We conducted a genome-wide search for childhood obesity-associated traits, including BMI >/==" BORDER="0">95th percentile (PCT95), 97th percentile (PCT97), and 99th percentile (PCT99) as well as age ...of adiposity rebound (AAR), which corresponds to the beginning of the second rise in childhood adiposity. A set of 431 microsatellite markers was genotyped in 506 subjects from 115 multiplex French Caucasian families, with at least one child with a BMI >/==" BORDER="0">95th percentile. Among these 115 pedigrees, 97 had at least two sibs with a BMI >/==" BORDER="0">95th percentile. Fine-mapping was performed in the seven most positive loci. Nonparametric multipoint analyses revealed six regions of significant or suggestive linkage on chromosomes 2q33.2-q36.3, 6q22.31-q23.2, and 17p13 for PCT95, PCT97, or PCT99 and 15q12-q15.1, 16q22.1-q24.1, and 19p13.3-p13.11 for AAR. The strongest evidence of linkage was detected on chromosome 6q22.31 for PCT97 (maximum likelihood score: 4.06) at the marker D6S287. This logarithm of odds score meets genome-wide significance tested through simulation (empirical genome-wide P = 0.01 0.0027-0.0254). Six independent ge-nome scans in adults have reported quantitative trait loci on 6q linked to energy or glucose homeostasis-associated phenotypes. Possible candidate genes in this region include SIM1, MCHR2, and PC-1.
Mechanisms accounting for the protection of the fetal semi-allograft from maternal immune cells remain incompletely understood. In previous studies, we showed that galectin-1 (Gal1), an ...immunoregulatory glycan-binding protein, hierarchically triggers a cascade of tolerogenic events at the mouse fetomaternal interface. Here, we show that Gal1 confers immune privilege to human trophoblast cells through the modulation of a number of regulatory mechanisms. Gal1 was mainly expressed in invasive extravillous trophoblast cells of human first trimester and term placenta in direct contact with maternal tissue. Expression of Gal1 by the human trophoblast cell line JEG-3 was primarily controlled by progesterone and pro-inflammatory cytokines and impaired T-cell responses by limiting T cell viability, suppressing the secretion of Th1-type cytokines and favoring the expansion of CD4(+)CD25(+)FoxP3(+) regulatory T (T(reg)) cells. Targeted inhibition of Gal1 expression through antibody (Ab)-mediated blockade, addition of the specific disaccharide lactose or retroviral-mediated siRNA strategies prevented these immunoregulatory effects. Consistent with a homeostatic role of endogenous Gal1, patients with recurrent pregnancy loss showed considerably lower levels of circulating Gal1 and had higher frequency of anti-Gal1 auto-Abs in their sera compared with fertile women. Thus, endogenous Gal1 confers immune privilege to human trophoblast cells by triggering a broad tolerogenic program with potential implications in threatened pregnancies.
Denitrification, the anaerobic microbial conversion of nitrate (NO
), a common water pollutant, to nitrogen (N) gases, is often high in the soil of natural wetlands. In areas where natural wetlands ...have been degraded or destroyed, constructed and restored wetlands have been used to restore ecosystem services like denitrification. Thus, denitrification in restored and constructed wetlands could play an important role in treating anthropogenic N sources such as combined sewer overflow discharges which can be high in NO
. In this study, we measured denitrification potential using an anaerobic slurry assay and made a suite of ancillary measurements (soil moisture content, microbial biomass carbon C and N content, potential net N mineralization and nitrification, soil inorganic N pools, and soil respiration) in four constructed salt marsh wetlands, and a series of wetland habitat basins in Newtown Creek, NY, an urban superfund site. Samples were also taken from natural salt marshes located at Paerdegat Basin, Jamaica Bay, NY. Our results show that constructed Spartina alterniflora marshes in ultra-urban Newtown Creek support denitrification potential equivalent to rates of natural marshes in Jamaica Bay and reference marshes in other urban estuaries. There were significant positive correlations between microbial biomass C and N content and organic matter content and denitrification potential. Results suggest that constructed wetlands can support wetland vegetation, soils, and microbial life and contribute to N removal under ultra-urban conditions.
Both rs17782313 (near MC4R) and rs1421085 (FTO) polymorphisms have been consistently associated with increased risk of obesity and with body mass index (BMI) variation. An effect of both ...polymorphisms on satiety has recently been suggested. We genotyped rs17782313 and rs1421085 in 5764 relatives from 1109 French pedigrees with familial obesity, 1274 Swiss class III obese adults as well as in 4877 French adults and 5612 Finnish teenagers from two randomly selected population cohorts. In all subjects, eating behaviour traits were documented through questionnaires. We first assessed the association of both single nucleotide polymorphisms with BMI and then studied eating behaviour. Under an additive model, the rs17782313-C MC4R allele showed a trend towards higher percentages of snacking in both French obese children (P=0.01) and Swiss obese adults (P=0.04) as well as in adolescents from the Finnish general population (P=0.04). In French adults with familial obesity, this allele tended to be also associated with a higher Stunkard hunger score (P=0.02) and in obese children with a higher prevalence of eating large amounts of food (P=0.04). However, no consistent association of the FTO rs1421085-C allele and available eating behaviour trait was found in our studied populations. The rs17782313-C allele nearby MC4R may modulate eating behaviour-related phenotypes in European obese and randomly selected populations, in both children and adults, supporting a regulatory role of this genetic variant on eating behaviour, as previously shown for MC4R non-synonymous loss-of-function mutations. The potential effect of the obesity-associated FTO gene on eating behaviour deserves additional investigation.
The K+ inwardly rectifier channel (KIR) is one of the two sub-units of the pancreatic islet ATP-sensitive potassium channel complex (I(KATP)), which has a key role in glucose-stimulated insulin ...secretion and thus is a potential candidate for a genetic defect in Type II (non-insulin-dependent) diabetes mellitus. We did a molecular screening of the KIR6.2 gene by single strand conformational polymorphism (SSCP) and direct sequencing in 72 French Caucasian Type II diabetic families. We identified three nucleotide substitutions resulting in three amino acid changes (E23K, L270V and 1337V), that have also been identified in other Caucasian Type II diabetic subjects. These variants were genotyped in French cohorts of 191 unrelated Type II diabetic probands and 119 normoglycaemic control subjects and association studies were done. The genotype frequencies of the L270V and 1337V variants were not very different between Type II diabetic subjects and control groups. In contrast, analysis of the E23K variant showed that the KK homozygocity was more frequent in Type II diabetic than in control subjects (27 vs 14%, p = 0.015). Analyses in a recessive model (KK vs EK/EE) tended to show a stronger association of the K allele with diabetes (p = 0.0097, corrected p-value for multiple testing < 0.02). The data for the E23K variant obtained here and those obtained from three other Caucasian groups studied so far were combined and investigated by meta-analysis. Overall, the E23K variant was found to be significantly associated with Type II diabetes (0.001 < or = p < or = .00106, corrected p-values for multiple testing p < or = 0.01). This study shows that KIR6.2 polymorphisms are frequently associated with Type II diabetes in French Caucasians. Furthermore, a meta-analysis combining different Caucasian groups suggests an significant role of KIR6.2 in the polygenic context of Type II diabetes.
Abstract Objective To document eating practices and socio-economic profiles of patients seen in the social and medical healthcare centres (CASOs in its French acronym) run by Doctors of the World ...(Médecins du Monde, MdM) in France and evaluate their nutritional and health status. Study design The survey was carried out between April and May 2014 in seven CASOs in France. Methods All the patients attending MdM clinics were given a nutrition and health questionnaire. Their anthropometric measurements were taken on site. Results 77.7% of the households surveyed were food insecure due to constrained resources. On average, the patients interviewed declared spending €2.5 per person per day on food. A total of 46.3% of adults declared not having eaten for a whole day at least once in the month preceding the survey. One third of the patients declared having lost weight over the last two weeks. A chronic pathology was diagnosed in more than one in two patients; 19% were obese and 34% were overweight. Conclusions Constrained resources lead people living in very precarious conditions to eat without adequate nutrition, which could have consequences for their health, such as diabetes, obesity and cardiovascular disease.
Mesenteric lymphatic malformations result from abnormal proliferation of disorganized mesenteric lymphatic channels. Sclerotherapy is often preferred over surgery as it is less invasive and has lower ...post-procedure morbidity. Sclerotherapy has been described as durable and effective with a low complication rate. We describe a serious complication from sclerotherapy of a lymphatic malformation extending from the mesentery through the bowel wall, highlighting the spectrum of this pathology and the need for multidisciplinary management of complex cases.
PDF
