bluuebunny/crossref_metadata_2025 huggingface dataset:
Bimodal speech: early suppressive visual effects in human auditory cortex
Authors: Besle Julien , Fort Alexandra , Delpuech Claude , Giard Marie‐Hélène
Published: September 2004

While everyone has experienced that seeing lip movements may improve speech perception, little is known about the neural mechanisms by which audiovisual speech information is combined. Event‐related potentials (ERPs) were recorded while subjects performed an auditory recognition task among four different natural syllables randomly presented in the auditory (A), visual (V) or congruent bimodal (AV) condition. We found that: (i) bimodal syllables were identified more rapidly than auditory alone stimuli; (ii) this behavioural facilitation was associated with cross‐modal [AV − (A + V)] ERP effects around 120–190 ms latency, expressed mainly as a decrease of unimodal N1 generator activities in the auditory cortex. This finding provides evidence for suppressive, speech‐specific audiovisual integration mechanisms, which are likely to be related to the dominance of the auditory modality for speech perception. Furthermore, the latency of the effect indicates that integration operates at pre‐representational stages of stimulus analysis, probably via feedback projections from visual and/or polymodal areas.
Nitric oxide increases the spontaneous firing rate of rat medial vestibular nucleus neurons in vitro via a cyclic GMP‐mediated PKG‐independent mechanism
Authors: Podda Maria Vittoria , Marcocci Maria Elena , Oggiano Leonardo , D'Ascenzo Marcello , Tolu Eusebio , Palamara Anna Teresa , Azzena Gian Battista , Grassi Claudio
Published: September 2004

The effects of nitric oxide (NO) on the discharge rate of medial vestibular nucleus neurons (MVNn) were investigated in rat brainstem slices. The NO‐donor sodium nitroprusside (SNP, 200 µm) caused a marked enhancement (+36.7%) of MVNn spontaneous firing rate, which was prevented by the NO‐scavenger, carboxy‐PTIO (300 µm). The SNP effects were not modified (+37.4%) by synaptic uncoupling, suggesting that NO influences intrinsic membrane properties of MVNn rather than the synaptic input they receive. The excitatory action of SNP was virtually abolished by slice pretreatment with the soluble guanylyl cyclase inhibitor, ODQ (10 µm), and it was mimicked (+33.1%) by the cGMP analogue 8‐Br‐cGMP (400 µm). Protein kinase G (PKG) and cAMP/protein kinase A (PKA) were both excluded as downstream effectors of the NO/cGMP‐induced excitation. However, the cyclic nucleotide‐gated (CNG) channel blockers, l‐cis‐diltiazem (LCD, 100 µm) and Sp‐8‐Br‐PET‐cGMPS (100 µm), significantly reduced the firing rate increase produced by 8‐Br‐cGMP. Moreover, LCD alone decreased spontaneous MVNn firing (−19.7%), suggesting that putative CNG channels may contribute to the tonic control of resting MVNn discharge. 8‐Br‐cAMP (1 mm) also elicited excitatory effects in MVNn (+40.8%), which occluded those induced by 8‐Br‐cGMP, indicating that the two nucleotides share a common target. Finally, nested‐polymerase chain reaction assay revealed the expression of CNG channel α subunit transcript in MVNn. Our data provide the first demonstration that NO/cGMP signalling modulates MVNn spontaneous firing through a mechanism that is independent of PKG or PKA and probably involves activation of CNG channels.
In vivo contribution of h‐channels in the septal pacemaker to theta rhythm generation
Authors: Kocsis Bernat , Li Shaomin
Published: September 2004

One of the most intriguing network‐level inferences made on the basis of in vitro and modelling data regarding the role of Ih current was that they participate in rhythmogenesis in different parts of the brain. The nature of Ih contribution to various neuronal oscillations is far from uniform however, and the proper evaluation of the role of Ih in each particular structure requires in situ investigations in the intact brain. In this study we tested the effect of Ih blockade in the medial septum on hippocampal theta rhythm in anaesthetized and freely behaving rats. We could not confirm the recent report of elimination of theta by septal injection of ZD7288 [C. Xu et al. (2004) Eur. J. Neurosci., 19, 2299–2309]; the observed effects were more subtle and more specific. We found that Ih blockade in the medial septum substantially decreased the frequency of hippocampal oscillations without changing the context in which theta occurred, i.e. specific behaviours in freely moving rats and spontaneous switching and brainstem stimulation under anaesthesia. Septal injection of ZD7288 eliminated atropine‐resistant theta elicited by high intensity electrical stimulation of the reticular formation in anaesthetized rats but was ineffective in combination with the muscarinic agonist, carbachol. Thus, functional Ih was necessary for the septum to generate or transmit high frequency theta rhythm elicited by strong ascending activation, whereas low frequency theta persisted after Ih blockade. These results suggest that Ih plays a specific role in septal theta generation by promoting fast oscillations during exploratory behaviour and rapid eye movement sleep.
Atypical Working Hours: Consequences for Childcare Arrangements
Authors: Bihan Blanche Le , Martin Claude
Published: September 2004

This paper analyses the care arrangements of those dual‐earner couples and lone‐parent families who are under strong pressure because of atypical and unpredictable working hours. In these situations, the parents have to invent day‐to‐day, week‐to‐week solutions for the care needs of their children, mobilizing all available formal and informal resources. The objective is to understand the different ways in which families manage such atypical working hours in three different countries (Finland, France and Portugal). What are the main strategies of the parents in facing this pressure? Do these include negotiations between the parents on the division of tasks, mobilization of ex‐partners, grandparents, brothers and sisters, neighbours, and the different solutions offered by the formal resources? In the first part of the paper, we present the challenges and consequences of atypical working hours for families and institutions in Europe, in particular in Finland, France and Portugal. We then analyse some of the childcare arrangements as well as the impact of the provision of childcare services.
Rating Teams and Analysing Outcomes in One-Day and Test Cricket
Authors: Allsopp P. E. , Clarke Stephen R.
Published: September 2004

Multiple linear regression techniques are applied to determine the relative batting and bowling strengths and a common home advantage for teams playing both innings of international one-day cricket and the first innings of a test-match. It is established that in both forms of the game Australia and South Africa were rated substantially above the other teams. It is also shown that home teams generally enjoyed a significant advantage. Using the relative batting and bowling strengths of teams, together with parameters that are associated with common home advantage, winning the toss and the establishment of a first-innings lead, multinomial logistic regression techniques are applied to explore further how these factors critically affect outcomes of test-matches. It is established that in test cricket a team’s first-innings batting and bowling strength, first-innings lead, batting order and home advantage are strong predictors of a winning match outcome. Contrary to popular opinion, it is found that the team batting second in a test enjoys a significant advantage. Notably, the relative superiority of teams during the fourth innings of a test-match, but not the third innings, is a strong predictor of a winning outcome. There is no evidence to suggest that teams generally gained a winning advantage as a result of winning the toss.
In Defense of Seeking Wisdom
Authors: Maxwell Nicholas
Published: September 2004

Abstract: Steven Yates has criticized my claim that we need to bring about a revolution in the aims and methods of academic inquiry so that the aim becomes to promote wisdom rather than just acquire knowledge. Yates's main criticism is that the proposed revolution does not have a clear strategy for its implementation and is, in any case, Utopian, unrealizable, and undesirable. It is argued, here, that Yates has misconstrued what the proposed revolution amounts to; in fact it is realizable, is urgently needed, and involves exploiting the kind of strategies utilized so effectively by the philosophes of the eighteenth‐century French Enlightenment.
‘Belonging’ and ‘Otherness’: Sex Equality in Banking in Turkey and Britain
Authors: Özbilgin Mustafa F. , Woodward Diana
Published: September 2004

The struggle for sex equality at work has largely been achieved in the developed world, it is claimed. The number of well‐qualified young women entering white‐collar employment and achieving promotion to first‐line and middle management positions now matches or exceeds their male peers. Many young women have high career aspirations and argue that sex discrimination no longer exists. However, this perception is over‐optimistic. Major sex inequalities persist at senior management level in the salaries and benefits offered to female and male staff and in access to certain favoured occupations and sectors of employment. Questionnaires, interviews and documentary evidence from three Turkish and six British banks and high street financial organizations showed that their claimed commitment to equal opportunities by sex was not matched by their practices. Members of managerial elites (who were almost exclusively male) held firm views about the characteristics of ‘the ideal worker’, which informed organizational ideologies, including human resource policies and practices concerning recruitment and promotion. They also permeated organizational cultures, which affected employees’ working practices and experiences. The outcome of these internal negotiation processes was to differentiate between a favoured group of staff seen as fully committed to the companies’ values, who were promoted and rewarded, and an ‘out’ group, whose members were denied these privileges. This distinction between ‘belonging’ and ‘otherness’ is gendered not only along the traditional lines of class, age, sexual orientation, religion and physical ability, but also along the new dimensions of marriage, networking, safety, mobility and space. Despite local and cross‐cultural differences in the significance of these factors, the cumulative disadvantage suffered by women staff seeking career development in the industry was remarkably similar.
Re‐inventing the Gendered Organization: Staff Attitudes towards Women and Gender Mainstreaming in NGOs in Malawi
Authors: Tiessen Rebecca
Published: September 2004

Gender inequality within non‐governmental organizations (NGOs) is constructed on a daily basis through the gendered norms, attitudes and practices of individuals within them. The continual re‐invention of a gendered organization ensures the maintenance of the status quo and therefore the privileging of male/masculine interests over female/feminine interests. Gender mainstreaming is an approach designed to alter the status quo and facilitate women's empowerment. In Malawi, many NGOs have adopted gender mainstreaming as a strategy to address gender inequality both within their organizations and with the communities where they work. Gender mainstreaming initiatives involve a variety of activities including hiring more women staff members, designing policies within the organization to promote gender equality and educating staff members about gender issues through training workshops. While these strategies represent important steps forward for gender equality, it is not clear to what extent these policies and initiatives are translating into meaningful change within the organization.
Chagas' disease parasite promotes neuron survival and differentiation through TrkA nerve growth factor receptor
Authors: Chuenkova Marina V. , PereiraPerrin Mercio
Published: September 2004

TrkA is a receptor tyrosine kinase activated primarily by nerve growth factor (NGF) to regulate differentiation, survival, and other important functions of neurons. Given the critical role TrkA plays in neural maintenance, it may be that microbial invaders of the nervous system utilize this receptor to reduce tissue damage for maximizing host‐parasite equilibrium. Candidate pathogens could be those, like Trypanosoma cruzi, which may produce relatively little brain or nerve damage in long‐lasting infections. We show here that T. cruzi, via its neuraminidase, binds TrkA in a NGF‐inhibitable manner, induces TrkA autophosphorylation, and, through TrkA‐dependent mechanisms, triggers phosphatidylinositol 3‐kinase (PI3K)/Akt kinase signaling, cell survival, and neurite outgrowth. Unlike NGF, the neuraminidase does not react with the apoptosis‐causing pan‐neurotrophin receptor p75NTR. Therefore, these studies identify a novel and unique TrkA ligand in a microbial invader of the nervous system, raising the thus far unsuspected prospect of TrkA underlying clinical progression of an important human infectious disease.
Induction of cyclooxygenase‐2 in reactive glial cells by the CD40 pathway: relevance to amyotrophic lateral sclerosis
Authors: Okuno Tatsusada , Nakatsuji Yuji , Kumanogoh Atsushi , Koguchi Ken , Moriya Masayuki , Fujimura Harutoshi , Kikutani Hitoshi , Sakoda Saburo
Published: September 2004

An inflammatory process in association with reactive gliosis has been suggested to play an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). One of the key findings is a marked increase in the level of cyclooxygenase‐2 (COX‐2), a therapeutic target of ALS. We investigated the expression of CD40 in the spinal cord of a transgenic mouse model of ALS (G93A mice), and its relevance to COX‐2 upregulation. CD40 was predominantly expressed in neurons in normal spinal cord and upregulated in reactive glial cells in spinal cord injury. In the spinal cord of G93A mice, the expression of CD40 was increased in both reactive microglia and astrocytes, where COX‐2 was especially increased. The level of COX‐2 was upregulated in microglia and astrocytes by CD40 stimulation in vitro. CD40 stimulation in primary spinal cord cultures caused motor neuron loss that was protected by selective COX‐2 inhibitor. These results suggest that CD40, which is upregulated in reactive glial cells in ALS, participates in motor neuron loss via induction of COX‐2.
Sex differences in Little Auk Alle alle parental care: transition from biparental to paternal‐only care
Authors: Harding Ann M. A. , Van Pelt Thomas I. , Lifjeld Jan T. , Mehlum Fridtjof
Published: September 2004

Understanding differences in male and female care in biparental care systems can help interpret the selective pressures that shape parental strategies. We examined Little Auk Alle alle parental care at a breeding colony during the chick‐rearing and fledging periods by conducting observations on marked, known‐sex pairs, and by examining the sex ratio of birds carrying food to the colony. Little Auks transitioned from biparental to mostly paternal‐only care during late chick‐rearing. Males delivered more meals and spent more time at the colony than females during late chick‐rearing. Very few females were present at the colony by the end of chick‐rearing and through the fledging period, and all marked parents observed accompanying their chick to sea were male. Chick mass loss prior to fledging was associated with the lack of provisioning by the female parent, rather than a reduction in feeding frequency by both parents. The occurrence of paternal‐only care during and after fledging is discussed in relation to physiological, ecological and phylogenetic constraints.
Calcium supplementation of breeding birds: directions for future research
Authors: Reynolds S. James , Mänd Raivo , Tilgar Vallo
Published: September 2004

Calcium is an essential nutrient for avian reproduction. Calcium‐rich foods are consumed by breeding birds for production of eggshells and for provisioning chicks that are mineralizing skeletal tissues. A number of studies have documented calcium‐limited reproduction, and calcium supplementation has been employed over the last decade to demonstrate degrees, causes and consequences of calcium limitation. However, supplementation studies have produced equivocal findings resulting from an absence of calcium limitation in the study species, a poorly designed supplementation procedure or both. Prior to effective calcium supplementation, many factors need to be considered. Calcium‐limited breeding in birds can only be detected by monitoring breeding attempts for more than one year and by ensuring that the measured breeding parameters are sensitive to calcium availability. Natural calcium availability needs to be estimated, and daily calcium budgets for the appropriate reproductive stages determined for the study species. Most crucially, if calcium limitation of breeding is caused by secondary calcium limitation (e.g. through heavy metal toxicity), calcium supplementation will probably be ineffective. Effective calcium supplementation will then be achieved through careful planning – a study over several years using appropriate supplements (i.e. naturally occurring ones used by breeding birds), applied at the appropriate time of year (i.e. prelaying and/or chick‐rearing phases) and using a response variable that is highly sensitive to calcium availability. If properly planned and performed, calcium supplementation is a cost‐effective and potent tool for the study of bird breeding biology.
Effects of Childcare Activities on the Duration of Self–Employment in Europe
Authors: Williams Donald R.
Published: September 2004

This article examines the determinants of success in self–employment, with a focus on the effects of the time spent caring for children. Many public policies are designed to encourage self–employment, especially among women. In addition, it has been argued that one of the reasons individuals, and women in particular, choose self–employment over wage and salary sector employment is to spend more time with their children. The effect of time spent with children on the probability of continuing in self–employment has not been studied in previous work, however. This study analyzes spells of self–employment among workers in eight European nations. Using data from the European Community Household Panel survey for 1994–1999, we estimate the effect of time spent caring for children on the duration of self–employment, controlling for other factors that affect self–employment success rates. The estimates indicate that caring for children significantly reduces the duration of self–employment ventures, for both males and females, and in most countries studied. The results suggest that policy makers need to consider child care policies in conjunction with self–employment policies.
Electroconvulsive Therapy in Patients with Cardiac Pacemakers and Implantable Cardioverter Defibrillators
Authors: DOLENC TAMARA J. , BARNES ROXANN D. , HAYES DAVID L. , RASMUSSEN KEITH G.
Published: September 2004

Electroconvulsive therapy (ECT) is used to treat major depressive illness, especially in elderly and medically frail patients. Not uncommonly, these patients have cardiac pacemakers or implantable cardioverter defibrillators (ICDs). Only a few case reports in the literature describe the use of ECT in such patients. Herein we review our ECT experience treating 26 pacemaker patients and 3 ICD patients. All patients obtained significant antidepressant benefits with ETC. Only one serious cardiac event occurred, a case of supraventricular tachycardia (SVT) requiring a stay on the cardiac intensive care unit. The SVT resolved and the patient went on to receive further uncomplicated ECT treatments. We conclude from this experience that with proper pre‐ECT cardiac and pacemaker/defibrillator assessment, ECT can be safely and effectively administered to patients with an implanted cardiac device.
Relation Between History of Paroxysmal Atrial Fibrillation and Electrophysiological Abnormalities of Atrial Muscle
Authors: NAKAO KOJIRO , SETO SHINJI , SHIBATA RIYAKO , DOI YOSHIYUKI , FUKAE SATOKI , KOMIYA NORIHIRO , YANO KATSUSUKE
Published: September 2004

Although electrophysiological abnormalities of atrial muscle have been evaluated in patients with paroxysmal atrial fibrillation (PAF), no prior study has determined the contribution of the patient's history of PAF to electrophysiological abnormalities. The study population consisted of 108 patients (71 men; mean age, 57 ± 14 years) with symptomatic and idiopathic PAF who underwent electrophysiological study. Before electrophysiological study, histories of frequency, number of PAF episodes per month, and duration, a time interval from the first episode of PAF to electrophysiological study, were examined. At electrophysiological study, endocardial electrograms from 12 right atrial sites were recorded during sinus rhythm, and the right atrial effective refractory period was determined. Longest duration of atrial electrograms, maximal number of fragmented deflections, and number of abnormal atrial electrograms recorded at the right atrial sites were significantly greater in the frequent group (> 1 PAF episode per month, n = 57) than in the infrequent group (< 1 PAF episode per month, n = 51) (98 ± 18 ms vs 88 ± 16 ms, P < 0.005; 8.7 ± 2.6 vs 7.5 ± 2.6, P < 0.05; and 2.2 ± 2.2 vs 1.4 ± 1.6, P < 0.05, respectively). Indices of atrial vulnerability were also greater in the frequent group. Duration of PAF history was significantly correlated with longest duration r = 0.52, P < 0.0001), maximal number of fragmented deflections r = 0.51, P < 0.0001), and number of abnormal atrial electrograms r = 0.58, P < 0.0001). More frequent episodes and longer history of PAF significantly increased the electrophysiological abnormalities of the atrial muscle, suggesting that PAF results in gradual electrical remodeling of the atrial muscle.
Quantification of Atrial Tachyarrhythmia Burden with an Implantable Pacemaker Before and After Pulmonary Vein Isolation
Authors: PÜRERFELLNER HELMUT , AICHINGER JOSEF , MARTINEK MARTIN , NESSER HANS JOACHIM , ZIEGLER PAUL , KOEHLER JODI , WARMAN EDUARDO , HETTRICK DOUGLAS
Published: September 2004

Long‐term efficacy of pulmonary vein (PV) ostial isolation for paroxysmal atrial fibrillation is difficult to assess. We evaluated the net duration of atrial tachyarrhythmia episodes (burden), atrial tachyarrhythmia episode frequency, and quality‐of‐life (QOL) before and after PV isolation in patients with an existing pacemaker featuring extensive diagnostic capabilities. Due to frequent recurrences of paroxysmal atrial fibrillation, PV isolation was performed 21 ± 10 months following pacemaker implantation on 12 patients (57 ± 5 years) with normal left ventricular function. Atrial tachyarrhythmia burden (ATB) and episode frequency were monitored daily by the device both pre‐ and postablation. QOL questionnaires were collected at ablation and 1, 3, and 6 months thereafter. Patients were followed for 20 ± 9 and 11 ± 9 months pre‐ and postablation, respectively. Membrane‐active antiarrhythmic medications were discontinued after ablation in 8 of 12 patients. PV isolation resulted in a significant reduction of ATB from a median of 3.2 hours/day (preablation) to 0.2 hours/day (postablation, P < 0.01, Wilcoxon signed‐rank test). The median tachyarrhythmia frequency was 6.4 episodes/day (preablation) and 0.3 episodes/day (postablation, P = 0.09). QOL measures significantly improved over the data collection intervals (P < 0.05). Tachyarrhythmia burden was positively associated with Symptom Checklist frequency and severity (P < 0.01). Significant long‐term reductions in total ATB (symptomatic and asymptomatic) were observed. Furthermore, reductions in ATB were associated with improvements in QOL measures. Extensive monitoring capabilities in implantable devices help provide complete disclosure on the effect of PV isolation in paroxysmal atrial fibrillation patients.
Brugada Electrocardiographic Pattern Elicited by Inadvertent Flecainide Overdose
Authors: HUDSON CHRISTOPHER J. , WHITNER TANYA E. , RINALDI MICHAEL J. , LITTMANN LASZLO
Published: September 2004

In a 70‐year‐old man, without clinical suggestion of the hereditary form of the Brugada syndrome, severe flecainide overdose resulted in profound widening of the QRS complex and the development of ST‐T abnormalities typical of the Brugada sign. Serial ECGs recorded over a 5‐day period revealed a parallel pattern of dynamic intraventricular conduction defect and ST‐segment elevation. Resolution of ST‐segment elevation lagged behind resolution of the QRS widening by 16–20 hours. Despite the marked Brugada abnormality no arrhythmia occurred and the patient recovered without complications.
Transvenous Biventricular Defibrillation Can Improve Defibrillation Threshold
Authors: SNOW JEFFREY S. , LARSEN ANDERS , COHEN TODD J.
Published: September 2004

A case report of a patient with a high defibrillation threshold at initial implantation that was improved by the insertion of a shocking coil in the left lateral cardiac vein is discussed.
Omeprazole Treatment of Korean Patients: Effects on Gastric pH and Gastrin Release in Relation to CYP2C19 Geno‐ and Phenotypes
Authors: Roh Hyung‐Keun , Kim Pum‐Soo , Lee Don‐Haeng , Tybring Gunnel , Sagar Mohamed , Park Chang‐Shin , Seensalu Rein , Bertilsson Leif
Published: September 2004

Abstract: This study aimed to investigate the effect of omeprazole on intragastric pH and gastrin release as well as the plasma concentration of omeprazole in relation to CYP2C19 genotypes after repeated doses in Korean patients. Twenty‐six Korean patients with acid related disease were genotyped for CYP2C19 by allele specific PCR (wt/wt, CYP2C19*1/*1; wt/mut, CYP2C19*1/*2 or *1/*3; mut/mut, CYP2C19*2/*2, *2/*3 or *3/*3). Intragastric pH was monitored during 24 hr, and the plasma concentrations of omeprazole, hydroxyomeprazole, omeprazole sulfone and meal‐stimulated gastrin were measured during 4 hr before and after 8 consecutive daily doses of 20 mg omeprazole. Unexpectedly the AUCs of omeprazole in the three genotypes were similarly high on Day 8. The mean 24 hr pH increased significantly in all three genotypes (paired t‐test; P<0.0001), and the AUCs (4 hr) of gastrin in all patients increased markedly from 129±73 to 298±142 pMhr (P<0.0001). However, there was no statistically significant difference between the three genotypes in the mean pH and gastrin AUCs on Day 8. After 8 consecutive doses of 20 mg omeprazole, the gastric pH and the plasma gastrin were increased significantly in all three CYP2C19 genotypes, which were confirmed by high plasma concentrations of omeprazole in all three genotype groups. We suggest that the reason why the wt/wt had high concentrations of omeprazole similar to those in the other two genotype groups is that some of them were old with low CYP2C19 activity. In these patients omeprazole accumulated from the first to the eighth dose similar to that in the heterozygotes.
Regulation of transmitter release by synapsin II in mouse motor terminals
Authors: Samigullin Dmitry , Bill Cynthia A. , Coleman William L. , Bykhovskaia Maria
Published: September 2004

We investigated quantal release and ultrastructure in the neuromuscular junctions of synapsin II knockout (Syn II KO) mice. Synaptic responses were recorded focally from the diaphragm synapses during electrical stimulation of the phrenic nerve. We found that synapsin II affects transmitter release in a Ca2+‐dependent manner. At reduced extracellular Ca2+ (0.5 mm), Syn II KO mice demonstrated a significant increase in evoked and spontaneous quantal release, while at the physiological Ca2+ concentration (2 mm), quantal release in Syn II KO synapses was unaffected. Protein kinase inhibitor H7 (100 μm) suppressed quantal release significantly stronger in Syn II KO synapses than in wild type (WT), indicating that Syn II KO synapses may compensate for the lack of synapsin II via a phosphorylation‐dependent pathway. Electron microscopy analysis demonstrated that the lack of synapsin II results in an approximately 40% decrease in the density of synaptic vesicles in the reserve pool, while the number of vesicles docked to the presynaptic membrane remained unchanged. Synaptic depression in Syn II KO synapses was slightly increased, which is consistent with the depleted vesicle store in these synapses. At reduced Ca2+ frequency facilitation of synchronous release was significantly increased in Syn II KO, while facilitation of asynchronous release was unaffected. Thus, at the reduced Ca2+ concentration, synapsin II suppressed transmitter release and facilitation. These results demonstrate that synapsin II can regulate vesicle clustering, transmitter release, and facilitation.
Epigenetic Regulation of Aging in Honeybee Workers
Authors: Omholt Stig W. , Amdam Gro V.
Published: September 2004

Aging and longevity are complex life history traits that are influenced by both genes and environment and exhibit significant phenotypic plasticity in a broad range of organisms. A striking example of this plasticity is seen in social insects, such as ants and bees, where different castes can have very different life spans. In particular, the honeybee worker offers an intriguing example of environmental control on aging rate, because workers are conditionally sterile and display very different aging patterns depending on which temporal caste they belong to (hive bee, forager, or a long-lived caste capable of surviving for several months on honey alone). The ubiquitous yolk protein vitellogenin appears to play a key role in the regulatory circuitry that controls this variation. Here we outline the current understanding of the relation between vitellogenin and somatic maintenance in honeybee workers, and how this relation can be understood in a life history context.
A Twist in an Early End
Authors: Davenport R. John
Published: September 2004

Patients with Werner syndrome show signs of rapid aging, perhaps because their chromosomes come to an abrupt end, two new studies suggest. Mice that lack the Werner syndrome protein (WRN) deteriorate quickly only if they also harbor short telomeres, protective caps that guard the ends of chromosomes. Furthermore, WRN flocks to telomeres and unravels structures there. The work solidifies the idea that telomere malfunction contributes to the disease.
Immunotherapy for Alzheimer's Disease
Authors: McGeer Patrick L. , McGeer Edith
Published: September 2004

Strong evidence exists indicating that chronic neuroinflammation contributes to the progression of Alzheimer's disease (AD). A major focus of AD-associated research has been amyloid-β (Aβ) protein deposits. Vaccination with Aβ stimulates phagocytosis of Aβ in transgenic mouse models of AD, leading to clearance of the deposits. Similar vaccination in humans with AD has, however, led to meningoencephalitis in some cases. The difference probably depends on the initial level of brain inflammation, which is much higher in bona fide AD in humans than in the transgenic mice. Because both pro- and anti-inflammatory activation of immune cells are possible, stimulating the phagocytic action of microglia while simultaneously stimulating anti-inflammatory activity might be beneficial in AD.
Eating Yourself to Life
Authors: Davenport John
Published: September 2004

Hungry flies sometimes recycle their own cells, and new studies unearth some of the molecular intricacies behind this self-consuming tendency. Cellular cannibalism--called autophagy--slows with age in mammals, and the findings might help researchers gauge its contribution to decrepitude.
Osteoarthritis
Authors: Shakoor Najia , Loeser Richard F.
Published: September 2004

In this case study, we describe the symptoms, evaluation, and management of a woman with osteoarthritis (OA). OA is the most common form of arthritis worldwide and it is a major cause of disability in the elderly. Although there are several aging-related changes in the musculoskeletal system that may contribute to the pathogenesis of this disease, research suggests that OA is not merely an inevitable result of aging. OA is most likely a multifactorial process whereby non-aging-related factors also contribute to the onset, progression, and symptomatology of the disease. Specifically, both biochemical factors, including physiological properties of cartilage and bone, and biomechanical factors such as muscle strength, proprioception, and joint loading have been implicated in the pathogenesis of OA. Newer nonpharmacological treatment options are focusing on how to improve symptoms and prevent progression of the disease through mechanical interventions.
Yin and Yang
Authors: Leslie Mitch
Published: September 2004

The circulatory system sends mixed messages when it faces atherosclerosis. Cells exude one compound that inhibits fatty buildup in arteries and another molecule that promotes it, according to a new study. Adjusting the proportions of the two molecules might check the obstructions that can lead to heart attacks and strokes.
Accelerated Sea-Level Rise from West Antarctica
Authors: Thomas R. , Rignot E. , Casassa G. , Kanagaratnam P. , Acuña C. , Akins T. , Brecher H. , Frederick E. , Gogineni P. , Krabill W. , Manizade S. , Ramamoorthy H. , Rivera A. , Russell R. , Sonntag J. , Swift R. , Yungel J. , Zwally J.
Published: September 2004

Recent aircraft and satellite laser altimeter surveys of the Amundsen Sea sector of West Antarctica show that local glaciers are discharging about 250 cubic kilometers of ice per year to the ocean, almost 60% more than is accumulated within their catchment basins. This discharge is sufficient to raise sea level by more than 0.2 millimeters per year. Glacier thinning rates near the coast during 2002–2003 are much larger than those observed during the 1990s. Most of these glaciers flow into floating ice shelves over bedrock up to hundreds of meters deeper than previous estimates, providing exit routes for ice from further inland if ice-sheet collapse is under way.
Focus Issue—Tailoring the Immune Response
Authors: Adler Elizabeth M.
Published: September 2004

Recent advances have led to increasing sophistication in our ability to manipulate the immune response to prevent or treat disease. Monoclonal antibodies have emerged as a viable therapeutic approach against both cancer and autoimmune disease. Rituximab, the first monoclonal antibody approved by the FDA for cancer therapy, appears to achieve its therapeutic effects through a combination of mechanisms that may include antibody-dependent cell-mediated cytotoxicity, complement-mediated cell lysis, and the direct stimulation of apoptotic signaling pathways in target cells. Moreover, an increased understanding of the factors that govern immune tolerance has poised us on the brink of further breakthroughs in the immunotherapy of cancer and autoimmune disease. Manipulation of the signaling pathways that lead to T cell anergy may allow us to promote or overcome tolerance as appropriate in the therapy of autimmune disease and cancer. Activation of toll-like receptor pathways in dendritic cells is one approach that may help break tumor tolerance and thereby enhance the efficacy of anti-cancer dendritic cell vaccines.
Using Signaling Pathways to Overcome Immune Tolerance to Tumors
Authors: Engleman Edgar G. , Brody Joshua , Soares Luis
Published: September 2004

The ability of tumors to evade the immune system is thought to result from the inability of T lymphocytes to recognize and respond to tumor antigens. This lack of T cell response may depend on a failure of dendritic cells to present antigen in the proper context so that T cells become tolerant to tumor antigens rather than primed to undergo an immune response. The inability of tumor-associated dendritic cells to effectively present antigen may in turn depend on inhibitory factors in the tumor milieu. Recent experiments suggest that the administration of toll-like receptor ligands stimulate dendritic cell activation and maturation and may thus help overcome T cell tolerance to tumor antigens. Whether or not such an approach is clinically feasible remains to be seen.
Interwoven Ubiquitination Oscillators and Control of Cell Cycle Transitions
Authors: Ang Xiaolu L. , Harper J. Wade
Published: September 2004

Ubiquitin-mediated proteolysis has emerged as a paramount mechanism for regulating the cell division cycle. Changes in the activities of certain E3 ligases can promote the interconversion of cell cycle states or transitions. Recent studies have revealed how distinct E3 ligases control the activity of other E3 ligases and how the interplay between these degradation machines sets up the timing of cell cycle transitions. For example, during G
1
, the anaphase-promoting complex in conjunction with Cdh1 (APC
Cdh1
) catalyzes destruction of the S-phase activator Skp2, helping to define the G
1
state. In response to poorly defined signals, APC
Cdh1
activity is reduced, allowing accumulation of Skp2 and therefore entry into S phase. In many cases, E3 ligases also function to ubiquitinate proteins that negatively regulate cell cycle transitions. Recent work indicates that cyclin-dependent kinase 2 and Polo kinase collaborate to phosphorylate Wee1, thereby promoting its ubiquitination by SCF
β-TRCP
. Thus, activation of the mitotic transition produces feedback signals that help to turn off the negative upstream pathway to further reenforce the transition.
Receptor-Operated Cation Entry—More Than Esoteric Terminology?
Authors: Gudermann Thomas , Mederos y Schnitzler Michael , Dietrich Alexander
Published: September 2004

Many hormones and neurotransmitters elicit an increase in the intracellular calcium concentration by binding to phospholipase C–linked G protein–coupled receptors. Activated receptors signal to calcium-permeable cation channels in the plasma membrane, which are distinct from those engaged by emptying of intracellular stores of calcium. The TRPC family of the mammalian homologs of the
Drosophila
transient receptor potential (TRP) cation channel represents likely molecular correlates underlying receptor-operated cation entry. While all TRPC family members are gated in a phospholipase C–dependent manner, the exact activation mechanism still remains elusive, although lipids such as diacylglycerol and polyunsaturated fatty acids are potential diffusible messengers. Functional TRPC channel complexes in the plasma membrane are thought to be composed of four distinct subunits whose stoichiometry and composition under physiological conditions are still largely unknown. However, recent progress in defining the combinatorial rules of TRPC channel assembly may lead to the identification of TRPC-dependent ion fluxes in living cells. Because of the large number of TRP proteins and their frequently overlapping functional characteristics, the central question is whether TRP proteins are functionally interchangeable or whether unique physiological roles can be ascribed to them. Receptor-operated cation entry is critically involved in the control of airway and vascular smooth muscle tone; hence, TRPC proteins are promising new drug targets.
Designer Androgens in Sport: When Too Much Is Never Enough
Authors: Handelsman David J.
Published: September 2004

The recent identification of tetrahydrogestrinone (THG), the first true "designer androgen," as a sports doping agent reflects both an alarmingly sophisticated illicit manufacturing facility and an underground network of androgen abusers in elite sports, as well as the still untapped potential for designer androgens in medicine. Never marketed, THG was apparently developed as a potent androgen that was undetectable by conventional International Olympic Committee–mandated urinary sports doping tests. As a potent androgen and progestin with unspecified contaminants, its distribution for use at high doses without any prior biological or toxicological evaluation poses significant health risks. Yet this diversion of science also highlights the prospect of designer androgens for use in human medicine. Designer androgens also offer the possibility of tissue-specific effects enhancing the beneficial effects of androgens while mitigating the undesirable ones. Further developments require better understanding of the postreceptor tissue selectivity of androgens, comparable to the mechanism underlying that of partial estrogen agonists (SERMs). This experience highlights the ongoing need for vigilance to detect novel drug doping strategies in order to maintain fairness and safety in elite sports. This will require the deployment of generic catch-all tests, such as sensitive and specific in vitro androgen bioassays, coupled with the development of mass spectrometry–based tests for specific doping agents.
RUELLE TYPE ZETA FUNCTIONS FOR TORI AND SOME ARITHMETICS
Authors: KUROKAWA NOBUSHIGE , WAKAYAMA MASATO
Published: September 2004

We introduce various Ruelle type zeta functions ζL(s) according to a choice of homogeneous "length functions" for a lattice L in [Formula: see text] via Euler products. The logarithm of each ζL(s) yields naturally a certain arithmetic function. We study the asymptotic distribution of averages of such arithmetic functions. Asymptotic behavior of the zeta functions at the origin s=0 are also investigated.
LOCATIONAL CHOICE FOR EXPORT PROCESSING ZONES IN DEVELOPING COUNTRIES
Authors: TETSU KAZUHIRO
Published: September 2004

Little attention has been given to the issue of the locational choice for EPZs, from a theoretical point of view, except by Miyagiwa (1993). In this paper, using a three-sector general equilibrium model with unemployment, we will examine theoretically the issue of where to locate EPZs. This model gives policy makers in developing countries four policy options. An interesting result is as follows: it reveals that attracting foreign firms which are more labor-intensive (capital-intensive) than the rural domestic firms into the rural-based EPZ is the best (worst) policy for developing countries.
THE SCHWARZSCHILD SOLUTION IN THE DGP MODEL
Authors: MIDDLETON CHAD , SIOPSIS GEORGE
Published: September 2004

We discuss the Schwarzschild solution in the Dvali–Gabadadze–Porrati (DGP) model. We obtain a perturbative expansion and find the explicit form of the lowest-order contribution. By keeping off-diagonal terms in the metric, we arrive at a perturbative expansion which is valid both far from and near the Schwarzschild radius. We calculate the lowest-order contribution explicitly and obtain the form of the metric both on the brane and in the bulk. As we approach the Schwarzschild radius, the perturbative expansion yields the standard four-dimensional Schwarzschild solution on the brane which is non-singular in the decoupling limit. This non-singular behavior is similar to the Vainshtein solution in massive gravity demonstrating the absence of the van Dam–Veltman–Zakharov (vDVZ) discontinuity in the DGP model.
QUANTUM TREATMENT OF TWO COUPLED OSCILLATORS IN INTERACTION WITH A TWO-LEVEL ATOM: PARAMETRIC AMPLIFIER MODEL
Authors: KHALIL E. M. , ABDALLA M. SEBAWE , OBADA A. S.-F.
Published: September 2004

In this communication we handle a modified model representing the interaction between a two-level atom and two modes of the electromagnetic field in a cavity. The interaction between the modes is assumed to be of a parametric amplifier type. The model consists of two different systems, one represents the Jaynes–Cummings model (atom–field interaction) and the other represents the two mode parametric amplifier model (field–field interaction). After some canonical transformations the constants of the motion have been obtained and used to derive the time evolution operator. The wave function in the Schrödinger picture is constructed and employed to discuss some statistical properties related to the system. Further discussion related to the statistical properties of some physical quantities is given where we have taken into account an initial correlated pair-coherent state for the modes. We concentrate in our examination on the system behavior that occurred as a result of the variation of the parametric amplifier coupling parameter as well as the detuning parameter. It has been shown that the interaction of the parametric amplifier term increases the revival period and consequently longer period of strong interaction between the atom and the fields.
CLOSED ESSENTIAL SURFACES AND WEAKLY REDUCIBLE HEEGAARD SPLITTINGS IN MANIFOLDS WITH BOUNDARY
Authors: MORIAH YOAV , SEDGWICK ERIC
Published: September 2004

We show that there are infinitely many two component links in S3 whose complements have weakly reducible and irreducible non-minimal genus Heegaard splittings, yet the construction given in the theorem of Casson and Gordon does not produce an essential closed surface. The situation for manifolds with a single boundary component is still unresolved though we obtain partial results regarding manifolds with a non-minimal genus weakly reducible and irreducible Heegaard splitting.
THE COMPUTATION OF THE NON-COMMUTATIVE GENERALIZATION OF THE A-POLYNOMIAL OF THE FIGURE-EIGHT KNOT
Authors: GELCA RĂZVAN , SAIN JEREMY
Published: September 2004

The paper computes the noncommutative A-ideal of the figure-eight knot, a noncommutative generalization of the A-polynomial. It is shown that if a knot has the same A-ideal as the figure-eight knot, then all colored Kauffman brackets are the same as those of the figure eight knot.
Perivascular gene transfer of NADPH oxidase inhibitor suppresses angioplasty-induced neointimal proliferation of rat carotid artery
Authors: Dourron Hector M. , Jacobson Gary M. , Park James L. , Liu Jianhua , Reddy Daniel J. , Scheel Maria L. , Pagano Patrick J.
Published: September 2004

Vascular stretch induces NADPH oxidase-derived superoxide anion (O2−), which has been implicated in hypertrophy and cell proliferation. We hypothesized that targeted delivery of an NADPH oxidase inhibitor to the adventitia would reduce stretch-induced vascular O2− and attenuate neointima formation. We designed a novel replication-deficient adenovirus containing a fibroblast-active promoter driving expression of NADPH oxidase inhibitory sequence gp91ds (Ad-PDGFβR-gp91ds/eGFP). 1) We characterized the specificity of this promoter using pPDGFβR-luciferase by showing induction of luciferase in cultured rat aortic fibroblasts but not in vascular smooth muscle cells. 2) Using RT-PCR, we observed expression of gp91ds and the reporter gene in fibroblasts after infection with Ad-PDGFβR-gp91ds/eGFP. 3) Using Ad-CMV-eGFP as a control, we delivered Ad-PDGFβR-gp91ds/eGFP to the adventitia of the rat common carotid artery (CCA). Immunohistochemistry confirmed localized delivery of the inhibitor to the adventitia. After CCAs were injured with an embolectomy catheter, we observed a significant increase in neointima-to-media area ratio in control CCAs, which was significantly attenuated in CCAs treated with the gp91ds-expressing virus. In a second group of rats, we detected a 10-fold increase in distension-stimulated O2−, which was significantly reduced in CCAs infected with gp91ds-expressing virus. These data demonstrate that localized adventitial delivery of an NADPH oxidase inhibitor is effective in reducing overall vascular O2− and neointima formation, suggesting that adventitial NADPH oxidase plays a functional role in development of neointimal hyperplasia.