bluuebunny/crossref_metadata_2025 huggingface dataset:
State‐dependent regulation of sensory‐motor transmission: role of muscarinic receptors in sensory‐motor integration in the crayfish walking system
Authors: Le Bon‐Jego Morgane , Masante‐Roca Ingwild , Cattaert Daniel
Published: March 2006

The aim of this study was to investigate a potential mechanism for state‐dependent regulation of sensory‐motor transmission from sensory afferents of a proprioceptor to motoneurons (MNs) in the walking system of the crayfish. This study was performed using an in vitro preparation of thoracic ganglia including motor nerves and the proprioceptor that codes movements of the second joint (coxo‐basal chordotonal organ − CBCO) of the leg. Application of movements to the CBCO elicits resistance reflex responses intracellularly recorded from Dep MNs. This reflex response is enhanced when Dep MNs are depolarized either spontaneously or by current injection. This enhancement is abolished in the presence of scopolamine (an antagonist of muscarinic acetylcholine receptors). Using pharmacology, we demonstrate that the monosynaptic connection from CBCO sensory neurons to the Dep MNs includes both nicotinic and muscarinic components. In addition, the shape of monosynaptic excitatory postsynaptic potentials (EPSPs) depends on the membrane potential: at a subthreshold depolarizing membrane potential, the time constant of the falling phase of the EPSPs is significantly increased compared with its value at resting potential. This change is suppressed in the presence of scopolamine, indicating that the muscarinic component may contribute to the activation of the Dep MN pool by sensory activity. This state‐dependent amplification of the sensory input may be important for increasing the strength of sensory feedback at times when central activation of the Dep MNs is very strong (e.g. during walking).
Enhanced novelty‐induced activity, reduced anxiety, delayed resynchronization to daylight reversal and weaker muscle strength in tenascin‐C‐deficient mice
Authors: Morellini Fabio , Schachner Melitta
Published: March 2006

Tenascin‐C (TNC) is an extracellular matrix protein with multiple and important functions during development and in the adult. We here present a study on the behaviour of TNC‐deficient (knockout, KO) mice. Longitudinal experiments including tests for circadian activity, exploration, state and trait anxiety, motor coordination and cognition were performed. KO mice showed increased reactivity to explore a novel environment and decreased anxiety. Spontaneous circadian activity was unaffected, but KO mice showed delayed resynchronization to daylight reversal. TNC deficiency caused weaker muscle strength, whereas gait, coordination and motor learning were unaltered. Short‐ and long‐term memory in the fear conditioning task and working memory in the spontaneous alternation test were normal in KO mice. KO mice showed impaired memory recall in the step‐down, but not in the step‐through, passive avoidance task. Ethological observation of mice behaviour and principal component analyses indicated that the higher novelty‐ and stress‐induced active responses of KO mice account for their poorer performance in passive avoidance tasks, whereas cognitive abilities are unaltered. The present study extends and corrects previous results, and is an example of how an ethological approach allows a precise description and interpretation of the behavioural alterations of mutant mice.
Distinct kinds of novelty processing differentially increase extracellular dopamine in different brain regions
Authors: De Leonibus Elvira , Verheij Michel M. M. , Mele Andrea , Cools Alexander
Published: March 2006

Behaviourally relevant novel stimuli are known to activate the mesocorticolimbic dopaminergic (DAergic) system. In this study we tested the reactivity of this system in response to distinct kinds of novelty processing. Using the in vivo microdialysis technique, we measured extracellular amounts of dopamine (DA) in different DAergic terminal regions during a social learning task in rats. In the first session (40 min) rats were exposed to two never previously encountered juveniles (i.e. unconditional novelty). Afterwards, the animals were divided into three groups: Control group was not exposed to any other stimulus; Discrimination group was exposed to one familiar and one new juvenile (i.e. novel stimulus discrimination); and Recognition group was re‐exposed to the two familiar juveniles (i.e. familiarity recognition). In both the medial prefrontal cortex and the nucleus accumbens shell DA increased in response to the first presentation of the juveniles, showing that both structures are involved in processing unconditional social novelty. During the novel stimulus discrimination, we found no change in the prefrontal cortex, although DA increased in the accumbal shell in comparison with the group exposed to two familiar juveniles, showing that the shell is also involved in processing novel social stimulus discrimination. None of the stimuli presented affected DA in the accumbal core. This study provided the original evidence that DA in the various terminal regions is differentially coupled to distinct aspects of novelty processing.
Transcranial fluorescence imaging of auditory cortical plasticity regulated by acoustic environments in mice
Authors: Takahashi Kuniyuki , Hishida Ryuichi , Kubota Yamato , Kudoh Masaharu , Takahashi Sugata , Shibuki Katsuei
Published: March 2006

Functional brain imaging using endogenous fluorescence of mitochondrial flavoprotein is useful for investigating mouse cortical activities via the intact skull, which is thin and sufficiently transparent in mice. We applied this method to investigate auditory cortical plasticity regulated by acoustic environments. Normal mice of the C57BL/6 strain, reared in various acoustic environments for at least 4 weeks after birth, were anaesthetized with urethane (1.7 g/kg, i.p.). Auditory cortical images of endogenous green fluorescence in blue light were recorded by a cooled CCD camera via the intact skull. Cortical responses elicited by tonal stimuli (5, 10 and 20 kHz) exhibited mirror‐symmetrical tonotopic maps in the primary auditory cortex (AI) and anterior auditory field (AAF). Depression of auditory cortical responses regarding response duration was observed in sound‐deprived mice compared with naïve mice reared in a normal acoustic environment. When mice were exposed to an environmental tonal stimulus at 10 kHz for more than 4 weeks after birth, the cortical responses were potentiated in a frequency‐specific manner in respect to peak amplitude of the responses in AI, but not for the size of the responsive areas. Changes in AAF were less clear than those in AI. To determine the modified synapses by acoustic environments, neural responses in cortical slices were investigated with endogenous fluorescence imaging. The vertical thickness of responsive areas after supragranular electrical stimulation was significantly reduced in the slices obtained from sound‐deprived mice. These results suggest that acoustic environments regulate the development of vertical intracortical circuits in the mouse auditory cortex.
Effects of species diversity on disease risk
Authors: Keesing F. , Holt R. D. , Ostfeld R. S.
Published: March 2006

The transmission of infectious diseases is an inherently ecological process involving interactions among at least two, and often many, species. Not surprisingly, then, the species diversity of ecological communities can potentially affect the prevalence of infectious diseases. Although a number of studies have now identified effects of diversity on disease prevalence, the mechanisms underlying these effects remain unclear in many cases. Starting with simple epidemiological models, we describe a suite of mechanisms through which diversity could increase or decrease disease risk, and illustrate the potential applicability of these mechanisms for both vector‐borne and non‐vector‐borne diseases, and for both specialist and generalist pathogens. We review examples of how these mechanisms may operate in specific disease systems. Because the effects of diversity on multi‐host disease systems have been the subject of much recent research and controversy, we describe several recent efforts to delineate under what general conditions host diversity should increase or decrease disease prevalence, and illustrate these with examples. Both models and literature reviews suggest that high host diversity is more likely to decrease than increase disease risk. Reduced disease risk with increasing host diversity is especially likely when pathogen transmission is frequency‐dependent, and when pathogen transmission is greater within species than between species, particularly when the most competent hosts are also relatively abundant and widespread. We conclude by identifying focal areas for future research, including (1) describing patterns of change in disease risk with changing diversity; (2) identifying the mechanisms responsible for observed changes in risk; (3) clarifying additional mechanisms in a wider range of epidemiological models; and (4) experimentally manipulating disease systems to assess the impact of proposed mechanisms.
A double mutant of Pseudomonas putida JLR11 deficient in the synthesis of the nitroreductase PnrA and assimilatory nitrite reductase NasB is impaired for growth on 2,4,6‐trinitrotoluene (TNT)
Authors: Caballero Antonio , Ramos Juan L.
Published: March 2006

Pseudomonas putida JLR11 can grow on 2,4,6‐trinitrotoluene (TNT) as the sole nitrogen source. We created nasB (nitrite reductase), pnrA (nitroaromatic reductase) and pnrA nasB mutants and tested their growth with TNT as the sole N source. The nasB and pnrA mutants grew at a reduced rate on TNT, whereas the double nasB pnrA mutant did not. This suggests that P. putida JLR11 carries out multiple enzymatic attacks on TNT‐releasing nitrite and/or ammonium. The PnrA nitroreductase plays a key role in the reduction of TNT to 2,6‐dinitro‐4‐hydroxylaminotoluene and the subsequent release of ammonium for growth.
Endoglucanase‐producing fungi isolated from Cape Evans historic expedition hut on Ross Island, Antarctica
Authors: Duncan Shona M. , Farrell Roberta L. , Thwaites Joanne M. , Held Benjamin W. , Arenz Brett E. , Jurgens Joel A. , Blanchette Robert A.
Published: March 2006

Early explorers of Antarctica’s Heroic Era erected wooden buildings and brought large quantities of supplies to survive in Antarctica. The introduction of wood and other organic materials provided nutrient sources for fungi that were indigenous to Antarctica or were brought in with the materials and adapted to the harsh conditions. Seventy‐two isolates of filamentous fungi were cultured on selective media from interior structural wood of the Cape Evans historic hut and 27 of these screened positive for the ability to degrade carboxymethyl cellulose (CMC). Four non‐CMC‐degrading isolates were added to a group of 14 CMC‐degrading isolates for further study, and endo‐1, 4‐β‐glucanase activity was demonstrated in the extracellular supernatant from all of these 18 isolates when grown at 4°C, and also when they were grown at 15°C. Isolates of Penicillium roquefortii and Cadophora malorum showed preference for growth at 15°C rather than 25°C or 4°C indicating psychrotrophic characteristics. These results demonstrate that cellulolytic filamentous fungi found in Antarctica are capable of growth at cold temperatures and possess the ability to produce extracellular endo‐1, 4‐β‐glucanase when cultured at cold and temperate temperatures.
Three‐Dimensional Nonlinear Dispersive Waves on Shear Flows
Authors: Teshukov V. M. , Gavrilyuk S. L.
Published: March 2006

The Green–Naghdi equations describing three‐dimensional water waves are considered. Assuming that transverse variations of the flow occur at a much shorter lengthscale than variations along the wave propagation direction, we derive simplified asymptotic equations from the Green–Naghdi model. For steady flows, we show that the approximate model reduces to a one‐dimensional Hamiltonian system along each stream line. Exact solutions describing a wide class of free‐boundary flows depending on several arbitrary functions of one argument are found. The numerical results showing different patterns of steady three‐dimensional waves are presented.
On the Nevanlinna Order of Meromorphic Solutions to Linear Analytic Difference Equations
Authors: Chiang Yik‐Man , Ruijsenaars Simon N. M.
Published: March 2006

For various classes of linear ordinary analytic difference equations with meromorphic coefficients, we study Nevanlinna order properties of suitable meromorphic solutions. For a large class of first‐order equations with coefficient of order ρ∈[0, ∞), we explicitly construct meromorphic solutions of order ≤ρ+ 1. For higher‐order equations with coefficients of order ρ∈[0, ∞), we show that meromorphic solutions with increase of order ≤ρ+ 1 in a certain strip have order ≤ρ+ 1. The assumptions made in the latter setting may seem quite restrictive, but they are satisfied for several classes of second‐order difference equations that have been studied in recent years. The latter include Harper‐type equations, “reflectionless” equations, Askey–Wilson‐type equations, and equations of relativistic Calogero–Moser type.
Evolution of Packets of Surface Gravity Waves over Strong Smooth Topography
Authors: Benilov E. S. , Howlin C. P.
Published: March 2006

Wave packets in a smoothly inhomogeneous medium are governed by a nonlinear Schrödinger (NLS) equation with variable coefficients. There are two spatial scales in the problem: the spatial scale of the inhomogeneities and the distance over which nonlinearity and dispersion affect the packet. Accordingly, there are two limits where the problem can be approached asymptotically: when the former scale is much larger than the latter, and vice versa. In this paper, we examine the limit where the spatial scale of (periodic or random) inhomogeneities is much smaller than that of nonlinearity/dispersion (i.e., the latter effects are much weaker than the former). In this case, the packet undergoes rapid oscillations of the geometric‐optical type, and also evolves slowly due to nonlinearity and dispersion. We demonstrate that the latter evolution is governed by an NLS equation with constant (averaged) coefficients. The general theory is illustrated by the example of surface gravity waves in a channel of variable depth. In particular, it is shown that topography increases the critical frequency, for which the nonlinearity coefficient of the NLS equation changes sign (in such cases, no steady solutions exist, i.e., waves with frequencies lower than the critical one disperse and cannot form packets).
Managing memories in post‐war Sarajevo: individuals, bad memories, and new wars
Authors: Sorabji Cornelia
Published: March 2006

In the wake of the 1992‐5 war in Bosnia a number of anthropologists have written about the role of memory in creating and sustaining hostility in the region. One trend focuses on the authenticity and power of personal memories of Second World War violence and on the possibility of transmitting such memories down the generations to the 1990s. Another focuses less on memory as a phenomenon which determines human action than on the ‘politics of memory’: the political dynamics which play on and channel individuals’ memories. In this article I use the example of three Sarajevo Bosniacs whom I have known since the pre‐war 1980s in order to propose the merit of a third, additional, focus on the individual as an active manager of his or her own memories. I briefly consider whether work by Maurice Bloch on the nature of semantic and of autobiographic memory supports a strong version of the first interpretative trend, or whether, as I suggest, the conclusions of this work instead leave room for individual memory management and for change down the generations.
Forty years on and still going strong: the use of hominin‐cercopithecid comparisons in palaeoanthropology
Authors: Elton Sarah
Published: March 2006

Hominin‐cercopithecid comparisons have been used in palaeoanthropology for over forty years. Fossil cercopithecids can be used as a ‘control group’ to contextualize the adaptations and evolutionary trends of hominins. Observations made on modern cercopithecids can also be applied to questions about human evolution. This article reviews the history of hominin‐cercopithecid comparisons, assesses the strengths and weaknesses of cercopithecids as comparators in studies of human evolution, and uses cercopithecid models to explore hominin inter‐specific dynamics. Cercopithecids appear to be excellent ecological referents, but may be less good when considering the cognitive abilities and cultural adaptations of hominins. Comparison of cercopithecid and hominin adaptations at Koobi Fora in East Africa indicates that, whereas the cercopithecids were largely grass‐ or leaf‐eating, the hominins occupied a generalist niche, apparently excluding other primate generalist‐frugivores. If any of the hominin species at Koobi Fora were sympatric, analogies with modern cercopithecids suggest that inter‐specific contact cannot be discounted and may even have been beneficial.
The utopian promise of government
Authors: Lattas Andrew
Published: March 2006

Today academic debate and public discourse about the Pacific often focuses on the collapse of government – on failed nation‐states. Yet ever since Self‐Government and Independence, Melanesians have experimented with developing their own alternative forms of local government, which have often embraced but also side‐tracked official governmental schemes, structures, and practices. Using the Pomio Kivung movement in East New Britain, this article explores how government, together with its projects and promises of sovereignty, civilization, and development, is displaced and re‐mediated through the world of the dead. The customary shamanic worlds of dreams and possession are redeployed and merged with the pastoral practices and disciplinary schemes of civilizing projects originally belonging to Western churches and governments.
Apprenticeship in western India
Authors: Simpson Edward
Published: March 2006

A number of recent attempts to describe what happens in the ‘embodied’ space between action and the discursive language used to describe that action have been primarily informed by various Western theories of mind. In this article, I present an indigenous theory of what happens among Sunni Muslims in a South Asian context in the gap between linguistic utterances and the actions they purport to represent. The ethnography focuses on learning craft and social skills among apprentices in the shipyards in the Indian state of Gujarat. It is argued that acquiring both kinds of skills is underscored by particular conceptions of the body and the possible transformations of the soul through physical activity.
Videotaped Confessions: Panacea or Pandora's Box?
Authors: LASSITER G. DANIEL , RATCLIFF JENNIFER J. , WARE LEZLEE J. , IRVIN CLINTON R.
Published: March 2006

Videotape is becoming an increasingly common means of recording and presenting confessions that are obtained during custodial interrogations. Many scientific, legal, and political experts view this procedural advance as a solution to the growing problem of some innocent people being induced to incriminate themselves when confronted by standard police interrogation tactics. We review a program of research that indicates, however, that the indiscriminate application of videotaping to solve the problem of coerced or false confessions slipping through the system could ironically exacerbate the situation.
The Jury Persuaded (and Not): Computer Animation in the Courtroom
Authors: DUNN MEGHAN A. , SALOVEY PETER , FEIGENSON NEAL
Published: March 2006

In two experiments, we examined the persuasiveness of computer animation on juror decision making by comparing animation to diagrams in two mock trials—a plane crash case and a car accident case. The persuasiveness of the animation on verdicts was dependent on the case; in the plane crash case, participants rendered verdicts in favor of the side presenting the animation. In the car accident case, the animation had no effect on verdicts. The role of familiarity with the depicted scenario is discussed as a possible explanation for the differing impact of animation. Additionally, jurors’ expectations about the persuasiveness of animations were discrepant with the animations’ actual influence on jurors’ verdicts.
Technological and geographical knowledge spillover in the German empire 1877–1918
Authors: STREB JOCHEN , BATEN JÖRG , YIN SHUXI
Published: March 2006

We use a newly developed data set of 39,343 high‐value patents granted between 1877 and 1918 to demonstrate that technological progress during German industrialization occurred in at least four different technological waves. We distinguish the railway wave (1877–86), the dye wave (1887–96), the chemical wave (1897–1902), and the wave of electrical engineering (1903–18). Evidence is presented that inter‐industry knowledge spillovers between technologically, economically, and geographically related industries were a major source for innovative activities during German industrialization. We also show that technological change affected the geographical distribution of innovative regions. Using an index of technologically revealed comparative advantage we find that regions that increased their innovativeness during the waves of technological progress revealed special strength in technological clusters like electrical engineering, mechanical engineering, or chemicals.
The impact of limited liability on ownership and control: Irish banking, 1877–19141
Authors: ACHESON GRAEME G. , TURNER JOHN D.
Published: March 2006

Limited liability is regarded as the sine qua non of the modern company, enabling firms to raise capital from a broad spectrum of investors who have well‐diversified portfolios. This article uses the ownership records of an Irish bank, which converted to limited liability in 1883, to explore the impact of introducing limited liability upon ownership and control. We find that ownership becomes more dispersed amongst individuals from a broader social and geographical spectrum. However, there appears to be little impact on portfolio diversification. Furthermore, although limited liability appears to contribute to the rise of the professional director, the evidence suggests that managerial incentives may have been weakened.
Error estimation of the fractal dimension measurements of cranial sutures
Authors: Górski Andrzej Z. , Skrzat Janusz
Published: March 2006

The fractal exponents used to quantify the complexity of cranial sutures were computed for 17 coronal and 17 sagittal sutures of adults from different populations, using the box‐counting algorithm. This paper discusses the main sources of error for the fractal exponents, and gives the error estimates. We then compare our results with those obtained by other authors. We suggest that the usual error estimates implied by the standard deviation for the regression line are too low. We emphasize the crucial role played by the choice of regression line in the log–log plot. For the coronal and sagittal sutures we found mean fractal dimensions of 1.48 and 1.56, respectively. Our values are close to the value for Brownian random walk.
The immune tissues of the endangered red‐tailed phascogale (Phascogale calura)
Authors: Old J. M. , Carman R. L. , Fry G. , Deane E. M.
Published: March 2006

The lymphoid tissues of the red‐tailed phascogale (Phascogale calura) were examined using histological and immunohistochemical techniques. The distribution of immune cells in the tissue beds was documented using antibodies to surface markers CD3 and an MHC Class II antigen (equivalent to HLA DRII). Spleen, gut‐associated lymphoid tissues (GALT), lung, bronchus‐associated lymphoid tissue (BALT) and liver were examined. The spleen had defined areas of red and white pulp, with follicles containing tingible‐bodied macrophages. Anti‐CD3 and anti‐HLA DRII antibodies revealed the presence of T cells in areas of white pulp and around the peri‐arterial lymphatic sheaths. GALT and BALT were detected and appeared as scattered areas of lymphocytes in the tissues beds. This is the first study to report on the lymphoid tissues of this endangered species of marsupial and the first report of the capacity of anti‐human antibodies to a surface MHC molecule to react with Dasyurid cells.
The structural basis of interlamellar cohesion in the intervertebral disc wall
Authors: Pezowicz Celina A. , Robertson Peter A. , Broom Neil D.
Published: March 2006

The purpose of this study was to investigate the structural mechanisms that create cohesion between the concentric lamellae comprising the disc annulus. Sections, 50–60 µm thick, were obtained using a carefully chosen cutting plane that incorporated the fibrous component in alternating lamellae as in‐plane and cross‐sectioned arrays. These sections were then subjected to microtensile stretching both across (radial) and along (tangential) the in‐plane fibre direction, in their fully hydrated state. Structural responses were studied by simultaneously viewing the sections using high‐resolution Nomarski interference contrast light microscopy. Additional bulk samples of annulus were fixed while held in a constant, radially stretched state in order to investigate the potential for interlamellar separation to occur in a state more representative of the intact disc wall. The study has provided a detailed picture of the structural architecture creating disc wall cohesion, revealing a complex hierarchy of interconnecting relationships within the disc wall, not previously described. Importantly, because our experimental approach offers a high‐resolution view of the response of the interlamellar junction to deformation in its fully hydrated condition, it is a potentially useful method for investigating subtle changes in junction cohesion resulting from both early degeneration and whole‐disc trauma.
Expression of Concern: Antioxidant compounds have potent anti‐fibrillogenic and fibril‐destabilizing effects for α‐synuclein fibrils in vitro
Authors: Ono Kenjiro , Yamada Masahito
Published: March 2006

The aggregation of α‐synuclein (αS) in the brain has been implicated as a critical step in the development of Lewy body diseases (LBD) and multiple system atrophy (MSA). Various antioxidants not only inhibit the formation of β‐amyloid fibrils (fAβ), but also destabilize preformed fAb in vitro. Using fluorescence spectroscopy with thioflavin S and electron microscopy, here we examined the effects of the antioxidants nordihydroguaiaretic acid, curcumin, rosmarinic acid, ferulic acid, wine‐related polyphenols [tannic acid, myricetin, kaempferol (+)‐catechin and (–)‐epicatechin], docosahexaenoic acid, eicosapentaenoic acid, rifampicin and tetracycline on the formation of αS fibrils (fαS) and on preformed fαS. All molecules, except for docosahexaenoic acid and eicosapentaenoic acid, dose‐dependently inhibited the formation of fαS. Moreover, these molecules dose‐dependently destabilized preformed fαS. The overall activity of the molecules examined was in the order of: tannic acid = nordihydroguaiaretic acid = curcumin = rosmarinic acid = myricetin > kaempferol = ferulic acid > (+)‐catechin = (–)‐epicatechin > rifampicin = tetracycline. These compounds with anti‐fibrillogenic as well as antioxidant activities could be key molecules for the development of preventives and therapeutics for LBD and MSA as well as Alzheimer's disease.
Dopamine transporter is essential for the maintenance of spontaneous activity of auditory nerve neurones and their responsiveness to sound stimulation
Authors: Ruel Jérôme , Wang Jing , Demêmes Danielle , Gobaille Serge , Puel Jean‐Luc , Rebillard Guy
Published: March 2006

Dopamine, a neurotransmitter released by the lateral olivocochlear efferents, has been shown tonically to inhibit the spontaneous and sound‐evoked activity of auditory nerve fibres. This permanent inhibition probably requires the presence of an efficient transporter to remove dopamine from the synaptic cleft. Here, we report that the dopamine transporter is located in the lateral efferent fibres both below the inner hair cells and in the inner spiral bundle. Perilymphatic perfusion of the dopamine transporter inhibitors nomifensine and N‐[1‐(2‐benzo[b]thiophenyl)cyclohexyl]piperidine into the cochlea reduced the spontaneous neural noise and the sound‐evoked compound action potential of the auditory nerve in a dose‐dependent manner, leading to both neural responses being completely abolished. We observed no significant change in cochlear responses generated by sensory hair cells (cochlear microphonic, summating potential, distortion products otoacoustic emissions) or in the endocochlear potential reflecting the functional state of the stria vascularis. This is consistent with a selective action of dopamine transporter inhibitors on auditory nerve activity. Capillary electrophoresis with laser‐induced fluorescence (EC‐LIF) measurements showed that nomifensine‐induced inhibition of auditory nerve responses was due to increased extracellular dopamine levels in the cochlea. Altogether, these results show that the dopamine transporter is essential for maintaining the spontaneous activity of auditory nerve neurones and their responsiveness to sound stimulation.
Amino acid sequence motifs and mechanistic features of the membrane translocation of α‐synuclein
Authors: Ahn Keun Jae , Paik Seung R. , Chung Kwang Chul , Kim Jongsun
Published: March 2006

Many lines of evidence suggest that α‐synuclein can be secreted from cells and can penetrate into them, although the detailed mechanism is not known. In this study, we investigated the amino acid sequence motifs required for the membrane translocation of α‐synuclein, and the mechanistic features of the phenomenon. We first showed that not only α‐synuclein but also β‐ and γ‐synucleins penetrated into live cells, indicating that the conserved N‐terminal region might be responsible for the membrane translocation. Using a series of deletion mutants, we demonstrated that the 11‐amino acid imperfect repeats found in synuclein family members play a critical role in the membrane translocation of these proteins. We further demonstrated that fusion peptides containing the 11‐amino acid imperfect repeats of α‐synuclein can transverse the plasma membrane, and that the membrane translocation efficiency is optimal when the peptide contains two repeat motifs. α‐Synuclein appeared to be imported rapidly and efficiently into cells, with detectable protein in the cytoplasm within 5 min after exogenous treatment. Interestingly, the import of α‐synuclein at 4°C was comparable with the import observed at 37°C. Furthermore, membrane translocation of α‐synuclein was not significantly affected by treatment with inhibitors of endocytosis. These results suggest that the internalization of α‐synuclein is temperature‐insensitive and occurs very rapidly via a mechanism distinct from normal endocytosis.
Increased glutathione biosynthesis by Nrf2 activation in astrocytes prevents p75NTR‐dependent motor neuron apoptosis
Authors: Vargas Marcelo R. , Pehar Mariana , Cassina Patricia , Beckman Joseph S. , Barbeito Luis
Published: March 2006

Astrocytes may modulate the survival of motor neurons in amyotrophic lateral sclerosis (ALS). We have previously shown that fibroblast growth factor‐1 (FGF‐1) activates astrocytes to increase secretion of nerve growth factor (NGF). NGF in turn induces apoptosis in co‐cultured motor neurons expressing the p75 neurotrophin receptor (p75NTR) by a mechanism involving nitric oxide (NO) and peroxynitrite formation. We show here that FGF‐1 increased the expression of inducible nitric oxide synthase and NO production in astrocytes, making adjacent motor neurons vulnerable to NGF‐induced apoptosis. Spinal cord astrocytes isolated from transgenic SOD1G93Arats displayed increased NO production and spontaneously induced apoptosis of co‐cultured motor neurons. FGF‐1 also activates the redox‐sensitive transcription factor nuclear factor erythroid 2‐related factor 2 (Nrf2) in astrocytes. Because Nrf2 increases glutathione (GSH) biosynthesis, we investigated the role of GSH production by astrocytes on p75NTR‐dependent motor neuron apoptosis. The combined treatment of astrocytes with FGF‐1 andt‐butylhydroquinone (tBHQ) increased GSH production and secretion, preventing motor neuron apoptosis. Moreover, Nrf2 activation in SOD1G93Aastrocytes abolished their apoptotic activity. The protection exerted by increased Nrf2 activity was overcome by adding the NO donor DETA‐NONOate to the co‐cultures or by inhibiting GSH synthesis and release from astrocytes. These results suggest that activation of Nrf2 in astrocytes can reduce NO‐dependent toxicity to motor neurons by increasing GSH biosynthesis.
Nitrogen and sulphur management: challenges for organic sources in temperate agricultural systems
Authors: McNeill A.M. , Eriksen J. , Bergström L. , Smith K.A. , Marstorp H. , Kirchmann H. , Nilsson I.
Published: March 2006

Abstract. A current global trend towards intensification or specialization of agricultural enterprises has been accompanied by increasing public awareness of associated environmental consequences. Air and water pollution from losses of nutrients, such as nitrogen (N) and sulphur (S), are a major concern. Governments have initiated extensive regulatory frameworks, including various land use policies, in an attempt to control or reduce the losses. This paper presents an overview of critical input and loss processes affecting N and S for temperate climates, and provides some background to the discussion in subsequent papers evaluating specific farming systems. Management effects on potential gaseous and leaching losses, the lack of synchrony between supply of nutrients and plant demand, and options for optimizing the efficiency of N and S use are reviewed. Integration of inorganic and organic fertilizer inputs and the equitable re‐distribution of nutrients from manure are discussed. The paper concludes by highlighting a need for innovative research that is also targeted to practical approaches for reducing N and S losses, and improving the overall synchrony between supply and demand.
Phosphorus management in balanced agricultural systems
Authors: Djodjic F. , Bergström L. , Grant C.
Published: March 2006

Abstract. The practice of large phosphorus (P) additions to agricultural land has resulted in an increased depletion of limited mineable rock phosphate resources, P accumulation in soils with an increased risk for P losses, and intensified eutrophication and deterioration of water quality in recipient water bodies. A number of measures have been used to reach balance between P inputs and outputs in agricultural systems, with the goal of achieving improved P use efficiency, sustained high crop yields and reduced P losses. This paper discusses how this goal may be achieved. Results from a Swedish long‐term fertility experiment combined with results of a P leaching study using a selection of soils from the fertility experiment are used to evaluate the effects of a balanced P system on yields, soil P levels and P leaching. Three P fertilizer application strategies are compared (zero P, replacement P, and a treatment where surplus P fertilization was used to achieve a rapid increase in the soil P status). The replacement P strategy appeared to be the most sustainable system but P fixation in this system must be accounted for. When surplus P rates were applied, increased crop yields were counterbalanced by poorer use efficiency and P accumulation in soil. Topsoil P content was a poor predictor of P leaching. Instead, balancing P inputs and outputs represents a first step in the management of P losses, but additional, site‐specific measures are required to counteract site‐specific factors responsible for P losses.
Perspectives on nutrient management in arable farming systems
Authors: Wivstad M. , Dahlin A.S. , Grant C.
Published: March 2006

Abstract. Sustainable nutrient management includes economizing on finite natural resources such as fossil energy and limited phosphorus (P) resources. Arable farms with exclusively crop production are characterized by large nutrient export in farm products. In the long term, nutrient export from soils and losses must be balanced by adequate inputs of fertilizers, biological N2 fixation or recycled products from the human food system. Critical issues associated in particular with arable systems discussed in this paper include organic matter depletion and lack of synchronization between nitrogen (N) release from organic N pools (such as plant residues and green manures) and crop demand, leading to N losses and/or N deficiency. Further critical issues identified include efficient use of indigenous soil P and applied P fertilizers and, especially in organic systems, risk of depletion of P and K, which if realized reduce soil fertility and limit production. The risk of enrichment of trace elements to levels toxic to soil microbes, plants, animals or man is also discussed. Suggested measures for managing these critical issues include choice of crop rotation, residue and green manure management.
Nutrient management for intensive animal agriculture: policies and practices for sustainability
Authors: Sims J.T. , Bergström L. , Bowman B.T. , Oenema O.
Published: March 2006

Abstract. The intensity of animal production around the world has increased substantially during the last half‐century, which has led to large problems with the disposal of manures and waste waters. The focus of this paper is on the development of national policies to improve the nutrient management of concentrated animal feeding operations (CAFOs), where nutrients are invariably in surplus. To create proper nutrient management strategies for CAFOs, and to avoid environmental problems when surplus nutrients enter air, soil and water, we need to know the number of animals/birds in the unit, the quantity of manure/slurry produced, how this material is stored and handled and how much land is available for manure spreading. In this paper, we discuss the development of nutrient management strategies for CAFOs in Europe and North America, and the voluntary measures and environmental regulations related to this. For the planning of nutrient management to be comprehensive and efficient, we need expertise from several disciplines. This planning includes development of: animal diets that reduce the amounts of excreted nutrients; efficient storage and land application technologies; land application programmes to optimize yields and reduce nutrient losses; and strategies for use of excess manure outside the farm. Also, large‐scale efforts involving many stakeholders (farmers, governments and private industry) are needed to solve problems with nutrient imbalances over the long term. Efforts along these lines include manure relocation, alternative uses of manures, nutrient trading, and a general extensification of animal agriculture. The overall guiding principle for policies and planning should be a balance of nutrients, on farms as well as at larger scales.
Recycling municipal wastes in the future: from organic to inorganic forms?
Authors: Kirchmann H. , Nyamangara J. , Cohen Y.
Published: March 2006

Abstract. This paper highlights the principal problems related to the recycling of municipal wastes to arable land and outlines future solutions. History reveals that transport of sewage with water was introduced early (2500 bc), but only some Asian societies, which did not utilize sewage flushing, redistributed toilet wastes to arable land effectively. Nutrient flow analyses in developed countries indicate a withdrawal of 20 kg N and 3kgP ha−1 yr−1 from arable land because of non‐return of organic human wastes. Limited reuse of municipal organic wastes in agriculture in several European countries is often seen as a question of waste quality. However, we believe that despite acceptable quality levels only minor progress in recycling has been achieved. Higher water contents in organic wastes than in harvested crops and, consequently, high costs for drying or transportation of wastes, often in combination with non‐optimal plant nutrient composition, will remain the bottleneck which restricts the recycling of nutrients in wastes. One solution is to extract nutrients out of organic wastes and thereby derive concentrated compounds similar to those in inorganic fertilizers that can be redistributed and applied to soil. The challenge for modern sewage treatment systems is to shift perspective from removal to recovery of nutrients.
Prevalence of Helicobacter pylori in Georgian Patients with Dyspepsia
Authors: Olivares Asalia , Buadze Merab , Kutubidze Tina , Lobjanidze Manana , Labauri Levani , Kutubidze Ramaz , Chikviladze Daredjan , Zhvania Manana , Kharzeishvili Omar , Lomidze Nodar , Perez‐Perez Guillermo I.
Published: March 2006

Background:  Georgia has showed a high prevalence of peptic ulcer disease (PUD), but the prevalence of Helicobacter pylori in this country is practically unknown. The purpose of this study was to determine the prevalence of H. pylori and specific genotypes in different populations in Georgia.

Materials and Methods:  We studied 62 patients from several hospitals in Tbilisi, Georgia. More than 55% of patients had PUD. We determined H. pylori presence as well as specific genotypes cagA and vacA by polymerase chain reaction. In addition, we studied serum samples from 94 healthy persons to determine H. pylori and CagA prevalence by ELISA.

Results:  We found a high prevalence of H. pylori and CagA in the healthy population (70.2 and 57.4%, respectively) and a high prevalence of CagA among the H. pylori‐positive persons (71.2%). Prevalence increased with age as reported in other countries (p = .05). Among symptomatic persons, we found nearly the same high prevalence of H. pylori (64.5%) as in the asymptomatic population. Furthermore, in symptomatic H. pylori patients, we found 65.0 and 67.5% prevalence of cagA and vacA, respectively. For 33 patients with PUD, 24 patients (72.7%) were H. pylori positive and 66.7% of them were cagA positive. In contrast, among the patients with non‐ulcer dyspepsia (NUD), 16 (55.2%) were H. pylori positive and 62.5% of them were colonized with cagA‐positive strains. H. pylori and cagA prevalence were not significantly different between PUD and patients with NUD.

Conclusions:  We confirmed that among individuals in Georgia, the prevalence of H. pylori is high and cagA‐positive strains were equally present among H. pylori‐positive patients with PUD and NUD and asymptomatic persons.
Helicobacter pylori Infection and Colorectal Cancer Risk: A Meta‐Analysis
Authors: Zumkeller Natalia , Brenner Hermann , Zwahlen Marcel , Rothenbacher Dietrich
Published: March 2006

Background:  Several studies suggested an association between Helicobacter pylori infection and colorectal carcinoma or adenoma risk. However, different authors reported quite varying estimates. We carried out a systematic review and meta‐analysis of published studies investigating this association and paid special attention to the possibility of publication bias and sources of heterogeneity between studies.

Materials and Methods:  An extensive literature search and cross‐referencing were performed to identify all published studies. Summary estimates were obtained using random‐effects models. The presence of possible publication bias was assessed using different statistical approaches.

Results:  In a meta‐analysis of the 11 identified human studies, published between 1991 and 2002, a summary odds ratio of 1.4 (95% CI, 1.1–1.8) was estimated for the association between H. pylori infection and colorectal cancer risk. The graphical funnel plot appeared asymmetrical, but the formal statistical evaluations did not provide strong evidence of publication bias. The proportion of variation of study results because of heterogeneity was small (36.5%).

Conclusions:  The results of our meta‐analysis are consistent with a possible small increase in risk of colorectal cancer because of H. pylori infection. However, the possibility of some publication bias cannot be ruled out, although it could not be statistically confirmed. Larger, better designed and better controlled studies are needed to clarify the situation.
The Mechanism of Heat‐Shock Protein 70 Gene Expression Abolition in Gastric Epithelium Caused byHelicobacter pyloriInfection
Authors: Pierzchalski Piotr , Krawiec Agata , Ptak‐Belowska Agata , Barańska Aleksandra , Konturek Stanisław J. , Pawlik Wiesław W.
Published: March 2006

Background: The members of the family of heat shock factors coordinate the inducible transcription of heat shock genes in response to diverse stimuli. Any disturbances in signal transduction may lead to the attenuation of heat shock proteins synthesis and to cell death due to apoptosis. It has been shown by others that different nuclear factors, such as nuclear factor interleukine 6 or signal transducer and activator of transcription 3, co‐operate with heat shock factors, mostly enhancing their activator effect on heat shock proteins genes expression. Therefore, we sought to determine whether apoptosis induced in the gastric epithelium exposed to liveHelicobacter pylorimight occur due to the elimination of HSP70 expression and deregulation of the heat shock response of the cell.

Materials and Methods: Experiments were performed on KATO III gastric epithelial cells exposed to live cagA, vacA expressingHpover different periods of time. Total cellular RNA, cytoplasmic and nuclear proteins were isolated for polimerase chain reaction, western‐blot, electrophoretic mobility shift assay, decoy and co‐immunoprecipitation studies.

Results: We found that in human gastric epithelium exposed toHelicobacter pylori, heat shock factor 1 is bound and restrained in complexes by phosphorylated signal transducer and activator of transcription 3 protein. In consequence, heat shock factor 1 bound up with phosphorylated signal transducer and activator of transcription 3 protein is unable to activate HSP70 protein synthesis in KATO III cells under stress conditions.Helicobacter pylorialso causes changes in bax/bcl‐2 cellular equilibrium, leading to the induction of apoptosis.

Conclusions: The observed phenomenon might be the mechanism whereby gastric epithelium adapts to the infection ofHelicobacter pylori, eliminating cells which are damaged or altered by bacterial cytotoxic products from the tissue.
The Effects of Genetic Polymorphisms of IL‐1 and TNF‐A on Helicobacter pylori–Induced Gastroduodenal Diseases in Korea
Authors: Kim Nayoung , Cho Sung‐Il , Yim Jeong‐Yoon , Kim Jung Mogg , Lee Dong Ho , Park Ji Hyun , Kim Joo Sung , Jung Hyun Chae , Song In Sung
Published: March 2006

Objective:  To evaluate whether or not genetic polymorphism of IL‐1B, IL‐1RN, and TNF‐Α is an important factor in the different expression of gastroduodenal diseases after Helicobacter pylori infection.

Methods:  This study consisted of 1360 subjects: control, gastric cancer (GC, intestinal type, and diffuse type), benign gastric ulcer (BGU), duodenal ulcer, and first‐degree gastric cancer relative (GCR). IL‐1Β‐511 and TNF‐A‐308 biallelic polymorphism were genotyped by 5′ nuclease polymerase chain reaction (PCR) assays, and PCR‐restriction fragment length polymorphism (PCR‐RFLP). IL‐1RN penta‐allelic variable number of tandem repeats was genotyped by PCR.

Results: There was no difference in the genetic polymorphism of IL‐1Β‐511, IL‐1RN and TNF‐A in the patients with gastric cancer regardless of H. pylori positivity compared with control. However, the frequencies of IL‐1B‐511 C/T (OR: 0.5, 95% CI: 0.3–0.7) and T carrier (OR: 0.6, 95% CI: 0.4–0.8) were lower in the H. pylori‐positive BGU patients. The IL‐1RN 2/2 was higher (OR: 5.5, 95% CI: 1.1–28.5) in the H. pylori‐positive GCR. There was no significance in the polymorphism of TNF‐Α‐308 regardless of H. pylori‐induced gastroduodenal diseases.

Conclusions:  The IL‐1Β‐511 T‐carrier polymorphism has a negative effect on the development of H. pylori‐positive BGU, and high frequency of IL‐1RN 2/2 was found in the H. pylori‐positive relatives of GC patients, which suggest that this genetic polymorphism could play some role in the H. pylori‐induced gastroduodenal diseases in Korea.