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

As discussed in Part I, a large accumulation of mammalian faeces at the mire site in the upper Guil Valley near Mt. Viso, dated to 2168cal 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 2000years 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.

Snakes on an island: independent introductions have different potentials for invasion

[EN] Snakes introduced to islands can be devastating to naïve native fauna. However, introduced populations must establish before range expansion (invasion) can occur. The factors that can determine successful invasion are those associated with the introduction event (e.g., characteristics of the founding population), the location (e.g., suitable environment and prey availability) and the species (e.g. life history characteristics). Here, we collected morphometric, ecological and genetic data on the recently introduced California Kingsnake (Lampropeltis californiae) in Gran Canaria.

The invasion risk in the Pacific Northwest of two closely related grass species in the Genus Cortaderia

Thesis (Master's)--University of Washington, 2016-08

Study of feeding competition between invasion ctenophore (M. leidyi) and anchovy (C. engrauliformis) in the Southern Caspian Sea (Mazandran Coast)

Mnemiopsis leidyi one species of phylum Ctenophora, is a native species in America. It has most likely moved across the Atlantic in the ballast water of cargo ships to the Black sea in 1982, and then to the Caspian Sea thought the Volga-Don Channel, in Nov 1999. The population of M. leidyi rows rapidly and by end of 2000, the entire sea was teeming with them. This survey was arranged In order to study the relationship between the invasion of M. leidyi and sharp decline in main stocks pelagic fish such as Kilka. Dietary analysis was conducted on Anchovy Killka (Clupeonella engrauliformis) and M. leidyi from August 2001 to October 2002 in two stations, located at the costal water near Babolsar (52.38° E ,36.42° N ) and Noshahar (51.33° E,36.39° N) in the Caspian Sea province of Mazandaran, Iran. M. leidyi was caught by plankton net, at three vertical strata of both station at surface 5 in, 10m, and 15 m the Kilka was caught by fisheries boat at Babolasar fishery harbour. Samples of M. leidyi were not fixed in its common fixative, we used 96% Ethanol In order to study of M. leidyi digestion system some alive samples, directly, were studied by the fluorescence microscope which was connected to a computer prepared specially for this process. In many cases, the light was directly reflected on the sample and microscopic image was prepared in dark background. We found that there were some common organisms in diet of both species. The Schoener index analysis reflected these similarities, as values more than critical level of overlap (>89 in Babolsar samples and >84 in Noshahar samples) were found. Results from this study suggests that M. leidyi and Anchovy have a similar feeding niche and computation between them is one of the reasons to decline in anchovy stocks. Economical effects of M. leidyi s invasion in research area were studied by data on kilka caught before and after introducing M. leidyi.

Global change and climate-driven invasion of the Pacific oyster (Crassostrea gigas) along European coasts: a bioenergetics modelling approach

Aim The spread of non-indigenous species in marine ecosystems world-wide is one of today's most serious environmental concerns. Using mechanistic modelling, we investigated how global change relates to the invasion of European coasts by a non-native marine invertebrate, the Pacific oyster Crassostrea gigas. Location Bourgneuf Bay on the French Atlantic coast was considered as the northern boundary of C. gigas expansion at the time of its introduction to Europe in the 1970s. From this latitudinal reference, variations in the spatial distribution of the C. gigas reproductive niche were analysed along the north-western European coast from Gibraltar to Norway. Methods The effects of environmental variations on C. gigas physiology and phenology were studied using a bioenergetics model based on Dynamic Energy Budget theory. The model was forced with environmental time series including in situ phytoplankton data, and satellite data of sea surface temperature and suspended particulate matter concentration. Results Simulation outputs were successfully validated against in situ oyster growth data. In Bourgneuf Bay, the rise in seawater temperature and phytoplankton concentration has increased C. gigas reproductive effort and led to precocious spawning periods since the 1960s. At the European scale, seawater temperature increase caused a drastic northward shift (1400 km within 30 years) in the C. gigas reproductive niche and optimal thermal conditions for early life stage development. Main conclusions We demonstrated that the poleward expansion of the invasive species C. gigas is related to global warming and increase in phytoplankton abundance. The combination of mechanistic bioenergetics modelling with in situ and satellite environmental data is a valuable framework for ecosystem studies. It offers a generic approach to analyse historical geographical shifts and to predict the biogeographical changes expected to occur in a climate-changing world.

Preoperative assessment of deep myometrial and cervical invasion in endometrial carcinoma: comparison of magnetic resonance imaging and histopathologic evaluation

This study aimed to evaluate the accuracy of magnetic resonance imaging (MRI) in the detection of deep myometrial invasion and cervical extension by endometrial carcinoma. This prospective study included 101 patients with histologically documented endometrial carcinoma, between July 1998 and April 2004. The findings of preoperative pelvic MRI were compared with histological diagnosis. From 101 cases studied by pelvic MRI, 43 were classified as deep myometrial invasion (50% of myometrium), where the pathological evaluation confirmed as having deep myometrial invasion. Cervical extension in the MRI study was found in 19 cases. Pathologic study found cervical extension and/or invasion in 31 cases including all cases identified by MRI. The accuracy, sensitivity and specificity of MRI were 95%, 89%, 100%, detecting deep myometrial invasion and 88%, 61%, 100%, detecting cervical invasion, respectively. The high accuracy achieved makes MRI an adequate method for determine the depth of myometrial and cervical invasion in endometrial carcinoma.

Inhibition of proliferation, migration and invasion of human non-small cell lung cancer cell line A549 by phlomisoside F from Phlomis younghusbandii Mukerjee

Purpose: To determine the effect of phlomisoside F (PMF) on the proliferation, migration and invasion of human non-small cell lung cancer cell line A549 and explore the possible mechanisms. Methods: The anti-proliferative effect of PMF on A549 cells was determined by CCK-8. Subsequently, migration and invasion were evaluated by Transwell and Transwell with matrigel assays, respectively. Furthermore, cell cycle and apoptosis were assessed by flow cytometry, while the mechanisms of action were determined by Western blotting. Results: PMF exhibited significant anti-proliferative effect on A549 cells in concentration-dependent and time-dependent manners, with half maximal inhibitory concentration (IC50) of 54.51 μM. Treatment with PMF (10, 20 and 40 μM) for 48 h resulted in significantly decreased migration and invasion in A549 cells. In addition, PMF at concentrations of 25, 50 and 75 μM induced cell cycle arrest in G0/G1phase and enhanced cell apoptosis in A549 cells. Furthermore, caspase-3, caspase-9 and Bax protein expressions were up-regulated while Bacl-2 and COX-2 protein expressions were significantly downregulated at 10, 20 and 40 μM concentrations of PMF. Conclusion: PMF suppresses A549 cell growth, migration and invasion. The mechanism may be related to the induction of mitochondria-mediated apoptosis pathway via regulation of caspase-3, caspase-9, Bcl-2 and Bax expressions, and inhibition of PGE2 synthesis by reducing COX-2 expression.

Intracellular signaling and trafficking in cancer: Role of Rab5-GTPases in migration and invasion of breast cancer cells

Metastasis is characterized pathologically by uncontrolled cell invasion, proliferation, migration and angiogenesis. Steroid hormones, such as estrogen, and growth factors, which include insulin growth factor I/II (IGF-1/IGF-2) therapy has been associated with most if not all of the features of metastasis. It has been determined that IGF-1 increases cell survival of cancer cells and potentiate the effect of E2 and other ligand growth factors on breast cancer cells. However not much information is available that comprehensively expounds on the roles of insulin growth factor receptor (IGFR) and Rab GTPases may play in breast cancer. The latter, Rab GTPases, are small signaling molecules and critical in the regulation of many cellular processes including cell migration, growth via the endocytic pathway. This research involves the role of Rab GTPases, specifically Rab5 and its guanine exchange factors (GEFs), in the promotion of cancer cell migration and invasion. Two important questions abound: Are IGFR stimulation and downstream effect involved the endocytic pathway in carcinogenesis? What role does Rab5 play in cell migration and invasion of cancer cells? The hypothesis is that growth factor signaling is dependent on Rab5 activity in mediating the aggressiveness of cancer cells. The goal is to demonstrate that IGF-1 signaling is dependent on Rab5 function in breast cancer progression. Here, the results thus far, have shown that while activation of Rab5 may mediate increased cell proliferation, migration and invasion in breast cancer cells, the Rab5 GEF, RIN1 interacts with the IGFR thereby facilitating migration and invasion activities in breast cells. Furthermore, endocytosis of the IGFR in breast cancer cells seems to be caveolin dependent as the data has shown. This taken together, the data shows that IGF-1 signaling in breast cancer cells relies on IGF-1R phosphorylation, caveolae internalization and sequestration to the early endosome RIN1 function and Rab5 activation.^

L'enseignement des jeux sportifs collectifs d'invasion à l'école: enseignants experts vs enseignants débutants

Les modèles d'enseignement sur les aspects pédagogiques portant sur la pratique sportive servent de base à l'élaboration de cette étude. Ces modèles renvoient au type d'approche et d'intervention des enseignants en ce qui concerne l’enseignement des jeux sportifs collectifs d’invasion (ci-après JSC), selon l'expertise. 8 professeurs d'éducation physique ont fait partie de cette étude, dont 4 experts et 4 débutants, sur un total de 16 cours observés. Les données statistiques ont été analysées en utilisant le logiciel IBM SPSS. L'analyse des résultats a démontré que les professeurs experts tendent à utiliser de plus amples espaces, et tendent, par défaut, à recourir au jeu formel, au détriment des jeux réduits ou conditionnés, plus couramment utilisés par le groupe d'enseignants débutants. Quant au niveau de feedback proposé, nous avons pu détecter quelques différences. Les enseignants débutants procèdent davantage à des feedbacks descriptifs, alors que le groupe d'experts opte plutôt pour des feedbacks prescriptifs.

Role of CARM1 (PRMT4) in high grade serous ovarian cancer metabolism and function of PRMT5 in ARID1A- deficient endometrial cancer invasion

The arginine methyltransferase CARM1 (PRMT4) is amplified and overexpressed in ~20% of high-grade serous ovarian cancer (HGSOC) and correlates with a poor survival. Therapeutic approaches based on CARM1 expression remain to be an unmet need. Here we show that fatty acid metabolism represents a metabolic vulnerability for HGSOC in a CARM1 expression status dependent manner. CARM1 promotes the de novo synthesis of fatty acids and monounsaturated fatty acids (MUFAs). The disruption of MUFAs synthesis by inhibition of SCD1 results in excessive accumulation of cytotoxic saturated fatty acids and it is synthetic lethal with CARM1 expression. Collectively, our data show that the pharmacological inhibition of MUFAs synthesis via SCD1 inhibition represents a therapeutic strategy for CARM1-high HGSOC. Another arginine methyltransferase, PRMT5, has been identified by our CRISPR screening analysis as a promising candidate for invasive ARID1A-deficient endometrial cancer. Endometrial Cancer frequently harbor somatic inactivating mutation of ARID1A that can promote an invasive phenotype. Our in vitro approach validated the CRISPR screening showing that both PRTM5 knock down and its pharmaceutical inhibition specifically hamper the invasion of ARID1A inactivated cells. Mechanistically, PRMT5 directly regulates the epithelia to mesenchymal transition pathway genes interacting with the SWI/SNF complexes. Moreover, in vivo experiments showed that PRMT5 inhibition contrasted the myometrium invasion highlighting PRMT5 inhibition as promising therapeutic strategy for ARID1A- inactivated aggressive endometrial cancer.

Integrated Proteomics Identified Up-regulated Focal Adhesion-mediated Proteins In Human Squamous Cell Carcinoma In An Orthotopic Murine Model.

Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules.

Fatty Acid Synthase Inhibitors Induce Apoptosis In Non-tumorigenic Melan-a Cells Associated With Inhibition Of Mitochondrial Respiration.

The metabolic enzyme fatty acid synthase (FASN) is responsible for the endogenous synthesis of palmitate, a saturated long-chain fatty acid. In contrast to most normal tissues, a variety of human cancers overexpress FASN. One such cancer is cutaneous melanoma, in which the level of FASN expression is associated with tumor invasion and poor prognosis. We previously reported that two FASN inhibitors, cerulenin and orlistat, induce apoptosis in B16-F10 mouse melanoma cells via the intrinsic apoptosis pathway. Here, we investigated the effects of these inhibitors on non-tumorigenic melan-a cells. Cerulenin and orlistat treatments were found to induce apoptosis and decrease cell proliferation, in addition to inducing the release of mitochondrial cytochrome c and activating caspases-9 and -3. Transfection with FASN siRNA did not result in apoptosis. Mass spectrometry analysis demonstrated that treatment with the FASN inhibitors did not alter either the mitochondrial free fatty acid content or composition. This result suggests that cerulenin- and orlistat-induced apoptosis events are independent of FASN inhibition. Analysis of the energy-linked functions of melan-a mitochondria demonstrated the inhibition of respiration, followed by a significant decrease in mitochondrial membrane potential (ΔΨm) and the stimulation of superoxide anion generation. The inhibition of NADH-linked substrate oxidation was approximately 40% and 61% for cerulenin and orlistat treatments, respectively, and the inhibition of succinate oxidation was approximately 46% and 52%, respectively. In contrast, no significant inhibition occurred when respiration was supported by the complex IV substrate N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD). The protection conferred by the free radical scavenger N-acetyl-cysteine indicates that the FASN inhibitors induced apoptosis through an oxidative stress-associated mechanism. In combination, the present results demonstrate that cerulenin and orlistat induce apoptosis in non-tumorigenic cells via mitochondrial dysfunction, independent of FASN inhibition.

Histologic Correlation Of Expression Of Ki-67 In Squamous Cell Carcinoma Of The Glottis According To The Degree Of Cell Differentiation.

Squamous cell carcinoma is the most common neoplasm of the larynx and glottis, and its prognosis depends on the size of the lesion, level of local invasion, cervical lymphatic spread, and presence of distant metastases. Ki-67 (MKI67) is a protein present in the core, whose function is related to cell proliferation. To evaluate the expression of marker Ki-67 in squamous cell carcinoma of the larynx and glottis and its correlation to pathological findings. Experimental study with immunohistochemistry analysis of Ki-67, calculating the percentage of the cell proliferation index in glottic squamous cell carcinomas. Sixteen cases were analyzed, with six well-differentiated and 10 poorly/moderately differentiated tumors. There was a correlation between cell proliferation index and degree of cell differentiation, with higher proliferation in poorly/moderately differentiated tumors. The cell proliferation index, as measured by Ki-67, may be useful in the characterization of histological degree in glottic squamous cell tumors.