bluuebunny/crossref_metadata_2025 huggingface dataset:
A multicopy Y-chromosomal SGNH hydrolase gene expressed in the testis of the platyfish has been captured and mobilized by a Helitron transposon
Authors: Tomaszkiewicz Marta , Chalopin Domitille , Schartl Manfred , Galiana Delphine , Volff Jean-Nicolas
Published: April 2014

Background

Teleost fish present a high diversity of sex determination systems, with possible frequent evolutionary turnover of sex chromosomes and sex-determining genes. In order to identify genes involved in male sex determination and differentiation in the platyfishXiphophorus maculatus, bacterial artificial chromosome contigs from the sex-determining region differentiating the Y from the X chromosome have been assembled and analyzed.

Results

A novel three-copy gene calledteximY(for testis-expressed inXiphophorus maculatuson the Y) was identified on the Y but not on the X chromosome. A highly related sequence calledtexim1, probably at the origin of the Y-linked genes, as well as three more divergentteximgenes were detected in (pseudo)autosomal regions of the platyfish genome.Teximgenes, for which no functional data are available so far in any organism, encode predicted esterases/lipases with a SGNH hydrolase domain. Texim proteins are related to proteins from very different origins, including proteins encoded by animal CR1 retrotransposons, animal platelet-activating factor acetylhydrolases (PAFah) and bacterial hydrolases.Teximgene distribution is patchy in animals.Teximsequences were detected in several fish species including killifish, medaka, pufferfish, sea bass, cod and gar, but not in zebrafish.Texim-like genes are also present inOikopleura(urochordate), Amphioxus (cephalochordate) and sea urchin (echinoderm) but absent from mammals and other tetrapods. Interestingly,teximgenes are associated with a Helitron transposon in different fish species but not in urochordates, cephalochordates and echinoderms, suggesting capture and mobilization of an ancestralteximgene in the bony fish lineage. RT-qPCR analyses showed that Y-linkedteximYgenes are preferentially expressed in testis, with expression at late stages of spermatogenesis (late spermatids and spermatozeugmata).

Conclusions

These observations suggest either that TeximY proteins play a role inHelitrontransposition in the male germ line in fish, or thatteximgenes are spermatogenesis genes mobilized and spread by transposable elements in fish genomes.
Depressive mood mediates the influence of social support on health-related quality of life in elderly, multimorbid patients
Authors: Wicke Felix S , Güthlin Corina , Mergenthal Karola , Gensichen Jochen , Löffler Christin , Bickel Horst , Maier Wolfgang , Riedel-Heller Steffi G , Weyerer Siegfried , Wiese Birgitt , König Hans-Helmut , Schön Gerhard , Hansen Heike , van den Bussche Hendrik , Scherer Martin , Dahlhaus Anne
Published: April 2014

Background

It is not well established how psychosocial factors like social support and depression affect health-related quality of life in multimorbid and elderly patients. We investigated whether depressive mood mediates the influence of social support on health-related quality of life.

Methods

Cross-sectional data of 3,189 multimorbid patients from the baseline assessment of the German MultiCare cohort study were used. Mediation was tested using the approach described by Baron and Kenny based on multiple linear regression, and controlling for socioeconomic variables and burden of multimorbidity.

Results

Mediation analyses confirmed that depressive mood mediates the influence of social support on health-related quality of life (Sobel’s p < 0.001). Multiple linear regression showed that the influence of depressive mood (β = −0.341, p < 0.01) on health-related quality of life is greater than the influence of multimorbidity (β = −0.234, p < 0.01).

Conclusion

Social support influences health-related quality of life, but this association is strongly mediated by depressive mood. Depression should be taken into consideration in research on multimorbidity, and clinicians should be aware of its importance when caring for multimorbid patients.

Trial registration

ISRCTN89818205
Multi-informant reports of mental health in Swedish-born children of immigrants and children born to non-immigrants – the SESBiC-study
Authors: deKeyser Linda , Svedin Carl Göran , Agnafors Sara , Bladh Marie , Sydsjö Gunilla
Published: April 2014

Background

The European literature on mental health of the children of immigrants is limited. Therefore this study aims to investigate gender-specific mental health reported by teachers, parents and the children themselves in 12-year old children of immigrants and non-immigrants and also to study the level of agreement between the different informants.

Methods

This cross-sectional study is a part of the longitudinal South East Sweden Birth Cohort-study (the SESBiC-study) on children’s health. All children born in town in the south of Sweden 1995-1996 were invited to take part. The mothers of 1723 children (88%) consented. In this part 87 Swedish-born 12-year old children of immigrants and 687 12-year old children of non-immigrants were investigated regarding gender-specific differences in mental health as reported by teachers (Teacher-report form), parents (Child behavior checklist), and children (Strengths and Difficulties Questionnaire) and the agreement reached between the informants.

Results

Parental immigrant status was not associated with mental health in any of the groups, but living arrangements and parental educational level were mainly found to have an effect on the health status of boys (TRF-Internalizing β = .77 95% CI = .02-1.52; TRF-Externalizing.β = 2.31 95% CI = .63-3.99; TRF-Total β = 6.22 95% CI = 2.27-10.18) The agreement between different informants was generally low, except for externalizing problems among boys (Boys of immigrant parents: Parent and teacher correlation ρ = .422 and Child teacher correlation ρ = .524, p-value < .05, respectively). The correlation between teachers and parents were lower in the index group compared to the reference group. In the index group, the correlations between teacher’s and children’s assessments were fairly high for boys but not for girls (ρ Total = .400, ρ Internalizing = .240 and ρ Externalizing = .524, p-value < .05 for Total and Externalizing).

Conclusion

This study confirms previous findings that the mental health of children of immigrants is similar to that of children of non-immigrants. We found that family factors have a greater impact on the reported mental health than immigrant status does. This might be of clinical importance for healthcare workers to recognize when investigating and treating children from other cultures.
The status and correlates of depression and anxiety among breast-cancer survivors in Eastern China: a population-based, cross-sectional case–control study
Authors: Wang Feng , Liu Jiajia , Liu Liyuan , Wang Fei , Ma Zhongbing , Gao Dezong , Zhang Qiang , Yu Zhigang
Published: April 2014

Background

Breast cancer presents specific challenges both physiologically and psychologically to women, and consequently affect the patients’ mental health. Psychosocial factors may play important roles in the symptoms and development of mental disorders among breast-cancer survivors. This study assesses the depression and anxiety status of breast-cancer survivors and further identifies the risk factors.

Methods

A 1:1 matched, case–control study was conducted with a total sample of 222 individuals. Participants were selected from a national epidemiological survey. The Center for Epidemiological Studies—Depression Scale and State-Trait Anxiety Inventory were used to assess depression and anxiety. The Social Support Rating Scale and Perceived Social Support Scale were used as measures of social support and perceived social support, and the Rosenberg Self-Esteem Scale as a measure of self-esteem. Coping style was assessed using the Simplified Coping Style Questionnaire. The predictive effect of these psychosocial factors for depression and anxiety was investigated with hierarchical linear regressions.

Results

Breast-cancer survivors experienced a high level of depressive and anxious symptoms. Multivariate analysis revealed that breast cancer functions as an independent but not a main risk factor of both depression and anxiety. Higher levels of depression and anxiety were positively associated with a higher level of passive coping style, and negatively with perceived social support, objective social support and an active coping style.

Conclusions

The mental health of breast-cancer survivors should be promoted through the transformation of coping styles and improvement of social support.
Influence of anisotropic pressure on viscosity and electrorheology of diethylene glycol-based MgAl2O4 nanofluids
Authors: Żyła Gaweł , Grzywa Joanna , Witek Adam , Cholewa Marian
Published: April 2014

The paper presents results of rheological experiments on viscosity under anisotropic pressure and in electric field of diethylene glycol-based MgAl2O4 nanofluids. Nanofluids have been prepared in a two-step method. The dynamic viscosity of nanofluids with various mass concentrations of nanoparticles was measured in the range of shear rates from 10 s −1 to 1,000 s −1 in constant temperature under the pressure of 7.5 MPa. In the second type of experiments, different values of the electric field up to 2,000 V/mm was used. Thixotropy structure of MgAl2O4-DG nanofluids has been studied in electrical field.
Genome-wide identification and transcriptional profiling analysis of auxin response-related gene families in cucumber
Authors: Wu Jian , Liu Songyu , Guan Xiaoyan , Chen Lifei , He Yanjun , Wang Jie , Lu Gang
Published: April 2014

Background

Auxin signaling has a vital function in the regulation of plant growth and development, both which are known to be mediated by auxin-responsive genes. So far, significant progress has been made toward the identification and characterization of auxin-response genes in several model plants, while no systematic analysis for these families was reported in cucumber (Cucumis sativus L.), a reference species for Cucurbitaceae crops. The comprehensive analyses will help design experiments for functional validation of their precise roles in plant development and stress responses.

Results

A genome-wide search for auxin-response gene homologues identified 16 auxin-response factors (ARFs), 27 auxin/indole acetic acids (Aux/IAAs), 10 Gretchen Hagen 3 (GH3s), 61 small auxin-up mRNAs (SAURs), and 39 lateral organ boundaries (LBDs) in cucumber. Sequence analysis together with the organization of putative motifs indicated the potential diverse functions of these five auxin-related family members. The distribution and density of auxin response-related genes on chromosomes were not uniform. Evolutionary analysis showed that the chromosomal segment duplications mainly contributed to the expansion of the CsARF, CsIAA, CsGH3, and CsLBD gene families. Quantitative real-time RT-PCR analysis demonstrated that many ARFs, AUX/IAAs, GH3s, SAURs, and LBD genes were expressed in diverse patterns within different organs/tissues and during different development stages. They were also implicated in IAA, methyl jasmonic acid, or salicylic acid response, which is consistent with the finding that a great number of diverse cis-elements are present in their promoter regions involving a variety of signaling transduction pathways.

Conclusion

Genome-wide comparative analysis of auxin response-related family genes and their expression analysis provide new evidence for the potential role of auxin in development and hormone response of plants. Our data imply that the auxin response genes may be involved in various vegetative and reproductive developmental processes. Furthermore, they will be involved in different signal pathways and may mediate the crosstalk between various hormone responses.
Burchellin: study of bioactivity against Aedes aegypti
Authors: Narciso Juliana Oliveira Abreu , Soares Renata Oliveira de Araújo , Reis dos Santos Mallet Jacenir , Guimarães Anthony Érico , de Oliveira Chaves Maria Célia , Barbosa-Filho José Maria , Maleck Marise
Published: April 2014

Background

The dengue mosquito Aedes aegypti Linnaeus, 1762 is a widespread insect pest of serious medical importance. Since no effective vaccine is available for treating dengue, the eradication or control of the main mosquito vector is regarded as essential. Since conventional insecticides have limited success, plants may be an alternative source of larvicidal agents, since they contain a rich source of bioactive chemicals. The aim of this study was to evaluate the larvicidal activity of the neolignan burchellin isolated from Ocotea cymbarum (Lauraceae), a plant from the Amazon region, against third instar larvae of A. aegypti.

Methods

Burchellin obtained from O. cymbarum was analyzed. The inhibitory activity against A. aegypti eggs and larvae and histological changes in the digestive system of treated L3 larvae were evaluated. In addition, nitric oxide synthase activity and nitric oxide levels were determined, and cytotoxicity bioassays performed.

Results

The data showed that burchellin interfered with the development cycle of the mosquito, where its strongest toxic effect was 100% mortality in larvae (L3) at concentrations ≥ 30 ppm. This compound did not show target cell toxicity in peritoneal macrophages from BALB/c mice, and proved to have molecular stability when dissolved in water. The L3 and L4 larvae treated with the compound showed cellular destruction and disorganization, cell spacing, and vacuolization of epithelial cells in small regions of the midgut.

Conclusion

The neolignan burchellin proved to be a strong candidate for a natural, safe and stable phytolarvicidal to be used in population control of A. aegypti.
A new tool for assessment and monitoring of community and ecosystem change based on multivariate abundance data integration from different taxonomic groups
Authors: Mueller Melanie , Pander Joachim , Geist Juergen
Published: April 2014

Background

The integrative assessment of responses to environmental disturbance simultaneously considering multiple taxonomic groups or guilds has become increasingly important in ecological monitoring. The most common solution to combine data of different taxonomic groups is the calculation of compound indices comprising several individual indicators. However, these indices run the risk of cancelling out underlying trends when single components change in different directions. In contrast, multivariate community analyses are supposed to be more sensitive to detect environmental responses, since information on the abundance of multiple species is not reduced to a single dimension.

Results

We propose a new standardised approach for multivariate community analyses on ecosystem scale, based on a combined data matrix from different taxonomic groups. The power of these multivariate analyses is compared with two single score indices integrating data from all involved taxonomic groups (Ecological Quality Class according to the European Water Framework Directive and Shannon diversity). The multivariate indication of ecosystem change was much more sensitive and powerful in detecting and monitoring environmental impacts and restoration effects than single numeric score indices.

Conclusions

Compared to common monitoring systems based on compound indices, the multivariate analysis of multiple taxonomic groups is feasible with the same sampling effort, and independent of the investigation scale and the occurrence of certain indicator taxa. Since ecological community data are structured similarly throughout freshwater, marine and terrestrial ecosystems, the presented methods for data combination and multivariate indication can be analogously applied in any other habitats and can improve data integration across ecosystem borders.
Quality of Life in MAP.3 (Mammary Prevention 3): A Randomized, Placebo-Controlled Trial Evaluating Exemestane for Prevention of Breast Cancer
Authors: Maunsell Elizabeth , Goss Paul E. , Chlebowski Rowan T. , Ingle James N. , Alés-Martínez José E. , Sarto Gloria E. , Fabian Carol J. , Pujol Pascal , Ruiz Amparao , Cooke Andrew L. , Hendrix Susan , Thayer Debra W. , Rowland Kendrith M. , Dubé Pierre , Spadafora Silvana , Pruthi Sandhya , Lickley Lavina , Ellard Susan L. , Cheung Angela M. , Wactawski-Wende Jean , Gelmon Karen A. , Johnston Dianne , Hiltz Andrea , Brundage Michael , Pater Joseph L. , Tu Dongsheng , Richardson Harriet
Published: April 2014

Purpose

Exemestane, a steroidal aromatase inhibitor, reduced invasive breast cancer incidence by 65% among 4,560 postmenopausal women randomly assigned to exemestane (25 mg per day) compared with placebo in the National Cancer Institute of Canada (NCIC) Clinical Trials Group MAP.3 (Mammary Prevention 3) trial, but effects on quality of life (QOL) were not fully described.

Patients and Methods

Menopause-specific and health-related QOL were assessed by using the four Menopause-Specific Quality of Life Questionnaire (MENQOL) domains and the eight Medical Outcomes Study Short Form Health Survey (SF-36) scales at baseline, 6 months, and yearly thereafter. MENQOL questionnaire completion was high (88% to 98%) in both groups at each follow-up visit. Change scores for each MENQOL and SF-36 scale, calculated at each assessment time relative to baseline, were compared by using the Wilcoxon rank-sum test. Clinically important worsened QOL was defined as a MENQOL change score increase of more than 0.5 (of 8) points and an SF-36 change score decrease of more than 5 (of 100) points from baseline.

Results

Exemestane had small negative effects on women's self-reported vasomotor symptoms, sexual symptoms, and pain, which occurred mainly in the first 6 months to 2 years after random assignment. However, these changes represented only a small excess number of women being given exemestane with clinically important worsening of QOL at one time or another; specifically, 8% more in the vasomotor domain and 4% more each in the sexual domain and for pain. No other between-group differences were observed. Overall, slightly more women in the exemestane arm (32%) than in the placebo arm (28%) discontinued assigned treatment.

Conclusion

Exemestane given for prevention has limited negative impact on menopause-specific and health-related QOL in healthy postmenopausal women at risk for breast cancer.
Phase I Dose-Escalation Study of 5-Day Intermittent Oral Lapatinib Therapy in Patients With Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer
Authors: Chien A. Jo , Munster Pamela N. , Melisko Michelle E. , Rugo Hope S. , Park John W. , Goga Andrei , Auerback Glenna , Khanafshar Elham , Ordovas Karen , Koch Kevin M. , Moasser Mark M.
Published: April 2014

Purpose

The highly effective treatment of human epidermal growth factor receptor (HER) 2–amplified breast cancer has proven challenging because of a signal buffering capacity inherent in the functionally relevant HER2-HER3 target. HER2-HER3 signaling can be inactivated by doses of lapatinib that fully inactivate the HER2 kinase. In mouse models, such doses are not tolerable in continuous administration, but they are tolerable and highly effective in intermittent dosing. We pursued the clinical translation of this treatment hypothesis.

Patients and Methods

We conducted a phase I dose-escalation study in women with advanced HER2-overexpressing breast cancer. Lapatinib was administered on days 1 through 5 of repeating 14-day cycles. Dose escalation was conducted using a 3+3 design with plasma lapatinib level monitoring.

Results

Forty patients were evaluable for toxicity, and 34 patients were evaluable for dose-limiting toxicity (DLT). Lapatinib dose was escalated to 7,000 mg per day in twice-daily dosing with no DLTs; however, plasma lapatinib concentrations plateaued in this dose range. Additional cohorts evaluated strategies to increase lapatinib exposure, including the food effect, CYP3A4 inhibition, and dose fractionation. Of these, only ketoconazole was able to increase lapatinib exposure, despite highly variable lapatinib bioavailability. Intolerable exposure levels were not encountered. Eight patients (20%) experienced grade 3 diarrhea. Six patients achieved a response, and dramatic responses were seen in three patients with lapatinib concentrations approaching 10,000 ng/mL.

Conclusion

Lapatinib exposure can be safely and significantly increased through intermittent dosing but reaches a ceiling that currently impedes clinical translation of the treatment hypothesis. Preliminary efficacy data suggest that exposures approaching those seen in mouse models can result in highly significant tumor responses.
Oral Anticancer Drugs: How Limited Dosing Options and Dose Reductions May Affect Outcomes in Comparative Trials and Efficacy in Patients
Authors: Prasad Vinay , Massey Paul R. , Fojo Tito
Published: April 2014

Historically, cancer medicine has avoided the problem of unequal dosing by comparing maximum-tolerated doses of intravenous regimens with proportionate dose reductions for toxicity. However, in recent years, with the development of numerous oral anticancer agents, dosing options are arbitrarily and increasingly limited by the size of pills. We contend that an underappreciated consequence of pill size is unequal dosing in comparative clinical trials and that this can have an impact on outcomes. We discuss how comparative effectiveness trials can be unbalanced and how the use of doses that are not sustainable might affect outcomes, especially marginal ones. We further argue that because of their poor tolerability and their limited dosing options, which often result in large dose adjustments in response to toxicity, the real-world clinical effectiveness of oral anticancer agents may be diminished and may not emulate results achieved in registration trials.
What Is the Value of the Routine Use of Patient-Reported Outcome Measures Toward Improvement of Patient Outcomes, Processes of Care, and Health Service Outcomes in Cancer Care? A Systematic Review of Controlled Trials
Authors: Kotronoulas Grigorios , Kearney Nora , Maguire Roma , Harrow Alison , Di Domenico David , Croy Suzanne , MacGillivray Stephen
Published: April 2014

Purpose

The systematic use of patient-reported outcome measures (PROMs) has been advocated as an effective way to standardize cancer practice. Yet, the question of whether PROMs can lead to actual improvements in the quality of patient care remains under debate. This review examined whether inclusion of PROM in routine clinical practice is associated with improvements in patient outcomes, processes of care, and health service outcomes during active anticancer treatment.

Methods

A systematic review of five electronic databases (Medline, EMBASE, CINAHL [Cumulative Index to Nursing and Allied Health Literature], PsycINFO, and Psychology and Behavioral Sciences Collection [PBSC]) was conducted from database inception to May 2012 to locate randomized and nonrandomized controlled trials of patients receiving active anticancer treatment or supportive care irrespective of type of cancer.

Results

Based on prespecified eligibility criteria, we included 26 articles that reported on 24 unique controlled trials. Wide variability in the design and use of interventions delivered, outcomes evaluated, and cancer- and modality-specific context was apparent. Health service outcomes were only scarcely included as end points. Overall, the number of statistically significant findings were limited and PROMs' intervention effect sizes were predominantly small-to-moderate.

Conclusion

The routine use of PROMs increases the frequency of discussion of patient outcomes during consultations. In some studies, PROMs are associated with improved symptom control, increased supportive care measures, and patient satisfaction. Additional effort is required to ensure patient adherence, as well as additional support to clinicians who will respond to patient concerns and issues, with clear system guidelines in place to guide their responses. More research is required to support PROM cost-benefit in terms of patient safety, clinician burden, and health services usage.
Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stage I and II Invasive Breast Cancer: American Society of Clinical Oncology Endorsement of the Society of Surgical Oncology/American Society for Radiation Oncology Consensus Guideline
Authors: Buchholz Thomas A. , Somerfield Mark R. , Griggs Jennifer J. , El-Eid Souzan , Hammond M. Elizabeth H. , Lyman Gary H. , Mason Ginny , Newman Lisa A.
Published: April 2014

Purpose

The Society of Surgical Oncology (SSO)/American Society for Radiation Oncology (ASTRO) guideline on surgical margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer was considered for endorsement.

Methods

The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing practice guidelines developed by other organizations. ASCO staff reviewed the SSO/ASTRO guideline for developmental rigor; an ASCO ad hoc review panel of experts reviewed the guideline content.

Results

The ASCO ad hoc guideline review panel concurred that the recommendations are clear, thorough, and based on the most relevant scientific evidence in this content area and that they present options acceptable to patients. According to the SSO/ASTRO guideline, the use of no ink on tumor (ie, no cancer cells adjacent to any inked edge/surface of specimen) as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of ipsilateral breast tumor recurrence and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.

Conclusion

The ASCO review panel endorses the SSO/ASTRO recommendations with qualifications, as follows. The panel reinforces and amplifies the guideline authors' call for the monitoring of outcomes of the guideline at the institutional level, as institutions transition to adopting the SSO/ASTRO recommendations; would place greater emphasis on the importance of postlumpectomy mammography for cases involving microcalcifications; and calls for flexibility in the application of the guideline in light of the generally weak evidence supporting the recommendations.
Effects of the Antitumor Drug OSI-906, a Dual Inhibitor of IGF-1 Receptor and Insulin Receptor, on the Glycemic Control, β-Cell Functions, and β-Cell Proliferation in Male Mice
Authors: Shirakawa Jun , Okuyama Tomoko , Yoshida Eiko , Shimizu Mari , Horigome Yuka , Tuno Takayuki , Hayasaka Moe , Abe Shiori , Fuse Masahiro , Togashi Yu , Terauchi Yasuo
Published: April 2014

The IGF-1 receptor has become a therapeutic target for the treatment of cancer. The efficacy of OSI-906 (linstinib), a dual inhibitor of IGF-1 receptor and insulin receptor, for solid cancers has been examined in clinical trials. The effects of OSI-906, however, on the blood glucose levels and pancreatic β-cell functions have not yet been reported. We investigated the impact of OSI-906 on glycemic control, insulin secretion, β-cell mass, and β-cell proliferation in male mice. Oral administration of OSI-906 worsened glucose tolerance in a dose-dependent manner in the wild-type mice. OSI-906 at a dose equivalent to the clinical daily dose (7.5 mg/kg) transiently evoked glucose intolerance and hyperinsulinemia. Insulin receptor substrate (IRS)-2-deficient mice and mice with diet-induced obesity, both models of peripheral insulin resistance, exhibited more severe glucose intolerance after OSI-906 administration than glucokinase-haploinsufficient mice, a model of impaired insulin secretion. Phloridzin improved the hyperglycemia induced by OSI-906 in mice. In vitro, OSI-906 showed no effect on insulin secretion from isolated islets. After daily administration of OSI-906 for a week to mice, the β-cell mass and β-cell proliferation rate were significantly increased. The insulin signals in the β-cells were apparently unaffected in those mice. Taken together, the results suggest that OSI-906 could exacerbate diabetes, especially in patients with insulin resistance. On the other hand, the results suggest that the β-cell mass may expand in response to chemotherapy with this drug.
Testosterone Dose-Response Relationships With Cardiovascular Risk Markers in Androgen-Deficient Women: A Randomized, Placebo-Controlled Trial
Authors: Huang Grace , Tang Elizabeth , Aakil Adam , Anderson Stephan , Jara Hernan , Davda Maithili , Stroh Helene , Travison Thomas G. , Bhasin Shalender , Basaria Shehzad
Published: April 2014

Objective:

To determine dose-dependent effects of T administration on cardiovascular risk markers in women with low T levels.

Methods:

Seventy-one hysterectomized women with or without oophorectomy with total T < 31 ng/dL and/or free T < 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly im injections of placebo or 3-, 6.25-, 12.5-, or 25-mg T enanthate for 24 weeks. Total and free T levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. Insulin resistance and inflammatory markers were measured at baseline and 24 weeks. In a subset of women, magnetic resonance imaging of the abdomen was performed to quantify abdominal fat volume.

Results:

Fifty-nine women who completed the 24-week intervention were included in the final analysis. The five groups were similar at baseline. Mean on-treatment nadir total T concentrations were 14, 79, 105, 130, and 232 ng/dL in the placebo group and the 3-, 6.25-, 12.5-, and 25-mg groups, respectively. No significant changes in fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, high sensitivity C-reactive protein, adiponectin, blood pressure, and heart rate were observed at any T dose when compared to placebo. Similarly, no dose- or concentration-dependent changes were observed in abdominal fat on magnetic resonance imaging.

Conclusion:

Short-term T administration over a wide range of doses for 24 weeks in women with low T levels was not associated with worsening of cardiovascular risk markers.
Novel DNA Motif Binding Activity Observed In Vivo With an Estrogen Receptor α Mutant Mouse
Authors: Hewitt Sylvia C. , Li Leping , Grimm Sara A. , Winuthayanon Wipawee , Hamilton Katherine J. , Pockette Brianna , Rubel Cory A. , Pedersen Lars C. , Fargo David , Lanz Rainer B. , DeMayo Francesco J. , Schütz Günther , Korach Kenneth S.
Published: April 2014

Estrogen receptor α (ERα) interacts with DNA directly or indirectly via other transcription factors, referred to as “tethering.” Evidence for tethering is based on in vitro studies and a widely used “KIKO” mouse model containing mutations that prevent direct estrogen response element DNA- binding. KIKO mice are infertile, due in part to the inability of estradiol (E2) to induce uterine epithelial proliferation. To elucidate the molecular events that prevent KIKO uterine growth, regulation of the pro-proliferative E2 target gene Klf4 and of Klf15, a progesterone (P4) target gene that opposes the pro-proliferative activity of KLF4, was evaluated. Klf4 induction was impaired in KIKO uteri; however, Klf15 was induced by E2 rather than by P4. Whole uterine chromatin immunoprecipitation-sequencing revealed enrichment of KIKO ERα binding to hormone response elements (HREs) motifs. KIKO binding to HRE motifs was verified using reporter gene and DNA-binding assays. Because the KIKO ERα has HRE DNA-binding activity, we evaluated the “EAAE” ERα, which has more severe DNA-binding domain mutations, and demonstrated a lack of estrogen response element or HRE reporter gene induction or DNA-binding. The EAAE mouse has an ERα null–like phenotype, with impaired uterine growth and transcriptional activity. Our findings demonstrate that the KIKO mouse model, which has been used by numerous investigators, cannot be used to establish biological functions for ERα tethering, because KIKO ERα effectively stimulates transcription using HRE motifs. The EAAE-ERα DNA-binding domain mutant mouse demonstrates that ERα DNA-binding is crucial for biological and transcriptional processes in reproductive tissues and that ERα tethering may not contribute to estrogen responsiveness in vivo.
Development of five digits is controlled by a bipartite long-range cis-regulator
Authors: Lettice Laura A. , Williamson Iain , Devenney Paul S. , Kilanowski Fiona , Dorin Julia , Hill Robert E.
Published: April 2014

Conservation within intergenic DNA often highlights regulatory elements that control gene expression from a long range. How conservation within a single element relates to regulatory information and how internal composition relates to function is unknown. Here, we examine the structural features of the highly conserved ZRS (also called MFCS1) cis-regulator responsible for the spatiotemporal control of Shh in the limb bud. By systematically dissecting the ZRS, both in transgenic assays and within in the endogenous locus, we show that the ZRS is, in effect, composed of two distinct domains of activity: one domain directs spatiotemporal activity but functions predominantly from a short range, whereas a second domain is required to promote long-range activity. We show further that these two domains encode activities that are highly integrated and that the second domain is crucial in promoting the chromosomal conformational changes correlated with gene activity. During limb bud development, these activities encoded by the ZRS are interpreted differently by the fore limbs and the hind limbs; in the absence of the second domain there is no Shh activity in the fore limb, and in the hind limb low levels of Shh lead to a variant digit pattern ranging from two to four digits. Hence, in the embryo, the second domain stabilises the developmental programme providing a buffer for SHH morphogen activity and this ensures that five digits form in both sets of limbs.
Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates
Authors: Hatakeyama Jun , Wakamatsu Yoshio , Nagafuchi Akira , Kageyama Ryoichiro , Shigemoto Ryuichi , Shimamura Kenji
Published: April 2014

The development of the vertebrate brain requires an exquisite balance between proliferation and differentiation of neural progenitors. Notch signaling plays a pivotal role in regulating this balance, yet the interaction between signaling and receiving cells remains poorly understood. We have found that numerous nascent neurons and/or intermediate neurogenic progenitors expressing the ligand of Notch retain apical endfeet transiently at the ventricular lumen that form adherens junctions (AJs) with the endfeet of progenitors. Forced detachment of the apical endfeet of those differentiating cells by disrupting AJs resulted in precocious neurogenesis that was preceded by the downregulation of Notch signaling. Both Notch1 and its ligand Dll1 are distributed around AJs in the apical endfeet, and these proteins physically interact with ZO-1, a constituent of the AJ. Furthermore, live imaging of a fluorescently tagged Notch1 demonstrated its trafficking from the apical endfoot to the nucleus upon cleavage. Our results identified the apical endfoot as the central site of active Notch signaling to securely prohibit inappropriate differentiation of neural progenitors.
The maternal nucleolus plays a key role in centromere satellite maintenance during the oocyte to embryo transition
Authors: Fulka Helena , Langerova Alena
Published: April 2014

The oocyte (maternal) nucleolus is essential for early embryonic development and embryos originating from enucleolated oocytes arrest at the 2-cell stage. The reason for this is unclear. Surprisingly, RNA polymerase I activity in nucleolus-less mouse embryos, as manifested by pre-rRNA synthesis, and pre-rRNA processing are not affected, indicating an unusual role of the nucleolus. We report here that the maternal nucleolus is indispensable for the regulation of major and minor satellite repeats soon after fertilisation. During the first embryonic cell cycle, absence of the nucleolus causes a significant reduction in major and minor satellite DNA by 12% and 18%, respectively. The expression of satellite transcripts is also affected, being reduced by more than half. Moreover, extensive chromosome bridging of the major and minor satellite sequences was observed during the first mitosis. Finally, we show that the absence of the maternal nucleolus alters S-phase dynamics and causes abnormal deposition of the H3.3 histone chaperone DAXX in pronuclei of nucleolus-less zygotes.
Immunohistochemical Evaluation of GATA-3 Expression in ER-Negative Breast Carcinomas
Authors: Liu Haiyan , Shi Jianhui , Prichard Jeffrey W. , Gong Yun , Lin Fan
Published: April 2014

Objectives

Estrogen receptor (ER), gross cystic disease fluid protein 15 (GCDFP-15), and mammaglobin (MGB) are commonly used breast-specific immunomarkers; however, about half of metastatic breast carcinomas are negative for all three. GATA-binding protein 3 (GATA-3) has emerged recently as a sensitive and relatively specific immunomarker for breast and urothelial carcinomas, but the data documenting its expression in ER-negative breast carcinomas are limited; this often poses a dilemma in the setting of metastases. The purpose of this study is to investigate expression of GATA-3 in ER-negative breast carcinomas.

Methods

Immunohistochemical evaluation of GATA-3, GCDFP-15, and MGB on 96 ER-negative breast carcinomas was performed.

Results

Overall, 69% (66/96), 15% (14/96), and 35% (34/96) of ER-negative breast carcinomas expressed GATA-3, GCDFP-15, and MGB, respectively.

Conclusions

Our data suggest that GATA-3 is, so far, the best breast-specific immunomarker, especially when encountering ER-negative metastatic breast carcinomas. GATA-3 should be included in the panel of immunomarkers in the workup of tumors of unknown primary.
Fluorescence study, Raman spectroscopy, crystal structure, antimicrobial and antioxidant activities of cobalt (III) complex with a tridentate coumarin ligand
Authors: Ketata Imen , Bouzaiene Taroub , Ben Ayed Taicir , Ben Hassen Rached
Published: April 2014

Cobalt (III) complex diamine chloride was obtained from the reaction of Co (OAc)2, 4H2O; ethylene diamine and 3-acetyl-4-hydroxy-chromene- 2-one. The obtained product was characterized by Raman scattering, fluorescence and UV-visible spectroscopy. The room temperature structure was determined by single-crystal X-ray diffraction. The purity of the product was checked by X-ray powder diffraction analysis. Rietveld refinement using powder XRD confirms structure model determined by single-crystal X-ray diffraction (space group Pcca, a = 20.599(2) Ã…, b = 7.888(4) Ã…, c = 18.3820(1) Ã… and Z = 4). The metal complex was checked for its antimicrobial activity using well diffusion method and shows significant results by comparison with commercial antibiotics. Antioxidant tests indicate that the complex is an effective DPPH radical scavenger with an IC50 value of 26.32 Î¼M.
Writing ritual, resisting resolution: The short story cycles of Hemingway and Steinbeck
Authors: Smith Jennifer J.
Published: April 2014

This article argues that writing about fishing and marine biology allowed Ernest Hemingway and John Steinbeck, respectively, to express a resistance to narrative resolution. Hemingway’s In Our Time ([1925] 1980) addresses the meaning and aftermath of World War I, while Steinbeck’s
Cannery Row (1945) responds to World War II by not talking about it at all. Both books submerge war to discuss its effects on the psyche and landscape and seek solace by depicting rituals that have meaning but do not insist on finality. In this, fishing and specimen collecting provide non-teleological
models for cognition and writing that resist the tyranny of resolution. Steinbeck and Hemingway render that celebration of open-endedness and process in the short story cycle because it allows them to meditate on the ongoing ritual of thinking and, by extension, writing.
Walking in circles: Helen Simpson’s Constitutional as short story cycle
Authors: Cox Ailsa
Published: April 2014

This article examines thematic and formal concepts of circularity in the British writer Helen Simpson’s Constitutional (2005), in a reading of the collection as a short story cycle. Circularity recurs in the turning of the seasons, the circulation of the blood, compulsive behaviour
and the sometimes futile repetitions enforced by daily routine. Combining Bakhtinian theory with a close reading of the text and Simpson’s own comments on the compositional process, the article shows how Simpson contextualizes the human life cycle in relation to seasonal change and renewal.
Augusto Monterroso’s short story collections: More than stories in a box
Authors: Hecke An Van
Published: April 2014

This article considers the work of the Guatemalan author Augusto Monterroso as it offers an interesting perspective on the theory and practice of the short story collection. In his essays, Monterroso often comments on the formal features of the short story, its relation to the novel
and its marginal status in literary criticism. In addition, he frequently refers to the work of other short story writers. About his own books, Monterroso has said that they are ‘simple deposits’ or ‘boxes’, because they include different kinds of texts: short stories
and essays, but also translations of the work of other authors. Examples in case are the collections Movimiento Perpetuo (1972), translated as Perpetual Motion (1995), and La palabra mágica (1983). In this article I analyse Perpetual Motion with a view to determining the precise organization
and structure of the collection. Using the concepts of homogeneity and heterogeneity, proposed by theorists such as René Audet and Robert Luscher, I try to discern a pattern in the disparate texts and issues of Perpetual Motion.
Analysis on Conflicts and Crises of Multiculturalism in European Countries and Reflection on Multicultural Education
Authors: Kim Jinhee
Published: April 2014

This study attempts to examine the features of conflicts and crises regarding multiculturalism and multicultural policy in European countries. To align the context, this study also aims to investigate Korean situation and domains of conflicts regarding multicultural social settings. Major findings have been revealed; First, declaration of failure and death of multiculturalism in Germany, UK and France showed that a critical debate of multiculturalism has climbed in the international society. Second, main targets and issues of multiculturalism in Europe have highly focused on immigrants, muslim, and immigration policy. Third, suspicious discourses on multiculturalism and its negative impact has provided pivotal ground of anti-immigration policy. Fourth, multiculturalism has played its role as tool of governmentality, rather than celebrating diversity. Fifth, European conflicts and crises on multicultural policy displayed that heterogeneous groups' co-existence is hardly achieved and assimilation and integration is still programmed in the nation state. Sixth, discourse of multiculturalism could be a ideology and mean as well. In Korean context, there are pandemic conflicts and exclusion for immigrants. Marginalised and alienated foreign residents have been highly othered in the Korean society. Current interfutures and practice of multicultural education are poorly meager. That is why, this study argued that empowering multicultural education is inevitably required to combat conflicts and crisis of multicultural social setting. It is time to re-design multicultural education in a reflective mode. Keywords: migrant students; multiculturalism; multicultural
Gendering the Islamic Judiciary: Female Judges in the Religious Courts of Indonesia
Authors: Nurlaelawati Euis , Salim Arskal
Published: April 2014

Compared to other Muslim countries, Indonesia has been the forefront, if not the frontrunner, in welcoming women to occupy a position as judges at the Islamic court. Despite few Indonesian women were already sitting at Islamic courtrooms and hearing cases on family law issues as early as in 1960s, it was only in 1989 that Indonesia fully accommodated female judges at the religious courts. From this onwards, female judges were recruited more than ever and began accessing a number of rights and positions like their male counterparts. This paper discusses female judge and women litigants at Islamic courts of Indonesia. This paper not only discusses the way in which women were recruited to be judges at the Indonesian Islamic courts, but also explores some factors leading Indonesian women to engage in the judicial practice. In addition, this paper looks at the way in which female judges exercise their authority to protect rights of disadvantaged women litigants. This paper argues that despite female judges have the same skills in interpreting law as their male colleagues do and that they have to some extent better gender sensitivity, they unfortunately have not maximised utilising these legal skills for the benefits of women litigants.

 [Dibandingkan dengan negara-negara Islam lainnya, Indonesia telah menjadi garda depan –jika tidak disebut pelopor– dalam mengangkat perempuan sebagai hakim di Pengadilan Agama. Meski pada decade 1960-an sejumlah perempuan sudah menduduki jabatan hakim dan telah menyidangkan kasus-kasus keluarga di Pengadilan Agama, hanya pada tahun 1989 pengangkatan perempuan pada Pengadilan Agama ditegaskan secara formal dan legaal oleh pemerintah Indonesia. Sejak saat itu, jumlah hakim perempuan di pengadilan agama meningkat dan mereka memiliki kesemepatan untuk memperoleh hak dan posisi penting di Pengadilan Agama, sejajar dengan hakim laki-laki. Artikel ini mendiskusikan keterlibatan perempuan, baik sebagai hakim maupun pihak yang berperkara, di Pengadilan Agama. Tidak hanya menjelaskan bagaimana perempuan direkrut sebagai hakim di Pengadilan Agama, artikel ini juga mengulas faktor-faktor penting yang mendorong keterlibatan perempuan dalam praktek peradilan. Selain itu, juga dijelaskan peran hakim perempuan dalam melindungi hak para perempuan yang berperkara di pengadilan. Penulis berkesimpulan bahwa meski para hakim perempuan memiliki kompetensi yang sama dalam memutus perkara seperti para hakim laki-laki dan dalam batas tertentu memiliki sensitifitas gender yang lebih kuat ketimbang laki-laki, peran mereka masih terlihat belum maksimal, terutama dalam memberikan perlindungan terhadap pemenuhan hak-hak perempuan.]
The Institutional Transformation of China’s Stock Exchanges: A Comparative Perspective
Authors: Lyu Kai
Published: April 2014

A stock exchange is a place to list and trade stocks. Many Anglo-American exchanges have seen a dramatic transformation from mutual membership organizations to for-profit and even self-listed corporations. In contrast, China’s exchanges still maintain the “strange” characteristic – they are a hybrid body of membership and bureaucracy. Their distinctions can be explained through the market-induced approach and authority-imposed approach. The advent of Anglo-American exchanges is mainly induced by market players, while their compelling transformations are jointly driven by market players and pro-competition authorities. However, the creation, formulation and evolution of China’s exchanges are imposed firstly by local authorities for institutional control and then by central authorities for institutional control. Although the growing market factors have been to some extent considered by Chinese authorities over the last few years, there is little possibility that market forces will fundamentally change the structure of China’s exchanges. The exchanges will be continuously dominated and controlled by authorities, so the same institutional transformations as Anglo-American exchanges will not occur in China in the foreseeable future.