The Anti-Metastatic nm23-1 Gene Is Needed for the Final Step of Mammary Duct Maturation of the Mouse Nipple

Nm23/NDP kinases are multifunctional enzymes involved in the general homeostasis of triphosphate nucleosides. Numerous studies have shown that NDPKs also serve as regulatory factors of various cell activities, not always connected to nucleotide phosphorylation. In particular, the nme-1 gene, encoding the NM23-1/NDPKA protein, has been reported as a metastasis suppressor gene. This activity was validated in hepatocellular tumors induced in nm23-1 deficient mice. Yet, data describing the primary physiological functions of nm23-1/NDPKA is still scarce. We have characterized in depth the phenotype of nm23-1 deletion in the mammary gland in mice carrying whole body nm23-M1 invalidation. We also asked why the nm23-M1−/− mutant females displayed severe nursing disability. We found that the growth retardation of mutant virgin glands was due to reduced proliferation and apoptosis of the epithelial cells within the terminal end buds. The balance of pro/anti-apoptotic factors was impaired in comparison with wild type glands. In the lactating glands, the reduced proliferation rate persisted, but the apoptotic factors were unchanged. However, those defects did not seem to affect the gland maturation since the glands lacking nm23-1/NDPKA appeared morphologically normal. Thorough examination of all the functional aspects of the mammary glands revealed that lack of nm23-1/NDPKA does not impact the production or the ejection of milk in the lumen of lobuloalveolae. Interestingly, an epithelial plug was found to obstruct the extremity of the unique lactiferous duct delivering the milk out of the nipple. These cells, normally disappearing after lactation takes place, persisted in the mutant nipples. This work provides a rare instance of nm23-1/NDPKA physiological functions in the mammary glands and reveals its implication as a modulator factor of proliferation and apoptosis in this tissue

Procedures and Frequencies of Embalming and Heart Extractions in Modern Period in Brittany. Contribution to the Evolution of Ritual Funerary in Europe.

The evolution of funeral practices from the Middle Ages through the Modern era in Europe is generally seen as a process of secularization. The study, through imaging and autopsy, of two mummies, five lead urns containing hearts, and more than six hundred skeletons of nobles and clergymen from a Renaissance convent in Brittany has led us to reject this view. In addition to exceptional embalming, we observed instances in which hearts alone had been extracted, a phenomenon that had never before been described, and brains alone as well, and instances in which each spouse's heart had been placed on the other's coffin. In some identified cases we were able to establish links between the religious attitudes of given individuals and either ancient Medieval practices or more modern ones generated by the Council of Trent. All of these practices, which were a function of social status, were rooted in religion. They offer no evidence of secularization whatsoever

Les pratiques de subsistance de la population Néolithique final de la grotte I des Treilles (commune de Saint-Jean-et-Saint-Paul, Aveyron)

La Grotte I des Treilles (commune de Saint-Jean-et-Saint-Paul, Aveyron) se situe sur l’extrémité sud-occidentale du Causse du Larzac. C’est une grotte sépulcrale à caractère collectif et des datations radiocarbone l’ont attribuée au Néolithique final (3030-2890 cal B.C, phase moyenne du Groupe des Treilles). Cette recherche a pour objectif (1) d’appréhender le type d’écosystème exploité par la population de la Grotte I des Treilles pour subvenir à ses besoins nutritionnels et (2) d’étudier les relations entre les pratiques alimentaires et des données anthropométriques. Pour cela, une analyse isotopique a été menée sur 42 individus adultes (pour un total de 86 individus adultes mis au jour) ainsi que sur 14 ossements de faune découverts sur plusieurs sites archéologiques contemporains régionaux. Les résultats isotopiques montrent une consommation locale des protéines par la population de la Grotte I des Treilles. La contribution des protéines animales apparait importante relativement aux protéines végétales. Nos résultats suggèreraient également la contribution de viande de jeunes animaux non encore sevrés dans l’alimentation. La quantité de protéines animales consommée par cette population est très variable entre les individus du groupe. Toutefois, cette diversité de comportement alimentaire n’est pas corrélée aux données anthropométriques (longueurs des os longs et robustesse). Les choix alimentaires n’apparaissent pas liés aux paramètres biologiques testés et ne sont donc probablement pas dictés par le sexe des individus.The Grotte I des Treilles (Saint-Jean-et-Saint-Paul, Aveyron, France), is located on the South-Western side of Larzac Causse. It is a funerary cave with collective inhumations, used during Final Neolithic after the radiocarbon dates (3030-2890 cal BC, middle phase of the “Groupe des Treilles”). This study aims to know (1) the ecosystem exploited for food consumption by humans from the Grotte I des Treilles, and (2) the relationship between dietary choices and biometric data. Stable isotope analyses were thus performed on 42 mature individuals (selected from 86 adults) as well as 14 faunal remains from different regional sites. Isotopic results show a relationship between production/consumption by humans of animal species locally found. Dietary practices are mainly focused on meat consumption compared to plant resources. Our results also highlight a probable consumption of meat of young animal (not weaned) and various animal protein intake according to individuals. This variability was not correlated to anthropometric data (stature and robustness), and food choices seem not sex-related

Les pratiques de subsistance de la population Néolithique final de la grotte I des Treilles (commune de Saint-Jean-et-Saint-Paul, Aveyron)

La Grotte I des Treilles (commune de Saint-Jean-et-Saint-Paul, Aveyron) se situe sur l’extrémité sud-occidentale du Causse du Larzac. C’est une grotte sépulcrale à caractère collectif et des datations radiocarbone l’ont attribuée au Néolithique final (3030-2890 cal B.C, phase moyenne du Groupe des Treilles). Cette recherche a pour objectif (1) d’appréhender le type d’écosystème exploité par la population de la Grotte I des Treilles pour subvenir à ses besoins nutritionnels et (2) d’étudier les relations entre les pratiques alimentaires et des données anthropométriques. Pour cela, une analyse isotopique a été menée sur 42 individus adultes (pour un total de 86 individus adultes mis au jour) ainsi que sur 14 ossements de faune découverts sur plusieurs sites archéologiques contemporains régionaux. Les résultats isotopiques montrent une consommation locale des protéines par la population de la Grotte I des Treilles. La contribution des protéines animales apparait importante relativement aux protéines végétales. Nos résultats suggèreraient également la contribution de viande de jeunes animaux non encore sevrés dans l’alimentation. La quantité de protéines animales consommée par cette population est très variable entre les individus du groupe. Toutefois, cette diversité de comportement alimentaire n’est pas corrélée aux données anthropométriques (longueurs des os longs et robustesse). Les choix alimentaires n’apparaissent pas liés aux paramètres biologiques testés et ne sont donc probablement pas dictés par le sexe des individus.The Grotte I des Treilles (Saint-Jean-et-Saint-Paul, Aveyron, France), is located on the South-Western side of Larzac Causse. It is a funerary cave with collective inhumations, used during Final Neolithic after the radiocarbon dates (3030-2890 cal BC, middle phase of the “Groupe des Treilles”). This study aims to know (1) the ecosystem exploited for food consumption by humans from the Grotte I des Treilles, and (2) the relationship between dietary choices and biometric data. Stable isotope analyses were thus performed on 42 mature individuals (selected from 86 adults) as well as 14 faunal remains from different regional sites. Isotopic results show a relationship between production/consumption by humans of animal species locally found. Dietary practices are mainly focused on meat consumption compared to plant resources. Our results also highlight a probable consumption of meat of young animal (not weaned) and various animal protein intake according to individuals. This variability was not correlated to anthropometric data (stature and robustness), and food choices seem not sex-related

Pro-oncogenic potential of NM23-H2 in hepatocellular carcinoma

NM23 is a family of structurally and functionally conserved proteins known as nucleoside diphosphate kinases (NDPK). There is abundant mRNA expression of NM23-H1, NM23-H2, or a read through transcript (NM23-LV) in the primary sites of hepatocellular carcinoma (HCC). Although the NM23-H1 protein is implicated as a metastasis suppressor, the role of NM23-H2 appears to be less understood. Thus, the aim of this study was to examine whether NM23-H2 is associated with hepatocarcinogenesis. The level of NM23-H2 expression in tumor tissues and the surrounding matrix appeared to be independent of etiology and tumor differentiation. Its subcellular localization was confined to mainly the cytoplasm and to a lesser extent in the nucleus. Ectopic expression of NM23-H2 in NIH3T3 fibroblasts and HLK3 hepatocytes showed a transformed morphology, enhanced focus formation, and allowed anchorage-independent growth. Finally, NIH3T3 fibroblasts and HLK3 hepatocytes stably expressing NM23-H2 produced tumors in athymic mice and showed c-Myc over-expression. In addition, NF-κB and cyclin D1 expression were also increased by NM23-H2. Lentiviral delivery of NM23-H2 shRNA inhibited tumor growth of xenotransplanted tumors produced from HLK3 cells stably expressing NM23-H2. Collectively, these results indicate that NM23-H2 may be pro-oncogenic in hepatocarcinogenesis

Global Genetic Structure and Molecular Epidemiology of Encapsulated Haemophilus influenzae

A collection of 2,209 isolates of six polysaccharide capsule types of Haemophilus influenzoe, including 1,975 serotype b isolates recovered in 30 countries was characterized for electrophoretically demonstrable allele profiles at 17 metabolic enzyme loci. Two hundred eighty distinct multilocus genotypes were distinguished, and cluster analysis revealed two primary phylogenetic divisions. The population structure of encapsulated H. influenzae is clonal. Currently, most of the invasive disease worldwide is caused by serotype b strains of nine clones, Strains producing serotype c, e, and f capsules belong to single divisions and have no close genetic relationships to strains of other serotypes, Serotype a and b strains occur in both primary phylogenetic divisions, probably as a result of transfer and recombination of serotype-specific sequences of the cap region between clonal lineages. A close genetic relatedness between serotype d isolates and some strains of serotypes a and b was identified, There are strong patterns of geographic variation, on an intercontinental scale, in both the extent of genetic diversity and the clonal composition of populations of encapsulated strains, The analysis suggests that the present distribution of clones is, in part, related to patterns of racial or ethnic differentiation and historical demographic movements of the human host population