bluuebunny/crossref_metadata_2025 huggingface dataset:
Human iron regulatory protein 2 is easily cleaved in its specific domain: consequences for the haem binding properties of the protein
Authors: Dycke Camille , Bougault Catherine , Gaillard Jacques , Andrieu Jean-Pierre , Pantopoulos Kostas , Moulis Jean-Marc
Published: January 2008

Mammalian IRPs (iron regulatory proteins), IRP1 and IRP2, are cytosolic RNA-binding proteins that post-transcriptionally control the mRNA of proteins involved in storage, transport, and utilization of iron. In iron-replete cells, IRP2 undergoes degradation by the ubiquitin/proteasome pathway. Binding of haem to a 73aa-Domain (73-amino-acid domain) that is unique in IRP2 has been previously proposed as the initial iron-sensing mechanism. It is shown here that recombinant IRP2 and the 73aa-Domain are sensitive to proteolysis at the same site. NMR results suggest that the isolated 73aa-Domain is not structured. Iron-independent cleavage of IRP2 within the 73aa-Domain also occurs in lung cancer (H1299) cells. Haem interacts with a cysteine residue only in truncated forms of the 73aa-Domain, as shown by a series of complementary physicochemical approaches, including NMR, EPR and UV–visible absorption spectroscopy. In contrast, the cofactor is not ligated by the same residue in the full-length peptide or intact IRP2, although non-specific interaction occurs between these molecular forms and haem. Therefore it is unlikely that the iron-dependent degradation of IRP2 is mediated by haem binding to the intact 73aa-Domain, since the sequence resembling an HRM (haem-regulatory motif) in the 73aa-Domain does not provide an axial ligand of the cofactor unless this domain is cleaved.
PIAS proteins as regulators of small ubiquitin-related modifier (SUMO) modifications and transcription
Authors: Palvimo J.J.
Published: January 2008

Transcriptional activity of signal-dependent transcription factors, including nuclear receptors, relies on interacting co-regulator proteins, many of which possess protein-modifying activity. SUMOs (small ubiquitin-related modifiers) and their conjugation pathway components act as co-regulator proteins for numerous transcription factors that also are often targets for SUMO modification. PIAS [protein inhibitor of activated STAT (signal transducer and activator of transcription)] proteins promote SUMOylation in a manner that resembles the action of RING-type ubiquitin E3 ligases. PIAS proteins were initially named for their ability to interact with STAT proteins and inhibit their activity, but their interactions and functions are not restricted to the STATs. Moreover, PIAS proteins do not operate merely as SUMO E3s, since their co-regulator effects are often independent of their RING finger but dependent on their SIM (SUMO-interacting motif) or SAP (scaffold attachment factor-A/B/acinus/PIAS) domain capable of interacting with DNA. The modulator activity imparted by the PIAS/SUMO system involves altered subnuclear targeting and/or assembly of transcription complexes. PIAS proteins may act as platforms that facilitate both removal and recruitment of other regulatory proteins in the transcription complexes.
SUMO: getting it on
Authors: Anckar J. , Sistonen L.
Published: January 2008

Post-translational modification of cellular proteins by the SUMO (small ubiquitin-related modifier) is involved in numerous modes of regulation in widely different biological processes. In contrast with ubiquitination, SUMO conjugation is highly specific in terms of target lysine residues, but many aspects of substrate and lysine selection by the SUMO conjugating machinery are still poorly understood. SUMOylation events usually occur on the ΨKXE SUMO consensus motifs, which mediate binding to Ubc9 (ubiquitin-conjugating enzyme 9), the SUMO E2 conjugating enzyme. Although most, if not all, SUMO conjugations are catalysed by Ubc9, far from all ΨKXE tetrapeptides are modified, demonstrating a need for additional specificity determinants in SUMOylation. Recent results intimately link regulation of SUMOylation to other post-translational modifications, including phosphorylation and acetylation and reveal that certain lysine residues are marked for SUMOylation by negatively charged amino acid residues or phosphorylation events immediately downstream of the consensus site. In the present review, we explore the intriguing role of extended motifs in the regulation of SUMO conjugation.
Role of pattern-recognition receptors in cardiovascular health and disease
Authors: Mitchell J.A. , Ryffel B. , Quesniaux V.F.J. , Cartwright N. , Paul-Clark M.
Published: January 2008

A role for PRRs (pattern-recognition receptors) in immune cell function is now well established. In macrophages and other immune cells, activation of TLRs (Toll-like receptors) and cytosolic NLRs [NOD (nucleotide oligomerization domain) proteins containing a leucine-rich repeat] results in the induction of genes and release of imunoregulator hormones including cytokines and NO (nitric oxide). In addition to immune cells, structural cells of the cardiovascular system including endothelial cells, vascular smooth muscle and cardiac myocytes express functional PRRs and sense PAMPs (pathogen-associated molecular patterns). Furthermore, bacteria and PAMPs activate the coagulation system and platelets. TLRs are now implicated in a range of cardiovascular diseases and syndromes including atherosclerosis and sepsis. Our group is working on the hypotheses that differences exist in how tissues of the cardiovascular system, including vessels, endothelium, heart and blood, sense pathogens compared with immune cells (principally macrophages) and that identifying such differences will reveal new therapeutic targets for the treatment of cardiovascular disease. We have identified examples of similarities and differences in how cardiovascular tissues and macrophages sense PAMPs. These findings will be discussed together with our interpretation of how this information may lead to new treatments.
Toll-like receptors in atherosclerosis
Authors: Tobias P.S. , Curtiss L.K.
Published: January 2008

At one time, atherosclerosis was thought to be a simple lipid storage disease. However, it is now recognized as a chronic and progressive inflammation of the arterial wall. Gene deletion experiments in murine models of atherosclerosis that reduce the inflammatory process also reduce disease severity. Identifying the initiators and mediators of that inflammation can provide promising avenues for prevention or therapy. Two prominent risk factors, hyperlipidaemia and infectious disease, point to innate immune mechanisms as potential contributors to proatherogenic inflammation. The TLRs (Toll-like receptors), pro-inflammatory sensors of pathogens, are potential links between inflammation, infectious disease and atherosclerosis. A mechanism for hyperlipidaemic initiation of sterile inflammation can be postulated because oxidized lipoproteins or their component oxidized lipids have been identified as TLR ligands. Moreover, infectious agents are correlated with atherosclerosis risk. We have identified a role for TLR2 in atherosclerosis in mice deficient in low-density lipoprotein receptor. We observed that proatherogenic TLR2 responses to unknown endogenous or unknown endemic exogenous agonists are mediated by non-BMDC (bone-marrow-derived cells), which can include endothelial cells. In contrast, the proatherogenic TLR2 responses to the defined synthetic exogenous agonist Pam3 CSK4 are mediated at least in part by BMDC, which can include lymphocytes, monocytes/macrophages and dendritic cells. TLR2-mediated cell activation in response to endogenous and exogenous agents is proatherogenic in hyperlipidaemic mice.
TLR4 signalling in the intestine in health and disease
Authors: Fukata M. , Abreu M.T.
Published: January 2008

The colonic epithelium is lined along its apical membrane with ∼1014 bacteria/g of tissue. Commensal bacteria outnumber mammalian cells in the gut severalfold. The reason for this degree of commensalism probably resides in the recent recognition of the microbiome as an important source of metabolic energy in the setting of poorly digestible nutrients. As in many themes in biology, the host may have sacrificed short-term benefit, i.e. nutritional advantages, for long-term consequences, such as chronic inflammation or colon cancer. In the present review, we examine the role of TLR (Toll-like receptor) signalling in the healthy host and the diseased host. We pay particular attention to the role of TLR signalling in idiopathic IBD (inflammatory bowel disease) and colitis-associated carcinogenesis. In general, TLR signalling in health contributes to homoeostatic functions. These include induction of antimicrobial peptides, proliferation and wound healing in the intestine. The pathogenesis of IBD, ulcerative colitis and Crohn's disease may be due to increased TLR or decreased TLR signalling respectively. Finally, we discuss the possible role of TLR signalling in colitis-associated neoplasia.
A phylogenetic and functional overview of inflammatory caspases and caspase-1-related CARD-only proteins
Authors: Kersse K. , Berghe T. Vanden , Lamkanfi M. , Vandenabeele P.
Published: January 2008

Caspase 1 is a cysteinyl aspartate-specific proteinase involved in the maturation of inflammatory cytokines such as pro-IL-1β (interleukin-1β) and pro-IL-18. Caspase 1 clusters phylogenetically together with human caspases 4, 5 and 12 and murine caspases 11 and 12, and forms the group of the so-called inflammatory caspases. Caspase 1 consists of an N-terminal CARD (caspase recruitment domain) and a proteolytic domain containing the catalytic residues. The CARD-containing prodomain is involved in the formation of the protease-activating inflammasome complex. We have also found that the prodomain is necessary and sufficient for the activation of NF-κB (nuclear factor κB). The human genome also contains three caspase-1-related CARD-only decoy proteins [COP (CARD-only protein), INCA (inhibitory CARD) and ICEBERG], which are located near the caspase 1 locus. In this mini-review, we focus on the evolutionary aspects of the inflammatory caspase locus in the human, chimpanzee, Rhesus monkey, mouse and rat. Furthermore, we discuss the functional characteristics of the caspase-1-related CARD-only proteins in relation to caspase-1-mediated IL-1β maturation and NF-κB activation.
Structure–function relationships of Toll-like receptor domains through homology modelling and molecular dynamics
Authors: Kubarenko A. , Frank M. , Weber A.N.R.
Published: January 2008

TLRs (Toll-like receptors) are pattern-recognition receptors of the immune system and recognize pathogens based on distinct molecular signatures. Although different TLRs within the same species (orthologues) or individual TLRs across different species (homologues) are similar in protein sequence, they differ considerably with regard to their function, for example with regard to ligand discrimination or adaptor selection. Owing to the lack of structural information, explanations for these phenomena have been difficult to provide. We have combined homology modelling with energy minimization and Molecular Dynamics simulation in order to address these interesting biological phenomena from a structural angle. Thus three-dimensional models of human and mouse TLR3 and TLR4 domains were successfully generated. Apart from providing a structural framework in which mutagenesis studies (both site-directed and random) can be interpreted and designed, Molecular Dynamics also allowed us to study and simulate protein structure under solution-like conditions. We have applied this approach to the human TLR3 and TLR4 ECDs (ectodomains) providing insights into the dynamics of TLR ECDs. Other conclusions drawn from our structural models are also discussed. We hope that our structural modelling approach, which can be extended to other members of the TLR family or other signal transduction pathways, will serve as a valuable tool for the design of experiments to address questions of TLR biology further.
Insight into stability of CotA laccase from the spore coat of Bacillus subtilis
Authors: Melo E.P. , Fernandes A.T. , Durão P. , Martins L.O.
Published: January 2008

The axial ligand of the catalytic mononuclear T1 copper site (Met502) of the CotA laccase was replaced by a leucine or phenylalanine residue to increase the redox potential of the enzyme. These mutations led to an increase in the redox potential by approx. 100 mV relative to the wild-type enzyme but the catalytic constant kcat in the mutant enzymes was severely compromised. This decrease in the catalytic efficiency was unexpected as the X-ray analysis of mutants has shown that replacement of methionine ligand did not lead to major structural changes in the geometry of the T1 centre or in the overall fold of the enzyme. However, the mutations have a profound impact on the thermodynamic stability of the enzyme. The fold of the enzyme has become unstable especially with the introduction of the larger phenylalanine residue and this instability should be related to the decrease in the catalytic efficiency. The instability of the fold for the mutant proteins resulted in the accumulation of an intermediate state, partly unfolded, in-between native and unfolded states. Quenching of tryptophan fluorescence by acrylamide has further revealed that the intermediate state is partly unfolded.
Stabilization of the active form(s) of human paraoxonase by human phosphate-binding protein
Authors: Rochu D. , Chabrière E. , Renault F. , Elias M. , Cléry-Barraud C. , Masson P.
Published: January 2008

While there is a consensus that human PON1 (paraoxonase-1) has a protective role, its primary biological function remains unclear. A protective role against poisoning by organophosphates [OPs (organophosphorus compounds)] drove earlier works. Clinical interest has recently focused on a protective role of PON1 against vascular diseases. PON1 resides mainly on HDL (high-density lipoprotein) particles, and converging recent works show that both its activities and stability dramatically depend on this versatile and dynamic molecular environment. The discovery that HPBP (human phosphate-binding protein) has a firm tendency to associate with PON1 has steered new directions for characterizing PON1 functional state(s). Storage stability studies provided evidence that HPBP is involved in maintaining physiologically active PON1 conformation(s). Thermal stability studies showed that human PON1 is remarkably thermostable and that its association with HPBP strongly contributes to slowing down the denaturation rate. A hybrid PON1, displaying mutations that stabilized recombinant enzyme expressed in Escherichia coli, was shown to be more thermostable than natural human PON1. Predictably, its stability was unaffected by the presence of HPBP. Synergistic efforts on characterizing natural PON1 and rPON1 (recombinant PON1) provide information for the design of future stable mutants of PON1-based bioscavengers to be used as safe and effective countermeasures to challenge OPs. Maintaining a stable environment for such administrable human rPON1 should, at least, preserve the anti-atherogenic activity of the enzyme.
On the background of enhanced stability and reusability of enzymes in ionic liquids
Authors: Fehér E. , Major B. , Bélafi-Bakó K. , Gubicza L.
Published: January 2008

The ability of ILs (ionic liquids) to provide an environment of increased stability and, in this way, improve the recyclability of enzymes has been studied. The description of this phenomenon is not easy; there are several approaches for explanation. In this mini-review, the results from different research groups are summarized, with the aim of explaining the strong stability effect of ILs on several enzymes. Spectroscopic methods (e.g. fluorescence and CD, IR spectroscopy, mass spectroscopy and NMR) and investigations of polarity and kosmotropicity of ions are promising methods. Since higher stability means that we may be able to reuse enzymes more times, the recyclability of enzymes was also in the focus. From this point of view, the advantages and disadvantages of applying monophasic or biphasic systems are discussed too, presenting the coupled techniques as well.
Women, Migration and Precarity
Authors: Coppola Manuela , Curti Lidia , Fantone Laura , Laforest Marie-Hélène , Poole Susanna
Published: January 2008

This focus group took place at the Università di Napoli ‘L'Orientale’ and was structured around recent female migration patterns in the south of Italy. The discussion included academics, artists, and care workers. The condition of women migrants was seen as one of precarity in the two main contexts we discussed: work and places of encounter. In an effort to move away from the purely material dimension of migration and deal with its emotional and creative sides, many facets of the question of being away from home and creating a new home were fleshed out: expectations, defence mechanisms, nostalgia, stereotyping, racism, and multi-culturalism. Participants raised a wide range of issues and proposed different perspectives which also point to larger tensions and challenges in gender and race relations.
Simulation of semidilute suspensions of non-Brownian fibers in shear flow
Authors: Lindström Stefan B. , Uesaka Tetsu
Published: January 2008

Particle-level simulations are performed to study semidilute suspensions of monodispersed non-Brownian fibers in shear flow, with a Newtonian fluid medium. The incompressible three-dimensional Navier-Stokes equations are used to describe the motion of the medium, while fibers are modeled as chains of fiber segments, interacting with the fluid through viscous drag forces. The two-way coupling between the solids and the fluid phase is taken into account by enforcing momentum conservation. The model includes long-range and short-range hydrodynamic fiber-fiber interactions, as well as mechanical interactions. The simulations rendered the time-dependent fiber orientation distribution, whose time average was found to agree with experimental data in the literature. The viscosity and first normal stress difference was calculated from the orientation distribution using the slender body theory of Batchelor [J. Fluid Mech. 46, 813 (1971)], with corrections for the finite fiber aspect ratios. The viscosity was also obtained from direct computation of the shear stresses of the suspension for comparison. These two types of predictions compared well in the semidilute regime. At higher concentrations, however, a discrepancy was seen, most likely due to mechanical interactions, which are only accounted for in the direct computation method. The simulated viscosity determined directly from shear stresses was in fair agreement with experimental data found in the literature. The first normal stress difference was found to be proportional to the square of the volume concentration of fibers in the semidilute regime. As concentrations approached the concentrated regime, the first normal stress difference became proportional to volume concentration. It was also found that the coefficient of friction has a strong influence on the tendency for flocculation as well as the apparent viscosity of the suspension in the semidilute regime.
Ab initio study on the ground and low-lying excited states of cesium iodide (CsI)
Authors: Kurosaki Yuzuru , Matsuoka Leo , Yokoyama Keiichi , Yokoyama Atsushi
Published: January 2008

Potential energy curves (PECs) for the ground and low-lying excited states of the cesium iodide (CsI) molecule have been calculated using the internally contracted multireference configuration interaction calculation with single and double excitation method with the relativistic pseudopotentials. PECs for seven Λ-S states, XΣ+1, 2Σ+1, Σ+3, Π1, and Π3 are first calculated and then those for 13 Ω states are obtained by diagonalizing the matrix of the electronic Hamiltonian Ĥel plus the effective one-electron spin-orbit (SO) Hamiltonian ĤSO. Spectroscopic constants for the calculated ground X0+-state PEC with the Davidson correction are found to agree well with the experiment. Transition dipole moments (TDMs) between X0+ and the other Ω states are also obtained and the TDM between X0+ and A0+ is predicted to be the largest and that between X0+ and B0+ is the second largest around the equilibrium internuclear distance. The TDMs between X0+ and the Ω=1 states are estimated to be nonzero, but they are notably small as compared with those between the 0+ states. Finally, vibrational levels of the X0+ PEC for the two isotopic analogs, Cs133I and Cs135I, are numerically obtained to investigate the isotope effect on the vibrational-level shift. It has been found that the maximized available isotope shift is ∼30cm−1 around v=136.
Full configuration interaction study of the metal-insulator transition in model systems: LiN linear chains (N=2,4,6,8)
Authors: Vetere Valentina , Monari Antonio , Bendazzoli Gian Luigi , Evangelisti Stefano , Paulus Beate
Published: January 2008

The precursor of the metal-insulator transition is studied at ab initio level in linear chains of equally spaced lithium atoms. In particular, full configuration interaction calculations (up to 1×109 determinants) are performed, in order to take into account the different nature of the wave function at different internuclear distances. Several indicators of the Metal-Insulator transition (minimum of the energy gap, maximum of the localization tensor or of the polarizability) are considered and discussed. It is shown that the different indicators give concordant results, showing a rapid change in the nature of the wave function at an internuclear distance of about 7bohrs.
Composition-dependent polarization switching behaviors of (111)-preferred polycrystalline Pb(ZrxTi1−x)O3 thin films
Authors: Jo J. Y. , Yang S. M. , Han H. S. , Kim D. J. , Choi W. S. , Noh T. W. , Song T. K. , Yoon J.-G. , Koo C.-Y. , Cheon J.-H. , Kim S.-H.
Published: January 2008

We investigated the time-dependent polarization switching behaviors of (111)-preferred polycrystalline Pb(ZrxTi1−x)O3 thin films with various Zr concentrations. We could explain all the polarization switching behaviors well by assuming Lorentzian distributions in the logarithmic polarization switching time [refer to J. Y. Jo et al., Phys. Rev. Lett. 99, 267602 (2007)]. Based on this analysis, we found that the Zr ion substitution for Ti ions would induce broad distributions in the local field due to defect dipoles, which makes the ferroelectric domain switching occur more easily.
Role of radial nonuniformities in the interaction of an intense laser with atomic clusters
Authors: Holkundkar Amol R. , Gupta N. K.
Published: January 2008

A model for the interaction of an intense laser with atomic clusters is presented. The model takes into account the spatial nonuniformities of the cluster as it evolves in time. The cluster is treated as a stratified sphere having an arbitrary number of layers. Electric and magnetic fields are obtained by solving the vector Helmholtz equation coupled with one-dimensional Lagrangian hydrodynamics. Results are compared with the uniform density nanoplasma model. Enhancement in the amount of energy absorbed is seen over the uniform density model. In some cases the absorbed energy increases by as much as a factor of 40.
Systematic investigation of localized surface plasmon resonance of long-range ordered Au nanodisk arrays
Authors: Zheng Yue Bing , Juluri Bala Krishna , Mao Xiaole , Walker Thomas R. , Huang Tony Jun
Published: January 2008

Ordered Au nanodisk arrays were fabricated on glass substrates using nanosphere lithography combined with a two-step reactive ion etching technique. The optical properties of these arrays were investigated both experimentally and theoretically. Specifically, the effects of disk diameter on localized surface plasmon resonance (LSPR) were characterized and compared with results from discrete dipole approximation (DDA) calculations. The effects of glass substrate, Cr interfacial layer, and Au thickness on LSPR were investigated computationally. Furthermore, thermal treatment was found to be essential in improving the nanodisk arrays’ LSPR properties. Using atomic force microscopy and DDA calculations, it was established that the improvements in LSPR properties were due to thermally induced morphologic changes. Finally, microfluidic channels were integrated with the annealed disk arrays to study the sensitivity of LSPR to the change in surroundings’ refractive index. The dependence of LSPR on surroundings’ refractive index was measured and compared with calculated results.
Enhanced dielectric properties in single crystal-like BiFeO3 thin films grown by flux-mediated epitaxy
Authors: Lim S.-H. , Murakami M. , Yang J. H. , Young S.-Y. , Hattrick-Simpers J. , Wuttig M. , Salamanca-Riba L. G. , Takeuchi I.
Published: January 2008

We have fabricated single crystal-like BiFeO3 (BFO) thin films by flux-mediated epitaxy using pulsed laser deposition (PLD). The Bi–Cu–O flux composition and its thickness were optimized using composition spread, thickness gradient, and temperature gradient libraries. The optimized BFO thin films grown with this technique showed larger grain size of ∼2μm and higher dielectric constant in the range of 260–340 than those for standard PLD grown films. In addition, the leakage current density of the films was reduced by two orders of magnitude compared to that of standard PLD grown films.
Femtosecond laser heat affected zones profiled in Co∕Si multilayer thin films
Authors: Picard Yoosuf N. , Yalisove Steven M.
Published: January 2008

In this letter, we describe an approach for assessing collateral thermal damage resulting from high intensity, femtosecond laser irradiation. Polycrystalline Co thin films deposited on Si (100) substrates and buried under an amorphous Si film were prepared for plan-view transmission electron microscopy (TEM) prior to laser irradiation by femtosecond laser pulses. A heat affected zone (HAZ) resulting from single pulse irradiation at a fluence of 0.9J∕cm2 was determined by TEM imaging and point-wise selected area diffraction. The spatially Gaussian laser pulse generated a HAZ extending up to 3μm radially from the femtosecond laser irradiated region.
Optical properties of InP nanowires on Si substrates with varied synthesis parameters
Authors: Chuang Linus C. , Moewe Michael , Crankshaw Shanna , Chang-Hasnain Connie
Published: January 2008

We report the effect of synthesis parameters on the physical appearance and optical properties of InP nanowires (NWs) grown on Si substrates by metal-organic chemical vapor deposition. A strong dependence on the group V to III precursor ratio is observed on the NW shape and, consequently, its photoluminescence (PL). Narrow, uniform-diameter NWs are achieved with an optimized V/III ratio. The uniform NWs exhibit PL widths as low as 1.4meV. Their peak wavelength does not vary much with excitation, which is important for NW lasers on Si. These characteristics are attributed to the one-dimensional density of states in uniform-diameter NWs.
The Devil's Staircase
Authors: Bak Per
Published: January 2008

In the 17th century the Dutch physicist Christian Huyghens observed that two clocks hanging back to back on the wall tend to synchronize their motion. This phenomenon is known as phase locking, frequency locking or resonance, and is generally present in dynamical systems with two competing frequencies. The two frequencies may arise dynamically within the system, as with Huyghens's coupled clocks, or through the coupling of an oscillator to an external periodic force, as with the swing and attendant shown in figure 1. If some parameter is varied—the length of a pendulum or the frequency of the force that drives it, for instance—the system will pass through regimes that are phase locked and regimes that are not. When systems are phase locked the ratio between their frequencies is a rational number. For weak coupling the phase-locked intervals are narrow, so that even if there is an infinity of intervals, the motion is quasiperiodic for most driving frequencies; that is, the ratio between the two frequencies is more likely to be irrational. When the coupling increases, the phase-locked portions increase, and it becomes less likely that the motion is quasiperiodic. This is a unique situation, where it makes sense, despite experimental uncertainty, to ask whether a physical quantity is rational or irrational.
Sustainability and Scale: US Milk-Market Orders as Relocalization Policy
Authors: DuPuis E Melanie , Block Daniel
Published: January 2008

There has been a recent wave of political and theoretical interest in localism and relocalization as a political strategy in resistance to the hegemonic power of globalization. Some geographers and other observers of spatial politics have been skeptical of these efforts, questioning the effectiveness and the effects of relocalization movements. In response, DuPuis and Goodman have argued for a ‘reflexive localism’ that takes a more pragmatic approach, understanding the ways in which this form of politics can or cannot provide a powerful alternative to globalization. Building on current realist studies, this analysis seeks to build a more reflexive framework with which to understand the politics of localism. To do this the study draws upon the perspectives of political ecology and the politics of scale and uses a comparative historical methodology to look at one of the most effective forms of localized governance in US agriculture: the milk-market-order system. The analysis shows that market orders created economic enclaves that enabled particular agroecological practices, or ‘farming styles’. Market orders functioned as mesolevel institutions that both territorially fixed local agroecologies and mediated with institutions at other spatial scales, a process in which ‘local’, ‘state’, and ‘national’ were coproduced.
Nogo receptor antagonizes p75NTR-dependent motor neuron death
Authors: Dupuis Luc , Pehar Mariana , Cassina Patricia , Rene Frédérique , Castellanos Raquel , Rouaux Caroline , Gandelman Mandi , Dimou Leda , Schwab Martin E. , Loeffler Jean-Philippe , Barbeito Luis , Gonzalez de Aguilar Jose-Luis
Published: January 2008

The Nogo-66 receptor (NgR) plays a critical role in restricting axon regeneration in the central nervous system. This inhibitory action is in part mediated by a neuronal receptor complex containing p75NTR, a multifunctional receptor also well known to trigger cell death upon binding to neurotrophins such as NGF. In the present study, we show that Pep4 and NEP1–40, which are two peptides derived from the Nogo-66 sequence that modulate NgR-mediated neurite outgrowth inhibition, prevent NGF-stimulated p75NTR-dependent death of cultured embryonic motor neurons. They also confer protection on spinal cord motor neurons after neonatal sciatic nerve axotomy. These findings demonstrate an as-yet-unknown function of NgR in maintaining neuronal survival that may be relevant for motor neuron development and degeneration.
Temperature dependence of the two-dimensional infrared spectrum of liquid H2O
Authors: Kraemer D. , Cowan M. L. , Paarmann A. , Huse N. , Nibbering E. T. J. , Elsaesser T. , Miller R. J. Dwayne
Published: January 2008

Two-dimensional infrared photon-echo measurements of the OH stretching vibration in liquid H2O are performed at various temperatures. Spectral diffusion and resonant energy transfer occur on a time scale much shorter than the average hydrogen bond lifetime of ≈1 ps. Room temperature measurements show a loss of frequency and, thus, structural correlations on a 50-fs time scale. Weakly hydrogen-bonded OH stretching oscillators absorbing at high frequencies undergo slower spectral diffusion than strongly bonded oscillators. In the temperature range from 340 to 274 K, the loss in memory slows down with decreasing temperature. At 274 K, frequency correlations in the OH stretch vibration persist beyond ≈200 fs, pointing to a reduction in dephasing by librational excitations. Polarization-resolved pump-probe studies give a resonant intermolecular energy transfer time of 80 fs, which is unaffected by temperature. At low temperature, structural correlations persist longer than the energy transfer time, suggesting a delocalization of OH stretching excitations over several water molecules.
A safeguard eliminates T cell receptor gene-modified autoreactive T cells after adoptive transfer
Authors: Kieback Elisa , Charo Jehad , Sommermeyer Daniel , Blankenstein Thomas , Uckert Wolfgang
Published: January 2008

By transfer of T cell receptor (TCR) genes, antigen specificity of T cells can be redirected to target any antigen. Adoptive transfer of TCR-redirected T cells into patients has shown promising results. However, this immunotherapy bears the risk of autoreactive side effects if the TCR recognizes antigens on self-tissue. Here, we introduce a safeguard based on a TCR-intrinsic depletion mechanism to eliminate autoreactive TCR-redirected T cells
in vivo
. By the introduction of a 10-aa tag of the human c-myc protein into murine (OT-I, P14) and human (gp100) TCR sequences, we were able to deplete T cells that were transduced with these myc-tagged TCRs with a tag-specific antibody
in vitro
. T cells transduced with the modified TCR maintained equal properties compared with cells transduced with the wild-type receptor concerning antigen binding and effector function. More importantly, therapeutic
in vivo
depletion of adoptively transferred T cells rescued mice showing severe signs of autoimmune insulitis from lethal diabetes. This safeguard allows termination of adoptive therapy in case of severe side effects.
Developmental switch of intestinal antimicrobial peptide expression
Authors: Ménard Sandrine , Förster Valentina , Lotz Michael , Gütle Dominique , Duerr Claudia U. , Gallo Richard L. , Henriques-Normark Birgitta , Pütsep Katrin , Andersson Mats , Glocker Erik O. , Hornef Mathias W.
Published: January 2008

Paneth cell–derived enteric antimicrobial peptides provide protection from intestinal infection and maintenance of enteric homeostasis. Paneth cells, however, evolve only after the neonatal period, and the antimicrobial mechanisms that protect the newborn intestine are ill defined. Using quantitative reverse transcription–polymerase chain reaction, immunohistology, reverse-phase high-performance liquid chromatography, and mass spectrometry, we analyzed the antimicrobial repertoire in intestinal epithelial cells during postnatal development. Surprisingly, constitutive expression of the cathelin-related antimicrobial peptide (CRAMP) was observed, and the processed, antimicrobially active form was identified in neonatal epithelium. Peptide synthesis was limited to the first two weeks after birth and gradually disappeared with the onset of increased stem cell proliferation and epithelial cell migration along the crypt–villus axis. CRAMP conferred significant protection from intestinal bacterial growth of the newborn enteric pathogen Listeria monocytogenes. Thus, we describe the first example of a complete developmental switch in innate immune effector expression and anatomical distribution. Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period.
Molecular mechanisms linking wound inflammation and fibrosis: knockdown of osteopontin leads to rapid repair and reduced scarring
Authors: Mori Ryoichi , Shaw Tanya J. , Martin Paul
Published: January 2008

Previous studies of tissue repair have revealed osteopontin (OPN) to be up-regulated in association with the wound inflammatory response. We hypothesize that OPN may contribute to inflammation-associated fibrosis. In a series of in vitro and in vivo studies, we analyze the effects of blocking OPN expression at the wound, and determine which inflammatory cells, and which paracrine factors from these cells, may be responsible for triggering OPN expression in wound fibroblasts. Delivery of OPN antisense oligodeoxynucleotides into mouse skin wounds by release from Pluronic gel decreases OPN protein levels at the wound and results in accelerated healing and reduced granulation tissue formation and scarring. To identify which leukocytic lineages may be responsible for OPN expression, we cultured fibroblasts in macrophage-, neutrophil-, or mast cell–conditioned media (CM), and found that macrophage- and mast cell–secreted factors, specifically platelet-derived growth factor (PDGF), induced fibroblast OPN expression. Correspondingly, Gleevec, which blocks PDGF receptor signaling, and PDGF-Rβ–neutralizing antibodies, inhibited OPN induction by macrophage-CM. These studies indicate that inflammation-triggered expression of OPN both hinders the rate of repair and contributes to wound fibrosis. Thus, OPN and PDGF are potential targets for therapeutic modulation of skin repair to improve healing rate and quality.
Medical Honey for Wound Care—Still the ‘Latest Resort’?
Authors: Simon Arne , Traynor Kirsten , Santos Kai , Blaser Gisela , Bode Udo , Molan Peter
Published: January 2008

While the ancient Egyptians and Greeks used honey for wound care, and a broad spectrum of wounds are treated all over the world with natural unprocessed honeys from different sources, Medihoney™ has been one of the first medically certified honeys licensed as a medical product for professional wound care in Europe and Australia. Our experience with medical honey in wound care refers only to this product. In this review, we put our clinical experience into a broader perspective to comment on the use of medical honey in wound care. More prospective randomized studies on a wider range of types of wounds are needed to confirm the safety and efficacy of medical honey in wound care. Nonetheless, the current evidence confirming the antibacterial properties and additional beneficial effects of medical honey on wound healing should encourage other wound care professionals to use CE‐certified honey dressings with standardized antibacterial activity, such as Medihoney™ products, as an alternative treatment approach in wounds of different natures.
Two-Component Signal Transduction Systems of Xanthomonas spp.: A Lesson from Genomics
Authors: Qian Wei , Han Zhong-Ji , He Chaozu
Published: January 2008

The two-component signal transduction systems (TCSTSs), consisting of a histidine kinase sensor (HK) and a response regulator (RR), are the dominant molecular mechanisms by which prokaryotes sense and respond to environmental stimuli. Genomes of Xanthomonas generally contain a large repertoire of TCSTS genes (approximately 92 to 121 for each genome), which encode diverse structural groups of HKs and RRs. Among them, although a core set of 70 TCSTS genes (about two-thirds in total) which accumulates point mutations with a slow rate are shared by these genomes, the other genes, especially hybrid HKs, experienced extensive genetic recombination, including genomic rearrangement, gene duplication, addition or deletion, and fusion or fission. The recombinations potentially promote the efficiency and complexity of TCSTSs in regulating gene expression. In addition, our analysis suggests that a co-evolutionary model, rather than a selfish operon model, is the major mechanism for the maintenance and microevolution of TCSTS genes in the genomes of Xanthomonas. Genomic annotation, secondary protein structure prediction, and comparative genomic analyses of TCSTS genes reviewed here provide insights into our understanding of signal networks in these important phytopathogenic bacteria.
RIVET—A Tool for In Vivo Analysis of Symbiotically Relevant Gene Expression in Sinorhizobium meliloti
Authors: Gao Mengsheng , Teplitski Max
Published: January 2008

Despite significant advances in the development of sensitive tools for studying genetics and signal exchange in legume–rhizobium symbioses, many uncertainties remain about the in vivo role of bacterial and plant signals in symbiotic gene regulation. In this study, we adapted TnpR recombinase-based in vivo expression technology (RIVET) to document gene regulation in Sinorhizobium meliloti. The substrate for TnpR, the res1-tet-res1 cassette, is stably inherited when cloned into a neutral site of the S. meliloti genome. Bicistronic promoterless tnpR-β-glucuronidase (GUS) reporters were constructed to track expression (“resolution”) of symbiotically relevant S. meliloti genes during different stages of the interaction. In proof of principle experiments, the resolution of the nodC::tnpR reporter was detected within 4 h of exposure to micromolar levels of the nod operon inducer luteolin and after overnight incubation in the rhizosphere. RIVET demonstrated that cell division gene ftsZ2 was not strongly expressed in the rhizosphere but was activated inside the nodules and on agar surfaces. Rhizosphere expression of the N-acyl homoserine lactone (AHL) synthase sinI::tnpR-GUS reporter was modest in prequorate microcolonies, and then increased with time. AHL synthase sinI and an AHL-regulated gene, expG, were activated inside the nodules.
Polymerase Chain Reaction-Based Detection of Spiroplasma citri Associated with Citrus Stubborn Disease
Authors: Yokomi Raymond K. , Mello Alexandre F. S. , Saponari Maria , Fletcher Jacqueline
Published: January 2008

Polymerase chain reaction (PCR)-based detection of citrus stubborn disease was improved using primers based on sequences of the P89 putative adhesin gene and the P58 putative adhesin multigene of Spiroplasma citri. Real-time PCR also was developed with detection limits estimated to be between 10–4 and 10–4 ng by serial dilution of a recombinant S. citri plasmid into DNA extracts from healthy Madam Vinous sweet orange. PCR for the detection of S. citri by these new primers was validated by comparing culturing of the pathogen, the traditional method of diagnosis, with PCR assays from samples taken from two citrus plots in Kern County, CA. Fruit columella was collected from 384 and 377 individual trees in each of two fields, respectively; one portion was used for culturing and the other for DNA extraction and PCR. PCR results matched those of culturing 85 to 100% of the time depending on the primers used. More importantly, PCR detected S. citri from culture-negative trees in 5 to 15% of the cases, suggesting that PCR performed as well or better than culturing for detection of S. citri in field samples. Real-time PCR proved to be the best method for detection. Differential reaction of the samples to the P58 primer pairs suggested that two populations of S. citri occur in historical and present-day field isolates. Citrus stubborn disease incidence was estimated to be 58.3 and 3.7% in the two orchards. The results presented here support the use of PCR for reliable detection of S. citri in field trees.
Baseline Sensitivities for New Postharvest Fungicides Against Penicillium spp. on Citrus and Multiple Resistance Evaluations in P. digitatum
Authors: Kanetis Loukas , Förster Helga , Adaskaveg James E.
Published: January 2008

For the first time in over 25 years, three new fungicides (azoxystrobin, fludioxonil, and pyrimethanil), all belonging to different chemical classes, are being registered for postharvest use against Penicillium decays of citrus fruit in the United States. Baseline sensitivities of Penicillium digitatum and P. italicum were developed using isolates collected before the commercial use of these new fungicides. In a comparison of methods, EC50 values obtained using the spiral gradient dilution method were very similar to those obtained using traditional agar dilutions of fungicides. For azoxystrobin, the addition of salicylhydroxamic acid (SHAM) did not significantly affect EC50 values for mycelial growth of both species. In additional studies on conidial germination of P. digitatum, SHAM significantly reduced EC50 values for azoxystrobin. For pyrimethanil, the mean EC50 value for mycelial growth obtained using a minimum growth medium for anilinopyrimidine fungicides was significantly lower but comparable to values obtained when using potato dextrose agar . For mycelial growth of P. digitatum, mean EC50 values were 0.014, 0.025, and 0.313 μg/ml, whereas for conidial germination, they were 0.074, 0.163, and 1.195 μg/ml for azoxystrobin, fludioxonil, and pyrimethanil, respectively. For P. italicum, mean EC50 values for mycelial growth for fludioxonil and pyrimethanil were 0.005 and 0.040 μg/ml, respectively. For azoxystrobin, the mean EC50 value for mycelial growth for 33 isolates was 0.029 μg/ml. Four isolates had EC50 values ≥0.772 μg/ml and were considered part of a resistant subpopulation. Multiple resistance between the older and new postharvest fungicide classes on citrus was not detected in P. digitatum, and all isolates that were sensitive or resistant to imazalil or thiabendazole were sensitive to the new compounds. This information is important for monitoring populations of P. digitatum, where resistance against the older fungicides has commonly developed.
First Report of Chestnut Ink Disease by Phytophthora katsurae on Chestnut in Korea
Authors: Oh E. , Lee S. H. , Kim K. H. , Lee J. K. , Shin K. C.
Published: January 2008

Since the late 1970s, chestnut (Castanea spp.) has been one of the most commonly cultivated nuts for human consumption in Korea. In 1998, as much as 100,000 t of chestnut seeds were produced from 79,000 ha of plantations for export (2). Most cultivated chestnuts are hybrids of Castanea crenata and C. mollissima that have resulted in 27 cultivars commonly grown in Korea. In 2004, dead trees of two cultivars (Tsukuba and Ginyose) from different locations were found with black ooze emanating from reddish, sunken tissues on the trunks. When the bark was peeled off, a distinct necrotic region was observed on the basal trunk with the discoloration extending up and girdling the trunk. In November 2006, a Phytophthora species was isolated from the necrotic areas with a CARP selective medium (4). Eleven isolates were obtained from three locations: Hadong, Hapcheon, and Youngqwang. The isolates produced numerous homothallic oogonia (34.0 to 46.2 × 21.9 to 26.7 μm) with warty protuberances on the surface. Antheridia were amphigynous with long, funnel-shaped stalks at the base of the oogonia. The formation of papillate, ovoid to obpyriform sporangia (17.0 to 38.9 × 14.6 to 29.2 μm) was induced by cold treatment in filtered (through 25-μm particle retention) creek water or deionized water. Chlamydospores were not observed. Comparison of the rDNA ITS sequence using ITS1/4 (3) showed 99.6% similarity to P. katsurae (GenBank Accession No. AF266771) with three base pair differences. All eleven isolates showed identical ITS sequences. Pathogenicity studies were conducted on excised three 15-cm-long × 5-cm-diameter logs from each of three chestnut cultivars (Moriwase, Parkmi 2, and Ibuki). Bark (5 mm in diameter) was taken with a cork borer on each log followed by inoculation with a 5-mm agar disk of two isolates, PH.K01 and PH.K07. The logs were placed in a moist chamber for 7 days. Noninoculated controls consisted of log sections from each cultivar treated with agar disks. The pathogencity test was repeated three times. The entire log of cv. Parkmi 2 became necrotic, whereas the other two cultivars developed only small lesions (P < 0.0001). The noninoculated control logs of each cultivar did not develop lesions and no pathogen was reisolated from them. This suggests that cultivars differ in susceptibility. P. katsurae (synonym = P. castaneae) was first described from Japan in 1931. P. cambivora, P. cinnamomi, and P. katsurae are commonly responsible for ink disease on chestnut species in Europe, the United States, and Asia (1). The impact of P. katsurae on chestnut production in Korea is currently unknown.

References: (1) A. Boutard et al. The West. Chestnut. 3:6, 2001. (2) S. H. Lee et al. J. Korean For. Soc. 95:61, 2006. (3) E. Oh et al. Forest Pathol. 36:388, 2006. (4) T. J. White et al. Page 315 in: PCR Protocols. Academic Press Inc., New York, 1990.