Estimates for heritability and consumer-validation of a penetrometer method for phenotyping softness of cooked cassava roots

Although breeders have made significant progress in the genetic improvement of cassava ( Manihot esculenta Crantz) for agronomic traits, lack of information on heritability and limited testing of high-throughput phenotyping methods are major limitations to improving root quality traits, such as softness after cooking, which rank high among Ugandan consumers. The objectives of this study were to determine heritability for softness of cooked cassava roots, and quantify the relationship between penetrometer and consumer testing methods for phenotyping softness of cassava roots. Softness defined as the maximum force (N) needed to penetrate cooked root samples using a penetrometer, was evaluated at four cooking time intervals: 15, 30, 45, and 60 min on 268 cassava genotypes. Estimates of broad-sense heritability (repeatability) ranged from 0.17 to 0.37, with the highest value observed at 45 min of cooking time interval. In the second study involving 135 cassava consumers from Kibaale district in Uganda, penetrometer measurements of cooked roots from six cassava varieties were found to be in strong agreement (r2 = 0.91; P-value = 0.003) with ordinal scores of root softness from consumer testing. These results suggest that: (a) softness of cooked cassava roots is a trait amenable for evaluation and selection; and (b) a penetrometer can readily be used for assessment of cooked root softness. These findings form the basis for operationalising the routine assessment of root softness in cassava breeding trials, an output that will enhance ongoing efforts to breed for desired end-user root quality traits.Les s\ue9lectionneurs ont fait des progr\ue8s consid\ue9rables dans l\u2019am\ue9lioration g\ue9n\ue9tique des caract\ue8res agronomiques du manioc ( Manihot esculenta Crantz). Cependant un manque de m\ue9thodes de ph\ue9notypage haut-d\ue9bit adapt\ue9es aux caract\ue8res de qualit\ue9s tel que la fermet\ue9 de la racine apr\ue8s cuisson, essentiel pour les consommateurs Ougandais. Cette \ue9tude ambitionne a) de determiner l\u2019h\ue9ritabilit\ue9 de la fermete de racine cuite b) de quantifier la relation entre l \ue9valuation de la fermet\ue9 de racine cuite au p\ue9n\ue9trom\ue8tre et un panel consommateurs. Cette \ue9valuation a \ue9t\ue9 realisee a quatre intervals de temps: 15, 30, 45 et 60 minutes sur 268 genotypes de manioc. Pour d\ue9finir l\u2019h\ue9ritabilit\ue9 de la fermet\ue9 de la racine, celle ci a \ue9t\ue9 d\ue9finie par la force maximum (N) n\ue9cessaire pour p\ue9n\ue9trer des \ue9chantillons de racines incluant diff\ue8rent temps de cuisson (15, 30, 45, and 60 min) a l\u2019aide d\u2019un p\ue9n\ue9trom\ue8tre. L\u2019h\ue9ritabilit\ue9 au sens large (ou r\ue9p\ue9tabilit\ue9) observ\ue9e varie de 0.17 a 0.37, la valeur la plus \ue9lev\ue9 \ue9tant observ\ue9e pour un temps de cuisson de 45 minutes. Dans une seconde \ue9tude impliquant 135 consommateurs du district de Kibaale (Ouest de l\u2019Ouganda), les mesures au p\ue9n\ue9trom\ue8tre de racines cuites de six vari\ue9t\ue9s ont confirm\ue9es la forte correlation (r2 = 0.91; P-value = 0.003) avec les valeurs ordinales de fermet\ue9 de racine du panel consommateur. Les r\ue9sultats de cette \ue9tude indiquent que cette m\ue9thodologie de ph\ue9notypage est a) utile pour l\u2019 \ue9valuation de la fermet\ue9 sur des racines cuites en selection et b) d\ue9montre que l\u2019usage du p\ue9n\ue9trom\ue8tre est efficace pour celle ci. Ces r\ue9sultats offrent aux s\ue9lectionneurs une methode d\u2019 \ue9valuation de routine de la qualite de racine pour les essais experimentaux. Ceux ci contribueront aux efforts actuels pour l\u2019am\ue9lioration des caract\ue8res qualit\ue9s chers aux consommateurs

Modulation of endogenous antioxidant defense and the progression of kidney disease in multi-heritage groups of patients with type 2 diabetes: PRospective EValuation of Early Nephropathy and its Treatment (PREVENT).

BACKGROUND: Diabetes is the western world's leading cause of end-stage renal disease. Glucose-dependent, oxidative stress is linked to the development of renal inflammation and sclerosis, which, in animal models of diabetes, can be prevented by anti-oxidative treatment. Patients of non-Caucasian heritage have low activity of the selenoprotein, antioxidant enzyme, glutathione peroxidase (GPx) and its co-factor vitamin E, which may be linked to their increased propensity to developing end-stage renal disease. RESEARCH DESIGN AND METHODS: We have designed a double-blind, randomized, placebo controlled study with selenium and/or vitamin E versus placebo as the interventions for patients with type 2 diabetes and chronic kidney disease (CKD) stages 1-3. A 2 × 2 factorial design will allow a balanced representation of the heritage groups exposed to each intervention. The primary biochemical outcome is change in GPx activity, and clinical outcome measure is the actual, rate of-and/or percentage change in estimated glomerular filtration rate (eGFR) from baseline. Analysis will be with a marginal model for longitudinal data using Generalized Estimating Equations corrected for measures of baseline serum antioxidant enzyme activities (GPx, superoxide dismutase and catalase), micronutrient levels (vitamins E and C), measures of inflammation (interleukin 6, c-reactive protein and monocyte chemoattractant protein-1) and markers of oxidative damage (plasma 8-isoprostaglandin F2α and urinary 8-hydroxydeoxyguanosine). EXPECTED RESULTS: The study will assess the relationship between GPx activity, oxidative stress, inflammation and eGFR. It will test the null hypothesis that antioxidant therapy does not influence the activity of GPx or other antioxidant enzymes and/or alter the rate of change in eGFR in these patient groups. CONCLUSIONS: Outcome data on the effect of antioxidants in human diabetic renal disease is limited. Previous post hoc analyses have not shown a beneficial effect of vitamin E on renal function. A recent trial of a pharmaceutical antioxidant agent, improved eGFR, but in patients with advanced diabetes-related chronic kidney disease its use was associated with an increased incidence of cardiovascular events. We will explore whether the nutritional antioxidants, vitamin E and selenium alone, or in combination in patients at high risk of renal disease progression, forestalls a reduction in eGFR. The study will describe whether endogenous antioxidant enzyme defenses can be safely modified by this intervention and how this is associated with changes in markers of oxidative stress. Trial registration ISRCTN 97358113. Registered 21st September 2009

Resource limitation drives spatial organization in microbial groups.

Dense microbial groups such as bacterial biofilms commonly contain a diversity of cell types that define their functioning. However, we have a limited understanding of what maintains, or purges, this diversity. Theory suggests that resource levels are key to understanding diversity and the spatial arrangement of genotypes in microbial groups, but we need empirical tests. Here we use theory and experiments to study the effects of nutrient level on spatio-genetic structuring and diversity in bacterial colonies. Well-fed colonies maintain larger well-mixed areas, but they also expand more rapidly compared with poorly-fed ones. Given enough space to expand, therefore, well-fed colonies lose diversity and separate in space over a similar timescale to poorly fed ones. In sum, as long as there is some degree of nutrient limitation, we observe the emergence of structured communities. We conclude that resource-driven structuring is central to understanding both pattern and process in diverse microbial communities

Separate worlds? Explaining the current wave of regional economic polarization

Inter-regional and inter-metropolitan economic divergence is greater in many western developed countries than it has been in many decades. Divergence manifests itself in many ways, including per capita income, labor force participation, and the spatial the distribution of skills and returns to education. At the same time, geographical polarization of political preferences and electoral choices has increased, with gains in populism and nationalism in some regions, and broadening of socially liberal, pro-trade, and multicultural attitudes in other regions. The task of explaining these developments poses challenges to economic geography and regional and urban economics. These fields have already developed some of the building blocks of an account, but a number of important gaps persist. This article is devoted to identifying priorities for regional science and urban economics, the new economic geography, and proper economic geography to tackle the key mechanisms behind divergence as well as to integrate them in a common overall framework

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

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

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 hospitalization2–4 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 first update on mapping the human genetic architecture of COVID-19

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