bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and properties of stereociliary link types in hair cells of the mouse cochlea
Authors: Goodyear Richard J. , Marcotti Walter , Kros Corné J. , Richardson Guy P.
Published: March 2005

The hair bundles of outer hair cells in the mature mouse cochlea possess three distinct cell‐surface specializations: tip links, horizontal top connectors, and tectorial membrane attachment crowns. Electron microscopy was used to study the appearance and maturation of these link types and examine additional structures transiently associated with the developing hair bundle. At embryonic day 17.5 (E17.5), the stereocilia are interconnected by fine lateral links and have punctate elements distributed over their surface. Oblique tip links are also seen at this stage. By postnatal day 2 (P2), outer hair cell bundles have a dense cell coat, but have lost many of the lateral links seen at E17.5. At P2, ankle links appear around the base of the bundle and tectorial membrane attachment crowns are seen at the stereociliary tips. Ankle links become less apparent by P9 and are completely lost by P12. The appearance of horizontal top connectors, which persist into adulthood, occurs concomitant with this loss of ankle links. Treatment with the calcium chelator BAPTA or the protease subtilisin enabled these links to be further distinguished. Ankle links are susceptible to both treatments, tip links are only sensitive to BAPTA, and tectorial membrane attachment crowns are removed by subtilisin but not BAPTA. The cell‐coat material is partially sensitive to subtilisin alone, while horizontal top connectors resist both treatments. These results indicate there is a rich, rapidly changing array of different links covering the developing hair bundle that becomes progressively refined to generate the mature complement by P19. J. Comp. Neurol. 485:75–85, 2005. © 2005 Wiley‐Liss, Inc.
HnRNP A3 genes and pseudogenes in the vertebrate genomes
Authors: Makeyev Aleksandr V. , Kim Chang Bae , Ruddle Frank H. , Enkhmandakh Badam , Erdenechimeg Lkhamsuren , Bayarsaihan Dashzeveg
Published: March 2005

The hnRNP A/B type proteins are abundant nuclear factors that bind to Pol II transcripts and are involved in numerous RNA‐related activities. To date most data on the hnRNP A/B family have been obtained with recombinant proteins and cell cultures. Further characterization can result from an examination of the impact of various modifications in intact functional loci; however, such characterization is hampered by the presence of numerous and widely dispersed hnRNP A/B‐related sequences in the mammalian genome. We have found hnRNP A3, a poorly recognized member of the hnRNP A/B family, among candidate transcription factors that interact with the regulatory region of the Hoxc8 gene and screened the human and mouse genomes for genes that encode hnRNP A3. We demonstrate that the sequence reported previously as the human hnRNP A3 gene (Accession number S63912) and located on 10p11.1 belongs to a processed pseudogene of the functional intron‐containing locus HNRPA3, which we have identified on 2q31.2. We have also identified its murine orthologs on mouse chromosome 2D and rat chromosome 3q23. Alternative splices were revealed at the N‐terminus and in the middle of hnRNP A3. 14 and 28 additional loci in the human and mouse genome, respectively, were mapped and identified as hnRNP A3 processed pseudogenes. In addition, we have found and compared hnRNP A3 orthologous genes in Gallus gallus, Xenopus tropicalis, and Danio rerio. The present in silico analysis serves as a necessary step toward a further functional characterization of hnRNP A3. J. Exp. Zool. 303A:259–271, 2005. © 2005 Wiley‐Liss, Inc.
Osmotic stress stimulates the organic osmolyte channel in Xenopus laevis oocytes expressing skate (Raja erinacea) AE1
Authors: Koomoa Dana‐Lynn T. , Musch Mark W. , Goldstein Leon
Published: March 2005

The aim of this study was to determine whether hypo‐osmolarity, which activates taurine transport through the volume‐sensitive organic osmolyte channel in skate (Raja erinacea) erythrocytes, also activates the organic osmolyte channel activity of skate AE1 (skAE1) expressed in oocytes. When Xenopus laevis oocytes expressing skAE1 were incubated in hypo‐osmotic ND 96 (210 mOsm) media, taurine was transported at a significantly higher rate than when incubated in ND 96 (235 mOsm), which is iso‐osmotic to Xenopus plasma. Therefore, hypo‐osmotic stress is part of the activation mechanism of the organic osmolyte channel in skAE1 expressing oocytes. J. Exp. Zool. 303A:319–322, 2005. © 2005 Wiley‐Liss, Inc.
Stability and accuracy of finite element methods for flow acoustics. I: general theory and application to one‐dimensional propagation
Authors: Gabard G. , Astley R. J. , Ben Tahar M.
Published: March 2005

The dispersion properties of finite element models for aeroacoustic propagation based on the convected scalar Helmholtz equation and on the Galbrun equation are examined. The current study focusses on the effect of the mean flow on the dispersion and amplitude errors present in the discrete numerical solutions. A general two‐dimensional dispersion analysis is presented for the discrete problem on a regular unbounded mesh, and results are presented for the particular case of one‐dimensional acoustic propagation in which the wave direction is aligned with the mean flow. The magnitude and sign of the mean flow is shown to have a significant effect on the accuracy of the numerical schemes. Quadratic Helmholtz elements in particular are shown to be much less effective for downstream—as opposed to upstream—propagation, even when the effect of wave shortening or elongation due to the mean flow is taken into account. These trends are also observed in solutions obtained for simple test problems on finite meshes. A similar analysis of two‐dimensional propagation is presented in an accompanying article. Copyright © 2005 John Wiley & Sons, Ltd.
Aftiphilin is a component of the clathrin machinery in neurons
Authors: Burman Jonathon L. , Wasiak Sylwia , Ritter Brigitte , de Heuvel Elaine , McPherson Peter S.
Published: March 2005

Aftiphilin was identified through a database search for proteins containing binding motifs for the γ‐ear domain of clathrin adaptor protein 1 (AP‐1). Here, we demonstrate that aftiphilin is expressed predominantly in brain where it is enriched on clathrin‐coated vesicles. In addition to eight γ‐ear‐binding motifs, aftiphilin contains two WXXF‐acidic motifs that mediate binding to the α‐ear of clathrin adaptor protein 2 (AP‐2) and three FXXFXXF/L motifs that mediate binding to the α‐ and β2‐ear. We demonstrate that aftiphilin uses these motifs for interactions with AP‐1 and AP‐2 and that it immunoprecipitates these APs but not AP‐3 or AP‐4 from brain extracts. Aftiphilin demonstrates a brefeldin A sensitive localization to the trans‐Golgi network in hippocampal neurons where it co‐localizes with AP‐1. Aftiphilin is also found at synapses where it co‐localizes with synaptophysin and AP‐2. Our data suggest a role for aftiphilin in clathrin‐mediated trafficking in neurons.
Quantum wave packet ab initio molecular dynamics: An approach to study quantum dynamics in large systems
Authors: Iyengar Srinivasan S. , Jakowski Jacek
Published: March 2005

A methodology to efficiently conduct simultaneous dynamics of electrons and nuclei is presented. The approach involves quantum wave packet dynamics using an accurate banded, sparse and Toeplitz representation for the discrete free propagator, in conjunction with ab initio molecular dynamics treatment of the electronic and classical nuclear degree of freedom. The latter may be achieved either by using atom-centered density-matrix propagation or by using Born–Oppenheimer dynamics. The two components of the methodology, namely, quantum dynamics and ab initio molecular dynamics, are harnessed together using a time-dependent self-consistent field-like coupling procedure. The quantum wave packet dynamics is made computationally robust by using adaptive grids to achieve optimized sampling. One notable feature of the approach is that important quantum dynamical effects including zero-point effects, tunneling, as well as over-barrier reflections are treated accurately. The electronic degrees of freedom are simultaneously handled at accurate levels of density functional theory, including hybrid or gradient corrected approximations. Benchmark calculations are provided for proton transfer systems and the dynamics results are compared with exact calculations to determine the accuracy of the approach.
Magnetism in BN nanotubes induced by carbon doping
Authors: Wu R. Q. , Liu L. , Peng G. W. , Feng Y. P.
Published: March 2005

We performed ab initio calculation on the pristine and carbon-doped (5,5) and (9,0) BN nanotubes. It was found that carbon substitution for either a single boron or a single nitrogen atom in the BN nanotubes can induce spontaneous magnetization. Calculations based on density functional theory with the local spin density approximation on the electronic band structure revealed a spin polarized, dispersionless band near the Fermi energy. The magnetization can be attributed to the carbon 2p electron. Compared to other theoretical models of light-element or metal-free magnetic materials, the carbon-doped BN nanotubes are more experimentally accessible and can be potentially useful.
Spectral responsivity measurements of photoconductive diamond detectors in the vacuum ultraviolet region distinguishing between internal photocurrent and photoemission current
Authors: Saito T. , Hayashi K.
Published: March 2005

Spectral responsivities of photoconductive diamond detectors were measured based on a standard detector calibrated by a rare-gas ionization chamber in the wavelength range from 10to60nm using synchrotron radiation. The photoemission current component was measured separately from the internally generated photocurrent component by using two electrical measurement configurations and by changing the polarity of the applied voltage to the detector. The photoemission current contribution to the total output current was not negligible but dominant in wavelengths longer than 40nm. On the other hand, the internal photocurrent played a major role in wavelengths shorter than approximately 25nm.
Electrical characterization of strained Si∕SiGe wafers using transient capacitance measurements
Authors: Wang Dong , Ninomiya Masaharu , Nakamae Masahiko , Nakashima Hiroshi
Published: March 2005

Interface states density (Nss) and minority carrier generation lifetime (τg) were evaluated for strained Si(St-Si)∕SiGe wafers using deep level transient spectroscopy and metal-oxide-semiconductor transient capacitance methods. Nss shows an independence on St-Si thickness (dSi) and an obvious dependence on Ge fraction (Ge%). τg shows a strong dependence on both dSi and Ge%. The reasons of these dependencies are discussed in detail.
Room-temperature operation of an exclusive-OR circuit using a highly doped Si single-electron transistor
Authors: Kitade Tetsuya , Ohkura Kensaku , Nakajima Anri
Published: March 2005

We fabricated highly doped Si single-electron transistors (SETs) with a series of geometrically defined multiple islands. Highly doped SETs have the advantage of being easy to fabricate. Moreover, SETs with multiple islands provide a larger peak-to-valley current ratio (PVCR) than SETs with a single island. A PVCR for the Coulomb oscillation of up to 77 was observed at room temperature. This large PVCR is advantageous for circuit operations. We applied the Coulomb oscillation and multiple-gate input characteristics of only one SET to obtain an exclusive-OR operation at room temperature.
S3b amino acid residues do not shuttle across the bilayer in voltage-dependent
Shaker
K
+
channels
Authors: Gonzalez Carlos , Morera Francisco J. , Rosenmann Eduardo , Alvarez Osvaldo , Latorre Ramon
Published: March 2005

In voltage-dependent channels, positive charges contained within the S4 domain are the voltage-sensing elements. The “voltage-sensor paddle” gating mechanism proposed for the KvAP K
+
channel has been the subject of intense discussion regarding its general applicability to the family of voltage-gated channels. In this model, the voltage sensor composed of the S3b and the S4 segment shuttles across the lipid bilayer during channel activation. Guided by this mechanism, we assessed here the accessibility of residues in the S3 segment of the
Shaker
K
+
channel by using cysteine-scanning mutagenesis. Mutants expressed robust K
+
currents in
Xenopus
oocytes and reacted with methanethiosulfonate ethyltrimethylammonium in both closed and open conformations of the channel. Because
Shaker
has a long S3–S4 linker segment, we generated a deletion mutant with only three residues to emulate the KvAP structure. In this short linker mutant, all of the tested residues in the S3b were accessible to methanethiosulfonate ethyltrimethylammonium in both closed and open conformations. Because the S3b moves together with the S4 domain in the paddle model, we tested the effects of deleting two negative charges or adding a positive charge to this region of the channel. We found that altering the S3b net charge does not modify the total gating charge involved in channel activation. We conclude that the S3b segment is always exposed to the external milieu of the
Shaker
K
+
channel. Our results are incompatible with any model involving a large membrane displacement of segment S3b.
To tell or not to tell: Men's disclosure of their HIV‐positive status to their mothers*
Authors: Shehan Constance L. , Uphold Constance R. , Bradshaw Patrick , Bender Joyce , Arce Natalie , Bender Bradley
Published: March 2005

Abstract: Disclosing an HIV diagnosis to his mother may be the first step in a man's successful management of his illness, but it may also lead to added stress due to stigmatization. Analyzing data provided by 166 HIV‐positive men who lived in the southeastern United States, we found that the most powerful correlate of disclosure was exposure to HIV through homosexual contact. Additionally, those who had AIDS rather than HIV and exhibited more severe symptoms were significantly more likely to have disclosed to their mothers; older and more highly educated men were significantly less likely to have done so. We discuss the implications of our findings for maternal caregiving to adult sons in middle and later life.
Recovery of a tropical stream after a harvest‐related chlorine poisoning event
Authors: GREATHOUSE EFFIE A. , MARCH JAMES G. , PRINGLE CATHERINE M.
Published: March 2005

1. Harvest‐related poisoning events are common in tropical streams, yet research on stream recovery has largely been limited to temperate streams and generally does not include any measures of ecosystem function, such as leaf breakdown.

2. We assessed recovery of a second‐order, high‐gradient stream draining the Luquillo Experimental Forest, Puerto Rico, 3 months after a chlorine‐bleach poisoning event. The illegal poisoning of freshwater shrimps for harvest caused massive mortality of shrimps and dramatic changes in those ecosystem properties influenced by shrimps. We determined recovery potential using an established recovery index and assessed actual recovery by examining whether the poisoned reach returned to conditions resembling an undisturbed upstream reference reach.

3. Recovery potential was excellent (score = 729 of a possible 729) and can be attributed to nearby sources of organisms for colonisation, the mobility of dominant organisms, unimpaired habitat, rapid flushing and processing of chlorine, and location within a national forest.

4. Actual recovery was substantial. Comparison of the reference reach with the formerly poisoned reach indicated: (1) complete recovery of xiphocaridid and palaemonid shrimp population abundances, shrimp size distributions, leaf breakdown rates, and abundances of oligochaetes and mayflies on leaves, and (2) only small differences in atyid shrimp abundance and community and ecosystem properties influenced by atyid shrimps (standing stocks of epilithic fine inorganic and organic matter, chlorophyll a, and abundances of chironomids and copepods on leaves).

5. There was no detectable pattern between any measured variables and distance downstream from the poisoning. However, shrimp size‐distributions indicated that the observed recovery may represent a source‐sink dynamic, in which the poisoned reach acts as a sink which depletes adult shrimp populations from surrounding undisturbed habitats. Thus, the rapid recovery observed in this study is consistent with results from other field studies of pulse chlorine disturbances, harvest‐related fish poisonings, and recovery of freshwater biotic interactions, but it is unlikely to be sustainable if multiple poisonings deplete adult populations to the extent that juvenile recruitment does not offset adult shrimp mortality.
Abdominal sacrocolpopexy for vault prolapse without burial of mesh: a case series
Authors: Elneil Sohier , Cutner Alfred S. , Remy Mary , Leather Andrew T. , Toozs‐Hobson Philip , Wise Brian
Published: March 2005

Objectives  To audit the clinical outcome of abdominal vault suspension (sacrocolpopexy, hysteropexy or cervicopexy) using non‐absorbable mesh, without burial by closure of the peritoneum.

Design  A case series.

Setting  Urogynaecology units of four hospitals.

Population  One hundred and twenty‐eight women having open or laparoscopic sacrocolpopexy (121), hysteropexy (6) or cervicopexy (1) using non‐absorbable mesh for vault prolapse.

Methods  Patients had suspension of the vault, uterus or cervix from the sacral promontory using a monofilament polypropylene mesh. The pelvic peritoneum was not closed over the mesh. Patients were followed up every six months.

Main outcome measures  Incidence of bowel complications as a consequence of the mesh; cure rate of prolapse and incidence of other post‐operative complications; rate of re‐operation for prolapse or incontinence.

Result  After a median follow up of 19 months (1.5–62), there were no bowel complications as a result of non‐burial of mesh. Three patients had asymptomatic vaginal mesh erosion, which required minor surgical intervention. Ninety percent of patients had good resolution of their prolapse symptoms while 10% of patients required further surgery.

Conclusion  Leaving the mesh uncovered by the pelvic peritoneum was not associated with complications. It appears safe to perform vault suspension without closing the peritoneum.
Marked fetal acidosis and specific changes in power spectrum analysis of fetal heart rate variability recorded during the last hour of labour
Authors: Siira Saila M. , Ojala Tiina H. , Vahlberg Tero J. , Jalonen Jarmo O. , Välimäki Ilkka A. , Rosén Karl G. , Ekholm Eeva M.
Published: March 2005

Objective  To assess whether intrapartum acidosis affects specific components of fetal heart rate variability.

Design  Prospective clinical study.

Setting  Twelve Nordic delivery units.

Subjects  Fetal heart rate variability was studied in 334 fetuses divided into two groups according to cord pH value: the acidotic group (cord arterial pH <7.05 at birth, n= 15) and the control group (cord arterial pH ≥7.05 at birth, n= 319).

Methods  In spectral analysis of fetal heart rate variability, frequencies were integrated over the total frequency band (0.04–1.0 Hz), low‐frequency band (0.04–0.15 Hz) and high‐frequency band (0.15–1.0 Hz). We also calculated the low‐to‐high frequency ratio.

Main outcome measures  The spectral bands of fetal heart rate variability were compared between the acidotic and control fetuses.

Results  We found that during the last hour of monitoring, baseline fetal heart rate gradually decreased, whereas total, low‐frequency and high‐frequency fetal heart rate variability initially increased but then, near the delivery, decreased in the acidotic fetuses when compared with the controls. Low‐to‐high frequency ratio was greater in the acidotic group during the whole study period (P= 0.002). Cord artery pH was inversely associated with total fetal heart rate variability (P < 0.001), low‐frequency fetal heart rate variability (P < 0.001) and low‐to‐high frequency ratio (P= 0.004).

Conclusions  Marked fetal acidosis was associated with frequency‐specific changes in fetal heart rate variability as reflecting the compensation ability of autonomic nervous activation during the last hour of labour.
Predictive factors for fibroids recurrence after uterine artery embolisation
Authors: Marret Henri , Cottier Jean Philippe , Alonso Ana Maria , Giraudeau Bruno , Body Gilles , Herbreteau Denis
Published: March 2005

Objectives  To assess clinical failure and symptom recurrence after uterine artery embolisation (UAE) and to define predictive factors.

Design  Prospective study of a case series.

Setting  Gynaecology and radiology departments of a French University Hospital.

Population  Eighty‐five women who underwent embolisation for the treatment of uterine fibroids.

Method  Vascular access was obtained via the right common femoral artery. Free‐flow embolisation was performed using 150–250 μm polyvinyl alcohol particles and an absorbable particle sponge.

Main outcome measures  Clinical failure was defined as persistence of symptoms at three months of follow up and recurrence as return of symptoms. The main outcome measure was the need for further treatment after UAE.

Results  Results are available for 81 patients. Median follow up was 30 months. There were 15 clinical failures and recurrences requiring further treatment (eight hysterectomies, five hysteroscopic resections for submucous fibroids, one second embolisation and one woman refusing further treatment). Recurrence‐free survival rate at 30 months (no clinical failure, no recurrence) was 82.8% (95% CI 73.7–91.8%). Multivariate analysis identified two predictive factors: dominant fibroid size on ultrasound imaging (each 1 cm increase: HR = 1.68, 95% CI 1.10–2.69) and number of fibroids (each additional fibroid: HR = 1.34, 95% CI 1.08–1.66).

Conclusions  Symptom recurrence rate 30 months after fibroid embolisation was 17.2%. Fibroid size and number were predictive factors for recurrence. As most recurrences occurred after two years, we recommend that patients be monitored clinically and that imaging be for more than two years after UAE.
Injuries in Swedish elite football—a prospective study on injury definitions, risk for injury and injury pattern during 2001
Authors: Waldén Markus , Hägglund Martin , Ekstrand Jan
Published: March 2005

The purpose of this study was to study the risk for injury and injury pattern in Swedish male elite football and to compare two different injury definitions. A prospective cohort study was conducted during 2001 on all 14 teams (310 players) in the Swedish top division. Injuries and individual exposure were recorded. Injury was defined as time‐lost injury (715 injuries) and for comparison as tissue injury (765 injuries). No significant difference in the risk for injury between tissue injuries and time‐lost injuries was found during matches (27.2 vs. 25.9 injuries per 1000 match hours, P=0.66) or training sessions (5.7 vs. 5.2 injuries per 1000 training hours, P=0.65). The risk for injury during training was significantly higher during the pre‐season compared with the competitive season (P=0.01).

Thigh strain was the single most common injury (14%). Knee sprain was the most common major injury (absence >4 weeks). Overuse injuries and re‐injuries were frequent and constituted 37% and 22% of all injuries. Re‐injuries caused significantly longer absence than their corresponding initial injuries (P=0.02). The risk for re‐injury (P=0.02) and overuse injury (P<0.01) was significantly higher during the pre‐season compared with the competitive season.
Target Cell-Dependent Normalization of Transmitter Release at Neocortical Synapses
Authors: Koester Helmut J. , Johnston Daniel
Published: March 2005

The efficacy and short-term modification of neocortical synaptic connections vary with the type of target neuron. We investigated presynaptic Ca
2+
and release probability at single synaptic contacts between pairs of neurons in layer 2/3 of the rat neocortex. The amplitude of Ca
2+
signals in boutons of pyramids contacting bitufted or multipolar interneurons or other pyramids was dependent on the target cell type. Optical quantal analysis at single synaptic contacts suggested that release probabilities are also target cell-specific. Both the Ca
2+
signal and the release probability of different boutons of a pyramid contacting the same target cell varied little. We propose that the mechanisms that regulate the functional properties of boutons of a pyramid normalize the presynaptic Ca
2+
influx and release probability for all those boutons that innervate the same target cell.
Uncharged tRNA and Sensing of Amino Acid Deficiency in Mammalian Piriform Cortex
Authors: Hao Shuzhen , Sharp James W. , Ross-Inta Catherine M. , McDaniel Brent J. , Anthony Tracy G. , Wek Ronald C. , Cavener Douglas R. , McGrath Barbara C. , Rudell John B. , Koehnle Thomas J. , Gietzen Dorothy W.
Published: March 2005

Recognizing a deficiency of indispensable amino acids (IAAs) for protein synthesis is vital for dietary selection in metazoans, including humans. Cells in the brain's anterior piriform cortex (APC) are sensitive to IAA deficiency, signaling diet rejection and foraging for complementary IAA sources, but the mechanism is unknown. Here we report that the mechanism for recognizing IAA-deficient foods follows the conserved general control (GC) system, wherein uncharged transfer RNA induces phosphorylation of eukaryotic initiation factor 2 (eIF2) via the GC nonderepressing 2 (GCN2) kinase. Thus, a basic mechanism of nutritional stress management functions in mammalian brain to guide food selection for survival.
Rheological Measurements of the Thermoviscoelastic Response of Ultrathin Polymer Films
Authors: O'Connell P. A. , McKenna G. B.
Published: March 2005

Measurement of the thermoviscoelastic behavior of glass-forming liquids in the nanometer size range offers the possibility of increased understanding of the fundamental nature of the glass-transition phenomenon itself. We present results from use of a previously unknown method for characterizing the rheological response of nanometer-thick polymer films. The method relies on the imaging capabilities of the atomic force microscope and the reduction in size of the classical bubble inflation method of measuring the biaxial creep response of ultrathin polymer films. Creep compliance as a function of time and temperature was measured in the linear viscoelastic regime for films of poly(vinyl acetate) at a thickness of 27.5 nanometers. Although little evidence for a change in the glass temperature is found, the material exhibits previously unobserved stiffening in the rubbery response regime.
How Much More Global Warming and Sea Level Rise?
Authors: Meehl Gerald A. , Washington Warren M. , Collins William D. , Arblaster Julie M. , Hu Aixue , Buja Lawrence E. , Strand Warren G. , Teng Haiyan
Published: March 2005

Two global coupled climate models show that even if the concentrations of greenhouse gases in the atmosphere had been stabilized in the year 2000, we are already committed to further global warming of about another half degree and an additional 320% sea level rise caused by thermal expansion by the end of the 21st century. Projected weakening of the meridional overturning circulation in the North Atlantic Ocean does not lead to a net cooling in Europe. At any given point in time, even if concentrations are stabilized, there is a commitment to future climate changes that will be greater than those we have already observed.
ON THE TOPOLOGY OF T-DUALITY
Authors: BUNKE ULRICH , SCHICK THOMAS
Published: March 2005

We study a topological version of the T-duality relation between pairs consisting of a principal U(1)-bundle equipped with a degree-three integral cohomology class. We describe the homotopy type of a classifying space for such pairs and show that it admits a selfmap which implements a T-duality transformation. We give a simple derivation of a T-duality isomorphism for certain twisted cohomology theories. We conclude with some explicit computations of twisted K-theory groups and discuss an example of iterated T-duality for higher-dimensional torus bundles.
ANALYTICAL TRANSMISSION ELECTRON MICROSCOPY
Authors: Sigle Wilfried
Published: March 2005

▪ Abstract  Chemical analysis at high spatial resolution is the domain of analytical transmission electron microscopy. Owing to rapid instrumental developments during the past decade, electron energy-loss spectroscopy offers now a spatial resolution close to 0.1 nm and an energy resolution close to 0.1 eV. This development has been accompanied by the introduction of numerous new techniques and methods for data acquisition and analysis, which are outlined in the present article. Recent results for a wide range of material systems are addressed. These comprise first-principles calculations, which have contributed to enormous progress in the calculation of near-edge fine structures, and fingerprinting methods, which are still important for the interpretation of experimental data.
MECHANISMS OF VERTEBRATE SYNAPTOGENESIS
Authors: Waites Clarissa L. , Craig Ann Marie , Garner Craig C.
Published: March 2005

The formation of synapses in the vertebrate central nervous system is a complex process that occurs over a protracted period of development. Recent work has begun to unravel the mysteries of synaptogenesis, demonstrating the existence of multiple molecules that influence not only when and where synapses form but also synaptic specificity and stability. Some of these molecules act at a distance, steering axons to their correct receptive fields and promoting neuronal differentiation and maturation, whereas others act at the time of contact, providing positional information about the appropriateness of targets and/or inductive signals that trigger the cascade of events leading to synapse formation. In addition, correlated synaptic activity provides critical information about the appropriateness of synaptic connections, thereby influencing synapse stability and elimination. Although synapse formation and elimination are hallmarks of early development, these processes are also fundamental to learning, memory, and cognition in the mature brain.
Epithelial dysfunction associated with the development of colitis in conventionally housed mdr1a−/− mice
Authors: Resta-Lenert Silvia , Smitham Jane , Barrett Kim E.
Published: March 2005

P-glycoprotein, the product of the multidrug resistance protein 1 (MDR1) gene, is a xenobiotic transporter that may contribute to the physiology of the intestinal barrier. Twenty-five percent of mdr1a-deficient (mdr1a−/−) mice spontaneously develop colitis at variable ages when maintained under specific pathogen-free conditions. We hypothesized that this disease would result from epithelial dysfunction and that conventional housing would increase incidence and severity of the colitis phenotype. Wild-type congenic FVB (+/+) mice were maintained under the same conditions as controls. Knockout and wild-type mice were matched for age and gender and observed for signs of colitis. Colonic tissues from both groups of mice were examined for macroscopic and microscopic injury and for basal ion transport and transepithelial resistance (TER). Translocation of bacteria across the intestine was assessed by culturing the spleen and mesenteric lymph nodes. Protein analysis was performed by Western blot analysis. All mdr1a−/− mice developed weight loss and signs of colitis, whereas wild-type mice never showed such signs. Within the mdr1a−/− group, males consistently developed severe colitis earlier than females. Knockout mice showed increased basal colonic ion transport (females, 162.7 ± 4.6 vs. 49.7 ± 3.8 μA/cm2; males, 172.6 ± 5.6 vs. 54.2 ± 3.1 μA/cm2; P < 0.01) and decreased TER (females, 25.4 ± 0.3 vs. 36.4 ± 0.8 Ω·cm2; males, 23.1 ± 1.0 vs. 38.3 ± 0.2 Ω·cm2; P < 0.01) compared with wild-type mice. Barrier dysfunction was accompanied by decreased phosphorylation of tight junction proteins. Expression of cyclooxygenase-2 and inducible nitric oxide synthase in intestinal tissues was increased in the mdr1a−/− group ( P < 0.01) and correlated with disease severity. Bacterial translocation was greater both in incidence ( P < 0.01) and severity ( P < 0.001) for the knockout group. With respect to all indexes studied, mdr1a−/− males performed worse than females. Our data support the hypothesis that alterations in the intestinal barrier alone, in the absence of immune dysfunction, may rapidly lead to colitis in the setting of a normal colonic flora.
Effects of high-fat diets with different carbohydrate-to-protein ratios on energy homeostasis in rats with impaired brain melanocortin receptor activity
Authors: Morens C. , Keijzer M. , de Vries K. , Scheurink A. , van Dijk G.
Published: March 2005

Changes in dietary macronutrient composition and/or central nervous system neuronal activity can underlie obesity and disturbed fuel homeostasis. We examined whether switching rats from a diet with high carbohydrate content (HC; i.e., regular chow) to diets with either high fat (HF) or high fat/high protein content at the expense of carbohydrates (LC-HF-HP) causes differential effects on body weight and glucose homeostasis that depend on the integrity of brain melanocortin (MC) signaling. In vehicle-treated rats, switching from HC to either HF or LC-HF-HP feeding caused similar reductions in food intake without alterations in body weight. A reduced caloric intake (−16% in HF and LC-HF-HP groups) required to maintain or increase body weight underlay these effects. Chronic third cerebroventricular infusion of the MC receptor antagonist SHU9119 (0.5 nmol/day) produced obesity and hyperphagia with an increased food efficiency again observed during HF (+19%) and LC-HF-HP (+33%) feeding. In this case, however, HF feeding exaggerated SHU9119-induced hyperphagia and weight gain relative to HC and LC-HF-HP feeding. Relative to vehicle-treated controls, SHU9119 treatment increased plasma insulin (2.8–4 fold), leptin (7.7–15 fold), and adiponectin levels (2.4–3.7 fold), but diet effects were only observed on plasma adiponectin (HC and LC-HF-HP<HF). Finally, SHU9119-treated LC-HF-HP-fed rats were less glucose tolerant than others. Relatively low plasma adiponectin levels likely contributed to this effect. Thus HF feeding amplifies obesity induced by impaired MC signaling, provided that the carbohydrate-to-protein (C/P) ratio is high enough. Reduction of the C/P ratio within a HF diet ameliorates hyperphagia and obesity in rats with impaired MC signaling but aggravates associated disturbances in fuel homeostasis.
Knee angle-dependent oxygen consumption during isometric contractions of the knee extensors determined with near-infrared spectroscopy
Authors: de Ruiter C. J. , de Boer M. D. , Spanjaard M. , de Haan A.
Published: March 2005

Fatigue resistance of knee extensor muscles is higher during voluntary isometric contractions at short compared with longer muscle lengths. In the present study we hypothesized that this would be due to lower energy consumption at short muscle lengths. Ten healthy male subjects performed isometric contractions with the knee extensor muscles at a 30, 60, and 90° knee angle (full extension = 0°). At each angle, muscle oxygen consumption (mV̇o2) of the rectus femoris, vastus lateralis, and vastus medialis muscle was obtained with near-infrared spectroscopy. mV̇o2 was measured during maximal isometric contractions and during contractions at 10, 30, and 50% of maximal torque capacity. During all contractions, blood flow to the muscle was occluded with a pressure cuff (450 mmHg). mV̇o2 significantly ( P < 0.05) increased with torque and at all torque levels, and for each of the three muscles mV̇o2 was significantly lower at 30° compared with 60° and 90° and mV̇o2 was similar ( P > 0.05) at 60° and 90°. Across all torque levels, average (± SD) mV̇o2 at the 30° angle for vastus medialis, rectus femoris, and vastus lateralis, respectively, was 70.0 ± 10.4, 72.2 ± 12.7, and 75.9 ± 8.0% of the average mV̇o2 obtained for each torque at 60 and 90°. In conclusion, oxygen consumption of the knee extensors was significantly lower during isometric contractions at the 30° than at the 60° and 90° knee angle, which probably contributes to the previously reported longer duration of sustained isometric contractions at relatively short muscle lengths.
Carotid Plaque Mast Cells Associate with Atherogenic Serum Lipids, High Grade Carotid Stenosis and Symptomatic Carotid Artery Disease
Authors: Lehtonen-Smeds Erno M.P. , Mäyränpää Mikko , Lindsberg Perttu J. , Soinne Lauri , Saimanen Eija , Järvinen Antero A.J. , Salonen Oili , Carpén Olli , Lassila Riitta , Sarna Seppo , Kaste Markku , Kovanen Petri T.
Published: March 2005

Objective: Increased numbers of mast cells (MCs) are present in ruptured coronary plaques, suggesting to play a role in acute coronary syndromes. We evaluated the distribution densities of MCs, macrophages and T cells in carotid plaques and correlated these findings to stroke risk factors as well as history of stroke or TIA. Methods and Results: Seventy-eight carotid samples from 75 patients (16 plaques from asymptomatic patients and 62 from patients with recent ischemic symptoms) undergoing carotid endarterectomy with an internal carotid stenosis >70% that were immunostained and quantified for MCs, macrophages and T cells. The MC distribution density showed positive correlation with the degree of carotid stenosis (p = 0.012), serum levels of total cholesterol (p = 0.021), LDL cholesterol (p = 0.013) and triglycerides (p = 0.005), and an inverse correlation with serum HDL cholesterol levels (p = 0.001). The average MC density (p = 0.023), but not the macrophage (p = 0.58) or T cell (p = 0.74) density, was higher in the symptomatic than in the asymptomatic patients. In a comparison of plaques ipsilateral and contralateral to the thromboembolic event, the densities of the three types of inflammatory cells were similar. Conclusions: Increased MC distribution density is associated with an atherogenic serum lipid profile, high-grade carotid artery stenosis and symptomatic carotid artery disease. These findings suggest a potential involvement of MCs in the pathophysiology of carotid artery stenosis.
N-Cadherin–Dependent Cell–Cell Contacts Promote Human Saphenous Vein Smooth Muscle Cell Survival
Authors: Koutsouki Evgenia , Beeching Cressida A. , Slater Sadie C. , Blaschuk Orest W. , Sala-Newby Graciela B. , George Sarah J.
Published: March 2005

Objective—

Vascular smooth muscle cell (VSMC) apoptosis is thought to contribute to atherosclerotic plaque instability. Cadherin mediates calcium-dependent homophilic cell–cell contact. We studied the role of N-cadherin in VSMC apoptosis.

Methods and Results—

Human saphenous vein VSMCs were grown in agarose-coated wells to allow cadherin-mediated aggregate formation. Cell death and apoptosis were determined after disruption of cadherins using several approaches (n≥3 per approach). Calcium removal from culture medium or addition of nonspecific cadherin antagonist peptides significantly decreased aggregate formation and increased cell death by apoptosis (34±6% versus 75±1% and 19±1% versus 40±5%, respectively;
P
<0.05). Specific inhibition of N-cadherin using antagonists and neutralizing antibodies similarly increased apoptosis. Supporting this, overexpression of full-length N-cadherin significantly reduced VSMC apoptosis from 44±10% to 20±3% (
P
<0.05), whereas abolishing N-cadherin expression by overexpression of a dominant-negative N-cadherin significantly, even in the presence of cell–matrix contacts, increased apoptosis from 9±2% to 50±1% (
P
<0.05). Interestingly, cell–cell contacts provided a similar degree of protection from apoptosis to cell–matrix contacts. Finally, N-cadherin–mediated cell–cell contacts initiated anti-apoptotic signaling by increasing Akt and Bad phosphorylation.

Conclusions—

Our results indicate that VSMC survival is dependent on N-cadherin–mediated cell–cell contacts, which could be important in the context of plaque instability.
Cleavage of ultralarge multimers of von Willebrand factor by C-terminal–truncated mutants of ADAMTS-13 under flow
Authors: Tao Zhenyin , Wang Yongtao , Choi Huiwei , Bernardo Aubrey , Nishio Kenji , Sadler J. Evan , López José A. , Dong Jing-fei
Published: March 2005

A disintegrin-like and metalloprotease with thrombospondin type 1-motif 13 (ADAMTS-13) cleaves the A2 domain of von Willebrand factor (VWF), converting the ultralarge (UL) and hyperactive VWF multimers freshly released from endothelial cells to smaller and less active forms found in plasma. Recombinant ADAMTS-13 lacking the C-terminal region is active under static conditions, but its functions under flow conditions have not been determined. Here, we show that VWF-cleaving activity measured under flow was preserved in an ADAMTS-13 mutant lacking the second to eighth thrombospondin-1 motifs and the complement components C1r/C1s, Uegf sea urchin fibropellins, and bone morphogenic protein 1 (CUB) domains, but was severely deficient in a mutant that was further truncated to remove the spacer domain. We also show that the mutant lacking the TSP-1 and CUB domains was hyperactive under flow, suggesting that the C-terminal region may negatively regulate ADAMTS-13 activity. The wild type and the mutant without the spacer were more active in the presence of plasma, raising the possibility of ADAMTS-13 cofactors in plasma.
CD8α–11b+ dendritic cells but not CD8α+ dendritic cells mediate cross-tolerance toward intestinal antigens
Authors: Chung Yeonseok , Chang Jae-Hoon , Kweon Mi-Na , Rennert Paul D. , Kang Chang-Yuil
Published: March 2005

Cross-presentation is a critical process by which antigen is displayed to CD8 T cells to induce tolerance. It is believed that CD8α+ dendritic cells (DCs) are responsible for cross-presentation, suggesting that the CD8α+ DC population is capable of inducing both cross-priming and cross-tolerance to antigen. We found that cross-tolerance against intestinal soluble antigen was abrogated in C57BL/6 mice lacking mesenteric lymph nodes (MLNs) and Peyer patches (PPs), whereas mice lacking PPs alone were capable of developing CD8 T-cell tolerance. CD8α–CD11b+ DCs but not CD8α+ DCs in the MLNs present intestinal antigens to relevant CD8 T cells, while CD8α+ DCs but not CD8α–CD11b+ DCs in the spleen exclusively cross-present intravenous soluble antigen. Thus, CD8α–CD11b+ DCs in the MLNs play a critical role for induction of cross-tolerance to dietary proteins.
Improved transduction of human sheep repopulating cells by retrovirus vectors pseudotyped with feline leukemia virus type C or RD114 envelopes
Authors: Lucas M. Lee , Seidel Nancy E. , Porada Christopher D. , Quigley John G. , Anderson Stacie M. , Malech Harry L. , Abkowitz Janis L. , Zanjani Esmail D. , Bodine David M.
Published: March 2005

Gene therapy for hematopoietic diseases has been hampered by the low frequency of transduction of human hematopoietic stem cells (HSCs) with retroviral vectors pseudotyped with amphotropic envelopes. We hypothesized that transduction could be increased by the use of retroviral vectors pseudotyped with envelopes that recognize more abundant cellular receptors. The levels of mRNA encoding the receptors of the feline retroviruses, RD114 and feline leukemia virus type C (FeLV-C), were significantly higher than the level of gibbon ape leukemia virus (GaLV) receptor mRNA in cells enriched for human HSCs (Lin– CD34+ CD38–). We cotransduced human peripheral blood CD34+ cells with equivalent numbers of FeLV-C and GALV or RD114 and GALV-pseudotyped retroviruses for injection into fetal sheep. Analysis of DNA from peripheral blood and bone marrow from recipient sheep demonstrated that FeLV-C– or RD114-pseudotyped vectors were present at significantly higher levels than GALV-pseudotyped vectors. Analysis of individual myeloid colonies demonstrated that retrovirus vectors with FeLV-C and RD114 pseudotypes were present at 1.5 to 1.6 copies per cell and were preferentially integrated near known genes We conclude that the more efficient transduction of human HSCs with either FeLV-C– or RD114-pseudotyped retroviral particles may improve gene transfer in human clinical trials.
Inflammation suppressor genes: please switch out all the lights
Authors: Wells Christine A , Ravasi Timothy , Hume David A
Published: March 2005

An effective immune system requires rapid and appropriate activation of inflammatory mechanisms but equally rapid and effective resolution of the inflammatory state. A review of the canonical host response to gram-negative bacteria, the lipopolysaccharide-Toll-like receptor 4 signaling cascade, highlights the induction of repressors that act at each step of the activation process. These inflammation suppressor genes are characterized by their induction in response to pathogen, typically late in the macrophage activation program, and include an expanding class of dominant-negative proteins derived from alternate splicing of common signaling components. Despite the expanse of anti-inflammatory mechanisms available to an activated macrophage, the frailty of this system is apparent in the large numbers of genes implicated in chronic inflammatory diseases. This apparent lack of redundancy between inflammation suppressor genes is discussed with regard to evolutionary benefits in generating a heterogeneous population of immune cells and consequential robustness in defense against new and evolving pathogens.
Effects of chronic ingestion of sodium fluoride on myocardium in a second generation of rats
Authors: Cicek Ekrem , Aydin Gulsen , Akdogan Mehmet , Okutan Huseyin
Published: March 2005

Possible effects of long term exposure (6 months) to sodium fluoride (NaF) through drinking water on the morphology and biochemistry of myocardial tissue in second generation adult male rats were investigated. Wistar strain female and male rats were reared until the second generation of rats obtained, during which they were given 1, 10, 50 and 100 mg/L NaF in drinking water. Of the second generation, 28 male rats were divided into four groups and had the same treatment. All the second generation rats were sacrificed and autopsied at the end of the 6 months. In the samples of myocardial tissues, the levels of serum fluoride and the activities of principal antioxidant enzymes were determined, and a histopathological examination was conducted. Significant histopathological changes were found in the myocardial tissue of rats treated with 50 and 100 mg/L NaF. These were myocardial cell necrosis, extensive cytoplasmic vacuole formation, nucleus dissolution in myosits, swollen and clumped myocardial fibers, fibrillolysis, interstitial oedema, small hemorrhagic areas and hyperaemic vessels. Additionally, the increased activities of superoxide dismutase (SOD), glutathione peroxidase (GSH–Px), catalase (CAT) and thiobarbituric acid–reactive substance (TBARS) levels were observed in the myocardial tissues of rats treated with 10 and 50 mg/L NaF. On the other hand, the activities of SOD, GSH–Px, and CAT decreased, but the TBARS levels increased in the myocardial tissues of rats treated with 100 mg/L. The present results revealed that prolonged ingestion of fluoride through drinking water, particularly with high doses, induced significant histopathological and biochemical changes leading to myocardial tissue damage.