bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlates across the structural, functional, and molecular phenotypes of fragile X syndrome
Authors: Beckel‐Mitchener Andrea , Greenough William T. 
Published: February 2004

AbstractFragile X syndrome (FXS) is characterized by a pattern of morphological, functional, and molecular characteristics with, in at least some cases, apparent relationships among phenotypic features at different levels. Gross morphology differences in the sizes of some human brain regions are accompanied by fine structural alterations in the shapes and in the numbers of dendritic spines in both humans and the knockout mouse model. The excess number of spines, their immature appearance, and the impaired withdrawal of inappropriately oriented dendrites in FXS or the mouse model suggest impairment of neuronal maturation, including dendritic and spine pruning. It is not clear how these differences arise, although regionally or globally impaired translation of the mRNAs that interact with the Fmr1 protein product, FMRP, in the vicinity of the synapse, including genes involved in synapse development and plasticity and dendritic retraction, is certainly plausible. FMRP binds mRNA and may be involved in both transport and translation of the mRNAs it binds. The mRNAs it binds belong to multiple functional classes, apparently indicating that FMRP may impact multiple cellular processes. In one example, the glucocorticoid receptor, whose mRNA binds FMRP, regulates the stress‐sensitive glucocorticosteroids. Both human FXS and the mouse model exhibit a protracted elevation in glucocorticosteroids after stress. Possible relationships of other genes to morphological and functional characteristics of FXS are also discussed. MRDD Research Reviews 2004;10:53–59. © 2004 Wiley‐Liss, Inc.
RNA interference: A new mechanism by which FMRP acts in the normal brain? What can Drosophila teach us?
Authors: Siomi Haruhiko , Ishizuka Akira , Siomi Mikiko C. 
Published: February 2004

AbstractFragile X syndrome is the most common heritable form of mental retardation caused by loss‐of‐function mutations in the FMR1 gene. The FMR1 gene encodes an RNA‐binding protein that associates with translating ribosomes and acts as a negative translational regulator. Recent work in Drosophila melanogaster has shown that the fly homolog of FMR1 (dFMR1) plays an important role in regulating neuronal morphology, which may underlie the observed deficits in behaviors of dFMR1 mutant flies. Biochemical analysis has revealed that dFMR1 forms a complex that includes ribosomal proteins and, surprisingly, Argonaute2 (AGO2), an essential component of the RNA‐induced silencing complex (RISC) that mediates RNA interference (RNAi) in Drosophila. dFMR1 also associates with Dicer, another essential processing enzyme of the RNAi pathway. Moreover, both a micro‐RNA (miRNA) and short interfering RNAs (siRNAs) can coimmunoprecipitate with dFMR1. Together these findings suggest that dFMR1 functions in an RNAi‐related apparatus to regulate the expression of its target genes at the level of translation. These findings raise the possibility that Fragile X syndrome may be the result of a protein synthesis abnormality caused by a defect in an RNAi‐related apparatus. Because the core mechanisms of complex behaviors such as learning and memory and circadian rhythms appear to be conserved, studies of Fragile X syndrome using Drosophila as a model provide an economy‐of‐scale for identifying biological processes that likely underlie the abnormal morphology of dendritic spines and behavioral disturbances observed in Fragile X patients. MRDD Research Reviews 2004;10:68–74. © 2004 Wiley‐Liss, Inc.
Prospects for gene therapy in the fragile X syndrome
Authors: Rattazzi Mario C. , LaFauci Giuseppe , Brown W. Ted 
Published: February 2004

Abstract“If politics is the art of the possible, research is the art of the soluble. Both are immensely practical‐minded affairs.” P. B. Medawar.Gene therapy is unarguably the definitive way to treat, and possibly cure, genetic diseases. A straightforward concept in theory, in practice it has proven difficult to realize, even when directed to easily accessed somatic cell systems. Gene therapy for diseases in which the central nervous system (CNS) is the target organ presents even greater challenges and diverse vectors and brain delivery approaches are under investigation. We argue that in the case of the fragile X syndrome the approach most likely to have a chance of being effective should consist of a small, diffusible vector derived from the adeno‐associated virus, carrying an FMR1 cDNA comprising the 5′ promoter region and the 3′ untranslated region of the gene, delivered to the entire brain by osmotic blood–brain barrier disruption. The approach can be tested in Fmr1 knockout mice, although changes in their neurobehavioral abnormalities may be difficult to evaluate. A defect in the expression of GABA(A) receptors in these mice—if shown to be a direct consequence of the Fmr1 defect—promises to be a more readily assessable marker of restored FMRp function on gene transfer. MRDD Research Reviews 2004;10:75–81. © 2004 Wiley‐Liss, Inc.
Novel RF coil geometry for lower extremity imaging
Authors: Brown Ryan , Mareyam Azma , Reid Eric , Wang Yi 
Published: February 2004

AbstractA receive‐only phased‐array coil was designed to image the lower extremities. The array consists of four volume coils placed on two cylindrical formers. The coil array has the ability to image both legs simultaneously over a 40 cm longitudinal field of view (FOV). Experiments using phantoms show an increase in signal‐to‐noise ratio (SNR) in regions of interest through the center of the coil by an average factor of 2.8 over the body coil and 1.5 over the GE 4‐channel torso array. In vivo data acquired from 10 subjects show that the X array provided similar SNR improvement in spin‐echo images and more vascular details in angiographic images compared to the torso array. Magn Reson Med 51:635–639, 2004. © 2004 Wiley‐Liss, Inc.
Linear combination of multiecho data: Short T2 component selection
Authors: Jones Craig K. , Xiang Qing‐San , Whittall Kenneth P. , MacKay Alex L. 
Published: February 2004

AbstractThe myelin sheath, which is wrapped around the axons in the brain, can be affected by many diseases, resulting in cognitive and physical disability. Other work showed water in the myelin sheath has a T2 ≈ 15 ms. The current standard technique to estimate the fraction of myelin water in vivo is to collect multiecho data and fit the decay curves using a nonnegative least‐squares (NNLS) algorithm. A new algorithm was developed to calculate optimized coefficients which were used to linearly combine multiecho data to estimate the myelin water signal. A set of simulations showed the new technique was accurate over a broad range of myelin water signal. The myelin water fraction from brain regions in scans from five volunteers, estimated by the linear combination method, agreed with the myelin water fraction estimated by the standard technique. The strength of the new technique is that the linear combination does not assume an underlying T2 model and is 20,000 times faster than NNLS. Magn Reson Med 51:495–502, 2004. © 2004 Wiley‐Liss, Inc.
Experimental method to eliminate frequency modulation sidebands in localized in vivo 1H MR spectra acquired without water suppression
Authors: Dong Zhengchao , Dreher Wolfgang , Leibfritz Dieter 
Published: February 2004

AbstractAn experimental method is described to eliminate frequency modulation sidebands in localized in vivo proton MR spectra acquired without water suppression. Based on the fact that the phases of the sideband artifact signals are coherent with the phases of the gradient pulses, the proposed method measures and combines signals with sequences using opposite gradients to cancel the sidebands. Factors effecting the results of the cancellation are investigated. Optimized cancellation is achieved by trimming the refocusing gradients, optimizing the spoiler gradients, or replacing the spoiler gradients with a 16‐step RF phase cycling. The performance of the method is demonstrated by phantom and in vivo experiments on the healthy rat brain. Magn Reson Med 51:602–606, 2004. © 2004 Wiley‐Liss, Inc.
Novel NMR approach to assessing gene transfection: 4‐fluoro‐2‐nitrophenyl‐β‐D‐galactopyranoside as a prototype reporter molecule for β‐galactosidase
Authors: Cui Weina , Otten Pieter , Li Yingming , Koeneman Kenneth S. , Yu Jianxin , Mason Ralph P. 
Published: February 2004

AbstractGene therapy holds great promise for the treatment of diverse diseases. However, widespread implementation is hindered by difficulties in assessing the success of transfection in terms of spatial extent, gene expression, and longevity of expression. The development of noninvasive reporter techniques based on appropriate molecules and imaging modalities may help to assay gene expression. 4‐Fluoro‐2‐nitrophenyl‐β‐D‐galactopyranoside (PFONPG) is a novel prototype NMR‐sensitive molecule, which is highly responsive to the action of β‐galactosidase (β‐gal), the product of the lacZ gene. The molecule is stable in solution and with respect to wild‐type cells, but the enzyme causes very rapid liberation of the aglycone, accompanied by color formation and a 19F NMR chemical shift of 5–10 ppm, depending on pH. Since the product is pH‐sensitive, this opens the possibility for direct pH determinations at the site of enzyme activity. Molecular and 19F NMR characteristics of PFONPG in solution, blood, and prostate tumor cells are presented. This prototype molecule facilitates a novel approach for assaying gene activity in vivo. Magn Reson Med 51:616–620, 2004. © 2004 Wiley‐Liss, Inc.
Maximum likelihood estimation of signal amplitude and noise variance from MR data
Authors: Sijbers J. , den Dekker A.J. 
Published: February 2004

AbstractIn MRI, the raw data, which are acquired in spatial frequency space, are intrinsically complex valued and corrupted by Gaussian‐distributed noise. After applying an inverse Fourier transform, the data remain complex valued and Gaussian distributed. If the signal amplitude is to be estimated, one has two options. It can be estimated directly from the complex valued data set, or one can first perform a magnitude operation on this data set, which changes the distribution of the data from Gaussian to Rician, and estimate the signal amplitude from the obtained magnitude image. Similarly, the noise variance can be estimated from both the complex and magnitude data sets. This article addresses the question whether it is better to use complex valued data or magnitude data for the estimation of these parameters using the maximum likelihood method. As a performance criterion, the mean‐squared error (MSE) is used. Magn Reson Med 51:586–594, 2004. © 2004 Wiley‐Liss, Inc.
Time‐resolved 3D contrast‐enhanced MRA of an extended FOV using continuous table motion
Authors: Madhuranthakam Ananth J. , Kruger David G. , Riederer Stephen J. , Glockner James F. , Hu Houchun H. 
Published: February 2004

AbstractA method is presented for acquiring 3D time‐resolved MR images of an extended (>100 cm) longitudinal field of view (FOV), as used for peripheral MR angiographic runoff studies. Previous techniques for long‐FOV peripheral MRA have generally provided a single image (i.e., with no time resolution). The technique presented here generates a time series of 3D images of the FOV that lies within the homogeneous volume of the magnet. This is achieved by differential sampling of 3D k‐space during continuous motion of the patient table. Each point in the object is interrogated in five consecutive 3D image sets generated at 2.5‐s intervals. The method was tested experimentally in eight human subjects, and the leading edge of the bolus was observed in real time and maintained within the imaging FOV. The data revealed differential bolus velocities along the vasculature of the legs. Magn Reson Med 51:568–576, 2004. © 2004 Wiley‐Liss, Inc.
MR properties of excised neural tissue following experimentally induced inflammation
Authors: Stanisz Greg J. , Webb Stephanie , Munro Catherine A. , Pun Teresa , Midha Rajiv 
Published: February 2004

AbstractChanges in the MR parameters of inflamed neural tissue were measured in vitro. Tumor necrosis factor‐alpha (TNF‐α) was injected into rat sciatic nerves to induce inflammation with negligible axonal loss and demyelination. The MR parameters, such as T1/T2 relaxation and magnetization transfer (MT), were measured 2 days after TNF‐α injection and were found to be substantially different from those of normal nerves. The average T1/T2 relaxation times increased, whereas the MT ratio (MTR) and the quantitative MT parameter M0B (which describes the semisolid pool of protons) decreased. The MR parameters correlated very well with the extracellular volume fraction (EM) of neural tissue evaluated by quantitative histopathology. The multicomponent T2 relaxation was shown to provide the best quantitative assessment of changes in neural tissue microstructure, and allowed us to distinguish between the processes of inflammation and demyelination. In comparison, the MT measurements were less successful due to competing contributions of demyelination and pH‐sensitive changes in the MT effect. Magn Reson Med 51:473–479, 2004. © 2004 Wiley‐Liss, Inc.
Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI
Authors: Morawski Anne M. , Winter Patrick M. , Crowder Kathryn C. , Caruthers Shelton D. , Fuhrhop Ralph W. , Scott Michael J. , Robertson J. David , Abendschein Dana R. , Lanza Gregory M. , Wickline Samuel A. 
Published: February 2004

AbstractBefore molecular imaging with MRI can be applied clinically, certain problems, such as the potential sparseness of molecular epitopes on targeted cell surfaces, and the relative weakness of conventional targeted MR contrast agents, must be overcome. Accordingly, the conditions for diagnostic conspicuity that apply to any paramagnetic MRI contrast agent with known intrinsic relaxivity were examined in this study. A highly potent paramagnetic liquid perfluorocarbon nanoparticle contrast agent (∼250 nm diameter, >90000 Gd3+/particle) was imaged at 1.5 T and used to successfully predict a range of sparse concentrations in experimental phantoms with the use of standard MR signal models. Additionally, we cultured and targeted the smooth muscle cell (SMC) monolayers that express “tissue factor,” a glycoprotein of crucial significance to hemostasis and response to vascular injury, by conjugating an anti‐tissue factor antibody fragment to the nanoparticles to effect specific binding. Quantification of the signal from cell monolayers imaged at 1.5 T demonstrated, as predicted via modeling, that only picomolar concentrations of paramagnetic perfluorocarbon nanoparticles were required for the detection and quantification of tissue factor at clinical field strengths. Thus, for targeted paramagnetic agents carrying high payloads of gadolinium, it is possible to quantify molecular epitopes present in picomolar concentrations in single cells with routine MRI. Magn Reson Med 51:480–486, 2004. © 2004 Wiley‐Liss, Inc.
Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C
Authors: Johansson E. , Månsson S. , Wirestam R. , Svensson J. , Petersson J.S. , Golman K. , Ståhlberg F. 
Published: February 2004

AbstractCerebral perfusion was assessed with 13C MRI in a rat model after intravenous injections of the 13C‐labeled compound bis‐1,1‐(hydroxymethyl)‐1‐13C‐cyclopropane‐D8 in aqueous solutions hyperpolarized by dynamic nuclear polarization (DNP). Since the tracer acted as a direct signal source, several of the problems associated with techniques based on traditional dynamic susceptibility contrast (DSC) MRI contrast agents were avoided. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were calculated. The MTT was determined to be 2.8 ± 0.8 sec. However, arterial partial‐volume effects in the animal model prevented accurate absolute quantification of CBF and CBV. It was demonstrated that depolarization of the hyperpolarized 13C tracer via relaxation and the imaging sequence had little influence on CBF assessment when the time resolution of the imaging sequence was short compared to the MTT. However, CBV and MTT were increasingly underestimated as MTT or the depolarization rate increased if depolarization was not taken into account. With a modified bolus‐tracking theory depolarization could be compensated for, assuming that the depolarization rate was known. Three separate compensation methods were investigated experimentally and by numerical simulations. Magn Reson Med 51:464–472, 2004. © 2004 Wiley‐Liss, Inc.
Finite calculus formulation for incompressible solids using linear triangles and tetrahedra
Authors: Oñate Eugenio , Rojek Jerzy , Taylor Robert L. , Zienkiewicz Olgierd C. 
Published: February 2004

AbstractMany finite elements exhibit the so‐called ‘volumetric locking’ in the analysis of incompressible or quasi‐incompressible problems.In this paper, a new approach is taken to overcome this undesirable effect. The starting point is a new setting of the governing differential equations using a finite calculus (FIC) formulation. The basis of the FIC method is the satisfaction of the standard equations for balance of momentum (equilibrium of forces) and mass conservation in a domain of finite size and retaining higher order terms in the Taylor expansions used to express the different terms of the differential equations over the balance domain. The modified differential equations contain additional terms which introduce the necessary stability in the equations to overcome the volumetric locking problem. The FIC approach has been successfully used for deriving stabilized finite element and meshless methods for a wide range of advective–diffusive and fluid flow problems. The same ideas are applied in this paper to derive a stabilized formulation for static and dynamic finite element analysis of incompressible solids using linear triangles and tetrahedra. Examples of application of the new stabilized formulation to linear static problems as well as to the semi‐implicit and explicit 2D and 3D non‐linear transient dynamic analysis of an impact problem and a bulk forming process are presented. Copyright © 2004 John Wiley & Sons, Ltd.
Patch recovery based on complementary energy
Authors: Ubertini F. 
Published: February 2004

AbstractIn this paper a new stress recovery procedure is presented. The formulation is very simple and based on improving stresses by enforcing compatibility over local patches of elements. This is obtained by minimizing the complementary energy, properly defined for the patch thought as a separate system, among an assumed set of equilibrated stress fields. The resultant implementation is simple, cost effective and numerically stable. Several numerical tests evidence an excellent performance which promises a wide applicability of the new procedure. Copyright © 2004 John Wiley & Sons, Ltd.
Modulation of BDNF expression by electrical stimulation in hindlimb muscles of rats
Authors: Park Byung Rim , Hwang Ji Hyo , Kim Min Sun , Lee Moon Young , Rhee Jeong Kyun , Lee Seong Ho 
Published: February 2004

AbstractTo evaluate the effects of electrical stimulation of the sciatic nerve on brain‐derived neurotrophic factor (BDNF) expression in the soleus and medial gastrocnemius muscles, we investigated temporal changes in BDNF protein and mRNA expression following electrical stimulation, and the optimal electrical stimulus paradigm for increasing BDNF expression in rats. The sciatic nerve was electrically stimulated with three different paradigms: 1 ms/40 Hz/30 min, 1 ms/40 Hz/40 Hz/5 min and 1 ms/1 Hz/30 min. Levels of BDNF protein and mRNA increased gradually over time after electrical stimulation in both muscles. Of the three stimulus paradigms, electrical stimulation at 1 ms/40 Hz/30 min produced the highest levels of BDNF protein and mRNA in both muscles, whereas stimulation at 1 ms/40 Hz/5 min produced the lowest expression levels. These results suggest that electrical stimulation could enhance neuronal plasticity by increasing BDNF production and paradigms of the stimulus can modulate the level of BDNF production.
GABA receptor‐mediated epileptiform discharges in the rat cortical slices in magnesium‐free aCSF
Authors: Lee Jae‐Kwang , Park En‐Jin , Koh Hae‐Young , Lee Chang‐Joong 
Published: February 2004

AbstractThis study examined the role of the GABAergic system in generating epileptiform discharges in rat cortical slices in Mg2+‐free aCSF by comparing two age groups using a whole cell patch recording. The discharges consisted of recurring slow bursts in the neonatal slices, whereas fast initial depolarization with after‐discharges on the top of the gradual repolarization was mainly observed in the young slices. APV, an NMDA receptor antagonist, suppressed the slow bursts in the neonatal slices, and blocked late afterdischarges, leaving the fast depolarization discharges unaltered in the young slices. Interestingly, BMI, a GABAA receptor antagonist, reduced the frequency and amplitude of the discharges in the neonatal slices, while increasing in the young slices. The reversal potential of the slow bursts was shifted with a chloride ion gradient change across the membrane in the neonatal slices, but not in the young slices. These results demonstrated that the GABAA receptor activation during the neonatal period causes depolarization leading to epileptiform discharges under Mg2+‐free conditions.
Does whisker stimulation induce c‐Fos expression in the rat ipsilateral deafferented cerebral cortex?
Authors: Jung Hyuk‐Sang , Lee Hyun‐Sam , Shin Jung‐Won , Lee Doo‐Jae , Won Ran , Sohn Nak‐Won 
Published: February 2004

AbstractRecent study has shown that whisker stimulation of intact whiskers causes c‐Fos expression in contralateral barrel layers. However, as few reports have investigated what kind of effect whisker stimuli has on c‐Fos expression in the ipsilateral cerebral cortex, we researched the effect of such whisker stimuli. One side of the whisker pad was deafferented on adult rats, so that the deafferented barrel no longer received direct external stimuli and only one side of the barrel‐whisker system remained. Whiskers on the intact side were then stimulated and the effects of these stimuli on the ipsilateral deafferented barrel cortex were investigated by observing levels of c‐Fos expression, which is known as an excellent marker for functionally excited neurons. Whisker stimulation caused significantly increased c‐Fos expression on the layers II/III, IV of the ipsilateral deafferented cerebral cortex (P < 0.05, P < 0.01). In conclusion, whisker stimulation caused c‐Fos expression not only in the contralateral cerebral cortex, but also in the ipsilateral cerebral cortex.