Analysis of endothelial protein C receptor gene and metabolic profile in Prader-Willi syndrome and obese subjects

The endothelial protein C receptor (EPCR) has a critical role in the regulation of anticoagulant and anti-inflammatory functions of activated protein C (APC). Abnormalities in EPCR might be associated with an increased risk of thrombosis. In this respect, a 23 bp insertion in the exon 3 of the EPCR gene predicts a truncated protein which cannot bind APC. High levels of C-reactive protein (CRP), a strong predictor of cardiovascular events, are found both in the obese and in subjects with Prader-Willi syndrome (PWS). Several cardiovascular risk factors are already present in prepubertal PWS children, but it is uncertain which mechanism contributes to the increased risk of cardiovascular disease in PWS. We analyzed the distribution of 23 bp insertion in the EPCR gene in 81 overweight and obese PWS subjects, 52 adults and 29 children, and in 58 overweight and obese children and adolescents (controls). We found that 1/58 (1.7%) of the controls was heterozygous for the 23 bp insertion, while this mutation was never found in PWS subjects. Furthermore, we evaluated CRP levels, glucose, insulin, and lipid profile, and we found higher CRP values in PWS adults with respect to children with PWS and controls, and a better insulin sensitivity in all PWS subjects than in the controls. This study suggests that in PWS subjects there is no predisposition to develop thrombotic events in association with EPCR gene alteration and demonstrates substantial differences regarding metabolic and inflammatory profile between PWS and non-PWS obese children, with further impairment in adults with PWS.     

Impaired Temperature Stress Response of a Streptococcus thermophilus deoD Mutant

An insertional deoD mutant of Streptococcus thermophilus strain SFi39 had a reduced growth rate at 20°C and an enhanced survival capacity to heat shock compared to the wild type, indicating that the deoD product is involved in temperature shock adaptation. We report evidence that ppGpp is implicated in this dual response.     

Convergent inductive signals specify midbrain, hindbrain, and spinal cord identity in gastrula stage chick embryos.

In the chick embryo, neural cells acquire midbrain, hindbrain, and spinal cord character over a approximately 6 hr period during gastrulation. The convergent actions of four signals appear to specify caudal neural character. Fibroblast growth factors (FGFs) and a paraxial mesoderm-caudalizing (PMC) activity are involved, but neither signal is sufficient to induce any single region. FGFs act indirectly by inducing mesoderm that expresses PMC and retinoid activity and also directly on prospective neural cells, in combination with PMC activity and a rostralizing signal, to induce midbrain character. Hindbrain character emerges from cells that possess the potential to acquire midbrain character upon exposure to higher levels of PMC activity. Induction of spinal cord character appears to involve PMC and retinoid activities.     

Fc gamma R-mediated killing by eosinophils

In this report we present data on the ability of the different Fc gamma R present on eosinophils to mediate killing of erythroid and tumor targets, and on a comparison of eosinophil and neutrophil Fc gamma R-mediated killing. Erythroid target killing was assessed using chicken erythrocytes (CE) and heteroantibodies composed of Fab fragments of anti-CE antibodies covalently coupled to Fab fragments of anti-Fc gamma R antibodies. Such anti-CE x anti-Fc gamma R reagents permit linkage of CE target cells with the FcR molecules on the eosinophil or neutrophil effector cells. Tumor target killing was assessed using hybridoma cell lines (HC) bearing anti-Fc gamma R antibodies on their cell surface. Freshly isolated eosinophils and neutrophils constitutively express similar amounts of the low affinity Fc gamma R, Fc gamma RII on their cell surface, but neither cell type expresses the high affinity Fc gamma R, Fc gamma RI. In contrast, eosinophils have only about 5% as much of the low affinity Fc gamma R found on human granulocytes and large granular lymphocytes (Fc gamma RIII) as neutrophils. Untreated, freshly prepared eosinophils or neutrophils did not lyse any of the anti-Fc gamma R bearing HC nor did they lyse CE in the presence of anti-Fc gamma R containing heteroantibodies. Upon treatment with granulocyte monocyte-CSF (GM-CSF), both cell types lysed HC-bearing antibody to Fc gamma RII (HC IV.3A) and CE in the presence of anti-CE x anti-Fc gamma RII heteroantibodies. However, neither cell type lysed HC-bearing antibody to Fc gamma RI or Fc gamma RIII, or CE in the presence of anti-CE x anti-Fc gamma RI HA. Treatment with GM-CSF did not significantly alter the number of Fc gamma R on either cell type. Treatment of neutrophils with IFN-gamma for 18 h induced the expression of Fc gamma RI on these cells and their ability to lyse anti-Fc gamma RI- or Fc gamma RII-bearing HC and CE through Fc gamma RI, Fc gamma RII, and Fc gamma RIII. In contrast, 6-h treatment of eosinophils or neutrophils with IFN-gamma induced neither Fc gamma RI expression on either cell type nor killing of HC or CE through Fc gamma R. In summary, incubation with GM-CSF, induced eosinophils and neutrophils to kill anti-Fc gamma RII-bearing HC and to lyse CE through Fc gamma RII. This augmented killing was not associated with enhanced expression of Fc gamma RII.(ABSTRACT TRUNCATED AT 400 WORDS)     

Involvement of host Fc receptors in antibody-mediated cutaneous basophil hypersensitivity reactions.

Cutaneous basophil hypersensitivity (CBH) reactions are heterogeneous delayed time course basophil-rich responses that can be mediated by either T cells, B cells, or serum antibodies. The current study examined the mechanism by which antibodies mediate CBH in guinea pigs. Fc competition experiments were constructed by passively transferring mixtures of anti-KLH serum and normal heterologous gamma-globulins. It was found that rabbit IgG and its isolated and purified Fc fragment [but not the (Fab')2 fragment] inhibited the ability of guinea pig immune serum to transfer CBH. Concurrent inhibition of transferred KLH-specific CBH and systemic passive cutaneous anaphylaxis (PCA) reactions by rabbit IgG or its Fc fragment, and not by sheep or bovine gamma-globulins, indicated that Fc receptors on cutaneous mast cells were probably involved in both CBH and PCA. It was also found that the basophil aspect of delayed cutaneous responses elicited by PHA was inhibited by Fc competition maneuvers. This could mean that some forms of apparently T cell-mediated CBH may be T cell dependent, but via secretion of molecules that bind to Fc receptors, as seems required in antibody-mediated CBH.     

Habitat‐related seed germination traits in alpine habitats

Understanding the key aspects of plant regeneration from seeds is crucial in assessing species assembly to their habitats. However, the regenerative traits of seed dormancy and germination are underrepresented in this context. In the alpine zone, the large species and microhabitat diversity provide an ideal context to assess habitat‐related regenerative strategies. To this end, seeds of 53 species growing in alpine siliceous and calcareous habitats (6230 and 6170 of EU Directive 92/43, respectively) were exposed to different temperature treatments under controlled laboratory conditions. Germination strategies in each habitat were identified by clustering with k‐means. Then, phylogenetic least squares correlations (PGLS) were fitted to assess germination and dormancy differences between species’ main habitat (calcareous and siliceous), microhabitat (grasslands, heaths, rocky, and species with no specific microhabitats), and chorology (arctic–alpine and continental). Calcareous and siliceous grasslands significantly differ in their germination behaviour with a slow, mostly overwinter germination and high germination under all conditions, respectively. Species with high overwinter germination occurs mostly in heaths and have an arctic–alpine distribution. Meanwhile, species with low or high germinability in general inhabit in grasslands or have no specific microhabitat (they belong to generalist), respectively. Alpine species use different germination strategies depending on habitat provenance, species’ main microhabitat, and chorotype. Such differences may reflect adaptations to local environmental conditions and highlight the functional role of germination and dormancy in community ecology.