bluuebunny/crossref_metadata_2025 huggingface dataset:
Employment-anchored social policy, gender equality and the open method of policy coordination in the European union
Authors: O'Connor Julia S.
Published: February 2005

This paper focuses on the development of an employment anchored social policy framework within the European Union and explores how changing governance structures within the EU may influence national policy in this area. National Action Plans on Employment and Social Inclusion are the key pillars of the EU employment anchored social policy framework. The associated open method of policy coordination (OMC) is the process through which these plans are formulated. The achievement of the EU employment objectives is considered as is the issue of quality in employment and the constraints on its achievement in the context of a labour market characterised not only by the growth of high quality jobs but also by a substantial proportion of low quality jobs and a policy framework that gives primacy to economic over social policy. I consider the potential and limitations of the OMC for enhancing social policy objectives in the EU, in particular the gender equality dimension and conclude that a single OMC process involving all member states is essential in employment-enhancing areas if an employment anchored social policy is to be sustained, gender equality is to be achieved and the radical potential of OMC realised. The theoretical context within which these questions are addressed encompasses issues relating to governance of social policy at the supra-national level and its linkage to national welfare regimes.
Social support networks in impoverished European neighbourhoods
Authors: Olagnero Manuela , Meo Antonella , Corcoran Mary P.
Published: February 2005

This paper examines the extent to which families living in precariousness in contemporary European cities draw on social support as a key resource in their struggle against poverty. The comparative observations and analysis presented draw on national level survey data as well as local level qualitative data collected in selected European neighbourhoods, under the auspices of the BETWIXT project.1 More specifically, our analysis focuses on the active modes and mechanisms for requesting and providing solidarity and support at times of familial crisis. The comparison of the Irish and Italian experiences illuminates the persistent involvement of households in informal support provision, even as family structures alter and welfare regimes change. We demonstrate the dynamics underlying the phenomenon of social support among precarious families living in deprived urban areas in the cities of Dublin and Turin. We address the dialectics between agency and structural constraint by examining whether or not family and/or social support networks are reinforced or further weakened by factors such as economic hardship, unemployment, and neighbourhood dereliction. We conclude that the effects of precariousness are multiple and contradictory: precariousness can create anomie and individualisation but it can also act as a spur to greater community cohesion. Such cohesion can also be expressed in terms of heightened social divisions along ethnic lines (the case in Aurora, Turin) and class lines (the case in Kilmainham, Dublin).
Refiguring the nature of undeclared work
Authors: Williams Colin C. , Windebank Jan
Published: February 2005

A recurring assumption is that undeclared work is market-like and motivated by monetary gain and thus that participants make a rational economic decision to engage in such an enterprise. In consequence, the predominant public policy response has been to seek to deter this work by ensuring that the expected cost of being caught and punished is greater than the economic benefit of participating. Here, however, and drawing upon evidence from 861 face-to-face interviews conducted in England, an alternative reading of undeclared work is presented more appreciative of the heterogeneous work relations and motives involved and its variable meanings. This identifies how although some undeclared work is market-like and conducted for monetary gain, there is also undeclared work conducted under social relations and for motives more akin to unpaid mutual aid. The paper then explores the various policy options that could be adopted and their implications.
Trust in food safety in Russia, Denmark and Norway
Authors: Berg Lisbet , Kjaernes Unni , Ganskau Elena , Minina Vera , Voltchkova Ludmila , Halkier Bente , Holm Lotte
Published: February 2005

In this paper we argue that institutional conditions should be taken into consideration when consumers trust in food safety is analysed. Our survey results demonstrate that levels of trust in food safety varies considerably across our three selected countries: Russian consumers expressing the lowest level of trust, Norwegian consumers the highest and Danish consumers expressing levels of trust in food safety which were in between. We find empirical evidence in all countries that consumers trust in food safety is related to their evaluation of how their national food control authorities perform, as well as to what extend they trust market mechanisms to secure food quality. However, while trust in food safety in the Scandinavian countries is more likely to rest on trust in public food control, trust in food safety more often depend on trust in market mechanisms in the St. Petersburg region.
Revolution, class and globalisation in the transition from state socialism
Authors: Lane David
Published: February 2005

With the disintegration of communist rule in central Europe and the USSR, the social formation of state socialism ended. What has followed is described in Western sociology and political science as a transformation or a ‘transition’ to democracy, markets and capitalism. The paper considers traditional Marxist approaches to the transition to capitalism and criticises the model of state capitalism as well as the world system approach. In contrast, it is contended that three social classes played a major role in the fall of state socialism and a move to capitalism: endogenously – the acquisition and administrative classes, and exogenously – the global political class. The political leadership of Gorbachev was crucial in tilting power away from the loyal administrative class. It is argued that different combinations of these class groupings determine the type of social formation which is evolving. The globalisation of capitalist companies and the direct role of global economic forces had little importance under state socialism, but have had more significance since 1989. With respect to the penetration of transnational companies, important differences have developed between the central European countries and those of the former USSR. Barriers limit the spread of global capitalism: among these are disparities between the interests of local domestic and export industries, the legacy of state socialism and the continued presence of state ownership. In this context, global capitalism is evolving in central Europe whereas in Russia and Ukraine there is a hybrid social formation containing elements of state economic control, national capitalism and global capitalism.
University under siege?
Authors: Baert Patrick , Shipman Alan
Published: February 2005

This paper explores the changes that are taking place in European higher education: a shift from the Humboldtian notion of the university to one that operates under quasi-market pressures. While increasing the culture of accountability in universities, this development, linked to shifts in their sponsorship and associated ‘missions’, is associated with an erosion of traditional mechanisms of trust. The focus is on UK experience, which is now extending internationally. Lessons are drawn on some of the institutional changes and problems that may lie ahead for European universities.
Glucose Intolerance and Hyperlipidemia Prior to Diabetes Onset in Female Spontaneously Diabetic Torii (SDT) Rats
Authors: Shinohara Masami , Oikawa Toshihiro , Sato Kahei , Kanazawa Yasunori
Published: February 2005

The Spontaneously Diabetic Torii (SDT) rat, a newly
established animal model for diabetes mellitus, presents
nonobese type 2 diabetes with ocular complications. In the
present study, oral glucose tolerance tests and biochemical
and histopathological examinations were performed in female
SDT rats at 16 and/or 25 weeks of age, before the onset
of diabetes. At 25 weeks of age, glucose tolerance was significantly
impaired, and plasma immunoreactive insulin levels
at 120 min after glucose loading were significantly higher
(P < 0.05). Body weight and fasting levels of plasma triglycerides
and nonesterified fatty acids were significantly higher
than those in control animals. Histopathologically, inflammatory
cell infiltration and fibrosis were observed in and
around the pancreatic islets. These results strongly suggest
that female SDT rats are useful as a model to investigate
impairment of glucose tolerance and hyperlipidemia prior
to the onset of diabetes.
Role of Glucose in IRS Signaling in Rat Pancreatic Islets: Specific Effects and Interplay with Insulin
Authors: Paris Maryline , Bernard-Kargar Catherine , Vilar José , Kassis Nadim , Ktorza Alain
Published: February 2005

We investigated the possible interplay between insulin
and glucose signaling pathways in rat pancreatic β‐cell
with a special focus on the role of glucose in IRS signaling
in vivo. Three groups of rats were constituted by combining
simultaneous infusion during 48 h either of glucose
and/or insulin, or glucose+diazoxide: Hyperglycemic‐
Hyperinsulinemic (HGHI), euglycemic‐Hyperinsulinemic
(eGHI), Hyperglycemic‐euinsulinemic (HGeI). Control rats
were infused with 0,9% NaCl. In HGHI and HGeI rats
plasma glucose levels were maintained at 20‐22 mmol/l. In
eGHI rats, plasma glucose was not different from that of
controls, whereas plasma insulin was much higher than
in controls. In HGHI rats, IRS‐2 mRNA expression, total
protein and phosphorylated protein amounts were increased
compared to controls. In HGeI rats, only IRS‐2
mRNA expression was increased. No change was observed
in eGHI rats whatever the parameter considered. In all
groups, mRNA concentration of IRS‐1 was similar to that
of controls. The quantity of total and phosphorylated IRS‐
1 protein was dramatically increased in HGHI rats and
to a lesser extent in eGHI rats. Neither mRNA nor IRS‐1
protein expression were modified in HGeI rats. The data
suggest that glucose and insulin play at once a specific
and a complementary role in islet IRSs signaling. Especially,
glucose stimulates IRS‐2 mRNA expression whatever
the insulin status and independently of the secretory
process. The differential regulation of IRS‐1 and
IRS‐2 expressions is in agreement with their supposed different involvement in the control of β‐cell growth and
function.
[Retracted] Fructose Diet‐Induced Skin Collagen Abnormalities Are Prevented by Lipoic Acid
Authors: Thirunavukkarasu V. , Nandhini A. T. Anitha , Anuradha C. V.
Published: February 2005

Nonenzymatic glycation of proteins, leading to chemical
modification and cross‐linking are of importance in the
pathology of diabetic complications.We studied the effect of
α‐lipoic acid (LA) on the content and characteristics of the
protein collagen from skin of high‐fructose fed rats. The
rats were divided into 4 groups of 6 each. Two groups of
rats were fed with a high fructose diet (60 g/100 g diet) and
administered either LA (35 mg/kg b.w., i.p) (FRU+LA) or
0.2 ml vehicle (saline) (FRU) for 45 days. The other 2 groups
were fed with control diet containing starch (60 g/100 g
diet) and administered either saline (CON) or lipoic acid
(CON+LA). The rats were maintained for 45 days and then
sacrificed. Plasma glucose, insulin, fructosamine, protein
glycation, and blood glycated hemoglobin (HbA1C) were
measured. Collagen was isolated from skin and the physicochemical
properties of collagen were studied. Fructose administration
caused accumulation of collagen in skin. Extensive
cross‐linking was evidenced by enhanced glycation
and AGE‐linked fluorescence. Increased peroxidation and
changes in physicochemical properties such as shrinkage
temperature, aldehyde content, solubililty pattern, susceptibility
to denaturing agents were observed in fructose‐fed
rats. SDS gel pattern of collagen from these rats showed
elevated β component of type I collagen. These changes
were alleviated by the simultaneous administration of LA.
Administration of LA to fructose‐fed rats had a positive
influence on both quantitative and qualitative properties of collagen. The results suggest a mechanism for the ability
of LA to delay diabetic complications.
Pentoxifylline Diminishes the Oxidative Damage to Renal Tissue Induced by Streptozotocin in the Rat
Authors: Dávila-Esqueda M. E. , Martínez-Morales F.
Published: February 2005

Oxidative damage has been suggested to be a contributing
factor in the development to diabetic nephropathy
(DN). Recently, there has been evidence that pentoxifylline
(PTX) has free radical‐scavenging properties; thus, its antiinflammatory
and renoprotective effects may be related to a
reduction in reactive oxygen species production. It is likely
that the pharmacological effects of PTX include an antioxidant
mechanism as shown in in vitro assays. The aim of
this study was to evaluate whether the reported renoprotective
effects of PTX could be the result of its antioxidant
actions in streptozotocin (STZ)‐induced DN in rats. The administration
of PTX over a period of 8 weeks, in addition
to displaying renoprotective effects, caused a significant reduction
in lipoperoxide levels (LPOS) in the diabetic kidney
(P < 0.05), compared to untreated rats. These levels were
comparable to those in the healthy kidney of experimental
animals (P > 0.05). All untreated STZ rats exhibited
an increase in LPOS as opposed to healthy controls (H)
(P < 0.001). The total antioxidant activity (TAA) in plasma
was increased significantly already after 2 days of STZ
(P < 0.05). When we examined the progression of TAA in
STZ rats, there was a significant decrease over 8 weeks
(P < 0.05). PTX treatment caused an increase in TAA
when compared to untreated STZ rats (P < 0.05).
Renal hypertrophy was less evident in PTX‐treated
STZ than in untreated STZ rats, evaluated by kidney
weight/body weight ratio. These results indicate
that PTX decreases the oxidative damage induced by these experimental procedures and may increase antioxidant
defense mechanisms in STZ‐induced diabetes in rats.
The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo
Authors: Liu Jianuo , Miwa Takashi , Hilliard Brendan , Chen Youhai , Lambris John D. , Wells Andrew D. , Song Wen-Chao
Published: February 2005

Decay-accelerating factor ([DAF] CD55) is a glycosylphosphatidylinositol-anchored membrane inhibitor of complement with broad clinical relevance. Here, we establish an additional and unexpected role for DAF in the suppression of adaptive immune responses in vivo. In both C57BL/6 and BALB/c mice, deficiency of the Daf1 gene, which encodes the murine homologue of human DAF, significantly enhanced T cell responses to active immunization. This phenotype was characterized by hypersecretion of interferon (IFN)-γ and interleukin (IL)-2, as well as down-regulation of the inhibitory cytokine IL-10 during antigen restimulation of lymphocytes in vitro. Compared with wild-type mice, Daf1−/− mice also displayed markedly exacerbated disease progression and pathology in a T cell–dependent experimental autoimmune encephalomyelitis (EAE) model. However, disabling the complement system in Daf1−/− mice normalized T cell secretion of IFN-γ and IL-2 and attenuated disease severity in the EAE model. These findings establish a critical link between complement and T cell immunity and have implications for the role of DAF and complement in organ transplantation, tumor evasion, and vaccine development.
Lineage relationships, homeostasis, and recall capacities of central– and effector–memory CD8 T cells in vivo
Authors: Bouneaud Cécile , Garcia Zacarias , Kourilsky Philippe , Pannetier Christophe
Published: February 2005

The lineage relationships of central–memory T cells (TCM) cells and effector–memory T cells (TEM), as well as their homeostasis and recall capacities, are still controversial. We investigated these issues in a murine model using two complementary approaches: T cell receptor repertoire analysis and adoptive transfer experiments of purified H-Y–specific TCM and TEM populations. Repertoire studies showed that approximately two thirds of TCM and TEM clones derived from a common naive precursor, whereas the other third was distinct. Both approaches highlighted that TCM and TEM had drastically distinct behaviors in vivo, both in the absence of antigen or upon restimulation. TCM clones were stable in the absence of restimulation and mounted a potent and sustained recall response upon secondary challenge, giving rise to both TCM and TEM, although only a fraction of TCM generated TEM. In contrast, TEM persisted for only a short time in the absence of antigen and, although a fraction of them were able to express CD62L, they were unable to mount a proliferative response upon secondary challenge in this model.
Private specificities of CD8 T cell responses control patterns of heterologous immunity
Authors: Kim Sung-Kwon , Cornberg Markus , Wang Xiaoting Z. , Chen Hong D. , Selin Liisa K. , Welsh Raymond M.
Published: February 2005

CD8 T cell cross-reactivity between viruses can play roles in protective heterologous immunity and damaging immunopathology. This cross-reactivity is sometimes predictable, such as between lymphocytic choriomeningitis virus (LCMV) and Pichinde virus, where cross-reactive epitopes share six out of eight amino acids. Here, however, we demonstrate more subtle and less predictable cross-reactivity between LCMV and the unrelated vaccinia virus (VV). Epitope-specific T cell receptor usage differed between individual LCMV-infected C57BL/6 mice, even though the mice had similar epitope-specific T cell hierarchies. LCMV-immune mice challenged with VV showed variations, albeit in a distinct hierarchy, in proliferative expansions of and down-regulation of IL-7Rα by T cells specific to different LCMV epitopes. T cell responses to a VV-encoded epitope that is cross-reactive with LCMV fluctuated greatly in VV-infected LCMV-immune mice. Adoptive transfers of splenocytes from individual LCMV-immune donors resulted in nearly identical VV-induced responses in each of several recipients, but responses differed depending on the donor. This indicates that the specificities of T cell responses that are not shared between individuals may influence cross-reactivity with other antigens and play roles in heterologous immunity upon encounter with another pathogen. This variability in cross-reactive T cell expansion that is unique to the individual may underlie variation in the pathogenesis of infectious diseases.
Mycobacterium tuberculosiscontrols host innate immune activation through cyclopropane modification of a glycolipid effector molecule
Authors: Rao Vivek , Fujiwara Nagatoshi , Porcelli Steven A. , Glickman Michael S.
Published: February 2005

Mycobacterium tuberculosis (Mtb) infection remains a global health crisis. Recent genetic evidence implicates specific cell envelope lipids in Mtb pathogenesis, but it is unclear whether these cell envelope compounds affect pathogenesis through a structural role in the cell wall or as pathogenesis effectors that interact directly with host cells. Here we show that cyclopropane modification of the Mtb cell envelope glycolipid trehalose dimycolate (TDM) is critical for Mtb growth during the first week of infection in mice. In addition, TDM modification by the cyclopropane synthase pcaA was both necessary and sufficient for proinflammatory activation of macrophages during early infection. Purified TDM isolated from a cyclopropane-deficient pcaA mutant was hypoinflammatory for macrophages and induced less severe granulomatous inflammation in mice, demonstrating that the fine structure of this glycolipid was critical to its proinflammatory activity. These results established the fine structure of lipids contained in the Mtb cell envelope as direct effectors of pathogenesis and identified temporal control of host immune activation through cyclopropane modification of TDM as a critical pathogenic strategy of Mtb.
MSH2–MSH6 stimulates DNA polymerase η, suggesting a role for A:T mutations in antibody genes
Authors: Wilson Teresa M. , Vaisman Alexandra , Martomo Stella A. , Sullivan Patsa , Lan Li , Hanaoka Fumio , Yasui Akira , Woodgate Roger , Gearhart Patricia J.
Published: February 2005

Activation-induced cytidine deaminase deaminates cytosine to uracil (dU) in DNA, which leads to mutations at C:G basepairs in immunoglobulin genes during somatic hypermutation. The mechanism that generates mutations at A:T basepairs, however, remains unclear. It appears to require the MSH2–MSH6 mismatch repair heterodimer and DNA polymerase (pol) η, as mutations of A:T are decreased in mice and humans lacking these proteins. Here, we demonstrate that these proteins interact physically and functionally. First, we show that MSH2–MSH6 binds to a U:G mismatch but not to other DNA intermediates produced during base excision repair of dUs, including an abasic site and a deoxyribose phosphate group. Second, MSH2 binds to pol η in solution, and endogenous MSH2 associates with the pol in cell extracts. Third, MSH2–MSH6 stimulates the catalytic activity of pol η in vitro. These observations suggest that the interaction between MSH2–MSH6 and DNA pol η stimulates synthesis of mutations at bases located downstream of the initial dU lesion, including A:T pairs.
Hysteresis in the Voltage Dependence of HCN Channels
Authors: Männikkö Roope , Pandey Shilpi , Larsson H. Peter , Elinder Fredrik
Published: February 2005

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) ion channels are important for rhythmic activity in the brain and in the heart. In this study, using ionic and gating current measurements, we show that cloned spHCN channels undergo a hysteresis in their voltage dependence during normal gating. For example, both the gating charge versus voltage curve, Q(V), and the conductance versus voltage curve, G(V), are shifted by about +60 mV when measured from a hyperpolarized holding potential compared with a depolarized holding potential. In addition, the kinetics of the tail current and the activation current change in parallel to the voltage shifts of the Q(V) and G(V) curves. Mammalian HCN1 channels display similar effects in their ionic currents, suggesting that the mammalian HCN channels also undergo voltage hysteresis. We propose a model in which HCN channels transit between two modes. The voltage dependence in the two modes is shifted relative to each other, and the occupancy of the two modes depends on the previous activation of the channel. The shifts in the voltage dependence are fast (τ ≈ 100 ms) and are not accompanied by any apparent inactivation. In HCN1 channels, the shift in voltage dependence is slower in a 100 mM K extracellular solution compared with a 1 mM K solution. Based on these findings, we suggest that molecular conformations similar to slow (C-type) inactivation of K channels underlie voltage hysteresis in HCN channels. The voltage hysteresis results in HCN channels displaying different voltage dependences during different phases in the pacemaker cycle. Computer simulations suggest that voltage hysteresis in HCN channels decreases the risk of arrhythmia in pacemaker cells.
PKC-induced Sensitization of Ca2+-dependent Exocytosis Is Mediated by Reducing the Ca2+ Cooperativity in Pituitary Gonadotropes
Authors: Yang Hua , Liu Huisheng , Hu Zhitao , Zhu Hongliang , Xu Tao
Published: February 2005

The highly cooperative nature of Ca2+-dependent exocytosis is very important for the precise regulation of transmitter release. It is not known whether the number of binding sites on the Ca2+ sensor can be modulated or not. We have previously reported that protein kinase C (PKC) activation sensitizes the Ca2+ sensor for exocytosis in pituitary gonadotropes. To further unravel the underlying mechanism of how the Ca2+ sensor is modulated by protein phosphorylation, we have performed kinetic modeling of the exocytotic burst and investigated how the kinetic parameters of Ca2+-triggered fusion are affected by PKC activation. We propose that PKC sensitizes exocytosis by reducing the number of calcium binding sites on the Ca2+ sensor (from three to two) without significantly altering the Ca2+-binding kinetics. The reduction in the number of Ca2+-binding steps lowers the threshold for release and up-regulates release of fusion-competent vesicles distant from Ca2+ channels.
Distribution of unique red feather pigments in parrots
Authors: McGraw Kevin J , Nogare Mary C
Published: February 2005

In many birds, red, orange and yellow feathers are coloured by carotenoid pigments, but parrots are an exception. For over a century, biochemists have known that parrots use an unusual set of pigments to produce their rainbow of plumage colours, but their biochemical identity has remained elusive until recently. Here, we use high-performance liquid chromatography to survey the pigments present in the red feathers of 44 species of parrots representing each of the three psittaciform families. We found that all species used the same suite of five polyenal lipochromes (or psittacofulvins) to colour their plumage red, indicating that this unique system of pigmentation is remarkably conserved evolutionarily in parrots. Species with redder feathers had higher concentrations of psittacofulvins in their plumage, but neither feather colouration nor historical relatedness predicted the ratios in which the different pigments appeared. These polyenes were absent from blood at the time when birds were replacing their colourful feathers, suggesting that parrots do not acquire red plumage pigments from the diet, but instead manufacture them endogenously at growing feathers.
Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing
Authors: Kanellopoulou Chryssa , Muljo Stefan A. , Kung Andrew L. , Ganesan Shridar , Drapkin Ronny , Jenuwein Thomas , Livingston David M. , Rajewsky Klaus
Published: February 2005

Dicer is the enzyme that cleaves double-stranded RNA (dsRNA) into 21–25-nt-long species responsible for sequence-specific RNA-induced gene silencing at the transcriptional, post-transcriptional, or translational level. We disrupted the dicer-1 (dcr-1) gene in mouse embryonic stem (ES) cells by conditional gene targeting and generated Dicer-null ES cells. These cells were viable, despite being completely defective in RNA interference (RNAi) and the generation of microRNAs (miRNAs). However, the mutant ES cells displayed severe defects in differentiation both in vitro and in vivo. Epigenetic silencing of centromeric repeat sequences and the expression of homologous small dsRNAs were markedly reduced. Re-expression of Dicer in the knockout cells rescued these phenotypes. Our data suggest that Dicer participates in multiple, fundamental biological processes in a mammalian organism, ranging from stem cell differentiation to the maintenance of centromeric heterochromatin structure and centromeric silencing.
SecM facilitates translocase function of SecA by localizing its biosynthesis
Authors: Nakatogawa Hitoshi , Murakami Akiko , Mori Hiroyuki , Ito Koreaki
Published: February 2005

“Arrest sequence” of Escherichia coli SecM interacts with the ribosomal exit tunnel and arrests its own translation elongation, which is released by cotranslational export of the nascent SecM chain. This property of SecM is essential for the basal and regulated expression of SecA. Here we report that SecM has an additional role of facilitating SecA activities. Systematic determinations of the SecA-abundance-protein export relationships of cells with different SecA contents revealed that SecA was less functional when SecM was absent from the upstream region of the secM–secA message, when SecM had the arrest-defective mutation, and also when SecM lacked the signal sequence. These results suggest that cotranslational targeting of nascent SecM to the translocon plays previously unrecognized roles of facilitating the formation of functional SecA molecules. Biosynthesis in the vicinity of the membrane and the Sec translocon will be beneficial for this multiconformation ATPase to adopt ready-to-function conformations.
Xenopus polo-like kinase Plx1 regulates XErp1, a novel inhibitor of APC/C activity
Authors: Schmidt Andreas , Duncan Peter I. , Rauh Nadine R. , Sauer Guido , Fry Andrew M. , Nigg Erich A. , Mayer Thomas U.
Published: February 2005

Metaphase-to-anaphase transition is a fundamental step in cell cycle progression where duplicated sister-chromatids segregate to the future daughter cells. The anaphase-promoting complex/cyclosome (APC/C) is a highly regulated ubiquitin-ligase that triggers anaphase onset and mitotic exit by targeting securin and mitotic cyclins for destruction. It was previously shown that the Xenopus polo-like kinase Plx1 is essential to activate APC/C upon release from cytostatic factor (CSF) arrest in Xenopus egg extract. Although the mechanism by which Plx1 regulates APC/C activation remained unclear, the existence of a putative APC/C inhibitor was postulated whose activity would be neutralized by Plx1 upon CSF release. Here we identify XErp1, a novel Plx1-regulated inhibitor of APC/C activity, and we demonstrate that XErp1 is required to prevent anaphase onset in CSF-arrested Xenopus egg extract. Inactivation of XErp1 leads to premature APC/C activation. Conversely, addition of excess XErp1 to Xenopus egg extract prevents APC/C activation. Plx1 phosphorylates XErp1 in vitro at a site that targets XErp1 for degradation upon CSF release. Thus, our data lead to a model of APC/C activation in Xenopus egg extract in which Plx1 targets the APC/C inhibitor XErp1 for degradation.
Ephrin-A2 reverse signaling negatively regulates neural progenitor proliferation and neurogenesis
Authors: Holmberg Johan , Armulik Annika , Senti Kirsten-André , Edoff Karin , Spalding Kirsty , Momma Stefan , Cassidy Rob , Flanagan John G. , Frisén Jonas
Published: February 2005

The number of cells in an organ is regulated by mitogens and trophic factors that impinge on intrinsic determinants of proliferation and apoptosis. We here report the identification of an additional mechanism to control cell number in the brain: EphA7 induces ephrin-A2 reverse signaling, which negatively regulates neural progenitor cell proliferation. Cells in the neural stem cell niche in the adult brain proliferate more and have a shorter cell cycle in mice lacking ephrin-A2. The increased progenitor proliferation is accompanied by a higher number of cells in the olfactory bulb. Disrupting the interaction between ephrin-A2 and EphA7 in the adult brain of wild-type mice disinhibits proliferation and results in increased neurogenesis. The identification of ephrin-A2 and EphA7 as negative regulators of progenitor cell proliferation reveals a novel mechanism to control cell numbers in the brain.
Protein interaction mapping: ADrosophilacase study
Authors: Formstecher Etienne , Aresta Sandra , Collura Vincent , Hamburger Alexandre , Meil Alain , Trehin Alexandra , Reverdy Céline , Betin Virginie , Maire Sophie , Brun Christine , Jacq Bernard , Arpin Monique , Bellaiche Yohanns , Bellusci Saverio , Benaroch Philippe , Bornens Michel , Chanet Roland , Chavrier Philippe , Delattre Olivier , Doye Valérie , Fehon Richard , Faye Gérard , Galli Thierry , Girault Jean-Antoine , Goud Bruno , de Gunzburg Jean , Johannes Ludger , Junier Marie-Pierre , Mirouse Vincent , Mukherjee Ashim , Papadopoulo Dora , Perez Franck , Plessis Anne , Rossé Carine , Saule Simon , Stoppa-Lyonnet Dominique , Vincent Alain , White Michael , Legrain Pierre , Wojcik Jérôme , Camonis Jacques , Daviet Laurent
Published: February 2005

TheDrosophila(fruit fly) model system has been instrumental in our current understanding of human biology, development, and diseases. Here, we used a high-throughput yeast two-hybrid (Y2H)-based technology to screen 102 bait proteins fromDrosophila melanogaster, most of them orthologous to human cancer-related and/or signaling proteins, against high-complexity fly cDNA libraries. More than 2300 protein-protein interactions (PPI) were identified, of which 710 are of high confidence. The computation of a reliability score for each protein-protein interaction and the systematic identification of the interacting domain combined with a prediction of structural/functional motifs allow the elaboration of known complexes and the identification of new ones. The full data set can be visualized using a graphical Web interface, the PIMRider (http://pim.hybrigenics.com), and is also accessible in the PSI standard Molecular Interaction data format. Our fly Protein Interaction Map (PIM) is surprisingly different from the one recently proposed by Giot et al. with little overlap between the two data sets. Analysis of the differences in data sets and methods suggests alternative strategies to enhance the accuracy and comprehensiveness of the post-genomic generation of broad-scale protein interaction maps.
Complete genome sequence of the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1 and comparison with Pyrococcus genomes
Authors: Fukui Toshiaki , Atomi Haruyuki , Kanai Tamotsu , Matsumi Rie , Fujiwara Shinsuke , Imanaka Tadayuki
Published: February 2005

The genus Thermococcus, comprised of sulfur-reducing hyperthermophilic archaea, belongs to the order Thermococcales in Euryarchaeota along with the closely related genus Pyrococcus. The members of Thermococcus are ubiquitously present in natural high-temperature environments, and are therefore considered to play a major role in the ecology and metabolic activity of microbial consortia within hot-water ecosystems. To obtain insight into this important genus, we have determined and annotated the complete 2,088,737-base genome of Thermococcus kodakaraensis strain KOD1, followed by a comparison with the three complete genomes of Pyrococcus spp. A total of 2306 coding DNA sequences (CDSs) have been identified, among which half (1165 CDSs) are annotatable, whereas the functions of 41% (936 CDSs) cannot be predicted from the primary structures. The genome contains seven genes for probable transposases and four virus-related regions. Several proteins within these genetic elements show high similarities to those in Pyrococcus spp., implying the natural occurrence of horizontal gene transfer of such mobile elements among the order Thermococcales. Comparative genomics clarified that 1204 proteins, including those for information processing and basic metabolisms, are shared among T. kodakaraensis and the three Pyrococcus spp. On the other hand, among the set of 689 proteins unique to T. kodakaraensis, there are several intriguing proteins that might be responsible for the specific trait of the genus Thermococcus, such as proteins involved in additional pyruvate oxidation, nucleotide metabolisms, unique or additional metal ion transporters, improved stress response system, and a distinct restriction system.
DIP-chip: Rapid and accurate determination of DNA-binding specificity
Authors: Liu Xiao , Noll David M. , Lieb Jason D. , Clarke Neil D.
Published: February 2005

We have developed a new method for determining the DNA-binding specificity of proteins. In DIP-chip (DNA immunoprecipitation with microarray detection), protein·DNA complexes are isolated from an in vitro mixture of purified protein and naked genomic DNA. Whole-genome DNA microarrays are used to identify the protein-bound DNA fragments, and the sequence of the identified fragments is used to derive binding-site descriptions. Using objective criteria for assessing the accuracy of DNA-binding motifs, and using yeast Leu3p as a model, we demonstrate that motifs determined by DIP-chip are as effective at predicting the location of bound proteins in vivo as are motifs determined by conventional low-throughput in vitro methods.
Complex genomic rearrangements lead to novel primate gene function
Authors: Ciccarelli Francesca D. , von Mering Christian , Suyama Mikita , Harrington Eoghan D. , Izaurralde Elisa , Bork Peer
Published: February 2005

Orthologous genes that maintain a single-copy status in a broad range of species may indicate a selection against gene duplication. If this is the case, then duplicates of such genes that do survive may have escaped the dosage control by rapid and sizable changes in their function. To test this hypothesis and to develop a strategy for the identification of novel gene functions, we have analyzed 22 primate-specific intrachromosomal duplications of genes with a single-copy ortholog in all other completely sequenced metazoans. When comparing this set to genes not exposed to the single-copy status constraint, we observed a higher tendency of the former to modify their gene structure, often through complex genomic rearrangements. The analysis of the most dramatic of these duplications, affecting ∼10% of human Chromosome 2, enabled a detailed reconstruction of the events leading to the appearance of a novel gene family. The eight members of this family originated from the highly conserved nucleoporin RanBP2 by several genetic rearrangements such as segmental duplications, inversions, translocations, exon loss, and domain accretion. We have experimentally verified that at least one of the newly formed proteins has a cellular localization different from RanBP2's, and we show that positive selection did act on specific domains during evolution.
Naturally occurring antisense: Transcriptional leakage or real overlap?
Authors: Dahary Dvir , Elroy-Stein Orna , Sorek Rotem
Published: February 2005

Naturally occurring antisense transcription is associated with the regulation of gene expression through a variety of biological mechanisms. Several recent genome-wide studies reported the identification of potential antisense transcripts for thousands of mammalian genes, many of them resulting from alternatively polyadenylated transcripts or heterogeneous transcription start sites. However, it is not clear whether this transcriptional plasticity is intentional, leading to regulated overlap between the transcripts, or, alternatively, represents a “leakage” of the RNA transcription machinery. To address this question through an evolutionary approach, we compared the genomic organization of genes, with or without antisense, between human, mouse, and the pufferfish Fugu rubripes. Our hypothesis was that if two neighboring genes overlap and have a sense-antisense relationship, we would expect negative selection acting on the evolutionary separation between them. We found that antisense gene pairs are twice as likely to preserve their genomic organization throughout vertebrates' evolution compared to nonantisense pairs, implying an overlap existence in the ancestral genome. In addition, we show that increasing the genomic distance between pairs of genes having a sense-antisense relationship is selected against. These findings indicate that, at least in part, the abundance of antisense transcripts observed in expressed data represents real overlap rather than transcriptional leakage. Moreover, our results imply that natural antisense transcription has considerably affected vertebrate genome evolution.
International space station mechanism contact simulation
Authors: Favero Jan P.
Published: February 2005

Purpose

To provide an overview of how the solid‐to‐solid contact force equation in MSC.ADAMS can be used to reduce contact model development, minimize the probability of introducing an error and reduce simulation run time by citing the example of the International Space Station (ISS).Design/methodology/approach – In early 2000, a redesign of the ISS required a more thorough representation of the contacting geometry. The MSC.ADAMS solid to solid contact force statement became available in time to solve this problem. This allowed simulation of the segment to segment attachment, including various combinations of contact feature misalignment.Findings – A structural failure of a “Zip” nut during qualification testing resulted in a NASA request for a force balance on the nut housing, internal nut segments and bolt. Using MSC.ADAMS solid to solid contact simulation, the desired force balance was obtained. The analysis showed the coarse guide to fine guide handoff did not bind and fine guide seating engaged, allowing the four motorized bolts to connect the segment‐to‐segment interface.Originality/value – MSC.ADAMS solid to solid contact algorithms decreased simulation time, allowing this very complicated contact problem to be completed in less than 30 min. Using CAD model solid geometry greatly reduced model development time. Solid to solid contact simulation eliminated the need for tedious derivation vector algebra contact equations and greatly advanced the level of geometric complexity that could be modeled as contacting interfaces. This also minimizes the probably of errors.
Feedforward neural network based non‐linear dynamic modelling of a TRMS using RPROP algorithm
Authors: Hasan Shaheed M.
Published: February 2005

Purpose

To develop a non‐linear modelling technique for modern air vehicles with an application to a twin rotor multi‐input‐multi‐output system (TRMS) which resembles the dynamics of a helicopter to a certain extent and presents formidable control challenges.Design/methodology/approach – A Non‐linear AutoRegressive process with eXternal input (NARX) approach with a feedforward neural work and a resilient propagation (RPROP) algorithm is used to model the system. The RPROP algorithm possesses direct weight update capability without considering the size of the partial derivative. The obtained model is shown to be adequate by carrying out convincing tests such as correlations, cross‐validations and prediction based on predicted output and, therefore, is deemed to be reliable.Findings – It is shown that the combination of the feedforward neural networks and RPROP algorithms is very useful and effective in modelling systems with high non‐linearity and other complex characteristics. It is always important to attain a model with minimum number of neurons in different layers of the network by overcoming the possibility of getting stuck in the shallow local minimum of error function by using RPROP algorithm.Research limitations/implications – The system is modelled off‐line. On‐line modelling will be required for real‐time control purpose.Practical implications – The non‐linear modelling approach presented in this study is shown to be appropriately applicable to model new generations' air vehicles and other complex mechatronic systems such as TRMS. So, the approach will be appealing to industrial applications.Originality/value – This paper addresses the problems of modelling modern sophisticated non‐linear systems with complex characteristics and uncertain dynamics.
Investigation of a 3D non‐contact measurement based blade repair integration system
Authors: Gao Jian , Folkes Janet , Yilmaz Oguzhan , Gindy Nabil
Published: February 2005

Purpose

The aim of the paper is to provide an economically viable solution for the blade repair process. There is a continual increase in the repair market, which requires an increased level of specialised technology to reduce the repair cost and to increase productivity of the process.Design/methodology/approach – This paper introduces the aerospace component defects to be repaired. Current repair technologies including building‐up and machining technology are reviewed. Through the analysis of these available technologies, this paper proposes an integrated repair strategy through information integration and processes concentration.Findings – Provides detailed description and discussion for the repair system, including 3D digitising system, repair inspection, reverse engineering‐based polygonal modelling, and adaptive laser cladding and adaptive machining process.Originality/value – This paper describes a 3D non‐contact measurement‐based repair integration system, and provides a solution to create an individual blade‐oriented nominal model to achieve adaptive repair process (laser cladding/machining) and automated inspection.
Analyses on ducted tail rotor and airfoil aerodynamic characteristics with CFD
Authors: Cao Yihua , Chen Ke , Wang Jian
Published: February 2005

Purpose

To establish a method for the calculations in the field of rotor aerodynamics.Design/methodology/approach – The calculations of the lift‐drag characteristics of OAF and NACA63A312 airfoils at low speed are made using Jameson/TVD mixed scheme. By means of finite volume approach for numerical discretization and Runge‐Kutta time‐stepping advance, Euler/Navier‐Stokes equations are solved. Furthermore, a model based on circular tiny segment momentum theory and blade element theory is established to study the thrust and power of ducted tail rotor.Findings – The results of the calculation demonstrate the feasibility of the established method for analyzing ducted tail rotor aerodynamic characteristics.Research limitations/implications – Although the global thrust and power of ducted tail‐rotor could be obtained using current method, the exact flow filed (such as shroud pressure field and the flow over fan blade) calculations still rely on the complex three‐dimensional CFD technique that should be studied in future.Practical implications – A very useful method for the preliminary design of the ducted tail rotor.Originality/value – By comparing the calculated results with those of relevant experiment, it is proved that the method developed here is suitable for the calculations in the field of rotor aerodynamics.
N‐heterocyclic amines and derivatives as corrosion inhibitors for iron in perchloric acid
Authors: Babić‐Samardžija K. , Khaled K.F. , Hackerman N.
Published: February 2005

Purpose

Work reported in the present paper investigated the inhibiting properties of a number of N‐heterocyclic amines in 0.1 mol/l HClO4. An attempt also was made to correlate some molecular parameters of these compounds with their corrosion inhibitor efficiency.

Design/methodology/approach

The test series included piperidine (pip), 2‐methylpiperidine (2mp), 3‐methylpiperidine (3mp), cis‐2,6‐dimethylpiperidine (26dp), 3,5‐dimethylpiperidine (35dp), 3‐hydroxy piperidine (3hp), 4‐hydroxypiperidine (4hp), 4‐aminopiperidine (4ap), piperazine (pz), 2‐methylpiperazine (2mpz) and cis‐2,6‐dimethylpiperazine (26dpz). The inhibiting effect was investigated in 0.1& mol/L HClO4 by potentiodynamic polarization (DC) and electrochemical impedance spectroscopy (EIS).

Findings

The results show that these compounds suppressed both cathodic and anodic processes of iron corrosion in 0.1 mol/l HClO4 by adsorption on the surface, which followed a Langmuir adsorption isotherm. Experimental observations indicated that basic piperidine and piperazine were better corrosion inhibitors than were their derivatives. The inhibition properties of N‐heterocyclic amines were found to be related to the charge on the nitrogen atom and the sum of the net charge of the all six atoms from the cyclic ring.

Originality/value

This paper provides useful information relative to corrosion inhibition efficiency of the group of N‐heterocyclic amines. It is concerned with a theoretical explanation between electronic and structural characteristics of these compounds and their inhibitor efficiency.