Publications by authors named "Paolo Scartezzini"

Background: The human SH3 domain Binding Glutamic acid Rich Like 3 (SH3BGRL3) gene is highly conserved in phylogeny and widely expressed in human tissues. However, its function is largely undetermined. The protein was found to be overexpressed in several tumors, and recent work suggested a possible relationship with EGFR family members.

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Recombinant-tagged proteins have a widespread use in experimental research as well as in clinical diagnostic and therapeutic approaches. Well-stocked sets of differently tagged variants of a same protein would be of great help. However, the construction of differently tagging vectors is a demanding task since cloning procedures need several tailored DNA inserts.

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Background: Although cancers are characterized by the deregulation of multiple signalling pathways, most current anticancer therapies involve the modulation of a single target. Because of the enormous biological diversity of cancer, strategic combination of agents targeted against the most critical of those alterations is needed. Due to their complex nature, plant products interact with numerous targets and influence several biochemical and molecular cascades.

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A central role for mitochondrial dysfunction has been proposed in the pathogenesis of DS (Down's syndrome), a multifactorial disorder caused by trisomy of human chromosome 21. To explore whether and how abnormalities in mitochondrial energy metabolism are involved in DS pathogenesis, we investigated the catalytic properties, gene expression and protein levels of certain proteins involved in mitochondrial ATP synthesis, such as F1F0-ATPase, ANT (adenine nucleotide translocator) and AK (adenylate kinase), in DS-HSF (human skin fibroblasts with trisomic karyotype), comparing them with euploid fibroblasts. In DS-HSF, we found a strong impairment of mitochondrial ATP synthesis due to a reduction in the catalytic efficiency of each of the investigated proteins.

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As a part of our endeavour to screen Mediterranean medicinal plants for various pharmacological activities, we evaluated antihistaminic, adaptogenic, anti-inflammatory, antinociceptive, hypotensive and locomotor properties, and antioxidant potential of Ephedra nebrodensis. (1)H-NMR spectroscopy was carried out to identify the plant metabolites, which confirmed the presence of ephedrinic skeleton alkaloids. The ethanol : acetone (1 : 1) extract exhibited dose-related antihistaminic, anti-inflammatory, antinociceptive, hypotensive, antioxidant and locomotor stimulant activity.

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The flavonoid fraction of the aerial parts of Genista cadasonensis Valsecchi (Leguminosae), an endemic plant from Sardinia, was examined and compared with the flavonoid pattern already known in the Genista genus. This comparison evidenced the endemic nature of this species, showing the presence of a rare flavonoid, the 6-hydroxy-genistein. The antioxidant activity of dichloromethanic, ethanolic and acetonic total extracts of aerial parts was evaluated.

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Teucrium marum and T. subspinosum have been extracted with different polarity solvents, each crude extract was analysed with (1)H-NMR to compare the overall metabolic component. The polar extracts showed antioxidant activity in vitro.

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One of the major fallouts of the human genome project relates to the investigation of the molecular mechanisms of diseases. Identification of genes which are involved in a specific pathological process and characterization of their interactions is of fundamental importance for supporting the drug design processes. Discovery of targets and the related experimental validation is a critical step in the development of new drugs.

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We report the 1.6 Angstrom resolution crystal structure of SH3BGRL3, a member of a new mammalian protein family of unknown function. The observed "thioredoxin fold" of SH3BGRL3 matches the tertiary structure of glutaredoxins, even in the N-terminal region where the sequence similarity between the two protein families is negligible.

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Congenital heart disease (CHD) is the most common birth defect in humans and is present in 40% of newborns affected by Down syndrome (DS). The SH3BGR gene maps to the DS-CHD region and is a potential candidate for the pathogenesis of CHD, since it is selectively expressed in cardiac and skeletal muscle. To determine whether overexpression of Sh3bgr in the murine heart may cause abnormal cardiac development, we have generated transgenic mice using a cardiac- and skeletal-muscle-specific promoter to drive the expression of a Sh3bgr transgene.

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We report the isolation and characterisation of the gene WDR9 (WD Repeat 9), located in the Down Syndrome critical region-2 (DCR-2) from the human chromosome 21. This gene spans 125 kb of genomic sequence and is organised in 41 exons and 40 introns. The WDR9 cDNA has a size of 13 kb and encodes for a putative protein of 2269 amino acids with a potential location in the nucleus.

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The SH3 binding glutamic acid-rich (SH3BGR) gene was cloned in an effort to identify genes located to human chromosome 21, within the congenital heart disease region, and expressed in the developing heart. After the identification of SH3BGR, two human homologous genes, SH3BGRL and SH3BGRL3, were identified and mapped to chromosome Xq13.3 and 1p34.

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