Detection of chromosomal regions showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma

BACKGROUND: Rhabdomyosarcoma is a relatively common tumour of the soft tissue, probably due to regulatory disruption of growth and differentiation of skeletal muscle stem cells. Identification of genes differentially expressed in normal skeletal muscle and in rhabdomyosarcoma may help in understanding mechanisms of tumour development, in discovering diagnostic and prognostic markers and in identifying novel targets for drug therapy. RESULTS: A Perl-code web client was developed to automatically obtain genome map positions of large sets of genes. The software, based on automatic search on Human Genome Browser by sequence alignment, only requires availability of a single transcribed sequence for each gene. In this way, we obtained tissue-specific chromosomal maps of genes expressed in rhabdomyosarcoma or skeletal muscle. Subsequently, Perl software was developed to calculate gene density along chromosomes, by using a sliding window. Thirty-three chromosomal regions harbouring genes mostly expressed in rhabdomyosarcoma were identified. Similarly, 48 chromosomal regions were detected including genes possibly related to function of differentiated skeletal muscle, but silenced in rhabdomyosarcoma. CONCLUSION: In this study we developed a method and the associated software for the comparative analysis of genomic expression in tissues and we identified chromosomal segments showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma, appearing as candidate regions for harbouring genes involved in origin of alveolar rhabdomyosarcoma representing possible targets for drug treatment and/or development of tumor markers

L\u2019evoluzione economica e competitiva delle imprese, dei settori e dei distretti del Friuli Venezia Giulia

La presente ricerca si pone l\u2019obiettivo di analizzare i cambiamenti avvenuti nella struttura economica della Regione Friuli Venezia Giulia nel periodo 2002-2010 e di cogliere le tendenze evolutive che stanno caratterizzando il comparto manifatturiero regionale, nei principali settori e distretti industriali in cui esso \ue8 articolato. La finalit\ue0 non \ue8 puramente di tipo conoscitivo,ma quella di fornire al policy maker delle pi\uf9 raffinate chiavi di lettura dei cambiamenti in atto, su cui dare fondamento pi\uf9 solido agli interventi di sostegno alle imprese

Seven- and eight-coordinate lanthanide(III) amidophosphate complexes: synthesis, characterization and photoluminescence

Diphenyl N-dimethylamidophosphate, O=P(OPh)2(NMe2), was introduced in the coordination sphere of trivalent lanthanide ions in combination with ß-diketonates, to obtain seven- and eight-coordinated complexes having general formula [Ln(ß-dike)3{O=P(OPh)2(NMe2)}n] (Ln = Eu, ß-dike = dibenzoylmethanate, n = 1; Ln = Eu, ß-dike = tenoyltrifluoroacetonate, n = 2; Ln = Tb, ß-dike = acetylacetonate, n = 2). The compounds were characterized spectroscopically and, in the case of the dibenzoylmethanate derivative, by means of single-crystal X-ray diffraction. The Eu(III) complexes exhibited bright red emission associated to the 5D0→7FJ transitions of the metal centre, with noticeable antenna-effect from the coordinated ligands and lifetimes strongly dependent upon the coordination number. The Tb(III) derivative showed intense green photoluminescence, related to the 5D4→7FJ transitions of the metal io

A multistep bioinformatic approach detects putative regulatory elements in gene promoters

BACKGROUND: Searching for approximate patterns in large promoter sequences frequently produces an exceedingly high numbers of results. Our aim was to exploit biological knowledge for definition of a sheltered search space and of appropriate search parameters, in order to develop a method for identification of a tractable number of sequence motifs. RESULTS: Novel software (COOP) was developed for extraction of sequence motifs, based on clustering of exact or approximate patterns according to the frequency of their overlapping occurrences. Genomic sequences of 1 Kb upstream of 91 genes differentially expressed and/or encoding proteins with relevant function in adult human retina were analyzed. Methodology and results were tested by analysing 1,000 groups of putatively unrelated sequences, randomly selected among 17,156 human gene promoters. When applied to a sample of human promoters, the method identified 279 putative motifs frequently occurring in retina promoters sequences. Most of them are localized in the proximal portion of promoters, less variable in central region than in lateral regions and similar to known regulatory sequences. COOP software and reference manual are freely available upon request to the Authors. CONCLUSION: The approach described in this paper seems effective for identifying a tractable number of sequence motifs with putative regulatory role

Mind the metal:a fragment library-derived zinc impurity binds the E2 ubiquitin-conjugating enzyme Ube2T and induces structural rearrangements

Efforts to develop inhibitors, activators, and effectors of biological reactions using small molecule libraries are often hampered by interference compounds, artifacts, and false positives that permeate the pool of initial hits. Here, we report the discovery of a promising initial hit compound targeting the Fanconi anemia ubiquitin-conjugating enzyme Ube2T and describe its biophysical and biochemical characterization. Analysis of the co-crystal structure led to the identification of a contaminating zinc ion as solely responsible for the observed effects. Zinc binding to the active site cysteine induces a domain swap in Ube2T that leads to cyclic trimerization organized in an open-ended linear assembly. Our study serves as a cautionary tale for screening small molecule libraries and provides insights into the structural plasticity of ubiquitin-conjugating enzymes

Manganese(ii) bromo- and iodo-complexes with phosphoramidate and phosphonate ligands: synthesis, characterization and photoluminescence

Tetrahedral Mn(II) bromo‐ and iodo‐complexes with phosphoramidate and phosphonate ligands were synthesized and characterized. Mononuclear complexes with general formula [MnX2L2] were isolated by using the monodentate ligands O=P(OPh)2(NMe2) and O=P(OPh)2Ph. The bidentate resorcinol derivative 1,3‐O=P(NMe2)O‐C6H4‐O(NMe2)2P=O behaved as bridging ligand, affording by reaction with MnX2 salts a dinuclear complex in the case of X = Br and a coordination polymer for X = I, as revealed by single crystal X‐ray diffraction. All the compounds showed the characteristic green photoluminescence of Mn(II) in tetrahedral environment. The lifetime values resulted influenced by the symmetry of the compounds. The complexes with O=P(OPh)2(NMe2) in the coordination sphere showed high photoluminescence quantum yields

Small RNA Sequencing Uncovers New miRNAs and moRNAs Differentially Expressed in Normal and Primary Myelofibrosis CD34+ Cells

Myeloproliferative neoplasms (MPN) are chronic myeloid cancers thought to arise at the level of CD34+ hematopoietic stem/progenitor cells. They include essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). All can progress to acute leukemia, but PMF carries the worst prognosis. Increasing evidences indicate that deregulation of microRNAs (miRNAs) might plays an important role in hematologic malignancies, including MPN. To attain deeper knowledge of short RNAs (sRNAs) expression pattern in CD34+ cells and of their possible role in mediating post-transcriptional regulation in PMF, we sequenced with Illumina HiSeq2000 technology CD34+ cells from healthy subjects and PMF patients. We detected the expression of 784 known miRNAs, with a prevalence of miRNA up-regulation in PMF samples, and discovered 34 new miRNAs and 99 new miRNA-offset RNAs (moRNAs), in CD34+ cells. Thirty-seven small RNAs were differentially expressed in PMF patients compared with healthy subjects, according to microRNA sequencing data. Five miRNAs (miR-10b-5p, miR-19b-3p, miR-29a-3p, miR-379-5p, and miR-543) were deregulated also in PMF granulocytes. Moreover, 3'-moR-128-2 resulted consistently downregulated in PMF according to RNA-seq and qRT-PCR data both in CD34+ cells and granulocytes. Target predictions of these validated small RNAs de-regulated in PMF and functional enrichment analyses highlighted many interesting pathways involved in tumor development and progression, such as signaling by FGFR and DAP12 and Oncogene Induced Senescence. As a whole, data obtained in this study deepened the knowledge of miRNAs and moRNAs altered expression in PMF CD34+ cells and allowed to identify and validate a specific small RNA profile that distinguishes PMF granulocytes from those of normal subjects. We thus provided new information regarding the possible role of miRNAs and, specifically, of new moRNAs in this disease

SME export performance, capabilities and emerging markets: the impact of institutional voids

In this paper we address the theme of the export performance of the SME in the context of emerging markets. Surveying a sample of 200 exporting SMEs, we test specific hypotheses concerning the role of Institutional Voids (IVs) both in directly affecting the export performance of the SME and in moderating the positive impact of the SME\u2019s resources and capabilities. Our results show that while directly hampering the export performance of the SME, IVs also have a negative moderating role on the firm\u2019s marketing capabilities

A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor mediating the toxicity and tumor-promoting properties of dioxin. AHR has been reported to be overexpressed and constitutively active in a variety of solid tumors, but few data are currently available concerning its role in thyroid cancer. In this study we quantitatively explored a series of 51 paired-normal and papillary thyroid carcinoma (PTC) tissues for AHR-related genes. We identified an increased AHR expression/activity in PTC, independently from its nuclear dimerization partner and repressor but strictly related to a constitutive active MAPK/ERK pathway. The AHR up-regulation followed by an increased expression of AHR target genes was confirmed by a meta-analysis of published microarray data, suggesting a ligand-independent active AHR pathway in PTC. In-vitro studies using a PTC-derived cell line (BCPAP) and HEK293 cells showed that BRAF(V600E) may directly modulate AHR localization, induce AHR expression and activity in an exogenous ligand-independent manner. The AHR pathway might represent a potential novel therapeutic target for PTC in the clinical practice

Disentangling resource and mode escalation in the context of emerging markets. Evidence from a sample of manufacturing SMEs

Our research paints a comprehensive picture of manufacturing SMEs' internationalization strategies in EMs that examines two types of escalation of commitment: the first (between modes) occurs through riskier modes of operation, as typically described by the stagebased internationalization theory; the second (within modes) results in the escalation of resource commitment within the initial mode of operation. In line with stage-based internationalization theory, we posit that market-specific experiential knowledge and performance obtained after initial market entry are associated with SMEs' decisions to escalate (reduce) their commitment in EMs. Our distinctive contribution to the literature lays in our assertion that unlike psychic distance, the obstacles created by insufficient institutional development in EMs i.e., institutional voids (IVs) are more difficult to overcome by foreign SMEs over time. IVs create uncertainties and risks for foreign SMEs, which likely hinder them from increasing their local market commitment. Our research follows previous contributions made by Meyer et al. (2009) and Santangelo and Meyer (2011) on the impact of IVs on MNE strategies, and shows that IVs have a negative direct effect on SMEs' mode escalation but not on resource escalation. Resource escalation is significantly affected by the interaction of market performance and IVs while mode escalation is significantly affected by the interaction of market experience and IVs. In sum, this paper extends the stage-based (Uppsala) model with insights from institutional theory (North, 1995) and aims for a more context-specific explanation of SMEs' escalation of commitment (resource and/or mode) in EMs