bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum back reactions in slow-roll cosmologies
Authors: Losic B , Unruh W G
Published: September 2006

We summarize the results of a calculation (B. Losic and W.G. Unruh. Phys. Rev. D, 72, 123510 (2005).) of cosmological back reactions about a slowly rolling background space-time. In particular, we evaluate the effect of the superhorizon second-order corrections on the (superhorizon) inhomogeneous modes of the linearized fluctuations. Their physical significance is quantified by studying their effective equation of state, where the isotropic pressure and energy density at second order are defined in terms of the averaged eigenvalues associated with timelike (spacelike) eigenvectors of a total stress energy for the metric and matter fluctuations. Given a well-defined gauge fixing at second order, we find that the higher order corrections may dominate those of the linear terms and, furthermore, that this result holds for other reasonable gauge-fixing procedures. Our work suggests that for many parameters of slow-roll inflation, the second-order effects may dominate over the first-order effects for the super-Hubble evolution. We also find that the contribution to the equation of state due to the back reactions is that of a negative cosmological constant in this coordinate gauge, confirming earlier work.PACS Nos.: 31.15.Pf, 31.30.Jv, 32.10.Hq
When is the lowest order WKB quantization exact?
Authors: Bhaduri R K , Sprung D W.L. , Suzuki A
Published: September 2006

First, two conditions are specified for the lowest order Wentzel–Kramers–Brillouin quantization rule to yield exact results. These rules are related to the periodic orbit decomposition of the quantum density of states. This approach is then applied to supersymmetric quantum mechanics. It leads to a new derivation of the result that shape-invariant potentials give exact results when the classical action is calculated with the square of the super potential, but without the Maslov index or the Langer correction.PACS Nos.: 03.65.Sq, 12.60.Jv
Black holes: Quantum trapping and singularity resolution
Authors: Husain V , Winkler O
Published: September 2006

We describe recent progress on the problem of gravitational collapse in quantum gravity. The model we study is the gravity-scalar field theory in spherical symmetry, which is the original setting for Hawking's semiclassical work on black-hole radiation. We present an approach to full quantization of this model in a Hamiltonian framework, with a view to understanding the late time behaviour of collapsing matter. We give operator realizations of curvature and null expansion variables. The first of these operators has a bounded spectrum indicating curvature singularity avoidance; the second provides a "quantum trapping" criterion for detecting whether a quantum state describes a black hole. It leads to the physical result that the boundary of a quantum black hole is subject to quantum fluctuations. We describe an approach to quantum dynamics, whereby an initial state can be evolved, and tracked to the point of quantum trapping and beyond.PACS Nos.: 04.60.m, 04.60.Ds, 04.70.Dy
Magnetic quantization over Riemannian manifolds
Authors: Karasev M V , Osborn T A
Published: September 2006

We demonstrate that Weyl's pioneering idea (1918) to intertwine metric and magnetic fields into a single joint connection can be naturally realized, on the phase space level, by the gauge-invariant quantization of the cotangent bundle with magnetic symplectic form. Quantization, for systems over a noncompact Riemannian configuration manifold, may be achieved by the introduction of a magneto-metric analog of the Stratonovich quantizer — a family of invertible, selfadjoint operators representing quantum δ functions. Based on the quantizer, we construct a generalized Wigner transform that maps Hilbert–Schmidt operators into L2 phase-space functions. The algebraic properties of the quantizer allow one to extract a family of symplectic reflections, which are then used to (i) derive a simple, explicit, and geometrically invariant formula for the noncommutative product of functions on phase space, and (ii) construct a magneto-metric connection on phase space. The classical limit of this product is given by the usual multiplication of functions (zeroth-order term), the magnetic Poisson bracket (first-order term), and by the magneto-metric connection (second-order term).PACS Nos.: 02.40.-k, 11.10.Nx
On local-hidden-variable no-go theorems
Authors: Méthot A A
Published: September 2006

The strongest attack against quantum mechanics came in 1935 in the form of a paper by Einstein, Podolsky, and Rosen. It was argued that the theory of quantum mechanics could not be called a complete theory of Nature, for every element of reality is not represented in the formalism as such. The authors then put forth a proposition: we must search for a theory where, upon knowing everything about the system, including possible hidden variables, one could make precise predictions concerning elements of reality. This project was ultimately doomed in 1964 with the work of Bell, who showed that the most general local hidden variable theory could not reproduce correlations that arise in quantum mechanics. There exist mainly three forms of no-go theorems for local hidden variable theories. Although almost every physicist knows the consequences of these no-go theorems, not every physicist is aware of the distinctions between the three or even their exact definitions. Thus, we will discuss here the three principal forms of no-go theorems for local hidden variable theories of Nature. We will define Bell theorems, Bell theorems without inequalities, and pseudo-telepathy. A discussion of the similarities and differences will follow. PACS Nos.: 03.65.–w, 03.65.Ud, 03.65.Ta
Variational wave equations for relativistic few-body systems in QFT
Authors: Darewych J W
Published: September 2006

The variational method in a reformulated Hamiltonian formalism of quantum field theory is used to derive relativistic few-body wave equations for scalar and Fermion fields. Analytic and approximate solutions of some two-body bound states are presented.PACS Nos.: 03.65.Pm, 03.65.Ge, 03.70.+k, 11.10.Ef, 11.10.St, 11.15.Tk, 36.10.Dr
Radiative electroweak symmetry breaking beyond leading logarithms
Authors: Elias V , Mann R B , McKeon D.G.C. , Steele T G
Published: September 2006

The top-quark Yukawa coupling is too large to permit radiative electroweak symmetry breaking to occur, to leading-logarithm order, for small values of y — the Higgs self-coupling. However, a large y solution leading to a viable Higgs mass of approximately 220 GeV does exist, and differs from conventional symmetry breaking by an approximately five-fold enhancement of the Higgs self-coupling. This scenario for radiative symmetry breaking is reviewed, and the order-by-order perturbative stability of this scenario is studied within the scalar-field theory projection of the Standard Model in which the Higgs self-coupling y represents the dominant Standard-Model coupling.PACS Nos.: 11.30.Qc, 11.10.Hi, 11.15.Tk, 12.15.Lk
Looking beyond inflationary cosmology
Authors: Brandenberger R H
Published: September 2006

In spite of the phenomenological successes of the inflationary universe scenario, the current realizations of inflation making use of scalar fields lead to serious conceptual problems that are reviewed in this lecture. String theory may provide an avenue towards addressing these problems. One particular approach to combining string theory and cosmology is String Gas Cosmology. The basic principles of this approach are summarized.PACS No.: 98.80.Cq}
A new mechanism for inducing currents on superconducting strings
Authors: Metlitski M A
Published: September 2006

It is well known that fermion zero modes concentrated in the core of a topological defect can endow the defect with highly nontrivial physical properties. A particular example of this phenomenon, due to Witten, is the so-called string superconductivity, when the application of an electric field along the string leads to the appearance of a persistent current in the string direction. In this paper, I will show that a current along the string can also be induced by placing the string in an environment with a nonzero fermion chemical potential and temperature. The resulting current is exactly calculable and topological in nature. I will also discuss how the interest in this problem was motivated by the study of topological defects in dense quark matter. PACS No.: 11.27.+d
Lorentz violation and super-symmetry
Authors: Pospelov M
Published: September 2006

We review recent progress in constructing supersymmetric field theories modified by the presence of constant vector and tensor backgrounds, or in other words SUSY field theories with Lorentz violation (LV). We show that the requirement of supersymmetry and gauge invariance limits the LV in the minimal supersymmetric Standard Model to dimension five and higher levels, giving a natural explanation to the smallness of the Lorentz violation. We show main phenomenological features of such models, among which is the absence of large LV corrections to dispersion relations, and include radiative corrections. We show that 1/MPlanck normalized corrections are ruled out at the 10–10 level. PACS Nos.: 11.30.Cp, 11.30.Pb, 11.10.Hi
Aspects of brane-antibrane inflation
Authors: Cline James M
Published: September 2006

I describe a dynamical mechanism for solving the fine-tuning problem of brane-antibrane inflation. By inflating with stacks of branes and antibranes, the branes can naturally be trapped at a metastable minimum of the potential. As branes tunnel out of this minimum, the shape of the potential changes to make the minimum shallower. Eventually the minimum disappears and the remaining branes roll slowly because the potential is nearly flat. I show that even with a small number of branes, there is a good chance of getting enough inflation. Running of the spectral index is correlated with the tilt in such a way as to provide a test of the model by future cosmic microwave background experiments.PACS Nos.: 11.25.Wx, 98.80.Cq
Photoionization of ground 1s2 2s2 2p6 1Se0 and excited 1s2 2S22p53S 3Po0,1,2 states of Si V using relativistic Breit–Pauli R-matrix method
Authors: Jha AK S , Singh N , Verma N , Mohan M
Published: September 2006

The close-coupling R-matrix method has been used to calculate photoionization cross sections for the ground and the lowest three excited states using the relativistic Breit–Pauli approximation. Configuration interaction wave-functions are used to represent eleven lowest LSJ target states of Si VI retained in the R-matrix expansion. Relativistic effects are clearly revealed from resonance converging on the excited states of Si VI.PACS No.: 32.80.Fb
The standard cosmological model
Authors: Scott D
Published: September 2006

The Standard Model of Particle Physics (SMPP) is an enormously successful description of high-energy physics, driving ever more precise measurements to find "physics beyond the standard model", as well as providing motivation for developing more fundamental ideas that might explain the values of its parameters. Simultaneously, a description of the entire three-dimensional structure of the present-day Universe is being built up painstakingly. Most of the structure is stochastic in nature, being merely the result of the particular realization of the "initial conditions" within our observable Universe patch. However, governing this structure is the Standard Model of Cosmology (SMC), which appears to require only about a dozen parameters. Cosmologists are now determining the values of these quantities with increasing precision to search for "physics beyond the standard model", as well as trying to develop an understanding of the more fundamental ideas that might explain the values of its parameters. Although it is natural to see analogies between the two Standard Models, some intrinsic differences also exist, which are discussed here. Nevertheless, a truly fundamental theory will have to explain both the SMPP and SMC, and this must include an appreciation of which elements are deterministic and which are accidental. Considering different levels of stochasticity within cosmology may make it easier to accept that physical parameters in general might have a nondeterministic aspect. PACS Nos.: 98.80.–k, 98.80.Bp, 98.80.Es, 12.60.–i
DESCRIPTION OF SEISMIC EVENTS USING WAVELET TRANSFORM
Authors: ČASTOVÁ NINA , HORÁK DAVID , KALÁB ZDENĚK
Published: September 2006

This paper deals with engineering application of wavelet transform for processing of real seismological signals. Methodology for processing of these slight signals using wavelet transform is presented in this paper. Briefly, three basic aims are connected with this procedure:.

1. Selection of optimal wavelet and optimal wavelet basis B opt for selected data set based on minimal entropy: B opt = arg min B E(X,B). The best results were reached by symmetric complex wavelets with scaling coefficients SCD-6.

2. Wavelet packet decomposition and filtration of data using universal criterion of thresholding of the form [Formula: see text], where σ is minimal variance of the sum of packet decomposition of chosen level.

3. Cluster analysis of decomposed data.

All programs were elaborated using program MATLAB 5.
REFINEMENT EQUATIONS AND CORRESPONDING LINEAR OPERATORS
Authors: PROTASOV VLADIMIR
Published: September 2006

Refinement equations of the type [Formula: see text] play an exceptional role in the theory of wavelets, subdivision algorithms and computer design. It is known that the regularity of their compactly supported solutions (refinable functions) depends on the spectral properties of special N-dimensional linear operators T0, T1constructed by the coefficients of the equation. In particular, the structure of kernels and of common invariant subspaces of these operators have been intensively studied in the literature. In this paper, we give a complete classification of the kernels and of all the root subspaces of T0and T1, as well as of their common invariant subspaces. This result answers several open questions stated in the literature and clarifies the structure of the space spanned by the integer translates of refinable functions. This also leads to some results on the moduli of continuity of refinable functions and wavelets in various functional spaces. In particular, it is proved that the Hölder exponent of those functions is sharp whenever it is not an integer.
PROPERTIES AND APPLICATIONS OF NEW POLYNOMIAL SPACES
Authors: COSTANTINI PAOLO
Published: September 2006

The aim of this paper is to describe a new five-dimensional, variable degree polynomial space. This space has the same properties of P4 and possesses generalized tension properties, in the sense that it is close to P2 for large values of the degrees. Its applications in the construction of spline functions will also be discussed.
A NOTE ON A MATRIX APPROACH TO MULTIWAVELET APPLICATIONS
Authors: BACCHELLI SILVIA , PAPI SERENA
Published: September 2006

In recent years, many papers have been devoted to the topic of balanced multiwavelets, namely, multiwavelet bases which are especially designed to avoid the prefiltering step in the implementation of the multiwavelet transform. In this work, we give a simple algebraic proof of how scalar wavelets can be reinterpreted as the most natural balanced multiwavelets, which maintain the good properties of the wavelet bases they come from. We then show how these new bases can be successfully used to apply matrix thresholding for the denoising of images corrupted by Gaussian noise. In fact, this new approach discovers a balanced matrix nature in Daubechies bases, hence obtaining better numerical results with respect to those achieved via scalar thresholding. In particular, this reinterpretation of scalar wavelets as balanced multiwavelets allows us to successfully use the thresholding filters, previously introduced in the scalar case, in a matrix setting.
WAVELET BASED MULTILEVEL BACKPROJECTION ALGORITHM FOR PARALLEL AND FAN BEAM SCANNING GEOMETRIES
Authors: SASTRY CHALLA S. , DAS P. C.
Published: September 2006

In the present work, a new multilevel backprojection procedure for both parallel and fan beam geometries based on 1D MRA wavelet is derived and analyzed. It is based on the characterization property of orthonormal wavelets via their autocorrelation functions. The algorithm does not involve any wavelet-based decomposition in the normal sense, yet it uses a multiresolution formula as a crucial element in a CBP type procedure valid for both the parallel and complex fan beam geometries. The algorithm can be used for wavelet based image analysis.
ON PERTURBATION OF BANACH FRAMES
Authors: JAIN P. K. , KAUSHIK S. K. , VASHISHT L. K.
Published: September 2006

A necessary and sufficient condition for the perturbation of a Banach frame by a non-zero functional to be a Banach frame has been obtained. Also a sufficient condition for the perturbation of a Banach frame by a sequence in E* to be a Banach frame has been given. Finally, a necessary condition for the perturbation of a Banach frame by a finite linear combination of linearly independent functionals in E* to be a Banach frame has been given.
EMPOWERING ENTREPRENEURSHIP THROUGH FORESIGHT AND INNOVATION: DEVELOPING A THEORETICAL FRAMEWORK FOR EMPOWERMENT IN ENTERPRISE PROGRAMS
Authors: O'CONNOR ALLAN , RAMOS JOSE M.
Published: September 2006

This study explores how education and development in the skills and knowledge of foresight, innovation and enterprise (FI and E) relate to the empowerment of young individuals with respect to creating a new venture. In 2003, three groups of young persons aged between 13 and 18 years participated in a program designed for empowerment. An evaluation was conducted nine months later that provided useful insight into the impact of the education design, content and delivery. This research provides deeper insight into the way FI and E education can be used to create empowerment through the derivation of a framework that addresses entry, process and agency factors.
SEARCHING FOR WORTMAN'S RURAL ECONOMIC DEVELOPMENT ZONES: A CASE STUDY OF THREE RURAL ELECTRIC COOPERATIVES
Authors: HERIOT KIRK C. , CAMPBELL NOEL D.
Published: September 2006

This study uses Wortman's Rural Economic Development Zones (Wortman, 1990a) and more recent work by Lyons (2002) as a point of departure to demonstrate entrepreneurship development suited to rural locations. We describe the current literature and rural electric cooperatives. Using a case method research design (Yin, 1994), we demonstrate the efforts of three modern rural electric cooperatives in the area of entrepreneurial development. The study concludes with a discussion of the implications to public policy makers, electric cooperative executives and researchers in the field of entrepreneurship.
Rethinking Electronic Health Records to Better Achieve Quality and Safety Goals
Authors: Stead William W.
Published: September 2006

Health care information technology changes the ecosystem of a practice. Human roles, process work flow, and technology infrastructure are tightly interrelated. Medical errors may increase if a change in one is not accommodated by a change in the others. Introduction of information technology should be approached as an iterative process of care improvement rather than as a one-time insertion of an information system into established practice. Information technology supports a family of technological approaches, each with distinct mechanisms of action, benefits, and side effects. By matching technological approach to task and staging introduction into practice, initial benefit can be obtained more quickly, at reduced cost, while managing risk of a misfit. A staged approach to turning direct access by patients to their health information into more effective care is presented as an example of this strategy.
Inflammatory Bowel Disease Genetics: Nod2
Authors: Cho Judy H. , Abraham Clara
Published: September 2006

The inflammatory bowel diseases (IBD) are comprised of two major subphenotypes, Crohn's disease (CD) and ulcerative colitis (UC). A significant role for genetic factors in IBD was established from epidemiologic studies and, more recently, the identification of well-established disease associations, notably the association of Nod2 (CARD15) polymorphisms with CD. The mapping to CD of Nod2 variants that alter protein function represents one of the earliest, most well-established, associations in complex genetic disorders. Since the initial discovery, genotype-phenotype correlations, definition of Nod2 expression and signaling pathways, association studies in other, related disorders, and features of Nod2 deficiency in murine models have been reported. Taken together, the Nod2 association to CD provides an illustrative model of the role of single gene variants in disease pathogenesis for common, complex multigenic disorders. Here we review general aspects of IBD genetics with particular focus on the role of Nod2 in CD.
New Reagents on the Horizon for Immune Tolerance
Authors: St. Clair E. William , Turka Larry A. , Saxon Andrew , Matthews Jeffrey B. , Sayegh Mohamed H. , Eisenbarth George S. , Bluestone Jeffrey
Published: September 2006

Recent advances in immunology and a growing arsenal of new drugs are bringing the focus of tolerance research from animal models into the clinical setting. The conceptual framework for therapeutic tolerance induction has shifted from a “sledgehammer” approach that relies solely on cellular depletion and cytokine targeting, to a strategy directed toward restoring a functional balance across the immune system, namely the different populations of naive cells, effector and memory cells, and regulatory cells. Unlocking the key to tolerance induction in the future will likely depend on our ability to harness the functions of T regulatory cells. Also, dendritic cells are strategically positioned at the interface between innate and adaptive immunity and may be subject to deliberate medical intervention in a way that can control a chronic inflammatory response. Many reagents with tolerance-inducing potential are currently undergoing clinical testing in transplantation, autoimmune diseases, and allergic diseases, and even more that are on the horizon promise to offer enormous benefits to human health.
Advances in the Treatment of Prostate Cancer
Authors: Pomerantz Mark , Kantoff Philip
Published: September 2006

Several recent advances have been made in the management of prostate cancer. Active surveillance is an increasingly attractive and reasonable approach for those with low-volume, low-risk disease. For locally advanced or localized high-risk disease, neoadjuvant and adjuvant therapies are emerging as the standard of care. Innovative uses of traditional hormonal treatments can potentially limit common side effects. Recent data also support the utility of second-line hormonal therapy. For the first time, a survival advantage with the use of chemotherapy has been established. Much work is under way to augment its efficacy with novel agents such as targeted therapeutics and tumor vaccines. Recent scientific breakthroughs suggest additional strategies in treating prostate cancer.
PPARα mediates the hypolipidemic action of fibrates by antagonizing FoxO1
Authors: Qu Shen , Su Dongming , Altomonte Jennifer , Kamagate Adama , He Jing , Perdomo German , Tse Tonia , Jiang Yu , Dong H. Henry
Published: September 2006

High-fructose consumption is associated with insulin resistance and diabetic dyslipidemia, but the underlying mechanism is unclear. We show in hamsters that high-fructose feeding stimulated forkhead box O1 (FoxO1) production and promoted its nuclear redistribution in liver, correlating with augmented apolipoprotein C-III (apoC-III) production and impaired triglyceride metabolism. High-fructose feeding upregulated peroxisome proliferator-activated receptor-γ coactivator-1β and sterol regulatory element binding protein-1c expression, accounting for increased fat infiltration in liver. High-fructose-fed hamsters developed hypertriglyceridemia, accompanied by hyperinsulinemia and glucose intolerance. These metabolic aberrations were reversible by fenofibrate, a commonly used anti-hypertriglyceridemia agent that is known to bind and activate peroxisome proliferator-activated receptor-α (PPARα). PPARα physically interacted with, but functionally antagonized, FoxO1 in hepatic apoC-III expression. These data underscore the importance of FoxO1 deregulation in the pathogenesis of hypertriglyceridemia in high-fructose-fed hamsters. Counterregulation of hepatic FoxO1 activity by PPARα constitutes an important mechanism by which fibrates act to curb apoC-III overproduction and ameliorate hypertriglyceridemia.
The dominant negative thyroid hormone receptor β-mutant Δ337T alters PPARα signaling in heart
Authors: Buroker Norman E. , Young Martin E. , Wei Caimiao , Serikawa Kyle , Ge Ming , Ning Xue-Han , Portman Michael A.
Published: September 2006

PPARα and TR independently regulate cardiac metabolism. Although ligands for both these receptors are currently under evaluation for treatment of congestive heart failure, their interactions or signaling cooperation have not been investigated in heart. We tested the hypothesis that cardiac TRs interact with PPARα regulation of target genes and used mice exhibiting a cardioselective Δ337T TRβ1 mutation (MUT) to reveal cross-talk between these nuclear receptors. This dominant negative transgene potently inhibits DNA binding for both wild-type (WT) TRα and TRβ. We used UCP3 and MTE-1 as principal reporters and analyzed gene expression from hearts of transgenic (MUT) and nontransgenic (WT) littermates 6 h after receiving either specific PPARα ligand (WY-14643) or vehicle. Interactions were determined through qRT-PCR analyses, and the extent of these interactions across multiple genes was determined using expression arrays. In the basal state, we detected no differences between groups for protein content for UCP3, PPARα, TRα2, RXRβ, or PGC-1α. However, protein content for TRα1 and the PPARα heterodimeric partner RXRα was diminished in MUT, whereas PPARβ increased. We demonstrated cross-talk between PPAR and TR for multiple genes, including the reporters UCP3 and MTE1. WY-14643 induced a twofold increase in UCP3 gene expression that was totally abrogated in MUT. We demonstrated variable cross-talk patterns, indicating that multiple mechanisms operate according to individual target genes. The non-ligand-binding TRβ1 mutation alters expression for multiple nuclear receptors, providing a novel mechanism for interaction that has not been previously demonstrated. These results indicate that therapeutic response to PPARα ligands may be determined by thyroid hormone state and TR function.
Effects of 3-phosphoglycerate and other metabolites on the activation of AMP-activated protein kinase by LKB1-STRAD-MO25
Authors: Ellingson W. J. , Chesser D. G. , Winder W. W.
Published: September 2006

Skeletal muscle contraction results in the phosphorylation and activation of the AMP-activated protein kinase (AMPK) by an upstream kinase (AMPKK). The LKB1-STE-related adaptor (STRAD)-mouse protein 25 (MO25) complex is the major AMPKK in skeletal muscle; however, LKB1-STRAD-MO25 activity is not increased by muscle contraction. This relationship suggests that phosphorylation of AMPK by LKB1-STRAD-MO25 during skeletal muscle contraction may be regulated by allosteric mechanisms. In this study, we tested an array of metabolites including, glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-bisphosphate, 3-phosphoglycerate (3-PG), glucose 1-phosphate, glucose 1,6-bisphosphate, ADP, carnitine, acetylcarnitine, IMP, inosine, and ammonia for allosteric regulation. ADP inhibited both AMPK and LKB1-STRAD-MO25 actions, but probably is not important physiologically because of the low free ADP inside the muscle fiber. We found that 3-PG stimulated LKB1-STRAD-MO25 activity and allowed for increased AMPK phosphorylation. 3-PG did not stimulate LKB1-STRAD-MO25 activity toward the peptide substrate LKB1tide. These results have identified 3-PG as an AMPK-specific regulator of AMPK phosphorylation and activation by LKB1-STRAD-MO25.
The LDL receptor is not necessary for acute adrenal steroidogenesis in mouse adrenocortical cells
Authors: Kraemer Fredric B. , Shen Wen-Jun , Patel Shailja , Osuga Jun-ichi , Ishibashi Shun , Azhar Salman
Published: September 2006

Steroid hormones are synthesized using cholesterol as precursor. To determine the functional importance of the low density lipoprotein (LDL) receptor and hormone-sensitive lipase (HSL) in adrenal steroidogenesis, adrenal cells were isolated from control, HSL−/−, LDLR−/−, and double LDLR/HSL−/−mice. The endocytic and selective uptake of apolipoprotein E-free human high density lipoprotein (HDL)-derived cholesteryl esters did not differ among the mice, with selective uptake accounting for >97% of uptake. In contrast, endocytic uptake of either human LDL- or rat HDL-derived cholesteryl esters was reduced 80–85% in LDLR−/−and double- LDLR/HSL−/−mice. There were no differences in the selective uptake of either human LDL- or rat HDL-derived cholesteryl esters among the mice. Maximum corticosterone production induced by ACTH or dibutyryl cyclic AMP and lipoproteins was not altered in LDLR−/−mice but was reduced 80–90% in HSL−/−mice. Maximum corticosterone production was identical in HSL−/−and double- LDLR/HSL−/−mice. These findings suggest that, although the LDL receptor is responsible for endocytic delivery of cholesteryl esters from LDL and rat HDL to mouse adrenal cells, it appears to play a negligible role in the delivery of cholesterol for acute adrenal steroidogenesis in the mouse. In contrast, HSL occupies a vital role in adrenal steroidogenesis because of its link to utilization of selectively delivered cholesteryl esters from lipoproteins.
Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in klotho mice
Authors: Segawa Hiroko , Yamanaka Setsuko , Ohno Yasue , Onitsuka Akemi , Shiozawa Kazuyo , Aranami Fumito , Furutani Junya , Tomoe Yuka , Ito Mikiko , Kuwahata Masashi , Imura Akihiro , Nabeshima Yoichi , Miyamoto Ken-ichi
Published: September 2006

Recent studies have demonstrated that klotho protein plays a role in calcium/phosphate homeostasis. The goal of the present study was to investigate the regulation of Na-Pi cotransporters in klotho mutant (kl/kl) mice. The kl/kl mice displayed hyperphosphatemia, high plasma 1,25(OH)2D3 levels, increased activity of the renal and intestinal sodium-dependent Pi cotransporters, and increased levels of the type IIa, type IIb, and type IIc transporter proteins compared with wild-type mice. Interestingly, transcript levels of the type IIa/type IIc transporter mRNA abundance, but not transcripts levels of type IIb transporter mRNA, were markedly decreased in kl/kl mice compared with wild-type mice. Furthermore, plasma fibroblast growth factor 23 (FGF23) levels were 150-fold higher in kl/kl mice than in wild-type mice. Feeding of a low-Pi diet induced the expression of klotho protein and decreased plasma FGF23 levels in kl/kl mice, whereas colchicine treatment experiments revealed evidence of abnormal membrane trafficking of the type IIa transporter in kl/kl mice. Finally, feeding of a low-Pi diet resulted in increased type IIa Na-Pi cotransporter protein in the apical membrane in the wild-type mice, but not in kl/kl mice. These results indicate that hyperphosphatemia in klotho mice is due to dysregulation of expression and trafficking of the renal type IIa/IIc transporters rather than to intestinal Pi uptake.
Dynamics of aquaporin-2 serine-261 phosphorylation in response to short-term vasopressin treatment in collecting duct
Authors: Hoffert Jason D. , Nielsen Jakob , Yu Ming-Jiun , Pisitkun Trairak , Schleicher Stephen M. , Nielsen Soren , Knepper Mark A.
Published: September 2006

We recently identified a novel phosphorylation site, serine-261 (pS261), in the COOH-terminus of the vasopressin-regulated water channel, aquaporin-2 (AQP2). To address whether phosphorylation at this site is regulated by vasopressin, a rabbit polyclonal phospho-specific antibody was generated. Dot blot and immunoblot analysis demonstrated that this antibody specifically recognizes AQP2 phosphorylated at pS261, and that phosphorylation of S256 (pS256), a site already known to be regulated by vasopressin, does not interfere with antibody recognition. Immunohistochemical analysis revealed intense pS261 labeling of inner medullary collecting duct (IMCD) from wild-type mice, while sections from AQP2 knockout animals showed a general absence of labeling. AQP2 pS261 was present in principal cells of all mouse and rat distal tubule segments from the connecting tubule to the terminal IMCD. Co-immunolabeling of collecting duct with phospho-specific and total AQP2 antibodies revealed that pS261 and pS256 have distinct subcellular distributions. Levels of pS256 increased, while the amount of pS261 significantly decreased in freshly isolated rat IMCD samples incubated with 1 nM [deamino-Cys1,d-Arg8]vasopressin for 30 min. Similarly, based on immunohistochemical labeling, the amount of pS261 was reduced in all collecting duct segments of Brattleboro rats treated with [deamino-Cys1,d-Arg8]vasopressin for 2 h. This study reveals a reciprocal change in S256 and S261 phosphorylation in response to short-term vasopressin exposure, suggesting that these residues may serve distinct roles in regulation of AQP2 subcellular distribution and collecting duct water permeability.
Aminoaciduria and altered renal expression of luminal amino acid transporters in mice lacking novel gene collectrin
Authors: Malakauskas Sandra M. , Quan Hui , Fields Timothy A. , McCall Shannon J. , Yu Ming-Jiun , Kourany Wissam M. , Frey Campbell W. , Le Thu H.
Published: September 2006

Defects in renal proximal tubule transport manifest in a number of human diseases. Although variable in clinical presentation, disorders such as Hartnup disease, Dent's disease, and Fanconi syndrome are characterized by wasting of solutes commonly recovered by the proximal tubule. One common feature of these disorders is aminoaciduria. There are distinct classes of amino acid transporters located in the apical and basal membranes of the proximal tubules that reabsorb >95% of filtered amino acids, yet few details are known about their regulation. We present our physiological characterization of a mouse line with targeted deletion of the gene collectrin that is highly expressed in the kidney. Collectrin-deficient mice display a reduced urinary concentrating capacity due to enhanced solute clearance resulting from profound aminoaciduria. The aminoaciduria is generalized, characterized by loss of nearly every amino acid, and results in marked crystalluria. Furthermore, in the kidney, collectrin-deficient mice have decreased plasma membrane populations of amino acid transporter subtypes B0AT1, rBAT, and b0,+AT, as well as altered cellular distribution of EAAC1. Our data suggest that collectrin is a novel mediator of renal amino acid transport and may provide further insight into the pathogenesis of a number of human disease correlates.
Pentoxifylline protects against endotoxin-induced acute renal failure in mice
Authors: Wang Wei , Zolty Einath , Falk Sandor , Basava Veena , Reznikov Leonid , Schrier Robert
Published: September 2006

Acute renal failure (ARF) in septic patients drastically increases the mortality to 50–80%. Sepsis induces several proinflammatory cytokines including tumor necrosis factor-α (TNF-α), a major pathogenetic factor in septic ARF. Pentoxifylline has several functions including downregulation of TNF-α and endothelia-dependent vascular relaxation. We hypothesized that pentoxifylline may afford renal protection during endotoxemia either by downregulating TNF-α and/or by improving endothelial function. In wild-type mice, pentoxifylline protected against the fall in glomerular filtration rate (GFR; 105.2 ± 6.6 vs. 50.2 ± 6.6 μl/min, P < 0.01) at 16 h of LPS administration (2.5 mg/kg ip). This renal protective effect of pentoxifylline was associated with an inhibition of the rise in serum TNF-α (1.00 ± 0.55 vs. 7.02 ± 2.40 pg/ml, P < 0.05) and serum IL-1β (31.3 ± 3.6 vs. 53.3 ± 5.9 pg/ml, P < 0.01) induced by LPS. Pentoxifylline also reversed the LPS-related increase in renal iNOS and ICAM-1 and rise in serum nitric oxide (NO). Enhanced red blood cell deformability by pentoxifylline may have increased shear rate and upregulated eNOS. Studies were therefore performed in eNOS knockout mice. The renal protection against endotoxemia with pentoxifylline was again observed as assessed by GFR (119.8 ± 18.0 vs. 44.5 ± 16.2 μl/min, P < 0.05) and renal blood flow (0.86 ± 0.08 vs. 0.59 ± 0.05 ml/min, P < 0.05). Renal vascular resistance significantly decreased with the pentoxifylline (91.0 ± 5.8 vs. 178.0 ± 7.6 mmHg·ml−1·min−1, P < 0.01). Thus pentoxifylline, an FDA-approved drug, protects against endotoxemia-related ARF and involves a decrease in serum TNF-α, IL-1β, and NO as well as a decrease in renal iNOS and ICAM-1.
Cytokine mRNA profiling of peripheral blood mononuclear cells from trypanotolerant and trypanosusceptible cattle infected withTrypanosoma congolense
Authors: O'Gorman Grace M. , Park Stephen D. E. , Hill Emmeline W. , Meade Kieran G. , Mitchell Laura C. , Agaba Morris , Gibson John P. , Hanotte Olivier , Naessens Jan , Kemp Stephen J. , MacHugh David E.
Published: September 2006

To examine differences in cytokine profiles that may confer tolerance/susceptibility to bovine African trypanosomiasis, N'Dama (trypanotolerant, n = 8) and Boran (trypanosusceptible, n = 8) cattle were experimentally challenged with Trypanosoma congolense. Blood samples were collected over a 34-day period, and RNA was extracted from peripheral blood mononuclear cells. The expression levels of a panel of 14 cytokines were profiled over the time course of infection and between breeds. Messenger RNA (mRNA) transcript levels for the IL2, IL8, and IL1RN genes were significantly downregulated across the time course of infection in both breeds. There was an early increase in transcripts for genes encoding proinflammatory mediators ( IFNG, IL1A, TNF, and IL12) in N'Dama by 14 days postinfection (dpi) compared with preinfection levels that was not detected in the susceptible Boran breed. By the time of peak parasitemia, a type 2 helper T cells (TH2)-like cytokine environment was prevalent that was particularly evident in the Boran. Increases in transcripts for the IL6 (29 and 34 dpi) and IL10 (21, 25, and 29 dpi) genes were detected that were higher in the Boran compared with N'Dama. These findings highlight the implications for using murine models to study the bovine immune response to trypanosomiasis, where in some cases cytokine expression patterns differ. Overall, these data suggest that the trypanotolerant N'Dama are more capable of responding very early in infection with proinflammatory and TH1 type cytokines than the trypanosusceptible Boran and may explain why N'Dama control parasitemia more efficiently than Boran during the early stages of infection.
Review of microarray experimental design strategies for genetical genomics studies
Authors: Rosa Guilherme J. M. , de Leon Natalia , Rosa Artur J. M.
Published: September 2006

Genetical genomics approaches provide a powerful tool for studying the genetic mechanisms governing variation in complex traits. By combining information on phenotypic traits, pedigree structure, molecular markers, and gene expression, such studies can be used for estimating heritability of mRNA transcript abundances, for mapping expression quantitative trait loci (eQTL), and for inferring regulatory gene networks. Microarray experiments, however, can be extremely costly and time consuming, which may limit sample sizes and statistical power. Thus it is crucial to optimize experimental designs by carefully choosing the subjects to be assayed, within a selective profiling approach, and by cautiously controlling systematic factors affecting the system. Also, a rigorous strategy should be used for allocating mRNA samples across assay batches, slides, and dye labeling, so that effects of interest are not confounded with nuisance factors. In this presentation, we review some selective profiling strategies for genetical genomics studies, including the selection of individuals for increased genetic dissimilarity and for a higher number of recombination events. Efficient designs for studying epistasis are also discussed, as well as experiments for inferring heritability of transcriptional levels. It is shown that solving an optimal design problem generally requires a numerical implementation and that the optimality criteria should be intimately related to the goals of the experiment, such as the estimation of additive, dominance, and interacting effects, localizing putative eQTL, or inferring genetic and environmental variance components associated with transcriptional abundances.
Microarray interrogation of human metanephric mesenchymal cells highlights potentially important molecules in vivo
Authors: Price Karen L. , Long David A. , Jina Nipurna , Liapis Helen , Hubank Mike , Woolf Adrian S. , Winyard Paul J. D.
Published: September 2006

Many molecules have been implicated in kidney development, often based on experimental animal studies with organ cultures and cell lines. There are very few studies, however, that have directly addressed equivalent living human embryonic tissues. We generated renal mesenchymal cell lines from normal human metanephroi and used a microarray strategy to define changes in gene expression after stimulation with growth factors which enhance nephrogenesis in rodents. Changes were observed in 1) genes modulating diverse general cellular processes, such as matrix metalloproteinase 1 and stanniocalcin 1; 2) genes previously implicated in organogenesis e.g., sprouty 4 and midline 1; and 3) genes involved in blood vessel growth, including angiopoietin 1 and 4. Expression of these same genes was subsequently confirmed in vivo. Our novel data have identified several previously unhighlighted genes that may be implicated in differentiation programs within early human nephrogenesis.
The Exocytoskeleton
Authors: Koch Arthur L.
Published: September 2006

The murein or peptidoglycan wall enclosing most bacteria is essential for the life style of most organisms in the Domain of Bacteria. Only in special situations does it not play a role in the bacterial growth cycle. When life first appeared on this planet the cellular osmotic pressure was probably low and a sacculus was probably not relevant, but became necessary as bacterial life evolved from the complex and sophisticated cell called the Last Universal Ancestor. The construction of the murein wall outside of the cytoplasmic membrane is complex and requires elaborate special biochemistry. Growth of the sacculus in some parts of the surface and not in others is important for bacteria cells and allows them to divide and grow without becoming larger and larger and for their being able to maintain a shape characteristic of individual species.
Resolving Chromosome Segregation in Bacteria
Authors: Hazan Ronen , Ben-Yehuda Sigal
Published: September 2006

Bacterial chromosomes are evenly distributed between daughter cells, however no equivalent eukaryotic mitotic apparatus has been identified yet. Nevertheless, an advance in our understanding of the dynamics of the bacterial chromosome has been accomplished in recent years by adopting fluorescence microscopy techniques to visualize living bacterial cells. Here, some of the most recent studies that yield new insights into the nature of bacterial chromosome dynamics are described. In addition, we review in detail the current models that attempt to illuminate the mechanism of chromosome segregation in bacteria and discuss the possibility that a bacterial mitotic apparatus does indeed exist.
Type IV Pilin Structures: Insights on Shared Architecture, Fiber Assembly, Receptor Binding and Type II Secretion
Authors: Hansen Johanna K. , Forest Katrina T.
Published: September 2006

Type IV pili are long, flexible filaments that extend from the surface of Gram-negative bacteria and are formed by the polymerization of pilin subunits. This review focuses on the structural information available for each pilin subclass, type IVa and type IVb, highlighting the contributions crystal and nuclear magnetic resonance structures have made in understanding pilus function and assembly. In addition, the type II secretion pseudopilus subunit structure and helical assembly is compared to that of the type IV pilus. The pilin subunits adopt an αβ-roll fold formed by the hydrophobic packing of the C-terminal half of a long α-helix against an antiparallel β-sheet. The conserved N-terminal half of the same α-helix, as well as two sequence- and structurally-variable regions, protrude from this globular head domain. Filament models have a hydrophobic core formed by the signature long α-helices, with variable regions at the filament surface.
Mycoplasmas: A Distinct Cytoskeleton for Wall-Less Bacteria
Authors: Balish Mitchell F. , Krause Duncan C.
Published: September 2006

The bacterial genus Mycoplasma includes a large number of highly genomically-reduced species which in nature are associated with hosts either commensally or pathogenically. Several Mycoplasma species, including Mycoplasma pneumoniae, feature a multifunctional polar structure, the terminal organelle. Essential for colonization of the host and for gliding motility, the terminal organelle is associated with an internal cytoskeleton crucial to its assembly and function. This cytoskeleton is structurally and compositionally novel as compared with the cytoskeletons of other organisms, including other bacteria, is also involved in the cell division process. In this review we discuss the cytoskeletal structures and protein components of the attachment organelle and how they might interact and contribute to its various functions.
Diet and Gene Expression: Delta-5 and Delta-6 Desaturases in Healthy Chinese and European Subjects
Authors: Xiang M. , Rahman M.A. , Ai H. , Li X. , Harbige L.S.
Published: September 2006

Aim: To compare the composition of fatty acids (FAs) in diet, and the expression of delta-6 desaturase (D6D) and delta-5 desaturase (D5D) genes in peripheral blood mononuclear cells (PBMCs) between Chinese and Europeans. Methods: Three-day dietary records from 20 subjects from Beijing, China (n = 10) and Kent, UK (n = 10) were analysed. Expression of PBMC D6D and D5D genes of the subjects was determined using RT-PCR. Results: The dietary intake of Chinese subjects contained less saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs), but more essential fatty acids (EFAs) than that of Europeans. Levels of expression of PBMC D6D and D5D genes of Chinese subjects were significantly lower than those of Europeans. A significant positive correlation was found between dietary intake of total SFAs and total MUFAs and expression of PBMC D6D and D5D genes, but a significant negative correlation between dietary intake of linoleic acid (LA) and α-linolenic acid (LNA) and the expression of PBMC D6D and D5D genes. Conclusion: Intake of high SFAs and MUFAs appears to increase expression of PBMC D6D and D5D genes, whilst high EFAs intake appears to decrease expression of PBMC D6D and D5D genes. A follow-up study of the expression of D6D and D5D genes in Chinese who live in European countries with high SFA and MUFA diets would be of interest.
Wings for Flying, Lymphocytes for Defense: Spandrels, Exaptation and Specific Immunity
Authors: Ramos Gustavo C. , Vaz Nelson M. , Saalfeld Kay
Published: September 2006

The evolution of the immune system of jawed vertebrates with its vast array of clonally expressed lymphocyte receptors is usually viewed as optimized for the defense of the organism. There is a clear association between neo-Darwinism, the dominant view in current biology, and the usual description of immunological activity as adaptive immunity. Herein, using the concepts of spandrels and exaptation created by Gould and coworkers, we review data from comparative immunology and claim that the immune system was not formed as a system optimized for the defense of the organism, but rather may be viewed as a spandrel, a consequence of processes not originally linked to interactions with foreign materials.