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Search Results: 1 - 10 of 31809 matches for " Olivia Thomas "
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Interactions among the A and T Units of an ECF-Type Biotin Transporter Analyzed by Site-Specific Crosslinking
Olivia Neubauer, Christin Reiffler, Laura Behrendt, Thomas Eitinger
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0029087
Abstract: Energy-coupling factor (ECF) transporters are a huge group of micronutrient importers in prokaryotes. They are composed of a substrate-specific transmembrane protein (S component) and a module consisting of a moderately conserved transmembrane protein (T component) and two ABC ATPase domains (A components). Modules of A and T units may be dedicated to a specific S component or shared by many different S units in an organism. The mode of subunit interactions in ECF transporters is largely unknown. BioMNY, the focus of the present study, is a biotin transporter with a dedicated AT module. It consists of the S unit BioY, the A unit BioM and the T unit BioN. Like all T units, BioN contains two three-amino-acid signatures with a central Arg residue in a cytoplasmic helical region. Our previous work had demonstrated a central role of the two motifs in T units for stability and function of BioMNY and other ECF transporters. Here we show by site-specific crosslinking of pairs of mono-cysteine variants that the Ala-Arg-Ser and Ala-Arg-Gly signatures in BioN are coupling sites to the BioM ATPases. Analysis of 64 BioN-BioM pairs uncovered interactions of both signatures predominantly with a segment of ~13 amino acid residues C-terminal of the Q loop of BioM. Our results further demonstrate that portions of all BioN variants with single Cys residues in the two signatures are crosslinked to homodimers. This finding may point to a dimeric architecture of the T unit in BioMNY complexes.
Persistence and Memory in Patchwork Dynamics for Glassy Models
Creighton K. Thomas,Olivia L. White,A. Alan Middleton
Physics , 2007, DOI: 10.1103/PhysRevB.77.092415
Abstract: Slow dynamics in disordered materials prohibits direct simulation of their rich nonequilibrium behavior at large scales. "Patchwork dynamics" is introduced to mimic relaxation over a very broad range of time scales by equilibrating or optimizing directly on successive length scales. This dynamics is used to study coarsening and to replicate memory effects for spin glasses and random ferromagnets. It is also used to find, with high confidence, exact ground states in large or toroidal samples.
GABAA Receptors Containing the α2 Subunit Are Critical for Direction-Selective Inhibition in the Retina
Olivia Nicola Auferkorte, Tom Baden, Sanjeev Kumar Kaushalya, Nawal Zabouri, Uwe Rudolph, Silke Haverkamp, Thomas Euler
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0035109
Abstract: Far from being a simple sensor, the retina actively participates in processing visual signals. One of the best understood aspects of this processing is the detection of motion direction. Direction-selective (DS) retinal circuits include several subtypes of ganglion cells (GCs) and inhibitory interneurons, such as starburst amacrine cells (SACs). Recent studies demonstrated a surprising complexity in the arrangement of synapses in the DS circuit, i.e. between SACs and DS ganglion cells. Thus, to fully understand retinal DS mechanisms, detailed knowledge of all synaptic elements involved, particularly the nature and localization of neurotransmitter receptors, is needed. Since inhibition from SACs onto DSGCs is crucial for generating retinal direction selectivity, we investigate here the nature of the GABA receptors mediating this interaction. We found that in the inner plexiform layer (IPL) of mouse and rabbit retina, GABAA receptor subunit α2 (GABAAR α2) aggregated in synaptic clusters along two bands overlapping the dendritic plexuses of both ON and OFF SACs. On distal dendrites of individually labeled SACs in rabbit, GABAAR α2 was aligned with the majority of varicosities, the cell's output structures, and found postsynaptically on DSGC dendrites, both in the ON and OFF portion of the IPL. In GABAAR α2 knock-out (KO) mice, light responses of retinal GCs recorded with two-photon calcium imaging revealed a significant impairment of DS responses compared to their wild-type littermates. We observed a dramatic drop in the proportion of cells exhibiting DS phenotype in both the ON and ON-OFF populations, which strongly supports our anatomical findings that α2-containing GABAARs are critical for mediating retinal DS inhibition. Our study reveals for the first time, to the best of our knowledge, the precise functional localization of a specific receptor subunit in the retinal DS circuit.
Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?
Olga Samsonova,Christian Pfeiffer,Markus Hellmund,Olivia M. Merkel,Thomas Kissel
Polymers , 2011, DOI: 10.3390/polym3020693
Abstract: The aim of this study was to investigate non-viral pDNA carriers based on diblock-copolymers consisting of poly(2-(dimethyl amino)ethyl methacrylate) (pDMAEMA) and poly(2-hydroxyethyl methacrylate) (pHEMA). Specifically the block-lengths and molecular weights were varied to determine the minimal requirements for transfection. Such vectors should allow better transfection at acceptable toxicity levels and the entire diblock-copolymer should be suitable for renal clearance. For this purpose, a library of linear poly(2-(dimethyl amino)ethyl methacrylate- block-poly(2-hydroxyl methacrylate) (pDMAEMA -block-pHEMA) copolymers was synthesized via RAFT (reversible addition-fragmentation chain transfer) polymerization in a molecular weight (Mw) range of 17–35.7 kDa and analyzed using 1H and 13C NMR (nuclear magnetic resonance), ATR (attenuated total reflectance), GPC (gel permeation chromatography) and DSC (differential scanning calorimetry). Copolymers possessing short pDMAEMA-polycation chains were 1.4–9.7 times less toxic in vitro than polyethylenimine (PEI) 25 kDa, and complexed DNA into polyplexes of 100–170 nm, favorable for cellular uptake. The DNA-binding affinity and polyplex stability against competing polyanions was comparable with PEI 25 kDa. The zeta-potential of polyplexes of pDMAEMA-grafted copolymers remained positive (+15–30 mV). In comparison with earlier reported low molecular weight homo pDMAEMA vectors, these diblock-copolymers showed enhanced transfection efficacy under in vitro conditions due to their lower cytotoxicity, efficient cellular uptake and DNA packaging. The homo pDMAEMA 115 (18.3 kDa) self-assembled with DNA into small positively charged polyplexes, but was not able to transfect cells. The grafting of 6 and 57 repeating units of pHEMA (0.8 and 7.4 kDa) to pDMAEMA 115 increased the transfection efficacy significantly, implying a crucial impact of pHEMA on vector-cell interactions. The intracellular trafficking, in vivo transfection efficacy and kinetics of low molecular weight pDMAEMA -block-pHEMA are subject of ongoing studies.
Crosstalks between integrin alpha 5 and IGF2/IGFBP2 signalling trigger human bone marrow-derived mesenchymal stromal osteogenic differentiation
Zahia Hamidouche, Olivia Fromigué, Jochen Ringe, Thomas H?upl, Pierre J Marie
BMC Cell Biology , 2010, DOI: 10.1186/1471-2121-11-44
Abstract: Microarray analysis and validation experiments showed that the expression of IGF2 and IGFBP2 was increased together with integrin alpha5 (ITGA5) during dexamethasone-induced osteoblast differentiation in human MSCs. This effect was functional since we found that IGF2 and IGFBP2 enhanced the expression of osteoblast phenotypic markers and in vitro osteogenic capacity of hMSCs. Interestingly, we showed that downregulation of endogenous ITGA5 using specific shRNA decreased IGF2 and IGFBP2 expression in hMSCs. Conversely, ITGA5 overexpression upregulated IGF2 and IGFBP2 expression in hMSCs, which indicates tight crosstalks between these molecules. Consistent with this concept, activation of endogenous ITGA5 using a specific antibody that primes the integrin, or a peptide that specifically activates ITGA5 increased IGF2 and IGFBP2 expression in hMSCs. Finally, we showed that pharmacological inhibition of FAK/ERK1/2-MAPKs or PI3K signalling pathways that are enhanced by ITGA5 activation, blunted IGF2 and IGFBP2 expression in hMSCs.The results show that ITGA5 is a key mediator of IGF2 and IGFBP2 expression that promotes osteoblast differentiation in human MSCs, and reveal that crosstalks between ITGA5 and IGF2/IGFBP2 signalling are important mechanisms that trigger osteogenic differentiation in human bone marrow derived mesenchymal stromal cells.Mesenchymal stromal cells (MSCs) can differentiate into chondroblasts, adipocytes or osteoblasts under appropriate stimulation [1-3]. Adult human MSCs (hMSCs) are therefore an important source for tissue repair and therapy in regenerative medicine [4,5]. Expanding the osteogenic capacity of hMSCs is thus of major interest for improving the osteogenic potential of hMSCs for optimal bone regeneration [6]. The osteogenic differentiation of MSCs is characterized by the expression of timely expressed genes such as Runx2, alkaline phosphatase (ALP) and type I collagen (Col1A1) followed by extracellular matrix mineralization [7,8]. Severa
Characterization of the Metabolic Syndrome in a Multi-Ethnic Sample of Children: Is it Useful?
Krista Casazza, Pedro del Corral, Olivia Thomas, Akilah Dulin-Keita, Barbara A. GowerJose R. Fernandez
The Open Obesity Journal , 2010, DOI: 10.2174/1876823700901010001]
Abstract: The pathophysiological relevance of the metabolic syndrome is not currently understood, particularly when attempting to apply the diagnosis to children with varying degrees of adiposity or from ethnically diverse populations. The aim of this study was to evaluate the applicability of the metabolic syndrome characterization when the associations are explored by sex, race/ethnicity, and weight status. Participants were 247 multi-ethnic (African American (AA); n=90; European American (EA); n=102; Hispanic American (HA); n=55) children aged 7-12y. Anthropometric measurements, body composition, blood pressure and fasting blood samples were obtained. Approximately 9% of the children met the criteria for a clinical diagnosis of the metabolic syndrome. There were no differences in prevalence by sex, nor were there differences between girls and boys for mean values of each component. However, there were ethnic differences in characterization of having the metabolic syndrome, with HA more likely to meet the criteria. HA had greater waist circumference, higher triglyceride and glucose concentration and lower HDL-C concentration; whereas AA had higher blood pressure. Weight status was also positively associated with mean values for each component. Due to inherent variations in body composition, physiology and genetics, the usefulness of a characterization of the metabolic syndrome may be limited in the pediatric population.
NSD1 Mitigates Caspase-1 Activation by Listeriolysin O in Macrophages
Olivia S. Sakhon, Kaitlin A. Victor, Anthony Choy, Tokuji Tsuchiya, Thomas Eulgem, Joao H. F. Pedra
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075911
Abstract: Mammals and plants share pathogen-sensing systems named nod-like receptors (NLRs). Some NLRs form the inflammasome, a protein scaffold that regulates the secretion of interleukin (IL)-1β and IL-18 by cleaving catalytically inactive substrates into mature cytokines. Here, we show an immune conservation between plant and mammalian NLRs and demonstrate that the murine nuclear receptor binding SET domain protein 1 (NSD1), a protein that bears similarity to the NLR regulator enhanced downy mildew 2 (EDM2) in Arabidopsis, diminishes caspase-1 activity during extracellular stimulation with Listeria monocytogenes listeriolysin O (LLO). EDM2 is known to regulate plant developmental processes, whereas NSD1 is associated with developmental disorders. We observed that NSD1 neither affects nuclear factor (NF)-κB signaling nor regulates NLRP3 inflammasome gene expression at the chromatin, transcriptional or translational level during LLO stimulation of macrophages. Silencing of Nsd1 followed by LLO stimulation led to increased caspase-1 activation, enhanced post-translational maturation of IL-1β and IL-18 and elevated pyroptosis, a form of cell death associated with inflammation. Furthermore, treatment of macrophages with LLOW492A, which lacks hemolytic activity due to a tryptophan to alanine substitution in the undecapeptide motif, indicates the importance of functional LLO for NSD1 regulation of the NLRP3 inflammasome. Taken together, our results indicate that NLR signaling in plants may be used for gene discovery in mammals.
Chungará (Arica) , 2010, DOI: 10.4067/S0717-73562010000100031
Abstract: sixteenth century sources associate the notion of labour in the andes with that of enjoyment, while most colonial spaniards and modern anthropologists see it as obligatory, ignoring its ritual dimensions. generally speaking, western theorists of labour, whether marxist or not, link labour and production with alienation. drawing on her fieldwork experience, the author notes that there is no aymara word for labour in general. more important is the purpose and beneficiary of labour. andeans not only value labour aimed at strengthening their own social networks, but more specifically labour that benefits the community to which they belong. the andean ethic of labour therefore leads it to be considered as a blessing, in opposition to judaeo-christian ways of considering it as a curse.
Pensadoras de peso: o pensamento de Judith Butler e Adriana Cavarero
Guaraldo, Olivia;
Revista Estudos Feministas , 2007, DOI: 10.1590/S0104-026X2007000300010
Abstract: the work presents the standpoint of two important contemporary feminist philosophers, adriana cavarero and judith butler, on subjectivity and relationality, showing how both moved away from the specific feminism motif in order to deepen and broaden their reflection on politics and ethics. calling tradition into question, cavarero agrees neither with the metaphysical binary, nor with the post-modern impersonality, combining a feminist and the arendtian perspectives of the subjectivity based on relationality. contrary to cavarero's thought, though, under butler's deconstructionist standpoint language shapes body and identity. subjectivity is "trapped" into social norms and values. both butler and cavarero rethink subjectivity based on relationality, that is, displacing politics from the immune individual and reallocating it on the vulnerable individual in relation with the other and with the social rules and values imposed on them.
Evaluación de un Sistema Discontinuo de Biodigestión Anaerobia para el tratamiento de desechos avicolas
Revista de la Facultad de Ingeniería Universidad Central de Venezuela , 2005,
Abstract: in the present study, carried out in guanare (venezuela), in the period between november 1998 and march 1999, the application of an anaerobic digestion process in a discontinuous flow (batch) system was evaluated for the treatment of hen manure and rice hulls, with the purpose of stabilization, biogas production and pathogen control. the main biogas production (0,249 m3/m3d) was obtained with a combination of the evaluated materials, in a retention time of 60 days. in the bacteriological study, we found bacteria of the escherichia, proteus, enterobacter and klebsiella groups. salmonella was not found. the parasitological study reported ascaridia, trichostrongylus, heterakis and eimeria. among the conclusions reached, we emphasize that the anaerobic mesophilic process exercises scarce control over bacteria of the enterobacteriaceae group, and no control was observed over the parasite eggs found. therefore, further studies into these aspects is considered important, so as to find alternatives of control and recommendations for a safe handling of manure.
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