2,316 research outputs found

    Increased cerebral iron uptake in Wilson's disease: A (52)Fe-citrate PET study

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    Toxicity of abundant copper is the main cause of brain and liver tissue damage in patients with Wilson's disease (WD). However, there is also evidence of a disturbed iron metabolism in this genetically determined disorder. This PET study was undertaken to assess cerebral iron metabolism in WD patients. Methods: We used (52)Fe-citrate, which converts to (52)Fe-transferrin in blood plasma, to study basic pharmacokinetic features of the cerebral iron transport in 6 WD patients and in 16 healthy volunteers (control subjects). A 2-tissue-compartment model and multiple time graphic plotting were used to calculate (52)Fe-transferrin distribution volumes and transport rates. Results: Net iron uptake (Ki) from plasma into brain tissue was significantly (P <0.001) higher in WD patients (Ki [mean +/- SEM] = 15.1E-05 +/- 7.13E-05 [1/min]) than in healthy volunteers (Ki = 2.66E-05 +/- 0.351E-05 [1/min]). There was no difference of tracer iron distribution in the cerebral plasma volume between patients and healthy volunteers. Iron uptake values resulting from 2 methods to model PET data of patients and healthy volunteers were highly correlated (P <0.001). Conclusion: An abnormally increased cerebral (52)Fe-transferrin uptake was found in WD patients

    Modeling promoter search by E. coli RNA polymerase: One-dimensional diffusion in a sequence-dependent energy landscape

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    We present a biophysical model of promoter search by Escherichia coli RNA polymerase. We use an unconventional weight matrix derived from promoter strength data to extract the energy landscape common to a large set of known promoters. This exhibits a continuous strengthening of the binding energy when approaching the transcription start site from either side. During promoter search, the RNA polymerase slides along the DNA double helix (one-dimensional diffusion) after randomly binding to it. We discuss the possibility that the sliding has a sequence-dependent component, which implies that the energy landscape influences the movement with respect to speed, direction and efficiency. Based on this assumption, we relate the obtained energy landscape around the promoters to the one-dimensional diffusion of the RNA polymerase. Our analytical results suggest that the sequence-dependent random walk slows down and gets directed upon entering a region of 500 bp around the transcription start site, which significantly increases the efficiency of promoter search. These results may explain how the RNA polymerase is able to find the promoter in biologically relevant times out of a vast excess of non-target sites. Moreover, they provide evidence for a sequence-dependent component of one-dimensional diffusion. © 2009 Elsevier Ltd. All rights reserved.Barbi M, 2004, PHYS REV E, V70, DOI 10.1103-PhysRevE.70.041901; Barbi M, 2004, J BIOL PHYS, V30, P203, DOI 10.1023-B:JOBP.0000046728.51620.14; BERG OG, 1981, BIOCHEMISTRY-US, V20, P6929, DOI 10.1021-bi00527a028; Blainey PC, 2006, P NATL ACAD SCI USA, V103, P5752, DOI 10.1073-pnas.0509723103; Bruinsma RF, 2002, PHYSICA A, V313, P211, DOI 10.1016-S0378-4371(02)01038-5; Bustamante C, 1999, J BIOL CHEM, V274, P16665, DOI 10.1074-jbc.274.24.16665; Dombroski AJ, 1996, P NATL ACAD SCI USA, V93, P8858, DOI 10.1073-pnas.93.17.8858; ERIE DA, 1994, SCIENCE, V266, P1562, DOI 10.1126-science.7985026; Flyvbjerg H, 2006, NUCLEIC ACIDS RES, V34, P2550, DOI 10.1093-nar-gkl271; Gowers DM, 2005, P NATL ACAD SCI USA, V102, P15883, DOI 10.1073-pnas.0505378102; Gruber TM, 2003, ANNU REV MICROBIOL, V57, P441, DOI 10.1146-annurev.micro.57.030502.090913; Guthold M, 1999, BIOPHYS J, V77, P2284; Halford SE, 2004, NUCLEIC ACIDS RES, V32, P3040, DOI 10.1093-nar-gkh624; Harada Y, 1999, BIOPHYS J, V76, P709, DOI 10.1016-S0006-3495(99)77237-1; Hosid S, 2004, BMC MOL BIOL, V5, DOI 10.1186-1471-2199-5-14; HU L, 2007, ARXIV07091495V1CONDM; JELTSCH A, 1994, BIOCHEMISTRY-US, V33, P10215, DOI 10.1021-bi00200a001; KABATA H, 1993, SCIENCE, V262, P1561, DOI 10.1126-science.8248804; Kalodimos CG, 2004, SCIENCE, V305, P386, DOI 10.1126-science.1097064; Kiryu H, 2005, BIOINFORMATICS, V21, P1062, DOI 10.1093-bioinformatics-bti094; KOBAYASHI M, 1990, NUCLEIC ACIDS RES, V18, P7367, DOI 10.1093-nar-18.24.7367; MULLIGAN ME, 1985, J BIOL CHEM, V260, P3529; MURTHY KPN, 1989, PHYS REV A, V40, P2082, DOI 10.1103-PhysRevA.40.2082; PAGET MSB, 2003, GENOME BIOL, V4, P230; RICCHETTI M, 1988, P NATL ACAD SCI USA, V85, P4610, DOI 10.1073-pnas.85.13.4610; RIGGS AD, 1970, J MOL BIOL, V53, P401, DOI 10.1016-0022-2836(70)90074-4; Sakata-Sogawa K, 2004, P NATL ACAD SCI USA, V101, P14731, DOI 10.1073-pnas.0406441101; Salgado H, 2006, NUCLEIC ACIDS RES, V34, pD394, DOI 10.1093-nar-gkj156; Saxton MJ, 2007, BIOPHYS J, V92, P1178, DOI 10.1529-biophysj.106.092619; Sengupta AM, 2002, P NATL ACAD SCI USA, V99, P2072, DOI 10.1073-pnas.022388499; Shimamoto N, 1999, J BIOL CHEM, V274, P15293, DOI 10.1074-jbc.274.22.15293; Slutsky M, 2004, BIOPHYS J, V87, P4021, DOI 10.1529-biophysj.104.050765; Slutsky M, 2004, PHYS REV E, V69, DOI 10.1103-PhysRevE.69.061903; VONHIPPEL PH, 1989, J BIOL CHEM, V264, P675; VONHIPPEL PH, 1986, P NATL ACAD SCI USA, V83, P1608; Weindl J, 2007, NUCLEIC ACIDS RES, V35, P7003, DOI 10.1093-nar-gkm720; WEINDL J, 2007, P IEEE INT C COMM IC, P833; Widom J, 2005, P NATL ACAD SCI USA, V102, P16909, DOI 10.1073-pnas.0508686102; WINTER RB, 1981, BIOCHEMISTRY-US, V20, P6961, DOI 10.1021-bi00527a03021

    D-2 receptor binding in dopa-responsive dystonia

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    We have studied dopamine D-2 receptor binding by [C-11]raclopride positron emission tomography in 14 patients with dopa-responsive dystonia (DRD). Data were compared with 16 levodopa-treated patients with Parkinson's disease (PD) and 26 healthy controls. The results revealed an elevated [C-11]raclopride binding index in the putamen and caudate nucleus of DRD patients compared with controls as well as a significant elevation in the caudate nucleus compared with PD patients. The increase of [C-11]raclopride binding may be interpreted either as reduced tracer displacement by endogenous dopamine, or as an alteration of the receptor features due to chronic dopamine deficiency. The difference in [C-11]raclopride binding in DRD and PD patients in the caudate nucleus suggests that this structure may be of pathophysiological relevance in the presentation of the clinical features of both diseases

    Decoupling Livestock from Land Use through Industrial Feed Production Pathways

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    : One of the main challenges for the 21st century is to balance the increasing demand for high-quality proteins while mitigating environmental impacts. In particular, cropland-based production of protein-rich animal feed for livestock rearing results in large-scale agricultural land-expansion, nitrogen pollution, and greenhouse gas emissions. Here we propose and analyze the long-term potential of alternative animal feed supply routes based on industrial production of microbial proteins (MP). Our analysis reveals that by 2050, MP can replace, depending on socio-economic development and MP production pathways, between 10-19% of conventional crop-based animal feed protein demand. As a result, global cropland area, global nitrogen losses from croplands and agricultural greenhouse gas emissions can be decreased by 6% (0-13%), 8% (-3-8%), and 7% (-6-9%), respectively. Interestingly, the technology to industrially produce MP at competitive costs is directly accessible for implementation and has the potential to cause a major structural change in the agro-food system

    Glycosylation of Candida albicans cell wall proteins is critical for induction of innate immune responses and apoptosis of epithelial cells.

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    C. albicans is one of the most common fungal pathogen of humans, causing local and superficial mucosal infections in immunocompromised individuals. Given that the key structure mediating host-C. albicans interactions is the fungal cell wall, we aimed to identify features of the cell wall inducing epithelial responses and be associated with fungal pathogenesis. We demonstrate here the importance of cell wall protein glycosylation in epithelial immune activation with a predominant role for the highly branched N-glycosylation residues. Moreover, these glycan moieties induce growth arrest and apoptosis of epithelial cells. Using an in vitro model of oral candidosis we demonstrate, that apoptosis induction by C. albicans wild-type occurs in early stage of infection and strongly depends on intact cell wall protein glycosylation. These novel findings demonstrate that glycosylation of the C. albicans cell wall proteins appears essential for modulation of epithelial immunity and apoptosis induction, both of which may promote fungal pathogenesis in vivo

    Benchmarking optimization methods for parameter estimation in large kinetic models

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    Software to reproduce the results presented in the paper "Benchmarking optimization methods for parameter estimation in large kinetic models". It includes two MATLAB toolboxes: AMICI and MEIGO, as well as MATLAB code to define the optimizations and to report the results as figures, tables, and summary files.</p

    The Amplifier - v. 8,(a-12) no. 12

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    In this issue...Ingersoll-Rand Company, Joseph Weindl, Sports Staff, M Club, Mother\u27s Tea, religious history, Al Huizanga, Photo Club, mining engineeringhttps://digitalcommons.mtech.edu/amplifier/1118/thumbnail.jp
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