Sea level rise scenario for 2100 A.D. for the archaeological site of Motya

In this study, we analyze the impact of the sea level rise induced by climate change on the coastal cultural heritage site of Motya, the Phoenician colony (IV–III millennium B.P.) located in the San Pantaleo island, NW corner of Sicily (southern Italy). In particular, we assessed the effects of this phenomenon on the human settlement in the past 2400 years and the expected sea level rise scenario for the next decades. A detailed flooding scenario for 2100 from direct observations and two models, taking into account the contribution of Vertical Land Movements (VLM), is provided. The surface topography is derived from a novel high-resolution/high-accuracy digital surface model (DSM), which was performed through an Unmanned Aerial Vehicles (UAV) survey, whereas the rate of VLM was estimated by the analysis of geodetic data at three Continuous Global Positioning System (CGPS) stations located close to the island. To estimate the local mean sea level and to correct the tide level (TL) at the epoch of UAV survey, the hydrometric recordings of the nearest sea level gauge station located at Porto Empedocle (Sicily), were used. Two flooding scenarios for 2100 were then represented on the high-resolution DSM, using the regional sea-level projections of the International Panel on Climate Change (IPCC) for the Mediterranean region. According to the RCP 8.5 climatic model, a difference of about + 59 cm above the local mean sea level between the current and the expected coastline positions at 2100 A.D., was found. In addition, by adding the average half amplitude of the daily tide, equal to about 30 cm, a maximum flooding scenario was determined. Finally, in the maximum condition of sea level rise, a significant flooding on the archaeological structures is expected for the Kothon area and along the North-West coast of the island

Decreased Langerhans Cell Responses to IL-36γ: Altered Innate Immunity in Patients with Recurrent Respiratory Papillomatosis

Recurrent respiratory papillomatosis (RRP) is a rare, chronic disease caused by human papillomaviruses (HPVs) types 6 and 11 that is characterized by the polarization of adaptive immune responses that support persistent HPV infection. Respiratory papillomas express elevated mRNA levels of IL-36γ, a proinflammatory cytokine in comparison to autologous clinically normal laryngeal tissues; however there is no evidence of inflammation in these lesions. Consistent with this, respiratory papillomas do not contain T(H)1-like CD4(+) T-cells or cytotoxic CD8(+) T-cells, but instead contain a predominance of T(H)2-like and T regulatory cells (Tregs). In addition, papillomas also are infiltrated with immature Langerhans cells (iLCs). In this study, we show that papilloma cells express IL-36γ protein, and that human keratinocytes transduced with HPV11 have reduced IL-36γ secretion. We now provide the first evidence that peripheral blood-derived iLCs respond to IL-36γ by expressing inflammatory cytokines and chemokines. When stimulated with IL-36γ, iLCs from patients with RRP had lower expression levels of the T(H)2-like chemokine CCL-20 as compared with controls. Patients’ iLCs also had decreased steady state levels of CCL-1, which is a proinflammatory chemokine. Moreover, CCL-1 levels in iLCs inversely correlated with the severity of RRP. The combined decrease of T(H)1- and a T(H)2-like chemokines by iLCs from patients could have consequences in the priming of IFN-γ expression by CD8(+) T-cells. Taken together, our results suggest that, in RRP, there is a defect in the proinflammatory innate immune responses made by iLCs in response to IL-36γ. The consequence of this defect may lead to persistent HPV infection by failing to support an effective HPV-specific, T(H)1-like and/or T(c)1-like adaptive response, thus resulting in the predominant T(H)2-like and/or Treg micromilieu present in papillomas

Immune Dysregulation and Tumor-Associated Gene Changes in Recurrent Respiratory Papillomatosis: A Paired Microarray Analysis

Recurrent respiratory papillomas (RRP) are benign airway tumors, caused primarily by human papillomaviruses (HPV) types 6 and 11. The disease is characterized by multiple recurrences after surgical removal, with limited effective therapy. To identify novel targets for future therapy, we established transcriptional profiles for actively growing papillomas compared with autologous, clinically normal, laryngeal epithelia (adjacent tissue). Total ribonucleic acid (RNA) from 12 papillomas and 12 adjacent tissues were analyzed by microarray, and the matched sets of tissues compared by paired t test, to identify differentially expressed genes in papilloma tissues while minimizing variations intrinsic to individual patients. Quantitative polymerase chain reaction (PCR) was used to confirm the relative expression levels for a subset of genes. Within the 109 differentially expressed transcripts whose expression varied at least three-fold were two large groups of genes with related functions. The first group consisted of 18 genes related to host defense, including both innate and adaptive immunity. The second group contained 37 genes that likely contribute to growth of papillomas as benign tumors, since the altered pattern of expression also had been reported previously in many cancers. Our results support our previous studies that document a systemic TH2-like adaptive immune response in RRP, and suggest that there is a role for altered innate immunity in RRP as well. We propose that HPV 6 and 11 infection establishes a tumorigenic microenvironment characterized by alteration of both innate inflammatory signals and adaptive immune responses that prevent effective TH1-like response, in conjunction with altered expression of numerous genes that regulate cellular growth and differentiation

Constitutive Overexpression of the Oncogene Rac1 in the Airway of Recurrent Respiratory Papillomatosis Patients Is a Targetable Host-Susceptibility Factor

Recurrent respiratory papillomatosis (RRP) is caused by human papillomaviruses (HPVs), primarily types 6 and 11. The disease is characterized by multiple recurrences of airway papillomas, resulting in high levels of morbidity and significant mortality. The prevalence of latent HPV in the larynx of the general population is much greater than the prevalence of RRP, suggesting a host-susceptibility factor for disease. We report that the oncogene Rac1 and its downstream product cyclooxygenase-2 (COX-2) are both constitutively expressed at high levels throughout the airway of these patients, independent of active HPV infection. Use of the COX-2 inhibitor celecoxib in primary papilloma cell culture resulted in the downregulation of HPV transcription. Furthermore, a proof-of-principle study treating three patients with severe RRP with celecoxib resulted in remission of disease in all cases. Therefore, we have identified the first pharmacologically targetable host-susceptibility pathway that contributes to RRP recurrence