bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying the Transtheoretical Model to Ethnically Diverse Women at Risk for HIV
Authors: Gazabon Shirley A. , Morokoff Patricia J. , Harlow Lisa L. , Ward Rose Marie , Quina Kathryn
Published: April 2007

The purpose of this study is to compare the reliability and predictability of transtheoretical model (TTM) constructs when applied to minority and White women at risk for HIV. Participants consisted of 332 women, including Blacks, Asians, Hispanics, Native Americans, other non-Whites, and Whites. The results supported the reliability and validity of the TTM variables for minority women as well as for White women. Hierarchical multiple regressions demonstrated that TTM variables were able to predict over and above demographic variables. Structural equation models indicate strong support for a mediational model in which the pros and cons predict condom stage of change and unprotected sex though the mediation of self-efficacy. This study provides strong support for TTM scales applied to minority as well as White women at risk for HIV. The authors discuss how these variables might be incorporated into interventions aimed at increasing condom use in minority women.
Social Influences, Social Context, and Health Behaviors Among Working-Class, Multi-Ethnic Adults
Authors: Emmons Karen M. , Barbeau Elizabeth M. , Gutheil Caitlin , Stryker Jo Ellen , Stoddard Anne M.
Published: April 2007

Little research has explored the relationship between social influences (e.g., social networks, social support, social norms) and health as related to modifying factors that may contribute to health disparities. This is a cross-sectional analysis of fruit and vegetable intake and physical activity, using baseline data from two cancer prevention studies with working-class, multi-ethnic adults. Several social influence and social contextual variables were associated with fruit and vegetable intake and physical activity in both samples. Fruit and vegetable consumption was associated with social norms and social networks, although different contextual variables also were related to intake across the two samples. Physical activity was associated with social networks, social norms, and competing demands. By examining how key social influence and contextual mediating variables relate to health behaviors, we can learn more about the types of interventions that might be needed to promote sustained health behavior change in this population.
Pesticides in the Homes of Farmworkers
Authors: Rao Pamela , Quandt Sara A. , Doran Alicia M. , Snively Beverly M. , Arcury Thomas A.
Published: April 2007

Pesticide exposure has been linked with immediate and delayed health effects. Anyone who lives in a farmworker household may be exposed to pesticides. Studies with farmworkers have found generally low levels of awareness of pesticide exposure and prevention. Less is known about the perceptions of nonfarmworkers living with farmworkers. This article presents the results of 41 in-depth interviews conducted with Latino women in farmworker households regarding their knowledge of pesticides and perceptions of risk to their children's health. Their perceptions and behavior differ from scientific understanding and policy recommendations for exposure management, resulting in behaviors that may increase children's risk of exposure and subsequent health problems. Because the level at which exposure becomes harmful remains a subject of scientific debate, the wisest course of action is to minimize exposure (the precautionary principle). Families living in farmworker households would benefit from health education programs that target their specific needs.
What Coalition Factors Foster Community Capacity? Lessons Learned From the Fighting Back Initiative
Authors: Zakocs Ronda C. , Guckenburg Sarah
Published: April 2007

Coalitions build community capacity by encouraging local organizations to expand services, programs, or policies (i.e., organizational capacity). The aim of the study was to identify coalition factors—resources, lead agency, governance, and leadership—that foster organizational capacity. Thirteen coalitions funded by Robert Wood Johnson Foundation's Fighting Back (FB) Initiative were examined in a multiple-site case study where coalition served as the unit of analysis. Organizational capacity was measured by creating a scale for each community based on changes in programs, services, or policies among eight types of organizations. Both qualitative and quantitative analyses were conducted to identify relationships among organizational capacity and coalition factors. FB sites with greater organizational capacity shared seven characteristics: received more funds for coalition building; delayed establishing new lead agencies; were housed in agencies supportive of FB; maintained stable, participatory decision-making bodies; cultivated active involvement of local government; practiced collaborative leadership; and had effective, long-serving project directors.
Experiences of Beginning Health Educators and Changes in Their High School Students' Health Behaviors and Attitudes
Authors: Vamos Sandra
Published: April 2007

This study explored the instructional experiences of beginning health educators and changes in their high school students' health-related behaviors and attitudes. Qualitative data were collected through observations and personal interviews from five novice health teachers two times per week over an 8-week period. Quantitative data were collected from 92 high school student participants using a 60-item survey with a pretest/posttest administration. Dependent t tests were calculated to detect mean differences between total sample pretest and posttest scores with a significance level, where p < .05. Mean raw scores were calculated in 12 health categories to detect differences between pretest and posttest scores for each of the five individual health classes. A deeper understanding of beginning health teachers' practices, thoughts, and potential effectiveness offered insight into the interplay between teaching, learning, and health. The contribution to the enhancement of professional teacher preparation programs is provided.
Syringe Disposal Among Injection Drug Users in Harlem and the Bronx During the New York State Expanded Syringe Access Demonstration Program
Authors: Cleland Charles M. , Deren Sherry , Fuller Crystal M. , Blaney Shannon , McMahon James M. , Tortu Stephanie , Des Jarlais Don C. , Vlahov David
Published: April 2007

Effective January 1, 2001, New York State enacted the Expanded Syringe Access Demonstration Program (ESAP), allowing syringes to be sold in pharmacies without a prescription or dispensed through doctors, hospitals, and clinics to adults. A concern in the assessment of ESAP is its effects on syringe disposal practices. Syringe use data regarding the last injection episode were combined from three projects ( N = 1,030) recruiting injection drug users. Disposal of syringes by methods known to be safe decreased significantly over time after the implementation of ESAP. Syringes obtained either from syringe exchange programs or ESAP sources were more likely to be disposed of safely than syringes obtained from other sources. Efforts to enlist pharmacists and others involved in ESAP implementation to encourage safe disposal are needed. More detailed information on disposal practices is needed to capture the continuum from least to most safe practices and variation within individuals.
Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)
Authors: Pfeifer Heike , Wassmann Barbara , Pavlova Anna , Wunderle Lydia , Oldenburg Johannes , Binckebanck Anja , Lange Thoralf , Hochhaus Andreas , Wystub Silvia , Brück Patrick , Hoelzer Dieter , Ottmann Oliver G.
Published: April 2007

Acquired imatinib resistance in advanced Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has been associated with mutations in the kinase domain (KD) of BCR-ABL. We examined the prevalence of KD mutations in newly diagnosed and imatinib-naive Ph+ ALL patients and assessed their clinical relevance in the setting of uniform frontline therapy with imatinib in combination with chemotherapy. Patients enrolled in the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) trial ADE10 for newly diagnosed elderly Ph+ ALL were retrospectively examined for the presence of BCR-ABL KD mutations by denaturing high-performance liquid chromatography (D-HPLC), cDNA sequencing, and allele-specific polymerase chain reaction (PCR). A KD mutation was detected in a minor subpopulation of leukemic cells in 40% of newly diagnosed and imatinib-naive patients. At relapse, the dominant cell clone harbored an identical mutation in 90% of cases, the overall prevalence of mutations at relapse was 80%. P-loop mutations predominated and were not associated with an inferior hematologic or molecular remission rate or shorter remission duration compared with unmutated BCR-ABL. BCR-ABL mutations conferring high-level imatinib resistance are present in a substantial proportion of patients with de novo Ph+ ALL and eventually give rise to relapse. This provides a rationale for the frontline use of kinase inhibitors active against these BCR-ABL mutants.
NF-κB2 mutation targets TRAF1 to induce lymphomagenesis
Authors: Zhang Baochun , Wang Zhe , Li Tai , Tsitsikov Erdyni N. , Ding Han-Fei
Published: April 2007

The NF-κB2 gene is recurrently mutated in human lymphoid malignancies. However, a causal relationship between NF-κB2 mutation and lymphomagenesis has not been established. It is also unclear how the mutation may lead to lymphoid malignancies. We report the generation of transgenic mice with targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, in lymphocytes. The transgenic mice display a marked expansion of peripheral B cell populations and develop predominantly small B cell lymphomas. p80HT expression has no apparent effect on the proliferation of B cells, but renders them specifically resistant to apoptosis induced by cytokine deprivation and mitogenic stimulation. Lymphocytes and lymphoma cells from p80HT mice express high levels of TRAF1, an antiapoptotic protein also implicated in lymphoid malignancies. p80HT binds the TRAF1 promoter in vivo and activates TRAF1 transcription. Moreover, TRAF1 knockdown abrogates the antiapoptotic activity of p80HT and TRAF1 deficiency reestablishes B cell homeostasis in p80HT mice. These findings demonstrate NF-κB2 mutation as an oncogenic event in vivo and suggest a molecular pathway for TRAF1 activation in the pathogenesis of lymphomas.
Alternative splicing due to an intronic SNP in HMSD generates a novel minor histocompatibility antigen
Authors: Kawase Takakazu , Akatsuka Yoshiki , Torikai Hiroki , Morishima Satoko , Oka Akira , Tsujimura Akane , Miyazaki Mikinori , Tsujimura Kunio , Miyamura Koichi , Ogawa Seishi , Inoko Hidetoshi , Morishima Yasuo , Kodera Yoshihisa , Kuzushima Kiyotaka , Takahashi Toshitada
Published: April 2007

Here we report the identification of a novel human leukocyte antigen (HLA)-B44–restricted minor histocompatibility antigen (mHA) with expression limited to hematopoietic cells. cDNA expression cloning studies demonstrated that the cytotoxic T lymphocyte (CTL) epitope of interest was encoded by a novel allelic splice variant of HMSD, hereafter designated as HMSD-v. The immunogenicity of the epitope was generated by differential protein expression due to alternative splicing, which was completely controlled by 1 intronic single-nucleotide polymorphism located in the consensus 5′ splice site adjacent to an exon. Both HMSD-v and HMSD transcripts were selectively expressed at higher levels in mature dendritic cells and primary leukemia cells, especially those of myeloid lineage. Engraftment of mHA+ myeloid leukemia stem cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID)/γcnull mice was completely inhibited by in vitro preincubation with the mHA-specific CTL clone, suggesting that this mHA is expressed on leukemic stem cells. The patient from whom the CTL clone was isolated demonstrated a significant increase of the mHA-specific T cells in posttransplantation peripheral blood, whereas mHA-specific T cells were undetectable in pretransplantation peripheral blood and in peripheral blood from his donor. These findings suggest that the HMSD–v–encoded mHA (designated ACC-6) could serve as a target antigen for immunotherapy against hematologic malignancies.
Microglia activation in retinal degeneration
Authors: Langmann Thomas
Published: April 2007

Microglia cells are phagocytic sentinels in the CNS and in the retina required for neuronal homeostasis and innate immune defense. Accumulating experimental evidence suggests that chronic microglia activation is associated with various neurodegenerative diseases including retinal dystrophies. Endogenous triggers alert microglia cells rapidly in the degenerating retina, leading to local proliferation, migration, enhanced phagocytosis, and secretion of cytokines, chemokines, and neurotoxins. This amplified, immunological cascade and the loss of limiting control mechanisms may contribute significantly to retinal tissue damage and proapoptotic events. This review summarizes the developmental and immune surveillance functions of microglia in the healthy retina and discusses early signaling events and transcriptional networks of microglia activation in retinal degeneration. The characterization of activation pathways at the molecular level may lead to innovative, therapeutic options in degenerative retinal diseases based on a selective, pharmacological interference with the neurotoxic activities of microglia cells, without compromising their homeostastic functions.
User-led assessment of a recovery service using DREEM
Authors: Dinniss Stephen , Roberts Glenn , Hubbard Charlotte , Hounsell Jenny , Webb Rachel
Published: April 2007

Aims and Method

To develop a service development plan supporting recovery-based practice through collaborative service user-led methodology, and contribute to the National Institute for Mental Health in England (NIMHE) pilot evaluation of recovery sensitive measures. Staff, residents and service user group representatives collaborated in implementing the Developing Recovery Enhancing Environments Measure (DREEM) in a residential rehabilitation service.

Results

Staff and residents demonstrated a shared vision of recovery. Many areas were being addressed to a high level but others showed areas of deficiency, and illustrated discrepant views between staff and residents, which provided a focus for the development of a clinical service action plan.

Clinical Implications

As an experimental measure DREEM provides a user-led structure, which enables services to measure their commitment to, and effectiveness in, providing recovery-based care. It focuses service development and enhances collaborative work with service users, thus mirroring the principles of recovery it measures. It merits further evaluation and consolidation.
Working with adults with personality disorder in the community: a multi-agency interview study
Authors: Huband Nick , Duggan Conor
Published: April 2007

Aims and Method

To explore the impact of adults with personality disorder on the professional groups that support them. Staff (n=72) from five agencies participated in interviews focusing on reactions to short case vignettes representing the three personality disorder clusters.

Results

Each presentation was relatively consistent in its impact on staff irrespective of the agency or setting. Several agency-specific themes were also identified, some illustrating areas of potential difficulty in inter-agency working. Many non-mental health workers reported considerable contact with this client group, although most felt dissatisfied with the training available and suggested solutions.

Clinical Implications

Findings from this study may help to match the content of training courses to need. Similar vignette-based surveys could be used to investigate the impact of staff training over time.
‘Stress-busting’ groups for consultant psychiatrists
Authors: Murdoch Jane M. , Eagles John M.
Published: April 2007

Aims and Method

To describe the formation and function of ‘stress-busting’ groups and report a survey on work-related stress among a small cohort of consultant psychiatrists.

Results

Of 37 questionnaires, 25 were returned and 16 respondents (64%) rated their overall level of stress at work as moderate or severe. Stressful factors included lack of staff, paperwork, high-risk patients, difficult/hostile relatives and job demands interfering with family life. The most helpful stress-reducing strategies were talking to colleagues for support and catharsis, outside interests, support from family and friends, effective time management and exercise. Among 15 current members of ‘stress-busting’ groups, 14 (93%) found these to be helpful. The most successful format in the ‘stress-busting’ groups was one of ‘problem-solving with ventilation of stresses'.

Clinical Implications

‘Stress-busting’ groups may constitute a helpful approach to work-related stress and a utilisation of the skills of psychiatrists to our mutual benefit.
Identification and Developmental Changes of Aromatase and Estrogen Receptor Expression in Prepubertal and Pubertal Human Adrenal Tissues
Authors: Baquedano María Sonia , Saraco Nora , Berensztein Esperanza , Pepe Carolina , Bianchini Michele , Levy Estrella , Goñi Javier , Rivarola Marco A. , Belgorosky Alicia
Published: April 2007

Context: The mechanisms of postnatal adrenal zonation remain unclear.

Objective: To provide a clue for a possible role of estrogens in adrenarche, we studied the expression of estrogen receptor (ER)α, ERβ, G protein-coupled receptor (GPR)30, and cP450aromatase (cP450arom) in human adrenal tissue.

Design: Human adrenal tissue was collected from three postnatal age groups (Grs): Gr 1, younger than 3 months (n = 12), fetal zone involution; Gr 2, 3 months to 6 yr (n = 17), pre-adrenarche; and Gr 3, older than 6–20 yr (n = 12), post-adrenarche period.

Results: ERβ mRNA in Grs 1 and 3 was higher than in Gr 2 (P < 0.05). By immunohistochemistry and laser capture microdissection followed by RT-PCR, ERβ was expressed in zona reticularis and fetal zone, GPR30 in zona glomerulosa (ZG) and adrenal medulla, while ERα mRNA and protein were undetectable. cP450arom mRNA in Gr 3 was higher than in Grs 1 and 2 (P < 0.05), and localized to ZG and adrenal medulla by laser capture microdissection. cP450arom Immunoreactivity was observed in adrenal medulla in the three Grs and in subcapsular ZG of Gr 3. Double-immunofluorescence studies revealed that cP450arom and chromogranin A only colocalize in adrenal medulla of subjects younger than 18 months. In these samples, exon 1.b-derived transcript was 3.5-fold higher, while exon 1.a-, 1.c-, and 1.d-derived transcripts were 3.3-, 1.9-, and 1.7-fold lower, respectively, than in subjects older than 6 yr.

Conclusions: Our results suggest that estrogens produced locally in adrenal medulla would play a role in zona reticularis functional differentiation through ERβ. The cP450arom and GPR30 expression in subcapsular ZG, colocalizing with a high-cell proliferation index, previously reported, suggests a local GPR30-dependent estrogen action in proliferation and migration of progenitor adrenal cells.
Effect of an Estrogen Receptor-α Intron 4 Polymorphism on Fat Mass in 11-Year-Old Children
Authors: Tobias J. H. , Steer C. D. , Vilariňo-Güell C. , Brown M. A.
Published: April 2007

Context: Polymorphisms in the ESR1 gene encoding estrogen receptor (ER)-α may be associated with fat mass in adults.

Objectives: The objective of the study was to establish whether ESR1 polymorphisms influence fat mass in childhood.

Design: This was a cross-sectional analysis after genotyping of rs9340799, rs2234693, and rs7757956 ESR1 polymorphisms.

Setting: The Avon Longitudinal Study of Parents and Children (ALSPAC) was a population-based prospective study.

Participants: Participants included 3097 11-yr-old children with results for ESR1 genotyping, puberty measures, and dual-energy x-ray absorptiometry results.

Outcomes: Relationships between ESR1 polymorphisms and indices of body composition were measured.

Results: The rs7757956 polymorphism was associated with fat mass (P = 0.002). Total body fat mass (adjusted for height) was reduced by 6% in children with TA/AA genotypes, and risk of being overweight (≥85th centile of fat mass) was decreased by 20%. This genetic effect appeared to interact with puberty in girls (P = 0.05 for interaction): in those with the TT genotype, total body fat mass (adjusted for height) was 18% higher in Tanner stages 3–5 vs. stages 1–2; the equivalent difference was 7% in those with TA/AA genotypes. Furthermore, the risk of being overweight was 36% lower in girls with TA/AA genotypes in Tanner stages 3–5, but no reduction was seen in those in stages 1–2. Neither rs9340799 nor rs2234693 polymorphisms were associated with body composition measures.

Conclusions: Fat mass in 11-yr-old children was related to the rs7757956 ESR1 polymorphism. This association was strongest in girls in more advanced puberty, in whom the risk of being overweight was reduced by 36% in those with the TA/AA genotype.
Genetic Variations at the Endocannabinoid Type 1 Receptor Gene (CNR1) Are Associated with Obesity Phenotypes in Men
Authors: Russo Paola , Strazzullo Pasquale , Cappuccio Francesco P. , Tregouet David A. , Lauria Fabio , Loguercio Maria , Barba Gianvincenzo , Versiero Marco , Siani Alfonso
Published: April 2007

Context: The endocannabinoid system modulates food intake and body weight in animal models. Treatment with the cannabinoid type 1 receptor blocker, rimonabant, reduces body weight in obese individuals.

Objective: The aim of this study was to determine whether single nucleotide polymorphisms of the gene encoding cannabinoid type 1 receptor, CNR1, are associated with body fat mass and distribution in two independent samples of white European adult men.

Design, Setting, and Participants: The 3813A/G and 4895A/G single nucleotide polymorphisms at the exon 4 of CNR1 were genotyped in 930 participants to the Olivetti Prospective Heart Study (OPHS) in Southern Italy and in 216 participants to the Wandsworth Heart and Stroke Study in the United Kingdom. Retrospective analysis was also performed on an OPHS subsample (n = 360) for which anthropometric data from 1987 and 1994–1995 examinations were available.

Main Outcome Measures: CNR1 genotypes and anthropometric measures of body fat distribution were determined.

Results: In the OPHS study, the 3813G allele was associated with increased subscapular skinfold thickness (24.2 ± 9.1 vs. 22.8 ± 7.7 mm; P = 0.031) and waist circumference (WC) (99.1 ± 8.8 vs. 97.7 ± 8.8 cm; P = 0.050). No association was observed with 4895A/G variant. Haplotype analysis confirmed that the unique haplotype carrying the 3813G was associated with increased WC and subscapular skinfold thickness. Similar results were observed in the OPHS retrospective subsample and the Wandsworth Heart and Stroke Study sample. In the latter, the 3813G was associated with increased WC (96.8 ± 11.3 vs. 91.6 ± 10.4 cm; P = 0.006).

Conclusions: Genetic variants at CNR1 are associated with obesity-related phenotypes in men. The detection of polymorphic variants in genes involved in the process of fat accumulation may help identify specific targets for pharmacological treatment of obesity and related metabolic abnormalities.
Direct Interactions with Gαi and Gβγ Mediate Nongenomic Signaling by Estrogen Receptor α
Authors: Kumar Premlata , Wu Qian , Chambliss Ken L. , Yuhanna Ivan S. , Mumby Susanne M. , Mineo Chieko , Tall Gregory G. , Shaul Philip W.
Published: April 2007

Estrogen induces G protein-dependent nongenomic signaling in a variety of cell types via the activation of a plasma membrane-associated subpopulation of estrogen receptor α (ERα). Using pull-down experiments with purified recombinant proteins, we now demonstrate that ERα binds directly to Gαi and Gβγ. Mutagenesis and the addition of blocking peptide reveals that this occurs via amino acids 251–260 and 271–595 of ERα, respectively. Studies of ERα complexed with heterotrimeric G proteins further show that estradiol causes the release of both Gαi and Gβγ without stimulating GTP binding to Gαi. Moreover, in COS-7 cells, the disruption of ERα-Gαi interaction by deletion mutagenesis of ERα or expression of blocking peptide, as well as Gβγ sequestration with β-adrenergic receptor kinase C terminus, prevents nongenomic responses to estradiol including src and erk activation. In endothelial cells, the disruption of ERα-Gαi interaction prevents estradiol-induced nitric oxide synthase activation and the resulting attenuation of monocyte adhesion that contributes to estrogen-related cardiovascular protection. Thus, through direct interactions, ERα mediates a novel mechanism of G protein activation that provides greater diversity of function of both the steroid hormone receptor and G proteins.
Crosstalk between neovessels and mural cells directs the site-specific expression of MT1-MMP to endothelial tip cells
Authors: Yana Ikuo , Sagara Hiroshi , Takaki Satoshi , Takatsu Kiyoshi , Nakamura Kenji , Nakao Kazuki , Katsuki Motoya , Taniguchi Shun-ichiro , Aoki Takanori , Sato Hiroshi , Weiss Stephen J. , Seiki Motoharu
Published: April 2007

The membrane-anchored matrix metalloproteinase MT1-MMP (also known as Mmp14) plays a key role in the angiogenic process, but the mechanisms underlying its spatiotemporal regulation in the in vivo setting have not been defined. Using whole-mount immunohistochemical analysis and the lacZ gene inserted into the Mmp14 gene, we demonstrate that MT1-MMP vascular expression in vivo is confined largely to the sprouting tip of neocapillary structures where endothelial cell proliferation and collagen degradation are coordinately localized. During angiogenesis in vitro, wherein endothelial cells are stimulated to undergo neovessel formation in the presence or absence of accessory mural cells, site-specific MT1-MMP expression is shown to be controlled by crosstalk between endothelial cells and vascular smooth muscle cells (VSMC). When vessel maturation induced by VSMCs is inhibited by introducing a soluble form of the receptor tyrosine kinase Tek, MT1-MMP distribution is no longer restricted to the endothelial tip cells, but instead distributes throughout the neovessel network in vitro as well as ex vivo. Taken together, these data demonstrate that vascular maturation coordinated by endothelial cell/mural cell interactions redirects MT1-MMP expression to the neovessel tip where the protease regulates matrix remodeling at the leading edge of the developing vasculature.
A regulatory role for CRM1 in the multi-directional trafficking of splicing snRNPs in the mammalian nucleus
Authors: Sleeman Judith
Published: April 2007

Distinct pathways of ribonucleoprotein transport exist within the nucleus, connected to their biogenesis and maturation. These occur despite evidence that the major mechanism for their movement within the nucleus is passive diffusion. Using fusions of Sm proteins to YFP, CFP and photoactivatable GFP, I have demonstrated that pathways with uni-directional bulk flow of complexes can be maintained within the nucleus despite multi-directional exchange of individual complexes. Newly imported splicing small nuclear ribonucleoproteins (snRNPs) exchange between Cajal bodies (CBs) within a nucleus and access the cytoplasm, but are unable to accumulate in speckles. By contrast, snRNPs at steady-state exchange freely in any direction between CBs and speckles, but cannot leave the nucleus. In addition to these surprising qualitative observations in the behaviour of nuclear complexes, sensitive live-cell microscopy techniques can detect subtle quantitative disturbances in nuclear dynamics before they have had an effect on overall nuclear organization. Inhibition of the nuclear export factor, CRM1, using leptomycin B results in a change in the dynamics of interaction of newly imported snRNPs with CBs. Together with the detection of interactions of CRM1 with Sm proteins and the survival of motor neurons (SMN) protein, these studies suggest that the export receptor CRM1 is a key player in the molecular mechanism for maintaining these pathways. Its role in snRNP trafficking, however, appears to be distinct from its previously identified role in small nucleolar RNP (snoRNP) maturation.
Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescence
Authors: Zhang Xiaoling , Sejas Daniel P. , Qiu Yuhui , Williams David A. , Pang Qishen
Published: April 2007

The proinflammatory cytokine tumor necrosis factor α (TNFα) inhibits hematopoietic stem cell (HSC) expansion, interferes with HSC self-renewal and compromises the ability of HSC to reconstitute hematopoiesis. We have investigated mechanisms by which TNFα suppresses hematopoiesis using the genomic instability syndrome Fanconi anemia mouse model deficient for the complementation-group-C gene (Fancc). Examination of senescence makers, such as senescence-associated β-galactosidase, HP1-γ, p53 and p16INK4A shows that TNFα induces premature senescence in bone marrow HSCs and progenitor cells as well as other tissues of Fancc–/– mice. TNFα-induced senescence correlates with the accumulation of reactive oxygen species (ROS) and oxidative DNA damage. Neutralization of TNFα or deletion of the TNF receptor in Fancc–/– mice (Fancc–/–;Tnfr1–/–) prevents excessive ROS production and hematopoietic senescence. Pretreatment of TNFα-injected Fancc–/– mice with a ROS scavenger significantly reduces oxidative base damage, DNA strand breaks and senescence. Furthermore, HSCs and progenitor cells from TNFα-treated Fancc–/– mice show increased chromosomal aberrations and have an impaired oxidative DNA-damage repair. These results indicate an intimate link between inflammatory reactive oxygen species and DNA-damage-induced premature senescence in HSCs and progenitor cells, which may play an important role in aging and anemia.
Sustained cell polarity and virulence in the phytopathogenic fungusUstilago maydisdepends on an essential cyclin-dependent kinase from the Cdk5/Pho85 family
Authors: Castillo-Lluva Sonia , Alvarez-Tabarés Isabel , Weber Isabella , Steinberg Gero , Pérez-Martín José
Published: April 2007

Cyclin-dependent kinases from the Cdk5/Pho85 family are thought to play important roles in morphogenesis in organisms as diverse as yeast and humans. Here we used the corn smut fungus Ustilago maydis to address the role of Cdk5/Pho85 kinases in the morphogenesis and virulence of dimorphic phytopathogens. We found that Cdk5 is essential for growth in U. maydis. A temperature-sensitive cdk5 mutant caused cell wall and morphology defects at the restrictive temperature. Actin patches labeled with a fimbrin-GFP fusion protein were delocalized and a GFP-Myo5 fusion was directed towards the growing cell pole and rapidly dissociated from the tip. These defects were found to be due to an impairment in the maintenance of cell polarity. Our results indicated that Cdk5 is required for the activity of Rac1, probably at the level of the localization of its GEF, Cdc24. Cdk5 was required for full virulence, probably because mutant cells are unable to sustain the dramatic polar growth required for the formation of the infective structures. These results support a major role for morphogenesis in the virulence program of dimorphic fungi.
Symmetrical localization of extrachromosomally replicating viral genomes on sister chromatids
Authors: Kanda Teru , Kamiya Masato , Maruo Seiji , Iwakiri Dai , Takada Kenzo
Published: April 2007

In eukaryotes, many latent viruses replicate as extrachromosomal molecules, called episomes, and efficiently segregate to daughter cells by noncovalently attaching to mitotic chromosomes. To understand the mechanism governing the processes, we analyzed the detailed subcellular localization of Epstein-Barr virus (EBV) genomes and a viral protein EBNA1, a bridging molecule between viral genomes and cellular chromatin. In the cells that were infected with a recombinant EBV expressing epitope-tagged EBNA1, EBNA1 localized to intranuclear punctate dots, which coincided with the localization of EBV genomes as revealed by fluorescence in situ hybridization (FISH). A significant number of EBNA1 dots were found to localize symmetrically on sister chromatids of mitotic chromosomes. Such symmetrical localization of EBNA1 dots was observed in prematurely condensed G2 chromosomes as well, correlating with the presence of closely spaced double dots of EBNA1 in G2-phase-enriched cells. The EBNA1 double dots were occasionally interconnected by the FISH signals of EBV episomes, exhibiting a dumbbell-like appearance. Thus, we propose that the partitioning of EBNA1 molecules onto sister chromatids during cellular DNA replication underlies the non-stochastic segregation of extrachromosomally replicating viral genomes.
RhoB plays an essential role in CXCR2 sorting decisions
Authors: Neel Nicole F. , Lapierre Lynne A. , Goldenring James R. , Richmond Ann
Published: April 2007

The CXCR2 chemokine receptor is a G-protein-coupled receptor that undergoes clathrin-mediated endocytosis upon ligand binding. The trafficking of CXCR2 is crucial for cells to maintain a proper chemotactic response. The mechanisms that regulate the recycling/degradation sorting decision are unknown. In this study, we used dominant-negative (T19N) and GTPase-deficient activated (Q63L) RhoB mutants, as well as RhoB small interfering RNA (siRNA) to investigate the role of RhoB in CXCR2 trafficking. Expression of either of the RhoB mutants or transfection of RhoB siRNA impaired CXCR2-mediated chemotaxis. Expression of RhoB T19N and transfection of RhoB siRNA impaired sorting of CXCR2 to the lysosome after 3 hours of CXCL8 stimulation and impaired CXCL8-induced CXCR2 degradation. In cells expressing the RhoB Q63L mutant, CXCR2 recycling through the Rab11a recycling compartment was impaired after 30 minutes of CXCL8 stimulation as was CXCL8-induced CXCR2 degradation. For cells expressing activated RhoB, CXCR2 colocalized with Rab4, a marker for the rapid recycling pathway, and with the mannose-6-phosphate receptor, which traffics between the trans-Golgi network and endosomes. These data suggest that CXCR2 recycles through alternative pathways. We conclude that oscillation of RhoB GTPase activity is essential for appropriate sorting decisions, and for directing CXCR2 degradation and recycling – events that are required for optimal chemotaxis.
Dose-dependent inhibition of proteasome activity by a mutant ubiquitin associated with neurodegenerative disease
Authors: van Tijn Paula , de Vrij Femke M. S. , Schuurman Karianne G. , Dantuma Nico P. , Fischer David F. , van Leeuwen Fred W. , Hol Elly M.
Published: April 2007

The ubiquitin-proteasome system is the main regulated intracellular proteolytic pathway. Increasing evidence implicates impairment of this system in the pathogenesis of diseases with ubiquitin-positive pathology. A mutant ubiquitin, UBB+1, accumulates in the pathological hallmarks of tauopathies, including Alzheimer's disease, polyglutamine diseases, liver disease and muscle disease and serves as an endogenous reporter for proteasomal dysfunction in these diseases. UBB+1 is a substrate for proteasomal degradation, however it can also inhibit the proteasome. Here, we show that UBB+1 properties shift from substrate to inhibitor in a dose-dependent manner in cell culture using an inducible UBB+1 expression system. At low expression levels, UBB+1 was efficiently degraded by the proteasome. At high levels, the proteasome failed to degrade UBB+1, causing its accumulation, which subsequently induced a reversible functional impairment of the ubiquitin-proteasome system. Also in brain slice cultures, UBB+1 accumulation and concomitant proteasome inhibition was only induced at high expression levels. Our findings show that by varying UBB+1 expression levels, the dual proteasome substrate and inhibitory properties can be optimally used to serve as a research tool to study the ubiquitin-proteasome system and to further elucidate the role of aberrations of this pathway in disease.
The control of tissue architecture over nuclear organization is crucial for epithelial cell fate
Authors: Chandramouly Gurushankar , Abad Patricia C. , Knowles David W. , Lelièvre Sophie A.
Published: April 2007

The remodeling of nuclear organization during differentiation and the dramatic alteration of nuclear organization associated with cancer development are well documented. However, the importance of tissue architecture in the control of nuclear organization remains to be determined. Differentiation of mammary epithelial cells into functional tissue structures, in three-dimensional culture, is characterized by a specific tissue architecture (i.e. a basoapical polarity axis), cell cycle exit and maintenance of cell survival. Here we show that induction of partial differentiation (i.e. basal polarity only, cell cycle exit and cell survival) by epigenetic mechanisms in malignant breast cells is sufficient to restore features of differentiation-specific nuclear organization, including perinucleolar heterochromatin, large splicing factor speckles, and distinct nuclear mitotic apparatus protein (NuMA) foci. Upon alteration of nuclear organization using an antibody against NuMA, differentiated non-neoplastic cells undergo apoptosis, whereas partially differentiated malignant cells enter the cell cycle. Non-neoplastic cells cultured under conditions that prevent the establishment of apical polarity also enter the cell cycle upon NuMA antibody treatment. These findings demonstrate that the differentiation status rather than the non-neoplastic or neoplastic origin of cells controls nuclear organization and suggest a link between nuclear organization and epigenetic mechanisms dictated by tissue architecture for the control of cell behavior.
Constructivist Coaching and Expertise Development as Action Research
Authors: Ollis Stewart , Sproule John
Published: April 2007

This case study assessed the efficacy of a constructivist development approach and subsequent action research methodology during sport-science support to an international shooting team (n=14) over a two-year period. Specific analysis focused on the benefits of a coach-focussed program to integrate the pluralism associated with the development of sporting expertise. The broadest possible range of methods and tools were utilised to ensure a multi-level awareness of change was provided This required monitoring and controlling change in organisational, team, relational and individual behaviour. Findings revealed that an emergenic, iterative, ecological and meta-level process of coaching and sport-science support was conducive to the needs of this particular squad due to the nesting and multi-dimensional issues related to performance behaviours within intra-personal, inter-personal, group and social domains, and the rich-interconnectedness associated with the relevant domains of expertise. Furthermore, the constructivist, coach-focussed program within the project was endorsed.
The Effectiveness of a Leg-Kicking Training Program on Performance and Physiological Measures of Competitive Swimmers
Authors: Konstantaki Maria , Winter Edward M.
Published: April 2007

This study investigated the adaptations in leg muscle metabolism of swimmers following a six-week, leg-kicking swimming training program Fifteen male competitive swimmers were randomly assigned to an experimental group (E; n=8) and a control group (C; n=7). E swimmers performed normal leg-kicking training three times per week, whereas C swimmers performed reduced leg-kicking training (20% and 4% of weekly training distance, respectively). Before and after the training program, all swimmers performed a 200 m leg-kicking and a 400 m full-stroke freestyle time trial and a dry-land exercise test during which peak oxygen uptake, oxygen uptake at 60 W and exercise intensity at ventilatory threshold were measured. After training, there were improvements in leg-kicking time in 200 m (s; −6.0 ± 2.0%, p = 0.044), oxygen uptake at 60 Watts (L·min−1; −20.4 ± 3.0%, p = 0.035) and exercise intensity at ventilatory threshold (Watts; +28.0 ± 5.0%, p = 0.023) in E swimmers, whereas time in 400 m and peak oxygen uptake remained unchanged (p > 0.05). There were no changes in any of the measures for C swimmers (P > 0.05). These results suggest that normal leg-kicking swimming training positively affects the conditioning of the legs, but does not improve aerobic power during the dry-land, leg-kicking exercise test or middle-distance, full-stroke, swimming performance.
Testing and Training Anticipation Skills in Softball Fielders
Authors: Gabbett Tim , Rubinoff Martin , Thorburn Lachlan , Farrow Damian
Published: April 2007

This study investigated whether a video-based perceptual training stimulus could improve anticipatory skill in softball fielders. Elite softball players (mean ± SE age, 19 ± 1 yr) were randomly allocated into a video-based perceptual training group (n = 9), a placebo group (n = 8), or a control group (n = 8). The athlete's decision accuracy and decision time were measured in the laboratory using a ‘life-like’ video-based test of a batter from the perspective of the in-fielder. Following four weeks of training, the video-based perceptual training group had superior decision accuracy and faster decision times than both the placebo and control groups. Importantly these improvements in anticipatory skill transferred to the field environment. The improvements in anticipatory skill were retained after a four week, non-training period. These findings suggest that video-based perceptual training should be used in conjunction with field training to enhance the anticipatory skill of softball fielders.
So You Want to Learn Implicitly? Coaching and Learning through Implicit Motor Learning Techniques
Authors: Poolton Jamie M. , Zachry Tiffany L.
Published: April 2007

Implicit motor learning is an established motor learning technique that has been largely overlooked outside of academia. It is beneficial to learners in that it allows them to perform undisrupted even in the face of stress and other adverse conditions. This is thought to be due to a reduced ability to ‘reinvest’ acquired knowledge – something that can cause the performer to ‘manually override’ what should be an automatic movement. The problem with traditional forms of implicit motor learning is their impracticality in applied settings. To that end, in this paper we attempt to provide a jumping off point for practitioners by briefly outlining the theoretical concepts of implicit learning and the difficulties it faces. From there, we explore alternative techniques that are more practical but impart similar, if not identical, benefits to performance.
Coaches' Preferences for Continuing Coaching Education
Authors: Vargas-Tonsing Tiffanye M.
Published: April 2007

As the popularity of youth sports has grown, so too has the need for qualified coaches. However, while multiple organizations have begun to offer, or even require, coaching education, more information is needed to fully understand how to best prepare and encourage youth sport coaches to obtain further education. Therefore, the purpose of this project was to explore coaches' preferences for continuing coaching education. Youth sport coaches were asked to indicate how helpful each of 15 continuing education topics would be to them as a coach on a scale from 1 (not at all helpful) to 5 (extremely helpful). Coaches were also asked to indicate their possible reasons and/or barriers towards pursuing advanced coaching education. Additionally coaches were asked questions assessing their personal beliefs on coaching education. Specifically coaches were asked if coaching education and certification should be mandatory. Practical implications for coaching educators are also discussed.
An Exploratory Description of Christian Athletes' Perceptions of Prayer in Sport: A Mixed Methodological Pilot Study
Authors: Czech Daniel R. , Bullet Erin
Published: April 2007

The purpose of this exploratory, pilot investigation was to examine intercollegiate Christian athletes' perceptions of prayer so that coaches can understand the thought processes of religious athletes. The data gathering process involved three levels (survey distribution, personal interviews, and prayer meeting observations). Nineteen athletes from a mid-western university in the USA from four different sports (women's basketball, track & field, and men's football & baseball) were administered the Johnson-Chan Prayer Effectiveness Survey (JCPES) and Religious Behavior Survey (RBS). After completion of the inventories, all participants were interviewed and prayer group meetings were observed. Results revealed that athletes strongly supported the notion of prayer before and after competition. However, all but one of the athletes prayed before a game, but not after a game. In addition, all athletes revealed that prayer intensity, prayer meaning, and the number of times praying increased with the importance of performance. The importance of coaches understanding all faiths in sport and future research ideas are discussed.
Hyponatremia: Current Treatment Strategies and the Role of Vasopressin Antagonists
Authors: Cawley Michael J
Published: April 2007

Objective:

Hyponatremia is a complex electrolyte disorder that results mainly from dysregulation of arginine vasopressin (AVP) by osmotic and nonosmotic mechanisms. Several populations, including the elderly, are at risk for the development of hyponatremia, and awareness of such risk factors can lead to an overall improvement in patient care. AVP receptor antagonists are promising new therapeutic options whose safety and efficacy have been clinically established for some forms of hyponatremia.

Data Sources:

A search of MEDLINE (1967–March 2007) was conducted, using the search terms aquaporins, AVP, AVP receptor antagonists, conivaptan, hyponatremia, lixivaptan, and tolvaptan. Additionally, data were obtained from manufacturers' prescribing information.

Study Selection and Data Extraction:

All articles identified from the reference search and data sources were evaluated. Material was included in this review if it was relevant to the pathophysiology and management of euvolemic and hypervolemic hyponatremia in hospitalized patients.

Data Synthesis:

A large percentage of hospitalized patients are found to have symptomatic or asymptomatic hyponatremia. One study reported that 24.5% of intensive care patients admitted over a 3 month period experienced hyponatremia at some time during their hospitalization. Conventional management techniques include water restriction, demeclocycline, lithium, and urea, which have demonstrated variable efficacy and toxicity. AVP receptor antagonists, whose safety and efficacy have been established in clinical trials, are providing new therapeutic options.

Conclusions:

AVP receptor antagonists appear to be safe and effective for the treatment of patients with hyponatremia. With conivaptan recently approved by the Food and Drug Administration for use in treating euvolemic and hypervolemic hyponatremia in hospitalized patients and lixivaptan and tolvaptan in the late stages of development, prudent use of these agents requires a thorough understanding of the clinical manifestations of hyponatremia to optimize therapeutic outcomes.