 0.88%, suburban 1.43%. Sex distribution prevalence was 1:1. This study is a contribution to the scarce epidemiology of preschool depression in the community

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Evaluation of Greenbug and Yellow Sugarcane Aphid Feeding Behavior on Resistant and Susceptible Switchgrass Cultivars

Switchgrass (Panicum virgatum L.) is an emerging biofuel crop that serves as host for aphids. To discern the effects of plant age and possible resistance mechanisms, the feeding behavior of greenbugs (Schizaphis graminum Rondani.) and the yellow sugarcane aphid (Sipha flava Forbes.) was monitored on three diverse switchgrasses by the electrical penetration graph (EPG) technique. Callose deposition and genes associated with callose metabolism were also analyzed to discern their association with plant resistance. There was a strong host effect on greenbugs feeding on lowland cultivar Kanlow at the V3 stage of development, as compared to the greenbug-susceptible upland cultivar Summer and plants derived from Kanlow (♂) × Summer (♀) (K×S) crosses. These data confirmed that Kanlow at the V3 stage had antibiosis to greenbugs, which was absent in the Summer and K×S plants. In contrast, similar effects were not observed for yellow sugarcane aphids, excluding significant differences in the time to first probe on Kanlow plants at the V1 stage and reduction in time spent on pathway processes on Kanlow plants at the V3 stage. These data demonstrated that Kanlow plants may have multiple sources of resistance to the two aphids, and possibly some were phloem based. Microscopy of leaf sections stained with aniline blue for callose was suggestive of increased callose deposition in the sieve elements in Kanlow plants relative to Summer and K×S plants. RT-qPCR analysis of several genes associated with callose metabolism in infested plants was equivocal. Overall, these studies suggest the presence of multiple defense mechanisms against aphids in Kanlow plants, relative to Summer and K×S plants

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice