bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracellular and extracellular T1 and T2 relaxivities of magneto‐optical nanoparticles at experimental high fields
Authors: Klug Gert , Kampf Thomas , Bloemer Steffen , Bremicker Johannes , Ziener Christian H. , Heymer Andrea , Gbureck Uwe , Rommel Eberhard , Nöth Ulrich , Schenk Wolfdieter A. , Jakob Peter M. , Bauer Wolfgang R. 
Published: July 2010

AbstractThis study reports the T1 and T2 relaxation rates of rhodamine‐labeled anionic magnetic nanoparticles determined at 7, 11.7, and 17.6 T both in solution and after cellular internalization. Therefore cells were incubated with rhodamine‐labeled anionic magnetic nanoparticles and were prepared at decreasing concentrations. Additionally, rhodamine‐labeled anionic magnetic nanoparticles in solution were used for extracellular measurements. T1 and T2 were determined at 7, 11.7, and 17.6 T. T1 times were determined with an inversion‐recovery snapshot‐flash sequence. T2 times were obtained from a multispin‐echo sequence. Inductively coupled plasma‐mass spectrometry was used to determine the iron content in all samples, and r1 and r2 were subsequently calculated. The results were then compared with cells labeled with AMI‐25 and VSOP C‐200. In solution, the r1 and r2 of rhodamine‐labeled anionic magnetic nanoparticles were 4.78/379 (7 T), 3.28/389 (11.7 T), and 2.00/354 (17.6 T). In cells, the r1 and r2 were 0.21/56 (7 T), 0.19/37 (11.7 T), and 0.1/23 (17.6 T). This corresponded to an 11‐ to 23‐fold decrease in r1 and an 8‐ to 15‐fold decrease in r2. A decrease in r1 was observed for AMI‐25 and VSOP C‐200. AMI‐25 and VSOP exhibited a 2‐ to 8‐fold decrease in r2. In conclusion, cellular internalization of iron oxide nanoparticles strongly decreased their T1 and T2 potency. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Modeling magnitude and phase neuronal current MRI signal dependence on echo time
Authors: Luo Qingfei , Gao Jia‐Hong 
Published: July 2010

AbstractTo enhance sensitivity in measuring neuronal current MRI (ncMRI) signal using T2*‐weighted sequences, appropriate selection of echo time (TE) is vital for optimizing data acquisition strategy. The purpose of this study is to establish the contrast‐to‐noise ratio of neuronal current MRI signal dependence on TE and determine the optimum TE (TEopt) in achieving its highest detection power. The TEopt in human brain and tissue preparation at 1.5, 3, and 7 T are estimated with different voxel sizes. Our results show that TEopt values are different between magnitude and phase images, and TEopt is larger in magnitude than phase imaging. This suggests that a dual‐echo data acquisition strategy would provide the best efficiency in detecting magnitude and phase neuronal current MRI signals simultaneously. Our results also indicated that the detection sensitivity will be stronger at lower magnetic fields for human brain, whereas the sensitivity will be enhanced/reduced as field strength increases for phase/magnitude imaging on tissue preparation. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
The in vivo influence of white matter fiber orientation towards B0 on T2* in the human brain
Authors: Bender B. , Klose U. 
Published: July 2010

AbstractIt is well known that, at higher field strength, T2*‐weighted images show an extensive heterogeneity in white matter fiber bundles. The basis of this phenomenon is still under discussion, as many factors, such as iron concentration, myelination and tissue microstructure, could influence relaxation times. Furthermore, fiber direction in relation to the main magnetic field seems to influence T2* relaxation times. In this study, diffusion tensor imaging and T2* measurements were combined in seven subjects with the head in a normal and tilted position. It was shown that fiber orientation has a strong influence on T2* in the human brain, with the average T2* value changing from 49 ms for a perpendicular orientation to B0 to 57 ms for a parallel orientation to B0. Nevertheless, T2* times showed a wide variety of values at any orientation towards B0. Copyright © 2010 John Wiley & Sons, Ltd.
Dynamics and fate of USPIO in the central nervous system in experimental autoimmune encephalomyelitis
Authors: Oude Engberink Raoul D. , Blezer Erwin L.A. , Dijkstra Christine D. , van der Pol Susanne M.A. , van der Toorn Annette , de Vries Helga E. 
Published: July 2010

AbstractSignal loss observed in the brain by MRI following the administration of ultrasmall superparamagnetic particles of iron oxide (USPIO) has been correlated with immune cell activity in inflammatory areas during multiple sclerosis. Uptake of USPIO by circulating monocytes and their migration towards inflammatory areas have been considered as the most important mechanism for USPIO uptake by the brain parenchyma. However, the involvement of a damaged blood–brain barrier is also debated as a possible mechanism for cerebral USPIO uptake. Compared with these uptake‐associated issues, little is known about the clearance of USPIO from the brain. The acute uptake and chronic clearance of USPIO in the brain were therefore studied with MRI in an animal model of multiple sclerosis. Lewis Hannover rats with acute experimental autoimmune encephalomyelitis received a single intravenous injection of USPIO (300 µmol Fe/kg), and repetitive MRI of the brain and cervical lymph nodes, a possible drainage pathway, was performed. USPIO were detected in the brain within 1 h after injection independent of the severity of experimental autoimmune encephalomyelitis, and histological analysis revealed extracellular iron clusters colocalising with a leaky blood–brain barrier. Loss of signal was not present 72 h after USPIO injection, irrespective of the disease state. MR images of cervical lymph nodes showed USPIO accumulation at 24 h after administration, which stabilised at 72 h. Histological analyses revealed that USPIO accumulated in infiltrated macrophages in the medulla and subcapsular sinus. The current study demonstrates that USPIO enter the central nervous system directly after administration, pointing to the involvement of a damaged blood–brain barrier in the appearance of USPIO‐associated MR abnormalities. Furthermore, a possible role of the cervical lymph nodes as a drainage pathway of USPIO is suggested. These data shed new light on the use of USPIO in neuroinflammatory diseases, identifying USPIO as a marker for both cellular infiltration and blood–brain barrier damage. Copyright © 2010 John Wiley & Sons, Ltd.
Selected control events and reporting odds ratio in signal detection methodology
Authors: Ooba Nobuhiro , Kubota Kiyoshi 
Published: July 2010

AbstractPurposeTo know whether the reporting odds ratio (ROR) using “control events” can detect signals hidden behind striking reports on one or more particular events.MethodsWe used data of 956 drug use investigations (DUIs) conducted between 1970 and 1998 in Japan and domestic spontaneous reports (SRs) between 1998 and 2008. The event terms in DUIs were converted to the preferred terms in Medical Dictionary for Regulatory Activities (MedDRA). We calculated the incidence proportion for various events and selected 20 “control events” with a relatively constant incidence proportion across DUIs and also reported regularly to the spontaneous reporting system. A “signal” was generated for the drug‐event combination when the lower limit of 95% confidence interval of the ROR exceeded 1. We also compared the ROR in SRs with the RR in DUIs.ResultsThe “control events” accounted for 18.2% of all reports. The ROR using “control events” may detect some hidden signals for a drug with the proportion of “control events” lower than the average. The median of the ratios of the ROR using “control events” to RR was around the unity indicating that “control events” roughly represented the exposure distribution though the range of the ratios was so diverse that the individual ROR might not be regarded as the estimate of RR.ConclusionsThe use of the ROR with “control events” may give an adjunctive to the traditional signal detection methods to find a signal hidden behind some major events. Copyright © 2010 John Wiley & Sons, Ltd.
Steps in reductive activation of the disulfide‐generating enzyme Ero1p
Authors: Heldman Nimrod , Vonshak Ohad , Sevier Carolyn S. , Vitu Elvira , Mehlman Tevie , Fass Deborah 
Published: July 2010

AbstractEro1p is the primary catalyst of disulfide bond formation in the yeast endoplasmic reticulum (ER). Ero1p contains a pair of essential disulfide bonds that participate directly in the electron transfer pathway from substrate thiol groups to oxygen. Remarkably, elimination of certain other Ero1p disulfides by mutation enhances enzyme activity. In particular, the C150A/C295A Ero1p mutant exhibits increased thiol oxidation in vitro and in vivo and interferes with redox homeostasis in yeast cells by hyperoxidizing the ER. Inhibitory disulfides of Ero1p are thus important for enzyme regulation. To visualize the differences between de‐regulated and wild‐type Ero1p, we determined the crystal structure of Ero1p C150A/C295A. The structure revealed local changes compared to the wild‐type enzyme around the sites of mutation, but no conformational transitions within 25 Å of the active site were observed. To determine how the C150C295 disulfide nonetheless participates in redox regulation of Ero1p, we analyzed using mass spectrometry the changes in Ero1p disulfide connectivity as a function of time after encounter with reducing substrates. We found that the C150C295 disulfide sets a physiologically appropriate threshold for enzyme activation by guarding a key neighboring disulfide from reduction. This study illustrates the diverse and interconnected roles that disulfides can play in redox regulation of protein activity.
The influence of involvement on the endowment effect: The moveable value function
Authors: Saqib Najam U. , Frohlich Norman , Bruning Edward 
Published: July 2010

AbstractThe endowment effect is based on the loss aversion built into Prospect Theory's asymmetric value function. This paper posits that the level of consumer involvement with a decision is a moderator of the endowment effect. It is proposed that high involvement increases the slope differential between the loss and gain regions of the value function, enhancing loss aversion. The research further posits that higher involvement is accompanied by higher arousal and cognitive processing which produces stronger negativity in thoughts. The argument for these effects is discussed in the context of evolutionary theory. We conclude that consumers are more loss averse in high versus low involvement conditions.
Cell cycle events mediate lactacystin‐induced apoptotic death of neuronal PC12 cells
Authors: Zhang Zhentao , Xu Yan , Qin Kairong , Wang Tao , Cao Xuebing 
Published: July 2010

AbstractDysfunction of the UPS (ubiquitin—proteasome system) has been implicated in dopaminergic neuronal death in PD (Parkinson's disease). Recent studies suggest that unregulated cell cycle events play a key role in neuronal death. In this study, the effects of UPS dysfunction on cell cycle events in neuronal differentiated PC12 cells were analysed using a specific inhibitor of proteasome, lactacystin. Lactacystin induced apoptosis, G2/M cell cycle arrest and sustained the phosphorylation of the pRB (retinoblastoma protein), the key molecular process of G1/S transition, in neuronal PC12 cells. Furthermore, inhibition of cell cycle progression protected against lactacystin‐induced cell apoptosis. Finally, we determined that lactacystin activated the ERK signalling pathway. Inhibition of ERK1/2 activation by MEK‐1 inhibitor PD98059 decreased cell cycle aberrant and prevented apoptosis induced by lactacystin. These results indicate that aberrant cell cycle events contribute to apoptotic death induced by UPS dysfunction.
Genome-wide histone acetylation data improve prediction of mammalian transcription factor binding sites
Authors: Ramsey Stephen A. , Knijnenburg Theo A. , Kennedy Kathleen A. , Zak Daniel E. , Gilchrist Mark , Gold Elizabeth S. , Johnson Carrie D. , Lampano Aaron E. , Litvak Vladimir , Navarro Garnet , Stolyar Tetyana , Aderem Alan , Shmulevich Ilya 
Published: July 2010

Abstract
Motivation: Histone acetylation (HAc) is associated with open chromatin, and HAc has been shown to facilitate transcription factor (TF) binding in mammalian cells. In the innate immune system context, epigenetic studies strongly implicate HAc in the transcriptional response of activated macrophages. We hypothesized that using data from large-scale sequencing of a HAc chromatin immunoprecipitation assay (ChIP-Seq) would improve the performance of computational prediction of binding locations of TFs mediating the response to a signaling event, namely, macrophage activation.
Results: We tested this hypothesis using a multi-evidence approach for predicting binding sites. As a training/test dataset, we used ChIP-Seq-derived TF binding site locations for five TFs in activated murine macrophages. Our model combined TF binding site motif scanning with evidence from sequence-based sources and from HAc ChIP-Seq data, using a weighted sum of thresholded scores. We find that using HAc data significantly improves the performance of motif-based TF binding site prediction. Furthermore, we find that within regions of high HAc, local minima of the HAc ChIP-Seq signal are particularly strongly correlated with TF binding locations. Our model, using motif scanning and HAc local minima, improves the sensitivity for TF binding site prediction by ∼50% over a model based on motif scanning alone, at a false positive rate cutoff of 0.01.
Availability: The data and software source code for model training and validation are freely available online at http://magnet.systemsbiology.net/hac.
Contact: aderem@systemsbiology.org; ishmulevich@systemsbiology.org
Supplementary information: Supplementary data are available at Bioinformatics online.
Interleukin‐9 as a T helper type 17 cytokine
Authors: Nowak Elizabeth C. , Noelle Randolph J. 
Published: July 2010

SummaryThe production of interleukin‐9 (IL‐9) by CD4 T cells has gathered renewed interest as the result of the observation that its expression is broader than originally thought. This includes the production of IL‐9 by a recently characterized subset of CD4 helper T (Th) cells that are termed Th9 as well as production by additional T‐cell subsets including Th17 cells. There is an incomplete understanding as to which IL‐9‐producing T‐cell subsets develop under physiological conditions. We describe the conditions used to generate IL‐9 in Th17 cells in vitro. We also summarize conditions where both IL‐9 and IL‐17 are found in vivo and propose that Th17 cells producing IL‐9 may co‐exist and interact with Th9 cells during conditions of autoimmunity, allergy and infection.
Exploring the Implications of Changing Census Output Geographies for the Measurement of Residential Segregation: The Example of Northern Ireland 1991–2001
Authors: Shuttleworth I. G. , Lloyd C. D. , Martin D. J. 
Published: July 2010

SummaryOne problem in analysing social and demographic change through time by using census data arises from differences in the size and shape of the geographical units that are used to output data between different years. Failure to correct for changing output geographies may lead to unknown and possibly large biases when comparing results through time between different censuses. The paper addresses this issue by using the example of residential segregation in Northern Ireland. It has two main objectives. Firstly, by compiling 2001 Northern Ireland census data on 1991 census output geographies it assesses the sensitivity of indices of residential segregation to these changes in geographical units. Secondly, it suggests a method by which census analysts can assess how sensitive their results are to changing output geographies when they cannot correct for these changes and must work with the data ‘as they are’. A subsidiary aim is to contribute to the evidence base on residential segregation in Northern Ireland. The paper finds that indices of residential segregation are insensitive to changes in output geographies between 1991 and 2001. The reason suggested for this is that the units in each zonal geography are smaller than the spatial scale over which population counts are positively auto-correlated. The use of spatially weighted segregation indices is advanced as a generalizable means of learning about the geographical patterning of population in different censuses. It is argued that these insights combined with knowledge of the size of geographical units used in each census can help researchers elsewhere to judge how sensitive their results might be to changing census output geographies through time.
Modelling Bias in Combining Small Area Prevalence Estimates from Multiple Surveys
Authors: Manzi Giancarlo , Spiegelhalter David J. , Turner Rebecca M. , Flowers Julian , Thompson Simon G. 
Published: July 2010

SummaryCombining information from multiple surveys can improve the quality of small area estimates. Customary approaches, such as the multiple-frame and statistical matching methods, require individual level data, whereas in practice often only multiple aggregate estimates are available. Commercial surveys usually produce such estimates without clear description of the methodology that is used. In this context, bias modelling is crucial, and we propose a series of Bayesian hierarchical models which allow for additive biases. Some of these models can also be fitted in a classical context, by using a mixed effects framework. We apply these methods to obtain estimates of smoking prevalence in local authorities across the east of England from seven surveys. All the surveys provide smoking prevalence estimates and confidence intervals at the local authority level, but they vary by time, sample size and transparency of methodology. Our models adjust for the biases in commercial surveys but incorporate information from all the sources to provide more accurate and precise estimates.
THE UPTAKE OF LOW CONCENTRATIONS OF LITHIUM IONS INTO RAT CEREBRAL CORTEX SLICES AND ITS DEPENDENCE ON CATIONS
Authors: Wraae O. , Hillman H. , Round Elizabeth 
Published: July 2010

Abstract—Rat cerebral slices were incubated in oxygenated Krebs‐Ringer bicarbonate glucose saline, and the uptake of Li+ was measured after periods of 15 s to 5 min. Saturation was not seen within the concentrations of Li+ employed (0·5‐2·0 mm). The half‐time of the uptake was 7·9 min. At steady state, after 1 h incubation, the concentration of Li+ in the tissue was linearly related to that of the medium (0·5‐1·5 mm Li+) with a concentration ratio of 1·29–1·66. The concentrations of K+ and Na+ in the slices incubated without Li+ were found to be (μmol/g incubated wt, mean ±s.d.) 63·8 ± 9·6 and 96·2 ± 7·8 respectively (n = 28). In the presence of media with 1·5 mm ‐Li+, the K+ and Na+ in the slices were 56·2 ± 8·8 and 101·0 ± 7·7 respectively (n = 37). The concentration of Li+ in the slices, after 1 h incubation, increased in a non linear way as the concentration of K+ in the medium was decreased within a range of 0·10 mm‐K+. In the absence of K+ in the medium the uptake of Li+ was approx 50% higher than in the presence of 4·9 mm‐K+. There was an inverse linear relationship between the concentration of Li+ in the slices and that of Ca2+ in the medium within the range of 0‐5·2 mm (‐0·13 mm‐Li+/mm Ca2+). The concentration of Li+ in the slices increased by approx 10% when the Mg2+ in the medium was increased from 1·3 mm to 2·6 mm. Changes of the concentration of Na+ between 120 mm and 170 mm in the medium had no significant effect on the Li+ uptake.
Artifactual High‐Affinity and Saturable Binding of [3H]5‐Hydroxytryptamine Induced by Radioligand Oxidation
Authors: Peroutka Stephen J. , Ison Pamela J. , Liu David U. , Barrett Ronald W. 
Published: July 2010

AbstractThe binding of [3H]5‐hydroxytryptamine (5‐HT, serotonin) to cerebellar membranes was examined after preincubation of [3H]5‐HT in the presence or absence of ascorbate. The tissue preparation was identical in all experiments and consisted of rat cerebellar homog‐enates in Tris‐HCl buffer with 0.1%ascorbate. Cerebellar membranes were used because of their low density of 5‐HT, binding sites. In the presence of ascorbate during a 4‐h preincubation period, minimal specific binding of 2 nM[3H]5‐HT is detected. Similar results are obtained with equimolar concentrations of other antioxidants (bu‐tylated hydroxytoluene, sodium dithionite, and sodium metabisulfite). Apparent specific binding increases 14‐fold following a 4‐h preincubation of [3H]5‐HT in the absence of ascorbate. The increase in apparent specific [3H]5‐HT binding is time‐dependent and plateaus after 4–6 h of preincubation. When ascorbate is present during the 4‐h preincubation, Scatchard analysis of [3H]5‐HT binding reveals aKDvalue of 3.0 ± 0.3nMand aBmaxvalue of 1.9 ± 0.2 pmol/g tissue. When ascorbate is absent during the preincubation, theKDis essentially un changed at 3.6 ± 0.1nMbut theBmaxis significantly increased to 36.5 ± 7 pmol/g tissue. Drug competition studies reveal that the apparent specific “[3H]5‐HT binding” in the absence of ascorbate appears to be displaced by nanomolar concentrations of hydroxylated tryptamines (5‐HT, bufotenine) but not by nonhydroxy‐lated tryptamines (5‐methoxytryptamine, tryptamine). HPLC analysis demonstrates that [3H]5‐HT is essentially destroyed by a 4‐h incubation at 22°C in the absence of ascorbate. We conclude that oxidation of [3H]5‐HT prior to the addition of membrane homogenates leads to the detection of an artifactual high‐affinity and saturable “[3H]5‐HT binding site” that appears to have a distinct pharmacological profile. The capacity of other ligands to compete for this binding site is related to their potential as antioxidants and not to their affinity for a novel membrane recognition site labeled by [3H]5‐HT.
β‐Amyloid regulates leptin expression and tau phosphorylation through the mTORC1 signaling pathway
Authors: Marwarha Gurdeep , Dasari Bhanu , Prabhakara Jaya Prasanthi Rantham , Schommer Jared , Ghribi Othman 
Published: July 2010

J. Neurochem. (2010) 115, 373–384.AbstractHigh levels of the adipocytokine leptin are associated with reduced risk of Alzheimer’s disease. Leptin treatment also reduces β‐amyloid (Aβ) levels in in vivo and in vitro models of Alzheimer’s disease. Aβ and leptin interact with the Akt/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Akt/mTORC1 activation reduces tau phosphorylation through the inhibition of the downstream enzyme GSK‐3β. mTORC1 also regulates translation of many proteins including leptin. While Aβ has been shown to inactivate Akt, inhibit mTORC1, and facilitate the phosphorylation of tau, leptin activates both Akt and mTORC1 and reduces tau phosphorylation. However, the extent to which Aβ may modulate leptin expression and increase tau phosphorylation involving Akt/mTORC1 has not been determined. In this study, we show that incubation of organotypic slices from rabbit hippocampus with Aβ down‐regulates leptin expression, inhibits Akt, activates GSK‐3β, increases tau phosphorylation, and inactivates mTORC1. Leptin treatment reverses Aβ effects by alleviating Akt inhibition, preventing GSK‐3β activation, reducing tau phosphorylation, and activating mTORC1. On the other hand, Rapamycin, an allosteric inhibitor of mTORC1, down‐regulates leptin expression, increases tau phosphorylation, and does not affect Akt and GSK‐3β. Our results demonstrate for the first time that Aβ regulates leptin expression and tau phosphorylation through mTORC1.