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

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

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

Structural basis for the broad-spectrum inhibition of metallo-beta-lactamases by thiols

The development of broad-spectrum metallo-beta-lactamase (MBL) inhibitors is challenging due to structural diversity and differences in metal utilisation by these enzymes. Analysis of structural data, followed by non-denturing mass spectrometric analyses, identified thiols proposed to inhibit representative MBLs from all three sub-classes: B1, B2 and B3. Solution analyses led to the identification of broad spectrum inhibitors, including potent inhibitors of the CphA MBL (Aeromonas hydrophila). Structural studies revealed that, as observed for other B1 and B3 MBLs, inhibition of the L1 MBL thiols involves metal chelation. Evidence is reported that this is not the case for inhibition of the CphA enzyme by some thiols; the crystal structure of the CphA-Zn-inhibitor complex reveals a binding mode in which the thiol does not interact with the zinc. The structural data enabled the design and the production of further more potent inhibitors. Overall the results suggest that the development of reasonably broad-spectrum MBL inhibitors should be possible.</p

Pleistocene vertebrate faunas of the Süttő Travertine Complex (Hungary)

Numerous fossil remains (vertebrates, molluscs and plants) were found in more than twenty sites of the Süttő Travertine Complex during the last 150 years. The majority of these remains were recovered from fissures of the travertine, but also from the travertine and an overlying loess-paleosol sequence. The aims of this study were to review the fossil content, to determine the stratigraphical positions of the various vertebrate faunas of Süttő and provide paleoecological interpretation of the periods on the basis of their faunas and floras. In addition, this paper describes new faunas and floras from the sites Süttő 16–20 and provides 14C dates for Süttő 16. On the basis of the new uranium series isotope and optical dating (OSL), the age of the travertine complex is Middle Pleistocene (235±21–314±45 ka, MIS 7–9), while the age of the loess-paleosol sequence in superposition of the travertine is Middle-Late Pleistocene (MIS 2–MIS 6). In contrast, the fossils of the travertine indicated an older, Pliocene–Early Pleistocene age. A fissure (Süttő 17) and a red clay layer (Süttő 19) contained mammal faunas of Early–Middle Pleistocene age. These results indicated the existence of older travertine in certain quarries (Hegyháti quarry, Cukor quarry). Sedimentological and OSL data of well-dated layers of the loess-paleosol sequence (Süttő/LPS) at Süttő allowed a correlation with the layers of Süttő 6. The paleosol layer in the upper part of the sequence of Süttő 6, was correlated with a pedocomplex of the overlying loess-paleosol sequence, which was dated to MIS 5c (upper, dark soil) and MIS 5e (lower, reddish brown soil). The paleoecological analysis of the mammal and mollusc faunas supported the former interpretation of Novothny et al., inferring warm, dry climate during the sedimentation of the upper layers, and more humid climate for the lower layers). However, the fauna of the lower soil layer indicated cold climate, so an age of MIS 5d is suggested. Dating of the fissure faunas is based on similarity studies. For some faunas, this method cannot be used, because of the low number of species. On the basis of the species compositions and former interpretations, these faunas originated mainly from sediments that were deposited under cold climatic conditions. Other fissure faunas were dated by AMS 14C (Süttő 16), or by correlation with soil layers of Süttő 6. According to these results, most of the fissure faunas can be correlated with different phases of MIS 5. However, there are a younger (MIS 2) and an older (Early–Middle Pleistocene) fissure fauna.status: publishe

Staying out in the cold: glacial refugia and mitochondrial DNA phylogeography in ancient European brown bears

Models for the development of species distribution in Europe typically invoke restriction in three temperate Mediterranean refugia during glaciations, from where recolonization of central and northern Europe occurred. The brown bear, Ursus arctos, is one of the taxa from which this model is derived. Sequence data generated from brown bear fossils show a complex phylogeographical history for western European populations. Long-term isolation in separate refugia is not required to explain our data when considering the palaeontological distribution of brown bears. We propose continuous gene flow across southern Europe, from which brown bear populations expanded after the last glaciation

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