Identification on I-Ak molecules of a functional site recognized by proliferating T-lymphocytes

The inhibitory capacity of 17 monoclonal antibodies (m.Ab.) specific for the products of the I-A ^k subregion was evaluated in proliferative responses of B10.BR T-lymphocytes to GAT, Keyhole limpet hemocyanin, and ovalbumin. Considered in isolation, each m.Ab. mediated inhibitory effects of comparable magnitude on these three different proliferative responses. On the other hand, clear differences were observed when the magnitude of the inhibitory effects was compared from one m.Ab. to another. The m.Ab. were consequently classified as strong or moderate-to-weak inhibitors of T-cell proliferative responses. Evidence was simultaneously gained indicating the following: (a) the determinants recognized by different m.Ab. were expressed on the same molecules; (b) the differences in affinity of the m.Ab. for I-A^k positive cells did not explain their differences in inhibitory capacities; (c) conversely, the inhibitory capacity of each m.Ab. followed its ability to inhibit the cell surface fixation of Ia.17-specific 10-2.16 m.Ab.; (d) the strong inhibitory capacity of some m.Ab. was not related to a special ability to modulate cell surface Ia molecules. These results suggest that antigen recognition by T lymphocytes is preferentially restricted by a functional site of the I-A^k molecules related to the Ia.17 and Ia.1 specificities.Abbreviations EDTA Ethylenediamine-tetraacetic acid disodium salt - EHAA Eagle's Hanks' amino acids medium - FCS fetal calf serum - in polypeptide G is glutamate, A, alanine, T, tyrosine - HEPES N-2-hydroxy-piperazine-N-2-ethane sulfonic acid - kd dissociation rate constant - KLH Keyhole limpet hemocyanin - LPS lipopolysaccharide - m.Ab. monoclonal antibodies - NP-40 nonidet P-40 - PBS phosphate buffered saline - PBS-BSA PBS supplemented with 1% bovine serum albumin - PBS-BSA-NP-40 PBS-BSA supplemented with 0.5% NP-40 - RT room temperature - SEM standard error of the mean - s.c. spleen cells     

Schistosoma mansoni: Ultrastructure of early transformation of skin- and shear-pressure-derived schistosomules

Against the background of cercarial fine structure, ultrastructural changes were compared in schistosomules of Schistosoma mansoni 30 min and 1 hr after their production in vivo by skin penetration and in vitro by shear pressure. The same developmental pattern was observed in schistosomules of both derivations. In vitro schistosomules, however, developed more slowly, resembled cercariae more closely, and varied less among organisms than did in vivo schistosomules. The greatest morphological changes were observed in the 1-hr in vivo schistosomules. These were as follows: (1) in tegument, formation of transient microvilli, a hepatalaminate outer membrane and accented surface invaginations, loss of glycocalyx, movement outward of cyton vesicles via bridges, accumulation of multilaminate bodies around bridge openings; (2) in the anterior organ (oral sucker), movement of head gland vesicles via the ducts into tegument followed by collapse of the gland fundus, disappearance of the circumfundal cells and two large support cells, and the appearance in these areas of membranes and parenchymal cells; (3) secretion of the acetabular gland contents, collapse of the glands and replacement by membranes and parenchymal cells; (4) peristaltic activity of the digestive tract as shown by alternate areas of lumen constriction and dilation; (5) loss of bladder and contraction of the small aboral collecting tubules; and (6) conversion of heterochromatic parenchymal cell nuclei to euchromatic. In contrast, the 1-hr in vitro shear schistosomules resembled 30-min in vivo schistosomules, retaining many cercarial features.     

Les ostracodes neogenes du bassin de Savigne-sur-Lathan(Faluns de Touraine) I. Biostratigraphie et paleoecologie

The Neogen formations from the basin of Savigné-su-Lathan (Indre-et-Loire) have yielded 53 species of ostracods.The connections with the best known fauna from the Aquitaine basin and the Rhône basin are discussed.     

Uncouplers of oxidative phosphorylation a structure-activity study of their inhibitory effect on passive chloride permeability

Uncoupling agents inhibit chloride transport in red blood cells, which is a metabolism-independent process. An analysis of the molecular requirements shows that this inhibitory activity is closely correlated with the electronic and the hydrophobic bonding properties of phenols: the more lipophilic and the more electron-attracting the substituent groups are, the greater the activity they confer on the parent molecule. A recent structure-activity study concerning various classes of reversible inhibitors of chloride transport led to the same conclusion (Motais, R. and Cousin, J.L. (1977) in International Conference on Biological Membranes: Drugs, Hormones and Membranes (Bolis, L., Hoffman, J.F. and Straub, R.W., eds.), Raven Press, New York, in the press).The effects of substituents on the activity of phenols as uncouplers have been recently examined (Stockdale, M. and Selwyn, M.J. (1971) Eur. J. Biochem. 21, 565). The comparison of these results with our data shows that uncoupling depends more on electronic properties of phenols than does chloride inhibition.     

Molecular Epidemiology of Carbapenem Non-Susceptible Acinetobacter baumannii in France

Carbapenem-resistant Acinetobacter baumannii have emerged globally. The objective of this study was to investigate the epidemiology, clonal diversity and resistance mechanisms of imipenem non-susceptible A. baumannii isolates in France. Between December 2010 and August 2011, 132 notifications were collected, including 37 outbreaks corresponding to 242 cases (2 to 55 per cluster). Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on 110 non-repetitive isolates. Gene bla _OXA-23 was the most frequently detected (82%), followed by bla _OXA-24 (11%) and bla _OXA-58 (7%). Eleven sequence types (ST) were distinguished, among which sequence types ST1, ST2 (64%), ST20, ST25, ST85 and ST107. Isolates from epidemiological clusters had the same ST and resistance genes, indicating probable transmission within centres. In contrast, PFGE types of isolates differed among centres, arguing against transmission among centers. This study provides the first epidemiological snapshot of the population of A. baumannii with reduced susceptibility to carbapenems from France, and further underlines the predominance of international clones.     

Foster rather than biological parental telomere length predicts offspring survival and telomere length in king penguins

Because telomere length and dynamics relate to individual growth, reproductive investment and survival, telomeres have emerged as possible markers of individual quality. Here, we tested the hypothesis that, in species with parental care, parental telomere length can be a marker of parental quality that predicts offspring phenotype and survival. In king penguins (Aptenodytes patagonicus), we experimentally swapped the single egg of 66 breeding pairs just after egg laying to disentangle the contribution of prelaying parental quality (e.g., genetics, investment in the egg) and/or postlaying parental quality (e.g., incubation, postnatal feeding rate) on offspring growth, telomere length and survival. Parental quality was estimated through the joint effects of biological and foster parent telomere length on offspring traits, both soon after hatching (day 10) and at the end of the prewinter growth period (day 105). We expected that offspring traits would be mostly related to the telomere lengths (i.e., quality) of biological parents at day 10 and to the telomere lengths of foster parents at day 105. Results show that chick survival up to 10 days was negatively related to biological fathers’ telomere length, whereas survival up to 105 days was positively related to foster fathers’ telomere lengths. Chick growth was not related to either biological or foster parents’ telomere length. Chick telomere length was positively related to foster mothers’ telomere length at both 10 and 105 days. Overall, our study shows that, in a species with biparental care, parents’ telomere length is foremost a proxy of postlaying parental care quality, supporting the “telomere – parental quality hypothesis.”     

Preface to the Special Issue “Presynaptic Dysfunction and Disease”

The synapse is formed between a presynapse (which releases neurotransmitter) and the postsynapse (which transduces this chemical signal). Over the past decade, presynaptic dysfunction has emerged as a key mediator of a series of neurodevelopmental and neurodegenerative disorders. This special issue will highlight some of the important presynaptic molecules and mechanisms that are disrupted in these conditions and reveal potential routes for therapy.     

Accurate modelling of unsteady flows in collapsible tubes

The context of this paper is the development of a general and efficient numerical haemodynamic tool to help clinicians and researchers in understanding of physiological flow phenomena. We propose an accurate one-dimensional Runge–Kutta discontinuous Galerkin (RK-DG) method coupled with lumped parameter models for the boundary conditions. The suggested model has already been successfully applied to haemodynamics in arteries and is now extended for the flow in collapsible tubes such as veins. The main difference with cardiovascular simulations is that the flow may become supercritical and elastic jumps may appear with the numerical consequence that scheme may not remain monotone if no limiting procedure is introduced. We show that our second-order RK-DG method equipped with an approximate Roe's Riemann solver and a slope-limiting procedure allows us to capture elastic jumps accurately. Moreover, this paper demonstrates that the complex physics associated with such flows is more accurately modelled than with traditional methods such as finite difference methods or finite volumes. We present various benchmark problems that show the flexibility and applicability of the numerical method. Our solutions are compared with analytical solutions when they are available and with solutions obtained using other numerical methods. Finally, to illustrate the clinical interest, we study the emptying process in a calf vein squeezed by contracting skeletal muscle in a normal and pathological subject. We compare our results with experimental simulations and discuss the sensitivity to parameters of our model.     

Characterization of Free Radical Defense System in High Glucose Cultured HeLa-tat Cells: Consequences for Glucose-induced Cytotoxicity

HeLa cell line stably transfected with the tat gene from human immunodeficiency virus type 1 has a decreased antioxidant potential. In this work, we used this model to investigate the effect of a high glucose level (20 mM) on the glucose induced cytotoxicity and on the antioxidant system. In comparison to cell culture under control medium, HeLa-wild cell cultured under 20 mM glucose did not exhibit necrosis or apoptosis, contrary to HeLa-tat cell presenting a significant increase in necrotic or apoptotic state. Moreover after 48 h culture under high glucose level the HeLa-tat proliferation rate was not higher than the one of HeLa-wild cells. In HeLa-wild cell high glucose level resulted in an induction of glutathione reductase activity in opposition to HeLa-tat cells where no change was observed. High glucose level resulted in 20% increase in GSSG/GSH ratio in HeLa-wild cells and 38% increase in HeLa-tat cells. Moreover, high glucose level resulted in a dramatic cytosolic thiol decrease and an important lipid peroxidation in HeLa-tat cells. No significant change of these two parameters was observed in HeLa-wild cells. In both cell lines, high glucose resulted in an increase of total SOD activity, as a consequence of the increase in Cu,Zn-SOD activity. High glucose did not result in an increase of Mn-SOD activity in both cell lines. As a consequence of tat tranfection Mn-SOD activity was 50% lower in HeLa-tat cells in comparison to HeLa-wild cells. This work emphasizes the importance of the antioxidant system in the glucose induced cytotoxicity.