Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Interactions between Streptococcus pneumoniae and influenza virus: a mutually beneficial relationship?

Item does not contain fulltextHistorically, most research on infectious diseases has focused on infections with single pathogens. However, infections with pathogens often occur in the context of pre-existing viral and bacterial infections. Clinically, this is of particular relevance for coinfections with Streptococcus pneumoniae and influenza virus, which together are an important cause of global morbidity and mortality. In recent years new evidence has emerged regarding the underlying mechanisms of influenza virus-induced susceptibility to secondary pneumococcal infections, in particular regarding the sustained suppression of innate recognition of S. pneumoniae. Conversely, it is also increasingly being recognized that there is not a unidirectional effect of the virus on S. pneumoniae, but that asymptomatic pneumococcal carriage may also affect subsequent influenza virus infection and the clinical outcome. Here, we will review both aspects of pneumococcal influenza virus infection, with a particular focus on the age-related differences in pneumococcal colonization rates and invasive pneumococcal disease.1 mei 201

Geology and Ore Deposits of the Superior Mining Area, Arizona

The Superior mining area is in northeastern Pinal County, Arizona (Fig. 1). The area was officially organized as the Pioneer mining district but is better known as the Superior mining area. Superior, the principal settlement within the area, in 1940had a population of about 5,000,depending principally upon operations of the Magma Copper Company. The old town of Silver King, now largely deserted, was at the Silver King mine, in the northern part of the area shown on Plate 1. The Magma Arizona Railroad, 35 miles long, extends from Superior to Magma, a station on the Winkelman branch of the Southern Pacific, 9 miles west of Florence. It is maintained by the Magma Copper Company. Superior is on U.S. Highway 70, about 64 miles east of Phoenix and 20 miles west of Miami. A graveled state highway extends from Superior to Ray, 15 miles south. A graded county road 7 miles long connects Superior with Silver King. Various secondary roads lead to ranches and mines. 159 p.Oversized plates are marred by vertical scanner artifact lines.Documents in the AZGS Document Repository collection are made available by the Arizona Geological Survey (AZGS) and the University Libraries at the University of Arizona. For more information about items in this collection, please contact [email protected]

Criterios para las Relaciones de Edad de los Minerales con Especial Referencias a Cortes Pulidos de Minerales Metalíferos

Fil: Bastin, E.S.Fil: Graton, L.C.Fil: Lindgren, W.Fil: Newhouse, W.H.Fil: Schwartz, G.M.Fil: Short, M.N.Traducido y condensado de Economic Geology T.XXVI 1931 por los doctores Natalia I. Rossi, Fernando L. Sesana y Jorge A. Valvano

Influenza A virus induced bacterial otitis media is independent of virus tropism for alpha2,6-linked sialic acid.

BACKGROUND: Otitis media (OM) affects >/=80% of children before the age of three. OM can arise following co-infection with influenza A virus (IAV) and the bacterium Streptococcus pneumoniae. We have previously shown that H3 IAV strains (such as Udorn/72) induced a higher rate of bacterial OM than H1 strains (such as PR8/34). This was associated with more efficient replication of H3 strains in the middle ear. FINDINGS: Here, we assess if the increased replication of IAV strains such as Udorn/72 in the middle ear is dependent upon the binding of the viral HA to alpha2,6-linked sialic acid. Using murine and in vitro models, the present study shows that recognition of alpha2,6-linked sialic acid was not required to facilitate bacterial OM. CONCLUSIONS: Taken together, these data suggest that other features of the HA mediate bacterial OM

Biocontrol of Pythium in the pea rhizosphere by antifungal metabolite producing and non-producing Pseudomonas strains

The definitive version is available at www.blackwell-synergy.com. Copyright Blackwell Publishing DOI : 10.1046/j.1365-2672.2001.01260.xFour well-described strains of Pseudomonas fluorescens were assessed for their effect upon pea growth and their antagonistic activity against large Pythium ultimum inocula. The effect of Pseudomonas strains upon the indigenous soil microflora, soil enzyme activities and plant growth in the presence and absence of Pythium is assessed. Pythium inoculation reduced the shoot and root weights, root length, and the number of lateral roots. The effect of Pythium was reduced by the Pseudomonas strains as follows: F113, SBW25 and CHAO increased the shoot weights (by 20%, 22% and 35% respectively); strains Q2-87, SBW25 and CHAO increased root weights (14%, 14% and 52%); Strains SBW25 and CHAO increased the root lengths (19% and 69%), and increased the number of lateral roots (14% and 29%). All the Pseudomonas strains reduced the number of lesions and the root and soil Pythium populations, whilst SBW25 and CHAO increased the number of lateral roots. Pythium inoculation increased root and soil microbial populations but the magnitude of this effect was Pseudomonas strain specific. Pythium increased the activity of C, N and P cycle enzymes, whilst the Pseudomonas strains reduced this effect, indicating reduced plant damage. Overall, strains SBW25 and CHAO had the greatest beneficial characteristics as these strains produced the greatest reductions in the side effects of Pythium infection (microbial populations and enzyme activities) and resulted in significantly improved plant growth. Surprisingly strain SBW25 does not produce antifungal metabolites, and its biocontrol activity was related to a greater colonisation ability in the rhizosphere.Peer reviewe

Some Arizona Ore Deposits

The principal ore deposits of Arizona are in the southern, central, and western portions of the state, which physiographically are part of the Basin and Range province, southwest of the Colorado Plateau (PI. I). The Basin and Range province is characterized by numerous subparallel mountain ranges separated by plains or valleys. Most of these ranges trend northwest to north, parallel to the margin of the Colorado Plateau; but in southeastern Arizona, southern New Mexico, and northeastern Sonora, they trend northward, transverse to the edge of the Plateau. The mountains rise abruptly from plains or valleys, the margins of which in many places are pediments cut on hard rock. Some of the plains form closed basins (bolsons, playas), but most of them are drained. The Basin and Range province in Arizona is divisible into the Mountain Region and the Desert Region- (PIs. I and II). The Mountain Region forms a belt 60 to 100 miles wide that contains most of the large ore deposits. Its longest range measures about 55 miles, the widest 20 miles, and the highest peak more than 10,000 feet above sea level or 7,000 feet above adjacent valleys or plains. Broad plain-forming valleys are exceptional, but several with maximum widths of 20 to more than 30 miles appear in the southeastern portion. 136 p.Missing PlatesDocuments in the AZGS Document Repository collection are made available by the Arizona Geological Survey (AZGS) and the University Libraries at the University of Arizona. For more information about items in this collection, please contact [email protected]