Nitrous Oxide Emission from Forage Plantain and Perennial Ryegrass Swards Is Affected by Belowground Resource Allocation Dynamics

Soil–plant interactions affecting nitrous oxide (N2O) are not well-understood, and experimental data are scarce. Therefore, a greenhouse experiment was conducted in a 3 × 3 full factorial design, comprising three mineral N fertilizer rates (0, 150 and 300 kg N ha−1) applied to monoculture swards and a binary mixture of Plantago lanceolata and Lolium perenne. The parameters measured included daily N2O emissions, aboveground (AG) and belowground biomass (BG), N and C yields, as well as leucine aminopeptidase (LAP) activity in the soil as an indicator for soil microbial activity. Nitrous oxide emission and LAP were measured using the static chamber method and fluorimetric microplate assays, respectively. Cumulative N2O emissions were about two times higher for P. lanceolata than L. perenne monoculture swards or the mixture (p < 0.05). The binary mixtures also showed the highest N use efficiency and LAP activity, which significantly (p < 0.05) correlated with the C concentration in the belowground biomass. Plantago lanceolata was generally ineffective at reducing N2O emissions, probably due to the young age of the swards. Among the biological factors, N2O emission was significantly associated with biomass productivity, belowground C yield, belowground N use efficiency and soil microbial activity. Thus, the results suggested belowground resource allocation dynamics as a possible means by which swards impacted N2O emission from the soils. However, a high N deposition might reduce the N2O mitigation potential of grasslands

Molecular study of the perforin gene in familial hematological malignancies

Perforin gene (PRF1) mutations have been identified in some patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH) and in patients with lymphoma. The aim of the present study was to determine whether patients with a familial aggregation of hematological malignancies harbor germline perforin gene mutations. For this purpose, 81 unrelated families from Tunisia and France with aggregated hematological malignancies were investigated. The variants detected in the PRF1 coding region amounted to 3.7% (3/81). Two of the three variants identified were previously described: the p.Ala91Val pathogenic mutation and the p.Asn252Ser polymorphism. A new p.Ala 211Val missense substitution was identified in two related Tunisian patients. In order to assess the pathogenicity of this new variation, bioinformatic tools were used to predict its effects on the perforin protein structure and at the mRNA level. The segregation of the mutant allele was studied in the family of interest and a control population was screened. The fact that this variant was not found to occur in 200 control chromosomes suggests that it may be pathogenic. However, overexpression of mutated PRF1 in rat basophilic leukemia cells did not affect the lytic function of perforin differently from the wild type protein

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Membrane anchored and lipid raft targeted β-secretase inhibitors for Alzheimer's disease therapy

β-secretase, a key enzyme involved in amyloid-β generation, is an attractive candidate for Alzheimer's disease therapy. Transition-state inhibitors of β-secretase are designed to achieve specificity. However, these inhibitors bind only to the active conformation of the enzyme and as the active β-secretase is sequestered in subcellular compartments, new strategies have to be implemented. We propose that membrane-anchoring of β-secretase inhibitors would render them endocytosis-competent thereby enabling the inhibitors to reach these compartments that harbor active β-secretase. By choosing cholesterol as a membrane anchor, we also enrich the inhibitor in lipid rafts where much of the β-secretase is present. In addition, membrane-anchoring of soluble inhibitors reduces the dimensionality of the inhibitor and consequently increases the inhibitor concentration at the target membrane plane. Such inhibitors have great potential in terms of substrate selectivity and reduced side effects. Not only for β-secretase, this strategy could be applied for many membrane targets that are localized either at the plasma membrane or in the endocytic compartments