Therapeutic electrical stimulation of the central nervous system

The electrical effects on the nervous system have been known for long. The excitatory effect has been used for diagnostic purposes or even for therapeutic applications, like in pain using low-frequency stimulation of the spinal cord or of the thalamus. The discovery that High-Frequency Stimulation (HFS) mimics the effect of lesioning has opened a new field of therapeutic application of electrical stimulation in all places where lesion of neuronal structures, such as nuclei of the basal ganglia, had proven some therapeutic efficiency. This was first applied to the thalamus to mimic thalamotomy for the treatment of tremor, then to the subthalamic nucleus and the pallidum to treat some advanced forms of Parkinson's disease and control not only the tremor but also akinesia, rigidity and dyskinesias. The field of application is increasingly growing, currently encompassing dystonias, epilepsy, obsessive compulsive disease, cluster headaches, and experimental approaches are being made in the field of obesity and food intake control. Although the effects of stimulation are clear-cut and the therapeutic benefit is clearly recognized, the mechanism of action of HFS is not yet understood. The similarity between HFS and the effect of lesions in several places of the brain suggests that this might induce an inhibition-like process, which is difficult to explain with the classical concept of physiology where electrical stimulation means excitation of neural elements. The current data coming from either clinical or experimental observations are providing elements to shape a beginning of an understanding. Intra-cerebral recordings in human patients with artefact suppression tend to show the arrest of electrical firing in the recorded places. Animal experiments, either in vitro or in vivo, show complex patterns mixing inhibitory effects and frequency stimulation induced bursting activity, which would suggest that the mechanism is based upon the jamming of the neuronal message, which is by this way functionally suppressed. More recent data from in vitro biological studies show that HFS profoundly affects the cellular functioning and particularly the protein synthesis, suggesting that it could alter the synaptic transmission by reducing the production of neurotransmitters. It is now clear that this method has a larger field of application than currently known and that its therapeutical applications will benefit to several diseases of the nervous system. The understanding of the mechanism has opened a new field of research, which will call for reappraisal of the basic effects of electricity on the living tissues.     

SNP-based large-scale identification of allele-specific gene expression in human B cells

Polymorphism and variations in gene expression provide the genetic basis for human variation. Allelic variation of gene expression, in particular, may play a crucial role in phenotypic variation and disease susceptibility. To identify genes with allelic expression in human cells, we genotyped genomic DNA and cDNA isolated from 31 immortalized B cell lines from three Centre d'Etude du Polymorphisme Humain (CEPH) families using high-density single-nucleotide polymorphism (SNP) chips containing 13,900 exonic SNPs. We identified seven SNPs in five genes with monoallelic expression, 146 SNPs in 125 genes with allelic imbalance in expression with preferentially higher expression of one allele in a heterozygous individual. The monoallelically expressed genes (ERAP2, MDGA1, LOC644422, SDCCAG3P1 and CLTCL1) were regulated by cis-acting, non-imprinted differential allelic control. In addition, all monoallelic gene expression patterns and allelic imbalances in gene expression in B cells were transmitted from parents to offspring in the pedigree, indicating genetic transmission of allelic gene expression. Furthermore, frequent allele substitution, probably due to RNA editing, was also observed in 21 genes in 23 SNPs as well as in 48 SNPs located in regions containing no known genes. In this study, we demonstrated that allelic gene expression is frequently observed in human B cells, and SNP chips are very useful tools for detecting allelic gene expression. Overall, our data provide a valuable framework for better understanding allelic gene expression in human B cells.     

Plaidoyer pour un outillage lithique de l’Âge du fer : le cas des maillets à gorge de l’Ouest de la France

The attention is turned here to one kind of tools, characterized by a special morphology: the grooved hammer-stones. They are known in Europe and all over the world in various cultures, as Neolithic or Bronze Age remains and generally linked to extraction or mining activity; but, the discovery of several of these tools in western France, within pre-roman archaeological contexts, especially in sites devoted to marine salt production, leads us to a discussion on dating and the function of such tools, and feeds a more general reflexion about the existence of a specialised lithic set of tools during the Iron Age.     

Brittle stars from the upper Cenomanian of the Preafrican platform: First ophiuroid remains for the Cretaceous of Algeria

While Late Cretaceous ophiuroids are relatively well known in Europe, these faunas have been much less studied in North Africa. With the exception of some Tunisian assemblages preliminary described at the turn of the 21st century, nothing is known about the Cretaceous brittle stars of the southwestern Tethyan margin. The present paper seeks to bring the first data about hitherto unknown ophiuroids recently found in the early upper Cenomanian succession of the eastern side of the Preafrican trough (Menaguir section, Algeria). This “community” of brittle stars comprises at least eight species. Most of them are probably new, but have not been formally named here. These are representatives of the families Hemieuryalidae, Amphiuridae, Ophiodermatidae, Ophiacanthidae, Ophiopezidae and probably also Ophiomyxidae and Ophiobyrsidae. Almost all vertebrae are zygospondylous; no streptospondylous vertebrae indicate the absence of the order Euryalida here. Most of the ophiuroids belong to the orders Amphilepidida and Ophiacanthida. Ophiotitanos serrata, Ophiomyxa? aff. jekerica, Ophiojagtus? sp. and some other taxa resembling ophiuroid assemblages from the Late Cretaceous of central, western and northern Europe. With respect to the late Cenomanian age, the depth of the sea and the taxonomic composition, there are some similarities with ophiuroids of the Bohemian Cretaceous Basin. The mid-ramp subtidal facies suggests that brittle stars lived here in a warm, euphotic and probably shallow sea.     

Correlation between baseline 18F-FDG PET/CT features and pathological complete response after neoadjuvant chemotherapy in early triple negative breast cancer

Aim of the studyTo evaluate correlation between metabolic and textural parameters on baseline ¹⁸F-FDG PET/CT and pathological response after neoadjuvant chemotherapy in non-metastatic triple negative breast cancer (TNBC).MethodsAll consecutive non-metastatic TNBC women treated by neoadjuvant chemotherapy followed by breast surgery who underwent ¹⁸F-FDG PET/CT examination at diagnosis between 2012 and 2018 were retrospectively included. Metabolic parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG) of the primary tumour and lymph nodes, and textural features (entropy, homogeneity, SRE, LRE, LGZE, HGZE) of the primary tumour were collected. Pathological response was defined according to Sataloff classification.ResultsSeventy-four patients were enrolled. In univariate analysis, metabolic and textural features of the primary breast lesion or metabolic parameters of regional lymph nodes were not predictive of pathological complete response after neoadjuvant chemotherapy.ConclusionMetabolic and textural features of baseline PET/CT do not seem to predict pathological response after neoadjuvant chemotherapy in non-metastatic triple negative breast cancer.     

The fauna and associated artefacts from the Lower Pleistocene site of Mansourah (Constantine, Algeria)

The site of Mansourah (Constantine, Algeria) had yielded to the early authors, and more recently to the late G. Laplace, a lithic industry associated with a fauna of large Mammals, which looks contemporaneous with that of Aïn Hanech, although it is well-distinct ecologically, and might even be slightly older. The lithic assemblage is completely devoid of any bifacial artefact or cleaver and can only be referred to the Oldowan. Thus, the Mansourah site documents a very early human occupation of North Africa, and perhaps one of the earliest. To cite this article: Y. Chaid-Saoudi et al., C. R. Palevol 5 (2006).     

Enregistrement des fluctuations du niveau marin dans l’Holocène supérieur du lac Retba (Sénégal) par les foraminifères

A study of sea level fluctuation records based on foraminiferal assemblages was carried out for the first time in a sediment core taken at the Lac Retba edge. A total of 37 foraminifera species were collected along the core, among which most are known in the modern estuaries and lagoons of Senegal. A succession of four assemblages dominated by Ammonia parkinsoniana and A. tepida were identified; they correspond to different stages of evolution of the lake. The first association, at the base of the core, indicates a lagoon slightly opened to the sea and bordered with vegetation, under relatively humid climate. The second has the richest and most diversified microfauna with a high proportion of coastal, marine benthic and planktonic species (about 10%) that indicate a small coastal gulf bordered with mangroves. The third association is oligospecific and typical of a closed and hypersaline lagoon under a dry climate. The last association again contains coastal, marine benthic and scarce planktonic species (3%) indicating a change to a saltier and more open lagoon under dry climate. The disappearance of planktonic foraminifera at the top of the core indicates the closure of the lagoon. The biocenotic indicators are evidence for two marine intrusions that are referred to the Dakarian (3000 years B.P.) and Saint-Louisian (2140-680 years B.P.) stages of the Upper Holocene of the senegalo-mauritanian stratigraphic scale. Evidence of the Lac Retba closure since 680 years B. P. appears in the core by high reduction of foraminifers’ abundance and diversity absence of planktonic species, and salts precipitated at the bottom of the lake.     

Dynamic simulation of pollutant effects on the threonine pathway in Escherichia coli

The enzymatic activities of threonine pathway in Escherichia coli are sensitive to pollutants such as cadmium, copper and mercury, which, even at low concentration, can substantially decrease or even block the pathway at several steps. Our aim was to investigate the complex effects on a metabolic pathway of such general enzyme inhibitors with several sites of action, using a previously developed computer simulation of the pathway. For this purpose, the inhibition parameters were experimentally determined and incorporated in the model. The calculation of the flux control coefficient distribution between the five steps of the threonine pathway showed that control remains shared between the three first steps under most inhibition conditions. Response coefficient analysis shows that the inhibition of aspartate semialdehyde dehydrogenase is quantitatively dominant in most circumstances.     

Inhibition of soluble yeast mitochondria ATPase by ethidium-bromide.

Surface galactosyl residues of alive embryonal carcinoma cells were tritium-labeled by the galactose oxidase NaB(3H)4 method. The labeled glycopeptides isolated from Pronase digests of the cells, were found to be similar to those prepared from endogeneously labeled embryonal carcinoma cells. They consisted mostly of high molecular weight material, and contained receptors for peanut agglutinin. It is concluded that at least a fraction of the high molecular weight glycopeptides characteristic of early embryonic cells, is displayed on the cell suface.