Development of restoration trajectory metrics in reforested bottomland hardwood forests applying a rapid assessment approach

Large scale wetland restoration and reforestation efforts continue to expand throughout the Lower Mississippi Valley. Monitoring of restoration performance and the development of restoration trajectories pose challenges to resource managers and remain problematic due to (1) temporal patterns in forest succession, (2) budget constraints and short project monitoring timeframes, (3) disparity in the extent of pre-restoration hydrologic and landscape manipulations, and (4) lack of coherent restoration performance standards. The current work establishes a framework for identifying restoration trajectory metrics within project-relevant timescales. The study examined 17 variables commonly applied in rapid assessments. Four variables yielded positive restoration trajectories within a few years to 20 years. These include shrub-sapling density, ground vegetation cover, and development of organic and A soil horizons. Remaining variables including flood frequency and tree density provide limited useful information within critical early years following reforestation due to the time required for measurable changes to occur. As a result, assessment components are classified into three categories of rapid response, response, and stable variables. Restoring entities should maximize stable variables (e.g., afforestation species composition) during project implementation through site selection and planting techniques; while development of restoration milestones should focus on rapid response variables. Data collected at mature bottomland hardwood control sites displays the non-linearity of trajectory curves over decadal time scales

Development of restoration trajectory metrics in reforested bottomland hardwood forests applying a rapid assessment approach

Large scale wetland restoration and reforestation efforts continue to expand throughout the Lower Mississippi Valley. Monitoring of restoration performance and the development of restoration trajectories pose challenges to resource managers and remain problematic due to (1) temporal patterns in forest succession, (2) budget constraints and short project monitoring timeframes, (3) disparity in the extent of pre-restoration hydrologic and landscape manipulations, and (4) lack of coherent restoration performance standards. The current work establishes a framework for identifying restoration trajectory metrics within project-relevant timescales. The study examined 17 variables commonly applied in rapid assessments. Four variables yielded positive restoration trajectories within a few years to 20 years. These include shrub-sapling density, ground vegetation cover, and development of organic and A soil horizons. Remaining variables including flood frequency and tree density provide limited useful information within critical early years following reforestation due to the time required for measurable changes to occur. As a result, assessment components are classified into three categories of rapid response, response, and stable variables. Restoring entities should maximize stable variables (e.g., afforestation species composition) during project implementation through site selection and planting techniques; while development of restoration milestones should focus on rapid response variables. Data collected at mature bottomland hardwood control sites displays the non-linearity of trajectory curves over decadal time scales

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

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

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

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

peer reviewe

Halocarbocyclization Entry into the Oxabicyclo[4.3.1]decyl Exomethylene-δ-Lactone Cores of Linearifolin and Zaluzanin A - Exploiting Combinatorial Catalysis

A streamlined entry into the sesquiterpene lactones (SQL) cores of linearifolin and zaluzanin A is described. Stereochemistry is controlled through transformations uncovered by ISES (In-Situ- Enzymatic-Screening). Absolute stereochemistry derives from kinetic resolution of 5- benzyloxypentene-1,2-oxide, utilizing a β-pinene-derived-Co(III)-salen. Relative stereochemistry (1,3-cis-fusion)is set via formal halometalation/carbocyclization, mediated by [Rh(O2CC3F7)2]2/ LiBr. Subsequent ring-closing metathesis (RCM-Grubbs II) yields the title exomethylene-δ- lactone SQL-cores. In complementary fashion, RCM with Grubbs-I catalyst provides the oxabicyclo[3.3.1]nonyl-core of xerophilusin R and zinagrandinolide