bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenaline reveals the torsadogenic effect of combined blockade of potassium channels in anaesthetized guinea pigs
Authors: Michael G , Kane K A , Coker S J
Published: May 2008

Background and purpose:

Torsade de pointes (TdP) can be induced in several species by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether combinedIKrandIKsblockade could induce TdP in anaesthetized guinea pigs and whether short‐term variability (STV) or triangulation of action potentials could predict TdP.

Experimental approach:

Experiments were performed in open‐chest, pentobarbital‐anaesthetized, adrenaline‐stimulated male Dunkin Hartley guinea pigs, which received three consecutive i.v. infusions of either vehicle, theIKrblocker E‐4031 (3, 10 and 30 nmol kg−1 min−1), theIKsblocker HMR1556 (75, 250, 750 nmol kg−1 min−1) or E‐4031 and HMR1556 combined. Phenylephrine‐stimulated guinea pigs were also treated with the K+channel blockers in combination. Arterial blood pressure, ECGs and epicardial monophasic action potential (MAP) were recorded.

Key results:

TdP was observed in 75% of adrenaline‐stimulated guinea pigs given the K+channel blockers in combination, but was not observed in guinea pigs treated with eitherIKblocker alone, or in phenylephrine‐stimulated guinea pigs. Salvos and ventricular tachycardia occurred with adrenaline but not with phenylephrine. No changes in STV or triangulation of the MAP signals were observed before TdP.

Conclusions and implications:

Combined blockade of bothIKrandIKsplus the addition of adrenaline were required to induce TdP in anaesthetized guinea pigs. This suggests that there must be sufficient depletion of repolarization reserve and an appropriate trigger for TdP to occur.

British Journal of Pharmacology(2008)154, 1414–1426; doi:10.1038/bjp.2008.169; published online 19 May 2008
The selective MMP‐12 inhibitor, AS111793 reduces airway inflammation in mice exposed to cigarette smoke
Authors: Le Quément C , Guénon I , Gillon J‐Y , Valença S , Cayron‐Elizondo V , Lagente V , Boichot E
Published: May 2008

Background:

Macrophage elastase (MMP‐12) is involved in the inflammatory process of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate in mice the effect of MMP‐12 inhibition on the inflammatory process induced by cigarette smoke (CS) or by lipopolysaccharide (LPS) exposure of the airways.

Experimental approach:

C57BL/6 mice were given, orally, either the selective MMP‐12 inhibitor AS111793 (3, 10, 30 and 100 mg kg−1), the PDE‐4 inhibitor roflumilast (3 mg kg−1) or vehicle, then exposed to CS (for 3 days) or to LPS (100 μg mL−1, 30 min). Subsequent to the last smoke or LPS exposure, bronchoalveolar lavages (BAL) were performed and lungs were removed and homogenized to analyze various markers of inflammation at appropriate times.

Key results:

Inhibition of MMP‐12 by AS111793 (10 and 30 mg kg−1) was associated with a reduction of the increase in neutrophil number in BAL fluids after 4 days and of macrophages after 11 days. On day 4, AS111793 also significantly reduced all the inflammation markers that had increased after CS exposure, including soluble TNF receptors I and II, MIP‐1γ, IL‐6 and pro‐MMP‐9 activity in BAL fluids, and KC/CXCL1, fractalkine/CX3CL1, TIMP‐1 and I‐TAC/CXCL11 in lung parenchyma. In contrast, inhibition of MMP‐12 did not reduce neutrophil influx, pro‐MMP‐9 activity or KC/CXCL1 release in BAL fluids of mice exposed to LPS.

Conclusion:

Inhibition of MMP‐12 with AS111793, reduced the inflammatory process associated with exposure of mice to CS, strongly suggesting a specific involvement of MMP‐12 in lung inflammation following CS exposure.

British Journal of Pharmacology (2008) 154, 1206–1215; doi:10.1038/bjp.2008.180; published online 19 May 2008
Predicting drug‐induced changes in QT interval and arrhythmias: QT‐shortening drugs point to gaps in the ICHS7B Guidelines
Authors: Lu H R , Vlaminckx E , Hermans A N , Rohrbacher J , Van Ammel K , Towart R , Pugsley M , Gallacher D J
Published: May 2008

Background and purpose:

The regulatory guidelines (ICHS7B) recommending inhibition of the delayed rectifier K+ current (IKr), carried by human ether‐a‐go‐go‐related gene (hERG) channels in cardiac cells (the hERG test), as a ‘first line’ test for identifying compounds inducing QT prolongation, have limitations, some of which are outlined here.

Experimental approach:

hERG current was measured in HEK293 cells, stably transfected with hERG channels; action potential duration (APD) and arrhythmogenic effects were measured in isolated Purkinje fibres and perfused hearts from rabbits.

Key results:

576 compounds were screened in the hERG test: 58% were identified as hERG inhibitors, 39% had no effect and 3% were classified as stimulators. Of the hERG inhibitors, 92 were tested in the APD assay: 55.4% of these prolonged APD, 28.3% had no effect and 16.3% shortened APD. Of the 70 compounds without effect on hERG channels, 54.3% did not affect APD, 25.7% prolonged, while 20% significantly shortened APD. Dofetilide (hERG inhibitor; IC50, 29 nM) prolonged QT and elicited early after‐depolarizations and/or torsade de pointes (TdP) in isolated hearts. Mallotoxin and NS1643 (hERG current stimulators at 3 μM), levcromakalim and nicorandil (no effect on hERG current), all significantly shortened APD and QT, and elicited ventricular fibrillation (VF) in isolated hearts.

Conclusion and implications:

The hERG assay alone did not adequately identify drugs inducing QT prolongation. It is also important to detect drug‐induced QT shortening, as this effect is associated with a potential risk for ventricular tachycardia and VF, the latter being invariably fatal, whereas TdP has an ∼15–25% incidence of death.

British Journal of Pharmacology (2008) 154, 1427–1438; doi:10.1038/bjp.2008.191; published online 19 May 2008
Development of a momentum microscope for time resolved band structure imaging
Authors: Krömker B. , Escher M. , Funnemann D. , Hartung D. , Engelhard H. , Kirschner J.
Published: May 2008

We demonstrate the use of a novel design of a photoelectron microscope in combination to an imaging energy filter for momentum resolved photoelectron detection. Together with a time resolved imaging detector, it is possible to combine spatial, momentum, energy, and time resolution of photoelectrons within the same instrument. The time resolution of this type of energy analyzer can be reduced to below 100ps. The complete ARUPS pattern of a Cu(111) sample excited with HeI, is imaged in parallel and energy resolved up to the photoelectron emission horizon. Excited with a mercury light source (hν=4.9eV), the Shockley surface state at the energy threshold is clearly imaged in k-space. Electron-electron interactions are observed in momentum space as a correlation hole in two-electron photoemission. With the high transmission and the time resolution of this instrument, possible new measurements are discussed: Time and polarization resolved ARUPS measurements, probing change of bandstructure due to chemical reaction, growth of films, or phase transitions, e.g., melting or martensitic transformations.
Probing intermolecular couplings in liquid water with two-dimensional infrared photon echo spectroscopy
Authors: Paarmann A. , Hayashi T. , Mukamel S. , Miller R. J. D.
Published: May 2008

Two-dimensional infrared photon echo and pump probe studies of the OH stretch vibration provide a sensitive probe of the correlations and couplings in the hydrogen bond network of liquid water. The nonlinear response is simulated using numerical integration of the Schrödinger equation with a Hamiltonian constructed to explicitly treat intermolecular coupling and nonadiabatic effects in the highly disordered singly and doubly excited vibrational exciton manifolds. The simulated two-dimensional spectra are in close agreement with our recent experimental results. The high sensitivity of the OH stretch vibration to the bath dynamics is found to arise from intramolecular mixing between states in the two-dimensional anharmonic OH stretch potential. Surprisingly small intermolecular couplings reproduce the experimentally observed intermolecular energy transfer times.
Can the dodecahedral water cluster naturally form in methane aqueous solutions? A molecular dynamics study on the hydrate nucleation mechanisms
Authors: Guo Guang-Jun , Zhang Yi-Gang , Li Meng , Wu Chang-Hua
Published: May 2008

By performing a large scale of molecular dynamics simulations, we analyze 60×106 hydration shells of methane to examine whether the dodecahedral water cluster (DWC) can naturally form in methane aqueous solutions—a fundamental question relevant to the nucleation mechanisms of methane hydrate. The analyzing method is based on identifying the incomplete cages (ICs) from the hydration shells and quantifying their cagelike degrees (ζC=0−1). Here, the ζC is calculated according to the H-bond topological network of IC and reflects how the IC resembles the complete polyhedral cage. In this study, we obtain the ζC distributions of ICs in methane solutions and find the occurrence probabilities of ICs reduce with ζC very rapidly. The ICs with ζC⩾0.65 are studied, which can be regarded as the acceptable cagelike structures in appearance. Both increasing the methane concentration and lowering the temperature can increase their occurrence probabilities through slowing down the water molecules. Their shapes, cage-maker numbers, and average radii are also discussed. About 1∕3–1∕4 of these ICs are face saturated, meaning that every edges are shared by two faces. The face-saturated ICs have the potential to act as precursors of hydrate nucleus because they can prevent the encaged methane from directly contacting other dissolved methane when an event of methane aggregation occurs. The complete cages, i.e., the ICs with ζC=1, form only in the solutions with high methane concentration, and their occurrence probabilities are about 10−6. Most of their shapes are different from the known hydrate cages, but we indeed observe a standard 51262 hydrate cage. We do not find the expected DWC, and its occurrence probability is estimated to be far less than 10−7. Additionally, the IC analysis proposed in this work is also very useful in other studies not only on the formation, dissociation, and structural transition of hydrates but also on the hydrophobic hydration of apolar solutes.
Enhancing visibility and resolution in Nth-order intensity correlation of thermal light
Authors: Cao De-Zhong , Xiong Jun , Zhang Su-Heng , Lin Lu-Fang , Gao Lu , Wang Kaige
Published: May 2008

The arbitrary Nth-order intensity correlation measurement with thermal light is both theoretically and experimentally investigated. In a double-slit interference scheme with thermal light, we compare the results for higher- and lower-order intensity correlation and demonstrate that the visibility of the interference pattern can be dramatically enhanced while the resolution can also be improved when the order N becomes larger. The experimental results are in agreement with our theoretical analysis.
Modulating the reactivity of Ni-containing Pt(111)-skin catalysts by density functional theory calculations
Authors: Su Hai-Yan , Bao Xin-He , Li Wei-Xue
Published: May 2008

We present here a first principles density functional theory investigation of the reactivity of Pt(111)-skin catalysts, which are varied from surface alloys with Ni to bulk PtxNi1−x (x=0.25,0.50,0.75) alloys. Molecule (CO, O, and H) adsorption and oxidation of CO+O and H+O reactions were studied and analyzed in detail. Independent of the adsorbates, the interaction between adsorbates and substrates becomes weakened with increase in Ni, due to the downshift of d-band center of surface Pt atoms. Moreover, activation barriers of CO and H oxidation toward atomic oxygen gradually decrease. In term of CO preferential oxidation (PROX) in excess of hydrogen, it turns out that the overall reactivity and selectivity rely on the optimum of various elementary steps involved such as competitive molecular (dissociative) adsorption and oxidation reaction. The present calculations show that Pt3Ni(111) with Pt overlayer is an optimum catalyst for CO PROX in excess of hydrogen.
Two-dimensional photonic crystals in antimony-based films fabricated by holography
Authors: Nalin M. , Menezes J. W. , Cescato L. , Braga E. S. , Hernandez-Figueroa H. , Ribeiro S. J. L. , Messaddeq Y. , Siu Li M.
Published: May 2008

In this work, we demonstrated the fabrication of two-dimensional (2D) photonic crystals layers (2D-PCLs) by combining holographic recording and the evaporation of antimony-based glasses. Such materials present high refractive indices that can be tuned from 1.8 to 2.4, depending on the film composition; thus, they are interesting dielectric materials for fabrication of 2D-PCLs. The good quality of the obtained samples allowed the measurement of their PC properties through the well-defined Fano resonances that appear in the transmittance spectrum measurements at different incidence angles. The experimental results are in good agreement with the calculated band diagram for the hexagonal asymmetric structure.
Collapse of the Förster energy transfer in doped p-hexaphenylene thin films undergoing crystallization
Authors: Bardizza G. , Caniello R. , Milani P. , Casati N. , Srdanov V. I.
Published: May 2008

A fluorescence resonant energy transfer study is presented, which uses composition-spread libraries of para-hexaphenylene doped with tris-(8-hydroxyquinolinato)aluminum(III) (p6P:Alq3), prepared by a combinatorial physical vapor deposition technique. The p6P:Alq3 libraries deposited at room temperature are polycrystalline and exhibit an inefficient energy transfer. The energy transfer efficiency increases significantly in amorphous p6P:Alq3 libraries deposited at −78°C, yielding the Förster transfer radius of 22Å, in good agreement with the theory. The amorphous p6P:Alq3 libraries undergo slow spontaneous crystallization at room temperature accompanied by a gradual collapse of the energy transfer.
Nonlinear optical properties of Au nanoparticles colloidal system: Local and nonlocal responses
Authors: Souza Rogério F. , Alencar Márcio A. R. C. , da Silva Eid C. , Meneghetti Mario R. , Hickmann Jandir M.
Published: May 2008

Z -scan revealed thermal and electronic contributions for the nonlinear refractive index of highly stable colloid containing different concentrations of gold nanoparticles. Large enhancement factors were observed for values of n2 and dn∕dT of the colloid, due to the presence of the nanoparticles. Our results suggest that thermal effects will play an important role in the development of photonic applications involving nanostructured materials and in the investigation of nonlocal nonlinear phenomena.
Gigahertz quantum key distribution with InGaAs avalanche photodiodes
Authors: Yuan Z. L. , Dixon A. R. , Dynes J. F. , Sharpe A. W. , Shields A. J.
Published: May 2008

We report a demonstration of quantum key distribution (QKD) at gigahertz clock rates with InGaAs avalanche photodiodes (APDs) operating in a self-differencing mode. Such a mode of operation allows detection of extremely weak avalanches so that the detector afterpulse noise is sufficiently suppressed. The system is characterized by a secure bit rate of 2.37Mbit∕s at 5.6km and 27.9kbit∕s at 65.5km when the fiber dispersion is not compensated. After compensating the fiber dispersion, the QKD distance is extended to 101km, resulting in a secure key rate of 2.88kbit∕s. Our results suggest that InGaAs APDs are very well suited to gigahertz QKD applications.
X-ray characterization of dislocation density asymmetries in heteroepitaxial semiconductors
Authors: Yarlagadda B. , Rodriguez A. , Li P. , Velampati R. , Ocampo J. F. , Suarez E. N. , Rago P. B. , Shah D. , Ayers J. E. , Jain F. C.
Published: May 2008

We demonstrate an x-ray rocking curve method which allows detection of an asymmetry in the dislocation densities in an heteroepitaxial (001) zinc blende semiconductor layer. These dislocations exist on two types of slip systems with their misfit dislocation line segments oriented along either a [1−10] direction (type A) or a [110] direction (type B). An imbalance in the densities of dislocations on these slip systems produces an observable azimuthal variation in the rocking curve width for symmetric x-ray reflections. An approximate quantitative model allows the estimation of the dislocation densities on the two types of slip systems.
Participative Urban Renewal? Disability, Community, and Partnership in New Labour's Urban Policy
Authors: Edwards Claire
Published: May 2008

In recent years there has been significant debate regarding the potential of participatory forms of governance to engage with diverse groups and the ‘politics of difference’. This paper explores these debates in the context of disabled people's engagement in urban policy processes, as an arena in which participative imperatives have become manifest under the UK's New Labour government. Drawing on a case study of a Single Regeneration Budget partnership, I argue that there are significant limits to disabled people's engagement in urban policy, ranging from their perceived legitimacy and constitution as a ‘relevant public’, through to the processes of partnership in which managerialist objectives clash with participative agendas. The paper therefore raises issues about the rationale for participation and the extent to which notions of deliberative democracy are equipped to deal with issues of ‘difference’.
Art and Soul: Powerful and Powerless Art in Singapore
Authors: Chang T C
Published: May 2008

Public art in urban areas offers a window on a city's soul. Art in the form of sculptures, monuments, and other creative expressions can inform us of the ways artists think of the urban environment, the goals of policy makers in art installations, and the way members of the public interact with art and with each other in the city. Taking Singapore as a case study, I argue that contemporary public art has the power to inform place identity and inspire community aspirations. Unlike the hard power of industry, art offers a soft branding approach to imaging the city, its people, and their goals. However, such powers are not limitless, and concerns have also been raised about their publicness and artfulness. The power and powerlessness of public art in Singapore are not unlike those encountered in other cities where artful planning has taken centre stage in contemporary urban redevelopment.
Life-Course Influences on Nonearnings Income Migration in the United States
Authors: Nelson Peter B
Published: May 2008

This paper contributes to the emerging body of literature examining the interregional income migration in the United States and offers explanations for why certain areas emerge as magnets for nonearnings income flows while other areas are losing this increasingly important source of personal income. By synthesizing ideas from contemporary understandings of life-course influences on migration and earlier work on income migration, the paper builds a theoretical model of factors shaping income migration across space and tests the model with evidence from Census 2000 by using both ordinary least squares and geographically weighted regression techniques. The analysis highlights the importance of life-course understandings of migration in shaping nonearnings income flows across space. Demographic factors such as concentrations of married couples with no children combine with quality-of-life and economic variables to explain nonearnings income migration. Other factors such as housing-market costs and immigration rates shape nonearnings income flows more powerfully in certain regions than in others. The results have important policy implications. With the baby boomers on the cusp of retirement, an understanding of the geographies of nonearnings income will be important for future regional economic planning and forecasting, as these income sources will become increasingly large components of total personal income.
Living Roofs and Brownfield Wildlife: Towards a Fluid Biogeography of UK Nature Conservation
Authors: Lorimer Jamie
Published: May 2008

This paper follows the trials and tribulations of a loose alliance of urban conservationists seeking to create and maintain spaces for brownfield wildlife in East London. It focuses, in particular, on the construction of living roofs—an innovative conservation strategy where wildlife habitat is created on top of new and old buildings in the city. The paper identifies three obstacles that have challenged the development of brownfield conservation, which relate to the urban geographies, lively temporalities, and inconspicuous forms of brownfield wildlife and wild-living. These obstacles differ markedly from those of the nonhumans prioritised in mainstream conservation. Brownfield conservationists have developed a novel and fluid model of practice, whose emergence and characteristics can be linked to wider developments in UK nature conservation. This model chimes clearly with new approaches to theorising human-nonhuman interaction that have been developed in nonequilibrium ecology and relational geography. Drawing together these empirical and theoretical innovations, the paper concludes by outlining the parameters of a fluid biogeography of UK wildlife conservation to help understand and guide future conservation practice.
Ecosystem and competition impacts of introduced deer
Authors: Dolman Paul M. , Wäber Kristin
Published: May 2008

Numerous deer species have been introduced beyond their native range into ecosystems around the world. Their economic value leads to further accidental and deliberate releases and lack of control is contributing to range expansion in Australia, South America and Europe. Despite localised or regional concern, the scale and generality of detrimental impacts have not been widely recognised. We review the direct and indirect impacts on ecosystems and evidence for interspecific effects on native deer. In New Zealand, where large herbivores were previously absent, severe and novel impacts have been found in susceptible forests. Even where ecosystems contain native deer, invasion by taxonomically exotic deer species carries the risk of cascade effects on spatial plant dynamics and forest composition. In Patagonia, introduced deer have disrupted forest composition, whereas in Europe, ecosystem impacts of introduced species can differ from those of over-abundant native deer. Introduced Chinese muntjac (Muntiacus reevesi) within a coniferous forestry landscape in eastern England differ from native European roe deer (Capreolus capreolus) in their distribution of herbivory among differing habitats, and provide much lower rates of endozoochorous seed dispersal. Frequent concern is expressed that introduced deer species may have detrimental effects on native deer and other ungulates, although potential epidemiological effects have not been investigated. Apparent competition, with introduced prey resulting in increased predation rates on native deer, may be occurring between South American huemul (Hippocamelus bisulcus) and southern pudu (Pudu puda). Habitat and dietary overlap is often substantial among native and introduced ungulates, including deer, and exploitation competition is likely. Evidence includes spatial responses of native to non-native deer and negatively correlated changes in population abundance, but demographic mechanisms have not been demonstrated previously. In a coniferous forestry landscape in eastern England, substantial habitat and dietary overlap occurs between native roe deer and high-density introduced Chinese muntjac. This roe deer population has shown a reduction in body weight and fertility following establishment and increasing abundance of non-native Chinese muntjac, compatible with interspecific competition. European roe deer also appear susceptible to competition from larger grazing deer, including native red deer (Cervus elaphus) and introduced fallow (Dama dama). The widely introduced fallow deer may be a particularly effective competitor in sympatry with intermediate or concentrate feeders. There is need for further investigation of potential interactions of introduced and native deer species, and a wider recognition of the ecological impacts of introduced deer.
Embryology of a planktonic tunicate reveals traces of sessility
Authors: Stach Thomas , Winter Jonas , Bouquet Jean-Marie , Chourrout Daniel , Schnabel Ralf
Published: May 2008

A key problem in understanding deuterostome evolution has been the origin of the chordate body plan. A biphasic life cycle with a sessile adult and a free-swimming larva is traditionally considered ancestral in chordates with subsequent neotenic loss of the sessile adult stage. Molecular phylogenies challenged this view, suggesting that the primitive life cycle in chordates was entirely free-living as in modern day larvaceans. Here, we report the precise cell lineage and fate map in the normal embryo of the larvacean
Oikopleura dioica
, using 4D microscopy technique and transmission electron microscopy. We document the extraordinary rapidity of cleavage and morphogenetic events until hatching and demonstrate that—compared with ascidians—fate restriction occurs considerably earlier in
O. dioica
and that clonal organization of the cell lineage is more tightly coupled to tissue fate. We show that epidermal cells in the trunk migrate through 90°, reminiscent of events in ascidian metamorphosis and that the axis of bilateral symmetry in the tail rotates in relation to the trunk. We argue that part of the tail muscle cells are ectomesodermal, because they are more closely associated with prospective epidermis than with other tissues in the cell lineage. Cladistic comparison with other deuterostomes suggests that these traits are derived within tunicates strengthening the hypothesis that the last common ancestor of tunicates had a sessile adult and thus support traditional morphology-derived scenarios. Our results allow hypothesizing that molecular developmental mechanisms known from ascidian models are restricted to fewer, yet identifiable, cells in
O. dioica
.
Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry
Authors: Haga Shiori , Yamamoto Norio , Nakai-Murakami Chikako , Osawa Yoshiaki , Tokunaga Kenzo , Sata Tetsutaro , Yamamoto Naoki , Sasazuki Takehiko , Ishizaka Yukihito
Published: May 2008

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a high-risk infectious pathogen. In the proposed model of respiratory failure, SARS-CoV down-regulates its receptor, angiotensin-converting enzyme 2 (ACE2), but the mechanism involved is unknown. We found that the spike protein of SARS-CoV (SARS-S) induced TNF-α-converting enzyme (TACE)-dependent shedding of the ACE2 ectodomain. The modulation of TACE activity by SARS-S depended on the cytoplasmic domain of ACE2, because deletion mutants of ACE2 lacking the carboxyl-terminal region did not induce ACE2 shedding or TNF-α production. In contrast, the spike protein of HNL63-CoV (NL63-S), a CoV that uses ACE2 as a receptor and mainly induces the common cold, caused neither of these cellular responses. Intriguingly, viral infection, judged by real-time RT-PCR analysis of SARS-CoV mRNA expression, was significantly attenuated by deletion of the cytoplasmic tail of ACE2 or knock-down of TACE expression by siRNA. These data suggest that cellular signals triggered by the interaction of SARS-CoV with ACE2 are positively involved in viral entry but lead to tissue damage. These findings may lead to the development of anti-SARS-CoV agents.
Hyper innate responses in neonates lead to increased morbidity and mortality after infection
Authors: Zhao Jie , Kim Kwang Dong , Yang Xuanming , Auh Sogyong , Fu Yang-Xin , Tang Hong
Published: May 2008

Neonates suffer high morbidity and mortality in infection, presumably because of the lack of a fully developed adaptive and innate immune system. Evidence of poor innate responses in neonates has been shown by using a model that sensitizes the host to Toll-like receptor (TLR)-mediated inflammation withd-galactosamine (d-GalN). However, we show that neonatal mice demonstrate much stronger inflammatory responses than adult mice in response to LPS stimulation, and such hypersensitivity extends to other TLR agonists including actual viral infection. Our study reveals that the ensuing inflammatory reaction afterd-GalN sensitization reflects preferential toxicity ofd-GalN to adult liver cells, rather than accurately reflecting the TLR response to LPS. We show further that an uncontrolled proinflammatory innate response due to inadequate T cells makes neonates more vulnerable to TLR agonists or viral infection. Remarkably, through transfer of T cells into neonates or depletion of T cells in adult mice, we show that T cells are sufficient and necessary to control the early inflammatory response to LPS. Therefore, neonates might suffer from the unleashed innate responses caused by an insufficient number of T cells, which leads to increased morbidity and mortality.
Hexadecyloxypropyl-cidofovir, CMX001, prevents adenovirus-induced mortality in a permissive, immunosuppressed animal model
Authors: Toth Karoly , Spencer Jacqueline F. , Dhar Debanjan , Sagartz John E. , Buller R. Mark L. , Painter George R. , Wold William S. M.
Published: May 2008

Adenoviruses (Ads) cause a wide array of end-organ and disseminated diseases in severely immunosuppressed patients. For example, ≈20% of pediatric allogeneic hematopoietic stem cell transplant recipients develop disseminated Ad infection, and the disease proves fatal in as many as 50–80% of these patients. Ad infections are a serious problem for solid-organ transplant recipients and AIDS patients as well. Unfortunately, there are no antiviral drugs approved specifically to treat these infections. A suitable animal model that is permissive for Ad replication would help in the discovery process. Here we identify an animal model to study Ad pathogenesis and the efficacy of antiviral compounds. We show that human serotype 5 Ad (Ad5) causes severe systemic disease in immunosuppressed Syrian hamsters that is similar to that seen in immunocompromised patients. We also demonstrate that hexadecyloxypropyl-cidofovir (CMX001) rescues the hamsters from a lethal challenge with Ad5. The antiviral drug provided protection both prophylactically and when given up to 2 days after i.v. exposure to Ad5. CMX001 acts by reducing Ad replication in key target organs. Thus, the immunosuppressed Syrian hamster is a powerful model to evaluate anti-Ad drugs, and its use can facilitate the entry of drugs such as CMX001 into clinical trials.
Structural basis of actin recognition and arginine ADP-ribosylation by
Clostridium perfringens
ι-toxin
Authors: Tsuge Hideaki , Nagahama Masahiro , Oda Masataka , Iwamoto Shinobu , Utsunomiya Hiroko , Marquez Victor E. , Katunuma Nobuhiko , Nishizawa Mugio , Sakurai Jun
Published: May 2008

The ADP-ribosylating toxins (ADPRTs) produced by pathogenic bacteria modify intracellular protein and affect eukaryotic cell function. Actin-specific ADPRTs (including
Clostridium perfringens
ι-toxin and
Clostridium botulinum
C2 toxin) ADP-ribosylate G-actin at Arg-177, leading to disorganization of the cytoskeleton and cell death. Although the structures of many actin-specific ADPRTs are available, the mechanisms underlying actin recognition and selective ADP-ribosylation of Arg-177 remain unknown. Here we report the crystal structure of actin-Ia in complex with the nonhydrolyzable NAD analog βTAD at 2.8 Å resolution. The structure indicates that Ia recognizes actin via five loops around NAD: loop I (Tyr-60–Tyr-62 in the N domain), loop II (active-site loop), loop III, loop IV (PN loop), and loop V (ADP-ribosylating turn–turn loop). We used site-directed mutagenesis to confirm that loop I on the N domain and loop II are essential for the ADP-ribosyltransferase activity. Furthermore, we revealed that Glu-378 on the EXE loop is in close proximity to Arg-177 in actin, and we proposed that the ADP-ribosylation of Arg-177 proceeds by an SN1 reaction via first an oxocarbenium ion intermediate and second a cationic intermediate by alleviating the strained conformation of the first oxocarbenium ion. Our results suggest a common reaction mechanism for ADPRTs. Moreover, the structure might be of use in rational drug design to block toxin-substrate recognition.
Plant nutrient use efficiency in organic farming - consequences of exclusive use of organic manures and untreated minerals.
Authors: Kirchmann H. , Ryan M. H. , Bergström L.
Published: May 2008

On organic farms, nutrients are applied in organic or sparingly soluble inorganic form, with plants receiving the nutrients they require indirectly through the action of soil microbes. This review examines the implications of exclusive use of organic fertilizers for the sustainability of farming systems, primarily using examples from two contrasting regions, Europe and Australia. In both these regions, mean yields are generally 25-65% lower on organic farms than on conventional farms, primarily because of decreases in plant-available nutrients that cannot be overcome by enhancement of the soil biological community. Overall nutrient inputs are lower on organic farms, although organic farms in Europe are increasingly applying approved commercial fertilizers. However, these inputs simply allow organic farms to acquire nutrients originating from conventional systems. If organic crop production were to be widely adopted, lower yields would require more land (33-100%) to maintain current production levels. In Europe, organic farming increases nitrate leaching, especially if expressed per unit of food produced, because of lower N use efficiency by plants. Despite their aim of maximizing nutrient recycling, organic farming systems recycle only on-farm waste and approved food waste, with most types of municipal waste excluded due to concerns about pollutants. Readily soluble inorganic fertilizers can be extracted from municipal wastes through new nutrient recovery technologies, but current regulations do not allow their use in organic cropping systems. In conclusion, promotion of organic principles does not improve use and cycling of nutrients and does not reduce leaching of nutrients, but excludes other more effective solutions for nutrient use in agricultural systems.
Approaches to TMDL planning and implementation and policy tools for implementation to achieve water quality standards.
Authors: Jesiek J. B. , Benham B. L. , Bosch D. J. , Stephenson K.
Published: May 2008

This review is based primarily on information gathered in the TMDL Knowledgebase Clearinghouse developed by the Center for Total Maximum Daily Load (TMDL) and Watershed Studies at Virginia Tech. The TMDL programme has received renewed attention since the US Environmental Protection Agency (EPA) published revised guidelines in 1991. Under the TMDL programme, pollutant-specific TMDLs are developed for impaired waters. A TMDL specifies the pollutant load reductions needed to achieve water quality standards. The magnitude and distribution of the load reductions among pollution sources can have implications for watershed stakeholders. Implementing the TMDL load reductions is the responsibility of the individual US states. Adaptive implementation occurs when limited corrective actions designed to improve water quality are implemented using available information and data; and as information and data availability improve implementation adjustments are made, i.e. 'learn while doing'. While several policy tools are available to ensure that corrective actions are implemented, economic incentives are most often used, particularly for non-point source pollution sources. Typically, successful TMDL implementation depends on careful planning and stakeholder engagement. However, meaningful stakeholder engagement requires that stakeholders be empowered to make decisions about outcomes relevant to their goals, which may be problematic given the narrow way the TMDL process is currently enacted. Planning using watershed-scale models to assess plausible load reduction scenarios is most likely to produce credible TMDL pollutant load estimates. Models should be coupled with adaptive implementation so that pollutant load estimates can be revised as better information becomes available. TMDL implementation plans should consider both barriers to and opportunities for implementation.
Classical biological control of the cabbage root fly,
Delia radicum
, in Canadian canola: an analysis of research needs.
Authors: Andreassen L. D. , Kuhlmann U. , Mason P. G. , Holliday N. J.
Published: May 2008

The cabbage root fly (=cabbage maggot),
Delia radicum
, has increased in importance over the past two decades as a pest of canola (oilseed rape) in Canada. Although
D. radicum
has been a part of the North American insect fauna for some time, it is not native, so the introduction of natural enemy species from Europe is being considered for integration with existing management strategies. The biology of
D. radicum
, the injuries it causes to the crop, and strategies already available for its control are briefly reviewed, followed by the process by which
Aleochara bipustulata
, a predator and parasitoid of
D. radicum
, was identified as the most promising candidate for introduction in a classical biological control programme. The literature on
A. bipustulata
and other species in the same genus is then brought together to illustrate the importance of studies to evaluate the potential of
A. bipustulata
to provide control, and its effects on non-target species.
Food colours of plant origin.
Authors: Shamina A. , Shiva K. N. , Parthasarathy V. A.
Published: May 2008

Pigments of plant origin are gaining importance globally as a potential source of natural food colours for their versatility and so as to avoid a variety of health hazards caused by synthetic colours. Colour has been added to our foods in one or another form for centuries. Earlier studies of food colours have focused mainly on synthetic colours and their chemistry, stability, metabolism and toxicity, but recent attention has been directed towards biochemical aspects of food colours of plant origin and their utilization studies. This review gives up-to-date information on various aspects of food colours such as history, types, sources, uses, chemistry, properties, colour additives and regulations for use.
Therapeutic use of bacteriophages in animals and in foods to reduce contamination.
Authors: Owens J. , Heuzenroeder M. , Barton M. D.
Published: May 2008

Bacteriophages are viruses that are able to infect and kill bacterial cells. This capability indicates that they may have the potential to become new antibacterial agents, as an alternative to antibiotics. Yet, while bacteriophages are relatively new to Western researchers, they have been extensively used in the former Eastern Block and its successors, including use in human clinical medicine. Western research on this topic is far more limited. Bacteriophage products have recently been licensed in the USA for control of two different bacteria:
Listeria monocytogenes
and
Escherichia coli
O157:H7. Neither of these products is, however, approved for direct administration to humans or animals. The use of bacteriophages to treat bacterial infections in humans or animals is a much more complex issue, but there has been a considerable amount of research into this field, and results are quite promising. Bacteriophage therapy and prevention of bacterial pathogens has been assessed in numerous species, and animals are also used as models for human disease. The behaviour of bacteriophages is, however, not as predictable
in vivo
as it is in artificial laboratory models. There is also concern regarding possible undesirable outcomes of bacteriophage therapy, such as the development of bacterial resistance to bacteriophages, and even the possibility of transfer of virulence or resistance genes, via bacteriophages, into other bacteria. Therefore, extensive research is still required into the behaviour of bacteriophages in
vivo
, but research to date shows considerable promise.
Nutrition of juvenile saltwater crocodiles (
Crocodylus porosus
) in commercial production systems.
Authors: Isberg S. R.
Published: May 2008

Developing an artificial diet for saltwater crocodiles to replace feeding raw meat has received considerable research effort in Australia over the last 10 years. The advantages of developing an artificial diet include a reduction in labour costs, capital outlay and maintenance and operating costs. Considering labour and feed costs have been estimated to be approximately 80% of the operation costs on Australian farms, the economic benefits are substantial. Despite this effort, no review has been published to determine where gaps in the research exist. Many studies have been conducted to determine the optimal protein, fat and energy levels for crocodilian feeds. These have been used as a model for developing artificial diets but the fastidious feeding behaviour of saltwater crocodiles has resulted in very little progress being made. It is this fastidious feeding behaviour that is particularly delaying progress and strategies such as manipulating the texture, odour and/or taste have so far been unsuccessful.
Counting the cost of climate change at an agricultural level.
Authors: Quiggin J.
Published: May 2008

The effects of global climate change on agriculture will be diverse and complex. Some important qualitative conclusions emerge from the literature. First, it is important to focus on the rate at which climate changes and the capacity of farmers to adjust, rather than on absolute changes in temperature. Second, given that significant warming is inevitable, it is important to focus on the marginal effects of feasible changes in the rate of warming, rather than on the aggregate rate of warming. With a convex damage function, the expected marginal cost of warming may be large even when aggregate damage, given the expected rate of warming, is close to zero. Third, uncertainty is crucial and remains poorly understood. In particular, modelling of low-probability catastrophic outcomes remains very limited. Finally, it seems likely that global climate change will enhance extremes of all kinds.
What do purchasers of Fair Trade products want?
Authors: Sirieix L.
Published: May 2008

Fair Trade is a trading partnership that seeks greater equity in international trade, and is backed by Fair Trade consumers who accept to pay an 'ethical price premium' to contribute to sustainable development in the South. The question 'What do purchasers of Fair Trade products want?' can be split into two questions. First, what do they want to 'say' with their choice? To answer this question, it is necessary to examine buying motives, but also barriers that may explain the gap between attitudes and actual behaviour. Fair Trade consumption can be seen as a solidarity-based commitment, since Fair Trade consumers' concerns mainly relate to the well-being of workers and farmers in developing countries. These motives are mainly linked to universal personal values, but are combined with other motives such as taste or quality, linked with self-oriented values. Besides, several barriers contribute to an explanation of the gap between positive attitudes towards Fair Trade and consumers' actual behaviour: lack of awareness, social norms, perceived behaviour control and perceived consumer efficiency, but also price and taste. The second question is 'What do purchasers of Fair Trade products want to purchase, and where?' If results from initial studies are confirmed, not all Fair Trade consumers may want the same product: for most of them, a double 'organic and Fair Trade' label may add value to the product, but for some consumers this double label can devalue Fair Trade products. Besides, not all consumers want the same distribution channels: those who pay attention to convenience and availability want to find Fair Trade products in supermarkets, but more committed consumers seem to prefer alternative Fair Trade shops. Finally, this literature review highlights the diversity of consumer profiles and desires and dilemmas affecting Fair Trade, and suggests some research issues for a better understanding of the Fair Trade consumers and Fair Trade movement perspectives.
Priorities for conservation of soil animals.
Authors: Decaëns T. , Lavelle P. , Jiménez J. J.
Published: May 2008

Soils are recognized as one of the greatest biodiversity reservoirs of the planet, as communities of edaphic animals include an outstanding diversity of body sizes, life forms and behaviours, with representatives of virtually all the major taxa and trophic groups that form the terrestrial animal kingdom. Paradoxically, soils are also among the most poorly studied habitats of our planet, and we most likely only know an infinitesimal part of the global taxonomic and functional diversity of its biota. In this paper, we provide a 'state-of-the-art' review and reveal the main gaps in our knowledge of soil animal diversity, its function and how it contributes to the provision of important ecosystem services. We also propose some further research priorities for improving our knowledge of soil fauna and contributing to a better conservation of their communities.
Nutrition screening in long-term care facilities: an evaluation of the methodological quality of available instruments.
Authors: Miller M. D. , Loh W. N. , Watterson C. , Fraser A. , Nowson C.
Published: May 2008

A variety of nutrition screening instruments have been developed and implemented for identifying the risk of undernutrition among community and hospitalized older adults. Despite the high prevalence of undernutrition amongst older adults in long-term care, few screening instruments have been developed or evaluated in this setting. This review aims to evaluate the validity, reproducibility and feasibility of nutrition screening instruments developed for use, or described as being used, with older adults in long-term care. Ten publications encompassing nine independent nutrition screening tools were identified using electronic databases and manual searches of reference lists. The Mini Nutritional Assessment-Short Form (MNA-SF) was the most widely evaluated nutrition screening instrument and met the requirements for a valid instrument (sensitivity and specificity >0.9) for use in the long-term care setting. Modified versions of the MNA for use in China and South Africa also demonstrated acceptable levels of sensitivity and specificity. Other nutrition screening instruments were found to have variable levels of sensitivity and specificity and while some demonstrated levels consistent with the MNA-SF, only two were evaluated across more than one study population, Body Mass Index (BMI)+weight loss and BMI+albumin. These same instruments reported the highest levels of inter-rater and test-retest reproducibility, although this was only tested in one other instrument (Chinese Nutrition Screen - modified MNA). In conclusion, it is evident from this review that further work in this area is needed. Based on validity, reproducibility and feasibility it appears that BMI+weight loss is the most suitable nutrition screening instrument for use in the long-term care setting at this time. MNA-SF is promising; however, there is currently no data for inter-rater or test-retest reproducibility in the long-term care setting.