bluuebunny/crossref_metadata_2025 huggingface dataset:
An α-Helical Extension of the ELMO1 Pleckstrin Homology Domain Mediates Direct Interaction to DOCK180 and Is Critical in Rac Signaling
Authors: Komander David , Patel Manishha , Laurin Mélanie , Fradet Nadine , Pelletier Ariane , Barford David , Côté Jean-François
Published: September 2008

The mammalian DOCK180 protein belongs to an evolutionarily conserved protein family, which together with ELMO proteins, is essential for activation of Rac GTPase-dependent biological processes. Here, we have analyzed the DOCK180-ELMO1 interaction, and map direct interaction interfaces to the N-terminal 200 amino acids of DOCK180, and to the C-terminal 200 amino acids of ELMO1, comprising the ELMO1 PH domain. Structural and biochemical analysis of this PH domain reveals that it is incapable of phospholipid binding, but instead structurally resembles FERM domains. Moreover, the structure revealed an N-terminal amphiphatic α-helix, and point mutants of invariant hydrophobic residues in this helix disrupt ELMO1-DOCK180 complex formation. A secondary interaction between ELMO1 and DOCK180 is conferred by the DOCK180 SH3 domain and proline-rich motifs at the ELMO1 C-terminus. Mutation of both DOCK180-interaction sites on ELMO1 is required to disrupt the DOCK180-ELMO1 complex. Significantly, although this does not affect DOCK180 GEF activity toward Rac in vivo, Rac signaling is impaired, implying additional roles for ELMO in mediating intracellular Rac signaling.
The Checkpoint Kinase Hsl1p Is Activated by Elm1p-dependent Phosphorylation
Authors: Szkotnicki Lee , Crutchley John M. , Zyla Trevin R. , Bardes Elaine S.G. , Lew Daniel J.
Published: September 2008

Saccharomyces cerevisiae cells growing in the outdoor environment must adapt to sudden changes in temperature and other variables. Many such changes trigger stress responses that delay bud emergence until the cells can adapt. In such circumstances, the morphogenesis checkpoint delays mitosis until a bud has been formed. Mitotic delay is due to the Wee1 family mitotic inhibitor Swe1p, whose degradation is linked to bud emergence by the checkpoint kinase Hsl1p. Hsl1p is concentrated at the mother-bud neck through association with septin filaments, and it was reported that Hsl1p activation involved relief of autoinhibition in response to septin interaction. Here we challenge the previous identification of an autoinhibitory domain and show instead that Hsl1p activation involves the phosphorylation of threonine 273, promoted by the septin-associated kinase Elm1p. We identified elm1 mutants in a screen for defects in Swe1p degradation and show that a phosphomimic T273E mutation in HSL1 bypasses the need for Elm1p in this pathway.
Spirituality in the Flesh
Authors: Fuller Robert C.
Published: September 2008

This book examines the biological underpinnings of religion. We can only experience, the book argues, what our bodies allow us to experience. As a consequence, religious thought and feeling are heavily influenced by our sensory organs, emotional programs, sexual sensibilities, and the neural structure of our brains. Studying “spirituality in the flesh” opens up new and exciting agendas for understanding the nature and value of human religiosity. This exploration of embodied spirituality establishes middle ground between the explanations of religion typically made by either scientists or humanists. The book takes most scientific interpreters to task for failing to understand the inherently cultural aspects of embodied experience, even as he chides most religion scholars for ignoring new knowledge about the biological substrates of human thought and behavior. Each chapter takes up a different facet of embodied experience and shows the ways it helps us understand just how and why humans reconstruct their worlds in religious ways. Emotional programs such as fear or wonder, altered consciousness, sexuality, pain, and spatial orientation to the environment provide critical categories that are used to interpret selected episodes in American religious history. Topics as diverse as apocalypticism, nature religion, Native American peyotism, and the sexual experimentalism found in 19th‐century communal societies illustrate how the study of spirituality in the flesh enriches our appreciation of religion.
Mark–recapture studies and demography
Authors: Cordero-Rivera Adolfo , Stoks Robby
Published: September 2008

Population ecologists track wild animals over their lifetimes using mark-recapture methods. Odonates are easily marked and remain near water bodies, allowing for high recapture rates. In recent years, the focus in mark-recapture models has switched from population size estimates to survival and recapture rate estimation, and from testing hypotheses to model selection and inference. This chapter presents a review of the literature on mark-recapture studies, with a suggestion of areas where more research is needed. These include the effect of marking on survival and recapture rates, differences in survival between sexes and female colour morphs, the relative importance of processes in the larval and the adult stage in driving population dynamics, and the contribution of local and regional processes in shaping metapopulation dynamics.
Dragonflies as focal organisms in contemporary conservation biology
Authors: Samways Michael J.
Published: September 2008

Freshwater ecosystems worldwide are highly threatened. As a consequence, many dragonfly species are also threatened. The threats to them are many and varied, including invasive alien plants and habitat loss. Global climate change is also beginning to affect them, with some species changing their geographical ranges. Worldwide assessments are being made of dragonfly conservation status. They are one of the highest profile invertebrates in conservation awareness, planning, and action. One reason for this is that they are highly valued, being iconic, aesthetic, and sensitive bioindicators of landscape change. They are both important subjects in their own right as well as important role players in overall biodiversity conservation.
Valuing dragonflies as service providers
Authors: Simaika John P. , Samways Michael J.
Published: September 2008

Valuing the services provided by ecosystems and their components is emerging as a new, practical tool for conservation of biodiversity. One such framework for quantifying those components of biodiversity and their attributes, which are important for the diversity of ecosystem services, is the Service Providing Unit (SPU). This framework provides a conceptual link between ecosystem services and the role of populations of different species in providing these services. Dragonflies provide several ecosystem services to humanity at the population level. Their role as SPUs encompasses most of the 28 ecosystem services, directly or indirectly, as recognized by the Millennium Ecosystem Assessment, in the categories of provisioning, cultural, supporting, and regulating services. Service provision by dragonflies can be quantified, for example, in pest control and riparian restoration. As the SPU concept, as a value metric, has considerable currency with dragonflies, there is merit in investigating its application to other invertebrate taxa and ecosystems.
Evolution of morphological defences
Authors: Johansson Frank , Mikolajewski Dirk Johannes
Published: September 2008

Understanding the ecology and evolution of morphological defences in animals and plants may help us to understand and protect biodiversity. Several species of dragonfly larvae express lateral and dorsal abdominal spines. In some species these spines seem to be fixed, and in others they are induced by the presence of predatory fish. Larger spines are adaptations to reduce predation risk by fish, but incur a cost because large spines are associated with a higher predation risk by invertebrate predators. The difference in vulnerability to different predators has the potential to affect temporal and spatial variation in the morphology of dragonfly larvae, and may ultimately result in speciation. Future focus on the joint evolution of correlated defensive traits such as morphology and behaviour and their plasticity might be fruitful for a better understanding of the development of animal diversity.
Sexual size dimorphism: patterns and processes
Authors: Serrano-Meneses Martín Alejandro , Córdoba-Aguilar Alex , Székely Tamás
Published: September 2008

Odonates provide excellent model organisms for testing functional explanations of sexual size dimorphism (SSD) because of their wide variety of habitats, morphology, development, feeding behaviour, and mating strategies. This chapter discusses three major functional hypotheses of SSD and uses data on 133 odonate species to describe their patterns of SSD. It shows that SSD centres around monomorphism in dragonflies, whereas SSD is mostly male-biased in damselflies. Interestingly, phylogenetic comparative analyses suggest that damselflies — but not dragonflies — exhibit allometry consistent with Rensch's rule. Sexual selection acts mainly on males, whereas fecundity selection appears to influence female body size. Further tests, however, are essential, in particular of fecundity selection and the differential niche-utilization.
Directed Random Growth Models on the Plane
Authors: Seppäläinen Timo
Published: September 2008

This chapter discusses random growth models describing the evolution of an interface in the plane. For specific models, three basic questions are discussed. First, under appropriate scaling, what is the limiting shape of the interface and what is the partial differential equation governing its evolution? Second, how can random fluctuations around the limit behaviour be described? Third, how can atypical behaviour be characterized? The power of probabilistic tools is demonstrated by employing laws of large numbers, central limit theorems, and large deviation techniques to answer these questions, respectively.
The Pleasures and Pains of Studying the Two-Type Richardson Model
Authors: Deijfen Maria , Häggström Olle
Published: September 2008

This chapter provides a survey of known results and open problems for the two-type Richardson model, which is a stochastic model for competition on a lattice. In its simplest formulation, the Richardson model describes the evolution of a single infectious entity on the lattice, but more recently the dynamics have been extended to comprise two competing growing entities. For this version of the model, the main question is whether there is a positive probability for both entities to simultaneously grow to occupy infinite parts of the lattice, the conjecture being that the answer is yes if and only if the entities have the same intensity. In this paper attention focuses on the two-type model, but the most important results for the one-type version are also described.
Validity and Non-Validity of Propagation of Chaos
Authors: Matthies Karsten , Theil Florian
Published: September 2008

In this chapter a novel, rigorous approach to analyse the validity of continuum approximations for deterministic interacting particle systems is discussed. The focus is on the Boltzmann–Grad limit of ballistic annihilation, a topic which has has received considerable attention in the physics literature. In this situation, due to the deterministic nature of the evolution, it is possible that correlations build up and the mean–field approximation by the Boltzmann equation breaks down. A sharp condition on the initial distribution, which ensures the validity of the Boltzmann equation is given, together with an example demonstrating the failure of the mean-field theory if the condition is violated.
A Short Introduction to Anderson Localization
Authors: Hundertmark Dirk
Published: September 2008

Anderson localization is another physical problem that has spurred much mathematical research. The issue here is how disorder, such as random changes in the spacing of a crystal, influences the movement of electrons and thus the crystal's conductivity. In 1977, Anderson was awarded the Nobel prize for his investigations on this subject. This chapter introduces the physical model, based on a random Schrodinger operator, and carefully reviews different notions of localization as well as rigorous proofs of localization. A very readable introduction to finite-volume criteria for localization via percolation arguments is followed by an elegant proof of localization for large disorder.
Delegated Governance and the British State
Authors: Flinders Matthew
Published: September 2008

The delegation of functions and responsibilities to quasi-autonomous bodies operating with a significant degree of autonomy arguably empowers governments to address a wide range of social issues simultaneously without having to be involved with the minutiae of day-to-day socio-political interactions. Delegation therefore provides a structural and esoteric capacity beyond the cognitive and physical limits of politicians. There is nothing wrong with delegation as such. The problem relates to the failure to manage delegation in Britain. And yet we actually know very little about how the state beyond the core actually operates, how many bodies exist, what they do, how they are recruited, or why they were created. These gaps in our knowledge are all the more problematic in light of recent pronouncements by politicians at the national and European levels that ‘depoliticization’ is a central strand of their approach to governing. This book seeks to fill these gaps in our knowledge while at the same time cultivating a more balanced or sophisticated approach to the study of delegation. Delegated public bodies as they have been used as a tool of governance in the past should not be confused with how they might be used in the future. This book draws upon research conducted within the very core of the British political system during a Whitehall Fellowship within the Cabinet Office. It argues that the British state is ‘walking without order’ due to a general acceptance of the logic of delegation without any detailed or principled consideration of the administrative of democratic consequences of this process.
Different phases of long-term memory require distinct temporal patterns of PKA activity after single-trial classical conditioning
Authors: Michel Maximilian , Kemenes Ildikó , Müller Uli , Kemenes György
Published: September 2008

The cAMP-dependent protein kinase (PKA) is known to play a critical role in both transcription-independent short-term or intermediate-term memory and transcription-dependent long-term memory (LTM). Although distinct phases of LTM already have been demonstrated in some systems, it is not known whether these phases require distinct temporal patterns of learning-induced PKA activation. This question was addressed in a robust form of associative LTM that emerges within a matter of hours after single-trial food-reward classical conditioning in the pond snail Lymnaea stagnalis. After establishing the molecular and functional identity of the PKA catalytic subunit in the Lymnaea nervous system, we used a combination of PKA activity measurement and inhibition techniques to investigate its role in LTM in intact animals. PKA activity in ganglia involved in single-trial learning showed a short latency but prolonged increase after classical conditioning. However, while increased PKA activity immediately after training (0–10 min) was essential for an early phase of LTM (6 h), the late phase of LTM (24 h) required a prolonged increase in PKA activity. These observations indicate mechanistically different roles for PKA in recent and more remote phases of LTM, which may underpin different cellular and molecular mechanisms required for these phases.
Decreased parahippocampal activity in associative priming: Evidence from an event-related fMRI study
Authors: Yang Jiongjiong , Meckingler Axel , Xu Mingwei , Zhao Yanbing , Weng Xuchu
Published: September 2008

In recent years, there has been intense debate on the neural basis of associative priming, particularly on the role of the medial temporal lobe (MTL) in retrieving associative information without awareness. In this study, event-related fMRI was used while healthy subjects performed a perceptual identification task on briefly presented unrelated word pairs and an associative recognition memory task. Contamination of priming by explicit memory was successfully controlled, as associative priming and explicit memory were dissociated on the behavioral level. The fMRI results showed a functional dissociation within the MTL with respect to associative priming effects. The right parahippocampal cortex, but not the hippocampus, showed decreased activation for old vs. new pairs and old vs. recombined pairs (associative priming). The bilateral hippocampus and the right parahippocampal cortex were involved in explicit associative memory. These data provide evidence that subregions of the MTL participate in associative priming even when explicit involvement was controlled. Thus, different regions within the MTL play distinct roles in explicit and implicit associative memory.
Intra-amygdala injections of CREB antisense impair inhibitory avoidance memory: Role of norepinephrine and acetylcholine
Authors: Canal Clinton E. , Chang Qing , Gold Paul E.
Published: September 2008

Infusions of CREB antisense into the amygdala prior to training impair memory for aversive tasks, suggesting that the antisense may interfere with CRE-mediated gene transcription and protein synthesis important for the formation of new memories within the amygdala. However, the amygdala also appears to modulate memory formation in distributed brain sites, through mechanisms that include the release of norepinephrine and acetylcholine within the amygdala. Thus, CREB antisense injections may affect memory by interfering with mechanisms of modulation, rather than storage, of memory. In the present experiment, rats received bilateral intra-amygdala infusions of CREB antisense (2 nmol/1 μL) 6 h prior to inhibitory avoidance training. In vivo microdialysis samples were collected from the right amygdala before, during, and following training. CREB antisense produced amnesia tested at 48 h after training. In addition, CREB antisense infusions dampened the training-related release of norepinephrine, and to a lesser extent of acetylcholine, in the amygdala. Furthermore, intra-amygdala infusions of the β-adrenergic receptor agonist clenbuterol administered immediately after training attenuated memory impairments induced by intra-amygdala injections of CREB antisense. These findings suggest that intra-amygdala treatment with CREB antisense may affect processes involved in modulation of memory in part through interference with norepinephrine and acetylcholine neurotransmission in the amygdala.
Faster forgetting contributes to impaired spatial memory in the PDAPP mouse: Deficit in memory retrieval associated with increased sensitivity to interference?
Authors: Daumas Stephanie , Sandin Johan , Chen Karen S. , Kobayashi Dione , Tulloch Jane , Martin Stephen J. , Games Dora , Morris Richard G.M.
Published: September 2008

Two experiments were conducted to investigate the possibility of faster forgetting by PDAPP mice (a well-established model of Alzheimer’s disease as reported by Games and colleagues in an earlier paper). Experiment 1, using mice aged 13–16 mo, confirmed the presence of a deficit in a spatial reference memory task in the water maze by hemizygous PDAPP mice relative to littermate controls. However, after overtraining to a criterion of equivalent navigational performance, a series of memory retention tests revealed faster forgetting in the PDAPP group. Very limited retraining was sufficient to reinstate good memory in both groups, indicating that their faster forgetting may be due to retrieval failure rather than trace decay. In Experiment 2, 6-mo-old PDAPP and controls were required to learn each of a series of spatial locations to criterion with their memory assessed 10 min after learning each location. No memory deficit was apparent in the PDAPP mice initially, but a deficit built up through the series of locations suggestive of increased sensitivity to interference. Faster forgetting and increased interference may each reflect a difficulty in accessing memory traces. This interpretation of one aspect of the cognitive deficit in human mutant APP mice has parallels to deficits observed in patients with Alzheimer’s disease, further supporting the validity of transgenic models of the disease.
Neural and molecular mechanisms of microcognition inLimax
Authors: Watanabe Satoshi , Kirino Yutaka , Gelperin Alan
Published: September 2008

Various non-mammalian model systems are being explored in the search for mechanisms of learning and memory storage of sufficient generality to contribute to the understanding of mammalian learning mechanisms. The terrestrial molluskLimax maximusis one such model system in which mammalian-quality learning has been documented using odors as conditioned stimuli. TheLimaxodor information-processing circuits incorporate several system design features also found in mammalian odor-processing circuits, such as the use of cellular and network oscillations for making odor computations and the use of nitric oxide to control network oscillations. Learning and memory formation has been localized to a particular central circuit, the procerebral lobe, in which selective gene activation occurs through odor learning. Since the isolatedLimaxbrain can perform odor learning in vitro, the circuits and synapses causally linked to learning and memory formation are assessable for further detailed analysis.
Functional Analysis of the Cellulose Synthase-Like Genes CSLD1, CSLD2, and CSLD4 in Tip-Growing Arabidopsis Cells
Authors: Bernal Adriana J. , Yoo Cheol-Min , Mutwil Marek , Jensen Jakob Krüger , Hou Guichuan , Blaukopf Claudia , Sørensen Iben , Blancaflor Elison B. , Scheller Henrik Vibe , Willats William G.T.
Published: September 2008

A reverse genetic approach was used to investigate the functions of three members of the cellulose synthase superfamily in Arabidopsis (Arabidopsis thaliana), CELLULOSE SYNTHASE-LIKE D1 (CSLD1), CSLD2, and CSLD4. CSLD2 is required for normal root hair growth but has a different role from that previously described for CSLD3 (KOJAK). CSLD2 is required during a later stage of hair development than CSLD3, and CSLD2 mutants produce root hairs with a range of abnormalities, with many root hairs rupturing late in development. Remarkably, though, it was often the case that in CSLD2 mutants, tip growth would resume after rupturing of root hairs. In silico, semiquantitative reverse transcription-polymerase chain reaction, and promoter-reporter construct analyses indicated that the expression of both CSLD2 and CSLD3 is elevated at reduced temperatures, and the phenotypes of mutants homozygous for insertions in these genes were partially rescued by reduced temperature growth. However, this was not the case for a double mutant homozygous for insertions in both CSLD2 and CSLD3, suggesting that there may be partial redundancy in the functions of these genes. Mutants in CSLD1 and CSLD4 had a defect in male transmission, and plants heterozygous for insertions in CSLD1 or CSLD4 were defective in their ability to produce pollen tubes, although the number and morphology of pollen grains was normal. We propose that the CSLD family of putative glycosyltransferases synthesize a polysaccharide that has a specialized structural role in the cell walls of tip-growing cells.
Aγ-Glutamyl Transpeptidase-Independent Pathway of Glutathione Catabolism to Glutamate via 5-Oxoproline in Arabidopsis
Authors: Ohkama-Ohtsu Naoko , Oikawa Akira , Zhao Ping , Xiang Chengbin , Saito Kazuki , Oliver David J.
Published: September 2008

The degradation pathway of glutathione (GSH) in plants is not well understood. In mammals, GSH is predominantly metabolized through the γ-glutamyl cycle, where GSH is degraded by the sequential reaction of γ-glutamyl transpeptidase (GGT), γ-glutamyl cyclotransferase, and 5-oxoprolinase to yield glutamate (Glu) and dipeptides that are subject to peptidase action. In this study, we examined if GSH is degraded through the same pathway in Arabidopsis (Arabidopsis thaliana) as occurs in mammals. In Arabidopsis, the oxoprolinase knockout mutants (oxp1-1 and oxp1-2) accumulate more 5-oxoproline (5OP) and less Glu than wild-type plants, suggesting substantial metabolite flux though 5OP and that 5OP is a major contributor to Glu steady-state levels. In the ggt1-1/ggt4-1/oxp1-1 triple mutant with no GGT activity in any organs except young siliques, the 5OP concentration in leaves was not different from that in oxp1-1, suggesting that GGTs are not major contributors to 5OP production in Arabidopsis. 5OP formation strongly tracked the level of GSH in Arabidopsis plants, suggesting that GSH is the precursor of 5OP in a GGT-independent reaction. Kinetics analysis suggests that γ-glutamyl cyclotransferase is the major source of GSH degradation and 5OP formation in Arabidopsis. This discovery led us to propose a new pathway for GSH turnover in plants where GSH is converted to 5OP and then to Glu by the combined action of γ-glutamyl cyclotransferase and 5-oxoprolinase in the cytoplasm.
Applicability of real-space methods to diffraction strain measurements in single crystals
Authors: Kalenci Özgür , Noyan I. C.
Published: September 2008

It is shown through rigorous dynamical diffraction modeling that the ray tracing methods employed in kinematical diffraction analysis of strain become invalid for weakly deformed crystals that scatter in the dynamical limit. For an Si crystal illuminated by 12 keV X-rays, the kinematical formalisms should not be used if the strain gradient along the diffraction vector is smaller than 10−5 µm−1.
Inhibition of phosphoantigen‐mediated γδ T‐cell proliferation by CD4+ CD25+ FoxP3+ regulatory T cells
Authors: Kunzmann Volker , Kimmel Brigitte , Herrmann Thomas , Einsele Hermann , Wilhelm Martin
Published: September 2008

Tumour growth promotes the expansion of CD4+ CD25+ FoxP3+ regulatory T cells (Tregs) which suppress various arms of immune responses and might therefore contribute to tumour immunosurveillance. In this study, we found an inverse correlation between circulating Treg frequencies and phosphoantigen‐induced γδ T‐cell proliferation in cancer patients, which prompted us to address the role of Tregs in controlling the γδ T‐cell arm of innate immune responses. In vitro, human Treg–peripheral blood mononuclear cell (PBMC) co‐cultures strongly inhibited phosphoantigen‐induced proliferation of γδ T cells and depletion of Tregs restored the impaired phosphoantigen‐induced γδ T‐cell proliferation of cancer patients. Tregs did not suppress other effector functions of γδ T cells such as cytokine production or cytotoxicity. Our experiments indicate that Tregs do not mediate their suppressive activity via a cell–cell contact‐dependent mechanism, but rather secrete a soluble non‐proteinaceous factor, which is independent of known soluble factors interacting with amino acid depletion (e.g. arginase‐diminished arginine and indolamine 2,3‐dioxygenase‐diminished tryptophan) or nitric oxide (NO) production. However, the proliferative activity of αβ T cells was not affected by this cell–cell contact‐independent suppressive activity induced by Tregs. In conclusion, these findings indicate a potential new mechanism by which Tregs can specifically suppress γδ T cells and highlight the strategy of combining Treg inhibition with subsequent γδ T‐cell activation to enhance γδ T cell‐mediated immunotherapy.
Adverse effect of the anabolic–androgenic steroid mesterolone on cardiac remodelling and lipoprotein profile is attenuated by aerobicz exercise training
Authors: Fontana Karina , Oliveira Helena Coutinho Franco , Leonardo Marta Beatriz , Mandarim‐de‐Lacerda Carlos Alberto , Da Cruz‐Höfling Maria Alice
Published: September 2008

Abuse of anabolic–androgenic steroids (AAS) for improving physical performance is associated with serious, sometimes fatal, adverse effects. The aim of the present work was to investigate the effects of AAS on the cardiac structure and the plasma lipoprotein profile isolated and in combination with exercise. Transgenic mice with a human lipaemic phenotype (expressing cholesteryl ester transfer protein on the LDL receptor knockout background) were used in this study. Sedentary and exercised mice (treadmill running, five times per week for 6 weeks) were treated with mesterolone (2 μg/g body weight) or vehicle (control‐C) in the last 3 weeks. Four groups were compared: (i) exercise + mesterolone (Ex‐M), (ii) exercise + vehicle (Ex‐C), (iii) sedentary + mesterolone (Sed‐M) and (iv) sedentary + vehicle (Sed‐C). Arterial blood pressure and body mass increased in all groups along time, but Sed‐M reached the highest values and Ex‐C the lowest. Treatment with mesterolone increased total cholesterol, triglyceride, low‐density lipoprotein cholesterol (LDL‐c) and very LDL‐c (VLDL‐c) plasma levels. However, exercise blunted some of these deleterious effects by increasing high‐density lipoprotein cholesterol and decreasing LDL‐c, VLDL‐c and triglycerides. Exercise training induced beneficial effects, such as physiological cardiomyocyte hypertrophy, increase in myocardial circulation and decrease in cardiac interstitium. However, mesterolone impaired such physiological gains and in addition increased troponin T plasma levels both in sedentary and exercised mice. Thus, while mesterolone induced pro‐atherogenic lipoprotein profile and pathogenic cardiac hypertrophy, exercise counteracted these effects and modified favourably both the lipoprotein profile and the cardiac remodelling induced by mesterolone.
Isoproterenol induces primary loss of dystrophin in rat hearts: correlation with myocardial injury
Authors: Campos Erica C. , Romano Minna M. D. , Prado Cibele M. , Rossi Marcos A.
Published: September 2008

The mechanism of isoproterenol‐induced myocardial damage is unknown, but a mismatch of oxygen supply vs. demand following coronary hypotension and myocardial hyperactivity is the best explanation for the complex morphological alterations observed. Severe alterations in the structural integrity of the sarcolemma of cardiomyocytes have been demonstrated to be caused by isoproterenol. Taking into account that the sarcolemmal integrity is stabilized by the dystrophin‐glycoprotein complex (DGC) that connects actin and laminin in contractile machinery and extracellular matrix and by integrins, this study tests the hypothesis that isoproterenol affects sarcolemmal stability through changes in the DGC and integrins. We found different sensitivity of the DGC and integrin to isoproterenol subcutaneous administration. Immunofluorescent staining revealed that dystrophin is the most sensitive among the structures connecting the actin in the cardiomyocyte cytoskeleton and the extracellular matrix. The sarcomeric actin dissolution occurred after the reduction or loss of dystrophin. Subsequently, after lysis of myofilaments, γ‐sarcoglycan, β‐dystroglycan, β1‐integrin, and laminin α‐2 expressions were reduced followed by their breakdown, as epiphenomena of the myocytolytic process. In conclusion, administration of isoproterenol to rats results in primary loss of dystrophin, the most sensitive among the structural proteins that form the DGC that connects the extracellular matrix and the cytoskeleton in cardiomyocyte. These changes, related to ischaemic injury, explain the severe alterations in the structural integrity of the sarcolemma of cardiomyocytes and hence severe and irreversible injury induced by isoproterenol.
Role of inflammation in right ventricular damage and repair following experimental pulmonary embolism in rats
Authors: Watts John Albert , Gellar Michael Aaron , Obraztsova Maria , Kline Jeffrey Allen , Zagorski John
Published: September 2008

Right ventricular (RV) dysfunction is associated with poor clinical outcome following pulmonary embolism (PE). Previous studies in our laboratory show that influx of neutrophils contributes to acute RV damage seen in an 18 h rat model of PE. The present study describes the further progression of inflammation over 6 weeks and compares the neutrophil and monocyte responses. The RV outflow tract became white in colour by day 1 with influx of neutrophils (tissue myeloperoxidase activity increased 17‐fold) and mononuclear cells with characteristics of M1 phenotype (high in Ccl20, Cxcl10, CcR2, MHCII, DNA microarray analysis). Matrix metalloproteinase activities were increased and tissue was thinned to produce a translucent appearance in weeks 1 through 6 in 40% of hearts. RV contractile function was significantly reduced at 6 weeks of PE. In this later phase, there was accumulation of myofibroblasts, the presence of mononuclear cells with M2 characteristics (high in scavenger mannose receptors, macrophage galactose lectin 1, PDGFR1, PDGFRβ), enrichment of the subendocardial region of the RV outflow tract with neovesels (α‐smooth muscle immunohistochemistry) and deposition of collagen fibres (picrosirius red staining) beginning scar formation. Thus, while neutrophil response is associated with the early, acute inflammatory events, macrophage cells continue to be present during the proliferative phase and initial deposition of collagen in this model, changing from the M1 to the M2 phenotype. This suggests that the macrophage cell response is biphasic.
Intratubular transplantation as a strategy for establishing animal models of testicular germ cell tumours
Authors: Li Yunmin , Kido Tatsuo , Luo Jinping , Fukuda Michiko , Dobrinski Ina , Lau Yun‐Fai Chris
Published: September 2008

Testicular germ cell tumours (TGCTs) are prevalent cancers among young men. Currently, there is no reliable animal model for TGCTs. To establish such animal models, we have explored the possibility of intratubular testicular transplantation as means to deliver tumour cells into the seminiferous tubules of host animals. Our results demonstrated that transplanted cells could effectively populate the testis of a recipient mouse and develop into TGCTs. In addition, the donor cells could be transfected with a specific transgene before transplantation, thereby providing an approach to evaluate the specific effects of gene functions in the oncogenic processes. Hence, depending on selection of specific donor cells or mixtures of donor cells, transplantation models of TGCTs could be significant for studies on the pathogenesis, diagnosis and therapies of such a prevalent and important cancer in men.
Cellular expression of Bcl‐2 and Bax in atrophic submandibular glands of rats
Authors: Takahashi Shigeru , Yoshimura Yoshitaka , Yamamoto Tsuneyuki , Wakita Minoru
Published: September 2008

In submandibular gland atrophy, most acinar cells disappear by apoptosis, while many duct cells remain. The present study aimed to establish whether Bcl‐2 and Bax, members of the Bcl‐2 gene family, regulating the signalling pathway of apoptosis were involved in duct cell survival and acinar cell death in atrophic submandibular glands. The excretory duct of rat submandibular gland was doubly ligated with metal clips from 1 to 14 days to induce atrophy to the gland. The expressions of Bcl‐2 and Bax in the atrophic submandibular gland were examined using immunohistochemistry and reverse transcriptase‐polymerase chain reaction (RT‐PCR). Immunohistochemically, Bcl‐2 expression was identified in duct cells in the experimental glands at all time points. Some acinar cells showed Bax positivity 1 day after excretory duct ligation, and there were more Bax‐positive acinar cells on days 3 and 5 when many apoptotic acinar cells were observed. Analysis by RT‐PCR showed that the expression of mRNA for Bcl‐2 became stronger as the glandular atrophy progressed and that Bax mRNA strongly expressed on days 1 and 3. These observations suggest that Bcl‐2 inhibits duct cell apoptosis and Bax promotes apoptosis of acinar cells during atrophy of submandibular glands.
Laparoscopic pyeloplasty in children: Long‐term outcome
Authors: Ansari Mohd S , Mandhani Anil , Singh Partipal , Srivastava Aneesh , Kumar Anant , Kapoor Rakesh
Published: September 2008

Objectives:  To asses the safety and efficacy of laparoscopic pyeloplasty in pediatric patients.

Methods:  Data of pediatric patients under the age of 14 years, who had undergone laparoscopic pyeloplasty from January 2000 to December 2005, were prospectively analyzed. The various parameters recorded were: operative time, blood loss, need for analgesics, intra/postoperative complications, hospital stay and postoperative outcome. Success was defined as either symptomatic improvement and/or better drainage on postoperative isotope renography

Results:  There were 53 patients with a mean age of 9.12 years (1–14 years) and a male to female ratio of 4.3:1. Dismembered pyeloplasty was done in 41 patients and Foley Y‐V plasty in 12 patients via a transperitoneal approach using 3 ports in 50 children or 4 ports in 3 children. Mean operative time was 181 min (78–369); mean blood loss was 118.01 mL (50–250) with a mean hospital stay of 5.05 days (2–11). Conversion to open surgery was required in 4 (7.54%) patients. Follow‐up renograms were available in 49 patients, which showed improvement in drainage in 44 patients and an obstructed pattern in five; of these, two patients had significant deterioration in split function. Two patients among the obstructed group underwent redo pyeloplasty by open technique while the other three elected for a conservative approach. Thus at a mean follow up of 24.58 months (4–45) the overall success rate was 89.75%.

Conclusions:  Laparoscopic pyeloplasty is a safe and effective, minimally invasive procedure in pediatric patients with a good intermediate term success rate and minimal morbidity.
Balloon occlusion and hypothermic perfusion of the renal artery in laparoscopic partial nephectomy
Authors: Shen Heng‐Li , Chueh Shih‐Chieh , Lai Ming‐Kuen , Wu Chen‐Han Welfred , Huang Chun‐Chieh , Tsang Yuk‐Ming , Chuang Chiu‐Chen , Lai Ming‐Chih , Yu Hong‐Jeng
Published: September 2008

Objectives:  We describe our initial experience with renal arterial catheterization for temporary balloon occlusion of renal artery and hypothermic perfusion during laparoscopic partial nephectomy and compare the preoperative and postoperative nephron function.

Methods:  Fifteen patients received laparoscopic partial nephrectomy from September 2005 to December 2006. During the operations, the balloons of the arterial catheters were filled with distilled water to achieve pedicle control. Chilled Ringers lactate was continuously infused into the catheters for renal hypothermia. Postoperative Tc‐99m diethylenetriamine pentaacetic acid (DTPA) renal scintigraphies were carried out to estimate differential renal function. The volumes of the renal tumors, tumor‐bearing and contralateral kidneys from CT scans were measured using commercial software. Estimated creatinine clearance was calculated with Cockroft Gault formula.

Results:  All procedures were successfully completed. Mean tumor size was 18.4 mL (range 2.14 to 59.0). Estimated mean intraoperative blood loss was 287 mL (range minimal to 1200). Mean estimated creatinine clearance per unit volume of functional renal parenchyma did not change statistically after the operation. Multiple regression analysis revealed that ischemic time was a significant variable which correlated with the value of lost total estimated creatinine clearance of the tumor bearing kidney.

Conclusions:  The initial experience shows that renal arterial catheterization for temporary balloon occlusion and hypothermic perfusion of the renal artery in laparoscopic partial nephectomy is safe, feasible and effective. The postoperative kidney function measured by mean estimated creatinine clearance per unit of functional renal volume was similar to the preoperative measurement.
Combination chemotherapy of ifosfamide, 5‐fluorouracil, etoposide and cisplatin as perioperative treatment in lymph node positive bladder carcinoma patients treated by radical cystectomy
Authors: Komai Yoshinobu , Fujii Yasuhisa , Okubo Yuhei , Yamamoto Shinya , Kawakami Satoru , Yonese Junji , Fukui Iwao
Published: September 2008

Objectives:  To evaluate the efficacy and toxicity of perioperative combination chemotherapy with ifosfamide, 5‐fluorouracil, etoposide and cisplatin (IFEP) in bladder cancer patients with regional lymph node metastases treated by radical cystectomy.

Methods:  We reviewed the medical records of 183 consecutive patients who underwent radical cystectomy for invasive urothelial carcinoma of the bladder. Of those, 26 patients with regional lymph node metastasis who were regarded as being rendered surgically disease‐free (pT1‐4, N1‐2, cM0) and treated with perioperative IFEP chemotherapy were the subjects of the present study.

Results:  Median follow‐up of 26 patients was 49 months (range 4–150). Grade 3 and 4 bone marrow toxicities were seen in 15 and four patients, respectively. Neither chemotherapy‐related death nor febrile neutropenia occurred. The 5‐year overall and cancer‐specific survival rate was 60% and 68%, respectively. The overall survival rate of the patients with pT4 disease was significantly worse than that of patients with pT1‐3. There were four N2 patients who survived for over 5 years free of disease.

Conclusions:  Perioperative IFEP therapy appeared to be effective in the treatment of lymph node positive bladder cancer patients who underwent radical cystectomy. Further study may be warranted.
Hip fracture in Auckland: contrasting models of care in two major hospitals
Authors: Tha H. S. , Armstrong D. , Broad J , Paul S , Wood P.
Published: September 2008

Background:  The optimal setting and design of care for elderly patients with hip fracture is unknown. North Shore Hospital (NSH) and Middlemore Hospital (MMH) are two major hospitals in the Auckland region operating different models of orthogeriatric care. The aim of the study was to compare hip fracture care between NSH and MMH.

Methods:  A retrospective case record audit of patients aged 65 years and older with hip fracture from July to December 2004 at MMH and NSH was carried out.

Results:  Charts for 203 patients (101 MMH and 102 NSH) were reviewed. The two groups were similar in age (mean age 83.2 years), sex (80% women) and other casemix factors. Median time from admission to theatre was shorter in NSH (21 vs 44 h, P < 0.0001). Length of stay was significantly shorter at NSH (mean difference 4.4 days, 95% confidence interval 1.1–7.6 when adjusted for casemix factors). Significantly more NSH patients were transferred for rehabilitation than MMH patients (75 vs 51%). At discharge, significantly more MMH patients (34 vs 14%) were treated with alendronate. Of 126 patients admitted from home, 81% returned home, 4% went to rest homes, 13% to private hospitals and 2% died; differences between centres were not significant. Overall inpatient mortality was 3.9%.

Conclusion:  The orthogeriatric model of care at NSH was associated with a shorter overall length of stay, earlier transfer to the Assessment, Treatment and Rehabilitation setting, and a higher proportion rehabilitated in Assessment, Treatment and Rehabilitation. Outcomes in terms of discharge destination and 6‐month mortality were similar at both centres.
Global Distributive Justice and the State
Authors: Caney Simon
Published: September 2008

Many hold that the state has normative significance because its borders define the scope of egalitarian principles of distributive justice. On this view egalitarian principles of distributive justice should be applied within the state but should not be adopted at the global level. This article examines two reasons for accepting this view and for rejecting global egalitarianism, and finds both wanting. It then presents three challenges to any view that holds that the scope of principles of distributive justice should be determined by the boundaries of the state. It concludes by noting four distinct ways in which the state has normative significance, each of which can be endorsed by global egalitarians.
Crossroads of Religions: Shrines, Mobility and Urban Space in Goa
Authors: HENN ALEXANDER
Published: September 2008

Wayside shrines — representing Hindu and Catholic divinities and saints — show an astonishing dynamic in the cities of Goa and India. Not only do they persist in a milieu of drastic modern change that often seems to be at odds with their traditional locations, aesthetics and purposes, but also some of them surpass temples, churches and mosques in popularity. The popularity of these seemingly marginal religious monuments is a response to three forms of mobility characterizing modern Indian urban environments: cultural mobility — the diversification and fluctuation of religious ideas and practices; social mobility — the diversification and fluctuation of people from different castes, social classes and geographical regions, as well as the change of caste and class status due to socio‐economic change; and physical mobility — the movement of and movement around increasingly dense and complex flows of motorized traffic. The shrines modify and transform the centuries‐old spatio‐religious system of Hindus and Catholics to fit the conditions of late‐modern city life. They allow a culturally diversifying, socially changing and geographically fluctuating population to engage with a variety of personalized deities and saints whose charismatic authority is not only quite independent from formalized local social hierarchies, but often also cuts across orthodox divisions between religious traditions.

Les sanctuaires installés le long des voies de circulation — représentations de divinités et saints hindous et catholiques — présentent une dynamique étonnante dans les villes de Goa et d’Inde. D’une part, ils persistent dans un milieu qui connaît une modernisation radicale souvent en contradiction, semble‐t‐il, avec leur finalité, leur esthétique et leur emplacement traditionnels ; d’autre part, certains dépassent en popularité temples, églises ou mosquées. La fréquentation de ces monuments religieux apparemment marginaux tient à trois formes de mobilité propres aux environnements urbains indiens modernes : la mobilité culturelle (diversification et fluctuation des idées et pratiques religieuses), la mobilité sociale (diversification et fluctuation des individus venus de castes, classes sociales et régions géographiques diverses, et changement de statut de caste et de classe à cause de l’évolution socio‐économique), et la mobilité physique (mouvement et circulation autour de flux toujours plus denses et complexes de trafic motorisé). Ces sanctuaires modifient et transforment le système spatio‐religieux séculaire des hindous et des catholiques qui doit s’adapter aux conditions de la vie urbaine postmoderne. Ils permettent à une population qui se diversifie au plan culturel, évolue au plan social et fluctue au plan géographique de s’engager à l’égard de divinités ou de saints personnalisés plus variés dont l’autorité charismatique est totalement indépendante des hiérarchies sociales locales formalisées et transcende les divisions orthodoxes entre traditions religieuses.