β

A number of xenobiotic-inducible cytochrome P450s (CYPs) are now known to be localized in the mitochondrial compartment, though their pharmacological or toxicological roles remain unclear. Here, we show that BNF treatment markedly inhibits liver mitochondrial O2 consumption rate (OCR), ADP-dependent OCR, and also reserve OCR, in wild-type mice but not in Cyp1a1/1a2(−/−) double knockout mice. BNF treatment markedly affected mitochondrial complex I and complex IV activities and also attenuated mitochondrial gene expression. Furthermore, under in vitro conditions, BNF treatment induced cellular ROS production, which was inhibited by mitochondria-targeted antioxidant Mito-CP and CYP inhibitor proadefin, suggesting that most of the ROS production was intramitochondrial and probably involved the catalytic activity of mitochondrial CYP1 enzymes. Interestingly, our results also show that the AHR antagonist resveratrol, markedly attenuated BNF-induced liver mitochondrial defects in wild-type mice, confirming the role of AHR and AHR-regulated CYP1 genes in eliciting mitochondrial dysfunction. These results are consistent with reduced BNF-induced mitochondrial toxicity in Cyp1a1/1a2(−/−) mice and elevated ROS production in COS cells stably expressing CYP1A1. We propose that increased mitochondrial ROS production and respiratory dysfunction are part of xenobiotic toxicity. Resveratrol, a chemopreventive agent, renders protection against BNF-induced toxicity

Conditional Tek Promoter-Driven Deletion of Arginyltransferase in the Germ Line Causes Defects in Gametogenesis and Early Embryonic Lethality in Mice

Posttranslational protein arginylation mediated by Ate1 is essential for cardiovascular development, actin cytoskeleton functioning, and cell migration. Ate1 plays a role in the regulation of cytoskeleton and is essential for cardiovascular development and angiogenesis—capillary remodeling driven by in-tissue migration of endothelial cells. To address the role of Ate1 in cytoskeleton-dependent processes and endothelial cell function during development, we produced a conditional mouse knockout with Ate1 deletion driven by Tek endothelial receptor tyrosine kinase promoter expressed in the endothelium and in the germ line. Contrary to expectations, Tek-Ate1 mice were viable and had no visible angiogenesis-related phenotypes; however, these mice showed reproductive defects, with high rates of embryonic lethality in the second generation, at stages much earlier than the complete Ate1 knockout strain. While some of the early lethality originated from the subpopulation of embryos with homozygous Tek-Cre transgene—a problem that has not previously been reported for this commercial mouse strain—a distinct subpopulation of embryos had lethality at early post-implantation stages that could be explained only by a previously unknown defect in gametogenesis originating from Tek-driven Ate1 deletion in premeiotic germs cells. These results demonstrate a novel role of Ate1 in germ cell development

Mobility and social identity in the Mid Upper Paleolithic: New personal ornaments from Poiana Cireșului (Piatra Neamț, Romania).

Most of the Paleolithic art and ornaments discovered in Romania come from the site of Poiana Cireșului. Four Paleolithic layers have been studied at this site-the oldest one belongs to the Early Gravettian period between 30 ka and 31 ka BP. The ornaments discovered in this layer include perforated shells from three species of mollusks: freshwater Lithoglyphus naticoide and Lithoglyphus apertus as well as Homalopoma sanguineum (an exclusively Mediterranean species). Poiana Cireșului is one of the very few Gravettian sites where perforated Homalopoma sanguineum shells were found, and the importance of this discovery is stressed even more by the very long distance between the site and the nearest source located over 900 km away. This find suggests the connection of communities here with the Mediterranean area as well as a possible movement of populations from the south of the continent to the east of the Carpathians with significant implications in understanding human group mobility and the origin of the Early Gravettian in this area. Furthermore, Poiana Cireșului is the only Gravettian settlement where Lithoglyphus naticoides shells were used. The unique association of perforated shells-not found in any other Gravettian settlement-contributes to the identity of the Paleolithic community of Poiana Cireșului through their ornaments

The cultural dynamics of Upper Paleolithic to the East of the Carpathians reflected by the characteristics of the Bistrița Valley settlements (Romania), with special focus on the occupations from Poiana Cireșului site

International audienceMost of the Upper Paleolithic settlements in Romania are located at the East of the Carpathian Mountains, on the Bistriţa and Prut rivers valleys. By their chronological framework and their lithic technical system, most of them seem to belong to a gravettian technical tradition. Nowadays, around 20 settlements were described on the Bistriţa river alone, even though not all of them have been equally studied. One of the key-sites for this region is Poiana Cireşului-Piatra Neamţ, where several research campaigns have been carried out recently. The research in this site revealed four archaeological layers: one Epigravettian layer and three Gravettian ones, separated by thick sterile levels. Chronologically, these occupations overlap almostthe entire lato sensu Gravettian development period (20-27 ka uncal. BP), thus covering a wide time frame before and after the Last Glacial Maximum. Preliminary analysis of the archaeological assemblages showed a diversity of techno-economic and symbolic behaviors for each layer. This diversity reflects certainly the cultural variability of the groups that occupied the site, and more broadly, the one which is also expressed in the vast European technical entity named ‘Gravettian’La plupart des gisements du Paléolithique supérieur de Roumanie sont situés à l’est des Carpates, dans les vallées des rivières de la Bistriţa et du Prut. Par leur cadre chronologique et leur système technique lithique, ces gisements semblent se rattacher à une tradition technique gravettienne. A ce jour, une vingtaine de gisements ont été décrits pour la seule vallée de la Bistriţa, même si tous n’ont pas été étudiés de la même manière. Poiana Cireşului-Piatra Neamţ, où plusieurs campagnes de fouilles programmées ont été menées ces dernières années, est l’un des sites clés de cette région. Quatre couches archéologiques y ont été identifiées : une couche épigravettienne et trois couches gravettiennes, séparées par des niveaux stériles épais. Chronologiquement, ces occupations recouvrent presque toute la période de développement du Gravettien lato sensu (20 à 27 ka BP), couvrant ainsi une large période avant et après le dernier maximum glaciaire. Une analyse préliminaire des ensembles archéologiques a permis de mettre en évidence une diversité diachronique des comportements techno-économiques et symboliques pour chacun des niveaux; cette diversité reflète certainement la variabilité culturelle des groupes qui ont occupé le site, et plus largement, celle qui s’exprime aussi au sein de la vaste entité technique européenne nommée « Gravettien »

The cultural dynamics of Upper Paleolithic to the East of the Carpathians reflected by the characteristics of the Bistrița Valley settlements (Romania), with special focus on the occupations from Poiana Cireșului site

International audienceMost of the Upper Paleolithic settlements in Romania are located at the East of the Carpathian Mountains, on the Bistriţa and Prut rivers valleys. By their chronological framework and their lithic technical system, most of them seem to belong to a gravettian technical tradition. Nowadays, around 20 settlements were described on the Bistriţa river alone, even though not all of them have been equally studied. One of the key-sites for this region is Poiana Cireşului-Piatra Neamţ, where several research campaigns have been carried out recently. The research in this site revealed four archaeological layers: one Epigravettian layer and three Gravettian ones, separated by thick sterile levels. Chronologically, these occupations overlap almostthe entire lato sensu Gravettian development period (20-27 ka uncal. BP), thus covering a wide time frame before and after the Last Glacial Maximum. Preliminary analysis of the archaeological assemblages showed a diversity of techno-economic and symbolic behaviors for each layer. This diversity reflects certainly the cultural variability of the groups that occupied the site, and more broadly, the one which is also expressed in the vast European technical entity named ‘Gravettian’La plupart des gisements du Paléolithique supérieur de Roumanie sont situés à l’est des Carpates, dans les vallées des rivières de la Bistriţa et du Prut. Par leur cadre chronologique et leur système technique lithique, ces gisements semblent se rattacher à une tradition technique gravettienne. A ce jour, une vingtaine de gisements ont été décrits pour la seule vallée de la Bistriţa, même si tous n’ont pas été étudiés de la même manière. Poiana Cireşului-Piatra Neamţ, où plusieurs campagnes de fouilles programmées ont été menées ces dernières années, est l’un des sites clés de cette région. Quatre couches archéologiques y ont été identifiées : une couche épigravettienne et trois couches gravettiennes, séparées par des niveaux stériles épais. Chronologiquement, ces occupations recouvrent presque toute la période de développement du Gravettien lato sensu (20 à 27 ka BP), couvrant ainsi une large période avant et après le dernier maximum glaciaire. Une analyse préliminaire des ensembles archéologiques a permis de mettre en évidence une diversité diachronique des comportements techno-économiques et symboliques pour chacun des niveaux; cette diversité reflète certainement la variabilité culturelle des groupes qui ont occupé le site, et plus largement, celle qui s’exprime aussi au sein de la vaste entité technique européenne nommée « Gravettien »

Technical observations on the first Palaeolithic surface collection from Izvorul Alb (Bicaz, Romania)

Among the many Palaeolithic discoveries in the Bistriţei Valley, an impressive collection of lithic materials (almost 3,000 pieces) have been collected, over the years, from Izvorul Alb-Bicaz (north-eastern Romania). Most of the items come from surface recoveries and at this moment no site has been accurately located. We present an analysis of the first collection of lithic materials found at Izvorul Alb in 1977 and 1978, recovered from two distinct places, Baicu and Piciorul Gol. Our observations point to several differences between the items collected in the two places. Generally, some of the items come from a late Palaeolithic level, Epigravettian or even Epipalaeolithic, and the rest of lithic materials may belong to Gravettian traditions sensu lato.Niţu Elena-Cristina, Matei Mihai, Popa Daniel-Dumitru, Cârciumaru Marin, Leu Marian, Cîrstina Ovidiu, Ionuț Lupu Florin, Nicolae Adrian. Technical observations on the first Palaeolithic surface collection from Izvorul Alb (Bicaz, Romania). In: Annales d'Université "Valahia" Târgovişte. Section d'Archéologie et d'Histoire, Tome 20, 2018. pp. 17-27

Amber Deposits in Romania, with Particular Emphasis on Those Located on the Eastern Side of the Carpathians (Bibliographical Considerations and a few Field Investigations)

During the archaeological excavations of 2002, in the Palaeolithic site of Poiana Cireșului (north-eastern Romania) was discovered a fragment of amber in the first Gravettian layer. Recent investigations in this settlement have revealed four archaeological layers : one Epigravettian layer and three Gravettian ones. The first Gravettian layer, which is contemporary with the Last Glacial Maximum, has provided the richest habitation of the site, being dated around 20,000 B. P. In order to identify the provenance of this raw material, the research included several phases. The first stage of our research involved a re-evaluation of the amber deposits described in Romanian geological literature, beginning with the oldest mentions that had been sometimes overlooked or completely forgotten. The second stage involved carrying out field investigations with a view to verifying the deposits located in the vicinity of the Poiana Cireșului site. The results of these two stages are to be described in this article, while the physico-chemical analyses will be published in a future study.Cârciumaru Marin, Niţu Elena-Cristina, Miclăuș Crina, Ion Rodica-Mariana, Cîrstina Ovidiu, Ionuț Lupu Florin, Leu Marian, Văleanu Mădălin-Cornel, Nicolae Adrian, Grigore Stelian. Amber Deposits in Romania, with Particular Emphasis on Those Located on the Eastern Side of the Carpathians (Bibliographical Considerations and a few Field Investigations). In: Annales d'Université "Valahia" Târgovişte. Section d'Archéologie et d'Histoire, Tome 19, 2017. pp. 33-56

β-Naphthoflavone-Induced Mitochondrial Respiratory Damage in Cyp1 Knockout Mouse and in Cell Culture Systems: Attenuation by Resveratrol Treatment

A number of xenobiotic-inducible cytochrome P450s (CYPs) are now known to be localized in the mitochondrial compartment, though their pharmacological or toxicological roles remain unclear. Here, we show that BNF treatment markedly inhibits liver mitochondrial O2 consumption rate (OCR), ADP-dependent OCR, and also reserve OCR, in wild-type mice but not in Cyp1a1/1a2(−/−) double knockout mice. BNF treatment markedly affected mitochondrial complex I and complex IV activities and also attenuated mitochondrial gene expression. Furthermore, under in vitro conditions, BNF treatment induced cellular ROS production, which was inhibited by mitochondria-targeted antioxidant Mito-CP and CYP inhibitor proadefin, suggesting that most of the ROS production was intramitochondrial and probably involved the catalytic activity of mitochondrial CYP1 enzymes. Interestingly, our results also show that the AHR antagonist resveratrol, markedly attenuated BNF-induced liver mitochondrial defects in wild-type mice, confirming the role of AHR and AHR-regulated CYP1 genes in eliciting mitochondrial dysfunction. These results are consistent with reduced BNF-induced mitochondrial toxicity in Cyp1a1/1a2(−/−) mice and elevated ROS production in COS cells stably expressing CYP1A1. We propose that increased mitochondrial ROS production and respiratory dysfunction are part of xenobiotic toxicity. Resveratrol, a chemopreventive agent, renders protection against BNF-induced toxicity