bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhenium Calix[4]arenes: Precursors to Novel Imaging and Cancer Therapy Agents
Authors: Redshaw Carl , Liu Xiaoming , Zhan Shuzong , Hughes David L. , Baillie‐Johnson Hugo , Elsegood Mark R. J. , Dale Sophie H.
Published: May 2008

Interaction of [ReOCl3(PPh3)2] with tert‐butylcalix[4]areneH4, Cax(OH)4, in the presence of MOtBu (M = Na, K), or MH, under anaerobic conditions affords the isostructural rhenium(V) oxo complexes [Re(O)(PPh3)Cax(O)4M(NCMe)2] · 4MeCN [M = Na, (1); K, (2)] containing an alkali‐metal cation within an elliptical ligand conformation. In the presence of air, the same reaction affords dioxo rhenium(VII) complexes of the form [Re(O)2Cax(O)4M(NCMe)2] [M = Na, · ca. 2.8MeCN (3); K, · 3MeCN (4)]. Prolonged heating also led to the isolation of the first examples of rhenium–rhenium bonding supported by calixarene ligands, viz. [ReCax(O)4M(NCMe)2(μ‐O)]2 · 4MeCN [M = Na, (5); K, (6)], and in one case to {ReCax(O)4K(NCMe)2[μ‐OK(NCMe)2]}2Cax(O)2(OH)2 · 7MeCN (7). The use of 2 as starting material led to the isolation of the complex {[Re(O)Cax(O)4K(NCMe)2]2(μ‐O)} · 2MeCN (8). Given the diversity and complexity of the products arising from these “oxo” reactions, attention was switched to the isoelectronic organoimido [NR] group, and given its synthetic utility, the tert‐butylimido group [NtBu] was chosen as our entry point. Reaction of [Re(NtBu)2Cl3] with Cax(OH)4 in a 1:1 ratio afforded the orange [Re(NtBu)2ClCax(O)2(OH)2]· MeCN (9), containing both a linear and a bent imido group. Increasing the amount of Cax(OH)4 (2:3 ratio) afforded both 9 together with the dark red complex [Re(NtBu)Cax(O)4Cax(O)(OH)3]· 6MeCN (10), which contains both mono‐ and tetra‐dentate calixarene ligands. In the presence of adventitious oxygen, the complex {[Re(NtBu)Cax(O)4]2(μ‐O)} · 3MeCN (11) was formed. To favour monomeric complex formation, the lithium salt of the monomethoxycalix[4]arene, namely Cax(OLi)3(OMe), was treated with [Re(NtBu)2Cl3] affording the mono‐ and bisacetonitrile‐ligated species [Re(NtBu)2Cax(O)4Li(NCMe)2][Re(NtBu)2Cax(O)4Li(NCMe)] · MeCN (12). To avoid the lithium incorporation of 12, Cax(OH)3(OMe) was treated with [Re(NtBu)3(OSiMe3)] affording [Re(NtBu)2Cax(O)3(OMe)] (13), for which the methoxy ether group protudes into the calixarene cavity. The compounds 1–13 have been structurally characterised by single‐crystal X‐ray diffraction (synchrotron radiation was used for 4, 6, 7, 9, 11–13).(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Highly Enantioselective Syntheses of Chiral β‐Amino Alcohols in the Presence of Chiral TiIV Schiff Base Complexes as Catalysts
Authors: Kureshy Rukhsana I. , Prathap K. Jeya , Agrawal Santosh , Khan Noor‐ul H. , Abdi Sayed H. R. , Jasra Raksh V.
Published: May 2008

Two new chiral Schiff bases 1 and 2 were prepared by condensation of 3,3′‐di‐tert‐butyl‐5,5′‐methylenebis(salicylaldehyde) and 3,3′‐dimethyl‐5,5′‐methylenebis(salicylaldehyde) with (1R,2S)‐(–)‐2‐aminodiphenylethanol and were characterized by elemental analysis, 1H NMR, 13C NMR, IR, UV/Vis, and CD spectroscopy, optical rotation, and mass spectrometry. Highly enantioselective ring opening reactions of meso‐stilbene oxide, cyclohexene oxide, cyclooctene oxide, and cis‐butene oxide with anilines in the presence of several additives were carried out in the presence of TiIV complexes generated in situ through the interaction of Ti(OiPr)4 with chiral Schiff bases 1 and 2 at 0 °C. Excellent yields (>99 %) of chiral β‐amino alcohols with high enantioselectivity (ee, >99 %) were achieved in 10 h when chiral imines were used as additives. The catalyst 1‐Ti(OiPr)4 worked better than the catalyst 2‐Ti(OiPr)4 in terms of reactivity and enantioselecitivity for the epoxide ring opening reactions to produce chiral β‐amino alcohols in high optical purity. The chiral catalyst used in this study was recoverable and recyclable several times with retention of its performance. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Radical Carbodiazenylation – A Convenient and Effective Method to Achieve Carboamination of Non‐Activated Olefins
Authors: Blank Olga , Wetzel Alexander , Ullrich Daniela , Heinrich Markus R.
Published: May 2008

The regioselective addition of aryl and aryldiazenyl substituents to olefinic substrates can be described as carbodiazenylation. In this report we present our final results relating to this unique type of radical functionalization reaction, which has now been developed into a convenient, versatile and highly effective synthetic method. Starting from an investigation into rate constants for the addition of aryl radicals to monosubstituted, non‐activated olefins, this key step is shown to be both fast and selective in mixtures of dimethyl sulfoxide and water. The by‐products obtained in earlier reactions reveal that the main complication of carbodiazenylation is the formation of biaryl azo compounds. A carefuladjustment of the carbodiazenylation procedure led tosignificantly improved results and now permits the synthesis of previously inaccessible products. New applications of carbodiazenylation such as the synthesis of 1,2‐diazabutadienes, tetrahydropyridazines and substituted tricyclanes were investigated. Apart from this, we describe a convenient two‐step sequence for intermolecular carboamination.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
An experimental design for judging synergism on consideration to endocrine disruptor animal experiments
Authors: Matsunaga Nobuhito , Kanno Jun , Hamada Chikuma , Yoshimura Isao
Published: May 2008

This paper investigates an appropriate statistical design for an animal experiment to evaluate synergism of two test chemicals. It assumes a certain number of animals are divided into groups, each of which is treated with a combination of dose levels of two chemicals. A design is identified by the set of group size for each combination of doses, including the case where the dose of either one chemical is zero. The power of t‐test to detect synergism by positive surplus of response on a simultaneous administration group from the additivity plane composed of the responses on single administration groups is adopted as the criterion for the appropriate design. The applicable design is investigated for the application to real cases of endocrine disrupter study conducted at the National Institute of Health Sciences of Japan.

It revealed that the dose level of the simultaneous administration group should be located inside or on the boundary of a triangular region and that the total number of animals should be the same as those for single administration groups. Copyright © 2008 John Wiley & Sons, Ltd.
Duplication of paternal IGF2 or loss of maternal IGF2 imprinting occurs in half of Wilms tumors with various structural WT1 abnormalities
Authors: Haruta Masayuki , Arai Yasuhito , Sugawara Waka , Watanabe Naoki , Honda Shohei , Ohshima Junjiro , Soejima Hidenobu , Nakadate Hisaya , Okita Hajime , Hata Jun‐ichi , Fukuzawa Masahiro , Kaneko Yasuhiko
Published: May 2008

The WT1 gene essential for the embryonic kidney development is mutated in 15–25% of Wilms tumors (WTs). To clarify whether genetic subtypes of WT1 abnormalities are correlated with IGF2 or CTNNB1 alterations or clinicopathological characteristics, we performed comprehensive WT1, IGF2, and CTNNB1 analyses of 36 WTs with WT1 abnormalities using single nucleotide polymorphism arrays, and methylation analysis of the IGF2‐H19 differentially methylated region. The tumors were classified into three subtypes based on WT1 abnormalities: 13 with WT1 deletion, 12 with WT1 mutation, and 11 with both deletion and mutation. IGF2 alterations were found in 50% (18/36), paternal uniparental disomy (UPD) of 11p13‐11p15 in 13 tumors, UPD limited to 11p15 in 3, and loss of IGF2 imprinting in 2. Quantitative RT‐PCR analysis showed that tumors with IGF2 alteration had higher levels of IGF2 mRNA than tumors without IGF2 alteration (P = 0.02). WT1 mRNA levels were very low in six of eight WTs with WT1 deletion, whereas four of eight WTs with WT1 mutation or both deletion and mutation showed higher levels of WT1 mRNA than fetal kidneys. WTs with WT1 mutations occurred in younger patients (P < 0.01), and WTs with mutations or both deletion and mutation (12/23) were more frequent in syndromic patients than WTs (1/13) with the deletion (P = 0.02). WTs with WT1 mutations or both deletion and mutation had the triphasic histological‐type (15/23; P = 0.03) and CTNNB1 mutation (17/23; P = 0.03) more frequently than WTs with the deletion (2/13 and 4/13). Thus, three WT1 subtypes were correlated with certain genetic and clinicopathological characteristics. © 2008 Wiley‐Liss, Inc.
CAMcog as a screening tool for diagnosis of mild cognitive impairment and dementia in a Brazilian clinical sample of moderate to high education
Authors: Nunes Paula V. , Diniz Breno S. , Radanovic Marcia , Abreu Izabella D. , Borelli Danilo T. , Yassuda Monica S. , Forlenza Orestes V.
Published: May 2008

Background

The CAMCOG is a brief neuropsychological battery designed to assess global cognitive function and ascertain the impairments that are required for the diagnosis of dementia. To date, the cut‐off scores for mild cognitive impairment (MCI) have not been determined. Given the need for an earlier diagnosis of mild dementia, new cut‐off values are also necessary, taking into account cultural and educational effects.

Methods

One hundred and fifty‐seven older adults (mean age: 69.6 ± 7.4 years) with 8 or more years of formal education (mean years of schooling 14.2 ± 3.8) attending a memory clinic at the Institute of Psychiatry University of Sao Paulo were included. Subjects were divided into three groups according to their cognitive status, established through clinical and neuropsychological assessment: normal controls, n = 62; MCI, n = 65; and mild or moderate dementia, n = 30. ROC curve analyses were performed for dementia vs controls, MCI vs controls and MCI vs dementia.

Results

The cut‐off values were: 92/93 for dementia vs controls (AUC = 0.99: sensitivity: 100%, specificity: 95%); 95/96 for MCI vs controls (AUC = 0.83, sensitivity: 64%, specificity: 88%), and 85/86 for MCI vs dementia (AUC = 0.91, sensitivity: 81%, specificity: 88%). The total CAMCOG score was more accurate than its subtests Mini‐mental State Examination, Verbal Fluency Test and Clock Drawing Test when used separately.

Conclusions

The CAMCOG discriminated controls and MCI from demented patients, but was less accurate to discriminate MCI from controls. The best cut‐off value to differentiate controls and demented was higher than suggested in the original publication, probably because only cases of mild to moderate dementia were included. This is important given the need for a diagnostic at earlier stages of Alzheimer's disease. Copyright © 2008 John Wiley & Sons, Ltd.
Cortical sources of visual evoked potentials during consciousness of executive processes
Authors: Babiloni Claudio , Vecchio Fabrizio , Iacoboni Marco , Buffo Paola , Eusebi Fabrizio , Rossini Paolo Maria
Published: May 2008

What is the timing of cortical activation related to consciousness of visuo‐spatial executive functions? Electroencephalographic data (128 channels) were recorded in 13 adults. Cue stimulus briefly appeared on right or left (equal probability) monitor side for a period, inducing about 50% of recognitions. It was then masked and followed (2 s) by a central visual go stimulus. Left (right) mouse button had to be clicked after right (left) cue stimulus. This “inverted” response indexed executive processes. Afterward, subjects said “seen” if they had detected the cue stimulus or “not seen” when it was missed. Sources of event‐related potentials (ERPs) were estimated by LORETA software. The inverted responses were about 95% in seen trials and about 60% in not seen trials. Cue stimulus evoked frontal–parietooccipital potentials, having the same peak latencies in the seen and not seen data. Maximal difference in amplitude of the seen and not seen ERPs was detected at about +300‐ms post‐stimulus (P3). P3 sources were higher in amplitude in the seen than not seen trials in dorsolateral prefrontal, premotor and parietooccipital areas. This was true in dorsolateral prefrontal and premotor cortex even when percentage of the inverted responses and reaction time were paired in the seen and not seen trials. These results suggest that, in normal subjects, the primary consciousness enhances the efficacy of visuo‐spatial executive processes and is sub‐served by a late (100‐ to 400‐ms post‐stimulus) enhancement of the neural synchronization in frontal areas. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Selective detrending method for reducing task‐correlated motion artifact during speech in event‐related FMRI
Authors: Gopinath Kaundinya , Crosson Bruce , McGregor Keith , Peck Kyung K. , Chang Yu‐Ling , Moore Anna , Sherod Megan , Cavanagh Christy , Wabnitz Ashley , Wierenga Christina , White Keith , Cheshkov Sergey , Krishnamurthy Venkatagiri , Briggs Richard W.
Published: May 2008

Task‐correlated motion artifacts that occur during functional magnetic resonance imaging can be mistaken for brain activity. In this work, a new selective detrending method for reduction of artifacts associated with task‐correlated motion (TCM) during speech in event‐related functional magnetic resonance imaging is introduced and demonstrated in an overt word generation paradigm. The performance of this new method is compared with that of three existing methods for reducing artifacts because of TCM: (1) motion parameter regression, (2) ignoring images during speech, and (3) detrending time course datasets of signal components related to TCM (deduced from artifact corrupted voxels). The selective detrending method outperforms the other three methods in reducing TCM artifacts and in retaining blood oxygenation level dependent signal. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.
Rolandic alpha and beta EEG rhythms' strengths are inversely related to fMRI‐BOLD signal in primary somatosensory and motor cortex
Authors: Ritter Petra , Moosmann Matthias , Villringer Arno
Published: May 2008

Similar to the posterior alpha rhythm, pericentral (Rolandic) EEG rhythms in the alpha and beta frequency range are referred to as “idle rhythms” indicating a “resting state” of the respective system. The precise function of these rhythms is not clear. We used simultaneous EEG‐fMRI during a bimanual motor task to localize brain areas involved in Rolandic alpha and beta EEG rhythms. The identification of these rhythms in the MR environment was achieved by a blind source separation algorithm. Rhythm “strength”, i.e. spectral power determined by wavelet analysis, inversely correlated most strongly with the fMRI‐BOLD signal in the postcentral cortex for the Rolandic alpha (mu) rhythm and in the precentral cortex for the Rolandic beta rhythm. FMRI correlates of Rolandic alpha and beta rhythms were distinct from those associated with the posterior “classical” alpha rhythm, which correlated inversely with the BOLD signal in the occipital cortex. An inverse correlation with the BOLD signal in the respective sensory area seems to be a general feature of “idle rhythms”. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.
Monofractal and multifractal dynamics of low frequency endogenous brain oscillations in functional MRI
Authors: Wink Alle‐Meije , Bullmore Ed , Barnes Anna , Bernard Frederic , Suckling John
Published: May 2008

Fractal processes, like trees or coastlines, are defined by self‐similarity or power law scaling controlled by a single exponent, simply related to the fractal dimension or Hurst exponent (H) of the process. Multifractal processes, like turbulence, have more complex behaviours defined by a spectrum of possible local scaling behaviours or singularity exponents (h). Here, we report two experiments that explore the relationships between instrumental and cognitive variables and the monofractal and multifractal parameters of functional magnetic resonance imaging (fMRI) data acquired in a no‐task or resting state. First, we show that the Hurst exponent is greater in grey matter than in white matter regions, and it is maximal in grey matter when data were acquired with an echo time known to optimise BOLD contrast. Second, we show that latency of response in a fame decision/facial encoding task was negatively correlated with the Hurst exponent of resting state data acquired 30 min after task performance. This association was localised to a right inferior frontal cortical region activated by the fame decision task and indicated that people with shorter response latency had more persistent dynamics (higher values of H). Multifractal analysis revealed that faster responding participants had wider singularity spectra of resting fMRI time series in inferior frontal cortex. Endogenous brain oscillations measured by fMRI have monofractal and multifractal properties that can be related to instrumental and cognitive factors in a way, which indicates that these low frequency dynamics are relevant to neurocognitive function. Hum Brain Mapp 2008. © 2008 Wiley‐Liss, Inc.
Generation and detection of the radical cation and the dication derived from 4,9‐diethyl[1,4]dihydrodithiino[5,6‐f]benzotrithiole and its 5‐oxide
Authors: Kimura Takeshi , Ito Shinya , Sasaki Takashi , Ogawa Satoshi , Sato Ryu , Kawai Yasushi
Published: May 2008

4,9‐Diethyl[1,4]dihydrodithiino[5,6‐f]benzotrithiole (DTBT) gave a radical cation, DTBT(•+), and a dication, DTBT(2+), on treatment with a single‐electron oxidizing reagent. Both compounds showed an ESR signal, whereas the dication, generated by this procedure, was silent for 1H NMR. Hydrolysis of DTBT(2+) gave DTBT 1‐oxide (DTBT 1‐O) and 2‐oxide (DTBT 2‐O) together with DTBT and a mixture of several dioxides. A singlet‐state dication, DTBT(2+)‐S, which was generated upon treatment of DTBT 5‐oxide (DTBT 5‐O) with concentrated D2SO4, was detected by 1H and 13C NMR. After 20 h, the NMR signals disappeared while the solution was active for ESR. The results suggest that (i) a species generated from DTBT by oxidation with the single‐electron oxidizing reagent is a triplet‐state dication, DTBT(2+)‐T, and (ii) DTBT(2+)‐S, initially generated, gradually isomerizes to DTBT(2+)‐T in the solution, and DTBT(2+)‐T forms a partial spin pair. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:394–401, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20445
A comparative analysis of Medicaid long‐term care policies and their effects on elderly dual enrollees
Authors: Rice J. Bradford , Kasper Judith D. , Pezzin Liliana E.
Published: May 2008

Individuals with dual enrollment in Medicare and Medicaid have become the focus of heightened US federal and state policy interest in recent years. These beneficiaries are among the most vulnerable and costly persons served by either program. This analysis uses a reduced‐form econometric model and a unique survey of community‐resident dual enrollees to take a critical step toward understanding the relationships and combinations of state long‐term care (LTC) policies and their relative effectiveness in achieving their intended effects: increasing access to care, improving activities of daily living/instrumental activities of daily living (ADL/IADL) assistance, and reducing unmet needs. We then simulate the effects of alternative policies to determine the most effective combination.

The combination of policies that was most effective in reducing the percentage of individuals receiving low levels of assistance was high spending in the community relative to nursing home and low community LTC spending per recipient; that is, spending more on community care and spreading it across more people. Overall, this analysis confirms that Medicaid LTC policy decisions by states, and the combinations of policies that are implemented, result in important variations in levels of assistance to elderly persons with disabilities. Copyright © 2008 John Wiley & Sons, Ltd.
Fluid flow and heat transfer characteristics in rectangular microchannels
Authors: Jiang Jie , Hao Yingli , Shi Mingheng
Published: May 2008

Experiments were conducted to investigate flow and heat transfer characteristics of water in rectangular microchannels. All tests were performed with deionized water. The flow rate, the pressures, and temperatures at the inlet and outlet were measured. The friction factor, heat flux, and Nusselt number were obtained. The friction factor in the microchannel is lower than the conventional value. That is only 20% to 30% of the convectional value. The critical Reynolds number below which the flow remains laminar in the microchannel is also lower than the conventional value. The Nusselt number in the microchannel is quite different from the conventional value. The Nusselt number for the microchannel is lower than the conventional value when the flow rate is small. As the flow rate through the microchannel is increased, the Nusselt number significantly increases and exceeds the value of Nusselt number for the fully developed flow in the conventional channel. The micro‐scale effect was exhibited. The Nusselt number is also affected by the heat flux. The Nusselt number remains the constant value when the flow rate is small. The Nusselt number increases with the increase in the heat flux when the flow rate is large. © 2008 Wiley Periodicals, Inc. Heat Trans Asian Res, 37(4): 197–207, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20206
αvβ3 and αvβ5 integrins control glioma cell response to ionising radiation through ILK and RhoB
Authors: Monferran Sylvie , Skuli Nicolas , Delmas Caroline , Favre Gilles , Bonnet Jacques , Cohen‐Jonathan‐Moyal Elizabeth , Toulas Christine
Published: May 2008

Integrins are extracellular matrix receptors involved in tumour invasion and angiogenesis. Although there is evidence that inhibiting integrins might enhance the efficiency of radiotherapy, little is known about the exact mechanisms involved in the integrin‐dependent modulation of tumor radiosensitivity. The purpose of this study was to investigate the role of αvβ3 and αvβ5 integrins in glioblastoma cell radioresistance and overall to decipher the downstream biological pathways. We first demonstrated that silencing αvβ3 and αvβ5 integrins with specific siRNAs significantly reduced the survival after irradiation of 2 glioblastoma cell lines: U87 and SF763. We then showed that integrin activity and integrin signalling pathways controlled the glioma cell radiosensitivity. This regulation of glioma cell response to ionising radiation was mediated through the integrin‐linked kinase, ILK, and the small GTPase, RhoB, by two mechanisms. The first one, independent of ILK, consists in the regulation of the intracellular level of RhoB by αvβ3 or αvβ5 integrin. The second pathway involved in cell radiosensitivity consists in RhoB activation by ionising radiation through ILK. Furthermore, we demonstrated that the αvβ3/αvβ5 integrins/ILK/RhoB pathway controlled the glioma cells radiosensitivity by regulating radiation‐induced mitotic cell death. This work identifies a new biological pathway controlling glioblastoma cells radioresistance, activated from the membrane through αvβ3 and/or αvβ5 integrins via ILK and RhoB. Our results are clues that downstream effectors of αvβ3 and αvβ5 integrins as ILK and RhoB might also be promising candidate targets for improving the efficiency of radiotherapy and thus the clinical outcome of patients with glioblastoma. © 2008 Wiley‐Liss, Inc.
Insig2 is associated with colon tumorigenesis and inhibits Bax‐mediated apoptosis
Authors: Li Chang Gong , Gruidl Mike , Eschrich Steven , McCarthy Susan , Wang Hong‐Gang , Alexandrow Mark G. , Yeatman Timothy J.
Published: May 2008

Insulin‐induced gene 2 (Insig2) was recently identified as a putative positive prognostic biomarker for colon cancer prognosis. Insig2 has been previously reported to be an endoplasmic reticulum (ER) membrane protein, and a negative regulator of cholesterol synthesis. Here we report that Insig2 was validated as a gene with univariate negative prognostic capacity to discriminate human colon cancer survivorship. To investigate the functional roles it plays in tumor development and malignancy, Insig2 was over‐expressed in colon cancer cells resulting in increased cellular proliferation, invasion, anchorage independent growth and inhibition of apoptosis. Over‐expression of Insig2 appeared to suppress chemotherapeutic drug treatment‐induced Bcl2 associated X protein (Bax) expression and activation. Insig2 was also found to localize to the mitochondria/heavy membrane fraction and associate with conformationally changed Bax. Moreover, Insig2 altered the expression of several additional apoptosis genes located in mitochondria, further supporting its new functional role in regulating mitochondrial mediated apoptosis. Our findings show that Insig2 is a novel colon cancer biomarker, and suggest, for the first time, a reasonable connection between Insig2 and Bax‐mediated apoptosis through the mitochondrial pathway. © 2008 Wiley‐Liss, Inc.
An in‐silico study of alphaherpesviruses ICP0 genes: Positive selection or strong mutational GC‐pressure?
Authors: Khrustalev Vladislav Victorovich , Barkovsky Eugene Victorovich
Published: May 2008

The purpose of our work was to analyze the case of the strong mutational GC‐pressure influence on the ratio between nonsynonymous (DN) and synonymous (DS) distances (DN/DS ratio). We have used as the material the genes coding for ICP0 from five completely sequenced genomes of simplexviruses. DN/DS ratio, total GC‐content (G + C), and GC‐content in first, second, and third codon positions (1GC, 2GC, and 3GC, respectively) have been calculated separately for exon 2, nonconserved part of exon 3, and conserved part of exon 3 from ICP0 genes. Results showed that DN is more than DS only in the conserved part of exon 3 of ICP0 genes from cercopithecine herpesvirus 2 and cercopithecine herpesvirus 16. However, the cause of this result (DN/DS = 2.54) is the GC‐pressure acting on the coding districts with 3GC = 99% rather than the biological process called positive selection. Only in these two viruses, because of the strong GC‐pressure, 3GC has reached 99% in the conserved part of ICP0 exon 3, and so nucleotide substitutions that increase the GC‐content practically cannot occur in third codon positions, where most substitutions are synonymous. In this case, GC‐pressure has a substrate for nucleotide substitutions only in first and second codon positions, where most substitutions are nonsynonymous. © 2008 IUBMB IUBMB Life, 60(7): 456–460, 2008
ATP and fructose‐2,6‐bisphosphate regulate skeletal muscle 6‐phosphofructo‐1‐kinase by altering its quaternary structure
Authors: Zancan Patricia , Marinho‐Carvalho Monica M. , Faber‐Barata Joana , Dellias João M.M. , Sola‐Penna Mauro
Published: May 2008

Recently, it has been demonstrated that fructose‐2,6‐bisphosphate (F2,6BP) protects skeletal muscle 6‐phosphofructo‐1‐kinase (PFK) from thermal inactivation (50 °C) and against the deleterious effects of guanidinium hydrochloride (GdmCl). On the other hand, ATP, when added at its inhibitory concentrations, that is, >1 mM, enhanced either the thermal‐ or GdmCl‐induced inactivation of PFK. Moreover, we concluded that these phenomena were probably due to the stabilization of PFK tetrameric structure by F2,6BP, and the dissociation of this structure into dimers induced by ATP. Aimed at elucidating the effects of F2,6BP and ATP on PFK at the structural and functional levels, the present work correlates the effects of these metabolites on the equilibrium between PFK dimers and tetramers to the regulation promoted on the enzyme catalytic activity. We show that ATP present a dual effect on PFK structure, favoring the formation of tetramer at stimulatory concentrations (up to 1 mM), and dissociating tetramers into dimers at inhibitory concentrations (>1 mM). Furthermore, F2,6BP counteracted this later ATP effect at either the structural or catalytic levels. Additionally, the effects of both F2,6BP or ATP on the equilibrium between PFK tetramers and dimers and on the enzyme activity presented a striking parallelism. Therefore, we concluded that modulation of PFK activity by ATP and F2,6BP is due to the effects of these ligands on PFK quaternary structure, altering the oligomeric equilibrium between PFK tetramers and dimers. © 2008 IUBMB IUBMB Life, 60(8): 526–533, 2008
Shaping mitochondria: The complex posttranslational regulation of the mitochondrial fission protein DRP1
Authors: Santel Ansgar , Frank Stephan
Published: May 2008

Mitochondria are essential and dynamic cellular organelles differing in size, subcellular distribution, and internal structure. These aspects of mitochondrial morphology are intimately controlled by a growing number of mitochondrial morphology shaping proteins. The past decade has revealed remarkable and often unexpected new insights into the molecular regulation and physiological impact of mitochondrial morphology maintenance. Obviously, proper mitochondrial dynamics, resulting from a tightly regulated equilibrium between opposing mitochondrial fusion and fission activities, is a prerequisite for normal organelle function. Consequently, a disturbance of these activities results in mitochondrial dysfunction and, thus, can lay the foundation for human disorders. Here we specifically focus on recent advances in our understanding of the regulation, activity, and function of dynamin‐related protein 1, the main factor for controlled mitochondrial fission. © 2008 IUBMB IUBMB Life, 60(7): 448–455, 2008
Work of fracture of a composite resin: Fracture‐toughening mechanisms
Authors: Baudin Carmen , Osorio Raquel , Toledano Manuel , de Aza Salvador
Published: May 2008

The aim of this work was to investigate those mechanical parameters able to describe the fracture behavior of dental composite resins. A commercially available fine‐particle micro‐hybrid resin composite was used. Classical parameters as Young's modulus, strength distribution, and critical stress intensity factor were considered. Strength values were determined using the diametrical compression of discs test and for the critical stress intensity factor both unstable and controlled fracture tests were used. Controlled fracture tests allowed determining the work of fracture. Microstructure was studied by optical and field emission scanning electron microscopy. The obtained properties have been Young's modulus, 17.7 ± 0.6 GPa; Weibull modulus, m = 14 (upper and lower limits for 90% confidence: 17 and 10); characteristic strength 51 MPa (upper and lower limits for 90% confidence: 53 and 49 MPa); critical stress intensity factor in mode I, KIC = 1.3 ± 0.1 and work of fracture, γwof = 8–9 J/m2. Pores and bubbles formed during the packing of the composite were identified as critical defects in the tested specimens. Crack deflection and branching have been identified as toughening mechanisms. Classical mechanical parameters (Young's modulus, hardness…) are not able to efficiently predict the major clinical failure mode of composite resins by fatigue. Work of fracture analysis, which is dependant on microstructural parameters such as particle size and shape, have to be included when testing mechanical properties of dental composite resins in future research studies. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Amidine surface modification of poly(acrylonitrile‐co‐vinyl chloride) reduces platelet adhesion
Authors: Yim Evelyn K. F. , Sefton Michael V.
Published: May 2008

The surface nitrile groups of solvent‐cast polyacrylonitrile‐co‐vinyl chloride (PAN‐VC) films were converted into amidine groups through a two‐step process analogous to Pinner's method of 1877. The amidine groups were hypothesized to reduce platelet adhesion and activation through the inhibition of the classical complement pathway, as was noted for benzamidine and pentamidine in earlier studies. A slightly higher nitrogen content was detected on the amidine‐surface modified (ASM) samples by X‐ray photoelectron spectroscopy relative to the solvent‐treated and unmodified controls. Reaction with pentafluoroaldehyde resulted in increased fluorine and decreased nitrogen contents (relative), consistent with the formation of a Schiff base with the primary nitrogen of the amidine on ASM PAN‐VC surface. The corresponding yield was 17.2% based on nitrile groups and 9.6% based on all repeating units of the base polymer. Despite this low degree of amidine modification, platelet adhesion was ∼40% lower on the amidine‐modified film compared to the solvent‐treated and unmodified controls. The scanning electron micrographs also showed less activation in the adherent platelets. A small reduction in C1s binding was also noted on the amidine‐modified surface. Taken together, these results support the notion that amidine modification may be a useful approach to improve the nonthrombogenicity of a biomaterial. However, much effort is required to improve the degree of surface modification and to provide unequivocal evidence linking amidines to the improved thrombogenicity. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Factorial design optimization and in vivo feasibility of poly(ε‐caprolactone)‐micro‐ and nanofiber‐based small diameter vascular grafts
Authors: Nottelet B. , Pektok E. , Mandracchia D. , Tille J.‐C. , Walpoth B. , Gurny R. , Möller M.
Published: May 2008

Because of the severe increase of mortality by cardiovascular diseases, there has been rising interest among the tissue‐engineering community for small‐sized blood vessel substitutes. Here we present small diameter vascular grafts made of slow degradable poly(ε‐caprolactone) nanofibers obtained by electrospinning. The process was optimized by a factorial design approach that led to reproducible grafts with inner diameters of 2 and 4 mm, respectively. Fiber sizes, graft morphology, and the resulting tensile stress and tensile strain values were studied as a function of various parameters in order to obtain optimal vascular grafts for implantation after γ‐sterilization. The influence of polymer concentration, solvent, needle‐collector distance, applied voltage, flow rate, and spinning time has been studied. Consequently, an optimized vascular graft was implanted as an abdominal aortic substitute in nine rats for a feasibility study. Results are given following up a 12‐week implantation period showing good patency, endothelization, and cell ingrowth. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Cytocompatibility and hemocompatibility of a novel chitosan‐alginate gel system
Authors: Notara M. , Scotchford C. A. , Grant D. M. , Weston N. , Roberts G. A. F.
Published: May 2008

Two chitosan‐alginate gel systems in the form of membranes were produced and evaluated. The first membrane was produced by a novel gel system formed after blending N‐(methylsulfonic acid) chitosan with ammonium alginate (CAG1) and the second was an N‐(methylsulfonic acid) chitosan‐sodium alginate blend cross‐linked with glutaraldehyde and calcium chloride (CAG2). The cytocompatibility and hemocompatibility of the gels were examined by assessing the cell viability of 3T3 Swiss mouse fibroblasts, whole blood hemolysis, and platelet activation. Cell viability was not significantly different by exposure to these gels compared to the controls. Both gel types had minimal effect on hemolysis of whole heparinized rabbit blood after 1‐h exposure. Further platelet activation by the surfaces was also minimal. These results indicate that these novel gels merit further investigation for blood contact applications. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Interstitial pregnancy undetected during earlier first‐trimester screening for fetal aneuploidy at 13 weeks' gestation
Authors: Sherer David M. , Dalloul Mudar , Sokolovski Margarita , Borawski Dorota , Granderson Freda , Abulafia, Ovadia
Published: May 2008

First‐trimester screening for fetal aneuploidy using nuchal translucency (NT), pregnancy‐associated plasma protein A, free or total β‐hCG, and maternal age constitutes a very effective screening test for fetal Down syndrome. We describe a case in which a patient presented at 14 weeks' gestation with an acute abdomen 1 week after first‐trimester screening (including NT measurement) performed elsewhere, which was negative for trisomies 21 and 18. Sonographic examination revealed an interstitial pregnancy with a singleton fetus with present cardiac activity, which had not been noted 1 week earlier at the time of earlier transabdominal NT measurement. This case indicates that successful acquisition of a NT measurement during first‐trimester screening for fetal aneuploidy does not negate the rare possibility of an unusual ectopic pregnancy. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2009
Structural characterization of isoprenylated flavonoids from Kushen by electrospray ionization multistage tandem mass spectrometry
Authors: Zhang Yufeng , Zhang Peng , Cheng Yiyu
Published: May 2008

Eighteen isoprenylated flavonoids (8 flavanones, 3 flavanols, and 7 chalcones) isolated from Kushen or synthesized were studied by positive and negative ion electrospray ionization multistage tandem mass spectrometry (ESI‐MSn). Plausible fragmentation patterns were obtained by comparing their MSn spectra with each other, which were further supported by high‐resolution MS data and two model compounds. It was shown that the 2′‐OH group would make the C‐ring of flavonoids studied more labile through a six‐membered mechanism, resulting in base peaks of 1, 3A+ (positive mode) and 1, 4A− (negative mode). In addition, the 2′‐OH is also responsible for the neutral loss of water in (+)ESI/MS2 of flavanones. The neutral loss of water (or methanol) in (−)ESI/MS2 of flavanols was elucidated by a E2 elimination mechanism. Different relative abundances (RA) of 1, 3A+ and S+ in (+)ESI/MS2 spectra were used to discriminate flavanones with their open‐ring products, chalcones, since the equilibrium for flavanone$\leftrightarrow$chalcone isomerization in ESI ion source could not be obtained in positive mode. Copyright © 2008 John Wiley & Sons, Ltd.
Prolonged‐efficacy of bisphosphonate in postmenopausal women with osteoporosis and chronic liver disease
Authors: Arase Yasuji , Suzuki Fumitaka , Suzuki Yoshiyuki , Akuta Norio , Kobayashi Masahiro , Kawamura Yusuke , Yatsuji Hiromi , Sezaki Hitomi , Hosaka Tetsuya , Ikeda Kenji , Kumada Hiromitsu
Published: May 2008

Osteoporosis is present often in postmenopausal women. The aim of this retrospective cohort study is to assess the cumulative appearance incidence and predictive factors for bone fracture in postmenopausal women with osteoporosis and chronic liver disease. The patients were 80 postmenopausal women with osteoporosis and chronic liver disease due to hepatitis virus B or C. These patients were given cyclic etidronate therapy within 3 months after diagnosis of osteoporosis (etidronate‐group). Another 400 postmenopausal women with osteoporosis and chronic liver disease were selected as controls (control group). Patients in control group were matched 1:5 with etidronate‐group for age. Patients in control group were not given any drugs after diagnosis of postmenopausal osteoporosis. The mean observation period was 8.1 years. Four patients in the etidronate‐group and 46 in control group developed bone fracture. The 10th year cumulative appearance rates of bone fracture were 4.9% in etidronate‐group and 13.8% in control group. Cox regression model showed that the appearance rate of bone fracture decreased with statistical significance in the following cases: (1) patients < 65 years (P < 0.001), (2) patients with serum albumin level of ≥3.5 g/dl (P = 0.003), and (3) patients treated with etidronate (P = 0.020). The cumulative survival rate after bone fracture was 82.2% at the second year, and 57.6% at the fifth year. The present study suggests that a serum albumin level of ≥3.5 g/dl and cyclic etidronate treatment reduce the appearance of bone fracture. J. Med. Virol. 80: 1302–1307, 2008. © 2008 Wiley‐Liss, Inc.
The unique HCV genotype distribution and the discovery of a novel subtype 6u among IDUs co‐infected with HIV‐1 in Yunnan, China
Authors: Xia Xueshan , Lu Ling , Tee Kok Keng , Zhao Wenhua , Wu Jianguo , Yu Jing , Li Xiaojie , Lin Yixiong , Mukhtar Muhammad Mahmood , Hagedorn Curt H. , Takebe Yutaka
Published: May 2008

The Yunnan province is the epicenter of HIV‐1 epidemics in China and a center for drug trafficking to the other parts of the world. In six prefectures of this province, a total of 132 IDUs were recruited to determine the sero‐prevalence of HCV and HIV‐1 and the positive rates were 93.94% and 68.18%, respectively (P < 0.001). Co‐infection with HCV and HIV‐1 was found among 89 IDUs, of whom several HCV fragments were amplified and sequenced. Sequences of the HCV 5′NCR‐C and NS5B region were determined from 82 IDUs. Phylogenetic analyses showed consistent genotyping among 80 IDUs. Among them HCV genotypes 1a, 1b, 3a, 3b, 6a, 6n, and a tentatively assigned novel 6u subtype were found in 1 (1.25%), 16 (20%), 19 (23.75%), 24 (30%), 4 (5%), 9 (11.25%) and 7 (8.75%) individuals, respectively. In two IDUs, genotyping results were discordant, suggesting mixed HCV infections or recombination. The proportion of patients with HCV 1b tended to decrease from the north to south and from the east to west in this province. Genotype 3 and 6 strains were more frequent in the southern prefectures. The novel subtype 6u strains were only detected in Dehong which borders Myanmar. Our findings showed a unique pattern of HCV genotype distribution, which is similar to that in the southeastern Asian countries but distinct from that among the general population in China. Routes of drug trafficking and the resulting high prevalence of HIV‐1 infection may have contributed to this pattern of HCV genotype distribution. J. Med. Virol. 80: 1142–1152, 2008. © 2008 Wiley‐Liss, Inc.
Dynamics of lamivudine‐resistant hepatitis B virus during adefovir monotherapy versus lamivudine plus adefovir combination therapy
Authors: Ijaz Samreen , Arnold Catherine , Dervisevic Samir , Mechurova Jana , Tatman Nick , Tedder Richard S. , Naoumov Nikolai V.
Published: May 2008

Adefovir dipivoxil has been used alone or together with lamivudine to suppress lamivudine‐resistant hepatitis B virus (HBV). However, the dynamics of HBV populations under different selection pressures and their impact on treatment outcome are poorly understood. Pyrosequencing® was applied to quantify longitudinally the evolution of wild type and lamivudine/ adefovir‐resistant HBV. Eight patients, with lamivudine‐resistant HBV, were randomized to receive adefovir monotherapy or adefovir/lamivudine combination therapy for a median of 79 and 71 weeks, respectively. Pyrosequencing® proved highly sensitive with a lower limit of quantitation of minor HBV populations of 2% irrespective of viraemia levels. Adefovir/lamivudine treatment resulted in greater viraemia reduction than adefovir monotherapy. During combination therapy, lamivudine‐resistant HBV populations (codons 180 and 204) remained dominant (>90%) and no adefovir‐resistance developed. During adefovir monotherapy, reversion to wild‐type HBV was detected in two patients with one patient accumulating rapidly adefovir‐resistant HBV along with increased viraemia. In conclusion, the dynamics of drug‐resistant HBV strains vary under different selection pressures which have a significant impact on the success of rescue therapy, as well as for the selection of new mutations. The use of techniques such as Pyrosequencing provides an evidence‐based approach for successful management of drug‐resistant HBV. J. Med. Virol. 80: 1160–1170, 2008. © 2008 Wiley‐Liss, Inc.
The prevalence of hepatitis B virus preS deletions occurring naturally in Korean patients infected chronically with genotype C
Authors: Mun Ho‐Suk , Lee Seoung‐Ae , Jee Youngmee , Kim Hong , Park Joo‐Hee , Song Byung‐Cheol , Yoon Jung‐Hwan , Kim Yoon Jun , Lee Hyo‐Suk , Hyun Jin‐won , Hwang Eung‐Soo , Kook Yoon‐Hoh , Kim Bum‐Joon
Published: May 2008

Although Korea is one of the endemic areas for hepatitis B virus infection (HBV), the prevalence of deletions in HBV preS region occurring naturally have not been determined. In the present study, the prevalence of preS deletions was determined in terms of clinical state and HBeAg serostatus in 120 patients with different clinical features [59 HBeAg positive, 61 HBeAg negative; 38 asymptomatic carriers, 21 patients with chronic hepatitis, 21 patients with liver cirrhosis, 40 patients with hepatocellular carcinoma (HCC)]. A total of 37 strains (30.8%) harbored deletions in the preS region. Overall, the frequencies of preS deletions tended to increase gradually according to the degree of the clinical severity of liver disease. The prevalence of preS1 deletions in HCC patients tended to be higher than in patients with liver cirrhosis (32.5% vs. 19%). The prevalence of preS2 deletions in HBeAg negative patients was significantly higher than in HBeAg positive patients (23% vs. 6.8%). The type of deletion encountered most frequently was one disrupting the preS1 start codon [14/37 strains (37.8%)], which showed a very high prevalence in HCC patients (9/40, 22.5%; HCC vs. asymptomatic carriers, P = 0.048). These results suggest that there might be the discrepancy between preS1 and preS2 mutations in the mechanism of enhancing the progression of chronic liver disease, especially the development of HCC and to maintain tolerance during the stage of immune tolerance. Specific deletion of the type disrupting preS1 start codon may play important roles in hepatocarcinogenesis, at least in Korean patients with chronic HBV infection. J. Med. Virol. 80: 1189–1194, 2008. © 2008 Wiley‐Liss, Inc.
Serum and tissue cytokines and chemokines increase with repetitive upper extremity tasks
Authors: Barbe Mary F. , Elliott Melanie B. , Abdelmagid Samir M. , Amin Mamta , Popoff Steven N. , Safadi Fayez F. , Barr Ann E.
Published: May 2008

We investigated inflammation in rats performing a low repetition, negligible force (LRNF) or high repetition, negligible force (HRNF) task of reaching and retrieving food pellets at target rates of two or four reaches/min for 2 h/day, for 6–8 weeks. Serum was assayed for 11 cytokines and chemokines; forelimb tissues for four cytokines. Macrophages were counted in forelimb tissues of LRNF rats to add to results from our previous studies of HRNF rats. In HRNF rats, serum IL‐1α, IL‐1β, TNFα, MIP2, MIP3a, and RANTES were elevated in weeks 6 and 8. In contrast, only MIP2 and MIP3a increased in serum of LRNF rats. In 8 week HRNF reach limb tissues, IL‐1α, IL‐1β, TNFα, and IL‐10 increased in distal bones, IL‐1α and ‐β in muscles, and TNFα in tendons. Only IL‐10 increased in LRNF reach limb muscles in week 8. Serum IL‐1α and MIP2 correlated with macrophages in LRNF loose connective tissues, serum MIP3a and MIP2 correlated negatively with grip strength, while serum TNFα, MIP3a, and MIP2 correlated positively with total number of reaches. Thus, several tissue and circulating cytokines/chemokines increase in an exposure dependent manner following short‐term performance of repetitive reaching tasks and correlate with macrophage infiltration and decreasing grip strength. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1320–1326, 2008