bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraarterial chemotherapy and osmotic blood‐brain barrier disruption for patients with embryonal and germ cell tumors of the central nervous system
Authors: Jahnke Kristoph , Kraemer Dale F. , Knight Kristin R. , Fortin David , Bell Susan , Doolittle Nancy D. , Muldoon Leslie L. , Neuwelt Edward A.
Published: December 2007

BACKGROUND.

The rate of durable responses in embryonal and certain germ cell tumors of the central nervous system (CNS) is unsatisfactory. Intraarterial chemotherapy and osmotic blood‐brain barrier disruption (IA/BBBD) increases drug delivery to the CNS.

METHODS.

Data of patients treated with carboplatin or methotrexate‐based IA/BBBD on prospective phase 2 trials conducted at 3 centers were collected. Study outcomes included overall survival (OS), time to progression (TTP), and toxicity.

RESULTS.

Fifty‐four patients were treated. Twenty‐seven patients received IA/BBBD as salvage treatment. The median OS was 2.8 years for all patients, 2.5 years for supratentorial and disseminated primitive neuroectodermal tumors (PNETs, n = 29), 1.7 years for medulloblastomas (n = 12), and 5.4 years for germ cell tumors (n = 13). OS and TTP for all patients were better with a Karnofsky Performance Status ≥70% (P= .0013 and .0070) and IA/BBBD as first‐line treatment (P= .0059 and .029). In PNETs, OS was higher with pineal location (P= .045) and IA/BBBD as first‐line treatment (P= .0036), and TTP was improved with radiotherapy before IA/BBBD (P= .036) and IA/BBBD as first‐line treatment (P= .0079). Seventeen of 54 patients (31%) are alive, and 16 are alive at 4+ to 18+ years. Three survivors were not treated with radiotherapy and 4 were treated with focal radiotherapy only. The patients who were not irradiated did not develop dementia.

CONCLUSIONS.

Survival and toxicity data appear promising, considering the cohort's adverse prognostic profile. A plateau in survival curves suggests a cure for some patients. Long‐term survival may be achieved with focal or reduced‐dose radiotherapy in some IA/BBBD patients. Cancer 2008. © 2007 American Cancer Society.
Effect of the Magnetic Field on the Supramolecular Structure of Chiral Smectic C Phases: 2H NMR Studies
Authors: Domenici Valentina , Marini Alberto , Veracini Carlo Alberto , Zhang Jing , Dong Ronald Y.
Published: December 2007

We present a theoretical and experimental 2H NMR study of the effect of external magnetic fields on the supramolecular organization of chiral smectic liquid‐crystalline mesophases, such as SmC* and re‐entrant SmC*. Three experimental cases in which the supramolecular helical structure of the smectic C* phase is unwound by a magnetic field (H), parallel to the helical axes of this phase, are discussed in detail. Unwinding of the helical structure is described by using a theoretical model based on the Landau‐de Gennes theory, which allows us to explain the transition temperatures among the SmA, SmC*, and uSmC* phases. The energy‐density behavior in the vicinity of the transitions and the value of the critical magnetic field HC for unwinding the helical structure are discussed by applying this model to three ferroelectric smectogens (MBHB, 11EB1M7, ZLL7/*), which are studied by 2H NMR spectroscopy at different magnetic fields (from 2.4 to 9.4 Tesla). Furthermore, the tilt angle of the three smectogens in the SmC* phase has been directly evaluated, for the first time, by comparing the quadrupolar splittings at different magnetic fields. In one case, 2H NMR angular measurements are used to obtain the tilt angle in the re‐entrant smectic C phase.
Photoelectrochemical Manifestation of Photoelectron Transport Properties of Vertically Aligned Nanotubular TiO2 Photoanodes
Authors: Zhang Haimin , Zhao Huijun , Zhang Shanqing , Quan Xie
Published: December 2007

A simple photoelectrochemical method was proposed to quantitatively evaluate the electron transport process of photoelectrocatalytic oxidation of water at vertically aligned nanotubular TiO2 photoanodes. The photoelectrocatalysis reaction resistance (R=k/Jsph+R0=RI+R0) was measured and used to express the electron transport characteristics of a nanotubular TiO2 electrode. The overall resistance was found to consist of a variant (RI) and an invariant component (R0). RI was found to be inversely proportional to the saturation photocurrent and it depends on the experimental conditions. The proportional constant, k, represents the minimum applied potential bias required to remove 100 % of the photogenerated electrons from the photocatalyst layer and was found to be independent of the anodization time. The invariant component of the resistance (R0) is an inherent property of the semiconductor photocatalyst that represents the sum of Ohmic contact impedance at the conducting substrate/TiO2 interface and crystalline boundary impedance. The magnitude of R0 linearly increased with anodization time. The real saturated photocurrent density (Jreal‐sphd) was found to be independent of R0 indicating that the electron collection efficiency is independent of the nanotube length.
Synthesis of “Trioxaquantel”® Derivatives as Potential New Antischistosomal Drugs
Authors: Laurent Sophie A.‐L. , Boissier Jérôme , Coslédan Frédéric , Gornitzka Heinz , Robert Anne , Meunier Bernard
Published: December 2007

Over the past 20 years, praziquantel, a pyrazinoisoquinoline derivative, has become the mainstay for morbidity control of human and animal schistosomiasis. From early in their lives in vertebrate hosts, schistosomes ingest hemoglobin and aggregate the released heme as a dark pigment very similar to the hemozoin produced by Plasmodium in malaria infection. The antimalarial artemisinin derivatives have real, though low, schistosomicide activity. Because of the complementarity of the two drug classes – praziquantel and artemisinin derivatives – we designed new molecules, named trioxaquantels®, that combine the 1,2,4‐trioxane unit responsible for the activity of artemisinin, and the pyrazinoisoquinoline moiety of praziquantel within a single drug. The synthesis of these new drugs and their preliminary evaluation in mice infected with Schistosoma mansoni is reported here.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Transport of charged samples in fluidic channels with large zeta potentials
Authors: Dutta Debashis
Published: December 2007

In this article, we present an analysis on the transport of charged samples through micro‐ and nanofluidic channels with large zeta potentials (|ζ| > (kBT)/e). Using the Method of Moments formulation, the diffusion‐convection equation has been solved to evaluate the mean velocity and the dispersion of analyte bands in a parallel‐plate device under electrokinetically‐ and pressure‐driven flow conditions. The effect of electromigration induced by the lateral electric field within the Debye layer has been quantified in our work using a Peclet number (Pet) based on the characteristic electrophoretic velocity of the solute molecules in the transverse direction. It has been shown that while the effects of transverse electromigration on analyte transport only depends on the product Petζ* for |ζ*| = (eζ)/kBT << 1, both these parameters independently affect the flow of charged species in large zeta potential systems. For a given value of Petζ*, the mean velocity and the slug dispersivity can vary by as much as an order of magnitude in going from a small zeta potential system (|ζ*| << 1) to a channel with |ζ*| = 4.
Ionic liquid‐assisted PDMS microchannel modification for efficiently resolving fluorescent dye and protein adsorption
Authors: Xu Yuanhong , Jiang Hong , Wang Erkang
Published: December 2007

Herein, a hybrid system consisting of ionic liquid (IL) and nonionic surfactant has been successfully developed for dynamic modification of PDMS microchips and analyte adsorption such as fluoresent dyes and proteins has been efficiently suppressed. Mutual authentication between microchip electrophoresis and confocal laser scanning microscope was carried out to characterize the multiple novel functions of the IL‐containing system and a possible mechanism was raised. Soluble IL used herein not only played the role as supporting electrolyte, but also provided increased EOF in the PDMS microchannel compared with common electrolytes such as phosphate buffer. Due to the high ionic conductivity of IL, on‐column field‐amplified sample stacking effect was four‐fold higher than that without IL. Furthermore, an excellent synergistic effect existed between IL and nonionic surfactant, which enhanced the ability of resolving analyte adsorption to PDMS surface, and was demonstrated in the sensitive and efficient determination of rhodamine B (with detection limit of 8 nM) and a well separated mixture of proteins.
Dielectrophoresis for the manipulation of nanobioparticles
Authors: Lapizco‐Encinas Blanca H. , Rito‐Palomares Marco
Published: December 2007

Dielectrophoresis (DEP) is a nondestructive electrokinetic mechanism with great potential for the manipulation of bioparticles. DEP is the movement of particles induced by polarization effects in nonuniform electric fields. Since the 1960s, this technique has been successfully used for the manipulation of microbioparticles, such as microorganisms. Moreover, due to the advances in microfabrication techniques, that allowed progressively smaller microstructures to be constructed, DEP can now be used for the manipulation of nanobioparticles. The first research studies on the DEP of nanobioparticles started in the 1990s. Since then, many research groups have carried out outstanding work with DEP of nanobioparticles such as macromolecules, virus, and spores. However, the need of a critical report that integrates these findings is evident. The aim of the present review is to depict the state‐of–the‐art on the use of DEP for the separation of nanobioparticles and the potential trends of novel applications of this technique. This review compiles and analyzes the significant findings obtained by many researchers. This publication is intended to provide the reader with state‐of‐the‐art information on many research studies focused on DEP to handle nanobioparticles.
Further improvement of hydrostatic pressure sample injection for microchip electrophoresis
Authors: Luo Yong , Zhang Qingquan , Qin Jianhua , Lin Bingcheng
Published: December 2007

Hydrostatic pressure sample injection method is able to minimize the number of electrodes needed for a microchip electrophoresis process; however, it neither can be applied for electrophoretic DNA sizing, nor can be implemented on the widely used single‐cross microchip. This paper presents an injector design that makes the hydrostatic pressure sample injection method suitable for DNA sizing. By introducing an assistant channel into the normal double‐cross injector, a rugged DNA sample plug suitable for sizing can be successfully formed within the cross area during the sample loading. This paper also demonstrates that the hydrostatic pressure sample injection can be performed in the single‐cross microchip by controlling the radial position of the detection point in the separation channel. Rhodamine 123 and its derivative as model sample were successfully separated.
A well‐balanced Runge–Kutta discontinuous Galerkin method for the shallow‐water equations with flooding and drying
Authors: Ern A. , Piperno S. , Djadel K.
Published: December 2007

We build and analyze a Runge–Kutta discontinuous Galerkin method to approximate the one‐ and two‐dimensional shallow‐water equations. We introduce a flux modification technique to derive a well‐balanced scheme preserving steady states at rest with variable ground elevation and a slope modification technique to deal satisfactorily with flooding and drying. Numerical results illustrating the performance of the proposed scheme are presented. Copyright © 2007 John Wiley & Sons, Ltd.
Telomerase activity is a biomarker for high grade malignant peripheral nerve sheath tumors in neurofibromatosis type 1 individuals
Authors: Mantripragada Kiran K. , Caley Matthew , Stephens Phil , Jones Christopher J. , Kluwe Lan , Guha Abhijit , Mautner Victor , Upadhyaya Meena
Published: December 2007

Telomerase activity (TA) and the expression of its enzymatic subunits, which have been demonstrated in many tumors, remain poorly investigated in tumors associated with neurofibromatosis type 1 (NF1). In this study, we analysed the association of TA and the expression of telomerase RNA (TR) and telomerase reverse transcriptase (TERT) in 23 malignant peripheral nerve sheath tumors (MPNST) (17 high grade and 6 low grade tumors), 11 plexiform neurofibromas (PNF) and 6 dermal neurofibromas (DNF). TA was studied using telomerase repeat amplification protocol (TRAP) assay and expression of TR and TERT was investigated using reverse transcription PCR (RT‐PCR) and real‐time PCR. TA was detected in 14 out of 17 (82%) high grade MPNST, whereas all 6 low grade MPNST and 17 benign tumors were telomerase negative. The TERT transcripts were detected in all high grade MPNST, 50% of the low grade MPNST, and 4 benign tumors. However, the expression level of the TERT strikingly correlated with TA and high grade MPNST. Thus, while TERT expression was similar in both low grade MPNST and PNF (P = 0.115), it was significantly higher in high grade MPNST when compared to either low grade MPNST (P = 0.042), PNF (P = 0.001) or DNF tumors (P = 0.010). These findings indicate that TA and expression level of TERT are potential markers for high grade malignancy in NF1 patients. © 2007 Wiley‐Liss, Inc.
Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors
Authors: Linger Rachel , Dudakia Darshna , Huddart Robert , Tucker Kathy , Friedlander Michael , Phillips Kelly‐Anne , Hogg David , Jewett Michael A. S. , Lohynska Radka , Daugaard Gedske , Richard Stéphane , Chompret Agnes , Stoppa‐Lyonnet Dominique , Bonaïti‐Pellié Catherine , Heidenreich Axel , Albers Peter , Olah Edith , Geczi Lajos , Bodrogi Istvan , Daly Peter A. , Guilford Parry , Fosså Sophie D. , Heimdal Ketil , Tjulandin Sergei A. , Liubchenko Ludmila , Stoll Hans , Weber Walter , Einhorn Lawrence , McMaster Mary , Korde Larissa , Greene Mark H. , Nathanson Katherine L. , Cortessis Victoria , Easton Douglas F. , Bishop D. Timothy , Stratton Michael R. , Rapley Elizabeth A.
Published: December 2007

A base substitution in the mouse Dnd1 gene resulting in a truncated Dnd protein has been shown to be responsible for germ cell loss and the development of testicular germ cell tumors (TGCT) in the 129 strain of mice. We investigated the human orthologue of this gene in 263 patients (165 with a family history of TGCT and 98 without) and found a rare heterozygous variant, p. Glu86Ala, in a single case. This variant was not present in control chromosomes (0/4,132). Analysis of the variant in an additional 842 index TGCT cases (269 with a family history of TGCT and 573 without) did not reveal any additional instances. The variant, p. Glu86Ala, is within a known functional domain of DND1 and is highly conserved through evolution. Although the variant may be a rare polymorphism, a change at such a highly conserved residue is characteristic of a disease‐causing variant. Whether it is disease‐causing or not, mutations in DND1 make, at most, a very small contribution to TGCT susceptibility in adults and adolescents. © 2007 Wiley‐Liss, Inc.
Differential regulation of trophic and proinflammatory microglial effectors is dependent on severity of neuronal injury
Authors: Lai Aaron Y. , Todd Kathryn G.
Published: December 2007

Microglial activation has been reported to promote neurotoxicity and also neuroprotective effects. A possible contributor to this dichotomy of responses may be the degree to which proximal neurons are injured. The aim of this study was to determine whether varying the severity of neuronal injury influenced whether microglia were neuroprotective or neurotoxic. We exposed cortical neuronal cultures to varying degrees of hypoxia thereby generating mild (<20% death, 30min hypoxia), moderate (40–60% death, 2 h hypoxia), or severe (>70% death, 6 h hypoxia) injuries. Twenty‐four hours after hypoxia, the media from the neuronal cultures was collected and incubated with primary microglial cultures for 24 h. Results showed that the classic microglial proinflammatory mediators including inducible nitric oxide synthase, tumor necrosis factor α, and interleukin‐1‐β were upregulated only in response to mild neuronal injuries, while the trophic microglial effectors brain‐derived neurotrophic factor and glial cell line‐derived neurotrophic factor were upregulated in response to all degrees of neuronal injury. Microglia stimulated with media from damaged neurons were co‐cultured with hypoxic neurons. Microglia stimulated by moderate, but not mild or severe damage were neuroprotective in these co‐cultures. We also showed that the severity‐dependent phenomenon was not related to autocrine microglial signaling and was dependent on the neurotransmitters released by neurons after injury, namely glutamate and adenosine 5′‐triphosphate. Together our results show that severity of neuronal injury is an important factor in determining microglial release of “toxic” versus “protective” effectors and the resulting neurotoxicity versus neuroprotection. © 2007 Wiley‐Liss, Inc.
Aging and the interaction of sensory cortical function and structure
Authors: Peiffer Ann M. , Hugenschmidt Christina E. , Maldjian Joseph A. , Casanova Ramon , Srikanth Ryali , Hayasaka Satoru , Burdette Jonathan H. , Kraft Robert A. , Laurienti Paul J.
Published: December 2007

Even the healthiest older adults experience changes in cognitive and sensory function. Studies show that older adults have reduced neural responses to sensory information. However, it is well known that sensory systems do not act in isolation but function cooperatively to either enhance or suppress neural responses to individual environmental stimuli. Very little research has been dedicated to understanding how aging affects the interactions between sensory systems, especially cross‐modal deactivations or the ability of one sensory system (e.g., audition) to suppress the neural responses in another sensory system cortex (e.g., vision). Such cross‐modal interactions have been implicated in attentional shifts between sensory modalities and could account for increased distractibility in older adults. To assess age‐related changes in cross‐modal deactivations, functional MRI studies were performed in 61 adults between 18 and 80 years old during simple auditory and visual discrimination tasks. Results within visual cortex confirmed previous findings of decreased responses to visual stimuli for older adults. Age‐related changes in the visual cortical response to auditory stimuli were, however, much more complex and suggested an alteration with age in the functional interactions between the senses. Ventral visual cortical regions exhibited cross‐modal deactivations in younger but not older adults, whereas more dorsal aspects of visual cortex were suppressed in older but not younger adults. These differences in deactivation also remained after adjusting for age‐related reductions in brain volume of sensory cortex. Thus, functional differences in cortical activity between older and younger adults cannot solely be accounted for by differences in gray matter volume. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.
Neural activations at the junction of the inferior frontal sulcus and the inferior precentral sulcus: Interindividual variability, reliability, and association with sulcal morphology
Authors: Derrfuss Jan , Brass Marcel , von Cramon D. Yves , Lohmann Gabriele , Amunts Katrin
Published: December 2007

The sulcal morphology of the human frontal lobe is highly variable. Although the structural images usually acquired in functional magnetic resonance imaging studies provide information about this interindividual variability, this information is only rarely used to relate structure and function. Here, we investigated the spatial relationship between posterior frontolateral activations in a task‐switching paradigm and the junction of the inferior frontal sulcus and the inferior precentral sulcus (inferior frontal junction, IFJ) on an individual‐subject basis. Results show that, although variable in terms of stereotaxic coordinates, the posterior frontolateral activations observed in task‐switching are consistently and reliably located at the IFJ in the brains of individual participants. The IFJ shares such consistent localization with other nonprimary areas as motion‐sensitive area V5/MT and the frontal eye field. Building on tension‐based models of morphogenesis, this structure–function correspondence might indicate that the cytoarchitectonic area underlying activations of the IFJ develops at early stages of cortical folding. Hum Brain Mapp, 2009. © 2007 Wiley‐Liss, Inc.
Selective neurophysiologic responses to music in instrumentalists with different listening biographies
Authors: Margulis Elizabeth Hellmuth , Mlsna Lauren M. , Uppunda Ajith K. , Parrish Todd B. , Wong Patrick C. M.
Published: December 2007

To appropriately adapt to constant sensory stimulation, neurons in the auditory system are tuned to various acoustic characteristics, such as center frequencies, frequency modulations, and their combinations, particularly those combinations that carry species‐specific communicative functions. The present study asks whether such tunings extend beyond acoustic and communicative functions to auditory self‐relevance and expertise. More specifically, we examined the role of the listening biography—an individual's long term experience with a particular type of auditory input—on perceptual‐neural plasticity. Two groups of expert instrumentalists (violinists and flutists) listened to matched musical excerpts played on the two instruments (J.S. Bach Partitas for solo violin and flute) while their cerebral hemodynamic responses were measured using fMRI. Our experimental design allowed for a comprehensive investigation of the neurophysiology (cerebral hemodynamic responses as measured by fMRI) of auditory expertise (i.e., when violinists listened to violin music and when flutists listened to flute music) and nonexpertise (i.e., when subjects listened to music played on the other instrument). We found an extensive cerebral network of expertise, which implicates increased sensitivity to musical syntax (BA 44), timbre (auditory association cortex), and sound–motor interactions (precentral gyrus) when listening to music played on the instrument of expertise (the instrument for which subjects had a unique listening biography). These findings highlight auditory self‐relevance and expertise as a mechanism of perceptual‐neural plasticity, and implicate neural tuning that includes and extends beyond acoustic and communication‐relevant structures. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.
Preceding attention and the dorsomedial prefrontal cortex: Process specificity versus domain dependence
Authors: Walter Martin , Matthiä Christian , Wiebking Christine , Rotte Michael , Tempelmann Claus , Bogerts Bernhard , Heinze Hans‐Jochen , Northoff Georg
Published: December 2007

The dorsomedial prefrontal cortex (DMPFC) has been shown to be involved in attending different states, all including a strong emotional component. It remains unclear, though, whether neural activity in the DMPFC is predominantly determined by either a particular domain, as emotional stimuli, or by a specific process, as attention. Here, we used functional magnetic resonance imaging to test the alternative hypotheses of domain‐ versus process‐specificity in DMPFC. Subjects had to perceive pictures from three different domains, sexual, emotional, and neutral stimuli, in both a nonattended, i.e., unexpected, and attended, i.e., expected mode. Our results show DMPFC activation during attended, i.e., expected stimulus perception when compared with nonattended, i.e., unexpected stimuli perception. DMPFC activation and corresponding behavioral changes (reaction time, subjective ratings) were observed in all three domains, sexual, emotional, and neutral stimuli. As opposed to those process‐specific effects that were found predominantly in posterior DMPFC, a process by domain interaction was found to be characteristic for more anterior parts of the DMPFC. Taken together, our findings favour the hypothesis that neural activity in the posterior DMPFC is determined by a specific process, i.e., attending stimuli, and thus characterized by process‐specificity rather than by a particular domain, i.e., sexual, emotional, or neutral stimuli, reflecting domain‐specificity. This suggests that the anterior and posterior DMPFC is involved in the process of attending mental states while remaining more (posterior DMPFC) or less (anterior DMPFC) independent of the type or domain of the respective stimulus. Hum Brain Mapp, 2009. © 2007 Wiley‐Liss, Inc.
Combining fMRI and SNP data to investigate connections between brain function and genetics using parallel ICA
Authors: Liu Jingyu , Pearlson Godfrey , Windemuth Andreas , Ruano Gualberto , Perrone‐Bizzozero Nora I. , Calhoun Vince
Published: December 2007

There is current interest in understanding genetic influences on both healthy and disordered brain function. We assessed brain function with functional magnetic resonance imaging (fMRI) data collected during an auditory oddball task—detecting an infrequent sound within a series of frequent sounds. Then, task‐related imaging findings were utilized as potential intermediate phenotypes (endophenotypes) to investigate genomic factors derived from a single nucleotide polymorphism (SNP) array. Our target is the linkage of these genomic factors to normal/abnormal brain functionality. We explored parallel independent component analysis (paraICA) as a new method for analyzing multimodal data. The method was aimed to identify simultaneously independent components of each modality and the relationships between them. When 43 healthy controls and 20 schizophrenia patients, all Caucasian, were studied, we found a correlation of 0.38 between one fMRI component and one SNP component. This fMRI component consisted mainly of parietal lobe activations. The relevant SNP component was contributed to significantly by 10 SNPs located in genes, including those coding for the nicotinic α‐7cholinergic receptor, aromatic amino acid decarboxylase, disrupted in schizophrenia 1, among others. Both fMRI and SNP components showed significant differences in loading parameters between the schizophrenia and control groups (P = 0.0006 for the fMRI component; P = 0.001 for the SNP component). In summary, we constructed a framework to identify interactions between brain functional and genetic information; our findings provide a proof‐of‐concept that genomic SNP factors can be investigated by using endophenotypic imaging findings in a multivariate format. Hum Brain Mapp, 2009. © 2007 Wiley‐Liss, Inc.
Small‐world properties of nonlinear brain activity in schizophrenia
Authors: Rubinov Mikail , Knock Stuart A. , Stam Cornelis J. , Micheloyannis Sifis , Harris Anthony W.F. , Williams Leanne M. , Breakspear Michael
Published: December 2007

A disturbance in the interactions between distributed cortical regions may underlie the cognitive and perceptual dysfunction associated with schizophrenia. In this article, nonlinear measures of cortical interactions and graph‐theoretical metrics of network topography are combined to investigate this schizophrenia “disconnection hypothesis.” This is achieved by analyzing the spatiotemporal structure of resting state scalp EEG data previously acquired from 40 young subjects with a recent first episode of schizophrenia and 40 healthy matched controls. In each subject, a method of mapping the topography of nonlinear interactions between cortical regions was applied to a widely distributed array of these data. The resulting nonlinear correlation matrices were converted to weighted graphs. The path length (a measure of large‐scale network integration), clustering coefficient (a measure of “cliquishness”), and hub structure of these graphs were used as metrics of the underlying brain network activity. The graphs of both groups exhibited high levels of local clustering combined with comparatively short path lengths—features consistent with a “small‐world” topology—as well as the presence of strong, central hubs. The graphs in the schizophrenia group displayed lower clustering and shorter path lengths in comparison to the healthy group. Whilst still “small‐world,” these effects are consistent with a subtle randomization in the underlying network architecture—likely associated with a greater number of links connecting disparate clusters. This randomization may underlie the cognitive disturbances characteristic of schizophrenia. Hum Brain Mapp, 2009. © 2007 Wiley‐Liss, Inc.
At‐a‐station hydraulic geometry relations, 2: calibration and testing
Authors: Singh Vijay P. , Zhang Lan
Published: December 2007

Using a large number of data sets obtained from various sources, the geometric relations derived in Part 1 are calibrated and verified using the split sampling approach. The calibration of parameters shows that the change in stream power is not shared equally among hydraulic variables and that the unevenness depends on the boundary conditions to be satisfied by the channel under consideration. The agreement between the observed values of the hydraulic variables and those predicted by the derived relations is close for the verification data set and lends credence to the hypotheses employed in this study. Copyright © 2007 John Wiley & Sons, Ltd.
Maintenance of mitochondrial DNA copy number and expression are essential for preservation of mitochondrial function and cell growth
Authors: Jeng Jaan‐Yeh , Yeh Tien‐Shun , Lee Jing‐Wen , Lin Shyh‐Hsiang , Fong Tsorng‐Han , Hsieh Rong‐Hong
Published: December 2007

To examine whether a reduction in the mtDNA level will compromise mitochondrial biogenesis and mitochondrial function, we created a cell model with depleted mtDNA. Stable transfection of small interfering (si)RNA of mitochondrial transcription factor A (Tfam) was used to interfere with Tfam gene expression. Selected stable clones showed 60–95% reduction in Tfam gene expression and 50–90% reduction in cytochrome b (Cyt b) gene expression. Tfam gene knockdown clones also showed decreased mtDNA‐encoded cytochrome c oxidase subunit I (COX I) protein expression. However, no significant differences in protein expression were observed in nuclear DNA (nDNA)‐encoded mitochondrial respiratory enzyme subunits. The cell morphology changed from a rhombus‐like to a spindle‐like form as determined in clones with decreased expressions of Tfam, mtRNA, and mitochondrial proteins. The mitochondrial respiratory enzyme activities and ATP production in such clones were significantly lower. The proportions of mtDNA mutations including 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), a 4,977‐bp deletion, and a 3,243‐point mutation were also examined in these clones. No obvious increase in mtDNA mutations was observed in mitochondrial dysfunctional cell clones. The mitochondrial respiratory activity and ATP production ability recovered in cells with increased mtDNA levels after removal of the specific siRNA treatment. These experimental results provide direct evidence to substantiate that downregulation of mtDNA copy number and expression may compromise mitochondrial function and subsequent cell growth and morphology. J. Cell. Biochem. 103: 347–357, 2008. © 2007 Wiley‐Liss, Inc.
The implementation of a fast and accurate QM/MM potential method in Amber
Authors: Walker Ross C. , Crowley Michael F. , Case David A.
Published: December 2007

Version 9 of the Amber simulation programs includes a new semi‐empirical hybrid QM/MM functionality. This includes support for implicit solvent (generalized Born) and for periodic explicit solvent simulations using a newly developed QM/MM implementation of the particle mesh Ewald (PME) method. The code provides sufficiently accurate gradients to run constant energy QM/MM MD simulations for many nanoseconds. The link atom approach used for treating the QM/MM boundary shows improved performance, and the user interface has been rewritten to bring the format into line with classical MD simulations. Support is provided for the PM3, PDDG/PM3, PM3CARB1, AM1, MNDO, and PDDG/MNDO semi‐empirical Hamiltonians as well as the self‐consistent charge density functional tight binding (SCC‐DFTB) method. Performance has been improved to the point where using QM/MM, for a QM system of 71 atoms within an explicitly solvated protein using periodic boundaries and PME requires less than twice the cpu time of the corresponding classical simulation. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Reactive force fields for proton transfer dynamics
Authors: Lammers Sven , Lutz Stephan , Meuwly Markus
Published: December 2007

A force field‐inspired method based on fitted, high‐quality multidimensional potential energy surfaces to follow proton transfer (PT) reactions in molecular dynamics simulations is presented. In molecular mechanics with proton transfer (MMPT) a system is partitioned into a region where proton transfer takes place and the remaining degrees of freedom which are treated with a conventional force field. The implementation of the method and applications to specific chemically and biologically relevant scenarios are presented. MMPT is developed in view of two primary areas in mind: to follow the molecular dynamics of proton transfer in the condensed phase on realistic time scales and to adapt the shape (morphing) of the potential energy surface for specific applications. MMPT is applied to PT in protonated ammonia dimer, double proton transfer in 2‐pyridone‐2‐hydroxypyridine, and the first step of PT from a protein side‐chain towards a buried [3Fe4S] cluster in ferredoxin I. Specific findings of the work include the fundamental role of the N–N vibration as the gating mode for PT in NH···NH3 and the qualitative understanding of PT from the protein to a metastable active‐site water molecule in Ferredoxin I. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
An intramolecular induction correction model of the molecular dipole moment
Authors: Holt Asbjørn , Karlström Gunnar
Published: December 2007

A model for intramolecular polarization is presented. It is used to describe the changes in the molecular charge distribution occurring as a response to changes of dihedral angles in the molecule. The model is based on a multicenter multipole distribution of the molecular charge distribution. The electric field from this charge distribution induce dipole moments in the same molecule. The model contains atom type parameters to describe the damping of the electric field. A total of four atom types are used. The parameters are fitted to a calibration set with various functional groups, and tested against a validation set. The error obtained for the calibration set is reduced by 92% and by 88% for the validation set, if compared to an accurate state‐of‐the‐art force field. It is shown that rotating the non‐polarizable multicenter multipole distribution for the equilibrium geometry gives too large dipole moments for dihedral angles deviating from the equilibrium geometry. This will lead to too large long‐range attractions in simulations. This problem is overcome by using the dipole polarizability correction suggested here, which gives dipole moments very close to the Hartree‐Fock dipole moments obtained from reference calculations. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Computational protein design: Software implementation, parameter optimization, and performance of a simple model
Authors: Schmidt Am Busch Marcel , Lopes Anne , Mignon David , Simonson Thomas
Published: December 2007

Computational protein design will continue to improve as new implementations and parameterizations are explored. An automated protein design procedure is implemented and applied to the full redesign of 16 globular proteins. We combine established but simple ingredients: a molecular mechanics description of the protein where nonpolar hydrogens are implicit, a simple solvent model, a folded state where the backbone is fixed, and a tripeptide model of the unfolded state. Sequences are selected to optimize the folding free energy, using a simple heuristic algorithm to explore sequence and conformational space. We show that a balanced parametrization, obtained here and in our previous work, makes this procedure effective, despite the simplicity of the ingredients. Calculations were done using our Proteins @ Home distributed computing platform, with the help of several thousand volunteers. We describe the software implementation, the optimization of selected terms in the energy function, and the performance of the method. We allowed all amino acids to mutate except glycines, prolines, and cysteines. For 15 of the 16 test proteins, the scores of the computed sequences were comparable to those of natural homologues. Using the low energy computed sequences in a BLAST search of the SWISSPROT database, we could retrieve natural sequences for all protein families considered, with no high‐ranking false‐positives. The good stability of the designed sequences was supported by molecular dynamics simulations of selected sequences, which gave structures close to the experimental native structure. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Mastoparan effects in skeletal muscle damage: An ultrastructural view until now concealed
Authors: Rocha Thalita , Leonardo Marta Beatriz , De Souza Bibiana Monson , Palma Mario Sérgio , Da Cruz‐Höfling Maria Alice
Published: December 2007

Animal venoms have been valuable sources for development of new drugs and important tools to understand cellular functioning in health and disease. The venom of Polybia paulista, a neotropical social wasp belonging to the subfamily Polistinae, has been sampled by headspace solid phase microextraction and analyzed by gas chromatography‐mass spectrometry. Recent study has shown that mastoparan, a major basic peptide isolated from the venom, reproduces the myotoxic effect of the whole venom. In this study, Polybia‐MPII mastoparan was synthesized and studies using transmission electron microscopy were carried out in mice tibial anterior muscle to identify the subcellular targets of its myotoxic action. The effects were followed at 3 and 24 h, 3, 7, and 21 days after mastoparan (0.25 μg/μL) intramuscular injection. The peptide caused disruption of the sarcolemma and collapse of myofibril arrangement in myofibers. As a consequence, fibers presented heteromorphic amorphous masses of agglutinated myofilaments very often intermingled with denuded sarcoplasmic areas sometimes only surrounded by a persistent basal lamina. To a lesser extent, a number of fibers apparently did not present sarcolemma rupture but instead appeared with multiple small vacuoles. The results showed that sarcolemma, sarcoplasmic reticulum (SR), and mitochondria were the main targets for mastoparan. In addition, a number of fibers showed apoptotic‐like nuclei suggesting that the peptide causes death both by necrosis and apoptosis. This study presents a hitherto unexplored view of the effects of mastoparan in skeletal muscle and contributes to discuss how the known pharmacology of the peptide is reflected in the sarcolemma, SR, mitochondria, and nucleus of muscle fibers, apparently its subcellular targets. Microsc. Res. Tech., 2008. © 2007 Wiley‐Liss, Inc.
Preservation and fluorescence of the microfossils from Neoproterozoic Doushantuo formation
Authors: Chi Huimei , Feng Man , Xiao Zhongdang , Lu Zuhong
Published: December 2007

The phosphatized microfossils from Doushantuo Formation, Southeast China show us the biodiversity about 600 million years ago, which is a unique window for the evolution of the early life on earth. However, the process of phosphatic fossilization in detail still remains unknown. Here we report our study on the preservation state of the fossils by using confocal laser scanning microscopy. We found that fluorescent signal of the fossil could reflect the preservation state when compared with the transmission light microscopy. First, we found the fluorescent signal of the decayed cells of the fossil was weaker than that of the nondecayed part. Second, we found that the three‐dimensional reconstruction of the fluorescent signals could help to judge the degree of mineralization of the fossil cells, compared with the observation by transmission light microscope. Third, we found that almost all of the fossil specimens we observed could fluoresce more or less when excited by laser light. Therefore, the fluorescent microscopy provides a useful method for the study of the preservation state of the phosphatic fossil cells. Microsc. Res. Tech., 2008. © 2007 Wiley‐Liss, Inc.
Colocalization of MCM8 and MCM7 with proteins involved in distinct aspects of DNA replication
Authors: Kinoshita Yayoi , Johnson Edward M. , Gordon Ronald E. , Negri‐Bell Heather , Evans Mark T. , Coolbaugh Jennifer , Rosario‐Peralta Yaseris , Samet Joseph , Slusser Evelyn , Birkenbach Mark P. , Daniel Dianne C.
Published: December 2007

Minichromosome maintenance (MCM) proteins are essential for DNA replication in eukaryotes. A subcomplex of the MCM2‐7 family members, initially characterized in yeast, is thought to serve as a eukaryotic DNA replicative helicase. MCM8 is a new family member, not present in yeast, which may function alone or with other family members in aspects of DNA metabolism, including replication initiation and elongation. Through the use of chromatin immunoprecipitation, we find that MCM8, like MCM7, colocalizes on a specific DNA segment of the c‐MYC replication initiation zone (c‐MYC replicator) with Cdc6, a protein potentially involved in loading MCM proteins onto DNA. The association between MCM8 and MCM7 peaks in mid G1, at the time of assembly of the prereplication complex. The association of both MCM proteins with Cdc6, however, continues even after DNA replication is complete. We also find that MCM8 colocalizes at the c‐MYC replicator with chromatin‐bound Cdk2. Our data indicate that any role MCM8 may play in elongation is likely to be discontinuous, in its association with DNA, from a potential role in initiation. Using immunogold electron microscopy we show that MCM8 and MCM7 differ in spatial relation to RPA70 during S phase. Our data strongly suggest that MCM8 functions with other known replication proteins in processes which accompany DNA replication, especially initiation, and which are specifically adapted to suit higher eukaryotes. Microsc. Res. Tech, 2008. © 2007 Wiley‐Liss, Inc.
Automated recognition system to classify subcellular protein localizations in images of different cell lines acquired by different imaging systems
Authors: Tsai Yuh‐Show , Chung I‐Fang , Simpson Jeremy C. , Lee Mei‐I , Hsiung Chia‐Cheng , Chiu Tai‐Yu , Kao Lung‐Sen , Chiu Te‐Cheng , Lin Chin‐Teng , Lin Wen‐Chieh , Liang Sheng‐Fu , Lin Chung‐Chih
Published: December 2007

Systemic analysis of subcellular protein localization (location proteomics) provides clues for understanding gene functions and physiological condition of the cells. However, recognition of cell images of subcellular structures highly depends on experience and becomes the rate‐limiting step when classifying subcellular protein localization. Several research groups have extracted specific numerical features for the recognition of subcellular protein localization, but these recognition systems are restricted to images of single particular cell line acquired by one specific imaging system and not applied to recognize a range of cell image sources. In this study, we establish a single system for automated subcellular structure recognition to identify cell images from various sources. Two different sources of cell images, 317 Vero (http://gfp‐cdna.embl.de) and 875 CHO cell images of subcellular structures, were used to train and test the system. When the system was trained by a single source of images, the recognition rate is high and specific to the trained source. The system trained by the CHO cell images gave high average recognition accuracy for CHO cells of 96%, but this was reduced to 46% with Vero images. When we trained the system using a mixture of CHO and Vero cell images, an average accuracy of recognition reached 86.6% for both CHO and Vero cell images. The system can reject images with low confidence and identify the cell images correctly recognized to avoid manual reconfirmation. In summary, we have established a single system that can recognize subcellular protein localizations from two different sources for location‐proteomic studies. studies. Microsc. Res. Tech., 2008. © 2007 Wiley‐Liss, Inc.
Gene delivery to the vasculature mediated by low‐titre adeno‐associated virus serotypes 1 and 5
Authors: Sen S. , Conroy S. , Hynes S. O. , McMahon J. , O'Doherty A. , Bartlett J. S. , Akhtar Y. , Adegbola T. , Connolly C. E. , Sultan S. , Barry F. , Katusic Z. S. , O'Brien T.
Published: December 2007

Background

Vascular gene therapy requires safe and efficient gene transfer in vivo. Recombinant adeno‐associated virus (AAV) is a promising viral vector but its use in the vasculature has produced conflicting results and serotypes other than AAV2 have not been intensively studied. We investigated the efficiency of alternative AAV serotypes for vascular gene delivery in vitro and in vivo.

Methods

Vascular cell lines were transduced in vitro with AAV vectors. Rabbit carotid arteries were transduced with AAV1, 2 and 5 encoding enhanced green fluorescent protein (eGFP) (∼1.4 × 109 DNAse‐resistant particles (drp)). Gene transfer in vivo was assessed at 14 and 28 days. High‐titre doses of AAV2 encoding β‐galactosidase in vivo were also studied.

Results

In vitro, transgene expression was not observed in endothelial cells using AAV2 whereas the use of serotypes 1 and 5 resulted in detectable levels of transgene expression. Coronary artery smooth muscle cells (CASMCs) transduced with AAV2 demonstrated higher levels of GFP expression than AAV1 or 5. Transgene expression in vivo was noted using low‐titre AAV1 and AAV5 (∼1.4 × 109 drp) in the media and adventitia. Only delivery of AAV1eGFP resulted in neointimal formation (3/7 vessels examined), with transgene expression noted in the neointima. Transgene expression with AAV2 was not detected in any layer of the blood vessel wall using low titre (∼109 drp). However, high‐titre (∼1011 drp) AAV2 resulted in transduction of cells in the media and adventitia but not the endothelium.

Conclusions

AAV1 and AAV5 have advantages over AAV2 for vascular gene delivery at low titres. Copyright © 2007 John Wiley & Sons, Ltd.
Microbial diversity of mine water at Zhong Tiaoshan copper mine, China
Authors: He Zhiguo , Xie Xuehui , Xiao Shengmu , Liu Jianshe , Qiu Guanzhou
Published: December 2007

Microbial diversity of mine water at Zhong Tiaoshan copper mine, Shanxi province, China, was analyzed using a culture‐independent 16S rRNA gene (rDNA) based on cloning approach. A total of 59 Operational Taxonomic Units (OTUs) were obtained from 226 clones from all three samples (8 OTUs from sample SX1, 25 from SX2 and 26 from SX3). 46 of them were representative OTUs and were sequenced. 93.5% of the total clones had sequences that were less than 5% difference from those in the nucleic acids database. The percentage of overlapping OTUs among samples was from 12.1% to 35.3%. Phylogenetic analysis indicated that 60.62% of the clones were affiliated with members of the Proteobacteria (α ‐3.10%, β ‐24.78%, γ ‐31.41%, δ ‐1.33%), whereas 29.20% of the clones were closely related to the Nitrospira (Leptospirillum ferrooxidans 20.80%, Leptospirillum ferriphilum 0.88% and Leptospirillum group III 7.52%, respectively). The rest clones were affiliated with the Firmicutes (2.65%) and the Bacteroidetes (7.52%). The results of Principal Component Analysis (PCA) based on the percentages of OTUs and biogeochemical data revealed that biogeochemical properties affected the diversity of microbial communities in mine water. Especially, the pH value, temperature and different concentrations of elements such as lead, zinc, sulfur, iron and copper seemed to be key factors affecting the composition and structure of microbial communities in this study. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)