1,720,997 research outputs found
Effects of peptide T derivatives on the proliferation of cultured human keratinocytes.
[D-Ala1]peptideT-amide, the linear hexapeptide H-Thr-Hse-Asn-Tyr-Thr-Asp-OH (LPT) and its cyclic analog, cyclo(-Thr-Hse-Asn-Tyr-Thr-Asp-) (CPT), were tested for their effects on the proliferation of cultured normal human keratinocytes (KTs) in comparison with vasoactive intestinal peptide (VIP). [D-Ala1]PT-NH2, LPT and VIP (all 0.1 mumol/l) increased the cell number in KT cultures, whereas CPT was ineffective. The VIP antagonist [N-Ac-Tyr1,D-Phe2]GRF (1-29)-NH2 significantly inhibited the VIP effects on KTs. On the other hand this antagonist did not affect the peptide T (PT) compounds-induced stimulation of KTs, providing indirect evidence that the mitogenic effects of VIP and PT peptides are probably mediated via different receptors
Mammalian microRNAs: a small world for fine-tuning gene expression
The basis of eukaryotic complexity is an intricate genetic architecture where parallel systems are involved in tuning gene expression, via RNA-DNA, RNA-RNA, RNA-protein, and DNA-protein interactions. In higher organisms, about 97% of the transcriptional output is represented by noncoding RNA (ncRNA) encompassing not only rRNA, tRNA, introns, 5' and 3' untranslated regions, transposable elements, and intergenic regions, but also a large, rapidly emerging family named microRNAs. MicroRNAs are short 20-22-nucleotide RNA molecules that have been shown to regulate the expression of other genes in a variety of eukaryotic systems. MicroRNAs are formed from larger transcripts that fold to produce hairpin structures and serve as substrates for the cytoplasmic Dicer, a member of the RNase III enzyme family. A recent analysis of the genomic location of human microRNA genes suggested that 50% of microRNA genes are located in cancer-associated genomic regions or in fragile sites. This review focuses on the possible implications of microRNAs in post-transcriptional gene regulation in mammalian diseases, with particular focus on cancer. We argue that developing mouse models for deleted and/or overexpressed microRNAs will be of invaluable interest to decipher the regulatory networks where microRNAs are involved
Tumor induced by Moloney sarcoma virus causes periosteal osteogenesis engaging osteopontin, fibronectin, stromelysin-1 and tenascin.
Excessive bone formation occurring in such conditions as paravertebral ligamentous ossification, hallux osteophytes or some neoplastic tumors, presents a significant problem, both epidemiological and clinical. Since pathogenesis of this disorder is still unclear, we studied its mechanism in experimental model utilizing inducible orthotopic osteogenesis. Periosteal bone apposition stimulated by Moloney sarcoma is characterized by unusually high volume of new bone tissue appearing subperiosteally in the bone adjacent to the tumor. Genes engaged in this growth have not been characterized so far. Here we show the results of mRNA Representation Difference Analysis in Moloney sarcoma, which reveal high expression of four genes coding extracellular matrix proteins: osteopontin, fibronectin, stromelysin-1 and tenascin. These findings suggest that the uncommon dynamics of the Moloney sarcoma-induced osteogenesis depends on high expression of these extracellular matrix proteins
Spontaneous and mutagen-induced transformation of primary coltures of Msh2-/- p53-/- colonocytes
Loss of function of mismatch repair (MMR) genes underlies hereditary nonpolyposis colorectal cancer (HNPCC). However, the inability to maintain primary colon epithelial cells in culture has limited the analysis of the contribution of MMR gene defects to colorectal tumorigenesis. We have now established primary cultures of epithelial cells from the colon crypts of Msh2-/- p53-/- double-knockout mice. These cells undergo spontaneous transformation (soft agar colonies and s.c. tumor formation), with a progressively shorter latency as a function of increasing passages in culture. Treatment of early passage cells with the mutagen methylmethane thiosulfonate (MMS) further decreases the transformation latency of Msh2-/- p53-/- cells. Spontaneous transformation of p53-/- colonocytes is only observed using late passage cells, and methylmethane thiosulfonate-treated early passage p53-/- colonocytes do not form tumors when injected into immunodeficient mice. Together, these findings support the pathogenic role of MMR gene inactivation in colorectal tumorigenesis and provide an experimental model for the serial assessment of the molecular phenotype associated with Msh2 deficiency
Tumorigenic conversion of p53 deficient colon epithelial cells by an activated Ki-ras gene
Distinct genetic abnormalities (loss-of-function mutationsof APC and p53 and oncogenic activation of Ki-ras) are as-sociated with specific stages of the sporadic, most commontypes of colorectal tumors. However, the inability to main-tain primary colon epithelial cells in culture has hinderedthe analysis of the pathogenetic role of these abnormalitiesin colorectal tumorigenesis. We have now established pri-mary cultures of epithelial cells from the colon crypts ofp53-deficient mice; these cells are nontumorigenic as indi-cated by their failure to form colonies in soft agar and togrow as tumors in immunodeficient SCID mice and in im-munocompetent syngeneic hosts. Upon ectopic expressionof an activated Ki-ras gene, p53-deficient colon epithelialcells form colonies in soft agar and highly invasive subcuta-neous tumors in both immunodeficient and immunocompe-tent mice. Ectopic expression of wild-type p53, but not of aDNA-binding–deficient mutant, markedly suppressed thecolony-forming ability of the Ki-ras–transformed p53-defi-cient epithelial cells. Together, these findings establish afunctional synergism in colorectal tumorigenesis dependenton the effects of an oncogenic Ki-ras in a p53-deficientbackground. This model of tumorigenic conversion of colonepithelial cells might be useful to identify genetic changesassociated with disease progression and to evaluate thetherapeutic response to conventional and novel anticancerdrugs
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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