bluuebunny/crossref_metadata_2025 huggingface dataset:
Colombo Twin and Singleton Study (CoTASS): A description of a population based twin study of mental disorders in Sri Lanka
Authors: Siribaddana Sisira H , Ball Harriet A , Hewage Suwin N , Glozier Nick , Kovas Yulia , Dayaratne DARK , Sumathipala Athula , McGuffin Peter , Hotopf Matthew
Published: June 2008

Background

The Sri Lankan twin registry is one of the first to be established in a developing country, and its design has ensured sampling from a wide range of environmental conditions. It thus has great potential to examine environmental and genetic influences on diverse phenotypes, including psychiatric disorders, in the context of a diversity of environmental exposures, which may not have been fully explored in previous twin studies in developed countries. This paper presents the rationale for the study, describes its context, and the methods for twin ascertainment and data collection.

Methods

A population-based twin register was established in the Colombo district of Sri Lanka using infrastructure designed to periodically update the electoral register. We invited a subsample from this register to participate in the project on common mental disorders, using random ascertainment. A separate non-twin sample was randomly selected from the geographical areas where twins were found. Home interviewers collected diagnostic information on common mental disorders, as well as environmental exposures including life events, socio-economic conditions, and the impact of the civil war and the Tsunami of 2004.

Results

We identified 19,302 individuals in the creation of the population based twin register. We randomly selected a subsample, of whom 4,387 were eligible to participate and 4,024 agreed to be interviewed (including data on 1,954 complete pairs of twins and 5 sets of triplets). Those who refused consent had a similar mean age and sex ratio to those who were interviewed. We invited 2,485 singletons to participate and 2,019 were interviewed.

Conclusion

Initial exploration of the data suggests the samples are very representative of the Colombo district of Sri Lanka, so we have created a unique resource for understanding the influences on mental disorders in developing countries, and to compare to the influences found in developed countries.
Pregnancy success of lactating Holstein cows after a single administration of a sustained-release formulation of recombinant bovine somatotropin
Authors: Bell A , Rodríguez OA , de Castro e Paula LA , Padua MB , Hernández-Cerón J , Gutiérrez CG , De Vries A , Hansen PJ
Published: June 2008

Background

Results regarding the use of bovine somatotropin for enhancing fertility in dairy cattle are variable. Here, the hypothesis was tested that a single injection of a sustained-release preparation of bovine somatotropin (bST) during the preovulatory period would improve pregnancy success of lactating dairy cows at first service.

Results

The first experiment was conducted in a temperate region of Mexico. Cows inseminated following natural estrus or timed artificial insemination were given a single injection of bST or a placebo injection at insemination (n = 100 cows per group). There was no significant difference between bST and control groups in the proportion of inseminated cows diagnosed pregnant (29 vs 31% pregnant). The second experiment was performed during heat stress in Florida. Cows were subjected to an ovulation synchronization regimen for first insemination. Cows treated with bST received a single injection at 3 days before insemination. Controls received no additional treatment. As expected, bST did not increase vaginal temperature. Treatment with bST did not significantly increase the proportion of inseminated cows diagnosed pregnant although it was numerically greater for the bST group (24.2% vs 17.8%, 124–132 cows per group). There was a tendency (p = 0.10) for a smaller percent of control cows to have high plasma progesterone concentrations (≥ 1 ng/ml) at Day 7 after insemination than for bST-treated cows (72.6 vs 81.1%). When only cows that were successfully synchronized were considered, the magnitude of the absolute difference in the percentage of inseminated cows that were diagnosed pregnant between bST and control cows was reduced (24.8 vs 22.4% pregnant for bST and control).

Conclusion

Results failed to indicate a beneficial effect of bST treatment on fertility of lactating dairy cows.
Pericardial effusion as the only manifestation of infection with Francisella tularensis: a case report
Authors: Landais Cécile , Levy Pierre-Yves , Habib Gilbert , Raoult Didier
Published: June 2008

Introduction

Francisella tularensis, a facultative intracellular Gram-negative bacterium, has rarely been reported as an agent of pericarditis, generally described as a complication of tularemia sepsis. F. tularensis is a fastidious organism that grows poorly on standard culture media and diagnosis is usually based on serological tests. However, cross-reactions may occur. Western blotting allows the correct diagnosis.

Case presentation

A non-smoking 53-year-old woman was admitted to hospital with a large posterior pericardial effusion. Serological tests showed a seroconversion in antibody titers to F. tularensis (IgG titer = 400) and Legionella pneumophila (IgG titer = 512). F. tularensis was identified by Western immunoblotting following cross-adsorption. The patient reported close contact with rabbits 2 weeks prior to the beginning of symptoms of pericarditis.

Conclusion

We report a rare case of pericardial effusion as the only manifestation of infection by F. tularensis. The etiological diagnosis is based on serology. Western blotting and cross-adsorption allow differential diagnosis.
Behavioral recovery from traumatic brain injury after membrane reconstruction using polyethylene glycol
Authors: Koob Andrew O , Colby Julia M , Borgens Richard B
Published: June 2008

Polyethylene glycol (PEG; 2000 MW, 30% by volume) has been shown to mechanically repair damaged cellular membranes and reduce secondary axotomy after traumatic brain and spinal cord injury (TBI and SCI respectively). This repair is achieved following spontaneous reassembly of cell membranes made possible by the action of targeted hydrophilic polymers which first seal the compromised portion of the plasmalemma, and secondarily, allow the lipidic core of the compromised membranes to resolve into each other. Here we compared PEG-treated to untreated rats using a computer-managed open-field behavioral test subsequent to a standardized brain injury. Animals were evaluated after a 2-, 4-, and 6-hour delay in treatment after TBI. Treated animals receive a single subcutaneous injection of PEG. When treated within 2 hours of the injury, injured PEG-treated rats showed statistically significant improvement in their exploratory behavior recorded in the activity box when compared to untreated but brain-injured controls. A delay of 4 hours reduced this level of achievement, but a statistically significant improvement due to PEG injection was still clearly evident in most outcome measures compared at the various evaluation times. A further delay of 2 more hours, however, eradicated the beneficial effects of PEG injection as revealed using this behavioral assessment. Thus, there appears to be a critical window of time in which PEG administration after TBI can provide neuroprotection resulting in an enhanced functional recovery. As is often seen in clinically applied acute treatments for trauma, the earlier the intervention can be applied, the better the outcome.
PMC42, a breast progenitor cancer cell line, has normal-like mRNA and microRNA transcriptomes
Authors: Git Anna , Spiteri Inmaculada , Blenkiron Cherie , Dunning Mark J , Pole Jessica CM , Chin Suet-Feung , Wang Yanzhong , Smith James , Livesey Frederick J , Caldas Carlos
Published: June 2008

Introduction

The use of cultured cell lines as model systems for normal tissue is limited by the molecular alterations accompanying the immortalisation process, including changes in the mRNA and microRNA (miRNA) repertoire. Therefore, identification of cell lines with normal-like expression profiles is of paramount importance in studies of normal gene regulation.

Methods

The mRNA and miRNA expression profiles of several breast cell lines of cancerous or normal origin were measured using printed slide arrays, Luminex bead arrays, and real-time reverse transcription-polymerase chain reaction.

Results

We demonstrate that the mRNA expression profiles of two breast cell lines are similar to that of normal breast tissue: HB4a, immortalised normal breast epithelium, and PMC42, a breast cancer cell line that retains progenitor pluripotency allowing in-culture differentiation to both secretory and myoepithelial fates. In contrast, only PMC42 exhibits a normal-like miRNA expression profile. We identified a group of miRNAs that are highly expressed in normal breast tissue and PMC42 but are lost in all other cancerous and normal-origin breast cell lines and observed a similar loss in immortalised lymphoblastoid cell lines compared with healthy uncultured B cells. Moreover, like tumour suppressor genes, these miRNAs are lost in a variety of tumours. We show that the mechanism leading to the loss of these miRNAs in breast cancer cell lines has genomic, transcriptional, and post-transcriptional components.

Conclusion

We propose that, despite its neoplastic origin, PMC42 is an excellent molecular model for normal breast epithelium, providing a unique tool to study breast differentiation and the function of key miRNAs that are typically lost in cancer.
A critical assessment of Mus musculusgene function prediction using integrated genomic evidence
Authors: Peña-Castillo Lourdes , Tasan Murat , Myers Chad L , Lee Hyunju , Joshi Trupti , Zhang Chao , Guan Yuanfang , Leone Michele , Pagnani Andrea , Kim Wan Kyu , Krumpelman Chase , Tian Weidong , Obozinski Guillaume , Qi Yanjun , Mostafavi Sara , Lin Guan Ning , Berriz Gabriel F , Gibbons Francis D , Lanckriet Gert , Qiu Jian , Grant Charles , Barutcuoglu Zafer , Hill David P , Warde-Farley David , Grouios Chris , Ray Debajyoti , Blake Judith A , Deng Minghua , Jordan Michael I , Noble William S , Morris Quaid , Klein-Seetharaman Judith , Bar-Joseph Ziv , Chen Ting , Sun Fengzhu , Troyanskaya Olga G , Marcotte Edward M , Xu Dong , Hughes Timothy R , Roth Frederick P
Published: June 2008

Background:

Several years after sequencing the human genome and the mouse genome, much remains to be discovered about the functions of most human and mouse genes. Computational prediction of gene function promises to help focus limited experimental resources on the most likely hypotheses. Several algorithms using diverse genomic data have been applied to this task in model organisms; however, the performance of such approaches in mammals has not yet been evaluated.

Results:

In this study, a standardized collection of mouse functional genomic data was assembled; nine bioinformatics teams used this data set to independently train classifiers and generate predictions of function, as defined by Gene Ontology (GO) terms, for 21,603 mouse genes; and the best performing submissions were combined in a single set of predictions. We identified strengths and weaknesses of current functional genomic data sets and compared the performance of function prediction algorithms. This analysis inferred functions for 76% of mouse genes, including 5,000 currently uncharacterized genes. At a recall rate of 20%, a unified set of predictions averaged 41% precision, with 26% of GO terms achieving a precision better than 90%.

Conclusion:

We performed a systematic evaluation of diverse, independently developed computational approaches for predicting gene function from heterogeneous data sources in mammals. The results show that currently available data for mammals allows predictions with both breadth and accuracy. Importantly, many highly novel predictions emerge for the 38% of mouse genes that remain uncharacterized.
Predicting gene function in a hierarchical context with an ensemble of classifiers
Authors: Guan Yuanfang , Myers Chad L , Hess David C , Barutcuoglu Zafer , Caudy Amy A , Troyanskaya Olga G
Published: June 2008

Background:

The wide availability of genome-scale data for several organisms has stimulated interest in computational approaches to gene function prediction. Diverse machine learning methods have been applied to unicellular organisms with some success, but few have been extensively tested on higher level, multicellular organisms. A recent mouse function prediction project (MouseFunc) brought together nine bioinformatics teams applying a diverse array of methodologies to mount the first large-scale effort to predict gene function in the laboratory mouse.

Results:

In this paper, we describe our contribution to this project, an ensemble framework based on the support vector machine that integrates diverse datasets in the context of the Gene Ontology hierarchy. We carry out a detailed analysis of the performance of our ensemble and provide insights into which methods work best under a variety of prediction scenarios. In addition, we applied our method to Saccharomyces cerevisiae and have experimentally confirmed functions for a novel mitochondrial protein.

Conclusion:

Our method consistently performs among the top methods in the MouseFunc evaluation. Furthermore, it exhibits good classification performance across a variety of cellular processes and functions in both a multicellular organism and a unicellular organism, indicating its ability to discover novel biology in diverse settings.
GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function
Authors: Mostafavi Sara , Ray Debajyoti , Warde-Farley David , Grouios Chris , Morris Quaid
Published: June 2008

Background:

Most successful computational approaches for protein function prediction integrate multiple genomics and proteomics data sources to make inferences about the function of unknown proteins. The most accurate of these algorithms have long running times, making them unsuitable for real-time protein function prediction in large genomes. As a result, the predictions of these algorithms are stored in static databases that can easily become outdated. We propose a new algorithm, GeneMANIA, that is as accurate as the leading methods, while capable of predicting protein function in real-time.

Results:

We use a fast heuristic algorithm, derived from ridge regression, to integrate multiple functional association networks and predict gene function from a single process-specific network using label propagation. Our algorithm is efficient enough to be deployed on a modern webserver and is as accurate as, or more so than, the leading methods on the MouseFunc I benchmark and a new yeast function prediction benchmark; it is robust to redundant and irrelevant data and requires, on average, less than ten seconds of computation time on tasks from these benchmarks.

Conclusion:

GeneMANIA is fast enough to predict gene function on-the-fly while achieving state-of-the-art accuracy. A prototype version of a GeneMANIA-based webserver is available at http://morrislab.med.utoronto.ca/prototype.
Combining guilt-by-association and guilt-by-profiling to predict Saccharomyces cerevisiaegene function
Authors: Tian Weidong , Zhang Lan V , Taşan Murat , Gibbons Francis D , King Oliver D , Park Julie , Wunderlich Zeba , Cherry J Michael , Roth Frederick P
Published: June 2008

Background:

Learning the function of genes is a major goal of computational genomics. Methods for inferring gene function have typically fallen into two categories: 'guilt-by-profiling', which exploits correlation between function and other gene characteristics; and 'guilt-by-association', which transfers function from one gene to another via biological relationships.

Results:

We have developed a strategy ('Funckenstein') that performs guilt-by-profiling and guilt-by-association and combines the results. Using a benchmark set of functional categories and input data for protein-coding genes in Saccharomyces cerevisiae, Funckenstein was compared with a previous combined strategy. Subsequently, we applied Funckenstein to 2,455 Gene Ontology terms. In the process, we developed 2,455 guilt-by-profiling classifiers based on 8,848 gene characteristics and 12 functional linkage graphs based on 23 biological relationships.

Conclusion:

Funckenstein outperforms a previous combined strategy using a common benchmark dataset. The combination of 'guilt-by-profiling' and 'guilt-by-association' gave significant improvement over the component classifiers, showing the greatest synergy for the most specific functions. Performance was evaluated by cross-validation and by literature examination of the top-scoring novel predictions. These quantitative predictions should help prioritize experimental study of yeast gene functions.
An en masse phenotype and function prediction system for Mus musculus
Authors: Taşan Murat , Tian Weidong , Hill David P , Gibbons Francis D , Blake Judith A , Roth Frederick P
Published: June 2008

Background:

Individual researchers are struggling to keep up with the accelerating emergence of high-throughput biological data, and to extract information that relates to their specific questions. Integration of accumulated evidence should permit researchers to form fewer - and more accurate - hypotheses for further study through experimentation.

Results:

Here a method previously used to predict Gene Ontology (GO) terms for Saccharomyces cerevisiae (Tian et al.: Combining guilt-by-association and guilt-by-profiling to predict Saccharomyces cerevisiae gene function. Genome Biol 2008, 9(Suppl 1):S7) is applied to predict GO terms and phenotypes for 21,603 Mus musculus genes, using a diverse collection of integrated data sources (including expression, interaction, and sequence-based data). This combined 'guilt-by-profiling' and 'guilt-by-association' approach optimizes the combination of two inference methodologies. Predictions at all levels of confidence are evaluated by examining genes not used in training, and top predictions are examined manually using available literature and knowledge base resources.

Conclusion:

We assigned a confidence score to each gene/term combination. The results provided high prediction performance, with nearly every GO term achieving greater than 40% precision at 1% recall. Among the 36 novel predictions for GO terms and 40 for phenotypes that were studied manually, >80% and >40%, respectively, were identified as accurate. We also illustrate that a combination of 'guilt-by-profiling' and 'guilt-by-association' outperforms either approach alone in their application to M. musculus.
Changes in crack aspect-ratio concentration from heat treatment: A comparison between velocity inversion and experimental data
Authors: Tran Dung T. , Rai Chandra S. , Sondergeld Carl H.
Published: June 2008

We report petrophysical changes on a suite of Berea sandstones undergoing heat-cycling treatment. Crack concentrations from experimental data (e.g., nuclear magnetic resonance [NMR], mercury injection, and thin sections) are compared with results from a modified Cheng-Toksöz velocity inversion model using a differential effective medium to investigate the physical significance of the inversion. We propose a deterministic methodology to estimate grain properties, pore-crack aspect-ratio spectrum, and consistent pore-crack insertion ordering for the inversion. Our inversion scheme reproduces velocity profiles to within [Formula: see text]. Moreover, we demonstrate for the first time that velocity inversion can resolve the increase in concentrations of small cracks as rock samples are heat-treated. The crack concentration changes calculated from the inversion are consistent with other independent experimental data of porosity, density, thin-section observations, NMR spectra, and mercury injection spectra, lending credence to the use of velocity inversion in microstructural characterization.
Sensitivity study of marine CSEM data for reservoir production monitoring
Authors: Lien Martha , Mannseth Trond
Published: June 2008

Using numerical and analytical modeling, we assess the feasibility of marine controlled-source electromagnetic (CSEM) data for monitoring the flooding front during water flooding of an oil reservoir. We discuss the ability of time-lapse CSEM data to resolve changes in the electric conductivity small enough to be of interest for monitoring purposes. Measurement and modeling errors are discussed briefly, and analytical calculations comparing time-lapse signals with a certain type of time-lapse modeling errors are performed. Numerical calculations, performed with a volume integral-equation method, are used to study the effect on the electromagnetic (EM) fields of relevant conductivity changes. The numerical investigation includes robustness with respect to survey parameter values, discrimination between different front shapes, and ability to overcome time-lapse error. Simulated signals are found to be strong enough to overtake typical measurement errors and are fairly robust toward perturbations of survey parameters. It is found analytically and numerically that certain modeling errors experience a high degree of time-lapse cancellation.
Modulation of Caveolin-1 Expression Can Affect Signalling through the Phosphatidylinositol 3-Kinase/Akt Pathway and Cellular Proliferation in Response to Insulin-Like Growth Factor I
Authors: Matthews Laura C. , Taggart Michael J. , Westwood Melissa
Published: June 2008

The IGFs mediate their effects on cell function through the type I IGF receptor and numerous intracellular signalling molecules, including the phosphatidylinositol 3-kinase (PI-3K)/Akt pathway. The type I IGF receptor also binds to the caveolae protein caveolin-1, but the impact of caveolae on IGF/PI-3K/Akt signalling remains controversial. We have examined the effect of complete (knockout) and partial (knockdown) caveolin-1 deficiency on cellular IGF effects mediated via the PI-3K/Akt pathway. Under basal conditions, caveolin-1-deficient mouse embryonic fibroblast cells [MF(−/−)] incorporated significantly more [3H]thymidine than wild-type mouse embryonic fibroblast cells [MF(+/+)]; however, small hairpin RNA-mediated knockdown of caveolin-1 (80% reduction) in 3T3L1 fibroblasts had no effect on basal proliferation. Interestingly, IGF-I induced proliferation was similar in MF(−/−) and MF(+/+) cells, whereas caveolin-1 knockdown promoted a hyperproliferative response to IGF-I [pkDCav3T3L1(80) 12.4 ± 0.4-fold; pkDShuffle3T3L1 4.3 ± 0.2-fold induction; P < 0.01]. Immunoblot analysis showed that caveolin-1 knockdown had no affect on Akt expression or activation. However, in MF(−/−) cells, IGF-I-stimulated phosphorylation of Akt was reduced despite up-regulated Akt levels. Further investigation demonstrated that caveolin knockout up-regulated Akt-2 and Akt-3 isoform expression, but Akt-1 expression was down-regulated; interestingly, coimmunoprecipitation studies revealed Akt-1 as the predominant isoform to be phosphorylated in response to IGF-I. In summary, caveolin-1 deficiency promotes a hyperproliferative response to IGF-I that is unrelated to Akt expression/activation. However, cells that lack caveolin are able to respond appropriately to IGF-I through compensatory changes in Akt isoform expression. These data posit caveolin-1 as a component of the IGF/PI-3K/Akt signalling modulus regulating cellular proliferation with implications for diseases, including cancers, which have altered caveolin expression.
Effects of Vasopressin V1b Receptor Deficiency on Adrenocorticotropin Release from Anterior Pituitary Cells in Response to Oxytocin Stimulation
Authors: Nakamura Kazuaki , Fujiwara Yoko , Mizutani Reiko , Sanbe Atsushi , Miyauchi Noriko , Hiroyama Masami , Yamauchi Junji , Yamashita Tatsuya , Nakamura Shigeki , Mori Toyoki , Tsujimoto Gozoh , Tanoue Akito
Published: June 2008

Oxytocin (OT) is one of the secretagogues for stress-induced ACTH release. OT-induced ACTH release is reported to be mediated by the vasopressin V1b receptor in the rat pituitary gland, which contains both OT and V1b receptors. We examined OT-induced ACTH release using primary cultures of anterior pituitary cells from wild-type (V1bR+/+) and V1b receptor knockout (V1bR−/−) mice. OT stimulated similar levels of ACTH release from pituitary cells of V1bR+/+ and V1bR−/− mice. OT-induced ACTH release was significantly inhibited by the selective V1b receptor antagonist SSR149415 and the OT receptor antagonist CL-14-26 in V1bR+/+ mice. In addition, cotreatment with SSR149415 at 10−6m and CL-14-26 at 10−6m inhibited OT-induced ACTH release to the control level inV1bR+/+ mice. In V1bR−/− mice, OT-induced ACTH release was significantly inhibited by CL-14-26 at 10−8m and completely inhibited at 10−7m. These results indicate that OT induces the ACTH response via OT and V1b receptors inV1bR+/+ mice but via only OT receptors in V1bR−/− mice. The gene expression level of the OT receptor was significantly higher in the anterior pituitary gland of V1bR−/− mice than in that of V1bR+/+ mice, suggesting that the OT receptor is up-regulated to compensate for ACTH release under conditions of V1b receptor deficiency.
Nongenomic Glucocorticoid Effects on Activity-Dependent Potentiation of Catecholamine Release in Chromaffin Cells
Authors: Park Yong-Soo , Ha Choi Yoon , Park Choon-Ho , Kim Kyong-Tai
Published: June 2008

Adrenal medulla chromaffin cells are neuroendocrine and modified sympathetic ganglion cells. Catecholamines released from chromaffin cells mediate the fight-or-flight response or alert reaction against dangerous conditions. Here we report that short-term treatment with glucocorticoids, released from adrenal cortex cells in response to chronic stress, inhibits activity-dependent potentiation (ADP) of catecholamine release. First, short-term treatment with dexamethasone (DEX), a synthetic glucocorticoid, reduces ADP in a concentration-dependent manner (IC50 324.2 ± 54.5 nm). The inhibitory effect of DEX is not reversed by RU-486 treatment, suggesting that the rapid inhibitory effect of DEX on ADP of catecholamine release is independent of glucocorticoid receptors. Second, DEX treatment reduces the frequency of fusion between vesicles and plasma membrane without affecting calcium influx. DEX disrupts activity-induced vesicle translocation and F-actin disassembly, thereby leading to inhibition of the vesicle fusion frequency. Third, we provide evidence that DEX reduces F-actin disassembly via inhibiting phosphorylation and translocation of myristoylated alanine-rich C kinase substrate and its upstream kinase protein kinase Cε. Altogether, we suggest that glucocorticoids inhibit ADP of catecholamine release by decreasing myristoylated alanine-rich C kinase substrate phosphorylation, which inhibits F-actin disassembly and vesicle translocation.
Age Affects Spontaneous Activity and Depolarizing Afterpotentials in Isolated Gonadotropin-Releasing Hormone Neurons
Authors: Wang Yong , Garro Mona , Dantzler Heather A. , Taylor Julia A. , Kline David D. , Kuehl-Kovarik M. Cathleen
Published: June 2008

Neuronal activity underlying the pulsatile secretion of GnRH remains poorly understood, as does the endogenous generation of such activity. It is clear that changes at the level of the hypothalamus are taking place during reproductive aging, yet virtually nothing is known about GnRH neuronal physiology in aging and postreproductive animals. In these studies, we performed cell-attached and whole-cell recordings in GnRH-enhanced green fluorescent protein neurons dissociated from young (3 months), middle-aged (10 months), and old (15–18 months) female mice. All mice were ovariectomized; half were estradiol replaced. Neurons from all ages fired spontaneously, most in a short-burst pattern that is characteristic of GnRH neuronal firing. Membrane characteristics were not affected by age. However, firing frequency was significantly reduced in neurons from old animals, as was spike patterning. The amplitude of the depolarizing afterpotential, evoked by a 200-msec current pulse, was significantly smaller in aged animals. In addition, inward whole-cell currents were reduced in estradiol-treated animals, although they were not significantly affected by age. Because depolarizing afterpotentials have been shown to contribute to prolonged discharges of activity after a very brief excitatory input, a decreased depolarizing afterpotential could lead to attenuated pulses in older animals. In addition, decreases in frequency and pattern generation could lead to improper information coding. Therefore, changes in the GnRH neuron during aging could lead to dysregulated activity, potentially resulting in the attenuated LH pulses observed in the transition to reproductive senescence.
Leptin Acts in the Periphery to Protect Thymocytes from Glucocorticoid-Mediated Apoptosis in the Absence of Weight Loss
Authors: Trotter-Mayo Robert N. , Roberts Margo R.
Published: June 2008

Leptin is a member of the IL-6 cytokine family and is primarily produced by adipose tissue. At high enough concentration, leptin engages leptin receptors expressed in the hypothalamus that regulate a variety of functions, including induction of weight loss. Mice deficient in leptin (ob/ob) or leptin receptor (db/db) function exhibit thymic atrophy associated with a reduction in double-positive (DP) thymocytes. However, the mediator of such thymic atrophy remains to be identified, and the extent to which leptin acts in the periphery vs. the hypothalamus to promote thymocyte cellularity is unknown. In the present study, we first demonstrate that thymic cellularity and composition is fully restored in ob/ob mice subjected to adrenalectomy. Second, we observe that ob/ob mice treated with low-dose leptin peripherally but not centrally exhibit increased thymocyte cellularity in the absence of any weight loss or significant reduction in systemic corticosterone levels. Third, we demonstrate that reconstitution of db/db mice with wild-type bone marrow augments thymocyte cellularity and restores DP cell frequency despite elevated corticosterone levels. These and additional data support a mode of action whereby leptin acts in the periphery to reduce the sensitivity of DP thymocytes to glucocorticoid-mediated apoptosis in vivo. Strikingly, our data reveal that leptin’s actions on thymic cellularity in the periphery can be uncoupled from its anorectic actions in the hypothalamus.
Gene Expression in RET/PTC3 and E7 Transgenic Mouse Thyroids: RET/PTC3 But Not E7 Tumors Are Partial and Transient Models of Human Papillary Thyroid Cancers
Authors: Burniat Agnès , Jin Ling , Detours Vincent , Driessens Natacha , Goffard Jean-Christophe , Santoro Massimo , Rothstein Jay , Dumont Jacques E. , Miot Françoise , Corvilain Bernard
Published: June 2008

We studied gene expression profiles in two mouse models of human thyroid carcinoma: the Tg-RET/PTC3 (RP3) and Tg-E7 mice. RP3 fusion gene is the most frequent mutation found in the first wave post-Chernobyl papillary thyroid cancers (PTCs). E7 is an oncoprotein derived from the human papillomavirus 16 responsible for most cervical carcinoma in women. Both transgenic mice develop thyroid hyperplasia followed by solid differentiated carcinoma in older animals. To understand the different steps leading to carcinoma, we analyzed thyroid gene expression in both strains at different ages by microarray technology. Important biological processes were differentially regulated in the two tumor types. In E7 thyroids, cell cycle was the most up-regulated process, an observation consistent with the huge size of these tumors. In RP3 thyroids, contrary to E7 tumors, several human PTC characteristics were observed: overexpression of many immune-related genes, regulation of human PTC markers, up-regulation of EGF-like growth factors and significant regulation of angiogenesis and extracellular matrix remodeling-related genes. However, similarities were incomplete; they did not concern the overall gene expression and were not conserved in old animals. Therefore, RP3 tumors are partial and transient models of human PTC. They constitute a good model, especially in young animals, to study the respective role of the biological processes shared with human PTC and will allow testing drugs targeting these validated variables.
Rosiglitazone Treatment Reduces Diabetic Neuropathy in Streptozotocin-Treated DBA/2J Mice
Authors: Wiggin Timothy D. , Kretzler Matthias , Pennathur Subramaniam , Sullivan Kelli A. , Brosius Frank C. , Feldman Eva L.
Published: June 2008

Diabetic neuropathy (DN) is a common complication of diabetes. Currently, there is no drug treatment to prevent or slow the development of DN. Rosiglitazone (Rosi) is a potent insulin sensitizer and may also slow the development of DN by a mechanism independent of its effect on hyperglycemia. A two by two design was used to test the effect of Rosi treatment on the development of DN. Streptozotocin-induced diabetic DBA/2J mice were treated with Rosi. DN and oxidative stress were quantified, and gene expression was profiled using the Affymetrix Mouse Genome 430 2.0 microarray platform. An informatics approach identified key regulatory elements activated by Rosi. Diabetic DBA/2J mice developed severe hyperglycemia, DN, and elevated oxidative stress. Rosi treatment did not affect hyperglycemia but did reduce oxidative stress and prevented the development of thermal hypoalgesia. Two novel transcription factor binding modules were identified that may control genes correlated to changes in DN after Rosi treatment: SP1F_ZBPF and EGRF_EGRF. These targets may be useful in designing drugs with the same efficacy as Rosi in treating DN but with fewer undesirable effects.
The Need for Leadership and Vision in Dentistry. A Personal View
Authors: Holt Vernon P
Published: June 2008

This paper considers how dentistry has developed in the United Kingdom (UK) over the last 60 years and concludes that dentists have failed to be proactive and to shape the systems for the delivery of an optimal level of care to the population. It suggests that there is a need for far better leadership and for dentists, as individuals and as a profession, to rediscover the sense of vision that they once had and to shape their destinies, rather than accepting the current situation. The author goes on to explain how this might be done.

Since the inception of the National Health Service (NHS), the dental profession in the UK has, to a large extent, been dominated by the politics of the NHS, by changing fee structures and contracts, by reports from the Review Body on Doctors’ and Dentists’ Remuneration (DDRB), and by strategies adopted by successive governments, especially during the last two decades. These strategies have resulted in cohorts of disillusioned dental practitioners reducing their commitment to, or opting out of, NHS contracts and committing themselves, to a greater or lesser extent, to private practice.1 It is now over three years since, for the first time, the proportion of dentistry provided under private contact in the UK, as measured by gross fees, exceeded that provided under NHS contract.

The profession has shown a remarkable lack of imagination in organising itself to provide the best kind of care for patients. Instead of being proactive and visionary, it has allowed itself to become a political football. This has led to the progressive deskilling of many practitioners, and a manifest failure to secure the long-term oral health of patients.

This paper considers how the situation could be improved and looks at four aspects, which are:

1. 21st century dentistry: state of the art versus reality? The contrast between what is clinically possible and what the profession currently delivers.

2. What are we here for? The need for a new vision for dentistry, the profession and the future, and the need for a new sense of mission.

3. A responsibility for the profession. The responsibility of the profession for providing patients (and funding bodies) with advice.

4. Leading the way: a new-look personal development plan. The personal development needs of dentists, with much more emphasis on interpersonal and leadership skills.
Provision of Domiciliary Dental Care in North and West Belfast
Authors: Stevens Anne , Crealey Grainne E , Murray Ashley M
Published: June 2008

Aim

To determine the level of domiciliary care currently provided for patients by general dental practitioners (GDPs) and to investigate factors that influence the provision of domiciliary dental care in an area of high socioeconomic deprivation in North and West Belfast.

Method

A descriptive study, involving a self-administered postal questionnaire sent to GDPs (n=89) in North and West Belfast.

Results

A valid response rate of 67% was achieved. Almost 20% of responding GDPs reported that they did not routinely offer domiciliary dental care. Of those who did, prosthetic treatment was undertaken most commonly, and other more time-consuming treatments such as fillings were referred to the Community Dental Services (CDS). Many GDPs reported not having a full range of domiciliary equipment, with only half of the GDPs surveyed carrying emergency drugs. Reasons cited for not providing the service were lack of time, the perception that patients would be too difficult to manage, and not having the appropriate equipment. The majority of responding dentists (85%) felt that domiciliary care should be referred to the community service.

Conclusion

The rate of domiciliary care provision in North and West Belfast appears to be falling, despite it being an area of high socioeconomic deprivation where the demand for the service is growing. The general perception was that domiciliary care is too time-consuming, that the patients are too difficult to manage, and that there was a lack of appropriate equipment. As a result, the majority of GDPs in North and West Belfast felt that the CDS should care for all domiciliary patients.
NCEPOD: celebrating 20 years
Authors: Martin Ian
Published: June 2008

The National Confidential Enquiry into Patient Outcome and Death (NCEPOD) started life in 1988 as the National Confidential Enquiry into Perioperative Deaths, largely thanks to a positive and rapid response by the government of the day to the publication of The Report of a Confidential Enquiry into Perioperative Deaths, which identified remediable factors in the quality of surgical and anaesthetic care in a sample of patients who had died following surgery. It is fair to say that the prospect of a national programme was not universally applauded, particularly by the surgical fraternity; nonetheless, the dogged determination of the founding fathers, Brendan Devlin and John Lunn, prevailed.
Yorkshire school of surgery opens
Authors: Ronald Nick
Published: June 2008

The College held a launch event on Friday 18 April 2008 at York to mark the opening of a new school of surgery for the region. The event included an education conference to update Yorkshire consultant surgeons and other local surgical trainers on the latest national curriculum and to exchange ideas on how to give their trainees the best skills.
National surgical fellowship scheme
Authors: Williams Norman
Published: June 2008

Traditionally many UK trainees in all surgical specialties have towards the end of their training sought out fellowships in order to enhance their skills and to prepare them for consultancy. Although some of these posts exist in this country others are available overseas. Their availability is spread by word of mouth, their quality is variable, vacancies are often erratic and workforce considerations within the specialty are rarely considered.
Surgical anatomy in the age of EWTD and ISCP
Authors: Mahadevan Vishy
Published: June 2008

Four major new initiatives being implemented nationally are set to have a considerable impact on the nature of surgical training in the UK. When fully operational, these developments will alter the face of surgical training: the European Working Time Directive (EWTD), Modernising Medical Careers (MMC), the Intercollegiate Surgical Curriculum Programme (ISCP) and the new MRCS examination.
How do cancer patients manage unattainable personal goals and regulate their emotions/
Authors: Schroevers Maya , Kraaij Vivian , Garnefski Nadia
Published: June 2008

Objectives This article addressed the role of goal adjustment (i.e. disengagement from unattainable goals and reengagement in alternative goals) and cognitive emotion‐regulation strategies (i.e. rumination, catastrophizing, positive refocusing) in cancer patients' psychological well‐being. We expected that patients who are better able to disengage from unattainable goals, identify alternative goals, and regulate their emotions by positive refocusing and not engaging in rumination and catastrophizing would experience less negative and more positive affect.

Design In this cross‐sectional study, data were collected using a self‐report questionnaire.

Methods Cancer patients (N = 108) were recruited on a psychoeducational meeting aimed to inform them about the illness and its consequences. To examine the relationships between goal adjustment, cognitive emotion‐regulation strategies, and affect, Pearson correlations were calculated and regression analyses were performed.

Results Regression analyses showed that reengaging in meaningful goals and focusing on pleasant issues were significantly associated with more positive affect. Focusing on pleasant issues was also significantly associated with less negative affect, whereas rumination and catastrophizing were significantly associated with more negative affect.

Conclusions Goal reengagement as well as cognitive emotion‐regulation strategies seems to play an important role in cancer patients' psychological well‐being. Health care professionals may assist patients in paying more attention to positive experiences in their daily life and in finding new meaningful goals. Techniques based on mindfulness may be used to assist cancer patients in decreasing the repetitive negative thinking about causes, meanings, and consequences of the illness and helping them to focus attention on the present moment.
Review of Financial Reporting and Global Capital Markets: A History of the International Accounting Standards Committee, 1973–2000
Authors: Richardson Alan J.
Published: June 2008

This review of K. Camfferman and S. A. Zeff, Financial Reporting and Global Capital Markets: A History of the International Accounting Standards Committee, 1973–2000 (Oxford: Oxford University Press, 2007) provides an overview of the work, comments on the authors' approach to the history of the IASC, and comments on the book's contribution to our understanding of the IASC and its place in global financial governance.
Lack of association of liver fat with model parameters of β-cell function in men with impaired glucose tolerance and type 2 diabetes
Authors: Tushuizen Maarten E , Bunck Mathijs C , Pouwels Petra J W , Bontemps Saskia , Mari Andrea , Diamant Michaela
Published: June 2008

Objective

Hepatic steatosis and obesity are components of the metabolic syndrome and risk factors for developing type 2 diabetes (T2DM). We studied how liver fat and body fat distribution relate to various aspects of β-cell function.

Methods

In 12 men with T2DM, 10 men with impaired glucose tolerance (IGT), and 14 age- and body mass index-matched controls, we measured body fat distribution and liver fat by magnetic resonance imaging and spectroscopy. An oral glucose tolerance test was performed to calculate insulin secretory rate (ISR) by C-peptide deconvolution, and β-cell function using a mathematical model that describes ISR as a function of absolute glucose levels (insulin secretory tone and glucose sensitivity), the glucose rate of change (rate sensitivity), and a potentiation factor.

Results

Waist circumference and the various body fat compartments did not differ among groups. IGT had the highest total and late phase insulin secretion (P<0.001), whereas patients had the lowest insulinogenic index adjusted for insulin resistance (P=0.006). In spite of the hypersecretion, IGT had β-cell glucose sensitivity, rate sensitivity, and potentiation similar to controls. Liver fat content was highest in diabetic patients (P=0.004) and showed the strongest association with total and late phase of insulin secretion in the IGT group (r=0.657, P=0.039 and r=0.732, P=0.016 respectively). Model β-cell function variables showed no association with liver fat or body fat compartments.

Conclusions

These data suggest that, in spite of the association of central adiposity and liver fat with T2DM risk, additional, hitherto unknown factors may contribute to β-cell dysfunction in susceptible humans.
‘You’re Wearing That?: Understanding Mothers and Daughters in Conversation’
Authors: Williams Ashley M.
Published: June 2008

Book review of ‘You’re Wearing That? Understanding Mothers and Daughters in Conversation’ by Deborah Tannen, published in 2006 by Ballantine Books, New York.

Deborah Tannen, as Michael Billig (2000: 129) noted in his review of her 1998 book ‘The Argument Culture’, has a particular knack for writing best-sellers that ‘can outstrip the celebrity biographies, cookery books and sex manuals that dominate the non-fiction book trade’. Indeed, Tannen’s latest addition to her oeuvre meant for popular consumption, ‘You’re Wearing That?’ a New York Times bestseller, is no different.
Young women in the Meiji period as linguistic trendsetters
Authors: Bohn Mariko T. , Matsumoto Yoshiko
Published: June 2008

The normative speech associated with Japanese women today has been identified as a product of the Meiji government’s modernization project in the early 20th Century. In this article, we examine the speech style in question, which is found in novels, magazines, and other print media during the Meiji period (1868--1912), in conjunction with other notable expressions of the time (e.g. foreign borrowings). We also examine other cultural expressions of femininity, for example, female students’ clothing and hairstyle. The analysis reveals that female students’ speech style that is now categorized as ‘feminine’ was part of the vernacular, rather than emanating from the context of the school, as is generally asserted. It was criticized by older linguistic norm holders (e.g. educators, novelists) as being coarse, crude and unladylike, in contrast to upper-class women’s speech in the preceding Edo period. Drawing comparisons with the linguistic innovation of current young Japanese women, we suggest that young female speakers of the Meiji period can be viewed as the trendsetters of the era, not simply as passive targets of ideological conditioning.
The Role of Court Lady’s Language in the Historical Norm Construction of Japanese Women’s Language
Authors: Endo Orie
Published: June 2008

This paper traces the development of a pre-modern speech variety known as nyooboo kotoba ‘court lady’s language’ and its role in the construction of normative language for Japanese women. I argue that what is today called joseego or onna kotoba (women’s language) originates in the attempt to regulate women’s speech in pre-modern Japan, in particular, the idea that the language of women in the imperial court (nyooboo kotoba) is gentle, elegant and, hence, feminine, and thus should serve as the ideal model of women’s speech. I also discuss the word formation processes used in nyooboo kotoba, which were believed at the time to render words refined and elegant. I then argue that these word formation processes share much in common with those of the modern wakamonogo ‘youth language’, which is considered rude and corrupt, and that this contradiction illustrates the subjective and ideological nature of these kinds of evaluations.