bluuebunny/crossref_metadata_2025 huggingface dataset:
Tpl2 and ERK transduce antiproliferative T cell receptor signals and inhibit transformation of chronically stimulated T cells
Authors: Tsatsanis Christos , Vaporidi Katerina , Zacharioudaki Vassiliki , Androulidaki Ariadne , Sykulev Yuri , Margioris Andrew N. , Tsichlis Philip N.
Published: February 2008

The protein kinase encoded by theTpl2protooncogene plays an obligatory role in the transduction of Toll-like receptor and death receptor signals in macrophages, B cells, mouse embryo fibroblasts, and epithelial cells in culture and promotes inflammatory responses in animals. To address its role in T cell activation, we crossed the T cell receptor (TCR) transgene 2C, which recognizes class I MHC presented peptides, into the Tpl2−/−genetic background. Surprisingly, the TCR2Ctg/tg/Tpl2−/−mice developed T cell lymphomas with a latency of 4–6 months. The tumor cells were consistently TCR2C+CD8+CD4−, suggesting that they were derived either from chronically stimulated mature T cells or from immature single positive (ISP) cells. Further studies showed that the population of CD8+ISP cells was not expanded in the thymus of TCR2Ctg/tg/Tpl2−/−mice, making the latter hypothesis unlikely. Mature peripheral T cells of Tpl2−/−mice were defective in ERK activation and exhibited enhanced proliferation after TCR stimulation. The same cells were defective in the induction of CTLA4, a negative regulator of the T cell response, which is induced by TCR signals via ERK. These findings suggest that Tpl2 functions normally in a feedback loop that switches off the T cell response to TCR stimulation. As a result, Tpl2, a potent oncogene, functions as a tumor suppressor gene in chronically stimulated T cells.
TRIMCyp expression in Old World primates
Macaca nemestrina
and
Macaca fascicularis
Authors: Brennan Greg , Kozyrev Yury , Hu Shiu-Lok
Published: February 2008

Primates have evolved a variety of restriction factors that prevent retroviral replication. One such factor, TRIM5α, mediates a postentry restriction in many Old World primates. Among New World primates,
Aotus trivirgatus
exerts a similar early restriction mediated by TRIMCyp, a TRIM5–cyclophilin A (CypA) chimera resulting from a
CypA
retrotransposition between exons 7 and 8 of the
TRIM5
gene.
Macaca nemestrina
do not express TRIM5α; therefore, we asked whether these animals and related Old World primates express TRIMCyp. RT-PCR of total RNA from
M. nemestrina
and
Macaca fascicularis
yielded three TRIMCyp amplification products, one of which is predicted to encode a TRIMCyp chimera containing a full-length CypA. Unlike
A. trivirgatus
, genomic sequencing of
M. nemestrina
and
M. fascicularis
identifies a
CypA
retrotransposition in the 3′ untranslated region of the
TRIM5
locus. There is ≈78% homology between the predicted protein sequences of Old World and New World primate TRIMCyp, with most of the differences found in the
TRIM5
-derived sequence. Notably, exon 7 is absent from both
M. nemestrina
and
M. fascicularis
TRIMCyp. Neither
M. nemestrina
nor
M. fascicularis
TRIMCyp could restrict HIV-1 or simian immunodeficiency virus SIVmac in an
in vitro
infectivity assay. The discovery of TRIMCyp in both
M. nemestrina
and
M. fascicularis
indicates that TRIMCyp expression may be more common among Old World primates than previously believed. Convergent evolution of TRIMCyp in both Old World and New World primates suggests that TRIMCyp may have provided evolutionary advantages.
PDC-TREM, a plasmacytoid dendritic cell-specific receptor, is responsible for augmented production of type I interferon
Authors: Watarai Hiroshi , Sekine Etsuko , Inoue Sayo , Nakagawa Ryusuke , Kaisho Tsuneyasu , Taniguchi Masaru
Published: February 2008

Type I interferons (IFNs) derived from plasmacytoid dendritic cells (PDCs) are critical for antiviral responses; however, the mechanisms underlying their production remain unclear. We have identified a receptor, PDC-TREM, which is associated with Plexin-A1 (PlxnA1) on the PDC cell surface and is preferentially expressed after TLR-stimulation. Limited TLR signals induced PDC-TREM expression but failed to induce IFN-α production. However, when coupled with Sema6D, a ligand for Plexin-A1, limited TLR-stimulation resulted in PDC-TREM-mediated DAP12-dependent phosphorylation of phosphoinositide 3-kinase (PI3K) and extracellular regulated kinase (Erk) 1/2 at 6–9 h, and IFN-α was produced. Inhibition of PDC-TREM expression by
pdctrem
-shRNA, blocking of PDC-TREM-binding with PlxnA1 by PDC-TREM mAb, and DAP12 deficiency all resulted in greatly reduced PDC-TREM-dependent activation of signaling molecules and IFN-α production. Thus, PDC-TREM is responsible for IFN-α production, whereas TLR signals are essential for PDC-TREM expression.
Synthesis and structural characterization of isolable phosphine coinage metal π-complexes
Authors: Shapiro Nathan D. , Toste F. Dean
Published: February 2008

The chemical community has recently witnessed a dramatic increase in the application of cationic gold(I)-phosphine complexes as homogeneous catalysts for organic synthesis. The majority of gold(I)-catalyzed reactions rely on nucleophilic additions to carbon–carbon multiple bonds, which have been activated by coordination to a cationic gold(I) catalyst. However, structural evidence for coordination of cationic gold(I) complexes to alkynes has been limited. Here, we report the crystal structure of a gold(I)-phosphine η
2
-coordinated alkyne. Related Ag(I) and Cu(I) complexes have been synthesized for comparison. The crystallization of these complexes was enabled by tethering a labile alkyne ligand to a strongly coordinating triarylphosphine. This approach also proved applicable to crystallization of the first gold(I)-phosphine η
2
-coordinated alkene.
Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus
Authors: Pappas Claudia , Aguilar Patricia V. , Basler Christopher F. , Solórzano Alicia , Zeng Hui , Perrone Lucy A. , Palese Peter , García-Sastre Adolfo , Katz Jacqueline M. , Tumpey Terrence M.
Published: February 2008

The 1918 influenza pandemic was exceptionally severe, resulting in the death of up to 50 million people worldwide. Here, we show which virus genes contributed to the replication and virulence of the 1918 influenza virus. Recombinant viruses, in which genes of the 1918 virus were replaced with genes from a contemporary human H1N1 influenza virus, A/Texas/36/91 (Tx/91), were generated. The exchange of most 1918 influenza virus genes with seasonal influenza H1N1 virus genes did not alter the virulence of the 1918 virus; however, substitution of the hemagglutinin (HA), neuraminidase (NA), or polymerase subunit PB1 genes significantly affected the ability of this virus to cause severe disease in mice. The 1918 virus virulence observed in mice correlated with the ability of 1918 recombinant viruses to replicate efficiently in human airway cells. In a second series of experiments, eight 1918 1:7 recombinants were generated, in which each Tx/91 virus gene was individually replaced by a corresponding gene from 1918 virus. Replication capacity of the individual 1:7 reassortant viruses was assessed in mouse lungs and human airway cells. Increased virus titers were observed among 1:7 viruses containing individual 1918 HA, NA, and PB1 genes. In addition, the 1918 PB1:Tx/91 (1:7) virus showed a distinctly larger plaque size phenotype than the small plaque phenotype of the 1918 PA:Tx/91 and 1918 PB2:Tx/91 1:7 reassortants. These results highlight the importance of the 1918 HA, NA, and PB1 genes for optimal virus replication and virulence of this pandemic strain.
Dual regulation by the Hunchback gradient in the
Drosophila
embryo
Authors: Papatsenko Dmitri , Levine Michael S.
Published: February 2008

The regulation of segmentation gene expression is investigated by computational modeling using quantitative expression data. Previous tissue culture assays and transgene analyses raised the possibility that Hunchback (Hb) might function as both an activator and repressor of transcription. At low concentrations, Hb activates gene expression, whereas at high concentrations it mediates repression. Under the same experimental conditions, transcription factors encoded by other gap genes appear to function as dedicated repressors. Models based on dual regulation suggest that the Hb gradient can be sufficient for establishing the initial
Kruppel
(
Kr
) expression pattern in central regions of the precellular embryo. The subsequent refinement of the
Kr
pattern depends on the combination of Hb and the Giant (Gt) repressor. The dual-regulation models developed for
Kr
also explain some of the properties of the
even-skipped
(
eve
) stripe 3+7 enhancer. Computational simulations suggest that repression results from the dimerization of Hb monomers on the DNA template.
Quantitative biochemical rationale for differences in transmissibility of 1918 pandemic influenza A viruses
Authors: Srinivasan Aravind , Viswanathan Karthik , Raman Rahul , Chandrasekaran Aarthi , Raguram S. , Tumpey Terrence M. , Sasisekharan V. , Sasisekharan Ram
Published: February 2008

The human adaptation of influenza A viruses is critically governed by the binding specificity of the viral surface hemagglutinin (HA) to long (chain length) α2-6 sialylated glycan (α2-6) receptors on the human upper respiratory tissues. A recent study demonstrated that whereas the 1918 H1N1 pandemic virus, A/South Carolina/1/1918 (SC18), with α2-6 binding preference transmitted efficiently, a single amino acid mutation on HA resulted in a mixed α2-3 sialylated glycan (α2-3)/α2-6 binding virus (NY18) that transmitted inefficiently. To define the biochemical basis for the observed differences in virus transmission, in this study, we have developed an approach to quantify the multivalent HA–glycan interactions. Analysis of the molecular HA–glycan contacts showed subtle changes resulting from the single amino acid variations between SC18 and NY18. The effect of these changes on glycan binding is amplified by multivalency, resulting in quantitative differences in their long α2-6 glycan binding affinities. Furthermore, these differences are also reflected in the markedly distinct binding pattern of SC18 and NY18 HA to the physiological glycans present in human upper respiratory tissues. Thus, the dramatic lower binding affinity of NY18 to long α2-6 glycans, as against a mixed α2-3/6 binding, correlates with its inefficient transmission. In summary, this study establishes a quantitative biochemical correlate for influenza A virus transmission.
Dynamics of
Pseudomonas aeruginosa
genome evolution
Authors: Mathee Kalai , Narasimhan Giri , Valdes Camilo , Qiu Xiaoyun , Matewish Jody M. , Koehrsen Michael , Rokas Antonis , Yandava Chandri N. , Engels Reinhard , Zeng Erliang , Olavarietta Raquel , Doud Melissa , Smith Roger S. , Montgomery Philip , White Jared R. , Godfrey Paul A. , Kodira Chinnappa , Birren Bruce , Galagan James E. , Lory Stephen
Published: February 2008

One of the hallmarks of the Gram-negative bacterium
Pseudomonas aeruginosa
is its ability to thrive in diverse environments that includes humans with a variety of debilitating diseases or immune deficiencies. Here we report the complete sequence and comparative analysis of the genomes of two representative
P. aeruginosa
strains isolated from cystic fibrosis (CF) patients whose genetic disorder predisposes them to infections by this pathogen. The comparison of the genomes of the two CF strains with those of other
P. aeruginosa
presents a picture of a mosaic genome, consisting of a conserved core component, interrupted in each strain by combinations of specific blocks of genes. These strain-specific segments of the genome are found in limited chromosomal locations, referred to as regions of genomic plasticity. The ability of
P. aeruginosa
to shape its genomic composition to favor survival in the widest range of environmental reservoirs, with corresponding enhancement of its metabolic capacity is supported by the identification of a genomic island in one of the sequenced CF isolates, encoding enzymes capable of degrading terpenoids produced by trees. This work suggests that niche adaptation is a major evolutionary force influencing the composition of bacterial genomes. Unlike genome reduction seen in host-adapted bacterial pathogens, the genetic capacity of
P. aeruginosa
is determined by the ability of individual strains to acquire or discard genomic segments, giving rise to strains with customized genomic repertoires. Consequently, this organism can survive in a wide range of environmental reservoirs that can serve as sources of the infecting organisms.
p
-Type semiconducting nickel oxide as an efficiency-enhancing anode interfacial layer in polymer bulk-heterojunction solar cells
Authors: Irwin Michael D. , Buchholz D. Bruce , Hains Alexander W. , Chang Robert P. H. , Marks Tobin J.
Published: February 2008

To minimize interfacial power losses, thin (5–80 nm) layers of NiO, a
p
-type oxide semiconductor, are inserted between the active organic layer, poly(3-hexylthiophene) (P3HT) + [6,6]-phenyl-C
61
butyric acid methyl ester (PCBM), and the ITO (tin-doped indium oxide) anode of bulk-heterojunction ITO/P3HT:PCBM/LiF/Al solar cells. The interfacial NiO layer is deposited by pulsed laser deposition directly onto cleaned ITO, and the active layer is subsequently deposited by spin-coating. Insertion of the NiO layer affords cell power conversion efficiencies as high as 5.2% and enhances the fill factor to 69% and the open-circuit voltage (
V
oc
) to 638 mV versus an ITO/P3HT:PCBM/LiF/Al control device. The value of such hole-transporting/electron-blocking interfacial layers is clearly demonstrated and should be applicable to other organic photovoltaics.
HSP90 affects the expression of genetic variation and developmental stability in quantitative traits
Authors: Sangster Todd A. , Salathia Neeraj , Undurraga Soledad , Milo Ron , Schellenberg Kurt , Lindquist Susan , Queitsch Christine
Published: February 2008

Modulation of the activity of the molecular chaperone HSP90 has been extensively discussed as a means to alter phenotype in many traits and organisms. Such changes can be due to the exposure of cryptic genetic variation, which in some instances may also be accomplished by mild environmental alteration. Should such polymorphisms be widespread, natural selection may be more effective at producing phenotypic change in suboptimal environments. However, the frequency and identity of buffered polymorphisms in natural populations are unknown. Here, we employ quantitative genetic dissection of an
Arabidopsis thaliana
developmental response, hypocotyl elongation in the dark, to detail the underpinnings of genetic variation responsive to HSP90 modulation. We demonstrate that HSP90-dependent alleles occur in continuously distributed, environmentally responsive traits and are amenable to quantitative genetic mapping techniques. Furthermore, such alleles are frequent in natural populations and can have significant effects on natural phenotypic variation. We also find that HSP90 modulation has both general and allele-specific effects on developmental stability; that is, developmental stability is a phenotypic trait that can be affected by natural variation. However, effects of revealed variation on trait means outweigh effects of decreased developmental stability, and the HSP90-dependent trait alterations could be acted on by natural selection. Thus, HSP90 may centrally influence canalization, assimilation, and the rapid evolutionary alteration of phenotype through the concealment and exposure of cryptic genetic variation.
HSP90-buffered genetic variation is common in
Arabidopsis thaliana
Authors: Sangster Todd A. , Salathia Neeraj , Lee Hana N. , Watanabe Etsuko , Schellenberg Kurt , Morneau Keith , Wang Hui , Undurraga Soledad , Queitsch Christine , Lindquist Susan
Published: February 2008

HSP90 is a protein chaperone particularly important in the maturation of a diverse set of proteins that regulate key steps in a multitude of biological processes. Alterations in HSP90 function produce altered phenotypes at low penetrance in natural populations. Previous work has shown that at least some of these phenotypes are due to genetic variation that remains phenotypically cryptic until it is revealed by the impairment of HSP90 function. Exposure of such “buffered” genetic polymorphisms can also be accomplished by environmental stress, linking the appearance of new phenotypes to defects in protein homeostasis. Should such polymorphisms be widespread, natural selection may be more effective at producing phenotypic change in suboptimal environments. In evaluating this hypothesis, a key unknown factor is the frequency with which HSP90-buffered polymorphisms occur in natural populations. Here, we present
Arabidopsis thaliana
populations suitable for genetic mapping that have constitutively reduced HSP90 levels. We employ quantitative genetic techniques to examine the HSP90-dependent polymorphisms affecting a host of plastic plant life-history traits. Our results demonstrate that HSP90-dependent natural variation is present at high frequencies in
A. thaliana
, with an expectation that at least one HSP90-dependent polymorphism will affect nearly every quantitative trait in progeny of two different wild lines. Hence, HSP90 is likely to occupy a central position in the translation of genotypic variation into phenotypic differences.
Ca
2+
oscillation frequency decoding in cardiac cell hypertrophy: Role of calcineurin/NFAT as Ca
2+
signal integrators
Authors: Colella Matilde , Grisan Francesca , Robert Valerie , Turner Jay D. , Thomas Andrew P. , Pozzan Tullio
Published: February 2008

The role of Ca
2+
signaling in triggering hypertrophy was investigated in neonatal rat cardiomyocytes
in vitro
. We show that an increase in cell size and sarcomere reorganization were elicited by receptor agonists such as Angiotensin II, aldosterone, and norepinephrine and by a small rise in medium KCl concentration, a treatment devoid of direct effects on receptor functions. All these treatments increased the frequency of spontaneous [Ca
2+
] transients, caused nuclear translocation of transfected NFAT(GFP), and increased the expression of a NFAT-sensitive reporter gene. There was no increase in Ca
2+
spark frequency in the whole cell or in the perinuclear region under these conditions. Hypertrophy and NFAT translocation but not the increased frequency of [Ca
2+
] transients were inhibited by the calcineurin inhibitor cyclosporine A. Hypertrophy by the different stimuli was insensitive to inhibition of myofilament contraction. We concluded that calcineurin–NFAT can act as integrators of the contractile Ca
2+
signal, and that they can decode alterations in the frequency even of rapid Ca
2+
oscillations.
Protein area occupancy at the center of the red blood cell membrane
Authors: Dupuy Allison D. , Engelman Donald M.
Published: February 2008

In the Fluid Mosaic Model for biological membrane structure, proposed by Singer and Nicolson in 1972, the lipid bilayer is represented as a neutral two-dimensional solvent in which the proteins of the membrane are dispersed and distributed randomly. The model portrays the membrane as dominated by a membrane lipid bilayer, directly exposed to the aqueous environment, and only occasionally interrupted by transmembrane proteins. This view is reproduced in virtually every textbook in biochemistry and cell biology, yet some critical features have yet to be closely examined, including the key parameter of the relative occupancy of protein and lipid at the center of a natural membrane. Here we show that the area occupied by protein and lipid at the center of the human red blood cell (RBC) plasma membrane is at least ≈23% protein and less than ≈77% lipid. This measurement is in close agreement with previous estimates for the RBC plasma membrane and the recently published measurements for the synaptic vesicle. Given that transmembrane proteins are surrounded by phospholipids that are perturbed by their presence, the occupancy by protein of more than ≈20% of the RBC plasma membrane and the synaptic vesicle plasma membrane implies that natural membrane bilayers may be more rigid and less fluid than has been thought for the past several decades, and that studies of pure lipid bilayers do not fully reveal the properties of lipids in membranes. Thus, it appears to be the case that membranes may be more mosaic than fluid, with little unperturbed phospholipid bilayer.
Synapse elimination accompanies functional plasticity in hippocampal neurons
Authors: Bastrikova Natalia , Gardner Gregory A. , Reece Jeff M. , Jeromin Andreas , Dudek Serena M.
Published: February 2008

A critical component of nervous system development is synapse elimination during early postnatal life, a process known to depend on neuronal activity. Changes in synaptic strength in the form of long-term potentiation (LTP) and long-term depression (LTD) correlate with dendritic spine enlargement or shrinkage, respectively, but whether LTD can lead to an actual separation of the synaptic structures when the spine shrinks or is lost remains unknown. Here, we addressed this issue by using concurrent imaging and electrophysiological recording of live synapses. Slices of rat hippocampus were cultured on multielectrode arrays, and the neurons were labeled with genes encoding red or green fluorescent proteins to visualize presynaptic and postsynaptic neuronal processes, respectively. LTD-inducing stimulation led to a reduction in the synaptic green and red colocalization, and, in many cases, it induced a complete separation of the presynaptic bouton from the dendritic spine. This type of synapse loss was associated with smaller initial spine size and greater synaptic depression but not spine shrinkage during LTD. All cases of synapse separation were observed without an accompanying loss of the spine during this period. We suggest that repeated low-frequency stimulation simultaneous with LTD induction is capable of restructuring synaptic contacts. Future work with this model will be able to provide critical insight into the molecular mechanisms of activity- and experience-dependent refinement of brain circuitry during development.
Cell Cycle-dependent Binding of HMGN Proteins to Chromatin
Authors: Cherukuri Srujana , Hock Robert , Ueda Tetsuya , Catez Frédéric , Rochman Mark , Bustin Michael
Published: February 2008

Throughout the cell cycle, the histones remain associated with DNA, but the repertoire of proteins associated with the chromatin fiber continuously changes. The chromatin interaction of HMGNs, a family of nucleosome binding proteins that modulates the structure and activity of chromatin, during the cell cycle is controversial. Immunofluorescence studies demonstrated that HMGNs are not associated with chromatin, whereas live cell imaging indicated that they are present in mitotic chromosomes.

To resolve this controversy, we examined the organization of wild-type and mutated HMGN1 and HMGN2 proteins in the cell nucleus by using immunofluorescence studies, live cell imaging, gel mobility shift assays, and bimolecular fluorescence complementation (BiFC). We find that during interphase, HMGNs bind specifically to nucleosomes and form homodimeric complexes that yield distinct BiFC signals. In metaphase, the nucleosomal binding domain of the protein is inactivated, and the proteins associate with chromatin with low affinity as monomers, and they do not form specific complexes. Our studies demonstrate that the mode of binding of HMGNs to chromatin is cell cycle dependent.
Localized RanGTP Accumulation Promotes Microtubule Nucleation at Kinetochores in Somatic Mammalian Cells
Authors: Torosantucci Liliana , De Luca Maria , Guarguaglini Giulia , Lavia Patrizia , Degrassi Francesca
Published: February 2008

Centrosomes are the major sites for microtubule nucleation in mammalian cells, although both chromatin- and kinetochore-mediated microtubule nucleation have been observed during spindle assembly. As yet, it is still unclear whether these pathways are coregulated, and the molecular requirements for microtubule nucleation at kinetochore are not fully understood. This work demonstrates that kinetochores are initial sites for microtubule nucleation during spindle reassembly after nocodazole. This process requires local RanGTP accumulation concomitant with delocalization from kinetochores of the hydrolysis factor RanGAP1. Kinetochore-driven microtubule nucleation is also activated after cold-induced microtubule disassembly when centrosome nucleation is impaired, e.g., after Polo-like kinase 1 depletion, indicating that dominant centrosome activity normally masks the kinetochore-driven pathway. In cells with unperturbed centrosome nucleation, defective RanGAP1 recruitment at kinetochores after treatment with the Crm1 inhibitor leptomycin B activates kinetochore microtubule nucleation after cold. Finally, nascent microtubules associate with the RanGTP-regulated microtubule-stabilizing protein HURP in both cold- and nocodazole-treated cells. These data support a model for spindle assembly in which RanGTP-dependent abundance of nucleation/stabilization factors at centrosomes and kinetochores orchestrates the contribution of the two spindle assembly pathways in mammalian cells. The complex of RanGTP, the export receptor Crm1, and nuclear export signal-bearing proteins regulates microtubule nucleation at kinetochores.
Covalent attachment of functional protein to polymer surfaces: a novel one-step dry process
Authors: MacDonald Christopher , Morrow Richard , Weiss Anthony S , Bilek Marcela M.M
Published: February 2008

The attachment of bioactive protein to surfaces underpins the development of biosensors and diagnostic microarrays. We present a surface treatment using plasma immersion ion implantation (PIII) to create stable covalent binding sites for the attachment of functional soya-bean peroxidase (SBP). Fourier transform infrared spectra of the surfaces show that protein is retained on the surface after boiling in sodium dodecyl sulphate and sodium hydroxide, which is indicative of covalent attachment. The activity of SBP on the treated surfaces remains high in comparison with SBP attached to control surfaces over the course of 11 days. Surface plasmon resonance was used to show that the surface coverage of the attached protein is close to a monolayer. We describe the potential of the PIII treatment method to be used as a one-step dry process to create surfaces for large-scale protein micro- or nanopatterning.
Justification for wavefront propagation in a tumour growth model with contact inhibition
Authors: Zhu Huiyan , Yuan Wei , Ou Chunhua
Published: February 2008

Cancer is a disease characterized by abnormal division of cells combined with the malignant behaviour of these cells. Malignant cancer cells tend to spread, either by direct growth into adjacent tissue through invasion and dispersal or by implantation into distant sites by metastasis. In this paper, we will concentrate on the first type of tumour growth and consider a reaction–diffusion model for competition cells with
nonlinear diffusion term
modelling contact inhibition between normal and tumour cell populations for which wave propagation is usually observed in clinical data. Mathematically, based on a combination of perturbation methods, the Fredholm theory and the Banach fixed point theorem, we theoretically justify the existence of the travelling wave solution. Numerical simulations are finally illustrated to confirm our rigorous results.
The coefficient of restitution for the idealized impact of a spherical, nano-scale particle on a rigid plane
Authors: Weir Graham , McGavin Peter
Published: February 2008

The theory of low velocity impact between nano-sized, spherical particles and a rigid plane is developed by assuming fully plastic failure during approach and assuming the Johnson–Kandall–Roberts model of elasticity and adhesion applied during particle recoil. This model predicts initial particle acceleration on approach, followed by either deceleration and eventually instantaneous cessation of particle motion or extreme deformation and possible structural failure of the particle. If the approach motion ceases and the recoil begins, then either the particle is trapped on the surface or it separates. The typical frequency of oscillations of trapped particles is derived. Criteria for the occurrence of the various regimes are derived, together with conditions for when surface adhesion is important.
Micromechanics of friction: effects of nanometre-scale roughness
Authors: Li Qunyang , Kim Kyung-Suk
Published: February 2008

Nanometre-scale roughness on a solid surface has significant effects on friction, since intersurface forces operate predominantly within a nanometre-scale gap distance in frictional contact. To study the effects of nanometre-scale roughness, two novel atomic force microscope friction experiments were conducted, each using a gold surface sliding against a flat mica surface as the representative friction system. In one of the experiments, a pillar-shaped single nano-asperity of gold was used to measure the molecular-level frictional behaviour. The adhesive friction stress was measured to be 264 MPa and the molecular friction factor 0.0108 for a direct gold–mica contact. The nano-asperity was flattened in contact, although its hardness at this length scale is estimated to be 3.68 GPa. It was found that such a high pressure could be reached with the help of condensed water capillary forces. In the second experiment, a micrometre-scale asperity with nanometre-scale roughness exhibited a single-asperity-like response of friction. However, the apparent frictional stress, 40.5 MPa, fell well below the Hurtado–Kim model prediction of 208–245 MPa. In addition, the multiple nano-asperities were flattened during the frictional process, exhibiting load- and slip-history-dependent frictional behaviour.
A new large-number coincidence and a scaling law for the cosmological constant
Authors: Funkhouser Scott
Published: February 2008

An ensemble of pure numbers of the order of 10
122
is produced naturally from the fundamental parameters of modern cosmology. This new large-number coincidence problem is resolved by demonstrating implicit physical connections that follow from the standard cosmological model. However, the occurrence of the new large-number coincidence combined with the known coincidence among pure numbers of the order of 10
40
poses a distinct problem that is resolved with a scaling law for the cosmological constant that was originally proposed by Zel'dovich.
Colour pattern specification in the Mocker swallowtail
Papilio dardanus
: the transcription factor
invected
is a candidate for the mimicry locus
H
Authors: Clark Rebecca , Brown Sarah M , Collins Steve C , Jiggins Chris D , Heckel David G , Vogler Alfried P
Published: February 2008

The swallowtail butterfly,
Papilio dardanus
, is an iconic example of a polymorphic Batesian mimic. The expression of various female-limited colour forms is thought to be controlled by a single autosomal locus, termed
H
, whose function in determining the wing pattern remains elusive. As a step towards the physical mapping of
H
, we established a set of 272 polymorphic amplified fragment length polymorphism (AFLP) markers (
Eco
RI-
Mse
I). Segregation patterns in a ‘female-informative’ brood (exploiting the absence of crossing over in female Lepidoptera) mapped these AFLPs to 30 linkage groups (putative chromosomes). The difference between the
hippocoon
and
cenea
female forms segregating in this family resides on a single one of these linkage groups, defined by 14 AFLPs. In a ‘male-informative’ cross (markers segregating
within
a linkage group), a pair of AFLPs co-segregated closely with the two female forms, except in four recombinants out of 19 female offspring. Linkage with these AFLP markers using four further female-informative families demonstrated that the genetic factor determining other morphs (
poultoni
,
lamborni
and
trimeni
) also maps to this same linkage group. The candidate gene
invected
, obtained in a screen for co-segregation of developmental genes with the colour forms, resides in a 13.9 cM interval flanked by the two AFLP markers. In the male-informative family
invected
co-segregated perfectly with the
hippocoon
/
cenea
factor, despite the four crossovers with the AFLPs. These findings make
invected
, and possibly its closely linked paralogue
engrailed
, strong candidates for
H
. This is supported by their known role in eyespot specification in nymphalid butterfly wings.
Once a Batesian mimic, not always a Batesian mimic: mimic reverts back to ancestral phenotype when the model is absent
Authors: Prudic Kathleen L , Oliver Jeffrey C
Published: February 2008

Batesian mimics gain protection from predation through the evolution of physical similarities to a model species that possesses anti-predator defences. This protection should not be effective in the absence of the model since the predator does not identify the mimic as potentially dangerous and both the model and the mimic are highly conspicuous. Thus, Batesian mimics should probably encounter strong predation pressure outside the geographical range of the model species. There are several documented examples of Batesian mimics occurring in locations without their models, but the evolutionary responses remain largely unidentified. A mimetic species has four alternative evolutionary responses to the loss of model presence. If predation is weak, it could maintain its mimetic signal. If predation is intense, it is widely presumed the mimic will go extinct. However, the mimic could also evolve a new colour pattern to mimic another model species or it could revert back to its ancestral, less conspicuous phenotype. We used molecular phylogenetic approaches to reconstruct and test the evolution of mimicry in the North American admiral butterflies (Limenitis: Nymphalidae). We confirmed that the more cryptic white-banded form is the ancestral phenotype of North American admiral butterflies. However, one species,Limenitis arthemis, evolved the black pipevine swallowtail mimetic form but later reverted to the white-banded more cryptic ancestral form. This character reversion is strongly correlated with the geographical absence of the model species and its host plant, but not the host plant distribution ofL. arthemis. Our results support the prediction that a Batesian mimic does not persist in locations without its model, but it does not go extinct either. The mimic can revert back to its ancestral, less conspicuous form and persist.
The early evolution of feathers: fossil evidence from Cretaceous amber of France
Authors: Perrichot Vincent , Marion Loïc , Néraudeau Didier , Vullo Romain , Tafforeau Paul
Published: February 2008

The developmental stages of feathers are of major importance in the evolution of body covering and the origin of avian flight. Until now, there were significant gaps in knowledge of early morphologies in theoretical stages of feathers as well as in palaeontological material. Here we report fossil evidence of an intermediate and critical stage in the incremental evolution of feathers which has been predicted by developmental theories but hitherto undocumented by evidence from both the recent and the fossil records. Seven feathers have been found in an Early Cretaceous (Late Albian,
ca
100 Myr) amber of western France, which display a flattened shaft composed by the still distinct and incompletely fused bases of the barbs forming two irregular vanes. Considering their remarkably primitive features, and since recent discoveries have yielded feathers of modern type in some derived theropod dinosaurs, the Albian feathers from France might have been derived either from an early bird or from a non-avian dinosaur.
Self-referent MHC type matching in frog tadpoles
Authors: Villinger Jandouwe , Waldman Bruce
Published: February 2008

Self/non-self recognition mechanisms underlie the development, immunology and social behaviour of virtually all living organisms, from bacteria to humans. Indeed, recognition processes lie at the core of how social cooperation evolved. Much evidence suggests that the major histocompatibility complex (MHC) both facilitates nepotistic interactions and promotes inbreeding avoidance. Social discrimination based on MHC differences has been demonstrated in many vertebrates but whether the labels used in discrimination are directly associated with the MHC, rather than with other genes with which it covaries, has remained problematic. Furthermore, effects of familiarity on natural preferences have not been controlled in most previous studies. Here we show that African clawed frog (Xenopus laevis) tadpoles discriminate among familiar full siblings based on MHC haplotype differences. Subjects (N=261) from four parental crosses preferred siblings with which they shared MHC haplotypes to those with no MHC haplotypes in common. Using only full siblings in experimental tests, we controlled for genetic variation elsewhere in the genome that might influence schooling preferences. As test subjects were equally familiar with stimulus groups, we conclude that tadpole discrimination involves a self-referent genetic recognition mechanism whereby individuals compare their own MHC type with those of conspecifics.
Assessment of the clinical utility of serial β-d-glucan concentrations in patients with persistent neutropenic fever
Authors: Ellis Michael , al-Ramadi Basel , Finkelman Malcolm , Hedstrom Ulla , Kristensen Jorgen , Ali-Zadeh Hussein , Klingspor Lena
Published: February 2008

The performance of the Fungitell assay was investigated in 100 patients with haematological malignancy undergoing chemotherapy who developed antibiotic-unresponsive neutropenic fever (AUNF). Serum β-d-glucan (BG) concentrations were significantly elevated on the first day of AUNF and all subsequent alternate days to day 10 in 38 patients who developed an invasive fungal infection (IFI) compared to 42 patients remaining free of such infections. The mean and median values of BG were 171.9±29.6 and 95.8 pg ml−1, respectively, for patients with IFI and 64.4±17.1 and 32.9 pg ml−1 for patients with only AUNF (P<0.0001). The differences remained significant over the 10 days despite antifungal therapy. The occurrence of ≥2 sequential concentrations of ≥80 pg ml−1 (‘positive’ test) was found to give the best overall option for diagnosis, with an accuracy of 81.3 %, sensitivity of 86.8 %, positive predictive value of 76.7 % and negative predictive value of 86.5 %. Of the patients with an IFI, 78 % developed a positive test at or before the clinical diagnosis was made – this occurred at a mean (range) of 1.25 (−14 to +14) days prior to the IFI diagnosis. By starting sampling of blood from the first day of neutropenia rather than from the first day of AUNF, 50 % of the patients with subsequent IFI would have been identified 5 days earlier. Increasing sampling to daily from alternate-day frequency did not further improve this earlier timing of an IFI diagnosis. A greater proportion of patients with persistent high levels of BG without overt IFI had severe enterocyte damage or mucositis than those with lower levels of BG without IFI (P=0.002). If the results of the initial BG test had been acted on to change antifungal therapy, discontinuation would have been inappropriate in 30 % of patients and would have delayed definitive antifungal therapy. Although the findings for the cohort of patients studied are very useful, there is inter-patient variability in the test's performance. An holistic diagnostic approach is therefore necessary to interpret the test results optimally. Future studies should address this in further detail as well as the impact of empirical antifungal drug use and patient outcome.
Stomatococcus mucilaginosus meningitis in a healthy 2-month-old child
Authors: Rizvi Meher , Fatima Nazish , Shukla Indu , Afzal Kamran
Published: February 2008

Stomatococcus mucilaginosus is a Gram-positive, catalase-variable organism considered part of the normal human oral and upper respiratory tract flora. Although traditionally believed to be an organism of low virulence, Stomatococcus mucilaginosus has been reported to be an opportunistic pathogen in immunocompromised patients. We describe what we believe is the first reported case of Stomatococcus mucilaginosus meningitis in a healthy child. The isolate was multidrug-resistant, susceptible only to vancomycin. The patient was treated successfully with vancomycin after initial trials with amikacin and cefotaxime.
High-level carbapenem resistance in a Citrobacter freundii clinical isolate is due to a combination of KPC-2 production and decreased porin expression
Authors: Zhang Rong , Yang Lijiang , Cai Jia Chang , Zhou Hong Wei , Chen Gong-Xiang
Published: February 2008

An imipenem-resistant isolate of Citrobacter freundii ZJ163 (MIC 256 μg ml−1) isolated from a Chinese hospital was investigated. The C. freundii ZJ163 isolate exhibited high-level resistance to carbapenems, penicillins, cephalosporins, cefoxitin, aztreonam, quinolones and aminoglycosides. Isoelectric focusing (IEF) demonstrated three β-lactamases with pIs of 5.4 (TEM-1), 6.7 (KPC-2) and 7.9 (CTX-M-14). Two different transconjugants (types A and B) were obtained by conjugation studies. The type A transconjugant exhibited reduced susceptibility or resistance to penicillins, cephalosporins and aztreonam, but was susceptible to carbapenems, quinolones and aminoglycosides. The antimicrobial susceptibility patterns of the type B transconjugant were similar to that of type A, except for its significantly reduced carbapenem susceptibility (imipenem MIC 2 μg ml−1). IEF, specific PCRs and DNA sequence analysis indicated that the type A transconjugant produced CTX-M-14 β-lactamase with a pI of 7.9, that the type B transconjugant produced KPC-2 β-lactamase with a pI of 6.7 and that the β-lactamase with a pI of 5.4 was TEM-1. PCR analysis and sequencing confirmed the presence of the ampC gene in the chromosomal DNA from C. freundii ZJ163, although no activity of AmpC β-lactamase was detected by IEF. Urea/SDS-PAGE analysis of outer-membrane proteins revealed that the levels of the 41 and 38 kDa porins were decreased in C. freundii ZJ163. It was concluded that production of KPC-2 combined with decreased expression of porins contributes to high-level resistance to carbapenems in C. freundii ZJ163.
Improving molecular detection of Candida DNA in whole blood: comparison of seven fungal DNA extraction protocols using real-time PCR
Authors: Metwally L. , Fairley D. J. , Coyle P. V. , Hay R. J. , Hedderwick S. , McCloskey B. , O'Neill H. J. , Webb C. H. , Elbaz W. , McMullan R.
Published: February 2008

The limitations of classical diagnostic methods for invasive Candida infections have led to the development of molecular techniques such as real-time PCR to improve diagnosis. However, the detection of low titres of Candida DNA in blood from patients with candidaemia requires the use of extraction methods that efficiently lyse yeast cells and recover small amounts of DNA suitable for amplification. In this study, a Candida-specific real-time PCR assay was used to detect Candida albicans DNA in inoculated whole blood specimens extracted using seven different extraction protocols. The yield and quality of total nucleic acids were estimated using UV absorbance, and specific recovery of C. albicans genomic DNA was estimated quantitatively in comparison with a reference (Qiagen kit/lyticase) method currently in use in our laboratory. The extraction protocols were also compared with respect to sensitivity, cost and time required for completion. The TaqMan PCR assay used to amplify the DNA extracts achieved high levels of specificity, sensitivity and reproducibility. Of the seven extraction protocols evaluated, only the MasterPure yeast DNA extraction reagent kit gave significantly higher total nucleic acid yields than the reference method, although nucleic acid purity was highest using either the reference or YeaStar genomic DNA kit methods. More importantly, the YeaStar method enabled C. albicans DNA to be detected with highest sensitivity over the entire range of copy numbers evaluated, and appears to be an optimal method for extracting Candida DNA from whole blood.
Performance of chromID ESBL, a chromogenic medium for detection of Enterobacteriaceae producing extended-spectrum β-lactamases
Authors: Réglier-Poupet Hélène , Naas Thierry , Carrer Amélie , Cady Anne , Adam Jean-Marie , Fortineau Nicolas , Poyart Claire , Nordmann Patrice
Published: February 2008

The chromogenic agar medium chromID ESBL (bioMérieux) was compared with BLSE agar medium (AES) for selective isolation and presumptive identification of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae from clinical samples. A total of 765 samples (468 rectal swabs, 255 urine samples and 42 pulmonary aspirations) obtained from 547 patients was processed. All bacterial strains isolated on either medium were further characterized using biochemical tests, and ESBL producers were confirmed by synergy testing. Genetic characterization of ESBL genes was determined by PCR. A total of 33 ESBL-producing Enterobacteriaceae strains [Escherichia coli (n=16), Klebsiella pneumoniae (n=8), Enterobacter spp. (n=3), Citrobacter spp. (n=5) and Proteus mirabilis (n=1)] was recovered. The sensitivity after 24 h incubation was 88 % for chromID ESBL and 85 % for BLSE agar. At 48 h, the sensitivity of chromID ESBL increased to 94 % and was higher than that obtained with BLSE agar. The positive predictive value at 24 h for chromID ESBL was 38.7 % [95 % confidence interval (95 % CI) 28.3 –50.2 %)], which was significantly higher than that for BLSE agar [15.4 %, 95 % CI 10.1 –21.5 %]. On both media, false-positive results were mostly due to Pseudomonas aeruginosa and to Enterobacteriaceae overproducing chromosomal cephalosporinase (Enterobacter spp.) or a chromosomal penicillinase (Klebsiella oxytoca). This study showed that chromID ESBL, a ready-to-use chromogenic selective medium, is sensitive and specific for rapid, presumptive identification of ESBL-producing Enterobacteriaceae. Its chromogenic properties and its selectivity are particularly useful in specimens containing resident associated flora.
Age-specific prevalence of diffusely adherent Escherichia coli in Brazilian children with acute diarrhoea
Authors: Spano Liliana C. , Sadovsky Ana Daniela I. , Segui Paula N. , Saick Ketene W. , Kitagawa Sonia M. S. , Pereira Fausto E. L. , Fagundes-Neto Ulysses , Scaletsky Isabel C. A.
Published: February 2008

In a prospective study between February 2003 and June 2004, stool specimens of children less than 2 years of age with diarrhoea (n=218) and without diarrhoea (n=86), living in Vitória, Espírito Santo, Brazil, were examined for the presence of diarrhoeagenic Escherichia coli. E. coli isolates were tested by colony blot hybridization with specific DNA probes designed to detect EPEC, ETEC, EIEC, EAEC, DAEC and EHEC/STEC. Diarrhoeagenic E. coli strains were detected as the sole pathogen in stools of 92 (30.3 %) children, including 72 (33.0 %) with diarrhoea and 20 (23.2 %) without diarrhoea. DAEC was the most frequent pathotype and was found significantly more often from patients (18.3 %) than from controls (8.1 %) (P<0.05), particularly among children more than 1 year of age (P=0.01). Atypical EPEC and EAEC isolates were isolated from both patients (5.5 % and 4.6 %, respectively) and controls (6.9 % and 6.9 %, respectively). ETEC was more frequently isolated from patients (3.2 %) than controls (1.2 %). Typical EPEC (0.9 %) and EIEC (0.4 %) isolates were detected only in children with diarrhoea. In conclusion, our data suggest that DAEC should be considered potential pathogens in the region of Brazil studied.