bluuebunny/crossref_metadata_2025 huggingface dataset:
A Longitudinal Analysis of Public Satisfaction with the Police in the Volgograd Region of Russia 1998—2005
Authors: Reynolds K. Michael , Semukhina Olga B. , Demidov Nicolai N.
Published: July 2008

This study examines public satisfaction with police in a region of Russia and empirically confirms that dissatisfaction remains high and pervasive in the region. A brief historical summary is included that highlights the development of the Soviet police. The literature review includes a discussion of both Russian and English studies that have identified various factors related to public satisfaction with police. This study examines raw longitudinal citizen survey data ( N = 4,000) collected annually from 1998—2005 and focuses on citizen trust of criminal justice institutions and fear of crime as explanatory variables. An explanatory empirical model is developed to test whether low levels of public satisfaction with police in Russia can be attributed to the distrust of criminal justice institutions and fear of crime. The model is grounded in the motive-based theory of institutional trust. The findings of the study provide empirical evidence that criminal justice institutional trust is a major explanatory factor regarding public police satisfaction in Russia.
Visions of Urban Reform
Authors: Saltzstein Alan L. , Copus Colin , Sonenshein Raphael J. , Skelcher Chris
Published: July 2008

This article compares the logics and institutional consequences of urban government reform in the United States and in England. We focus on the politics of ideas, identifying four common visions of urban reform: efficient public interest management, improved representation, local political leadership, and metropolitan-wide governance. National pressure groups, locality effects, and the status of city charters and council constitutions are key factors mediating the direction and pace of reform. These are embedded in different institutional norms for city government, related to national political and governmental cultures. The strengths and weaknesses of both systems are discussed.
Tinnitus Outcomes Assessment
Authors: Meikle Mary B. , Stewart Barbara J. , Griest Susan E. , Henry James A.
Published: July 2008

Over the past two decades, recognition has grown that measures for evaluating treatment outcomes must be designed specifically to have high responsiveness. With that in mind, four major types of tinnitus measures are reviewed, including psychoacoustic measures, self-report questionnaires concerning functional effects of tinnitus, various rating scales, and global outcome measures. Nine commonly used tinnitus questionnaires, developed in the period 1980-2000, are reviewed. Because of many similarities between tinnitus and pain, comparisons between pain and tinnitus measures are discussed, and recommendations that have been made for developing a core set of measures to evaluate treatment-related changes in pain are presented as providing a fruitful path for developing a core set of measures for tinnitus. Finally, the importance of having both immediately obtainable outcome measures (psychoacoustic, rating scales, or single global measures) and longer term measures (questionnaires covering the negative effects of tinnitus) is emphasized for further work in tinnitus outcomes assessment.
Nation, Gender and Representations of (In)Securities in Indian Politics
Authors: Das Runa
Published: July 2008

This article examines the relationship between gender, nations and nationalisms vis-a-vis the Indian state's nationalist identity and perceptions of (in)security. It explores how the postcolonial Indian state's project of nation-building — reflective of a western secular-modern identity (under the Congress Party) and a Hindutva-dominated identity (under the BJP) — incorporates gender, with continuities and discontinuities, to articulate divergent forms of nationalist/communalist identities, `cartographic anxieties' and nuclear (in)securities. The article contends that with the recent rise of the Hindu-Right BJP, guided by Hindutva ideology, the nature of representing the Indian nation, its women and (in)securities has changed from a geopolitical to a cultural perception — thereby necessitating a rereading of the Indian nation, nationalism, gender and its perceptions of (in)security.
Religion, Citizenship and Participation
Authors: Predelli Line Nyhagen
Published: July 2008

This article analyses the increasing participation of Muslim women in mosques in Norway in light of current discourses on citizenship, gender and migration. It discusses how various processes in the mosques can be interpreted as contradictory and complex by sometimes increasing the participation of women and promoting liberation, while at other times constraining women'ss activities through various forms of discipline and control. Women are vital for the building of religious institutions among Muslim immigrant communities, and they are slowly achieving more space in such institutions. They are also being included in new forms of participation in some mosques. Recently, some Muslim women in Norway have made public calls for the reinterpretation of the Qur'an in ways that are more inclusive towards women. Despite pressures from both within and outside the mosques, however, Muslim congregations in Norway can still be described as patriarchal gender regimes where the participation and citi- zenship of women depends on the willingness of men to include them.
The Use of Alcohol and Condoms During Sexual Assault
Authors: Davis Kelly Cue , Schraufnagel Trevor J. , George William H. , Norris Jeanette
Published: July 2008

Sexual assault remains an important public health issue due to the violence involved as well as the potential for health risks such as sexually transmitted infections. Alcohol has been associated with both violent and risky sexual behavior. This study assessed the frequency of sexual assault perpetration, alcohol use, and condom use during sexual assault in a community sample of young, heterosexual male social drinkers. Participants completed measures of their sexual assault perpetration. More than 50% reported sexual assault perpetration; 60% of these reported repeat perpetration. Almost one half of perpetrators reported alcohol consumption prior to every sexual assault incident. Never having used a condom during penetrative sexually aggressive acts was reported by 41.2% of perpetrators. Alcohol use and condom nonuse were positively correlated for acts of forcible rape. Findings provide information about the infrequent use of condoms during sexual assault incidents and support prior evidence of the association between alcohol and sexual assault.
Writing fieldnotes in an ethnographic study of peers – collaborative experiences from the field
Authors: Condell Sarah L
Published: July 2008

Abstract

Fieldnotes and their processes tend to be implicit endeavours in the nursing and midwifery literature. The opportunity, therefore, to build an understanding of the social practice of this part of the research process is lost. This paper explores fieldnote generation in an ethnographic doctoral study examining the building of research capacity. Ethnographers claim that data is generated collaboratively. In this study, data was collected from two fields of ‘peers’. First data set contained 50 h of observation with doctoral research fellows, and the second data set contained 2 years diary recording of a nurse working in a national research funding agency. The paper shows that the levels of collaboration in constructing the ethnographic data can depend on the field itself, the stance of the researcher and the willingness of peer participants.
Searching one’s self: the autoethnography of a nurse teacher
Authors: Wright Jane
Published: July 2008

Abstract

This paper gives an example of the autoethnographic approach to research by examining the life of the author. The account considers her creative identity as a female nurse and life long learner from a white, middle class Northern Irish background. Autoethnography is a relatively new, and controversial, area of research. This paper evaluates the validity of the method with reference to nursing and nurse education. It concludes that autoethnography is a useful research tool, which provides personal insights, which can provide meaning to others. This is particularly true when creative methods of expression are harnessed.
Submerged arc welding of thick ferritic martensitic 12Cr stainless steel with a variety of consumables
Authors: Taban E. , Deleu E. , Dhooge A. , Kaluc E.
Published: July 2008

Modified X2CrNi12 stainless steel, conforming to EN 1·4003 and UNS S41003 grades, has been designed with less carbon (<0·015%) and impurities to improve the weldability and mechanical properties. The present paper deals with submerged arc welding (SAW) of 30 mm thick plates of this steel with austenitic and duplex stainless steel consumables. Several samples extracted from the welded joints were subjected to mechanical testing by means of tensile, bend, Charpy impact and crack tip opening displacement (CTOD) fracture toughness tests. Microstructural examination including grain size analysis, hardness and ferrite measurements was carried out. Salt spray and blister tests as corrosion testing were applied. Considering all data obtained, it can be recommended to use austenitic filler metals as an economic alternative for SAW of this steel in the areas where impact is anticipated and adequate atmospheric corrosion resistance is needed since the weld made with austenitic wires exhibited very encouraging low temperature impact toughness properties related with finer grained microstructure and adequate strength and corrosion properties.
Effects of oxide activating flux on laser welding of magnesium alloy
Authors: Sun H. , Song G. , Zhang L. F.
Published: July 2008

The behaviours of laser welding wrought magnesium AZ31B alloy with oxide activating fluxes (TiO2, SiO2 and Cr2O3) were studied in the present paper. The results showed that the three fluxes all can increase the weld penetration of the laser welding. A larger grain size was exhibited in the weld metal prepared with flux than that in the fusion zone prepared without flux by optical microscopy. Oxide particles were found in the weld metal by electron probe microanalysis (EPMA), when flux was used. The results of tensile tests showed that weld metal without flux has nearly 90% of base metal strength when compared to the ones with flux. The mixed mode fracture was showed in the weld with flux. The main mechanism for the increases in penetration was that the flux coat absorbed more laser energy during the early period of laser action.
Development of high quality thermal spraying process by shielding control
Authors: Sakakibara N. , Manabe Y. , Hiromoto Y. , Kobayashi Y.
Published: July 2008

The shielding controlled plasma spraying process was investigated to improve corrosion resistance of metal surfaces. In this process, a shielding nozzle that covered only spraying area was attached in front of the tip of a commercial plasma spray gun nozzle, and the environment surrounding the plasma jet was controlled by nitrogen flow. When the oxygen concentration in the shielding nozzle was maintained at 0·5%, the metal oxide contents in CoNiCrAlY coating and the porosity of the coating reduced to 0·2 and 0·3% at optimal spray particle size respectively. The corrosion potential in an acid solution including chloride ions was almost constant for 1000 h for CoNiCrAlY coating deposited by shielding controlled plasma spraying. On the other hand, those obtained by atmospheric plasma spraying process decreased in the corrosion potential largely after 10 h. Thus, it can be concluded that the shielding controlled plasma spraying process improves the corrosion resistance of the metal.
Novel laser surface treatment approach to suppress sensitisation in modified type 316(N) stainless steel weld metal
Authors: Parvathavarthini N. , Dayal R. K. , Kaul R. , Ganesh P. , Khare J. , Nath A. K. , Mishra S. K. , Samajdar I.
Published: July 2008

Welded components are subjected to solution annealing heat treatment for achieving full stress relief and restoration of mechanical properties and corrosion resistance. During such heat treatments, optimum cooling rate has to be selected because very slow cooling rate will result in sensitisation and susceptibility to intergranular corrosion whereas fast cooling will result in reintroduction of residual stress. For 316 LN stainless steel which is welded using modified E316-15 electrodes (0·045–0·055%C), critical cooling rate above which there is no risk of sensitisation is 75 K h−1. This paper presents a novel laser surface treatment which suppresses sensitisation in weld metal, even at a slower cooling rate of 65 K h−1. Experiments involving laser surface melting were carried out with 150 W average power pulsed Nd:YAG laser and 10 kW CO2 laser, in both continuous wave and pulse modulated (100 Hz) modes. Best results were obtained when surface melting was performed with high frequency pulse modulated CO2 laser beam. The processed weld metal remained unsensitised after solution annealing followed by slower rate of cooling at 65 K h−1. Numerical simulation study was performed with ANSYS 7·0 software to understand the physical reason behind the difference in sensitisation behaviour of CO2 laser melted specimens under continuous wave and high frequency pulse modulated conditions and the predictions were validated using results of electron backscattered diffraction studies. Weld metal specimens treated with high frequency pulse modulated CO2 laser clearly showed evolution of fine grains near the fusion boundary region which enhanced sensitisation resistance.
Microstructure and pitting corrosion of similar and dissimilar stainless steel welds
Authors: Reddy G. M. , Rao K. S. , Sekhar T.
Published: July 2008

Pitting Corrosion behaviour of similar and dissimilar metal welds of three classes of stainless steels, namely, austenitic stainless steel (AISI 304), ferritic stainless steel (AISI 430) and duplex stainless steel (AISI 2205), has been studied. Three regions of the weldment, i.e. fusion zone, heat affected zone and unaffected parent metal, were subjected to corrosion studies. Electron beam and friction welds have been compared. Optical, scanning electron microscopy and electron probe analysis were carried out to determine the mechanism of corrosion behaviour. Dissimilar metal electron beam welds of austenitic–ferritic (A–F), ferritic–duplex (F–D) and austenitic–duplex stainless steel (A–D) welds contained coarse grains which are predominantly equiaxed on austenitic and duplex stainless steel side while they were columnar on the ferritic stainless steel side. Microstructural features in the central region of dissimilar stainless steel friction welds exhibit fine equiaxed grains due to dynamic recrystallisation as a result of thermomechanical working during welding and is confined to ferritic stainless steel side in the case of A–F, D–F welds and duplex stainless steel side in the case of D–A welds. Beside this region bent and elongated grains were observed on ferritic stainless steel side in the case of A–F, D–F welds and duplex stainless steel side in the case of D–A welds. Interdiffusion of elements was significant in electron beam welding and insignificant in friction welds. Pitting corrosion has been observed to be predominantly confined to heat affected zone (HAZ) close to fusion boundary of ferritic stainless steel interface of A–F electron beam and D–F electron beam and friction weldments. The pitting resistance of stainless steel electron beam weldments was found to be lower than that of parent metal as a result of segregation and partitioning of alloying elements. In general, friction weldments exhibited better pitting corrosion resistance due to lower incidence of carbides in the microstructure.
Microstructure and mechanical properties of Sc modified Al–Cu alloy (AA2219) electron beam welds
Authors: Seshagiri P. C. , Madhusudan Reddy G. , Srinivasa Rao K. , Govinda Raju M. , Bhattacharya S. S. , Prasad Rao K.
Published: July 2008

Al alloy AA2219 is a high strength alloy belonging to the 2000 series Al alloys widely used for aerospace application. One of the drawbacks of most of the high strength Al alloys is that they suffer from poor weldability. However AA2219 is an exception due to the presence of more Cu that helps in healing cracks by providing extra eutectics. Although AA2219 has excellent weldability the strength of a welded joint is only 35–45% of the base metal. The loss of strength is due to the dissolution of the strengthening precipitates during melting. Therefore, there is a need to improve the fusion zone strength of AA2219 welds. In this study an attempt was made experimentally to use electron beam welding and modify the base metal chemistry with addition of Sc and Zr in order to improve the mechanical properties of the AA2219 weld joints. Fine equiaxed microstructure was obtained in the fusion zone of electron beam welds with improved mechanical properties. Eutectic was found to be distributed discontinuously which resulted in improved yield strength, tensile strength and ductility compared to welds made without Sc and Zr.
Interface phenomena in aluminium–magnesium magnetic pulse welding
Authors: Ben-Artzy A. , Stern A. , Frage N. , Shribman V.
Published: July 2008

The morphology and structure of the weld interface in magnetic pulse welding of similar and dissimilar metals were investigated. The interface zone of dissimilar metal couples such as Al–Mg, was studied in comparison to Al–Al welds. It was found that intermetallic phases (IMP) of different compositions are created during welding of the Al–Mg couple by rapid solidification of a thin melted layer at the interface. According to the calculated energy balance of magnetic pulse welding (MPW), there is enough energy to melt a thin interfacial layer and create IMP. Intensive characterisation techniques were used, including the focused ion beam (FIB) method that was used to prepare a cross-section of the Al–Mg interface for TEM characterisation. It was established that the jet action plays an important role in the melting process at the bonding zone.
Ethnicity and Matriarchal Protest: A Case of Dialoguing Shona Personal Names
Authors: Makondo Livingstone
Published: July 2008

AbstractThis paper examines the role of Zimbabwean (Shona) women in the naming of children in the patriarchal Shona society. The corpus of two thousand Shona personal/given names under review was gathered from Zimbabwe's seven predominantly Shona-speaking provinces. The discussion closely examines fifty-two personal names. It emerges that Zimbabwean (Shona) women are innovative as they manage to devise personal names that denotatively and connotatively put across their wishes, grievances, experiences, and preferences in acceptable and non-confrontational ways. The use of value-laden, palimpsest and emblematic-dialoguing personal names is a restrained strategy that ensures tranquility in the society. As a result, the name bearers become moving emblems of the frozen experiences and hopes of their mothers who might have directly or indirectly given the resultant name. In addition, a deconstructionist theory is promulgated as one of the means to get at the deeper meanings of the given names.
After Midnight: Naming, West Indians, and British Children's Literature
Authors: Sands-O'Connor Karen
Published: July 2008

AbstractAs British explorers and colonizers spread out over the world, they used the act of naming as one of many tools to indicate ownership of their new-found empire. British children's books, which were a major part of the colonizing and imperial effort, subtly (and not so subtly) indoctrinated young readers into their positions as owners and managers of the many nations around the world within the British sphere of influence. Because the area known as 'the West Indies' formed some of Britain's earliest colonies, it is instructive to follow the history of West Indian naming in British children's books. Naming in these books show how young readers were taught first to dominate, and then (as the empire crumbled) to try and contain, and only lastly to try and understand the lands and peoples of the Caribbean Sea.
Deducing topology of protein-protein interaction networks from experimentally measured sub-networks
Authors: Yang Ling , Vondriska Thomas M , Han Zhangang , MacLellan W Robb , Weiss James N , Qu Zhilin
Published: July 2008

Background

Protein-protein interaction networks are commonly sampled using yeast two hybrid approaches. However, whether topological information reaped from these experimentally-measured sub-networks can be extrapolated to complete protein-protein interaction networks is unclear.

Results

By analyzing various experimental protein-protein interaction datasets, we found that they are not random samples of the parent networks. Based on the experimental bait-prey behaviors, our computer simulations show that these non-random sampling features may affect the topological information. We tested the hypothesis that a core sub-network exists within the experimentally sampled network that better maintains the topological characteristics of the parent protein-protein interaction network. We developed a method to filter the experimentally sampled network to result in a core sub-network that more accurately reflects the topology of the parent network. These findings have fundamental implications for large-scale protein interaction studies and for our understanding of the behavior of cellular networks.

Conclusion

The topological information from experimental measured networks network as is may not be the correct source for topological information about the parent protein-protein interaction network. We define a core sub-network that more accurately reflects the topology of the parent network.
Synchrony between orientation-selective neurons is modulated during adaptation-induced plasticity in cat visual cortex
Authors: Ghisovan Narcis , Nemri Abdellatif , Shumikhina Svetlana , Molotchnikoff Stephane
Published: July 2008

Background

Visual neurons respond essentially to luminance variations occurring within their receptive fields. In primary visual cortex, each neuron is a filter for stimulus features such as orientation, motion direction and velocity, with the appropriate combination of features eliciting maximal firing rate. Temporal correlation of spike trains was proposed as a potential code for linking the neuronal responses evoked by various features of a same object. In the present study, synchrony strength was measured between cells following an adaptation protocol (prolonged exposure to a non-preferred stimulus) which induce plasticity of neurons' orientation preference.

Results

Multi-unit activity from area 17 of anesthetized adult cats was recorded. Single cells were sorted out and (1) orientation tuning curves were measured before and following 12 min adaptation and 60 min after adaptation (2) pairwise synchrony was measured by an index that was normalized in relation to the cells' firing rate. We first observed that the prolonged presentation of a non-preferred stimulus produces attractive (58%) and repulsive (42%) shifts of cell's tuning curves. It follows that the adaptation-induced plasticity leads to changes in preferred orientation difference, i.e. increase or decrease in tuning properties between neurons. We report here that, after adaptation, the neuron pairs that shared closer tuning properties display a significant increase of synchronization. Recovery from adaptation was accompanied by a return to the initial synchrony level.

Conclusion

We conclude that synchrony reflects the similarity in neurons' response properties, and varies accordingly when these properties change.
Analytical approaches to detect maternal/fetal genotype incompatibilities that increase risk of pre-eclampsia
Authors: Parimi Neeta , Tromp Gerard , Kuivaniemi Helena , Nien Jyh Kae , Gomez Ricardo , Romero Roberto , Goddard Katrina AB
Published: July 2008

Background

In utero interactions between incompatible maternal and fetal genotypes are a potential mechanism for the onset or progression of pregnancy related diseases such as pre-eclampsia (PE). However, the optimal analytical approach and study design for evaluating incompatible maternal/offspring genotype combinations is unclear.

Methods

Using simulation, we estimated the type I error and power of incompatible maternal/offspring genotype models for two analytical approaches: logistic regression used with case-control mother/offspring pairs and the log-linear regression used with case-parent triads. We evaluated a real dataset consisting of maternal/offspring pairs with and without PE for incompatibility effects using the optimal analysis based on the results of the simulation study.

Results

We identified a single coding scheme for the incompatibility effect that was equally or more powerful than all of the alternative analysis models evaluated, regardless of the true underlying model for the incompatibility effect. In addition, the log-linear regression was more powerful than the logistic regression when the heritability was low, and more robust to adjustment for maternal or fetal effects. For the PE data, this analysis revealed three genes, lymphotoxin alpha (LTA), von Willebrand factor (VWF), and alpha 2 chain of type IV collagen (COL4A2) with possible incompatibility effects.

Conclusion

The incompatibility model should be evaluated for complications of pregnancy, such as PE, where the genotypes of two individuals may contribute to the presence of disease.
Idiopathic central precocious puberty in girls: presentation factors
Authors: Prété Géraldine , Couto-Silva Ana-Claudia , Trivin Christine , Brauner Raja
Published: July 2008

Background

It is sometimes difficult to distinguish between premature thelarche and precocious puberty in girls who develop breasts before the age of 8 years. We evaluated the frequencies of the signs associated with breast development and the factors influencing the presentation of girls with idiopathic central precocious puberty (CPP).

Methods

353 girls monitored 0.9 ± 0.7 year after the onset of CPP.

Results

The age at CPP was < 3 years in 2%, 3–7 years in 38% and 7–8 years in 60% of cases. Pubic hair was present in 67%, growth rate greater than 2 SDS in 46% and bone age advance greater than 2 years in 33% of cases. Breast development was clinically isolated in 70 (20%) cases. However, only 31 of these (8.8% of the population) had a prepubertal length uterus and gonadotropin responses to gonadotropin releasing hormone and plasma estradiol. The clinical picture of CPP became complete during the year following the initial evaluation.

25% of cases were obese. The increase in weight during the previous year (3.7 ± 1.4 kg) and body mass index were positively correlated with the statural growth and bone age advance (P < 0.0001).

There was no relationship between the clinical-biological presentation and the age at puberty, the interval between the onset of puberty and evaluation, or the presence of familial CPP.

Conclusion

The variation in presentation of girls with CPP does not depend on their age, interval between the onset and evaluation, or familial factors. This suggests that there are degrees of hypothalamic-pituitary-ovarian activation that are not explained by these factors.
Simultaneous adrenal and extra-adrenal myelolipoma – an uncommon incident: case report and review of the literature
Authors: Zieker Derek , Königsrainer Ingmar , Miller Stephan , Vogel Ulrich , Sotlar Karl , Steurer Wolfgang , Königsrainer Alfred , Lehmann Thorsten G
Published: July 2008

Background

Extra-adrenal myelolipomas are rare benign tumours. Other soft tissue tumours such as well-differentiated liposarcomas appear morphological almost identical. Preoperative imaging and especially biopsy are important tools to diagnose these lesions.

Case presentation

We report a very seldom case of a simultaneous myelolipoma of the adrenal gland in association with an extra-adrenal myelolipoma in an 75-year-old man. With a review of the literature we describe and discuss the aetiology, differential diagnosis and treatment of patients with respect to adrenal and extra-adrenal lesions.

Conclusion

The appearance of a simultaneous adrenal and extra-adrenal myelolipoma is a rare incident. We conclude that such lesions should be considered in the differential diagnosis of a fat-containing tumour in the retroperitoneal tissue/compartment.
Expression of the Endocannabinoid System in Human First Trimester Placenta and Its Role in Trophoblast Proliferation
Authors: Habayeb Osama M. H. , Taylor Anthony H. , Bell Stephen C. , Taylor David J. , Konje Justin C.
Published: July 2008

The endocannabinoid, anandamide, which binds to two major receptor proteins, the cannabinoid receptors (CBs) 1 and 2 (CB1 and CB2), has been shown to play a role in first trimester miscarriage possibly through impairment of the developing trophoblast. Although the precise molecular mechanisms underlying this are unknown, plasma anandamide levels are known to be regulated by the progesterone-induced enzyme, fatty acid amide hydrolase (FAAH). Here, we tested the hypothesis that temporal-spatial expression of FAAH, CB1, and CB2 is regulated during early pregnancy and that anandamide detrimentally alters trophoblast proliferation. Transcripts for CB1, CB2, and FAAH were demonstrated in first trimester trophoblast extracts with only the CB1 transcript being significantly regulated. The significant 4.7-fold increase in expression at wk 10 gestation was reduced to 8.9% of the peak value by wk 12. Transcripts for CB2 showed a similar pattern of expression but were not significantly induced. By contrast, FAAH transcript levels appeared to increase toward the end of the first trimester, but again did not reach significance. These observations were supported by immunohistochemical studies that demonstrated a similar pattern of expression at the protein level, with cellular localization for all three proteins concentrated within the syncytiotrophoblast layer. Anandamide also prevented BeWo trophoblast cell proliferation in a dose-dependent manner, with a 50–60% significant inhibition of cell proliferation with concentrations in excess of 3 μm. This effect was mediated through CB2. Together, these data provide insights into how elevated plasma anandamide levels increase the risk of first trimester miscarriage.
Stimulation of N-Terminal Truncated Isoform of Androgen Receptor Stabilizes Human Ether-á-go-go-Related Gene-Encoded Potassium Channel Protein via Activation of Extracellular Signal Regulated Kinase 1/2
Authors: Wu Zhi-Yuan , Chen Kun , Haendler Bernard , McDonald Thomas V. , Bian Jin-Song
Published: July 2008

Proarrhythmic drugs induce long QT syndrome more frequently in women than men. The present study was designed to determine whether androgens regulate the function and expression of the human ether-á-go-go-related gene (HERG) encoded K+ channel, which is largely responsible for determining the QT interval. In a concentration-dependent manner (10−9 to 10−6m for 24 h), 5α-dihydrotestosterone (5α-DHT) increased HERG protein abundance in HEK293 cells stably expressing HERG in the presence of coexpressed cardiac androgen receptor (AR) variant [N-terminal truncated isoform of AR (AR45)]. The elevation of HERG protein was seen in endoplasmic reticulum, Golgi, and plasma membrane without clear preferential colocalization. Coexpression of the more common form of the AR did not confer 5α-DHT augmentation of HERG protein. Proteasome inhibitors, N-acetyl-L-leucyl-L-leucyl-L-norleucinal and MG132 prevented the 5α-DHT- dependent enhancement of HERG, as did the lysosome inhibitor, bafilomycin A1. Consistently, the cycloheximide-based protein chase study showed that 5α-DHT prolonged HERG protein half-life. 5α-DHT/AR45 signaling induced phosphorylation of ERK1/2. Blockade of ERK1/2 with PD98059 and U0126 prevented the effect of androgen on HERG protein abundance. Functional studies showed that 5α-DHT treatment for 24 h increased HERG K+ current density in Chinese hamster ovary cells cotransfected with cDNAs of AR45 and HERG channels. Moreover, 5α-DHT also increased ether-á-go-go-related gene-encoded K+ channel protein abundance in isolated rabbit cardiac myocytes. In conclusion, these data provide evidence that stimulation of AR45 receptors by androgens up-regulates HERG K+ channel abundance and activity mainly through stabilizing HERG protein in an ERK1/2 dependent mechanism, and suggest a mechanism to explain the sex difference in the long QT syndrome.
Inhibition of Cholesterol Biosynthesis Impairs Insulin Secretion and Voltage-Gated Calcium Channel Function in Pancreatic β-Cells
Authors: Xia Fuzhen , Xie Li , Mihic Anton , Gao Xiaodong , Chen Yi , Gaisano Herbert Y. , Tsushima Robert G.
Published: July 2008

Insulin secretion from pancreatic β-cells is mediated by the opening of voltage-gated Ca2+ channels (CaV) and exocytosis of insulin dense core vesicles facilitated by the secretory soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein machinery. We previously observed that β-cell exocytosis is sensitive to the acute removal of membrane cholesterol. However, less is known about the chronic changes in endogenous cholesterol and its biosynthesis in regulating β-cell stimulus-secretion coupling. We examined the effects of inhibiting endogenous β-cell cholesterol biosynthesis by using the squalene epoxidase inhibitor, NB598. The expression of squalene epoxidase in primary and clonal β-cells was confirmed by RT-PCR. Cholesterol reduction of 36–52% was observed in MIN6 cells, mouse and human pancreatic islets after a 48-h incubation with 10 μm NB598. A similar reduction in cholesterol was observed in the subcellular compartments of MIN6 cells. We found NB598 significantly inhibited both basal and glucose-stimulated insulin secretion from mouse pancreatic islets. CaV channels were markedly inhibited by NB598. Rapid photolytic release of intracellular caged Ca2+ and simultaneous measurements of the changes in membrane capacitance revealed that NB598 also inhibited exocytosis independently from CaV channels. These effects were reversed by cholesterol repletion. Our results indicate that endogenous cholesterol in pancreatic β-cells plays a critical role in regulating insulin secretion. Moreover, chronic inhibition of cholesterol biosynthesis regulates the functional activity of CaV channels and insulin secretory granule mobilization and membrane fusion. Dysregulation of cellular cholesterol may cause impairment of β-cell function, a possible pathogenesis leading to the development of type 2 diabetes.
Early Ghrelin Treatment after Myocardial Infarction Prevents an Increase in Cardiac Sympathetic Tone and Reduces Mortality
Authors: Schwenke Daryl O. , Tokudome Takeshi , Kishimoto Ichiro , Horio Takeshi , Shirai Mikiyasu , Cragg Patricia A. , Kangawa Kenji
Published: July 2008

Acute myocardial infarction (MI) initiates an increase in cardiac sympathetic nerve activity (CSNA), which ultimately exacerbates chronic cardiac dysfunction. Ghrelin (Ghr), a GH-releasing peptide, is an effective treatment for improving cardiac function in chronic heart failure. Ghr also suppresses renal sympathetic nerve activity (SNA) and, therefore, may have important therapeutic benefits in the early stages of acute MI: by reducing CSNA. In this study we hypothesized that early Ghr administration may prevent an increase in CSNA in the acute phase after MI. CSNA was continuously recorded in urethane-anaesthetized rats before and for 5 h after acute MI (or sham). MI was induced by ligation of the left anterior descending coronary artery. Rats received an injection of either saline or Ghr (150 μg/kg, sc) 1 min, or 2 h, after the infarct. CSNA remained stable during the 5-h recording duration in sham rats. MI induced a maximal 110% increase in SNA, which was prevented in rats that received Ghr 1 min after infarct. When Ghr was injected 2 h after MI (SNA had increased by ∼85%), SNA decreased to pre-MI activity. Importantly, early Ghr administration significantly reduced the high mortality rate associated with MI (61% mortality in untreated MI rats cf. ∼23% in Ghr-treated MI rats). These results show that early Ghr treatment prevents the increase in CSNA after MI, which may contribute to the improved chances of survival. Whether these early beneficial effects of Ghr also have long-term benefits for improving cardiac function is an area that requires further investigation.
Temporal Recruitment of Transcription Factors at the 3′,5′-Cyclic Adenosine 5′-Monophosphate-Response Element of the Human GnRH-II Promoter
Authors: Poon Song Ling , An Beum-Soo , So Wai-Kin , Hammond Geoffrey L. , Leung Peter C. K.
Published: July 2008

GnRH-II is a potent GnRH subtype involved in modulating OVCAR-3 cell proliferation and the invasive properties of JEG-3 cells, and an atypical cAMP-response element (CRE) in the human GnRH-II promoter influences its activation. We demonstrated that the GnRH-II promoter is activated by 8-bromoadenosine-cAMP in several cell lines including αT3, TE671, JEG-3, and OVCAR-3 cells and that cAMP enhances GnRH-II mRNA levels in JEG-3 and OVCAR-3 cells. Moreover, 8-bromoadenosine-cAMP increases cAMP response element-binding protein (CREB) phosphorylation in JEG-3 and OVCAR-3 cells and augments CBP and CCAAT/enhancer-binding protein (C/EBP)-β coimmunoprecipitation with phosphorylated CREB (p-CREB) in a temporally defined manner from nuclear extracts. When CREB, CBP, and C/EBPβ levels were knocked down by small interfering RNA, reductions in any of these transcription factors reduced cAMP-enhanced GnRH-II promoter activity and GnRH-II mRNA levels in JEG-3 and OVCAR-3 cells. Importantly, chromatin immunoprecipitation assay showed that p-CREB bound the CRE within the endogenous GnRH-II promoter within 1 h and that p-CREB association with C/EBPβ occurs within 2 h of cAMP stimulation, coincident with the first appearance of C/EBPβ at the CRE. By contrast, maximum interactions between p-CREB and CBP do not occur until at least 4 h after cAMP stimulation, and this is reflected in the progressive loading of CBP at the CRE at 2–4 h, as demonstrated by chromatin immunoprecipitation. Taken together, these data suggest that p-CREB, C/EBPβ, and CBP are recruited to the CRE of the GnRH-II promoter in a temporarily defined manner to enhance its transcription in JEG-3 and OVCAR-3 cells in response to cAMP.
Conditional Deletion of the Retinoblastoma (Rb) Gene in Ovarian Granulosa Cells Leads to Premature Ovarian Failure
Authors: Andreu-Vieyra Claudia , Chen Ruihong , Matzuk Martin M.
Published: July 2008

The retinoblastoma protein (RB) regulates cell proliferation and survival by binding to the E2F family of transcription factors. Recent studies suggest that RB also regulates differentiation in a variety of cell types, including myocytes, neurons, adipocytes, and chondrocytes. Rb mutations have been found in ovarian cancer; however, the role of RB in normal and abnormal ovarian function remains unclear. To test the hypothesis that loss of Rb induces ovarian tumorigenesis, we generated an ovarian granulosa cell conditional knockout of Rb (Rb cKO) using the Cre/lox recombination system. Rb cKO females showed 100% survival and no ovarian tumor formation through 9 months of age, but they developed progressive infertility. Prepubertal Rb cKO females showed increased ovulation rates compared with controls, correlating with increased follicle recruitment, higher Fshr and Kitl mRNA levels, and lower anti-Müllerian hormone levels. In contrast, the ovulation rate of 6-wk-old females was similar to that of controls. Morphometric analysis of Rb cKO ovaries from 6-wk-old and older females showed increased follicular atresia and apoptosis. Rb cKO ovaries and preantral follicles had abnormal levels of known direct and indirect target genes of RB, including Rbl2/p130, E2f1, Ccne2, Myc, Fos, and Tgfb2. In addition, preantral follicles showed increased expression of the granulosa cell differentiation marker Inha, decreased levels of Foxl2 and Cyp19a1 aromatase, and abnormal expression of the nuclear receptors Nr5a1, Nr5a2, and Nr0b1. Taken together, our results suggest that RB is required for the temporal-specific pattern of expression of key genes involved in follicular development.
Minireview: The Wnt Signaling Pathway Effector TCF7L2 and Type 2 Diabetes Mellitus
Authors: Jin Tianru , Liu Ling
Published: July 2008

Since the relationship between TCF7L2 (also known as TCF-4) polymorphisms and type 2 diabetes mellitus was identified in 2006, extensive genome-wide association examinations in different ethnic groups have further confirmed this relationship. As a component of the bipartite transcription factor β-catenin/TCF, TCF7L2 is important in conveying Wnt signaling during embryonic development and in regulating gene expression during adulthood. Although we still do not know mechanistically how the polymorphisms within the intron regions of TCF7L2 affect the risk of type 2 diabetes, this transcriptional regulator was shown to be involved in stimulating the proliferation of pancreatic β-cells and the production of the incretin hormone glucagon-like peptide-1 in intestinal endocrine L cells. In this review, we introduce background knowledge of TCF7L2 as a component of the Wnt signaling pathway, summarize recent findings demonstrating the association between TCF7L2 polymorphisms and the risk of type 2 diabetes, outline experimental evidence of the potential function of TCF7L2 in pancreatic and intestinal endocrine cells, and present our perspective views.
On Interpreting Cofitachequi
Authors: Hudson Charles , Beck Robin A. , DePratter Chester B. , Ethridge Robbie , Worth John E.
Published: July 2008

Scholars have developed two broad approaches to researching the history of the native peoples of the American South from the sixteenth century to the present: culture history and social history. The essential task in culture history is to classify native so-called tribes into cultural and/or linguistic categories, to list defining cultural traits, and to show how these “tribes” have persisted, disappeared, or become acculturated. The essential task in social history is to reconstruct the structure of the societies and polities into which native peoples organized themselves within the context of native worlds and to show what happened to them when they came into contact with the modern world-system. Both approaches have been used to depict and explicate Cofitachequi, a native people first encountered by the Hernando de Soto expedition in 1540. Our purpose here is to point out flaws in the culture history approach and to emphasize strengths in the social history approach.
Role for PADI6 and the cytoplasmic lattices in ribosomal storage in oocytes and translational control in the early mouse embryo
Authors: Yurttas Piraye , Vitale Alejandra M. , Fitzhenry Robert J. , Cohen-Gould Leona , Wu Wenzhu , Gossen Jan A. , Coonrod Scott A.
Published: July 2008

The mechanisms that mediate the establishment of totipotency during the egg-to-embryo transition in mammals remain poorly understood. However, it is clear that unique factors stored in the oocyte cytoplasm are crucial for orchestrating this complex cellular transition. The oocyte cytoplasmic lattices (CPLs) have long been predicted to function as a storage form for the maternal contribution of ribosomes to the early embryo. We recently demonstrated that the CPLs cannot be visualized in Padi6-/- oocytes and that Padi6-/-embryos arrest at the two-cell stage. Here, we present evidence further supporting the association of ribosomes with the CPLs by demonstrating that the sedimentation properties of the small ribosomal subunit protein, S6, are dramatically altered in Padi6-/- oocytes. We also show that the abundance and localization of ribosomal components is dramatically affected in Padi6-/- two-cell embryos and that de novo protein synthesis is also dysregulated in these embryos. Finally, we demonstrate that embryonic genome activation (EGA) is defective in Padi6-/- two-cell embryos. These results suggest that, in mammals, ribosomal components are stored in the oocyte CPLs and are required for protein translation during early development.
Gap junction communication between uterine stromal cells plays a critical role in pregnancy-associated neovascularization and embryo survival
Authors: Laws Mary J. , Taylor Robert N. , Sidell Neil , DeMayo Francesco J. , Lydon John P. , Gutstein David E. , Bagchi Milan K. , Bagchi Indrani C.
Published: July 2008

In the uterus, the formation of new maternal blood vessels in the stromal compartment at the time of embryonic implantation is critical for the establishment and maintenance of pregnancy. Although uterine angiogenesis is known to be influenced by the steroid hormones estrogen (E) and progesterone(P), the underlying molecular pathways remain poorly understood. Here, we report that the expression of connexin 43 (Cx43), a major gap junction protein, is markedly enhanced in response to E in uterine stromal cells surrounding the implanted embryo during the early phases of pregnancy. Conditional deletion of the Cx43 gene in these stromal cells and the consequent disruption of their gap junctions led to a striking impairment in the development of new blood vessels within the stromal compartment, resulting in the arrest of embryo growth and early pregnancy loss. Further analysis of this phenotypical defect revealed that loss of Cx43 expression resulted in aberrant differentiation of uterine stromal cells and impaired production of several key angiogenic factors, including the vascular endothelial growth factor (Vegf). Ablation of CX43 expression in human endometrial stromal cells in vitro led to similar findings. Collectively, these results uncovered a unique link between steroid hormone-regulated cell-cell communication within the pregnant uterus and the development of an elaborate vascular network that supports embryonic growth. Our study presents the first evidence that Cx43-type gap junctions play a critical and conserved role in modulating stromal differentiation, and regulate the consequent production of crucial paracrine signals that control uterine neovascularization during implantation.
Reactive oxygen species act remotely to cause synapse loss in aDrosophilamodel of developmental mitochondrial encephalopathy
Authors: Mast Joshua D. , Tomalty Katharine M. H. , Vogel Hannes , Clandinin Thomas R.
Published: July 2008

Mitochondrial dysfunction is a hallmark of many neurodegenerative diseases,yet its precise role in disease pathology remains unclear. To examine this link directly, we subtly perturbed electron transport chain function in the Drosophila retina, creating a model of Leigh Syndrome, an early-onset neurodegenerative disorder. Using mutations that affect mitochondrial complex II, we demonstrate that mild disruptions of mitochondrial function have no effect on the initial stages of photoreceptor development, but cause degeneration of their synapses and cell bodies in late pupal and adult animals. In this model, synapse loss is caused by reactive oxygen species(ROS) production, not energy depletion, as ATP levels are normal in mutant photoreceptors, and both pharmacological and targeted genetic manipulations that reduce ROS levels prevent synapse degeneration. Intriguingly, these manipulations of ROS uncouple synaptic effects from degenerative changes in the cell body, suggesting that mitochondrial dysfunction activates two genetically separable processes, one that induces morphological changes in the cell body, and another that causes synapse loss. Finally, by blocking mitochondrial trafficking into the axon using a mutation affecting a mitochondrial transport complex, we find that ROS action restricted to the cell body is sufficient to cause synaptic degeneration, demonstrating that ROS need not act locally at the synapse. Thus, alterations in electron transport chain function explain many of the neurodegenerative changes seen in both early- and late-onset disorders.