bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual interface substructure synthesis method for normal mode analysis of super-large molecular complexes at atomic resolution
Authors: Chen Xuehui , Sun Yunxiang , An Xiongbo , Ming Dengming
Published: October 2011

Normal mode analysis of large biomolecular complexes at atomic resolution remains challenging in computational structure biology due to the requirement of large amount of memory space and central processing unit time. In this paper, we present a method called virtual interface substructure synthesis method or VISSM to calculate approximate normal modes of large biomolecular complexes at atomic resolution. VISSM introduces the subunit interfaces as independent substructures that join contacting molecules so as to keep the integrity of the system. Compared with other approximate methods, VISSM delivers atomic modes with no need of a coarse-graining-then-projection procedure. The method was examined for 54 protein-complexes with the conventional all-atom normal mode analysis using CHARMM simulation program and the overlap of the first 100 low-frequency modes is greater than 0.7 for 49 complexes, indicating its accuracy and reliability. We then applied VISSM to the satellite panicum mosaic virus (SPMV, 78 300 atoms) and to F-actin filament structures of up to 39-mer, 228 813 atoms and found that VISSM calculations capture functionally important conformational changes accessible to these structures at atomic resolution. Our results support the idea that the dynamics of a large biomolecular complex might be understood based on the motions of its component subunits and the way in which subunits bind one another.
Coupled microstructural and magnetic transition in Co-doped Ni nano-arrays
Authors: Yang Chao-Yao , Huang Chun-Chao , Tseng Yuan-Chieh , Liu Chien-Min , Chen Chih , Lin Hong-Ji
Published: October 2011

A superparamagnetic (SM) to ferromagnetic (FM) phase transition was investigated in Co-doped (∼6%) electroless plated Ni arrays. The introduction of Co altered the microstructure of the Ni arrays from nanocrystalline to polycrystalline, resulting in a SM→FM transition. This Co-induced magnetic phase transition is similar to that observed after heat treatment of undoped samples [C. M. Liu, Y. C. Tseng, C. Chen, M. C. Hsu, T. Y. Chao, and Y. T. Cheng, Nanotechnology 20, 415703 (2009); C. C. Huang, C. C. Lo, Y. C. Tseng, C. M. Liu, and C. Chen, J. Appl. Phys. 109, 113905 (2011)]. The role of Co dopant was identified electronically using x-ray magnetic spectroscopy, revealing that the transition modified the Ni host’s electronic structure and enhanced its moment by effectively spin-polarizing the Ni 3d conduction band. This was distinctly different than in the heat treatment case, which underwent an electronically independent phase transition. The element-specific magnetic hysteresis of Co and Ni was also probed, which showed that the two elements were magnetically coupled.
Broad band invisibility cloak made of normal dielectric multilayer
Authors: Xu Xiaofei , Feng Yijun , Xiong Shuai , Fan Jinlong , Zhao Jun-Ming , Jiang Tian
Published: October 2011

We present the design, fabrication, and performance test of a quasi three-dimensional carpet cloak made of normal dielectric in the microwave regime. Taking advantage of a simple linear coordinate transformation, we design a carpet cloak with homogeneous anisotropic medium and then practically realize the device with multilayer of alternating normal dielectric slabs based on the effective medium theory. As a proof-of-concept example, we fabricate the carpet cloak with multilayer of FR4 dielectric slabs with air spacing. The performance of the fabricated design is verified through full-wave numerical simulation and measurement of the far-field scattering electromagnetic waves in a microwave anechoic chamber. Experimental results have demonstrated pronounced cloaking effect in a very broad band from 8 GHz to 18 GHz (whole X and Ku band) due to the low loss, non-dispersive feature of the multilayer dielectric structure.
Analytic energy gradients in combined second order Møller-Plesset perturbation theory and conductorlike polarizable continuum model calculation
Authors: Si Dejun , Li Hui
Published: October 2011

The analytic energy gradients in combined second order Møller-Plesset perturbation theory and conductorlike polarizable continuum model calculations are derived and implemented for spin-restricted closed shell (RMP2), Z-averaged spin-restricted open shell (ZAPT2), and spin-unrestricted open shell (UMP2) cases. Using these methods, the geometries of the S0 ground state and the T1 state of three nucleobase pairs (guanine-cytosine, adenine-thymine, and adenine-uracil) in the gas phase and aqueous solution phase are optimized. It is found that in both the gas phase and the aqueous solution phase the hydrogen bonds in the T1 state pairs are weakened by ∼1 kcal/mol as compared to those in the S0 state pairs.
Plastic evanescent microlaser
Authors: Kobayashi Takeyuki , Byrne Nuala
Published: October 2011

Lasing has been demonstrated in a photopumped microcavity via evanescent-wave-coupled gain. A 50 -μm-diameter unclad quartz fiber is coated with a polymer gain layer having a refractive index lower than that of the quartz fiber. Upon pulsed photoexcitaiton, the cylindrical microcavity exhibits whispering-gallery-mode lasing. A spectral analysis shows that the resonance inside the quartz fiber is responsible for the occurrence of lasing in the orange-red region of the spectrum. The proposed scheme allows the cavity resonant modes to achieve optical gain through evanescent-wave coupling. This is a step toward a device structure that facilitates current injection lasing.
Schottky and charge memory effects in InN nanodomains
Authors: Spyropoulos-Antonakakis N. , Sarantopoulou E. , Kollia Z. , Dražic G. , Kobe S.
Published: October 2011

Conductive atomic force microscopy on c-plane of ∼5-20 nm InN nanocrystals grown onto Si/Ta [100] substrates by 157 nm pulsed laser deposition exhibit thermionic Schottky emission between the Pt/Ir tip and the InN nanodomains and charge memory effects identified from the hysteresis loop between forward and reverse I-V curves. The effects are due to inhomogeneous electron distribution on the surface of nanodomains and the electron confinement at the edges of the boundaries that cause local modulation of the charge neutrality and Fermi levels and put an upper limit at the electron affinity of the c-plane.
Transport properties of gallium nitride nanowire metal-oxide-semiconductor transistor
Authors: Yu J.-W. , Li C.-K , Chen C.-Y. , Wu Y.-R. , Chou L.-J. , Peng L.-H.
Published: October 2011

We investigated the transport properties of [112¯0]-gallium nitride (GaN)/gallium oxide (Ga2O3) single nanowire metal-oxide-semiconductor field-effect-transistor grown on (0001) sapphire substrates. With 0.1 μm gate-length and 60 nm wire-size, the device exhibits maximum transconductance of 85 μS, saturation current of 105 μA, and unity current gain bandwidth ft at 95 GHz. From a three-dimensional (3D) diffusion-and-drift model analysis, polarization-induced negative space charge of −3 × 1012 cm−2 at the back interface of GaN/sapphire, positive space charge of 7 × 1012 cm−2 at the inclined semi-polar {11¯01¯} GaN/Ga2O3 interfaces with screening by two-dimensional electron gas to keep charge neutrality were found responsible for the high-speed transport characteristics.
Temperature-dependent energy band gap variation in self-organized InAs quantum dots
Authors: Yeo Inah , Dong Song Jin , Lee Jungil
Published: October 2011

We investigated the temperature-dependent variation of the photoluminescence emission energy of self-organized InAs/GaAs quantum dots (QDs) grown by conventional Stranski-Krastanov (SK) molecular beam epitaxy and migration-enhanced molecular beam epitaxy (MEMBE) and that of MEMBE InAs QDs in a symmetric and an asymmetric In0.2Ga0.8As/GaAs well. The temperature-dependent energy variation of each QD is analyzed in low and high temperature regions, including a sigmoidal behavior of conventional SK quantum dots with the well-known Varshni and semi-empirical Fan models.
Communication: Consistent picture of lateral subdiffusion in lipid bilayers: Molecular dynamics simulation and exact results
Authors: Kneller Gerald R. , Baczynski Krzysztof , Pasenkiewicz-Gierula Marta
Published: October 2011

This communication presents a molecular dynamics simulation study of a bilayer consisting of 128 dioleoyl-sn-glycero-3-phosphocholine molecules, which focusses on the center-of-mass diffusion of the lipid molecules parallel to the membrane plane. The analysis of the simulation results is performed within the framework of the generalized Langevin equation and leads to a consistent picture of subdiffusion. The mean square displacement of the lipid molecules evolves as ∝ tα, with α between 0.5 and 0.6, and the fractional diffusion coefficient is close to the experimental value for a similar system obtained by fluorescence correlation spectroscopy. We show that the long-time tails of the lateral velocity autocorrelation function and the associated memory function agree well with exact results which have been recently derived by asymptotic analysis [G. Kneller, J. Chem. Phys. 134, 224106 (2011)10.1063/1.3598483]. In this context, we define characteristic time scales for these two quantities.
Feeding-preference trials confirm unexpected stable isotope analysis results: freshwater macroinvertebrates do consume macrophytes
Authors: Watson Anne , Barmuta Leon A.
Published: October 2011

The loss of connectivity in intermittent streams can limit aquatic-invertebrate access to food resources, with different resources available in individual pools. Although leaf litter was abundant in the Macquarie River in Tasmania, stable carbon and nitrogen isotope analyses suggested that aquatic macrophytes were more prevalent in shredding macroinvertebrate diets. We tested this result with two multi-choice trials, which examined the feeding preferences of Atalophlebia albiterminata (Ephemeroptera) and the case-building trichopterans Lectrides varians, Notalina bifaria, Triplectides similis and T. ciuskus ciuskus. We first tested preferences for the dominant benthic leaf species (Acacia mucronata, Eucalyptus amygdalina, E. barberi, E. obliqua and E. viminalis). We hypothesised that macroinvertebrates would preferentially select leaves with lower chemical concentrations. However, there were no strong preferences for conditioned leaves by any invertebrate, although the leaves varied in toughness, tannin, nitrogen and allelochemical content. Second, we examined the preferences for E. amygdalina and E. barberi leaves or the fresh macrophytes Triglochin procerum, Myriophyllum salsugineum and Potamogeton tricarinatus. Macrophytes were preferred over leaves by all invertebrates, with T. procerum significantly preferred over the other macrophytes. This suggests that macrophytes may be undervalued in riverine food webs, and should be included in analyses of food webs using stable isotopes.
Continuous recruitment underpins fish persistence in the arid rivers of far-western Queensland, Australia
Authors: Kerezsy Adam , Balcombe Stephen R. , Arthington Angela H. , Bunn Stuart E.
Published: October 2011

Fish living in highly variable and unpredictable environments need to possess life-history strategies that enable them to survive environmental extremes such as floods and drought. We used the length–frequency distributions of multiple fish species in multiple seasons and highly variable hydrological conditions to infer antecedent breeding behaviour in rivers of far-western Queensland, Australia. Hypotheses tested were as follows: (1) recruitment of some or all species of fish would occur within waterholes during no-flow periods; (2) there would be seasonal recruitment responses in some fish species; (3) recruitment of some species would be enhanced by channel flows and/or flooding. Hydrology and the incidence of flooding were highly variable across the study area during 2006–2008. Flood-influenced recruitment was evident for Hyrtl's tandan, Barcoo grunter and Welch's grunter. Silver tandan, golden goby, Cooper Creek catfish and Australian smelt showed evidence of seasonal recruitment unrelated to antecedent hydrology. However, most species demonstrated continual recruitment in isolated waterholes, irrespective of antecedent flow conditions and season. Continual and seasonal recruitment capabilities have obvious advantages over flood-pulse recruitment in rivers with highly unpredictable flood regimes and underpin the persistence of many fish species in arid and semiarid rivers.
Analysis of mitochondrial DNA clarifies the taxonomy and distribution of the Australian snubfin dolphin (Orcaella heinsohni) in northern Australian waters
Authors: Palmer Carol , Murphy Stephen A. , Thiele Deborah , Parra Guido J. , Robertson Kelly M. , Beasley Isabel , Austin Chris M.
Published: October 2011

Conservation management relies on being able to identify and describe species. Recent morphological and molecular analyses of the dolphin genus Orcaella show a species-level disjunction between eastern Australia and South-east Asia. However, because of restricted sampling, the taxonomic affinities of the geographically intermediate populations in the Northern Territory and Western Australia remained uncertain. We sequenced 403 base pairs of the mitochondrial control region from five free-ranging Orcaella individuals sampled from north-western Western Australia and the Northern Territory. Low net nucleotide divergence (0.11–0.67%) among the Australian Orcaella populations show that populations occurring in the Northern Territory and Western Australia belong to the Australian snubfin (O. heinsohni) rather than the Asian Irrawaddy dolphin (O. brevirostris). Clarifying the distribution of Orcaella is an important first step in the conservation and management for both species; however, an understanding of the metapopulation structure and patterns of dispersal among populations is now needed.
The hyporheic refuge hypothesis reconsidered: a review of hydrological aspects
Authors: Dole-Olivier Marie-José
Published: October 2011

The hyporheic zone (HZ) is thought to serve multiple functions for lotic invertebrates, but its role in the persistence of benthic assemblages after disturbances (‘hyporheic refuge hypothesis’, HRH) has never been clearly demonstrated since its initial proposal in 1953. Water exchanges through the HZ appear to be crucial in determining most hyporheic processes and subsequently, in controlling directly or indirectly the distribution of hyporheic assemblages. At present, it seems that the distribution of hyporheic refugia would also be controlled by hyporheic flowpaths, explaining the non-uniform response to the HRH documented in the literature. In light of recent developments in hyporheic hydrology, it is timely to propose research directions for understanding the distribution and patchiness of hyporheic refugia. This review proposes a framework of hypotheses, based on the recognition of hyporheic flowpaths across several scales and predicting the highest refugial capacity in large-scale upwelling zones. Outcomes from this framework include the development of physical indicators measuring the ability of the HZ to protect invertebrates, the identification of river areas demonstrating the highest refuge capacity (hyporheic hotspots) and the promotion in restoration projects of suitable hydrologic exchanges for enhancing the development of hyporheic hotspots.
Evidence of large, local variations in recruitment and mortality in the small giant clam, Tridacna maxima, at Ningaloo Marine Park, Western Australia
Authors: Black Robert , Johnson Michael S. , Prince Jane , Brearley Anne , Bond Todd
Published: October 2011

Understanding variability of recruitment and mortality is essential for attempts to conserve populations or assessing changes resulting from perceived disturbances. In the absence of long-term studies, we examined population density and size-frequency distributions of the small giant clam, Tridacna maxima, at 20 sites in Ningaloo Marine Park, Western Australia, where the clams are abundant on discontinuous, intertidal rocky platforms attached to the shoreline. Density ranged over two orders of magnitude (0.04–8.27 m–2), and size ranged from 1.5 to 31.0 cm. The shapes of the size-frequency distributions varied substantially, indicating variability in recruitment and mortality, including failures of cohorts to recruit and catastrophic events of mortality. Consistency of recruitment, as indexed by the coefficient of variation of the size-frequency distribution, was greater towards the north of the Park, on intertidal platforms with greater complexity across their widths, and with smoother surfaces in the part of the platform occupied by the clams. The average turnover time was estimated at 5.4 years, giving a median age of 13 years. However, variation among sites was large, highlighting the importance of variability of the dynamics of local populations and the need for long-term studies to understand any particular population.
Distribution and movement of a stocked freshwater fish: implications of a variable habitat volume for stocking programs
Authors: Smith James A. , Baumgartner Lee J. , Suthers Iain M. , Taylor Matthew D.
Published: October 2011

Fish are commonly stocked into impoundments globally, yet their patterns of habitat use in this variable environment are rarely incorporated into the management of stocking density. The movement and distribution of Australian bass Macquaria novemaculata (Perchichthyidae) were monitored in two impoundments to assess whether: (1) impoundment populations exhibit behaviour typical of wild or riverine percichthyids; (2) changing gradients of temperature and dissolved oxygen influenced distribution; and (3) the volume of available habitat should be incorporated into the management of these fisheries. Habitat use was determined with a combination of gill netting and ultrasonic telemetry using depth-coded tags. Tagged fish displayed both crepuscular and migratory behaviour typical of the Percichthyidae, but also showed a previously unobserved division between littoral and pelagic foraging strategies. Australian bass showed no obvious thermal preferences, but avoided areas with dissolved oxygen <4 mg L–1. In one impoundment, a combination of hypoxia and water extraction reduced the volume of available habitat to 15% of maximum in March 2009, which coincided with increased catch per unit effort (CPUE) and decreased fish condition. The adaptive behaviour of Australian bass makes them well suited to the variability of impoundments, but annual and stochastic events of habitat reduction should be considered when planning stocking regimes for these fisheries.
Sympathetic control of bone mass regulated by osteopontin
Authors: Nagao Masashi , Feinstein Timothy N. , Ezura Yoichi , Hayata Tadayoshi , Notomi Takuya , Saita Yoshitomo , Hanyu Ryo , Hemmi Hiroaki , Izu Yayoi , Takeda Shu , Wang Kathryn , Rittling Susan , Nakamoto Tetsuya , Kaneko Kazuo , Kurosawa Hisashi , Karsenty Gerard , Denhardt David T. , Vilardaga Jean-Pierre , Noda Masaki
Published: October 2011

The sympathetic nervous system suppresses bone mass by mechanisms that remain incompletely elucidated. Using cell-based and murine genetics approaches, we show that this activity of the sympathetic nervous system requires osteopontin (OPN), a cytokine and one of the major members of the noncollagenous extracellular matrix proteins of bone. In this work, we found that the stimulation of the sympathetic tone by isoproterenol increased the level of OPN expression in the plasma and bone and that mice lacking OPN (OPN-KO) suppressed the isoproterenol-induced bone loss by preventing reduced osteoblastic and enhanced osteoclastic activities. In addition, we found that OPN is necessary for changes in the expression of genes related to bone resorption and bone formation that are induced by activation of the sympathetic tone. At the cellular level, we showed that intracellular OPN modulated the capacity of the β2-adrenergic receptor to generate cAMP with a corresponding modulation of cAMP-response element binding (CREB) phosphorylation and associated transcriptional events inside the cell. Our results indicate that OPN plays a critical role in sympathetic tone regulation of bone mass and that this OPN regulation is taking place through modulation of the β2-adrenergic receptor/cAMP signaling system.
Electron temperature fluctuations associated with the weakly coherent mode in the edge of I-mode plasmas
Authors: White A.E. , Phillips P. , Whyte D.G. , Hubbard A.E. , Sung C. , Hughes J.W. , Dominguez A. , Terry J. , Cziegler I.
Published: October 2011

New measurements of electron temperature fluctuations associated with the weakly coherent mode (WCM) during improved mode, or I-mode plasmas (Whyte et al
2010 Nucl. Fusion. 50 105005) at Alcator C-Mod (Marmar et al 2007 Fusion. Sci. Technol.
51 3261) are presented in this paper. The measurements are made with a 32-channel, high-resolution profile electron cyclotron emission radiometer. The WCM electron temperature fluctuations are localized to a 1 cm region inside the last closed flux surface. The WCM electron temperature fluctuation level is measured in several different I-mode discharges and is in the range
, which is an order of magnitude smaller than the WCM density fluctuation level. The WCM edge fluctuations observed in I-mode are believed to play a role in increasing particle transport but not energy transport in the edge of I-mode plasmas. The large difference between normalized density and electron temperature fluctuation amplitudes provides new evidence that the WCM fluctuations can separately affect energy and particle transport.
From materials development to their test in IFMIF: an overview
Authors: Baluc N. , Schäublin R. , Spätig P. , Ilchuk N. , Veleva L. , Oksiuta Z. , Theile J. , Tran M.Q.
Published: October 2011

R&D activities on fusion reactor materials in Switzerland focus on (1) the development of advanced metallic materials for structural applications in plasma-facing (first wall, divertor) and breeding blanket components of the future fusion power reactors, in particular oxide dispersion strengthened reduced activation ferritic steels and tungsten-base materials, (2) the modelling of radiation damage and radiation effects and (3) small specimen test technology for the future International Fusion Materials Irradiation Facility. The main objectives, examples of recent results and future activities are described in the case of these three R&D areas.
Structures and oscillations of rotationally and tidally distorted polytropic models of stars in the presence of the Coriolis force
Authors: Pathania A. , Lal A. K. , Mohan C.
Published: October 2011

The problems of equilibrium structures and periods of oscillations of rotationally and/or tidally distorted polytropic models of stars in binary systems have been studied previously. In the studies, only the effects of gravitational and centrifugal forces while obtaining the Roche equipotential of such stars were considered. The Coriolis force were not considered. In the present study, we have included the effects of the Coriolis force also. The objective of this study is to investigate as to how the inclusion of the Coriolis force in the Roche equipotential affects the equilibrium structures and periods of oscillations of rotationally and/or tidally distorted stars. The results of our study show that the Coriolis force has no appreciable effect on the equilibrium structures and periods of small oscillations of polytropic models of stars in binary systems. The present study also confirms the earlier conclusions that uniform rotation decreases the eigenfrequencies of various modes of oscillation.
Middle Eocene rodents from Peruvian Amazonia reveal the pattern and timing of caviomorph origins and biogeography
Authors: Antoine Pierre-Olivier , Marivaux Laurent , Croft Darin A. , Billet Guillaume , Ganerød Morgan , Jaramillo Carlos , Martin Thomas , Orliac Maëva J. , Tejada Julia , Altamirano Ali J. , Duranthon Francis , Fanjat Grégory , Rousse Sonia , Gismondi Rodolfo Salas
Published: October 2011

The long-term isolation of South America during most of the Cenozoic produced a highly peculiar terrestrial vertebrate biota, with a wide array of mammal groups, among which caviomorph rodents and platyrrhine primates are Mid-Cenozoic immigrants. In the absence of indisputable pre-Oligocene South American rodents or primates, the mode, timing and biogeography of these extraordinary dispersals remained debated. Here, we describe South America's oldest known rodents, based on a new diverse caviomorph assemblage from the late Middle Eocene (approx. 41 Ma) of Peru, including five small rodents with three stem caviomorphs. Instead of being tied to the Eocene/Oligocene global cooling and drying episode (approx. 34 Ma), as previously considered, the arrival of caviomorphs and their initial radiation in South America probably occurred under much warmer and wetter conditions, around the Mid-Eocene Climatic Optimum. Our phylogenetic results reaffirm the African origin of South American rodents and support a trans-Atlantic dispersal of these mammals during Middle Eocene times. This discovery further extends the gap (approx. 15 Myr) between first appearances of rodents and primates in South America.
Simultaneous Mendelian and clonal genome transmission in a sexually reproducing, all-triploid vertebrate
Authors: Stöck Matthias , Ustinova Jana , Betto-Colliard Caroline , Schartl Manfred , Moritz Craig , Perrin Nicolas
Published: October 2011

Meiosis in triploids faces the seemingly insuperable difficulty of dividing an odd number of chromosome sets by two. Triploid vertebrates usually circumvent this problem through either asexuality or some forms of hybridogenesis, including meiotic hybridogenesis that involve a reproductive community of different ploidy levels and genome composition. Batura toads (
Bufo baturae
; 3
n
= 33 chromosomes), however, present an all-triploid sexual reproduction. This hybrid species has two genome copies carrying a nucleolus-organizing region (NOR+) on chromosome 6, and a third copy without it (NOR−). Males only produce haploid NOR+ sperm, while ova are diploid, containing one NOR+ and one NOR− set. Here, we conduct sibship analyses with co-dominant microsatellite markers so as (i) to confirm the purely clonal and maternal transmission of the NOR− set, and (ii) to demonstrate Mendelian segregation and recombination of the NOR+ sets in both sexes. This new reproductive mode in vertebrates (‘pre-equalizing hybrid meiosis’) offers an ideal opportunity to study the evolution of non-recombining genomes. Elucidating the mechanisms that allow simultaneous transmission of two genomes, one of Mendelian, the other of clonal inheritance, might shed light on the general processes that regulate meiosis in vertebrates.
Bubbles in live-stranded dolphins
Authors: Dennison S. , Moore M. J. , Fahlman A. , Moore K. , Sharp S. , Harry C. T. , Hoppe J. , Niemeyer M. , Lentell B. , Wells R. S.
Published: October 2011

Bubbles in supersaturated tissues and blood occur in beaked whales stranded near sonar exercises, and post-mortem in dolphins bycaught at depth and then hauled to the surface. To evaluate live dolphins for bubbles, liver, kidneys, eyes and blubber–muscle interface of live-stranded and capture-release dolphins were scanned with B-mode ultrasound. Gas was identified in kidneys of 21 of 22 live-stranded dolphins and in the hepatic portal vasculature of 2 of 22. Nine then died or were euthanized and bubble presence corroborated by computer tomography and necropsy, 13 were released of which all but two did not re-strand. Bubbles were not detected in 20 live wild dolphins examined during health assessments in shallow water. Off-gassing of supersaturated blood and tissues was the most probable origin for the gas bubbles. In contrast to marine mammals repeatedly diving in the wild, stranded animals are unable to recompress by diving, and thus may retain bubbles. Since the majority of beached dolphins released did not re-strand it also suggests that minor bubble formation is tolerated and will not lead to clinically significant decompression sickness.
Genomic analysis of circulating cell-free DNA infers breast cancer dormancy
Authors: Shaw Jacqueline A. , Page Karen , Blighe Kevin , Hava Natasha , Guttery David , Ward Becky , Brown James , Ruangpratheep Chetana , Stebbing Justin , Payne Rachel , Palmieri Carlo , Cleator Suzy , Walker Rosemary A. , Coombes R. Charles
Published: October 2011

Biomarkers in breast cancer to monitor minimal residual disease have remained elusive. We hypothesized that genomic analysis of circulating free DNA (cfDNA) isolated from plasma may form the basis for a means of detecting and monitoring breast cancer. We profiled 251 genomes using Affymetrix SNP 6.0 arrays to determine copy number variations (CNVs) and loss of heterozygosity (LOH), comparing 138 cfDNA samples with matched primary tumor and normal leukocyte DNA in 65 breast cancer patients and eight healthy female controls. Concordance of SNP genotype calls in paired cfDNA and leukocyte DNA samples distinguished between breast cancer patients and healthy female controls (P < 0.0001) and between preoperative patients and patients on follow-up who had surgery and treatment (P = 0.0016). Principal component analyses of cfDNA SNP/copy number results also separated presurgical breast cancer patients from the healthy controls, suggesting specific CNVs in cfDNA have clinical significance. We identified focal high-level DNA amplification in paired tumor and cfDNA clustered in a number of chromosome arms, some of which harbor genes with oncogenic potential, including USP17L2 (DUB3), BRF1, MTA1, and JAG2. Remarkably, in 50 patients on follow-up, specific CNVs were detected in cfDNA, mirroring the primary tumor, up to 12 yr after diagnosis despite no other evidence of disease. These data demonstrate the potential of SNP/CNV analysis of cfDNA to distinguish between patients with breast cancer and healthy controls during routine follow-up. The genomic profiles of cfDNA infer dormancy/minimal residual disease in the majority of patients on follow-up.
Identification of a Gene for Pyruvate-Insensitive Mitochondrial Alternative Oxidase Expressed in the Thermogenic Appendices in Arum maculatum
Authors: Ito Kikukatsu , Ogata Takafumi , Kakizaki Yusuke , Elliott Catherine , Albury Mary S. , Moore Anthony L.
Published: October 2011

Heat production in thermogenic plants has been attributed to a large increase in the expression of the alternative oxidase (AOX). AOX acts as an alternative terminal oxidase in the mitochondrial respiratory chain, where it reduces molecular oxygen to water. In contrast to the mitochondrial terminal oxidase, cytochrome c oxidase, AOX is nonprotonmotive and thus allows the dramatic drop in free energy between ubiquinol and oxygen to be dissipated as heat. Using reverse transcription-polymerase chain reaction-based cloning, we reveal that, although at least seven cDNAs for AOX exist (AmAOX1a, -1b, -1c, -1d, -1e, -1f, and -1g) in Arum maculatum, the organ and developmental regulation for each is distinct. In particular, the expression of AmAOX1e transcripts appears to predominate in thermogenic appendices among the seven AmAOXs. Interestingly, the amino acid sequence of AmAOX1e indicates that the ENV element found in almost all other AOX sequences, including AmAOX1a, -1b, -1c, -1d, and -1f, is substituted by QNT. The existence of a QNT motif in AmAOX1e was confirmed by nano-liquid chromatography-tandem mass spectrometry analysis of mitochondrial proteins from thermogenic appendices. Further functional analyses with mitochondria prepared using a yeast heterologous expression system demonstrated that AmAOX1e is insensitive to stimulation by pyruvate. These data suggest that a QNT type of pyruvate-insensitive AOX, AmAOX1e, plays a crucial role in stage- and organ-specific heat production in the appendices of A. maculatum.
ArabidopsisSigma Factor Binding Proteins Are Activators of the WRKY33 Transcription Factor in Plant Defense
Authors: Lai Zhibing , Li Ying , Wang Fei , Cheng Yuan , Fan Baofang , Yu Jing-Quan , Chen Zhixiang
Published: October 2011

Necrotrophic pathogens are important plant pathogens that cause many devastating plant diseases. Despite their impact, our understanding of the plant defense response to necrotrophic pathogens is limited. The WRKY33 transcription factor is important for plant resistance to necrotrophic pathogens; therefore, elucidation of its functions will enhance our understanding of plant immunity to necrotrophic pathogens. Here, we report the identification of two WRKY33-interacting proteins, nuclear-encoded SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2, which also interact with plastid-encoded plastid RNA polymerase SIGMA FACTOR1. Both SIB1 and SIB2 contain an N-terminal chloroplast targeting signal and a putative nuclear localization signal, suggesting that they are dual targeted. Bimolecular fluorescence complementation indicates that WRKY33 interacts with SIBs in the nucleus of plant cells. Both SIB1 and SIB2 contain a short VQ motif that is important for interaction with WRKY33. The two VQ motif–containing proteins recognize the C-terminal WRKY domain and stimulate the DNA binding activity of WRKY33. Like WRKY33, both SIB1 and SIB2 are rapidly and strongly induced by the necrotrophic pathogen Botrytis cinerea. Resistance to B. cinerea is compromised in the sib1 and sib2 mutants but enhanced in SIB1-overexpressing transgenic plants. These results suggest that dual-targeted SIB1 and SIB2 function as activators of WRKY33 in plant defense against necrotrophic pathogens.
INDEHISCENT and SPATULA Interact to Specify Carpel and Valve Margin Tissue and Thus Promote Seed Dispersal inArabidopsis
Authors: Girin Thomas , Paicu Teodora , Stephenson Pauline , Fuentes Sara , Körner Evelyn , O’Brien Martin , Sorefan Karim , Wood Thomas A. , Balanzá Vicente , Ferrándiz Cristina , Smyth David R. , Østergaard Lars
Published: October 2011

Structural organization of organs in multicellular organisms occurs through intricate patterning mechanisms that often involve complex interactions between transcription factors in regulatory networks. For example, INDEHISCENT (IND), a basic helix-loop-helix (bHLH) transcription factor, specifies formation of the narrow stripes of valve margin tissue, where Arabidopsis  thaliana fruits open on maturity. Another bHLH transcription factor, SPATULA (SPT), is required for reproductive tissue development from carpel margins in the Arabidopsis gynoecium before fertilization. Previous studies have therefore assigned the function of SPT to early gynoecium stages and IND to later fruit stages of reproductive development. Here we report that these two transcription factors interact genetically and via protein–protein contact to mediate both gynoecium development and fruit opening. We show that IND directly and positively regulates the expression of SPT, and that spt mutants have partial defects in valve margin formation. Careful analysis of ind mutant gynoecia revealed slight defects in apical tissue formation, and combining mutations in IND and SPT dramatically enhanced both single-mutant phenotypes. Our data show that SPT and IND at least partially mediate their joint functions in gynoecium and fruit development by controlling auxin distribution and suggest that this occurs through cooperative binding to regulatory sequences in downstream target genes.
Do proteolytic antibodies complete the panoply of the autoimmune response in acquired haemophilia A?
Authors: Mahendra Ankit , Padiolleau‐Lefevre Séverine , Kaveri Srinivas V. , Lacroix‐Desmazes Sébastien
Published: October 2011

Acquired haemophilia A (AHA) is a rare bleeding disorder characterized by the sudden generation of autoantibodies against factor VIII (FVIII) in individuals with no previous history of abnormal haemostasis. Understanding the pathogenesis of this disease has been hampered by the rarity of the patients and the difficulty in obtaining biological material from untreated patients. Still, progress has been made recently in understanding the pathogenesis of AHA. In particular, the importance of CD4+ T cells in AHA development has been documented and the epitopes targeted by T cells on FVIII have been delineated. Accordingly, a polymorphism in the cytotoxic T‐lymphocyte‐associated protein 4 gene (CTLA4), known to participate in the regulation of CD4+ T‐cell responses, and a preferential usage of certain human leukocyte antigen class II haplotypes, have been associated with the disease. Recent findings have documented the presence of immunoglobulin G (IgG) with proteolytic activity against FVIII and factor IX (FIX) in patients with AHA. While FVIII‐hydrolysing IgG has been shown to inactivate FVIII, FIX‐hydrolysing IgG from AHA patients activate FIX in vitro. Here, we describe the latest findings on the immuno‐pathogenesis of AHA, with a special focus on the potential role played by antibodies endowed with proteolytic properties.
Child coping, parent coping assistance, and post‐traumatic stress following paediatric physical injury
Authors: Marsac M. L. , Donlon K. A. , Winston F. K. , Kassam‐Adams N.
Published: October 2011

Background  Following a physical injury, many children exhibit long‐term psychological reactions such as post‐traumatic stress symptoms (PTSS). Children's coping strategies, and the ways that others help them cope with injury (i.e. coping assistance), are understudied, potentially malleable variables that could be targeted in preventive interventions. The objectives of the current research were to describe child coping behaviour and parent coping assistance following a child's injury, and to investigate the relationships among coping, coping assistance and child PTSS.

Method  Participants included 82 children with injuries and one parent of each child. Children completed measures of coping and coping assistance 2 weeks after their injury (T1). Children also completed measures of coping and PTSS at a 3‐month follow‐up (T2). Parents reported on the coping assistance they provided to their child at T1.

Results  Children reported using an average of six coping strategies (out of 10) with wishful thinking, social support, distraction, and cognitive restructuring endorsed most frequently. Child‐reported social withdrawal and resignation 2 weeks after his or her injury (T1) were related to subsequent PTSS (T2). Social withdrawal at T2 was related to concurrent child PTSS (T2). Children were more likely to seek social support when their parents reported helping their child cope. No relationships were identified between active coping behaviours or parent coping assistance and PTSS outcomes.

Conclusions  Findings suggest that children's coping strategies (particularly social withdrawal and resignation) play a possibly important, complex role in the development of traumatic stress symptoms. When parents help their child cope, children are more likely to seek out social support, suggesting that they will be more able to ask their parents for help as needed. Future research should identify effective strategies to prevent PTSS including how parents can best support their child following paediatric injury.
Immunology in the Clinic Review Series; focus on metabolic diseases: development of islet autoimmune disease in type 2 diabetes patients: potential sequelae of chronic inflammation
Authors: Brooks-Worrell B , Palmer J P
Published: October 2011

OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES

Allergy, Host Responses, Cancer, Autoinflammatory Diseases, Type 1 diabetes and viruses.

Historically, the development of type 2 diabetes has been considered not to have an autoimmune component, in contrast to the autoimmune pathogenesis of type 1 diabetes. In this review we will discuss the accumulating data supporting the concept that islet autoreactivity and inflammation is present in type 2 diabetes pathogenesis, and the islet autoimmunity appears to be one of the factors associated with the progressive nature of the type 2 diabetes disease process.
Infiltrating cellular pattern in kidney graft biopsies translates into forkhead box protein 3 up-regulation and p16INK4α senescence protein down-regulation in patients treated with belatacept compared to cyclosporin A
Authors: Furuzawa-Carballeda J , Lima G , Alberú J , Palafox D , Uribe-Uribe N , Morales-Buenrostro L E , Reyes Acevedo R , Mondragón G , Chevaile A , Llorente L
Published: October 2011

Renal allograft survival is related directly to cell senescence. In the transplantation scenario many cellular events – participating as immunological and non-immunological factors – could contribute to accelerate this biological process, responsible for the ultimate fate of the graft. Mechanisms concerned in tolerance versus rejection are paramount in this outcome. For this reason, immunosuppressive treatment constitutes an extremely important decision to prevent organ dysfunction and, finally, graft loss. This study was conducted to document the proportion of CD4+/interleukin (IL)-17A+-, CD16+/indoleamine 2, 3-dioxygenase (IDO+)-, forkhead box protein P3 (FoxP3+)-expressing cells, senescent cells (p16INK4α) and the percentage of interstitial fibrosis (IF) in graft biopsies of kidney transplant recipients participating in the BENEFIT (Bristol-Myers Squibb IM103008) study. CD4+/IL-17A+, CD16+/IDO+, FoxP3+ and p16INK4α+ cells were evaluated by immunohistochemistry, and the percentage of IF by morphometry on graft biopsies obtained at time 0 (pre-implantation) and at 12 months post-transplant. Senescent cells and CD4+/IL-17A+ cells were increased among graft biopsies in subjects receiving cyclosporin A (CsA) compared to those under belatacept treatment. Meanwhile, CD16+/IDO+ and FoxP3+-expressing cells were lower in biopsies from CsA treatment compared to patients treated with Belatacept. Histological morphometric analyses disclosed more IF in 12-month CsA-treated patients in comparison to pre-implantation biopsy findings. Summing up, renal biopsies from patients receiving belatacept showed greater amounts of FoxP3+ cells and lower amounts of CD4+/IL-17A+ and senescent cells compared to patients under CsA treatment. Along with these findings, an increase in IF in annual CsA-treated-patients biopsies compared to pre-implantation and belatacept-treated patients were observed.
Immune complexes and late complement proteins trigger activation of Syk tyrosine kinase in human CD4+ T cells
Authors: Chauhan A K , Moore T L
Published: October 2011

In systemic lupus erythematosus (SLE), the autoantibodies that form immune complexes (ICs) trigger activation of the complement system. This results in the formation of membrane attack complex (MAC) on cell membrane and the soluble terminal complement complex (TCC). Hyperactive T cell responses are hallmark of SLE pathogenesis. How complement activation influences the T cell responses in SLE is not fully understood. We observed that aggregated human γ-globulin (AHG) bound to a subset of CD4+ T cells in peripheral blood mononuclear cells and this population increased in the SLE patients. Human naive CD4+ T cells, when treated with purified ICs and TCC, triggered recruitment of the FcRγ chain with the membrane receptor and co-localized with phosphorylated Syk. These events were also associated with aggregation of membrane rafts. Thus, results presented suggest a role for ICs and complement in the activation of Syk in CD4+ T cells. Thus, we propose that the shift in signalling from ζ-chain-ZAP70 to FcRγ chain-Syk observed in T cells of SLE patients is triggered by ICs and complement. These results demonstrate a link among ICs, complement activation and phosphorylation of Syk in CD4+ T cells.
Juvenile hormone titre and related gene expression during the change of reproductive modes in the pea aphid
Authors: Ishikawa A. , Ogawa K. , Gotoh H. , Walsh T. K. , Tagu D. , Brisson J. A. , Rispe C. , Jaubert‐Possamai S. , Kanbe T. , Tsubota T. , Shiotsuki T. , Miura T.
Published: October 2011

Most aphids show reproductive polyphenism, i.e. they alternate their reproductive modes from parthenogenesis to sexual reproduction in response to short photoperiods. Although juvenile hormone (JH) has been considered a likely candidate for regulating the transition from asexual to sexual reproduction after photoperiod sensing, there are few studies investigating the direct relationship between JH titres and the reproductive‐mode change. In addition, the sequencing of the pea aphid genome has allowed identification of the genes involved in the JH pathway, which in turn allows us to examine their expression levels in relation to the reproductive‐mode change. Using liquid chromatography‐mass spectrometry in the pea aphid, JHIII titre was shown to be lower in aphids producing sexual morphs under short‐day conditions than in aphids producing parthenogenetic morphs under long‐day conditions. The expression levels of genes upstream and downstream of JH action were quantified by real‐time quantitative reverse‐transcription‐PCR across the reproductive‐mode change. The expression level ofJH esterase, which is responsible for JH degradation, was significantly higher in aphids reared under short‐day conditions. This suggests that the upregulation of the JH degradation pathway may be responsible for the lower JHIII titre in aphids exposed to short‐days, leading to the production of sexual morphs.
Pain management in neonates: a survey of nurses and doctors
Authors: Akuma Akuma O , Jordan Sue
Published: October 2011

Akuma A.O. & Jordan S. (2012) Pain management in neonates: a survey of nurses and doctors. Journal of Advanced Nursing 68(6), 1288–1301.

Aim.  This paper is a report of a descriptive survey of nurses’ and doctors’ knowledge and reported practice regarding procedural pain assessment and management in neonatal intensive care units.

Background.  There are concerns that pain is often unrecognized and under‐treated in neonates. Current guidelines advocate administration of analgesia and comfort measures, but may be vulnerable to inter‐professional differences in guideline implementation.

Methods.  All nurses and doctors working in all seven neonatal intensive care units in one area of the United Kingdom were surveyed between January to August 2007. Lead clinicians distributed and collected anonymous questionnaires.

Findings.  Response rate was 44% (62 doctors, 137 nurses). Internal consistency was high, overall Cronbach’s alpha 0·976. Respondents were knowledgeable, mean score 82% (SD13·3%). They agreed that neonates feel pain and need analgesia. Chest drain insertion was perceived to be the most painful procedure, heel‐prick the least. Respondents reported that analgesia and comfort measures were not usually administered for most procedures: nurses were more likely than doctors to report adhering to guidelines advocating administration of analgesia and comfort measures. Statistically significant differences between current and optimal practice were acknowledged. Few (21% and 37%) had received training on neonatal pain and fewer (2·5%) employed recognized pain assessment instruments. Pain management guidelines were available to 29(47%) doctors and 85(62%) nurses; 20(18%) reported that these had been audited.

Conclusion.  Clinicians were knowledgeable about neonatal pain, but gaps between knowledge and practice remain. This hiatus could be bridged by providing research evidence for the efficacy of guidelines incorporating validated pain assessment instruments.