120 research outputs found

    Are Panel Unit Root Tests Useful for Real-Time Data?

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    With the development of real-time databases, N vintages are available for T observations instead of a single realization of the time series process. Although the use of panel unit root tests with the aim to gain in efficiency seems obvious, empirical and simulation results shown in this paper heavily mitigate the intuitive perspective.macroeconomics ;

    An intramolecular oxa-Michael reaction on α,β-unsaturated α-amino-δ-hydroxycarboxylic acid esters. Synthesis of functionalized 1,3-dioxanes

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    A highly diastereoselective intramolecular oxa-Michael reaction on α,β-unsaturated α-amino-δ-hydroxycarboxylic acid esters is presented; 1,3-dioxanes functionalized in positions 2,4 and 6 were obtained in good yields and with excellent selectivities; an experimental and computational study was carried out to understand the reaction course in terms of yields and selectivities. This reaction proceeds under mild reaction conditions using highly electrophilic aldehydes and ketones

    Body composition, muscle strength, and physical function of patients with Bethlem myopathy and Ullrich congenital muscular dystrophy.

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    Objective. To determine the contributions of body mass, adiposity, and muscularity to physical function and muscle strength in adult patients with Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). Materials and Methods. Evaluation involved one UCMD and 7 BM patients. Body composition was determined by body mass index (BMI) and dual-energy-X-ray-absorptiometry (DXA), muscle strength by dynamometry, physical function by the distance walked in 6 minutes (6MWD), forced vital capacity (FVC) by a spirometer. Results. Six participants were of normal weight and 2 overweight based on BMI; all were sarcopenic based on appendicular fat free mass index (AFFMI); and 7 were sarcopenic obese based on AFFMI and % fat mass. Average muscle strength was reduced below 50% of normal. The 6MWD was in BM patients 30% less than normal. FVC was reduced in 4 of the BM patients. Muscle strength had a good correlation with the physical function variables. Correlation between muscle strength and BMI was poor; it was very high with AFFMI. AFFMI was the best single explicator of muscle strength and physical function. Conclusion. Muscle mass determined by DXA explains most of the variability of the measures of muscle strength and physical function in patients with BM and UCMD

    Methylglyoxal Produced by Amyloid- Peptide-Induced Nitrotyrosination of Triosephosphate Isomerase Triggers Neuronal Death in Alzheimer’s Disease

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    Amyloid-β peptide (Aβ) aggregates induce nitro-oxidative stress, contributing to the characteristic neurodegeneration found in Alzheimer's disease (AD). One of the most strongly nitrotyrosinated proteins in AD is the triosephosphate isomerase (TPI) enzyme which regulates glycolytic flow, and its efficiency decreased when it is nitrotyrosinated. The main aims of this study were to analyze the impact of TPI nitrotyrosination on cell viability and to identify the mechanism behind this effect. In human neuroblastoma cells (SH-SY5Y), we evaluated the effects of Aβ42 oligomers on TPI nitrotyrosination. We found an increased production of methylglyoxal (MG), a toxic byproduct of the inefficient nitro-TPI function. The proapoptotic effects of Aβ42 oligomers, such as decreasing the protective Bcl2 and increasing the proapoptotic caspase-3 and Bax, were prevented with a MG chelator. Moreover, we used a double mutant TPI (Y165F and Y209F) to mimic nitrosative modifications due to Aβ action. Neuroblastoma cells transfected with the double mutant TPI consistently triggered MG production and a decrease in cell viability due to apoptotic mechanisms. Our data show for the first time that MG is playing a key role in the neuronal death induced by Aβ oligomers. This occurs because of TPI nitrotyrosination, which affects both tyrosines associated with the catalytic center

    HIPK2 and extrachromosomal histone H2B are separately recruited by Aurora-B for cytokinesis

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    Cytokinesis, the final phase of cell division, is necessary to form two distinct daughter cells with correct distribution of genomic and cytoplasmic materials. Its failure provokes genetically unstable states, such as tetraploidization and polyploidization, which can contribute to tumorigenesis. Aurora-B kinase controls multiple cytokinetic events, from chromosome condensation to abscission when the midbody is severed. We have previously shown that HIPK2, a kinase involved in DNA damage response and development, localizes at the midbody and contributes to abscission by phosphorylating extrachromosomal histone H2B at Ser14. Of relevance, HIPK2-defective cells do not phosphorylate H2B and do not successfully complete cytokinesis leading to accumulation of binucleated cells, chromosomal instability, and increased tumorigenicity. However, how HIPK2 and H2B are recruited to the midbody during cytokinesis is still unknown. Here, we show that regardless of their direct (H2B) and indirect (HIPK2) binding of chromosomal DNA, both H2B and HIPK2 localize at the midbody independently of nucleic acids. Instead, by using mitotic kinase-specific inhibitors in a spatio-temporal regulated manner, we found that Aurora-B kinase activity is required to recruit both HIPK2 and H2B to the midbody. Molecular characterization showed that Aurora-B directly binds and phosphorylates H2B at Ser32 while indirectly recruits HIPK2 through the central spindle components MgcRacGAP and PRC1. Thus, among different cytokinetic functions, Aurora-B separately recruits HIPK2 and H2B to the midbody and these activities contribute to faithful cytokinesis

    Congenital hip dysplasia treated by total hip arthroplasty using cementless tapered stem in patients younger than 50 years old: results after 12-years follow-up

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    Background Congenital hip dysplasia may lead to severe acetabular and femoral abnormalities that can make total hip arthroplasty a challenging procedure. We assessed a series of patients affected by developmental hip dysplasia treated with total hip arthroplasty using cementless tapered stem and here we report the outcomes at long-term follow-up. Materials and methods Twenty-eight patients (24 women and 4 men) aged between 44 and 50 years (mean 47 years) were observed. Clinical evaluation was rated with the Harris Hip Score. Radiographic evaluation consisted in standard anteroposterior and axial view radiographs of the hip. According to Crowe’s classification, 16 hips presented dysplasia grade 1, 14 grade 2, and 4 grade 3. All patients were treated with total hip arthroplasty using a cementless tapered stem (Wagner Cone Prosthesis). Six patients were operated bilaterally, with a totally of 34 hips operated. After surgery, the patients were clinically and radiographically checked at 3, 6, and 12 months and yearly thereafter until an average follow-up of 12 years (range 10–14 years). Results Average Harris Hip Score was 56 ± 9 (range 45–69) preoperatively, 90 ± 9 (range 81–100) 12 months after surgery, and 91 ± 8 (range 83–100) at last follow-up. Radiographic evaluation demonstrated excellent osteointegration of the implants. Signs of bone resorption were present in 6 hips, nevertheless no evidence of loosening was observed and none of the implants has been revised. Conclusions Even in dysplasic femur, the tapered stem allowed adequate stability and orientation of the implant. We consider tapered stem a suitable option for total hip arthroplasty in developmental hip dysplasia, also in case of young patients, thanks to the favourable long-term results
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