Control of dinucleoside polyphosphates by the FHIT-homologous HNT2 gene, adenine biosynthesis and heat shock in Saccharomyces cerevisiae

BACKGROUND: The FHIT gene is lost early in the development of many tumors. Fhit possesses intrinsic ApppA hydrolase activity though ApppA cleavage is not required for tumor suppression. Because a mutant form of Fhit that is functional in tumor suppression and defective in catalysis binds ApppA well, it was hypothesized that Fhit-substrate complexes are the active, signaling form of Fhit. Which substrates are most important for Fhit signaling remain unknown. RESULTS: Here we demonstrate that dinucleoside polyphosphate levels increase 500-fold to hundreds of micromolar in strains devoid of the Saccharomyces cerevisiae homolog of Fhit, Hnt2. Accumulation of dinucleoside polyphosphates is reversed by re-expression of Hnt2 and is active site-dependent. Dinucleoside polyphosphate levels depend on an intact adenine biosynthetic pathway and time in liquid culture, and are induced by heat shock to greater than 0.1 millimolar even in Hnt2+ cells. CONCLUSIONS: The data indicate that Hnt2 hydrolyzes both ApppN and AppppN in vivo and that, in heat-shocked, adenine prototrophic yeast strains, dinucleoside polyphosphates accumulate to levels in which they may saturate Hnt2

The Grizzly, December 2, 2004

UC Students Opposed to Drunk Driving • Post-election Blues Give Rise to New Interest Group on Campus • Behind Closed Doors: Secret Places on Campus • Wheelchair Basketball Rolls in the Money • Upcoming Choir Concert • Interview with the President: Strassburger Shares Plans for Ursinus • Dance Company Concert a Success • Holly Singh Presents Mistaken Identity: Sikhs in America at Unity House • Major Highlight: Gender and Women\u27s Studies • Opinions: Enjoy Your Carbs this Holiday Season; Freedom on the Line • Pro Athletes Brawling with Fans • Men\u27s Basketball Season Heating Uphttps://digitalcommons.ursinus.edu/grizzlynews/1573/thumbnail.jp

The Grizzly, November 11, 2004

USGA Passes Sigma Pi • Two Students Wear Questionable Costumes • Lonnie Graham is the Spark • Ursinus Proposes Possible Plans for Honor Code • The Benefits for a Professor on Sabbatical • Effects of Election Still Resonate in Ursinus Community • Do Ursinus Students Make use of Proximity to Philadelphia? • Opinions: Is Online Dating a Safe Alternative for Meeting People or a Risky Plea of Desperation?; All is not Lost for Liberals • Field Hockey Team Wins Centennial Conference Title • It\u27s All Over for Three Women Soccer Players • The Collegeville Cursehttps://digitalcommons.ursinus.edu/grizzlynews/1571/thumbnail.jp

The Grizzly, September 9, 2004

Make a Difference: How to Register to Vote • Computer Thefts Under Investigation • Republicans say Yes to Four More Years with Bush • A Costly Look at Carelessness • STAR Sponsors One Night • Turnpike Tolls Increase for Commuters • Insider\u27s Tips to Undergraduate and Graduate Awards • Been to Synagogue Lately? • Safety First • Segregation by Letter? • The Pop-up Problem • UC Fringe Festival Opens Wednesday • Parking at Ursinus Robs Convenience • Opinions: Is Technology Making Life Easier or Lazier?; Life During Wartime; Lick it, Stamp it, Mail it and then Rock the Vote • 2004 Bears Football Outlook • UC Hires new Cross Country / Track & Field Coach • Now that Stanton is Gone: Men\u27s Basketball Preview • Bearcox Preview • Olympic Games: Competitive or Controversial?https://digitalcommons.ursinus.edu/grizzlynews/1563/thumbnail.jp

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

Identifying gaps in the photographic record of the vascular plant flora of the Americas

International audienceField photographs of plant species are crucial for research and conservation, but the lack of a centralized database makes them difficult to locate. We surveyed 25 online databases of field photographs and found that they harboured only about 53% of the approximately 125,000 vascular plant species of the Americas. These results reflect the urgent need for a centralized database that can both integrate and complete the photographic record of the world’s flora