Search results for " Notch"
showing 10 items of 53 documents
Automatic or manual arterial path for the ankle-brachial differences pulse wave velocity
2018
Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206434 An automated method for measuring arterial path length with devices that determine pulse wave velocity (PWV) in peripheral arteries is frequently applied. We aimed to compare arterial path length measurements based on mathematical height-based formulas with those measured manually and to assess whether the ankle-brachial difference (abD-PWV) measured with the VOPITB device is comparable to that obtained by manual measurements. In 245 patients, a metric measuring tape was used to determine the arterial path length from the suprast…
NOTCH, a new signaling pathway implicated in holoprosencephaly.
2011
International audience; Genetics of Holoprosencephaly (HPE), a congenital malformation of the developing human forebrain, is due to multiple genetic defects. Most genes that have been implicated in HPE belong to the sonic hedgehog signaling pathway. Here we describe a new candidate gene isolated from array comparative genomic hybridization redundant 6qter deletions, DELTA Like 1 (DLL1), which is a ligand of NOTCH. We show that DLL1 is co-expressed in the developing chick forebrain with Fgf8. By treating chick embryos with a pharmacological inhibitor, we demonstrate that DLL1 interacts with FGF signaling pathway. Moreover, a mutation analysis of DLL1 in HPE patients revealed a three-nucleoti…
Haploinsufficiency of the NOTCH1 receptor as a cause of Adams-Oliver syndrome with variable cardiac anomalies
2015
Background— Adams–Oliver syndrome (AOS) is a rare disorder characterized by congenital limb defects and scalp cutis aplasia. In a proportion of cases, notable cardiac involvement is also apparent. Despite recent advances in the understanding of the genetic basis of AOS, for the majority of affected subjects, the underlying molecular defect remains unresolved. This study aimed to identify novel genetic determinants of AOS. Methods and Results— Whole-exome sequencing was performed for 12 probands, each with a clinical diagnosis of AOS. Analyses led to the identification of novel heterozygous truncating NOTCH1 mutations (c.1649dupA and c.6049_6050delTC) in 2 kindreds in which AOS was segregat…
Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease
2010
Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium) propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism that is altered by inhibitors of complex I and has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, we investigated the effects of mildronate in a rat model of Parkinson’s disease (PD) that was generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6‑OHDA). We assessed the expression of cell biomarkers that are involved in signaling cascades and provide neural and glial integration: the neuronal marker TH (tyrosine hydroxylase); …
Childhood-onset CADASIL: clinical, imaging, and neurocognitive features.
2010
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a progressive neurodegenerative condition, associated with mutations in the notch3 gene. Symptoms include migraine with aura, mood disorders, progressive cognitive decline, subcortical ischemic strokes, dementia, and premature death. We present an 8-year-old boy with attention and behavioral difficulties, as well as a family history of the condition. Magnetic resonance imaging revealed subcortical foci of increased T2 hyperintensity, and sequencing of the notch3 gene revealed 1 previously reported mutation and 1 novel sequence variant. Neurocognitive assessment revealed deficits in sever…
Identification of novel, clonally stable, somatic mutations targeting transcription factors PAX5 and NKX2-3, the epigenetic regulator LRIF1, and BRAF…
2021
Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) is usually straightforward, involving clinical, immunophenotypic (Matutes score), and (immuno)genetic analyses (to refine patient prognosis for treatment). CLL cases with atypical presentation (e.g., Matutes ≤ 3) are also encountered, and for these diseases, biology and prognostic impact are less clear. Here we report the genomic characterization of a case of atypical B-CLL in a 70-yr-old male patient; B-CLL cells showed a Matutes score of 3, chromosomal translocation t(14;18)(q32;q21) (BCL2/IGH), mutated IGHV, deletion 17p, and mutations in BCL2, NOTCH1 (subclonal), and TP53 (subclonal). Quite strikingly, a novel PAX5 mutation that w…
Expression pattern of Notch1, 2 and 3 and Jagged1 and 2 in lymphoid and stromal thymus components: distinct ligand–receptor interactions in intrathym…
1999
The suggested role of Notch1 or its mutants in thymocyte differentiation and T cell tumorigenesis raises the question of how the different members of the Notch family influence distinct steps in T cell development and the role played by Notch ligands in the thymus. We report here that different Notch receptor-ligand partnerships may occur inside the thymus, as we observed differential expression of Notch1, 2 and 3 receptors, their ligands Jagged1 and 2, and downstream intracellular effectors hairy and Enhancer of Split homolog 1 (HES-1) and hairy and Enhancer of Split homolog 5 (HES-5), depending on ontogenetic stage and thymic cell populations. Indeed, while Jagged2 is expressed in both st…
Fatigue crack growth of new FML composites for light ship buildings under predominant mode II loading condition
2019
The use of light but strong materials is largely studied in various area of the shipbuilding, this because the need of reducing the weight, and especially the weight of all the structures above the main deck assume primary importance for the stability. Traditionally in fast boats like fast ferries, hydrofoils, patrol boats, the typical materials are Aluminum alloy or composites, both those materials have advantages and disadvantages, but the new development of technologies made possible to combine them, in order to have a new material, combining the advantages of both, in terms of fatigue resistance, firefighting characteristics. In this paper, predominant mode II fatigue delamination tests…
Rapid evaluation of notch stress intensity factors using the peak stress method: Comparison of commercial finite element codes for a range of mesh pa…
2018
The peak stress method (PSM) is an engineering, finite element (FE)-oriented method to rapidly estimate the notch stress intensity factors by using the singular linear elastic peak stresses calculated from coarse FE analyses. The average element size adopted to generate the mesh pattern can be chosen arbitrarily within a given range. Originally, the PSM has been calibrated under pure mode I and pure mode II loadings by means of Ansys FE software. In the present contribution, a round robin between 10 Italian universities has been carried out to calibrate the PSM with 7 different commercial FE codes. To this aim, several two-dimensional mode I and mode II problems have been analysed independe…
Expression analysis of jagged genes in zebrafish embryos
2005
The interaction of transmembrane Delta and Jagged/Serrate ligands with Notch receptors on neighboring cells is critically involved in cell specification during development. In zebrafish, the early expression of delta but not of jagged genes has been investigated in some detail. We have analyzed the sequence and embryonic expression pattern of the three zebrafish genes jagged1a, jagged1b, and jagged2. These genes, whose transcripts are detectable by in situ hybridization from early somitogenesis, are widely and dynamically expressed in embryos. Coexpression is limited, however, to the notochord and lens (jagged1a and jagged1b) and to the otic vesicle and pronephros (jagged1b and jagged2). Co…