37 research outputs found

    Flexible Measures in Magnetic Active Shielding

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    Browse Conference Publications > Electromagnetic Field Computa ... Flexible measures in magnetic Active Shielding .This paper appears in: Electromagnetic Field Computation (CEFC), 2010 14th Biennial IEEE Conference on Date of Conference: 9-12 May 2010 Author(s): Formisano, A. Dip. Ing. dell'Inf., Seconda Univ. di Napoli, Aversa, Italy Lupoli, M.C. ; Martone, R. Page(s): 1 Product Type: Conference Publications 5481633 searchabstract .Abstract The reduction in protected regions of low frequency magnetic fields is a complex problem when the sources are not known. The paper proposes a procedure able to choose the best currents able to mitigate the disturbance field. The magnetic field is represented by suitable series of eigenfunctions in the domain of interest. The procedure includes a field identification step starting from a set of measurements and a current design step, possibly based on a preliminary design of specialized shimming coils sets

    Association of human leukocyte antigen-G 14 bp polymorphism with recurrent pregnancy loss in European countries: a meta-analysis of literature studies

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    Objective: To study the controversial association between human leukocyte antigen-G (HLA-G) 14 bp polymorphism and recurrent pregnancy loss (RPL). We performed a meta-analysis of studies in the literature that enrolled only women of European countries who experienced RPL spontaneously or after undergoing IVF.Design: Systematic meta-analysis of articles published before January 2019 pertaining the association of HLA-G genotype and RPL. The search was performed in electronic databases (PubMed, Web of Science, Scopus, EMBASE), without any language or publication year restriction.Setting: Academic hospitals and private clinics.Patient(s): Women who experienced RPL spontaneously or after undergoing IVF.Intervention(s): Genotyping of 14 bp polymorphism (insertion/insertion, insertion/deletion, deletion/deletion) in exon 8 of the HLA-G gene.Main Outcome Measure(s): Meta-analyses of the association between HLA-G 14 bp polymorphism in homozygosis (insertion/insertion) and heterozygosis (insertion/deletion) in women with RPL compared with pregnant controls with at least one live birth and no history of RPL.Result(s): Ten studies were analyzed comprising 1,091 women with RPL and 808 controls without RPL. Women with RPL showed significantly higher prevalence of HLA-G 14 bp insertion/insertion genotype compared with women without RPL (19.8% vs. 14.1%; odds ratio = 1.562; 95% confidence interval, 1.203-2.027), and this result was also confirmed when separately analyzing women with RPL during a spontaneous pregnancy (odds ratio, 1.562; 95% confidence interval, 1.203-2.027) and those undergoing IVF (odds ratio, 1.990; 95% confidence interval, 0.978-4.051).Conclusion(s): Women of European countries with the HLA-G 14 bp insertion/insertion genotype have a significantly higher prevalence of RPL. ((C) 2019 by American Society for Reproductive Medicine.

    Ret-mediated mitogenesis requires Src kinase activity

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    The proto-oncogene RET encodes a transmembrane growth neurotrophic receptor with tyrosine kinase (TK) activity. RET mutations are associated with several human neoplastic and nonneoplastic diseases, including thyroid papillary carcinoma, multiple endocrine neoplasia type 2 syndromes, and Hirschsprung's disease. Activation of receptor TKs results in the binding and activation of downstream signaling proteins, among which are nonreceptor TKs of the Src family. To test the involvement of c-Src in Ret-mediated signaling, we measured the levels of c-Src activity in NIH3T3 cells coexpressing Ret and the accessory GFR alpha-1 receptor or an epidermal growth factor receptor/Ret chimeric receptor when the cells were stimulated by glial cell line-derived neurotrophic factor or epidermal growth factor, respectively. Ret stimulation resulted in the activation of c-Src. We also measured the levels of Src kinase activity in cell lines expressing isoforms of the Ret receptor activated by different mutations. These cells showed higher Src kinase activity than the normal counterpart. Furthermore, we show that Ret is able to associate with the SH2 domain of Src in a phosphotyrosine-dependent fashion. Microinjection of a kinase inactive mutant of c-Src blocked Ret-mediated mitogenic effect. These experiments demonstrate that activated Ret is able to bind and stimulate c-Src kinase and that Src activation is essential for the mitogenic activity of Ret

    Exome sequencing identifies mutations in two genes encoding the LIM-proteins N-RAP and FHL1 in a BAG3 myofibrillar myopathy

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    Myofibrillar myopathies (MFMs) are genetically heterogeneous dystrophies characterized by disintegration of Z-disks and myofibrils. The characteristic degradation of myofibrils is followed by ectopic accumulation of multiple proteins. MFMs have been associated with mutations in genes encoding Z-disk or Z-disk-related proteins. Recently, BAG3 mutation has been described as causative of MFM. At now, the genetic basis of MFM with BAG 3 mutation is not fully traced. In this work we studied by exome sequencing a MFM female patient carrying the c.626 C>T (P209L) mutation in BAG3 gene. We found that this BAG3 variant is associated to mutations of N-RAP and FHL1 genes that encode muscle specific LIM domain containing proteins resulting in a decreased expression of NRAP and FLH1 accumulation in aggregates in affected skeletal muscle tissue. Molecular dynamic analysis of mutated FHL1 domain suggests a modification of its surface charge, which could explain its accumulation in muscle fibers. To our knowledge this is the first study reporting the simultaneous presence of genetic variants in three genes possibly causative of MFM: BAG3 and FHL1, already independently associated to MFMs, and NRAP linked for the first time to MFM

    Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

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    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

    Adomerus fuscipennis

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    Adomerus fuscipennis (Horváth, 1899), stat. resurr. (Figs 2 C; 3 C, D; 4 C, C′, D, D′) Sehirus fuscipennis Horváth, 1899: 83 [lectotype: France, Beaune]; Vidal, 1950: 43. Sehirus (Tritomegas) fuscipennis: Stichel, 1961: 676. Canthophorus fuscipennis: Fuente, 1972: 64. Canthophorus maculipes (non Mulsant & Rey, 1852): Aukema & Constant, 2016: 45. Adomerus maculipes (non Mulsant & Rey, 1852): Gapon, 2018: 222. Materials examined are mainly listed in Aukema & Constant (2016) and Gapon (2018); some specimens from the first paper were re-identified. Lectotype. France: Côte-d’Or: Beaune, ♂ (HNHM). Additional materials examined. France: Côte-d’Or: Beaune, 1 ♀ (RMNH), 20.VII.1966, 1 ♂, 25.VII, 1966, 1 ♂, 21.VII.1971, 5 ♀♀, G. Bank leg. (ZMAN [= RMNH]); Dijon, 1 ♂, 1 ♀ [on one pin], Puton leg. (RMNH); Pyrenées-Atlantiques, St Jean Pied de Portes, 6.IX.1950, 1 ♀, J.G.J. Kuiper leg. (ZMAN). Italy, Autonomous Province of Trento, Monte Brione, Lago di Garde, 1 ♀, O. Schmiedeknecht leg. (RMNH). Distribution (Fig. 1). France, Italy, Portugal, Spain (Aukema & Constant, 2016; Fuente, 1972; Gapon, 2018; Horváth, 1899; Lupoli & Dusoulier, 2015; Stichel, 1961). Note. Fokker (1894) recorded Sehirus maculipes from Monte Brione, collected by Schmiedeknecht; this is probably the same specimen that the first author dissected and identified as Adomerus fuscipennis (Monte Brione, Lago di Garde, 1 ♀, O. Schmiedeknecht leg.). We did not find reliable confirmation of the record of the species for Portugal (Stichel, 1961) in the literature, although its distribution there seems to be quite probable.Published as part of Aukema, Berend, Gapon, Dmitry & Heijerman, Theodoor, 2021, To the nomenclature of two species of the genus Adomerus (Heteroptera: Cydnidae), pp. 392-400 in Zootaxa 4969 (2) on page 397, DOI: 10.11646/zootaxa.4969.2.10, http://zenodo.org/record/474892

    Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.

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    PMCID: PMC3591419This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Parkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils
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