Methods of Administering IgG1 Antibodies and Methods of Suppressing Angiogenesis

A method of suppressing angiogenesis involves administering to a subject an isolated Fc fragment of an IgG1 antibody, or an IgG1 antibody

Identification of Placenta Growth Factor Determinants for Binding and Activation of Flt-1 Receptor

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Anti-angiogenic activity evaluation of secondary metabolites from Calycolpus moritzianus leaves.

Angiogenesis is a crucial step in many pathological conditions like cancer, inflammation and metastasis formation; on these basis the search for antiangiogenic agents has widened. In order to identify new compounds able to interfere in the Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1, also known as Flt-1) recognition by VEGFs family members, we screened Calycolpus moritzianus (O. Berg) Burret leaves extracts by a competitive ELISA-based assay. MeOH and CHCl3 extracts and several their fractions demonstrated to be able to prevent VEGF or PlGF interaction with Flt-1, with an inhibition about 50% at concentration of 100 μg/mL. Phytochemical and pharmacological investigation of the active fractions led to the isolation of flavonoids, and terpenes

L-Proline Induces a Mesenchymal-like Invasive Program in Embryonic Stem Cells by Remodeling H3K9 and H3K36 Methylation

SummaryMetabolites are emerging as key mediators of crosstalk between metabolic flux, cellular signaling, and epigenetic regulation of cell fate. We found that the nonessential amino acid L-proline (L-Pro) acts as a signaling molecule that promotes the conversion of embryonic stem cells into mesenchymal-like, spindle-shaped, highly motile, invasive pluripotent stem cells. This embryonic-stem-cell-to-mesenchymal-like transition (esMT) is accompanied by a genome-wide remodeling of the H3K9 and H3K36 methylation status. Consistently, L-Pro-induced esMT is fully reversible either after L-Pro withdrawal or by addition of ascorbic acid (vitamin C), which in turn reduces H3K9 and H3K36 methylation, promoting a mesenchymal-like-to-embryonic-stem-cell transition (MesT). These findings suggest that L-Pro, which is produced by proteolytic remodeling of the extracellular matrix, may act as a microenvironmental cue to control stem cell behavior

Relative Sea-Level Rise and Potential Submersion Risk for 2100 on 16 Coastal Plains of the Mediterranean Sea.

The coasts of the Mediterranean Sea are dynamic habitats in which human activities have been conducted for centuries and which feature micro-tidal environments with about 0.40 m of range. For this reason, human settlements are still concentrated along a narrow coastline strip, where any change in the sea level and coastal dynamics may impact anthropic activities. In the frame of the RITMARE and the Copernicus Projects, we analyzed light detection and ranging (LiDAR) and Copernicus Earth Observation data to provide estimates of potential marine submersion for 2100 for 16 small-sized coastal plains located in the Italian peninsula and four Mediterranean countries (France, Spain, Tunisia, Cyprus) all characterized by different geological, tectonic and morphological features. The objective of this multidisciplinary study is to provide the first maps of sea-level rise scenarios for 2100 for the IPCC RCP 8.5 and Rahmstorf (2007) projections for the above affected coastal zones, which are the locations of touristic resorts, railways, airports and heritage sites. On the basis of our model (eustatic projection for 2100, glaciohydrostasy values and tectonic vertical movement), we provide 16 high-definition submersion maps. We estimated a potential loss of land for the above areas of between about 148 km(2)(IPCC-RCP8.5 scenario) and 192 km(2)(Rahmstorf scenario), along a coastline length of about 400 km

Geomorphology and sedimentology of Porto Pino, SW Sardinia, Western Mediterranean

This paper presents a detailed (1:4000) geomorphological, sedimentological and ecological map of a Mediterranean microtidal wave-dominated beach system and adjacent inner shelf. This map is an innovative cartographic product that integrates a range of processes of present and past timeframes. It is part of a larger cartography on the coastal geomorphology of Sardinia (Italy) aiming to facilitate coastal management practices and future scientific research. The study area is located in SW Sardinia (Italy), and focuses on Porto Pino beach, an important tourist destination of semi-pristine nature, facing environmental pressures common to many coastal Mediterranean settings. In this context, the main human impact on coastal dune habitats is described and a full environmental characterization of the beach system is presented

Retinal Angiogenesis Suppression through Small Molecule Activation of p53

Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3-mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels in the adult mouse retina, suggesting that only proliferating retinal vessels are sensitive to Nutlin-3. Furthermore, Nutlin-3 inhibited angiogenesis in nonretinal models such as the hind limb ischemia model. Our work demonstrates that Nutlin-3 functions through an antiproliferative pathway with conceivable advantages over existing cytokine-targeted antiangiogenesis therapies

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Emergenza sismica nel centro Italia 2016-2017. Secondo rapporto del gruppo operativo SISMIKO. Sviluppo e mantenimento della rete sismica mobile a seguito del terremoto di Amatrice Mw 6.0 (24 agosto 2016, Italia centrale)

La rete sismica temporanea installata dal gruppo operativo INGV SISMIKO a seguito del terremoto del 24 agosto 2016 tra i Monti della Laga e la Valnerina, è stata ampliata nel settore settentrionale a seguito dei forti terremoti avvenuti alla fine del mese di ottobre 2016. Successivamente alle due scosse di Mw 5.4 e 5.9 che il 26 ottobre hanno interessato l’area al confine Marche-Umbria tra i Comuni di Castelsantangelo sul Nera (MC), Norcia (PG) e Arquata del Tronto (AP), la geometria della rete è stata estesa di circa 25 km verso nord con l’attivazione di ulteriori tre stazioni temporanee di cui una, da subito, disposta per la trasmissione dei dati in tempo reale e per l’inserimento nel sistema di sorveglianza sismica dell’Istituto Nazionale di Geofisica e Vulcanologia (INGV). Un’ultima stazione è stata inoltre installata nei pressi di Campello del Clitunno in provincia di Perugia ad ovest della sequenza, a seguito del terremoto Mw 6.5 che la mattina del 30 ottobre ha interessato l’intera area già fortemente provata dalla sequenza in corso; questo è stato il più forte terremoto registrato negli ultimi 30 in Italia. A circa 5 mesi dall’inizio dell’emergenza sismica, la rete temporanea conta quindi 23 stazioni che da metà dicembre sono tutte trasmesse in tempo reale ai diversi centri di acquisizione INGV, ovvero Milano, Ancona e Grottaminarda ma soprattutto Roma dove i dati vengono contestualmente archiviati nell’European Integrated Data Archive (EIDA) e integrati nel sistema di monitoraggio e sorveglianza sismica dell’INGV; per la sorveglianza sono incluse solo parte delle stazioni. Nelle ultime settimane, le attività di campagna del gruppo operativo SISMIKO sono state costantemente focalizzate alla cura e alla manutenzione della strumentazione per garantire la continuità della trasmissione e dell’acquisizione dei dati, a volte compromesse da malfunzionamenti legati al maltempo. Alla data di aggiornamento del presente report, non è ancora stata decretata una dismissione o una rimodulazione della geometria della rete sismica temporanea, anche in considerazione della attività sismica in corso a tutt’oggi molto sostenuta. Tutti i dati acquisiti dalle stazioni temporanee SISMIKO, sono distribuiti senza alcun vincolo, al pari dei dati della Rete Sismica Nazionale (RSN, codice di rete IV), ed utilizzati per prodotti scientifici in tempo reale (localizzazioni di sala, calcolo dei Time Domain Moment Tensor -TDMT delle ShakeMaps, ecc) e per l’aggiornamento dei database dell’INGV come l’Italian Seismological Instrumental and Parametric Database (ISIDe) con la revisione del Bollettino Sismico Italiano (BSI), dell’INGV Strong Motion Data (ISMD) e dell’ITalian ACcelerometric Archive (ITACA), dell’European-Mediterranean Regional Centroid Moment Tensors (RCMT) e nei lavori scientifici che utilizzano forme d’onda velocimetriche ed accelerometriche (ri- localizzazioni, studi della sorgente sismica ecc.).Istituto Nazionale di Geofisica e Vulcanologia (INGV)Published1SR. TERREMOTI - Servizi e ricerca per la Societ

Rapporto Preliminare Sulle Attività Svolte Nel Primo Mese Di Emergenza Dal Gruppo Operativo Sismiko A Seguito Del Terremoto Di Amatrice Mw 6.0 (24 Agosto 2016, Italia Centrale)

Sintesi delle attività svolte dal coordinamento delle reti sismiche mobili INGV in emergenza, denominato SISMIKO, nel primo mese della sequenza sismica “Amatrice” seguita al terremoto di Mw 6.0 del 24 agosto 2016 (01:36 UTC). Descrizione della rete sismica implementata e prime analisi dei dati acquisiti. Report on the activities in the first month of emergency by coordination of mobile seismic networks INGV emergency, called SISMIKO, after the Mw 6.0 Amatrice earthquake (August 24th, 2016, central italy). Description of the temporary seismic network implemented and preliminary analysis of the acquired data.INGV DPCPublished1IT. Reti di monitoraggi