1,721,045 research outputs found
Molecular understanding of the FMR1 premutation and fragile X-associated premature ovarian failure
No full textCGG repeats expansion (55-200 units, premutation range) in the 5’UTR of FMR1 gene (Xq27.3) is associated with Fragile-X Tremor/ Ataxia Syndrome and Premature Ovarian Failure (POF). FMR1 premutation represents the most significant single gene variant associated with POF, however no studies are available to evaluate its pathogenic effect in the ovary context. As for FXTAS, an RNA-mediated toxic gain of function could be hypothesized for FX-POF. Human granulosa cell line were transfected with plasmid containing 76CGG repeat elements in the 5’-UTR of EGFP reporter under the control of CMV immediate early promoter (CMV-76CGG-EGFP), or with CMVEGFP
as control. By RNA immunoprecipitation, the interaction of 76rCGG for rCGG-Repeat Binding Proteins (rCGG-RBPs), previously identified, was tested. 76rCGG solely immunoprecipitate with heat shock proteins, some hnRNPs and proteins involved in paraspeckles formation such as SFPQ and hnRNPM, suggesting that in vivo premutated FMR1 mRNA differs from the wild type in making RNA-protein complexes. In this regard in premutated granulosa cells a deregulation of structural components paraspeckles was observed suggesting an alteration of splicing. Furthermore an “heat shock like” response associated with a reduced cell viability in human ovary granulosa
cells expressing expanded CGG mRNA was observed, indicating a toxic role of premutated mRNA itself in the ovaries. This work is supported by Telethon grant GGP009126
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
Mutations in the coding region of the FOXL2 gene are not a major cause of idiopathic premature ovarian failure
No full textPremature ovarian failure (POF) is a heterogeneous disorder whose aetiology is
still unknown. Recently, the autosomal FOXL2 gene, highly expressed in the adult
ovary, has been correlated with the disorder. FOXL2 mutations, causing a
truncation of the FOXL2 protein in the forkhead domain or in the poly-Ala tract
lead to blepharophimosis-ptosis-epicanthus-inversus syndrome associated with POF
(BPES I). Interestingly, in two out of 70 idiopathic POF patients, a 30 bp
deletion (898-927del) and a missense mutation (1009T-->A) were identified. To
further evaluate the correlation between POF and FOXL2 mutations, 120
phenotypically normal women affected by POF were analysed by direct sequencing
of the FOXL2 coding region. The analysis did not reveal any mutation in the 240
analysed chromosomes, indicating that mutations in the FOXL2 coding region are
rarely associated with non-syndromic PO
Analysis of GC-rich repetitive nucleotide sequences in great apes
No full textThe genomes of four primate species, belonging to the families Pongidae (chimpanzee, gorilla, and orangutan) and Hylobatidae (gibbons), have been analyzed for the presence and organization of two human GC-rich heterochromatic repetitive sequences: beta Satellite (beta Sat) and LongSau (LSau) repeats. By Southern blot hybridization and PCR, both families of repeats were detected in all the analyzed species, thus indicating their origin in an ape ancestor. In the chimpanzee and gorilla, as in man, beta Sat sequences showed a 68-bp Sau3A periodicity and were preferentially organized in large clusters, whereas in the orangutan, they were organized in DNA fragments of 550 bp, which did not seem to be characterized by a tandem organization. On the contrary, in each of the analyzed species, the bulk of LSau sequences showed a longer Sau3A periodicity than that observed in man (450-550 bp). Furthermore, only in the chimpanzee genome some of LSau repeats seemed to be interspersed within blocks of beta Sat sequences. This sequence organization, which also characterizes the human genome, is probably absent in the gorilla. In fact, the analysis of a gorilla genomic library suggested that LSau repeats are not preferentially in linkage with beta Sat sequences. Moreover, LSau sequences were found in a genomic sector characterized by the simultaneous presence of L1 and (CA) repeats, as well as of anonymous sequences and known genes. In spite of the different sequence organization, the nucleotide differences between complete human and gorilla LSau repeats were very few, whereas one gorilla LSau repeat, interrupted by a probably-truncated L1 transposon, showed a higher degree of divergence.(ABSTRACT TRUNCATED AT 250 WORDS
Nitric oxide reduces nontransferrin-bound iron transport in HepG2 cells
No full textNitric oxide (NO) donors S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP) modulate iron regulatory protein (IRP) activity and may, therefore, affect iron uptake through transferrin receptor expression. However, iron also enters the cell as nontransferrin-bound iron (NTBI), and the aim of this study was to evaluate the effects of NO donors on NTBI transport in HepG2 cells, a model of liver physiology. Incubation with SNP and SNAP led to a time- and concentration-dependent reduction in Fe3+ and Fe2+ uptake, thus indicating an effect on the transporter rather than on the reductase. In terms of Fe2+ uptake, no variations in the Michaelis-Menten constant (Km) and a reduction in maximum uptake (Vmax) (50, 33, and 16.6 fmol/microgram protein/min in control, SNP-, and SNAP-treated cells, respectively) were detected, which suggested a decrease in the number of putative NTBI transport protein(s). Gel shift assays showed that IRP activity was reduced by SNP and slightly increased by SNAP. Northern blot analysis of transferrin receptor messenger RNA (mRNA) levels showed variations similar to those observed for IRPs, but both NO donors increased L-ferritin mRNA levels and had no effect on the stimulator of Fe transport (SFT) mRNA. In conclusion, NO donors significantly reduce NTBI transport in HepG2 cells, an effect that seems to be IRP and SFT independent. Moreover, the reduction in NTBI uptake after NO treatment suggests that this form of iron may play a minor role in the increased hepatic iron stores observed in inflammation or that other liver cells are more involved in this pathological condition
Variations on the Author
Full text link“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
Full text linkWe 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
Full text linkWe 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
- …
