bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophillic phase II inducers
Authors: Satoh T. , Okamoto S.-i. , Cui J. , Watanabe Y. , Furuta K. , Suzuki M. , Tohyama K. , Lipton S. A.
Published: January 2006

Electrophilic neurite outgrowth-promoting prostaglandin (NEPP) compounds protect neurons from oxidative insults. At least part of the neuroprotective action of NEPPs lies in induction of hemeoxygenase-1 (HO-1), which, along with other phase II enzymes, serve as a defense system against oxidative stress. Here, we found that, by using fluorescent tags and immunoprecipitation assays, NEPPs are taken up preferentially into neurons and bind in a thiol-dependent manner to Keap1, a negative regulator of the transcription factor Nrf2. By binding to Keap1, NEPPs prevent Keap1-mediated inactivation of Nrf2 and, thus, enhance Nrf2 translocation into the nucleus of cultured neuronal cells. In turn, Nrf2 binds to antioxidant/electrophile-responsive elements of the HO-1 promoter to induce HO-1 expression. Consistent with this notion, NEPP induction of an HO-1 reporter construct is prevented if the antioxidant-responsive elements are mutated. We show that NEPPs are neuroprotective both
in vitro
from glutamate-related excitotoxicity and
in vivo
in a model of cerebral ischemia/reperfusion injury (stroke). Our results suggest that NEPPs prevent excitotoxicity by activating the Keap1/Nrf2/HO-1 pathway. Because NEPPs accumulate preferentially in neurons, they may provide a category of neuroprotective compounds, distinct from other electrophilic compounds such as tert-butylhydroquinone, which activates the antioxidant-responsive element in astrocytes. NEPPs thus represent a therapeutic approach for stroke and neurodegenerative disorders.
Habitat history improves prediction of biodiversity in rainforest fauna
Authors: Graham Catherine H. , Moritz Craig , Williams Stephen E.
Published: January 2006

Patterns of biological diversity should be interpreted in light of both contemporary and historical influences; however, to date, most attempts to explain diversity patterns have largely ignored history or have been unable to quantify the influence of historical processes. The historical effects on patterns of diversity have been hypothesized to be most important for taxonomic groups with poor dispersal abilities. We quantified the relative stability of rainforests over the late Quaternary period by modeling rainforest expansion and contraction in 21 biogeographic subregions in northeast Australia across four time periods. We demonstrate that historical habitat stability can be as important, and in endemic low-dispersal taxa even more important, than current habitat area in explaining spatial patterns of species richness. In contrast, patterns of endemic species richness for taxa with high dispersal capacity are best predicted by using current environmental parameters. We also show that contemporary patterns of species turnover across the region are best explained by historical patterns of habitat connectivity. These results clearly demonstrate that spatially explicit analyses of the historical processes of persistence and colonization are both effective and necessary for understanding observed patterns of biodiversity.
Xbves
is a regulator of epithelial movement during early
Xenopus laevis
development
Authors: Ripley Anna N. , Osler Megan E. , Wright Christopher V. E. , Bader David
Published: January 2006

Bves/pop1a is a unique, highly conserved integral membrane protein expressed in embryonic epithelia and striated muscle. Although studies have proposed a role in epithelial morphogenesis, the function of Bves/pop1a in development is completely unknown. Here we show that
Xenopus laevis Bves
(
Xbves
) RNA and protein are expressed in epithelia of the early embryo. Transfection of
Xbves
into nonadherent mouse L cells confers cell/cell adhesion. Global inhibition of
Xbves
function by morpholino injection into two-cell embryos arrests development at gastrulation by deregulating the epithelial movements of epiboly and involution. Clonal inhibition of Xbves activity within the A1 blastomere and its derivatives completely randomizes movement of its progeny within otherwise normally differentiating embryos. These data demonstrate that Bves/pop1a proteins play a critical role in epithelial morphogenesis and, specifically, in the cell movements essential for epithelial rearrangements that occur during
X. laevis
development.
Nitric oxide inhibition of respiration involves both competitive (heme) and noncompetitive (copper) binding to cytochromecoxidase
Authors: Mason Maria G. , Nicholls Peter , Wilson Michael T. , Cooper Christopher E.
Published: January 2006

NO reversibly inhibits mitochondrial respiration via binding to cytochromecoxidase (CCO). This inhibition has been proposed to be a physiological control mechanism and/or to contribute to pathophysiology. Oxygen reacts with CCO at a heme iron:copper binuclear center (a3/CuB). Reports have variously suggested that during inhibition NO can interact with the binuclear center containing zero (fully oxidized), one (singly reduced), and two (fully reduced) additional electrons. It has also been suggested that two NO molecules can interact with the enzyme simultaneously. We used steady-state and kinetic modeling techniques to reevaluate NO inhibition of CCO. At high flux and low oxygen tensions NO interacts predominantly with the fully reduced (ferrous/cuprous) center in competition with oxygen. However, as the oxygen tension is raised (or the consumption rate is decreased) the reaction with the oxidized enzyme becomes increasingly important. There is no requirement for NO to bind to the singly reduced binuclear center. NO interacts with either ferrous heme iron or oxidized copper, but not both simultaneously. The affinity (KD) of NO for the oxygen-binding ferrous heme site is 0.2 nM. The noncompetitive interaction with oxidized copper results in oxidation of NO to nitrite and behaves kinetically as if it had an apparent affinity of 28 nM; at low levels of NO, significant binding to copper can occur without appreciable enzyme inhibition. The combination of competitive (heme) and noncompetitive (copper) modes of binding enables NO to interact with mitochondria across the fullin vivodynamic range of oxygen tension and consumption rates.
MgSiO
3
postperovskite at D″ conditions
Authors: Wentzcovitch Renata M. , Tsuchiya Taku , Tsuchiya Jun
Published: January 2006

The postperovskite transition in MgSiO
3
at conditions similar to those expected at the D″ discontinuity of Earth's lower mantle offers a paradigm for interpreting the properties of this region. Despite consistent experimental and theoretical predictions of this phase transformation, the complexity of the D″ region raises questions about its geophysical significance. Here we report the thermoelastic properties of
Cmcm
postperovskite at appropriate conditions and evidences of its presence in the lowermost mantle. These are (
i
) the jumps in shear and longitudinal velocities similar to those observed in certain places of the D″ discontinuity and (
ii
) the anticorrelation between shear and bulk velocity anomalies as detected within the D″ region. In addition, the increase in shear modulus across the phase transition provides a possible explanation for the reported discrepancy between the calculated shear modulus of postperovskite free aggregates and the seismological counterpart in the lowermost mantle.
Retrotransposon insertion in
SILV
is responsible for merle patterning of the domestic dog
Authors: Clark Leigh Anne , Wahl Jacquelyn M. , Rees Christine A. , Murphy Keith E.
Published: January 2006

Merle is a pattern of coloring observed in the coat of the domestic dog and is characterized by patches of diluted pigment. This trait is inherited in an autosomal, incompletely dominant fashion. Dogs heterozygous or homozygous for the merle locus exhibit a wide range of auditory and ophthalmologic abnormalities, which are similar to those observed for the human auditory–pigmentation disorder Waardenburg syndrome. Mutations in at least five genes have been identified as causative for Waardenburg syndrome; however, the genetic bases for all cases have not been determined. Linkage disequilibrium was identified for a microsatellite marker with the merle phenotype in the Shetland Sheepdog. The marker is located in a region of CFA10 that exhibits conservation of synteny with HSA12q13. This region of the human genome contains
SILV
, a gene important in mammalian pigmentation. Therefore, this gene was evaluated as a candidate for merle patterning. A short interspersed element insertion at the boundary of intron 10/exon 11 was found, and this insertion segregates with the merle phenotype in multiple breeds. Another finding was deletions within the oligo(dA)-rich tail of the short interspersed element. Such deletions permit normal pigmentation. These data show that
SILV
is responsible for merle patterning and is associated with impaired function of the auditory and ophthalmologic systems. Although the mutant phenotype of
SILV
in the human is unknown, these results make it an intriguing candidate gene for human auditory–pigmentation disorders.
Direct measurement of the free energy by optical microscopy
Authors: Dullens Roel P. A. , Aarts Dirk G. A. L. , Kegel Willem K.
Published: January 2006

We report the direct measurement of thermodynamic properties of colloidal hard spheres by optical microscopy. By using confocal microscopy, we obtain three-dimensional snapshots of a colloidal hard-sphere suspension over a wide range of densities. From these snapshots, the available volume to insert an additional sphere and the surface area of that volume are determined, which are directly related to the thermodynamics of the system. This procedure enables us to measure in a direct and noninterfering way, in principle, all thermodynamic properties, here demonstrated for the pressure, the chemical potential, and the free-energy density of a colloidal hard-sphere suspension. The “visual” determination of thermodynamic quantities opens up the possibility to experimentally study the relation between thermodynamics and geometry in real space beyond the hard-sphere potential.
Dual strategies for peptidoglycan discrimination by peptidoglycan recognition proteins (PGRPs)
Authors: Swaminathan Chittoor P. , Brown Patrick H. , Roychowdhury Abhijit , Wang Qian , Guan Rongjin , Silverman Neal , Goldman William E. , Boons Geert-Jan , Mariuzza Roy A.
Published: January 2006

The innate immune system constitutes the first line of defense against microorganisms in both vertebrates and invertebrates. Although much progress has been made toward identifying key receptors and understanding their role in host defense, far less is known about how these receptors recognize microbial ligands. Such studies have been severely hampered by the need to purify ligands from microbial sources and a reliance on biological assays, rather than direct binding, to monitor recognition. We used synthetic peptidoglycan (PGN) derivatives, combined with microcalorimetry, to define the binding specificities of human and insect peptidogycan recognition proteins (PGRPs). We demonstrate that these innate immune receptors use dual strategies to distinguish between PGNs from different bacteria: one based on the composition of the PGN peptide stem and another that senses the peptide bridge crosslinking the stems. To pinpoint the site of PGRPs that mediates discrimination, we engineered structure-based variants having altered PGN-binding properties. The plasticity of the PGRP-binding site revealed by these mutants suggests an intrinsic capacity of the innate immune system to rapidly evolve specificities to meet new microbial challenges.
Mammalian αI-spectrin is a neofunctionalized polypeptide adapted to small highly deformable erythrocytes
Authors: Salomao Marcela , An Xiuli , Guo Xinhua , Gratzer Walter B. , Mohandas Narla , Baines Anthony J.
Published: January 2006

Mammalian red blood cells, unlike those of other vertebrates, must withstand the rigors of circulation in the absence of new protein synthesis. Key to this is plasma membrane elasticity deriving from the protein spectrin, which forms a network on the cytoplasmic face. Spectrin is a tetramer (αβ)
2
, made up of αβ dimers linked head to head. We show here that one component of erythrocyte spectrin, αI, is encoded by a gene unique to mammals. Phylogenetic analysis suggests that the other α-spectrin gene (αII) common to all vertebrates was duplicated after the emergence of amphibia, and that the resulting αI gene was preserved only in mammals. The activities of αI and αII spectrins differ in the context of the human red cell membrane. An αI-spectrin fragment containing the site of head-to-head interaction with the β-chain binds more weakly than the corresponding αII fragment to this site. The latter competes so strongly with endogenous αI as to cause destabilization of membranes at 100-fold lower concentration than the αI fragment. The efficacies of αI/αII chimeras indicate that the partial structural repeat, which binds to the complementaryβ-spectrin element, and the adjacent complete repeat together determine the strength of the dimer–dimer interaction on the membrane. Alignment of all available α-spectrin N-terminal sequences reveals three blocks of sequence unique to αI. Furthermore, human αII-spectrin is closer to fruitfly α-spectrin than to human αI-spectrin, consistent with adaptation of αI to new functions. We conclude that αI-spectrin represents a neofunctionalized spectrin adapted to the rapid make and break of tetramers.
Global spectral representations of black hole spacetimes in the complex plane
Authors: van Putten Maurice H. P. M.
Published: January 2006

Binary black hole coalescence produces a finite burst of gravitational radiation, which propagates toward quiescent infinity. These spacetimes are analytic about infinity and contain a dimensionless coupling constant
M
/
s
, where
M
denotes the total mass-energy and
s
is an imaginary distance. This work introduces a globally convergent Fourier series in a complex radial coordinate, allowing spectral representations of black hole spacetimes in all three dimensions. This method circumvents singularities associated with black holes and includes infinity, thereby avoiding the need to impose radiative boundary conditions. We illustrate this representation theory on Boyer–Lindquist initial data of two black holes and a scalar wave equation with signal recovery by Cauchy's integral formula.
Manganese(II), iron(II), cobalt(II), and copper(II) complexes of an extended inherently chiral tris-bipyridyl cage
Authors: Perkins David F. , Lindoy Leonard F. , McAuley Alexander , Meehan George V. , Turner Peter
Published: January 2006

Manganese(II), iron(II), cobalt(II), and copper(II) derivatives of two inherently chiral, Tris(bipyridyl) cages (L and L′) of type [ML]-(PF6)2(solvent)nand [FeL′](ClO4)2are reported, where L is the hexa-tertiary butyl-substituted derivative of L′. These products were obtained by using the free cage and metal template procedures; the latter involved the reductive amination of the respective Tris-dialdehyde precursor complexes of iron(II), cobalt(II), or nickel(II). Electrochemical, EPR, and NMR studies have been used to probe the nature of the individual complexes. X-ray structures of the manganese(II), iron(II), and copper(II) complexes of L and the iron(II) complex of L′ are presented; these are compared with the previously reported structures of the corresponding nickel(II) complex and metal-free cage (L). In each complex the metal cation occupies the cage's central cavity and is coordinated to six nitrogens from the three bipyridyl groups. The cations [MnL]2+and [FeL]2+are isostructural but both exhibit a different arrangement of the bound cage to that observed in the corresponding nickel(II) and copper(II) complexes. The latter have anexo-exoarrangement of the bridgehead nitrogen lone pairs, with the metal inducing a triple helical twist that extends ≈22 Å along the axial length of each complex. In contrast, [MnL]2+and [FeL]2+have their terminal nitrogen lone pairs directedendo, causing a significant change in the configuration of the bound ligand. In [FeL′]2+, the cage has both bridgehead nitrogen lone pairs orientatedexo. Semiempirical calculations indicate that the observedendo-endoandexo-exoarrangements are of comparable energy.
P
versus
Q
: Structural reaction coordinates capture protein folding on smooth landscapes
Authors: Cho Samuel S. , Levy Yaakov , Wolynes Peter G.
Published: January 2006

Minding your p's and q's has become as important to protein-folding theorists as it is for those being instructed in the rules of etiquette. To assess the quality of structural reaction coordinates in predicting the transition-state ensemble (TSE) of protein folding, we benchmarked the accuracy of four structural reaction coordinates against the kinetic measure
P
fold
, whose value of 0.50 defines the stochastic separatrix for a two-state folding mechanism. For two proteins that fold by a simple two-state mechanism, c-src SH3 and CI-2, the Φ-values of the TSEs predicted by native topology-based reaction coordinates (including
Q
, the fraction of native contacts) are almost identical to those of the TSE based on
P
fold
, with correlation coefficients of >0.90. For proteins with complex folding mechanisms that have especially broad, asymmetrical free energy barriers such as the designed 3-ankyrin repeating protein (3ANK) or proteins with distinct intermediates such as cyanovirin-N (CV-N), we show that the ensemble of structures with
P
fold
= 0.50 generally does not include the chemically relevant transition states. This weakness of
P
fold
limits its usefulness in protein folding studies. For such systems, elucidating the essential features of folding mechanisms requires using multiple reaction coordinates, although the number is still rather small. At the same time, for simple folding mechanisms, there is no indication of superiority for
P
fold
over structurally chosen and thermodynamically relevant reaction coordinates that correctly measure the degree of nativeness.
Human medullary responses to cooling and rewarming the skin: A functional MRI study
Authors: McAllen Robin M. , Farrell Michael , Johnson John M. , Trevaks David , Cole Leonie , McKinley Michael J. , Jackson Graeme , Denton Derek A. , Egan Gary F.
Published: January 2006

A fall in skin temperature precipitates a repertoire of thermoregulatory responses that reduce the likelihood of a decrease in core temperature. Studies in animals suggest that medullary raphé neurons are essential for cold-defense, mediating both the cutaneous vasoconstrictor and thermogenic responses to ambient cooling; however, the involvement of raphé neurons in human thermoregulation has not been investigated. This study used functional MRI with an anatomically guided region of interest (ROI) approach to characterize changes in the blood oxygen level-dependent (BOLD) signal within the human medulla of nine normal subjects during non-noxious cooling and rewarming of the skin by a water-perfused body suit. An ROI covering 4.9 ± 0.3 mm
2
in the ventral midline of the medulla immediately caudal to the pons (the rostral medullary raphé) showed an increase in BOLD signal of 3.9% (
P
< 0.01) during periods of skin cooling, compared with other times. Overall, that signal showed a strong inverse correlation (
R
= 0.48,
P
< 0.001) with skin temperature. A larger ROI covering the internal medullary cross section at the same level (area, 126 ± 15 mm
2
) showed no significant change in mean BOLD signal with cooling (+0.2%,
P
> 0.05). These findings demonstrate that human rostral medullary raphé neurons are selectively activated in response to a thermoregulatory challenge and point to the location of thermoregulatory neurons homologous to those of the raphé pallidus nucleus in rodents.
Analysis of gene expression in pathophysiological states: Balancing false discovery and false negative rates
Authors: Norris Andrew W. , Kahn C. Ronald
Published: January 2006

Nucleotide-microarray technology, which allows the simultaneous measurement of the expression of tens of thousands of genes, has become an important tool in the study of disease. In disorders such as malignancy, gene expression often undergoes broad changes of sizable magnitude, whereas in many common multifactorial diseases, such as diabetes, obesity, and atherosclerosis, the changes in gene expression are modest. In the latter circumstance, it is therefore challenging to distinguish the truly changing from nonchanging genes, especially because statistical significance must be considered in the context of multiple hypothesis testing. Here, we present a balanced probability analysis (BPA), which provides the biologist with an approach to interpret results in the context of the total number of genes truly differentially expressed and false discovery and false negative rates for the list of genes reaching any significance threshold. In situations where the changes are of modest magnitude, sole consideration of the false discovery rate can result in poor power to detect genes truly differentially expressed. Concomitant analysis of the rate of truly differentially expressed genes not identified, i.e., the false negative rate, allows balancing of the two error rates and a more thorough insight into the data. To this end, we have developed a unique, model-based procedure for the estimation of false negative rates, which allows application of BPA to real data in which changes are modest.
Serotonin 1A receptors in the living brain of Alzheimer's disease patients
Authors: Kepe Vladimir , Barrio Jorge R. , Huang Sung-Cheng , Ercoli Linda , Siddarth Prabha , Shoghi-Jadid Kooresh , Cole Gregory M. , Satyamurthy Nagichettiar , Cummings Jeffrey L. , Small Gary W. , Phelps Michael E.
Published: January 2006

4-[F-18]fluoro-
N
-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-
N
-(2-pyridinyl)benzamide, a selective serotonin 1A (5-HT
1A
) molecular imaging probe, was used in conjunction with positron emission tomography (PET) for quantification of 5-HT
1A
receptor densities in the living brains of Alzheimer's disease patients (ADs) (
n
= 8), subjects with mild cognitive impairment (
n
= 6), and controls (
n
= 5). ADs had receptor densities significantly decreased in both hippocampi (binding potential: controls 1.62 ± 0.07; ADs 1.18 ± 0.26) and also in raphe nuclei (controls 0.63 ± 0.09; ADs 0.37 ± 0.20). When volume losses are included, 5-HT
1A
losses are even more severe (i.e., average mean decreases of 24% in mild cognitive impairment patients and 49% in ADs). A strong correlation of 5-HT
1A
receptor decreases in hippocampus with worsening of clinical symptoms (Mini Mental State Exam scores) was also found. Moreover, these decreases in 5-HT
1A
receptor measures correlate with decreased glucose utilization as measured with 2-deoxy-2-[F-18]fluoro-
d
-glucose PET in the brains of ADs (standardized uptake values; globally: controls 0.89 ± 0.04, ADs 0.72 ± 0.04; posterior cingulate gyrus: controls 1.05 ± 0.09, ADs 0.79 ± 0.11). They also inversely correlate with increased neuropathological loads measured with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile PET in several neocortical regions in the same subjects. The
in vivo
observations were confirmed independently by
in vitro
digital autoradiography with 4-[F-18]fluoro-
N
-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-
N
-(2-pyridinyl)benzamide and 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile on brain tissue specimens from two ADs and three nondemented subjects.
Natural variation and genetic covariance in adult hippocampal neurogenesis
Authors: Kempermann Gerd , Chesler Elissa J. , Lu Lu , Williams Robert W. , Gage Fred H.
Published: January 2006

Adult hippocampal neurogenesis is highly variable and heritable among laboratory strains of mice. Adult neurogenesis is also remarkably plastic and can be modulated by environment and activity. Here, we provide a systematic quantitative analysis of adult hippocampal neurogenesis in two large genetic reference panels of recombinant inbred strains (BXD and AXB/BXA,
n
= 52 strains). We combined data on variation in neurogenesis with a new transcriptome database to extract a set of 190 genes with expression patterns that are also highly variable and that covary with rates of (
i
) cell proliferation, (
ii
) cell survival, or the numbers of surviving (
iii
) new neurons, and (
iv
) astrocytes. Expression of a subset of these neurogenesis-associated transcripts was controlled in cis across the BXD set. These self-modulating genes are particularly interesting candidates to control neurogenesis. Among these were
musashi
(
Msi1h
) and
prominin1
/
CD133
(
Prom1
), both of which are linked to stem-cell maintenance and division. Twelve neurogenesis-associated transcripts had significant cis-acting quantitative trait loci, and, of these, six had plausible biological association with adult neurogenesis (
Prom1
,
Ssbp2
,
Kcnq2
,
Ndufs2
,
Camk4
, and
Kcnj9
). Only one cis-acting candidate was linked to both neurogenesis and gliogenesis,
Rapgef6
, a downstream target of ras signaling. The use of genetic reference panels coupled with phenotyping and global transcriptome profiling thus allowed insight into the complexity of the genetic control of adult neurogenesis.
Embolization of spontaneous rupture of an aneurysm of the ovarian artery supplying the uterus with fibroids
Authors: Nakajo M. , Ohkubo K. , Fukukura Y. , Nandate T. , Nakajo M.
Published: January 2006

We report a case of spontaneous retroperitoneal hemorrhage caused by rupture of an aneurysm of the right ovarian artery in a 55-year-old woman. Diagnosis was achieved by computed tomography and arteriography. The ruptured aneurysm was treated by transcatheter arterial embolization using microcoils and gelatin sponge particles. This is the first case of rupture of an aneurysm of the ovarian artery not related to pregnancy, and the third case of embolization of a ruptured ovarian artery aneurysm in the literature. We illustrate the usefulness of embolization in treatment of an ovarian artery aneurysm without surgery.
Complex genital malformation in a female with congenital adrenal hyperplasia: evaluation with magnetic resonance imaging
Authors: Klessen C. , Asbach P. , Hein P. A. , Beyersdorff D. , Hamm B. , Taupitz M.
Published: January 2006

This is a case of complex genital malformation in a young patient with congenital adrenal hyperplasia. The magnetic resonance imaging (MRI) findings included ostium of the vagina into the urethra (common urogenital opening), prostate-like tissue surrounding the urethra, and hyperplasia of the left adrenal gland. The report provides information on the clinical findings, the MRI examination, including the applied sequences and the MR findings, and gives an overview of the disease pattern and its frequency of occurrence.
Ultrasonography of the rotator cuff: a comparison with arthroscopy in one-hundred-and-ninety consecutive cases
Authors: Milosavljevic J. , Elvin A. , Rahme H.
Published: January 2006

Purpose: To evaluate the accuracy of high-resolution ultrasonography compared to arthroscopy in the detection of rotator cuff tears.

Material and Methods: Preoperative ultrasonography (US) with a 10-MHz commercially available linear-array transducer and a standardized study protocol was performed in 190 consecutive shoulders in 185 patients with a history of shoulder pain for more than 3 months. The findings at US were classified into intact cuff, partial-thickness, and full-thickness rotator cuff tears, and correlated with findings at shoulder arthroscopy.

Results: US correctly depicted 118 of 124 rotator cuff tears with sensitivity 95%, specificity 94%, PPV 97%, NPV 91% and accuracy 95%, all 94 full-thickness tears (sensitivity 100%, specificity 91%, PPV 91%, NPV 100%, and accuracy 95%), 24 of 30 partial-thickness tears (sensitivity 80%, specificity 98%, PPV 86%, NPV 96%, and accuracy 95%).

Conclusion: US is a highly accurate diagnostic method for detecting full-thickness rotator cuff tears, but is less sensitive in detecting partial-thickness rotator cuff tears.
Reliability of radiological and cosmetic measurements in hallux valgus
Authors: Saro C. , Johnson D. N. , Martinez de Aragón J. , Lindgren U. , Felländer-Tsai L.
Published: January 2006

Purpose: To evaluate the reliability of angular, linear, and sesamoid position measurements on preoperative and postoperative radiographs in hallux valgus (HV), as well as cosmetic foot appearance.

Material and Methods: Radiographs and photographs from 100 patients undergoing HV surgery were evaluated by two independent observers.

Results: Interobserver and intraobserver agreements for HV angle using coefficient of repeatability measures were 4.4° and 3.7°, respectively. Intraclass correlation coefficient measures within and between agreements were 0.97 for HV angle. For intermetatarsal distance, interobserver and intraobserver values were 0.90 and 0.94 when measuring from the midline of each metatarsal and 0.75 and 0.92 when measuring between cortices. Using the visual analog scale to evaluate esthetic appearance, interobserver and intraobserver agreements were 0.59 and 0.79, respectively. Sesamoid position values were also measured. Interobserver and intraobserver kappa values for preoperative and postoperative evaluations with two established methods (Mann or Smith) were 0.47 and 0.70 or 0.65 and 0.75, respectively.

Conclusion: Intraobserver reliability was higher than interobserver for intermetatarsal distance, cosmetics, and sesamoid position. Angular measurements were more accurate than linear. Esthetic evaluation was less reliable than radiographic, except in the case of sesamoid position measurements.
Assessing wear of the acetabular cup using computed tomography: an ex vivo study
Authors: Olivecrona L. , Jedenmalm A. , Aspelin P. , Weidenhielm L. , Noz M. E. , Maguire G. Q. , Zeleznik M. P. , Olivecrona H.
Published: January 2006

Purpose: To validate a clinically useful method for measuring acetabular cup wear using computed tomography (CT).

Material and Methods: Eight uncemented acetabular cups were scanned twice ex vivo using CT. The linear penetration depth of the femoral component head into the cup and the thickness of the remaining polyethylene liner were measured in the CT volumes using dedicated software. Two independent examiners twice assessed each volume. The CT measurements were compared to direct measurements using a coordinate measuring device and micrometer measurements.

Results: Accuracy of wear measurements expressed as penetration depth was ±0.6 and ±1.0 mm for the two examiners, respectively, with no significant differences between examiners, trials, and CT scans. Accuracy of measurements of remaining polyethylene was ±1.3 and ±1.0 mm, respectively, for the two examiners. Systematic differences between examiners were found, but no significant differences between trials and CT scans. These differences were due to different interpretations of metal artifacts in the volumes.

Conclusion: The proposed CT method for evaluating wear as head penetration depth allows for reliable wear detection at a clinically relevant level. Measurements of remaining polyethylene on CT volumes are not as reliable as wear measurements owing to metal artifacts.
F-18 FDG pet in detecting renal cell carcinoma
Authors: Ak İ. , Can C.
Published: January 2006

Purpose: To assess the role of F-18 FDG imaging with a dual head coincidence mode gamma camera (Co-PET) in the detection of renal cell carcinoma (RCC) in patients with renal masses.

Material and Methods: An F-18 FDG Co-PET study was performed in 19 patients (7 F, 12 M; mean age 58.15±2.5 years, age range 45–79 years) with suspected primary renal tumors based on conventional imaging techniques, including computed tomography (CT) and ultrasonography (US) before nephrectomy or surgical resection of the mass.

Results: Histologically documented RCC was present in 15 patients. Of the 19 patients with suspected primary renal tumors, F-18 FDG Co-PET was true-positive in 13, false-negative in 2, true-negative in 3, and false-positive in 1 patient. Two angiomyolipomas and one renal mass due to infarction and hemorrhage showed a true-negative Co-PET result. The patient with false-positive FDG Co-PET study was diagnosed as xantogranulomatous pyelonephritis. Overall sensitivity, specificity, and accuracy of FDG Co-PET for RCC were 86% (13/15), 75% (3/4), and 84% (16/19), respectively. Positive predictive value for RCC was 92% and negative predictive value 60%.

Conclusion: These findings suggest that F-18 FDG Co-PET may have a role in the diagnostic evaluation of patients with RCC and primary staging of disease. Positive F-18 FDG study may be predictive of the presence of RCC. However, a negative study does not exclude the RCC.
Adjunctive diagnostic value of targeted electrical impedance imaging to conventional methods in the evaluation of breast lesions
Authors: Szabó B. K. , Saracco A. , Wilczek B. , Boné B. , Aspelin P.
Published: January 2006

Purpose: To determine the diagnostic accuracy of targeted electrical impedance imaging in characterizing breast lesions, and to evaluate whether lesion size, depth and histopathology affect the diagnosis.

Material and Methods: A total of 137 women with 145 lesions (79 malignant and 66 benign) found by palpation or mammography were prospectively enrolled in this study. The patients were examined by means of clinical breast examination, mammography, ultrasonography, and electrical impedance imaging with TransScan TS2000. A level of suspicion (LOS) post-processing algorithm (v2.67) was used for TS2000 lesion assessment. Imaging findings were correlated with cytologic ( n = 54) and histologic diagnoses ( n = 91). Patients with benign lesions were followed up for a mean of 36 months.

Results: TS2000 showed a high sensitivity (86%) which did not differ significantly from that of mammography (87%) and ultrasonography (US) (75%). The specificity of TS2000 (49%) was significantly lower compared to mammography (97%, P<0.0001) and US (100%, P<0.0001). The additive use of TS2000 to mammography and US yielded no significant increase in sensitivity (97%), but the decrease in specificity was significant (46%, P<0.0001). Diagnostic effectiveness of TS2000 (Az = 0.68), as measured by the area under the ROC curve, was significantly lower than for mammography (Az = 0.93, P<0.0001) and for US (Az = 0.91, P<0.0001). When using TS2000 in addition to mammography and US (Az = 0.86), a significant impairment was found ( P = 0.0003).

Conclusion: The role of targeted electrical impedance imaging as an adjunct to mammography and ultrasonography in the diagnosis of breast lesions is not justified by the result of this study.
FFT analysis of the X-ray tube voltage waveforms of high-frequency generators for radiographic systems
Authors: Chida K. , Saito H. , Ito D. , Shimura H. , Zuguchi M. , Takai Y.
Published: January 2006

Purpose: To present a novel method for analyzing the voltage waveform from high-frequency X-ray generators for radiographic systems.

Material and Methods: The output signal of the actual voltage across the tube of a high-frequency generator was measured using the built-in voltage sense taps that are used for voltage regulation feedback in X-ray generators. The output signal was stored in an analyzing recorder, and the waveforms were analyzed using FFT analysis. The FFT analysis of high-frequency generators consisted of obtaining the power spectrum, comparing the major frequency components in the tube voltage waveforms, and examining the intensity of each frequency component.

Results: FFT analysis enables an objective comparison of the complex tube voltage waveforms in high-frequency X-ray generators. FFT analysis detected the change in the X-ray tube voltage waveform that occurred when there were problems with the high-frequency generator.

Conclusion: High-frequency X-ray generators are becoming the universal choice for radiographic systems. The X-ray tube voltage and its waveform are important features of an X-ray generator, and quality assurance (QA) is important, too. As a tool for engineers involved in the design and development of X-ray generators, we can see that our methods (FFT analysis) might have some value as a means of describing generator performance under varying conditions. Furthermore, since the X-ray tube voltage waveform of a high-frequency generator is complex, FFT analysis may be useful for QA of the waveform.
Experimental autologous osteochondral plug transfer in the treatment of focal chondral defects: magnetic resonance imaging signs of technical success in sheep
Authors: Uhl M. , Lahm A. , Bley T. A. , Haberstroh J. , Mrosek E. , Ghanem N. , Erggelet C.
Published: January 2006

Purpose: To describe the magnetic resonance imaging (MRI) signs of technically successful osteochondral plug transfer and to correlate the findings with histology using the Mankin score.

Material and Methods: The study was done in a prospective animal experiment: 11 adult black-head sheep underwent surgical treatment with osteochondral plug transfer of a knee joint. The animals were killed 6 months later and MRI of the joints was done immediately. MRI was applied with a 1.5T MR scanner using a spin-echo (SE) T1-weighted, turbo spin-echo (TSE) T2-weighted with spectral fat suppression and a fat-suppressed 3D-spoiled gradient echo (GRE) sequence (manufacturer's acronym: FLASH®) (TR 50.0 ms, TE 11.0 ms, flip 35°). After MRI, all knee joints were dissected and a biopsy of the plug and the adjacent cartilage was taken. Classification of the cartilage biopsies was carried out in accordance with a modified Mankin score.

Results: Cartilage repairs with a hypointense cartilage signal in the FLASH® 3D sequence were correlated with poor histological results (lower Mankin score). Histologically, the regions of cartilage with a hypointense signal showed a fibrocartilage-like repair tissue. Hyaline cartilage with well-defined layers had the same signal intensity in the FLASH® sequence relative to adjacent hyaline cartilage. There were two plugs with a surface defect, graded as Outerbridge grade 1 in MRI and histology. Both had a poor outcome in the histologic Mankin score. Grade 2–4 lesions were not observed in the MRI study nor in the histologic study.

Conclusion: MRI is a useful non-invasive tool for evaluating the morphologic status of osteochondral plug transfers. A good postoperative result of the cartilage repair was found histologically if an isointense cartilage signal of the graft was documented in the FLASH® 3D sequence, and the graft had good congruity with the articular surface without defects.
Acute knee trauma: analysis of multidetector computed tomography findings and comparison with conventional radiography
Authors: Mustonen A. O. T. , Koskinen S. K. , Kiuru M. J.
Published: January 2006

Purpose: To evaluate the multidetector computed tomography (MDCT) findings of acute knee trauma and to compare radiography with MDCT in patients referred to a level 1 trauma center.

Material and Methods: During a 5-year period, a total of 415 MDCT examinations were performed on 409 patients with acute knee trauma to reveal complex fracture anatomy or rule out a fracture. MDCT and primary radiographs were re-evaluated with respect to fracture location and trauma mechanism. Tibial plateau fractures were further analyzed depending on anatomical location: anterior-medial, anterior-lateral, posterior-lateral, and posterior-medial regions. Maximal depression of the tibial articular surface was measured. Findings on the primary knee radiographs were compared with MDCT findings.

Results: Of the 409 patients, 356 (87%) had a knee fracture. A total of 451 fractures were found in all anatomic regions: distal femur ( n = 49), proximal tibia ( n = 307), patella ( n = 23), and proximal fibula ( n = 72). Primary radiographs were available in 316 (76%) cases. Of these, 225 (71%) had MDCT in order to reveal the fracture anatomy better, and 91 (29%) had a subsequent MDCT after negative plain radiographs. Overall sensitivity of radiography was 83%, while negative predictive value was 49%. On radiography, tibial plateau articular depression was underestimated in all regions except when the fracture consisted of the whole half of the anterior or posterior plateau. The three main injury mechanisms were traffic accident, a simple fall, and sport. In 49 cases (15%), primary radiographs were suboptimal due to positioning.

Conclusion: In severely injured patients, diagnostically sufficient radiographs are difficult to obtain, and therefore a negative radiograph is not reliable in ruling out a fracture. In these patients, MDCT is a fast and accurate examination and is also recommended in patients with tibial plateau fractures or complex knee injuries in order to evaluate the fracture adequately.
Iodinated radiographic contrast media possess antioxidant properties in vitro
Authors: Berg K. , Skarra S. , Bruvold M. , Brurok H. , Karlsson J. O. G. , Jynge P.
Published: January 2006

Purpose: To study potential properties of iodinated radiographic contrast media (IRCM) for intravascular use in in vitro free radical generating reactions.

Material and Methods: Superoxide (·O2−) and hydroxyl (·OH) radicals were generated in xanthine oxidase and Fenton reactions. ·O2− was assayed by the nitroblue tetrazolium (NBT) method, whereas ·OH was assayed by an aromatic hydroxylation (2-hydroxy-benzoic acid) method. Total antioxidant status (TAS) of test substances was determined by a colorimetric assay. Finally, acetyl-cholinesterase (AChE) activity was measured in the absence and presence of IRCM.

Results: High concentrations (>50 mM) of IRCM inhibited ·O2− production, ionic more than non-ionic IRCM. Medium concentrations (25–50 mM) of IRCM reduced ·OH production, and both types of IRCM were equally potent. Low concentrations (<25 mM) of non-ionic IRCM displayed higher antioxidant capacity than their ionic counterparts when tested in the TAS assay. Visipaque 320® (iodixanol) was found to have the highest TAS value, followed by Omnipaque 350® (iohexol), Hexabrix 320® (ioxaglate), and Urografin 370® (diatrizoate).

Conclusion: IRCM have in vitro antioxidant properties in concentrations relevant for their clinical application. These properties may therefore be of potential importance when evaluating IRCM effects in vivo, particularly those concerning cardiovascular and renal function.
Receptor palmitoylation and ubiquitination regulate anthrax toxin endocytosis
Authors: Abrami Laurence , Leppla Stephen H. , van der Goot F. Gisou
Published: January 2006

The anthrax toxin is composed of three independent polypeptide chains. Successful intoxication only occurs when heptamerization of the receptor-binding polypeptide, the protective antigen (PA), allows binding of the two enzymatic subunits before endocytosis. We show that this tailored behavior is caused by two counteracting posttranslational modifications in the cytoplasmic tail of PA receptors. The receptor is palmitoylated, and this unexpectedly prevents its association with lipid rafts and, thus, its premature ubiquitination. This second modification, which is mediated by the E3 ubiquitin ligase Cbl, only occurs in rafts and is required for rapid endocytosis of the receptor. As a consequence, cells expressing palmitoylation-defective mutant receptors are less sensitive to anthrax toxin because of a lower number of surface receptors as well as premature internalization of PA without a requirement for heptamerization.
The Png1–Rad23 complex regulates glycoprotein turnover
Authors: Kim Ikjin , Ahn Jungmi , Liu Chang , Tanabe Kaori , Apodaca Jennifer , Suzuki Tadashi , Rao Hai
Published: January 2006

Misfolded proteins in the endoplasmic reticulum (ER) are destroyed by a pathway termed ER-associated protein degradation (ERAD). Glycans are often removed from glycosylated ERAD substrates in the cytosol before substrate degradation, which maintains the efficiency of the proteasome. Png1, a deglycosylating enzyme, has long been suspected, but not proven, to be crucial in this process. We demonstrate that the efficient degradation of glycosylated ricin A chain requires the Png1–Rad23 complex, suggesting that this complex couples protein deglycosylation and degradation. Rad23 is a ubiquitin (Ub) binding protein involved in the transfer of ubiquitylated substrates to the proteasome. How Rad23 achieves its substrate specificity is unknown. We show that Rad23 binds various regulators of proteolysis to facilitate the degradation of distinct substrates. We propose that the substrate specificity of Rad23 and other Ub binding proteins is determined by their interactions with various cofactors involved in specific degradation pathways.
Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization
Authors: Qin Gangjian , Ii Masaaki , Silver Marcy , Wecker Andrea , Bord Evelyn , Ma Hong , Gavin Mary , Goukassian David A. , Yoon Young-sup , Papayannopoulou Thalia , Asahara Takayuki , Kearney Marianne , Thorne Tina , Curry Cynthia , Eaton Liz , Heyd Lindsay , Dinesh Deepika , Kishore Raj , Zhu Yan , Losordo Douglas W.
Published: January 2006

The cell surface receptor α4 integrin plays a critical role in the homing, engraftment, and maintenance of hematopoietic progenitor cells (HPCs) in the bone marrow (BM). Down-regulation or functional blockade of α4 integrin or its ligand vascular cell adhesion molecule-1 mobilizes long-term HPCs. We investigated the role of α4 integrin in the mobilization and homing of BM endothelial progenitor cells (EPCs). EPCs with endothelial colony-forming activity in the BM are exclusively α4 integrin–expressing cells. In vivo, a single dose of anti–α4 integrin antibody resulted in increased circulating EPC counts for 3 d. In hindlimb ischemia and myocardial infarction, systemically administered anti–α4 integrin antibody increased recruitment and incorporation of BM EPCs in newly formed vasculature and improved functional blood flow recovery and tissue preservation. Interestingly, BM EPCs that had been preblocked with anti–α4 integrin ex vivo or collected from α4 integrin–deficient mice incorporated as well as control cells into the neovasculature in ischemic sites, suggesting that α4 integrin may be dispensable or play a redundant role in EPC homing to ischemic tissue. These data indicate that functional disruption of α4 integrin may represent a potential angiogenic therapy for ischemic disease by increasing the available circulating supply of EPCs.
Geometry of infinitely generated Veech groups
Authors: Hubert Pascal , Schmidt Thomas
Published: January 2006

Veech groups uniformize Teichmüller geodesics in Riemann moduli space. We gave examples of infinitely generated Veech groups; see Duke Math. J. 123 (2004), 49–69. Here we show that the associated Teichmüller geodesics can even have both infinitely many cusps and infinitely many infinite ends.
The Influence of Local Urban Containment Policies and Statewide Growth Management on the Size of United States Urban Areas*
Authors: Wassmer Robert W.
Published: January 2006

Abstract.  In an attempt to slow the consumption of urban land for a given population, and the negative outcomes thought by some to be generated by such sprawl, regulations in the form of (i) the local imposition of urban containment policies that restrict or prohibit the amount and/or the type of urban settlement beyond a certain line and (ii) the statewide enactment of mandatory growth management requirements for all local governments have been enacted in the United States. This paper describes a regression‐based analysis that finds that different forms of these policies are achieving their desired goal of shrinking the square mile size of an urban area. A comparison of the influence of the various forms of urban containment and growth management policies with other “natural evolution,”“flight from blight,” and “fiscalization of land use” factors that also influence the square mile size of an urban area is made, and policy implications are offered.