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

A review of new developments in type 2 diabetes in human beings and cats

Cats appear to be one of the few non-human species that develop a type of diabetes mellitus analogous to human Type 2, or non-insulin-dependent diabetes mellitus (NIDDM). In this review, some current theories on diabetogenesis are discussed. In both cats and human beings, Type 2 diabetes is characterized by impaired insulin secretion due to a functional defect in pancreatic -cells, and insulin resistance. In both species, amyloid deposition occurs in pancreatic islets and is derived from the newly discovered pancreatic hormone islet amyloid polypeptide (IAPP), or amylin. Amylin also reduces insulin secretion and induces insulin resistance. Thus, the hypothesis of amylin being intimately involved in the pathogenesis of human and feline Type 2 diabetes appears justified. Obesity is a frequent concomitant problem in feline and human Type 2 diabetes and contributes to the insulin resistance characteristic of the disease

Comparison of five commercial radioimmunoassay kits for the measurement of feline insulin

Five commercial RIA kits designed to measure human insulin concentrations were compared for their ability to measure feline insulin. Kit evaluation included dilutional parallelism for specificity, sensitivity and intra- and interassay precision. Three kits (RSL, Diagnostic Products and Pharmacia) performed well and can be recommended for use in cats. Two kits (Corning and Amersham) had poor specificity and precision and are not suitable for use in cats

Frequency of pancreatic amyloid deposition in cats from south-eastern Queensland.

Stereological procedures were used to estimate the amount of amyloid deposition in the pancreatic islets of 83 cats from random sources in south-eastern Queensland. Most had only minor deposits of less than 20% of islet volume (median 9%), but deposits equal to more than 50% of the islet volume were found in 10% of the cats. Amyloid deposition in pancreatic islets was correlated with the age of the cat. Although similar observations have been made previously in cats from the USA, the frequency of amyloid deposition was higher in this population of cats from south-eastern Queensland

The landscape context of trophic interactions : insect spillover across the crop-noncrop interface

Landscape structure influences local diversity and ecosystem processes, including cross-habitat fluxes of organisms coupling the dynamics of different habitats. The flow of organisms across system boundaries is known to occur between different natural habitats as well as across the crop¿noncrop interface. Several studies show how field boundaries can enhance predator populations invading arable crops and controlling pest populations. However, generalist arthropods may also spill over from land-use systems to natural areas (mainly grassland) modifying interactions therein. A view of land-use systems as sources and natural habitats as sinks is consistent with the idea that the direction of the organismsâ¿¿ fluxes is from high to low productivity systems, while noncrop habitats are important sources for recolonization of arable fields after they are cleared for harvest. From the perspective of landscape management, enhancement of population exchanges between crop and noncrop areas may include beneficial as well as unwelcome interaction

Glargine and protamine zinc insulin have a longer duration of action and result in lower mean daily glucose concentrations than lente insulin in healthy cats

The pharmacological effects of glargine, protamine zinc (PZI), and lente insulins were evaluated in nine healthy cats. A 3-way crossover study was performed and plasma concentrations of insulin and glucose were determined for 24 h after a single subcutaneous injection of each insulin at 3-day intervals. Time to onset of action did not differ between insulins. Mean time to first nadir glucose was longer for glargine (14 h) relative to PZI (4 h) and lente (5 h). PZI was biphasic in action with nadirs at 4 and 14 h with the second nadir occurring at a similar time to glargine. Nadir glucose did not differ significantly between insulin types. The duration of action was similar for glargine and PZI and was longer than that for lente insulin. Mean daily glucose after glargine and PZI were also similar and were lower than after lente insulin. Time to reach peak insulin did not differ between insulin types. Time to return to baseline insulin level for PZI was longer than glargine but did not differ significantly from lente. In conclusion, healthy cats injected subcutaneously with glargine, compared to those injected with lente insulin, have a later glucose nadir and longer duration of action. Glargine and PZI had similar durations of action in study cats but a larger study is required to obtain precise comparisons of duration of action

Conservation biological control and enemy diversity on a landscape scale

Conservation biological control in agroecosystems requires a landscape management perspective, because most arthropod species experience their habitat at spatial scales beyond the plot level, and there is spillover of natural enemies across the crop–noncrop interface. The species pool in the surrounding landscape and the distance of crop from natural habitat are important for the conservation of enemy diversity and, in particular, the conservation of poorly-dispersing and specialized enemies. Hence, structurally complex landscapes with high habitat connectivity may enhance the probability of pest regulation. In contrast, generalist and highly vagile enemies may even profit from the high primary productivity of crops at a landscape scale and their abundance may partly compensate for losses in enemy diversity. Conservation biological control also needs a multitrophic perspective. For example, entomopathogenic fungi, plant pathogens and endophytes as well as below- and above-ground microorganisms are known to influence pest-enemy interactions in ways that vary across spatiotemporal scales. Enemy distribution in agricultural landscapes is determined by beta diversity among patches. The diversity needed for conservation biological control may occur where patch heterogeneity at larger spatial scales is high. However, enemy communities in managed systems are more similar across space and time than those in natural systems, emphasizing the importance of natural habitat for a spillover of diverse enemies. According to the insurance hypothesis, species richness can buffer against spatiotemporal disturbances, thereby insuring functioning in changing environments. Seemingly redundant enemy species may become important under global change. Complex landscapes characterized by highly connected crop–noncrop mosaics may be best for long-term conservation biological control and sustainable crop production, but experimental evidence for detailed recommendations to design the composition and configuration of agricultural landscapes that maintain a diversity of generalist and specialist natural enemies is still needed