bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of Viral Gene Expression in Bovine Leukemia Virus-Associated B-Cell Malignancy: Interplay of Epigenetic Modifications Leading to Chromatin with a Repressive Histone Code
Authors: Merimi Makram , Klener Pavel , Szynal Maud , Cleuter Yvette , Kerkhofs Pierre , Burny Arsène , Martiat Philippe , Van den Broeke Anne
Published: March 2007

Ovine leukemia/lymphoma resulting from bovine leukemia virus infection of sheep offers a large animal model for studying mechanisms underlying leukemogenesis. Silencing of viral information including Tax, the major contributor to the oncogenic potential of the virus, is critical if not mandatory for tumor progression. In this study, we have identified epigenetic mechanisms that govern the complete suppression of viral expression, using a lymphoma-derived B-cell clone carrying a silent provirus. Silencing was not relieved by injection of the malignant B cells into sheep. However, exogenous expression of Tax or treatment with either the DNA methyltransferase inhibitor 5′azacytidine or the histone deacetylase (HDAC) inhibitor trichostatin A rescued viral expression, as demonstrated by in vivo infectivity trials. Comparing silent and reactivated provirus, we found mechanistic connections between chromatin conformation and tumor-associated transcriptional repression. Silencing is associated with DNA methylation and decreased accessibility of promoter sequences. HDAC1 and the transcriptional corepressor mSin3A are associated with the inactive but not the reactivated promoter. Silencing correlates with a repressed chromatin structure marked by histone H3 and H4 hypoacetylation, a loss of methylation at H3 lysine 4, and an increase of H3 lysine 9 methylation. These observations point to the critical role of epigenetic mechanisms in tumor-specific virus/oncogene silencing, a potential strategy to evade immune response and favor the propagation of the transformed cell.
Selective and Nonselective Packaging of Cellular RNAs in Retrovirus Particles
Authors: Rulli Samuel J. , Hibbert Catherine S. , Mirro Jane , Pederson Thoru , Biswal Shyam , Rein Alan
Published: March 2007

Assembly of retrovirus particles normally entails the selective encapsidation of viral genomic RNA. However, in the absence of packageable viral RNA, assembly is still efficient, and the released virus-like particles (termed “Ψ
−
” particles) still contain roughly normal amounts of RNA. We have proposed that cellular mRNAs replace the genome in Ψ
−
particles. We have now analyzed the mRNA content of Ψ
−
and Ψ
+
murine leukemia virus (MLV) particles using both microarray analysis and real-time reverse transcription-PCR. The majority of mRNA species present in the virus-producing cells were also detected in Ψ
−
particles. Remarkably, nearly all of them were packaged nonselectively; that is, their representation in the particles was simply proportional to their representation in the cells. However, a small number of low-abundance mRNAs were greatly enriched in the particles. In fact, one mRNA species was enriched to the same degree as Ψ
+
genomic RNA. Similar results were obtained with particles formed from the human immunodeficiency virus type 1 (HIV-1) Gag protein, and the same mRNAs were enriched in MLV and HIV-1 particles. The levels of individual cellular mRNAs were ∼5- to 10-fold higher in Ψ
−
than in Ψ
+
MLV particles, in agreement with the idea that they are replacing viral RNA in the former. In contrast, signal recognition particle RNA was present at the same level in Ψ
−
and Ψ
+
particles; a minor fraction of this RNA was weakly associated with genomic RNA in Ψ
+
MLV particles.
Vesicular Stomatitis Virus-Based Therapeutic Vaccination Targeted to the E1, E2, E6, and E7 Proteins of Cottontail Rabbit Papillomavirus
Authors: Brandsma Janet L. , Shylankevich Mark , Su Yuhua , Roberts Anjeanette , Rose John K. , Zelterman Daniel , Buonocore Linda
Published: March 2007

Persistent human papillomavirus (HPV)-associated benign and malignant lesions are a major cause of morbidity and mortality worldwide. Vaccination against HPV early proteins could provide an effective means of treating individuals with established infections. Recombinant vesicular stomatitis virus (VSV) vectors have been used previously to elicit strong humoral and cellular immune responses and develop prophylactic vaccines. We have shown that VSV vectors also can be used to elicit therapeutic immunity in the cottontail rabbit papillomavirus (CRPV)-rabbit model of high-risk HPV infection. In the present study, three new VSV vectors expressing the CRPV E1, E2, or E7 protein were produced and compared to the previously generated VSV-E6 vector for therapeutic efficacy. To determine whether vaccine efficacy could be augmented by simultaneous vaccination against two CRPV proteins, the four vaccines were delivered individually and in all possible pairings to rabbits 1 week after CRPV infection. Control rabbits received the recombinant wild-type VSV vector or medium only. Cumulative papilloma volumes were computed for analysis of the data. The analyses showed that VSV-based vaccination against the E1, E2, E6, or E7 protein significantly reduced papilloma volumes relative to those of the controls. Furthermore, VSV-based CRPV vaccination cured all of the papillomas in 5 of 30 rabbits. Of the individual vaccines, VSV-E7 was the most effective. The VSV-E7 vaccine alone was the most effective, as it reduced cumulative papilloma volumes by 96.9% overall, relative to those of the controls, and ultimately eliminated all of the disease in all of the vaccinees. Vaccine pairing was not, however, found to be beneficial, suggesting antigenic competition between the coexpressed CRPV proteins. These preclinical results, obtained in a physiologically relevant animal model of HPV infection, demonstrate that VSV vectors deserve serious consideration for further development as therapeutic antitumor vaccines.
Cytoplasmic Envelopment of Human Cytomegalovirus Requires the Postlocalization Function of Tegument Protein pp28 within the Assembly Compartment
Authors: Seo Jun-Young , Britt William J.
Published: March 2007

The assembly of herpesvirus remains incompletely defined due to the structural complexity of these viruses. Although the assembly of the capsid of these large DNA viruses is well studied and reasonably well conserved for all members of this diverse family of viruses, the cytoplasmic processes of tegumentation and envelopment are not well understood. The virion of the largest human herpesvirus, human cytomegalovirus (HCMV), contains over 70 virus-encoded proteins that are incorporated during a nuclear and cytoplasmic phase of assembly. Envelopment of this virus requires the function of at least one tegument protein, pp28, the product of the UL99 open reading frame. However, the role of pp28 in the envelopment of HCMV remains undefined. We have generated a pp28 mutant virus that encodes only the first 50 amino acids (aa) of this 190-aa virion protein. This virus is replication impaired and is defective in virus assembly. Characterization of both intracellular and extracellular virions from cells infected with this viral mutant indicated that the decrease in production of infectious virus was secondary to a defect in envelopment and the accumulation of tegumented, noninfectious intracellular particles. Image analysis using fluorescence recovery after photobleaching indicated that the pp28 mutant protein encoded by this virus failed to efficiently accumulate in the virus assembly compartment (AC). Our results suggest that pp28 must accumulate in the AC for efficient envelopment of the particle and provide evidence for a direct role of this tegument protein in the late stages of assembly, such as envelopment.
Lattice QCD at Finite Temperature and Density
Authors: LOMBARDO M. P.
Published: March 2007

A general introduction into the subject aimed at a general theoretical physics audience. We introduce the sign problem posed by finite density lattice QCD, and we discuss the main methods proposed to circumvent it, with emphasis on the imaginary chemical potential approach. The interrelation between Taylor expansion and analytic continuation from imaginary chemical potential is discussed in detail. The main applications to the calculation of the critical line, and to the thermodynamics of the hot and normal phase are reviewed.
A NUMERICAL STUDY OF IMPROVED WILSON QUARK ACTIONS ON ANISOTROPIC LATTICES
Authors: LIU LIUMING , SU SHIQUAN , LI XIN , LIU CHUAN
Published: March 2007

Tadpole improved Wilson quark actions with clover terms on anisotropic lattices are studied numerically. Using asymmetric lattice volumes, the pseudo-scalar meson dispersion relations are measured for 8 lowest lattice momentum modes with quark mass values ranging from the strange to the charm quark with various values of the gauge coupling β and 3 different values of the bare speed of light parameter ν. These results can be utilized to extrapolate or interpolate to obtain the optimal value for the bare speed of light parameter νopt(m) at a given gauge coupling for all bare quark mass values m. In particular, the optimal values of ν at the physical strange and charm quark mass are given for various gauge couplings. The lattice action with these optimized parameters can then be used to study physical properties of hadrons involving either light or heavy quarks.
Phase Structures of Strong Coupling Lattice QCD with Overlap Fermions at Finite Temperature and Chemical Potential
Authors: YU XIAO-LU , LUO XIANG-QIAN
Published: March 2007

Lattice QCD at finite temperature T and chemical potential μ is studied analytically in the strong coupling limit with overlap fermions. We start from the first order approximation of lattice action with generalized overlap (GO) fermions to derive an effective free energy written in terms of chiral condensate as a function of T and μ with the use of mean field approximation. We elucidate the phase structure on the (μ, T) plane and discover the tricritical point separating the first and the second order chiral phase transition. Discussion of the doubling problem and higher order terms are given.
COULOMB WAVE FUNCTIONS OF NUCLEON AND ROPER ON THE LATTICE
Authors: CHEN YING
Published: March 2007

By applying a spatially extended sink operator, the nucleon two-point functions are calculated in Coulomb gauge from quenched lattice QCD with overlap fermions. The Bethe-Salpeter wave functions of nucleon and Roper resonance are extracted at different quark masses. The typical size of nucleon is about 0.7 fm, which seems insensitive to the quark masses involved in this work. It is also found that the wave function of Roper has a radial node.
Phase Structure of Color Superconductivity and Chiral Restoration
Authors: Zhuang Pengfei
Published: March 2007

We investigate color superconductivity and chiral symmetry restoration at finite temperature and baryon density in the frame of standard two flavor Nambu–Jona-Lasinio model. We derive the diquark mass in RPA, discuss its constraint on the coupling constant in the diquark channel, and find a strong competition between the two phase transitions when the coupling constant is large enough.
THE INFLUENCE OF THE MAGNETIC FIELD ON THE PROPERTIES OF NEUTRON STAR MATTER
Authors: CHEN WEI , ZHANG PU-QING , LIU LIANG-GANG
Published: March 2007

In the mean field approximation of the relativistic σ-ω-ρ model, the magnetic fields are incorporated, and it's influence on the properties of n-p-e neutron star matter are studied. When the strength of the magnetic field is weaker than ~1018G, the particles' fractions and chemical potentials, matter's energy density and pressure hardly change with the magnetic field; when the strength of the magnetic field is stronger than ~1020G, the above quantities change with the magnetic field evidently. Furthermore, the pressure is studied in both thermodynamics and hydrodynamics. The difference between these two ways exits in the high density region, that is, the thermal self-consistency may not be satisfied in this region if the magnetic field is considered.
FRAME DRAGGING EFFECT ON MOMENT OF INERTIA AND RADIUS OF GYRATION OF NEUTRON STAR
Authors: WEN DE-HUA , CHEN WEI , LU YI-GANG , LIU LIANG-GANG
Published: March 2007

Accurate to the first order in the uniform angular velocity, the general relativistic frame dragging effect of the moments of inertia and the radii of gyration of two kinds of neutron stars are calculated in a relativistic σ – ω model. The calculation shows that the dragging effect will diminish the moments of inertia and radii of gyration.
Effect of UA(1) Breaking on Chiral Phase Structure and Pion Superfluidity at Finite Isospin Chemical Potential
Authors: He Lianyi , Jin Meng , Zhuang Pengfei
Published: March 2007

We investigate the isospin chemical potential effect in the frame of SU(2) Nambu-Jona-Lasinio model. When the isospin chemical potential is less than the vacuum pion mass, the phase structure with two chiral phase transition lines does not happen due to UA(1) breaking of QCD. When the isospin chemical potential is larger than the vacuum pion mass, the ground state of the system is a Bose-Einstein condensate of charged pions.
WEYL'S GAUGE TRANSFORM AND QUANTUM GEOMETRIC PHASE FACTORS
Authors: LI HUA-ZHONG
Published: March 2007

The historical and geometrical origin of Gauge Transformation and Yang's phase loop of gauge theory are discussed. In the present talk, we present the following points: 1. Parallel transport of a vector; 2. Weyl 1918 gauge transformation 3. Concept of non-integrable phase factor; 4. Berry's quantum geometrical phase; 5. Parallel transport of quantum state vector produces the phase physics.
LOOPS IN SUPER YANG-MILLS THEORIES
Authors: CHEN GENGSHENG , LUO MINGXING , WEN CONGKAO
Published: March 2007

We report recent analysis of one-loop scattering amplitudes in N =4 super Yang-Mills theories, in the paradigm of maximally helicity violating Feynman diagrams. Non-planar amplitudes are found to be related to planar ones in the same manners as those in conventional field theory. More so, there are are very limited number of loop integrals to be evaluated. For a process with n external particles, there are only [n/2]-1 generically independent integrals.
Hidden Local Symmetry and Effective Chiral Theory for Vector and Axial-vector Mesons
Authors: Li B. A. , Wu Y. L.
Published: March 2007

We present the effective chiral Lagrangian of mesons (peusodoscalars, vectors and axial-vectors) obtained in the chiral limit by using two approaches. The first approach is based on symmetries: the explicit global chiral symmetry and hidden local chiral symmetry. In this approach, it is noticed that there are in general fourteen interacting terms up to the dimension-four of covariant derivative for meson fields rather than the usual eleven interacting terms given in literature from hidden local symmetry approach. Of particular, the additional terms are found to be very important for understanding the vector meson dominance and providing consistent predictions on the decay rates of a1 → γπ and a1 → ρπ as well as for resulting a consistent effective chiral Lagrangian with chiral perturbation theory. The second approach is motivated from the chiral symmetry of chiral quarks and the bound state solutions of nonperturbative QCD at low energy and large Nc. The second approach is more fundamental in the sense that it is based on the QCD Lagrangian of quarks and only relies on two basic parameters in addition to the ones in the standard model. As a consequence, it allows us to extract, in terms of only two basic parameters, all the fourteen parameters in the more general effective Lagrangian constructed from symmetries in the first approach. It is surprising to note that except the necessity of three additional new interacting terms introduced in this paper, the resulting values of the coupling constants for other three interacting terms at the dimension-four are also quite different from the ones given in the literature. It is likely that the structures of the effective chiral Lagrangian for the dimension-four given in the literatures by using hidden local symmetry are incomplete and consequently the resulting coulpings are not reliable. It is shown that the more general effective chiral Lagrangian given in the present paper shall provide a more consistent prediction for all the low energy phenomenology of ρ - a1 system and result in a more consistent description on the low energy behavior of light flavor mesons. Its fourteen parameters up to the dimension-four of covariant derivative may be uniquely determined from the effective chiral theory based on the second approach, which is consistent with the chiral perturbation theory.
Can a Nonsymmetric Metric mimic NCQFT in e+e- → γγ?
Authors: Kersting Nick , Ma Yong-Liang
Published: March 2007

In the nonsymmetric gravitational theory (NGT) the space-time metric gμν departs from the flat-space Minkowski form ημν such that it is no longer symmetric, i.e.gμν ≠ gνμ. We find that in the most conservative such scenario coupled to quantum field theory, which we call Minimally Nonsymmetric Quantum Field Theory (MNQFT), there are experimentally measurable consequences similar to those from noncommutative quantum field theory (NCQFT). This can be expected from the Seiberg-Witten map which has recently been interpreted as equating gauge theories on noncommutative spacetimes with those in a field dependent gravitational background. In particular, in scattering processes such as the pair annihilation e+e- → γγ, both theories make the same striking prediction that the azimuthal cross section oscillates in ϕ. However the predicted number of oscillations differs in the two theories: MNQFT predicts between one and four, whereas NCQFT has no such restriction.
RIGOROUS RESULTS FOR THE QUANTUM PHASE TRANSITIONS IN A DIMERIZED S = 1 ISING LATTICE
Authors: WU HAINA , YANG ZHIHUA , DAI JIANHUI , YING HEPING
Published: March 2007

We examine the ground state properties of a dimerized ferromagnetic S = 1 Ising chain with single-ion crystal fields by mapping the model onto the dimerized S = 1/2 Ising chain with transverse fields. We show that the system exhibits a series of Ising transitions depending on the dimerization strength of the crystal fields, while the critical points can be determined exactly.
WEAK-COUPLING PHASE DIAGRAM OF THE ONE-DIMENSIONAL DEFORMED T-J MODEL
Authors: MA QINGSHAN , DAI JIANHUI , XU ZHAOXIN , ZHANG JUN
Published: March 2007

The deformed t-J lattice model is defined by replacing the fermion operators by the deformed Hubbard operators in the t-term but without changing the J-term in the conventional t-J model. The physics of this model was argued to be continuously connected to those of the t-J one when the deformation parameter λ varies from zero to unit. In this paper, by using the bosonization field theory and renormalization group technique, we study the phase diagram of the one dimension deformed t-J model in the regime where λ and J/t are both positively small but comparable to each other. By explicitly incorporating the contributions from the deformation-induced six-particle term and the antiferromagnetic exchange interaction, we find that at half-filling the system shows three distinct ground states characterized by the Luttinger liquid, the spin-density-wave and the bond-order-wave, respectively. These results indicate that the ground state phases of the deformed t-J model is neither connected smoothly to those of the system at λ = 1 nor to those of the conventional t-J model.
MONOTONIC INDEPENDENCE ASSOCIATED WITH PARTIALLY ORDERED SETS
Authors: WYSOCZAŃSKI JANUSZ
Published: March 2007

A generalization of Muraki's notion of monotonic independence onto the case of partially ordered index set is given: algebras indexed by chains are monotonically independent, and algebras indexed by non-comparable elements are boolean independent. Examples of central limit theorem are shown in two cases. For the integral-points lattices ℕd the moments of the limit measure are related to the combinatorics of the finite heap-ordered labelled rooted trees (if d = 2). For the integral-points lattice ℕ × ℤd in Minkowski spacetime the limit measure is given by the recurrence of it's moments, which, for the case d = 1 is related to the inverse error function. Various formulas for computing mixed moments are shown to be related to the boolean-monotonic non-crossing pair partitions.
SCALING LIMIT FOR A GENERAL CLASS OF QUANTUM FIELD MODELS AND ITS APPLICATIONS TO NUCLEAR PHYSICS AND CONDENSED MATTER PHYSICS
Authors: SUZUKI AKITO
Published: March 2007

We consider a scaling limit of the Hamiltonian of the generalized spin-boson (GSB) model which is an abstract quantum field theoretical model of particles interacting with a Bose field. Applying it to a Hamiltonian of the field of the nuclear force with isospin, we obtain an effective potential of the interaction between nucleons. Also, we discuss an application to a Hamiltonian of a lattice spin system interacting with a Bose field and obtain a spin–spin interaction in the vacuum of the Bose field. An interaction model between a Fermi field and a Bose field yields an interaction in the vacuum of the Bose field.
EXPANSION THEOREMS FOR GENERALIZED RANDOM PROCESSES, WICK PRODUCTS AND APPLICATIONS TO STOCHASTIC DIFFERENTIAL EQUATIONS
Authors: PILIPOVIĆ STEVAN , SELEŠI DORA
Published: March 2007

A new Gel'fand triple exp (S)1 ⊆ (L)2 ⊆ exp (S)-1 is constructed as extension of the known Kondratiev one (S)1 ⊆ (L)2 ⊆ (S)-1. Expansion theorems for generalized stochastic processes considered as elements of the spaces [Formula: see text] and [Formula: see text] are derived. This series expansion is used for solving a class of evolution stochastic differential equations. The Wick product is developed on the spaces exp (S)-1, [Formula: see text] and [Formula: see text]. The series expansion of generalized stochastic processes is used for solving a class of nonlinear stochastic differential equations by means of Wick products.
Intersubject differences in the effect of acidosis on phosphocreatine recovery kinetics in muscle after exercise are due to differences in proton efflux rates
Authors: van den Broek Nicole M. A. , De Feyter Henk M. M. L. , Graaf Larry de , Nicolay Klaas , Prompers Jeanine J.
Published: March 2007

31P magnetic resonance spectroscopy provides the possibility of obtaining bioenergetic data during skeletal muscle exercise and recovery. The time constant of phosphocreatine (PCr) recovery (τPCr) has been used as a measure of mitochondrial function. However, cytosolic pH has a strong influence on the kinetics of PCr recovery, and it has been suggested that τPCr should be normalized for end-exercise pH. A general correction can only be applied if there are no intersubject differences in the pH dependence of τPCr. We investigated the pH dependence of τPCr on a subject-by-subject basis. Furthermore, we determined the kinetics of proton efflux at the start of recovery. Intracellular acidosis slowed PCr recovery, and the pH dependence of τPCr differed among subjects, ranging from −33.0 to −75.3 s/pH unit. The slope of the relation between τPCr and end-exercise pH was positively correlated with both the proton efflux rate and the apparent proton efflux rate constant, indicating that subjects with a smaller pH dependence of τPCr have a higher proton efflux rate. Our study implies that simply correcting τPCr for end-exercise pH is not adequate, in particular when comparing patients and control subjects, because certain disorders are characterized by altered proton efflux from muscle fibers.
Functional analysis of Na+/K+-ATPase isoform distribution in rat ventricular myocytes
Authors: Despa Sanda , Bers Donald M.
Published: March 2007

The Na+/K+-ATPase (NKA) is the main route for Na+ extrusion from cardiac myocytes. Different NKA α-subunit isoforms are present in the heart. NKA-α1 is predominant, although there is a variable amount of NKA-α2 in adult ventricular myocytes of most species. It has been proposed that NKA-α2 is localized mainly in T-tubules (TT), where it could regulate local Na+/Ca2+ exchange and thus cardiac myocyte Ca2+. However, there is controversy as to where NKA-α1 vs. NKA-α2 are localized in ventricular myocytes. Here, we assess the TT vs. external sarcolemma (ESL) distribution functionally using formamide-induced detubulation of rat ventricular myocytes, NKA current (IPump) measurements and the different ouabain sensitivity of NKA-α1 (low) and NKA-α2 (high) in rat heart. Ouabain-dependent IPump inhibition in control myocytes indicates a high-affinity NKA isoform (NKA-α2, K1/2 = 0.38 ± 0.16 μM) that accounts for 29.5 ± 1.3% of IPump and a low-affinity isoform (NKA-α1, K1/2 = 141 ± 17 μM) that accounts for 70.5% of IPump. Detubulation decreased cell capacitance from 164 ± 6 to 120 ± 8 pF and reduced IPump density from 1.24 ± 0.05 to 1.02 ± 0.05 pA/pF, indicating that the functional density of NKA is significantly higher in TT vs. ESL. In detubulated myocytes, NKA-α2 accounted for only 18.2 ± 1.1% of IPump. Thus, ∼63% of IPump generated by NKA-α2 is from the TT (although TT are only 27% of the total sarcolemma), and the NKA-α2/NKA-α1 ratio in TT is significantly higher than in the ESL. The functional density of NKA-α2 is ∼4.5 times higher in the T-tubules vs. ESL, whereas NKA-α1 is almost uniformly distributed between the TT and ESL.
Potentiation of acid-sensing ion channels by sulfhydryl compounds
Authors: Cho Jun-Hyeong , Askwith Candice C.
Published: March 2007

The acid-sensing ion channels (ASICs) are voltage-independent ion channels activated by acidic extracellular pH. ASICs play a role in sensory transduction, behavior, and acidotoxic neuronal death, which occurs during stroke and ischemia. During these conditions, the extracellular concentration of sulfhydryl reducing agents increases. We used perforated patch-clamp technique to analyze the impact of sulfhydryls on H+-gated currents from Chinese hamster ovary (CHO) cells expressing human ASIC1a (hASIC1a). We found that hASIC1a currents activated by pH 6.5 were increased almost twofold by the sulfhydryl-containing reducing agents dithiothreitol (DTT) and glutathione. DTT shifted the pH-dose response of hASIC1a toward a more neutral pH (pH0.5 from 6.54 to 6.69) and slowed channel desensitization. The effect of reducing agents on native mouse hippocampal neurons and transfected mouse ASIC1a was similar. We found that the effect of DTT on hASIC1a was mimicked by the metal chelator TPEN, and mutant hASIC1a channels with reduced TPEN potentiation showed reduced DTT potentiation. Furthermore, the addition of DTT in the presence of TPEN did not result in further increases in current amplitude. These results suggest that the effect of DTT on hASIC1a is due to relief of tonic inhibition by transition metal ions. We found that all ASICs examined remained potentiated following the removal of DTT. This effect was reversed by the oxidizing agent DTNB in hASIC1a, supporting the hypothesis that DTT also impacts ASICs via a redox-sensitive site. Thus sulfhydryl compounds potentiate H+-gated currents via two mechanisms, metal chelation and redox modulation of target amino acids.
Exposure to hydrogen peroxide diminishes NF-κB activation, IκB-α degradation, and proteasome activity in neutrophils
Authors: Zmijewski Jaroslaw W. , Zhao Xia , Xu Zhiwei , Abraham Edward
Published: March 2007

Although ROS can participate in modulating the activity of the transcriptional factor NF-κB and expression of NF-κB-dependent genes, the mechanisms involved and the roles of specific ROS have not been fully determined. In particular, individual ROS appear to have differing effects on NF-κB activation dependent on the cell population studied. In the present study, we examined the ability of H2O2 to affect NF-κB activation in LPS-stimulated murine neutrophils and macrophages. Exposure of bone marrow or peritoneal neutrophils to H2O2 was associated with reduced nuclear translocation of NF-κB and decreased production of the NF-κB-dependent cytokines TNF-α and macrophage inhibitory protein-2. H2O2 treatment resulted in diminished trypsin- and chymotrypsin-like proteasome activity. The degradation of IκB-α normally found in LPS-treated neutrophils was prevented when H2O2 was added to cell cultures. In contrast to the effects found in neutrophils, H2O2 did not affect chymotrypsin-like proteasomal activity or cytokine production in LPS-stimulated macrophages, even though trypsin-like proteasomal activity was reduced. These results demonstrate that the effects of H2O2 on NF-κB and proteasomal activity are cell population specific.
Use of a novel and highly selective oxytocin receptor antagonist to characterize uterine contractions in the rat
Authors: McCafferty Gerald P. , Pullen Mark A. , Wu Charlene , Edwards Richard M. , Allen Michael J. , Woollard Patrick M. , Borthwick Alan D. , Liddle John , Hickey Deirdre M. B. , Brooks David P. , Westfall Timothy D.
Published: March 2007

Spontaneous and induced uterine contractions in the rat were found to be inhibited by a novel and selective oxytocin receptor antagonist GSK221149A (3 R,6 R)-3-Indan-2-yl-1-[(1 R)-1-(2-methyl-1,3-oxazol-4-yl)-2-morpholin-4-yl-2-oxoethyl]-6-[(1 S)-1-methylpropyl]-2,5-piperazinedione. GSK221149A displayed nanomolar affinity ( Ki = 0.65 nM) for human recombinant oxytocin receptors with >1,400-fold selectivity over human V1a, V1b, and V2 receptors. GSK221149A had similar affinity ( Ki = 4.1 nM) and selectivity for native oxytocin receptors from rat and produced a functional, competitive block of oxytocin-induced contractions in isolated rat myometrial strips with a pA2 value of 8.18. Intravenous administration of GSK221149A produced a dose-dependent decrease in oxytocin-induced uterine contractions in anesthetized rats with an ID50 = 0.27 ± 0.60 mg/kg (corresponding plasma concentrations were 88 ng/ml). Oral administration of GSK221149A (5 mg/kg) was effective in inhibiting oxytocin-induced uterine contractions after single and multiple (4-day) dosing. Spontaneous uterine contractions in late-term pregnant rats (19–21 days gestation) were significantly reduced by intravenous administration of 0.3 mg/kg of GSK221149A. These results provide further evidence that selective oxytocin receptor antagonism may offer an effective treatment for preterm labor.
Hyaluronan blocks porcine pancreatic elastase-induced mucociliary dysfunction in allergic sheep
Authors: Scuri Mario , Sabater Juan R. , Abraham William M.
Published: March 2007

Neutrophil elastase is a mediator common to asthma, chronic obstructive pulmonary disease, and cystic fibrosis and thought to contribute to the pathophysiology of these diseases. Previously, we found that inhaled hyaluronan blocked elastase-induced bronchoconstriction in allergic sheep through its control of tissue kallikrein. Here, we extend those studies by determining if inhaled hyaluronan can protect against the elastase-induced depression in tracheal mucus velocity, a surrogate marker of whole lung mucociliary clearance. We measured tracheal mucus velocity in allergic sheep before, and sequentially for 6 h after, aerosol challenge with porcine pancreatic elastase alone and after pretreatment with 1.5 or 6 mg aerosolized hyaluronan. Elastase (2.55 U) decreased tracheal mucus velocity. Pretreatment with 6 mg, but not 1.5 mg, hyaluronan inhibited the elastase-induced decrease in tracheal mucus velocity. Hyaluronan (6 mg) given 1 h after elastase challenge was ineffective, suggesting the involvement of secondary mediators. The elastase-induced depression in mucus transport appeared to be mediated, in part, by reactive oxygen species and bradykinin because pretreatment with either aerosolized catalase (38 mg/3 ml) or the bradykinin B2-receptor antagonist HOE140 (400 nM/kg) was also effective in blocking the response. These latter two findings are consistent with oxygen radical-induced degradation of hyaluronan with concomitant loss of its regulatory effect on tissue kallikrein, resulting in kinin generation. This hypothesis is supported by the demonstration that hyaluronan failed to block the oxygen radical-induced fall in tracheal mucus velocity resulting from xanthine-xanthine oxidase challenge and that inhaled bradykinin itself can slow mucociliary transport.
Vertical gradients in regional lung density and perfusion in the supine human lung: the Slinky effect
Authors: Hopkins Susan R. , Henderson A. Cortney , Levin David L. , Yamada Kei , Arai Tatsuya , Buxton Richard B. , Prisk G. Kim
Published: March 2007

In vivo radioactive tracer and microsphere studies have differing conclusions as to the magnitude of the gravitational effect on the distribution of pulmonary blood flow. We hypothesized that some of the apparent vertical perfusion gradient in vivo is due to compression of dependent lung increasing local lung density and therefore perfusion/volume. To test this, six normal subjects underwent functional magnetic resonance imaging with arterial spin labeling during breath holding at functional residual capacity, and perfusion quantified in nonoverlapping 15 mm sagittal slices covering most of the right lung. Lung proton density was measured in the same slices using a short echo 2D-Fast Low-Angle SHot (FLASH) sequence. Mean perfusion was 1.7 ± 0.6 ml·min−1·cm−3 and was related to vertical height above the dependent lung (slope = −3%/cm, P < 0.0001). Lung density averaged 0.34 ± 0.08 g/cm3 and was also related to vertical height (slope = −4.9%/cm, P < 0.0001). By contrast, when perfusion was normalized for regional lung density, the slope of the height-perfusion relationship was not significantly different from zero ( P = 0.2). This suggests that in vivo variations in regional lung density affect the interpretation of vertical gradients in pulmonary blood flow and is consistent with a simple conceptual model: the lung behaves like a Slinky (Slinky is a registered trademark of Poof-Slinky Incorporated), a deformable spring distorting under its own weight. The greater density of lung tissue in the dependent regions of the lung is analogous to a greater number of coils in the dependent portion of the vertically oriented spring. This implies that measurements of perfusion in vivo will be influenced by density distributions and will differ from excised lungs where density gradients are reduced by processing.
Differential Effects of CRF1 and CRF2 Receptor Antagonists on Pain-Related Sensitization of Neurons in the Central Nucleus of the Amygdala
Authors: Ji Guangchen , Neugebauer Volker
Published: March 2007

As a hormone in the hypothalamic–pituitary–adrenocortical (HPA) axis corticotropin-releasing factor (CRF) mediates stress responses. CRF can also act as a neuromodulator of synaptic transmission outside the HPA axis. A major site of extrahypothalamic expression of CRF and its G-protein–coupled receptors is the amygdala, a key player in affect-related disorders such as anxiety. The laterocapsular division of the central nucleus of the amygdala (CeLC) is important for the modulation of pain affect. This study determined the effects of CRF1 and CRF2 receptor antagonists in CeLC neurons in an arthritis pain model. Extracellular single-unit recordings were made from CeLC neurons in anesthetized adult rats. All neurons responded more strongly to noxious than to innocuous mechanical stimulation (compression) of peripheral tissues, including the knee. Evoked responses and background activity were measured before and during the development of a kaolin/carrageenan-induced knee joint arthritis. Drugs were administered into the CeLC by microdialysis before and/or after arthritis induction. All CeLC neurons showed increased responses to mechanical stimuli (“sensitization”) 5–6 h postinduction of arthritis. A selective CRF1 receptor antagonist ( NBI27914 ; 1–100 μM, concentration in microdialysis probe; 15 min) inhibited evoked responses and background activity in arthritis ( n = 9) but had no effect under normal conditions before arthritis ( n = 9). In contrast, a selective CRF2 receptor antagonist (Astressin-2B; 1–100 μM, 15 min) had no effect in arthritis ( n = 7) but increased the neurons' responses under normal conditions ( n = 8). These data suggest that CRF1 receptors in the amygdala contribute to pain-related sensitization, whereas the normally inhibitory function of CRF2 receptors is lost in the arthritis pain model.
Firing Properties of GABAergic Versus Non-GABAergic Vestibular Nucleus Neurons Conferred by a Differential Balance of Potassium Currents
Authors: Gittis Aryn H. , du Lac Sascha
Published: March 2007

Neural circuits are composed of diverse cell types, the firing properties of which reflect their intrinsic ionic currents. GABAergic and non-GABAergic neurons in the medial vestibular nuclei, identified in GIN and YFP-16 lines of transgenic mice, respectively, exhibit different firing properties in brain slices. The intrinsic ionic currents of these cell types were investigated in acutely dissociated neurons from 3- to 4-wk-old mice, where differences in spontaneous firing and action potential parameters observed in slice preparations are preserved. Both GIN and YFP-16 neurons express a combination of four major outward currents: Ca2+-dependent K+ currents ( IKCa), 1 mM TEA-sensitive delayed rectifier K+ currents ( I1TEA), 10 mM TEA-sensitive delayed rectifier K+ currents ( I10TEA), and A-type K+ currents ( IA). The balance of these currents varied across cells, with GIN neurons tending to express proportionately more IKCa and IA, and YFP-16 neurons tending to express proportionately more I1TEA and I10TEA. Correlations in charge densities suggested that several currents were coregulated. Variations in the kinetics and density of I1TEA could account for differences in repolarization rates observed both within and between cell types. These data indicate that diversity in the firing properties of GABAergic and non-GABAergic vestibular nucleus neurons arises from graded differences in the balance and kinetics of ionic currents.
Study of Cutaneous Reflex Compensation During Locomotion After Nerve Section in the Cat
Authors: Bernard Geneviève , Bouyer Laurent , Provencher Janyne , Rossignol Serge
Published: March 2007

In the cat, section of all cutaneous nerves of the hindfeet except the tibial (Tib) nerve supplying the plantar surface results in a long-lasting decrease in the intensity of Tib stimulation needed for a threshold response in flexor muscles and an increase in the amplitude of the phase-dependent responses recorded in various muscles during locomotion. Stimulating through chronically implanted nerve cuffs ensured a stable stimulation over time. The increase in reflex amplitude was well above the small increase in the amplitude of the locomotor bursts themselves that results from the denervation. Short latency responses (P1) were seen in flexor muscles, especially at the knee (semitendinosus) and ankle (tibialis anterior and extensor digitorum longus), with stimuli applied in the swing phase and also to a lesser degree in the later part of the cycle. Longer latency responses (P2) were increased in hip, knee, and ankle flexors, as well as in a contralateral extensor (vastus lateralis) when applied in late stance. Responses evoked from stimulating the proximal end of sectioned nerves were not larger than before neurectomy. This suggests that the increased responsiveness to Tib stimulation is not simply caused by an increase in motoneuron excitability, because this would have resulted in a nonspecific increase of responses to stimulation of any nerve. It is concluded that the adult locomotor system is capable of central reorganization to enhance specific remaining cutaneous reflex pathways after a partial cutaneous denervation of the paw.
Motor Adaptation as a Greedy Optimization of Error and Effort
Authors: Emken Jeremy L. , Benitez Raul , Sideris Athanasios , Bobrow James E. , Reinkensmeyer David J.
Published: March 2007

Motor adaptation to a novel dynamic environment is primarily thought of as a process in which the nervous system learns to anticipate the environmental forces to eliminate kinematic error. Here we show that motor adaptation can more generally be modeled as a process in which the motor system greedily minimizes a cost function that is the weighted sum of kinematic error and effort. The learning dynamics predicted by this minimization process are a linear, auto-regressive equation with only one state, which has been identified previously as providing a good fit to data from force-field-type experiments. Thus we provide a new theoretical result that shows how these previously identified learning dynamics can be viewed as arising from an optimization of error and effort. We also show that the coefficients of the learning dynamics must fall within a specific range for the optimization model to be valid and verify with experimental data from walking in a force field that they indeed fall in this range. Finally, we attempted to falsify the model by performing experiments in two conditions (repeated exposure to a force field, exposure to force fields of different strengths) for which the single-state, auto-regressive equation might be expected to not fit the data well. We found however that the equation adequately captured the pattern of errors and thus conclude that motor adaptation to a force field can be approximated as an optimization of effort and error for a range of experimental conditions.
Persistent Synaptic Activity Produces Long-Lasting Enhancement of Endocannabinoid Modulation and Alters Long-Term Synaptic Plasticity
Authors: Zhu Ping Jun , Lovinger David M.
Published: March 2007

Learning and memory are thought to involve activity-dependent changes in synaptic efficacy such as long-term potentiation (LTP) and long-term depression (LTD). Recent studies have indicated that endocannabinoid-dependent modulation of inhibitory transmission facilitates induction of hippocampal LTP and that endocannabinoids play a key role in certain forms of LTD. Here, we show that repetitive low-frequency synaptic stimulation (LFS) produces persistent up-regulation of endocannabinoid signaling at hippocampal CA1 GABAergic synapses. This LFS also produces LTD of inhibitory synapses and facilitates LTP at excitatory, glutamatergic synapses. These endocannabinoid-mediated plastic changes could contribute to information storage within the brain.
Vestibular Perception and Navigation in the Congenitally Blind
Authors: Seemungal Barry M. , Glasauer Stefan , Gresty Michael A. , Bronstein Adolfo M.
Published: March 2007

Vestibular input is required for accurate locomotion in the dark, yet blind subjects’ vestibular function is unexplored. Such investigation may also identify visually dependent aspects of vestibular function. We assessed vestibular function perceptually in six congenitally blind (and 12 sighted) subjects. Cupula deflection by a transient angular, horizontal acceleration generates a related vestibular nerve signal that declines exponentially with time constant ≈4–7 s, which is prolonged to 15 s in the evoked vestibular-ocular reflex by the brain stem “velocity storage.” We measured perceptual velocity storage in blind subjects following velocity steps (overall perceptual vestibular time constant, experiment 1) and found it to be significantly shorter (5.34 s; range: 2.39–8.58 s) than in control, sighted subjects (15.8 s; P < 0.001). Vestibular navigation was assessed by subjects steering a motorized Bárány-chair in response to imposed angular displacements in a path-reversal task, “go-back-to-start” (GBS: experiment 2); and a path-completion task, “complete-the-circle” (CTC: experiment 3). GBS performances (comparing response vs. stimulus displacement regression slopes and r2) were equal between groups ( P > 0.05), but the blind showed worse CTC performance ( P < 0.05). Two blind individuals showed ultrashort perceptual time constants, high lifetime physical activity scores and superior CTC performances; we speculate that these factors may be inter-related. In summary, the vestibular velocity storage as measured perceptually is visually dependent. Early blindness does not affect path reversal performance but is associated with worse path completion, a task requiring an absolute spatial strategy. Although congenitally blind subjects are overall less able to utilize spatial mechanisms during vestibular navigation, prior extensive physical spatial activity may enhance vestibular navigation.
Spectroscopic, Thermal and Biological Studies on Some Trivalent Ruthenium and Rhodium NS Chelating Thiosemicarbazone Complexes
Authors: Sharma Vinod K. , Srivastava Shipra , Srivastava Ankita
Published: March 2007

The synthetic, spectroscopic, and biological studies of sixteen ring-substituted 4-phenylthiosemicarbazones and 4-nitrophenyl-thiosemicarbazones of anisaldehyde, 4-chlorobenzaldehyde, 4-fluorobenzaldehyde, and vanillin with ruthenium(III) and rhodium(III) chlorides are reported here. Their structures were determined on the basis of the elemental analyses, spectroscopic data (IR, electronic,H1andC13NMR) along with magnetic susceptibility measurements, molar conductivity and thermogravimetric analyses. Electrical conductance measurement revealed a1:3electrolytic nature of the complexes. The resulting colored products are monomeric in nature. On the basis of the above studies, three ligands were suggested to be coordinated to each metal atom by thione sulphur and azomethine nitrogen to form low-spin octahedral complexes with ruthenium(III) while forming diamagnetic complexes with rhodium(III). Both ligands and their complexes have been screened for their bactericidal activities and the results indicate that they exhibit a significant activity.
Precise Rates in Log Laws for NA Sequences
Authors: Zhao Yuexu
Published: March 2007

LetX1,X2,…be a strictly stationary sequence of negatively associated (NA) random variables withEX1=0, setSn=X1+⋯+Xn, suppose thatσ2=EX12+2∑n=2∞EX1Xn>0andEX12<∞,if−1<α≤1;EX12(log|X1|)α<∞, ifα>1. We provelimε↓0ε2α+2∑n=1∞((logn)α/n)P(|Sn|≥σ(ε+κn)2nlogn)=2−(α+1)(α+1)−1E|N|2α+2, whereκn=O(1/logn)and N is the standard normal random variable.
Chemical Analysis through CL-Detection Assisted by Periodate Oxidation
Authors: Evmiridis Nicholaos P. , Vlessidis Athanasios G. , Thanasoulias Nicholas C.
Published: March 2007

The progress of the research work of the author and his colleagues on the field of CL-emission generated by pyrogallol oxidation and further application for the direct determination of periodate and indirect or direct determination of other compounds through flow-injection manifold/CL-detection set up is described. The instrumentation used for these studies was a simple flow-injection manifold that provides good reproducibility, coupled to a red sensitive photomultiplier that gives sensitive CL-detection. In addition, recent reports on studies and analytical methods based on CL-emission generated by periodate oxidation by other authors are included.
Defining Growth Hormone Status in Adults with Hypopituitarism
Authors: Kaushal K. , Shalet S.M.
Published: March 2007

The identification of adults with severe growth hormone (GH) deficiency (GHD) is not straightforward. The insulin tolerance test remains the gold standard diagnostic test, although other stimuli such as GH-releasing hormone-arginine are gaining acceptance. Insulin-like growth factor-I has a poor diagnostic sensitivity in adult-onset GHD, but is more useful in the subgroup of adults with childhood-onset GHD. Therapeutic developments include increasing recognition of the need to continue GH therapy beyond final height in young adults with severe GHD on retesting. Consensus guidelines have provided a useful algorithm to identify individuals requiring retesting and the number of tests needed. The concept of partial GHD, recognized by paediatric endocrinologists for many years, is being examined in adults with hypothalamic-pituitary disease. Preliminary evidence suggests that this entity is associated with metabolic and anthropometric abnormalities intermediate between those in severe GHD and in healthy controls. It remains to be seen whether this subgroup will derive benefit from GH therapy. To date, therapeutic benefits of GH have been demonstrated only in adults with severe GHD. It is, therefore, imperative that these individuals are unequivocally identified; the diagnosis becomes more uncertain in the presence of obesity, increasing age, and in the absence of additional pituitary hormone deficits.