Correction to: Comparison of optimization parametrizations for regional lung compliance estimation using personalized pulmonary poromechanical modelling

Biomechanics and Modeling in Mechanobiology -     

Screening for mutations causing X-linked severe combined immunodeficiency in the IL-2Rγ chain gene by single-strand conformation polymorphism analysis

Mutations in the common gamma chain (_c or IL2RG) of the interleukin-2, –4, –7, –9 and –15 receptors have been found to cause X-linked severe combined immunodeficiency (SCIDX1). We report here on the mutations identified in a further ten families. Two of the mutations identified have occurred twice in unrelated families, indicating two possible mutational hotspots. Seven of the mutations, which were identified by single-strand conformational polymorphism (SSCP) analysis, are point mutations, and the eighth is a small deletion. We also report on the first use of assays based on these mutations within IL2RG for unambiguous carrier determination. The consequences for the _c proteins produced as a result of these mutations are discussed.     

Dendritic Signals Command Firing Dynamics in a Mathematical Model of Cerebellar Purkinje Cells

Dendrites of cerebellar Purkinje cells (PCs) respond to brief excitations from parallel fibers with lasting plateau depolarizations. It is unknown whether these plateaus are local events that boost the synaptic signals or they propagate to the soma and directly take part in setting the cell firing dynamics. To address this issue, we analyzed a likely mechanism underlying plateaus in three representations of a reconstructed PC with increasing complexity. Analysis in an infinite cable suggests that Ca plateaus triggered by direct excitatory inputs from parallel fibers and their mirror signals, valleys (putatively triggered by the local feed forward inhibitory network), cannot propagate. However, simulations of the model in electrotonic equivalent cables prove that Ca plateaus (resp. valleys) are conducted over the entire cell with velocities typical of passive events once they are triggered by threshold synaptic inputs that turn the membrane current inward (resp. outward) over the whole cell surface. Bifurcation analysis of the model in equivalent cables, and simulations in a fully reconstructed PC both indicate that dendritic Ca plateaus and valleys, respectively, command epochs of firing and silencing of PCs.     

Osteoclast cell-surface changes during the egg-laying cycle in Japanese quail

The medullary bone serves as a source of labile calcium mobilized during calcification of the egg shell in birds. Quantitative histological methods demonstrate that the numbers of medullary bone osteoclasts and nuclei per osteoclast remain unchanged during the egg cycle in the Japanese quail (Coturnix). Therefore, cyclic changes in bone resorption cannot be explained by modulations of osteoclasts from and into other bone cells, a mechanism previously suggested for certain species of birds. Rather, dramatic changes in osteoclast cell-surface features occur during the egg cycle, which might account for cyclic variations in resorptive activity. During egg shell calcification, osteoclasts with ruffled borders are closely apposed to bone surfaces; the cytoplasm is rich in vacuoles that contain mineral crystals and seem to derive from the ruffled border. At the completion of egg shell calcification, the ruffled borders and vacuoles move away from the bone surface, although the osteoclast remains attached to the bone along the filamentous or "clear" zone. Associated with the disappearance of the ruffled borders is the appearance of extensive interdigitated cell processes along the peripheral surface of the osteoclast away from the bone. These unusual structures, which may serve as a reservoir of membrane, largely disappear when ruffled borders and associated structures reappear. Therefore, in these hens, the osteoclasts modulate their cell surface rather than their population during the egg cycle.     

Sensitive determination of vinorelbine and its metabolites in human serum using liquid chromatography-electrospray mass spectrometry

A liquid chromatography-electrospray mass spectrometry method was developed for the quantitation of vinorelbine (VNB) and two metabolites, vinorelbine N-oxide (VNO) and deacetyl vinorelbine (DAV) in human serum. The limits of quantitation (LOQ) reached 0.5 ng/ml for both VNB and VNO and 1 ng/ml for DAV. The method was proved linear in the range of LOQs up to 1000 ng/ml, and extraction recovery was 80% on average for the three compounds. It was applied to the pharmacokinetic monitoring of vinorelbine and, for the first time, to the detection of VNO in the serum of patients suffering from non-small-cell lung cancer.     

Synthesis and biological characterisation of [3H]BBL454, a new CCK2 selective radiolabelled agonist displaying original pharmacological properties

[(3)H]BBL454, a new CCK(2) selective tritiated agonist was prepared via the reductive tritiation of a 5-aminopentyn-1-yl moiety introduced on the N-terminal end of a pentapeptide derivative of cholecystokinin. The binding properties of this labelled compound were determined on CHO cells transfected with the rat CCK(2) receptor. [(3)H]BBL454 is able to discriminate two affinity states of the CCK(2) receptor a supplementary indication of its validity for further exploring the heterogeneity of this receptor.     

Seasonal variations of symbiotic ultrastructure and relationships of two natural ectomycorrhizae of beech (Fagus sylvatica/Lactarius blennius var. viridis and Fagus sylvatica/Lactarius subdulcis)

This study concerned two perennial ectomycorrhizae of beech: Fagus sylvatica L./Lactarius blennius var. viridis and Fagus sylvatica L./Lactarius subdulcis, collected in a natural forest site. Nutritional exchanges existing between beech roots and fungi were evaluated over a seasonal cycle by studying the variations of ultrastructure, polyphosphate and nitrogenous granules and glycogen content (periodic acid thiocarbohydrazide silver test). The acid phosphatase activity, which is an indicator of the intensity of the physiological activity of symbiosis partners, was also revealed by transmission electron microscopy. The occurrence of the two ectomycorrhizae in the soil was not related to the climatic conditions. In winter, the number of polyphosphate and nitrogenous granules was high in the fungi, and glycogen was abundant in the cytoplasm of hyphae. In late winter, an intense acid phosphatase activity was revealed on plasmalemmas of live hyphae. It could indicate the beginning of fungal reserve mobilization, which progressively disappeared as spring progressed. In summer, glycogen was quasi non-existent and only few polyphosphate and nitrogenous granules were observed. At this period, the acid phosphatase activity was weak. Finally, in autumn and early winter, glycogen and granules were progressively restored in fungal structures. Relationships between changes of granules and glycogen content and the physiological states of each symbiont throughout the year are discussed.