102,302 research outputs found
The adventurous life of Giuseppe Ferlini
No full textThe life of the physician and explorer Giuseppe Ferlini (1797-1870), who is mainly known for the discovery of the Kushite treasure of queen Amanishakheto at Meroe, is still largely shrouded in shadow, and the information preserved about him is often patchy, disordered and occasionally inaccurate. The article aims at describing the main stages of the life of Ferlini, from the first experiences in the military camps in the Balkans to his last adventures in Sudan, where he envisaged "archaeological research" as possible source of knowledge and income
A novel custom high density-comparative genomic hybridization array detects common rearrangements as well as deep intronic mutations in dystrophinopathies
No full textBackground: The commonest pathogenic DMD changes are intragenic deletions/duplications which make up to 78% of all cases and point mutations (roughly 20%) detectable through direct sequencing. The remaining mutations (about 2%) are thought to be pure intronic rearrangements/mutations or 5'-3' UTR changes. In order to screen the huge DMD gene for all types of copy number variation mutations we designed a novel custom high density comparative genomic hybridisation array which contains the full genomic region of the DMD gene and spans from 100 kb upstream to 100 kb downstream of the 2.2 Mb DMD gene.Results: We studied 12 DMD/BMD patients who either had no detectable mutations or carried previously identified quantitative pathogenic changes in the DMD gene. We validated the array on patients with previously known mutations as well as unaffected controls, we identified three novel pure intronic rearrangements and we defined all the mutation breakpoints both in the introns and in the 3' UTR region. We also detected a novel polymorphic intron 2 deletion/duplication variation. Despite the high resolution of this approach, RNA studies were required to confirm the functional significance of the intronic mutations identified by CGH. In addition, RNA analysis identified three intronic pathogenic variations affecting splicing which had not been detected by the CGH analysis.Conclusion: This novel technology represents an effective high throughput tool to identify both common and rarer DMD rearrangements. RNA studies are required in order to validate the significance of the CGH array findings. The combination of these tools will fully cover the identification of causative DMD rearrangements in both coding and non-coding regions, particularly in patients in whom standard although extensive techniques are unable to detect a mutation
Biomarkers in rare diseases
No full textNowadays 7,000 rare diseases (RDs) have been identified with a prevalence less than 5/10,000. Despite of the enormous effort the European Union (EU) has already invested in this field, still 4,000 RDs remain orphan of genetic diagnosis and causative gene identification. The genetic definition of RDs represents a prerequisite for being diagnosed, for having a robust prevention, for entering in a specific standard of care, and ultimately, for being included in clinical trials, often via personalized medicine. It is well established that biomarkers can offer a way to speed up research by understanding the pathophysiological mechanisms of diseases. In particular, biomarkers will offer an invaluable tool for monitoring disease progression, prognosis and response to drug treatment
Non-Coding RNAs in Muscle Dystrophies.
No full textncRNAs are the most recently identified class of regulatory RNAs with vital functions in gene expression regulation and cell development. Among the variety of roles they play, their involvement in human diseases has opened new avenues of research towards the discovery and development of novel therapeutic approaches. Important data come from the field of hereditary muscle dystrophies, like Duchenne muscle dystrophy and Myotonic dystrophies, rare diseases affecting 1 in 7000-15,000 newborns and is characterized by severe to mild muscle weakness associated with cardiac involvement. Novel therapeutic approaches are now ongoing for these diseases, also based on splicing modulation. In this review we provide an overview about ncRNAs and their behavior in muscular dystrophy and explore their links with diagnosis, prognosis and treatments, highlighting the role of regulatory RNAs in these pathologies
New instruments in molecular genetics for the prevention of X chromosome-linked muscular dystrophy
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Rett syndrome: lack of association with fragile site Xp22 and strategy for genetic mapping of X-linked new mutations
No full textThe hypothesis of X-linked new mutations which might cause early abortions of hemizygous male fetuses and a dominant phenotype in heterozygous females seems the most likely genetic explanation of the Rett syndrome. This hypothesis can be reconciled with the normal sex ratio observed in sibships of patients and with the rare recurrence of this disorder in sibs or half-sibs. The latter observation can be explained by germinal mosaicism in one of the two parents. Since in 14 patients no association was found with any particular fragile site or chromosome rearrangement, we propose to map the mutated gene (or loci) on the X through a strategy based on the reconstruction of X-linked haplotypes consisting of DNA polymorphisms, and on the identification of possible crossovers in affected sisters
Recurrent syncope as persistently isolated feature of transthyretin amyloidotic polyneuropathy
No full textIn transthyretin familial amyloid polyneuropathy (TTR-FAP), single clinical features rarely remain isolated and are usually accompanied by other symptoms. We describe a patient with TTR-FAP, who had recurrent episodes of syncope for 4 years as an overt and isolated symptom. Later, he experienced paresthesia in the hands, and impotence. Molecular analysis of the TTR gene revealed a Thr49Ala mutation. The unusual clinical presentation presents a diagnostic challenge
Effect of silicon particles and roughness on the surface treatments of cast aluminum alloys
No full textOver the last years, shape memory alloy materials have seen widespread usage in mechanical and automotive applications. The shape memory effect is the material’s ability to recover large mechanically-induced strains (up to 8%) by temperature increase. NiTi’s remarkable behavior is due to the presence of two material phases, the martensite stable at low temperature and the austenite stable at high temperature, and the presence of a thermoelastic martensitic transformation. By means of shape memory alloy materials, the component gains the ability to adjust itself to external stimuli automatically. Furthermore, the increasing attention on low energy consumption opens the way to a larger employment of such materials. In this context, a study dealing with power reduction in engine cooling fans, through integration of shape memory alloy wires, is presented. The goal of the paper is to highlight that shape memory alloys are successful, replacing mechanical/pneumatic devices, in the design of engine cooling fans. In particular they are able to actively modify their geometry according to operative conditions, in order to reduce the fan power absorption. NiTi shape memory alloy wires, pre-deformed in the martensitic state, are integrated in the blades’ structure and able to produce a macroscopic deformation when thermally activated. In this way, according to the temperature perceived by the NiTi wires, the blades’ configuration of the fan automatically modifies. As a consequence, the flow rate can be actively controlled with respect to the cooling requirement. Some relevant material properties, such as transformation temperatures, elastic moduli of the two material phases, maximum recoverable deformation and other constants, required for describing stress-temperature and strain-temperature dependences, have been determined experimentally. Thus, the design of a fan able to guarantee the necessary cooling flow rate in steady state conditions, but able to minimize power absorption when cooling conditions are not critical, has been performed. Comparing the simulated power absorptions of the fan in the critical and non critical conditions, it has been possible to quantify the improved cooling efficiency of the fan integrated with shape memory alloy wires
A New 3p14.2 Microdeletion in a Patient with Intellectual Disability and Language Impairment: Case Report and Review of the Literature
No full textInterstitial deletions of chromosome 3p are rare, and specific genotype-phenotype correlations cannot always be assessed. We report the case of a 3p14.2 proximal microdeletion in a 60-year-old female patient with mild intellectual disability, severe speech delay, and mild dysmorphism. An array-CGH analysis detected a 500-kb deletion in the 3p14.2 region, including FEZF2, CADPS, and PTPRG. FEZF2 and CADPS are known to network within the neurodevelopmental pathways. It is possible that their rearrangements lead to the phenotypic features observed in the patient, and therefore, they can be considered candidate genes responsible for such abnormalities
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