Mineralogical Characterization and Firing Temperature Delineation on Minoan Pottery, Focusing on the Application of Micro-Raman Spectroscopy

Ceramic objects in whole or in fragments usually account for the majority of findings in an archaeological excavation. Thus, through examination of the values these items bear, it is possible to extract important information regarding raw materials provenance and ceramic technology. For this purpose, either traditional examination protocols could be followed, focusing on the macroscopic/morphological characteristics of the ancient object, or more sophisticated physicochemical techniques are employed. Nevertheless, there are cases where, due to the uniqueness and the significance of an object of archaeological value, sampling is impossible. Then, the available analytical tools are extremely limited, especially when molecular information and mineral phase identification is required. In this context, the results acquired from a multiphase clay ceramic dated on Early Neopalatioal period ΜΜΙΙΙΑ-LMIA (1750 B.C.E.–1490 B.C.E.), from the Minoan Bronze Age site at Philioremos (Crete, Greece) through the application of Raman confocal spectroscopy, a non-destructive/ non-invasive method are reported. The spectroscopic results are confirmed through the application of X-ray microdiffraction and scanning electron microscopy coupled with energy dispersive X-ray spectrometry. Moreover, it is demonstrated how it is made possible through the application of micro-Raman spectroscopy to examine and collect crucial information from very small inclusions in the ceramic fabric. The aim of this approach is to develop an analytical protocol based on mRaman spectroscopy, for extracting firing temperature information from other ceramic finds (figurines) where due to their uniqueness sampling and analyses through other techniques is not possible. This information can lead to dating but also to firing kiln technology extrapolations that are very significant in archaeology

mTOR signaling is activated by FLT3 kinase and promotes survival of FLT3-mutated acute myeloid leukemia cells

Activating mutations of the FLT3 gene mediate leukemogenesis, at least in part, through activation of PI3K/AKT. The mammalian target of rapamycin (mTOR)-Raptor signaling pathway is known to act downstream of AKT. Here we show that the mTOR effectors, 4EBP1, p70S6K and rpS6, are highly activated in cultured and primary FLT3-mutated acute myeloid leukemia (AML) cells. Introduction of FLT3-ITD expressing constitutively activated FLT3 kinase further activates mTOR and its downstream effectors in BaF3 cells. We also found that mTOR signaling contributes to tumor cell survival, as demonstrated by pharmacologic inhibition of PI3K/AKT/mTOR, or total silencing of the mTOR gene. Furthermore, inhibition of FLT3 kinase results in downregulation of mTOR signaling associated with decreased survival of FLT3-mutated AML cells. These findings suggest that mTOR signaling operates downstream of activated FLT3 kinase thus contributing to tumor cell survival, and may represent a promising therapeutic target for AML patients with mutated-FLT3

Identification of MBNL1 and MBNL3 domains required for splicing activation and repression

Muscleblind-like 1 (MBNL1) is a splicing regulator that controls developmentally regulated alternative splicing of a large number of exons including exon 11 of the Insulin Receptor (IR) gene and exon 5 of the cardiac Troponin T (cTNT) gene. There are three paralogs of MBNL in humans, all of which promote IR exon 11 inclusion and cTNT exon 5 skipping. Here, we identify a cluster of three binding sequences located downstream of IR exon 11 that constitute the MBNL1 response element and a weaker response element in the upstream intron. In addition, we used sequential deletions to define the functional domains of MBNL1 and MBNL3. We demonstrate that the regions required for splicing regulation are separate from the two pairs of zinc-finger RNA-binding domains. MBNL1 and MBNL3 contain core regulatory regions for both activation and repression located within an 80-amino-acid segment located downstream of the N-terminal zinc-finger pair. Deletions of these regions abolished regulation without preventing RNA binding. These domains have common features with the CUG-BP and ETR3-like Factor (CELF) family of splicing regulators. These results have identified protein domains required for splicing repression and activation and provide insight into the mechanism of splicing regulation by MBNL proteins

Επίπεδα ινονεκτίνης σε φλεγμονώδη και κακοήθη γυναικολογικά νοσήματα

Introduction Fibronectin is a large multidomain glycoprotein found in connective tissue, on cell surfaces, and in plasma and other body fluids. It interacts with a variety of macromolecules including components of the cytoskeleton and the extracellular matrix, circulating components of the blood clotting, fibrinolytic, acute phase and complement systems, and with cell-surface receptors on a variety of cells including fibroblasts, neurons, phagocytes and bacteria. Fibronectin also interacts with itself, forming fibrillar entities whose structure is poorly understood. In addition, it reportedly binds several small molecules such as gangliosides, sugars, and Ca ions. These diverse recognition functions are located on distinct fragments or domains, many of which have been expressed in recombinant form or isolated from proteolytic digests with retention of specific binding properties. Tom Saba et al suggested that the cryoprecipitate fraction of human plasma was able to restore the levels of "Opsonic a2-Surface Binding Glycoprotein" i.e., fibronectin, in the circulation of septic surgical and trauma patients. Although fibronectin ultimately proved ineffective as a clinical product, it became adept at purifying gram quantities of this interesting protein at a time when the number of papers being published each year was rising exponentially. Fibronectin Modules The amino acid sequence of Fn reveals three types of internally homologous repeats or modules separated by (usually) short connecting sequences. There are 12 type I, 2 type II and 15 type III modules, also referred to as Fn1, Fn2 and Fn3. Each module constitutes an independently folded unit, often referred to as a domain but not to be confused with "functional domains" that frequently contain more than one module. Modules homologous to those in fibronectin are also found in other proteins, especially the type III which is one of the most ubiquitous of all modules, being found in ~2% of animal proteins (as low as xenopus) and occasionally in a plant. Amino acid sequences of fibronectin modules are highly conserved, differing from their counterparts in other species by only a few percent; by contrast the similarity between different modules of the same type within a given protein is much less. Fibronectin modules, like most, fold independently and thus can exist in isolation from their neighbors. This was demonstrated in a few cases with proteolytic fragments that were small enough to contain only a single module and which, upon exposure to heat or chemical denaturants, underwent reversible unfolding. Such unfolding can be monitored by changes in the intensity and/or wavelength distribution of fluorescence as buried tryptophan side chains are exposed to the aqueous environment. Circular dichroism and scanning calorimetry provide additional information. The three dimensional structures of several examples of each type of fibronectin module have been determined. As expected from the well-known relationship between amino acid sequence and 3D structure, modules of the same type 79 Summary have similar folds. All three types of module are composed almost exclusively of antiparallel sheets and turns with little or no helix. Alternate Splicing of Fibronectin There are five sites of alternate splicing of fibronectin mRNA. The first two result in the insertion of extra type III domains, EDA and EDB after modules III-11 and III-7 respectively . These modules are virtually absent from adult tissue but are differentially expressed during embryonic development and again in malignant or injured tissue and during angiogenesis. The inclusion of EDA renders fibronectin a better substrate for cell spreading and migration and has been used as a marker for certain types of cancer. EDA-containing fibronectin is upregulated as part of the response to wound healing and both forms are increased in human plasma following trauma. This module is reported to serve as a ligand for integrins α9β1 and α4β1. No specific receptors or other ligands have been identified for EDB although it also is reported to support cell adhesion. EDB is also of interest as a marker for angiogenesis and as a potential target for tumor therapy. The third site of splicing is in the V (variable) region, which can be included either in its entirety or only partially depending on the tissue. In plasma fibronectin the V region is fully incorporated into one chain but entirely absent from the other, as shown in the scheme. Since the V region has at least two different integrin binding sites, its presence or absence will affect the adhesion of some types of cells. A fourth site of splicing occurs primarily in cartilage where the dominant form of fibronectin lacks not only the entire V region but modules III-15 and I-10 as well. Functional Domains of Fibronectin Digestion of fibronectin with any of a variety of proteases generates a collection of fragments that are sometimes referred to as functional domains because they retain the ability to interact with other macromolecules. When thermolysin is used, one obtains an N-terminal 29 kDa Fib-1/Hep-1 fragment (I1-5) that binds to fibrin, heparin and some bacteria, and is important for fibronectin matrix assembly....Στη μελέτη αυτή έγινε προσπάθεια να μελετηθούν τα επίπεδα της φιμπρονεκτίνης του πλάσματος σε περιπτώσεις γυναικολογικών καρκίνων, καθώς και να επιβεβαιωθούν οι υπάρχουσες απόψεις σχετικά με τα αυξημένα επίπεδα της ουσίας σε γυναικολογικές φλεγμονές. Τα συμπεράσματα που προέκυψαν είναι τα ακόλουθα: 1) Επιβεβαιώνεται η αύξηση των επιπέδων της FBN πλάσματος σε κακοήθη νοσήματα ιδιαίτερα σε καρκίνο του τραχήλου και του μαστού 2) Καταγράφεται σημαντική διαφορά των επιπέδων σε καρκίνο του μαστού σε σχέση με τα άλλα κακοήθη νοσήματα 3) Επιβεβαιώνεται η ανίχνευση αυξημένων επιπέδων φιμπρονεκτίνης πλάσματος σε φλεγμονώδη γυναικολογικά νοσήματα 4) Φαίνεται ότι τα επίπεδα FBN πλάσματος μπορεί να αποτελέσουν αξιόπιστο προγνωστικό δείκτη, ωστόσο απαιτείται περαιτέρω επιστημονική έρευνα. Περιορισμένη φαίνεται να είναι η αξία της μέτρησης σε καρκίνο των ωοθηκών και του ενδομητρίου

Modulation of Cancer Traits by Tumor Suppressor microRNAs

Abstract: MicroRNAs (miRNAs) are potent post-transcriptional regulators of gene expression. In mammalian cells, miRNAs typically suppress mRNA stability and/or translation through partial complementarity with target mRNAs. Each miRNA can regulate a wide range of mRNAs, and a single mRNA can be regulated by multiple miRNAs. Through these complex regulatory interactions, miRNAs participate in many cellular processes, including carcinogenesis. By altering gene expression patterns, cancer cells can develop specific phenotypes that allow them to proliferate, survive, secure oxygen and nutrients, evade immune recognition, invade other tissues and metastasize. At the same time, cancer cells acquire miRNA signature patterns distinct from those of normal cells; the differentially expressed miRNAs contribute to enabling the cancer traits. Over the past decade, several miRNAs have been identified, which functioned as oncogenic miRNAs (oncomiRs) or tumor-suppressive miRNAs (TS-miRNAs). In this review, we focus specifically on TS-miRNAs and their effects on well-established cancer traits. We also discuss the rising interest in TS-miRNAs in cancer therapy

Posttranscriptional Regulation of Insulin Family Ligands and Receptors

Insulin system including ligands (insulin and IGFs) and their shared receptors (IR and IGFR) are critical regulators of insulin signaling and glucose homeostasis. Altered insulin system is associated with major pathological conditions like diabetes and cancer. The mRNAs encoding for these ligands and their receptors are posttranscriptionally controlled by three major groups of regulators; (i) alternative splicing regulatory factors; (ii) turnover and translation regulator RNA-binding proteins (TTR-RBPs); and (iii) non-coding RNAs including miRNAs and long non-coding RNAs (lncRNAs). In this review, we discuss the influence of these regulators on alternative splicing, mRNA stability and translation. Due to the pathological impacts of insulin system, we also discussed the possibilities of discovering new potential regulators which will improve understanding of insulin system and associated diseases