Search results for " enhancer"

Linking C5 deficiency to an exonic splicing enhancer mutation

2005

Abstract As an important component of the innate immune system, complement provides the initial response to prevent infections by pathogenic microorganisms. Patients with dysfunction of C5 display a propensity for severe recurrent infections. In this study, we present a patient with C5 deficiency demonstrated by immunochemical and functional analyses. Direct sequencing of all C5 exons displayed no mutation of obvious functional significance, except for an A to G transition in exon 10 predicting an exchange from lysine to arginine. This sequence alteration was present in only one allele of family members with a reduced serum C5 concentration and in both alleles of the patient with almost com…

Polymorphism of immunoglobulin enhancer element HS1,2A: allele *2 associates with systemic sclerosis. Comparison with HLA‐DR and DQ allele frequency

2007

OBJECTIVE: To investigate the relationship of the polymorphic enhancer HS1,2 central to the 3' enhancer complex regulatory region (IgH3'EC) of the immunoglobulin heavy chain genes with systemic sclerosis (SSc) disease and compare it with HLA-DR and DQ associations. METHODS: A total of 116 patients with SSc were classified as diffuse (dSSc) or limited (lSSc), and as carriers of antitopoisomerase I (anti-Scl70) or anticentromere (ACA) antibodies. Allele and genotype frequencies were assessed in the population as a whole and in the two major subsets, dSSc and lSSc. The concentration of peripheral blood immunoglobulin levels was also determined and analysed according to the genotypes. RESULTS: …

Further Delineation of Duplications of ARX Locus Detected in Male Patients with Varying Degrees of Intellectual Disability

2022

The X-linked gene encoding aristaless-related homeobox (ARX) is a bi-functional transcription factor capable of activating or repressing gene transcription, whose mutations have been found in a wide spectrum of neurodevelopmental disorders (NDDs); these include cortical malformations, paediatric epilepsy, intellectual disability (ID) and autism. In addition to point mutations, duplications of the ARX locus have been detected in male patients with ID. These rearrangements include telencephalon ultraconserved enhancers, whose structural alterations can interfere with the control of ARX expression in the developing brain. Here, we review the structural features of 15 gain copy-number variants …

Hyaluronic Acid-Based Micelles as Ocular Platform to Modulate the Loading, Release, and Corneal Permeation of Corticosteroids

2017

The aim of this work is to prepare hyaluronic acid-based micelles as a platform to load corticosteroid drugs and to improve their corneal permeation after administration on the ocular surface. Three amphiphilic derivatives of hyaluronic acid (HA) are synthesized using different amounts of hexadecylamine (C16 -NH2 ). HAC16 a, HAC16 b, and HAC16 c derivatives are able to form micelles by the cosolvent evaporation method and to entrap corticosteroids (dexamethasone, triamcinolone, triamcinolone acetonide). HAC16 a and HAC16 b micelles show the best results in terms of drug loading and particle size. They are also able to improve drug release compared to free drug solution or suspension. In add…

Oligonucleotide probes detect splicing variants insituinDrosophilaembryos

1992

We describe a method for the in situ detection of specific splicing variants. The method is based on the use of antisense oligonucleotides designed to span splice junctions labelled with digoxigenin by terminal transferase tailing. We find that the spatial patterns of Ubx splicing variants Ia and IIa are similar in early embryos, but differ in late embryos. Variant IVa is only detected in the CNS (ps6) at stages 16 and 17. We also present evidence indicating that the first splicing event is cotranscriptional.

Mucoadhesive micelles based on inulin derivative for ocular release of corticosteroids

2016

Diffusion of naltrexone across reconstituted human oral epithelium and histomorphological features

2006

Abstract In transbuccal absorption a major limitation could be the low permeability of the mucosa which implies low drug bioavailability. The ability of naltrexone hydrochloride (NLX) to penetrate a resembling histologically human buccal mucosa was assessed and the occurrence of any histomorphological changes observed. We used reconstituted human oral (RHO) non-keratinised epithelium as mucosal section and a Transwell diffusion cells system as bicompartmental model. Buccal permeation was expressed in terms of drug flux ( J s ) and permeability coefficients ( K p ). Data were collected using both artificial and natural human saliva. The main finding was that RHO does not restrain NLX permeat…

MICELLE POLIMERICHE A BASE DI NUOVI DERIVATI ANFIFILICI DELL’INULINA PER LA SOMMINISTRAZIONE OCULARE TOPICA DI CORTICOSTEROIDI NEL TRATTAMENTO DELLE …

2016

Al giorno d’oggi, la via di somministrazione oftalmica costituisce ancora una sfida per i tecnologi farmaceutici. Si tratta, inoltre, probabilmente di uno degli ambiti che più di ogni altro potrebbe beneficiare dello sviluppo di nuovi Drug Delivery Systems basati sull’utilizzo di nanovettori. Infatti, più del 50% delle patologie oculari maggiormente debilitanti (es. degenerazione maculare legata all’età, retinopatia diabetica ed edema maculare diabetico) ha origine a livello del segmento oculare posteriore. Ad oggi, la terapia intravitreale costituisce il gold standard per garantire il raggiungimento del sito target, ovvero la retina. Tuttavia, la necessità di ricorrere a frequenti somminis…

Enhancer, chromatin insulator, non-coding RNA and α-histone gene expression during embryogenesis of the sea urchin Paracentrotus lividus.

2009

Core promoters and chromatin insulators (ins) may direct a transcriptional enhancer (enh) to prefer a specific promoter in complex genetic loci. Enh and ins flank the sea urchin Paracentrotus lividus α-histone H2A transcription unit in a tandem repeated cluster containing the five histone genes. In vivo competition assays of enh and ins functions reveal that the H2A enh-bound MBF-1 activator participates also in the expression of the H3 gene and that the sns5 ins buffers the downstream H1 promoter from the H2A enh. These results suggest that both the H2A enh and the sns5 ins may account for the diverse accumulation of the linker vs core nucleosomal histones during early development of the s…

The sea urchin histone H2A enhancer-binding protein MBF-1 is needed for maximal expression also for the H3 gene, while is buffered by the sns5 insula…

2009

Enhancers are DNA elements which increase the transcription of associated gene in a position and distance independent manner relative to the transcription initiation site. Molecular mechanisms must operate to direct enhancers to specific promoters in complex genetic loci. The sea urchin a-histone genes are organized in several hundred tandem repeated units, each containing one copy of the five histone genes in the order 5’-H4-H2B-H3-H2A-H1-3’. Transcription is limited to the early cleavage and reaches its maximum at morula stage. After hatching these genes are repressed and maintained in the silenced state for whole life cycle of the animal. In Paracentrotus lividus, the MBF-1 activator bin…