Journals
2012 EN
Gunji Takahiro · Hayashi Yuki · Komatsubara Akemi
+2 more
Acid‐catalyzed controlled hydrolytic polycondensation of tetraethoxysilane (TEOS) and tetramethoxysilane (TMOS) provided polyalkoxysiloxanes PEOS and PMOS, with high molecular weight of 1100–12 000 or 2700–31 000, respectively. They were stable to self‐condensation, soluble in organic solvents, and especially characterized by high silica content of up to 62% (PEOS) and 72% (PMOS). Flexible and transparent free‐standing films with tensile strength of 1.6–5.2 MPa (PEOS) or 3.6–11.8 MPa (PMOS) were prepared by heating polyalkoxysilanes at 80°C for one to several days. They are also regarded to be a potential precursor for coatings and binders. Copyright © 2012 John Wiley & Sons, Ltd.
Journals
2012 EN
Ishikawa Masahiro · Ito Hiromu · Akiyoshi Miki
+12 more
Objective To determine whether lectin‐like oxidized low‐density lipoprotein (ox‐LDL) receptor 1 (LOX‐1) and the soluble form of LOX‐1 (sLOX‐1) are novel target molecules for the diagnosis and treatment of rheumatoid arthritis (RA). Methods Expression of ox‐LDL and LOX‐1 proteins in human RA synovium was evaluated by immunohistochemistry. Human RA fibroblast‐like synoviocytes (FLS) were assessed for ox‐LDL–induced expression of LOX‐1 and ox‐LDL–induced production of matrix metalloproteinase 1 (MMP‐1) and MMP‐3. Levels of sLOX‐1 in the plasma and synovial fluid of patients with RA, compared with patients with osteoarthritis (OA), were determined by a specific chemiluminescence enzyme‐linked immunoassay. In animal experiments, ox‐LDL was injected into the knee joints of mice, with or without an anti–LOX‐1 neutralizing antibody or sLOX‐1, and the severity of arthritis was analyzed by histology and immunohistochemistry. Results Oxidized LDL and LOX‐1 proteins were detected in the RA synovial tissue. Levels of MMP‐1 and MMP‐3 were enhanced by stimulation of RA FLS with ox‐LDL, and the production of both MMPs was inhibited by blockade of the ox‐LDL–LOX‐1 interaction with the anti–LOX‐1 neutralizing antibody or sLOX‐1. Levels of sLOX‐1 in the plasma and synovial fluid of RA patients were significantly higher than those in OA patients and healthy controls and were positively correlated with inflammation markers and the extent of RA disease activity. In the knees of mice, blockade of the ox‐LDL–LOX‐1 interaction suppressed arthritic changes and reduced the expression of MMP‐3 induced by ox‐LDL. Conclusion These findings strongly indicate that sLOX‐1 is a novel biomarker that may be useful for the diagnosis of RA and for the evaluation of disease activity in RA. Furthermore, the results suggest that LOX‐1 may be a potent therapeutic target for RA.
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Journals
2012 EN
Bernardi Andrea · Giarola Sara · Bezzo Fabrizio
Water consumption has become a serious concern in renewable fuels production. This paper proposes a framework to address sustainable transport systems design where both environmental (i.e. carbon and water footprints) and economic performances are taken into account along the bioethanol supply chain. A multi‐objective Mixed Integer Linear Programming modeling framework supporting strategic design and planning decisions for multi‐period and multi‐echelon upstream ethanol supply chains is developed. Hybrid biofuel production networks, where both corn grain and stover are used as suitable feedstocks, are optimized according to several features, involving technology selection and by‐products end‐use option. A case study is presented referring to the emerging Italian biofuels market. Results show the effectiveness of mathematical‐programming‐based tools to optimal design of biofuels supply chains, assessing the pros and cons of alternative configurations and, thus, allowing investors to drive planning decisions. © 2012 Society of Chemical Industry and John Wiley & Sons, Ltd
Journals
2012 EN
Fan Jin · Bernardi Silvia · Dam Nicholas T.
+10 more
Attentional dysfunction is among the most consistent observations of autism spectrum disorders ( ASD ). However, the neural nature of this deficit in ASD is still unclear. In this study, we aimed to identify the neurobehavioral correlates of attentional dysfunction in ASD . We used the A ttention N etwork T est‐ R evised and functional magnetic resonance imaging to examine alerting, orienting, and executive control functions, as well as the neural substrates underlying these attentional functions in unmedicated, high‐functioning adults with ASD ( n = 12) and matched healthy controls ( HC , n = 12). Compared with HC , individuals with ASD showed increased error rates in alerting and executive control, accompanied by lower activity in the mid‐frontal gyrus and the caudate nucleus for alerting, and by the absence of significant functional activation in the anterior cingulate cortex ( ACC ) for executive control. In addition, greater behavioral deficiency in executive control in ASD was correlated with less functional activation of the ACC . These findings of behavioral and neural abnormalities in alerting and executive control of attention in ASD may suggest core attentional deficits, which require further investigation.
Journals
2012 EN
Nisic Filippo · Speciale Gaetano · Bernardi Anna
A highly stereoselective synthesis of α‐ or β‐glycofuranosyl amides based on the traceless Staudinger ligation of glycofuranosyl azides of the galacto , ribo , and arabino series with 2‐diphenylphosphanyl‐phenyl esters has been developed. Both α‐ and β‐isomers can be obtained with excellent selectivity from a common, easily available precursor. The process does not depend on the anomeric configuration of the starting azide but appears to be controlled by the C2 configuration and by the protection/deprotection state of the substrates. A mechanistic interpretation of the results, supported by 31 P NMR experiments, is offered and merged with our previous mechanistic analysis of pyranosyl azide ligation reactions.
Journals
2012 EN
Scaglioni Pier Paolo · Rabellino Andrea · Yung Thomas M.
+6 more
Expression of oncogenic K‐RAS in primary cells elicits oncogene‐induced cellular senescence (OIS), a form of growth arrest that potently opposes tumourigenesis. This effect has been largely attributed to transcriptional mechanisms that depend on the p53 tumour suppressor protein. The PML tumour suppressor was initially identified as a component of the PML‐RARα oncoprotein of acute promyelocytic leukaemia (APL). PML, a critical OIS mediator, is upregulated by oncogenic K‐RAS in vivo and in vitro . We demonstrate here that oncogenic K‐RAS induces PML protein upregulation by activating the RAS/MEK1/mTOR/eIF4E pathway even in the absence of p53. Under these circumstances, PML mRNA is selectively associated to polysomes. Importantly, we find that the PML 5′ untranslated mRNA region plays a key role in mediating PML protein upregulation and that its presence is essential for an efficient OIS response. These findings demonstrate that upregulation of PML translation plays a central role in oncogenic K‐RAS‐induced OIS. Thus, selective translation initiation plays a critical role in tumour suppression with important therapeutic implications for the treatment of solid tumours and APL.
Journals
2012 EN
Bernardi Mauro · Caraceni Paolo · Navickis Roberta J.
+1 more
Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites, as compared with no treatment. Treatment alternatives to albumin, such as artificial colloids and vasoconstrictors, have been widely investigated. The aim of this meta‐analysis was to determine whether morbidity and mortality differ between patients receiving albumin versus alternative treatments. The meta‐analysis included randomized trials evaluating albumin infusion in patients with tense ascites. Primary endpoints were postparacentesis circulatory dysfunction, hyponatremia, and mortality. Eligible trials were sought by multiple methods, including computer searches of bibliographic and abstract databases and the Cochrane Library. Results were quantitatively combined under a fixed‐effects model. Seventeen trials with 1,225 total patients were included. There was no evidence of heterogeneity or publication bias. Compared with alternative treatments, albumin reduced the incidence of postparacentesis circulatory dysfunction (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.27‐0.55). Significant reductions in that complication by albumin were also shown in subgroup analyses versus each of the other volume expanders tested (e.g., dextran, gelatin, hydroxyethyl starch, and hypertonic saline). The occurrence of hyponatremia was also decreased by albumin, compared with alternative treatments (OR, 0.58; 95% CI, 0.39‐0.87). In addition, mortality was lower in patients receiving albumin than alternative treatments (OR, 0.64; 95% CI, 0.41‐0.98). Conclusions: This meta‐analysis provides evidence that albumin reduces morbidity and mortality among patients with tense ascites undergoing large‐volume paracentesis, as compared with alternative treatments investigated thus far. (H EPATOLOGY 2012)
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Journals
2012 EN
Pinotti Mirko · Caruso Pierpaolo · Canella Alessandro
+6 more
We investigated the spontaneous ribosome readthrough, virtually unexplored in genes encoding secreted proteins, over coagulation F9 nonsense mutations. Expression of recombinant factor IX (FIX) in eukaryotic cells demonstrated appreciable levels of secreted FIX molecules for the mutations p.R162* (5 ± 0.3% of rFIX‐wt antigen levels), p.R294* (3.1 ± 1.1%) and p.R298* (2.5 ± 0.7%), but not for the p.L103*. Western blotting revealed a large proportion of truncated molecules, which correlated with small amounts of full‐length FIX (rFIX‐162*, ∼0.5%; rFIX‐294*; and rFIX‐298*, ∼0.2%). Western blotting of plasma from FIX deficient (Hemophilia B) patients revealed traces of full‐length FIX for the p.R294* and p.R298* mutations, but not for the p.L103* mutation that triggered major FIX mRNA decay. The detection of full‐length proteins has clinical implication, particularly for post‐therapeutic immunological complications in Hemophilia. Data in patients' plasma and in vitro, obtained in the proper protein context, support a ribosome readthrough gradient, consistent with its predicted determinants of efficiency. Hum Mutat 33:1373–1376, 2012. © 2012 Wiley Periodicals, Inc.
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Journals
2012 EN
Sanchez Anthony MJ · Csibi Alfredo · Raibon Audrey
+4 more
In skeletal muscle, protein levels are determined by relative rates of protein synthesis and breakdown. The balance between synthesis and degradation of intracellular components determines the overall muscle fiber size. AMP‐activated protein kinase (AMPK), a sensor of cellular energy status, was recently shown to increase myofibrillar protein degradation through the expression of MAFbx and MuRF1. In the present study, the effect of AMPK activation by AICAR on autophagy was investigated in muscle cells. Our results show that FoxO3a transcription factor activation by AMPK induces the expression of the autophagy‐related proteins LC3B‐II, Gabarapl1, and Beclin1 in primary mouse skeletal muscle myotubes and in the Tibialis anterior (TA) muscle. Time course studies reveal that AMPK activation by AICAR leads to a transient nuclear relocalization of FoxO3a followed by an increase of its cytosolic level. Moreover, AMPK activation leads to the inhibition of mTORC1 and its subsequent dissociation of Ulk1, Atg13, and FIP200 complex. Interestingly, we identify Ulk1 as a new interacting partner of AMPK in muscle cells and we show that Ulk1 is associated with AMPK under normal conditions and dissociates from AMPK during autophagy process. Moreover, we find that AMPK phosphorylates FoxO3a and Ulk1. In conclusion, our data show that AMPK activation stimulates autophagy in skeletal muscle cells through its effects on the transcriptional function of FoxO3a and takes part in the initiation of autophagosome formation by interacting with Ulk1. Here, we present new evidences that AMPK plays a crucial role in the fine tuning of protein expression programs that control skeletal muscle mass. J. Cell. Biochem. 113: 695–710, 2012. © 2011 Wiley Periodicals, Inc.
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Journals
2012 EN
Sabatelli P. · Palma E. · Angelin A.
+9 more
Collagen VI myopathies (Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM), and myosclerosis myopathy) share a common pathogenesis, that is, mitochondrial dysfunction due to deregulation of the permeability transition pore (PTP). This effect was first identified in the Col6a1 −/− mouse model and then in muscle cell cultures from UCMD and BM patients; the normalizing effect of cyclosporin A (CsA) confirmed the pathogenic role of PTP opening. In order to determine whether mitochondrial performance can be used as a criterion for inclusion in clinical trials and as an outcome measure of the patient response to therapy, it is mandatory to establish whether mitochondrial dysfunction is conserved in primary cell cultures from UCMD and BM patients. In this study we report evidence that mitochondrial dysfunction and the consequent increase of apoptotic rate can be detected not only, as previously reported, in muscle, but also in fibroblast cell cultures established from muscle biopsies of collagen VI‐related myopathic patients. However, the mitochondrial phenotype is no longer maintained after nine passages in culture. These data demonstrate that the dire consequences of mitochondrial dysfunction are not limited to myogenic cells, and that this parameter can be used as a suitable diagnostic criterion, provided that the cell culture conditions are carefully established. J. Cell. Physiol. 227: 2927–2935, 2012. © 2011 Wiley Periodicals, Inc.
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