bluuebunny/crossref_metadata_2025 huggingface dataset:
Duloxetine vs placebo in the treatment of stress urinary incontinence: a four‐continent randomized clinical trial
Authors: Millard R.J. , Moore K. , Rencken R. , Yalcin I. , Bump R.C. ,   for the Duloxetine UI Study Group
Published: February 2004

OBJECTIVES

To further assess, in a phase 3 study, treatment with duloxetine for women with stress urinary incontinence (SUI) in other geographical regions, including Argentina, Australia, Brazil, Finland, Poland, South Africa and Spain, as previous trials in North America and Europe provided evidence for the safety and efficacy of duloxetine as a pharmacological treatment for SUI in women.

PATIENTS AND METHODS

The study included 458 women aged 27–79 years enrolled in a double‐blind, placebo‐controlled trial. The patients with predominantly SUI were identified using a validated clinical algorithm. They were randomly assigned to receive placebo (231) or duloxetine 40 mg twice daily (227) for 12 weeks. The primary outcome variables included the incontinence episode frequency (IEF) and the Incontinence Quality of Life (I‐QOL) questionnaire. Van Elteren's test was used to analyse the percentage changes in IEF where the stratification variable was weekly baseline IEF (IEF <14 and ≥14). Analysis of covariance was used to analyse I‐QOL scores.

RESULTS

The mean baseline IEF was 18.4/week; 55% of patients had a baseline IEF of ≥ 14. There was a significantly greater median decrease in IEF with duloxetine with placebo (54% vs 40%, P = 0.05), with comparable significant improvements in quality of life (I‐QOL score increases of 10.3 vs 6.4, P = 0.007). The improvements with duloxetine were associated with significantly greater increases in voiding intervals than with placebo (20.4 vs 8.5 min, P < 0.001). The placebo response was 10.7% and 12.5% higher than those reported in two European and North American phase 3 trials. This may have been related to more patients being naïve for incontinence management in the current trial. Discontinuation rates for adverse events were 1.7% for placebo and 17.2% for duloxetine (P < 0.001), with nausea being the most common reason for discontinuation (3.1%); it was the most common adverse event with duloxetine, but was mild or moderate in most (81%), did not worsen in any patient and resolved within 7 days in 60% and within 1 month in 86% of continuing patients; 88% of women who experienced nausea while taking duloxetine completed the trial.

CONCLUSIONS

These results show improvements in incontinence and quality of life with duloxetine 40 mg twice daily for 12 weeks that are in keeping with those reported in two other recently completed phase 3 trials in Europe and North America.
Transvaginal electrical stimulation in the treatment of urinary incontinence
Authors: Barroso J.C.V. , Ramos J.G.L. , Martins‐Costa S. , Sanches P.R.S. , Muller A.F.
Published: February 2004

OBJECTIVE

To determine the effectiveness of transvaginal electrical stimulation (TES) in treating urinary incontinence, and to assess the clinical improvement 6 months after ending the treatment.

PATIENTS AND METHODS

In a double‐blind randomized controlled clinical trial, 36 women (24 patients and 12 controls) with stress, urge or mixed urinary incontinence were chosen to use TES or placebo (identical equipment but with no electrical current). The patients had their treatment at home twice a day (20‐min sessions) for 12 weeks. They completed a voiding diary and had a urodynamic study at the beginning and end of treatment. They were clinically re‐evaluated after 6 months.

RESULTS

The mean time of use of TES was similar in both groups (≈ 40 h); the treatment group had a significant increase in maximum bladder capacity (P < 0.02), a significant reduction in the total number of voids (over 24 h; P < 0.02), in the number of episodes of voiding urgency (P < 0.001) and, importantly, in the number of episodes of urinary incontinence (P < 0.001). At the first evaluation, after ending the treatment, 88% of the patients had a significant reduction in symptoms or went into remission. At the 6‐month re‐evaluation, a third of the patients required another therapeutic approach.

CONCLUSION

TES is a practical alternative with few side‐effects, and is effective for treating the main forms of female urinary incontinence.
Moderate Level Alcohol During Pregnancy, Prenatal Stress, or Both and Limbic‐Hypothalamic‐Pituitary‐Adrenocortical Axis Response to Stress in Rhesus Monkeys
Authors: Schneider Mary L. , Moore Colleen F. , Kraemer Gary W.
Published: February 2004

This study examined the relationship between moderate‐level prenatal alcohol exposure, prenatal stress, and postnatal response to a challenging event in 6‐month‐old rhesus monkeys. Forty‐one rhesus monkey (Macaca mulatta) infants were exposed prenatally to moderate level alcohol, maternal stress, or both. Offspring plasma cortisol and adrenocorticotrophic hormone (ACTH) were determined from blood samples before maternal separation and after separation. Behavioral observations were made repeatedly across separation. Moderate‐level prenatal alcohol exposure was associated with significantly higher plasma ACTH response to maternal separation. Offspring exposed to prenatal alcohol, prenatal stress, and prenatal alcohol and stress showed reduced behavioral adaptation to stress compared with controls. Baseline, 2‐hr, and 26‐hr plasma ACTH levels were intercorrelated and predicted behavior during separation.
Psychophysiological and Behavioral Evidence for Varying Forms and Functions of Nonsocial Behavior in Preschoolers
Authors: Henderson Heather A. , Marshall Peter J. , Fox Nathan A. , Rubin Kenneth H.
Published: February 2004

Four‐year‐old children showing low levels of social behavior in a laboratory play session with unfamiliar peers were classified as reticent (unoccupied or onlooking behaviors) or solitary‐passive (solitary constructive or exploratory play). Compared with a group of more social children, the children in both low‐social groups were rated high on maternal reports of shyness and displayed a pattern of right frontal EEG asymmetry. However, only the reticent group was elevated on measures indicative of a fearful temperament, both concurrently and retrospectively. A subset of children in the solitary‐passive group showed increasing levels of reticent behavior over the course of the visit, suggesting that for some children solitary‐passive behaviors provide a means for coping with feelings of unease.
The
lgtABCDE
Gene Cluster, Involved in Lipooligosaccharide Biosynthesis in
Neisseria gonorrhoeae
, Contains Multiple Promoter Sequences
Authors: Braun Derek C. , Stein Daniel C.
Published: February 2004

Biosynthesis of the variable core domain of lipooligosaccharide (LOS) in
Neisseria gonorrhoeae
is mediated by glycosyl transferases encoded by
lgtABCDE
. Changes within homopolymeric runs within
lgtA
,
lgtC
, and
lgtD
affect the expression state of these genes, with the nature of the LOS expressed determined by the functionality of these genes. However, the mechanism for modulating the amount of multiple LOS chemotypes expressed in a single cell is not understood. Using mutants containing polar disruptions within the
lgtABCDE
locus, we determined that the expression of this locus is mediated by multiple promoters and that disruption of transcription from these promoters alters the relative levels of simultaneously expressed LOS chemotypes. Expression of the
lgtABCDE
locus was quantified by using
xylE
transcriptional fusions, and the data indicate that this locus is transcribed in trace amounts and that subtle changes in transcription result in phenotypic changes. By using rapid amplification of 5′ cDNA ends, transcriptional start sites and promoter sequences were identified within
lgtABCDE
. Most of these promoters possessed 50 to 67% homology with the consensus gearbox promoter sequence of
Escherichia coli
.
Interactions among CotB, CotG, and CotH during Assembly of the
Bacillus subtilis
Spore Coat
Authors: Zilhão Rita , Serrano Mónica , Isticato Rachele , Ricca Ezio , Moran Charles P. , Henriques Adriano O.
Published: February 2004

Spores formed by wild-type
Bacillus subtilis
are encased in a multilayered protein structure (called the coat) formed by the ordered assembly of over 30 polypeptides. One polypeptide (CotB) is a surface-exposed coat component that has been used as a vehicle for the display of heterologous antigens at the spore surface. The
cotB
gene was initially identified by reverse genetics as encoding an abundant coat component.
cotB
is predicted to code for a 43-kDa polypeptide, but the form that prevails in the spore coat has a molecular mass of about 66 kDa (herein designated CotB-66). Here we show that in good agreement with its predicted size, expression of
cotB
in
Escherichia coli
results in the accumulation of a 46-kDa protein (CotB-46). Expression of
cotB
in sporulating cells of
B. subtilis
also results in a 46-kDa polypeptide which appears to be rapidly converted into CotB-66. These results suggest that soon after synthesis, CotB undergoes a posttranslational modification. Assembly of CotB-66 has been shown to depend on expression of both the
cotH
and
cotG
loci. We found that CotB-46 is the predominant form found in extracts prepared from sporulating cells or in spore coat preparations of
cotH
or
cotG
mutants. Therefore, both
cotH
and
cotG
are required for the efficient conversion of CotB-46 into CotB-66 but are dispensable for the association of CotB-46 with the spore coat. We also show that CotG does not accumulate in sporulating cells of a
cotH
mutant, suggesting that CotH (or a CotH-controlled factor) stabilizes the otherwise unstable CotG. Thus, the need for CotH for formation of CotB-66 results in part from its role in the stabilization of CotG. We also found that CotB-46 is present in complexes with CotG at the time when formation of CotB-66 is detected. Moreover, using a yeast two-hybrid system, we found evidence that CotB directly interacts with CotG and that both CotB and CotG self-interact. We suggest that an interaction between CotG and CotB is required for the formation of CotB-66, which may represent a multimeric form of CotB.
Surface-Associated Flagellum Formation and Swarming Differentiation inBacillus subtilisAre Controlled by theifmLocus
Authors: Senesi Sonia , Ghelardi Emilia , Celandroni Francesco , Salvetti Sara , Parisio Eva , Galizzi Alessandro
Published: February 2004

Knowledge of the highly regulated processes governing the production of flagella inBacillus subtilisis the result of several observations obtained from growing this microorganism in liquid cultures. No information is available regarding the regulation of flagellar formation inB. subtilisin response to contact with a solid surface. One of the best-characterized responses of flagellated eubacteria to surfaces is swarming motility, a coordinate cell differentiation process that allows collective movement of bacteria over solid substrates. This study describes the swarming ability of aB. subtilishypermotile mutant harboring a mutation in theifmlocus that has long been known to affect the degree of flagellation and motility in liquid media. On solid media, the mutant produces elongated and hyperflagellated cells displaying a 10-fold increase in extracellular flagellin. In contrast to the mutant, the parental strain, as well as other laboratory strains carrying a wild-typeifmlocus, fails to activate a swarm response. Furthermore, it stops to produce flagella when transferred from liquid to solid medium. Evidence is provided that the absence of flagella is due to the lack of flagellin gene expression. However, restoration of flagellin synthesis in cells overexpressing σDor carrying a deletion offlgMdoes not recover the ability to assemble flagella. Thus, theifmgene plays a determinantal role in the ability ofB. subtilisto contact with solid surfaces.
PriA Is Essential for Viability of the
Escherichia coli
Topoisomerase IV
parE10
(Ts) Mutant
Authors: Grompone Gianfranco , Bidnenko Vladimir , Ehrlich S. Dusko , Michel Bénédicte
Published: February 2004

The
parE10
(Ts) mutation, which renders
Escherichia coli
thermosensitive for growth by inactivation of the essential
E. coli
topoisomerase topo IV, is lethal at all temperatures when PriA, the main replication restart protein, is absent. This lethality is suppressed by the activation of a PriA-independent replication restart pathway (
dnaC809
mutation). This result suggests that topo IV acts prior to full-chromosome replication completion.
H-NS Represses
Salmonella enterica
Serovar Typhimurium
dsbA
Expression during Exponential Growth
Authors: Gallant C. V. , Ponnampalam T. , Spencer H. , Hinton J. C. D. , Martin N. L.
Published: February 2004

Disulfide bond formation catalyzed by disulfide oxidoreductases occurs in the periplasm and plays a major role in the proper folding and integrity of many proteins. In this study, we were interested in elucidating factors that influence the regulation of
dsbA
, a gene coding for the primary disulfide oxidoreductase found in
Salmonella enterica
serovar Typhimurium. Strains with mutations created by transposon mutagenesis were screened for strains with altered expression of
dsbA
. A mutant (NLM2173) was found where maximal expression of a
dsbA
::
lacZ
transcriptional fusion occurred in the exponential growth phase in contrast to that observed in the wild type where maximal expression occurs in stationary phase. Sequence analysis of NLM2173 demonstrated that the transposon had inserted upstream of the gene encoding H-NS. Western immunoblot analysis using H-NS and StpA antibodies showed decreased amounts of H-NS protein in NLM2173, and this reduction in H-NS correlated with an increase of StpA protein. Northern blot analysis with a
dsbA
-specific probe showed an increase in
dsbA
transcript during exponential phase of growth. Direct binding of H-NS to the
dsbA
promoter region was verified using purified H-NS in electrophoretic mobility shift assays. Thus, a reduction in H-NS protein is correlated with a derepression of
dsbA
in NLM2173, suggesting that H-NS normally plays a role in suppressing the expression of
dsbA
during exponential phase growth.
Selective transport of cytokine-induced neutrophil chemoattractant from the lung to the blood facilitates pulmonary neutrophil recruitment
Authors: Quinton Lee J. , Nelson Steve , Zhang Ping , Boé Darren M. , Happel Kyle I. , Pan Weihong , Bagby Gregory J.
Published: February 2004

The CXC chemokines cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) are potent neutrophil chemoattractants in rats. We have previously shown that CINC, unlike MIP-2 and most other proinflammatory cytokines, is elevated in the systemic circulation in response to an intratracheal (IT) challenge. Therefore, we hypothesized that CINC generated within the lung selectively enters the vascular compartment to facilitate pulmonary neutrophil recruitment. Rats were administered IT LPS, and plasma CINC and MIP-2 levels were measured 90 min and 4 h after injection, along with mRNA expression in lung, spleen, liver, and kidney. Ninety minutes and 4 h after IT LPS, CINC and MIP-2 mRNA expression were largely confined to lung homogenate, but of the two chemokines, only CINC was present in plasma. In separate experiments, rats received IT injections of recombinant CINC and/or MIP-2. Here, plasma levels of CINC, but not MIP-2, were significantly increased throughout the 4-h observation period. This finding was verified by individually administering125I-labeled forms of each chemokine. Instillation of recombinant MIP-2 or CINC into the lung increased the number of neutrophils recovered in bronchoalveolar lavage fluid at 4 h, and this effect was enhanced when both chemokines were administered together. In addition, intravenous (IV) CINC, but not IV MIP-2, increased pulmonary neutrophil recruitment in response to IT MIP-2. Our results show that CINC, in contrast to MIP-2, is selectively transported from the lung to the systemic circulation, where it promotes neutrophil migration into the lung in response to a chemotactic stimulus.
Short-term modulation of interleukin-1β signaling by hyperoxia: uncoupling of IκB kinase activation and NF-κB-dependent gene expression
Authors: Odoms Kelli , Shanley Thomas P. , Wong Hector R.
Published: February 2004

We have been interested in elucidating how simultaneous stimuli modulate inflammation-related signal transduction pathways in lung parenchymal cells. We previously demonstrated that exposing respiratory epithelial cells to 95% oxygen (hyperoxia) synergistically increased tumor necrosis factor-α (TNF-α)-mediated activation of NF-κB and NF-κB-dependent gene expression by a mechanism involving increased activation of IκB kinase (IKK). Because the signal transduction mechanisms induced by IL-1β are distinct to that of TNF-α, herein we sought to determine whether hyperoxia modulates IL-1β-dependent signal transduction. In A549 cells, simultaneous treatment with hyperoxia and IL-1β caused increased activation of IKK, prolonged the degradation of IκBα, and prolonged the nuclear translocation and DNA binding of NF-κB compared with cells treated with IL-1β alone in room air. Hyperoxia did not affect IL-1β-dependent degradation of the interleukin receptor-associated kinase differently from treatment with IL-β alone. In contrast to the effects on the IKK/IκBα/NF-κB pathway, simultaneous treatment with hyperoxia and IL-1β did not augment NF-κB-dependent gene expression compared with treatment with IL-1β alone. Similar observations were made in a different human respiratory epithelial cell line, BEAS-2B cells. In addition, simultaneous treatment with hyperoxia and IL-1β caused hyperphosphorlyation of the NF-κB p65 subunit compared with treatment with IL-1β alone. In summary, concomitant treatment of A549 cells with hyperoxia and IL-1β augments activation of IKK, prolongs degradation of IκBα, and prolongs nuclear translocation and DNA binding of NF-κB. This activation, however, is not coupled to increased expression of NF-κB-dependent genes, and the mechanism of this decoupling is not related to decreased phosphorylation of p65.
Antimacrophage chemokine treatment prevents neutrophil and macrophage influx in hyperoxia-exposed newborn rat lung
Authors: Vozzelli Michael A. , Mason S. Nicholas , Whorton Mary H. , Auten Richard L.
Published: February 2004

Macrophage-derived cytokines may provoke the inflammatory response in lung injury. Because macrophage influx is a prominent feature of the cellular inflammatory response accompanying the development of bronchopulmonary dysplasia, we hypothesized that blocking macrophage influx would reduce overall cellular influx and oxidative damage. Newborn rats were exposed at birth to 95% O2or air for 1 wk, and hyperoxia-exposed pups were injected with anti-monocyte chemoattractant protein-1 (MCP-1) or IgG control on days 3–5. MCP-1 was increased in bronchoalveolar lavage fluid and in histological sections from the 95% O2-exposed, IgG-injected pups compared with air-exposed controls. At 1 wk, anti-MCP-1-treated pups had reduced leukocyte numbers, both macrophages and neutrophils, in bronchoalveolar lavage fluid compared with IgG-treated controls. Cytokine-induced neutrophil chemoattractant-1, the rat analog of IL-8, was not significantly decreased in lavage fluid but was reduced in lung cells in anti-MCP-1-treated pups. Tissue carbonyls, a measure of protein oxidation, were decreased in anti-MCP-1-treated pups. Anti-MCP-1 treatment prevented neutrophil influx and reduced protein oxidation in hyperoxia-exposed newborn rats.
Methods for detection of reactive metabolites of oxygen and nitrogen: in vitro and in vivo considerations
Authors: Tarpey Margaret M. , Wink David A. , Grisham Matthew B.
Published: February 2004

Facile detection of reactive oxygen and nitrogen species in biologic systems is often problematic. This is a result of the numerous cellular mechanisms, both enzymatic and nonenzymatic involved in their catabolism/decomposition, the complex and overlapping nature of their reactivities, as well as the often limited intracellular access of detector systems. This review describes approaches to the direct and indirect measurement of different reactive metabolites of oxygen and nitrogen. Particular attention to a method's applicability for in vivo determinations will be addressed.
Developmental-Dependent Action of Microtubule Depolymerization on the Function and Structure of Synaptic Glycine Receptor Clusters in Spinal Neurons
Authors: van Zundert Brigitte , Alvarez Francisco J. , Tapia Juan Carlos , Yeh Hermes H. , Diaz Emilio , Aguayo Luis G.
Published: February 2004

Microtubules have been proposed to interact with gephyrin/glycine receptors (GlyRs) in synaptic aggregates. However, the consequence of microtubule disruption on the structure of postsynaptic GlyR/gephyrin clusters is controversial and possible alterations in function are largely unknown. In this study, we have examined the physiological and morphological properties of GlyR/gephyrin clusters after colchicine treatment in cultured spinal neurons during development. In immature neurons (5-7 DIV), disruption of microtubules resulted in a 33 ± 4% decrease in the peak amplitude and a 72 ± 15% reduction in the frequency of spontaneous glycinergic miniature postsynaptic currents (mIPSCs) recorded in whole cell mode. However, similar colchicine treatments resulted in smaller effects on 10-12 DIV neurons and no effect on mature neurons (15-17 DIV). The decrease in glycinergic mIPSC amplitude and frequency reflects postsynaptic actions of colchicine, since postsynaptic stabilization of microtubules with GTP prevented both actions and similar reductions in mIPSC frequency were obtained by modifying the Cl-driving force to obtain parallel reductions in mIPSC amplitude. Confocal microscopy revealed that colchicine reduced the average length and immunofluorescence intensity of synaptic gephyrin/GlyR clusters in immature (approximately 30%) and intermediate (approximately 15%) neurons, but not in mature clusters. Thus the structural and functional changes of postsynaptic gephyrin/GlyR clusters after colchicine treatment were tightly correlated. Finally, RT-PCR, kinetic analysis and picrotoxin blockade of glycinergic mIPSCs indicated a reorganization of the postsynaptic region from containing both α2β and α1β GlyRs in immature neurons to only α1β GlyRs in mature neurons. Microtubule disruption preferentially affected postsynaptic sites containing α2β-containing synaptic receptors.
Nitric Oxide and Histamine Induce Neuronal Excitability by Blocking Background Currents in Neuron MCC of Aplysia
Authors: Jacklet Jon W. , Tieman David G.
Published: February 2004

Nitric oxide (NO) and histamine are important neurotransmitters and neuromodulators. We investigated their ability to modulate the membrane ionic currents and excitability of the metacerebral cell (MCC) of Aplysia using voltage clamp techniques. MCC is a serotonergic modulator of the feeding neural circuit. It receives powerful long-lasting excitatory synaptic input mediated by NO and histamine. NO donors reduced a background outward current at and above the resting potential, associated with decreased membrane conductance. This produced a substantial steady-state inward current that was relatively insensitive to cesium or cobalt. The NO response appears to be due to the reduction of a background potassium current and a small increase in persistent inward sodium current. Treatment with 8-bromoguanosine-3′5′-cyclic monophosphate mimics this response, suggesting it is mediated primarily by the NO–guanylyl cyclase–cGMP pathway. In some MCCs, NO blocked an additional potassium current that resulted in current reversal near the potassium equilibrium potential in current–voltage plots. Histamine also reduced a background outward current at and above the resting potential. However, treatment with cobalt, which blocks calcium and calcium-dependent currents, blocked the histamine response, suggesting that histamine decreases calcium activated potassium currents. Although nifedipine (L-type calcium channel blocker) and tetraethylammonium reduced some calcium and calcium-dependent potassium currents, they had only a slight effect on the NO and histamine responses. Both NO and histamine decreased steady-state membrane currents, and thereby depolarized MCC and increased its excitability, but different ionic currents and second messenger pathways are involved, allowing complex state and time dependent modulation of MCC's activity.
Silent Synapses in the Immature Visual Cortex: Layer-Specific Developmental Regulation
Authors: Rumpel Simon , Kattenstroth Gunnar , Gottmann Kurt
Published: February 2004

Central glutamatergic synapses are thought to initially form as immature, so-called silent synapses showing exclusively N-methyl-d-aspartate receptor-mediated synaptic transmission. Postsynaptic insertion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors during further development leads to a conversion into functional, mature synapses. Here, we tested the hypothesis that, according to the “inside first–outside last” pattern of neocortical layer formation and synaptogenesis, pyramidal cells in the superficial layers might show a higher fraction of silent synapses compared with pyramidal cells in the deep layers. We performed an electrophysiological analysis of glutamatergic synapses in acute rat visual cortex slices during postnatal development. In layer VI pyramidal neurons the incidence of silent synapses was high during the first postnatal week and strongly declined during further development. Surprisingly, in superficial cortical plate pyramidal neurons (immature layers II/III), the fraction of silent synapses was initially very low and increased up to the second postnatal week. Thereafter, a similar decline as found in layer VI pyramidal neurons was observed. Thus the developmental regulation of silent synapses was clearly different in pyramidal neurons from different neocortical layers. The almost complete absence of silent synapses at early stages in layer II/III pyramidal neurons indicates that an initially formed subset of synapses is constitutively functional. This might be important to enable spontaneous activity and latter activity-dependent maturation of synapses.
Signals That Modulate Gain Control for Smooth Pursuit Eye Movements in Monkeys
Authors: Carey Megan R. , Lisberger Stephen G.
Published: February 2004

The generation of primate smooth pursuit eye movements involves two processes. One process transforms the direction and speed of target motion into a motor command and the other regulates the strength, or “gain,” of the visual-motor transformation. We have conducted a behavioral analysis to identify the signals that modulate the internal gain of pursuit. To test whether the modulatory signals are related to eye velocity in the orbit or in the world (gaze velocity), we used brief perturbations of target motion to probe the gain of pursuit during tracking conditions that used head rotation to dissociate eye and gaze velocity. We found that the responses to perturbations varied primarily as a function of gaze velocity. To further understand the gaze velocity signals that control internal pursuit gain, we used adaptive modification of the gain of the vestibulo-ocular reflex (VOR) to dissociate physical gaze velocity from the component of gaze velocity that is driven by visual inputs. After VOR adaptation, perturbation responses were altered; the smallest perturbation responses now occurred during tracking conditions that required nonzero physical gaze velocity. However, perturbation responses during tracking conditions that mimicked the modified VOR were still enhanced relative to those obtained during fixation. We conclude that the signals that modulate the internal gain of pursuit are modified by VOR adaptation so that they are rendered intermediate between physical and visually driven gaze velocity. Similar changes in the gaze velocity signal have been reported in the cerebellar floccular complex following adaptive modification of the VOR and could be present in other brain areas that carry putative gaze velocity signals.
Detailed Model of Intersegmental Coordination in the Timing Network of the Leech Heartbeat Central Pattern Generator
Authors: Jezzini Sami H. , Hill Andrew A. V. , Kuzyk Pavlo , Calabrese Ronald L.
Published: February 2004

To address the general problem of intersegmental coordination of oscillatory neuronal networks, we have studied the leech heartbeat central pattern generator. The core of this pattern generator is a timing network that consists of two segmental oscillators, each of which comprises two identified, reciprocally inhibitory oscillator interneurons. Intersegmental coordination between the segmental oscillators is mediated by synaptic interactions between the oscillator interneurons and identified coordinating interneurons. The small number of neurons (8) and the distributed structure of the timing network have made the experimental analysis of the segmental oscillators as discrete, independent units possible. On the basis of this experimental work, we have made conductance-based models to explore how intersegmental phase and cycle period are determined. We show that although a previous simple model, which ignored many details of the living system, replicated some essential features of the living system, the incorporation of specific cellular and network properties is necessary to capture the behavior of the system seen under different experimental conditions. For example, spike frequency adaptation in the coordinating interneurons and details of asymmetries in intersegmental connectivity are necessary for replicating driving experiments in which one segmental oscillator was injected with periodic current pulses to entrain the activity of the entire network. Nevertheless, the basic mechanisms of phase and period control demonstrated here appear to be very general and could be used by other networks that produce coordinated segmental motor outflow.
Acetylcholine Increases Intracellular Ca2+Via Nicotinic Receptors in Cultured PDF-Containing Clock Neurons ofDrosophila
Authors: Wegener Christian , Hamasaka Yasutaka , Nässel Dick R.
Published: February 2004

Light entrains the biological clock both in adult and larval Drosophila melanogaster. The Bolwig organ photoreceptors most likely constitute one substrate for this light entrainment in larvae. Acetylcholine (ACh) has been suggested as the neurotransmitter in these photoreceptors, but there is no evidence that ACh signaling is involved in photic input onto circadian pacemaker neurons. Here we demonstrate that the putative targets of the Bolwig photoreceptors, the PDF-containing clock neurons (LNs), in the larval brain express functional ACh receptors (AChRs). With the use of GAL4-UAS-driven expression of green fluorescent protein (GFP), we were able to identify LNs in dissociated cell culture. After loading with the Ca2+-sensitive dye fura-2, we monitored changes in intracellular Ca2+levels ([Ca2+]i) in GFP-marked LNs while applying candidate neurotransmitters. ACh induced transient increases in [Ca2+]iat physiological concentrations. These increases were dependent on extracellular Ca2+and Na+and were likely caused by activation of voltage-dependent Ca2+channels. Application of nicotinic and muscarinic agonists and antagonists showed that the AChRs on cultured LNs have a nicotinic pharmacology. Antibodies to several subunits of nicotinic AChRs (nAChRs) labeled the putative contact site of the Bolwig organ axon terminals with the dendrites of LNs, as well as dissociated LNs in culture. Our findings support a role of ACh as input factor onto the LNs and suggest that Ca2+is used as a second messenger mediating cholinergic input within the LNs. Experiments using a more general GAL4-UAS-driven expression of GFP showed that functional expression of nAChRs is a widespread phenomenon in peptidergic neurons.
Response Growth With Sound Level in Auditory-Nerve Fibers After Noise-Induced Hearing Loss
Authors: Heinz Michael G. , Young Eric D.
Published: February 2004

People with sensorineural hearing loss are often constrained by a reduced acoustic dynamic range associated with loudness recruitment; however, the neural correlates of loudness and recruitment are still not well understood. The growth of auditory-nerve (AN) activity with sound level was compared in normal-hearing cats and in cats with a noise-induced hearing loss to test the hypothesis that AN-fiber rate-level functions are steeper in impaired ears. Stimuli included best-frequency and fixed-frequency tones, broadband noise, and a brief speech token. Three types of impaired responses were observed. 1) Fibers with rate-level functions that were similar across all stimuli typically had broad tuning, consistent with outer-hair-cell (OHC) damage. 2) Fibers with a wide dynamic range and shallow slope above threshold often retained sharp tuning, consistent with primarily inner-hair-cell (IHC) damage. 3) Fibers with very steep rate-level functions for all stimuli had thresholds above approximately 80 dB SPL and very broad tuning, consistent with severe IHC and OHC damage. Impaired rate-level slopes were on average shallower than normal for tones, and were steeper in only limited conditions. There was less variation in rate-level slopes across stimuli in impaired fibers, presumably attributable to the lack of suppression-induced reductions in slopes for complex stimuli relative to BF-tone slopes. Sloping saturation was observed less often in impaired fibers. These results illustrate that AN fibers do not provide a simple representation of the basilar-membrane I/O function and suggest that both OHC and IHC damage can affect AN response growth.
Quantification of the Factors That Influence Discharge Correlation in Model Motor Neurons
Authors: Taylor Anna M. , Enoka Roger M.
Published: February 2004

The purpose of this study was to quantify the influence of intrinsic properties, active dendritic conductances, and background excitation and inhibition on measures of discharge correlation in the time and frequency domains with known levels and patterns of common synaptic input. The study involved a computer simulation of a population of neurons with a range of input resistances (0.54–3.7 MΩ) and surface areas (407,000–712,000 μm2). The neurons were simulated with no, moderate, or high levels of active dendritic conductances and were activated with either excitatory input only or excitatory and inhibitory inputs. The patterns of common input, either branched common input or common modulation, were tested with 0, 30, 60, and 90% common input. The results confirm previous findings of an exponential relation between the level of common input and indexes of synchronization; only when the common input comprised ≥60% of the total excitatory input was there a significant effect on discharge correlation. Synchronization was greatest in models that had passive dendrites. Active dendritic conductances caused the discharge rate of the neuron to saturate and decreased motor-unit synchronization. However, the addition of 10% background inhibitory input increased synchronization in these models. In contrast, common rhythmic modulation of inputs at 24 Hz usually decreased synchronization. Significant coherence at the modulated frequency occurred in the commonly modulated neurons when ≥60% of the inputs were modulated. Furthermore, active dendritic conductances decreased coherence. Branched common input caused high levels of coherence across a broad spectrum and when combined with active dendritic conductances caused significant frequency peaks in the 30- to 50-Hz band. In conclusion, the level of inhibitory input and active dendritic conductances interact with the amount of common input to determine time- and frequency-domain discharge correlation.
A Network Model of Perceptual Suppression Induced by Transcranial Magnetic Stimulation
Authors: Miyawaki Yoichi , Okada Masato
Published: February 2004

We modeled the inhibitory effects of transcranial magnetic stimulation (TMS) on a neural population. TMS is a noninvasive technique, with high temporal resolution, that can stimulate the brain via a brief magnetic pulse from a coil placed on the scalp. Because of these advantages, TMS is extensively used as a powerful tool in experimental studies of motor, perception, and other functions in humans. However, the mechanisms by which TMS interferes with neural activities, especially in terms of theoretical aspects, are totally unknown. In this study, we focused on the temporal properties of TMS-induced perceptual suppression, and we computationally analyzed the response of a simple network model of a sensory feature detector system to a TMS-like perturbation. The perturbation caused the mean activity to transiently increase and then decrease for a long period, accompanied by a loss in the degree of activity localization. When the afferent input consisted of a dual phase, with a strong transient component and a weak sustained component, there was a critical latency period of the perturbation during which the network activity was completely suppressed and converged to the resting state. The range of the suppressive period increased with decreasing afferent input intensity and reached more than 10 times the time constant of the neuron. These results agree well with typical experimental data for occipital TMS and support the conclusion that dynamical interaction in a neural population plays an important role in TMS-induced perceptual suppression.
Soil temperature and egg mass formation by Meloidogyne arenaria on oriental melon (Cucumis melo L.)
Authors: Park So Deuk , Kim Dong Geun , Yeon Il Kweon
Published: February 2004

Egg masses of Meloidogyne arenaria race 2 were observed on the second planting of oriental melon by the time of its first harvest under glasshouse conditions in Korea. Time and degree-days above 5°C (DD5) for egg mass formation after April were about 24.5 days and 500 DD5. Higher mean soil temperature shortened the days required for egg mass formation. A threshold temperature for degree-days accumulation of 12.2°C was selected on the basis of lowest coefficient of variation among data sets of time to egg mass formation. We propose the use of DD12.2 for predicting the time to egg mass formation of M. arenaria under these glasshouse conditions.
Going Private? Exploring the Drift Away from the NHS
Authors: Silvester Stella , Calnan Michael , Manley Graham , Taylor-Gooby Peter
Published: February 2004

The perception that dentistry is being privatised is widespread. A two-phase study was undertaken to investigate the factors influencing dentists’ decisions to practise in the public and or private sectors. In phase I a national postal survey of general dental practitioners (n=1011) explored differences in working practices and experience of NHS and non-NHS work. Survey data were supplemented in phase II by in-depth interviews with four subsamples of dentists in two regions. The survey found that although the majority of dentists continued to treat the majority of their patients within the NHS since the introduction of the 1990 contract patterns of practice have changed. Where private dentistry was increasing, it was regionally variable and arose mainly from concerns with financial security, maintaining quality of work and autonomy. Ideological differences were apparent in relation to differences in practice mix. Those who continued to work in the NHS, because of insufficient demand for private dentistry, did so in order to provide access to treatment and to maintain a reliable source of income and pension rights. Dentists interviewed expressed reluctance in withdrawing from NHS practice. Disillusionment with government policy and recognition of the marginal nature of dental health issues suggests that current trends will continue.
KCNQ2 Is a Nodal K+Channel
Authors: Devaux Jérôme J. , Kleopa Kleopas A. , Cooper Edward C. , Scherer Steven S.
Published: February 2004

Mutations in the gene encoding the K+channel KCNQ2 cause neonatal epilepsy and myokymia, indicating that KCNQ2 regulates the excitability of CNS neurons and motor axons, respectively. We show here that KCNQ2 channels are functional components of axon initial segments and nodes of Ranvier, colocalizing with ankyrin-G and voltage-dependent Na+channels throughout the CNS and PNS. Retigabine, which opens KCNQ channels, diminishes axonal excitability. Linopirdine, which blocks KCNQ channels, prolongs the repolarization of the action potential in neonatal nerves. The clustering of KCNQ2 at nodes and initial segments lags that of ankyrin-G during development, and both ankyrin-G and KCNQ2 can be coimmunoprecipitated in the brain. KCNQ3 is also a component of some initial segments and nodes in the brain. The diminished activity of mutant KCNQ2 channels accounts for neonatal epilepsy and myokymia; the cellular locus of these effects may be axonal initial segments and nodes.
Cambodia in 2002: Decentralization and Its Effects on Party Politics
Authors: Un Kheang , Ledgerwood Judy
Published: February 2004

With its first internationally endorsed local election in decades, first rotational chairmanship of the Association of Southeast Asian Nations, and financial assistance pledged from donor countries and multilateral institutions, Cambodia made significant progress in 2002. Prime Minister Hun Sen's Cambodian People's Party swept to victory in local elections, but for the first time it will have to share power at the local level. The Royalist FUNCINPEC Party underwent further decline and infighting. Cambodia received $615 million in financial pledges from international donors, and economic growth increased by a modest 4.5% to 5%. In February, the United Nations withdrew from negotiations for a trial of surviving leaders of Pol Pot's regime in the 1970s, but late in the year the possibility of further discussions emerged.
Burma in 2002: A Year of Transition
Authors: Clark Allen L.
Published: February 2004

The year 2002 saw a consolidation of power within the ruling State Peace and Democracy Council that resulted in the confidence to free Aung San Suu Kyi from house arrest. This resulted almost immediately in a thawing, but certainly not any significant melting, of relations with the international community with respect to Burma (Myanmar). Despite her release, however, Aung San Suu Kyi has not given her approval for any significant non-humanitarian assistance to be given to the government. Positive developments in the reconciliation process are necessary before any significant lifting of sanctions, and thus overall development in the nation, will be possible; to date it appears that this process will be very slow and deliberate and will be undertaken according to the timetable of the government. In the interim, the economy of Burma teeters close to collapse and Burma continues to be the poorest country in the Association for Southeast Asian Nations (ASEAN) and Asia overall. Despite these problems, the fact that Burma lies at the crossroads of Asia and is being wooed by China, India, Russia, Pakistan, Bangladesh, and several ASEAN members gives the nation recognition beyond its size and economy. The overall future is not clear, but the "Dawn of a New Burma" may be breaking.
The Philippines in 2002: Playing Politics, Facing Deficits, and Embracing Uncle Sam
Authors: Montesano Michael J.
Published: February 2004

Philippine politics in 2002 was characterized by early maneuvering for the presidential election of 2004, which President Arroyo will be eligible to contest, and by continuing violence in the country's troubled South. Economic indicators looked promising in the first half of the year. But the second half brought signs of a downturn on several fronts. Crippling revenue shortfalls contributed to a mounting fiscal deficit. As part of Washington's international war on terror, Manila welcomed American troops to the southern Philippines early in 2002. Renewed Philippine-American military ties seemed to reflect long-term U.S. priorities in the region. Three issues shaped Philippine affairs in 2002: President Gloria Macapagal Arroyo's eligibility to contest the 2004 election, ever-greater government revenue shortfalls, and American determination to use the country as a venue for strategic posturing in Southeast Asia. The persistent problems of the Philippine South and continued economic sluggishness framed the ways in which these issues played out over the course of the year.
Afghanistan in 2002: The Struggle to Win the Peace
Authors: Jalali Ali A.
Published: February 2004

The year 2002 was one of rebirth and rebuilding in Afghanistan following a drawn-out civil strife that ended with the downfall of the Taliban regime in the U.S.-led coalition war on terrorism. But the struggle for peace proved to be much tougher than winning the war. International financial support and political backing helped Afghanistan move toward creating a broad-based government, improving security across the country, and rebuilding its devastated economy. However, the enormous humanitarian and development challenges involved require a sustained and multifaceted response as well as a long-term international commitment to assist the war-torn country in restoring peace, normalcy, and economic stability.
Vietnam in 2002: On the Road to Recovery
Authors: Abrami Regina M.
Published: February 2004

Vietnam underwent important changes in 2002. Most notably, the state and Party showed signs of increasing awareness of performance legitimacy as a basis for ongoing political legitimacy. Responses included public statements in favor of the private sector, a reshuffling of cabinet positions, as well as stepped-up efforts to end corruption. A series of events this year, ranging from the country's first trade war to tensions with its important trade partner, Japan, also made clear the growing importance of international political economic factors in shaping domestic politics. All in all, the year has been a successful one for Vietnam.
The Co-evolution of the Internet and Civil Society in China
Authors: Yang Guobin
Published: February 2004

Civil society and the Internet energize each other in their co-evolutionary development in China. The Internet facilitates civil society activities by offering new possibilities for citizen participation. Civil society facilitates the development of the Internet by providing the necessary social basis—citizens and citizen groups—for communication and interaction. These arguments are illustrated with an analysis of the discourse in Qiangguo Luntan [Strengthening the Nation Forum] and an ethnographic study of Huaxia Zhiqing [Chinese Educated Youth], .
Taiwan's Dilemma Across the Strait: Lifting the Ban on Semiconductor Investment in China
Authors: Yang Chyan , Hung Shiu-Wan
Published: February 2004

For more than two decades, Taiwanese semiconductor manufacturers have been banned from investing in China. There was a heated debate in 2001–02 for several months over whether to lift the ban. The purpose of this study is to report the dilemma that the Taiwanese government faced during the debate, and the decision-making process of allowing Taiwanese integrated circuit foundries to invest in China.