1,721,077 research outputs found
Inverted duplications deletions: underdiagnosed rearrangements??
No full textMolecular techniques led to the discovery that several chromosome rearrangements interpreted as terminal duplications were in fact inverted duplications contiguous to terminal deletions. Inv dup del rearrangements originate through a symmetric dicentric chromosome that, after asymmetric breakage, generates an inv dup del and a deleted chromosome. In recurrent inverted duplications the dicentric chromosome is formed at meiosis through non-allelic homologous recombination. In non-recurrent inv dup del cases, dicentric intermediates are formed by non-homologous end joining or intrastrand annealing. Some authors hypothesized that in these cases the dicentric may have been formed directly in the zygote. Healing of the broken dicentric chromosomes can occur not only in a telomerase-dependent way but also through telomere capture and circularization thus creating translocated or ring inv dup del chromosomes. In all the cases reported up to now, the duplicated region was always longer than the deleted one, but we can safely assume that there is another group of rearrangements where the deleted region is longer than the duplicated portion. In general, in these cases, the cytogeneticist will suspect the presence of a deletion and confirm it by FISH with a subtelomeric probe, but he/she will almost certainly miss the duplication. It is likely that the conventional analysis techniques used until now have led to a substantial underestimate of the frequency of inv dup del rearrangements and that the widespread use of array-CGH in routine analysis will allow a more realistic estimate. Obviously, the concomitant presence of deletion and duplication has important consequences in genotype/phenotype correlations
A de novo 2q interstitial deletion in a patient with a Turner phenotype
No full textWe report on a patient with a de novo interstitial deletion of the long arm of chromosome 2 involving the region 2q13-q14.2. She was the only daughter of unrelated parents and came to our observation for postnatal growth retardation, moderate mental retardation and minor dysmorphisms. At the age of 13+6/12 years, weight was Kg 37 (3-Y10- centile), height 133 cm (GG3- centile) and OFC 53,1 cm (50- centile).
She presented with short stature, triangular face with bitemporal narrowing, webbed neck and a low posterior hairline, drooping eyelids, thin nose, highly arched palate, shield chest, mild cubitus valgus, multiple pigmented nevi, atrial septal defect, and mild hypothyroidism. Overall, the phenotype was evocative of Turner syndrome. Two independent postnatal karyotypes on peripheral blood and cytogenetic investigation of cutaneous fibroblasts were normal, thus excluding chromosomal mosaicism. Molecular analysis of the SHOX gene was normal. Array-CGH
analysis allowed us to identify and characterize a 2q de novo interstitial deletion of about 8 Mb with proximal and distal breakpoints at 113,120 Mb and 122,079 Mb, respectively. The deleted region contains several genes, among which PAX8 and INHBB.
PAX8 is involved in thyroid follicular cell development and expression of thyroid-specific genes, and loss of function mutations affecting it cause a form of hypothyroidism. INHBB codes for a bB subunit of activin dimers. Activins are TGF-b superfamily members, that act as regulators of growth and differentiation in several tissues and cell types. Inhibins/activins are involved in regulating a number of diverse functions, such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, insulin secretion, nerve cell survival, embryonic axial development and bone growth, depending on their subunit composition. Therefore, INHBB may be a good candidate to explain the growth retardation observed in this patient
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
Studio array-based comparative genomic hybridization dei linfomi primitivi cutanei epidermotropi aggressivi CD8+
Full text linkIl linfoma cutaneo a cellule T citotossico CD8+ epidermotropo aggressivo (AeCD8+cx) è una forma molto rara di linfoma cutaneo a cellule T, appartenente al gruppo dei linfomi a cellule T primitivi cutanei periferici non altrimenti specificati (PC-PTL/NOS), secondo la classificazione WHO/EORTC del 2005, ed è stato descritto per la prima volta da Berti et al. nel 1999. Questo tipo di neoplasia presenta una proliferazione epidermotropa di linfociti T CD8+ citotossici (TIA-1+, GrB+, Perforin+), a decorso clinico aggressivo non responsivi alla polichemioterapia e al trapianto.
Abbiamo condotto un'analisi di Array-based Comparative Genomic Hybridization (arrayCGH) su DNA estratto dalle lesioni cutanee di 13 pazienti affetti da AeCD8+cx al momento della diagnosi.
Dai risultati è emersa la presenza di alcune regioni cromosomiche alterate in un numero significativo di pazienti. Tra queste le più interessanti risultano essere le amplificazioni del 3p21, 7q, 8q24, 11q12-q13, 16p, 17q, trisomia19, e 22q, oltre alla delezione del 9p21. All'interno di queste regioni sono contenuti molti geni coinvolti nella regolazione di processi biologici che possono giocare un ruolo fondamentale nella patogenesi o nello sviluppo di questo linfoma. Nella delezione del 9p21 emerge la nullisomia dei geni CDKN2A e CDKN2B che sono inibitori specifici delle chinasi ciclina-dipendente che si legano alla ciclina D. Risulta quindi che l'impossibilità di inibire l'attivazione di questa ciclina possa portare ad una iperattività di quest'ultima con conseguente aumentata proliferazione linfocitaria. Per quanto riguarda le regioni amplificate sembrerebbero essere importanti alcuni geni che portano ad una aumentata attivazione del JAK/STAT signaling pathway. In particolare le duplicazioni di JAK3, STAT3 e STAT5 potrebbero giustificare il fenotipo a cellule CD8 e il comportamento aggressivo dei linfociti neoplastici. L'amplificazione di JAK3 è dovuta alla presenza di trisomia 19 totale o parziale. In questo cromosoma sembrano essere contenuti diversi geni che se overespressi portano ad una proliferazione incontrollata di linfociti come ad esempio JUNB, JUND, KIR3DL2, AKT2, LYL1 e RELB.
Questi dati costituiscono la base per l'interpretazione molecolare di questa patologia e andranno corredati con le analisi di espressione genica e RT-PCR al fine di determinare un miglior approccio terapeutico
Deletion of specific sequences or modification of centromeric chromatin are responsible for Y chromosome centromere inactivation
No full textStable dicentric chromosomes behave as monocentrics because one of the centromeres is inactive. The cause of centromere inactivation is unknown; changes in centromere chromatin conformation and loss of centromeric DNA elements have been proposed as possible mechanisms. We studied the phenomenon of inactivation in two Y centromeres, having as a control genetically identical active Y centromeres. The two cases have the following karyotypes: 45, X/46,X,i(Y)(q12) and 46,XY/47,XY,+t(X;Y) (p22.3;p11.3). The analysis of the behavior of the active and inactive Y chromosome centromeres after Da-Dapi staining, CREST immunofluorescence, and in situ hybridization with centromeric probes leads us to conclude that, in the case of the isochromosome, a true deletion of centromeric chromatin is responsible for its stability, whereas in the second case, stability for its stability, whereas in the second case, stability of the dicentric (X;Y) is the result of centromere chromatin modification
Agenesis of the corpus callosum with Probst bundles owing to haploinsufficiency for a gene in an 8 cM region of 6q25
No full textAgenesis of the corpus callosum (ACC) is a relatively common brain abnormality resulting from developmental defects either limited to the structures leading to the proper formation of the corpus callosum or involving the embryo forebrain more generally. ACC is genetically heterogeneous with autosomal dominant, autosomal recessive, and X linked inheritance
and has also been reported in subjects with aneuploidies involving several chromosomes. Among them, distal 6q deletions have been consistently reported in association with ACC, suggesting that there is a gene in the deleted region whose
haploinsufficiency impairs normal corpus callosum development. We have studied a child with ACC with Probst bundles and a
deletion at 6q25 of about 8 cM, from D6S1496 to D6S437. Probst bundles are the axons that should have formed the corpus callosum but, unable to cross the midline owing to absence of the massa commissuralis, they run longitudinally along the medial walls of the lateral ventricles from the frontal to the occipital
lobes. Thus, their presence suggests that a gene located in the 6q deleted region is specifically involved in the formation of the massa commissuralis and that its haploinsufficiency leads to primary ACC
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
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