bluuebunny/crossref_metadata_2025 huggingface dataset:
Welfare for Profit: Moral, Empirical and Theoretical Perspectives
Authors: Gilbert Neil
Published: January 2009

Since the 1960s there has been an increasing number of proprietary agencies engaged in the delivery of social services in the United States. This development has generally been greeted with disfavour by welfare state advocates. Various arguments have been put forward against welfare for profit on moral, empirical and theoretical grounds. This paper analyzes these arguments and proposes several basic conditions that would seem to have significant bearing on the choice between profit and nonprofit providers for a given service.
Postmodern Social Policy: A Contradiction in Terms?
Authors: Hillyard Paddy , Watson Sophie
Published: January 2009

The aim of this article is to present a less negative and more rounded analysis of the potential contribution of postmodernism to social policy than that presented by Taylor-Gooby (1994) in this journal entitled ‘Postmodernism: A Great Leap Backwards?’. It covers four major themes. First, it examines Foucault's ideas on power/knowledge, the body, discipline and surveillance. Second, the article explores the connections between feminism, postmodernism and social policy. Third, it analyses theories of the poststructural state. Fourth, it considers a neglected topic in the subject of space and assesses the contribution of postmodern discourses of spatiality and their relevance to social policy. The article acknowledges the contradiction arising from post-modernism's critique of meta-theory and mainstream social policy's commitment to universalism, but concludes that the answer does not lie in the universal rejection of postmodernism but in the use of the ideas and insights to move the discipline in new directions.
Researching Living Standards: Some Problems and Some Findings
Authors: Morris Lydia
Published: January 2009

This article reports on comparative research into the living standards of unemployed couples claiming Income Support, couples claiming in-work benefits and couples in receipt of a male median wage. The data reveal high levels of debt and credit dependence across the whole sample, which have a particularly damaging impact on the daily consumption patterns of the unemployed group. The problems this raises for comparative judgements about living standards are discussed, most notably the need for a longitudinal perspective in both the analysis of financial circumstances and the interpretation of data on current standards of living.
Feminism and Child Daycare
Authors: Randall Vicky
Published: January 2009

This article explores some of the main reasons why feminist mobilisation around the issue of child daycare in Britain has been so limited and its impact so modest. It describes this mobilisation, comparing it with experience in other countries and with mobilisation on other issues. It suggests that the modest achievement to date is largely attributable to factors other than the lack of feminist pressure. Indeed feminist reservations were partly a realistic response to these external constraints. But they were also a consequence of the particular character of second wave feminism in Britain and of the questions posed by the issue of childcare for feminists. These questions included the nature and proper role of the state, motherhood, the value of paid employment for women, social class and the tension between short and long-term strategies for social change.
Women and Health in China: Anatomy, Destiny and Politics
Authors: Pearson Veronica
Published: January 2009

A number of circumstances have combined in the reform era in China to put women at a more disadvantageous position now than at any other time since 1949. Some of them reflect age-old prejudices, others are the result of the economic reforms, but the two join in a synthesis to threaten women's improved status. Health factors that have particularly impinged on women include: the one-child policy and the skewed birth ratio in favour of boys that this has led to; very clear problems in the area of mental health, including a suicide rate which is much higher for women than for men; kidnapping; and life-threatening exploitation in the new special economic zones. The government's desire to control women's fertility, however, has led to a marked improvement and increase in maternity and childcare health services in the last ten years. The central government has lost power to the provinces and is no longer able to take decisive action to protect women from the effects of discrimination.
Women, Taxes and Benefits: A Critique of Cuvillier's Proposals
Authors: Wilkinson Margaret
Published: January 2009

This comment examines proposals set out in this journal (Cuvillier, 1993) for taxing the imputed incomes of housewives in order to remove favourable treatment by the tax and benefit system which is an incentive to their remaining in the home. It briefly outlines Cuvillier's thesis and proposals and offers a critical assessment of the reforms she recommends. It finds that though the analysis of the problem is lucid and persuasive, the proposals are impracticable, unfair and largely irrelevant. It concludes that the distortions which affect women's choices about working outside the home are not implicit tax and benefit subsidies but obstacles: lack of affordable childcare and poverty traps in the tax and benefits systems.
Independence of color and luminance edges in natural scenes
Authors: HANSEN THORSTEN , GEGENFURTNER KARL R.
Published: January 2009

Form vision is traditionally regarded as processing primarily achromatic information. Previous investigations into the statistics of color and luminance in natural scenes have claimed that luminance and chromatic edges are not independent of each other and that any chromatic edge most likely occurs together with a luminance edge of similar strength. Here we computed the joint statistics of luminance and chromatic edges in over 700 calibrated color images from natural scenes. We found that isoluminant edges exist in natural scenes and were not rarer than pure luminance edges. Most edges combined luminance and chromatic information but to varying degrees such that luminance and chromatic edges were statistically independent of each other. Independence increased along successive stages of visual processing from cones via postreceptoral color-opponent channels to edges. The results show that chromatic edge contrast is an independent source of information that can be linearly combined with other cues for the proper segmentation of objects in natural and artificial vision systems. Color vision may have evolved in response to the natural scene statistics to gain access to this independent information.
Human respiratory syncytial virus infects and induces activation markers in mouse B lymphocytes
Authors: Ángel Rico Miguel , Trento Alfonsina , Ramos Manuel , Johnstone Carolina , Del Val Margarita , Melero José Antonio , López Daniel
Published: January 2009

Human respiratory syncytial virus (HRSV) is the most common cause of severe respiratory infections in infants and young children, often leading to hospitalization. Although human airway epithelial cells are the main target of HRSV, it has been reported that this virus can also infect professional antigen‐presenting cells such as macrophages and dendritic cells, promoting upregulation of maturation markers. Here, we report that mouse spleen B220+ B lymphocytes were susceptible to HRSV infection in vitro, probably involving a glycosaminoglycan‐dependent mechanism. In contrast, neither CD4+ nor CD8+ T lymphocytes were infected. In B lymphocytes, HRSV infection upregulated major histocompatibility complex (MHC) class II but not MHC class I molecules and induced the expression of the activation marker CD86.
Efficiently enhancing regioselective acylation of 5‐azacytidine catalysed by Candida antarctica lipase B with co‐solvent mixtures as the reaction media
Authors: Wu Hong , Zong Minhua , Chen Xiyu
Published: January 2009

A comparative study of regioselective acylation of 5‐azacytidine catalysed by CAL‐B (Candida antarctica lipase B) in co‐solvent mixtures and in pure organic solvents was performed, to our knowledge for the first time, and it was shown that a remarkable enhancement in the initial rate and substrate conversion in the reaction could be achieved with co‐solvents as the reaction medium instead of pure organic solvents. For the CAL‐B‐catalysed regioselective synthesis of 5′‐O‐butyryl‐5‐azacytidine in co‐solvent mixtures, the optimal conditions were as follows: optimal co‐solvent mixture, hexane/pyridine (40/60, v/v); initial aw (water activity), 0.07; enzyme dosage, 50 units/ml; vinyl butyrate/5‐azacytidine molar ratio, 15:1; temperature, 60 °C. Under the optimal conditions, v0 (the initial reaction rate), C (the substrate conversion) and the regioselectivity of the reaction were 0.75 mM/min, 99.0% and above 99% respectively. Similar phenomena were observed in the CAL‐B‐catalysed regioselective acylation of 5‐azacytidine with an extensive range of fatty acid vinyl esters (from C2 to C18). Compared with pure pyridine, the reactions were greatly accelerated in a hexane/pyridine (40/60, v/v) co‐solvent mixture and 5‐azacytidine could be biotransformed into its derivative 5′‐O‐acyl‐5‐azacytidine at a much higher conversion rate (91.4–99.0% as against 40.2–43.5%). Meanwhile, adoption of a co‐solvent mixture as the reaction medium could also greatly lower the enzyme dosage and the molar ratio of acyl donor to 5‐azacytidine.
Management of Himalayan thar (Hemitragus jemlahicus) in New Zealand: the influence of Graeme Caughley
Authors: Parkes J. P.
Published: January 2009

Graeme Caughley developed many of his ideas on wildlife management, and how it should be underpinned by evidence rather than by dogma, during the mid-1960s when he was working for the New Zealand Forest Service and doing the fieldwork for his Ph.D. on the population dynamics of Himalayan thar in the Southern Alps of New Zealand. However, there was a 30-year lag between the advice on the management of wild animals Caughley was providing to the New Zealand Government in the 1960s and its uptake in a national plan to manage thar in the 1990s. Eventually his ideas of setting measurable goals that were based on science, in this case on his ideas on interactive systems between herbivores and their food supply, and on management systems that led to stable outcomes were at least partially taken up. This paper reviews how some of Caughley’s ideas were, or were not, included in a plan developed in 1993 and its subsequent application to manage Himalayan thar in New Zealand.
Price dynamics in political prediction markets
Authors: Majumder Saikat Ray , Diermeier Daniel , Rietz Thomas A. , Amaral Luís A. Nunes
Published: January 2009

Prediction markets, in which contract prices are used to forecast future events, are increasingly applied to various domains ranging from political contests to scientific breakthroughs. However, the dynamics of such markets are not well understood. Here, we study the return dynamics of the oldest, most data-rich prediction markets, the Iowa Electronic Presidential Election “winner-takes-all” markets. As with other financial markets, we find uncorrelated returns, power-law decaying volatility correlations, and, usually, power-law decaying distributions of returns. However, unlike other financial markets, we find conditional diverging volatilities as the contract settlement date approaches. We propose a dynamic binary option model that captures all features of the empirical data and can potentially provide a tool with which one may extract true information events from a price time series.
Essential and unique roles of PIP5K-γ and -α in Fcγ receptor-mediated phagocytosis
Authors: Mao Yuntao S. , Yamaga Masaki , Zhu Xiaohui , Wei Yongjie , Sun Hui-Qiao , Wang Jing , Yun Mia , Wang Yanfeng , Di Paolo Gilbert , Bennett Michael , Mellman Ira , Abrams Charles S. , De Camilli Pietro , Lu Christopher Y. , Yin Helen L.
Published: January 2009

The actin cytoskeleton is dynamically remodeled during Fcγ receptor (FcγR)-mediated phagocytosis in a phosphatidylinositol (4,5)-bisphosphate (PIP2)-dependent manner. We investigated the role of type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) γ and α isoforms, which synthesize PIP2, during phagocytosis. PIP5K-γ−/− bone marrow–derived macrophages (BMM) have a highly polymerized actin cytoskeleton and are defective in attachment to IgG-opsonized particles and FcγR clustering. Delivery of exogenous PIP2 rescued these defects. PIP5K-γ knockout BMM also have more RhoA and less Rac1 activation, and pharmacological manipulations establish that they contribute to the abnormal phenotype. Likewise, depletion of PIP5K-γ by RNA interference inhibits particle attachment. In contrast, PIP5K-α knockout or silencing has no effect on attachment but inhibits ingestion by decreasing Wiskott-Aldrich syndrome protein activation, and hence actin polymerization, in the nascent phagocytic cup. In addition, PIP5K-γ but not PIP5K-α is transiently activated by spleen tyrosine kinase–mediated phosphorylation. We propose that PIP5K-γ acts upstream of Rac/Rho and that the differential regulation of PIP5K-γ and -α allows them to work in tandem to modulate the actin cytoskeleton during the attachment and ingestion phases of phagocytosis.
Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo
Authors: Yamamoto Masamichi , Beppu Hideyuki , Takaoka Katsuyoshi , Meno Chikara , Li En , Miyazono Kohei , Hamada Hiroshi
Published: January 2009

The anterior–posterior axis of the mouse embryo is established by formation of distal visceral endoderm (DVE) and its subsequent migration. The precise mechanism of DVE formation has remained unknown, however. Here we show that bone morphogenetic protein (BMP) signaling plays dual roles in DVE formation. BMP signaling is required at an early stage for differentiation of the primitive endoderm into the embryonic visceral endoderm (VE), whereas it inhibits DVE formation, restricting it to the distal region, at a later stage. A Smad2-activating factor such as Activin also contributes to DVE formation by generating a region of VE positive for the Smad2 signal and negative for Smad1 signal. DVE is thus formed at the distal end of the embryo, the only region of VE negative for the Smad1 signal and positive for Smad2 signal. An inverse relation between the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests an involvement of antagonism between Smad1- and Smad2-mediated signaling.
Host ER–parasitophorous vacuole interaction provides a route of entry for antigen cross-presentation in Toxoplasma gondii–infected dendritic cells
Authors: Goldszmid Romina S. , Coppens Isabelle , Lev Avital , Caspar Pat , Mellman Ira , Sher Alan
Published: January 2009

Toxoplasma gondii tachyzoites infect host cells by an active invasion process leading to the formation of a specialized compartment, the parasitophorous vacuole (PV). PVs resist fusion with host cell endosomes and lysosomes and are thus distinct from phagosomes. Because the parasite remains sequestered within the PV, it is unclear how T. gondii–derived antigens (Ag’s) access the major histocompatibility complex (MHC) class I pathway for presentation to CD8+ T cells. We demonstrate that recruitment of host endoplasmic reticulum (hER) to the PV in T. gondii–infected dendritic cells (DCs) directly correlates with cross-priming of CD8+ T cells. Furthermore, we document by immunoelectron microscopy the transfer of hER components into the PV, a process indicative of direct fusion between the two compartments. In strong contrast, no association between hER and phagosomes or Ag presentation activity was observed in DCs containing phagocytosed live or dead parasites. Importantly, cross-presentation of parasite-derived Ag in actively infected cells was blocked when hER retrotranslocation was inhibited, indicating that the hER serves as a conduit for the transport of Ag between the PV and host cytosol. Collectively, these findings demonstrate that pathogen-driven hER–PV interaction can serve as an important mechanism for Ag entry into the MHC class I pathway and CD8+ T cell cross-priming.
FrameDP: sensitive peptide detection on noisy matured sequences
Authors: Gouzy Jérôme , Carrere Sébastien , Schiex Thomas
Published: January 2009

Summary: Transcriptome sequencing represents a fundamental source of information for genome-wide studies and transcriptome analysis and will become increasingly important for expression analysis as new sequencing technologies takes over array technology. The identification of the protein-coding region in transcript sequences is a prerequisite for systematic amino acid-level analysis and more specifically for domain identification. In this article, we present FrameDP, a self-training integrative pipeline for predicting CDS in transcripts which can adapt itself to different levels of sequence qualities.

Availability: FrameDP for Linux (web-server and underlying pipeline) is available at {{http://iant.toulouse.inra.fr/FrameDP}} for direct use or a standalone installation.

Contact:  thomas.schiex@toulouse.inra.fr
Sequence-based prediction of protein interaction sites with an integrative method
Authors: Chen Xue-wen , Jeong Jong Cheol
Published: January 2009

Motivation: Identification of protein interaction sites has significant impact on understanding protein function, elucidating signal transduction networks and drug design studies. With the exponentially growing protein sequence data, predictive methods using sequence information only for protein interaction site prediction have drawn increasing interest. In this article, we propose a predictive model for identifying protein interaction sites. Without using any structure data, the proposed method extracts a wide range of features from protein sequences. A random forest-based integrative model is developed to effectively utilize these features and to deal with the imbalanced data classification problem commonly encountered in binding site predictions.

Results: We evaluate the predictive method using 2829 interface residues and 24 616 non-interface residues extracted from 99 polypeptide chains in the Protein Data Bank. The experimental results show that the proposed method performs significantly better than two other sequence-based predictive methods and can reliably predict residues involved in protein interaction sites. Furthermore, we apply the method to predict interaction sites and to construct three protein complexes: the DnaK molecular chaperone system, 1YUW and 1DKG, which provide new insight into the sequence–function relationship. We show that the predicted interaction sites can be valuable as a first approach for guiding experimental methods investigating protein–protein interactions and localizing the specific interface residues.

Availability: Datasets and software are available at http://ittc.ku.edu/~xwchen/bindingsite/prediction.

Contact:  xwchen@ku.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Performance of the far-IR beamline of the 6 MeV tabletop synchrotron light source
Authors: Monirul Haque Md. , Yamada Hironari , Moon Ahsa , Yamada Mami
Published: January 2009

The performance of the far-infrared (FIR) beamline of the 6 MeV tabletop synchrotron light source MIRRORCLE-6FIR dedicated to far-infrared spectroscopy is presented. MIRRORCLE-6FIR is equipped with a perfectly circular optical system (PhSR) placed around the 1 m-long circumference electron orbit. To illustrate the facility of this light source, the FIR output as well as its spectra were measured. The optimum optical system was designed by using the ray-tracing simulation code ZEMAX. The measured FIR intensity with the PhSR in place is about five times higher than that without the PhSR, which is in good agreement with the simulation results. The MIRRORCLE-6FIR spectral flux is compared with a standard thermal source and is found to be 1000 times greater than that from a typical thermal source at ∼15 cm−1. It is also observed that the MIRRORCLE-6FIR radiation has a highly coherent nature. The broadband infrared allows the facility to reach the spectral range from 10 cm−1 to 100 cm−1. MIRRORCLE-6FIR, owing to a large beam current, the PhSR mirror system, a large dynamic aperture and small ring energy, can deliver a bright flux of photons in the FIR/THz region useful for broadband spectroscopy.
Analysis of mitochondrial DNA diversity in Burkina Faso populations confirms the maternal genetic homogeneity of the West African goat
Authors: Royo L. J. , Traoré A. , Tambourá H. H. , Álvarez I. , Kaboré A. , Fernández I. , Ouédraogo‐Sanou G. , Toguyeni A. , Sawadogo L. , Goyache F.
Published: January 2009

To date, no comprehensive study has been performed on mitochondrial genetic diversity of the West African goat. Here, we analysed a 481‐bp fragment of the HVI region of 111 goats representing four native West African populations, namely the three main Burkina Faso breeds, zoo‐farm kept Dwarf goats and endangered Spanish goat breeds used as the outgroup. Analyses gave 83 different haplotypes with 102 variable sites. Most haplotypes (65) were unique. Only three haplotypes were shared between populations. Haplotypes were assigned to cluster A except for H45 (belonging to the Spanish Bermeya goat) which was assigned to cluster C. amova analysis showed that divergence between groups (ΦCT) was not statistically significant regardless of whether the partition in two hierarchical levels that was fitted included Spanish samples or not. The West African goat scenario shown here is consistent with that previously reported for the species: haplogroup A is predominant and has a very high haplotype diversity regardless of the geographic area or sampled breed. The large phenotypic differences observable between the West African Dwarf and Sahelian long‐legged goat populations are not detectable with mitochondrial markers. Moreover, a previously suggested introgression of Sahelian goat southwards because of desertification could not be assessed using mtDNA information.
Therapy of chemotherapy‐induced peripheral neuropathy
Authors: Kaley Thomas J. , DeAngelis Lisa M.
Published: January 2009

Chemotherapy‐induced peripheral neuropathy (CIPN) is still a common and disabling side effect of many chemotherapy agents in use today. Unfortunately, neither prophylactic strategies nor symptomatic treatments have proven useful yet. This review will discuss the diagnosis and evaluation of neuropathy in cancer patients, as well as reviewing the various prophylactic and symptomatic treatments that have been proposed or tried. However, sufficient evidence is lacking to recommend any of these treatments to patients suffering with CIPN. Therefore, the best approach is to treat symptomatically, and to start with broad‐spectrum analgesic medications such as non‐steroidal anti‐inflammatory drugs (NSAIDs). If NSAIDs fail, a reasonable second‐line agent in properly selected patients may be an opioid. Unfortunately, even when effective in other types of neuropathic pain, anti‐depressants and anticonvulsants have not yet proven effective for treating the symptoms of CIPN.
Clonal diversity in the myeloproliferative neoplasms: independent origins of genetically distinct clones
Authors: Beer Philip A. , Jones Amy V. , Bench Anthony J. , Goday‐Fernandez Andrea , Boyd Elaine M. , Vaghela Krishna J. , Erber Wendy N. , Odeh Bassam , Wright Christine , McMullin Mary Frances , Cullis Jonathan , Huntly Brian J. P. , Harrison Claire N. , Cross Nicholas C. P. , Green Anthony R.
Published: January 2009

This study looked for clonal diversity in patients with a myeloproliferative neoplasm associated with more than one acquired genetic lesion. A tyrosine kinase mutation and a cytogenetic lesion were present in the same clone in six of seven patients. By contrast, the genetic lesions were present in separate clones in all six patients with two tyrosine kinase pathway mutations. Moreover, in two patients the clones were genetically unrelated by X‐chromosome inactivation studies. These data demonstrated clonal diversity in a subset of patients with early stage haematopoietic malignancy and showed, for the first time, that such clones may arise independently.
Reduced plasma fibrinolytic capacity as a potential risk factor for a first myocardial infarction in young men
Authors: Meltzer Mirjam E. , Doggen Carine J. M. , De Groot Philip G. , Rosendaal Frits R. , Lisman Ton
Published: January 2009

Studies on the relationship between fibrinolysis and arterial thrombosis have been conflicting. Previously, we demonstrated that hypofibrinolysis, as measured by a plasma‐based assay, increased the risk of venous thrombosis. The present study investigated increased clot lysis time (CLT) measured with the same assay as a risk factor for myocardial infarction in a case‐control study including 421 men with a first myocardial infarction and 642 controls below 70 years. CLT was strongly associated with body‐mass index, lipid levels, blood pressure and C‐reactive protein. Overall, risk of myocardial infarction was 1·4‐fold (95% confidence interval (CI) 1·0–1·9) increased for CLT in the fourth quartile (longest CLT) compared with the first quartile. After adjusting for cardiovascular risk factors this risk disappeared (OR 1·0, 95%CI 0·6–1·5). In men aged <50 years the association was pronounced (OR 3·2, 95%CI 1·5–6·7). After adjustment for cardiovascular risk factors the risk was nearly twofold increased (OR 1·8, 95%CI 0·7–4·8). In men aged ≥50 years, no clear association between CLT and risk of myocardial infarction was found. Our study suggests that hypofibrinolysis increases the risk of a first myocardial infarction in young men, although the causality of this association remains to be determined.
The peptide‐semicarbazone S‐2209, a representative of a new class of proteasome inhibitors, induces apoptosis and cell growth arrest in multiple myeloma cells
Authors: Baumann Philipp , Müller Karin , Mandl‐Weber Sonja , Leban Johann , Doblhofer Robert , Ammendola Astrid , Baumgartner Roland , Oduncu Fuat , Schmidmaier Ralf
Published: January 2009

Bortezomib is the first approved member of a new class of anti‐myeloma agents, the proteasome inhibitors. Further proteasome inhibitors are needed to optimise this promising treatment option. S‐2209 [1‐[1‐{1‐[(2,4‐Dioxo‐imidazolidin‐1‐ylimino)‐methyl]‐2‐phenyl‐ethylcarbamoyl}‐2‐(1H‐indol‐3‐yl)‐ethylcarbamoyl]‐2‐(1H‐indol)] inhibits the chymotryptic activity of the human 20S proteasome (half maximal effective concentration, IC50∼220 nmol/l) which was determined by a proteasome inhibition assay. A nuclear factor κB inhibition assay revealed a half maximal effective concentration (EC50) of 0·9 μmol/l. The WST‐1 growth assay showed inhibition of cell growth of all tested multiple myeloma (MM) cell lines with an IC50 between 100 nmol/l and 600 nmol/l. Strong induction of apoptosis was seen in MM cells at nanomolar concentrations (IC50∼300 nm) as well as in primary myeloma cells. No induction of apoptosis was detected in peripheral blood mononuclear cells from healthy humans. Upregulation of p53, activation of JNK protein, and downregulation of Mcl‐1 was revealed. Despite the administration of 15 mg S‐2209/kg/d in wistar rats, no toxicity with respect to body weight, hepatic enzymes, creatinine or haemoglobin was seen. Proteasome inhibition in white blood cells isolated from the treated rats was higher in the S‐2209 treated animals in comparison with the control animals treated with 0·1 mg/kg/d bortezomib. S‐2209 is active in myeloma cells and shows a favourable toxicity profile in first in‐vivo studies. S‐2209 is a promising agent for further clinical development.
Novel insights into glucocorticoid‐mediated diabetogenic effects: towards expansion of therapeutic options?
Authors: Van Raalte D. H. , Ouwens D. M. , Diamant M.
Published: January 2009

At pharmacological concentrations, glucocorticoids (GCs) display potent anti‐inflammatory effects, and are therefore frequently prescribed by physicians to treat a wide variety of diseases. Despite excellent efficacy, GC therapy is hampered by their notorious metabolic side effect profile. Chronic exposure to increased levels of circulating GCs is associated with central adiposity, dyslipidaemia, skeletal muscle wasting, insulin resistance, glucose intolerance and overt diabetes. Remarkably, many of these side‐effects of GC treatment resemble the various components of the metabolic syndrome (MetS), in which indeed subtle disturbances in the hypothalamic‐pituitary‐adrenal (HPA) axis and/or increased tissue sensitivity to GCs have been reported. Recent developments have led to renewed interest in the mechanisms of GC's diabetogenic effects. First, ‘selective dissociating glucocorticoid receptor (GR) ligands’, which aim to segregate GC's anti‐inflammatory and metabolic actions, are currently being developed. Second, at present, selective 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) inhibitors, which may reduce local GC concentrations by inhibiting cortisone to cortisol conversion, are evaluated in clinical trials as a novel treatment modality for the MetS.

In this review, we provide an update of the current knowledge on the mechanisms that underlie GC‐induced dysmetabolic effects. In particular, recent progress in research into the role of GCs in the pathogenesis of insulin resistance and beta‐cell dysfunction will be discussed.
Iron‐induced platelet aggregation measurement: a novel method to measure platelet function in stenting for ST segment elevation myocardial infarction
Authors: Smit J. J. J. , Van Oeveren W. , Ottervanger J. P. , Slingerland R. J. , Remijn J. A. , Zijlstra F. , Van‘t Hof A. W. J.
Published: January 2009

Background  Iron and (stainless) steel are potent platelet aggregation activators, and may be involved in stent thrombosis, a serious complication after intracoronary stenting. Current platelet function tests are suboptimal, because of inappropriate agonists and/or lack of reproducibility. We tested the feasibility and reproducibility of a novel platelet function test using stainless steel as an agonist and compared it with other platelet function tests.

Materials and methods  In 111 patients with acute ST segment elevation myocardial infarction (STEMI), duplo measurements of iron (Fe)‐induced platelet aggregation (FIPA) were performed after clopidogrel, acetylsalicylic acid and/or tirofiban treatment. Within 1 h, citrated blood samples drawn from the femoral sheath before primary percutaneous coronary intervention were added to 100 mg of low carbon steel and after 5 s mixing with vortex, the samples were incubated for 15 min. The ratio between the non‐aggregated platelets in the agonist sample and platelets in a reference sample was calculated as the platelet aggregation inhibition.

Results  FIPA measurement was highly reproducible (correlation coefficient (R) = 0·942, P < 0·001 between duplo samples). FIPA correlated well with adenosine diphosphate‐induced platelet aggregation (R = 0·83, P < 0·001) but weakly with platelet function analyser‐100 bleeding time (R = 0·56, P < 0·001). FIPA could be measured in patients in which platelet aggregation could not be measured by platelet function analyser‐100 or after adenosine diphosphate.

Conclusion  This study showed good reproducibility of a novel platelet function test using stainless steel as an agonist and showed correlation with validated platelet function tests. We found that the novel platelet function test is a suitable test for measurement of platelet aggregation inhibition in patients undergoing stenting for STEMI, even when they are taking multiple antiplatelet regimens.
Nucleo‐cytoplasmic shuttling of protein arginine methyltransferase 1 (PRMT1) requires enzymatic activity
Authors: Herrmann Frank , Fackelmayer Frank O.
Published: January 2009

Methylation of arginine residues is a widespread post‐translational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMT), of which PRMT1 is the predominant member in human cells. We have previously described the localization and mobility of PRMT1 in live cells, and found that it shuttles between the nucleus and the cytoplasm depending on the methylation status of substrate proteins. Recently, amino‐terminal splicing isoforms of PRMT1 were shown to differ significantly in intracellular localization, the most interesting being splice variant 2 that carries a nuclear export signal in its amino terminus, and is expressed in increased levels in breast cancer cells. We show here that enzymatic activity is required for nucleo‐cytoplasmic shuttling of PRMT1v2, as a catalytically inactive mutant highly accumulates in the nucleus and displays altered intranuclear mobility as determined by fluorescence recovery after photobleaching experiments. Our results indicate that nuclear export of PRMT1v2 is dominant over activity‐independent nuclear import, but can only occur after activity‐dependent release of the enzyme from substrates, suggesting that shuttling of the enzyme provides a dynamic mechanism for the regulation of substrate methylation.
Unihemispheric sleep deprivation in bottlenose dolphins
Authors: OLEKSENKO A. I. , MUKHAMETOV L. M. , POLYAKOVA I. G. , SUPIN A. Y. , KOVALZON V. M.
Published: January 2009

SUMMARY  Unihemispheric and bihemispheric sleep deprivation were performed in bottlenose dolphins. One brain hemisphere was capable of being deprived of delta (0.5‐3.0 Hz) sleep in the former condition. Here, an increase in sleep pressure was observed during sleep deprivation in the deprived hemisphere. In the recovery sleep, following unihemispheric sleep deprivation, there was a rebound of delta sleep only in the deprived hemisphere. Following bihemispheric sleep deprivation the animals exhibited an increase in delta sleep in both hemispheres.
Generation of activity‐rest patterns by dual circadian pacemaker systems: a model
Authors: BEERSMA DOMIEN G. M. , DAAN SERGE
Published: January 2009

SUMMARY  Activity‐rest patterns displayed by an animal under various circumstances are suggested to result from the combined influences of two virtually identical circadian pacemaker components. Increased output of each component proportionally increases the probability of activity of the animal. Such a dual circadian pacemaker model explains much of the phenomenology of activity‐rest records. Under normal light‐dark schedules, the two components of the model have a similar phase relationship to the Zeitgeber. Differential synchronization of the components to dawn and dusk is not assumed.
Forced splitting of human sleep in free‐running rhythms
Authors: ZULLEY JÜRGEN , CARR DAVID
Published: January 2009

SUMMARY  The assumption of polyphasic sleep/wake regulation is based on the occurrence of nap‐sleep at specific phase positions in the circadian cycle. Further support would be the split of the normal long major sleep episode into shorter components. Evidence for this hypothesis comes from the discovery of bimodal distribution in sleep duration. An experimental approach to test this hypothesis has been carried out by restricting sleep duration in free‐running rhythms. The outcome was a biphasic distribution of sleep within a circadian cycle with sections of dissociation and synchronization of the two sleep blocks. The results show similarities with ‘splitting’, a phenomenon which has been found in animal studies. The relatively short duration of the different sections as well as the asymmetric distribution of the two sleep blocks in the circadian cycle leads to the assumption of a splitting of the major sleep episode and not of the circadian rhythm. Sleep split into two, relatively short sleep episodes of comparable duration contrasts with napping, which is characterized by an extra sleep episode in addition to the long major sleep.
Human slow‐wave sleep and the cerebral cortex
Authors: HORNE JIM
Published: January 2009

SUMMARY  Recent hypotheses about the roles of human slow‐wave sleep (hSWS—delta EEG activity) are appraised. The possible linkage between hSWS and the functions of the prefrontal cortex (PFC) are explored with respect to normal subjects and to disorders involving PFC deficits.
Models of sleep regulation in mammals
Authors: TOBLER IRENE , FRANKEN PAUL , TRACHSEL LORENZ , BORBÉLY ALEXANDER A.
Published: January 2009

SUMMARY  A brief overview of models on the regulation of sleep/waking or rest/activity is provided. Applications of the two‐process model are illustrated in two species: The homeostatic facet of the model (Process S) was used to quantitatively simulate sleep in the rat and guinea pig. The model parameters were estimated for rat sleep by an optimization procedure. A close correspondence between the time course of slow‐wave activity and Process S was obtained for both species under baseline conditions. Whereas in the rat a close fit was obtained also for the recovery period from sleep deprivation, some discrepancies were present in the guinea pig. It is concluded that the concept of sleep homeostasis that has been elaborated and formalized in the two‐process model for human sleep, can also be applied to simulate sleep in other mammals.
The duration of REM sleep episodes in normal sleep
Authors: BELYAVIN ANDREW J.
Published: January 2009

SUMMARY  The distributions of the durations of the first 3 REM sleep episodes have been analysed using a total of 134 overnight sleep recordings from 10 subjects. From investigation of the length of uninterrupted episodes of stage REM, it is shown that arousals to stage 0/1 could play an important part in the process of REM exit, and that by the middle of the sleep period, these arousals probably occur according to a Poisson process. During the first and second REM episodes a more complex process appears to be at work, which could reflect increased pressure for slow wave sleep. These findings suggest that the duration of a REM episode is determined by a process that has a large stochastic element, which is not necessarily tied to REM entry.
Neurobiological structure of the revised limit cycle reciprocal interaction model of REM cycle control
Authors: McCARLEY R.W. , MASSAQUOI S.G.
Published: January 2009

SUMMARY New data bearing on the neurobiological basis of REM sleep and on mechanisms of EEG synchronization/desynchronization are presented. The revision of the limit cycle reciprocal interaction model (LCRIM) of REM cycle control incorporates new information on monoamine inhibition of mesopontine cholinergic neurons and of cholinergic mechanisms promoting REM sleep. New data also show cortical slow‐wave activity is controlled by thalamocortical neurons' membrane potential level, which, in turn, is strongly controlled during sleep by brainstem cholinergic input arising from REM‐on neurons. This new knowledge leads to a neurobiologi‐cally justified integration of the LCRIM and of the two‐process model of sleep control.
Combining different models of sleep regulation
Authors: ACHERMANN PETER , BORBÉLY ALEXANDER A.
Published: January 2009

SUMMARY  Different models have been proposed to account for processes underlying the regulation of sleep and alertness. Specific models have addressed sleep homeostasis, the nonREM‐REM sleep cycle, the circadian sleep/wake rhythm, and changes of daytime alertness. We show that the different models are not mutually exclusive but that they can be integrated as ‘modules’ in a combined model.
Studies on sleep/wake effects of serotonin reuptake inhibitors and receptor subtype involvement
Authors: URSIN R. , BJORVATN B. , SOMMERFELT L. , NECKELMANN D. , BJØRKUM A. A.
Published: January 2009

SUMMARY  Studies with the serotonin uptake inhibitors zimeldine and alaproclate show biphasic effects on the sleep/wake axis in rats and cats. Zimeldine induced an initial waking response succeeded by a small SWS‐2 increase in rats. The waking increase was not blocked by the 5‐HT2 antagonist ritanserin nor by the putative 5‐HT1A antagonist (‐)‐alprenolol. In cats, zimeldine induced initial behavioural changes which were succeeded by a large SWS‐2 increase. Alaproclate gave similar initial responses as zimeldine in both species, and was succeeded by a moderate sleep increase in cats but not in rats. The complex sleep/wake effects following the serotonin uptake inhibitors may result from simultaneous induction of incompatible serotonergic effects.
Functional activity of 5‐HT2receptors in the modulation of the sleep/wakefulness states
Authors: DUGOVIC CHRISTINE
Published: January 2009

SUMMARY In the light of recent pharmacological investigations using agonists and antagonists that have potent actions on 5‐hydroxytryptamine‐2 (5‐HT2) receptors, the possible functional role of 5‐HT2receptors in the modulation of the sleep/wakefulness states was examined. Data obtained from animals and from clinical studies suggest that serotonin may exert an inhibitory control on deep slow‐wave sleep (SWS) through 5‐HT2receptors. In further investigations, the existence of a diurnal variation in the functional activity of 5‐HT2receptors, that depends on the day/night cycle and/or the melatonin rhythm, was revealed. Questions remain with regard to the physiological significance of the 5‐HT2receptor‐mediated deep SWS regulation, the anatomical site(s) of 5‐HT2receptors involved in this regulation and the mechanism underlying diurnal fluctuations in the functional activity of 5‐HT2receptors.
Epidemiology of snoring and obstructive sleep apnoea in a Danish population, age 30–60
Authors: JENNUM POUL , SJØL ANETTE
Published: January 2009

SUMMARY  Several epidemiological studies have estimated the prevalence of obstructive sleep apnoea syndrome (OSAS). As many of those suffering from sleep apnoea may be asymptomatic, the occurrence of sleep apnoea may be underestimated. The epidemiology of self‐reported snoring, sleep apnoea and OSAS, and their relationships with various symptoms, were evaluated in 1504 randomly selected males and females, aged 30, 40, 50 and 60 years. Nocturnal respiration was determined in 748 participants using inductive plethysmography.

Habitual snoring was reported by 19.1% (9.2–24.2%, age 30–60 years) of the males and 7.9% (3.8–11.7%, age 30–60 years) of the females. Respiratory Distress Index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour lasting longer than 10s. RDI≥5 per hour was found in 10.9% (7.1–18.3%, age 30–60 years) of the males and in 6.3% (5.3–7.6%, age 30–60 years) of the females. Hypersomnia increased with the severity of sleep apnoea (P< 0.005) and was reported by 15.9% of those with RDI≥5.

The prevalence of OSAS (hypersomnia and RDI ≥5) was 0.9% in the females, 1.9% in the males, and in total 1.4% of all aged 30–60 years. The sensitivity was 70.8% and the specificity was 47.7% for self‐reported snoring predicting RDI ≥5.

The following factors were associated with RDI ≥5: age (P<0.05), gender (P< 0.0001), BMI (P< 0.0001), tobacco (P<0.02) and alcohol (P<0.05) consumption. Snoring correlated with age (P<0.02), gender (P<0.001), BMI (P<0.0001) and alcohol consumption (P<0.05).

We conclude that sleep apnoea is common and many of those with sleep apnoea are asymptomatic. Self‐reported hypersomnia and snoring are not sensitive enough alone to identify those with sleep apnoea. Sufficient control of the questionnaire is thus essential in studies on snoring and the risk of cardiovascular diseases.
Sleep onset rapid‐eye‐movement episodes in narcolepsy: REM sleep pressure or nonREM‐REM sleep dysregulation?
Authors: TAFTI MEHDI , VILLEMIN ERIC , CARLANDER BERTRAND , BESSET ALAIN , BILLIARD MICHEL
Published: January 2009

SUMMARY  Thirty‐two narcoleptic subjects with excessive daytime sleepiness and cataplexy were recorded for 33 continuous hours. The continuous polysomnographic recording (CPSG) was followed by a standard MSLT at 2‐h intervals. There were 64 sleep onset REM episodes (SOREMs) vs 64 sleep onset nonREM episodes (SONREMs) during the CPSG, and 102 SOREMs vs 50 SONREMS during the MSLT. Both sleep onset types peaked at 13–15 h during the CPSG while sleep onsets were evenly distributed during the MSLT. In the latter procedure, the mean sleep latency was significantly shorter with SOREMs occurrence than with SONREMs occurrence. Two factors were extracted in each procedure by means of a Varimax Rotated Factor Analysis. During the CPSG, SOREMs were related to the preceding nocturnal sleep parameters in the first factor, and to the daytime total sleep time and the total number of sleep onsets in the second factor. During the MSLT, SOREMs were related only to the mean sleep latency and the total number of sleep onsets. It was concluded that the occurrence of SOREMs is primarily due to the residual somnolence in narcoleptic subjects. However, their occurrence during the MSLT is largely independent of the prior history of sleep and waking. Thus, we propose a nonREM‐REM sleep dysregulation hypothesis to account for the appearance of SOREMs in narcolepsy.
EEG spectral power analysis of phasic and tonic REM sleep In young and older male subjects
Authors: WATERMAN D. , ELTON M. , HOFMAN W. , WOESTENBURG J. C. , KOK A.
Published: January 2009

SUMMARY  EEG spectral power was studied during periods of rapid eye movements (REMs) and tonic intervals in REM sleep of 7 young and 7 older male subjects. Significant symmetrical decreases in alpha and betal power at central and occipital sites, concurrent with an increase in frontal theta power, were observed during the production of REMs. The former findings are discussed as sleep analogues to changes in alpha and betal during waking, showing increased information processing and behavioural activation, and that of theta is tentatively presented as reflecting an increase in afferent thresholds. Independent of the phasic‐tonic REM distinction, total EEG power markedly decreased as a function of time of night and did not interact with age. Significant age differences in the overall spectral composition of the EEG were obtained, namely, a lower level of delta power and a relative shift towards more power in frequencies above 12 Hz for the older group. Further, older subjects also demonstrated a more uniform topographical distribution of alpha and sigma power.
Effect of rapid eye movement sleep deprivation on rat brain Na‐K ATPase activity
Authors: GULYANI S. , MALLICK B. N.
Published: January 2009

SUMMARY  Since rapid eye movement (REM) sleep deprivation has been reported to affect the neuronal excitability in the brain, it was hypothesized that a change in the neuronal membrane‐bound Na‐K ATPase activity might be at least one of the factors inducing such a change. Therefore, in this study rats were deprived of REM sleep by using the platform technique and enzyme activity was estimated in the whole brain, in different regions of the brain and in microsomal preparations. Deprivation was carried out for varying periods and suitable control experiments were conducted to rule out the possibility of nonspecific effects. The observation supported our hypothesis and showed primarily that the deprivation increased the enzyme activity in the rat brain. It showed also that the pons and the medulla were the first sites to be affected by deprivation. The probable mechanism producing such a change is discussed.