1,660 research outputs found

    Age-related changes in the primary motor cortex of newborn to adult domestic pig sus scrofa domesticus

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    The pig has been increasingly used as a suitable animal model in translational neuroscience. However, several features of the fast-growing, immediately motor-competent cerebral cortex of this species have been adequately described. This study analyzes the cytoarchitecture of the primary motor cortex (M1) of newborn, young and adult pigs (Sus scrofa domesticus). Moreover, we investigated the distribution of the neural cells expressing the calcium-binding proteins (CaBPs) (calretinin, CR; parvalbumin, PV) throughout M1. The primary motor cortex of newborn piglets was characterized by a dense neuronal arrangement that made the discrimination of the cell layers difficult, except for layer one. The absence of a clearly recognizable layer four, typical of the agranular cortex, was noted in young and adult pigs. The morphometric and immunohistochemical analy-ses revealed age-associated changes characterized by (1) thickness increase and neuronal density (number of cells/mm2 of M1) reduction during the first year of life; (2) morphological changes of CR-immunoreactive neurons in the first months of life; (3) higher density of CR-and PV-immunopositive neurons in newborns when compared to young and adult pigs. Since most of the present findings match with those of the human M1, this study strengthens the growing evidence that the brain of the pig can be used as a potentially valuable translational animal model during growth and development

    Role of extracellular vesicle-based cell-to-cell communication in multiple myeloma progression

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    Multiple myeloma (MM) progression closely depends on the bidirectional crosstalk between tumor cells and the surrounding microenvironment, which leads to the creation of a tumor supportive niche. Extracellular vesicles (EVs) have emerged as key players in the pathological interplay between the malignant clone and near/distal bone marrow (BM) cells through their biologically active cargo. Here, we describe the role of EVs derived from MM and BM cells in reprogramming the tumor microenvironment and in fostering bone disease, angiogenesis, immunosuppression, drug resistance, and, ultimately, tumor progression. We also examine the emerging role of EVs as new therapeutic agents for the treatment of MM, and their potential use as clinical biomarkers for early diagnosis, disease classification, and therapy monitoring

    The Landscape of lncRNAs in Multiple Myeloma: Implications in the “Hallmarks of Cancer”, Clinical Perspectives and Therapeutic Opportunities

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    Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides that are not translated into proteins. Nowadays, lncRNAs are gaining importance as key regulators of gene expression and, consequently, of several biological functions in physiological and pathological conditions, including cancer. Here, we point out the role of lncRNAs in the pathogenesis of multiple myeloma (MM). We focus on their ability to regulate the biological processes identified as “hallmarks of cancer” that enable malignant cell transformation, early tumor onset and progression. The aberrant expression of lncRNAs in MM suggests their potential use as clinical biomarkers for diagnosis, patient stratification, and clinical management. Moreover, they represent ideal candidates for therapeutic targeting

    Design and synthesis of wm5 analogues as HIV-1 TAR RNA binders

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    The 6-aminoquinolone WM5, previously identified by us, is among the most selective small molecules known as TAR RNA binders to show anti-HIV activity. Methods: Starting from WM5, a series of analogues modified at N-1, C-6 or C-7 position was prepared by inserting guanidine or amidine groups as well as other protonable moieties intended to electrostatically bind the phosphate backbone of TAR. All the compounds were tested for their ability to inhibit HIV-1 replication in MT-4 cells and in parallel for their cytotoxicity. The active compounds were also evaluated for their ability to interfere with the formation of the Tat-TAR complex using a Fluorescence Quenching Assay (FQA). Results: Some of the synthesized compounds showed an anti-HIV-1 activity in the sub-micromolar range with the naphthyridone derivatives being the most potent. Three of the synthesized derivatives were able to interact with the Tat-TAR complex formation presenting Ki values improved as compared to the values obtained with WM5. Conclusion: The addition of a pyridine-based protonable side chain at the N-1 position of the quinolone/naphthyridone core imparted to the compounds the ability to interfere with Tat-TAR complex formation and HIV-1 replicatio

    Differential Expression and Localization of Glycosidic Residues in In Vitro and In Vivo Matured Cumulus-Oocyte Complexes in Equine and Porcine Species

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    Glycoprotein oligosaccharides play major roles during reproduction, yet their function in gamete interactions is not fully elucidated. Identification and comparison of the glycan pattern in cumulus-oocyte complexes (COCs) from species with different efficiencies of in vitro spermatozoa penetration through the zona pellucida (ZP) could help clarify how oligosaccharides affect gamete interactions. We compared the expression and localization of 12 glycosidic residues in equine and porcine in vitro-matured (IVM) and preovulatory COCs by means of lectin histochemistry. The COCs glycan pattern differed between animals and COC source (IVM versus preovulatory). Among the 12 carbohydrate residues investigated, the IVM COCs from these two species shared: (a) sialo- and bN-acetylgalactosamine (GalNAc)-termi- nating glycans in the ZP; (b) sialylated and fucosylated glycans in cumulus cells; and (c) GalNAc and N-acetylglucosamine (GlcNAc) glycans in the ooplasm. Differences in the preovulatory COCs of the two species included: (a) sialoglycans and GlcNAc terminating glycans in the equine ZP versus terminal GalNAc and internal GlcNAc in the porcine ZP; (b) terminal galactosides in equine cumulus cells versus terminal GlcNAc and fucose in porcine cohorts; and (c) fucose in the mare ooplasm versus lactosamine and internal GlcNAc in porcine oocyte cytoplasm. Furthermore, equine and porcine cumulus cells and oocytes contributed differently to the synthesis of ZP glycoproteins. These results could be attributed to the different in vitro fertilization efficiencies between these two divergent, large-animal models

    Reasons for tooth extractions and related risk factors in adult patients: a cohort study

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    Background: The aimof this studywas to evaluate oral status, the reasons for tooth extractions and related risk factors in adult patients attending a hospital dental practice. Methods: 120 consecutive patients ranging from23 to 91 years in age (mean age of 63.3 - 15.8) having a total of 554 teeth extracted were included. Surveys about general health status were conducted and potential risk factors such as smoking, diabetes and age were investigated. Results: a total of 1795 teeth weremissing after extraction procedures and the mean number of remaining teeth after the extraction process was 16.8 ± 9.1 per patient. Caries (52.2%) was the most common reason for extraction along with periodontal disease (35.7%). Males were more prone to extractions, with 394 of the teeth extracted out of the total of 554 (71.1%). Male sex (β = 2.89; 95% CI 1.26, 4.53; p = 0.001) and smoking habit (β = 2.95; 95% CI 1.12, 4.79; p = 0.002) were related to a higher number of teeth extracted. Age (β = -0.24; 95% CI -0.31, -0.16; p < 0.001) and diabetes (β = -4.47; 95% CI -7.61, -1.33; p = 0.006) were related to a higher number of missing teeth at evaluation time. Moreover, periodontal disease was more common as a reason of extraction among diabetic patients than among non-diabetic ones (p = 0.04). Conclusions: caries and periodontal disease were the most common causes of extraction in a relatively old study population: further screening strategies might be required for the early interception of caries and periodontal disease

    Worsening Glycemia increases the Odds of intermittent But Not Persistent Staphylococcus aureus Nasal Carriage in Two Cohorts of Mexican american adults

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    Numerous host and environmental factors contribute to persistent and intermittent nasal Staphylococcus aureus carriage in humans. The effects of worsening glycemia on the odds of S. aureus intermittent and persistent nasal carriage was established in two cohorts from an adult Mexican American population living in Starr County, Texas. The anterior nares were sampled at two time points and the presence of S. aureus determined by laboratory culture an

    Riflettanza di superfici vulcaniche:la campagna 2003 sul Monte Etna

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    The results obtained in Mt. Etna spectroradiometric field survey of June 2003 are presented and discussed. The goal of the survey was the analysis of the reflectance properties of the young pyroclastic deposits produced after the effusive activity of 2002-2003 and of the older lava flows. To achieve this goal, a template was created in order to organize the field data collected in a number of selected sites characterised by different surface materials. The results show that reflectance of pyroclastic flows is always very low and constant, besides grain size and composition of the flow. Pahoehoe units show higher reflectance values, even though the spectral characterisation of the older lava flows must take into account weathering products and vegetation coverage

    TaxMan : a server to trim rRNA reference databases and inspect taxonomic coverage

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    © The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nucleic Acids Research 40 (2012): W82-W87, doi:10.1093/nar/gks418.Amplicon sequencing of the hypervariable regions of the small subunit ribosomal RNA gene is a widely accepted method for identifying the members of complex bacterial communities. Several rRNA gene sequence reference databases can be used to assign taxonomic names to the sequencing reads using BLAST, USEARCH, GAST or the RDP classifier. Next-generation sequencing methods produce ample reads, but they are short, currently ∼100–450 nt (depending on the technology), as compared to the full rRNA gene of ∼1550 nt. It is important, therefore, to select the right rRNA gene region for sequencing. The primers should amplify the species of interest and the hypervariable regions should differentiate their taxonomy. Here, we introduce TaxMan: a web-based tool that trims reference sequences based on user-selected primer pairs and returns an assessment of the primer specificity by taxa. It allows interactive plotting of taxa, both amplified and missed in silico by the primers used. Additionally, using the trimmed sequences improves the speed of sequence matching algorithms. The smaller database greatly improves run times (up to 98%) and memory usage, not only of similarity searching (BLAST), but also of chimera checking (UCHIME) and of clustering the reads (UCLUST). TaxMan is available at http://www.ibi.vu.nl/programs/taxmanwww/.University of Amsterdam under the research priority area ‘Oral Infections and Inflammation’ (to B.W.B.); National Science Foundation [NSF/BDI 0960626 to S.M.H.]; the European Union Seventh Framework Programme (FP7/ 2007-2013) under ANTIRESDEV grant agreement no 241446 (to E.Z.)
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