bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetorheological fluid dampers: A review on structure design and analysis
Authors: Zhu Xiaocong , Jing Xingjian , Cheng Li
Published: March 2012

Magnetorheological fluid technology has gained significant development during the past decades. The application of magnetorheological fluids has grown rapidly in civil engineering, safety engineering, transportation, and life science with the development of magnetorheological fluid–based devices, especially magnetorheological fluid dampers. The magnetorheological fluid dampers could offer an outstanding capability in semiactive vibration control due to excellent dynamical features such as fast response, environmentally robust characteristics, large force capacity, low power consumption, and simple interfaces between electronic input and mechanical output. To address the fast growing demand on magnetorheological fluid damping technology in extensive engineering practices, the state-of-the-art development is presented in this article, which provides a comprehensive review on the structure design and its analysis of magnetorheological fluid dampers (or systems). This can be regarded as a useful complement to several existing reviews in the recent literature on magnetorheological fluids technology, magnetorheological fluid applications, modeling of magnetorheological fluids and dampers, control strategies of magnetorheological fluid systems, and so on. The review begins with an introduction of the basic features and relevant applications of magnetorheological fluids. Then several basic structure design issues of magnetorheological fluid dampers are introduced. Following this, typical magnetorheological dampers are discussed according to the arrangement configurations of magnetorheological fluid cylinders and magnetorheological fluid control valves. Furthermore, reinforced structure designs of magnetorheological fluid dampers are provided, which focus on coil configuration, fluid resistance channel design, and electromagnetic design. Thereafter, design issues of magnetorheological fluid damper systems are discussed, which involves sensor-based magnetorheological fluid damper systems, self-powered magnetorheological fluid damper systems, fail-safe magnetorheological fluid damper systems, and integrated spring magnetorheological fluid damper systems. Importantly, to have a systematic quantitative viewpoint of the analysis and design of magnetorheological fluid dampers, the review ends with a summary of performance analysis issues, including performance specification, analytical modeling, parameter optimization, and so on.
South African Serial Rapists
Authors: Woodhams Jessica , Labuschagne Gérard
Published: March 2012

Serial rapists have the propensity to cause harm to a significant number of victims, meaning that they are of concern to the police as well as to treatment providers. Despite the serious nature of their offending, there are surprisingly few studies that provide information regarding their characteristics, the types of victim they target, or the nature of the sexual offenses they commit, and those studies that do exist are varied in their findings. This study provides a descriptive analysis of serial rape in South Africa. One hundred and nineteen sexual offenses committed by 22 serial rapists were sampled. Information regarding the victims, the offenders, and the crimes they had committed were extracted from police files. The characteristics of victims and offenders are reported as well as the frequencies for 114 different crime scene behaviors. When compared with samples of serial sex offenders from other countries, differences emerged in victim characteristics and crime scene behaviors, including how the victims were targeted, the sexual behaviors engaged in, and the incidence of physical violence. The implications of these observed differences for practice are discussed.
Designing for Social Engagement in Online Social Networks Using Communities-of-Practice Theory and Cognitive Work Analysis
Authors: Euerby Adam , Burns Catherine M.
Published: March 2012

New social networking and social web tools are becoming available and are easing the process of customizing online social environments for enterprises. With these developments, core design efforts have been extending beyond usability for individual users and are beginning to include notions of sociability for the engagement of communities of users. In an effort to make it easier to design for social engagement in an online social environment, the authors developed a domain-community model based on the communities-of-practice concept and the work domain analysis used in cognitive work analysis. Through a case study of University-Community Partnerships for Social Action Research, an international development leadership community of practice, the authors illustrate how the domain-community model could be used to design web components of an online social environment that integrate internal issues of social engagement and external issues of domain effectiveness. It is expected that this model can provide a basis for designers of online communities to more systematically account for social phenomena of collective efforts in a given work domain.
Male Breast Cellular Myofibroblastoma With a Rich Reticulinic Network
Authors: Gurzu Simona , Jung Ioan
Published: March 2012

Myofibroblastoma is a rare mesenchymal tumor located not only in breast but also in extramammary sites. This is the 79th case of breast myofibroblastoma reported in the literature. This tumor presents a great variety of morphological features, which increase the difficulty of differential diagnosis. The authors report a breast myofibroblastoma diagnosed in a 73-year-old male. The article discusses a bilateral gynecomastia and a palpable right breast well-defined tumor, without calcifications on mammography, which was surgically removed. Macroscopically, a well-circumscribed uncapsulated nodule was seen with lobular arrangement on cut section, and microscopically, a nodule with pushing borders and a connective pseudocapsule was seen. The spindle cells were arranged in fascicular clusters, with focally collagen bundles and a rich reticulinic network stained black with Gömöri impregnation. Immunohistochemically, the tumor cells were marked by vimentin, CD34, desmin, and smooth muscle antigen and did not express cytokeratin, S-100 protein, CD99, CD10, and factor VIII–related antigen. More than 90% of the cells expressed estrogen receptor. No recurrences were reported 2 years after surgical excision. This case is a variant of cellular myofibroblastoma, with a rich reticulinic network and scanty collagen bands.
The role of nurses in meeting the health care needs of older people with intellectual disabilities
Authors: Jenkins Robert
Published: March 2012

People with intellectual disabilities are now living longer and as a consequence are likely to have greater physical and mental health needs compared to the general population. Nurses may have a crucial role to play in meeting such needs, although it is unclear whether nurses are prepared for this role. This review of the available literature found little evidence of nurses undertaking effective interventions in meeting the health needs of older people with intellectual disabilities in the UK and Ireland. Nurses have been alerted to the increase in numbers of older people with intellectual disabilities and offered some direction on their future role in this area. Most of the available literature is based mainly on informed opinion rather than research findings.
The Prospective Effect of Life Satisfaction on Life Events
Authors: Luhmann Maike , Lucas Richard E. , Eid Michael , Diener Ed
Published: March 2012

Life satisfaction (LS) is prospectively associated with the occurrence of several major events in work and family life. Analyzing longitudinal data from three nationally representative panel studies ( Ns between 2,321 and 18,692), the authors found that higher LS is associated with a higher likelihood of marriage and childbirth, and with a lower likelihood of marital separation, job loss, starting a new job, and relocating. These effects held even after controlling for gender, age, socioeconomic status, and the Big Five, and were highly consistent across the three samples. Discrete-time survival analyses indicated that for most of these events, temporary rather than stable mechanisms account for the prospective effect of LS. Together, these findings provide evidence that LS is an important predictor of major life outcomes.
Thinking spaces, differently?
Authors: Hubbard Phil
Published: March 2012

This commentary responds to the discussion on the shifting ways that geographers approach questions of space. Questioning what is at stake here, this response asks whether the viewpoints of those involved in the exchange can be said to represent the range of possible positions taken on the importance of space and spatiality in theory.
The footwork of critique
Authors: Asher Kiran
Published: March 2012

In this commentary Kiran Asher reflects on the theoretical and ethical implications of the Karatini-Wainwright exchange in the context of development theory, including its postcolonial, postdevelopment, and feminist variants.
'Online' geriatric assessment procedure for older adults referred for geriatric assessment during an acute care episode for consideration of reliability of triage decisions
Authors: Gray Len , Dakin Lucy , Counsell Steven , Edwards Helen , Wootton Richard , Martin-Khan Melinda
Published: March 2012

Background

Comprehensive geriatric assessment has been shown to improve patient outcomes, but the geriatricians who deliver it are in short-supply. A web-based method of comprehensive geriatric assessment has been developed with the potential to improve access to specialist geriatric expertise. The current study aims to test the reliability and safety of comprehensive geriatric assessment performed "online" in making geriatric triage decisions. It will also explore the accuracy of the procedure in identifying common geriatric syndromes, and its cost relative to conventional "live" consultations.

Methods/Design

The study population will consist of 270 acutely hospitalized patients referred for geriatric consultation at three sites. Paired assessments (live and online) will be conducted by independent, blinded geriatricians and the level of agreement examined. This will be compared with the level of agreement between two independent, blinded geriatricians each consulting with the patient in person (i.e. "live"). Agreement between the triage decision from live-live assessments and between the triage decision from live-online assessments will be calculated using kappa statistics. Agreement between the online and live detection of common geriatric syndromes will also be assessed using kappa statistics. Resource use data will be collected for online and live-live assessments to allow comparison between the two procedures.

Discussion

If the online approach is found to be less precise than live assessment, further analysis will seek to identify patient subgroups where disagreement is more likely. This may enable a protocol to be developed that avoids unsafe clinical decisions at a distance.

Trial registration

Trial registration number: ACTRN12611000936921
Differential expression of cancer associated proteins in breast milk based on age at first full term pregnancy
Authors: Qin Wenyi , Zhang Ke , Kliethermes Beth , Ruhlen Rachel L , Browne Eva P , Arcaro Kathleen F , Sauter Edward R
Published: March 2012

Background

First full term pregnancy (FFTP) completed at a young age has been linked to low long term breast cancer risk, whereas late FFTP pregnancy age confers high long term risk, compared to nulliparity. Our hypothesis was that proteins linked to breast cancer would be differentially expressed in human milk collected at three time points during lactation based on age at FFTP.

Methods

We analyzed breast milk from 72 lactating women. Samples were collected within 10 days of the onset of lactation (baseline-BL), two months after lactation started and during breast weaning (W). We measured 16 proteins (11 kallikreins (KLKs), basic fibroblast growth factor, YKL-40, neutrophil gelatinase-associated lipocalin and transforming growth factor (TGF) β-1 and -2) associated with breast cancer, most known to be secreted into milk.

Results

During lactation there was a significant change in the expression of 14 proteins in women < 26 years old and 9 proteins in women > = 26 at FFTP. The most significant (p < .001) changes from BL to W in women divided by FFTP age (< 26 vs. > = 26) were in KLK3,6, 8, and TGFβ2 in women < 26; and KLK6, 8, and TGFβ2 in women > = 26. There was a significant increase (p = .022) in KLK8 expression from BL to W depending on FFTP age. Examination of DNA methylation in the promoter region of KLK6 revealed high levels of methylation that did not explain the observed changes in protein levels. On the other hand, KLK6 and TGFβ1 expression were significantly associated (r2 = .43, p = .0050).

Conclusions

The expression profile of milk proteins linked to breast cancer is influenced by age at FFTP. These proteins may play a role in future cancer risk.
Synthetic Lethal Screen Identifies NF-κB as a Target for Combination Therapy with Topotecan for patients with Neuroblastoma
Authors: Tsang Patricia S , Cheuk Adam T , Chen Qing-Rong , Song Young K , Badgett Thomas C , Wei Jun S , Khan Javed
Published: March 2012

Background

Despite aggressive multimodal treatments the overall survival of patients with high-risk neuroblastoma remains poor. The aim of this study was to identify novel combination chemotherapy to improve survival rate in patients with high-risk neuroblastoma.

Methods

We took a synthetic lethal approach using a siRNA library targeting 418 apoptosis-related genes and identified genes and pathways whose inhibition synergized with topotecan. Microarray analyses of cells treated with topotecan were performed to identify if the same genes or pathways were altered by the drug. An inhibitor of this pathway was used in combination with topotecan to confirm synergism by in vitro and in vivo studies.

Results

We found that there were nine genes whose suppression synergized with topotecan to enhance cell death, and the NF-κB signaling pathway was significantly enriched. Microarray analysis of cells treated with topotecan revealed a significant enrichment of NF-κB target genes among the differentially altered genes, suggesting that NF-κB pathway was activated in the treated cells. Combination of topotecan and known NF-κB inhibitors (NSC 676914 or bortezomib) significantly reduced cell growth and induced caspase 3 activity in vitro. Furthermore, in a neuroblastoma xenograft mouse model, combined treatment of topotecan and bortezomib significantly delayed tumor formation compared to single-drug treatments.

Conclusions

Synthetic lethal screening provides a rational approach for selecting drugs for use in combination therapy and warrants clinical evaluation of the efficacy of the combination of topotecan and bortezomib or other NF-κB inhibitors in patients with high risk neuroblastoma.
Effects of some anti-diabetic and cardioprotective agents on proliferation and apoptosis of human coronary artery endothelial cells
Authors: Eriksson Linnéa , Erdogdu Özlem , Nyström Thomas , Zhang Qimin , Sjöholm Åke
Published: March 2012

Background

The leading cause of death for patients suffering from diabetes is macrovascular disease. Endothelial dysfunction is often observed in type 2 diabetic patients and it is considered to be an important early event in the pathogenesis of atherogenesis and cardiovascular disease. Many drugs are clinically applied to treat diabetic patients. However, little is known whether these agents directly interfere with endothelial cell proliferation and apoptosis. This study therefore aimed to investigate how anti-diabetic and cardioprotective agents affect human coronary artery endothelial cells (HCAECs).

Methods

The effect of anti-diabetic and cardioprotective agents on HCAEC viability, proliferation and apoptosis was studied. Viability was assessed using Trypan blue exclusion; proliferation in 5 mM and 11 mM of glucose was analyzed using [3H]thymidine incorporation. Lipoapoptosis of the cells was investigated by determining caspase-3 activity and the subsequent DNA fragmentation after incubation with the free fatty acid palmitate, mimicking diabetic lipotoxicity.

Results

Our data show that insulin, metformin, BLX-1002, and rosuvastatin improved HCAEC viability and they could also significantly increase cell proliferation in low glucose. The proliferative effect of insulin and BLX-1002 was also evident at 11 mM of glucose. In addition, insulin, metformin, BLX-1002, pioglitazone, and candesartan significantly decreased the caspase-3 activity and the subsequent DNA fragmentation evoked by palmitate, suggesting a protective effect of the drugs against lipoapoptosis.

Conclusion

Our results suggest that the anti-diabetic and cardioprotective agents mentioned above have direct and beneficial effects on endothelial cell viability, regeneration and apoptosis. This may add yet another valuable property to their therapeutic effect, increasing their clinical utility in type 2 diabetic patients in whom endothelial dysfunction is a prominent feature that adversely affect their survival.
Downregulation of HuR as a new mechanism of doxorubicin resistance in breast cancer cells
Authors: Latorre Elisa , Tebaldi Toma , Viero Gabriella , Spartà Antonino Maria , Quattrone Alessandro , Provenzani Alessandro
Published: March 2012

Background

HuR, an RNA binding protein involved in the post-transcriptional regulation of a wide spectrum of mRNAs, has been demonstrated to be a determinant of carcinogenesis and tumor aggressiveness in several cancer types. In this study, we investigated the role of HuR in the apoptosis and in the chemoresistance induced by the widely used anticancer drug doxorubicin in human breast cancer cells (MCF-7).

Results

We showed that HuR acts in the early phase of cell response to doxorubicin, being induced to translocate into the cytoplasm upon phosphorylation. Reducing HuR levels diminished the apoptotic response to doxorubicin. Doxorubicin-induced apoptosis was also correlated with the presence of HuR in the cytoplasm. Rottlerin, which was able to block HuR nuclear export, had correspondingly antagonistic effects with doxorubicin on cell toxicity. The proapoptotic activity of HuR was not due to cleavage to an active form, as was previously reported. In in vitro selected doxorubicin resistant MCF-7 cells (MCF-7/doxoR) overexpressing the multidrug resistance (MDR) related ABCG2 transporter, we observed a significant HuR downregulation that was paralleled by a corresponding downregulation of HuR targets and by loss of rottlerin toxicity. Restoration of HuR expression in these cells resensitized MCF-7/doxoR cells to doxorubicin, reactivating the apoptotic response.

Conclusions

The present study shows that HuR is necessary to elicit the apoptotic cell response to doxorubicin and that restoration of HuR expression in resistant cells resensitizes them to the action of this drug, thereby identifying HuR as a key protein in doxorubicin pharmacology.
Timing and source of subtype-C HIV-1 superinfection in the newly infected partner of Zambian couples with disparate viruses
Authors: Kraft Colleen S , Basu Debby , Hawkins Paulina A , Hraber Peter T , Chomba Elwyn , Mulenga Joseph , Kilembe William , Khu Naw H , Derdeyn Cynthia A , Allen Susan A , Manigart Olivier , Hunter Eric
Published: March 2012

Background

HIV-1 superinfection occurs at varying frequencies in different at risk populations. Though seroincidence is decreased, in the negative partner of HIV-discordant couples after joint testing and counseling in the Zambia Emory HIV Research Project (ZEHRP) cohort, the annual infection rate remains relatively high at 7-8%. Based on sequencing within the gp41 region of each partner's virus, 24% of new infections between 2004 and 2008 were the result of transmission from a non-spousal partner. Since these seroconvertors and their spouses have disparate epidemiologically-unlinked viruses, there is a risk of superinfection within the marriage. We have, therefore, investigated the incidence and viral origin of superinfection in these couples.

Results

Superinfection was detected by heteroduplex mobility assay (HMA), degenerate base counting of the gp41 sequence, or by phylogenetic analysis of the longitudinal sequences. It was confirmed by full-length env single genome amplification and phylogenetic analysis. In 22 couples (44 individuals), followed for up to five years, three of the newly infected (initially HIV uninfected) partners became superinfected. In each case superinfection occurred during the first 12 months following initial infection of the negative partner, and in each case the superinfecting virus was derived from a non-spousal partner. In addition, one probable case of intra-couple HIV-1 superinfection was observed in a chronically infected partner at the time of his seroconverting spouse's initial viremia. Extensive recombination within the env gene was observed following superinfection.

Conclusions

In this subtype-C discordant couple cohort, superinfection, during the first year after HIV-1 infection of the previously negative partner, occurred at a rate similar to primary infection (13.6% [95% CI 5.2-34.8] vs 7.8% [7.1-8.6]). While limited intra-couple superinfection may in part reflect continued condom usage within couples, this and our lack of detecting newly superinfected individuals after one year of primary infection raise the possibility that immunological resistance to intra-subtype superinfection may develop over time in subtype C infected individuals.
Serum 25-hydroxyvitamin D3, parathyroid hormone and blood pressure in an elderly cohort from Germany: a cross-sectional study
Authors: Jungert Alexandra , Roth Heinz J , Neuhäuser-Berthold Monika
Published: March 2012

Background

Although several studies indicate a link between vitamin D status and blood pressure (BP), the results are inconsistent. The purpose of this study is to investigate whether in predominantly non-obese elderly people without vitamin D deficiency or very high intact parathyroid hormone (iPTH) levels serum 25-hydroxyvitamin D3 [25(OH)D3] and iPTH are independently associated with BP.

Methods

Cross-sectional data of 132 non-institutionalised subjects (90 women and 42 men, aged 66- 96 years) from Giessen, Germany, were analysed. Serum 25(OH)D3 and iPTH were measured by an electrochemiluminescence immunoassay and BP was determined with a sphygmomanometer. We performed univariate and multiple regression analyses to examine the influence of 25(OH)D3 and iPTH on BP with adjustments for age, body composition and lifestyle factors.

Results

While iPTH had no impact on BP, 25(OH)D3 was negatively associated with systolic BP in men, but not in women. After splitting the cohort into antihypertensive medication users and non-users, 25(OH)D3 was a significant predictor for systolic and diastolic BP only in men not receiving antihypertensive medicine, even after multiple adjustment. Adjustment for 25(OH)D3 resulted in an inverse association of iPTH with diastolic BP also only in men without intake of antihypertensive medicine.

Conclusions

In elderly men without vitamin D deficiency and not taking antihypertensive medicine, 25(OH)D3 may be a negative determinant of BP, independent of iPTH, body composition and lifestyle factors. Furthermore, iPTH may be an independent negative determinant of diastolic BP in men not taking antihypertensive medicine.
Clostridium difficile infection in an Iranian hospital
Authors: Jalali Mohammad , Khorvash Farzin , Warriner Keith , Weese J Scott
Published: March 2012

Background

Clostridium difficile infection (CDI) is an important cause of morbidity and mortality internationally, yet there are important regional differences in the epidemiology and microbiology of disease. Most reports have come from North America and Europe, with limited information from other regions, including the Middle East. Given the changes in the epidemiology of CDI in developed countries, particularly associated with the dissemination of hypervirulent epidemic clones, an understanding of the epidemiology and microbiology of CDI in diverse regions is warranted. This study involved collection of stool samples from individuals with diarrhea at the Isfahan University of Medical Sciences Teaching Hospital, Isfahan, Iran, between October 2010 and March 2011. Selective enrichment culture for C. difficile was performed and isolates were characterised using ribotyping, PCR for the detection of tcdA, tcdB and cdtB genes, and tcdC sequence analysis.

Findings

Clostridium difficile was isolated from 19/89 (21%) stool samples of 17/86 (20%) patients. 13/17 (77%) cases of CDI were hospital-associated. Patients with CDI were significantly older (43 ± 28y) than those with non-CDI diarrhea (24, ± 26y)(P = 0.018). All isolates were toxigenic, and possessed genes encoding for toxins A and B. Six (32%) of 19 isolates also possessed cdtB. Twelve ribotypes were identified. Ribotype 078/toxinotype V was most common, accounting for 4 (21%) of isolates. A single isolate of a different toxinotype V ribotype was identified, as was a toxinotype XXIV isolate. The remaining isolates consisted of 9 different toxinotype 0 ribotypes.

Conclusions

CDI is an important cause of diarrhea in patients in this hospital. The diversity of ribotypes was striking, and the number of different types suggests the presence of a broad range of strains in the community, the hospital or both. The predominance of toxinotype V strains, which have been associated with community-associated disease and food animals, was unexpected and possible sources of this type require further investigation.
The ERβ Ligand 5α-androstane, 3β,17β-diol (3β-diol) Regulates Hypothalamic Oxytocin (Oxt) Gene Expression
Authors: Sharma Dharmendra , Handa Robert J. , Uht Rosalie M.
Published: March 2012

The endocrine component of the stress response is regulated by glucocorticoids and sex steroids. Testosterone down-regulates hypothalamic-pituitary-adrenal (HPA) axis activity; however, the mechanisms by which it does so are poorly understood. A candidate testosterone target is the oxytocin gene (Oxt), given that it too inhibits HPA activity. Within the paraventricular nucleus of the hypothalamus, oxytocinergic neurons involved in regulating the stress response do not express androgen receptors but do express estrogen receptor-β (ERβ), which binds the dihydrotestosterone metabolite 3β,17β-diol (3β-diol). Testosterone regulation of the HPA axis thus appears to involve the conversion to the ERβ-selective ligand 5α-androstane, 3β-diol. To study mechanisms by which 3β-diol could regulate Oxt expression, we used a hypothalamic neuronal cell line derived from embryonic mice that expresses Oxt constitutively and compared 3β-diol with estradiol (E2) effects. E2 and 3β-diol elicited a phasic response in Oxt mRNA levels. In the presence of either ligand, Oxt mRNA levels were increased for at least 60 min and returned to baseline by 2 h. ERβ occupancy preceded an increase in Oxt mRNA levels in the presence of 3β-diol but not E2. In tandem with ERβ occupancy, 3β-diol increased occupancy of the Oxt promoter by cAMP response element-binding protein and steroid receptor coactivator-1 at 30 min. At the same time, 3β-diol led to the increased acetylation of histone H4 but not H3. Taken together, the data suggest that in the presence of 3β-diol, ERβ associates with cAMP response element-binding protein and steroid receptor coactivator-1 to form a functional complex that drives Oxt gene expression.
AMPK Enhances Insulin-Stimulated GLUT4 Regulation via Lowering Membrane Cholesterol
Authors: Habegger Kirk M. , Hoffman Nolan J. , Ridenour Colin M. , Brozinick Joseph T. , Elmendorf Jeffrey S.
Published: March 2012

AMP-activated protein kinase (AMPK) enhances glucose transporter GLUT4 regulation. AMPK also suppresses energy-consuming pathways such as cholesterol synthesis. Interestingly, recent in vitro and in vivo data suggest that excess membrane cholesterol impairs GLUT4 regulation. Therefore, this study tested whether a beneficial, GLUT4-regulatory aspect of AMPK stimulation involved cholesterol lowering. Using L6 myotubes stably expressing an exofacial myc-epitope-tagged-GLUT4, AMPK stimulation by 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR; 45 min, 1 mm) or 2,4-dinitrophenol (DNP; 30 min, 200 μm) increased cell surface GLUT4myc labeling by approximately ∼25% (P < 0.05). Insulin (20 min, 100 nm) also increased GLUT4myc labeling by about 50% (P < 0.05), which was further enhanced (∼25%, P < 0.05) by AICAR or DNP. Consistent with AMPK-mediated suppression of cholesterol synthesis, AICAR and DNP decreased membrane cholesterol by 20–25% (P < 0.05). Whereas AMPK knockdown prevented the enhanced basal and insulin-stimulated GLUT4myc labeling by AICAR and DNP, cholesterol replenishment only blocked the AMPK-associated enhancement in insulin action. Cells cultured in a hyperinsulinemic milieu, resembling conditions in vivo that promote the progression/worsening of insulin resistance, displayed an increase in membrane cholesterol. This occurred concomitantly with a loss of cortical filamentous actin (F-actin) and defects in GLUT4 regulation by insulin. These derangements were prevented by AMPK stimulation. Examination of skeletal muscle from insulin-resistant Zucker rats revealed a similar elevation in membrane cholesterol and loss of F-actin. Lowering cholesterol to control levels restored F-actin structure and insulin sensitivity. In conclusion, these data suggest a novel aspect of GLUT4 regulation by AMPK involves membrane cholesterol lowering. Moreover, this AMPK-mediated process protected against hyperinsulinemia-induced insulin resistance.
Effects of a High-Fat Diet Exposure in Utero on the Metabolic Syndrome-Like Phenomenon in Mouse Offspring through Epigenetic Changes in Adipocytokine Gene Expression
Authors: Masuyama Hisashi , Hiramatsu Yuji
Published: March 2012

The links between obesity in parents and their offspring and the role of genes and a shared environment are not completely understood. Adipocytokines such as leptin and adiponectin play important roles in glucose and lipid metabolism. Therefore, we examined whether the offspring from dams exposed to a high-fat diet during pregnancy (OH mice) exhibited hypertension, insulin resistance, and hyperlipidemia along with epigenetic changes in the expression of adipocytokine genes. OH mice were significantly heavier than the offspring of dams exposed to a control diet during pregnancy (OC mice) from 14 wk of age after an increased caloric intake from 8 wk. OH mice exhibited higher blood pressure and worse glucose tolerance than the OC mice at 24 wk. Total triglyceride and leptin levels were significantly higher and the adiponectin level was significantly lower in OH compared with OC mice at 12 wk of age. This was associated with changes in leptin and adiponectin expression in white adipose tissue. There were lower acetylation and higher methylation levels of histone H3 at lysine 9 of the promoter of adiponectin in adipose tissues of OH mice at 2 wk of age as well as at 12 and 24 wk of age compared with OC mice. In contrast, methylation of histone 4 at lysine 20 in the leptin promoter was significantly higher in OH compared with OC mice. Thus, exposure to a high-fat diet in utero might cause a metabolic syndrome-like phenomenon through epigenetic modifications of adipocytokine, adiponectin, and leptin gene expression.
The diversity of hydrostatic skeletons
Authors: Kier William M.
Published: March 2012

A remarkably diverse group of organisms rely on a hydrostatic skeleton for support, movement, muscular antagonism and the amplification of the force and displacement of muscle contraction. In hydrostatic skeletons, force is transmitted not through rigid skeletal elements but instead by internal pressure. Functioning of these systems depends on the fact that they are essentially constant in volume as they consist of relatively incompressible fluids and tissue. Contraction of muscle and the resulting decrease in one of the dimensions thus results in an increase in another dimension. By actively (with muscle) or passively (with connective tissue) controlling the various dimensions, a wide array of deformations, movements and changes in stiffness can be created. An amazing range of animals and animal structures rely on this form of skeletal support, including anemones and other polyps, the extremely diverse wormlike invertebrates, the tube feet of echinoderms, mammalian and turtle penises, the feet of burrowing bivalves and snails, and the legs of spiders. In addition, there are structures such as the arms and tentacles of cephalopods, the tongue of mammals and the trunk of the elephant that also rely on hydrostatic skeletal support but lack the fluid-filled cavities that characterize this skeletal type. Although we normally consider arthropods to rely on a rigid exoskeleton, a hydrostatic skeleton provides skeletal support immediately following molting and also during the larval stage for many insects. Thus, the majority of animals on earth rely on hydrostatic skeletons.
Maternal influences on early development: preferred temperature prior to oviposition hastens embryogenesis and enhances offspring traits in the Children’s python, Antaresia childreni
Authors: Lorioux Sophie , DeNardo Dale F. , Gorelick Root , Lourdais Olivier
Published: March 2012

Embryonic life is particularly sensitive to its surroundings, and the developmental environment can have long-lasting effects on offspring. In oviparous species, the impacts of the developmental environment on offspring traits are mostly examined during development within the egg. However, as more than 25% of the development of squamate reptiles can occur prior to oviposition, we explored the effect of thermal conditions on development prior to oviposition in an oviparous snake species, the Children’s python (Antaresia childreni). We housed gravid female pythons under three thermal cycles: an optimal regime that reflected maternal preference in a non-constrained environment (constant preferred body temperature of gravid females, Tset=31.5°C) and two mildly suboptimal regimes that shared the same mean temperature of 27.7°C, but differed in the duration at Tset. In one of the constraining regimes, females had access to Tset for 4 h daily whereas in the other regime, females never reached Tset (maximal temperature of 29.0°C). Thermal treatments were maintained throughout gravidity in all three groups, but, after oviposition, all eggs were incubated at Tset until hatching. Compared with the optimal regime, the two suboptimal regimes had a longer duration of gravidity, which resulted in delayed hatching. Between the two suboptimal regimes, gravidity was significantly shorter in the treatment that included time at Tset. Furthermore, suboptimal regimes influenced offspring traits at hatching, including body morphology, antipredator behavior, strength and metabolism. However, partial access to maternal Tset significantly enhanced several offspring traits, including performance. Our results demonstrate the importance of time at Tset on early development and suggest an adaptive significance of maternal thermoregulation prior to oviposition.
The metabolism of histamine in theDrosophilaoptic lobe involves an ommatidial pathway: β-alanine recycles through the retina
Authors: Borycz Janusz , Borycz Jolanta A. , Edwards Tara N. , Boulianne Gabrielle L. , Meinertzhagen Ian A.
Published: March 2012

Flies recycle the photoreceptor neurotransmitter histamine by conjugating it to β-alanine to form β-alanyl-histamine (carcinine). The conjugation is regulated by Ebony, while Tan hydrolyses carcinine, releasing histamine and β-alanine. In Drosophila, β-alanine synthesis occurs either from uracil or from the decarboxylation of aspartate but detailed roles for the enzymes responsible remain unclear. Immunohistochemically detected β-alanine is present throughout the fly’s entire brain, and is enhanced in the retina especially in the pseudocone, pigment and photoreceptor cells of the ommatidia. HPLC determinations reveal 10.7 ng of β-alanine in the wild-type head, roughly five times more than histamine. When wild-type flies drink uracil their head β-alanine increases more than after drinking l-aspartic acid, indicating the effectiveness of the uracil pathway. Mutants of black, which lack aspartate decarboxylase, cannot synthesize β-alanine from l-aspartate but can still synthesize it efficiently from uracil. Our findings demonstrate a novel function for pigment cells, which not only screen ommatidia from stray light but also store and transport β-alanine and carcinine. This role is consistent with a β-alanine-dependent histamine recycling pathway occurring not only in the photoreceptor terminals in the lamina neuropile, where carcinine occurs in marginal glia, but vertically via a long pathway that involves the retina. The lamina’s marginal glia are also a hub involved in the storage and/or disposal of carcinine and β-alanine.
Adiponectin effects and gene expression in rainbow trout: an in vivo and in vitro approach
Authors: Sánchez-Gurmaches Juan , Cruz-Garcia Lourdes , Gutiérrez Joaquím , Navarro Isabel
Published: March 2012

Here we present the presence of adiponectin and adiponectin receptors [type 1 (adipoR1) and type 2 (adipoR2)] in rainbow trout (Oncorhynchus mykiss) tissues and cell cultures together with the response to different scenarios. In response to fasting, adiponectin expression was up-regulated in adipose tissue, while the expression of its receptors increased in white and red muscle. Insulin injection decreased adipoR1 expression in white and red muscles. We deduce that the adipoRs in trout muscle show opposite responses to increasing insulin plasma levels, which may maintain sensitivity to insulin in this tissue. Adiponectin expression was inhibited by the inflammatory effect of lipopolysaccharide (LPS) in adipose tissue and red muscle. Moreover, results indicate that LPS may lead to mobilization of fat reserves, increasing adipoR1 expression in adipose tissue. The effects of LPS could be mediated through tumour necrosis factor α (TNFα), at least in red muscle. Insulin, growth hormone and TNFα all diminished expression of adipoR2 in adipocytes and adipoR1 in myotubes, while insulin increased the expression of adipoR2 in the muscle cells. Adiponectin activates Akt in rainbow trout myotubes, which may lead to an increase in fatty acid uptake and oxidation. Overall, our results show that the adiponectin system responds differently to various physiological challenges and that it is hormonally controlled in vivo and in vitro. To the best of our knowledge, this is the first time this has been demonstrated in teleosts, and it may be a valuable contribution to our understanding of adipokines in fish.
Exceptional cardiac anoxia tolerance in tilapia (Oreochromis hybrid)
Authors: Lague Sabine L. , Speers-Roesch Ben , Richards Jeffrey G. , Farrell Anthony P.
Published: March 2012

Anoxic survival requires the matching of cardiac ATP supply (i.e. maximum glycolytic potential, MGP) and demand (i.e. cardiac power output, PO). We examined the idea that the previously observed in vivo downregulation of cardiac function during exposure to severe hypoxia in tilapia (Oreochromis hybrid) represents a physiological strategy to reduce routine PO to within the heart’s MGP. The MGP of the ectothermic vertebrate heart has previously been suggested to be ∼70 nmol ATP s–1 g–1, sustaining a PO of ∼0.7 mW g–1 at 15°C. We developed an in situ perfused heart preparation for tilapia (Oreochromis hybrid) and characterized the routine and maximum cardiac performance under both normoxic (>20 kPa O2) and severely hypoxic perfusion conditions (<0.20 kPa O2) at pH 7.75 and 22°C. The additive effects of acidosis (pH 7.25) and chemical anoxia (1 mmol l–1 NaCN) on cardiac performance in severe hypoxia were also examined. Under normoxic conditions, cardiac performance and myocardial oxygen consumption rate were comparable to those of other teleosts. The tilapia heart maintained a routine normoxic cardiac output (Q) and PO under all hypoxic conditions, a result that contrasts with the hypoxic cardiac downregulation previously observed in vivo under less severe conditions. Thus, we conclude that the in vivo downregulation of routine cardiac performance in hypoxia is not needed in tilapia to balance cardiac energy supply and demand. Indeed, the MGP of the tilapia heart proved to be quite exceptional. Measurements of myocardial lactate efflux during severe hypoxia were used to calculate the MGP of the tilapia heart. The MGP was estimated to be 172 nmol ATP s–1 g–1 at 22°C, and allowed the heart to generate a POmax of at least ∼3.1 mW g–1, which is only 30% lower than the POmax observed with normoxia. Even with this MGP, the additional challenge of acidosis during severe hypoxia decreased maximum ATP turnover rate and POmax by 30% compared with severe hypoxia alone, suggesting that there are probably direct effects of acidosis on cardiac contractility. We conclude that the high maximum glycolytic ATP turnover rate and levels of PO, which exceed those measured in other ectothermic vertebrate hearts, probably convey a previously unreported anoxia tolerance of the tilapia heart, but a tolerance that may be tempered in vivo by the accumulation of acidotic waste during anoxia.
Relative contributions of pigments and biophotonic nanostructures to natural color production: a case study in budgerigar (Melopsittacus undulatus) feathers
Authors: D’Alba Liliana , Kieffer Leah , Shawkey Matthew D.
Published: March 2012

Understanding the mechanistic bases of natural color diversity can provide insight into its evolution and inspiration for biomimetic optical structures. Metazoans can be colored by absorption of light from pigments or by scattering of light from biophotonic nanostructures, and these mechanisms have largely been treated as distinct. However, the interactions between them have rarely been examined. Captive breeding of budgerigars (Aves, Psittacidae, Melopsittacus undulatus) has produced a wide variety of color morphs spanning the majority of the spectrum visible to birds, including the ultraviolet, and thus they have been used as examples of hypothesized structure–pigment interactions. However, empirical data testing these interactions in this excellent model system are lacking. Here we used ultraviolet–visible spectrometry, light and electron microscopy, pigment extraction experiments and optical modeling to examine the physical bases of color production in seven budgerigar morphs, including grey and chromatic (purple to yellow) colors. Feathers from all morphs contained quasi-ordered air–keratin ‘spongy layer’ matrices, but these were highly reduced and irregular in grey and yellow feathers. Similarly, all feathers but yellow and grey had a layer of melanin-containing melanosomes basal to the spongy layer. The presence of melanosomes likely increases color saturation produced by spongy layers whereas their absence may allow increased expression of yellow colors. Finally, extraction of yellow pigments caused some degree of color change in all feathers except purple and grey, suggesting that their presence and contribution to color production is more widespread than previously thought. These data illustrate how interactions between structures and pigments can increase the range of colors attainable in birds and potentially in synthetic systems.
Experience with a two-tier reflex gFOBT/FIT strategy in a national bowel screening programme
Authors: Fraser Callum G , Digby Jayne , McDonald Paula J , Strachan Judith A , Carey Francis A , Steele Robert J C
Published: March 2012

Objectives

To evaluate a two-tier reflex guaiac-based faecal occult blood test (gFOBT)/faecal immunochemical test (FIT) algorithm in screening for colorectal cancer.

Setting

Fourth screening round in NHS Tayside (Scotland).

Methods

gFOBT were sent to 50–74-year-olds. Participants with five or six windows positive were offered colonoscopy. Participants with one to four windows positive were sent a FIT and, if positive, were offered colonoscopy. Participants providing an untestable gFOBT were sent a FIT and, if positive, were offered colonoscopy. Outcomes following positive results, cancer stages and key performance indicators were assessed.

Results

Of 131,885 invited, 73,315 (55.6%) responded. There were 66,957 (91.3%) negative, 241 (0.3%) strong positive, 5230 (7.1%) weak positive and 887 (1.2%) untestable results. The 241 participants who had five or six windows positive had more cancers than those positive by other routes: only 3 of the 30 cancers (9.7%) were Dukes' A. Among the 983 positive results from the weak positive gFOBT then positive FIT route, there were fewer cancers and more normal colonoscopies, but more adenomas than in the group with a strong positive gFOBT. In those with an untestable gFOBT, 77 had a positive FIT result, with fewer true and more false positive results than in the other groups. Fewer males had cancer and stages were earlier than in females, but more had adenoma. The detection rate for cancer was 0.18% and the PPV for cancer and all adenomas was 41.3%.

Conclusions

The algorithm and FIT following a weak positive gFOBT have advantages. FIT following an untestable gFOBT warrants review.
Comparison of screening methods for conductive hearing loss identification in children: low-cost proposal
Authors: Samelli A G , Rabelo C M , Pereira M B , Portela M N , Sanches S G G , Neves-Lobo I F
Published: March 2012

Objective

To evaluate the effectiveness of two screening methods (imitanciometry screening and questionnaire) to identify children at risk for conductive hearing loss, comparing this data with complete audiologic evaluation.

Methods

Of 507 children aged between three and six, 111 completed all procedures. The observational methods used were: imitanciometry screening, a questionnaire to identify risk factors for hearing loss and complete audiologic evaluation. Results obtained in the first two instruments were compared with results from complete audiologic evaluation (gold standard). From these comparisons, sensitivity and specificity, accuracy, positive and negative predictive values, and odds ratio were determined for the two screening methods and for the combination of both methods.

Results

The two methods applied in series (questionnaire and after imitanciometry screening) showed a greater odds ratio and better correlation between sensitivity and proportion of false-positives (ROC curve).

Conclusion

Combining the two tests in series improved screening accuracy. This combination was the best tool for identifying children at risk for conductive hearing loss.
A Re-Solving Heuristic with Bounded Revenue Loss for Network Revenue Management with Customer Choice
Authors: Jasin Stefanus , Kumar Sunil
Published: March 2012

We consider a network revenue management problem with customer choice and exogenous prices. We study the performance of a class of certainty-equivalent heuristic control policies. These heuristics periodically re-solve the deterministic linear program (DLP) that results when all future random variables are replaced by their average values and implement the solutions in a probabilistic manner. We provide an upper bound for the expected revenue loss under such policies when compared to the optimal policy. Using this bound, we construct a schedule of re-solving times such that the resulting expected revenue loss, obtained by re-solving the DLP at these times and implementing the solution as a probabilistic scheme, is bounded by a constant that is independent of the size of the problem.