Données paléoenvironnementales sur le Vraconnien/Cénomanien de la région de Tébessa (Atlas Saharien,nord-est Algérie). Caractérisation de l’OAE2

The micropalaeontological content of five sections, located in Northeastern Algeria (Saharan Atlas) was investigated by means of washing/counting of microfossils in marly levels, and microfacies analyses of calcareous levels. In these levels of Upper Cretaceous age, hundred species of foraminifera were identified but only about 15 species of ostracoda and about ten of radiolaria. This work allows, first of all, to establish a rather precise stratigraphic frame, in particular by means of studying planktonic foraminifera. Two to five biozones were defined, between the Vraconnian (Th. Appenninica biozone) and the early Turonian (Whiteinella archaeocretacea biozone, then Helvetoglobotruncana Helvetica biozone for certain sections). Secondly, the quantitative analyses led on foraminifera allowed the definition of palaeoenvironment. The ratio P/P+B, generally very high, coupled with a little diversified benthonic microfauna, indicates a calm and deep environment, of external platform or slope type. Furthermore, at numerous levels, various indications give evidence of the existence of a strong surface productivity (presence of upwellings), responsible for the proliferation of radiolaria (late Vraconnian/early Cenomanian especially) or of globular planktonic foraminifera (hedbergellids/heterohelicids); being both associated with low-oxygen deep waters. Two anoxic events were also revealed, the first one at the end of Vraconnian (OAE1d) and the second at the end of Cenomanian (OAE2). This last event in particular was characterized on all the sections, in a more or less detailed way, thanks to the identification of certain indicator: Heterohelix “bloom”, “filament” event, disappearance of rotaliporids, presence of “blackshales” strongly enriched in organic matter (Bahloul levels).     

Biostratigraphie d’après les foraminifères et paléoenvironnements des séries post-Éocène du sondage ASHTART 28, golfe de Gabès (Tunisie)

The Cenozoic sequence of Ashtart 28 well drilled in the Gulf of Gabes (Tunisia) is the subject of a biostratigraphical study. The samples recovered in cuttings from 390 m and downwards allowed to recognize, above the Late Eocene sediments, a sedimentary series, lithologically diversified, nearly 1600 m thick. Marine Pliocene deposits, generally attesting a low bathymetry, lie unconformably above the Messinian (Oued Bel Khedim formation), which shows the usual features of the Mediterranean confinement. The underlying Messinian pre-evaporitic platform series (Melqart formation), that is over 250 m thick, is typical of a perireefal environment. The sediments assigned to the Tortonian (Somâa Sands formation) are continental and occur unconformably above the approximately 500-metres-thick Middle Miocene strata (Saouaf, Mahmoud, Aïn Grab and Salammbô pars formations). The marine Lower Miocene and Oligocene sediments (Salammbô pars and Ketatna formations), that are more than 300 m thick, lie in continuity under the Middle Miocene. The infralittoral Chattian sequence has especially supplied a diversified assemblage of larger foraminifera recovered in other west-mediterranean basins. Datings were obtained based on planktonic and larger benthic foraminifera (Miogypsinidae, Nummulitidae, Lepidocyclinidae) and by correlations obtained by means of well loggings and lithostratigraphy. Benthic foraminifera, mainly listed for the Miocene and Oligocene, are studied from a systematic, stratigraphic and paleogeographic point of view. The paleoenvironments of deposits are defined for each considered stratigraphic interval. Comparisons are sketched with other drillings of the Gulf of Gabes. Thanks to the numerous data obtained by this detailed study, the Ashtart drilling can serve as a reference for the Tertiary sequence of this part of the Mediterranean domain.     

L'industrie lithique du Paléolithique dans la région de Jungwon en Corée

Prehistoric people have been often lived in the Jungwon region during the Paleolithic. It is a reference for development of the Paleolithic cultures in Korea. During the lower Paleolithic, pebble tool culture has been developed: tools were made with local raw materials and direct percussion and anvil technique were utilized. Debitage and raw material of the middle Paleolithic did not make a great difference to the lower Paleolithic. Otherwise, tool size became small and the number of flake tools increased. The crucial changes occurred during the upper Paleolithic. Technique, acquisition of raw material and tool kits were thoroughly innovated. All of these changes would reveal that the upper Paleolithic people have carried out more various activities, that earlier periods and their social structure would be more complex than other ones'.     

The loops facing the active site of prolyl oligopeptidase are crucial components in substrate gating and specificity

Prolyl oligopeptidase (POP) has emerged as a drug target for neurological diseases. A flexible loop structure comprising loop A (res. 189–209) and loop B (res. 577–608) at the domain interface is implicated in substrate entry to the active site. Here we determined kinetic and structural properties of POP with mutations in loop A, loop B, and in two additional flexible loops (the catalytic His loop, propeller Asp/Glu loop). POP lacking loop A proved to be an inefficient enzyme, as did POP with a mutation in loop B (T590C). Both variants displayed an altered substrate preference profile, with reduced ligand binding capacity. Conversely, the T202C mutation increased the flexibility of loop A, enhancing the catalytic efficiency beyond that of the native enzyme. The T590C mutation in loop B increased the preference for shorter peptides, indicating a role in substrate gating. Loop A and the His loop are disordered in the H680A mutant crystal structure, as seen in previous bacterial POP structures, implying coordinated structural dynamics of these loops. Unlike native POP, variants with a malfunctioning loop A were not inhibited by a 17-mer peptide that may bind non-productively to an exosite involving loop A. Biophysical studies suggest a predominantly closed resting state for POP with higher flexibility at the physiological temperature. The flexible loop A, loop B and His loop system at the active site is the main regulator of substrate gating and specificity and represents a new inhibitor target.     

Nuclease Activity of the Human SAMHD1 Protein Implicated in the Aicardi-Goutières Syndrome and HIV-1 Restriction

The human HD domain protein SAMHD1 is implicated in the Aicardi-Goutières autoimmune syndrome and in the restriction of HIV-1 replication in myeloid cells. Recently, this protein has been shown to possess dNTP triphosphatase activity, which is proposed to inhibit HIV-1 replication and the autoimmune response by hydrolyzing cellular dNTPs. Here, we show that the purified full-length human SAMHD1 protein also possesses metal-dependent 3′→5′ exonuclease activity against single-stranded DNAs and RNAs in vitro. In double-stranded substrates, this protein preferentially cleaved 3′-overhangs and RNA in blunt-ended DNA/RNA duplexes. Full-length SAMHD1 also exhibited strong DNA and RNA binding to substrates with complex secondary structures. Both nuclease and dNTP triphosphatase activities of SAMHD1 are associated with its HD domain, but the SAM domain is required for maximal activity and nucleic acid binding. The nuclease activity of SAMHD1 could represent an additional mechanism contributing to HIV-1 restriction and suppression of the autoimmune response through direct cleavage of viral and endogenous nucleic acids. In addition, we demonstrated the presence of dGTP triphosphohydrolase and nuclease activities in several microbial HD domain proteins, suggesting that these proteins might contribute to antiviral defense in prokaryotes.     

The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutières syndrome defects

RNase H2 cleaves RNA sequences that are part of RNA/DNA hybrids or that are incorporated into DNA, thus, preventing genomic instability and the accumulation of aberrant nucleic acid, which in humans induces Aicardi-Goutières syndrome, a severe autoimmune disorder. The 3.1 Å crystal structure of human RNase H2 presented here allowed us to map the positions of all 29 mutations found in Aicardi-Goutières syndrome patients, several of which were not visible in the previously reported mouse RNase H2. We propose the possible effects of these mutations on the protein stability and function. Bacterial and eukaryotic RNases H2 differ in composition and substrate specificity. Bacterial RNases H2 are monomeric proteins and homologs of the eukaryotic RNases H2 catalytic subunit, which in addition possesses two accessory proteins. The eukaryotic RNase H2 heterotrimeric complex recognizes RNA/DNA hybrids and (5′)RNA-DNA(3′)/DNA junction hybrids as substrates with similar efficiency, whereas bacterial RNases H2 are highly specialized in the recognition of the (5′)RNA-DNA(3′) junction and very poorly cleave RNA/DNA hybrids in the presence of Mg²⁺ ions. Using the crystal structure of the Thermotoga maritima RNase H2-substrate complex, we modeled the human RNase H2-substrate complex and verified the model by mutational analysis. Our model indicates that the difference in substrate preference stems from the different position of the crucial tyrosine residue involved in substrate binding and recognition.     

Radioembolisation des tumeurs hépatiques par microsphères marquées à l’yttrium-90

This study is a retrospective analysis of 64 patients with a primary or secondary liver malignancy, referred for yttrium-90 radioembolisation between December 2006 and September 2010. Among these 64 patients, 54 received a total number of 69 injections (one to three treatments per patient). The mean activity injected per treatment was 3.1 ± 1.6 GBq. The liver targeted dose was 123.1 ± 39 Gy. Pulmonary shunt, detected in 55% of treatments, was 5.7% ± 7.4. The pulmonary dose was 4.7 ± 7.1 Gy. Overall, response rate per patient, evaluated at 3 months by EASL or modified RECIST criteria, was 72.9%, 70% for hepatocellular carcinoma. The complication rate was relatively low (17%) with only two serious events. ⁹⁰Y-microspheres radioembolisation of liver malignancies is an effective and well-tolerated therapy. Until now often used as a salvage therapy, the recent and ongoing studies should better define its place in the therapeutic strategy (adjuvant, neoadjuvant, first line) and possible association with chemotherapy and targeted therapies.     

Répartition des Hippopotamidae(Mammalia,Artiodactyla) en Europe occidentale implications stratigraphiques et paléoécologiques

The present note is intended to disparage a certain number of groundless but commonly accepted assertions concerning the quaternary Hippopotamidae of Western Europe.The remains of European quaternary hippopotamusare not as rare as it is generally believed: more than 270 localities prove it. The most important sites are described here.The quaternary European hippopotamus do notnecessarily characterise an «interglacial age and, besides, even though some of them belong to the Cromerian or to the Eemian, some other belong to colder periods, from the beginning of the middle Pleistocene until the end of the ancient Würm. The paleoecological implications compel us to moderate the value of hippopotamus remains considered as paleoclimatic indicators, in any case as far as temperature is concerned.