Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal

There exists a set of factors termed oncofetal proteins that play key roles in ontogeny before they decline or disappear as the organism’s tissues achieve homeostasis, only to then re-emerge in cancer. Although the unique therapeutic potential presented by such factors has been recognized for more than a century, their clinical utility has yet to be fully realized1. This review highlights the small signaling protein CRIPTO encoded by the tumor derived growth factor 1 (TDGF1/Tdgf1) gene, an oft cited oncofetal protein whose presence in the cancer literature as a tumor promoter, diagnostic marker and viable therapeutic target continues to grow. We touch lightly on features well established and well-reviewed since its discovery more than 30 years ago, including CRIPTO’s early developmental roles and modulation of SMAD2/3 activation by a selected set of transforming growth factor β (TGF-β) family ligands. We predominantly focus instead on more recent and less well understood additions to the CRIPTO signaling repertoire, on its potential upstream regulators and on new conceptual ground for understanding its mode of action in the multicellular and often stressful contexts of neoplastic transformation and progression. We ask whence it re-emerges in cancer and where it ‘hides’ between the time of its fetal activity and its oncogenic reemergence. In this regard, we examine CRIPTO’s restriction to rare cells in the adult, its potential for paracrine crosstalk, and its emerging role in inflammation and tissue regeneration—roles it may reprise in tumorigenesis, acting on subsets of tumor cells to foster cancer initiation and progression. We also consider critical gaps in knowledge and resources that stand between the recent, exciting momentum in the CRIPTO field and highly actionable CRIPTO manipulation for cancer therapy and beyond.     

The AFLATOX® Project: Approaching the Development of New Generation,Natural-Based Compounds for the Containment of the Mycotoxigenic Phytopathogen Aspergillus flavus and Aflatoxin Contamination

The control of the fungal contamination on crops is considered a priority by the sanitary authorities of an increasing number of countries, and this is also due to the fact that the geographic areas interested in mycotoxin outbreaks are widening. Among the different pre- and post-harvest strategies that may be applied to prevent fungal and/or aflatoxin contamination, fungicides still play a prominent role; however, despite of countless efforts, to date the problem of food and feed contamination remains unsolved, since the essential factors that affect aflatoxins production are various and hardly to handle as a whole. In this scenario, the exploitation of bioactive natural sources to obtain new agents presenting novel mechanisms of action may represent a successful strategy to minimize, at the same time, aflatoxin contamination and the use of toxic pesticides. The Aflatox^® Project was aimed at the development of new-generation inhibitors of aflatoxigenic Aspergillus spp. proliferation and toxin production, through the modification of naturally occurring molecules: a panel of 177 compounds, belonging to the thiosemicarbazones class, have been synthesized and screened for their antifungal and anti-aflatoxigenic potential. The most effective compounds, selected as the best candidates as aflatoxin containment agents, were also evaluated in terms of cytotoxicity, genotoxicity and epi-genotoxicity to exclude potential harmful effect on the human health, the plants on which fungi grow and the whole ecosystem.     

Solid acid (superacid) catalyzed regioselective adamantylation of substituted benzenes

Adamantylation of substituted benzenes with 1-bromo-adamantane was catalyzed by solid acids including acidic ion exchange and ionomer resins, HY zeolite, sulfated zirconia and supported superacids on HY zeolite and SiO₂. Adamantylation generally takes place in excellent yield giving predominantly para products without formation of byproducts. The reactions did not require the usual workup of Friedel-Crafts reactions as catalysts were simply filtered of. Cross-linked polystyrene resin sulfonic acid (Amberlyst) was found particularly suitable as besides its high catalytic activity, high regioselectivity was observed with almost exclusive formation ofp-adamantylated benzenes. AMI, PM3 and MNDO semiempirical calculations of heats of formation showed that of all regioisomers, the para isomer is the most stable. The temperature dependence of adamantylation was also investigated allowing the optimization ofp-substituted product in high yield and excellent selectivity. Lack of isomerization of 1-p-tolyla-damantane using solid (Amberlyst, Nafion-H) and liquid acids (neat and modified trifluoromethanesulfonic acid) indicates absence of product isomerization, while the intramolecular rearrangement of the intermediate arenium complex is still possible.Catalysis by solid superacids, Part 30. For part 29, see ref.[1A].     

Chemical Composition of Seed Oils Recovered from Different Pear (Pyrus communis L.) Cultivars

Lipophilic bioactive compounds in oils recovered from the seeds of eight pear (Pyrus communis L.) cultivars were studied. Oil yield in pear seeds ranged between 16.3 and 31.5 % (w/w) dw. The main fatty acids were palmitic acid (6.13–8.52 %), oleic acid (27.39–38.17 %) and linoleic acid (50.73–63.78 %), all three representing 96–99 % of the total detected fatty acids. The range of total tocochromanols was between 120.5 and 216.1 mg/100 g of oil. Independent of the cultivar, the γ‐tocopherol was the main tocochromanol and constituted approximately 88 %. The contents of the carotenoids and squalene were between 0.69–2.99 and 25.5–40.8 mg/100 g of oil, respectively. The β‐sitosterol constituted 83.4–87.6 % of total sterols contents, which ranged between 276.4 and 600.1 mg/100 g of oil. Three significant correlations were found between oil yield and total contents of sterols (r = ?0.893), tocochromanols (r = ?0.955) and carotenoids (r = ?0.685) in pear seed oils.     

An ergonomic study on plate shears, applying physical, physiological and psychophysical methods

An ergonomic evaluation model for hand tools was developed and applied in a project aiming at assessment of work with plate shears. Measurement variables were physical, physiological and psychophysical. They included tool force and opening angle, wrist movements, muscular strain and fatigue, subjective rating of symptoms, and localization of symptoms, in a group of male professional platers. Different hand grips were studied in a series of cutting tasks (4.2 m cutting length). Results showed that working with conventional plate shears is extremely physically demanding. The peak force required was in the range of 26 to 72 per cent of the subjects' maximal hand grip force. There was ample localized muscle fatigue in the forearm. Psychophysical and electrophysiological data agreed with respect to aspects of muscular strain and fatigue. Workers' preferences in the short run seemed to focus on productivity rather than on ergonomic quality. There is a need for development of improved tools, based on formulated requirements.     

ITEA—interactive trajectories and events analysis: exploring sequences of spatio-temporal events in movement data

Widespread use of GPS and similar technologies makes it possible to collect extensive amounts of trajectory data. These data sets are essential for reasonable decision making in various application domains. Additional information, such as events taking place along a trajectory, makes data analysis challenging, due to data size and complexity. We present an integrated solution for interactive visual analysis and exploration of events along trajectories data. Our approach supports analysis of event sequences at three different levels of abstraction, namely spatial, temporal, and events themselves. Customized views as well as standard views are combined to form a coordinated multiple views system. In addition to trajectories and events, we include on-the-fly derived data in the analysis. We evaluate our integrated solution using the IEEE VAST 2015 Challenge data set. A successful detection and characterization of malicious activity indicate the usefulness and efficiency of the presented approach.     

Multispectral image compression using eigenregion-based segmentation

In the study, a novel segmentation technique is proposed for multispectral satellite image compression. A segmentation decision rule composed of the principal eigenvectors of the image correlation matrix is derived to determine the similarity of image characteristics of two image blocks. Based on the decision rule, we develop an eigenregion-based segmentation technique. The proposed segmentation technique can divide the original image into some proper eigenregions according to their local terrain characteristics. To achieve better compression efficiency, each eigenregion image is then compressed by an efficient compression algorithm eigenregion-based eigensubspace transform (ER-EST). The ER-EST contains 1D eigensubspace transform (EST) and 2D-DCT to decorrelate the data in spectral and spatial domains. Before performing EST, the dimension of transformation matrix of EST is estimated by an information criterion. In this way, the eigenregion image may be approximated by a lower-dimensional components in the eigensubspace. Simulation tests performed on SPOT and Landsat TM images have demonstrated that the proposed compression scheme is suitable for multispectral satellite image.     

Proteomic analysis of secretory proteins and vesicles in vascular research

The release of proteins and membrane vesicles in the bloodstream regulates diverse vascular processes, both physiological, such as angiogenesis and haemostasis, and pathological, such as atherosclerosis and atherothrombosis. Proteomics, beside its canonical application for the expression profiling in cells and organs, can be applied to the study of secreted proteins and microvesicles, which play a significant role in the homeostasis of the vasculature, and the development of the atherosclerotic disease.