bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigenic Divergence between
Bordetella pertussis
Clinical Isolates from Moscow, Russia, and Vaccine Strains
Authors: Borisova Olga , Kombarova Svetlana Yu , Zakharova Nelli S. , van Gent Marjolein , Aleshkin Vladimir A. , Mazurova Isabella , Mooi Frits R.
Published: January 2007

We analyzed temporal changes in the frequencies of the
ptxA
,
prn
,
fim2
, and
fim3
alleles in
Bordetella pertussis
strains isolated from pertussis patients in Moscow, Russia, from 1948 to 2004. The three strains used for the whole-cell vaccine harbored the alleles
ptxA2
,
ptxA4
,
prn1
,
fim2-1
, and
fim3A
. Vaccine-type alleles of
ptxA
(
ptxA2
and
ptxA4
) were characteristic for all prevaccination strains and for 96% of the strains isolated in the 1960s and 1970s. At the beginning of the 1970s,
ptxA2
and
ptxA4
were replaced by the
ptxA1
allele. In the 1980s and to the present, strains with
ptxA1
were predominant in the
B. pertussis
population. All prevaccination strains harbored the
prn1
allele, which corresponds to the vaccine-type allele. In subsequent years, the proportion of strains with the
prn1
allele decreased and the proportion of
prn3
and
prn2
strains increased. From 2002 to 2004 strains with
prn2
or
prn3
were predominant in the
B. pertussis
population. The vaccine-type alleles
fim2-1
and
fim3A
were found in all prevaccination strains and in 92% of the strains isolated from 1960 to 1989. The
fim2-2
and
fim3B
alleles were first observed at the beginning of the 1980s. In subsequent years, these strains became predominant. Together with waning immunity, the antigenic divergence between vaccine strains and clinical isolates observed in the Moscow area may explain the persistence of pertussis, despite the high rates of vaccine coverage. The results demonstrate that the selection of
B. pertussis
strains for vaccine manufacturing must be based on a thorough study of the
B. pertussis
population.
Intranasal Coadministration of Live Lactococci Producing Interleukin-12 and a Major Cow's Milk Allergen Inhibits Allergic Reaction in Mice
Authors: Cortes-Perez Naima G. , Ah-Leung Sandrine , Bermúdez-Humarán Luis G. , Corthier Gérard , Wal Jean-Michel , Langella Philippe , Adel-Patient Karine
Published: January 2007

The Th1/Th2 balance deregulation toward a Th2 immune response plays a central role in allergy. We previously demonstrated that administration of recombinantLactococcus lactisstrains expressing bovine β-lactoglobulin (BLG), a major cow's milk allergen, partially prevents mice from sensitization. In the present study, we aimed to improve this preventive effect by coadministration ofL. lactisBLG and a second recombinantL. lactisstrain producing biologically active interleukin-12 (IL-12). ThisL. lactisstrain producing IL-12 was previously used to enhance the Th1 immune response in a tumoral murine model (L. G. Bermúdez-Humarán et al., J. Immunol. 175:7297-7302, 2005). A comparison of the administration of either BLG alone or BLG in the presence of IL-12 was conducted. A BLG-specific primary Th1 immune response was observed only after intranasal coadministration of bothL. lactisBLG and IL-12-producingL. lactis, as demonstrated by the induction of serum-specific immunoglobulin G2a (IgG2a) concomitant with gamma interferon secretion by splenocytes, confirming the adjuvanticity of IL-12-producingL. lactis. Immunized mice were further sensitized by intraperitoneal administration of purified BLG, and the allergic reaction was elicited by intranasal challenge with purified BLG. Mice pretreated with BLG in either the presence or the absence of IL-12 were rendered completely tolerant to further allergic sensitization and elicitation. Pretreatment with eitherL. lactisBLG orL. lactisBLG and IL-12-producingL. lactisinduces specific anti-BLG IgG2a production in serum and bronchoalveolar lavage (BAL) fluid. Although specific serum IgE was not affected by these pretreatments, the levels of eosinophilia and IL-5 secretion in BAL fluid were significantly reduced after BLG challenge in the groups pretreated withL. lactisBLG andL. lactisBLG-IL-12-producingL. lactis, demonstrating a decreased allergic reaction. Our data demonstrate for the first time (i) the induction of a protective Th1 response by the association ofL. lactisBLG and IL-12-producingL. lactiswhich inhibits the elicitation of the allergic reaction to BLG in mice and (ii) the efficiency of intranasal administration of BLG for the induction of tolerance.
Natural Antibody and Complement Mediate Neutralization of Influenza Virus in the Absence of Prior Immunity
Authors: Jayasekera Jerome P. , Moseman E. Ashley , Carroll Michael C.
Published: January 2007

Early control of virus replication by the innate immune response is essential to allow time for the generation of a more effective adaptive immune response. As an important component of innate immunity, complement has been shown to be necessary for protection against numerous microbial infections. This study was undertaken to investigate the role of complement in neutralizing influenza virus. Results demonstrated that the classical pathway of complement mediated serum neutralization of influenza virus. Although nonimmune serum neutralized influenza virus, the mechanism of virus neutralization (VN) required antibody, as sera from RAG1-deficient mice lacked VN activity; moreover, purified natural immunoglobulin M (IgM) restored VN activity to antibody-deficient sera. The mechanism of VN by natural IgM and complement was associated with virion aggregation and coating of the viral hemagglutinin receptor; however, viral lysis did not significantly contribute to VN. Additionally, reconstitution of RAG1-deficient mice with natural IgM resulted in delayed morbidity during influenza virus infection. Collectively, these results provide evidence that natural IgM and the early components of the classical pathway of complement work in concert to neutralize influenza virus and that this interaction may have a significant impact on the course of influenza viral pneumonia.
Efficient DNA Packaging of Bacteriophage PRD1 Requires the Unique Vertex Protein P6
Authors: Karhu Nelli J. , Ziedaite Gabija , Bamford Dennis H. , Bamford Jaana K. H.
Published: January 2007

The assembly of bacteriophage PRD1 proceeds via formation of empty procapsids containing an internal lipid membrane, into which the linear double-stranded DNA genome is subsequently packaged. The packaging ATPase P9 and other putative packaging proteins have been shown to be located at a unique vertex of the PRD1 capsid. Here, we describe the isolation and characterization of a suppressor-sensitive PRD1 mutant deficient in the unique vertex protein P6. Protein P6 was found to be an essential part of the PRD1 packaging machinery; its absence leads to greatly reduced packaging efficiency. Lack of P6 was not found to affect particle assembly, because in the P6-deficient mutant infection, wild-type (wt) amounts of particles were produced, although most were empty. P6 was determined not to be a specificity factor, as the few filled particles seen in the P6-deficient infection contained only PRD1-specific DNA. The presence of P6 was not necessary for retention of DNA in the capsid once packaging had occurred, and P6-deficient DNA-containing particles were found to be stable and infectious, albeit not as infectious as wt PRD1 virions. A packaging model for bacteriophage PRD1, based on previous results and those obtained in this study, is presented.
Characterization of the Nuclear Export Signal in the Coronavirus Infectious Bronchitis Virus Nucleocapsid Protein
Authors: Reed Mark L. , Howell Gareth , Harrison Sally M. , Spencer Kelly-Anne , Hiscox Julian A.
Published: January 2007

The nucleocapsid (N) protein of infectious bronchitis virus (IBV) localizes to the cytoplasm and nucleolus and contains an eight-amino-acid nucleolar retention motif. In this study, a leucine-rich nuclear export signal (NES) (291-LQLDGLHL-298) present in the C-terminal region of the IBV N protein was analyzed by using alanine substitution and deletion mutagenesis to investigate the relative contributions that leucine residues make to nuclear export and where these residues are located on the structure of the IBV N protein. The analysis indicated that Leu296 and Leu298 are required for efficient nuclear export of the protein. Structural information indicated that both of these amino acids are available for interaction with protein complexes involved in this process. However, export of N protein from the nucleus/nucleolus was not inhibited by leptomycin B treatment, indicating that N protein nuclear export is independent of the CRM1-mediated export pathway.
Distinct Synaptic Dynamics of Heterogeneous Pacemaker Neurons in an Oscillatory Network
Authors: Rabbah Pascale , Nadim Farzan
Published: January 2007

Many rhythmically active networks involve heterogeneous populations of pacemaker neurons with potentially distinct synaptic outputs that can be differentially targeted by extrinsic inputs or neuromodulators, thereby increasing possible network output patterns. To understand the roles of heterogeneous pacemaker neurons, we characterized differences in synaptic output from the anterior burster (AB) and pyloric dilator (PD) neurons in the lobster pyloric network. These intrinsically distinct neurons are strongly electrically coupled, coactive, and constitute the pyloric pacemaker ensemble. During pyloric oscillations, the pacemaker neurons produce compound inhibitory synaptic connections to the follower lateral pyloric (LP) and pyloric constrictor (PY) neurons, which fire out of phase with AB/PD and with different delay times. Using pharmacological blockers, we separated the synapses originating from the AB and PD neurons and investigated their temporal dynamics. These synapses exhibited distinct short-term dynamics, depending on the presynaptic neuron type, and had different relative contributions to the total synaptic output depending on waveform shape and cycle frequency. However, paired comparisons revealed that the amplitude or dynamics of synapses from either the AB or PD neuron did not depend on the postsynaptic neuron type, LP or PY. To address the functional implications of these findings, we examined the correlation between synaptic inputs from the pacemakers and the burst onset phase of the LP and PY neurons in the ongoing pyloric rhythm. These comparisons showed that the activity of the LP and PY neurons is influenced by the peak phase and amplitude of the synaptic inputs from the pacemaker neurons.
Presumed Influence of DTC Prescription Drug Advertising: Do Experts and Novices Think Differently?
Authors: Huh Jisu , Langteau Rita
Published: January 2007

Davison's original third-person-effect proposal notes that experts, because of their special knowledge, may exhibit a greater third-person effect than do nonexperts. To gather empirical evidence on this notion, this research investigates whether experts perceive a greater influence of direct-to-consumer (DTC) advertising on others than do novices. The expert-novice distinction is made in two different ways: (a) physicians versus consumers, based on objective knowledge of prescription drugs and (b) consumer experts versus consumer novices, based on familiarity with DTC advertising. Results show that consumer experts clearly exhibit greater perceived DTC advertising influence on others than do novices, and the differences between experts and novices vary by presumed DTC advertising influence dimensions. Future research is advocated on expert views in presumed media influence studies.
Dynamic Representations of Threatening Trends: The Role of Rationality and Experientiality in Potentiating Trepidation
Authors: Berger Charles R. , Lee Eun-Ju
Published: January 2007

Two experiments evaluated the role graph schemata play in potentiating trepidation-related responses to static and dynamic graphical depictions of increasingly threatening trends. Rational and experiential processing systems' role in responding to the graphic depictions was examined. High rationals reported significantly less trepidation than lows when concrete trends exhibited attenuated recent growth but equal amounts when the trends showed linear or recent explosive growth. Low experientials were more apprehensive than highs when graphs were presented dynamically (Experiment 1). The same functions were presented as undefined threats in Experiment 2. High rational–low experientials were significantly less apprehensive than high rational–high experientials when the trend exhibited attenuated recent growth. Low rationals were more apprehensive than highs when graphs were presented dynamically. Graph schemata do not map graphical information on to trepidation-related metrics in any simple way, and stimulus ambiguity may activate experiential processing to the point that it dominates the rational system.
Investigation of Electrical Properties of Elastomer Composites Filled with TiB2
Authors: Todorova Z. , Dishovsky N. , Dimitrov R. , El-Tantawy F.
Published: January 2007

The volume resistivity (ρv) of natural rubber (NR) and nitrile butadiene rubber (NBR)-based composites filled with different amounts of titanium diboride (TiB2) decreases with increasing filler concentration. Volume resistivity decreases with increasing pressure and temperature and there is no hysteresis loop formed. The conduction mechanism of the composites is interpreted by calculation of the activation energy (Ea) and hopping energy (Eh). The defined electrical properties classify the investigated samples as polymer composite semiconductors. The possibilities for real application of these composites as linear thermistors and transducers in pressure sensors are studied.
Self-determination in Oceania
Authors: Wesley-Smith Terence
Published: January 2007

The interplay between national self-determination, the colonial legacy, the concept of sovereignty and the nature of state formation is what is at issue in any understanding of political development in the Pacific Islands. These complex territorial entities, scattered over thousands of square miles of ocean, embrace a vast range of cultural, geographical and linguistic diversity. Indigenous social and political organisation has been overlaid by arbitrary colonial divisions, and a model of western-style nation state formation promulgated by UN agencies. In the event, many of the fundamental economic and political problems of these societies have never been properly addressed-a situation exacerbated by the growing recourse to interventionism against ‘failed’ states by the most powerful. Any starting point for true self-determination in Oceania has to be found in indigenous practices of self-government.
Research assessment and the production of geographical knowledge
Authors: Castree Noel
Published: January 2007

This Forum examines the research assessment systems (RASs) that affect professional human geography, and offers perspectives on the whole idea of formal research assessment. The Forum aims to assist professional geographers in their reflections on present and future research assessment in their own countries. It comprises two parts. The first offers highly succinct and detailed descriptions of the RASs currently in place in a range of countries -be they highly centralized, standardized and formal systems, or devolved and relatively informal ones. Many professional geographers know little about the assessment procedures outside their own countries and the first part allows a comparative understanding to be developed. The second part (‘Whither research assessment?’) offers reflections on the whole notion of research assessment beyond the ‘normal’ assessment offered by peer review of papers, books and chapters; considers whether actually existing systems of research assessment in one or more countries embody the values conducive to an ‘appropriate’ form of research assessment; and it also considers the actual or probable impacts on the content and form of geographical knowledge of real or possible RASs.
The Experience of Feeling Unsure for Women at End-Of-Life
Authors: Bunkers Sandra Schmidt
Published: January 2007

The purpose of this study was to answer the research question, What is the structure of the lived experience of feeling unsure? The participants were 9 women at end-of-life. The Parse research method, a phenomenological- hermeneutic method, was used to discover the structure of feeling unsure. Through the process of extraction- synthesis three core concepts were identified: disquieting apprehensiveness, pressing on, and intimate sorrows. Thus, the lived experience of feeling unsure for these 9 women is disquieting apprehensiveness arising while pressing on with intimate sorrows. The structure provides knowledge about feeling unsure and its connection to health and quality of life. Feeling unsure will be discussed in relation to the principles and concepts of human becoming and in relation to how it can inform nursing practice and future research.
Self-Care Requirements for Activity and Rest: An Orem Nursing Focus
Authors: Allison Sarah E.
Published: January 2007

According to Orem's self-care deficit nursing theory, helping people to maintain a balance between activity and rest (a universal self-care requisite) is a legitimate concern of nursing. The meaning of activity and rest, the requirements and potential measures for meeting this self-care requisite, and factors that might influence the process are explored. Criteria for determining a need for nursing, guides for a nursing clinical assessment, and guides for nursing action are suggested as potential ways to assist persons to meet the action demands associated with this self-care requisite.
Treating Older Adults as Ends Rather Than Means Only
Authors: Baumann Steven L.
Published: January 2007

The treatment of older adults by nurses requires professional knowledge, skills, and attitudes which are carefully thought out and put into practice in organizations and societies that do not always respect the perspectives and priorities of older adults. McCormack's person-centered nursing with older adults approach seeks to help nurses deal with this bind. His approach, as critiqued by Landers and McCarthy, is discussed here.
Review of Research Related to Parse's Theory of Human Becoming
Authors: Doucet Thomas J. , Bournes Debra A.
Published: January 2007

Ninety-three retrievable studies guided by the human becoming theory between 1985 and 2006, are reviewed. A summary of the studies is tabulated according to the two basic human becoming research methods, the human becoming applied research method, and other qualitative research methods using human becoming as the frame of reference. The authors provide an overview of the studies and the human becoming research methods and further illuminate the findings of studies reviewed under four major themes that describe the phenomena studied.
Women’s Stories of Abortion in Southern Gabon, Africa
Authors: Hess Rosanna F.
Published: January 2007

The purpose of this study was to explore the reasons women in rural, southern Gabon, Africa, chose to terminate their pregnancies, the methods used to induce abortions, and postabortion effects experienced by these women. Abortion is illegal in this country. A descriptive qualitative design guided the methodology for this study. Five women with a history of induced abortion were interviewed in-depth for their abortion story. Reasons cited for an abortion included lack of financial and partner support. Abortion methods included oral, rectal, and vaginal concoctions of leaves, bark, and water and over-the-counter medications, including misoprostol. Affects were physical, spiritual, and relational. Health care professionals need to provide women with guidance for appropriate contraceptive usage. Abortion after-care of women with physical and spiritual needs is important. Future research is suggested on the use of misoprostol in Gabon to understand its affects on women’s reproductive health.
Child-Related Strain for Mothers in a Japanese Community
Authors: Hirokawa Kumi , Asano Junichi , Masuno Mitsuo , Usui Yoko , Yoshida Izumi , Shimizu Hiroyuki
Published: January 2007

The purpose of the study was to identify risk and protective factors for child-related strain among Japanese mothers. The present study focused not only on mothers’ employment status and gender role attitudes, but also on partner’s gender role attitudes. A sample of 322 married Japanese couples (mean age: 31.2 years for mothers and 34.0 years for fathers) in Gifu, Japan, completed a self-administered questionnaire concerning child-related strain, number of children, distance from their parents, employment status, educational level, marital quality, and gender role attitudes. Results from multiple regression analyses showed that, among the mother’s variables, employment status and marital quality were negatively associated with child-related strain. The number of years of education was also negatively associated with child-related strain. Except for years of education, partner’s variables did not have strong effects on child-related strain. For Japanese mothers of toddlers, working may be protective against child-related strain.
Exploring the Knowledge, Attitudes, Beliefs, and Communication Preferences of the General Public Regarding HPV
Authors: Friedman Allison L. , Shepeard Hilda
Published: January 2007

Genital human papillomavirus (HPV) infection is the most common sexually transmitted virus in the United States, causing genital warts, cervical cell abnormalities, and cervical cancer in women. To inform HPV education efforts, 35 focus groups were conducted with members of the general public, stratified by gender, race/ethnicity, and urban/rural location. Focus groups explored participants' knowledge, attitudes, and beliefs about HPV and a hypothetical HPV vaccine as well as their communication preferences for HPV-related educational messages. Audience awareness and knowledge of HPV were low across all groups. This, along with an apparent STD-associated stigma, served as barriers to participants' hypothetical acceptance of a future vaccine. Although information about HPV's high prevalence and link to cervical cancer motivated participants to learn more about HPV, it also produced audience fear and anxiety. This research suggests that HPV- and HPV-vaccine-related education efforts must be approached with extreme caution. Other practical implications are discussed.
Knowledge in Four Deformation Dimensions
Authors: Tywoniak Stephane A.
Published: January 2007

This paper sketches a complexity conceptualization of knowledge. Building from evolutionary theories, it defi nes knowledge as rules that reduce environmental uncertainty through connections between ideas and facts. Knowledge is conceived as a structure validated through action, a process contextualized in individual experience and a system embedded in social and cultural experience. It exhibits four characteristics of a complex system: it is sensitive to initial conditions, exhibits multiple feedback loops, is non-linear and is recursively symmetrical. Knowledge's four interdependent deformation dimensions are identified (personal, common, tacit and explicit) and their interactions are discussed. This conceptualization of knowledge as a complex system contributes to the knowledge-based theory of the firm by providing some micro-foundations to organizational knowledge, and it opens the opportunity to re-think theories of communities of practice, entrepreneurship and firm creation, the role of managers, and knowledge management.
Impact of a traffic light nutrition tool in a primary school
Authors: Ellis Rona M , Ellis Robert C T
Published: January 2007

Aims: To evaluate the impact of a school traffic light nutrition tool on the knowledge, attitude and behaviour of Key Stage 1 children (aged five to seven years).

Methods: A school traffic light nutrition tool is created, adopting the principles advocated by the House of Commons Health Select Committee on Obesity, 1which seeks to encourage children to freely eat green food, eat amber food in moderation and stop and think before eating red food. A single sample pre-and post-test design is used to measure changes in children's knowledge, attitude and behaviour. A state primary school in the UK, located in an area of mixed private and social housing, with a non-selective admission policy is the setting for the study. In total 69 children, aged five to seven, were tested three weeks before and three weeks after nutrition education.

Results: Knowledge improved significantly following nutrition education. Positive attitude scores and asking behaviour for red food decreased, but disappointingly positive feelings and asking behaviour for green food also diminished. Children's refusing behaviour for red food increased.

Conclusion: Beneficial changes in knowledge, attitude and behaviour were observed, but negative changes in attitude scores and behaviour towards green food suggested that children misunderstood some nutritional messages. A lack of wider school involvement and only the partial support of parents weakened the effectiveness of this approach. The nutrition tool is cost neutral and may have applicability in other settings.
Are children attending child play areas at risk of infectious diseases? What can be done?
Authors: Gauci Charmaine , Borg Doreen
Published: January 2007

Aims: Child play areas can pose a risk to children of infectious diseases. The prolonged presence of micro-organisms in the environment has already been established. In order to quantify this risk, specific studies are required when carrying out a risk assessment.

Methods: In order to assess the microbiological hazard in play areas in Malta, a study was performed during 2005, which consisted of an examination of the hygienic practices carried out in play areas by means of face-to-face interviews; inspections of the premises; environmental sampling and testing, and a study on the awareness and attitudes of parents to risk factors (face-to-face interviews). Follow up studies were performed after recommendations on risk management were provided.

Results: Overall, the hygienic practices in play areas were satisfactory. Of the premises 66% were licensed, 55% of the food handlers were registered, appropriate cooking and cooling facilities were available for most of the premises, temperature control records were available at 80% of premises, 60% were using disinfectant for cleaning play area surfaces and monitoring of refrigerated vehicles was carried out by 60%. There was an overall improvement after recommendations were given.

At the first inspection, 67% of the premises were categorized as being fair and 33% as being good. On repeat inspection, after recommendations were made, the grading of the premises were: excellent 7%, satisfactory 33%, good 53% and fair 7%.

The results of the environmental swabs taken had low counts of indicator organisms indicating a good overall hygienic condition.

Parents stated that 58% of the areas were in good hygienic condition but lacked adequate hand-washing facilities for children. All parents agreed with the importance of hand hygiene and that infectious diseases can be transmitted via contaminated objects and from one person to another.

Conclusion: An effective control strategy needs to be implemented involving all stakeholders to ensure that effective hygienic practices in play areas are available to protect children from infectious diseases.
Protocol for the Smoking, Nicotine and Pregnancy (SNAP) trial: double-blind, placebo-randomised, controlled trial of nicotine replacement therapy in pregnancy
Authors: Coleman Tim , Thornton Jim , Britton John , Lewis Sarah , Watts Kim , Coughtrie Michael WH , Mannion Clare , Marlow Neil , Godfrey Christine
Published: January 2007

Background

Smoking in pregnancy remains a public health challenge. Nicotine replacement therapy (NRT) is effective for smoking cessation in non-pregnant people, but because women metabolise nicotine and cotinine much faster in pregnancy, it is unclear whether this will be effective for smoking cessation in pregnancy. The NHS Health Technology Assessment Programme (HTA)-funded smoking, nicotine and pregnancy (SNAP) trial will investigate whether or not nicotine replacement therapy (NRT) is effective, cost-effective and safe when used for smoking cessation by pregnant women.

Methods/Design

Over two years, in 5 trial centres, 1050 pregnant women who are between 12 and 24 weeks pregnant will be randomised as they attend hospital for ante-natal ultrasound scans. Women will receive either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure is biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date (defined before randomisation and set within two weeks of this) and delivery. At six months after childbirth self-reported maternal smoking status will be ascertained and two years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial will be compared in both groups.

Discussion

This trial is designed to ascertain whether or not standard doses of NRT (as transdermal patches) are effective and safe when used for smoking cessation during pregnancy.
All-trans retinoic acid induces COX-2 and prostaglandin E2 synthesis in SH-SY5Y human neuroblastoma cells: involvement of retinoic acid receptors and extracellular-regulated kinase 1/2
Authors: Alique Matilde , Herrero Juan F , Lucio-Cazana Francisco Javier
Published: January 2007

Background

Our recent results show that all-trans retinoic acid (ATRA), an active metabolite of vitamin A, induces COX-dependent hyperalgesia and allodynia in rats. This effect was mediated by retinoic acid receptors (RARs) and was associated with increased COX-2 expression in the spinal cord. Since ATRA also up-regulated COX-2 expression in SH-SY5Y human neuroblastoma cells, the current study was undertaken to analyze in these cells the mechanism through which ATRA increases COX activity.

Methods

Cultured SH-SY5Y neuroblastoma cells were treated with ATRA. COX expression and kinase activity were analyzed by western blot. Transcriptional mechanisms were analyzed by RT-PCR and promoter assays. Pharmacological inhibitors of kinase activity and pan-antagonists of RAR or RXR were used to assess the relevance of these signaling pathways. Production of prostaglandin E2 (PGE2) was quantified by enzyme immunoabsorbent assay. Statistical significance between individual groups was tested using the non-parametric unpaired Mann-Whitney U test.

Results

ATRA induced a significant increase of COX-2 expression in a dose- and time-dependent manner in SH-SY5Y human neuroblastoma cells, while COX-1 expression remained unchanged. Morphological features of differentiation were not observed in ATRA-treated cells. Up-regulation of COX-2 protein expression was followed by increased production of PGE2. ATRA also up-regulated COX-2 mRNA expression and increased the activity of a human COX-2 promoter construct. We next explored the participation of RARs and mitogen-activated peptide kinases (MAPK). Pre-incubation of SH-SY5Y human neuroblastoma cells with either RAR-pan-antagonist LE540 or MAP kinase kinase 1 (MEK-1) inhibitor PD98059 resulted in the abolition of ATRA-induced COX-2 promoter activity, COX-2 protein expression and PGE2 production whereas the retinoid X receptor pan-antagonist HX531, the p38 MAPK inhibitor SB203580 or the c-Jun kinase inhibitor SP600125 did not have any effect. The increase in RAR-β expression and extracellular-regulated kinase 1/2(ERK1/2) phosphorylation in ATRA-incubated cells suggested that RARs and ERK1/2 were in fact activated by ATRA in SH-SY5Y human neuroblastoma cells.

Conclusion

These results highlight the importance of RAR-dependent and kinase-dependent mechanisms for ATRA-induced COX-2 expression and activity.
Abelson kinase (Abl) and RhoGEF2 regulate actin organization during cell constriction inDrosophila
Authors: Fox Donald T. , Peifer Mark
Published: January 2007

Morphogenesis involves the interplay of different cytoskeletal regulators. Investigating how they interact during a given morphogenetic event will help us understand animal development. Studies of ventral furrow formation, a morphogenetic event during Drosophila gastrulation, have identified a signaling pathway involving the G-protein Concertina (Cta) and the Rho activator RhoGEF2. Although these regulators act to promote stable myosin accumulation and apical cell constriction, loss-of-function phenotypes for each of these pathway members is not equivalent, suggesting the existence of additional ventral furrow regulators. Here, we report the identification of Abelson kinase (Abl) as a novel ventral furrow regulator. We find that Abl acts apically to suppress the accumulation of both Enabled (Ena) and actin in mesodermal cells during ventral furrow formation. Further, RhoGEF2 also regulates ordered actin localization during ventral furrow formation, whereas its activator, Cta, does not. Taken together, our data suggest that there are two crucial preconditions for apical constriction in the ventral furrow:myosin stabilization/activation, regulated by Cta and RhoGEF2; and the organization of apical actin, regulated by Abl and RhoGEF2. These observations identify an important morphogenetic role for Abl and suggest a conserved mechanism for this kinase during apical cell constriction.
Descartes and Leibniz on Human Free-Will and the Ability to Do Otherwise
Authors: Wee Cecilia
Published: January 2007

Both Descartes and Leibniz are on record as maintaining that acting freely requires that the agent ‘could have done otherwise.’ However, it is not clear how they could maintain this, given their other metaphysical commitments. In Leibniz's case, the arguments connected with this are well-rehearsed: it is argued, for example, that Leibnizian doctrines such as the Principle of Sufficient Reason and the thesis that God must will the best possible world preclude that the human could ever do other than she did. The question of whether Descartes can maintain that the agent is able to do otherwise in the face of his wider metaphysical commitments has received comparatively little attention. However, Chappell has recently noted that Descartes's thesis that God is the ‘total cause’ of everything seems to preclude the possibility of human freedom (where this includes the ability to do otherwise).
RalA and RalB Function as the Critical GTP Sensors for GTP-Dependent Exocytosis
Authors: Li Gang , Han Liping , Chou Ting-Chieh , Fujita Yoshihito , Arunachalam Lakshmanan , Xu Ainan , Wong Aaron , Chiew Soon-Kwang , Wan Qi , Wang Li , Sugita Shuzo
Published: January 2007

Although it has been established that the activation of GTPases by non-hydrolyzable GTP stimulates neurotransmitter release from many different secretory cell types, the underlying mechanisms remain unclear. In the present study we aimed to elucidate the functional role(s) for endogenous Ras-like protein A (RalA) and RalB GTPases in GTP-dependent exocytosis. For this purpose stable neuroendocrine pheochromocytoma 12 (PC12) cell lines were generated in which the expressions of both RalA and RalB were strongly downregulated. In these double knock-down cells GTP-dependent exocytosis was reduced severely and was restored after the expression of RalA or RalB was reintroduced by transfection. In contrast, Ca2+-dependent exocytosis and the docking of dense core vesicles analyzed by electron microscopy remained unchanged in the double knock-down cells. Furthermore, the transfected RalA and RalB appeared to be localized primarily on the dense core vesicles in undifferentiated and nerve growth factor-differentiated PC12 cells. Our results indicate that endogenous RalA and RalB function specifically as GTP sensors for the GTP-dependent exocytosis of dense core vesicles, but they are not required for the general secretory pathways, including tethering of vesicles to the plasma membrane and Ca2+-dependent exocytosis.
Passive Immunization with Anti-Ganglioside Antibodies Directly Inhibits Axon Regeneration in an Animal Model
Authors: Lehmann Helmar C. , Lopez Pablo H. H. , Zhang Gang , Ngyuen Thien , Zhang Jiangyang , Kieseier Bernd C. , Mori Susumu , Sheikh Kazim A.
Published: January 2007

Recent studies have proposed that neurite outgrowth is influenced by specific nerve cell surface gangliosides, which are sialic acid-containing glycosphingolipids highly enriched in the mammalian nervous system. For example, the endogenous lectin, myelin-associated glycoprotein (MAG), is reported to bind to axonal gangliosides (GD1a and GT1b) to inhibit neurite outgrowth. Clustering of gangliosides in the absence of inhibitors such as MAG is also shown to inhibit neurite outgrowth in culture. In some human autoimmune PNS and CNS disorders, autoantibodies against GD1a or other gangliosides are implicated in pathophysiology. Because of neurobiological and clinical relevance, we asked whether anti-GD1a antibodies inhibit regeneration of injured axonsin vivo. Passive transfer of anti-GD1a antibody severely inhibited axon regeneration after PNS injury in mice. In mutant mice with altered ganglioside or complement expression, inhibition by antibodies was mediated directly through GD1a and was independent of complement-induced cytolytic injury. The impaired regenerative responses and ultrastructure of injured peripheral axons mimicked the abortive regeneration typically seen after CNS injury. These data demonstrate that inhibition of axon regeneration is induced directly by engaging cell surface gangliosidesin vivoand imply that circulating autoimmune antibodies can inhibit axon regeneration through neuronal gangliosides independent of endogenous regeneration inhibitors such as MAG.
Previous Cocaine Exposure Makes Rats Hypersensitive to Both Delay and Reward Magnitude
Authors: Roesch Matthew R. , Takahashi Yuji , Gugsa Nishan , Bissonette Gregory B. , Schoenbaum Geoffrey
Published: January 2007

Animals prefer an immediate over a delayed reward, just as they prefer a large over a small reward. Exposure to psychostimulants causes long-lasting changes in structures critical for this behavior and might disrupt normal time-discounting performance. To test this hypothesis, we exposed rats to cocaine daily for 2 weeks (30 mg/kg, i.p.). Approximately 6 weeks later, we tested them on a variant of a time-discounting task, in which the rats responded to one of two locations to obtain reward while we independently manipulated the delay to reward and reward magnitude. Performance did not differ between cocaine-treated and saline-treated (control) rats when delay lengths and reward magnitudes were equal at the two locations. However, cocaine-treated rats were significantly more likely to shift their responding when we increased the delay or reward size asymmetrically. Furthermore, they were slower to respond and made more errors when forced to the side associated with the lower value. We conclude that previous exposure to cocaine makes choice behavior hypersensitive to differences in the time to and size of available rewards, consistent with a general effect of cocaine exposure on reward valuation mechanisms.
A Comparative Study on the Electronic Structure of the 1-Ethyl-3-Methylimidazolium Bis(trifluoromethylsulfonyl)amide RT-Ionic Liquid by Electron Spectroscopy and First Principles Calculations
Authors: Krischok S. , Öttking R. , Beenken W. J. D. , Himmerlich M. , Lorenz P. , Höfft O. , Bahr S. , Kempter V. , Schaefer J. A.
Published: January 2007

The near-surface electronic structure of the room-temperature ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide has been investigated with ultraviolet and X-ray photoelectron spectroscopy as well as metastable induced electron spectroscopy. The results have been compared with density functional theory calculations. The good agreement between the experimental and theoretical data provides detailed insight into the origin of the observed spectral features. In particular, we found that a simple composition of the spectra of the isolated ions does not suffice to fit to the experimental results, but interionic interactions have to be considered.
Phase Separation in Solutions of Room Temperature Ionic Liquids in Hydrocarbons
Authors: Saracsan D. , Rybarsch C. , Schröer W.
Published: January 2007

The room temperature ionic liquids (RTIL) trihexyl-tetradecyl phosphonium chloride (P666 14Cl) and the bromide (P666 14Br) are soluble in hydrocarbons. The investigated solutions in heptane, octane, nonane and decane show liquid–liquid phase separation with an upper critical solution point at ambient temperatures at molar fractions near 0.03 of the salt. Phase diagrams are reported and analysed presuming Ising criticality. The critical temperatures and the critical densities increase with the chain length of the hydrocarbons, where the figures corresponding to the bromides are above that of the chlorides. Scaled by the critical data the phase diagrams show corresponding state behaviour. In accordance with the prediction of the restricted primitive model (RPM), which is a model fluid of equal sized, charged hard spheres in a dielectric continuum, the critical points are located at low temperature and low concentration, when the corresponding state variables of this model are used. However, the critical temperature T
c
* and the critical density ρc
* are well below the figures of the RPM prediction. Comparison is made with the phase diagrams of alcohol solutions of imidazolium ionic liquids and with simulation results of the RPM.
Electrochemistry at Negative Potentials in Bis(trifluoromethanesulfonyl)amide Ionic Liquids
Authors: Howlett Patrick C. , Izgorodina Ekaterina I. , Forsyth Maria , MacFarlane Douglas R.
Published: January 2007

The bis(trifluoromethanesulfonyl)amide (TFSA) anion is widely studied as an ionic liquid (IL) forming anion which imparts many useful properties, notably electrochemical stability. Here we present electrochemical and spectroscopic evidence indicating that reductive decomposition of the bis(trifluoromethanesulfonyl)amide (TFSA) anion begins at ~ −2.0 Vvs.Fc+/Fc, well before the reported cathodic limit for many of these ILs. These processes are shown to be dependent upon the electrode substrate and are influenced by the water content of the IL. Supportingab initiocalculations are presented which suggest a possible mechanism for the anion decomposition. The products appear to passivate the electrode surface and the implications of this behaviour are discussed.
Electrodeposition of Metals for Micro- and Nanostructuring at Interfaces between Solid, Liquid and Gaseous Conductors: Dendrites, Whiskers and Nanoparticles
Authors: Peppler Klaus , Pölleth Manuel , Meiss Sebastian , Rohnke Marcus , Janek Jürgen
Published: January 2007

Electrodeposition of a metal requires the reduction of metal ions by electrons and can in principle occur at any interface or in any boundary region between two electrically conducting phases with different ionic transference numbers. Here we summarize and review metal deposition at all possible five interfaces: solid|solid (short s|s), liquid|liquid (l|l), solid|liquid (s|l), solid|gas (s|g), liquid|gas (l|g), emphasizing processes at less studied interfaces. Cathodic deposition of a metal from a liquid electrolyte (s|l interface) is the most typical case and forms the basis of numerous applied galvanic processes. The equivalent deposition of a metal on a solid electrolyte (s|s interface) is much less usual, but phenomenologically identical. The deposition processes of a metal at the interface between two liquid electrolytes, or between a gaseous conductor and either a solid or a liquid conductor form three other possible situations. Examples for these five general cases (the s|l interface is only briefly treated) are reviewed and discussed with respect to the growth kinetics and the product morphology. Nano-sized memory devices, switches, electron beam induced formation of metals on solid electrolytes and plasma-cathodic metal deposition from ionic liquids, where in the first place the very low vapour pressure of ionic liquids facilitates the application of low-temperature plasmas, are discussed as possible new and unusual applications of electrochemical metal deposition.
Periodontal Disease in Kuna Albinism: A Comparative Study
Authors: Champsaur Andre
Published: January 2007

Background: In classic albinism, all parts of the body are normal except for the absence of melanin. It is believed that lack of this pigment in periodontal tissues might influence periodontal disease progression. This study was designed to determine the relationship between periodontal diseases and albinism by comparing the clinical periodontal status of a group of native Panamanian Kuna albinos (from San Blas, Panama) to Kuna non‐albinos of the same communities.

Methods: An experimental group of 30 subjects (Kuna albinos aged ≥12 years) was selected and divided into three subgroups according to age. Likewise, a control group of 30 subjects (Kuna non‐albinos) was selected and divided in subgroups.

Results: Assessment of oral hygiene and gingival inflammation in albinos by the Silness and Löe plaque index and Löe and Silness gingival index, respectively, was unremarkable compared to control groups. No statistically significant differences were found for number of teeth present, gingival index, plaque index, clinical attachment loss (CAL), probing depth, or gingival recession. As expected, age was a factor in the severity of the periodontal disease; 58% of individuals aged ≥36 years had at least one site with CAL ≥7 mm.

Conclusion: Based on the overwhelming similarity of results found between experimental and control groups, albinism does not represent a clinical risk factor in the pathogenesis or exacerbation of periodontal diseases for these individuals.
Influence of the Period After Ovariectomy on Femoral and Mandibular Bone Density and on Induced Periodontal Disease
Authors: Orrico Silvana R.P. , Giro Gabriela , Gonçalves Daniela , Takayama Lilian , Pereira Rosa M.R.
Published: January 2007

Background: This study investigated the influence of the period after ovariectomy on femoral and mandibular bone mineral density (BMD) and on induced periodontal disease.

Methods: One hundred and twenty‐six female Holtzman rats were divided into nine groups: control, sham surgery (SHAM) with and without induction of periodontal disease for 51 and 150 days, and ovariectomy (OVX) with and without induction of periodontal disease for 51 and 150 days. Periodontal disease was induced by placing ligatures on the first lower molars during the last 30 days of each period. BMD was measured by dual‐energy x‐ray absorptiometry. Vertical bone loss was determined by measuring the distance from the alveolar bone crest to the cemento‐enamel junction on the mesial side of the first lower molar.

Results: Statistical analyses (Kruskal‐Wallis test) revealed a significant difference between the OVX and SHAM groups' global and femoral proximal epiphysis BMD (P <0.001) for 150 days and in the global evaluation for 51 days. For mandibular BMD, no difference was found between the groups of each period. Influence of the period on femoral BMD was found only for the SHAM groups, with lower BMD for the 51‐day period compared to the 150‐day period (P <0.05). In the global evaluation of the mandible, a lower BMD was found after 51 days. The period was a contributing factor for the vertical bone loss, and it resulted in higher values for the 51‐day period (P <0.05).

Conclusion: The period influenced the femoral BMD and the vertical bone loss in induced periodontal disease.