bluuebunny/crossref_metadata_2025 huggingface dataset:
1H Magnetic Resonance Spectroscopy of the Brain in Paediatrics: the Diagnosis of Creatine Deficiencies
Authors: Sijens P. E. , Oudkerk M.
Published: December 2005

The diagnosis of creatine deficiencies, a paediatric application of magnetic resonance spectroscopy that has already become a diagnostic tool in clinical practice, is reviewed and illustrated with results from recent examinations.
Localized 4.7 T Proton Magnetic Resonance Spectroscopy in Neonatal Encephalopathy: Implementation, Safety and Preliminary Interpretation of Results
Authors: De Vita E. , Bainbridge A. , Cheong J. , Kinchesh P. , Huertas‐Ceballos A. , Ordidge R. J. , Robertson N. J. , Cady E. B.
Published: December 2005

Magnetic resonance (MR) techniques have revolutionized the assessment of brain development and injury in the newborn. MR studies at 3 T or above are becoming widespread; however, given the high cost and complexity of high‐field MR systems, it is important to assess their benefits and limitations for clinical practice.

MR spectroscopy (MRS) studies at high field carry potential benefits such as improved signal‐to‐noise ratio (SNR) and chemical shift dispersion compared with 1.5 T. However, safety is a very important consideration as radiofrequency (RF) tissue heating and acoustic noise also increase with field strength. Furthermore, increased chemical‐shift dependence of the position of the volume of interest (VOI), shorter transverse and longer longitudinal relaxation times constitute additional challenges.

We describe the first in‐vivo, proton MRS studies of newborn human brain at 4.7 T. Nine infants with neonatal encephalopathy, all ventilated and with continuous physiological monitoring, were studied. We used L‐FOCI localization, mostly with a VOI centred on the thalami.

The absence of 4.7 T results from healthy infants made it impossible to interpret pathological metabolite peak‐area ratios. However, concentration ratios and concentrations should be field‐strength independent and interpretable using control values acquired at lower field. Of eight infants with concentration‐ratio measurements, seven had low [N‐acetylaspartate (NAA)]/[choline (Cho)] and three increased [lactate]/[NAA]. Of the two infants with ‘concentration’ measurements both had low [NAA] and one reduced [creatine].

We used an adult coil and consequent RF power restrictions had repercussions for the minimum magnetization recovery time (TR). A smaller, neonatal coil should improve SNR and, with less RF power, relax TR constraints thereby enabling fuller exploitation of the potential of high‐field MRS.
Lack of association between the TNF‐α promoter gene polymorphism and susceptibility to B‐cell chronic lymphocytic leukaemia
Authors: Bogunia‐Kubik K. , Mazur G. , Urbanowicz I. , Wróbel T. , Kuliczkowski K. , Woźniak M. , Lange A.
Published: December 2005

B‐cell chronic lymphocytic leukaemia (B‐CLL) is a lymphoproliferative disorder characterized by clonal expansion of B lymphocytes. The present study aimed to determine whether there is an association between the polymorphic features located within the promoter/enhancer region of tumour necrosis factor‐α (TNFA) gene and susceptibility to B‐CLL.

TNFA (−308 G/A) promoter single nucleotide polymorphism (SNP) was determined by polymerase chain reaction with sequence‐specific primers (PCR‐SSP) using commercial oligonucleotides. No significant association was found between the distribution of TNFA alleles and B‐CLL in Polish patients with B‐CLL. Our single centre results were compared with other literature data and combined in a cumulative analysis employing the Mantel–Haenszel method. Among 183 B‐CLL patients, 47 (26%) were carrying TNFA*2 allele and this allele was present in 98 out of 348 controls (28%). Also, the results of the Mantel–Haenszel test did not show a significant correlation [Mantel‐Haenszel estimate of approximate relative risk (RMH) = 0.86, P = 0.294]. These results suggest that TNFA (–308) alleles are not involved in the predisposition to the development of B‐CLL.
Polymorphism of HLA‐DRB1 gene shows no strong association with ulcerative colitis in Chinese patients
Authors: Lü M. , Xia B.
Published: December 2005

The genetic factors predisposing to ulcerative colitis (UC) have remained totally unclear to date. This study aimed to investigate the role of HLA‐DRB1 genetic polymorphism in the susceptibility to develop UC in Chinese patients. HLA‐DRB1 genotyping was carried out in 72 unrelated patients with UC and 314 healthy controls by using polymerase chain reaction–sequence‐specific primers (PCR‐SSP). All of the patients and healthy controls are Han people in China. The frequency of DRB1*07 allele was increased in UC patients compared with healthy controls (19.4% vs. 9.2%, P = 0.0229, OR = 2.372, 95%CI: 1.181–4.766), but the significance disappeared when given Bonferroni correction (PC = 0.2977). Furthermore, compared with healthy controls, although HLA‐DRB1*07, DRB1*16/DRB1*09 and DRB1*07/DRB1*12 genotypes were increased in frequency in the patients with extensive colitis, and the patients without extraintestinal manifestations (EIMs) carried an increased frequency of HLA‐DRB1*07 and DRB1*07/DRB1*12 genotypes, these differences did not reach statistical significance after Bonferroni correction. HLA‐DRB1 alleles showed no strong association with UC, and no HLA‐DRB1 alleles or genotypes were strongly associated with clinical subgroups of UC in Chinese patients.
Parasites from feral pigeons as a health hazard for humans
Authors: Haag‐Wackernagel D.
Published: December 2005

Feral pigeons live in almost every large city in the world. The feeding of pigeons by humans, deliberately or accidentally, allows the build‐up of large populations that can cause a variety of problems, primarily the fouling of buildings and monuments by their droppings. Excreta of wild birds are a well‐known source of pathogenic microorganisms that can cause infection in man. The most important ectoparasites of feral pigeons are the red blood mite,Dermanyssus gallinae, and the pigeon tick,Argas reflexus, both of which can migrate into human living space when they lose their natural hosts. The bites of the red blood mite are irritating but harmless, whereas the pigeon tick can cause severe health problems to predisposed persons. After repeated bites fromA. reflexus, people can develop IgE‐mediated (type I) allergy, which in extreme situations may lead to life‐threatening symptoms of anaphylactic shock. So far, one fatality due toA. reflexusderiving from feral pigeons has been reported. In the case of parasitic infestations of humans, the source must be removed by excluding pigeons from further breeding and by disinfection of the environment of pigeon‐breeding sites.
COMPARATIVE ANALYSIS OF CLOSTRIDIUM PERFRINGENS, ESCHERICHIA COLI AND ENTEROCOCCI AS INDICATORS OF FECAL CONTAMINATION OF GROUND BEEF
Authors: OBAIDAT MOHAMMAD M. , FUNG DANIEL Y.C.
Published: December 2005

This research aimed to compare Clostridium perfringens with Escherichia coli and enterococci as indicators of fecal contamination of raw ground beef. The first experiment evaluated the natural occurrence of C. perfringens, E. coli and enterococci in raw ground beef. The second experiment compared the linear regression curve of C. perfringens, E. coli and enterococci from ground beef intentionally spiked with bovine feces at different levels (0, 0.1, 0.3, 0.5 and 0.7% [w/w]). The biochemical profiles of C. perfringens, E. coli and Enterococcus faecalis from raw ground beef and raw ground beef spiked with feces were also studied. The results of the first experiment showed that the prevalence rates of C. perfringens, E. coli and enterococci in raw ground beef were 45.0, 79.0 and 60.0%, respectively. The results of the second experiment showed that C. perfringens, E. coli and enterococci have a positive correlation with the level of inoculated fecal material. However, the average R2for C. perfringens, E. coli and enterococci models were 0.86, 0.71 and 0.93, respectively. The results also showed that the biochemical profiles of C. perfringens, E. coli and E. faecalis cultures from raw ground beef spiked with feces had high variations, and differ from those for the cultures isolated from raw ground beef. The compiled data indicate that C. perfringens should be considered a viable alternative to current fecal indicators.
Structural vibrations of buried land mines
Authors: Zagrai Andrei , Donskoy Dimitri , Ekimov Alexander
Published: December 2005

Buried landmines exhibit complex structural vibrations, which are dependent on interaction between soil and mines as well as on their respective properties. This paper presents experimental and theoretical studies of multimodal vibrations of buried mines and discusses the effects of burial depth and soil properties on dynamics of the soil-mine system. The two-dimensional model of the soil-mine system that accounts for soil-coupled mine’s multiple vibration modes and spatial distribution of vibrations over the soil surface is introduced. The model was tested using experiments with the plastic mine simulant. The study reveals that the soil shear stiffness is one of the key governing parameters determining the resonance vibration frequency and the amplitude of the soil-mine system. Burial depth, soil moisture, and consolidation are among factors leading to the increase of the soil shear stiffness, therefore effectively influencing modal vibrations of buried mines.
Detection of spectrally complex signals in comodulated maskers: Effect of temporal fringe
Authors: Grose John H. , Hall Joseph W. , Buss Emily , Hatch Debora R.
Published: December 2005

This study tested the hypothesis that masking release for a complex signal under conditions where signal energy is present in all frequency regions occupied by the masker is attributable to an across-frequency-channel comodulation masking release (CMR) process. The approach was to identify a signature CMR trait, and to then determine if that trait was associated with the detection advantage for complex signals. The selected trait was the decline of CMR in the presence of a random temporal fringe. In experiment 1, a masking release was observed for a four-component harmonic signal presented in a comodulated masker, and this masking release was diminished by the random temporal fringe. A similar effect was observed in experiment 2 for a four-component inharmonic signal. These results support the hypothesis that a CMR can be measured for a complex signal even when there is substantial spectral overlap between the signal and its comodulated masker. This finding has consequences for CMR models since it demonstrates that the presence of “signal-free” cue bands is not a prerequisite for CMR, and that the presence of comodulation during the signal window is not sufficient to result in CMR.
On the holographic reconstruction of vibroacoustic fields using equivalent sources and inverse boundary element method
Authors: Jeon In-Youl , Ih Jeong-Guon
Published: December 2005

In using the near-field acoustical holography based on the inverse boundary element method (BEM) for the reconstruction of vibroacoustic source parameters, an enormous number of measurements required in practice have limited the extended application of this method. To obtain the sufficient field data with a small number of actual measured data, the regeneration method of the radiated field using the multipoint equivalent sources is attempted in this paper. In using the equivalent source method, a vibrating source can be represented by distributed spherical sources inside the actual source surface. In this paper, the radiated field is expressed with a series of spherical Hankel functions and spherical harmonics. For suppressing the adverse effect of high-order spherical functions, spatial filtering of coefficients and wave-vector components by a regularization scheme is adopted. Restored field data appended with actual measured data can be used as input for the inverse BEM to reconstruct the source field. Numerical tests for spherical sources were performed for investigating the characteristics of the proposed technique. In order to validate the usefulness of the proposed method to actual irregular sources, a vacuum cleaner was taken as a demonstration example and good agreement between measured and reconstructed results could be observed.
Time-domain calculation of acoustical wave propagation in discontinuous media using acoustical wave propagator with mapped pseudospectral method
Authors: Lu Jing , Pan Jie , Xu Boling
Published: December 2005

The acoustical Wave Propagator (AWP) scheme involves an effective time-domain calculation of sound propagation using the combination of Chebyshev polynomial expansion and the Fourier pseudospectral method. The accuracy of this scheme degrades when the media has discontinuities due to the well-known Gibbs phenomenon. In this paper, several issues concerning AWP are addressed, including an analysis of the effect of Gibbs phenomenon on the accuracy. A mapped pseudospectral method is proposed wherein the grid points are redistributed, with the emphasis across the media discontinuities by a pre-determined smooth mapping curve, then the spatial derivatives are calculated through a modified Fourier pseudospectral method. Using this method, the influence of the Gibbs phenomenon is effectively alleviated while the computational efficiency of AWP is still maintained. The superiority of this improved AWP scheme is illustrated by three one-dimensional (1-D) numerical examples.
Discrimination of speaker size from syllable phrases
Authors: Ives D. Timothy , Smith David R. R. , Patterson Roy D.
Published: December 2005

The length of the vocal tract is correlated with speaker size and, so, speech sounds have information about the size of the speaker in a form that is interpretable by the listener. A wide range of different vocal tract lengths exist in the population and humans are able to distinguish speaker size from the speech. Smith et al. [J. Acoust. Soc. Am. 117, 305–318 (2005)] presented vowel sounds to listeners and showed that the ability to discriminate speaker size extends beyond the normal range of speaker sizes which suggests that information about the size and shape of the vocal tract is segregated automatically at an early stage in the processing. This paper reports an extension of the size discrimination research using a much larger set of speech sounds, namely, 180 consonant-vowel and vowel-consonant syllables. Despite the pronounced increase in stimulus variability, there was actually an improvement in discrimination performance over that supported by vowel sounds alone. Performance with vowel-consonant syllables was slightly better than with consonant-vowel syllables. These results support the hypothesis that information about the length of the vocal tract is segregated at an early stage in auditory processing.
Reduced contribution of a nonsimultaneous mistuned harmonic to residue pitch
Authors: Gockel Hedwig , Plack Christopher J. , Carlyon Robert P.
Published: December 2005

Ciocca and Darwin [V. Ciocca and C. J. Darwin, J. Acoust. Soc. Am. 105, 2421–2430 (1999)] reported that the shift in residue pitch caused by mistuning a single harmonic (the fourth out of the first 12) was the same when the mistuned harmonic was presented after the remainder of the complex as when it was simultaneous, even though subjects were asked to ignore the pure-tone percept. The present study tried to replicate this result, and investigated the role of the presence of the nominally mistuned harmonic in the matching sound. Subjects adjusted a “matching” sound so that its pitch equaled that of a subsequent 90-ms complex tone (12 harmonics of a 155-Hz F0), whose mistuned (±3%) third harmonic was presented either simultaneously with or after the remaining harmonics. In experiment 1, the matching sound was a harmonic complex whose third harmonic was either present or absent. In experiments 2A and 2B, the target and matching sound had nonoverlapping spectra. Pitch shifts were reduced both when the mistuned component was nonsimultaneous, and when the third harmonic was absent in the matching sound. The results indicate a shorter than originally estimated time window for obligatory integration of nonsimultaneous components into a virtual pitch.
Nonlinear resonant ultrasound spectroscopy (NRUS) applied to damage assessment in bone
Authors: Muller Marie , Sutin Alexander , Guyer Robert , Talmant Maryline , Laugier Pascal , Johnson Paul A.
Published: December 2005

Nonlinear resonant ultrasound spectroscopy (NRUS) is a resonance-based technique exploiting the significant nonlinear behavior of damaged materials. In NRUS, the resonant frequency(ies) of an object is studied as a function of the excitation level. As the excitation level increases, the elastic nonlinearity is manifest by a shift in the resonance frequency. This study shows the feasibility of this technique for application to damage assessment in bone. Two samples of bovine cortical bone were subjected to progressive damage induced by application of mechanical cycling. Before cycling commenced, and at each step in the cycling process, NRUS was applied for damage assessment. For independent assessment of damage, high-energy x-ray computed tomography imaging was performed but was only useful in identifying the prominent cracks. As the integral quantity of damage increased, NRUS revealed a corresponding increase in the nonlinear response. The measured change in nonlinear response is much more sensitive than the change in linear modulus. The results suggest that NRUS could be a potential tool for micro-damage assessment in bone. Further work must be carried out for a better understanding of the physical nature of damaged bone and for the ultimate goal of the challenging in vivo implementation of the technique.
A Conserved Checkpoint Monitors Meiotic Chromosome Synapsis in
Caenorhabditis elegans
Authors: Bhalla Needhi , Dernburg Abby F.
Published: December 2005

We report the discovery of a checkpoint that monitors synapsis between homologous chromosomes to ensure accurate meiotic segregation. Oocytes containing unsynapsed chromosomes selectively undergo apoptosis even if a germline DNA damage checkpoint is inactivated. This culling mechanism is specifically activated by unsynapsed pairing centers,
cis
-acting chromosome sites that are also required to promote synapsis in
Caenorhabditis elegans
. Apoptosis due to synaptic failure also requires the
C. elegans
homolog of
PCH2
, a budding yeast pachytene checkpoint gene, which suggests that this surveillance mechanism is widely conserved.
The Importance of Land-Cover Change in Simulating Future Climates
Authors: Feddema Johannes J. , Oleson Keith W. , Bonan Gordon B. , Mearns Linda O. , Buja Lawrence E. , Meehl Gerald A. , Washington Warren M.
Published: December 2005

Adding the effects of changes in land cover to the A2 and B1 transient climate simulations described in the Special Report on Emissions Scenarios (SRES) by the Intergovernmental Panel on Climate Change leads to significantly different regional climates in 2100 as compared with climates resulting from atmospheric SRES forcings alone. Agricultural expansion in the A2 scenario results in significant additional warming over the Amazon and cooling of the upper air column and nearby oceans. These and other influences on the Hadley and monsoon circulations affect extratropical climates. Agricultural expansion in the mid-latitudes produces cooling and decreases in the mean daily temperature range over many areas. The A2 scenario results in more significant change, often of opposite sign, than does the B1 scenario.
Increase in Activity During Calorie Restriction Requires Sirt1
Authors: Chen Danica , Steele Andrew D. , Lindquist Susan , Guarente Leonard
Published: December 2005

Sir2 (silent information regulator 2) is a nicotinamide adenine dinucletide‐dependent deacetylase required for longevity due to calorie restriction in yeast and Drosophila. In mammals, calorie restriction induces a complex pattern of physiological and behavioral changes. Here we report that the mammalian Sir2 ortholog, Sirt1, is required for the induction of a phenotype by calorie restriction in mice.
Rapid Glacial Erosion at 1.8 Ma Revealed by
4
He/
3
He Thermochronometry
Authors: Shuster David L. , Ehlers Todd A. , Rusmoren Margaret E. , Farley Kenneth A.
Published: December 2005

Alpine glaciation and river incision control the topography of mountain ranges, but their relative contributions have been debated for years. Apatite
4
He/
3
He thermochronometry tightly constrains the timing and rate of glacial erosion within one of the largest valleys in the southern Coast Mountains of British Columbia, Canada. Five proximate samples require accelerated denudation of the Klinaklini Valley initiating 1.8 ± 0.2 million years ago (Ma). At least 2 kilometers of overlying rock were removed from the valley at ≥5 millimeters per year, indicating that glacial valley deepening proceeded ≥6 times as fast as erosion rates before ∼1.8 Ma. This intense erosion may be related to a global transition to enhanced climate instability ∼1.9 Ma.
Many Perspectives on Swinging
Authors: Rojo Alberto G.
Published: December 2005

The Pendulum
. A Case Study in Physics.
By Gregory L. Baker and James A. Blackburn
. Oxford University Press, Oxford, 2005. 300 pp. $89.50, £45. ISBN 0-19-856754-5.

Offering the pendulum as a case study of a physical system, the authors examine it from the perspectives of elementary and advanced classical physics, chaos dynamics, and quantum mechanics.
Equivalent Effects of Snake PLA2 Neurotoxins and Lysophospholipid-Fatty Acid Mixtures
Authors: Rigoni Michela , Caccin Paola , Gschmeissner Steve , Koster Grielof , Postle Anthony D. , Rossetto Ornella , Schiavo Giampietro , Montecucco Cesare
Published: December 2005

Snake presynaptic phospholipase A2 neurotoxins (SPANs) paralyze the neuromuscular junction (NMJ). Upon intoxication, the NMJ enlarges and has a reduced content of synaptic vesicles, and primary neuronal cultures show synaptic swelling with surface exposure of the lumenal domain of the synaptic vesicle protein synaptotagmin I. Concomitantly, these neurotoxins induce exocytosis of neurotransmitters. We found that an equimolar mixture of lysophospholipids and fatty acids closely mimics all of the biological effects of SPANs. These results draw attention to the possible role of local lipid changes in synaptic vesicle release and provide new tools for the study of exocytosis.
Pde1 Phosphodiesterase Modulates Cyclic AMP Levels through a Protein Kinase A-Mediated Negative Feedback Loop in
Cryptococcus neoformans
Authors: Hicks Julie K. , Bahn Yong-Sun , Heitman Joseph
Published: December 2005

The virulence of the human pathogenic fungus
Cryptococcus neoformans
is regulated by a cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling cascade that promotes mating and the production of melanin and capsule. In this study, genes encoding homologs of the
Saccharomyces cerevisiae
low- and high-affinity phosphodiesterases,
PDE1
and
PDE2
, respectively, were deleted in serotype A strains of
C. neoformans
. The resulting mutants exhibited moderately elevated levels of melanin and capsule production relative to the wild type. Epistasis experiments indicate that Pde1 functions downstream of the Gα subunit Gpa1, which initiates cAMP-dependent signaling in response to an extracellular signal. Previous work has shown that the PKA catalytic subunit Pka1 governs cAMP levels via a negative feedback loop. Here we show that a
pde1
Δ
pka1
Δ mutant strain exhibits cAMP levels that are dramatically increased (
∼
15-fold) relative to those in a
pka1
Δ single mutant strain and that a site-directed mutation in a consensus PKA phosphorylation site reduces Pde1 function. These data provide evidence that fluctuations in cAMP levels are modulated by both Pka1-dependent regulation of Pde1 and another target that comprise a robust negative feedback loop to tightly constrain intracellular cAMP levels.
A Fungus-Specific Ras Homolog Contributes to the Hyphal Growth and Virulence of
Aspergillus fumigatus
Authors: Fortwendel Jarrod R. , Zhao Wei , Bhabhra Ruchi , Park Steven , Perlin David S. , Askew David S. , Rhodes Judith C.
Published: December 2005

The Ras family of GTPase proteins has been shown to control morphogenesis in many organisms, including several species of pathogenic fungi. In a previous study, we identified a gene encoding a fungus-specific Ras subfamily homolog,
rasB
, in
Aspergillus fumigatus
. Here we report that deletion of
A. fumigatus rasB
caused decreased germination and growth rates on solid media but had no effect on total biomass accumulation after 24 h of growth in liquid culture. The Δ
rasB
mutant had an irregular hyphal morphology characterized by increased branching. Expression of
rasB
Δ
113-135
, a mutant transgene lacking the conserved
rasB
internal amino acid insertion, did not complement the deletion phenotype of delayed growth and germination rates and abnormal hyphal morphology. Virulence of the
rasB
deletion strain was diminished; mice infected with this strain exhibited ∼65% survival compared to ∼10% with wild-type and reconstituted strains. These data support the hypothesis that
rasB
homologs, which are highly conserved among fungi that undergo hyphal growth, control signaling modules important to the directional growth of fungal hyphae.
Serial Analysis of Gene Expression Reveals Conserved Links between Protein Kinase A, Ribosome Biogenesis, and Phosphate Metabolism in
Ustilago maydis
Authors: Larraya Luis M. , Boyce Kylie J. , So Austin , Steen Barbara R. , Jones Steven , Marra Marco , Kronstad James W.
Published: December 2005

The switch from budding to filamentous growth is a key aspect of invasive growth and virulence for the fungal phytopathogen
Ustilago maydis
. The cyclic AMP (cAMP) signaling pathway regulates dimorphism in
U. maydis
, as demonstrated by the phenotypes of mutants with defects in protein kinase A (PKA). Specifically, a mutant lacking the regulatory subunit of PKA encoded by the
ubc1
gene displays a multiple-budded phenotype and fails to incite disease symptoms, although proliferation does occur in the plant host. A mutant with a defect in a catalytic subunit of PKA, encoded by
adr1
, has a constitutively filamentous phenotype and is nonpathogenic. We employed serial analysis of gene expression to examine the transcriptomes of a wild-type strain and the
ubc1
and
adr1
mutants to further define the role of PKA in
U. maydis
. The mutants displayed changes in the transcript levels for genes encoding ribosomal proteins, genes regulated by the
b
mating-type proteins, and genes for metabolic functions. Importantly, the
ubc1
mutant displayed elevated transcript levels for genes involved in phosphate acquisition and storage, thus revealing a connection between cAMP and phosphate metabolism. Further experimentation indicated a phosphate storage defect and elevated acid phosphatase activity for the
ubc1
mutant. Elevated phosphate levels in culture media also enhanced the filamentous growth of wild-type cells in response to lipids, a finding consistent with PKA regulation of morphogenesis in
U. maydis
. Overall, these findings extend our understanding of cAMP signaling in
U. maydis
and reveal a link between phosphate metabolism and morphogenesis.
Formation of an Energized Inner Membrane in Mitochondria with a γ-Deficient F
1
-ATPase
Authors: Smith Christopher P. , Thorsness Peter E.
Published: December 2005

Eukaryotic cells require mitochondrial compartments for viability. However, the budding yeast
Saccharomyces cerevisiae
is able to survive when mitochondrial DNA suffers substantial deletions or is completely absent, so long as a sufficient mitochondrial inner membrane potential is generated. In the absence of functional mitochondrial DNA, and consequently a functional electron transport chain and F
1
F
o
-ATPase, the essential electrical potential is maintained by the electrogenic exchange of ATP
4−
for ADP
3−
through the adenine nucleotide translocator. An essential aspect of this electrogenic process is the conversion of ATP
4−
to ADP
3−
in the mitochondrial matrix, and the nuclear-encoded subunits of F
1
-ATPase are hypothesized to be required for this process in vivo. Deletion of
ATP3
, the structural gene for the γ subunit of the F
1
-ATPase, causes yeast to quantitatively lose mitochondrial DNA and grow extremely slowly, presumably by interfering with the generation of an energized inner membrane. A spontaneous suppressor of this slow-growth phenotype was found to convert a conserved glycine to serine in the β subunit of F
1
-ATPase (
atp2-227
). This mutation allowed substantial ATP hydrolysis by the F
1
-ATPase even in the absence of the γ subunit, enabling yeast to generate a twofold greater inner membrane potential in response to ATP compared to mitochondria isolated from yeast lacking the γ subunit and containing wild-type β subunits. Analysis of the suppressing mutation by blue native polyacrylamide gel electrophoresis also revealed that the α
3
β
3
heterohexamer can form in the absence of the γ subunit.
Molecules into Cells: Specifying Spatial Architecture
Authors: Harold Franklin M.
Published: December 2005

A living cell is not an aggregate of molecules but an organized pattern, structured in space and in time. This article addresses some conceptual issues in the genesis of spatial architecture, including how molecules find their proper location in cell space, the origins of supramolecular order, the role of the genes, cell morphology, the continuity of cells, and the inheritance of order. The discussion is framed around a hierarchy of physiological processes that bridge the gap between nanometer-sized molecules and cells three to six orders of magnitude larger. Stepping stones include molecular self-organization, directional physiology, spatial markers, gradients, fields, and physical forces. The knowledge at hand leads to an unconventional interpretation of biological order. I have come to think of cells as self-organized systems composed of genetically specified elements plus heritable structures. The smallest self that can be fairly said to organize itself is the whole cell. If structure, form, and function are ever to be computed from data at a lower level, the starting point will be not the genome, but a spatially organized system of molecules. This conclusion invites us to reconsider our understanding of what genes do, what organisms are, and how living systems could have arisen on the early Earth.
The 2-Hydroxycarboxylate Transporter Family: Physiology, Structure, and Mechanism
Authors: Sobczak Iwona , Lolkema Juke S.
Published: December 2005

The 2-hydroxycarboxylate transporter family is a family of secondary transporters found exclusively in the bacterial kingdom. They function in the metabolism of the di- and tricarboxylates malate and citrate, mostly in fermentative pathways involving decarboxylation of malate or oxaloacetate. These pathways are found in the class Bacillales of the low-CG gram-positive bacteria and in the gamma subdivision of the Proteobacteria. The pathways have evolved into a remarkable diversity in terms of the combinations of enzymes and transporters that built the pathways and of energy conservation mechanisms. The transporter family includes H
+
and Na
+
symporters and precursor/product exchangers. The proteins consist of a bundle of 11 transmembrane helices formed from two homologous domains containing five transmembrane segments each, plus one additional segment at the N terminus. The two domains have opposite orientations in the membrane and contain a pore-loop or reentrant loop structure between the fourth and fifth transmembrane segments. The two pore-loops enter the membrane from opposite sides and are believed to be part of the translocation site. The binding site is located asymmetrically in the membrane, close to the interface of membrane and cytoplasm. The binding site in the translocation pore is believed to be alternatively exposed to the internal and external media. The proposed structure of the 2HCT transporters is different from any known structure of a membrane protein and represents a new structural class of secondary transporters.
ON HYPERGEOMETRIC SERIES REDUCTIONS FROM INTEGRAL REPRESENTATIONS, THE KAMPÉ DE FÉRIET FUNCTION AND ELSEWHERE
Authors: COFFEY MARK W.
Published: December 2005

Single variable hypergeometric functions pFq arise in connection with the power series solution of the Schrödinger equation or in the summation of perturbation expansions in quantum mechanics. For these applications, it is of interest to obtain analytic expressions, and we present the reduction of a number of cases of pFp and p+1Fp, mainly for p=2 and p=3. These and related series have additional applications in quantum and statistical physics and chemistry.
LARGE ROOM TEMPERATURE MAGNETORESISTANCE IN (La0.7Sm0.3)0.7Sr0.3MnO3/Agx COMPOSITES
Authors: YUAN XIAO-BO , LIU YI-HUA , WANG CHENG-JIAN , MEI LIANG-MO
Published: December 2005

The effects of Ag addition in the composite ( La 0.7 Sm 0.3)0.7 Sr 0.3 MnO 3/ Ag x (abbreviated as LSSMO/Ag x) has been studied. The results showed that Ag addition induces the decrease in resistivity (ρ) due to the improvement of grain boundaries resulted from the segregation of Ag on the grain surfaces. In addition, 27% molar ratio of Ag addition induces a large room temperature magnetoresistance (MR) ratio of 35%. The good agreement of experimental data with Brillouin function indicates that the MR behavior in this composite system accounts for the spin-dependent hopping of the electrons between the spin clusters.
OPTIMAL COUPLED-CLUSTER APPROXIMATION FOR THE E⊗(b1+b2) JAHN–TELLER EFFECT
Authors: LO L. P. , LO C. F.
Published: December 2005

In this work we have applied the optimal coupled-cluster approximation to study the ground state of the E⊗(b1+b2) Jahn–Teller effect. The effectiveness of the optimal coupled-cluster approximation has been investigated for the whole range of the asymmetry parameter and various coupling strengths. It is shown that our results up to the third level of approximation are in very good agreement with the exact numerical diagonalization results and are better than those from earlier variational treatments. Furthermore, unlike previous variational treatments, the optimal coupled-cluster approximation has the advantage that the accuracy of both the ground state energy and wavefunction estimates is being taken care of and can be systematically improved. Since the mathematical treatment in this work is simple, the optimal coupled-cluster approximation could be easily extended to the studies of other fermion-boson interacting systems, e.g. the extended Jahn–Teller system.
ANALYSIS OF A DISEASE TRANSMISSION MODEL OF HEPATITIS C
Authors: DAS PRASENJIT , MUKHERJEE DEBASIS , SARKAR A. K.
Published: December 2005

This study analyzes a model of hepatitis C with acute infectious, chronic infectious and the recovery or immune classes. Stability characters of disease-free and endemic proportionate equilibrium points are discussed. The role of immune system on the long-term survival of the susceptible population is derived. It has been shown that chronic infected populations persist whenever acute infected class persists and conversely. Lastly, the criterion for robustness of the system is established under stochastic perturbations. Numerical simulations are also performed to validate the results obtained.
STRUCTURED PSYCHOSOCIAL STRESS AND THE US OBESITY EPIDEMIC
Authors: WALLACE RODRICK , WALLACE DEBORAH N.
Published: December 2005

We examine the accelerating "obesity epidemic" in the US from the perspective of generalized language-of-thought arguments relating a cognitive hypothalamic-pituitary-adrenal axis to an embedding context of structured psychosocial stress. From a rate distortion perspective, the obesity epidemic is an image of ratcheting social pathology — indexed by massive, policy-driven, deurbanization and deindustrialization — impressed upon the bodies of American adults and children. The resulting pattern of developmental disorder, while stratified by expected divisions of class and ethnicity, is nonetheless relentlessly engulfing even affluent majority populations.
THEORETICAL MORPHOSPACE AND ITS RELATION TO FRESHWATER GOMPHONEMOID–CYMBELLOID DIATOM (BACILLARIOPHYTA) LINEAGES
Authors: PAPPAS JANICE L.
Published: December 2005

A number of basic forms in the gomphonemoid–cymbelloid diatom lineages were generated using three-dimensional (3D) parametric equations. The same boundary intervals and differentials for the parameters were used for all forms. From this, the absolute value of the Riemann sum of differences was determined for each variable between pairs of forms. The results were coordinate triplets, and they were plotted in 3D morphospace. Naviculoid forms occupied lower-valued morphospace in contrast to gomphonemoid and cymbelloid morphospaces. However, gomphonemoid and cymbelloid forms occupied different morphospaces. Forms representing Brebissonia occupied morphospace at the base of gomphonemoid forms, but occupied high-valued morphospace with respect to cymbelloid forms. Forms representing Encyonema had lower-valued coordinates compared to other cymbelloid forms. These results support hypotheses of Kociolek and Stoermer that state that naviculoid forms (and in particular, Placoneis) are ancestral to gomphonemoid and cymbelloid forms, Brebissonia is basal to gomphonemoid (but not cymbelloid) forms, and Encyonema is more primitive than other cymbelloid forms. This approach was useful in inferring the relation between theoretical morphospace and hypothesized phylogenies in the gomphonemoid–cymbelloid diatom lineages.
eNOS translocation but not eNOS phosphorylation is dependent on intracellular Ca2+ in human atrial myocardium
Authors: Pott Christian , Steinritz Dirk , Bölck Birgit , Mehlhorn Uwe , Brixius Klara , Schwinger Robert H. G. , Bloch Wilhelm
Published: December 2005

In endothelial cells, two ways of endothelial nitric oxide (NO) synthase (eNOS) activation are known: 1) translocation and 2) Akt-dependent phosphorylation of the enzyme at Ser1177 (Ser1177 eNOS). We have recently shown that agonist-induced Ser1177 eNOS phosphorylation also occurs in human myocardium ( 10 ). In this study, we investigated the Ca2+ dependency of these two mechanisms in human atrium. Therefore, atrial tissue was obtained from patients who underwent coronary artery bypass operations. In immunohistochemical experiments, the translocated form of eNOS and phosphorylated Ser1177 eNOS were labeled using specific antibodies. eNOS translocation was measured in the absence and presence of the Ca2+ chelator BAPTA before and after application of BRL 37344 (BRL), a β3-adrenoceptor agonist that increases eNOS activity ( 34 ). In the absence of BAPTA, BRL time dependently increased the staining intensity of translocated eNOS, whereas in the presence of BAPTA, this effect was blunted. In contrast, BRL clearly increased the staining of phosphorylated Ser1177 eNOS even in the presence of BAPTA. This observation was confirmed using Western blot analysis. Using the NO-sensitive dye diaminofluorescein, we have demonstrated that BRL induced a strong NO release. This effect was completely abolished in the presence of BAPTA but was unaffected by LY-292004, an inhibitor of phosphatidylinositol 3-kinase activity and eNOS phosphorylation. Although Ca2+ dependent, neither the translocation of eNOS nor NO release was changed by the adenylate cyclase activator forskolin. In conclusion, 1) in human atrial myocardium, BRL-induced eNOS translocation but not Ser1177 eNOS phosphorylation is dependent on intracellular Ca2+. 2) In atrial myocardium, eNOS-translocation and not Ser1177 eNOS phosphorylation is responsible for generating the main amount of NO. 3) Although Ca2+ dependent, eNOS translocation and NO release could not be mimicked by adenylate cyclase activation as a mediator of β-adrenergic stimulation.
Regulation of epithelial tubule formation by Rho family GTPases
Authors: Eisen Randi , Walid Shereaf , Ratcliffe Don R. , Ojakian George K.
Published: December 2005

Previous work has established that the integrin signal transduction pathway plays an important role in the regulation of epithelial tubule formation. Furthermore, it has been demonstrated that Rho-kinase, an effector of the Rho signaling pathway, is an important downstream modulator of collagen-mediated renal and mammary epithelial tubule morphogenesis. In the present study, MDCK cells that expressed mutant dominant-negative, constitutively active Rho family GTPases were used to provide further insight into Rho-GTPase signaling and the regulation of epithelial tubule formation. Using collagen gel overlays on MDCK cells as a model system, we observed phosphorylated myosin light chain (pMLC) at the leading edge of migrating lamellipodia. This epithelial remodeling led to the formation of multicellular branching epithelial tubular structures with extensive tight junctions. However, in cells expressing dominant-negative RhoN19, MLC phosphorylation, epithelial remodeling, and tubule formation were inhibited. Instead, only small apical lumens with a solitary tight junctional ring were observed, providing further evidence that Rho signaling through Rho-kinase is important in the regulation of epithelial tubule formation. Because the present model for the Rho signaling pathway proposes that Rac plays a prominent but reciprocal role in cell regulation, experiments were conducted using cells that expressed constitutively active RacV12. When incubated with collagen gels, RacV12-expressing cells formed small apical lumens with simple tight junctions, suggesting that Rac1 signaling also has a prominent role in the regulation of epithelial morphogenesis. Complementary collagen gel overlay experiments with wild-type MDCK cells demonstrated that endogenous Rac1 activation levels decreased over a time course consistent with lamellipodia and tubule formation. Under these conditions, Rac1 was initially localized to the basolateral membrane. However, after epithelial remodeling, activated Rac1 was observed primarily in lamellipodia. These studies support a model in which Rac1 and RhoA are important modulators of epithelial tubule formation.
NAD(P)H oxidase contributes to the progression of remote hepatic parenchymal injury and endothelial dysfunction, but not microvascular perfusion deficits
Authors: Dorman Robert B. , Wunder Christian , Saba Hamida , Shoemaker Jennifer L. , MacMillan-Crow Lee Ann , Brock Robert W.
Published: December 2005

Oxidative stress occurs in remote liver injury, but the origin of the oxidant generation has yet to be thoroughly delineated. Some reports suggest that the source of the distant oxidative stress originates from the site of initial insult [i.e., xanthine oxidase (XO)]; however, it could also be derived from sources such as phagocytic and/or vascular NAD(P)H oxidase (Nox) enzymes. With a murine model of bilateral hindlimb ischemia-reperfusion, we describe here a mechanism for Nox-dependent oxidant production that contributes, at least in part, to remote hepatic parenchymal injury and sinusoidal endothelial cell (SEC) dysfunction. To determine whether Nox enzymes were the source of oxidants, mice were treated immediately after the onset of hindlimb ischemia with specific inhibitors to XO (50 mg/kg ip allopurinol) or Nox (10 mg/kg ip gp91ds-tat and 3 mg/kg ip apocynin). After 1 h of ischemia, hindlimbs were reperfused for either 3 or 6 h. Inhibition of XO failed to provide any improvement in parenchymal injury, SEC dysfunction, neutrophil accumulation, or microvascular dysfunction. In contrast, the inhibition of Nox enzymes prevented the progression (6 h) of parenchymal injury, significantly protected against SEC dysfunction, and completely prevented signs of neutrophil-derived oxidant stress. At the same time, however, inhibition of Nox failed to protect against the early parenchymal injury and microvascular dysfunction at 3 h of reperfusion. These data confirm that microvascular perfusion deficits are not essential for the pathogenesis of remote hepatic parenchymal injury. The data also suggest that Nox enzymes, not XO, are involved in the progression of compromised hepatic parenchymal and endothelial integrity during a systemic inflammatory response.
Analysis of factors that influence rates of carbon monoxide uptake, distribution, and washout from blood and extravascular tissues using a multicompartment model
Authors: Bruce Margaret C. , Bruce Eugene N.
Published: December 2005

To better understand factors that influence carbon monoxide (CO) washout rates, we utilized a multicompartment mathematical model to predict rates of CO uptake, distribution in vascular and extravascular (muscle vs. other soft tissue) compartments, and washout over a range of exposure and washout conditions with varied subject-specific parameters. We fitted this model to experimental data from 15 human subjects, for whom subject-specific parameters were known, multiple washout carboxyhemoglobin (COHb) levels were available, and CO exposure conditions were identical, to investigate the contributions of exposure conditions and individual variability to CO washout from blood. We found that CO washout from venous blood was biphasic and that postexposure times at which COHb samples were obtained significantly influenced the calculated CO half times ( P < 0.0001). The first, more rapid, phase of CO washout from the blood reflected the loss of CO to the expired air and to a slow uptake by the muscle compartment, whereas the second, slower washout phase was attributable to CO flow from the muscle compartment back to the blood and removal from blood via the expired air. When the model was used to predict the effects of varying exposure conditions for these subjects, the CO exposure duration, concentration, peak COHb levels, and subject-specific parameters each influenced washout half times. Blood volume divided by ventilation correlated better with half-time predictions than did cardiac output, muscle mass, or ventilation, but it explained only ∼50% of half-time variability. Thus exposure conditions, COHb sampling times, and individual parameters should be considered when estimating CO washout rates for poisoning victims.
Acute vibration increases α2C-adrenergic smooth muscle constriction and alters thermosensitivity of cutaneous arteries
Authors: Krajnak K. , Dong R. G. , Flavahan S. , Welcome D. , Flavahan N. A.
Published: December 2005

The vascular symptoms of hand-arm vibration syndrome, including cold-induced vasospasm, are in part mediated by increased sensitivity of cutaneous arteries to sympathetic stimulation. The goal of the present study was to use a rat tail model to analyze the effects of vibration on vascular function and α-adrenoceptor (AR) responsiveness. Rats were exposed to a single period of vibration (4 h, 125 Hz, constant acceleration 49 m/s2root mean square). The physical or biodynamic response of the tail demonstrated increased transmissibility or resonance at this frequency, similar to that observed during vibration of human fingers. Morphological analysis demonstrated that vibration did not appear to cause structural injury to vascular cells. In vitro analysis of vascular function demonstrated that constriction to the α1-AR agonist phenylephrine was similar in vibrated and control arteries. In contrast, constriction to the α2-AR agonist UK14304 was increased in vibrated compared with control arteries, both in endothelium-containing or endothelium-denuded arteries. The α2C-AR antagonist MK912 (3 × 10−10M) inhibited constriction to UK14304 in vibrated but not control arteries, reversing the vibration-induced increase in α2-AR activity. Moderate cooling (to 28°C) increased constriction to the α2-AR agonist in control and vibrated arteries, but the magnitude of the amplification was less in vibrated compared with control arteries. Endothelium-dependent relaxation to acetylcholine was similar in control and vibrated arteries. Based on these results, we conclude that a single exposure to vibration caused a persistent increase in α2C-AR-mediated vasoconstriction, which may contribute to the pathogenesis of vibration-induced vascular disease.