Development of a Space Bioreactor using Microtechnology

A miniature bio-reactor for the cultivation of cells aboard Spacelab is presented. Yeast cells are grown in a 3 milliliter reactor chamber. A supply of fresh nutrient medium is provided by a piezo-electric silicon micro-pump. In the reactor, pH, temperature, and redox potential are monitored and the pH is regulated at a constant value. The complete instrument is fitted in a standard experiment container of 63 x 63 x 85 mm. The bioreactor was used on the IML-2 mission in July 1994 and is being refurbished for a reflight in the spring of 1996

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Photoproduction of pi(0)pi(0)- and pi(0)pi(+)-pairs off the proton from threshold to the second resonance region

Precise total cross-sections and invariant-mass distributions have been measured for photoproduction of pion pairs off the proton producing p pi(0)pi(0) and n pi(+)pi(0) final states from the threshold region up to 800 MeV incident photon energy. Additionally, beam helicity asymmetries have been measured in the second resonance region (550 MeV-820 MeV). The experiment was performed at the tagged photon beam of the Mainz MAMI accelerator with the Crystal Ball and TAPS detectors combined to give an almost 4 pi solid-angle electromagnetic calorimeter. The results are much more precise than any previous measurements and confirm the chiral perturbation theory predictions for the threshold behavior of these reactions. In the second resonance region, the invariant-mass distributions of meson-meson and meson-nucleon pairs are in reasonable agreement with model predictions, but none of the models reproduce the asymmetries for the mixed-charge channel

Incoherent neutral pion photoproduction on (12)C

We present the first detailed measurement of incoherent photoproduction of neutral pions to a discrete state of a residual nucleus. The (12)C(gamma,pi(0))(12)C(4.4 MeV)(*) reaction has been studied with the Glasgow photon tagger at MAMI employing a new technique which uses the large solid angle Crystal Ball detector both as a pi(0) spectrometer and to detect decay photons from the excited residual nucleus. The technique has potential applications to a broad range of future nuclear measurements with the Crystal Ball and similar detector systems elsewhere. Such data are sensitive to the propagation of the Delta in the nuclear medium and will give the first information on matter transition form factors from measurements with an electromagnetic probe. The incoherent cross sections are compared to two theoretical predictions including a Delta-hole model

Photoproduction of pi(0)eta on protons and the Delta(1700)D-33-resonance

Total and differential cross-sections for the reaction gamma p -> pi(0)eta p have been measured with the Crystal Ball/TAPS detector using the tagged photon facility at the MAMI C accelerator in Mainz. In the energy range E-gamma = 0.95-1.4 GeV the reaction is dominated by the excitation and sequential decay of the Delta(1700)D-33-resonance. Angular distributions measured with high statistics allow us to determine the ratio of hadronic decay widths Gamma(eta Delta)/Gamma pi S-11 and the ratio of the helicity amplitudes A(3/2)/A(1/2) for this resonance

Measurement of the slope parameter alpha for the eta → 3 pi(0) decay with the Crystal Ball detector at the Mainz Microtron (MAMI-C)

The dynamics of the eta -> 3 pi(0) decay have been studied with the Crystal Ball multiphoton spectrometer and the TAPS calorimeter. Bremsstrahlung photons produced by the 1.5-GeV electron beam of the Mainz microtron MAMI-C and tagged by the Glasgow photon spectrometer were used for eta-meson production. The analysis of 3x10(6) gamma p ->eta p -> 3 pi(0)p -> 6 gamma p events yields the value alpha=-0.032 +/- 0.003 for the eta -> 3 pi(0) slope parameter, which agrees with the majority of recent experimental results and has the smallest uncertainty. The pi(0)pi(0) invariant-mass spectrum was investigated for the occurrence of a cusplike structure in the vicinity of the pi(+)pi(-) threshold. The observed effect is small and does not affect our measured value for the slope parameter

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

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization 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