Additional data to the stratigraphy and the chronology of the Kostenki 1 (Poliakov) sequence, Voronezh, Russia:Le Sungirien, Saint-Petersbourg 2016

Kostenki 1 is one of the many sites of the Kostenki- Borshchevo site cluster south of Voronezh, which has a long sequence covering the Early and Mid Upper Palaeo- lithic, including the Streletskian Cultural Layer V. Here we present stratigraphic data from our 1994 eldwork (sections of the 1981-1982 excavations) and radiocarbon dates for the CL IV and V. For dating we used our cross- dating approach on high quality conifer charcoal with ABA and ABOx-SC pre-treatment on sub-samples of the same charcoal sample. Our results show that the Strelets- kian CL V dates to ~42,500 14C uncal BP and is signi - cantly older than previously though

Streptomyces K15 active-site serine DD-transpeptidase: specificity profile for peptide, thiol ester and ester carbonyl donors and pathways of the transfer reactions.

The Streptomyces K15 transferase is a penicillin-binding protein presumed to be involved in bacterial wall peptidoglycan crosslinking. It catalyses cleavage of the peptide, thiol ester or ester bond of carbonyl donors Z-R1-CONH-CHR2-COX-CHR3-COO- (where X is NH, S or O) and transfers the electrophilic group Z-R1-CONH-CHR2-CO to amino acceptors via an acyl-enzyme intermediate. Kinetic data suggest that the amino acceptor behaves as a simple alternative nucleophile at the level of the acyl-enzyme in the case of thiol ester and ester donors, and that it binds to the enzyme.carbonyl donor Michaelis complex and influences the rate of enzyme acylation by the carbonyl donor in the case of amide donors. Depending on the nature of the scissile bond, the enzyme has different requirements for substituents at positions R1, R2 and R3

G-quadruplex DNA motifs in the malaria parasite Plasmodium falciparum and their potential as novel antimalarial drug targets

G-quadruplexes are DNA or RNA secondary structures that can be formed from guanine-rich nucleic acids. These four-stranded structures, composed of stacked quartets of guanine bases, can be highly stable and have been demonstrated to occur in vivo in the DNA of human cells and other systems, where they play important biological roles, influencing processes such as telomere maintenance, DNA replication and transcription, or, in the case of RNA G-quadruplexes, RNA translation and processing. We report for the first time that DNA G-quadruplexes can be detected in the nuclei of the malaria parasite Plasmodium falciparum, which has one of the most A/T-biased genomes sequenced and therefore possesses few guanine-rich sequences with the potential to form G-quadruplexes. We show that despite this paucity of putative G-quadruplex-forming sequences, P. falciparum parasites are sensitive to several G-quadruplex-stabilizing drugs, including quarfloxin, which previously reached phase 2 clinical trials as an anticancer drug. Quarfloxin has a rapid initial rate of kill and is active against ring stages as well as replicative stages of intraerythrocytic development. We show that several G-quadruplex-stabilizing drugs, including quarfloxin, can suppress the transcription of a G-quadruplex-containing reporter gene in P. falciparum but that quarfloxin does not appear to disrupt the transcription of rRNAs, which was proposed as its mode of action in both human cells and trypanosomes. These data suggest that quarfloxin has potential for repositioning as an antimalarial with a novel mode of action. Furthermore, G-quadruplex biology in P. falciparum may present a target for development of other new antimalarial drugs

Cadre stratigraphique et chronologique du Gravettien en Europe centrale

Dans le bassin du Danube moyen, les sites de Willendorf II (Autriche), de Dolní Vestonice, de Pavlov et de Stránská Skála (République tchèque) ont permis de reconstruire une séquence régionale bien documentée pour les loess du pléniglaciaire moyen (de ± 45 000 à 26 000 BP), tandis que le contrôle chronologique pour le pléniglaciaire supérieur et le Tardiglaciaire (de 26 000 à 10 000 BP) restait limité en raison du faible nombre de gisements du Paléolithique supérieur relevant de cette période. Depuis 1991, de nouvelles données obtenues dans la région est-carpatique (bassins du Prut moyen et du Dniestr moyen) sont basées sur trois enregistrements loessiques exceptionnels : Mitoc-Malu Galben (Roumanie), Cosautsi (République de Moldavie) et Molodova (Ukraine). Pour la période comprise entre 33 000 et 10 000 BP, plus de 15 oscillations climatiques positives marquées par des sols humifères en alternance avec des loess et des sols cryogéniques ont été enregistrées et positionnées chronologiquement sur la base de plus de 120 nouvelles datations 14 C réalisées dans les laboratoires de Groningen et d’Oxford. L’ensemble des données issues des deux régions ouest- et est-carpatique a fourni une séquence globale au niveau paléoclimatique, chronologique et archéologique conduisant à une meilleure compréhension des changements de l’environnement par rapport aux témoins matériels du Paléolithique supérieur à l’échelle de l’Europe centrale.In the Middle Danube basin, the sites of Willendorf II (Austria), Dolní Vestonice, Pavlov and Stránská Skála (Czech Republic) allowed the reconstruction of a well documented regional loess sequence for the middle pleniglacial (± 45,000 to 26,000 BP), but the chronological setting of the late pleniglacial and late glacial (26,000 to 10,000 BP) remained limited due to the low amount of Upper Palaeolithic sites of this period. Since 1991, new data obtained in the East Carpathian Area (Middle Prut and Middle Dniester basins) are based on three well documented local loess records: Mitoc-Malu Galben (Romania), Cosautsi (Republic of Moldova) and Molodova (Ukraine). In the time-span between 33,000 and 10,000 BP, more than 15 positive climatic oscillations marked by humiferous soils in alternation with loess and cryogenic soils were recorded and chronologically positioned on the ground of some 120 new radiocarbon dates from Groningen and Oxford laboratories. The whole data from both West and East Carpathian areas provided a global palaeoclimatic, chronological and archaeological sequence allowing a better understanding of the environmental changes with regard to the Upper Palaeolithic occurrences at the scale of Central Europe

Putative DNA G-quadruplex formation within the promoters of Plasmodium falciparum var genes

Background. Guanine-rich nucleic acid sequences are capable of folding into an intramolecular four-stranded structure called a G-quadruplex. When found in gene promoter regions, G-quadruplexes can downregulate gene expression, possibly by blocking the transcriptional machinery. Here we have used a genome-wide bioinformatic approach to identify Putative G-Quadruplex Sequences (PQS) in the Plasmodium falciparum genome, along with biophysical techniques to examine the physiological stability of P. falciparum PQS in vitro. Results. We identified 63 PQS in the non-telomeric regions of the P. falciparum clone 3D7. Interestingly, 16 of these PQS occurred in the upstream region of a subset of the P. falciparum var genes (group B var genes). The var gene family encodes PfEMP1, the parasite’s major variant antigen and adhesin expressed at the surface of infected erythrocytes, that plays a key role in malaria pathogenesis and immune evasion. The ability of the PQS found in the upstream regions of group B var genes (UpsB-Q) to form stable Gquadruplex structures in vitro was confirmed using 1H NMR, circular dichroism, UV spectroscopy, and thermal denaturation experiments. Moreover, the synthetic compound BOQ1 that shows a higher affinity for DNA forming quadruplex rather than duplex structures was found to bind with high affinity to the UpsB-Q. Conclusions. This is the first demonstration of non-telomeric PQS in the genome of P. falciparum that form stable G-quadruplexes under physiological conditions in vitro. These results allow the generation of a novel hypothesis that the G-quadruplex sequences in the upstream regions of var genes have the potential to play a role in the transcriptional control of this major virulence-associated multi-gene family

Early modern human settlement of Europe north of the Alps occurred 43,500 years ago in a cold steppe-type environment.

The first settlement of Europe by modern humans is thought to have occurred between 50,000 and 40,000 calendar years ago (cal B.P.). In Europe, modern human remains of this time period are scarce and often are not associated with archaeology or originate from old excavations with no contextual information. Hence, the behavior of the first modern humans in Europe is still unknown. Aurignacian assemblages--demonstrably made by modern humans--are commonly used as proxies for the presence of fully behaviorally and anatomically modern humans. The site of Willendorf II (Austria) is well known for its Early Upper Paleolithic horizons, which are among the oldest in Europe. However, their age and attribution to the Aurignacian remain an issue of debate. Here, we show that archaeological horizon 3 (AH 3) consists of faunal remains and Early Aurignacian lithic artifacts. By using stratigraphic, paleoenvironmental, and chronological data, AH 3 is ascribed to the onset of Greenland Interstadial 11, around 43,500 cal B.P., and thus is older than any other Aurignacian assemblage. Furthermore, the AH 3 assemblage overlaps with the latest directly radiocarbon-dated Neanderthal remains, suggesting that Neanderthal and modern human presence overlapped in Europe for some millennia, possibly at rather close geographical range. Most importantly, for the first time to our knowledge, we have a high-resolution environmental context for an Early Aurignacian site in Central Europe, demonstrating an early appearance of behaviorally modern humans in a medium-cold steppe-type environment with some boreal trees along valleys around 43,500 cal B.P.We thank the Leakey Foundation (2006–2012), Max Planck Society (2006–2012), University of Vienna (2006–2011), Hugo Obermaier Society (2006), Federal Office for Scientific Affairs of the State of Belgium (projects Sc-004, Sc-09, MO/36/021), and the Hochschuljubiläumsfonds of the City of Vienna (2007) for funding our research. We further acknowledge the support of the Department of Prehistory (Natural History Museum, Vienna, Austria; W. Antl-Weiser), Marktgemeinde Aggsbach (H. Gerstbauer), Museumsverein Willendorf (K. Kappelmüller), and the Satzl and Perzl families.This is the accepted manuscript version of the article. The final version is available from PNAS at http://www.pnas.org/content/early/2014/09/16/1412201111.abstract

Cadre stratigraphique et chronologique du Gravettien en Europe centrale

Dans le bassin du Danube moyen, les sites de Willendorf II (Autriche), de Dolní Vestonice, de Pavlov et de Stránská Skála (République tchèque) ont permis de reconstruire une séquence régionale bien documentée pour les loess du pléniglaciaire moyen (de ± 45 000 à 26 000 BP), tandis que le contrôle chronologique pour le pléniglaciaire supérieur et le Tardiglaciaire (de 26 000 à 10 000 BP) restait limité en raison du faible nombre de gisements du Paléolithique supérieur relevant de cette période. Depuis 1991, de nouvelles données obtenues dans la région est-carpatique (bassins du Prut moyen et du Dniestr moyen) sont basées sur trois enregistrements loessiques exceptionnels : Mitoc-Malu Galben (Roumanie), Cosautsi (République de Moldavie) et Molodova (Ukraine). Pour la période comprise entre 33 000 et 10 000 BP, plus de 15 oscillations climatiques positives marquées par des sols humifères en alternance avec des loess et des sols cryogéniques ont été enregistrées et positionnées chronologiquement sur la base de plus de 120 nouvelles datations 14 C réalisées dans les laboratoires de Groningen et d’Oxford. L’ensemble des données issues des deux régions ouest- et est-carpatique a fourni une séquence globale au niveau paléoclimatique, chronologique et archéologique conduisant à une meilleure compréhension des changements de l’environnement par rapport aux témoins matériels du Paléolithique supérieur à l’échelle de l’Europe centrale.In the Middle Danube basin, the sites of Willendorf II (Austria), Dolní Vestonice, Pavlov and Stránská Skála (Czech Republic) allowed the reconstruction of a well documented regional loess sequence for the middle pleniglacial (± 45,000 to 26,000 BP), but the chronological setting of the late pleniglacial and late glacial (26,000 to 10,000 BP) remained limited due to the low amount of Upper Palaeolithic sites of this period. Since 1991, new data obtained in the East Carpathian Area (Middle Prut and Middle Dniester basins) are based on three well documented local loess records: Mitoc-Malu Galben (Romania), Cosautsi (Republic of Moldova) and Molodova (Ukraine). In the time-span between 33,000 and 10,000 BP, more than 15 positive climatic oscillations marked by humiferous soils in alternation with loess and cryogenic soils were recorded and chronologically positioned on the ground of some 120 new radiocarbon dates from Groningen and Oxford laboratories. The whole data from both West and East Carpathian areas provided a global palaeoclimatic, chronological and archaeological sequence allowing a better understanding of the environmental changes with regard to the Upper Palaeolithic occurrences at the scale of Central Europe