bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence and interactions of cathepsin D, HLA‐DRB1 and APOE on cognitive abilities in an older non‐demented population
Authors: Payton A. , Van Den Boogerd E. , Davidson Y. , Gibbons L. , Ollier W. , Rabbitt P. , Worthington J. , Horan M. , Pendleton N.
Published: January 2006

Cathepsin D (CTSD), human leukocyte antigen DRB1 (HLA‐DRB1) and apolipoprotein E (APOE) have all been associated with cognitive ability in both demented and non‐demented individuals. CTSD is a pleiotrophic protein whose functions include the processing of proteins prior to presentation by HLA. Several studies have also reported that a functional exon 2 polymorphism in the CTSD gene interacts with APOEɛ4 resulting in an increased risk of developing Alzheimer's disease (AD). We have previously reported that the CTSD exon 2 polymorphism regulates fluid intelligence. In this study, we extend this finding to other cognitive domains and investigate interactions with APOE and HLA‐DRB1. Using a cohort of 766 non‐demented volunteers, we found that the CTSD exon 2 T allele was associated with a decrease in several cognitive domains that comprise processing speed [random letters (RLs) test, P = 0.012; alphabet‐coding task (ACT), P = 0.001], spatial recall (SR) (P = 0.016) and an additional test of fluid intelligence (P = 0.010). We also observed that the HLA‐DR1 was associated with enhanced cumulative recall ability (P = 0.006), and conversely HLA‐DR5 was associated with diminished delayed verbal recall and SR abilities (P = 0.014 and P = 0.003, respectively). When analysed independently, APOEɛ4 did not influence any cognitive domains. In contrast, CTSD T/APOEɛ4‐positive volunteers scored lower on tests of fluid intelligence (P = 0.015), processing speed (ACT, P = 0.001; RL, P = 0.013) and immediate recall (P = 0.029). Scores were lower for all these tests than when CTSD and APOE were analysed independently. This supports previous findings in AD that have also reported an epistatic interaction. In addition, we found that CTSD T/HLA‐DR2‐positive volunteers had reduced processing speed (ACT, P = 0.040; RL, P = 0.014) and had significantly lower cumulative and SR abilities (P = 0.003 and P = 0.001, respectively). Biological interaction between these two proteins has previously been shown where HLA‐DR2 binds more readily to the myelin basic protein (MBP) compared with other DR antigens, preventing MBP cleavage by CTSD.
Quantitative trait loci for IQ and other complex traits: single‐nucleotide polymorphism genotyping using pooled DNA and microarrays
Authors: Craig I. , Plomin R.
Published: January 2006

Similar to other complex traits, it is likely that many DNA polymorphisms of small effect size [quantitative trait loci (QTLs)] are responsible for the high heritability of intelligence, in addition to many rare monogenic disorders known to contribute to lowered intelligence. We review the current status of approaches to identify QTLs associations for intelligence employing genome‐wide strategies using pooled DNA from many individuals and evaluate the innovative approach of microarray analysis to genotype DNA pools for large numbers of single nucleotide polymorphisms.
Gene expression profiling of primate neocortex: molecular neuroanatomy of cortical areas
Authors: Watakabe A. , Komatsu Y. , Nawa H. , Yamamori T.
Published: January 2006

One hundred years have passed since Brodmann's mapping of the mammalian neocortex. Solely on the basis of morphological observations, he envisaged the conservation and differentiation of cortical areal structures across various species. We now know that neurochemical, connectional and functional heterogeneity of the neocortex accompanies the morphological divergence observed in such cytoarchitectonic studies. Nevertheless, we are yet far from fully understanding the biological significance of this cortical heterogeneity. In this article, we review our past works on the gene expression profiling of the postnatal primate cortical areas, by quantitative real‐time polymerase chain reaction (PCR), DNA array, differential display PCR and in situ hybridization analyses. These studies revealed both the overall homogeneity of gene expression across different cortical areas and the presence of a small number of genes that show markedly area‐specific expression patterns. In situ hybridization showed that, among such genes, occ1 and retinol‐binding protein (RBP) mRNAs are selectively expressed in the neuronal populations that seem to be involved in distinct neural processing such as sensory reception (for occ1) and associative function (for RBP). Such a molecular neuroanatomical approach has the promise to provide an important link between structure and function of the cerebral cortex.
Investigating cognitive genetics and its implications for the treatment of cognitive deficit
Authors: Payton A.
Published: January 2006

Cognitive impairment in the elderly, caused by either normal ageing process or dementia, is an increasing problem in developed countries that has enormous social and economic considerations. Research investigating the genetic basis of cognition is a new and rapidly developing field that may aid in the development of new treatments for age‐related cognitive deficit. Over the past 6 years, a number of quantitative trait loci (QTLs) have been associated with cognitive functioning in humans including loci within the genes catechol‐o‐methyltransferase, brain‐derived neurotrophic factor, muscle segment homeobox 1, serotonin transporter 2A (HTR2A), cholinergic muscarinic receptor 2, cathepsin D, metabotrophic glutamate receptor and most recently the class II human leukocyte antigens. Unfortunately, inconsistency within the literature, which is a hallmark of almost all association studies investigating complex diseases and traits, is casting doubt as to which genes are truly associated with cognition and which are a result of Type 2 error. This review will highlight implicated intelligence QTLs, examine the probable reasons for the current discrepancies between reports and discuss the potential advantages that may be procured from the study of cognitive genetics.
Deconstructing language by comparative gene expression: from neurobiology to microarray
Authors: Oldham M. C. , Geschwind D. H.
Published: January 2006

Language is a defining characteristic of our species that has emerged quite recently on an evolutionary timescale. Understanding the neurobiological substrates and genetic underpinnings of language constitutes a basic challenge for both neuroscience and genetics. The functional localization of language in the brain has been progressively refined over the last century through studies of aphasics and more recently through neuroimaging. Concurrently, structural specializations in these brain regions have been identified by virtue of their lateralization in humans and also through comparisons with homologous brain regions in non‐human primate species. Comparative genomics has revealed the genome of our closest living relative, the chimpanzee, to be astonishingly similar to our own. To explore the role that changes in the regulation of gene expression have had in recent human evolution, several groups have used microarrays to compare expression levels for thousands of genes in the brain between humans and chimpanzees. By applying this approach to the increasingly refined peri‐sylvian network of brain regions involved in language, it may be possible to discern functionally significant changes in gene expression that are universal among humans but unique to our species, thus casting light on the molecular basis of language in the brain.
Comparative gene expression in brain regions of human alcoholics
Authors: Flatscher‐Bader T. , Van Der Brug M. P. , Landis N. , Hwang J. W. , Harrison E. , Wilce P. A.
Published: January 2006

The mesocorticolimbic system is the reward centre of the brain and the major target for drugs of abuse including alcohol. Neuroadaptive changes in this region are thought to underlie the process of tolerance and dependence. Recently, several research groups have searched for alcohol‐responsive genes using high‐throughput microarrays and well‐characterized human post‐mortem material. Comparison of data from these studies of cortical regions highlights the differences in experimental approach and selection of cases. However, alcohol‐responsive gene sets associated with transcription, oxidative stress and energy production were common to these studies. In marked contrast, alcohol‐responsive genes in the nucleus accumbens and the ventral tegmental area are primarily associated with changes in neurotransmission and signal transduction. These data support the concept that, within cortical regions, changes in gene expression are associated with alcoholism‐related pathology. In the dopaminergic tract of the mesocorticolimbic system, alcohol‐responsive gene sets suggest long‐term neuroplastic changes in synaptic transmission.
Effect of Low Vegetation on the Recruitment of Plants in Successional Habitat Types1
Authors: Benitez‐Malvido Julieta
Published: January 2006

I assessed the role of low vegetation (plants ca 1 yr old and ≤50 cm tall) as a biotic facilitator or barrier in the recruitment of different growth forms and species in primary forests, secondary forests, and old‐fields (abandoned pastures) in southeastern Mexico. I removed by hand all plants (≤100 cm tall, including roots) and litter from 20, 0.25 m2 plots in each habitat. For 1 yr, I counted the number of plant species (5–50 cm tall) recruited, grouped them into different growth forms, and compared them to undisturbed control plots. Prior to manipulation, the standing density of trees and lianas was highest in primary and secondary forests. Shrubs were more abundant in secondary forests, whereas herbs, epiphytes, and hemi‐epiphytes were more abundant in old‐fields. Herbaceous plants appeared as important components of the community in all habitats. The removal of low vegetation increased total plant recruitment in all habitats. Considering each growth form, the absence of vegetation increased recruitment in primary forests for herbs, in secondary forests for epiphytes and hemi‐epiphytes, in old‐fields for trees, and for lianas in primary forests and old‐fields. In vegetation removal plots, recruitment of species was greater in pastures, lower in secondary forest, and similar in primary forest with respect to control plots. Depending on habitat type, species, and growth form, the presence of low vegetation may act as a recruitment barrier or facilitator for different species, affecting plant community structure, diversity, and composition in different habitats.
Mechanisms underlying variations in excitation–contraction coupling across the mouse left ventricular free wall
Authors: Dilly Keith W. , Rossow Charles F. , Votaw V. Scott , Meabon James S. , Cabarrus Jennifer L. , Santana Luis F.
Published: January 2006

Ca2+ release during excitation–contraction (EC) coupling varies across the left ventricular free wall. Here, we investigated the mechanisms underlying EC coupling differences between mouse left ventricular epicardial (Epi) and endocardial (Endo) myocytes. We found that diastolic and systolic [Ca2+]i was higher in paced Endo than in Epi myocytes. Our data indicated that differences in action potential (AP) waveform between Epi and Endo cells only partially accounted for differences in [Ca2+]i. Rather, we found that the amplitude of the [Ca2+]i transient, but not its trigger – the Ca2+ current – was larger in Endo than in Epi cells. We also found that spontaneous Ca2+ spark activity was about 2.8‐fold higher in Endo than in Epi cells. Interestingly, ryanodine receptor type 2 (RyR2) protein expression was nearly 2‐fold higher in Endo than in Epi myocytes. Finally, we observed less Na+–Ca2+ exchanger function in Endo than in Epi cells, which was associated with decreased Ca2+ efflux during the AP; this contributed to higher diastolic [Ca2+]i and SR Ca2+ in Endo than in Epi cells during pacing. We propose that transmural differences in AP waveform, SR Ca2+ release, and Na+–Ca2+ exchanger function underlie differences in [Ca2+]i and EC coupling across the left ventricular free wall.
Differential effects of prenatal exposure to dexamethasone or cortisol on circulatory control mechanisms mediated by angiotensin II in the central nervous system of adult sheep
Authors: Dodic M. , McAlinden A. T. , Jefferies A. J. , Wintour E. M. , Cock M. L. , May C. N. , Evans R. G. , Moritz K. M.
Published: January 2006

Prenatal exposure to elevated maternal glucocorticoids (dexamethasone (DEX) or cortisol (CORT)) for 2 days early in pregnancy can ‘programme’ alterations in adult offspring of sheep, including elevated arterial pressure. DEX treatment also results in greater angiotensin II type 1 (AT1) receptor expression in the medulla oblongata in late gestation fetuses than in saline (SAL)‐ or CORT‐exposed animals. We hypothesized that this would result in functional changes in brainstem angiotensinergic control of cardiovascular function in DEX‐ but not CORT‐exposed animals. To test this hypothesis, cardiovascular responses to intracerebroventricular (i.c.v.) angiotensin II were examined in adult male offspring exposed to DEX (0.48 mg h−1; n= 7), CORT (5 mg h−1, n= 6) or SAL (n= 9) from 26 to 28 days of gestation. Increases in mean arterial pressure during i.c.v. infusion of angiotensin II (1 or 10 μg h−1) were significantly greater in the DEX group (10 ± 1 mmHg at 1 μg h−1) compared with SAL (6 ± 1 mmHg) or CORT (6 ± 1 mmHg) animals (P < 0.05). i.c.v. infusion of the AT1 antagonist losartan significantly decreased cardiac output and heart rate in DEX animals, but not in SAL or CORT animals. Thus, increased expression of brainstem AT1 receptor mRNA after prenatal DEX is associated with increased responsiveness of cardiovascular control to activation of brain AT receptors by exogenous and endogenous angiotensin II. The altered role of the brain RAS in sheep exposed prenatally to DEX was not observed in sheep exposed prenatally to cortisol, suggesting these two glucocorticoids have distinct programming actions.
Neonatal programming of the rat neuroimmune response: stimulus specific changes elicited by bacterial and viral mimetics
Authors: Ellis Shaun , Mouihate Abdeslam , Pittman Quentin J.
Published: January 2006

Recently, it has been shown that the neonatal immune environment can have significant programming effects on the adult neuroimmune response. A single neonatal immune challenge with the bacterial mimetic lipopolysaccharide (LPS) can alter the neuroendocrine, neurochemical and febrile responses to a subsequent, homotypic (LPS) immune challenge as adults. As the programming effects of viral stimuli during this neonatal period are unknown, we tested whether the viral mimetic polyinosinic–polycytidylic acid (PolyIC), administered on postnatal day 14 (P14) would alter the adult neuroimmune responses to a subsequent PolyIC challenge. Our results show that animals treated neonatally with PolyIC had significantly attenuated febrile responses to an adult PolyIC challenge, which coincided with a heightened corticosteroid response. When the corticosteroid receptor blocker RU486 was administered prior to the adult PolyIC challenge, animals treated neonatally with PolyIC no longer displayed attenuated febrile responses. Similar responses to an adult LPS challenge have been seen in animals that were exposed neonatally to LPS, indicating that both neonatal immune stimuli elicit highly similar programming effects on the adult neuroimmune responses. However, we find that neither neonatal PolyIC nor neonatal LPS challenges led to an alteration in the adult febrile or corticosteroid responses to a heterotypic adult immune challenge, indicating that the programming effects of the neonatal immune environment are stimulus specific, and do not alter the adult responses to other immune stimuli.
T‐type Ca2+ channels encode prior neuronal activity as modulated recovery rates
Authors: Uebachs M. , Schaub C. , Perez‐Reyes E. , Beck H.
Published: January 2006

T‐type Ca2+ channels give rise to low‐threshold inward currents that are central determinants of neuronal excitability. The availability of T‐type Ca2+ channels is strongly influenced by voltage‐dependent inactivation and recovery from inactivation. Here, we show that native and cloned T‐type Ca2+ channel subunits selectively encode specific aspects of prior membrane potential changes via a powerful modulation of the rates with which these channels recover from inactivation. Increasing the duration of subthreshold (−70 to −55 mV) conditioning depolarizations caused a pronounced slowing of subsequent recovery from inactivation of both cloned (Cav3.1–3.3) and native T‐type channels (thalamic neurones). The scaling of recovery rates with increasing duration of conditioning depolarizations could be well described by a power law function. Different T‐type channel isoforms exhibited overlapping but complementary ranges of recovery rates. Intriguingly, scaling of recovery rates was dramatically reduced in Cav3.2 and Cav3.3, but not Cav3.1 subunits, when mock action potentials were superimposed on conditioning depolarizations. Our results suggest that different T‐type channel subunits exhibit dramatic differences in scaling relationships, in addition to well‐described differences in other biophysical properties. Furthermore, the availability of T‐type channels is powerfully modulated over time, depending on the patterns of prior activity that these channels have encountered. These data provide a novel mechanism for cellular short‐term plasticity on the millisecond to second time scale that relies on biophysical properties of specific T‐type Ca2+ channel subunits.
Demonstration of Infrared-Photovoltaics for a Full-Spectrum Solar Energy System
Authors: Dye Dan , Wood Byard , Fraas Lewis , Kretschmer Jeanette
Published: January 2006

A nonimaging (NI) device and infrared-photovoltaic (IR-PV) array for use in a full-spectrum solar energy system has been designed, built, and tested (Dye et al., 2003, “Optical Design of an Infrared Non-Imaging Device for a Full-Spectrum Solar Energy System,” Proceedings of the ASME International Solar Energy Society Conference; Dye and Wood, 2003, Infrared Transmission Efficiency of Refractive and Reflective Non-Imaging Devices for a Full-Spectrum Solar Energy System,” Nonimaging Optics: Maximum Efficiency Light Transfer VII, Proc. SPIE, 5185; Fraas et al., 2001, Infrared Photovoltaics for Combined Solar Lighting and Electricity for Buildings,” Proceedings of 17th European Photovoltaic Solar Energy Conference}. This system was designed to utilize the otherwise wasted infrared (IR) energy that is separated from the visible portion of the solar spectrum before the visible light is harvested. The IR energy will be converted to electricity via a gallium antimonide (GaSb) IR-PV array. The experimental apparatus for the testing of the IR optics and IR-PV performance is described. Array performance data will be presented, along with a comparison between outdoor experimental tests and laboratory flash tests. An analysis of the flow of the infrared energy through the collection system will be presented, and recommendations will be made for improvements. The IR-PV array generated a maximum of 26.7W, demonstrating a conversion efficiency of the IR energy of 12%.
An Axisymmetric Computational Fluid Dynamics Approach to the Analysis of the Working Process of a Solar Stirling Engine
Authors: Mahkamov K.
Published: January 2006

The use of computational fluid dynamics (CFD) models significantly extends the capabilities for the detailed analysis of the complex heat transfer and gas dynamic processes that occur in the internal gas circuit of a Stirling engine by more accurately predicting the engine’s performance. This accurate data on operational characteristics of the engine can then contribute to more precise calculations of the dimensions of a parabolic concentrator in a dish/Stirling engine installation. In this paper a successful axisymmetric CFD simulation of a solar “V”-type Stirling engine is described for the first time. The standard κ-ε turbulence model, with a moving mesh to reflect the reciprocating motion of the pistons, has been employed for the analysis of the engine’s working process. The gas temperature and pressure distributions and velocity fields in the internal gas circuit of the machine have been obtained and the pressure-volume diagrams have been calculated. Comparison of the numerical results produced from the axisymmetric CFD simulation of the engine’s working process with those computed with the use of second-order mathematical analysis shows that there are considerable differences. In particular, analysis of the data obtained indicates that the gas temperature in the compression space depends on the location in the cylinder for the given moment in the cycle and it may differ substantially from being harmonic in time.
Computation of Wave-Body Interactions Using the Panel-Free Method and Exact Geometry
Authors: Qiu W. , Peng H. , Chuang J. M.
Published: January 2006

A panel-free method was developed earlier to solve the radiation and the diffraction problems of floating bodies in waves in the time domain. This method has been extended to compute wave interactions with bodies in water of infinite depth and finite depth in the frequency domain. After removing the singularities in the boundary integral equation and representing the body surface exactly by either analytical description or NURBS surfaces, the boundary integral equation can be discretized over the exact body surface by Gaussian quadratures. Accuracy of the method is demonstrated by its application to the radiation and the diffraction problems of a floating hemisphere, a vertically floating axisymmetric cylinder, and a Wigley hull. Computed added-mass, damping coefficients, and wave exciting forces agree well with published results.
Application of a Discontinuous Galerkin Finite Element Method to Liquid Sloshing
Authors: Guillot Martin J.
Published: January 2006

A Runge-Kutta discontinuous Galerkin (RKDG) finite element method is applied to the liquid sloshing problem using the depth-averaged shallow water equations in a rotating frame of reference. A weak statement formulation is developed by multiplying the equations by a test function and integrating over a typical element. The basis functions are Legendre polynomials of degree one, resulting in formally second-order spatial accuracy. Second-order time integration is achieved using a second-order Runge-Kutta method. A minmod slope limiter is incorporated into the solution near discontinuities to control nonphysical oscillations and to ensure nonlinear total variation bounded stability. The method is first applied to the dam-breaking problem with zero rotation to validate the basic numerical implementation. Grid independence of the solutions is established and solution error is quantified by computing the L1 norm and comparing the estimated convergence rates to theoretical convergence rates. Stability is demonstrated subject to a Courant-Fredricks-Lewey restriction. Sloshing in a nonrotating tank with a prescribed initial water surface elevation is first investigated to demonstrate the ability of the method to capture the wave speed of traveling waves, followed by a tank undergoing sinusoidal rotation. Time histories of water surface elevation at selected locations, as well as pressure distribution on the tank walls and the corresponding moment about the tank centerline are computed and compared to experimental data and to previous computations. Finally, a limited parameter study is performed to determine the effect of varying roll angle, depth to width ratio, and forcing frequency on the resulting maximum moment about the tank centerline.
Riser-Soil
Interaction: Local Dynamics at TDP and a Discussion on the Eigenvalue and the VIV
Problems
Authors: Pesce Celso
P. , Martins Clóvis de
A. , da Silveira Lauro M. Y.
Published: January 2006

The eigenvalue problem of risers is of utmost importance, particularly if vortex-induced vibration (VIV) is concerned. Design procedures rely on the determination of eigenvalues and eigenmodes. Natural frequencies are not too sensitive to the proper consideration of boundary condition, within a certain extent where dynamics at the touchdown area (TDA) may be modeled as dominated by the dynamics of the suspended part. However, eigenmodes may be strongly affected in this region because, strictly speaking, this is a nonlinear one-side (contact-type) boundary condition. Actually, we shall consider a nonlinear eigenvalue problem. Locally, at TDA, riser flexural rigidity and soil interaction play important roles and may affect the dynamic curvature. Extending and merging former analytical solutions on touchdown point (TDP) dynamics and on the eigenvalue problem, obtained through asymptotic and perturbation methods, the present work critically address soil and bending stiffness effects a little further. As far as linear soil stiffness and planar dynamics hypotheses may be considered valid, it is shown that penetration in the soil is small and that its effect does not change significantly the bending loading that is mainly caused by the cyclic excursion of the TDP and corresponding dynamic tension. A comparison of the analytical results with a full nonlinear time-domain simulation shows a remarkable agreement for a typical steel catenary riser. The WKB approximation for the eigenvalue problem gives good estimates for TDP excursion. As the dynamic tension caused solely by VIV is very small, the merged analytical solution may be used as a first estimate of the curvature variation at TDP in the cases of current perpendicular to the “riser plane.”
Optimizing the Power Take Off of a Wave Energy Converter With Regard to the Wave Climate
Authors: Duclos Gaelle , Babarit Aurelien , Clément Alain H.
Published: January 2006

Considered as a source of renewable energy, wave is a resource featuring high variability at all time scales. Furthermore wave climate also changes significantly from place to place. Wave energy converters are very often tuned to suit the more frequent significant wave period at the project site. In this paper we show that optimizing the device necessitates accounting for all possible wave conditions weighted by their annual occurrence frequency, as generally given by the classical wave climate scatter diagrams. A generic and very simple wave energy converter is considered here. It is shown how the optimal parameters can be different considering whether all wave conditions are accounted for or not, whether the device is controlled or not, whether the productive motion is limited or not. We also show how they depend on the area where the device is to be deployed, by applying the same method to three sites with very different wave climate.
Content Exams for Pre-Service Physics Teachers: A Failing Grade
Authors: Kanim Stephen , Loverude Michael
Published: January 2006

Among other qualifications, effective teachers must have a robust knowledge of the subject matter that they teach. Many states require that prospective teachers of physics pass one or more standardized tests designed to measure content knowledge. Our survey of sample questions from these tests and from commercial examination preparation booklets suggests that there are significant deficiencies in these materials. Some questions contain physics errors. More often, the questions probe only the ability of test-takers to memorize facts or plug numbers into a formula, with little emphasis on conceptual understanding or pedagogical content knowledge. These deficiencies undermine the very purpose of such content tests.
A Block Dragging a Cart
Authors: Sullivan Peter , Novak Joseph , Sancilio Philip
Published: January 2006

This paper describes an experiment in which a block is pulled by a string across the top of a cart and drags the cart along with it (see Fig. 1). The ratio of the block's displacement to the cart's displacement can be modeled using the algebra-based Newtonian mechanics available to introductory college and advanced high school students. We examined the effect of the mass of the block on this ratio. Displacement data for the block and cart were obtained using video analysis. This experiment was originally conceived of and carried out by students in my honors physics course. We present the results of this experiment. The results are in good agreement with the model derived here.
Explaining the Color Distributions of Globular Cluster Systems in Elliptical Galaxies
Authors: Yoon Suk-Jin , Yi Sukyoung Ken , Lee Young-Wook
Published: January 2006

The colors of globular clusters in most large elliptical galaxies are bimodal. This is generally taken as evidence for the presence of two cluster subpopulations that have different geneses. However, here we find that, because of the nonlinear nature of the metallicity-to-color transformation, a coeval group of old clusters with a unimodal metallicity spread can exhibit color bimodality. The models of cluster colors indicate that horizontal-branch stars are the main drivers behind the empirical nonlinearity. We show that the scenario gives simple and cohesive explanations for all the key observations and could simplify theories of elliptical galaxy formation.
Identification and Characterization of RbmA, a Novel Protein Required for the Development of Rugose Colony Morphology and Biofilm Structure in
Vibrio cholerae
Authors: Fong Jiunn C. N. , Karplus Kevin , Schoolnik Gary K. , Yildiz Fitnat H.
Published: January 2006

Phase variation between smooth and rugose colony variants of
Vibrio cholerae
is predicted to be important for the pathogen's survival in its natural aquatic ecosystems. The rugose variant forms corrugated colonies, exhibits increased levels of resistance to osmotic, acid, and oxidative stresses, and has an enhanced capacity to form biofilms. Many of these phenotypes are mediated in part by increased production of an exopolysaccharide termed VPS. In this study, we compared total protein profiles of the smooth and rugose variants using two-dimensional gel electrophoresis and identified one protein that is present at a higher level in the rugose variant. A mutation in the gene encoding this protein, which does not have any known homologs in the protein databases, causes cells to form biofilms that are more fragile and sensitive to sodium dodecyl sulfate than wild-type biofilms. The results indicate that the gene, termed
rbmA
(
r
ugosity and
b
iofilm structure
m
odulator A), is required for rugose colony formation and biofilm structure integrity in
V. cholerae
. Transcription of
rbmA
is positively regulated by the response regulator VpsR but not VpsT.
Bacillus anthracisIsdG, a Heme-Degrading Monooxygenase
Authors: Skaar Eric P. , Gaspar Andrew H. , Schneewind Olaf
Published: January 2006

Bacillus anthracis, the causative agent of anthrax, utilizes hemin and hemoglobin for growth in culture, suggesting that these host molecules serve as sources for the nutrient iron during bacterial infection. Bioinformatic analyses of theB. anthracisgenome revealed genes with similarity to theiron-regulatedsurfacedeterminant (isd) system responsible for heme uptake inStaphylococcus aureus. We show that the protein product of one of these genes,isdG, binds hemin in a manner resembling the heme binding of known heme oxygenases. Formation of IsdG:hemin complexes in the presence of a suitable electron donor, e.g., ascorbate or cytochrome P450 reductase, promotes catalytic degradation of hemin to biliverdin with concomitant release of iron. IsdG is required forB. anthracisutilization of hemin as a sole iron source, and it is also necessary for bacterial protection against heme-mediated toxicity. These data suggest that IsdG functions as a heme-degrading monooxygenase inB. anthracis.
Regulation and Properties of PstSCAB, a High-Affinity, High-Velocity Phosphate Transport System ofSinorhizobium meliloti
Authors: Yuan Ze-Chun , Zaheer Rahat , Finan Turlough M.
Published: January 2006

The properties and regulation of thepstSCAB-encoded Piuptake system from the alfalfa symbiontSinorhizobium melilotiare reported. We present evidence that thepstSCABgenes and the regulatoryphoUBgenes are transcribed from a single promoter that contains two PhoB binding sites and that transcription requires PhoB.S. melilotistrain 1021 (Rm1021) and its derivatives were found to carry a C deletion frameshift mutation in thepstCgene (designatedpstC1021) that severely impairs activity of the PstSCAB Pitransport system. This mutation is absent in RCR2011, the parent of Rm1021. Correction of thepstC1021mutation in Rm1021 by site-directed mutagenesis revealed that PstSCAB is a Pi-specific, high-affinity (Km, 0.2 μM), high-velocity (Vmax, 70 nmol/min/mg protein) transport system. ThepstC1021allele was shown to generate a partialphoregulon constitutive phenotype, in which transcription is activated by PhoB even under Pi-excess conditions that render PhoB inactive in a wild-type background. The previously reported symbiotic Fix−phenotype ofphoCDETmutants was found to be dependent on thepstC1021mutation, as Rm1021phoCDETmutants formed small white nodules on alfalfa that failed to reduce N2, whereasphoCDETmutant strains with a correctedpstCallele (RmP110) formed pink nodules on alfalfa that fixed N2like the wild type. Alfalfa root nodules formed by the wild-type RCR2011 strain expressed the low-affinityorfA-pit-encoded Piuptake system and neither thepstSCABgenes nor thephoCDETgenes. Thus, metabolism of alfalfa nodule bacteroids is not Pilimited.
Steady-State Kinetic Analysis of Phosphotransacetylase from
Methanosarcina thermophila
Authors: Lawrence Sarah H. , Ferry James G.
Published: January 2006

Phosphotransacetylase (EC 2.3.1.8) catalyzes the reversible transfer of the acetyl group from acetyl phosphate to coenzyme A (CoA), forming acetyl-CoA and inorganic phosphate. A steady-state kinetic analysis of the phosphotransacetylase from
Methanosarcina thermophila
indicated that there is a ternary complex kinetic mechanism rather than a ping-pong kinetic mechanism. Additionally, inhibition patterns of products and a nonreactive substrate analog suggested that the substrates bind to the enzyme in a random order. Dynamic light scattering revealed that the enzyme is dimeric in solution.
Mutations in the
waaR
Gene of
Escherichia coli
Which Disrupt Lipopolysaccharide Outer Core Biosynthesis Affect Cell Surface Retention of Group 2 Capsular Polysaccharides
Authors: Taylor Clare M. , Goldrick Marie , Lord Liz , Roberts Ian S.
Published: January 2006

On the basis of increased resistance to K5 capsule-specific bacteriophage, a
waaR
transposon mutant defective in the biosynthesis of lipopolysaccharide outer core was isolated. In a K1-expressing strain the mutation equally affected sensitivity to K1 capsule-specific bacteriophage, indicating a general effect on group 2 capsules. The
waaR
mutation affected retention on the cell surface of the K5 polysaccharide, with increased polysaccharide accumulating in the culture supernatant. This indicates that interactions between the outer core of lipopolysaccharide and group 2 capsular polysaccharides are important for the stabilization of group 2 capsular polysaccharides on the cell surface.
Comparative Genomic Analysis of 18
Pseudomonas aeruginosa
Bacteriophages
Authors: Kwan Tony , Liu Jing , DuBow Michael , Gros Philippe , Pelletier Jerry
Published: January 2006

A genomic analysis of 18
P. aeruginosa
phages, including nine newly sequenced DNA genomes, indicates a tremendous reservoir of proteome diversity, with 55% of open reading frames (ORFs) being novel. Comparative sequence analysis and ORF map organization revealed that most of the phages analyzed displayed little relationship to each other.
Mammalian Steroid Hormones Are Substrates for the Major RND- and MFS-Type Tripartite Multidrug Efflux Pumps of
Escherichia coli
Authors: Elkins Christopher A. , Mullis Lisa B.
Published: January 2006

A steroid-hormone-dependent growth suppression was observed in
Escherichia coli
efflux-deficient backgrounds containing mutations in the major RND- and MFS-type tripartite multidrug efflux systems, AcrAB-TolC and EmrAB-TolC, respectively. In addition to their previously known natural steroid spectrum, which includes bile acids, both systems were shown to transport the hormones estradiol and progesterone, whereas hydrocortisone served as a substrate of only AcrAB-TolC. Furthermore, at least two other RND-type pumps, YhiV and AcrD, were capable of transporting such hormones when overexpressed on plasmid vectors (with some demonstrable specificity observed with AcrD). When this activity was examined in a wild-type background, cell-associated estradiol levels remained largely unaffected by competition with exogenous bile acids and hydrocortisone, in contrast to progesterone, which produced a significant modulation in estradiol uptake.
TheVibrio harveyiGTPase CgtAVIs Essential and Is Associated with the 50S Ribosomal Subunit
Authors: Sikora A. E. , Zielke R. , Datta K. , Maddock J. R.
Published: January 2006

It was previously reported that unlike the otherobg/cgtAGTPases, theVibrio harveyi cgtAVis not essential. Here we show thatcgtAVwas not disrupted in these studies and is, in fact, essential for viability. Depletion of CgtAVdid not result in cell elongation. CgtAVis associated with the large ribosomal particle. In light of our results, we predict that theV. harveyiCgtAVprotein plays a similar essential role to that seen for Obg/CgtA proteins in other bacteria.
Evidence for Mutagenesis by Nitric Oxide during Nitrate Metabolism in
Escherichia coli
Authors: Weiss Bernard
Published: January 2006

In
Escherichia coli
, nitrosative mutagenesis may occur during nitrate or nitrite respiration. The endogenous nitrosating agent N
2
O
3
(dinitrogen trioxide, nitrous anhydride) may be formed either by the condensation of nitrous acid or by the autooxidation of nitric oxide, both of which are metabolic by-products. The purpose of this study was to determine which of these two agents is more responsible for endogenous nitrosative mutagenesis. An
nfi
(endonuclease V) mutant was grown anaerobically with nitrate or nitrite, conditions under which it has a high frequency of A:T-to-G:C transition mutations because of a defect in the repair of hypoxanthine (nitrosatively deaminated adenine) in DNA. These mutations could be greatly reduced by two means: (i) introduction of an
nirB
mutation, which affects the inducible cytoplasmic nitrite reductase, the major source of nitric oxide during nitrate or nitrite metabolism, or (ii) flushing the anaerobic culture with argon (which should purge it of nitric oxide) before it was exposed to air. The results suggest that nitrosative mutagenesis occurs during a shift from nitrate/nitrite-dependent respiration under hypoxic conditions to aerobic respiration, when accumulated nitric oxide reacts with oxygen to form endogenous nitrosating agents such as N
2
O
3
. In contrast, mutagenesis of nongrowing cells by nitrous acid was unaffected by an
nirB
mutation, suggesting that this mutagenesis is mediated by N
2
O
3
that is formed directly by the condensation of nitrous acid.
Functional and Topological Characterization of Novel Components of the
comB
DNA Transformation Competence System in
Helicobacter pylori
Authors: Karnholz Arno , Hoefler Claudia , Odenbreit Stefan , Fischer Wolfgang , Hofreuter Dirk , Haas Rainer
Published: January 2006

Helicobacter pylori
is one of the most diverse bacterial species known. A rational basis for this genetic variation may be provided by its natural competence for genetic transformation and high-frequency recombination. Many bacterial competence systems have homology with proteins that are involved in the assembly of type IV pili and type II secretion systems. In
H. pylori
, DNA uptake relies on a transport system related to type IV secretion systems (T4SS) designated the
comB
system. The prototype of a T4SS in
Agrobacterium tumefaciens
consists of 11 VirB proteins and VirD4, which form the core unit necessary for the delivery of single proteins or large nucleoprotein complexes into target cells. In the past we identified proteins ComB4 and ComB7 through ComB10 as being involved in the process of DNA uptake in
H. pylori
. In this study we identified and functionally characterized further (T4SS-homologous) components of the
comB
transformation competence system. By combining computer prediction modeling, experimental topology determination, generation of knockout strains, and genetic complementation studies we identified ComB2, ComB3, and ComB6 as essential components of the transformation apparatus, structurally and functionally homologous to VirB2, VirB3, and VirB6, respectively.
comB2
,
comB3
, and
comB4
are organized as a separate operon. Thus, for the
H. pylori comB
system, all T4SS core components have been identified except for homologues to VirB1, VirD4, VirB5, and VirB11.
Polyamine-Mediated Resistance of Uropathogenic
Escherichia coli
to Nitrosative Stress
Authors: Bower Jean M. , Mulvey Matthew A.
Published: January 2006

During the course of a urinary tract infection, substantial levels of nitric oxide and reactive nitrogen intermediates are generated. We have found that many uropathogenic strains of
Escherichia coli
display far greater resistance to nitrosative stress than the K-12 reference strain MG1655. By selecting and screening for uropathogenic
E. coli
transposon mutants that are unable to grow in the presence of acidified nitrite, the
cadC
gene product was identified as a key facilitator of nitrosative stress resistance. Mutation of
cadC
, or its transcriptional targets
cadA
and
cadB
, results in loss of significant production of the polyamine cadaverine and increased sensitivity to acidified nitrite. Exogenous addition of cadaverine or other polyamines rescues growth of
cad
mutants under nitrosative stress. In wild-type cells, the concentration of cadaverine produced per cell is substantially increased by exposure to acidified nitrite. The mechanism behind polyamine-mediated rescue from nitrosative stress is unclear, but it is not attributable solely to chemical quenching of reactive nitrogen species or reduction in mutation frequency.
Effect of Nitrogen Source on Cyanophycin Synthesis in
Synechocystis
sp. Strain PCC 6308
Authors: Kolodny Nancy H. , Bauer Deborah , Bryce Kerstyn , Klucevsek Kristen , Lane Amy , Medeiros Lea , Mercer Wendy , Moin Sogole , Park Deborah , Petersen Juliette , Wright Julie , Yuen Courtney , Wolfson Adele J. , Allen Mary M.
Published: January 2006

Experiments were carried out to examine the effects of nitrogen source on nitrogen incorporation into cyanophycin during nitrogen limitation and repletion, both with or without inhibition of protein synthesis, in cyanobacteria grown on either nitrate or ammonium. The use of nitrate and ammonium,
14
N labeled in the growth medium and
15
N labeled in the repletion medium, allows the determination of the source of nitrogen in cyanophycin using proton nuclear magnetic resonance spectroscopy. The data suggest that nitrogen from both the breakdown of cellular protein (
14
N) and directly from the medium (
15
N) is incorporated into cyanophycin. Nitrogen is incorporated into cyanophycin at different rates and to different extents, depending on the source of nitrogen (ammonium or nitrate) and whether the cells are first starved for nitrogen. These differences appear to be related to the activity of nitrate reductase in cells and to the possible expression of cyanophycin synthetase during nitrogen starvation.
Characterization of
cis-
Acting Sites Controlling Arginine Deiminase Gene Expression in
Streptococcus gordonii
Authors: Zeng Lin , Dong Yiqian , Burne Robert A.
Published: January 2006

The arginine deiminase system (ADS) is responsible for the production of ornithine, CO
2
, ammonia, and ATP from arginine. The ADS of the oral bacterium
Streptococcus gordonii
plays major roles in physiologic homeostasis, acid tolerance, and oral biofilm ecology. To further our understanding of the transcriptional regulation of the ADS (
arc
) operon, the binding of the ArcR transcriptional activator, which governs expression of the ADS in response to arginine, was investigated by DNase I protection and gel mobility shift assays. An ArcR binding sequence was found that was 27 bp in length and had little sequence similarity to binding sites of other arginine metabolism regulators. The presence of arginine at physiologically relevant concentrations enhanced the binding of ArcR to its target. Using
cat
fusions, various deletion and substitution mutations within the putative ArcR footprint were shown to cause dramatic reductions in expression from the
arcA
promoter in vivo, confirming that the 27-bp sequence is required for optimal expression and induction of the ADS by arginine. Mutation of two putative catabolite response elements (CREs) within the
arc
promoter region showed that both CREs contribute to catabolite repression. A thorough understanding of the regulation of the ADS in
S. gordonii
and related organisms is needed to develop ways to exploit arginine catabolism for the control of oral diseases. Identification of the ArcR and CcpA binding sites lays the foundation for a more complete understanding of the complex interactions of multiple regulatory proteins with elements in the
arc
promoter region.
THE ΩDE-ΩM PLANE IN DARK ENERGY COSMOLOGY
Authors: QIANG YUAN , ZHANG TONG-JIE
Published: January 2006

The dark energy cosmology with the equation of state w= const. is considered in this paper. The ΩDE-ΩM plane has been used to study the present state and expansion history of the universe. Through the mathematical analysis, we give the theoretical constraint of cosmological parameters. Together with some observations such as the transition redshift from deceleration to acceleration, more precise constraint on cosmological parameters can be acquired.
WHERE ARE ELKO SPINOR FIELDS IN LOUNESTO SPINOR FIELD CLASSIFICATION?
Authors: DA ROCHA R. , RODRIGUES W. A.
Published: January 2006

This paper proves that from the algebraic point of view ELKO spinor fields belong together with Majorana spinor fields to a wider class, the so-called flagpole spinor fields, corresponding to the class 5, according to Lounesto spinor field classification. We show moreover that algebraic constraints imply that any class 5 spinor field is such that the 2-component spinor fields entering its structure have opposite helicities. The proof of our statement is based on Lounesto general classification of all spinor fields, according to the relations and values taken by their associated bilinear covariants, and can eventually shed some new light on the algebraic investigations concerning dark matter.
CRITICAL BEHAVIOR OF STRONGLY COUPLED LATTICE QCD AT FINITE TEMPERATURE
Authors: UMINO YASUO
Published: January 2006

We study the critical behavior of lattice Quantum Chromodynamics (QCD) in the strong coupling approximation with Kogut–Susskind and Wilson fermions at finite temperature (T) and zero chemical potential. Using the Hamiltonian formulation we construct a mean field solution to the equation of motion at finite T and use it to study the elementary thermal excitations and to extract some critical exponents characterizing the observed second-order phase transition. We find similar critical behaviors for Kogut–Susskind and Wilson fermions at finite T.
DO WE HAVE EVIDENCE FOR NEW PHYSICS IN THE SKY?
Authors: MERSINI-HOUGHTON LAURA
Published: January 2006

Predicting signatures of string theory on cosmological observables is not sufficient. Often the observable effects string theory may impact upon the cosmological arena which may equally be predicted by features of inflationary physics. The question: what observable signatures are unique to new physics, is thus of crucial importance for claiming evidence for the theory. Here we discuss recent progress in addressing the above question. The evidence relies on identifying discrepancies between the source terms that give rise to large scale structure (LSS) and CMB, by cross-correlating the weak lensing potential that maps LSS with the CMB spectra.