Approaching ‘kit-type’ labelling with 68Ga: the DATA chelators

The DATA chelators are a novel class of tri-anionic ligands based on 6-amino-1,4-diazepine-triacetic acid, which have been introduced recently for the chelation of 68Ga. Compared with macrocyclic chelators based on the cyclen scaffold (i.e., DOTA, DO3A, and DO2A derivatives), DATA chelators undergo quantitative radiolabelling more rapidly and under milder conditions. In this study, a systematic evaluation of the labelling of four DATA chelators—DATAM, DATAP, DATAPh, and DATAPPh—with 68Ga is presented. The results highlight the extraordinary potential of this new class of chelators for application in molecular imaging using 68Ga positron emission tomography (PET)

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

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

Annual variation in Great Skua diets: The importance of commercial fisheries and predation on seabirds revealed by combining dietary analyses

This study combines conventional dietary assessment with stable isotope techniques to describe Great Skua (Stercorarius skua) diet. Stable carbon and nitrogen isotope ratios in feathers of Great Skua chicks collected over three years were analyzed in conjunction with pellet and regurgitate collection. A significant drop in trophic status was detected in 1997, which likely resulted from an increase in herring and mackerel in the diet. These items were almost certainly obtained from a commercial trawler, as evidenced by a significant drop in territorial attendance during the ship's absence. Feathers yielded significantly different delta C-13 values among years, and part of this may have been related to a period of enhanced phytoplankton growth during 1996. A combined approach, such as the one described here, is likely to become increasingly useful in elucidating the diets of polyphagous birds