48 research outputs found
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
Skill premia and intergenerational education mobility: The French case
International audienceIn the case of France, we analyse the changes in the wage value of each education level and the impact of parents’ education and income upon the education attainment of children, sons and daughters. We find a critical decline in the skill premium of the Baccalauréat (‘bac’) in relation to the lowest educational level, and an increase in the skill premia of higher education degrees in relation to the bac, which is however not large enough to erase the decrease in all the skill premia relative to the lowest education. We also find a significant rise in the impact of family backgrounds upon education from 1993 to 2003, i.e., a decrease in intergenerational education mobility, which primarily derives from higher impact of parental incomes. Finally, the gender wage gap is particularly large for the lowest and the highest education degrees, and intergenerational persistence is greater for sons than for daughters
Palladium-Catalyzed Suzuki–Miyaura Coupling of Aryl Esters
The
Suzuki–Miyaura coupling is among the most important
C–C bond-forming reactions available due to its reliability,
chemoselectivity, and diversity. Aryl halides and pseudohalides such
as iodides, bromides, and triflates are traditionally used as the
electrophilic coupling partner. The expansion of the reaction scope
to nontraditional electrophiles is an ongoing challenge to enable
an even greater number of useful products to be made from simple starting
materials. Herein, we present how an NHC-based Pd catalyst can enable
Suzuki–Miyaura coupling where the C(acyl)–O bond of
aryl esters takes on the role of electrophile, allowing the synthesis
of various ketone-containing products. This contrasts known reactions
of similar esters that provide biaryls via nickel catalysis. The underlying
cause of this mechanistic divergence is investigated by DFT calculations,
and the robustness of esters compared to more electrophilic acylative
coupling partners is analyzed