bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of an Internal and Two 3′-Terminal RNA Elements in Assembly of Tombusvirus Replicase
Authors: Panaviene Zivile , Panavas Tadas , Nagy Peter D.
Published: July 2005

Plus-strand RNA virus replication requires the assembly of the viral replicase complexes on intracellular membranes in the host cells. The replicase of
Cucumber necrosis virus
(CNV), a tombusvirus, contains the viral p33 and p92 replication proteins and possible host factors. In addition, the assembly of CNV replicase is stimulated in the presence of plus-stranded viral RNA (Z. Panaviene et al., J. Virol.
78:
8254-8263, 2004). To define
cis
-acting viral RNA sequences that stimulate replicase assembly, we performed a systematic deletion approach with a model tombusvirus replicon RNA in
Saccharomyces cerevisiae
, which also coexpressed p33 and p92 replication proteins. In vitro replicase assays performed with purified CNV replicase preparations from yeast revealed critical roles for three RNA elements in CNV replicase assembly: the internal p33 recognition element (p33RE), the replication silencer element (RSE), and the 3′-terminal minus-strand initiation promoter (gPR). Deletion or mutagenesis of these elements reduced the activity of the CNV replicase to a minimal level. In addition to the primary sequences of gPR, RSE, and p33RE, formation of two alternative structures among these elements may also play a role in replicase assembly. Altogether, the role of multiple RNA elements in tombusvirus replicase assembly could be an important factor to ensure fidelity of template selection during replication.
Effect of a Protease Inhibitor-Induced Genetic Bottleneck on Human Immunodeficiency Virus Type 1
env
Gene Populations
Authors: Kitrinos Kathryn M. , Nelson Julie A. E. , Resch Wolfgang , Swanstrom Ronald
Published: July 2005

The initiation of drug therapy or the addition of a new drug to preexisting therapy can have a significant impact on human immunodeficiency virus type 1 (HIV-1) populations within a person. Drug therapy directed at reverse transcriptase and protease can result in dramatic decreases in virus load, causing a contraction in the virus population that represents a potential genetic bottleneck as a subset of virus with genomes carrying resistance mutations repopulate the host. While this bottleneck exerts an effect directly on the region that is being targeted by the drugs, it also affects other regions of the viral genome. We have applied heteroduplex tracking assays (HTA) specific to variable regions 1 and 2 (V1/V2) and variable region 3 (V3) of the HIV-1
env
gene to analyze the effect of a genetic bottleneck created by the selection of resistance to ritonavir, a protease inhibitor. Subjects were classified into groups on the basis of the extent of the initial drop in virus load and the duration of virus load reduction. Subjects with a strong initial drop in virus load exhibited a loss of heterogeneity in the
env
region at virus load rebound; in contrast, subjects with a weak initial drop in virus load exhibited little to no loss of heterogeneity at virus load rebound in either region of
env
examined. The duration of virus load reduction also affected
env
populations. Subjects that had prolonged reductions exhibited slower population diversification and the appearance of new V1/V2 species after rebound. The longer reduction of virus load in these subjects may have allowed for improved immune system function, which in turn could have selected for new escape mutants. Subjects with rapid rebound quickly reequilibrated the entry
env
variants back into the resistant population. When the
pro
gene developed further resistance mutations subsequent to virus load rebound, no changes were observed in V1/V2 or V3 populations, suggesting that the high virus loads allowed the
env
populations to reequilibrate rapidly. The rapid equilibration of
env
variants during
pro
gene sequence transitions at high virus load suggests that recombination is active in defining the HIV-1 sequence population. Conversely, part of the success of suppressive antiviral therapy may be to limit the potential for evolution through recombination, which requires dually infected cells.
The Ebola Virus Genomic Replication Promoter Is Bipartite and Follows the Rule of Six
Authors: Weik Michael , Enterlein Sven , Schlenz Kathrin , Mühlberger Elke
Published: July 2005

In this work we investigated the
cis
-acting signals involved in replication of Ebola virus (EBOV) genomic RNA. A set of mingenomes with mutant 3′ ends were generated and used in a reconstituted replication and transcription system. Our results suggest that the EBOV genomic replication promoter is bipartite, consisting of a first element located within the leader region of the genome and a second, downstream element separated by a spacer region. While proper spacing of the two promoter elements is a prerequisite for replication, the nucleotide sequence of the spacer is not important. Replication activity was only observed when six or a multiple of six nucleotides were deleted or inserted, while all other changes in length abolished replication completely. These data indicate that the EBOV replication promoter obeys the rule of six, although the genome length is not divisible by six. The second promoter element is located in the 3′ nontranslated region of the first gene and consists of eight UN
5
hexamer repeats, where N is any nucleotide. However, three consecutive hexamers, which could be located anywhere within the promoter element, were sufficient to support replication as long as the hexameric phase was preserved. By using chemical modification assays, we could demonstrate that nucleotides 5 to 44 of the EBOV leader are involved in the formation of a stable secondary structure. Formation of the RNA stem-loop occurred independently of the presence of the trailer, indicating that a panhandle structure is not formed between the 3′ and 5′ ends.
Generation of an Influenza A Virus Vector Expressing Biologically Active Human Interleukin-2 from the NS Gene Segment
Authors: Kittel Christian , Ferko Boris , Kurz Martina , Voglauer Regina , Sereinig Sabine , Romanova Julia , Stiegler Gabriela , Katinger Hermann , Egorov Andrej
Published: July 2005

Engineering of the influenza A virus NS1 protein became an attractive approach to the development of influenza vaccine vectors since it can tolerate large inserts of foreign proteins. However, influenza virus vectors expressing long foreign sequences from the NS1 open reading frame (ORF) are usually replication deficient in animals due to the abrogation of their NS1 protein function. In this study, we describe a bicistronic expression strategy based on the insertion of an overlapping UAAUG stop-start codon cassette into the NS gene, allowing the reinitiation of translation of a foreign sequence. Although the expression level of green fluorescent protein (GFP) from the newly created reading frame was significantly lower than that obtained previously from an influenza virus vector expressing GFP from the NS1 ORF, the bicistronic vector appeared to be replication competent in mice and showed outstanding genetic stability. All viral isolates derived from mouse lungs at 10 days postinfection were still capable of expressing GFP in infected cells. Utilizing this bicistronic approach, we constructed another recombinant influenza virus, allowing the secretion of biologically active human interleukin-2 (IL-2). Although this virus also replicated to high titers in mouse lungs, it did not display any mortality rate in infected animals, in contrast to control viruses. Moreover, the IL-2-expressing virus showed an enhanced CD8
+
response to viral antigens in mice after a single intranasal immunization. These results indicate that influenza viruses could be engineered for the expression of biologically active molecules such as cytokines for immune modulation purposes.
Herpes Simplex Virus Type 1 DNA Polymerase Requires the Mammalian Chaperone Hsp90 for Proper Localization to the Nucleus
Authors: Burch April D. , Weller Sandra K.
Published: July 2005

Many viruses and bacteriophage utilize chaperone systems for DNA replication and viral morphogenesis. We have previously shown that in the herpes simplex virus type 1 (HSV-1)-infected cell nucleus, foci enriched in the Hsp70/Hsp40 chaperone machinery are formed adjacent to viral replication compartments (A. D. Burch and S. K. Weller, J. Virol.
78:
7175-7185, 2004). These foci have now been named virus-induced chaperone-enriched (VICE) foci. Since the Hsp90 chaperone machinery is known to engage the Hsp70/Hsp40 system in eukaryotes, the subcellular localization of Hsp90 in HSV-1-infected cells was analyzed. Hsp90 is found within viral replication compartments as well as in the Hsp70/Hsp40-enriched foci. Geldanamycin, an inhibitor of Hsp90, results in decreased HSV-1 yields and blocks viral DNA synthesis. Furthermore, we have found that the viral DNA polymerase is mislocalized to the cytoplasm in both infected and transfected cells in the presence of geldanamycin. Additionally, in the presence of an Hsp90 inhibitor, proteasome-dependent degradation of the viral polymerase was detected by Western blot analysis. These data identify the HSV-1 polymerase as a putative client protein of the Hsp90 chaperone system. Perturbations in this association appear to result in degradation, aberrant folding, and/or intracellular localization of the viral polymerase.
Myxoma Virus M-T5 Protects Infected Cells from the Stress of Cell Cycle Arrest through Its Interaction with Host Cell Cullin-1
Authors: Johnston J. B. , Wang G. , Barrett J. W. , Nazarian S. H. , Colwill K. , Moran M. , McFadden G.
Published: July 2005

The myxoma virus (MV) M-T5 gene encodes an ankyrin repeat protein that is important for virus replication in cells from several species. Insight was gained into the molecular mechanisms underlying the role of M-T5 as a host range determinant when the cell cycle regulatory protein cullin-1 (cul-1) was identified as a cellular binding partner of M-T5 and found to colocalize with the protein in both nuclear and cytosolic compartments. Consistent with this interaction, infection with wild-type MV (vMyxlac) or a deletion mutant lacking M-T5 (vMyxT5KO) differentially altered cell cycle progression in a panel of permissive and nonpermissive cells. Cells infected with vMyxlac transitioned rapidly out of the G
0
/G
1
phase and preferentially accumulated at the G
2
/M checkpoint, whereas infection with vMyxT5KO impeded progression through the cell cycle, resulting in a greater percentage of cells retained at G
0
/G
1
. Levels of the cul-1 substrate, p27/Kip-1, were selectively increased in cells infected with vMyxT5KO compared to vMyxlac, concurrent with decreased phosphorylation of p27/Kip-1 at Thr187 and decreased ubiquitination. Compared to cells infected with vMyxlac, cell death was increased in vMyxT5KO-infected cells following treatment with diverse stimuli known to induce cell cycle arrest, including infection itself, serum deprivation, and exposure to proteasome inhibitors or double-stranded RNA. Moreover, infection with vMyxlac, but not vMyxT5KO, was sufficient to overcome the G
0
/G
1
arrest induced by these stimuli. These findings suggest that M-T5 regulates cell cycle progression at the G
0
/G
1
checkpoint, thereby protecting infected cells from diverse innate host antiviral responses normally triggered by G
0
/G
1
cell cycle arrest.
Mouse Cytomegalovirus M33 Is Necessary and Sufficient in Virus-Induced Vascular Smooth Muscle Cell Migration
Authors: Melnychuk Ryan M. , Smith Patsy , Kreklywich Craig N. , Ruchti Franziska , Vomaske Jennifer , Hall Laurel , Loh Lambert , Nelson Jay A. , Orloff Susan L. , Streblow Daniel N.
Published: July 2005

Mouse cytomegalovirus (MCMV) encodes two potential seven-transmembrane-spanning proteins with homologies to cellular chemokine receptors, M33 and M78. While these virus-encoded chemokine receptors are necessary for the in vivo pathogenesis of MCMV, the function of these proteins is unknown. Since vascular smooth muscle cell (SMC) migration is of critical importance for the development of atherosclerosis and other vascular diseases, the ability of M33 to promote SMC motility was assessed. Similar to human CMV, MCMV induced the migration of mouse aortic SMCs but not mouse fibroblasts. To demonstrate whether M33 was required for MCMV-induced SMC migration, we employed interfering-RNA technology to specifically knock down M33 expression in the context of viral infection. The knockdown of M33 resulted in the specific reduction of M33 protein expression and ablation of MCMV-mediated SMC migration but failed to reduce viral growth in cultured cells. Adenovirus vector expression of M33 was sufficient to promote SMC migration, which was enhanced in the presence of recombinant mouse RANTES (mRANTES). In addition, M33 promoted the activation of Rac1 and extracellular signal-related kinase 1/2 upon stimulation with mRANTES. These findings demonstrate that mRANTES is a ligand for this chemokine receptor and that the activation of M33 occurs in a ligand-dependent manner. Thus, M33 is a functional homologue of US28 that is required for MCMV-induced vascular SMC migration.
Increased Human Immunodeficiency Virus Type 1 (HIV-1)
env
Compartmentalization in the Presence of HIV-1-Associated Dementia
Authors: Ritola Kimberly , Robertson Kevin , Fiscus Susan A. , Hall Colin , Swanstrom Ronald
Published: July 2005

The human immunodeficiency virus type 1 (HIV-1) surface Env protein has been implicated in the development of HIV-1-associated dementia (HAD). HIV-1
env
diversity was analyzed by heteroduplex tracking assay in 27 infected subjects with various neurological statuses.
env
compartmentalization between the blood and cerebral spinal fluid (CSF) was apparent with all neurological categories. However, in subjects with HAD, significantly more CSF virus was represented by CNS-unique
env
variants. Variants specialized for replication in the CNS may play a larger role in the development of HAD. Alternatively, HAD may be associated with a more pronounced state of immunosuppression that permits more extensive replication and independent evolution within the CNS compartment.
INFLUENCE OF GRAVITY ON NONCOMMUTATIVE DIRAC EQUATION
Authors: BOUROUAINE SOFIANE , BENSLAMA ACHOUR
Published: July 2005

In this paper, we investigate the influence of gravity and noncommutativity on Dirac particles. By adopting the tetrad formalism, we show that the modified Dirac equation keeps the same form. The only modification is in the expression of the covariant derivative. The new form of this derivative is the product of its counterpart given in curved spacetime with an operator which depends on the noncommutative θ-parameter. As an application, we have computed the density number of the created particles in the presence of constant strong electric field in an anisotropic Bianchi universe.
INDUCED PHANTOM AND 5D ATTRACTOR SOLUTION IN SPACETIME–MATTER THEORY
Authors: LIU HONGYA , LIU HUANYING , CHANG BAORONG , XU LIXIN
Published: July 2005

In Spacetime–Matter theory we assume that the 4D induced matter of the 5D Ricci-flat bouncing cosmological solutions contains a perfect fluid as well as an induced scalar field. Then we show that the conventional 4D quintessence and phantom models of dark energy could be recovered from the 5D cosmological solutions. By using the phase-plane analysis to study the stability of evolution of the 5D models, we find that the conventional 4D late-time attractor solution is also recovered. This attractor solution shows that the scale factors of the phantom dominated universes in both the 4D and 5D theories will reach infinity in a finite time and the universes will be ended at a new kind of spacetime singularity at which everything will be annihilated. We also find that the repulsive force of the phantom may provide us with a mechanics to explain the bounce.
AN INFINITESIMAL ANALYSIS OF THE STOP-LOSS-START-GAIN STRATEGY
Authors: NG SIU-AH
Published: July 2005

The paradox of the Stop-Loss-Start-Gain trading strategy is resolved by showing that along the hyperfinite timeline the strategy incurs infinitesimal losses summing up to a non-infinitesimal amount. As a consequence, the Black–Scholes formula is derived using only hyperreal arithmetic and Riemann sum, probably the most elementary derivation thus far.
LOCALIZED MONTE CARLO ALGORITHM TO COMPUTE PRICES OF PATH DEPENDENT OPTIONS ON TREES
Authors: FERRANDO SEBASTIAN E. , BERNAL ARIEL J.
Published: July 2005

A new simulation based algorithm to approximate prices of path dependent European options is introduced. The algorithm is defined for tree-like approximations to the underlying process and makes extensive use of structural properties of the discrete approximation. We indicate the advantages of the new algorithm in comparison to standard Monte Carlo algorithms. In particular, we prove a probabilistic error bound that compares the quality of both approximations. The algorithm is of general applicability and, for a large class of options, it has the same computational complexity as Monte Carlo.
A SIMPLE NOISE MODEL WITH MEMORY FOR BIOLOGICAL SYSTEMS
Authors: CHICHIGINA O. , VALENTI D. , SPAGNOLO B.
Published: July 2005

A noise source model, consisting of a pulse sequence at random times with memory, is presented. By varying the memory we can obtain variable randomness of the stochastic process. The delay time between pulses, i.e. the noise memory, produces different kinds of correlated noise ranging from white noise, without delay, to quasi-periodical process, with delay close to the average period of the pulses. The spectral density is calculated. This type of noise could be useful to describe physical and biological systems where some delay is present. In particular it could be useful in population dynamics. A simple dynamical model for epidemiological infection with this noise source is presented. We find that the time behavior of the illness depends on the noise parameters. Specifically the amplitude and the memory of the noise affect the number of infected people.
ANOMALOUS DIFFUSION AND GENERALIZED DIFFUSION EQUATIONS
Authors: SOKOLOV I. M. , CHECHKIN A. V.
Published: July 2005

Fractional diffusion equations are widely used to describe anomalous diffusion processes where the characteristic displacement scales as a power of time. The forms of such equations might differ with respect to the position of the corresponding fractional operator in addition to or instead of the whole-number derivative in the Fick's equation. For processes lacking simple scaling the corresponding description may be given by distributed-order equations. In the present paper different forms of distributed-order diffusion equations are considered. The properties of their solutions are discussed for a simple special case.
Divergent transcriptional enhancer factor-1 regulates the cardiac troponin T promoter
Authors: Azakie Anthony , LaMont Lauren , Fineman Jeffrey R. , He Youping
Published: July 2005

MCAT elements are essential for cardiac gene expression during development. Avian transcriptional enhancer factor-1 (TEF-1) proteins are muscle-enriched and contribute to MCAT binding activities. However, direct activation of MCAT-driven promoters by TEF-1-related proteins has not been uniformly achieved. Divergent TEF (DTEF)-1 is a unique member of the TEF-1 multigene family with abundant transcripts in the heart but not in skeletal muscle. Herein we show that DTEF-1 proteins are highly expressed in the heart. Protein expression is activated at very early stages of chick embryogenesis (Hamburger-Hamilton stage 4, 16–18 h), after which DTEF-1 becomes abundant in the sinus venosus and is expressed in the trabeculated ventricular myocardium and ventricular outflow tracts. By chromatin immunoprecipitation, DTEF-1 interacts with the cardiac troponin T (cTnT) promoter in vivo. DTEF-1 also interacts with MEF- 2 by coimmunoprecipitation and independently or cooperatively (with MEF-2) trans-activates the cTnT promoter. DTEF-1 isoforms do not activate the cTnT promoter in fibroblasts or skeletal muscle. DTEF-1 expression occurs very early in chick embryogenesis (16–18 h), preceding sarcomeric protein expression, and it activates cardiac promoters. As such, DTEF-1 may be an early marker of the myocardial phenotype. DTEF-1 trans-activates the cTnT promoter in a tissue-specific fashion independent of AT-rich, MEF-2, or GATA sites. The observed spatial pattern suggests decreasing levels of expression from the cardiac inlet to the ventricular outflow tracts, which may mark a cardiogenic or differentiation pathway that parallels the direction of flow through the developing chick heart.
Association between Hsp90 and the ClC-2 chloride channel upregulates channel function
Authors: Hinzpeter Alexandre , Lipecka Joanna , Brouillard Franck , Baudoin-Legros Maryvonne , Dadlez Michal , Edelman Aleksander , Fritsch Janine
Published: July 2005

The voltage-dependent ClC-2 chloride channel has been implicated in a variety of physiological functions, including fluid transport across specific epithelia. ClC-2 is activated by hyperpolarization, weakly acidic external pH, intracellular Cl−, and cell swelling. To add more insight into the mechanisms involved in ClC-2 regulation, we searched for associated proteins that may influence ClC-2 activity. With the use of immunoprecipitation of ClC-2 from human embryonic kidney-293 cells stably expressing the channel, followed by electrophoretic separation of coimmunoprecipitated proteins and mass spectrometry identification, Hsp70 and Hsp90 were unmasked as possible ClC-2 interacting partners. Association of Hsp90 with ClC-2 was confirmed in mouse brain. Inhibition of Hsp90 by two specific inhibitors, geldanamycin or radicicol, did not affect total amounts of ClC-2 but did reduce plasma membrane channel abundance. Functional experiments using the whole cell configuration of the patch-clamp technique showed that inhibition of Hsp90 reduced ClC-2 current amplitude and impaired the intracellular Cl− concentration [Cl−]-dependent rightward shift of the fractional conductance. Geldanamycin and radicicol increased both the slow and fast activation time constants in a chloride-dependent manner. Heat shock treatment had the opposite effect. These results indicate that association of Hsp90 with ClC-2 results in greater channel activity due to increased cell surface channel expression, facilitation of channel opening, and enhanced channel sensitivity to intracellular [Cl−]. This association may have important pathophysiological consequences, enabling increased ClC-2 activity in response to cellular stresses such as elevated temperature, ischemia, or oxidative reagents.
KATPchannel conductance of descending vasa recta pericytes
Authors: Cao Chunhua , Lee-Kwon Whaseon , Silldorff Erik P. , Pallone Thomas L.
Published: July 2005

Using nystatin-perforated patch-clamp and whole cell recording, we tested the hypothesis that KATPchannels contribute to resting conductance of rat descending vasa recta (DVR) pericytes and are modulated by vasoconstrictors. The KATPblocker glybenclamide (Glb; 10 μM) depolarized pericytes and inhibited outward currents of cells held at −40 mV. KATPopeners pinacidil (Pnc; 10 μM) and P-1075 (1 μM) hyperpolarized pericytes and transiently augmented outward currents. All effects of Pnc and P-1075 were fully reversed by Glb. Inward currents of pericytes held at −60 mV in symmetrical 140 mM K+were markedly augmented by Pnc and fully reversed by Glb. Ramp depolarizations in symmetrical K+, performed in Pnc and Pnc + Glb, yielded a Pnc-induced, Glb-sensitive KATPdifference current that lacked rectification and reversed at 0 mV. Immunostaining identified both KIR6.1, KIR6.2 inward rectifier subunits and sulfonurea receptor subtype 2B. ANG II (1 and 10 nM) and endothelin-1 (10 nM) but not vasopressin (100 nM) significantly lowered holding current at −40 mV and abolished Pnc-stimulated outward currents. We conclude that DVR pericytes express KATPchannels that make a significant contribution to basal K+conductance and are inhibited by ANG II and endothelin-1.
Signal Propagation Along Unidimensional Neuronal Networks
Authors: Feinerman Ofer , Segal Menahem , Moses Elisha
Published: July 2005

Dissociated neurons were cultured on lines of various lengths covered with adhesive material to obtain an experimental model system of linear signal transmission. The neuronal connectivity in the linear culture is characterized, and it is demonstrated that local spiking activity is relayed by synaptic transmission along the line of neurons to develop into a large-scale population burst. Formally, this can be treated as a one-dimensional information channel. Directional propagation of both spontaneous and stimulated bursts along the line, imaged with the calcium indicator Fluo-4, revealed the existence of two different propagation velocities. Initially, a small number of neighboring neurons fire, leading to a slow, small and presumably asynchronous wave of activity. The signal then spontaneously develops to encompass much larger and further populations, and is characterized by fast propagation of high-amplitude activity, which is presumed to be synchronous. These results are well described by an existing theoretical framework for propagation based on an integrate-and-fire model.
Polarization-Sensitive and Light-Sensitive Neurons in Two Parallel Pathways Passing Through the Anterior Optic Tubercle in the Locust Brain
Authors: Pfeiffer Keram , Kinoshita Michiyo , Homberg Uwe
Published: July 2005

Many migrating animals use a sun compass for long-range navigation. One of the guiding cues used by insects is the polarization pattern of the blue sky. In the desert locust Schistocerca gregaria, neurons of the central complex, a neuropil in the center of the brain, are sensitive to polarized light and might serve a key role in compass navigation. Visual pathways to the central complex include signal processing in the upper and lower units of the anterior optic tubercle. To determine whether these pathways carry polarization-vision signals, we have recorded the responses of interneurons of the optic tubercle of the locust to visual stimuli including polarized light. All neurons of the lower unit but only one of five recorded neurons of the upper unit of the tubercle were sensitive to linearly polarized light presented in the dorsal visual field. These neurons showed polarization opponency, or a sinusoidal modulation of activity, during stimulation through a rotating polarizer. Two types of bilateral interneurons preferred particular e-vector orientations, reflecting the presence of bilateral pairs of these neurons in the brain. We show here for the first time neurons with projections to the lateral accessory lobe that are suited to provide polarization input to the central complex. All neurons of the tubercle, furthermore, responded to unpolarized light, mostly with tonic activity changes. These responses strongly depended on stimulus position and might reflect navigation-relevant signals such as direct sunlight or visual landmarks that are integrated with polarization responses in neurons of the lower unit.
Impairment and Recovery of Postural Control in Rabbits With Spinal Cord Lesions
Authors: Lyalka V. F. , Zelenin P. V. , Karayannidou A. , Orlovsky G. N. , Grillner S. , Deliagina T. G.
Published: July 2005

The aim of this study was to characterize impairment and subsequent recovery of postural control after spinal cord injuries. Experiments were carried out on rabbits with three types of lesion—a dorsal (D), lateral (L), or ventral (V) hemisection (HS) at T12level. The animals were maintaining equilibrium on a platform periodically tilted in the frontal plane. We assessed the postural limb/trunk configuration from video recordings and postural reflexes in the hindquarters from kinematical and electromyographic (EMG) recordings. We found that for a few days after DHS or LHS, the animals were not able to maintain the dorsal-side-up position of their hindquarters. This ability was then gradually restored, and the dynamic postural reflexes reached the prelesion value within 2–3 wk. By contrast, a VHS almost completely abolished postural reflexes, and they did not recover for ≥7 wk. The DHS, LHS, and VHS caused immediate and slowly compensated changes in the postural limb/trunk configuration as well as gradually developing changes. After DHS, both hind limbs were placed in an abnormal rostral and medial position. After LHS, the limb on the undamaged side was turned inward and occurred at the abnormal medial position; LHS also caused a gradually developing twisting of the caudal trunk. VHS caused gradually developing extension of the ankle and knee joints. These findings show that ventral spinal pathways are of crucial importance for postural control. When a part of these pathways is spared, postural reflexes can be restored rapidly, but not the postural limb/trunk configuration. Spinal and supraspinal mechanisms responsible for postural deficits and their compensation are discussed.
Ionotropic 5-HT3 Receptor Agonist-Induced Motor Responses in the Hindlimbs of Paraplegic Mice
Authors: Guertin Pierre A. , Steuer Inge
Published: July 2005

Centrally expressed 5-HT3 receptors (5-HTR3) are well known for their role in wakefulness, cognition, and nociception. However, clear evidence of their participation in motor control is still lacking despite specific 5-HTR3 expression in hindlimb motor areas of the spinal cord (i.e., lumbar laminae VII-IX). Here, we studied the acute effects of 4-amino-(6-chloro-2-pyridyl)-1-piperidine hydrochloride (SR 57227A), a potent and selective 5-HTR3 agonist, on hindlimb movement generation in complete paraplegic mice. The induced movements were assessed in open-field, air-stepping, and treadmill conditions using a combination of qualitative and quantitative methods. The results revealed that SR 57227A (1–4 mg/kg ip) produced hindlimb movements corresponding to scores ranging from 1 to 5 on the motor scales of Basso, Beattie, and Bresnahan and of Antri, Orsal, and Barthe. Additional analyses revealed that one-third of the movements displayed on a treadmill were “locomotor-like” (i.e., bilateral alternation), whereas only nonlocomotor movements were observed in the other testing conditions suggesting a task-dependent contribution of peripheral afferent inputs to these effects. Locomotor-like movements could also be induced in open field and air stepping if SR 57227A was combined with subthreshold doses of 5-carboxytryptamine (5-HT1A/7 receptor agonist), suggesting synergistic actions of these drugs on central neurons. These results demonstrate that 5-HTR3 activation can induce motor activity and, under some conditions, rhythmic locomotor-like movements in the hindlimbs of paraplegic mice providing evidence of an unsuspected role for this receptor subtype in hindlimb motor control.
Endotoxin-Induced Uveitis Causes Long-Term Changes in Trigeminal Subnucleus Caudalis Neurons
Authors: Bereiter David A. , Okamoto Keiichiro , Tashiro Akimasa , Hirata Harumitsu
Published: July 2005

Endotoxin-induced uveitis (EIU) is commonly used in animals to mimic ocular inflammation in humans. Although the peripheral aspects of EIU have been well studied, little is known of the central neural effects of anterior eye inflammation. EIU was induced in male rats by endotoxin or lipopolysaccharide (LPS, 1 mg/kg ip) given 2 or 7 days earlier. Neurons responsive to mechanical stimulation of the ocular surface were recorded under barbiturate anesthesia at the trigeminal subnucleus interpolaris/caudalis (Vi/Vc) transition and subnucleus caudalis/cervical cord (Vc/C1) junction, the main terminal regions for corneal nociceptors. Two days after LPS, Vc/C1 units had reduced responses to histamine, nicotine, and CO2gas applied to the ocular surface, whereas unit responses were increased 7 days after LPS. Those units with convergent cutaneous receptive fields at Vc/C1 were enlarged 7 days after LPS. Units at the Vi/Vc transition also had reduced responses to histamine and CO22 days after LPS but no enhancement was seen at 7 days. Tear volume evoked by CO2was reduced 2 days after LPS and returned toward control values by 7 days, whereas CO2-evoked eye blinks were normal at 2 days and increased 7 days after LPS. These results indicate that a single exposure to endotoxin causes long-term changes in the excitability of second-order neurons responsive to noxious ocular stimulation. The differential effects of EIU on tear volume and eye blink lend further support for the hypothesis that ocular-sensitive neurons at the Vi/Vc transition and Vc/C1 junction regions mediate different aspects of pain during intraocular inflammation.
Michael Polanyi and Jewish Identity
Authors: Knepper Paul
Published: July 2005

Michael Polanyi’s Jewish identity contributed to his philosophical outlook. His life in a Hungarian-acculturated, nonobservant Jewish family in the last decades of the Austro-Hungarian Empire; his experience as a Jew emigrating from Hitler’s Germany; and his thoughts about Zionism informed his theory of knowledge. During the late 1930s and 1940s, he worked to reconcile his Jewish identity with his commitments to Christianity, and this tension contributed to his thinking about the nature of scientific discovery. The malapropism baptized Jew characterizes the scientist on the verge of discovery, one who occupies a twilight world between adherence and apostasy with regard to the scientific community.
Reasons, Causes, and Action Explanation
Authors: Risjord Mark
Published: July 2005

To explain an intentional action one must exhibit the agent’s reasons. Donald Davidson famously argued that the only clear way to understand action explanation is to hold that reasons are causes. Davidson’s discussion conflated two issues: whether reasons are causes and whether reasons causally explain intentional action. Contemporary work on explanation and normativity help disentangle these issues and ground an argument that intentional action explanations cannot be a species of causal explanation. Interestingly, this conclusion is consistent with Davidson’s conclusion that reasons are causes. In other words, reasons are causes, but rationalizing explanations are not causal explanations.
Book Review: The English Heidegger
Authors: Turner Stephen
Published: July 2005

Terry Nardin’s book on Oakeshott is an attempt to compare him to other 20th-century philosophers and to track the development of his philosophical thought. The project of comparison is made relevant by the fact that Oakeshott’s philosophy, like that of Heidegger and others, was the product of the dissolution of neo-Kantianism. Nardin stresses the idea of “modal confusion,” meaning responding to a question of one kind with an answer appropriate to another kind of inquiry, as a key to Oakeshott’s thought from Experience and Its Modes through to On Human Conduct itself, where Oakeshott changes his terminology. But why does Oakeshott change? One reason might be the critique of Oakeshott by Peter Winch, as Oakeshott appears to have reformulated his views in response to it in On Human Conduct, in the course of constructing an alternative to ‘conceptual analysis’ as practiced in contemporary Oxbridge.
Book Review: How and How Not to Write on a “Legendary” Philosopher
Authors: Read Rupert
Published: July 2005

The author argues that Fuller’s book, with the single exception of its correct reinterpretation of Kuhn as no apostle of postmodernism—such that his “fans” and “foes” alike are boxing with (or cheering on) only a shadow Kuhn—is worse than worthless. For, in a disreputable and outright propagandistic fashion, it consists in a series of serious distortions of and outright falsehoods about Kuhn and recent philosophy of science, distortions and falsehoods which may well mislead the unwary reader. Nickles’ s collection by contrast is a competent, useful, and workmanlike performance, although the author argues that the editor’s focus on cognitive science uses of Kuhn (and of Wittgenstein) is unhelpful, in that these uses again distort the philosophy of Kuhn (as of Wittgenstein), who was on balance no apostle of cognitive science either.
Bullying and Sexual Harassment Among Brazilian High School Students
Authors: DeSouza Eros R. , Ribeiro J’aims
Published: July 2005

Bullying and sexual harassment at school have received recent attention in developed countries; however, they have been neglected in Latin America. Thus, the authors investigated these phenomena among 400 Brazilian high school students from two high schools (one private and one public). Analyses using t -tests showed that boys bullied and sexually harassed their peers more often than girls did. Hierarchical multiple regression analyses showed that boys and girls who scored high on general misconduct bullied their peers more often than those who scored low on general misconduct. Boys who believed they would be punished by their teachers for bullying and who scored low on benevolent sexism bullied more often than boys who believed they would not be punished by their teachers and who scored high on benevolent sexism. Moreover, bullying predicted peer sexual harassment for boys and girls. Recommendations to prevent bullying and sexual harassment are offered.
The 5-Year Course of Intimate Partner Violence Among White, Black, and Hispanic Couples in the United States
Authors: Caetano Raul , Field Craig A. , Ramisetty-Mikler Suhasini , McGrath Christine
Published: July 2005

This article examines the 5-year incidence, prevalence, and recurrence of intimate partner violence (IPV) among White, Black, and Hispanic intact couples in the United States. A national multistage household probability sample of couples, age 18 years or older, was interviewed in 1995 with a response rate of 85%, and reinter-viewed in 2000 with a response rate of 72%. Results indicate that the incidence and recurrence of IPV are higher for Blacks and Hispanics than for Whites. Compared to Whites, Hispanics are 2.5 times more likely to initiate IPV between baseline and follow-up and Blacks are 3.7 times more likely to report IPV at baseline and follow-up. Couples reporting severe IPV in 1995 are more likely than others to report severe IPV at follow-up. The rate of recurrence for severe IPV among Black and Hispanic couples is 6 and 4 times higher, respectively, than the rate among Whites. The results suggest that Blacks and Hispanics may be more affected by IPV.
Perceived Control and Emotional Status in Abusive College Student Relationships
Authors: Clements Caroline , Ogle Richard , Sabourin Caryn
Published: July 2005

The authors assessed perceived control, dysphoria, hopelessness, self-esteem, and optimism in 280 college students involved in abusive and nonabusive relationships. Women reported higher levels of dysphoria and lower levels of self-esteem and optimism than men. Women in abusive relationships reported more psychological symptoms than men in abusive relationships. After controlling for gender differences in emotional status, participants in abusive relationships showed more psychological symptoms than those in nonabusive relationships. Women showed lower perceived control of relationship conflicts than men. Men experiencing high levels of abuse reported higher perceived control of relationship conflict than females experiencing low levels of abuse. Perceived control was affected more by gender than emotional status, abuse level, and gender-affected emotional status. The authors discuss the results in terms of their implications for future investigations of emotional reactions to abuse.
Psychopathy, Treatment Behavior, and Recidivism
Authors: Barbaree Howard E.
Published: July 2005

Seto and Barbaree reported the unexpected finding that adult male sex offenders who scored higher on psychopathy and exhibited better behavior in treatment were almost four times more likely to commit a new serious offence than other offenders once released. The present study reexamined this sample after a longer follow-up time using more complete recidivism data from a national police database. Although psychopathy continued to be a significant predictor of general and serious recidivism, treatment behavior was no longer related to either general or serious recidivism, and there was no statistically significant interaction between psychopathy and treatment behavior. Additional analyses ruled out the possibility that the differences between studies could be accounted for by the different average length of follow-up. A direct comparison of the two sources of recidivism data showed that differences in recidivism between subgroups were reduced by using the more complete recidivism data.
Portuguese Immigrant Women’s Perspectives on Wife Abuse
Authors: Barata Paula C. , McNally Mary Jane , Sales Isabel M. , Stewart Donna E.
Published: July 2005

This descriptive study seeks to understand what first and second generation Portuguese women believe about wife abuse and what actions they believe are appropriate for an abused wife. Eighty first generation and 54 second generation women participated. The researcher read the questionnaire items aloud in one-on-one meetings. Overall, participants defined wife abuse broadly, did not approve of wife abuse, were most likely to believe that women should seek external help, and did not hold strong patriarchal beliefs. However, a number of generational differences were found. Second generation women were more likely to label an abusive behavior as abuse, and first generation women were more likely to approve of abuse, endorse indirect or traditional options to deal with wife abuse, and hold stronger patriarchal beliefs. The study’s implications for research and practice within Portuguese communities are discussed.
Money and Machine Politics
Authors: Krebs Timothy B.
Published: July 2005

Machine coalitions use their influence to reward supporters with public goods. In this article, the author examines the link between machine coalitions and corporate and labor contributions in Chicago city council elections. He argues that machine coalition members are at a strategic advantage relative to those outside of it, all things being equal. The results of Tobit regression models applied to both nonincumbent and incumbent candidates support the theory. In practice, what it means in Chicago is that Whites and Latinos are favored over Blacks in the increasingly important quest for campaign money.
Family Self-Sufficiency Programs
Authors: Anthony Jerry
Published: July 2005

Since the mid-1980s, family self-sufficiency programs have been set up in over 1,000 cities and counties across the United States. These programs are aimed at helping public-housing residents and Section 8 tenants, who often have very little or no wage income, become economically self-sufficient and move into private housing. Though much has been written about the potential of such programs, research examining their benefits is virtually nonexistent. This article seeks to partly fill this void. The research reported here examined data on 135 participants of the City of Rockford, Illinois’ s Family Self-Sufficiency program. Using logistic regression techniques, the effects of several factors on program completion were explored. The author reports that Rockford’s Family Self-Sufficiency program graduates derived significant economic and housing benefits, and that race did not seem to affect graduation while other factors, such as age and the number of skills acquired in the program, seemed to.
Be Careful what You wish for
Authors: Mikelbank Brian A.
Published: July 2005

Although it is commonly held that accessibility plays a role in house price determination, there is less explicit recognition that it is transportation infrastructure that is primarily delivering that accessibility. Large additions to the transportation infrastructure tend to be well studied, but there is a dearth of empirical research that investigates the house price impacts when local transportation infrastructure is incrementally invested in. If these smaller investments also impact accessibility, then there should be a measurable impact in the housing market. Although results show that this is in fact the case for Cuyahoga County, Ohio, over the years 1995-2000, the price impact is not universally positive. The nature of the price impact depends on the location of the investment, relative to the house and regional accessibility points, and on how long ago the investment was completed.
Is neutrophil elastase the missing link between emphysema and fibrosis? Evidence from two mouse models
Authors: Lucattelli Monica , Bartalesi Barbara , Cavarra Eleonora , Fineschi Silvia , Lunghi Benedetta , Martorana Piero A , Lungarella Giuseppe
Published: July 2005

Background

The separation of emphysema from fibrosis is not as clear-cut as it was thought in early studies. These two pathologies may be present at the same time in human lungs and in mice either instilled with elastolytic enzymes or bleomycin or exposed to cigarette-smoke. According to a current view, emphysema originates from a protease/antiprotease imbalance, and a role for antiproteases has also been suggested in the modulation of the fibrotic process. In this study we investigate in experimental animal models of emphysema and fibrosis whether neutrophil elastase may constitute a pathogenic link between these two pathologies.

Methods

This study was done in two animal models in which emphysema and fibrosis were induced either by bleomycin (BLM) or by chronic exposure to cigarette-smoke. In order to assess the protease-dependence of the BLM-induced lesion, a group mice was treated with 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride, a serine proteinase inhibitor active toward neutrophil elastase. Lungs from each experimental group were used for the immunohistochemical assessment of transforming growth factor-β (TGF-β) and transforming growth factor-α (TGF-α) and for determination of the mean linear intercept as well as the percent volume densities of fibrosis and of emphysematous changes. Additionally, the lungs were also assessed for desmosine content and for the determination of elastase levels in the pulmonary interstitium by means of immunoelectron microscopy.

Results

We demonstrate that in BLM-treated mice (i) the development of elastolytic emphysema precedes that of fibrosis; (ii) significant amount of elastase in alveolar interstitium is associated with an increased expression of TGF-β and TGF-α; and finally, (iii) emphysematous and fibrotic lesions can be significantly attenuated by using a protease inhibitor active against neutrophil elastase.

Also, in a strain of mice that develop both emphysema and fibrosis after chronic cigarette-smoke exposure, the presence of elastase in alveolar structures is associated with a positive immunohistochemical reaction for reaction for both TGF-β and TGF-α.

Conclusion

The results of the present study strongly suggest that neutrophil elastase may represent a common pathogenic link between emphysema and fibrosis. Proteases and in particular neutrophil elastase could act as regulatory factors in the generation of soluble cytokines with mitogenic activity for mesenchymal cells resulting either in emphysema or in fibrosis or both.