bluuebunny/crossref_metadata_2025 huggingface dataset:
Catalytic Hydrolysis and Alcoholysis of Alkenyl Esters and Ethers and Its Application to Kinetic Resolution
Authors: Tokunaga Makoto , Aoyama Hiroshi , Obora Yasushi , Tsuji Yasushi
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Development of Fluorous Lewis Acid Catalyzed Reactions
Authors: Yoshida Akihiro , Hao Xiuhua , Yamazaki Osamu , Nishikido Joji
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
C2‐Symmetric Chiral Bis(oxazoline) Ligands in Asymmetric Catalysis
Authors: Desimoni Giovanni , Faita Giuseppe , Joergensen Karl Anker
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Advances in the Synthesis and Catalytic Applications of Organosulfonic‐Functionalized Mesostructured Materials
Authors: Melero Juan A. , van Grieken Rafael , Morales Gabriel
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
The Structural Biology of Protein Aggregation Diseases: Fundamental Questions and Some Answers
Authors: Eisenberg David , Nelson Rebecca , Sawaya Michael R. , Balbirnie Melinda , Sambashivan Shilpa , Ivanova Magdalena I. , Madsen Anders O. , Riekel Christian
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Normal and Aberrant Biological Self‐Assembly: Insights from Studies of Human Lysozyme and Its Amyloidogenic Variants
Authors: Dumoulin Mireille , Kumita Janet R. , Dobson Christopher M.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Magnitude and Physical Origin of Intermolecular Interactions of Aromatic Molecules: Recent Progress of Computational Studies
Authors: Tsuzuki S. , Uchimaru T.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Theory of Substituent Effects: Recent Advances
Authors: Exner O. , Bohm S.
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
The Structural Chemistry of Acyclic Organic Peroxides
Authors: Hartung Jens , Svoboda Ingrid
Published: November 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Size‐Dependent Structural Evolution and Chemical Reactivity of Gold Clusters
Authors: Yoon Bokwon , Koskinen Pekka , Huber Bernd , Kostko Oleg , von Issendorff Bernd , Häkkinen Hannu , Moseler Michael , Landman Uzi
Published: November 2006

Ground‐state structures and other experimentally relevant isomers of Au15− to Au24− clusters are determined through joint first‐principles density functional theory and photoelectron spectroscopy measurements. Subsequent calculations of molecular O2 adsorption to the optimal cluster structures reveal a size‐dependent reactivity pattern that agrees well with earlier experiments. A detailed analysis of the underlying electronic structure shows that the chemical reactivity of the gold cluster anions can be elucidated in terms of a partial‐jellium picture, where delocalized electrons occupying electronic shells move over the ionic skeleton, whose geometric structure is strongly influenced by the directional bonding associated with the highly localized “d‐band” electrons.
Drosophila melanogasterp24 genes have developmental, tissue‐specific, and sex‐specific expression patterns and functions
Authors: Boltz Kara A. , Ellis Lisa L. , Carney Ginger E.
Published: November 2006

Genes encoding members of the p24 family of intracellular trafficking proteins are present throughout animal and plant lineages. However, very little is known about p24 developmental, spatial, or sex‐specific expression patterns or how localized expression affects function. We investigated these problems inDrosophila melanogaster, which contains nine genes encoding p24 proteins. One of these genes,logjam(loj), is expressed in the adult female nervous system and ovaries and is essential for oviposition. Nervous system‐specific expression ofloj, but not ovary‐specific expression, rescues the behavioral defect of mutants. The Loj protein localizes to punctate structures in the cellular cytoplasm. These structures colocalize with a marker specific to the intermediate compartment andcis‐Golgi, consistent with experimental evidence from other systems suggesting that p24 proteins function in intracellular transport between the endoplasmic reticulum and Golgi. Our findings reveal thatDrosophilap24 transcripts are developmentally and tissue‐specifically expressed.CG31787is male‐specifically expressed gene that is present during the larval, pupal, and adult stages. FemaleCG9053mRNA is limited to the head, whereas males express this gene widely. Together, our studies provide experimental evidence indicating that some p24 genes have sex‐specific expression patterns and tissue‐ and sex‐limited functions. Developmental Dynamics 236:544–555, 2007. © 2006 Wiley‐Liss, Inc.
Thermal Behavior of Tetrahydropyran‐Intercalated VOPO4: Structural and Dynamics Study
Authors: Melánová Klára , Beneš Ludvík , Zima Vítězslav , Černošková Eva , Brus Jiří , Urbanová Martina , Trchová Miroslava , Dybal Jiří
Published: November 2006

The thermal behavior of tetrahydropyran‐(THP‐)intercalated VOPO4 was probed by an extensive combination of experimental methods (XRD, DSC, FTIR, solid‐state NMR) and quantum chemical calculations. Two temperature‐induced transitions were detected and all polymorphs exhibit a high degree of molecular order and tight packing of THP in VOPO4. The first reversible thermal transition at around 100 °C was attributed to boat/chair conformation changes of the THP molecules. Most probably, a low‐temperature boat conformation of the guest molecules present in the interlayer space of VOPO4 changes to a high‐temperature chair conformation. This rearrangement of the THP molecules was confirmed by variable‐temperature 13C CP/MAS NMR spectroscopy. Quantum chemical calculations using a B3LYP functional and 6‐31G(d) basis set also support this idea. The second change at around 140 °C is probably caused by a weakening of the donor–acceptor bond between the oxygen molecule of THP and the vanadium atom of the host and the formation of a disorder in packing of the THP molecules. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
(Indenyl)ruthenium Complexes Containing 1,1′‐Bis(diphenylphosphanyl)ferrocene (dppf) and Thiolato Ligands: Synthesis, X‐ray Structure Analysis, Electrochemistry and Magnetic Studies
Authors: Ng Sin Yee , Leong Weng Kee , Goh Lai Yoong , Webster Richard D.
Published: November 2006

The reaction of [(Ind)Ru(dppf)Cl] (Ind = η5‐C9H7) (2) with RSNa {R = Me, Et, Ph, Ph2P(CH2)2} proceeds in MeOH to give [(Ind)Ru(dppf)(SR)] {R = Me (3), Et (4), Ph (5), Ph2P(CH2)2 (7)}, as well as [(Ind)Ru(dppf)H] (6), in all cases except for R = Ph. This R‐dependence of the product mixture was rationalised on a RS–/MeOH ↔ MeO–/RSH equilibrium involving the interaction of thiolate (RS–) with MeOH, and the relative nucleophilicities of RS– versus MeO–; 6 arose from β‐H elimination from an OMe derivative. Cyclic voltammetric measurements on 2, 3, 4 and 5, as well as the Cp (η5‐C5H5) and Cp* (η5‐C5Me5) analogues of 2, indicated that the formal oxidation potentials for [LRu(dppf)Cl] complexes {L = Ind (2), Cp (2A) and Cp* (2B)} occurred in the order Cp* < Ind < Cp, correlating with the more electron‐donating groups lowering the oxidation potentials. EPR experiments performed on the one‐electron oxidised forms of 3 and 5 indicated paramagnetic compounds with g values close to 2, while the two‐electron oxidised forms of 3 and 5 were diamagnetic. All the complexes were characterised spectroscopically, and 5 and 6 also crystallographically. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis of Diazen‐1‐ium‐1,2‐diolates Monitored by the “NOtizer” Apparatus: Relationship between Formation Rates, Molecular Structure and the Release of Nitric Oxide
Authors: Konter Joerg , Abuo‐Rahma Gamal El‐Din A. A. , El‐Emam Ali , Lehmann Jochen
Published: November 2006

Nitrogen‐bound diazen‐1‐ium‐1,2‐diolates (diazeniumdiolates, “NONOates”, “solid NO”) are generally prepared from secondary amines and nitric oxide and are compounds of first choice for the direct release of nitric oxide (NO). First, we report on the relationships between the structures of the amines and the formation rates of the corresponding NONOates, second on the structures of the NONOates and the rate of NO release and finally between the rates of NONOate formation and NO release from these species. A series of differently sized and substituted cyclic and aliphatic amines were used to quantify the reactivity of amines towards NO by monitoring the decrease in NO pressure with the NOtizer, an apparatus developed for this study. The release of NO was measured amperometrically with an NO‐sensitive electrode and the half‐lives of novel diazeniumdiolates were determined by UV spectroscopy. It was found that steric hindrance and heteroatomic substituents in the amines' side chains reduce the formation rates of the sodium salts of the NONOates and also slow down NO release from them. Exceptions were found with piperidine‐2‐carboxylic acid derivatives which react to give NONOates more slowly than piperidine but release NO much faster despite steric hindrance. A secondary amine carrying an additional primary amine reacted quickly with NO, but the corresponding NONOate showed slower releaser of NO owing to the formation of an intramolecular NONOate salt as well as the sodium salt derivative. Azetidine reacts faster with NO than all of the other amines, but decomposition of the corresponding NONOate proved to be unexpectedly slow.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Chiral 6,6′‐Bis(oxazolyl)‐1,1′‐biphenyls as Ligands for Copper(I)‐Catalyzed Asymmetric Cyclopropanation
Authors: Khanbabaee Karamali , Basceken Sinan , Flörke Ulrich
Published: November 2006

A series of chiral bis(oxazoline)s with biphenyl backbones were synthesized from enantiomerically pure (S)‐ and (R)‐hexabenzyloxydiphenic acid (1) and their utility in copper(I)‐catalyzed asymmetric cyclopropanation was investigated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Total Synthesis of (±)‐Decursivine
Authors: Leduc Andrew B. , Kerr Michael A.
Published: November 2006

The first preparation of the antimalarial natural product decursivine is described. A Diels–Alder/Plieninger indolization protocol allows convenient preparation of the indole 15 which, in turn is a suitable substrate for a boron–enolate aldol reaction with piperonal (16). The resulting adduct 14 is transformed efficiently to the natural product. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Numerical study of transitional separated–reattached flow over surface‐mounted obstacles using large‐eddy simulation
Authors: Abdalla Ibrahim E. , Cook Malcolm J. , Yang Zhiyin
Published: November 2006

Large‐eddy simulation (LES) of transitional separating–reattaching flow on a square surface mounted obstacle has been performed. The Reynolds number based on the uniform inlet velocity and the obstacle height is 4.5 × 103. A dynamic subgrid‐scale model is employed in this work. The mean LES results compare favourably with the available experimental and direct numerical simulation (DNS) data. Extensive analysis of the time series signals of the velocity and pressure fields at different locations including positions close to solid surfaces, at the centre and edge of the separated–reattached boundary layer using the windowed Fourier transform (WFT) and the wavelet transform was performed. The spectra analysis revealed the nature of the amplified frequencies at all the important locations of the flow field. Excited modes that could be due to the movement (shedding) of large‐scale structures and pairing of such types of structures are identified. A clear frequency peak was captured just upstream of the separation line. The value of the frequency peak and the low percentage of the back flow velocity compared to the freestream velocity in the current case strongly support the idea that this amplified frequency is most likely due to the Kelvin–Helmholtz (K–H) instability mechanism of the shear layer forming in the boundary of the small upstream separated region rather than being attributed to the flapping of the shear layer. Copyright © 2006 John Wiley & Sons, Ltd.
Influence of Thermal Treatment on RuSe Cathode Materials for Direct Methanol Fuel Cells
Authors: Cheng H. , Yuan W. , Scott K.
Published: November 2006

The effect of thermal treatment on the activity of the carbon‐supported ruthenium and selenium cathode catalysts for the oxygen reduction reaction is evaluated in both half‐cells and in fuel cells, using voltammetric and steady‐state polarisation techniques. The catalysts treated at 300 and 400 °C give a better performance compared to that of the as prepared samples. The catalysts are characterised by scanning electron microscopy, energy‐dispersive X‐ray spectrometry, and X‐ray diffractometry in terms of the crystalline state, morphology, and composition of the materials. The formation of porous RuSe binary interfaces and the transformation from the amorphous to crystalline state are directly linked to the heat treatment temperatures, which in turn, affect the activity and methanol tolerance of the catalysts. The RuSe/C is compared to Pt/C cathode materials.
Characteristics of La0.85Sr0.15MnO3–δ Powders Synthesized by a Glycine‐Nitrate Process
Authors: Peng R. , Fan X. , Jiang Z. , Xia C.
Published: November 2006

The amount of glycine added, i.e., the glycine/oxide molar ratio, k, is optimized for synthesizing La0.85Sr0.15MnO3‐δ (LSM) powders by a glycine‐nitrate process. The specific surface area of the resultant LSM powders increases with this ratio, which indicates the deviation of the required glycine from the stoichiometric reaction. The powder is further characterized as a precursor for LSM‐SDC (samarium‐doped ceria) composite electrodes for solid oxide fuel cells. The electronic conductivity of the LSM‐SDC composite increases with increases in the glycine/oxide ratio. In addition, the ratio has an effect on the interfacial polarization resistance of the LSM‐SDC electrodes, as determined with symmetric cells using AC impedance spectroscopy. The lowest resistance is achieved using a LSM powder prepared with 20% more glycine than the stoichiometric requirement (k = 1.2). The activation energies for electrochemical oxygen reduction are about 1.3 eV, when the ratio is below 1.2, and about 1.0 eV, when it exceeds 1.2. The activation energy suggests that oxygen ion transfer is the rate determining process for the LSM‐SDC electrode when k ≥ 1.2, whereas both mass transfer and charge transfer are the rate limiting steps when k < 1.2.
Regulation of emotional responses elicited by threat‐related stimuli
Authors: Eippert Falk , Veit Ralf , Weiskopf Nikolaus , Erb Michael , Birbaumer Niels , Anders Silke
Published: November 2006

The capacity to voluntarily regulate emotions is critical for mental health, especially when coping with aversive events. Several neuroimaging studies of emotion regulation found the amygdala to be a target for downregulation and prefrontal regions to be associated with downregulation. To characterize the role of prefrontal regions in bidirectional emotion regulation and to investigate regulatory influences on amygdala activity and peripheral physiological measures, a functional magnetic resonance imaging (fMRI) study with simultaneous recording of self‐report, startle eyeblink, and skin conductance responses was carried out. Subjects viewed threat‐related pictures and were asked to up‐ and downregulate their emotional responses using reappraisal strategies. While startle eyeblink responses (in successful regulators) and skin conductance responses were amplified during upregulation, but showed no consistent effect during downregulation, amygdala activity was increased and decreased according to the regulation instructions. Trial‐by‐trial ratings of regulation success correlated positively with activity in amygdala during upregulation and orbitofrontal cortex during downregulation. Downregulation was characterized by left‐hemispheric activation peaks in anterior cingulate cortex, dorsolateral prefrontal cortex, and orbitofrontal cortex and upregulation was characterized by a pattern of prefrontal activation not restricted to the left hemisphere. Further analyses showed significant overlap of prefrontal activation across both regulation conditions, possibly reflecting cognitive processes underlying both up‐ and downregulation, but also showed distinct activations in each condition. The present study demonstrates that amygdala responses to threat‐related stimuli can be controlled through the use of cognitive strategies depending on recruitment of prefrontal areas, thereby changing the subject's affective state. Hum Brain Mapp, 2007. © 2006 Wiley‐Liss, Inc.
fMRI study of effort and information processing in a working memory task
Authors: Jansma J.M. , Ramsey N.F. , de Zwart J.A. , van Gelderen P. , Duyn J.H.
Published: November 2006

It is unclear how effort translates into brain function. In this study we endeavored to identify the activity in a working memory task that is related to the allocation of mental resources. Such activity, if present, would be a likely candidate to explain how effort works in terms of brain function. Eleven healthy participants performed a Sternberg task with a memory‐set of one, three, or five consonants in an fMRI study. Probe stimuli were either one consonant or one digit. We expected digits to be processed automatically and consonants to require working memory. Because the probe type was unpredictable and subjects had to respond as fast as possible, we expected subjects to allocate mental resources on the basis of the memory‐set size, not the probe type. Accordingly, we anticipated that activity in regions involved in effort would be a function of the size of the memory‐set, but independent of the type of probe. We found that the reaction‐time for digits increased in line with our expectation of automatic processing and the reaction time for letters increased in line with our expectation of controlled processing. fMRI revealed that activity in the right ventral‐prefrontal cortex changed as a function of effort. The ventral anterior cingulate cortex and hypothalamus showed reduced activity as a function of effort. Activity in regions regarded as pivotal for working memory (among others, the left dorsolateral prefrontal cortex, anterior cingulate cortex) appeared to be predominantly related to information processing and not involved in effort. Hum Brain Mapp, 2007. © 2006 Wiley‐Liss, Inc.
The interaction between orthographic and phonological information in children: An fMRI study
Authors: Bitan Tali , Burman Douglas D. , Chou Tai‐Li , Lu Dong , Cone Nadia E. , Cao Fan , Bigio Jordan D. , Booth James R.
Published: November 2006

We examined the neural representations of orthographic and phonological processing in children, while manipulating the consistency between orthographic and phonological information. Participants, aged 9–15, were scanned while performing rhyming and spelling judgments on pairs of visually presented words. The orthographic and phonological similarity between words in the pair was independently manipulated, resulting in four conditions. In the nonconflicting conditions, both orthography and phonology of the words were either (1) similar (lime‐dime) or (2) different (staff‐gain); in conflicting conditions, words had (3) similar phonology and different orthography (jazz‐has) or (4) different phonology and similar orthography (pint‐mint). The comparison between tasks resulted in greater activation for the rhyming task in bilateral inferior frontal gyri (BA 45/47), and greater activation for the spelling task in bilateral inferior/superior parietal lobules (BA 40/7), suggesting greater involvement of phonological and semantic processing in the rhyming task, and nonlinguistic spatial processing in the spelling task. Conflicting conditions were more difficult in both tasks and resulted in greater activation in the above regions. The results suggest that when children encounter inconsistency between orthographic and phonological information they show greater engagement of both orthographic and phonological processing. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.
Altered functional connectivity in early Alzheimer's disease: A resting‐state fMRI study
Authors: Wang Kun , Liang Meng , Wang Liang , Tian Lixia , Zhang Xinqing , Li Kuncheng , Jiang Tianzi
Published: November 2006

Previous studies have led to the proposal that patients with Alzheimer's disease (AD) may have disturbed functional connectivity between different brain regions. Furthermore, recent resting‐state functional magnetic resonance imaging (fMRI) studies have also shown that low‐frequency (<0.08 Hz) fluctuations (LFF) of the blood oxygenation level‐dependent signals were abnormal in several brain areas of AD patients. However, few studies have investigated disturbed LFF connectivity in AD patients. By using resting‐state fMRI, this study sought to investigate the abnormal functional connectivities throughout the entire brain of early AD patients, and analyze the global distribution of these abnormalities. For this purpose, the authors divided the whole brain into 116 regions and identified abnormal connectivities by comparing the correlation coefficients of each pair. Compared with healthy controls, AD patients had decreased positive correlations between the prefrontal and parietal lobes, but increased positive correlations within the prefrontal lobe, parietal lobe, and occipital lobe. The AD patients also had decreased negative correlations (closer to zero) between two intrinsically anti‐correlated networks that had previously been found in the resting brain. By using resting‐state fMRI, our results supported previous studies that have reported an anterior–posterior disconnection phenomenon and increased within‐lobe functional connectivity in AD patients. In addition, the results also suggest that AD may disturb the correlation/anti‐correlation effect in the two intrinsically anti‐correlated networks. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.
Real‐time fMRI using brain‐state classification
Authors: LaConte Stephen M. , Peltier Scott J. , Hu Xiaoping P.
Published: November 2006

We have implemented a real‐time functional magnetic resonance imaging system based on multivariate classification. This approach is distinctly different from spatially localized real‐time implementations, since it does not require prior assumptions about functional localization and individual performance strategies, and has the ability to provide feedback based on intuitive translations of brain state rather than localized fluctuations. Thus this approach provides the capability for a new class of experimental designs in which real‐time feedback control of the stimulus is possible—rather than using a fixed paradigm, experiments can adaptively evolve as subjects receive brain‐state feedback. In this report, we describe our implementation and characterize its performance capabilities. We observed ∼80% classification accuracy using whole brain, block‐design, motor data. Within both left and right motor task conditions, important differences exist between the initial transient period produced by task switching (changing between rapid left or right index finger button presses) and the subsequent stable period during sustained activity. Further analysis revealed that very high accuracy is achievable during stable task periods, and that the responsiveness of the classifier to changes in task condition can be much faster than signal time‐to‐peak rates. Finally, we demonstrate the versatility of this implementation with respect to behavioral task, suggesting that our results are applicable across a spectrum of cognitive domains. Beyond basic research, this technology can complement electroencephalography‐based brain computer interface research, and has potential applications in the areas of biofeedback rehabilitation, lie detection, learning studies, virtual reality‐based training, and enhanced conscious awareness. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.
Bayesian comparison of spatially regularised general linear models
Authors: Penny Will , Flandin Guillaume , Trujillo‐Barreto Nelson
Published: November 2006

In previous work (Penny et al., [2005]: Neuroimage 24:350–362) we have developed a spatially regularised General Linear Model for the analysis of functional magnetic resonance imaging data that allows for the characterisation of regionally specific effects using Posterior Probability Maps (PPMs). In this paper we show how it also provides an approximation to the model evidence. This is important as it is the basis of Bayesian model comparison and provides a unified framework for Bayesian Analysis of Variance, Cluster of Interest analyses and the principled selection of signal and noise models. We also provide extensions that implement spatial and anatomical regularisation of noise process parameters. Hum Brain Mapp 2007. © 2006 Wiley‐Liss, Inc.
High‐resolution fMRI investigation of the medial temporal lobe
Authors: Kirwan C. Brock , Jones Craig K. , Miller Michael I. , Stark Craig E.L.
Published: November 2006

The medial temporal lobe (MTL) is critical for declarative memory formation. Several theories of MTL function propose functional distinctions between the different structures of the MTL, namely the hippocampus and the surrounding cortical areas. Furthermore, computational models and electrophysiological studies in animals suggest distinctions between the subregions of the hippocampus itself. Standard fMRI resolution is not sufficiently fine to resolve activity on the scale of hippocampal subregions. Several approaches to scanning the MTL at high resolutions have been made, however there are limitations to these approaches, namely difficulty in conducting group‐level analyses. We demonstrate here techniques for scanning the MTL at high resolution and analyzing the high‐resolution fMRI data at the group level. To address the issue of cross‐participant alignment, we employ the ROI‐LDDMM alignment technique, which is demonstrated to result in smaller alignment errors when compared with several other common normalization techniques. Finally, we demonstrate that the pattern of activation obtained in the high‐resolution functional data is similar to that obtained at lower resolution, although the spatial extent is smaller and the percent signal change is greater. This difference in the pattern of activation may be due to less partial volume sampling in the high‐resolution data, resulting in more accentuated regions of activation. Hum Brain Mapp 2006. © 2006 Wiley‐Liss, Inc.
Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system
Authors: Lavie Muriel , Voisset Cécile , Vu-Dac Ngoc , Zurawski Virginie , Duverlie Gilles , Wychowski Czeslaw , Dubuisson Jean
Published: November 2006

Serum amyloid A (SAA) is an acute phase protein produced by the liver. SAA concentration increases markedly in the serum following inflammation and infection. Large increases in SAA concentration during the acute phase response suggest that SAA has a beneficial role in host defense. This study sought to determine the effect of SAA on hepatitis C virus (HCV) infectivity using retroviral particles pseudotyped with HCV envelope glycoproteins (HCVpp) and the recently developed cell culture system for HCV (HCVcc). SAA inhibited HCVpp and HCVcc infection in a dose-dependent manner by affecting an early step of the virus life cycle. Further characterization with HCVpp indicated that SAA blocks virus entry by interacting with the viral particle. In addition, the antiviral activity of SAA was strongly reduced when high-density lipoproteins (HDL) were coincubated with SAA. However, HDL had only a slight effect on the antiviral activity of SAA when HCVpp was first preincubated with SAA. Furthermore, analyses of SAA in sera of chronic HCV patients revealed the presence of variable levels of SAA with abnormally elevated concentrations in some cases. However, no obvious clinical correlation was found between SAA levels and HCV viral loads.

In conclusion

, our data demonstrate an antiviral activity for SAA and suggest a tight relationship between SAA and HDL in modulating HCV infectivity.

Supplementary material for this article can be found on the HEPATOLOGY website
(http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Aquaporin-1 and aquaporin-2 urinary excretion in cirrhosis: Relationship with ascites and hepatorenal syndrome
Authors: Esteva-Font Christina , Baccaro Maria E. , Fernández-Llama Patricia , Sans Laia , Guevara Monica , Ars Elisabet , Jiménez Wladimiro , Arroyo Vicente , Ballarín Jose A. , Ginès Pere
Published: November 2006

Several experimental models of cirrhosis have shown dysregulation of renal aquaporins in different phases of liver disease. We investigated the urinary excretion of both aquaporin-1 and aquaporin-2 in patients with cirrhosis at different stages of the disease. Twenty-four-hour urine was collected from 11 healthy volunteers, 13 patients with compensated cirrhosis (without ascites), and 20 patients with decompensated cirrhosis (11 with ascites without renal failure and 9 with hepatorenal syndrome). Aquaporin-1 and aquaporin-2 excretion was analyzed by immunoblotting. Urinary aquaporin-2 excretion was reduced in patients with cirrhosis compared to healthy subjects. A progressive decrease in urinary aquaporin-2 excretion was observed as the severity of cirrhosis increased, from compensated cirrhosis to cirrhosis with ascites and hepatorenal syndrome. Patients with hyponatremia had lower urinary aquaporin-2 excretion than patients without hyponatremia. Vasopressin plasma level did not correlate with aquaporin-2 excretion. There were no differences between healthy subjects and patients with cirrhosis with or without ascites in urinary excretion of aquaporin-1, but urinary aquaporin-1 excretion of those with hepatorenal syndrome was extremely low.

In conclusion

, patients with cirrhosis appear to exhibit a decreased abundance of renal aquaporin-2 and therefore lower water permeability in the collecting tubules. This may represent an adaptive renal response to sodium retention, with expansion of extracellular fluid volume and dilutional hyponatremia observed in those who have cirrhosis with ascites. Finally, aquaporin-1 does not appear to play a role in the progressive dysregulation of extracellular fluid volume in cirrhosis.
Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis
Authors: Mazzaferro Vincenzo , Romito Raffaele , Schiavo Marcello , Mariani Luigi , Camerini Tiziana , Bhoori Sherrie , Capussotti Lorenzo , Calise Fulvio , Pellicci Riccardo , Belli Giulio , Tagger Alessandro , Colombo Massimo , Bonino Ferruccio , Majno Pietro , Llovet Josep M.
Published: November 2006

Tumor recurrence after resection of hepatocellular carcinoma (HCC) can occur early (<2 years) or late (>2 years) as metastases or

de novo

tumors. Interferon (IFN) has the potential for chemoprevention against hepatitis C virus (HCV)-related cirrhosis. A predetermined group of 150 HCV RNA–positive patients undergoing resection of early- to intermediate-stage HCC was stratified into 80 HCV-pure (hepatitis B anticore antibody [anti-HBc]–negative) and 70 mixed HCV+hepatitis B virus (HBV) (anti-HBc–positive) groups, then randomized to IFN-α (3 million units 3 times every week for 48 weeks [n = 76]) versus control (n = 74). The primary end point was recurrence-free survival (RFS); secondary end points were disease-specific and overall survival. Intention-to-treat and subgroup analysis on adherent patients were conducted. Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis. No patient experienced life-threatening adverse events. There were 28 adherent patients (37%). After 45 months of median follow-up, overall survival was 58.5%, and no significant difference in RFS was detectable between the two study arms (24.3% vs. 5.8%;

P

= .49). HCC recurred in 100 patients (48 IFN-treated, 52 controls), with a 50% reduction in late recurrence rate in the treatment arm. HCC multiplicity and vascular invasion were significantly related to recurrence (

P

= .01 and .0003). After viral status stratification, while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences (72 events), there was a significant benefit on late recurrences (28 events) in HCV-pure patients adherent to treatment (HR: 0.3; 95% CI: 0.09–0.9;

P

= .04).

In conclusion

, IFN does not affect overall prevention of HCC recurrence after resection, but it may reduce late recurrence in HCV-pure patients receiving effective treatment.
Oxidative-stress and IL-6 mediate the fibrogenic effects of rodent Kupffer cells on stellate cells
Authors: Nieto Natalia
Published: November 2006

The impact of Kupffer cells (KCs) on the hepatic stellate cell (HSC) fibrogenic response was examined in an

in vitro

coculture model of primary KCs and HSCs. Coculture with KCs induced a more activated phenotype and greater proliferation compared to HSC cultured alone. Similar results were obtained on Matrigel which maintains HSCs quiescent. The effect of KCs on HSC collagen I involved transcriptional regulation, as determined by nuclear

in vitro

transcription run-on assays, promoter studies, and Northern blot analysis, while stability of the

COL1A1

and

COL1A2

mRNA were similar. The minimal

COL1A1

and

COL1A2

promoter regions responsible for the KC effects were localized to the −515 and −378 base pair (bp) regions, respectively. Intracellular and extracellular collagen I protein, H2O2, and IL-6 increased in a time-dependent fashion, especially for HSCs in coculture. Catalase prevented these effects as well as the transactivation of both collagen promoters. The rate of collagen I protein synthesis and intracellular collagen I degradation remained similar but the

t

1/2 of the secreted collagen I was lower for HSC in coculture. MMP13, a protease that degrades extracellular collagen I, decreased in the cocultures, while TIMP1, a MMP13 inhibitor, increased; and these effects were prevented by catalase, anti-IL-6, and siRNA-IL-6. Cocultured HSC showed elevated phosphorylation of p38 which when inhibited by catalase, anti-IL-6, and siRNA-IL-6 it blocked TIMP1 upregulation and collagen I accumulation.

In conclusion

, these results unveil a novel dual mechanism mediated by H2O2 and IL-6 by which KCs may modulate the fibrogenic response in HSCs.

Supplementary material for this article can be found on the HEPATOLOGY website
(http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis
Authors: Primignani Massimo , Barosi Giovanni , Bergamaschi Gaetano , Gianelli Umberto , Fabris Federica , Reati Raffaella , Dell'Era Alessandra , Bucciarelli Paolo , Mannucci Pier Mannuccio
Published: November 2006

The diagnosis of an underlying chronic myeloproliferative disorder (CMPD) is often problematic in patients with primary extrahepatic portal vein obstruction (EHPVO) or Budd-Chiari syndrome (BCS); indeed, conventional clinical and hematological parameters usually yield insufficient information. To assess the diagnostic contribution of the gain-of-function mutation V617F of the

JAK2

gene, 93 patients with EHPVO or BCS were investigated.

JAK2

V617F was identified in 35.6% of 73 patients with EHPVO and in 40% of 20 patients with BCS. Taking the

JAK2

mutation as a test with the highest positive predictive value for the diagnosis of CMPD, conventional clinical-hematological parameters had a sensitivity for CMPD lower than 48%. Bone marrow (BM) histology provided a diagnosis of CMPD in 41/74 (55.4%) patients, with a sensitivity of 93.5%. Clonality of hematopoiesis as assessed by granulocyte X-chromosome inactivation was present in 65.1% of 43 informative female patients, with a sensitivity of 86.6%. By resolving the sensitivity bias of the

JAK2

mutation with the results of BM histology and clonality assay, CMPD was diagnosed in 53% of patients with EHPVO or BCS.

In conclusion

, CMPD is the major cause of primary EHPVO or BCS.

JAK2

V617F is a very reliable and noninvasive molecular marker for CMPD and should be used as a first test for diagnosis.
JunD is a profibrogenic transcription factor regulated by Jun N-terminal kinase-independent phosphorylation
Authors: Smart David E. , Green Karen , Oakley Fiona , Weitzman Jonathan B. , Yaniv Moshe , Reynolds Gary , Mann Jelena , Millward-Sadler Harry , Mann Derek A.
Published: November 2006

JunD is implicated in the regulation of hepatic stellate cell (HSC) activation and liver fibrosis via its transcriptional regulation of the tissue inhibitor of metalloproteinases-1 (TIMP-1) gene. In the present study we found

in vivo

evidence of a role for JunD in fibrogenesis. Expression of JunD was demonstrated in alpha-SMA-positive activated HSCs of fibrotic rodents and human livers. The

junD

−/− mice were protected from carbon tetrachloride–induced fibrosis. The livers of injured

junD

−/− mice displayed significantly reduced formation of fibrotic crosslinked collagen and a smaller number of alpha-SMA-positive HSCs compared with those of wild-type (wt) mice. Hepatic TIMP-1 mRNA expression in injured

junD

−/− mice was 78% lower and in culture activated

junD

−/− HSCs was 50%-80% lower than that in wt mice. In examining the signal transduction mechanisms that regulate JunD-dependent TIMP-1 expression, we found a role for phosphorylation of the Ser100 residue of JunD but ruled out JNK as a mediator of this event, suggesting ERK1/2 is utilized.

In conclusion

, a signaling pathway for the development of fibrosis involves the regulation of TIMP-1 expression by phosphorylated JunD.

Supplementary material for this article can be found on the HEPATOLOGY website
(http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Fulminant hepatitis A virus infection in the United States: Incidence, prognosis, and outcomes
Authors: Taylor Ryan M. , Davern Timothy , Munoz Santiago , Han Stephen-Huy , McGuire Brendan , Larson Anne M. , Hynan Linda , Lee William M. , Fontana Robert J.
Published: November 2006

Acute liver failure (ALF) due to hepatitis A virus (HAV) infection is an uncommon but potentially lethal illness. The aim of this study was to identify readily available laboratory and clinical features associated with a poor prognosis among ALF patients with HAV infection. The presenting features of 29 adults with anti-HAV IgM positive ALF enrolled in the ALFSG_between 1998 and 2005 were reviewed. The HAV patients listed for transplantation by UNOS were also reviewed. Acute HAV accounted for 3.1% of patients enrolled in the ALFSG. At 3 weeks follow-up, 16 had spontaneously recovered (55%), 9 underwent transplantation (31%), and 4 had died (14%). A prognostic model incorporating 4 presenting features (serum ALT <2,600 IU/L, creatinine >2.0 mg/dL, intubation, pressors) had an AUROC for transplant/death of 0.899 which was significantly better than the King's College criteria (0.623,

P

= .018) and MELD scores (0.707,

P

= .0503). Between 1988 and 2005, the frequency of patients requiring liver transplantation for HAV in the UNOS database significantly decreased from 0.7 % to 0.1% (

P

< .001). In addition, the proportion of HAV cases enrolled in the ALFSG significantly decreased from 5% to 0.8% (

P

= .007).

In conclusion

, the frequency of HAV patients enrolling in the ALFSG and being listed for liver transplantation in the United States has declined in parallel. A prognostic index consisting of 4 clinical and laboratory features predicted the likelihood of transplant/death significantly better than other published models suggesting that disease specific prognostic models may be of value in non-acetaminophen ALF.
Hepatic precursors derived from murine embryonic stem cells contribute to regeneration of injured liver
Authors: Heo Jeonghoon , Factor Valentina M. , Uren Tania , Takahama Yasushi , Lee Ju-Seog , Major Marian , Feinstone Stephen M. , Thorgeirsson Snorri S.
Published: November 2006

We established an efficient system for differentiation, expansion and isolation of hepatic progenitor cells from mouse embryonic stem (ES) cells and evaluated their capacity to repopulate injured liver. Using mouse ES cells transfected with the green fluorescent protein (GFP) reporter gene regulated by albumin (ALB) enhancer/promoter, we found that a serum-free chemically defined medium supports formation of embryoid bodies (EBs) and differentiation of hepatic lineage cells in the absence of exogenous growth factors or feeder cell layers. The first GFP+ cells expressing ALB were detected in close proximity to “beating” myocytes after 7 days of EB cultures. GFP+ cells increased in number, acquired hepatocyte-like morphology and hepatocyte-specific markers (

i.e.

, ALB, AAT, TO, and G6P), and by 28 days represented more than 30% of cells isolated from EB outgrowths. The FACS-purified GFP+ cells developed into functional hepatocytes without evidence of cell fusion and participated in the repairing of diseased liver when transplanted into MUP-uPA/SCID mice. The ES cell-derived hepatocytes were responsive to normal growth regulation and proliferated at the same rate as the host hepatocytes after an additional growth stimulus from CCl4-induced liver injury. The transplanted GFP+ cells also differentiated into biliary epithelial cells.

In conclusion

, a highly enriched population of committed hepatocyte precursors can be generated from ES cells

in vitro

for effective cell replacement therapy.

Supplementary material for this article can be found on the HEPATOLOGY website
(http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
A picture says more than a thousand words: Structural insights into hepatitis C virus translation initiation
Authors: Bellecave Pantxika , Moradpour Darius
Published: November 2006

Protein synthesis in mammalian cells requires initiation factor eIF3, a ˜750-kilodalton complex that controls assembly of 40S ribosomal subunits on messenger RNAs (mRNAs) bearing either a 5′-cap or an internal ribosome entry site (IRES). Cryoelectron microscopy reconstructions show that eIF3, a five-lobed particle, interacts with the hepatitis C virus (HCV) IRES RNA and the 5′-cap binding complex eIF4F via the same domain. Detailed modeling of eIF3 and eIF4F onto the 40S ribosomal subunit reveals that eIF3 uses eIF4F or the HCV IRES in structurally similar ways to position the mRNA strand near the exit site of 40S, promoting initiation complex assembly.
H. pylori and platelet counts
Authors: Arnold Hays L. , Harrison Stephen A.
Published: November 2006

Helicobacter pylori (HP) eradication therapy is a useful treatment for idiopathic thrombocytopenic purpura (ITP). Some investigators have also reported the effects of proton pump inhibitor (PPI) monotherapy on ITP. We performed a randomized study of HP eradication therapy and PPI monotherapy on ITP. Four of nine patients achieved complete remission (CR), two of nine achieved partial remission (PR) in HP eradication therapy, three of eight achieved CR, and two of eight achieved PR in PPI monotherapy. No significant differences were observed in the CR + PR of these patients between HP eradication therapy and PPI monotherapy. As for cost comparisons, HP eradication therapy is cheaper than PPI monotherapy, but it is less effective.
Laparoscopic liver surgery: Shifting the management of liver tumors
Authors: Koffron Alan , Geller David , Gamblin Clark T. , Abecassis Michael
Published: November 2006

Laparoscopic liver surgery has evolved rapidly over the past 5 years in a select number of centers. The growing experience with these procedures has resulted in a shift in the diagnostic and therapeutic approach to common liver tumors. The fact that resection of benign and malignant hepatic masses can now be accomplished laparoscopically with relatively low morbidity has influenced the decision-making process for physicians involved in the diagnosis and management of these lesions. For example, should a gastroenterologist or hepatologist seeing a 32-year-old woman with an asymptomatic 4 cm hepatic lesion that is radiologically indeterminate for adenoma or focal nodular hyperplasia (FNH): (1) continue to observe with annual computed tomography/magnetic resonance imaging (CT/MRI) scans, (2) subject the patient to a liver biopsy, or (3) refer for laparoscopic resection? For a solitary malignant liver tumor in the left lateral segment, should laparoscopic resection be considered the new standard of care, assuming the surgeon can perform the operation safely? We present current data and representative case studies on the use of laparoscopic liver resection at 2 major medical centers in the United States. We propose that surgical engagement defined by the managing physician's decision to proceed with a surgical intervention is increasingly affected by the availability of, and experience with, laparoscopic liver resection.
Apoptotic signaling in methylglyoxal‐treated human osteoblasts involves oxidative stress, c‐Jun N‐terminal kinase, caspase‐3, and p21‐activated kinase 2
Authors: Chan Wen‐Hsiung , Wu Hsin‐Jung , Shiao Nion‐Heng
Published: November 2006

Methylglyoxal (MG) is a reactive dicarbonyl compound endogenously produced mainly from glycolytic intermediates. MG is cytotoxic through induction of cell death, and elevated MG levels in diabetes patients are believed to contribute to diabetic complications. In this report, we show for the first time that MG treatment triggers apoptosis in human osteoblasts. We further show that MG‐induced apoptosis of osteoblasts involves specific apoptotic biochemical changes, including oxidative stress, c‐Jun N‐terminal kinase (JNK) activation, mitochondrial membrane potential changes, cytochrome C release, increased Bax/Bcl‐2 protein ratios, and activation of caspases (caspase‐9, caspase‐3) and p21‐activated protein kinase 2 (PAK2). Treatment of osteoblasts with SP600125, a JNK‐specific inhibitor, led to a reduction in MG‐induced apoptosis and decreased activation of caspase‐3 and PAK2, indicating that JNK activity is upstream of these events. Experiments using anti‐sense oligonucleotides against PAK2 further showed that PAK2 activation is required for MG‐induced apoptosis in osteoblasts. Interestingly, we also found that MG treatment triggered nuclear translocation of NF‐κB, although the precise regulatory role of NF‐κB activation in MG‐induced apoptosis remains unclear. Lastly, we examined the effect of MG on osteoblasts in vivo, and found that exposure of rats to dietary water containing 100–200 µM MG caused bone mineral density (BMD) loss. Collectively, these results reveal for the first time that MG treatment triggers apoptosis in osteoblasts via specific apoptotic signaling, and causes BMD loss in vivo. J. Cell. Biochem. 100: 1056–1069, 2007. © 2006 Wiley‐Liss, Inc.