bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractTelomerase 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

AbstractA 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

AbstractMicroglial 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

AbstractEven 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

AbstractThe 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

AbstractTo 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

AbstractThe 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

AbstractThere 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

AbstractA 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

AbstractUsing 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

AbstractTo 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

AbstractVersion 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

AbstractA 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

AbstractA 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