Search results for "Notch"
showing 10 items of 93 documents
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…
AN ACCURATE METHOD TO PREDICT THE STRESS CONCENTRATION IN COMPOSITE LAMINATES WITH A CIRCULAR HOLE UNDER TENSILE LOADING
2007
The paper presents a theoretical-numerical hybrid method for determining the stresses distribution in composite laminates containing a circular hole and subjected to uniaxial tensile loading. The method is based upon an appropriate corrective function allowing a simple and rapid evaluation of stress distributions in a generic plate of finite width with a hole based on the theoretical stresses distribution in an infinite plate with the same hole geometry and material. In order to verify the accuracy of the method proposed, various numerical and experimental tests have been performed by considering different laminate lay-ups; in particular, the experimental results have shown that a combined …
Assessment of multiaxial fatigue behaviour of welded joints under combined bending and torsion by application of a fictitious notch radius
2004
Abstract A major problem in the assessment of the multiaxial fatigue behaviour in welded joints is the determination of local notch stresses, since the real local radii in most cases are not known. This can be circumvented by introducing a fictitious notch radius, according to Neuber and Radaj. The calculations of local equivalent stress amplitudes for welded joints (tube–tube and flange–tube) under pure bending, pure torsion and combined in- and out-of-phase bending with torsion can then be carried out by stress-based and strain energy density-based criteria. Among the investigated methods, the most reliable results are obtained with the effective equivalent stress hypothesis, an integral …
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…
Aspilota-group (Hymenoptera: Braconidae: Alysiinae) diversity in Mediterranean Natural Parks of Spain
2014
This work analyses the biodiversity of the Aspilota-group (Hymenoptera: Braconidae: Alysiinae) in three Mediterranean Natural parks: Natural Park of La Font Roja, Natural Park of Las Lagunas de la Mata-Torrevieja and Natural Park of La Tinença de Benifassà. Samples were carried out from April 2004 to December 2007. In total, 822 specimens, belonging to 52 species, were collected. Alpha, beta and gamma diversities were analysed, and the Tinença Park was proven to have higher diversity than the Font Roja and Torrevieja. Also, the structure of the Aspilota-group community was analysed.