bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards Fluoride Sensing with Positively Charged Lanthanide Complexes
Authors: Tripier Raphaël , Platas‐Iglesias Carlos , Boos Anne , Morfin Jean‐François , Charbonnière Loïc 
Published: January 2010

AbstractHerein we report a series of [LnL(H2O)]Cl3 complexes, in which L is a 1,4,7,10‐tetrazacyclododecane framework (cyclen) functionalized with 2‐methylpyridyl pendants on the nitrogen atoms at the 1‐ and 7‐positions and with N‐[2‐(2‐hydroxyethoxy)ethyl]acetamide groups on those at the 4‐ and 10‐positions, and Ln stands for Eu, La, and Tb. The complexes were isolated and characterized by elemental analysis, mass spectrometry, infrared spectroscopy, and 1H NMR spectroscopy for the La and Eu complexes. 1H NMR spectroscopy indicates that the complexes display a major twisted square antiprismatic (TSAP) geometry in solution, which was confirmed by using DFT calculations. 1H and 13C variable‐temperature NMR spectroscopic experiments on the La complex provided an activation free energy of ΔG≠ = (58 ± 3) kJ mol–1 for the enantiomerization process of the TSAP isomer, which requires both the inversion of the five‐membered chelate rings formed upon coordination of the cyclen moiety and the rotation of the pendant arms. The photophysical properties of the complexes were studied by means of absorption, steady‐state, and time‐resolved luminescence spectroscopy. Upon ligand excitation, the Eu and Tb complexes displayed the typical lanthanide‐centered emission spectra with weak emission efficiencies (Φov = 0.11 and 0.68 %, respectively, for Eu and Tb in H2O). Luminescence lifetime measurements in water and heavy water allowed the determination of the hydration number of the complexes; these were (1.0 ± 0.2) for Eu and Tb. Spectrophotometric titrations of the [LnL(H2O)]Cl3 complexes (Ln = Eu and Tb) with F–, Cl–, and Br– anions (in buffered water solutions, 0.01 M tris(hydroxymethyl)aminomethane (TRIS)/HClO4, pH = 7.0) showed the complexes to interact selectively with fluoride anions, whereas no interactions were observed with Cl– and Br–. The interaction with F– was monitored by luminescence spectroscopy with [EuL(H2O)], which evidenced dramatic changes in the shape of the luminescence spectra, and an association constant of (2.86 ± 0.06) log units was determined. In the case of the Eu complex, time‐resolved and high‐resolution emission spectroscopy showed that the interaction resulted in the displacement of the coordinated water molecule, which led to an increase of the overall luminescence quantum yield, with almost no impact on the ligand‐to‐metal sensitization efficiency. Investigation of the Eu and La complexes by potentiometry (0.1 M NaCl) allowed the determination of the protonation constants of the complexes as well as the association constants with fluoride anions. DFT calculations on the fluoride adduct of the Eu complex confirmed the higher stability of the TSAP isomer and evidenced large structural changes upon F– binding, in agreement with spectrophotometric observations in solution.
Total Synthesis of (+)‐Brefeldin C, (+)‐nor‐Me Brefeldin A and (+)‐4‐epi‐nor‐Me Brefeldin A
Authors: Archambaud Sylvie , Legrand Frédéric , Aphecetche‐Julienne Karine , Collet Sylvain , Guingant André , Evain M. 
Published: January 2010

AbstractA total synthesis of (+)‐brefeldin C (BFC) and two brefeldin A (BFA) analogues – (+)‐nor‐Me BFA and (+)‐4‐epi‐nor‐Me BFA – has been developed. Key features of the syntheses include desymmetrization of meso anhydrides, a Carreira reaction to control the absolute configuration at C4 of BFC, a Suzuki–Miyaura cross‐coupling reaction to create the C11–C12 bond and a Yamaguchi reaction to form the 13‐membered lactone ring.
Passive regulation of volume‐flow ratio for microfluidic streams with different hydrophilicity and viscosity
Authors: Kim Sung‐Jin , Lim Yong Taik , Yang Haesik , Kim Kyuwon , Kim Youn Tae 
Published: January 2010

AbstractBiochemical solutions have a wide range of hydrophilicity (contact angle and surface tension) and viscosity. A critical challenge is that microfluidic systems typically need expensive or complex pumps to control the various parallel biochemical streams. In this study, without using any pumps, we present a simple scheme that controls the ratio of the volumetric flow rate (VFR) of the parallel streams that have highly different hydrophilicity and viscosity. We accomplish this process by using capillarity to drive and merge two streams, and by regulating relative flow resistance to control the VFR ratio. Our results will significantly simplify the control of the VFR ratio for the various biochemical solutions that are used in microfluidic applications.
The concept of minimized integrated exponential error for low dispersion and low dissipation schemes
Authors: Appadu A. R. , Dauhoo M. Z. 
Published: January 2010

AbstractWe devise two novel techniques to optimize parameters which regulate dispersion and dissipation effects in numerical methods using the notion that dissipation neutralizes dispersion. These techniques are baptized as the minimized integrated error for low dispersion and low dissipation (MIELDLD) and the minimized integrated exponential error for low dispersion and low dissipation (MIEELDLD).These two techniques of optimization have an advantage over the concept of minimized integrated square difference error (MISDE), especially in the case when more than one optimal cfl is obtained, out of which only one of these values satisfy the shift condition. For instance, when MISDE is applied to the 1‐D Fromm's scheme, we have obtained two optimal cfl numbers: 0.28 and 1.0. However, it is known that Fromm's scheme satisfies shift condition only at r=1.0. Using MIELDLD and MIEELDLD, the optimal cfl of Fromm's scheme is computed as 1.0.We show that like the MISDE concept, both the techniques MIELDLD and MIEELDLD are effective to control dissipation and dispersion. The condition ν2>4µ is satisfied for all these three techniques of optimization, where ν and µ are parameters present in the Korteweg‐de‐Vries‐Burgers equation.The optimal cfl number for some numerical schemes namely Lax–Wendroff, Beam–Warming, Crowley and Upwind Leap‐Frog when discretized by the 1‐D linear advection equation is computed. The optimal cfl number obtained is in agreement with the shift condition. Some numerical experiments in 1‐D have been performed which consist of discontinuities and shocks. The dissipation and dispersion errors at some different cfl numbers for these experiments are quantified. Copyright © 2010 John Wiley & Sons, Ltd.
Activation of an oncogenic TBC1D7 (TBC1 domain family, member 7) protein in pulmonary carcinogenesis
Authors: Sato Nagato , Koinuma Junkichi , Ito Tomoo , Tsuchiya Eiju , Kondo Satoshi , Nakamura Yusuke , Daigo Yataro 
Published: January 2010

AbstractTo develop novel biomarkers and therapeutic agents for lung cancers, we screened molecules that were highly expressed in lung cancers by means of cDNA microarray analysis and found an elevated expression of TBC1 domain family, member 7 (TBC1D7) in the majority of lung cancers. Northern‐blot analysis using mRNAs from 16 normal tissues detected its expression only in testis. Immunohistochemical staining using tumor tissue microarrays consisting of 261 archived non‐small cell lung cancer (NSCLC) specimens suggested an association of TBC1D7 expression with poor prognosis for NSCLC patients (P = 0.0063). Treatment of lung cancer cells using siRNA against TBC1D7, suppressed its expression and resulted in inhibition of the cell growth. Furthermore, the induction of exogenous expression of TBC1D7 conferred growth‐promoting activity at in vitro and in vivo conditions. We also identified TBC1D7 to interact with TSC1 protein in lung cancer cells. TSC1 introduction into cells increased the level of TBC1D7 protein, whereas knockdown of TSC1 expression decreased the level of TBC1D7 protein, suggesting that TBC1D7 is stabilized probably through interaction with TSC1. In addition, inhibition of the binding between TBC1D7 and TSC1 by a TBC1D7‐derived 20‐amino acid cell‐permeable peptide (11R‐TBC1D7152‐171), which corresponded to the binding domain to TSC1, effectively suppressed growth of lung cancer cells. Selective suppression of TBC1D7 and/or inhibition of the TBC1D7‐TSC1 complex formation could be promising therapeutic strategies for lung cancer therapy. © 2010 Wiley‐Liss, Inc.
FOXO1 and TCF7L2 genes involved in metastasis and poor prognosis in clear cell renal cell carcinoma
Authors: Kojima Takahiro , Shimazui Toru , Horie Ryo , Hinotsu Shiro , Oikawa Takehiro , Kawai Koji , Suzuki Hideaki , Meno Kohji , Akaza Hideyuki , Uchida Kazuhiko 
Published: January 2010

AbstractThe goal of this study was to identify genes related to the metastasis of clear cell renal cell carcinoma (CRCC). We analyzed copy number alterations in renal tissue specimens of patients with CRCC patients with or without metastasis by using high‐resolution single‐nucleotide polymorphism (SNP) arrays and then integrated these data with gene expression profiling data obtained using oligonucleotide microarrays. The expression levels of target genes were determined by quantitative real‐time RT‐PCR (qRT‐PCR) with an independent tumor set. An analysis of specimens from 23 CRCC cases with SNP arrays revealed that hemizygous deletions at 10q and 13q were found only in cases of metastatic disease. We found the homozygous deletion of TCF7L2 at 10q25.2 in an aggressive case that had hemizygous deletions at 10q. In addition, a qRT‐PCR analysis of TCF7L2 mRNA levels in tumor samples revealed significantly lower levels in patients with metastasis when compared with those without metastasis. FOXO1 was identified as a down‐regulated gene in the minimal overlapping region of the 13q hemizygous deletion in CRCC. Decreased FOXO1 expression was significantly correlated with metastasis and poor survival outcome. Knockdown of FOXO1 inhibited apoptosis after doxorubicin treatment in CRCC cells and reduced the expression of downstream genes involved in cell proliferation (CDKN1B) and survival (BCL2L11). Lower levels of FOXO1 expression were associated with decreased expression of CDKN1B and BCL2L11 in CRCC specimens. We conclude that FOXO1 and TCF7L2 are involved in metastasis and that molecules in these signaling pathways may be targets for diagnostic procedures and therapies for CRCC. © 2010 Wiley‐Liss, Inc.
Alterations of white matter tracts following neurotoxic hippocampal lesions in macaque monkeys: A diffusion tensor imaging study
Authors: Shamy J.L. , Carpenter D.M. , Fong S.G. , Murray E.A. , Tang C.Y. , Hof P.R. , Rapp P.R. 
Published: January 2010

AbstractDiffusion tensor imaging (DTI) is a valuable tool for assessing presumptive white matter alterations in human disease and animal models. The current study used DTI to examine the effects of selective neurotoxic lesions of the hippocampus on major white matter tracts and anatomically related brain regions in macaque monkeys. Two years postlesion, structural MRI, and DTI sequences were acquired for each subject. Volumetric assessment revealed a substantial reduction in the size of the hippocampus in experimental subjects, averaging 72% relative to controls, without apparent damage to adjacent regions. DTI images were processed to yield measures of fractional anisotropy (FA), apparent diffusion coefficient (ADC), parallel diffusivity (lADC), and perpendicular diffusivity (tADC), as well as directional color maps. To evaluate potential changes in major projection systems, a region of interest (ROI) analysis was conducted including the corpus callosum, fornix, temporal stem, cingulum bundle, ventromedial prefrontal white matter, and optic radiations. Lesion‐related abnormalities in the integrity of the fiber tracts examined were limited to known hippocampal circuitry, including the fornix and ventromedial prefrontal white matter. These findings are consistent with the notion that hippocampal damage results in altered interactions with multiple memory‐related brain regions, including portions of the prefrontal cortex. © 2010 Wiley‐Liss, Inc.
Layered silicate epoxy nanocomposites: formation of the inorganic‐carbonaceous fire protection layer
Authors: Schartel B. , Weiß A. , Sturm H. , Kleemeier M. , Hartwig A. , Vogt C. , Fischer R. X. 
Published: January 2010

AbstractThe layered silicate (LS) modification and processing parameters applied control the morphology of the LS/polymer composites. Here, increasing the surface area of the LS particles by using alternative drying processes increases dispersion towards a more typical nanocomposite morphology, which is a basic requirement for promising flame retardancy. Nevertheless, the morphology at room temperature does not act itself with respect to flame retardancy, but serves as a prerequisite for the formation of an efficient surface protection layer during pyrolysis. The formation of this residue layer was addressed experimentally for the actual pyrolysis region of a burning nanocomposite and thus our results are valid without any assumptions or compromises on the time period, dimension, surrounding atmosphere or temperature. The formation of the inorganic‐carbonaceous residue is influenced by bubbling, migration, reorientation, agglomeration, ablation, and perhaps also delamination induced thermally and by decomposition, whereas true sintering of the inorganic particles was ruled out as an important mechanism. Multiple, quite different mechanisms are relevant during the formation of the residue, and the importance of each mechanism probably differs from one nanocomposite system to another. The main fire protection effect of the surface layer in polymer nanocomposites based on non‐charring or nearly non‐charring polymers is the increase in surface temperature, resulting in a substantial increase in reradiated heat flux (heat shielding). Copyright © 2010 John Wiley & Sons, Ltd.
The role of autocrine TGFβ1 in endothelial cell activation induced by phagocytosis of necrotic trophoblasts: a possible role in the pathogenesis of pre‐eclampsia
Authors: Chen Qi , Chen Limei , Liu Bonnia , Vialli Chez , Stone Peter , Ching Lai‐Ming , Chamley Lawrence 
Published: January 2010

AbstractPre‐eclampsia is a disorder of pregnancy characterized by hypertension and endothelial cell dysfunction. The causes of pre‐eclampsia are unclear but it is proposed that a factor released from the placenta triggers the maternal symptoms. One possible triggering factor is dead trophoblasts that are shed from the placenta, then deported to become trapped in the maternal pulmonary capillaries. It is hypothesized that trophoblasts die by apoptosis in normal pregnancy, but by necrosis in pre‐eclampsia. Deported trophoblasts may be phagocytosed by the pulmonary endothelial cells and we have previously shown that phagocytosis of necrotic trophoblasts leads to the activation of endothelial cells, accompanied by the release of interleukin‐6 from these cells. However, the mechanistic pathway linking phagocytosis of necrotic trophoblasts and endothelial cell activation is unknown. Here we show that, after phagocytosis of necrotic, but not apoptotic, trophoblasts, endothelial cells secrete TGFβ1. Using recombinant endoglin to inhibit the function of TGFβ1 we have shown that the TGFβ1 does not directly activate endothelial cells but rather it induces endothelial IL‐6 secretion. The IL‐6 then induces endothelial cell activation. Inhibiting either TGFβ1 or IL‐6 prevented endothelial cell activation in response to phagocytosing necrotic trophoblasts, but inhibiting IL‐6 did not prevent secretion of TGFβ1, confirming the order of signalling. IL‐6 also reduced endothelial cell‐surface endoglin but increased the amount of soluble endoglin released from placental explants. These interactions between the IL‐6 and TGFβ1 pathways in both the endothelium and placenta may help to regulate the maternal response to deported trophoblasts in pregnancy. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cysteine‐free rop: A four‐helix bundle core mutant has wild‐type stability and structure but dramatically different unfolding kinetics
Authors: Hari Sanjay B. , Byeon Chang , Lavinder Jason J. , Magliery Thomas J. 
Published: January 2010

AbstractCysteine residues can complicate the folding and storage of proteins due to improper formation of disulfide bonds or oxidation of residues that are natively reduced. Wild‐type Rop is a homodimeric four‐helix bundle protein and an important model for protein design in the understanding of protein stability, structure and folding kinetics. In the native state, Rop has two buried, reduced cysteine residues in its core, but these are prone to oxidation in destabilized variants, particularly upon extended storage. To circumvent this problem, we designed and characterized a Cys‐free variant of Rop, including solving the 2.3 Å X‐ray crystal structure. We show that the C38A C52V variant has similar structure, stability and in vivo activity to wild‐type Rop, but that it has dramatically faster unfolding kinetics like virtually every other mutant of Rop that has been characterized. This cysteine‐free Rop has already proven useful for studies on solution topology and on the relationship of core mutations to stability. It also suggests a general strategy for removal of pairs of Cys residues in proteins, both to make them more experimentally tractable and to improve their storage properties for therapeutic or industrial purposes.
Lessons from the lysozyme of phage T4
Authors: Baase Walter A. , Liu Lijun , Tronrud Dale E. , Matthews Brian W. 
Published: January 2010

AbstractAn overview is presented of some of the major insights that have come from studies of the structure, stability, and folding of T4 phage lysozyme. A major purpose of this review is to provide the reader with a complete tabulation of all of the variants that have been characterized, including melting temperatures, crystallographic data, Protein Data Bank access codes, and references to the original literature. The greatest increase in melting temperature (Tm) for any point mutant is 5.1°C for the mutant Ser 117 → Val. This is achieved in part not only by hydrophobic stabilization but also by eliminating an unusually short hydrogen bond of 2.48 Å that apparently has an unfavorable van der Waals contact. Increases in Tm of more than 3–4°C for point mutants are rare, whereas several different types of destabilizing substitutions decrease Tm by 20°C or thereabouts. The energetic cost of cavity creation and its relation to the hydrophobic effect, derived from early studies of “large‐to‐small” mutants in the core of T4 lysozyme, has recently been strongly supported by related studies of the intrinsic membrane protein bacteriorhodopsin. The L99A cavity in the C‐terminal domain of the protein, which readily binds benzene and many other ligands, has been the subject of extensive study. Crystallographic evidence, together with recent NMR analysis, suggest that these ligands are admitted by a conformational change involving Helix F and its neighbors. A total of 43 nonisomorphous crystal forms of different monomeric lysozyme mutants were obtained plus three more for synthetically‐engineered dimers. Among the 43 space groups, P212121 and P21 were observed most frequently, consistent with the prediction of Wukovitz and Yeates.
The proline‐rich domain of TonB possesses an extended polyproline II‐like conformation of sufficient length to span the periplasm of Gram‐negative bacteria
Authors: Domingo Köhler Silvia , Weber Annemarie , Howard S. Peter , Welte Wolfram , Drescher Malte 
Published: January 2010

AbstractTonB from Escherichia coli and its homologues are critical for the uptake of siderophores through the outer membrane of Gram‐negative bacteria using chemiosmotic energy. When different models for the mechanism of TonB mediated energy transfer from the inner to the outer membrane are discussed, one of the key questions is whether TonB spans the periplasm. In this article, we use long range distance measurements by spin‐label pulsed EPR (Double Electron–Electron Resonance, DEER) and CD spectroscopy to show that the proline‐rich segment of TonB exists in a PPII‐like conformation. The result implies that the proline‐rich segment of TonB possesses a length of more than 15 nm, sufficient to span the periplasm of Gram‐negative bacteria.
Structural basis for unfolding pathway‐dependent stability of proteins: Vectorial unfolding versus global unfolding
Authors: Yagawa Keisuke , Yamano Koji , Oguro Takaomi , Maeda Masahiro , Sato Takehiro , Momose Takaki , Kawano Shin , Endo Toshiya 
Published: January 2010

AbstractPoint mutations in proteins can have different effects on protein stability depending on the mechanism of unfolding. In the most interesting case of I27, the Ig‐like module of the muscle protein titin, one point mutation (Y9P) yields opposite effects on protein stability during denaturant‐induced “global unfolding” versus “vectorial unfolding” by mechanical pulling force or cellular unfolding systems. Here, we assessed the reason for the different effects of the Y9P mutation of I27 on the overall molecular stability and N‐terminal unraveling by NMR. We found that the Y9P mutation causes a conformational change that is transmitted through β‐sheet structures to reach the central hydrophobic core in the interior and alters its accessibility to bulk solvent, which leads to destabilization of the hydrophobic core. On the other hand, the Y9P mutation causes a bend in the backbone structure, which leads to the formation of a more stable N‐terminal structure probably through enhanced hydrophobic interactions.
Structural and dynamical characterization of tubular HIV‐1 capsid protein assemblies by solid state nuclear magnetic resonance and electron microscopy
Authors: Chen Bo , Tycko Robert 
Published: January 2010

AbstractThe wild‐type HIV‐1 capsid protein (CA) self‐assembles in vitro into tubular structures at high ionic strength. We report solid state nuclear magnetic resonance (NMR) and electron microscopy measurements on these tubular CA assemblies, which are believed to contain a triangular lattice of hexameric CA proteins that is similar or identical to the lattice of capsids in intact HIV‐1. Mass‐per‐length values of CA assemblies determined by dark‐field transmission electron microscopy indicate a variety of structures, ranging from single‐wall tubes to multiwall tubes that approximate solid rods. Two‐dimensional (2D) solid state 13C13C and 15N13C NMR spectra of uniformly 15N,13C‐labeled CA assemblies are highly congested, as expected for a 25.6 kDa protein in which nearly the entire amino acid sequence is immobilized. Solid state NMR spectra of partially labeled CA assemblies, expressed in 1,3‐13C2‐glycerol medium, are better resolved, allowing the identification of individual signals with line widths below 1 ppm. Comparison of crosspeak patterns in the experimental 2D spectra with simulated patterns based on solution NMR chemical shifts of the individual N‐terminal (NTD) and C‐terminal (CTD) domains indicates that NTD and CTD retain their individual structures upon self‐assembly of full‐length CA into tubes. 2D 1H‐13C NMR spectra of CA assemblies recorded under solution NMR conditions show relatively few signals, primarily from segments that link the α‐helices of NTD and CTD and from the N‐ and C‐terminal ends. Taken together, the data support the idea that CA assemblies contain a highly ordered 2D protein lattice in which the NTD and CTD structures are retained and largely immobilized.