1,721,027 research outputs found
Gypsy-Ty3 like elements in the genome of the terrestrial salamander Hydromantes (Amphibia: Urodela)
No full textWe have studied a family of long repetitive DNA sequences (Hsr1) interspersed in the large genome of the European plethodontid salamander Hydromantes. The sequence analysis of a 5-kb fragment (Hsr1A) of one member has revealed significant similarities with aminoacidic domains of retroviruses and retrotransposons. The similarity of the reverse transcriptase domain and the gene organization identifies Hsr1A as a member of the gypsy/Ty3 class of retrotransposons. We hypothesize that Hsr1 sequences are vestiges of an invasion of the Hydromantes genome that occurred early in the evolutionary history of these European plethodontids. About 10(6) Hsr1 sequences are present in the large Hydromantes genome. This is the highest number of copies so far discovered for retrotransposon-like elements in eukaryote organisms
A method for prediction of accessible sites on an mRNA sequence for target selection of hammehead ribozymes
No full textHammerhead ribozymes are short RNA molecules endowed with endoribonucleolytic activity. Their use as molecular tools for specific inhibition of gene translation is affected by many factors including the target accessibility. A method for the prediction of accessible target sites for hammerhead ribozymes within a given RNA sequence is described. This method maps all putative NUH cleavage sites (N = A, C, G, U and H = A, C, U) and picks out short flanking regions as the binding domain for the corresponding ribozyme. The probabilistic level of unfolding, accessibility score (AS), is then calculated for each target region on the basis of a comparison of all folding structures obtained for the target RNA and arranged according to the Boltzmann's distribution. At the end, a series of imposed limits gives the best target sequences endowed with highly probable accessibility and with a potentially active catalytic structure of the hammerhead sequence. A successive experimental approach to verify the effective accessibility of selected targets was used. For that, antisense oligonucleotides addressed to the coding region of bcl2 mRNA were synthesized and administered to the MCF7 human cell line. The inhibition of gene expression, as measured by western analysis of the BCL2 protein, demonstrated that all target sites selected on the basis of their putative accessibility were actually sensitive to antisense treatments while the inaccessible ones were not. The application of this target discovery method to ribozyme design is proposed in order to satisfy a crucial condition
Proteomica e medicina personalizzata
No full textWith the disclosure of the human genome a new
era for bio-medicine has arisen, characterized by the challenge
to investigate pathogenic mechanisms, studying simultaneously
metabolites, DNA, RNA, and proteins. As a result,
the “omics” revolution boomed, giving birth to a new
medicine named “omics-based medicine”. Among the other
“omics”, proteomics has been widely used in medicine,
since it can produce a more “holistic” overview of a disease
and provide a “constellation” of possible specific markers, a
molecular fingerprinting that defines the clinical condition
of an individual. Endpoint of this comprehensive and detailed
analysis is the diagnostic-“omics”, i.e. the achievement
of personalized diagnoses with obvious benefits for prevention
and therapy and this goal can be reached only with
a perfect integration between clinicians and proteomists.
To impact on the possible key factors involved in the pathological
processes, oligonucleotide-based knock-down
strategies can be helpful. They exploit omics-derived molecular
tools (antisense, siRNA, ribozymes, decoys, and aptamers)
that can be used to inhibit, at the transcriptional or
post-transcriptional levels, the events leading to protein
synthesis, thus decreasing its expression. The identification
of the pivotal mechanisms involved in diseases using global,
“scenic” approaches such as the “omics” ones, and the
subsequent validation and detailed description of the
processes by specific molecular tools, can result in a more
preventive, predictive and personalized medicine
Il concetto di legge naturale in Lucrezio e Seneca
No full textIl saggio esplora le differenze tra Lucrezio e Seneca nell'elaborazione di una filosofia della natura entro la quale contemplare la regolarità dei fenomeni natural
Vascular smooth muscle cell activation: proteomics point of view
No full textVascular smooth-muscle cells (VSMCs) are the main component of the artery medial layer. Thanks to their great plasticity, when stimulated by external inputs, VSMCs react by changing morphology and functions and activating new signaling pathways while switching others off. In this way, they are able to increase the cell proliferation, migration, and synthetic capacity significantly in response to vascular injury assuming a more dedifferentiated state. In different states of differentiation, VSMCs are characterized by various repertories of activated pathways and differentially expressed proteins. In this context, great interest is addressed to proteomics technology, in particular to differential proteomics. In recent years, many authors have investigated proteomics in order to identify the molecular factors putatively involved in VSMC phenotypic modulation, focusing on metabolic networks linking the differentially expressed proteins. Some of the identified proteins may be markers of pathology and become useful tools of diagnosis. These proteins could also represent appropriately validated targets and be useful either for prevention, if related to early events of atherosclerosis, or for treatment, if specific of the acute, mid, and late phases of the pathology. RNA-dependent gene silencing, obtained against the putative targets with high selective and specific molecular tools, might be able to reverse a pathological drift and be suitable candidates for innovative therapeutic approaches
Gypsy/Ty3-like elements in the genome of the terrestrial salamander Hydromantes (Amphibia, Urodela)
No full textHammerhead ribozymes in therapeutic target discovery and validation
No full textGene function assessment is a main task in biological networking investigations and system biology. High throughput technologies provide an impressive body of data that enables the design of hypotheses linking genes to phenotypes. When a putative scenario is depicted, gene knockdown technologies and RNA-dependent gene silencing are the most frequent approaches to assess the role of key effectors. In this paper, we discuss the relevance of hammerhead ribozymes in target discovery and validation, describing their properties and applications and highlighting their selectivity. In particular, similarities with siRNAs are presented and advantages and drawbacks are discussed. A description of the perspectives of ribozyme application in wide range studies is also provided, strengthening the value of these inhibitors for target validation purposes
INSULIN KINETICS AND GLUCOSE-INDUCED INSULIN DELIVERY IN CHRONICALLY DIALYZED SUBJECTS - ACUTE EFFECTS OF DIALYSIS
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
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