180 research outputs found

    Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

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    Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

    Quantitative trait locus mapping associated with earliness and fruit weight in tomato

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    ABSTRACT The flowering time is regarded as an important factor that affects yield in various crops. In order to understand how the molecular basis controlling main components of earliness in tomato (Solanum lycopersicum L.), and to deduce whether the correlation between fruit weight, days to flowering and seed weight, is caused by pleiotropic effects or genetic linkage, a QTLs analysis was carried out using an F2 interspecific population derived from the cross of S. lycopersicum and S. pimpinellifolium. The analysis revealed that most of the components related to earliness were independent due to the absence of phenotypic correlation and lack of co-localization of their QTLs. QTLs affecting the flowering time showed considerable variation over time in values of explained phenotypic variation and average effects, which suggested dominance becomes more evident over time. The path analysis showed that traits such as days to flowering, seed weight, and length of the first leaf had a significant effect on the expression of fruit weight, confirming that their correlations were due to linkage. This result was also confirmed in two genomic regions located on chromosomes 1 and 4, where despite showing high co-localization of QTLs associated to days to flowering, seed weight and fruit weight, the presence and absence of epistasis in dfft1.1 × dftt4.1 and fw1.1 × fw4.1, suggested that the linkage was the main cause of the co-localization

    Measurement of differential cross sections for Z bosons produced in association with charm jets in pp collisions at √s = 13 TeV

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    Search for light pseudoscalar boson pairs produced from decays of the 125 GeV Higgs boson in final states with two muons and two nearby tracks in pp collisions at √s = 13 TeV

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    Search for MSSM Higgs bosons decaying to μ⁺μ⁻ in proton-proton collisions at √s = 13 TeV

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    Search for heavy resonances decaying to a top quark and a bottom quark in the lepton+jets final state in proton–proton collisions at 13 TeV

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    A search is presented for narrow heavy resonances decaying to a top quark and a bottom quark using data collected by the CMS experiment at √s = 13TeV in 2016. The data set analyzed corresponds to an integrated luminosity of 35.9 fb−1. Final states that include a single lepton (e, μ), multiple jets, and missing transverse momentum are analyzed. No evidence is found for the production of a W′ boson, and the production of right-handed W′ bosons is excluded at 95% confidence level for masses up to 3.6 TeV depending on the scenario considered. Exclusion limits for W′ bosons are also presented as a function of their coupling strength to left- and right-handed fermions. These limits on a W′ boson decaying via a top and a bottom quark are the most stringent published to date

    Search for Higgs and Z boson decays to J/ψ or Y pairs in the four-muon final state in proton-proton collisions at √s = 13 TeV

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    Observation of the Higgs boson decay to a pair of τ leptons with the CMS detector

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    Observation of nuclear modifications in W±^{±} boson production in pPb collisions at √S^{S}NN = 8.16 TeV

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