The lagoonal harbour of Portus Pisanus (N Tyrrhen- ian Sea, Italy): a long history of human adaptation to changing coastline

During the last millennia human and natural processes have become increasingly intertwined, especially in the Mediterranean coastal and alluvial plains where major urban and trade centres developed since protohistoric times. The construction of ports represents one of the human activities that have mostly contributed to modify coastal environments, inducing a variety of hydrodynamic and hydrochemical changes especially since Roman times (Marriner et al., 2014). Exceptions in this common manner to plan harbours have been recognised along the N Tyrrhenian coast, where no high-impact defense works are explicitly documented by either historical sources or archaeological excavations for three main harbours developed during Etruscan-Roman times (IV-I century BC): Portus Lunae (Bini et al., 2012), Portus Pisanus and Vada Volterrana. Roman literary sources (i.e., Itinerarium Maritimum 501; Rutilio Namaziano) mentioned Portus Pisanus as a flourishing commercial site within a natural protected area (called Sinus Pisanus by Tacito) characterized by Posidonia meadows and located at the foot of Leghorn hills, ca. 18.5 km south of the Pisa city. Accordingly, recent excavations undertaken close to the hills slope, 3 km inland from modern coastline, unearthed a wooden palisade, stone piers and a warehouse dated to the Roman period (Pasquinucci, 2013; Morhange et al., 2015). However, the precise location of the lagoonal harbour basin is still controversial. This study aims to contribute to fill this knowledge gap and shed new light on the main stages of harbour history in the framework of the mid-late Holocene palaeogeographic evolution of the Pisa Plain. The application of a multidisciplinary approach (sedimentological and micropalaeontological core analyses, radiocarbon dating, geomorphological field survey, remote sensing and historical cartography) has revealed that a wide lagoonal basin formed in the study area during the marine transgression peak (ca. 8000 cal yr BP). This basin, recorded by a m-thick subsurface succession of soft grey clays with brackish meiofauna, persisted for several millennia and corresponds to Sinus Pisanus. The available stratigraphic data document that during Roman times the lagoon became progressively less connected to the sea and turned into a coastal lake/pond. Filling processes started two-three millennia later respect to the lagoon occupying the Pisa city area during the Holocene (Rossi et al., 2011). This seaward facies shift forced the westward transferring of the Middle Ages harbour. These results show that natural sheltered conditions along with the distance from coeval Arno River made more advantageous for humans following the shoreline changes, rather than making high-impact interventions. 2012, Bini M., Bruckner H., Chelli A., Da Prato S., Gervasini L., Palaeogeographies of the Magra Valley coastal plain to costrain the location of the Roman harbour of Luna (NW Italy), Palaeogeography, Palaeoclimatology, Palaeoecology, 337-338, 37–51. 2014, Marriner N., Morhange C., Kaniewski D., Carayon N., Ancient harbour infrastructure in the Levant: tracking the birth and rise of new forms of anthropogenic pressure, Nature Scientific Reports, 4, 5554. 2015, Morhange C., Marriner N., Baralis A., Blot M.L., Bony G., Carayon N., Carmona P., Flaux C., Giaime M., Goiran J.-P., Kouka M., Lena A., Oueslati A., Pasquinucci M., Porotov A., Dynamiques géomorphologiques et typologie géoarcheologique des ports antiques en contextes lagunaires, Quaternaire, 26, (2), 117–139. 2013, Pasquinucci M., Guida all’archeologia delle coste livornesi. Nardini Editore. Provincia di Livorno. 271 pp. 2011, Rossi V., Amorosi A., Sarti G., Potenza M., Influence of inherited topography on the Holocene sedimentary evolution of coastal systems: An example from Arno coastal plain (Tuscany, Italy), Geomorphology, 135 (1-2), 117–128

MAPPA cores: an interdisciplinary approach

In the urban and periurban area of Pisa, 18 cores ranging in depth between 7 and 15 m were performed and analysed through an interdisciplinary approach, which led to an improved stratigraphic log representation. The acquired data also improved our knowledge about the palaeoenvironmental and human settlement evolution of Pisa area over the past 6000 years, evidencing the mutual interaction existing between landscape and human activities

I carotaggi MAPPA: un’integrazione interdisciplinare

Una consistente campagna di acquisizione di dati di sottosuolo (18 carotaggi con profondità da 7 a 15 m) condotta con approccio interdisciplinare, finalizzato a una rappresentazione integrata del log stratigrafico, ha permesso di incrementare in modo significativo le conoscenze del contesto paleoambientale ed insediativo della zona urbana e suburbana della città di Pisa durante gli ultimi 6000 anni circa e di valutare il reciproco condizionamento fra l’ambiente naturale e le caratteristiche dell’insediamento uman

Characterization of the effects of cross-linking of macrophage CD44 associated with increased phagocytosis of apoptotic PMN

Control of macrophage capacity for apoptotic cell clearance by soluble mediators such as cytokines, prostaglandins and lipoxins, serum proteins, and glucocorticoids may critically determine the rate at which inflammation resolves. Previous studies suggested that macrophage capacity for clearance of apoptotic neutrophils was profoundly altered following binding of CD44 antibodies. We have used a number of different approaches to further define the mechanism by which CD44 rapidly and specifically augment phagocytosis of apoptotic neutrophils. Use of Fab ’ fragments unequivocally demonstrated a requirement for cross-linking of macrophage surface CD44. The molecular mechanism of CD44-augmented phagocytosis was shown to be opsonin-independent and to be distinct from the Mer/protein S pathway induced by glucocorticoids and was not functional for clearance of apoptotic eosinophils. CD44-cross-linking also altered macrophage migration and induced cytoskeletal re-organisation together with phosphorylation of paxillin and activation of Rac2. Investigation of signal transduction pathways that might be critical for CD44 augmentation of phagocytosis revealed that Ca 2+ signalling, PI-3 kinase pathways and altered cAMP signalling were not involved, but did implicate a key role for tyrosine phosphorylation events. Finally, although CD44 antibodies were able to augment phagocytosis of apoptotic neutrophils by murine peritoneal and bone marrow-derived macrophages, we did not observe a difference in the clearance of neutrophils following induction of peritonitis with thioglycollate in CD44-deficient animals. Together, these data demonstrate that CD4

Red Listing plants under full national responsibility: Extinction risk and threats in the vascular flora endemic to Italy

Taxa endemic to a country are key elements for setting national conservation priorities and for driving conservation strategies, since their persistence is entirely dependent on national policy. We applied the IUCN Red List categories to all Italian endemic vascular plants (1340 taxa) to assess their current risk of extinction and to highlight their major threats. Our results revealed that six taxa are already extinct and that 22.4% (300 taxa) are threatened with extinction, while 18.4% (247; especially belonging to apomictic groups) have been categorized as Data Deficient. Italian endemic vascular plants are primarily threatened by natural habitat modification due to agriculture, residential and tourism development. Taxa occurring in coastal areas and lowlands, where anthropogenic impacts and habitat destruction are concentrated, display the greatest population decline and extinction. The national network of protected areas could be considered effective in protecting endemic-rich areas (ERAs) and endemic taxa, but ineffective in protecting narrow endemic-rich areas (NERAs), accordingly changes to the existing network may increase the effectiveness of protection. For the first time in the Mediterranean Basin biodiversity hotspot, we present a comprehensive extinction assessment for endemic plants under the full responsibility of a single country. This would provide an important step towards the prioritization and conservation of threatened endemic flora at Italian, European, and Mediterranean level. A successful conservation strategy of the Italian endemic vascular flora should implement the protected area system, solve some taxonomical criticism in poorly known genera, and should rely on monitoring threatened species, and on developing species-specific action plans

Induction of Eosinophil Apoptosis by the Cyclin-Dependent Kinase Inhibitor AT7519 Promotes the Resolution of Eosinophil-Dominant Allergic Inflammation

Eosinophils not only defend the body against parasitic infection but are also involved in pathological inflammatory allergic diseases such as asthma, allergic rhinitis and contact dermatitis. Clearance of apoptotic eosinophils by macrophages is a key process responsible for driving the resolution of eosinophilic inflammation and can be defective in allergic diseases. However, enhanced resolution of eosinophilic inflammation by deliberate induction of eosinophil apoptosis using pharmacological agents has not been previously demonstrated. Here we investigated the effect of a novel cyclin-dependent kinase inhibitor drug, AT7519, on human and mouse eosinophil apoptosis and examined whether it could enhance the resolution of a murine model of eosinophil-dominant inflammation in vivo.Eosinophils from blood of healthy donors were treated with AT7519 and apoptosis assessed morphologically and by flow-cytometric detection of annexin-V/propidium iodide staining. AT7519 induced eosinophil apoptosis in a concentration dependent manner. Therapeutic administration of AT7519 in eosinophil-dominant allergic inflammation was investigated using an established ovalbumin-sensitised mouse model of allergic pleurisy. Following ovalbumin challenge AT7519 was administered systemically at the peak of pleural inflammation and inflammatory cell infiltrate, apoptosis and evidence of macrophage phagocytosis of apoptotic eosinophils assessed at appropriate time points. Administration of AT7519 dramatically enhanced the resolution of allergic pleurisy via direct induction of eosinophil apoptosis without detriment to macrophage clearance of these cells. This enhanced resolution of inflammation was shown to be caspase-dependent as the effects of AT7519 were reduced by treatment with a broad spectrum caspase inhibitor (z-vad-fmk).Our data show that AT7519 induces human eosinophil apoptosis and enhances the resolution of a murine model of allergic pleurisy by inducing caspase-dependent eosinophil apoptosis and enhancing macrophage ingestion of apoptotic eosinophils. These findings demonstrate the utility of cyclin-dependent kinase inhibitors such as AT7519 as potential therapeutic agents for the treatment of eosinophil dominant allergic disorders

Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial

<p>Abstract</p> <p>Background</p> <p>To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer.</p> <p>Methods</p> <p>Patients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed.</p> <p>Results</p> <p>From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm.</p> <p>Conclusions</p> <p>In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00540800">NCT00540800</a>.</p

The large trans-Neptunian object 2002 TC302 from combined stellar occultation, photometry, and astrometry data

Context. Deriving physical properties of trans-Neptunian objects is important for the understanding of our Solar System. This requires observational efforts and the development of techniques suitable for these studies. Aims. Our aim is to characterize the large trans-Neptunian object (TNO) 2002 TC302. Methods. Stellar occultations offer unique opportunities to determine key physical properties of TNOs. On 28 January 2018, 2002 TC302 occulted a mv ~ 15.3 star with designation 593-005847 in the UCAC4 stellar catalog, corresponding to Gaia source 130957813463146112. Twelve positive occultation chords were obtained from Italy, France, Slovenia, and Switzerland. Also, four negative detections were obtained near the north and south limbs. This represents the best observed stellar occultation by a TNO other than Pluto in terms of the number of chords published thus far. From the 12 chords, an accurate elliptical fit to the instantaneous projection of the body can be obtained that is compatible with the near misses. Results. The resulting ellipse has major and minor axes of 543 ± 18 km and 460 ± 11 km, respectively, with a position angle of 3 ± 1 degrees for the minor axis. This information, combined with rotational light curves obtained with the 1.5 m telescope at Sierra Nevada Observatory and the 1.23 m telescope at Calar Alto observatory, allows us to derive possible three-dimensional shapes and density estimations for the body based on hydrostatic equilibrium assumptions. The effective diameter in equivalent area is around 84 km smaller than the radiometrically derived diameter using thermal data from Herschel and Spitzer Space Telescopes. This might indicate the existence of an unresolved satellite of up to ~300 km in diameter, which is required to account for all the thermal flux, although the occultation and thermal diameters are compatible within their error bars given the considerable uncertainty of the thermal results. The existence of a potential satellite also appears to be consistent with other ground-based data presented here. From the effective occultation diameter combined with absolute magnitude measurements we derive a geometric albedo of 0.147 ± 0.005, which would be somewhat smaller if 2002 TC302 has a satellite. The best occultation light curves do not show any signs of ring features or any signatures of a global atmosphere.Funding from Spanish projects AYA2014-56637-C2-1-P, AYA2017-89637-R, from FEDER, and Proyecto de Excelencia de la Junta de Andalucía 2012-FQM1776 is acknowledged. We would like to acknowledge financial support by the Spanish grant AYA-RTI2018-098657-JI00 “LEO-SBNAF” (MCIU/AEI/FEDER, UE) and the financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award for the Instituto de Astrofísica de Andalucía (SEV- 2017-0709). Part of the research received funding from the European Union’s Horizon 2020 Research and Innovation Programme, under grant agreement no. 687378 and from the ERC programme under Grant Agreement no. 669416 Lucky Star. The following authors acknowledge the respective CNPq grants: FB-R 309578/2017-5; RV-M 304544/2017-5, 401903/2016-8; J.I.B.C. 308150/2016-3; MA 427700/2018-3, 310683/2017-3, 473002/2013-2. This study was financed in part by the Coordenação de Aperfeiaçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001 and the National Institute of Science and Technology of the e-Universe project (INCT do e-Universo, CNPq grant 465376/2014-2). GBR acknowledges CAPES-FAPERJ/PAPDRJ grant E26/203.173/2016, MA FAPERJ grant E-26/111.488/2013 and ARGJr FAPESP grant 2018/11239-8. E.F.-V. acknowledges support from the 2017 Preeminent Postdoctoral Program (P3) at UCF. C.K., R.S., A.F-T., and G.M. have been supported by the K-125015 and GINOP-2.3.2-15-2016-00003 grants of the Hungarian National Research, Development and Innovation Office (NKFIH), Hungary. G.M. was also supported by the Hungarian National Research, Development and Innovation Office (NKFIH) grant PD-128 360. R.K. and T.P. were supported by the VEGA 2/0031/18 grant

The Dimorphos ejecta plume properties revealed by LICIACube

The Double Asteroid Redirection Test (DART) had an impact with Dimorphos (a satellite of the asteroid Didymos) on 26 September 20221. Ground-based observations showed that the Didymos system brightened by a factor of 8.3 after the impact because of ejecta, returning to the pre-impact brightness 23.7 days afterwards2. Hubble Space Telescope observations made from 15 minutes after impact to 18.5 days after, with a spatial resolution of 2.1 kilometres per pixel, showed a complex evolution of the ejecta3, consistent with other asteroid impact events. The momentum enhancement factor, determined using the measured binary period change4, ranges between 2.2 and 4.9, depending on the assumptions about the mass and density of Dimorphos5. Here we report observations from the LUKE and LEIA instruments on the LICIACube cube satellite, which was deployed 15 days in advance of the impact of DART. Data were taken from 71 seconds before the impact until 320 seconds afterwards. The ejecta plume was a cone with an aperture angle of 140 ± 4 degrees. The inner region of the plume was blue, becoming redder with increasing distance from Dimorphos. The ejecta plume exhibited a complex and inhomogeneous structure, characterized by filaments, dust grains and single or clustered boulders. The ejecta velocities ranged from a few tens of metres per second to about 500 metres per second.This work was supported by the Italian Space Agency (ASI) in the LICIACube project (ASI-INAF agreement AC no. 2019-31-HH.0) and by the DART mission, NASA contract 80MSFC20D0004. M.Z. acknowledges Caltech and the Jet Propulsion Laboratory for granting the University of Bologna a licence to an executable version of MONTE Project Edition software. M.Z. is grateful to D. Lubey, M. Smith, D. Mages, C. Hollenberg and S. Bhaskaran of NASA/JPL for the discussions and suggestions regarding the operational navigation of LICIACube. G.P. acknowledges financial support from the Centre national d’études spatiales (CNES, France). A.C.B. acknowledges funding by the NEO-MAPP project (grant agreement 870377, EC H2020-SPACE-2019) and by the Ministerio de Ciencia Innovación (PGC 2018) RTI2018-099464-B-I00. F.F. acknowledges funding from the Swiss National Science Foundation (SNSF) Ambizione (grant no. 193346). J.-Y.L. acknowledges the support from the NASA DART Participating Scientist Program (grant no. 80NSSC21K1131). S.D.R. and M.J. acknowledge support from the Swiss National Science Foundation (project no. 200021_207359)