bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrahost Evolutionary Dynamics of Canine Influenza Virus in Naïve and Partially Immune Dogs
Authors: Hoelzer Karin , Murcia Pablo R. , Baillie Gregory J. , Wood James L. N. , Metzger Stephan M. , Osterrieder Nikolaus , Dubovi Edward J. , Holmes Edward C. , Parrish Colin R.
Published: March 2010

The patterns and dynamics of evolution in acutely infecting viruses within individual hosts are largely unknown. To this end, we investigated the intrahost variation of canine influenza virus (CIV) during the course of experimental infections in naïve and partially immune dogs and in naturally infected dogs. Tracing sequence diversity in the gene encoding domain 1 of the hemagglutinin (HA1) protein over the time course of infection provided information on the patterns and processes of intrahost viral evolution and revealed some of the effects of partial host immunity. Viral populations sampled on any given day were generally characterized by mean pairwise genetic diversities between 0.1 and 0.2% and by mutational spectra that changed considerably on different days. Some observed mutations may have affected antigenicity or host range, including reversions of CIV host-associated mutations. Patterns of sequence diversity differed between naïve and vaccinated dogs, with some presumably antigenic mutations transiently reaching high frequency in the latter. CIV populations are therefore characterized by the rapid generation and clearance of genetic diversity. Potentially advantageous mutations arise readily during the course of single infections and may give rise to antigenic escape or host range variants.
5′ to 3′ mRNA Decay Factors Colocalize with Ty1 Gag and Human APOBEC3G and Promote Ty1 Retrotransposition
Authors: Dutko James A. , Kenny Alison E. , Gamache Eric R. , Curcio M. Joan
Published: March 2010

The genomic RNA of retroviruses and retrovirus-like transposons must be sequestered from the cellular translational machinery so that it can be packaged into viral particles. Eukaryotic mRNA processing bodies (P bodies) play a central role in segregating cellular mRNAs from the translational machinery for storage or decay. In this work, we provide evidence that the RNA of theSaccharomyces cerevisiaeTy1 retrotransposon is packaged into virus-like particles (VLPs) in P bodies. Ty1 RNA is translationally repressed, and Ty1 Gag, the capsid and RNA binding protein, accumulates in discrete cytoplasmic foci, a subset of which localize to P bodies. Human APOBEC3G, a potent Ty1 restriction factor that is packaged into Ty1 VLPs via an interaction with Gag, also localizes to P bodies. The association of APOBEC3G with P bodies does not require Ty1 element expression, suggesting that P-body localization of APOBEC3G and Ty1 Gag precedes VLP assembly. Additionally, we report that two P-body-associated 5′ to 3′ mRNA decay pathways, deadenylation-dependent mRNA decay (DDD) and nonsense-mediated decay (NMD), stimulate Ty1 retrotransposition. The additive contributions of DDD and NMD explain the strong requirement for general 5′ to 3′ mRNA degradation factors Dcp1, Dcp2, and Xrn1 in Ty1 retromobility. 5′ to 3′ decay factors act at a posttranslational step in retrotransposition, and Ty1 RNA packaging into VLPs is abolished in the absence of the 5′ to 3′ exonuclease Xrn1. Together, the results suggest that VLPs assemble in P bodies and that 5′ to 3′ mRNA decay is essential for the packaging of Ty1 RNA in VLPs.
Novel Type II Transmembrane Serine Proteases, MSPL and TMPRSS13, Proteolytically Activate Membrane Fusion Activity of the Hemagglutinin of Highly Pathogenic Avian Influenza Viruses and Induce Their Multicycle Replication
Authors: Okumura Yuushi , Takahashi Etsuhisa , Yano Mihiro , Ohuchi Masanobu , Daidoji Tomo , Nakaya Takaaki , Böttcher Eva , Garten Wolfgang , Klenk Hans-Dieter , Kido Hiroshi
Published: March 2010

Host cellular proteases induce influenza virus entry into cells by cleaving the viral surface envelope glycoprotein hemagglutinin (HA). However, details on the cellular proteases involved in this event are not fully available. We report here that ubiquitous type II transmembrane serine proteases, MSPL and its splice variant TMPRSS13, are novel candidates for proteases processing HA proteins of highly pathogenic avian influenza (HPAI) viruses, apart from the previously identified furin and proprotein convertases 5 and 6. HAs from all HPAI virus H5 and H7 strains have one of two cleavage site motifs, theR-X-K/R-R motif withRat position P4 and theK-K/R-K/T-R motif withKat position P4. In studies of synthetic 14-residue HPAI virus HA peptides with these cleavage site motifs, furin preferentially cleaved only HA peptides with theR-K-K-R motif in the presence of calcium and not peptides with the other motif, whereas MSPL and TMPRSS13 cleaved both types of HA peptides (those with theR/K-K-K-R motif) efficiently in the absence of calcium. Full-length recombinant HPAI virus HA with theK-K-K-R cleavage motif exhibited poor susceptibility to cleavage in the absence of MSPL or TMPRSS13 and the presence of furin in infected cells, but it was converted to mature HA subunits in transfected cells expressing MSPL or TMPRSS13, with membrane-fused giant-cell formation. This conversion and membrane fusion were suppressed by inhibitors of MSPL and TMPRSS13. Furthermore, infection with and multiplication of genetically modified live HPAI virus A/Crow/Kyoto/53/2004 (H5N1) with theK-K-K-R cleavage site motif were detected only in MSPL- and TMPRSS13-expressing cells.
Complex Interactions between the Major and Minor Envelope Proteins of Equine Arteritis Virus Determine Its Tropism for Equine CD3+T Lymphocytes and CD14+Monocytes
Authors: Go Yun Young , Zhang Jianqiang , Timoney Peter J. , Cook R. Frank , Horohov David W. , Balasuriya Udeni B. R.
Published: March 2010

Extensive cell culture passage of the virulent Bucyrus (VB) strain of equine arteritis virus (EAV) to produce the modified live virus (MLV) vaccine strain has altered its tropism for equine CD3+T lymphocytes and CD14+monocytes. The VB strain primarily infects CD14+monocytes and a small subpopulation of CD3+T lymphocytes (predominantly CD4+T lymphocytes), as determined by dual-color flow cytometry. In contrast, the MLV vaccine strain has a significantly reduced ability to infect CD14+monocytes and has lost its capability to infect CD3+T lymphocytes. Using a panel of five recombinant chimeric viruses, we demonstrated that interactions among the GP2, GP3, GP4, GP5, and M envelope proteins play a major role in determining the CD14+monocyte tropism while the tropism for CD3+T lymphocytes is determined by the GP2, GP4, GP5, and M envelope proteins but not the GP3 protein. The data clearly suggest that there are intricate interactions among these envelope proteins that affect the binding of EAV to different cell receptors on CD3+T lymphocytes and CD14+monocytes. This study shows, for the first time, that CD3+T lymphocytes may play an important role in the pathogenesis of equine viral arteritis when horses are infected with the virulent strains of EAV.
Occupational exposure to asbestos in New South Wales, Australia (1970–1989): development of an asbestos task exposure matrix
Authors: Hyland Rebecca A , Yates Deborah H , Benke Geza , Sim Malcolm , Johnson Anthony R
Published: March 2010

Objectives

To design and construct a standardised tool to provide exposure information associated with commonly used asbestos products and their related tasks in New South Wales (NSW), Australia.

Methods

Asbestos dust exposure measurements taken during workplace inspections in the 1970s and 1980s were collected and stored in an exposure database. Measurements were assigned to specific asbestos product and task groups and divided into two sampling periods 1970–1979 and 1980–1989.

Results

A total of 1578 asbestos air measurements collected from WorkCover and Dust Diseases Board company records were entered into a custom built exposure database. An asbestos-specific exposure matrix (ASTEM) was constructed in Microsoft Excel 2000, consisting of 3 axes incorporating 12 tasks, 8 asbestos products and the 2 time periods based on 872 individual measurements extracted from the exposure database. Each matrix cell contains the mean asbestos exposure levels measured in fibres/ml, 5th and 95th percentiles and number of data points in the set.

Conclusion

An ASTEM has been developed which provides exposure levels for different task/product combinations. When used in conjunction with a detailed occupational history, it will improve exposure estimates of a worker's cumulative asbestos exposure.
THE AUTOMORPHIC COHOMOLOGY AND THE RESIDUAL SPECTRUM OF HERMITIAN GROUPS OF RANK ONE
Authors: GROBNER HARALD
Published: March 2010

Let G/ℚ be an inner form of Sp4/ℚ which does not split over ℝ. Consequently, it is not quasi-split. In this paper we determine completely the automorphic cohomology of G. That is, we describe the Eisenstein and the cuspidal cohomology of congruence subgroups Γ of G with respect to arbitrary coefficient systems. In particular we establish precise nonvanishing results for cuspidal cohomology. In addition, we calculate the residual spectrum [Formula: see text] of G.
THE GENERALIZED MATRIX VALUED HYPERGEOMETRIC EQUATION
Authors: ROMÁN P. , SIMONDI S.
Published: March 2010

The matrix valued analog of the Euler's hypergeometric differential equation was introduced by Tirao in [4]. This equation arises in the study of matrix valued spherical functions and in the theory of matrix valued orthogonal polynomials. The goal of this paper is to extend naturally the number of parameters of Tirao's equation in order to get a generalized matrix valued hypergeometric equation. We take advantage of the tools and strategies developed in [4] to identify the corresponding matrix hypergeometric functions nFm. We prove that, if n = m + 1, these functions are analytic for |z| < 1 and we give a necessary condition for the convergence on the unit circle |z| = 1.
BOCHNER–MARTINELLI FORMULAS ON SINGULAR COMPLEX SPACES
Authors: ANCONA VINCENZO , GAVEAU BERNARD
Published: March 2010

Let U be a complex space of complex dimension n ≥ 2, P a point of U, π : Ũ → U a modification such that Ũ is nonsingular and D = π-1(P) is a divisor with normal crossings. A Bochner–Martinelli form on U\{P} is a [Formula: see text]-closed differential form ω on Ũ\D, of pure type (n,n - 1), logarithmic along D. Such form detects a cohomology class of H2n - 1(U\{P},ℂ) on the singular space U\{P}. Thanks to a general residue formula we prove that the forms ω give rise to an integral formula of Bochner–Martinelli type for holomorphic functions.

If U satisfies the following assumption that {there exists a compact complex space X bimeromorphic to a Kähler manifold, and a closed subspace T ⊂ X, such that X\T = U (an affine, or a quasi-projective variety satisfies the above property), we relate Bochner–Martinelli forms to the mixed Hodge structure carried by H2n-1(U\{P},ℂ). Most of our results hold for complex spaces which are not Stein.
SECOND VARIATION OF INDUCED CURVATURE TERM IN BRANE-WORLD ACTION
Authors: IOFA MIKHAIL Z.
Published: March 2010

In a 5D spacetime with a 3-brane embedded we calculate the second variation of the scalar 4D curvature term on the brane under variations of the 5D metric. It is shown that the second variation of the 4D scalar curvature term in adapted coordinates is expressed only through variations of the components of the 5D metric with 4D indices.
A NEW TWO-BODY RELATIVISTIC POTENTIAL MODEL FOR PIONIC HYDROGEN
Authors: KULIKOV D. A. , TUTIK R. S.
Published: March 2010

The new potential model for pionic hydrogen, constructed with the employment of the two-body relativistic equation, is offered. The relativistic equation, based on the extension of the SL(2, C) group to the Sp(4, C) one, describes the effect of the proton spin and anomalous magnetic moment in accordance with the results of the quantum electrodynamics. Within this approach, using the experimental data on the strong energy level shift and width of the 1s state in pionic hydrogen as input, the pion–nucleon scattering lengths have been evaluated to be [Formula: see text] and [Formula: see text]
HIDDEN ENTANGLEMENT AND UNITARITY AT THE PLANCK SCALE
Authors: ARZANO MICHELE , HAMMA ALIOSCIA , SEVERINI SIMONE
Published: March 2010

Attempts to go beyond the framework of local quantum field theory include scenarios in which the action of external symmetries on the quantum fields Hilbert space is deformed. We show how the Fock spaces of such theories exhibit a richer structure in their multi-particle sectors. When the deformation scale is proportional to the Planck energy, such new structure leads to the emergence of a "planckian" mode-entanglement, invisible to an observer that cannot probe the Planck scale. To the same observer, certain unitary processes would appear non-unitary. We show how entanglement transfer to the additional degrees of freedom can provide a potential way out of the black hole information paradox.
TWO COMPOSITE HIGGS DOUBLETS: IS IT THE LOW ENERGY LIMIT OF A NATURAL STRONG ELECTROWEAK SYMMETRY BREAKING SECTOR?
Authors: ZERWEKH ALFONSO R.
Published: March 2010

In this paper, we propose an effective model scheme that describes the electroweak symmetry breaking sector by means of composite Higgs-like scalars, following the ideas of Minimal Walking Technicolor (MWT). We argue that, because of the general failure of Extended Technicolor (ETC) to explain the mass of the top quark, it is necessary to introduce two composite Higgs bosons: one of them originated by a MWT–ETC sector and the other produced by a Topcolor sector. We focus on the phenomenological differences between the light composite Higgs present in our model and the fundamental Higgs boson predicted by the Standard Model and their production at the LHC. We show that in this scheme the main production channel of the lighter Higgs boson is the associated production with a gauge boson and WW fusion but not the gluon–gluon fusion channel which is substantially suppressed.
TOWARDS AN EFFECTIVE FIELD THEORY FOR COLD COMPRESSED BARYONIC MATTER
Authors: PAENG WON-GI , RHO MANNQUE
Published: March 2010

This is an extended version of the note taken by the first author (W.-G.P.) on a lecture given by the second author (M.R.) as a first part of the series on "Hadronic Matter Under Extreme Conditions," the principal theme of the WCU-Hanyang Program. It covers the attempts to go in a framework anchored on effective field theory of QCD from zero density to the nuclear matter density and slightly beyond, with the ultimate goal of arriving at the density relevant to compact stars, including chiral phase transition and quark matter. The focus is on the conceptual aspects rather than detailed "fitting" of the data on the kinds of physics that are being addressed to in radioactive-ion-beam machines in operation as well as in project (such as "KoRIA" in Korea) and will be explored at such forthcoming accelerators as FAIR/GSI. The approach presented here is basically different from the standard ones found in the literature in that the notion of hidden local symmetry — which underlies the chiral symmetry of the strong interactions — and its generalization to dual gravity description involving infinite tower of hidden gauge fields are closely relied on.
THE PONTRJAGIN–HOPF INVARIANTS FOR SOBOLEV MAPS
Authors: AUCKLY DAVE , KAPITANSKI LEV
Published: March 2010

Subtle issues arise when extending homotopy invariants to spaces of functions having little regularity, e.g., Sobolev spaces containing discontinuous functions. Sometimes it is not possible to extend the invariant at all, and sometimes, even when the formulas defining the invariants make sense, they may not have expected properties (e.g., there are maps having non-integral degree).

In this paper, we define a complete set of homotopy invariants for maps from three-manifolds to the two-sphere and show that these invariants extend to finite Faddeev energy maps and maps in suitable Sobolev spaces. For smooth maps, our description is proved to be equivalent to Pontrjagin's original homotopy classification from the 1930's. We further show that for the finite energy maps the invariants take on exactly the same values as for smooth maps. We include applications to the Faddeev model.

The techniques that we use would also apply to many more problems and/or other functionals. We have tried to make the paper accessible to analysts, geometers and mathematical physicists.
MINIMAL CLASSES ON THE INTERMEDIATE JACOBIAN OF A GENERIC CUBIC THREEFOLD
Authors: HÖRING ANDREAS
Published: March 2010

Let X be a smooth cubic threefold. We can associate two objects to X: the intermediate Jacobian J and the Fano surface F parametrizing lines on X. By a theorem of Clemens and Griffiths, the Fano surface can be embedded in the intermediate Jacobian and the cohomology class of its image is minimal. In this paper, we show that if X is generic, the Fano surface is the only surface of minimal class in J.
A CHARACTERIZATION OF HARDY SPACE ON STRONGLY LIPSCHITZ DOMAINS OF ℝn BY LITTLEWOOD–PALEY–STEIN FUNCTION
Authors: HUANG JIZHENG
Published: March 2010

Let Ω be a strongly Lipschitz domain of ℝn and define Hardy spaces on Ω by non-tangential maximal function. In this paper, we will give a characterization of the Hardy spaces on Ω by Littlwood–Paley–Stein function associated to L, where L is an elliptic second-order divergence operator. In order to get our result, we also consider the Lusin area integral characterization of the Hardy spaces on Ω.
MOTION PLANNING IN SPACES WITH SMALL FUNDAMENTAL GROUPS
Authors: COSTA ARMINDO , FARBER MICHAEL
Published: March 2010

We establish sharp upper bounds for the topological complexity TC(X) of motion planning algorithms in topological spaces X such that the fundamental group is "small", i.e. when π1(X) is cyclic of order ≤ 3 or has small cohomological dimension.
GH101 FAMILY OF GLYCOSIDE HYDROLASES: SUBFAMILY STRUCTURE AND EVOLUTIONARY CONNECTIONS WITH OTHER FAMILIES
Authors: NAUMOFF DANIIL G.
Published: March 2010

The GH101 family is composed of endo-α-N-acetylgalactosaminidases and their homologues. Pairwise sequence comparison and phylogenetic analysis allowed us to distinguish five to six subfamilies in this family. Diverse domain structures were found among the family members. Usually they have five irreplaceable and some optional domains. Iterative screening of the protein database revealed an evolutionary relationship of the GH101 catalytic domain with glycoside hydrolase domains from GH13, GH31, and GH70 families. Among other homologous proteins we have found representatives of COG1649, as well as members of four new families of predicted glycoside hydrolases (GHL1-GHL4).
COMPARATIVE MODELING OF COEVOLUTION IN COMMUNITIES OF UNICELLULAR ORGANISMS: ADAPTABILITY AND BIODIVERSITY
Authors: LASHIN SERGEY A. , SUSLOV VALENTIN V. , MATUSHKIN YURI G.
Published: March 2010

We propose an original program "Evolutionary constructor" that is capable of computationally efficient modeling of both population-genetic and ecological problems, combining these directions in one model of required detail level. We also present results of comparative modeling of stability, adaptability and biodiversity dynamics in populations of unicellular haploid organisms which form symbiotic ecosystems. The advantages and disadvantages of two evolutionary strategies of biota formation — a few generalists' taxa-based biota formation and biodiversity-based biota formation — are discussed.
Through space singlet energy transfers in light-harvesting systems and cofacial bisporphyrin dyads
Authors: Harvey Pierre D. , Stern Christine , Gros Claude P. , Guilard Roger
Published: March 2010

Recent discoveries from our research groups on the photophysics of a few cofacial bisporphyrin dyads for through space singlet and triplet energy transfers raised several important investigations about the mechanism of energy transfers and energy migration in light-harvesting devices, notably LH II, in the heavily investigated purple photosynthetic bacteria. The key feature is that for face-to-face and slipped dyads with controlled structure using rigid spacers or spacers with limited flexibilities, our fastest rates for singlet energy transfer are in the 10 × 109 s -1 (i.e. 100 ps time scale) for donor-acceptor distances of ~3.5–3.6 Å. The time scale for energy transfers between different bacteriochlorophylls, notably B800*→B850, is in the ps despite the long Mg ⋯ Mg separation (~18 Å). This short rate drastically contrasts with the well-accepted Förster theory. This review focuses on the photophysical processes and dynamics in LH II and compares these parameters with our investigated model dyads build upon octa-etio-porphyrin chromophores and rigid and semi-rigid spacers. The recently discovered role of the rhodopin glucoside (carotenoid) will be analyzed as possible relay for energy transfers, including the possibility of uphill processes at room temperature. In this context the concept of energy migration may be complemented by parallel relays and uphill processes. It is also becoming more obvious that the irreversible electron transfer at the reaction center (electron transfer from the special pair to the phaeophytin) renders the rates for energy transfer and migration faster precluding all possibility of back transfers.
Synthesis of near-infrared absorbed metal phthalocyanine with S-aryl groups at non-peripheral positions
Authors: Sakamoto Keiichi , Ohno-Okumura Eiko , Kato Taku , Soga Hisashi
Published: March 2010

Phthalocyanines are used as various applications, including as organic charge carriers in photocopiers, laser light absorbers in data storage systems, photoconductors in photovoltaic cells and electrochromic displays, and non-colored transparent film in visible region. The absorption maxima of phthalocyanines are best if moved near the infrared region for these applications. The Q band of phthalocyanines can be moved to bathochromic effects through extension of a π conjugation system such as naphthalocyanines and anthracyanines. Yields of naphthalocyanines and anthracyanines are, however, low. To solve the problem, novel metal phthalocyanines having non-peripheral S-aryl substituent were synthesized. The novel phthalocyanines show a high strain structure and no liquid crystal property. The target compounds were synthesized: 15 phthalocyanines from 2,3-dicyanohydroquinone in 3 steps via 1,2-dicyanobenzene-3,6-bis(trifluorate) and 1,2-dicyanobenzene-3,6-thiophenols. The Q bands of obtained compounds appeared in the near-infrared region. In particular, lead 1,4,8,11,15,18,22,25-octakis(thiophenylmethyl)phthalocyanine shows a Q band at 857 nm. Furthermore, non-colored transparent films in the visible region can be produced.
Syntheses and structural studies of η5-pentamethylcyclopentadienyl rhodium(III) and iridium(III) complexes of a Schiff-base expanded porphyrin
Authors: Cuesta Luciano , Lynch Vincent M. , Sessler Jonathan L.
Published: March 2010

Reported here is the synthesis of new binuclear rhodium(III) and iridium(III) semi-sandwich complexes of a Schiff-base expanded porphyrin. Single crystals of these new complexes were subject to X-ray diffraction analysis. The resulting structures revealed that the Schiff-base macrocycle adopts a V-shape in which two {(η5- C 5 Me 5) MCl } ( M = Rh and Ir ) fragments are accommodated within the macrocyclic pocket. The coordination environment of the metal centers is typical to that of "piano stool"-type complexes. The X-ray analyses and complementary NMR studies (carried out in CD 2 Cl 2) provide evidence for the existence of strong intramolecular hydrogen-bonding interactions between the pyrrolic NH protons and the chloride counteranion both in solution and in the solid state.
Photooxidation of phenol derivatives using μ-(dihydroxo)dipalladium(II) bisporphyrin complex
Authors: Takao Yuko , Ohno Toshinobu , Moriwaki Kazuyuki , Matsumoto Fukashi , Setsune Jun-ichiro
Published: March 2010

μ-(dihydroxo)dipalladium(II) complex with N21, N22-etheno bridged tetraphenylporphyrin ligand was employed in the catalytic photooxidation of phenol derivative in aerated homogeneous solution with visible light irradiation. The Pd complex promoted the degradation of p-tert-butylphenol as well as Cu phthalocyanine under basic conditions and it worked as a photosensitizer even in neutral conditions in contrast with Cu phthalocyanine. Some phenol derivatives afforded corresponding quinones selectively in this photooxidation. The present Pd complex coordinated by the bidentate porphyrin ligand showed higher photosensitizing ability than tetraphenylporphyrin free-base and ordinary tetradentate tetraphenylporphyrin palladium(II) complex for photooxidation of 2,6-di-tert-butylphenol. This bidentate Pd complex showed higher light durability even under the conditions where photodegradation of porphyrin free-base and tetradentate Pd porphyrin were observed by extensive irradiation.
Efficient synthesis of an A-B-C-tricycle fragment for a structural model of tolyporphin
Authors: Hu Bing C. , Zhou Wei Y. , Liu Zu L. , Cai Chao J. , Xu Shi C.
Published: March 2010

This paper is no longer available. Please contact jpp@wspc.com
The key role of peripheral substituents in the chemistry of phthalocyanines and their analogs
Authors: Lukyanets Evgeny A. , Nemykin Victor N.
Published: March 2010

The preparation and optical properties of peripherally substituted phthalocyanines and their analogs (i.e. naphthalocyanines, anthracyanines, aza-analogs of phthalocyanines, and tetraazaporphyrins) have been widely discussed. This review highlights methodologies that have been published in poorly known and mostly unavailable Russian journals.
Apolipoprotein A-I mimetic 4F alters the function of human monocyte-derived macrophages
Authors: Smythies Lesley E. , White C. Roger , Maheshwari Akhil , Palgunachari M. N. , Anantharamaiah G. M. , Chaddha Manjula , Kurundkar Ashish R. , Datta Geeta
Published: March 2010

HDL and its major protein component apolipoprotein A-I (apoA-I) exert anti-inflammatory effects, inhibit monocyte chemotaxis/adhesion, and reduce vascular macrophage content in inflammatory conditions. In this study, we tested the hypothesis that the apoA-I mimetic 4F modulates the function of monocyte-derived macrophages (MDMs) by regulating the expression of key cell surface receptors on MDMs. Primary human monocytes and THP-1 cells were treated with 4F, apoA-I, or vehicle for 7 days and analyzed for expression of cell surface markers, adhesion to human endothelial cells, phagocytic function, cholesterol efflux capacity, and lipid raft organization. 4F and apoA-I treatment decreased the expression of HLA-DR, CD86, CD11b, CD11c, CD14, and Toll-like receptor-4 (TLR-4) compared with control cells, suggesting the induction of monocyte differentiation. Both treatments abolished LPS-induced mRNA for monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 (MIP-1), regulated on activation, normal T-expressed and presumably secreted (RANTES), IL-6, and TNF-α but significantly upregulated LPS-induced IL-10 expression. Moreover, 4F and apoA-I induced a 90% reduction in the expression of CD49d, a ligand for the VCAM-1 receptor, with a concurrent decrease in monocyte adhesion (55% reduction) to human endothelial cells and transendothelial migration (34 and 27% for 4F and apoA-I treatments) compared with vehicle treatment. In addition, phagocytosis of dextran-FITC beads was inhibited by 4F and apoA-I, a response associated with reduced expression of CD32. Finally, 4F and apoA-I stimulated cholesterol efflux from MDMs, leading to cholesterol depletion and disruption of lipid rafts. These data provide evidence that 4F, similar to apoA-I, induces profound functional changes in MDMs, possibly due to differentiation to an anti-inflammatory phenotype.
Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring
Authors: Ojeda Norma B. , Royals Thomas P. , Black Joshua T. , Dasinger John Henry , Johnson Jeremy M. , Alexander Barbara T.
Published: March 2010

Placental insufficiency results in intrauterine growth restriction (IUGR) and hypertension in adult male growth-restricted rats. Although renal ANG II and plasma renin activity do not differ between growth-restricted and control rats, blockade of the renin-angiotensin system (RAS) abolishes hypertension in growth-restricted rats, suggesting that the RAS contributes to IUGR-induced hypertension. Moreover, castration abolishes hypertension in growth-restricted rats, indicating an important role for testosterone. Therefore, we hypothesized that enhanced responsiveness to ANG II contributes to hypertension in this model of IUGR and that androgens may play a pivotal role in this enhanced response. Physiological parameters were determined at 16 wk of age in male rats pretreated with enalapril (40 mg·kg−1·day−1) for 1 wk. Baseline blood pressures were similar between growth-restricted (112 ± 3 mmHg) and control (110 ± 2 mmHg) rats; however, an enhanced pressor response to acute ANG II (100 ng·kg−1·min−1for 30 min) was observed in growth-restricted (160 ± 2 mmHg) vs. control (136 ± 2 mmHg; P < 0.05) rats. Castration abolished the enhanced pressor response to acute ANG II in growth-restricted (130 ± 2 mmHg) rats with no significant effect on blood pressure in controls (130 ± 2 mmHg). Blood pressure was increased to a similar extent above baseline in response to acute phenylephrine (100 μg/min) in control (184 ± 5 mmHg) and growth-restricted (184 ± 8 mmHg) rats, suggesting the enhanced pressor response in growth-restricted rats is ANG II specific. Thus, these results suggest that growth-restricted rats exhibit an enhanced responsiveness to ANG II that is testosterone dependent and indicate that the RAS may serve as an underlying mechanism in mediating hypertension programmed in response to IUGR.
Bradycardia in serotonin-deficientPet-1−/−mice: influence of respiratory dysfunction and hyperthermia over the first 2 postnatal weeks
Authors: Cummings Kevin J. , Li Aihua , Deneris Evan S. , Nattie Eugene E.
Published: March 2010

Neonatal rodents deficient in medullary serotonin neurons have respiratory instability and enhanced spontaneous bradycardias. This study asks if, in Pet-1−/−mice over development: 1) the respiratory instability leads to hypoxia; 2) greater bradycardia is related to the degree of hypoxia or concomitant hypopnea; and 3) hyperthermia exacerbates bradycardias. Pet-1+/+, Pet-1+/−, and Pet-1−/−mice [postnatal days (P) 4–5, P11–12, P14–15] were held at normal body temperature (Tb) and were then made 2°C hypo- and hyperthermic. Using a pneumotach-mask system with ECG, we measured heart rate, metabolic rate (V̇o2), and ventilation. We also calculated indexes for apnea-induced hypoxia (total hypoxia: apnea incidence × O2consumed during apnea = μl·g−1·min−1) and bradycardia (total bradycardia: bradycardia incidence × magnitude = beats missed/min). Resting heart rate was significantly lower in all Pet-1−/−animals, irrespective of Tb. At P4–5, Pet-1−/−animals had approximately four- to eightfold greater total bradycardia ( P < 0.001), owing to an approximately two- to threefold increase in bradycardia magnitude and a near doubling in bradycardia incidence. Pet-1−/−animals had a significantly reduced V̇o2at all Tb; thus there was no genotype effect on total hypoxia. At P11–12, total bradycardia was nearly threefold greater in hyperthermic Pet-1−/−animals compared with controls ( P < 0.01). In both genotypes, bradycardia magnitude was positively related to the degree of hypopnea ( P = 0.02), but there was no genotype effect on degree of hypopnea or total hypoxia. At P14–15, genotype had no effect on total bradycardia, but Pet-1−/−animals had up to seven times more total hypoxia ( P < 0.001), owing to longer and more frequent apneas and a normalized V̇o2. We infer from these data that 1) Pet-1−/−neonates are probably not hypoxic from respiratory dysfunction until P14–15; 2) neither apnea-related hypoxia nor greater hypopnea contribute to the enhanced bradycardias of Pet-1−/−neonates from approximately P4 to approximately P12; and 3) an enhancement of a temperature-sensitive reflex may contribute to the greater bradycardia in hyperthermic Pet-1−/−animals at approximately P12.
Regulatory interactions between muscle and the immune system during muscle regeneration
Authors: Tidball James G. , Villalta S. Armando
Published: March 2010

Recent discoveries reveal complex interactions between skeletal muscle and the immune system that regulate muscle regeneration. In this review, we evaluate evidence that indicates that the response of myeloid cells to muscle injury promotes muscle regeneration and growth. Acute perturbations of muscle activate a sequence of interactions between muscle and inflammatory cells. The initial inflammatory response is a characteristic Th1 inflammatory response, first dominated by neutrophils and subsequently by CD68+M1 macrophages. M1 macrophages can propagate the Th1 response by releasing proinflammatory cytokines and cause further tissue damage through the release of nitric oxide. Myeloid cells in the early Th1 response stimulate the proliferative phase of myogenesis through mechanisms mediated by TNF-α and IL-6; experimental prolongation of their presence is associated with delayed transition to the early differentiation stage of myogenesis. Subsequent invasion by CD163+/CD206+M2 macrophages attenuates M1 populations through the release of anti-inflammatory cytokines, including IL-10. M2 macrophages play a major role in promoting growth and regeneration; their absence greatly slows muscle growth following injury or modified use and inhibits muscle differentiation and regeneration. Chronic muscle injury leads to profiles of macrophage invasion and function that differ from acute injuries. For example, mdx muscular dystrophy yields invasion of muscle by M1 macrophages, but their early invasion is accompanied by a subpopulation of M2a macrophages. M2a macrophages are IL-4 receptor+/CD206+cells that reduce cytotoxicity of M1 macrophages. Subsequent invasion of dystrophic muscle by M2c macrophages is associated with progression of the regenerative phase in pathophysiology. Together, these findings show that transitions in macrophage phenotype are an essential component of muscle regeneration in vivo following acute or chronic muscle damage.
Losartan increases NO release in afferent arterioles during regression ofl-NAME-induced renal damage
Authors: Helle Frank , Iversen Bjarne M. , Chatziantoniou Christos
Published: March 2010

Inhibition of nitric oxide synthesis (NOS) induces hypertension and heavy proteinuria. Renal structure and function have shown striking improvement after interventions targeting ANG II or endothelin (ET) receptors in rats recovering after long-term NOS inhibition. To search for mechanisms underlying losartan-assisted regression of renal disease in rodents, we measured NO release and contractility to ET in afferent arterioles (AAs) from Sprague-Dawley rats recovering for 2 wk after 4 wk of NG-nitro-l-arginine methyl ester treatment. Losartan administration during the recovery period decreased blood pressure (113 ± 4 vs. 146 ± 5 mmHg, P < 0.01), reduced protein/creatinine ratio more (proteinuria decrease: Δ1,836 ± 214 vs. Δ1,024 ± 180 mg/mmol, P < 0.01), and normalized microvascular hypertrophy (AA media/lumen ratio: 1.74 ± 0.05 vs. 2.09 ± 0.08, P < 0.05) compared with no treatment. In diaminofluorescein-FM-loaded AAs from losartan-treated animals, NO release (% of baseline) was increased compared with untreated animals after stimulation with 10−7M ACh (118 ± 4 vs. 90 ± 7%, t = 560 s, P < 0.001) and 10−9M ET (123 ± 4 vs. 101 ± 5%, t = 560 s, P < 0.001). There was also a blunted contractile response to 10−7M ET in AAs from losartan-treated animals compared with untreated animals (Δ4.01 ± 2.9 vs. Δ14.6 ± 1.7 μm, P < 0.01), which disappeared after acute NOS inhibition (Δ10.7 ± 3.7 vs. Δ12.5 ± 2.9 μm, not significant). Contractile dose responses to ET (10−9, 10−8, 10−7M) were enhanced by NOS inhibition and blunted by exogenous NO (10−2mM S-nitroso- N-acetyl-penicillamine) in losartan-treated but not in untreated vessels. Reducing blood pressure similar to losartan with hydralazine did not improve AA hypertrophy, ET-induced contractility, ET-induced NO release, and NO sensitivity. In conclusion, blockade of the local action of ANG II improved endothelial function in AAs, a mechanism that is likely to contribute to the beneficial effects of AT1aR antagonism during the recovery of renal function after long-term NOS inhibition in rats.
Mutation of the Na+-K+-2Cl−cotransporter NKCC2 in mice is associated with severe polyuria and a urea-selective concentrating defect without hyperreninemia
Authors: Kemter Elisabeth , Rathkolb Birgit , Bankir Lise , Schrewe Anja , Hans Wolfgang , Landbrecht Christina , Klaften Matthias , Ivandic Boris , Fuchs Helmut , Gailus-Durner Valérie , Hrabé de Angelis Martin , Wolf Eckhard , Wanke Ruediger , Aigner Bernhard
Published: March 2010

The bumetanide-sensitive Na+-K+-2Cl−cotransporter NKCC2, located in the thick ascending limb of Henle's loop, plays a critical role in the kidney's ability to concentrate urine. In humans, loss-of-function mutations of the solute carrier family 12 member 1 gene ( SLC12A1), coding for NKCC2, cause type I Bartter syndrome, which is characterized by prenatal onset of a severe polyuria, salt-wasting tubulopathy, and hyperreninemia. In this study, we describe a novel chemically induced, recessive mutant mouse line termed Slc12a1I299Fexhibiting late-onset manifestation of type I Bartter syndrome. Homozygous mutant mice are viable and exhibit severe polyuria, metabolic alkalosis, marked increase in plasma urea but close to normal creatininemia, hypermagnesemia, hyperprostaglandinuria, hypotension,, and osteopenia. Fractional excretion of urea is markedly decreased. In addition, calcium and magnesium excretions are more than doubled compared with wild-type mice, while uric acid excretion is twofold lower. In contrast to hyperreninemia present in human disease, plasma renin concentration in homozygotes is not increased. The polyuria observed in homozygotes may be due to the combination of two additive factors, a decrease in activity of mutant NKCC2 and an increase in medullary blood flow, due to prostaglandin-induced vasodilation, that impairs countercurrent exchange of urea in the medulla. In conclusion, this novel viable mouse line with a missense Slc12a1 mutation exhibits most of the features of type I Bartter syndrome and may represent a new model for the study of this human disease.
Omi/HtrA2 protease is associated with tubular cell apoptosis and fibrosis induced by unilateral ureteral obstruction
Authors: Kim Jinu , Kim Dong Sun , Park Mae Ja , Cho Hee-Jung , Zervos Antonis S. , Bonventre Joseph V. , Park Kwon Moo
Published: March 2010

Kidney fibrosis, a typical characteristic of chronic renal disease, is associated with tubular epithelial cell apoptosis. The results of our recent studies have shown that Omi/HtrA2 (Omi), a proapoptotic mitochondrial serine protease, performs a crucial function in renal tubular epithelial apoptotic cell death in animal models of acute kidney injury, including cisplatin toxicity and ischemia-reperfusion insult. However, the role of Omi in tubulointerstitial disease-associated fibrosis in the kidney remains to be clearly defined. We evaluated the potential function and molecular mechanism of Omi in ureteral obstruction-induced kidney epithelial cell apoptosis and fibrosis. The mice were subjected to unilateral ureteral obstruction (UUO) via the ligation of the left ureter near the renal pelvis. UUO increased the protein level of Omi in the cytosolic fraction of the kidney, with a concomitant reduction in the mitochondrial fraction. UUO reduced the X-linked inhibitor of apoptosis protein (XIAP), a substrate of Omi, and pro-caspase-3, whereas it increased cleaved poly(ADP-ribose) polymerase (cleaved PARP) and the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells. When mice were treated with ucf-101, an inhibitor of the proteolytic activity of Omi (6.19 μg/day ip), on a daily basis beginning 2 days before UUO and continuing until the end of the experiment, the Omi inhibitor protected XIAP cleavage after UUO and reduced the increment of PARP cleavage and the numbers of TUNEL-positive cells. Furthermore, the Omi inhibitor significantly attenuated UUO-induced increases in fibrotic characteristics in the kidney, including the atrophy and dilation of tubules, expansion of the interstitium, and increases in the expression of collagens, α-smooth muscle actin, and fibronectin. In conclusion, Omi/HtrA2 is associated with apoptotic signaling pathways in tubular epithelial cells activated by unilateral ureteral obstruction, thereby resulting in kidney fibrosis.
Fundamental relationships between arterial baroreflex sensitivity and dynamic cerebral autoregulation in humans
Authors: Tzeng Yu-Chieh , Lucas Samuel J. E. , Atkinson Greg , Willie Chris K. , Ainslie Philip N.
Published: March 2010

The functional relationship between dynamic cerebral autoregulation (CA) and arterial baroreflex sensitivity (BRS) in humans is unknown. Given that adequate cerebral perfusion during normal physiological challenges requires the integrated control of CA and the arterial baroreflex, we hypothesized that between-individual variability in dynamic CA would be related to BRS in humans. We measured R-R interval, blood pressure, and cerebral blood flow velocity (transcranial Doppler) in 19 volunteers. BRS was estimated with the modified Oxford method (nitroprusside-phenylephrine injections) and spontaneous low-frequency (0.04–0.15) α-index. Dynamic CA was quantified using the rate of regulation (RoR) and autoregulatory index (ARI) derived from the thigh-cuff release technique and transfer function analysis of spontaneous oscillations in blood pressure and mean cerebral blood flow velocity. Results show that RoR and ARI were inversely related to nitroprusside BRS [ R = −0.72, confidence interval (CI) −0.89 to −0.40, P = 0.0005 vs. RoR; R = −0.69, CI −0.88 to −0.35, P = 0.001 vs. ARI], phenylephrine BRS ( R = −0.66, CI −0.86 to −0.29, P = 0.0002 vs. RoR; R = −0.71, CI −0.89 to −0.38, P = 0.0001 vs. ARI), and α-index ( R = −0.70, CI −0.89 to −0.40, P = 0.0008 vs. RoR; R = −0.62, CI −0.84 to −0.24, P = 0.005 vs. ARI). Transfer function gain was positively related to nitroprusside BRS ( R = 0.62, CI 0.24–0.84, P = 0.0042), phenylephrine BRS ( R = 0.52, CI 0.10–0.79, P = 0.021), and α-index ( R = 0.69, CI 0.35–0.88, P = 0.001). These findings indicate that individuals with an attenuated dynamic CA have greater BRS (and vice versa), suggesting the presence of possible compensatory interactions between blood pressure and mechanisms of cerebral blood flow control in humans. Such compensatory adjustments may account for the divergent changes in dynamic CA and BRS seen, for example, in chronic hypotension and spontaneous hypertension.
Differential Temporal Storage Capacity in the Baseline Activity of Neurons in Macaque Frontal Eye Field and Area V4
Authors: Ogawa Tadashi , Komatsu Hidehiko
Published: March 2010

Previous studies have suggested that spontaneous fluctuations in neuronal activity reflect intrinsic functional brain architecture. Inspired by these findings, we analyzed baseline neuronal activity in the monkey frontal eye field (FEF; a visuomotor area) and area V4 (a visual area) during the fixation period of a cognitive behavioral task in the absence of any task-specific stimuli or behaviors. Specifically, we examined the temporal storage capacity of the instantaneous discharge rate in FEF and V4 neurons by calculating the correlation of the spike count in a bin with that in another bin during the baseline activity of a trial. We found that most FEF neurons fired significantly more (or less) in one bin if they fired more (or less) in another bin within a trial, even when these two time bins were separated by hundreds of milliseconds. By contrast, similar long time-lag correlations were observed in only a small fraction of V4 neurons, indicating that temporal correlations were considerably stronger in FEF compared with those in V4 neurons. Additional analyses revealed that the findings were not attributable to other task-related variables or ongoing behavioral performance, suggesting that the differences in temporal correlation strength reflect differences in intrinsic structural and functional architecture between visual and visuomotor areas. Thus FEF neurons probably play a greater role than V4 neurons in neural circuits responsible for temporal storage in activity.
Idiopathic Gingival Fibromatosis: Case Report and Its Management
Authors: Jaju Prashant P. , Desai Ankit , Desai Rajiv S. , Jaju Sushma P.
Published: March 2010

Idiopathic gingival fibromatosis is a rare condition. We present a case of idiopathic gingival fibromatosis with its multidisciplinary approach of management. The clinical, radiographic, and histopathological features have been described in detail.
RMT Assessments of the Market Latent Information Embedded in the Stocks′ Raw, Normalized, and Partial Correlations
Authors: Kenett Dror Y. , Shapira Yoash , Ben-Jacob Eshel
Published: March 2010

We present here
assessment of the latent market information
embedded in the raw, affinity (normalized), and
partial correlations. We compared the Zipf plot,
spectrum, and distribution of the eigenvalues
for each matrix with the results of the
corresponding random matrix. The analysis was
performed on stocks belonging to the New York
and Tel Aviv Stock Exchange, for the time period
of January 2000 to March 2009. Our results show
that in comparison to the raw correlations, the
affinity matrices highlight the dominant factors
of the system, and the partial correlation
matrices contain more information. We propose
that significant stock market information, which
cannot be captured by the raw correlations, is
embedded in the affinity and partial
correlations. Our results further demonstrate
the differences between NY and TA
markets.
Acoustic Pressure Waves in Vibrating 3‐D Laminated Beam‐Plate Enclosures
Authors: Osheku Charles A. , Olunloyo Vincent O. S. , Damisa O. , Akano Theddeus T.
Published: March 2010

The effect of structural vibration on the propagation of acoustic pressure waves through a cantilevered 3‐D laminated beam‐plate enclosure is investigated analytically. For this problem, a set of well‐posed partial differential equations governing the vibroacoustic wave interaction phenomenon are formulated and matched for the various vibrating boundary surfaces. By employing integral transforms, a closed form analytical expression is computed suitable for vibroacoustic modeling, design analysis, and general aerospace defensive applications. The closed‐form expression takes the form of a kernel of polynomials for acoustic pressure waves showing the influence of linear interface pressure variation across the axes of vibrating boundary surfaces. Simulated results demonstrate how the mode shapes and the associated natural frequencies can be easily computed. It is shown in this paper that acoustic pressure waves propagation are dynamically stable through laminated enclosures with progressive decrement in interfacial pressure distribution under the influence of high excitation frequencies irrespective of whether the induced flow is subsonic, sonic , supersonic, or hypersonic. Hence, in practice, dynamic stability of hypersonic aircrafts or jet airplanes can be further enhanced by replacing their noise transmission systems with laminated enclosures.