An overview of the geochemical characteristics of oceanic carbonatites: New insights from Fuerteventura carbonatites (Canary islands)

The occurrence of carbonatites in oceanic settings is very rare if compared with their continental counterpart, having been reported only in Cape Verde and Canary Islands. This paper provides an overview of the main geochemical characteristics of oceanic carbonatites, around which many debates still exist regarding their petrogenesis. We present new data on trace elements in minerals and whole-rock, together with the first noble gases isotopic study (He, Ne, Ar) in apatite, calcite, and clinopyroxene from Fuerteventura carbonatites (Canary Islands). Trace elements show a similar trend as Cape Verde carbonatites, almost tracing the same patterns on multi-element and REE abundance diagrams.3He/4He isotopic ratios of Fuerteventura carbonatites reflect a shallow (sub-continental lithospheric mantle, SCLM) He signature in their petrogenesis, and they clearly differ from Cape Verde carbonatites, i.e., fluids from a deep and low degassed mantle with a primitive plume-derived He signature are involved in their petrogenesis

Myeloid derived suppressor cells in multiple myeloma: Preclinical research and translational opportunities

Immunosuppressive cells have been reported to play an important role in tumor progression mainly because of their capability to promote immuneescape, angiogenesis and metastasis. Among them, myeloid derived suppressor cells (MDSCs) have been recently identified as immature myeloid cells, induced by tumor-associated inflammation, able to impair both innate and adaptive immunity. While murine MDSCs are usually identified by the expression of CD11b and Gr-1, human MDSCs represent a more heterogeneous population characterized by the expression of CD33 and CD11b, low or no HLA-DR and variable CD14 and CD15. In particular, the last two may alternatively identify monocyte-like or granulocyte-like MDSC subsets with different immunosuppressive properties. Recently, a substantial increase of MDSCs has been found in peripheral blood and bone marrow (BM) of multiple myeloma (MM) patients with a role in disease progression and/or drug resistance. Preclinical models recapitulating the complexity of the MM-related BM microenvironment (BMM) are major tools for the study of the interactions between MM cells and cells of the BMM (including MDSCs) and for the development of new agents targeting MM-associated immune suppressive cells. This review will focus on current strategies for human MDSCs generation and investigation of their immunosuppressive function in vitro and in vivo, taking into account the relevant relationship occurring within the MM-BMM. We will then provide trends in MDSC-associated research and suggest potential application for the treatment of MM

Reaction between quinone and thiazolidine. A study on the formation mechanism of new antiproliferative quinolindiones

Reaction between quinolinquinone and thiazolidine in basic medium was investigated. 2-Arylthiazolidine-4-carboxylic acid ethyl esters undergo two different cleavages in basic medium, yielding the 1-aryl-2-azadiene and a thiolic species. In the presence of quinolinquinone, the isomeric 1-aryl-3-ethoxycarbonyl-pyridoisoquinolin-5,10-diones and 3-amino-3-ethoxycarbonyl-dihydrothienoquinolin- 4,9-diones are formed by a hetero-Diels–Alder reaction and 1,4-Michael addition reaction, respectively. A mechanism for the formation of the reaction products is presented

A two-component mantle source feeding Mt. Etna magmatism; insights from the geochemistry of primitive magmas.

The major elements, trace elements and Sr and Nd isotopes of selected Etnean primitive rocks (b15 ky BP) were studied in order to characterize their mantle source. The noble-gas geochemistry of fluid inclusions in minerals fromthe same lavaswas also investigated. Themajor element compositions ofwhole rocks and minerals showed that these products are among the most primitive atMt. Etna, comprising 6.3–17.5 wt.% MgO. The variable LREE (Light Rare Earth Elements) enrichment relative to MORB (Mid-Ocean Ridge Basalt) (Lan/Ybn = 11–26), togetherwith the patterns of certain trace-element ratios (i.e., Ce/Yb versus Zr/Nb and Th/Y versus La/Yb), can be attributed to varying degrees of melting of a common mantle source. Numerical simulations performed with the MELTS program allowed the melting percentages associated with each product to be estimated. This led us to recalculate the hypothetical parental trace-element content of the Etneanmantle source, whichwas common to all of the investigated rocks. The characteristics of the Sr, Nd and He isotopes confirmed the primitive nature of the rocks,with themost-depleted and primitive lava being that ofMt. Spagnolo (SPA; 143Nd/144Nd = 0.512908 87Sr/ 86Sr = 0.703317–0.703325 and 3He/4He = 7.6 Ra), and highlighted the similarity of the mantle sources feeding the volcanic activity of Mt. Etna and the Hyblean Plateau (a region to the south of Mt. Etna and characterized by oldermagmatismthan Mt. Etna). The coupling of noble gases and trace elements suggests an origin for the investigated Etnean lavas from melting of a Hyblean-like mantle, consisting of a two-component source where a peridotitic matrix is veined by 10% pyroxenite. A variable degree of mantle contamination by crustal-like fluids, probably related to subduction, is proposed to explain the higher Sr-isotope and lowerNd-isotope values in some rocks (143Nd/144Nd up to 0.512865 and 87Sr/86Sr up to 0.703707). This process probably occurred in the source prior tomagma generation, refertilizing some portions of themantle. Accordingly, the estimated degree of melting responsible for each magma appears to be related to its 87Sr/86Sr enrichment. In contrast, the decoupling between 3He/4He and 87Sr/86Sr ratios requires the occurrence in the crustal reservoirs of further processes capable of shifting the He isotope ratio towards slightly more radiogenic values, such as magma aging or a contribution of shallow fluid. Therefore, different residence times in the Etnean reservoir and/or various rates of magma ascent could be key parameters for preserving the original He isotope marker of the Etnean mantle source. © 2013 Published by Elsevier

A LA-ICP-MS STUDY OF CARBONATITES FROM FUERTEVENTURA, CANARY ISLAND

Carbonatites complexes are very rare in oceanic environments and in the Atlantic Ocean they can be only found at Cape Verde islands and Fuerteventura. Fuerteventura is the second largest island in the Canary Archipelago and is located on a transitional, continental to oceanic, crust. It consists essentially of Mesozoic sediments, submarine volcanic rocks, subaerial basaltic and trachytic series, ultramafic, mafic to felsic intrusives (clinopyroxenites, melteijites-ijolites, nepheline-monzogabbros, nepheline-sienites) and carbonatitic dike swarms (age 25 Ma). Carbonatite dike (Ca-carbonatites) mineralogy consists of calcite, aegirine-augite, albite, K-feldspar, biotite, apatite, Fe-Ti oxides and accessory minerals, such as zircon, barite, monazite and pyrochlore. The degree of alteration of carbonatites (evaluated by DTA and XRD) is generally low, with the occurrence of illite-montmorillonite mixed layers, vermiculite and chlorite. Whole rock samples (XRF) are high in CaO (> 50 %) and SrO (> 2-3 %) and very low in MgO (< 1-2 %). Trace elements were determined by LA-ICP-MS on calcite and accessory minerals (pyrochlore, monazite, zircon). Results show in calcite phenocrysts REE patterns highly enriched in all REEs (sum REE= 1186-2943 ppm) and particularly in LREE: LaN = 2178 (chondrite normalized), CeN = 1499, with respect to HREE (YbN = 37, LuN = 34) and rather fractionated pattern (La/Yb)N = 58. Small negative Eu anomalies do also occur (Eu/Eu* = 0.77 - 0.94) and these are coupled with high Sr anomalies (Sr/Sr* = 28.3 - 58.7). REE in pyrochlore are extremely enriched in REE (sum REE= 12.8 wt %) with very high LREE (LaN = 71214 and CeN = 62803) and HREE (YbN = 997, LuN = 695) with a slightly steeper pattern if compared to calcite: (La/Yb)N = 71. No significative Eu anomalies were found (Eu/Eu* = 1.06), while there is a conisistent Sr positive anomaly in spiderdiagrams (Sr/Sr* = 1.74). Preliminar results show that pyrochlore is the main mineral repository of REEs and its occurrence, even in trace amounts, gives the fingerprint to trace element to whole rock

Vascular endothelial growth factor C disrupts the endothelial lymphatic barrier to promote colorectal cancer invasion

Background & Aims Colorectal cancer (CRC) is highly metastatic. Metastases spread directly into local tissue or invade distant organs via blood and lymphatic vessels, but the role of lymphangiogenesis in CRC progression has not been determined. Lymphangiogenesis is induced via vascular endothelial growth factor C (VEGFC) activation of its receptor, VEGFR3; high levels of VEGFC have been measured in colorectal tumors undergoing lymphangiogenesis, and correlated with metastasis. We investigated VEGFC signaling and lymphatic barriers in human tumor tissues and mice with orthotopic colorectal tumors. Methods We performed immunohistochemical, immunoblot, and real-time PCR analyses of colorectal tumor specimens collected from patients; healthy intestinal tissues collected during surgeries of patients without CRC were used as controls. CT26 CRC cells were injected into the distal posterior rectum of BALB/c-nude mice. Mice were given injections of an antibody against VEGFR3 or an adenovirus encoding human VEGFC before orthotopic tumors and metastases formed. Lymph node, lung, and liver tissues were collected and evaluated by flow cytometry. We measured expression of vascular endothelial cadherin (CDH5) on lymphatic vessels in mice and in human intestinal lymphatic endothelial cells. Results Levels of podoplanin (a marker of lymphatic vessels), VEGFC, and VEGFR3 were increased in colorectal tumor tissues, compared with controls. Mice that expressed VEGFC from the adenoviral vector had increased lymphatic vessel density and more metastases in lymph nodes, lungs, and livers, compared with control mice. Anti-VEGR3 antibody reduced numbers of lymphatic vessels in colons and prevented metastasis. Expression of VEGFC compromised the lymphatic endothelial barrier in mice and endothelial cells, reducing expression of CDH5, increasing permeability, and increasing trans-endothelial migration by CRC cells. Opposite effects were observed in mice and cells when VEGFR3 was blocked. Conclusions VEGFC signaling via VEGFR3 promotes lymphangiogenesis and metastasis by orthotopic colorectal tumors in mice and reduces lymphatic endothelial barrier integrity. Levels of VEGFC and markers of lymphatic vessels are increased in CRC tissues from patients, compared with healthy intestine. Strategies to block VEGFR3 might be developed to prevent CRC metastasis in patients

Finite size corrections to random Boolean networks

Since their introduction, Boolean networks have been traditionally studied in view of their rich dynamical behavior under different update protocols and for their qualitative analogy with cell regulatory networks. More recently, tools borrowed from statistical physics of disordered systems and from computer science have provided a more complete characterization of their equilibrium behavior. However, the largest part of the results have been obtained in the thermodynamic limit, which is often far from being reached when dealing with realistic instances of the problem. The numerical analysis presented here aims at comparing - for a specific family of models - the outcomes given by the heuristic belief propagation algorithm with those given by exhaustive enumeration. In the second part of the paper some analytical considerations on the validity of the annealed approximation are discussed.Comment: Minor correction

Population screening for colorectal cancer by flexible sigmoidoscopy or CT colonography: Study protocol for a multicenter randomized trial

BACKGROUND: Colorectal cancer (CRC) is the second most prevalent type of cancer in Europe. A single flexible sigmoidoscopy (FS) screening at around the age of 60 years prevents about one-third of CRC cases. However, FS screens only the distal colon, and thus mortality from proximal CRC is unaffected. Computed tomography colonography (CTC) is a highly accurate examination that allows assessment of the entire colon. However, the benefit of CTC testing as a CRC screening test is uncertain. We designed a randomized trial to compare participation rate, detection rates, and costs between CTC (with computer-aided detection) and FS as primary tests for population-based screening. METHODS/DESIGN: An invitation letter to participate in a randomized screening trial comparing CTC versus FS will be mailed to a sample of 20,000 people aged 58 or 60 years, living in the Piedmont region and the Verona district of Italy. Individuals with a history of CRC, adenomas, inflammatory bowel disease, or recent colonoscopy, or with two first-degree relatives with CRC will be excluded from the study by their general practitioners. Individuals responding positively to the invitation letter will be then randomized to the intervention group (CTC) or control group (FS), and scheduled for the screening procedure. The primary outcome parameter of this part of the trial is the difference in advanced neoplasia detection between the two screening tests. Secondary outcomes are cost-effectiveness analysis, referral rates for colonoscopy induced by CTC versus FS, and the expected and perceived burden of the procedures. To compare participation rates for CTC versus FS, 2,000 additional eligible subjects will be randomly assigned to receive an invitation for screening with CTC or FS. In the CTC arm, non-responders will be offered fecal occult blood test (FOBT) as alternative screening test, while in the FS arm, non-responders will receive an invitation letter to undergo screening with either FOBT or CTC. Data on reasons for participation and non-participation will also be collected. DISCUSSION: This study will provide reliable information concerning benefits and risks of the adoption of CTC as a mass screening intervention in comparison with FS. The trial will also evaluate the role of computer-aided detection in a screening setting. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0173960

The Cavity Approach to Parallel Dynamics of Ising Spins on a Graph

We use the cavity method to study parallel dynamics of disordered Ising models on a graph. In particular, we derive a set of recursive equations in single site probabilities of paths propagating along the edges of the graph. These equations are analogous to the cavity equations for equilibrium models and are exact on a tree. On graphs with exclusively directed edges we find an exact expression for the stationary distribution of the spins. We present the phase diagrams for an Ising model on an asymmetric Bethe lattice and for a neural network with Hebbian interactions on an asymmetric scale-free graph. For graphs with a nonzero fraction of symmetric edges the equations can be solved for a finite number of time steps. Theoretical predictions are confirmed by simulation results. Using a heuristic method, the cavity equations are extended to a set of equations that determine the marginals of the stationary distribution of Ising models on graphs with a nonzero fraction of symmetric edges. The results of this method are discussed and compared with simulations