bluuebunny/crossref_metadata_2025 huggingface dataset:
Recollection versus strength as the primary determinant of hippocampal engagement at retrieval
Authors: Cohn Melanie , Moscovitch Morris , Lahat Ayelet , McAndrews Mary Pat
Published: December 2009

We examined whether hippocampal activity in recognition relates to the strength of the memory or to recollective experience, a subject of considerable current debate. Participants studied word pairs and then made two successive recognition decisions on each item: first on the uncued target and then on the target presented with the studied cue word. We compared recollection and familiarity patterns of activation in fMRI for these decisions. Critically, our analyses attempted in two ways to equate perceived memory strength while varying the associative information available. First, activity for targets judged familiar before cueing was contrasted with activity for the same items in the second decision as a function of whether the targets converted to recollection or remained familiar when the context cues were provided. We found increased hippocampal activity following cueing only with recollective conversion. Second, we investigated whether hippocampal activity was modulated by the rated familiarity strength of cued items or whether it increased uniquely in recollection. Hippocampal activation was not modulated parametrically by familiarity strength and recollected items were associated with greater activity relative to highly familiar items. Together, our results support the notion that it is recollection of context, rather than memory strength, that underlies hippocampal engagement at retrieval.
Distinguishing influence-based contagion from homophily-driven diffusion in dynamic networks
Authors: Aral Sinan , Muchnik Lev , Sundararajan Arun
Published: December 2009

Node characteristics and behaviors are often correlated with the structure of social networks over time. While evidence of this type of assortative mixing and temporal clustering of behaviors among linked nodes is used to support claims of peer influence and social contagion in networks, homophily may also explain such evidence. Here we develop a dynamic matched sample estimation framework to distinguish influence and homophily effects in dynamic networks, and we apply this framework to a global instant messaging network of 27.4 million users, using data on the day-by-day adoption of a mobile service application and users' longitudinal behavioral, demographic, and geographic data. We find that previous methods overestimate peer influence in product adoption decisions in this network by 300–700%, and that homophily explains >50% of the perceived behavioral contagion. These findings and methods are essential to both our understanding of the mechanisms that drive contagions in networks and our knowledge of how to propagate or combat them in domains as diverse as epidemiology, marketing, development economics, and public health.
Large-scale patterns in biodiversity of microbial eukaryotes from the abyssal sea floor
Authors: Scheckenbach Frank , Hausmann Klaus , Wylezich Claudia , Weitere Markus , Arndt Hartmut
Published: December 2009

Eukaryotic microbial life at abyssal depths remains “uncharted territory” in eukaryotic microbiology. No phylogenetic surveys have focused on the largest benthic environment on this planet, the abyssal plains. Moreover, knowledge of the spatial patterns of deep-sea community structure is scanty, and what little is known originates primarily from morphology-based studies of foraminiferans. Here we report on the great phylogenetic diversity of microbial eukaryotic communities of all 3 abyssal plains of the southeastern Atlantic Ocean---the Angola, Cape, and Guinea Abyssal Plains---from depths of 5,000 m. A high percentage of retrieved clones had no close representatives in genetic databases. Many clones were affiliated with parasitic species. Furthermore, differences between the communities of the Cape Abyssal Plain and the other 2 abyssal plains point to environmental gradients apparently shaping community structure at the landscape level. On a regional scale, local species diversity showed much less variation. Our study provides insight into the community composition of microbial eukaryotes on larger scales from the wide abyssal sea floor realm and marks a direction for more detailed future studies aimed at improving our understanding of deep-sea microbes at the community and ecosystem levels, as well as the ecological principles at play.
Network analyses structure genetic diversity in independent genetic worlds
Authors: Halary Sébastien , Leigh Jessica W. , Cheaib Bachar , Lopez Philippe , Bapteste Eric
Published: December 2009

DNA flows between chromosomes and mobile elements, following rules that are poorly understood. This limited knowledge is partly explained by the limits of current approaches to study the structure and evolution of genetic diversity. Network analyses of 119,381 homologous DNA families, sampled from 111 cellular genomes and from 165,529 phage, plasmid, and environmental virome sequences, offer challenging insights. Our results support a disconnected yet highly structured network of genetic diversity, revealing the existence of multiple “genetic worlds.” These divides define multiple isolated groups of DNA vehicles drawing on distinct gene pools. Mathematical studies of the centralities of these worlds’ subnetworks demonstrate that plasmids, not viruses, were key vectors of genetic exchange between bacterial chromosomes, both recently and in the past. Furthermore, network methodology introduces new ways of quantifying current sampling of genetic diversity.
Differences in human and chimpanzee gene expression patterns define an evolving network of transcription factors in brain
Authors: Nowick Katja , Gernat Tim , Almaas Eivind , Stubbs Lisa
Published: December 2009

Humans differ from other primates by marked differences in cognitive abilities and a significantly larger brain. These differences correlate with metabolic changes, as evidenced by the relative up-regulation of energy-related genes and metabolites in human brain. While the mechanisms underlying these evolutionary changes have not been elucidated, altered activities of key transcription factors (TFs) could play a pivotal role. To assess this possibility, we analyzed microarray data from five tissues from humans and chimpanzees. We identified 90 TF genes with significantly different expression levels in human and chimpanzee brain among which the rapidly evolving KRAB-zinc finger genes are markedly over-represented. The differentially expressed TFs cluster within a robust regulatory network consisting of two distinct but interlinked modules, one strongly associated with energy metabolism functions, and the other with transcription, vesicular transport, and ubiquitination. Our results suggest that concerted changes in a relatively small number of interacting TFs may coordinate major gene expression differences in human and chimpanzee brain.
Mitaplatin, a potent fusion of cisplatin and the orphan drug dichloroacetate
Authors: Dhar Shanta , Lippard Stephen J.
Published: December 2009

The unique glycolytic metabolism of most solid tumors, known as the Warburg effect, is associated with resistance to apoptosis that enables cancer cells to survive. Dichloroacetate (DCA) is an anticancer agent that can reverse the Warburg effect by inhibiting a key enzyme in cancer cells, pyruvate dehydrogenase kinase (PDK), that is required for the process. DCA is currently not approved for cancer treatment in the USA. Here, we present the synthesis, characterization, and anticancer properties ofc,t,c-[Pt(NH3)2(O2CHCl2)2Cl2], mitaplatin, in which two DCA units are appended to the axial positions of a six-coordinate Pt(IV) center. The negative intracellular redox potential reduces the platinum to release cisplatin, a Pt(II) compound, and two equivalents of DCA. By a unique mechanism, mitaplatin thereby attacks both nuclear DNA with cisplatin and mitochondria with DCA selectively in cancer cells. The cytotoxicity of mitaplatin in a variety of cancer cell lines equals or exceeds that of all known Pt(IV) compounds and is comparable to that of cisplatin. Mitaplatin alters the mitochondrial membrane potential gradient (Δψm) of cancer cells, promoting apoptosis by releasing cytochromecand translocating apoptosis inducing factor from mitochondria to the nucleus. Cisplatin formed upon cellular reduction of mitaplatin enters the nucleus and targets DNA to form 1,2-intrastrand d(GpG) cross-links characteristic of its own potency as an anticancer drug. These properties of mitaplatin are manifest in its ability to selectively kill cancer cells cocultured with normal fibroblasts and to partially overcome cisplatin resistance.
QDD: a user-friendly program to select microsatellite markers and design primers from large sequencing projects
Authors: Meglécz Emese , Costedoat Caroline , Dubut Vincent , Gilles André , Malausa Thibaut , Pech Nicolas , Martin Jean-François
Published: December 2009

Summary: QDD is an open access program providing a user-friendly tool for microsatellite detection and primer design from large sets of DNA sequences. The program is designed to deal with all steps of treatment of raw sequences obtained from pyrosequencing of enriched DNA libraries, but it is also applicable to data obtained through other sequencing methods, using FASTA files as input. The following tasks are completed by QDD: tag sorting, adapter/vector removal, elimination of redundant sequences, detection of possible genomic multicopies (duplicated loci or transposable elements), stringent selection of target microsatellites and customizable primer design. It can treat up to one million sequences of a few hundred base pairs in the tag-sorting step, and up to 50 000 sequences in a single input file for the steps involving estimation of sequence similarity.

Availability: QDD is freely available under the GPL licence for Windows and Linux from the following web site: http://www.univ-provence.fr/gsite/Local/egee/dir/meglecz/QDD.html

Contact:  emese.meglecz@univ-provence.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Tmod: toolbox of motif discovery
Authors: Sun Hanchang , Yuan Yuan , Wu Yibo , Liu Hui , Liu Jun S. , Xie Hongwei
Published: December 2009

Summary: Motif discovery is an important topic in computational transcriptional regulation studies. In the past decade, many researchers have contributed to the field and many de novo motif-finding tools have been developed, each may have a different strength. However, most of these tools do not have a user-friendly interface and their results are not easily comparable. We present a software called Toolbox of Motif Discovery (Tmod) for Windows operating systems. The current version of Tmod integrates 12 widely used motif discovery programs: MDscan, BioProspector, AlignACE, Gibbs Motif Sampler, MEME, CONSENSUS, MotifRegressor, GLAM, MotifSampler, SeSiMCMC, Weeder and YMF. Tmod provides a unified interface to ease the use of these programs and help users to understand the tuning parameters. It allows plug-in motif-finding programs to run either separately or in a batch mode with predetermined parameters, and provides a summary comprising of outputs from multiple programs. Tmod is developed in C++ with the support of Microsoft Foundation Classes and Cygwin. Tmod can also be easily expanded to include future algorithms.

Availability: Tmod is available for download at http://www.fas.harvard.edu/∼junliu/Tmod/

Contact:  xhwei65@nudt.edu.cn; jliu@stat.harvard.edu
WebPARE: web-computing for inferring genetic or transcriptional interactions
Authors: Chuang Cheng-Long , Wu Jia-Hong , Cheng Chi-Sheng , Shieh Grace S.
Published: December 2009

Summary: Inferring genetic or transcriptional interactions, when done successfully, may provide insights into biological processes or biochemical pathways of interest. Unfortunately, most computational algorithms require a certain level of programming expertise. To provide a simple web interface for users to infer interactions from time course gene expression data, we present WebPARE, which is based on the pattern recognition algorithm (PARE). For expression data, in which each type of interaction (e.g. activator target) and the corresponding paired gene expression pattern are significantly associated, PARE uses a non-linear score to classify gene pairs of interest into a few subclasses of various time lags. In each subclass, PARE learns the parameters in the decision score using known interactions from biological experiments or published literature. Subsequently, the trained algorithm predicts interactions of a similar nature. Previously, PARE was shown to infer two sets of interactions in yeast successfully. Moreover, several predicted genetic interactions coincided with existing pathways; this indicates the potential of PARE in predicting partial pathway components. Given a list of gene pairs or genes of interest and expression data, WebPARE invokes PARE and outputs predicted interactions and their networks in directed graphs.

Availability: A web-computing service WebPARE is publicly available at: http://www.stat.sinica.edu.tw/WebPARE

Contact:  gshieh@stat.sinica.edu.tw

Supplementary information:  Supplementary data are available at Bioinformatics online.
Fitness-related consequences of competitive interactions between farmed and wild Atlantic salmon at different proportional representations of wild–farmed hybrids
Authors: Houde Aimee Lee S. , Fraser Dylan J. , Hutchings Jeffrey A.
Published: December 2009

Houde, A. S., Fraser, D. J., and Hutchings, J. A. 2010. Fitness-related consequences of competitive interactions between farmed and wild Atlantic salmon at different proportional representations of wild–farmed hybrids. – ICES Journal of Marine Science, 67: 657–667. Escaped farmed fish possess heritable characteristics that may give them and their wild–farmed hybrid offspring a competitive advantage over wild fish. Limited research has examined whether the results of wild vs. farmed pairwise behavioural contests can predict the change in fitness-related traits of wild fish when exposed to wild–farmed hybrids, or to different proportions of such hybrids, within stream environments. Pairwise aggression tests on North American Atlantic salmon (Salmo salar) revealed that regional farmed salmon and wild–farmed hybrids (F1, F2, and wild backcrosses) were more competitive than wild fish from two divergent populations. The ranking by which hybrids differed in competitive ability from wild fish also depended on the wild population. However, the magnitude of change in fitness-related traits of wild fish, such as mortality, size, and condition, from the same two populations could not be predicted from pairwise test results when replicate groups of wild fish were exposed to different proportions of hybrids (wild:hybrid ratios of 50:50, 70:30, and 85:15) in semi-natural stream environments. Notably, there was greater mortality of both wild and hybrid fish in treatments containing 30% hybrids for both populations; at a composition of 50% hybrids, the mortality of wild fish in one population increased more than it did in the other. The results suggest that for the life stage examined and provided the rate of farmed intrusion and wild–farmed interbreeding remains low (i.e. ≤15% hybrids), the effects of competitive interaction with their farmed counterparts may have comparatively little effect on the mortality of wild populations.
Isolation of a bacteriophage specific for CS7-expressing strains of enterotoxigenic Escherichia coli
Authors: Begum Y. A. , Chakraborty S. , Chowdhury A. , Ghosh A. N. , Nair G. B. , Sack R. B. , Svennerholm A.-M. , Qadri F.
Published: December 2009

EnterotoxigenicEscherichia coli(ETEC) is the most common bacterial cause of childhood diarrhoea in Bangladesh. Among the virulence factors of ETEC, toxins and colonization factors (CFs) play a major role in pathogenesis. UnlikeVibrio cholerae, the relationship between ETEC and ETEC-specific phages is poorly understood and the possible role of ETEC phages in the evolution of ETEC strains in the environment is yet to be established. This study was designed specifically to isolate phages that are specific for ETEC virulence factors. Among the 49 phages isolated from 12 different surface water samples, 13 were tested against 211 ETEC strains collected from clinical and environmental sources. One phage, designated IMM-001, showed a significant specificity towards CS7 CF as it attacked all the CS7-expressing ETEC. Electron microscopic analyses showed that the isolated phage possessed an isomeric hexagonal head and a long filamentous tail. An antibody blocking method and phage neutralization assay confirmed that CS7 pilus is required for the phage infection process, indicating the role of CS7 fimbrial protein as a potential receptor for IMM-001. In summary, this study showed the presence of a lytic phage in environmental water that is specific for the CS7 CF of ETEC.
Prevalence of trimethoprim resistance genes in Escherichia coli isolates of human and animal origin in Lithuania
Authors: Šeputienė Vaida , Povilonis Justas , Ružauskas Modestas , Pavilonis Alvydas , Sužiedėlienė Edita
Published: December 2009

A total of 456 non-repetitive Escherichia coli isolates from human clinical specimens (urinary, n=134; cervix, vagina and prostate, n=52; blood, pus and wounds, n=45), healthy animals (cattle, n=45; poultry, n=20) and diseased animals (cattle, n=53; swine, n=64; poultry, n=43) obtained in Lithuania during the period 2005–2008 were studied for trimethoprim (TMP) resistance and the prevalence of dfr genes. A TMP resistance rate in the range of 18–26 % respective to the origin was found in clinical isolates, 23–40 % in isolates from diseased animals and 9–20 % in isolates from healthy animals. Of 112 TMP-resistant isolates, 103 carried at least one of the six dfrA genes (dfrA1, dfrA5, dfrA8, dfrA12, dfrA14 and dfrA17) as determined by multiplex PCR and RFLP. The dfrA1 and dfrA17 genes were found most frequently in clinical isolates (17 and 19 isolates, respectively), whilst dfrA1 and dfrA14 genes dominated in isolates of animal origin (25 and 13 isolates, respectively). The dfrA5, dfrA12 and dfrA8 genes were detected at lower frequencies. The association with class 1/class 2 integrons was confirmed for 73–100 % of dfr genes found in most groups of isolates, except for the isolates from diseased swine. In this group, the majority of dfr-positive isolates (67 %, 8/12) carried dfrA8 (6/12) or dfrA14 genes (2/12) that were not associated with integrons. Non-integron location was also confirmed for the remaining dfrA8 genes (six clinical isolates and one isolate from diseased cattle) and for dfrA14 genes (two isolates from diseased cattle and swine each). All cassette-independent dfrA14 genes were found to be located within the strA gene. This study on the prevalence and distribution of TMP resistance genes among E. coli isolates of human and animal origin in Lithuania demonstrates that dfr genes are carried most frequently as gene cassettes within class 1 and/or class 2 integrons. However, TMP resistance in some of the isolates was found to be mediated by non-integron-associated dfrA8 and dfrA14 genes, indicating the existence of alternative sources for the spread of resistance.
Diversity of staphylococcal cassette chromosome mec structures in coagulase-negative staphylococci and relationship to drug resistance
Authors: Garza-González Elvira , López Daniel , Pezina Cesar , Muruet Walter , Bocanegra-García Virgilio , Muñoz Ivan , Ramírez Camilo , LLaca-Díaz Jorge M.
Published: December 2009

The objective of this study was to determine the distribution of staphylococcal cassette chromosome mec (SCCmec) elements in meticillin-resistant coagulase-negative staphylococci (MR-CoNS) isolated from a tertiary-care hospital in Mexico and to examine the relationship to drug resistance. Fifty selected MR-CoNS isolates collected from catheters (n=15), blood (n=15), bone (n=9), bronchial lavage (n=2) and urine (n=2) and one isolate each from an abscess, cerebrospinal fluid, eye, pleural effusion, synovial fluid, tracheal aspirate and wound secretion were examined. Susceptibility testing was performed by the broth microdilution method. SCCmec types were determined by multiplex PCR and PFGE was carried out as described previously for Staphylococcus aureus. Among the MR-CoNS strains studied, the most frequently isolated species were Staphylococcus epidermidis (n=26) and Staphylococcus haemolyticus (n=13). Staphylococcus cohnii (n=5), Staphylococcus hominis (n=3), Staphylococcus sciuri (n=1), Staphylococcus pasteuri (n=1) and the recently described species Staphylococcus pettenkoferi (n=1) were also identified. The most frequent MR-CoNS genotype identified was SCCmec type IVa in S. epidermidis isolates, which also showed a high diversity in their PFGE patterns. A clone was found that amplified both SCCmec III and V elements in five isolates examined. The single MR S. pettenkoferi isolate harboured SCCmec type IVd and the single MR S. pasteuri isolate harboured SCCmec type I. The carriage of SCCmec type III was associated with resistance or intermediate resistance to meropenem (P <0.05). These results confirm the high prevalence of S. epidermidis SCCmec IVa and the high genetic diversity among MR-CoNS strains. As far as is known, this is the first report describing the newly identified S. pettenkoferi possessing SCCmec IVd and S. pasteuri harbouring SCCmec type I. MR-CoNS harbouring SCCmec type III were found to be more resistant to meropenem.
Superoxide radical induces sclerotial differentiation in filamentous phytopathogenic fungi: a superoxide dismutase mimetics study
Authors: Papapostolou Ioannis , Georgiou Christos D.
Published: December 2009

This study shows that the superoxide radical (O2•−), a direct indicator of oxidative stress, is involved in the differentiation of the phytopathogenic filamentous fungiRhizoctonia solani,Sclerotinia sclerotiorum,Sclerotium rolfsiiandSclerotinia minor, shown by using superoxide dismutase (SOD) mimetics to decrease their sclerotial differentiation. The production rate of O2•−and SOD levels in these fungi, as expected, were significantly lowered by the SOD mimetics, with concomitant decrease of the indirect indicator of oxidative stress, lipid peroxidation.
Racemase activity effected by two dehydrogenases in sulfolactate degradation by Chromohalobacter salexigens: purification of (S)-sulfolactate dehydrogenase
Authors: Denger Karin , Cook Alasdair M.
Published: December 2009

Chromohalobacter salexigensDSM 3043, whose genome has been sequenced, is known to degrade (R,S)-sulfolactate as a sole carbon and energy source for growth. Utilization of the compound(s) was shown to be quantitative, and an eight-gene cluster (Csal_1764–Csal_1771) was hypothesized to encode the enzymes in the degradative pathway. It comprised a transcriptional regulator (SuyR), a Tripartite Tricarboxylate Transporter-family uptake system for sulfolactate (SlcHFG), two sulfolactate dehydrogenases of opposite sulfonate stereochemistry, namely novel SlcC and ComC [(R)-sulfolactate dehydrogenase] [EC1.1.1.272] and desulfonative sulfolactate sulfo-lyase (SuyAB) [EC4.4.1.24]. Inducible reduction of 3-sulfopyruvate, inducible SuyAB activity and induction of an unknown protein were detected. Separation of the soluble proteins from induced cells on an anion-exchange column yielded four relevant fractions. Two different fractions reduced sulfopyruvate with NAD(P)H, a third yielded SuyAB activity, and the fourth contained the unknown protein. The latter was identified by peptide-mass fingerprinting as SlcH, the candidate periplasmic binding protein of the transport system. Separated SuyB was also identified by peptide-mass fingerprinting. ComC was partially purified and identified by peptide-mass fingerprinting. The (R)-sulfolactate that ComC produced from sulfopyruvate was a substrate for SuyAB, which showed that SuyAB is (R)-sulfolactate sulfo-lyase. SlcC was purified to homogeneity. This enzyme also formed sulfolactate from sulfopyruvate, but the latter enantiomer was not a substrate for SuyAB. SlcC was obviously (S)-sulfolactate dehydrogenase.
Direct interaction of iron-regulated surface determinant IsdB of Staphylococcus aureus with the GPIIb/IIIa receptor on platelets
Authors: Miajlovic Helen , Zapotoczna Marta , Geoghegan Joan A. , Kerrigan Steven W. , Speziale Pietro , Foster Timothy J.
Published: December 2009

The interaction of bacteria with platelets is implicated in the pathogenesis of endovascular infections, including infective endocarditis, of whichStaphylococcus aureusis the leading cause. SeveralS. aureussurface proteins mediate aggregation of platelets by fibrinogen- or fibronectin-dependent processes, which also requires specific antibodies. In this studyS. aureuswas grown in iron-limited medium to mimicin vivoconditions in which iron is unavailable to pathogens. Under such conditions, aS. aureusmutant lacking the known platelet-activating surface proteins adhered directly to platelets in the absence of plasma proteins and triggered aggregation. Platelet adhesion and aggregation was prevented by inhibiting expression of iron-regulated surface determinant (Isd) proteins. Mutants defective in IsdB, but not IsdA or IsdH, were unable to adhere to or aggregate platelets. Antibodies to the platelet integrin GPIIb/IIIa inhibited platelet adhesion by IsdB-expressing strains, as did antagonists of GPIIb/IIIa. Surface plasmon resonance demonstrated that recombinant IsdB interacts directly with GPIIb/IIIa.
Structure solution of the new titanate Li4Ti8Ni3O21using precession electron diffraction
Authors: Gemmi Mauro , Klein Holger , Rageau Amelie , Strobel Pierre , Le Cras Federic
Published: December 2009

A sample having stoichiometry Li[Ti1.5Ni0.5]O4has been synthesized to obtain a spinel structure. The resulting crystalline powder revealed a multiphase nature with spinel as the minor phase. The main phase is a new trigonal phase havinga= 5.05910 (1),c= 32.5371 (1) Å. The structure has been solved by direct methods working on a three-dimensional set of intensities obtained from a precession electron-diffraction experiment, and refined on synchrotron powder diffraction data in the space group P\bar 3c1. The model consists of hexagonal layers of edge-sharing octahedra occupied either by the heavy cations Ti and Ni, or preferentially by Li. On the basis of cation-site occupancies the stoichiometry becomes Li4Ti8Ni3O21, which is compatible with the microanalysis results.
Octahedral tilting in cation-ordered Jahn–Teller distorted perovskites – a group-theoretical analysis
Authors: Howard Christopher J. , Carpenter Michael A.
Published: December 2009

Computer-based group-theoretical methods are used to enumerate structures arising in A
2
BB′X
6 perovskites, with either rock-salt or checkerboard ordering of the B and B′ cations, under the additional assumption that one of these two cations is Jahn–Teller active and thereby induces a distortion of the BX
6 (or B′X
6) octahedron. The requirement to match the pattern of Jahn–Teller distortions to the cation ordering implies that the corresponding irreducible representations should be associated with the same point in the Brillouin zone. Effects of BX
6 (and B′X
6) octahedral tilting are included in the usual way. Finally, an analysis is presented of more complex models of ordering and distortion as might lead to the doubling of the long axis of the common Pnma perovskite, observed in systems such as Pr1 − x
Ca
x
MnO3 (x ≃ 0.5). The structural hierarchies derived in this work should prove useful in interpreting experimental results.
Zur Kristallchemie von Graphen und Graphit
Authors: Trömel M.
Published: December 2009

The crystal structure of single-layer graphene in comparison to graphite is discussed with regard to its crystallographic and chemical properties. In both of these polymorphs of carbon, the atomic volume of carbon, reduced to the closest packing of atoms, is practically the same and considerably smaller than in diamond. This indicates pentavalent carbon in graphene as well as in graphite. The observed elastic corrugations of the graphene layers which probably cause their amazing rigidity seem to be due to numerous weak chemical bonds within the layers.
Inhibition of mTORC1 activity by REDD1 induction in myeloma cells resistant to bortezomib cytotoxicity
Authors: Decaux Olivier , Clément Monique , Magrangeas Florence , Gouraud Wilfried , Charbonnel Catherine , Campion Loïc , Loiseau Hervé Avet , Minvielle Stéphane
Published: December 2009

The combination of bortezomib and dexamethasone is becoming the reference induction treatment for multiple myeloma patients younger than 65 years. Despite its advantage over vincristin adryamicin dexamethasone induction treatment, bortezomib does not benefit all patients. We hypothesize that heterogeneity of the response experienced by myeloma patients is, at least in part, due to genomic variations in the malignant plasma cells. To test this hypothesis we used gene expression profiling to identify early responsive genes induced by bortezomib in resistant myeloma cells. Our study revealed: (i) a dramatic induction of REDD1, a negative regulator of mammalian target of rapamycin kinase complex 1 (mTORC1) activity, in these cells; (ii) a transient cell size decrease associated with REDD1 overexpression; and (iii) partial restoration of bortezomib sensitivity in REDD1 knockdown bortezomib‐resistant myeloma cells. Together, these results identify a possible novel mechanism of bortezomib resistance in myeloma patients mediated by REDD1 overexpression involving inhibition of mTORC1 activity and suggest that the use of mammalian target of rapamycin inhibitors in myeloma patients could be deleterious.

(Cancer Sci 2010; 101: 889–897)
3‐Methylcholanthrene‐induced transforming growth factor‐β‐producing carcinomas, but not sarcomas, are refractory to regulatory T cell‐depletion therapy
Authors: Chamoto Kenji , Wakita Daiko , Ohkuri Takayuki , Uchinami Yusuke , Matsushima Kouji , Kitamura Hidemitsu , Nishimura Takashi
Published: December 2009

Regulatory T cells (Tregs) are major immunosuppressors in tumor‐bearing hosts. Although Treg‐depletion therapy has been shown to induce a complete cure in tumor‐bearing mice, this treatment is not always successful. Using 3‐methylcholanthrene‐induced primary mouse tumors, we examined the distinct regulation of Treg‐mediated immunosuppression between carcinomas and sarcomas. We showed that the number of Tregs was greatly increased in squamous cell carcinoma (SCC)‐bearing mice compared with sarcoma‐bearing mice. This appeared to be because SCC produced higher levels of active transforming growth factor (TGF)‐β, which is essential for inducing Tregs, compared with sarcoma. Moreover, SCC, but not sarcomas, were refractory to Treg‐depletion therapy by treatment with anti‐CD25 mAb. The refractoriness of SCC against Treg‐depletion therapy was due to the rapid recovery of Tregs in SCC‐bearing mice compared with sarcoma‐bearing mice. However, combination treatment of anti‐TGF‐β mAb with anti‐CD25 mAb caused a significant reduction in Treg recovery and induced a complete cure in SCC‐bearing mice. Thus, we showed the refractoriness of mouse carcinoma against Treg‐depletion therapy using anti‐CD25 mAb treatment. We also proposed a novel Treg‐blocking combination therapy using anti‐CD25 mAb and anti‐TGF‐β mAb to induce a complete cure of tumor‐bearing hosts.

(Cancer Sci 2010; 101: 855–861)
Elective peri‐operative intra‐aortic balloon counterpulsation during maxillofacial free flap reconstructive surgery in a patient with severe cardiomyopathy
Authors: Jennings A. , Norman A. , Whitelock D. , Haynes S. , James G.
Published: December 2009

A key anaesthetic goal in reconstructive free flap surgery is to maintain optimum blood flow to maximise flap survival. We describe the use of intra‐aortic balloon counterpulsation in a patient with severe cardiac dysfunction, in whom surgery was initially felt to be contraindicated.
Newborn hearing screening programme outcomes in a research hospital from Turkey
Authors: Tasci Y. , Muderris I. I. , Erkaya S. , Altinbas S. , Yucel H. , Haberal A.
Published: December 2009

Background  Universal neonatal hearing screening programmes are encouraged to define and manage hearing loss in early ages of life. The aim of this study is to introduce our 14‐month three‐step hearing screening programme results with 16 975 births in Turkey.

Methods  In healthy neonates, Transient Evoked Otoacoustic Emission (TEOAE) is served as the initial screening in the first day of life. In newborns that did not meet pass criteria TEOAE was repeated in 10‐day period. If the second test was ‘refer’ again, the screening was completed with auditory brainstem response (ABR). Additionally, ABR was performed for the neonates with neonatal intensive care unit (NICU) requirement and at high audiologic risk. Neonates who failed the screening test with ABR were referred for further evaluation.

Results  A total of 15 323 newborns and 1652 NICU infants were tested. The screening coverage was 94.4%; 14 521 neonates (94.7%) passed the first screening step (TEOAE), while 802 (5.2%) neonate failed. In total, 322 (40.1%) of the neonates out of 802 was subjected to the second TEOAE after 10 days have failed and ABR was applied. From the neonates participated the third step (ABR) totalling 1974, 43 (2.17%) of neonates obtained a ‘refer’ response. Out of these 43 neonates, 17 neonates were (39.5%) NICU infants. From the 43 neonates, 38 cases (88.4%) were found to have hearing impairment. The false‐positive rate for first step screening with TEOAE was 4.9%; second step with TEOAE was 1.85% and for ABR was 0.25%.

Conclusions  It is apparent that three step national hearing screening programme which has been applied for the latest years in Turkey is an accurate and non‐invasive method to determine the congenital hearing loss. In the future, screening programmes could be rearranged with two steps as initial with TEOAE and retest with ABR and the coverage of the screening programme can be extended.
Parents' descriptions and experiences of young children recently diagnosed with intellectual disability
Authors: Boström P.K. , Broberg M. , Hwang P.
Published: December 2009

Aim  The aim of the present study was to explore the variation of parents' descriptions and experiences of their child that was recently identified to have an intellectual disability (ID).

Methods  The study applied interpretative phenomenological analysis and analysis of narrative style looking at content and form of parental narratives. Data was collected from nine fathers and eight mothers through semi‐structured interviews within 6 months following diagnosis.

Results  Analysis revealed three factors indicating the parents' level of processing: (1) emotional expressions regarding the child – varying between limited (distanced or idealized) and balanced/affectionate; (2) experience of the disability – varying between preoccupation and acceptance; and (3) time orientation – varying in terms of flexibility and temporal focus.

Conclusions  Although parents of children with ID describe negative emotions in relation to the child and the disability, most of these parents also describe positive emotions that seemed to balance the negative experiences.
Circulating mononuclear cells nuclear factor‐kappa B activity, plasma xanthine oxidase, and low grade inflammatory markers in adult patients with familial hypercholesterolaemia
Authors: Real J. T. , Martínez‐Hervás S. , García‐García A. B. , Civera M. , Pallardó F. V. , Ascaso J. F. , Viña J. R. , Chaves F. J. , Carmena R.
Published: December 2009

Eur J Clin Invest 2010; 40 (2): 89–94

Background  Few data are available on circulating mononuclear cells nuclear factor‐kappa B (NF‐kB) activity and plasma xanthine oxidase (XO) activity in heterozygous familial hypercholesterolaemia (FH). The goal of the study was to analyse circulating mononuclear cells NF‐kB and plasma XO activities in FH patients.

Materials and methods  Thirty FH index patients and 30 normoglycaemic normocholesterolaemic controls matched by age, gender, body mass index, abdominal circumference and homeostasis model assessment index were studied. Plasma XO and inflammatory markers were measured by standard methods. NF‐kB was assayed in circulating mononuclear cells.

Results  Familial hypercholesterolaemia patients showed a significantly higher NF‐kB (75·0 ± 20·7 vs. 42·7 ± 16·8 relative luminiscence units) and XO (0·44 ± 0·13 vs. 0·32 ± 0·09 mU mL–1) activities than controls. In addition, interleukin‐1, interleukin‐6, high sensitivity C reactive protein (hsCRP) and oxidized LDL (LDL‐ox) were also significantly higher in FH patients. In the total group (FH and controls), XO was significantly associated with LDL‐cholesterol (LDL‐C), apolipoprotein B (apoB), NF‐kB and hsCPR, and NF‐kB activity was significantly associated with XO, hsCPR, LDL‐ox, LDL‐C and apoB plasma values. Using multiple regression analysis, XO was independently associated with hsCPR and NF‐kB, and NF‐kB activity in circulating mononuclear cells was independently associated with apoB and LDL‐ox plasma values.

Conclusion  Familial hypercholesterolaemia patients show increased activities of NF‐kB and XO, and higher values of low grade inflammatory markers related to atherosclerosis. NF‐kB activity was independently associated with apoB plasma values. These data could explain in part the high cardiovascular disease risk present in these patients.
The effects of mating and instrumental insemination on queen honey bee flight behaviour and gene expression
Authors: Kocher S. D. , Tarpy D. R. , Grozinger C. M.
Published: December 2009

Mating is fundamental to most organisms, although the physiological and transcriptional changes associated with this process have been largely characterized only in Drosophila melanogaster. In this study, we use honey bees as a model system because their queens undergo massive and permanent physiological and behavioural changes following mating. Previous studies have identified changes associated with the transition from a virgin queen to a fully mated, egg‐laying queen. Here, we further uncouple the mating process to examine the effects of natural mating vs. instrumental insemination and saline vs. semen insemination. We observed effects on flight behaviour, vitellogenin expression and significant overlap in transcriptional profiles between our study and analogous studies in D. melanogaster, suggesting that some post‐mating mechanisms are conserved across insect orders.
Periadventitial delivery of anti‐EGF receptor antibody inhibits neointimal macrophage accumulation after angioplasty in a hypercholesterolaemic rabbit
Authors: Shafi Shahida , Lamb David , Modjtahedi Helmout , Ferns Gordon
Published: December 2009

Monocyte recruitment and their differentiation into macrophages are both early events in native and accelerated atherosclerosis that follows angioplasty. We have investigated the putative functional role of the epidermal growth factor receptor (EGFR) present on rabbit monocytes/macrophages. The impact of periadventitial delivery of an EGFR‐specific, blocking monoclonal antibody (ICR62, which inhibits EGF‐binding to its receptor) was investigated in a rabbit model of accelerated atherosclerosis induced by a combination of carotid injury and 4 weeks of a 2% cholesterol‐diet. Two weeks after the initiation of the diet, a balloon‐catheter angioplasty of the left common carotid artery was performed and a collar placed around the injured carotid artery immediately, for the delivery of ICR62 antibody, isotype‐matched antibody or saline control. Monocyte/macrophage accumulation, cell proliferation and neointimal thickening were determined 2 weeks after the delivery of the antibodies. The function of the EGFR on rabbit monocytes was also investigated in vitro, using chemotaxis assays. Treatment with ICR62 was associated with a significant reduction in macrophage accumulation and neointimal thickening and a 76% reduction in neointimal area of the vessel wall compared with controls. In vitro ICR62 inhibited macrophage and smooth muscle cell migration towards EGFR ligands including EGF and HB‐EGF. These findings suggest that EGFR ligation may be important in the development of early atherosclerotic lesions following balloon‐catheter angioplasty, and periadventitial delivery may provide a feasible approach for administration of the inhibitors of EGFR‐binding such as ICR62.
Environmental variance, population growth and evolution
Authors: Tuljapurkar Shripad
Published: December 2009

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N. Jonzén, T. Pople, K. Knape & M. Skjöld (2009) Stochastic demography and population dynamics in the red kangaroo (Macropus rufus). Journal of Animal Ecology, 79, 109–116.

Environmental fluctuations on time scales of one to tens of generations are increasingly recognized as important determinants of population dynamics and microevolution. Jonzén et al. in this issue analyse how the vital rates of red kangaroos depend on annual rainfall, and estimate the elasticities of stochastic growth rate to the means and variances of the vital rates, as well as to the mean and variance of rainfall. Their results demonstrate how ecological and evolutionary studies can benefit from including explicit environmental drivers when modelling populations, and from the use of mean and variance elasticities.
An ecologist’s guide to the animal model
Authors: Wilson Alastair J. , Réale Denis , Clements Michelle N. , Morrissey Michael M. , Postma Erik , Walling Craig A. , Kruuk Loeske E. B. , Nussey Daniel H.
Published: December 2009

1. Efforts to understand the links between evolutionary and ecological dynamics hinge on our ability to measure and understand how genes influence phenotypes, fitness and population dynamics. Quantitative genetics provides a range of theoretical and empirical tools with which to achieve this when the relatedness between individuals within a population is known.

2. A number of recent studies have used a type of mixed‐effects model, known as the animal model, to estimate the genetic component of phenotypic variation using data collected in the field. Here, we provide a practical guide for ecologists interested in exploring the potential to apply this quantitative genetic method in their research.

3. We begin by outlining, in simple terms, key concepts in quantitative genetics and how an animal model estimates relevant quantitative genetic parameters, such as heritabilities or genetic correlations.

4. We then provide three detailed example tutorials, for implementation in a variety of software packages, for some basic applications of the animal model. We discuss several important statistical issues relating to best practice when fitting different kinds of mixed models.

5. We conclude by briefly summarizing more complex applications of the animal model, and by highlighting key pitfalls and dangers for the researcher wanting to begin using quantitative genetic tools to address ecological and evolutionary questions.
Markers of eosinophilic and neutrophilic inflammation in bronchoalveolar lavage of asthmatic and atopic children
Authors: Snijders D. , Agostini S. , Bertuola F. , Panizzolo C. , Baraldo S. , Turato G. , Faggian D. , Plebani M. , Saetta M. , Barbato A.
Published: December 2009

To cite this article: Snijders D, Agostini S, Bertuola F, Panizzolo C, Baraldo S, Turato G, Faggian D, Plebani M, Saetta M, Barbato A. Markers of eosinophilic and neutrophilic inflammation in bronchoalveolar lavage of asthmatic and atopic children. Allergy 2010; 65: 978–985.

Background:  Recent studies performing fiberoptic bronchoscopy in children have improved our understanding of asthma pathophysiology. Eosinophilic, but also neutrophilic, inflammation has been described in asthma, but the relationship with atopy was incompletely investigated. The aim of this study is to examine inflammatory cells and mediators in children with asthma compared to the appropriate controls, i.e. atopic children without asthma and children with no atopy or asthma. Moreover, asthmatic children were analysed separately based on the presence of atopy and stratified by age.

Methods:  We recruited 191 children undergoing fiberoptic bronchoscopy for appropriate indications: 91 asthmatics (aged 1.4–17 years), 44 atopics without asthma (1.6–17.8 years) and 56 nonasthmatic nonatopic controls (1.4–14 years). In bronchoalveolar lavage, total and differential cell counts and inflammatory mediators, including ECP, eotaxin, IL‐8 and TNFα, were analysed.

Results:  Eosinophils and ECP levels were increased in asthmatic children when compared to controls (P = 0.002 and P = 0.01, respectively), but also atopic children without asthma had increased ECP levels compared to controls (P = 0.0001). Among asthmatic children, eosinophils and ECP levels were not different between atopic and nonatopic individuals. Neither neutrophils nor the related mediators (IL‐8 and TNFα) differed significantly in the three groups. This pattern of inflammation was observed in both preschool and school‐aged asthmatic children.

Conclusions:  This study suggests that markers of eosinophilic, but not neutrophilic inflammation, are increased in asthmatic children and also in atopic children without asthma. Of interest, in asthmatic children, the activation of the eosinophilic response is not solely because of the presence of atopy.
Influence of acupuncture on type I hypersensitivity itch and the wheal and flare response in adults with atopic eczema – a blinded, randomized, placebo‐controlled, crossover trial
Authors: Pfab F. , Huss‐Marp J. , Gatti A. , Fuqin J. , Athanasiadis G. I. , Irnich D. , Raap U. , Schober W. , Behrendt H. , Ring J. , Darsow U.
Published: December 2009

To cite this article: Pfab F, Huss‐Marp J, Gatti A, Fuqin J, Athanasiadis GI, Irnich D, Raap U, Schober W, Behrendt H, Ring J, Darsow U. Influence of acupuncture on type I hypersensitivity itch and the wheal and flare response in adults with atopic eczema – a blinded, randomized, placebo‐controlled, crossover trial. Allergy 2010; 65: 903–910.

Background:  Itch is a major symptom of allergic skin disease. Acupuncture has been shown to exhibit a significant effect on histamine‐induced itch in healthy volunteers. We investigated the effect of acupuncture on type I hypersensitivity itch and skin reaction in a double‐blind, randomized, placebo‐controlled, crossover trial.

Methods:  An allergen stimulus (house dust mite or grass pollen skin prick) was applied to 30 patients with atopic eczema before (direct effect) and after (preventive effect) two experimental approaches or control observation: acupuncture at points Quchi and Xuehai [verum acupuncture (VA), dominant side], ‘placebo‐point’ acupuncture (PA, dominant side), no acupuncture (NA). Itch intensity was recorded on a visual analogue scale. After 10 min, wheal and flare size and skin perfusion (via LASER‐Doppler) were measured at the stimulus site, and the validated Eppendorf Itch Questionnaire (EIQ) was answered.

Results:  Mean itch intensity was significantly lower in VA (35.7 ± 6.4) compared to NA (45.9 ± 7.8) and PA (40.4 ± 5.8) regarding the direct effect; and significantly lower in VA (34.3 ± 7.1) and PA (37.8 ± 5.6) compared to NA (44.6 ± 6.2) regarding the preventive effect. In the preventive approach, mean wheal and flare size were significantly smaller in VA (0.38 ± 0.12 cm2/8.1 ± 2.0 cm2) compared to PA (0.54 ± 0.13 cm2/13.5 ± 2.8 cm2) and NA (0.73 ± 0.28 cm2/15.1 ± 4.1 cm2), and mean perfusion in VA (72.4 ± 10.7) compared to NA (84.1 ± 10.7). Mean EIQ ratings were significantly lower in VA compared to NA and PA in the treatment approach; and significantly lower in VA and PA compared to NA in the preventive approach.

Conclusions:  Acupuncture at the correct points showed a significant reduction in type I hypersensitivity itch in patients with atopic eczema. With time the preventive point‐specific effect diminished with regard to subjective itch sensation, whereas it increased in suppressing skin‐prick reactions.