Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium

This study was prompted by the observation that decidual endothelial cells (DECs), unlike endothelial cells (ECs) of blood vessels in normal skin, kidney glomeruli and brain, express surface-bound C1q in physiologic pregnancy. This finding was unexpected, because deposits of C1q are usually observed in pathologic conditions and are associated with complement activation. In the case of DECs, we failed to detect immunoglobulins and C4 co-localized with C1q on the cell surface. Surprisingly, DECs expressed mRNA for the three chains of C1q and secreted detectable level of this component in serum-free medium. The ability to synthesize C1q is acquired by DECs during pregnancy and is not shared by ECs obtained from endometrium and from other sources. Cell-associated C1q has a molecular weight similar to that of secreted C1q and is released from DECs following treatment with heparinase or incubation at low pH. This suggests that C1q binds to DECs and it is not constitutively expressed on the cell surface. C1q is localized at contact sites between endovascular trophoblast and DECs and acts as an intercellular molecular bridge because adhesion of endovascular trophoblast to DECs was inhibited by antibodies to C1q and to a receptor recognizing its globular portion expressed on trophoblast. © 2008 Elsevier Ltd. All rights reserved

La Ceramica nuragica della prima età del ferro

The present study focuses on the production of nuragic pottery during the early Iron Age (about 950-730 BC.). As widely known ceramic productions enables to make large scale comparisons, both synchronic and diachronic, allowing to underline chronological, functional, economic and cultural differences, whereas each stage of the processes related to ceramic production is affected by the functions of the objects and by a wide range of human and natural factors. A substantial part of the work has involved a careful review of ceramic ware already known and published, taking into account more than one hundred islanders archaeological contexts. Furthermore, the data collected were crossed with those coming from the context of the partially published site of Nuracraba in Oristano (OR), through the study of pottery from the remains of a large dump, named discarica D1, filled by ashes and animal bones together with a great number of ceramic fragments

Comunicar las relaciones entre las islas del mediterraneo: el caso de Menorca y Cerdeña en la Prehistoria

In the last 50 years, archaeologists who studied the prehistory of Sardinia have shown great interest in other islands of the western Mediterranean. This interest has grown out of the need to expand our knowledge about the archaeology of typical island environments. In the early 1990s the project “Cap de Forma (Menorca): The Navigation in the Western Mediterranean from the Bronze Age to the Iron Age” was initiated, sponsored by the Universities of Cagliari (G. Tore, C. Del Vais) and Sassari (G. Tanda, A. Depalmas) and the Museu de Menorca (Ll. Plantalamor Massanet). The goal was to make a detailed comparison of some peculiar aspects of pre- and protohistorical periods in Sardinia and Menorca. One aim of the project is to acquire the means to verify whether insularity really stopped the cultural development of island communities (as often claimed) or whether, instead, it contributed significantly to the construction of specific cultures of extraordinary value and importance, some of which showed signs of advanced social and economic development, as seems to have been the case with the Nuragic civilization in Sardinia and the Talayotic culture in the Balearic Islands. Therefore, the specific objective of this research is to analyse whether there were relationships and cultural influences between the islands of Menorca and Sardinia during the Bronze and Iron Age. The investigation focused on the coastal fortification and the hypogeal necropolis of Cap de Forma (Mahon, Menorca). The idea was to identify potential similarities and differences with archaeological sites in Nuragic Sardinia. Cap de Forma is an archaeological complex of particular importance. It is coastal and fortified, as are few other sites on the island. Moreover, its strategic position, which overlooks and provides vistas of all the south coast of Menorca, is of particular relevance to the study of navigation and routes to and from the islands. Recently, research excavations at the site were completed and in the project for accommodation of the area aiming to visits, it seems important to think about the message we want to give to the visitor. The information that we would like to communicate to the public are not only technical ones, related to the excavated structures, but also about the type of research in international cooperation that has allowed the discoveries and about suggestions that a fortified site as Cap de Forma, gives us on the study of ancient navigation and contacts between Mediterranean peoples.En los últimos 50 años los arqueólogos que estudian la prehistoria de Cerdeña se interesaron mucho a las otras islas del Mediterráneo occidental. El interés nació de la la necesidad de acrecer el conocimiento sobre el arqueología de los ambientes típicos de las islas. En los primeros años noventa se empezó el proyecto “Cap de Forma (Menorca): la navegación en el Mediterráneo occidental entre la Edad del Bronce y la Edad del Hierro”, financiado por las universidades de Cagliari (G. Tore, C. Del Vais) y Sassari (G. Tanda, A. Depalmas) y por el Museo de Menorca (Ll. Plantalamor Massanet), con el fin de comparar algunos aspectos peculiares de la prehistoria y protohistoria de Cerdeña y Menorca. Uno de los objetivos del proyecto es adquirir los medios para verificar si la insularidad limitó el desarrollo cultural de las comunidades de las islas (como muchos creen) o si, al contrario, ayudó de manera importante a la creación de culturas especificas de valor extraordinario, algunas con un desarrollo social y económico muy avanzado, como la civilización nurágica en Cerdeña y la cultura talayótica en las Islas Baleares. Por lo tanto el objetivo especifico de esta investigación es analizar si existieron relaciones e influencias culturales entre las islas de Menorca y Cerdeña durante la Edad del Bronce y la Edad del Hierro. El estudio se encentró sobre la fortificación costera y la necrópolis hipogea de Cap de Forma (Menorca), con la idea de identificar semejanzas y diferencias con otros yacimientos nurágicos de Cerdeña. Cap de Forma es un complejo arqueológico muy importante, costero y fortificado como otros pocos en la misma isla. Además su posición estratégica, que controla el Sur de la isla de Menorca es de particular interés para el estudio de la navegación y de las rutas desde y hacia las islas. En los últimos tiempos se acabaron las excavaciones en el yacimiento y parece importante, en el proyecto de acomodación del área para las visitas, pensar al mensaje que se quiere dar a los visitantes. La información que se pretende dar al publico no es simplemente de carácter técnico, relacionada a las estructuras que se excavaron, sino que también sobre la cooperación internacional en la investigación y sobre los indicios y la información que aporta un yacimiento fortificado como Cap de Forma al estudio de la navegación antigua y de los contactos entre los pueblos del Mediterráneo.Depto. de Prehistoria, Historia Antigua y ArqueologíaFac. de Geografía e HistoriaTRUEMinisterio de Economía y Competitividad (MINECO)pu

New data from fortified coastal settlement of Cap de Forma, Maó-Menorca (Balearic Islands)

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Endothelial cells and the complement component C1q as novel therapeutic tools for the treatment of chronic ulcers

One of the major limitation of the current treatments for burns and chronic ulcers is the absence of a rapid functional vascular plexus formation. The impaired angiogenic condition leads to a poor nutritional intake and to increased microbial contamination. To evaluate novel potential therapeutic strategies to improve new vessel formation we set up a method for the isolation of human adult dermal endothelial cells (ADMEC) from skin biopsies. We then evaluated the ability of ADMEC to adhere and to grow into a tridimensional matrix of collagen and of human decellularized dermis. A wound healing model was established in rats to investigate the role of endothelial cells in an in vivo angiogenic process. The data show an increase of vascular structures in the wounds treated with endothelial cells compared to the controls. Several soluble factors can be produced by endothelial cells and promote angiogenesis. We have recently showed that decidual endothelial cells are able to synthesize C1q and express surface-bound C1q under physiological conditions. Since decidua is a site of active angiogenesis, we sought to ascertain whether C1q can play a role in this process. To confirm our hypothesis we used different approaches such as permeability, cell migration and proliferation assay, besides wound healing and aortic ring assay. C1q acts as a permeabilizing factor inducing the FITC-BSA leakage through a monolayer of endothelial cells (ECs). Next, we found that C1q was able to promote motility of ECs in a wound healing assay, and to recruit ECs acting as a chemotactic factor, furthermore C1q was also found to have an additional effect on EC inducing cell proliferation. To confirm and extend these data, we used the rat aortic ring assay to evaluate the ex vivo effect of C1q. C1q was also found to stimulate the formation of tubular structures in a matrigel assay and to promote sprouting formation in the aortic ring assay. The presence of both ECs and pericytes were documented in the sprouts indicating that complete new vessels are being formed. The in vivo proangiogenic activity of C1q was evaluated in rats using a wound healing assay. C1q, VEGF or saline was topically applied to the wounds and the skin lesions removed after 14 days were examined for vessel formation. The wounds treated with C1q exhibited a number of new vessels increased to that of saline treated wounds and comparable to that of VEGF. The results suggest that the topical application of endothelial cells or C1q are of potential therapeutic interest as a pro angiogenic treatment of chronic ulcers

Pathological significance and prognostic value of Surfactant Protein D in cancer

Surfactant protein D (SP-D) is a pattern recognition molecule belonging to the Collectin (collagen-containing C-type lectin) family that has pulmonary as well as extra-pulmonary existence. In the lungs, it is a well-established opsonin that can agglutinate a range of microbes, and enhance their clearance via phagocytosis and super-oxidative burst. It can interfere with allergen-IgE interaction and suppress basophil and mast cell activation. However, it is now becoming evident that SP-D is likely to be an innate immune surveillance molecule against tumor development. SP-D has been shown to induce apoptosis in sensitized eosinophils derived from allergic patients and a leukemic cell line via p53 pathway. Recently, SP-D has been shown to suppress lung cancer progression via interference with the epidermal growth factor signaling. In addition, a truncated form of recombinant human SP-D has been reported to induce apoptosis in pancreatic adenocarcinoma via Fas-mediated pathway in a p53-independent manner. To further establish a correlation between SP-D presence/levels and normal and cancer tissues, we performed a bioinformatics analysis, using Oncomine dataset and the survival analysis platforms Kaplan-Meier plotter, to assess if SP-D can serve as a potential prognostic marker for human lung cancer, in addition to human gastric, breast and ovarian cancers. We also analyzed immunohistochemically the presence of SP-D in normal and tumor human tissues. We conclude that (1) in the lung, gastric and breast cancers, there is a lower expression of SP-D than normal tissues; (2) in ovarian cancer, there is a higher expression of SP-D than normal tissue; and (3) in lung cancer, the presence of SP-D could be associated with a favorable prognosis. On the contrary, at non-pulmonary sites such as gastric, breast and ovarian cancers, the presence of SP-D could be associated with unfavorable prognosis. Correlation between the levels of SP-D and overall survival requires further investigation. Our analysis involves a large number of dataset; therefore, any trend observed is reliable. Despite apparent complexity within the results, it is evident that cancer tissues that produce less levels of SP-D compared to their normal tissue counterparts, are probably less susceptible to SP-D-mediated immune surveillance mechanisms via infiltrating immune cells

Observation of γγ → ττ in proton-proton collisions and limits on the anomalous electromagnetic moments of the τ lepton

The production of a pair of τ leptons via photon–photon fusion, γγ → ττ, is observed for the f irst time in proton–proton collisions, with a significance of 5.3 standard deviations. This observation is based on a data set recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 138 fb−1. Events with a pair of τ leptons produced via photon–photon fusion are selected by requiring them to be back-to-back in the azimuthal direction and to have a minimum number of charged hadrons associated with their production vertex. The τ leptons are reconstructed in their leptonic and hadronic decay modes. The measured fiducial cross section of γγ → ττ is σfid obs = 12.4+3.8 −3.1 fb. Constraints are set on the contributions to the anomalous magnetic moment (aτ) and electric dipole moments (dτ) of the τ lepton originating from potential effects of new physics on the γττ vertex: aτ = 0.0009+0.0032 −0.0031 and |dτ| < 2.9×10−17ecm (95% confidence level), consistent with the standard model

Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study

INTRODUCTION: Increased mortality has been demonstrated in older adults with COVID-19, but the effect of frailty has been unclear.METHODS: This multi-centre cohort study involved patients aged 18years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty, and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation, and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS), and delirium on risk of increased care requirements on discharge, adjusting for the same variables.RESULTS: Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, IQR 54-83; 55.2% male). The risk of death increased independently with increasing age (>80 vs 18-49: HR 3.57, CI 2.54-5.02), frailty (CFS 8 vs 1-3: HR 3.03, CI 2.29-4.00) inflammation, renal disease, cardiovascular disease, and cancer, but not delirium. Age, frailty (CFS 7 vs 1-3: OR 7.00, CI 5.27-9.32), delirium, dementia, and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9.CONCLUSIONS: Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age