Biostratigraphic Evidence Relating to the Age-Old Question of Hannibal's Invasion of Italy, I: History and Geological Reconstruction

Controversy over the alpine route that Hannibal of Carthage followed from the Rhône Basin into Italia has raged amongst classicists and ancient historians for over two millennia. The motivation for identifying the route taken by the Punic Army through the Alps lies in its potential for identifying sites of historical archaeological significance and for the resolution of one of history's most enduring quandaries. Here, we present stratigraphic, geochemical and microbiological evidence recovered from an alluvial floodplain mire located below the Col de la Traversette (~3000 m asl—above sea level) on the French/Italian border that potentially identifies the invasion route as the one originally proposed by Sir Gavin de Beer (de Beer 1974). The dated layer is termed the MAD bed (mass animal deposition) based on disrupted bedding, greatly increased organic carbon and key/specialized biological components/compounds, the latter reported in Part II of this paper. We propose that the highly abnormal churned up (bioturbated) bed was contaminated by the passage of Hannibal's animals, possibly thousands, feeding and watering at the site, during the early stage of Hannibal's invasion of Italia (218 bc)

Biostratigraphic Evidence Relating to the Age-Old Question of Hannibal's Invasion of Italy, II: Chemical Biomarkers and Microbial Signatures

Open access article. Creative Commons Attribution 4.0 International License (CC BY 4.0) appliesAs discussed in Part I, a large accumulation of mammalian faeces at the mire site in the upper Guil Valley near Mt. Viso, dated to 2168 cal 14C yr., provides the first evidence of the passage of substantial but indeterminate numbers of mammals within the time frame of the Punic invasion of Italia. Specialized organic biomarkers bound up in a highly convoluted and bioturbated bed constitute an unusual anomaly in a histosol comprised of fibric and hemist horizons that are usually expected to display horizontal bedding. The presence of deoxycholic acid and ethylcoprostanol derived from faecal matter, coupled with high relative numbers of Clostridia 16S rRNA genes, suggests a substantial accumulation of mammalian faeces at the site over 2000 years ago. The results reported here constitute the first chemical and biological evidence of the passage of large numbers of mammals, possibly indicating the route of the Hannibalic army at this time. Combined with the geological analysis reported in Part I, these data provide a background supporting the need for further historical archaeological exploration in this area.Ye

Comparative genomics of small RNA regulatory pathway components in vector mosquitoes

<p>Abstract</p> <p>Background</p> <p>Small RNA regulatory pathways (SRRPs) control key aspects of development and anti-viral defense in metazoans. Members of the Argonaute family of catalytic enzymes degrade target RNAs in each of these pathways. SRRPs include the microRNA, small interfering RNA (siRNA) and PIWI-type gene silencing pathways. Mosquitoes generate viral siRNAs when infected with RNA arboviruses. However, in some mosquitoes, arboviruses survive antiviral RNA interference (RNAi) and are transmitted via mosquito bite to a subsequent host. Increased knowledge of these pathways and functional components should increase understanding of the limitations of anti-viral defense in vector mosquitoes. To do this, we compared the genomic structure of SRRP components across three mosquito species and three major small RNA pathways.</p> <p>Results</p> <p>The <it>Ae. aegypti, An. gambiae </it>and <it>Cx. pipiens </it>genomes encode putative orthologs for all major components of the miRNA, siRNA, and piRNA pathways. <it>Ae. aegypti </it>and <it>Cx. pipiens </it>have undergone expansion of Argonaute and PIWI subfamily genes. Phylogenetic analyses were performed for these protein families. In addition, sequence pattern recognition algorithms MEME, MDScan and Weeder were used to identify upstream regulatory motifs for all SRRP components. Statistical analyses confirmed enrichment of species-specific and pathway-specific cis-elements over the rest of the genome.</p> <p>Conclusion</p> <p>Analysis of Argonaute and PIWI subfamily genes suggests that the small regulatory RNA pathways of the major arbovirus vectors, <it>Ae. aegypti and Cx. pipiens</it>, are evolving faster than those of the malaria vector <it>An. gambiae </it>and <it>D. melanogaster</it>. Further, protein and genomic features suggest functional differences between subclasses of PIWI proteins and provide a basis for future analyses. Common UCR elements among SRRP components indicate that 1) key components from the miRNA, siRNA, and piRNA pathways contain NF-kappaB-related and Broad complex transcription factor binding sites, 2) purifying selection has occurred to maintain common pathway-specific elements across mosquito species and 3) species-specific differences in upstream elements suggest that there may be differences in regulatory control among mosquito species. Implications for arbovirus vector competence in mosquitoes are discussed.</p

Characterisation of a Desmosterol Reductase Involved in Phytosterol Dealkylation in the Silkworm, Bombyx mori

Most species of invertebrate animals cannot synthesise sterols de novo and many that feed on plants dealkylate phytosterols (mostly C29 and C28) yielding cholesterol (C27). The final step of this dealkylation pathway involves desmosterol reductase (DHCR24)-catalysed reduction of desmosterol to cholesterol. We now report the molecular characterisation in the silkworm, Bombyx mori, of such a desmosterol reductase involved in production of cholesterol from phytosterol, rather than in de novo synthesis of cholesterol. Phylogenomic analysis of putative desmosterol reductases revealed the occurrence of various clades that allowed for the identification of a strong reductase candidate gene in Bombyx mori (BGIBMGA 005735). Following PCR-based cloning of the cDNA (1.6 kb) and its heterologous expression in Saccharomyces cerevisae, the recombinant protein catalysed reduction of desmosterol to cholesterol in an NADH- and FAD- dependent reaction

International longitudinal registry of patients with atrial fibrillation and treated with rivaroxaban: RIVaroxaban Evaluation in Real life setting (RIVER)

Background Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment. Methods and results Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20 mg (76.5%) and 15 mg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet therapy. Most patients enrolled in RIVER met the recommended threshold for AC therapy (86.6% for 2012 ESC Guidelines, and 79.8% of patients according to 2016 ESC Guidelines). Conclusions The RIVER prospective registry will expand our knowledge of how rivaroxaban is prescribed in everyday practice and whether evidence from clinical trials can be translated to the broader cross-section of patients in the real world

Lithostratigraphy of Late Weichselian tills on the West Estonian Islands

Glacial stratigraphy of the West Estonian Islands comprises three different diamicton units which are correlated event-stratigraphically to the Pandivere and Palivere ice advances of the most recent (Late Weichselian) glaciation and included into the Vörtsjärve Subformation according to Estonian stratigraphic nomenclature. A large number of till samples (1136) and drillcore sections (2500) were analysed in order to determine the genesis and composition of sediments from which the lithostratigraphical conclusions are derived. The two topmost diamictons are interpreted as genetic varieties of the Palivere Till – waterline melt-out and basal till. The Pandivere Till is the lowermost widespread till layer on the islands, which lies unconformably between the Palivere Till and carbonaceous bedrock. Lacustrine Köpu Sands separate the Palivere and Pandivere Tills in a few boreholes on the Köpu and Sörve Peninsulas. In deeply buried valleys on the Sörve Peninsula the Pandivere Till is underlain by lacustrine Viieristi Sands and greenish-grey compact till of unknown age. The correlatives of the Palivere and Pandivere Tills in southern Finland, south of Salpausselkä I (SSI), are thought to be the Espoo and Siuntio Tills, respectively