Katholieke Universiteit Leuven

About: Katholieke Universiteit Leuven is a education organization based out in Leuven, Belgium. It is known for research contribution in the topics: Population & Transplantation. The organization has 61109 authors who have published 176584 publications receiving 6210872 citations.

Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil.

Abstract: Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

Peripheral muscle weakness contributes to exercise limitation in COPD.

Abstract: Recently, it was suggested that fatigue of peripheral muscles could contribute to exercise limitation in patients with chronic obstructive pulmonary disease (COPD). In order to quantify the role of peripheral muscle force, we restudied potential determinants of exercise capacity (6-min walking distance [6 MWD] and maximal oxygen consumption [V02max]) in 41 consecutive COPD patients (FEV1, 43 +/- 19% of predicted, TLCO, 56 +/- 25% of predicted) admitted to our pulmonary rehabilitation program. VO2max (incremental cycle ergometer test), 6 MWD (best of three), lung function (FEV1, FVC, TLC, FRC), diffusing capacity (TLCO), isometric quadriceps force (QF), hand grip force (HF), and maximal inspiratory (PImax) and expiratory (PEmax) pressures were measured. Patients had a poor 6 MWD (372 +/- 136 m) and VO2max (1.35 +/- 0.60 L, 71%), reduced respiratory (PImax 65 +/- 27%) and peripheral muscle force (QF 74 +/- 27%, HF 82 +/- 23%). In single regression analysis, significant correlations (r) were found for VO2max and TLCO (0.68), FEV1 (0.64), QF (0.55), HF (0.53), and body weight (0.49). Walking distance was significantly correlated with QF (0.63), HF (0.61), PImax (0.49), and TLCO (0.38). In stepwise multiple regression analysis, the variables significantly contributing to 6 MWD were QF and Plmax. For VO2max, variables significantly contributing were TLCO, QF, and FEV1. We conclude that lung function and peripheral muscle force are important determinants of exercise capacity in COPD.

Pathogen-induced systemic activation of a plant defensin gene in Arabidopsis follows a salicylic acid-independent pathway.

Abstract: A 5-kD plant defensin was purified from Arabidopsis leaves challenged with the fungus Alternaria brassicicola and shown to possess antifungal properties in vitro. The corresponding plant defensin gene was induced after treatment of leaves with methyl jasmonate or ethylene but not with salicylic acid or 2,6-dichloroisonicotinic acid. When challenged with A. brassicicola, the levels of the plant defensin protein and mRNA rose both in inoculated leaves and in nontreated leaves of inoculated plants (systemic leaves). These events coincided with an increase in the endogenous jasmonic acid content of both types of leaves. Systemic pathogen-induced expression of the plant defensin gene was unaffected in Arabidopsis transformants (nahG) or mutants (npr1 and cpr1) affected in the salicylic acid response but was strongly reduced in the Arabidopsis mutants eln2 and col1 that are blocked in their response to ethylene and methyl jasmonate, respectively. Our results indicate that systemic pathogen-induced expression of the plant defensin gene in Arabidopsis is independent of salicylic acid but requires components of the ethylene and jasmonic acid response.

Human metabolic phenotype diversity and its association with diet and blood pressure

Abstract: Metabolic phenotypes are the products of interactions among a variety of factors-dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10(-16)), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure. Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P < 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities, are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk.