bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychoanalysis, religious experience, and the study of religion: Not “religious studies”
Authors: Hewitt Marsha Aileen
Published: April 2013

Psychoanalytic critical theory explores the dynamics of individual identity formation within specific cultural contexts. Freud understood that psychoanalysis is a critical social theory as well as a therapeutic practice. His studies on religion illustrate the depths of society and culture within the mind. Freud was thus able to respond to Romain Rolland's experience of an “oceanic” or mystical feeling in thoroughly explanatory psychoanalytic terms that led him to speculate about pre-Oedipal memories of maternal care. Freud made an important contribution to the psychoanalytic study of religion that remains relevant to contemporary academic studies of religion.
North American Women's Surname Choice Based on Ethnicity and Self-Identification as Feminists
Authors: Kerns Myleah Y
Published: April 2013

AbstractUsing empirical data gathered through surveys, this paper analyzes how surname choices of women residing in the United States — whether to acquire her spouse's surname or retain her birth surname — differ based on their ethnicity, age, and feminist self-identification. From a sample of 260 Black and White females, ages 16–70+, data were categorized for participants' responses to eight questions. Crosstabs were calculated to explore correlative patterns among participants for marital status, race/ethnicity, age, surname decision upon marriage, perception of feminists, and feminist orientation. The research reveals that women's self-identification as feminists are not direct predictors of their surname choices. Fully 81 percent of women surveyed, regardless of their ethnicity and age, reported that they did change or will change their surname upon marriage. Of the 19 percent of women who responded that they would retain their birth surname when married, only 14 percent identified themselves as feminists. This study leads to further questions about trends in naming choices and perceptions of feminism and feminist actions particularly among women aged 16–39.
Fev regulates hematopoietic stem cell development via ERK signaling
Authors: Wang Lu , Liu Tianhui , Xu Linjie , Gao Ya , Wei Yonglong , Duan Caiwen , Chen Guo-Qiang , Lin Shuo , Patient Roger , Zhang Bo , Hong Dengli , Liu Feng
Published: April 2013

Key Points

Fev is required for endothelium-based HSC emergence. Fev directly regulates ERK signaling to regulate HSC development cell-autonomously.
Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia
Authors: Rajala Hanna L. M. , Eldfors Samuli , Kuusanmäki Heikki , van Adrichem Arjan J. , Olson Thomas , Lagström Sonja , Andersson Emma I. , Jerez Andres , Clemente Michael J. , Yan Yiyi , Zhang Dan , Awwad Andy , Ellonen Pekka , Kallioniemi Olli , Wennerberg Krister , Porkka Kimmo , Maciejewski Jaroslaw P. , Loughran Thomas P. , Heckman Caroline , Mustjoki Satu
Published: April 2013

Key Points

Somatic mutations were discovered for the first time in the SH2 domain of the STAT5b gene in LGL leukemia. The mutations are activating and lead to increased phosphorylation and transcriptional activity of STAT5b.
Factors associated with HIV infection among men who have sex with men in Henan Province, China: a cross-sectional study
Authors: Liu Jie , Qu Bo , C Ezeakile Moses , Zhang Yang , Liang Shijie
Published: April 2013

Background

HIV prevalence among men who have sex with men (MSM) has increased rapidly in China. Behavioral and biological interventions are key to controlling the spread of HIV in the MSM population and the primary strategy for reducing the spread of AIDS in China. The purpose of this study is to investigate the prevalence of HIV among MSM in Henan province and to assess their knowledge levels and risk behaviors related to HIV/AIDS.

Method

A cross-sectional survey was conducted among 388 MSM in 2010 in Zhengzhou City, Henan province, China.

Results

Of the 388 respondents, 13.1% were infected with HIV and 10.3% were infected with syphilis. The results of multivariate analysis showed that participants who had a history of being infected by syphilis were more than 4 times more likely to be HIV positive (AOR=4.91; 95% CI: 1.70 to 12.02). For those who were residents from other provinces, the risk of HIV infection was 5.53 times higher (OR=5.53, 95% CI: 1.14, 6.25). Receipt of condoms (AOR = 0.15; 95% CI: 0.02 to 0.87), consistent condom use during last intercourse with a male (AOR=0.35; 95% CI: 0.14 to 0.87), and consistent condom use during last intercourse with a female (AOR=0.16; 95% CI: 0.08 to 0.90) were associated with a lower risk of HIV infection.

Conclusion

The study suggests that some intervention strategies, including education intervention, condom promotion and distribution, and HIV counseling and testing are necessary to control HIV infection among MSM.
The true cost of cardiovascular imaging: focusing on downstream, indirect, and environmental costs
Authors: Braga Larissa , Vinci Bruna , Leo Carlo G , Picano Eugenio
Published: April 2013

To develop a more realistic assessment of costs, herein named “true” costs, the extra-cancer from medical radiation, environmental damage from imaging paraphernalia and radioactive wastes must be included as long-term costs from imaging examinations. It is urgent to define the “true” costs across imaging modalities as it interferes on physicians’ decision to request an exam and on research projects such as cost-effectiveness analysis. Cardiology is the specialty that most will benefit from the outcome as cardiovascular exams represent almost 30% of the total exams acquired annually worldwide.
The ion implantation-induced properties of one-dimensional nanomaterials
Authors: Li Wen Qing , Xiao Xiang Heng , Stepanov Andrey L , Dai Zhi Gao , Wu Wei , Cai Guang Xu , Ren Feng , Jiang Chang Zhong
Published: April 2013

Nowadays, ion implantation is an extensively used technique for material modification. Using this method, we can tailor the properties of target materials, including morphological, mechanical, electronic, and optical properties. All of these modifications impel nanomaterials to be a more useful application to fabricate more high-performance nanomaterial-based devices. Ion implantation is an accurate and controlled doping method for one-dimensional nanomaterials. In this article, we review recent research on ion implantation-induced effects in one-dimensional nanostructure, such as nanowires, nanotubes, and nanobelts. In addition, the optical property of single cadmium sulfide nanobelt implanted by N+ ions has been researched.
Controllable synthesis of MnO2/polyaniline nanocomposite and its electrochemical capacitive property
Authors: Meng Fanhui , Yan Xiuling , Zhu Ye , Si Pengchao
Published: April 2013

Polyaniline (PANI) and MnO2/PANI composites are simply fabricated by one-step interfacial polymerization. The morphologies and components of MnO2/PANI composites are modulated by changing the pH of the solution. Formation procedure and capacitive property of the products are investigated by XRD, FTIR, TEM, and electrochemical techniques. We demonstrate that MnO2 as an intermedia material plays a key role in the formation of sample structures. The MnO2/PANI composites exhibit good cycling stability as well as a high capacitance close to 207 F g−1. Samples fabricated with the facile one-step method are also expected to be adopted in other field such as catalysis, lithium ion battery, and biosensor.
Existence of solutions for a class of degenerate quasilinear elliptic equation in "Equation missing" with vanishing potentials
Authors: Bastos Waldemar D , Miyagaki Olimpio H , Vieira Rônei S
Published: April 2013

We establish the existence of positive solution for the following class of degenerate quasilinear elliptic problem

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denote the Hardy-Sobolev’s critical exponent, V is a bounded nonnegative vanishing potential and f has a subcritical growth at infinity. The technique used here is a truncation argument together with the variational approach.

MSC:35B09, 35J10, 35J20, 35J70.
Oral administration of Lactobacillus reuteri GMNL-263 improves insulin resistance and ameliorates hepatic steatosis in high fructose-fed rats
Authors: Hsieh Feng-Ching , Lee Chia-Lin , Chai Chee-Yin , Chen Wan-Tzu , Lu Ying-Chen , Wu Ching-Shuang
Published: April 2013

Background

Type 2 diabetes mellitus (DM), characterized by peripheral insulin resistance, is the most common form of diabetes. Probiotics are live micro-organisms that, when administered in adequate amounts, confer delaying effect on DM development. In this study, the effects Lactobacillus reuteri GMNL-263 (Lr263), a new probiotic strain developed by our laboratory, on insulin resistance and the development of hepatic steatosis in high-fructose fed rats were explored. Furthermore, the relevant regulatory pathways involved were also investigated.

Method

Male Sprague–Dawley rats were fed a high-fructose diet with or without Lr263 administration for 14 weeks. The composition of fecal microbiota, oral glucose tolerance, glycated haemoglobin, insulin, leptin, C-peptide, and incretins were measured. The markers of liver injury, serum and hepatic lipids profile, activity of hepatic antioxidant enzyme, and proinflammatory cytokines in adipose tissue were investigated. Additionally, the expression of hepatic lipogenic genes and insulin signaling related genes in adipose tissue were also studied. Liver sections were examined for hepatic steatosis using hematoxylin-eosin staining.

Results

The levels of serum glucose, insulin, leptin, C-peptide, glycated hemoglobin, GLP-1, liver injury markers, lipid profile in serum and liver were significantly increased in high-fructose-fed rats. However, after Lr263 administration, the elevation of these parameters was significantly suppressed. Feeding of Lr263 reversed the decreased number of bifidobacterium species and lactobacillus species and increased number of clostridium species induced by high fructose treatment. The decreased activities of hepatic antioxidant enzymes in HFD rats were dramatically reversed by Lr263 treatment. Concentrations of IL-6 and TNF-α in adipose tissue which were elevated in high fructose treatment were markedly decreased after Lr263 feeding. Decreased levels of PPAR-γ and GLUT4 mRNA after high fructose treatment were significantly enhanced by Lr263 administration. Lr263 consumption normalized the increased lipogenic gene (Srebp-1c, FAS, and Elvol6) expressions stimulated by high fructose. Administration of Lr263 significantly ameliorated hepatic steatosis observed in high fructose treated rats.

Conclusion

Our study provided evidences clarifying the effectiveness of Lr263 on reducing insulin resistance as well as hepatic steatosis formation in high-fructose-fed rats and suggested that Lr263 may be a promising therapeutic agent in treating type 2 diabetes.
Determination of mitral valve area with echocardiography, using intra-operative 3-dimensional versus intra- & post-operative pressure half-time technique in mitral valve repair surgery
Authors: Kang Woon-Seok , Choi Jae Won , Kang Joo-Eun , Chung Jin Woo , Kim Seong-Hyop
Published: April 2013

Background

We hypothesized that mitral valve areas (MVAs) with echocardiography, using 3D planimetry technique (measured at one point at maximal opening of mitral valve) versus pressure half-time technique (PHT, measured during entire diastolic phase) in mitral valve repair surgery (MVR) would be different.

Methods

Patients who had undergone MVR were retrospectively reviewed, and two different observers measured the MVAs using PHT and 3D planimetry technique. The MVAs derived from recorded medical data, using PHT and 3D planimetry technique were abbreviated to MVA-PHT1 and MVA-3D1, and data from the PHT and 3D planimetry techniques by observer A and observer B were determined as MVA-PHT2 and MVA-3D2, and MVA-PHT3 and MVA-3D3, respectively. The MVA derived by post-operative transthoracic echocardiography using the PHT technique was determined as MVA-TTE.

Results

Intraclass correlation coefficients were 0.90 for the intra-operative PHT technique and 0.78 for the intra-operative 3D planimetry technique. MVA-3D1 (2.91 ± 0.65 cm2), MVA-3D2 (3.00 ± 0.63 cm2) and MVA-3D3 (2.97 ± 0.88 cm2) were significantly larger than MVA-TTE (2.40 ± 0.59 cm2), but intra-operative MVAs-PHT were not. The biases and precisions were larger, and the correlation coefficients were lower in 3D planimetry technique compared with PHT technique.

Conclusions

MVA measured by 3D planimetry technique with TEE at the intra-operative post-MVR period was seemed to be larger than that measured by the PHT technique with TTE at the post-operative period. However, it did not mean that the 3D planimetry technique was inaccurate but needs cautions at determination of MVA using different techniques.
Reproductive performance in pigs reared under organic conditions compared with conventionally reared pigs
Authors: Lindgren Ylva , Lundeheim Nils , Boqvist Sofia , Magnusson Ulf
Published: April 2013

Background

To achieve a competitive reproductive performance in organic pig farming is a major challenge for this farming practise. Practices and research data regarding conventional pig production are not always applicable to organic production, why field studies are needed to identify differences in performance between organic and conventional pig farms in order to identify areas for improvement.

Results

Performance data for one year was collected from 5 organic herds that had more than 30 sows in production and used a computerized recording system, and data from five nearby conventional farms with more than 30 sows and the same recording system were used as a comparison. In total data from 4697 farrowings were analyzed. In the organic pig herds, there were a higher total number of piglets born per litter (p=0.001), a higher number of piglets stillborn per litter (p<0.001), but a tendency (p<0.06) to lower number of weaned pigs per litter and longer nursing period (p<0.001) and farrowing interval (p<0.001).

Conclusions

The reproductive performance was lower in the organic herds and the variation in reproductive performance among the organic herds was larger than among the conventional ones, suggesting options for improvement in the organic herds.
Comparative kinetic analysis on thermal degradation of some cephalosporins using TG and DSC data
Authors: Fuliaş Adriana , Vlase Gabriela , Vlase Titus , Soica Codruţa , Heghes Alina , Craina Marius , Ledeti Ionuţ
Published: April 2013

Background

The thermal decomposition of cephalexine, cefadroxil and cefoperazone under non-isothermal conditions using the TG, respectively DSC methods, was studied. In case of TG, a hyphenated technique, including EGA, was used.

Results

The kinetic analysis was performed using the TG and DSC data in air for the first step of cephalosporin’s decomposition at four heating rates. The both TG and DSC data were processed according to an appropriate strategy to the following kinetic methods: Kissinger-Akahira-Sunose, Friedman, and NPK, in order to obtain realistic kinetic parameters, even if the decomposition process is a complex one.

The EGA data offer some valuable indications about a possible decomposition mechanism. The obtained data indicate a rather good agreement between the activation energy’s values obtained by different methods, whereas the EGA data and the chemical structures give a possible explanation of the observed differences on the thermal stability. A complete kinetic analysis needs a data processing strategy using two or more methods, but the kinetic methods must also be applied to the different types of experimental data (TG and DSC).

Conclusion

The simultaneous use of DSC and TG data for the kinetic analysis coupled with evolved gas analysis (EGA) provided us a more complete picture of the degradation of the three cephalosporins. It was possible to estimate kinetic parameters by using three different kinetic methods and this allowed us to compare the E

a
values obtained from different experimental data, TG and DSC. The thermodegradation being a complex process, the both differential and integral methods based on the single step hypothesis are inadequate for obtaining believable kinetic parameters. Only the modified NPK method allowed an objective separation of the temperature, respective conversion influence on the reaction rate and in the same time to ascertain the existence of two simultaneous steps.
Not all depression is created equal: sex interacts with disease to precipitate depression
Authors: Nemeth Christina L , Harrell Constance S , Beck Kevin D , Neigh Gretchen N
Published: April 2013

Depression is a common mental disorder that co-occurs in other neurological and somatic diseases. Further, sex differences exist in the prevalence rates of many of these diseases, as well as within non-disease associated depression. In this review, the case is made for needing a better recognition of the source of the symptoms of depression with respect to the sex of the individual; in that, some disease states, which includes the neuroendocrine and immune reactions to the underlying pathophysiology of the disease, may initiate depressive symptoms more often in one sex over the other. The diseases specifically addressed to make this argument are: epilepsy, Alzheimer’s disease, cancer, and cardiovascular disease. For each of these conditions, a review of the following are presented: prevalence rates of the conditions within each sex, prevalence rates of depressive symptoms within the conditions, identified relationships to gonadal hormones, and possible interactions between gonadal hormones, adrenal hormones, and immune signaling. Conclusions are drawn suggesting that an evaluation of the root causes for depressive symptoms in patients with these conditions is necessary, as the underlying mechanisms for eliciting the depressive symptoms may be qualitatively different across the four diseases discussed. This review attempts to identify and understand the mechanisms of depression associated with these diseases, in the context of the known sex differences in the disease prevalence and its age of onset. Hence, more extensive, sex-specific model systems are warranted that utilize these disease states to elicit depressive symptoms in order to create more focused, efficient, and sex-specific treatments for patients suffering from these diseases and concurrent depressive symptoms.
Domestic scale vermicomposting for solid waste management
Authors: Pirsaheb Meghdad , Khosravi Touba , Sharafi Kiomars
Published: April 2013

Background

Vermicomposting has recently been recognized as one of the most appropriate methods to stabilize organic waste. In terms of a system for waste management, vermicomposting is sustainable, economically viable, and without detrimental effects to human health or to the environment. The aim of this study was to evaluate the process of vermicomposting using an indigenous species of earthworms (Eisenia fetida) on a small domestic scale as a system for waste management.

Results

This study was carried out as an experiment using the following procedure: a plastic container was prepared for vermicomposting; then, a bed was prepared in a ready container with a layer of initial bedding, sieved garden soil, and compostable waste. It was inoculated with Eisenia fetida earthworms. Samples were taken after 30 and 90 days of vermicomposting, and measurements were taken for the following parameters: percentage of organic matter, phosphorus, total carbon, total nitrogen, moisture content, ash, electrical conductivity, and pH. Results for percentage of organic matter, phosphorous, ash, total carbon, total nitrogen, carbon/nitrogen ratio, electrical conductivity, moisture content, and pH of mature compost after 90 days were 42 ± 2.8, 53 ± 0.17, 22 ± 0.170, 1.12 ± 0.003, 20 ± 0.25, 2.8 ± 0.6, 1, 200 ± 200 cSu, 56 ± 5.5%, 8.3 ± 0.2, respectively, and all these parameters except moisture content were compared with the standards.

Conclusion

According to these results, vermicomposting of municipal biodegradable waste by homeowners can be recommended as the best and most suitable method for solid waste disposal. This determines small-scale domestic vermicomposting as a suitable method for solid waste management. Reducing domestic waste at the source is an effective way to implement the main priorities of a waste management system in terms of its economy and its impact on the environment.
Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study
Authors: Arabi Yaseen M , Dara Saqib I , Tamim Hani M , Rishu Asgar H , Bouchama Abderrezak , Khedr Mohammad K , Feinstein Daniel , Parrillo Joseph E , Wood Kenneth E , Keenan Sean P , Zanotti Sergio , Martinka Greg , Kumar Aseem , Kumar Anand ,   The Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group
Published: April 2013

Introduction

Data are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients.

Methods

We performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality.

Results

Of the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0 ± 40.1 ml/kg for underweight, 43.2 ± 33.4 for normal BMI, 37.1 ± 30.8 for obese and 27.7 ± 22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese).

Conclusions

The obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome.

See related commentary by Dickerson, http://ccforum.com/content/17/3/154
Isoform level expression profiles provide better cancer signatures than gene level expression profiles
Authors: Zhang ZhongFa , Pal Sharmistha , Bi Yingtao , Tchou Julia , Davuluri Ramana V
Published: April 2013

Background

The majority of mammalian genes generate multiple transcript variants and protein isoforms through alternative transcription and/or alternative splicing, and the dynamic changes at the transcript/isoform level between non-oncogenic and cancer cells remain largely unexplored. We hypothesized that isoform level expression profiles would be better than gene level expression profiles at discriminating between non-oncogenic and cancer cellsgene level.

Methods

We analyzed 160 Affymetrix exon-array datasets, comprising cell lines of non-oncogenic or oncogenic tissue origins. We obtained the transcript-level and gene level expression estimates, and used unsupervised and supervised clustering algorithms to study the profile similarity between the samples at both gene and isoform levels.

Results

Hierarchical clustering, based on isoform level expressions, effectively grouped the non-oncogenic and oncogenic cell lines with a virtually perfect homogeneity-grouping rate (97.5%), regardless of the tissue origin of the cell lines. However, gene levelthis rate was much lower, being 75% at best based on the gene level expressions. Statistical analyses of the difference between cancer and non-oncogenic samples identified the existence of numerous genes with differentially expressed isoforms, which otherwise were not significant at the gene level. We also found that canonical pathways of protein ubiquitination, purine metabolism, and breast-cancer regulation by stathmin1 were significantly enriched among genes thatshow differential expression at isoform level but not at gene level.

Conclusions

In summary, cancer cell lines, regardless of their tissue of origin, can be effectively discriminated from non-cancer cell lines at isoform level, but not at gene level. This study suggests the existence of an isoform signature, rather than a gene signature, which could be used to distinguish cancer cells from normal cells.
Epitope Recognition in HLA-DR3 Transgenic Mice Immunized to TSH-R Protein or Peptides
Authors: Inaba Hidefumi , Moise Leonard , Martin William , De Groot Anne S. , Desrosiers Joe , Tassone Ryan , Buchman George , Akamizu Takashi , De Groot Leslie J.
Published: April 2013

Development of Graves' disease is related to HLA-DR3. The extracellular domain (ECD) of human TSH receptor (hTSH-R) is a crucial antigen in Graves' disease. hTSH-R peptide 37 (amino acids 78–94) is an important immunogenic peptide in DR3 transgenic mice immunized to hTSH-R. This study examined the epitope recognition in DR3 transgenic mice immunized to hTSH-R protein and evaluated the ability of a mutant hTSH-R peptide to attenuate the immunogenicity of hTSH-R peptide 37. DR3 transgenic mice were immunized to recombinant hTSH-R-ECD protein or peptides. A mutant hTSH-R 37 peptide (ISRIYVSIDATLSQLES: 37m), in which DR3 binding motif position 5 was mutated V>A, and position 8 Q>S, was synthesized. 37m should bind to HLA-DR3 but not bind T cell receptors. DR3 transgenic mice were immunized to hTSH-R 37 and 37m. Mice immunized to hTSH-R-ECD protein developed strong anti-hTSH-R antibody, and antisera reacted strongly with hTSH-R peptides 1–5 (20–94), 21 (258–277), 41 (283–297), 36 (376–389), and 31 (399–418). Strikingly, antisera raised to hTSH-R peptide 37 bound to hTSH-R peptides 1–7 (20–112), 10 (132–50), 33 (137–150), 41, 23 (286–305), 24 (301–320), 36, and 31 as well as to hTSH-R-ECD protein. Both antibody titers to hTSH-R 37 and reaction of splenocytes to hTSH-R 37 were significantly reduced in mice immunized to hTSH-R 37 plus 37m, compared with mice immunized to hTSH-R 37 alone. The ability of immunization to a single peptide to induce antibodies that bind hTSH-R-ECD protein, and multiple unrelated peptides, is a unique observation. Immunogenic reaction to hTSH-R peptide 37 was partially suppressed by 37m, and this may contribute to immunotherapy of autoimmune thyroid disease.
Selective Smad4 Knockout in Ovarian Preovulatory Follicles Results in Multiple Defects in Ovulation
Authors: Yu Chao , Zhang Yin-Li , Fan Heng-Yu
Published: April 2013

The TGF-β signaling pathway is involved with multiple processes in the mammalian ovary, including primordial follicle formation, granulosa cell (GC) proliferation, follicle atresia, ovulation, and feedback regulation between the pituitary and ovary. The transcriptional factor SMAD4 (Sma- and Mad-related protein 4) is the central component of the canonical TGF-β signaling pathway. Smad4 knockout (KO) using Amhr2-Cre, which is expressed in GCs of immature developing follicles, causes premature luteinization. In this study, we specifically depleted Smad4 in GCs of preovulatory follicles using Cyp19-Cre mice. As different from results with Smad4fl/fl;Amhr2-Cre mice, Smad4 depletion in preovulatory follicles did not cause premature luteinization or suppress GC proliferation; rather, it increased follicle atresia. In addition, Nppc and Npr2 expressions were reduced by Smad4 depletion; thus, their effect of maintaining oocyte meiotic arrest was weakened in Smad4 conditional KO mice. Smad4fl/fl;Cyp19-Cre female mice were subfertile and had irregular estrous cycles and ovulation defects. Smad4 KO also blocked LH-induced cumulus expansion and follicle rupture, but not oocyte meiotic resumption. Our results also indicated that SMAD4 was required for LH-stimulated activation of ERK1/2 and the expressions of ovulation-related genes. The defects arising from SMAD4 depletion could not be rescued by intraovarian mediators of LH actions, such as epidermal growth factor-like factors and prostaglandin E2. Furthermore, corpus lutea did not form in Smad4fl/fl;Cyp19-Cre female mice, indicating that SMAD4 was crucial for GCs terminal differentiation. Thus, by characterizing the ovarian phenotypes of preovulatory follicle-specific Smad4 KO mice, we identified the developmental stage-specific functions of the canonical TGF-β signaling pathway in ovulation and luteinization.
Visualizing the effect of dynamin inhibition on annular gap vesicle formation and fission
Authors: Nickel Beth , Boller Marie , Schneider Kimberly , Shakespeare Teresa , Gay Vernon , Murray Sandra A.
Published: April 2013

While gap junction plaque assembly has been extensively studied, mechanisms involved in plaque disassembly are not well understood. Disassembly involves an internalization process in which annular gap junction vesicles are formed. These vesicles undergo fission, but the molecular machinery needed for these fissions has not been described. Dynamin, a mechanoenzyme, has been however previously demonstrated to play a role in gap junction plaque internalization. To investigate the role of dynamin in annular gap junction vesicle fission, immunocytochemical, time-lapse, and transmission electron microscopy were used to analyze SW-13 adrenocortical cells in culture. Dynamin was demonstrated to colocalize with gap junction plaques and vesicles, and dynamin inhibition, by siRNA knockdown or treatment with a dynamin GTPase inhibitor, dynasore, increased the number and size of gap junction “buds” suspended from the gap junction plaques. Buds, in control populations, were frequently released to form annular gap junction vesicles. In dynamin-inhibited populations, however the buds were larger and infrequently released and thus fewer annular gap junction vesicles were formed. In addition, the number of annular gap junction vesicles fissions/hour were reduced in the dynamin inhibited populations. We believe this to be the first report addressing the details of annular gap junction vesicle fissions and demonstrating a role of dynamin in this process. This information is critical to elucidating the relationship between gap junctions, membrane regulation and cell behaviors.
Identification of an estrogen receptor alpha non-covalent ubiquitin binding surface: role in 17beta-estradiol-induced transcriptional activity
Authors: Pesiri Valeria , La Rosa Piergiorgio , Stano Pasquale , Acconcia Filippo
Published: April 2013

Ubiquitin (Ub)-binding domains (UBDs) located in Ub receptors decode the ubiquitination signal by non-covalently engaging the Ub modification on their binding partners and transduce the Ub signalling through Ub-based molecular interactions. In this way, inducible protein ubiquitination regulates diverse biological processes.

The estrogen receptor alpha (ERα) is a ligand-activated transcription factor that mediates the pleiotropic effects of the sex hormone 17β-estradiol (E2). Fine regulation of E2 pleiotropic actions depends on E2-dependent ERα association with a plethora of binding partners and/or on the E2 modulation of receptor ubiquitination. Indeed, E2-induced ERα polyubiquitination triggers receptor degradation and transcriptional activity and E2-dependent reduction in ERα monoubiquitination is critical for E2 signalling.

Monoubiquitinated proteins often contain UBDs but whether non-covalent Ub:ERα binding could occur and play a role in E2:ERα signalling is unknown. Here, we report an Ub-binding surface within ERα ligand binding domain that directs in vitro the receptor interaction with both ubiquitinated proteins and recombinant Ub-chains. Mutational analysis reveals that L429 and A430 ERα residues are involved in Ub-binding. Moreover, impairment of ERα association to ubiquitinated species strongly affects E2-induced ERα transcriptional activity.

Considering the importance of UBDs in the Ub-based signalling network and the central role of different ERα binding partners in the modulation of E2-dependent effects, our discoveries provide novel insights into ERα activity that could be relevant also for ERα-dependent diseases.
Loss of Git2 induces epithelial-mesenchymal transition by miR146a-Cnot6L controlled expression of Zeb1
Authors: Zhou Wu , Thiery Jean Paul
Published: April 2013

Epithelial-mesenchymal transition (EMT) can be induced by several pleiotropically activated transcription factors, including the zinc-finger, E-box-binding protein, Zeb1. Mechanisms regulating Zeb1 expression have been partly uncovered, showing a critical role for the miR-200 family members. Here, we show that Zeb1 is regulated by the Arf GTPase-activating protein (GAP), Git2. Following the loss of Git2, we found that miR-146a maturation is enhanced, which in turn promotes the expression of Zeb1 and induction of EMT. Furthermore, we found that Cnot6L, a validated target of miR-146a, affects the stability of Zeb1 mRNA through its deadenylase activity. Our results present evidence for a new role for loss of Git2 in promoting EMT through a novel regulatory pathway.
Flexible strategies for flight control: an active role for the abdomen
Authors: Dyhr Jonathan P. , Morgansen Kristi A. , Daniel Thomas L. , Cowan Noah J.
Published: April 2013

Moving animals orchestrate myriad motor systems in response to multimodal sensory inputs. Coordinating movement is particularly challenging in flight control, where animals deal with potential instability and multiple degrees of freedom of movement. Prior studies have focused on wings as the primary flight control structures, for which changes in angle of attack or shape are used to modulate lift and drag forces. However, other actuators that may impact flight performance are reflexively activated during flight. We investigated the visual–abdominal reflex displayed by the hawkmoth Manduca sexta to determine its role in flight control. We measured the open-loop stimulus–response characteristics (measured as a transfer function) between the visual stimulus and abdominal response in tethered moths. The transfer function reveals a 41 ms delay and a high-pass filter behavior with a pass band starting at ~0.5 Hz. We also developed a simplified mathematical model of hovering flight wherein articulation of the thoracic–abdominal joint redirects an average lift force provided by the wings. We show that control of the joint, subject to a high-pass filter, is sufficient to maintain stable hovering, but with a slim stability margin. Our experiments and models suggest a novel mechanism by which articulation of the body or ‘airframe’ of an animal can be used to redirect lift forces for effective flight control. Furthermore, the small stability margin may increase flight agility by easing the transition from stable flight to a more maneuverable, unstable regime.
Hearing threshold shifts and recovery after noise exposure in beluga whales, Delphinapterus leucas
Authors: Popov Vladimir V. , Supin Alexander Ya. , Rozhnov Viatcheslav V. , Nechaev Dmitry I. , Sysuyeva Evgenia V. , Klishin Vladimir O. , Pletenko Mikhail G. , Tarakanov Mikhail B.
Published: April 2013

Temporary threshold shift (TTS) after loud noise exposure was investigated in a male and a female beluga whale (Delphinapterus leucas). The thresholds were evaluated using the evoked-potential technique, which allowed for threshold tracing with a resolution of ~1 min. The fatiguing noise had a 0.5 octave bandwidth, with center frequencies ranging from 11.2 to 90 kHz, a level of 165 dB re. 1 μPa and exposure durations from 1 to 30 min. The effects of the noise were tested at probe frequencies ranging from −0.5 to +1.5 octaves relative to the noise center frequency. The effect was estimated in terms of both immediate (1.5 min) post-exposure TTS and recovery duration. The highest TTS with the longest recovery duration was produced by noises of lower frequencies (11.2 and 22.5 kHz) and appeared at a test frequency of +0.5 octave. At higher noise frequencies (45 and 90 kHz), the TTS decreased. The TTS effect gradually increased with prolonged exposures ranging from 1 to 30 min. There was a considerable TTS difference between the two subjects.
Matrix-Assisted Laser Desorption/Ionization Matrices for Negative Mode Metabolomics
Authors: Fagerer Stephan R. , Nielsen Simone , Ibáñez Alfredo , Zenobi Renato
Published: April 2013

Matrix-assisted laser desorption/ionization (MALDI) has been shown to be highly sensitive for analyzing low-mass compounds such as metabolites if the right matrix is used. 9-aminoacridine (9AA) is the most commonly employed matrix for negative mode MALDI-MS in metabolomics. However, matrix interferences and the strongly varying sensitivity for different metabolites make a search for alternative matrices desirable, in order to identify compounds with a different chemical background and/or favoring a different range of analytes. We tested the performance of a series of potential negative mode MALDI matrices with a mix of 29 metabolites containing amino acids, nucleotide phosphates and Krebs cycle intermediates. While ethacridine lactate was found to provide limits of detection (LODs) in the low femtomole range for nucleotide phosphates, amino acids and Krebs cycle intermediates in the low picomole range, 4-amino-2-methylquinoline showed LODs in the picomole range for most metabolites, but is capable of ionizing a broader range of analytes than both 9AA and ethacridine.
Consideration of the degree of increase in urine metadrenalines provides superior specificity in the diagnosis of phaeochromocytoma than additional urine catecholamine measurement
Authors: Scargill J J , Reed P , Kane J
Published: April 2013

Background

Measurement of fractionated plasma or urine metadrenalines is the recommended screening test in the diagnosis of phaeochromocytoma, with clinical cut-offs geared towards diagnostic sensitivity. Current practice at Salford Royal Hospital is to add urine catecholamines onto samples with raised urine metadrenalines, with the aim of adding specificity to a diagnosis of phaeochromocytoma.

Methods

This practice was reviewed by identifying a series of patients with raised urine metadrenalines who had catecholamines reflectively added. A total of 358 samples were identified from 242 patients, of which 228 had urine catecholamines measured.

Results

A diagnosis of ‘phaeochromocytoma‘ (n = 41) or ‘no phaeochromocytoma‘ (n = 90) was obtained in 131 of 228 patients, giving raised urine metadrenalines a positive predictive value for phaeochromocytoma of 31%. The finding of increased urine catecholamines in samples with raised urine metadrenalines increased specificity for phaeochromocytoma to 70%. However, 95% diagnostic specificity for phaeochromocytoma could be achieved by the introduction of a second cut-off for urine metadrenalines geared towards maximizing specificity.

Conclusions

Consideration of the degree of increase in urine metadrenalines is a superior method of determining the likelihood of phaeochromocytoma than measurement of urine catecholamines.
Thrombocytosis Is Associated With Mycobacterium tuberculosis Infection and Positive Acid-Fast Stains in Granulomas
Authors: Renshaw Andrew A. , Gould Edwin W.
Published: April 2013

Mycobacterium tuberculosis infection is associated with thrombocytosis. We sought to determine if this information might be valuable in evaluating granulomas using acid-fast stains (AFS). Fifty-eight patients with culture-confirmed M tuberculosis infection were compared with 75 patients with atypical mycobacterial infection and 48 patients negative for mycobacteria. Thrombocytosis (platelet count >360 × 103/μL [360 × 109/L]) was significantly more common in patients with M tuberculosis (50%) than those with either atypical mycobacterial infection (12%) or negative for mycobacteria (4%, P < .001 for each). In 67 patients, histologic evaluation of tissue samples showed granulomatous inflammation; 37 (55%) had positive AFS results. Of 19 patients with thrombocytosis, 16 (84%) had a positive AFS result compared with 21 (44%) of 48 without thrombocytosis (P = .003). Fifteen of 16 M tuberculosis cases with thrombocytosis had positive AFS findings on histologic evaluation; the single negative case had a platelet count of 362 × 103/μL (362 × 109/L). However, 3 of these cases of positive results on staining were initially diagnosed as negative and only recognized as positive on review. We conclude that patients whose specimens were sent for mycobacterial culture and thrombocytosis had an increased risk for M tuberculosis. Patients with granulomas and thrombocytosis are more likely to have a positive AFS result usually showing M tuberculosis. Finally, patients with initially negative AFS results and thrombocytosis deserve to have additional evaluation of the AFS specimens.
Clinical Characteristics and Survival Data of Melanoma Patients With Nevus Cell Aggregates Within Sentinel Lymph Nodes
Authors: Gambichler Thilo , Scholl Lisa , Stücker Markus , Bechara Falk G. , Hoffmann Klaus , Altmeyer Peter , Othlinghaus Nick
Published: April 2013

Histopathologic differentiation of nevus cell aggregates and metastatic melanoma in lymph nodes is challenging. Patients with melanoma who had undergone sentinel lymph node (SLN) biopsy were evaluated using univariate and multivariate analyses as well as Kaplan-Meier statistics. Of the 651 patients, 50 (7.7%) had a nodal nevus in the SLN. In the logistic regression model, primary melanoma on the lower extremities proved to be the strongest independent negative predictor of nodal nevi with an odds ratio of 0.11 (95% confidence interval, 0.034–0.36; P = .0002). Overall 5-year survival (P = .17) and 5-year disease-free survival (P = .45) of patients with nodal nevi did not significantly differ from that of patients with negative SLNs. The frequency and anatomic localization of nodal nevi observed in the present study are in line with previous studies. Our 5-year survival data clearly demonstrate that nevus cell aggregates in lymph nodes have to be considered a benign condition even though it occurs in patients with melanoma. This study provides an indirect proof of validity and accuracy of current histopathologic methods for differentiation between nodal nevi and melanoma metastasis.
Microfluidic Assay of Platelet Deposition on Collagen by Perfusion of Whole Blood from Healthy Individuals Taking Aspirin
Authors: Li Ruizhi , Fries Susanne , Li Xuanwen , Grosser Tilo , Diamond Scott L
Published: April 2013

BACKGROUND

Microfluidic devices can create hemodynamic conditions for platelet assays. We validated an 8-channel device in a study of interdonor response to acetylsalicylic acid (ASA, aspirin) with whole blood from 28 healthy individuals.

METHODS

Platelet deposition was assessed before treatment or 24 h after ingestion of 325 mg ASA. Whole blood (plus 100 μmol/L H-d-Phe-Pro-Arg-chloromethylketone to inhibit thrombin) was further treated ex vivo with ASA (0–500 μmol/L) and perfused over fibrillar collagen for 300 s at a venous wall shear rate (200 s−1).

RESULTS

Ex vivo ASA addition to blood drawn before aspirin ingestion caused a reduction in platelet deposition [half-maximal inhibitory concentration (IC50) approximately 10–20 μmol/L], especially between 150 and 300 s of perfusion, when secondary aggregation mediated by thromboxane was expected. Twenty-seven of 28 individuals displayed smaller deposits (45% mean reduction; range 10%–90%; P < 0.001) from blood obtained 24 h after ASA ingestion (no ASA added ex vivo). In replicate tests, an R value to score secondary aggregation [deposition rate from 150 to 300 s normalized by rate from 60 to 150 s] showed R < 1 in only 2 of 28 individuals without ASA ingestion, with R > 1 in only 3 of 28 individuals after 500 μmol/L ASA addition ex vivo. At 24 h after ASA ingestion, 21 of 28 individuals displayed poor secondary aggregation (R < 1) without ex vivo ASA addition, whereas the 7 individuals with residual secondary aggregation (R > 1) displayed insensitivity to ex vivo ASA addition. Platelet deposition was not correlated with platelet count. Ex vivo ASA addition caused similar inhibition at venous and arterial wall shear rates.

CONCLUSIONS

Microfluidic devices quantified platelet deposition after ingestion or ex vivo addition of aspirin.
A Dynamic Deep Sleep Stage inDrosophila
Authors: van Alphen Bart , Yap Melvyn H.W. , Kirszenblat Leonie , Kottler Benjamin , van Swinderen Bruno
Published: April 2013

How might one determine whether simple animals such as flies sleep in stages? Sleep in mammals is a dynamic process involving different stages of sleep intensity, and these are typically associated with measurable changes in brain activity (Blake and Gerard, 1937; Rechtschaffen and Kales, 1968; Webb and Agnew, 1971). Evidence for different sleep stages in invertebrates remains elusive, even though it has been well established that many invertebrate species require sleep (Campbell and Tobler, 1984; Hendricks et al., 2000; Shaw et al., 2000; Sauer et al., 2003). Here we used electrophysiology and arousal-testing paradigms to show that the fruit fly,Drosophila melanogaster, transitions between deeper and lighter sleep within extended bouts of inactivity, with deeper sleep intensities after ∼15 and ∼30 min of inactivity. As in mammals, the timing and intensity of these dynamic sleep processes in flies is homeostatically regulated and modulated by behavioral experience. Two molecules linked to synaptic plasticity regulate the intensity of the first deep sleep stage. Optogenetic upregulation of cyclic adenosine monophosphate during the day increases sleep intensity at night, whereas loss of function of a molecule involved in synaptic pruning, the fragile-X mental retardation protein, increases sleep intensity during the day. Our results show that sleep is not homogenous in insects, and suggest that waking behavior and the associated synaptic plasticity mechanisms determine the timing and intensity of deep sleep stages inDrosophila.