p53-dependent ceramide response to genotoxic stress

Both p53 and ceramide have been implicated in the regulation of growth suppression. p53 has been proposed as the "guardian of the genome" and ceramide has been suggested as a "tumor suppressor lipid. " Both molecules appear to regulate cell cycle arrest, senescence, and apoptosis. In this study, we investigated the relationship between p53 and ceramide. We found that treatment of Molt-4 cells with low concentrations of actinomycin D or gamma-irradiation, which activate p53-dependent apoptosis, induces apoptosis only in cells expressing normal levels of p53. In these cells, p53 activation was followed by a dose- and time-dependent increase in endogenous ceramide levels which was not seen in cells lacking functional p53 and treated similarly. Similar results were seen in irradiated L929 cells whereby the p53-deficient clone was significantly more resistant to irradiation and exhibited no ceramide response. However, in p53-independent systems, such as growth suppression induced by TNF-alpha or serum deprivation, ceramide accumulated irrespective of the upregulation of p53, indicating that p53 regulates ceramide accumulation in only a subset of growth-suppressive pathways. Finally, ceramide did not increase p53 levels when used at growth-suppressive concentrations. Also, when cells lacking functional p53, either due to mutation or the expression of the E6 protein of human papilloma virus, were treated with exogenous ceramide, there was equal growth suppression, cell cycle arrest, and apoptosis as compared with cells expressing normal p53. These results indicate that p53 is unlikely to function "downstream" of ceramide. Instead, they suggest that, in situations where p53 performs a critical regulatory role, such as the response to genotoxic stress, it functions "upstream" of ceramide. These studies begin to define a relationship between these two pathways of growth inhibition.     

Evaluation of spike-detection algorithms for a brain-machine interface application

Real time spike detection is an important requirement for developing brain machine interfaces (BMIs). We examined three classes of spike-detection algorithms to determine which is best suited for a wireless BMI with a limited transmission bandwidth and computational capabilities. The algorithms were analyzed by tabulating true and false detections when applied to a set of realistic artificial neural signals with known spike times and varying signal to noise ratios. A design-specific cost function was developed to score the relative merits of each detector; correct detections increased the score, while false detections and computational burden reduced it. Test signals both with and without overlapping action potentials were considered. We also investigated the utility of rejecting spikes that violate a minimum refractory period by occurring within a fixed time window after the preceding threshold crossing. Our results indicate that the cost-function scores for the absolute value operator were comparable to those for more elaborate nonlinear energy operator based detectors. The absolute value operator scores were enhanced when the refractory period check was used. Matched-filter-based detectors scored poorly due to their relatively large computational requirements that would be difficult to implement in a real-time system.     

The similarity and differences in the circadian fluctuations in the central nervous system reaction of animals to acute gamma radiation and alcohol exposures

24-h fluctuations in the response of CNS (occurrence of the complex of neurological disorders) were studied in white rat males which were exposed to gamma radiation (Co-50, 62.5 Gy, craniocaudally) or injected alcohol (2.25 g/kg, 15% solution, i.p.). After alcohol administration, the above fluctuations were at first almost similar to those in response to the radiation. Later, the curve of the CNS sensitivity to alcohol was leveling, rhythm phases shifted without the rhythm inversion. Neurological symptoms induced by alcohol and radiation were very much alike suggesting the existence of common mechanisms of nonspecific regulation evident early after exposure to these two factors.     

Binding of phosphoorganic cholinesterase inhibitors in rat brain tissue

Hydrophobity (coefficient in distribution in the hexane water system) and the content of cholinesterase organophosphorous inhibitors (OPI) of the structure Ro (CH3) P (O) SC2H4 SC2H5 were studied in the rat brain. When the O-alkyl radical is increased hydrophobity rises and the relative content of free OPI in the brain extracted by chloroform decreases. With an increase in R from the ethyl to butyl one the ability to the additional inhibition of the brain own cholinesterase lowers due to incubation of homogenate at 37 degrees C, that evidences for an essential drop in the studied series of the free OPI fraction relative to the free OPI extracted by chloroform.     

Elevated alpha-fetoprotein secondary to Hodgkin's lymphoma

We describe the case of a 26-year-old man with an elevated level of alpha-fetoprotein who had no evidence of intragonadal or extragonadal germ cell tumor. The patient was found to have Hodgkin's lymphoma within an anterior mediastinal mass. We review the significance of elevated alpha-fetoprotein levels and discuss the clinical relevance of this unusual presentation of a possible primary Hodgkin's lymphoma.     

Experimental identification of Biot's hydro-mechanical coupling coefficient for cement mortar

The objective of the present paper is to show an experimental method allowing the characterisation of Biot's hydro-mechanical coupling coefficient for cement mortar. This coefficient results from the mathematical formulation of a thermo-hygro-mechanical coupling model for non-saturated media [3, 8, 9, 11]. In the literature, the expression of Biot's coefficient is based on an empirical formula. The proposed method of its identification is bosed on two experiments: the dimensional variation tests and the characterisation of the elastic properties as a function of different relative humidity. We deduce Biot's coefficient by using the thermal-porous-elastic behaviour law of Coussy [2, 3]. In the literature, liquid Biot's coefficientb _l is often approached with the degree of liquid, saturationS _l . By comparing the results of liquid Biot's coefficientb _l determined experimentally and the coefficient of liquid saturationS _l , we show a good agreement between the two coefficients for small to moderate relative humidity. For important relative humidity (i.e. higher than 70%), the value of liquid Biot's coefficient is slightly lower than saturation.

---

Résumé L'objectif de ce papier consiste à montrer une méthode expérimentale permettant la caractérisation du coefficient de couplage hydromécanique de Biot pour le mortier de ciment. Ce coefficient résulte de la formulation mathématique d'un modèle de couplage thermo-hygro-méchanique pour les milieux poreux non-saturés [3, 8, 9, 11]. Dans la littérature, l'expression du coefficient de Biot est basée sur deux expériences: l'essai de variation dimensionnelle et de caractérisation des propriétés élastiques à différentes humidités relatives. Nous déduisons ainsi le coefficient de Biot en se servant de la loi de comportement thermo-poro-élastique de Coussy [2, 3]. Dans la littérature, le coefficient de Biot liquide b_l est souvent rapproché avec le degré de la saturation liquide S_l. En comparant les résultats de ces deux coefficients, nous montrons une bonne concordance entre eux pour des humidités relatives faibles et moyennes. Par contre, pour des humidités relatives importantes (c'est-à-dire supérieures à 70%), nous trouvons que le coefficient de Biot liquide est légèrement inférieur au degré de la saturation.

---

---

Editorial Note CSTB is a RILEM Titular Member.