Inhibition of LtxA Toxicity by Blocking Cholesterol Binding with Peptides

The leukotoxin (LtxA) produced by Aggregatibacter actinomycetemcomitans kills host immune cells, allowing the bacterium to establish an ecological niche in the upper aerodigestive tract of its human host. The interaction of LtxA with human immune cells is both complex and multifaceted, involving membrane lipids as well as cell-surface proteins. In the initial encounter with the host cell, LtxA associates with lymphocyte function-associated antigen-1, a cell surface adhesion glycoprotein. However, we have also demonstrated that the toxin associates strongly with the plasma membrane lipids, specifically cholesterol. This association with cholesterol is regulated by a cholesterol recognition amino acid consensus (CRAC) motif, with a sequence of 334LEEYSKR340, in the N-terminal region of the toxin. Here, we have demonstrated that removal of cholesterol from the plasma membrane or mutation of the LtxA CRAC motif inhibits the activity of the toxin in THP-1 cells. To inhibit LtxA activity, we designed a short peptide corresponding to the CRAC336 motif of LtxA (CRAC336WT). This peptide binds to cholesterol and thereby inhibits the toxicity of LtxA in THP-1 cells. Previously, we showed that this peptide inhibits LtxA toxicity against Jn.9 (Jurkat) cells, indicating that peptides derived from the cholesterol-binding site of LtxA may have a potential clinical applicability in controllinginfections of repeats-in-toxin-producing organisms. © 2016 John Wiley & Sons A/S

Project AUTONOMAD : The design of an unmanned coast guard vessel integrating the use of drones for emission regulation enforcement and territorial water protection in the Mediterranean

Project AUTONOMAD examines the design of an unmanned trimaran vessel for unmanned application, integrating the deployment, recovery and storage of various Unmanned Aerial Vehicles (UAVs) and Unmanned Surface Vehicles (USVs). It is tailor made for the needs of EU Coastguards in order to provide a platform for emission regulation enforcement, maritime monitoring and surveillance in the Mediterranean. This project includes the design of the unmanned vessel, the selection of its payload and the integration of the unmanned technologies in order to create a robust and reliable engineering system. The feasibility of such a vessel is then assessed in terms of reliability and overall benefit

Correction: Konidaris et al. Dating of the Lower Pleistocene Vertebrate Site of Tsiotra Vryssi (Mygdonia Basin, Greece): Biochronology, Magnetostratigraphy, and Cosmogenic Radionuclides. Quaternary 2021, 4, 1

Background and scope: The late Villafranchian large mammal age (~2.0–1.2 Ma) of the Early Pleistocene is a crucial interval of time for mammal/hominin migrations and faunal turnovers in western Eurasia. However, an accurate chronological framework for the Balkans and adjacent territories is still missing, preventing pan-European biogeographic correlations and schemes. In this article, we report the first detailed chronological scheme for the late Villafranchian of southeastern Europe through a comprehensive and multidisciplinary dating approach (biochronology, magnetostratigraphy, and cosmogenic radionuclides) of the recently discovered Lower Pleistocene vertebrate site Tsiotra Vryssi (TSR) in the Mygdonia Basin, Greece. Results: The minimum burial ages (1.88 ± 0.16 Ma, 2.10 ± 0.18 Ma, and 1.98 ± 0.18 Ma) provided by the method of cosmogenic radionuclides indicate that the normal magnetic polarity identified below the fossiliferous layer correlates to the Olduvai subchron (1.95–1.78 Ma; C2n). Therefore, an age younger than 1.78 Ma is indicated for the fossiliferous layer, which was deposited during reverse polarity chron C1r. These results are in agreement with the biochronological data, which further point to an upper age limit at ~1.5 Ma. Overall, an age between 1.78 and ~1.5 Ma (i.e., within the first part of the late Villafranchian) is proposed for the TSR fauna. Conclusions: Our results not only provide age constraints for the local mammal faunal succession, thus allowing for a better understanding of faunal changes within the same sedimentary basin, but also contribute to improving correlations on a broader scale, leading to more accurate biogeographic, palaeoecological, and taphonomic interpretations

Discretization Provides a Conceptually Simple Tool to Build Expression Networks

Biomarker identification, using network methods, depends on finding regular co-expression patterns; the overall connectivity is of greater importance than any single relationship. A second requirement is a simple algorithm for ranking patients on how relevant a gene-set is. For both of these requirements discretized data helps to first identify gene cliques, and then to stratify patients

Kretzoiarctos gen. nov., the Oldest Member of the Giant Panda Clade

The phylogenetic position of the giant panda, Ailuropoda melanoleuca (Carnivora: Ursidae: Ailuropodinae), has been one of the most hotly debated topics by mammalian biologists and paleontologists during the last century. Based on molecular data, it is currently recognized as a true ursid, sister-taxon of the remaining extant bears, from which it would have diverged by the Early Miocene. However, from a paleobiogeographic and chronological perspective, the origin of the giant panda lineage has remained elusive due to the scarcity of the available Miocene fossil record. Until recently, the genus Ailurarctos from the Late Miocene of China (ca. 8–7 mya) was recognized as the oldest undoubted member of the Ailuropodinae, suggesting that the panda lineage might have originated from an Ursavus ancestor. The role of the purported ailuropodine Agriarctos, from the Miocene of Europe, in the origins of this clade has been generally dismissed due to the paucity of the available material. Here, we describe a new ailuropodine genus, Kretzoiarctos gen. nov., based on remains from two Middle Miocene (ca. 12–11 Ma) Spanish localities. A cladistic analysis of fossil and extant members of the Ursoidea confirms the inclusion of the new genus into the Ailuropodinae. Moreover, Kretzoiarctos precedes in time the previously-known, Late Miocene members of the giant panda clade from Eurasia (Agriarctos and Ailurarctos). The former can be therefore considered the oldest recorded member of the giant panda lineage, which has significant implications for understanding the origins of this clade from a paleobiogeographic viewpoint

First description of a fossil chamaeleonid from Greece and its relevance for the European biogeographic history of the group

The fossil record of Chamaeleonidae is very scarce and any new specimen is therefore considered important for our understanding of the evolutionary and biogeographic history of the group. New specimens from the early Miocene of Aliveri (Evia Island), Greece constitute the only fossils of these lizards from southeastern Europe. Skull roofing material is tentatively attributed to the Czech species Chamaeleo cf. andrusovi, revealing a range extension for this taxon, whereas tooth-bearing elements are described as indeterminate chamaeleonids. The Aliveri fossils rank well among the oldest known reptiles from Greece, provide evidence for the dispersal routes of chameleons out of Africa towards the European continent and, additionally, imply strong affinities with coeval chamaeleonids from Central Europe

A Genome-Wide Homozygosity Association Study Identifies Runs of Homozygosity Associated with Rheumatoid Arthritis in the Human Major Histocompatibility Complex

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with a polygenic mode of inheritance. This study examined the hypothesis that runs of homozygosity (ROHs) play a recessive-acting role in the underlying RA genetic mechanism and identified RA-associated ROHs. Ours is the first genome-wide homozygosity association study for RA and characterized the ROH patterns associated with RA in the genomes of 2,000 RA patients and 3,000 normal controls of the Wellcome Trust Case Control Consortium. Genome scans consistently pinpointed two regions within the human major histocompatibility complex region containing RA-associated ROHs. The first region is from 32,451,664 bp to 32,846,093 bp (−log10(p)>22.6591). RA-susceptibility genes, such as HLA-DRB1, are contained in this region. The second region ranges from 32,933,485 bp to 33,585,118 bp (−log10(p)>8.3644) and contains other HLA-DPA1 and HLA-DPB1 genes. These two regions are physically close but are located in different blocks of linkage disequilibrium, and ∼40% of the RA patients' genomes carry these ROHs in the two regions. By analyzing homozygote intensities, an ROH that is anchored by the single nucleotide polymorphism rs2027852 and flanked by HLA-DRB6 and HLA-DRB1 was found associated with increased risk for RA. The presence of this risky ROH provides a 62% accuracy to predict RA disease status. An independent genomic dataset from 868 RA patients and 1,194 control subjects of the North American Rheumatoid Arthritis Consortium successfully validated the results obtained using the Wellcome Trust Case Control Consortium data. In conclusion, this genome-wide homozygosity association study provides an alternative to allelic association mapping for the identification of recessive variants responsible for RA. The identified RA-associated ROHs uncover recessive components and missing heritability associated with RA and other autoimmune diseases

Bone histology provides insights into the life history mechanisms underlying dwarfing in hipparionins

Size shifts may be a by-product of alterations in life history traits driven by natural selection. Although this approach has been proposed for islands, it has not yet been explored in continental faunas. The trends towards size decrease experienced by some hipparionins constitute a good case study for the application of a life history framework to understand the size shifts on the continent. Here, we analysed bone microstructure to reconstruct the growth of some different-sized hipparionins from Greece and Spain. The two dwarfed lineages studied show different growth strategies. The Greek hipparions ceased growth early at a small size thus advancing maturity, whilst the slower-growing Spanish hipparion matured later at a small size. Based on predictive life history models, we suggest that high adult mortality was the likely selective force behind early maturity and associated size decrease in the Greek lineage. Conversely, we infer that resource limitation accompanied by high juvenile mortality triggered decrease in growth rate and a relative late maturity in the Spanish lineage. Our results provide evidence that different selective pressures can precipitate different changes in life history that lead to similar size shifts

Reconciling the stratigraphy and depositional history of the Lycian orogen-top basins, SW Anatolia

Terrestrial fossil records from the SWAnatolian basins are crucial both for regional correlations and palaeoenvironmental reconstructions. By reassessing biostratigraphic constraints and incorporating new fossil data, we calibrated and reconstructed the late Neogene andQuaternary palaeoenvironments within a regional palaeogeographical framework. The culmination of the Taurides inSWAnatolia was followed by a regional crustal extension from the late Tortonian onwards that created a broad array of NE-trending orogen-top basins with synchronic associations of alluvial fan, fluvial and lacustrine deposits. The terrestrial basins are superimposed on the upper Burdigalian marine units with a c. 7 myr of hiatus that corresponds to a shift from regional shortening to extension. The initial infill of these basins is documented by a transition from marginal alluvial fans and axial fluvial systems into central shallow-perennial lakes coinciding with a climatic shift from warm/humid to arid conditions. The basal alluvial fan deposits abound in fossil macro-mammals of an early Turolian (MN11–12; late Tortonian) age. The Pliocene epoch in the region was punctuated by subhumid/humid conditions resulting in a rise of local base levels and expansion of lakes as evidenced by marsh-swamp deposits containing diverse fossilmammal assemblages indicating late Ruscinian (lateMN15; late Zanclean) ageWe are grateful for the support of the international bilateral project between The Scientific and Technological Research Council of Turkey (TUBITAK) and The Russian Scientific Foundation (RFBR) with grant a number of 111Y192. M.C.A. is grateful to the Turkish Academy of Sciences (TUBA) for a GEBIP (Young Scientist Award) grant. T.K. and S.M. are grateful to the Ege University Scientific Research Center for the TTM/002/2016 and TTM/001/2016 projects. M.C.A., H.A., S.M. and M.B. have obtained Martin and Temmick Fellowships at Naturalis Biodiversity Center (Leiden). F.A.D. is supported by a Mehmet Akif Ersoy University Scientific Research Grant. T.A.N. is supported by an Alexander-von-Humboldt Scholarship. L.H.O. received support from TUBITAK under the 2221 program for visiting scientists