bluuebunny/crossref_metadata_2025 huggingface dataset:
Odd electron diffraction patterns in silicon nanowires and silicon thin films explained by microtwins and nanotwins
Authors: Cayron Cyril , Den Hertog Martien , Latu-Romain Laurence , Mouchet Céline , Secouard Christopher , Rouviere Jean-Luc , Rouviere Emmanuelle , Simonato Jean-Pierre
Published: January 2009

Odd electron diffraction patterns (EDPs) have been obtained by transmission electron microscopy (TEM) on silicon nanowires grownviathe vapour–liquid–solid method and on silicon thin films deposited by electron beam evaporation. Many explanations have been given in the past, without consensus among the scientific community: size artifacts, twinning artifacts or, more widely accepted, the existence of new hexagonal Si phases. In order to resolve this issue, the microstructures of Si nanowires and Si thin films have been characterized by TEM, high-resolution transmission electron microscopy (HRTEM) and high-resolution scanning transmission electron microscopy. Despite the differences in the geometries and elaboration processes, the EDPs of the materials show great similarities. The different hypotheses reported in the literature have been investigated. It was found that the positions of the diffraction spots in the EDPs could be reproduced by simulating a hexagonal structure withc/a= 12(2/3)1/2, but the intensities in many EDPs remained unexplained. Finally, it was established that all the experimental data,i.e.EDPs and HRTEM images, agree with a classical cubic silicon structure containing two microstructural defects: (i) overlapping Σ3 microtwins which induce extra spots by double diffraction, and (ii) nanotwins which induce extra spots as a result of streaking effects. It is concluded that there is no hexagonal phase in the Si nanowires and the Si thin films presented in this work.
On the determination of partial structure functions in small-angle scattering exemplified by Al89Ni6La5alloy
Authors: Hoell Armin , Tatchev Dragomir , Haas Sylvio , Haug Jörg , Boesecke Peter
Published: January 2009

A comparison between the resonant scattering curve obtained by anomalous small-angle X-ray scattering at the X-ray absorption edge of Ni and the complementary small-angle neutron scattering curve from an Al89Ni6La5alloy sample is reported. The sample does not comply with the two-phase approximation. The two resulting scattering curves are approximately proportional to each other in this particular case. The anomalous small-angle X-ray scattering resonant curve at the Ni absorption edge equals the Ni–Ni partial structure factor and, owing to the favourable neutron scattering lengths of Ni, La and Al, the neutron scattering curve is also proportional to that partial structure factor.
OLEX2: a complete structure solution, refinement and analysis program
Authors: Dolomanov Oleg V. , Bourhis Luc J. , Gildea Richard J. , Howard Judith A. K. , Puschmann Horst
Published: January 2009

New software,OLEX2, has been developed for the determination, visualization and analysis of molecular crystal structures. The software has a portable mouse-driven workflow-oriented and fully comprehensive graphical user interface for structure solution, refinement and report generation, as well as novel tools for structure analysis.OLEX2seamlessly links all aspects of the structure solution, refinement and publication process and presents them in a single workflow-driven package, with the ultimate goal of producing an application which will be useful to both chemists and crystallographers.
CSSP(Consensus Secondary Structure Prediction): a web-based server for structural biologists
Authors: Gupta Ankit , Deshpande Avnish , Amburi Janardhan Kumar , Sabarinathan Radhakrishnan , Senthilkumar Ramaswamy , Sekar Kanagaraj
Published: January 2009

Sequence–structure correlation studies are important in deciphering the relationships between various structural aspects, which may shed light on the protein-folding problem. The first step of this process is the prediction of secondary structure for a protein sequence of unknown three-dimensional structure. To this end, a web server has been created to predict the consensus secondary structure using well known algorithms from the literature. Furthermore, the server allows users to see the occurrence of predicted secondary structural elements in other structure and sequence databases and to visualize predicted helices as a helical wheel plot. The web server is accessible at http://bioserver1.physics.iisc.ernet.in/cssp/.
Evolution of basin architecture in an incipient continental rift: the Cenozoic Most Basin, Eger Graben (Central Europe)
Authors: Rajchl Michal , Uličný David , Grygar Radomír , Mach Karel
Published: January 2009

The Oligo‐Miocene Most Basin is the largest preserved sedimentary basin within the Eger Graben, the easternmost part of the European Cenozoic Rift System (ECRIS). The basin is interpreted as a part of an incipient rift system that underwent two distinct phases of extension. The first phase, characterised by NNE–SSW‐ to N–S‐oriented horizontal extension between the end of Eocene and early Miocene, was oblique to the rift axis and caused evolution of a fault system characterised by en‐échelon‐arranged E–W (ENE–WSW) faults. These faults defined a number of small, shallow initial depocentres of very small subsidence rates that gradually merged during the growth and linkage of the normal fault segments. The youngest part of the basin fill indicates accelerated subsidence caused probably by the concentration of displacement at several major bounding faults. Major post‐depositional faulting and forced folding were related to a change in the extension vector to an orthogonal position with respect to the rift axis and overprinting of the E–W faults by an NE–SW normal fault system. The origin of the palaeostress field of the earlier, oblique, extensional phase remains controversial and can be attributed either to the effects of the Alpine lithospheric root or (perhaps more likely because of the dominant volcanism at the onset of Eger Graben formation) to doming due to thermal perturbation of the lithosphere. The later, orthogonal, extensional phase is explained by stretching along the crest of a growing regional‐scale anticlinal feature, which supports the recent hypothesis of lithospheric folding in the Alpine–Carpathian foreland.
Siglec‐8 on human eosinophils and mast cells, and Siglec‐F on murine eosinophils, are functionally related inhibitory receptors
Authors: Bochner B. S.
Published: January 2009

Siglecs (sialic acid‐binding, Ig‐like lectins) are a family of single‐pass transmembrane cell surface proteins found predominantly on leucocytes. Their unique structural characteristics include an N‐terminal carbohydrate‐binding (‘lectin’) domain that binds sialic acid, followed by a variable number of Ig‐like domains, hence these structures are a subset of the Ig gene superfamily. Another unique feature of Siglecs is that most, but not all, possess so‐called immunoreceptor tyrosine‐based inhibitory motifs in their cytoplasmic domains, suggesting that these molecules function in an inhibitory capacity. Siglec‐8, the eighth member identified at the time, was discovered as part of an effort initiated almost a decade ago to identify novel human eosinophil and mast cell proteins. Since that time, its selective expression on human eosinophils and mast cells has been confirmed. On eosinophils, Siglec‐8 engagement results in apoptosis, whereas on mast cells, inhibition of FcɛRI‐dependent mediator release, without apoptosis, is seen. It has subsequently been determined that the closest functional paralog in the mouse is Siglec‐F, selectively expressed by eosinophils but not expressed on mast cells. Despite only modest homology, both Siglec‐8 and Siglec‐F preferentially recognize a sulphated glycan ligand closely related to sialyl Lewis X, a common ligand for the selectin family of adhesion molecules. Murine experiments in normal, Siglec‐F‐deficient mice and hypereosinophilic mice have resulted in similar conclusions that Siglec‐F, like Siglec‐8, plays a distinctive and important role in regulating eosinophil accumulation and survival in vivo. Given the resurgent interest in eosinophil‐directed therapies for a variety of disorders, plus its unique additional ability to also target the mast cell, therapies focusing on Siglec‐8 could some day prove to be a useful adjunct to our current armamentarium for the treatment of asthma, allergies and related disorders where overproduction and overactivity of eosinophils and mast cells is occurring.
Characterization of the major allergens of Pachycondyla chinensis in ant sting anaphylaxis patients
Authors: Lee E. K. , Jeong K. Y. , Lyu D‐P. , Lee Y‐W. , Sohn J‐H. , Lim K‐J. , Hong C‐S. , Park J‐W.
Published: January 2009

Background
The ant species Pachycondyla chinensis, which has spread from Far Eastern Asia to New Zealand and North America, induces anaphylactic reactions in human with its sting. However, the major allergens of P. chinensis have not yet been characterized.

Methods
We selected seven patients with histories of anaphylaxis induced by P. chinensis. Two‐dimensional electrophoresis (2‐DE) was used to identify the major allergens. We subsequently performed Western blots for P. chinensis‐specific IgEs, N‐terminal amino acid sequencing, ESI‐MS/MS, and RT‐PCR using primers based on the N‐terminal sequence.

Results
Six of the anaphylactic subjects had an IgE specific to a 23 kDa allergen of P. chinensis. Two candidates for major allergens, 23 kDa (pI 8.7) and 25 kDa (pI 6.2), were revealed by 2‐DE using P. chinensis‐specific IgE immunoblotting. In N‐terminal sequencing and ESI‐MS/MS analysis, 23 kDa (pI 8.7) and 25 kDa (pI 6.2) allergens, belonging to the protein families of antigen 5, were identified and share marked amino acid sequence similarity. The 23 kDa allergen is 206 amino acids in length and homology searches showed 54.0% and 50.0% homology with Sol i 3 and Ves v 5, respectively.

Conclusion
The major allergens of P. chinensis are 23 kDa (pI 8.7) and 25 kDa (pI 6.2) proteins that belong to the antigen 5 family of proteins.
Comparative analysis of mononuclear cells isolated from mucosal lymphoid follicles of the human ileum and colon
Authors: Junker Y , Bode H , Wahnschaffe U , Kroesen A , Loddenkemper C , Duchmann R , Zeitz M , Ullrich R
Published: January 2009

Studies of human mucosal lymphoid follicles are rare and have been limited to children's Peyer's patches, which are visible at endoscopy. We investigated lymphoid follicles in ileum biopsies of 87 patients and surgical colon specimens from 66 cancer patients, and examined phenotype and function of isolated follicular immune cells. Two (0–10) and 12 (0–117) follicles per patient were found in ileum and colon samples respectively (P < 0·001). The number of lymphoid follicles mononuclear cells (LFMC) that could be isolated per patient was higher from colon compared with ileum specimens [725 000 (0–23 Mio) versus 100 000 (0–1·3 Mio), P < 0·001]. T cells were predominant in both LFMC and lamina propria mononuclear cells (LPMC), but B cells were more and plasma cells less frequent in LFMC. T cells from mucosal follicles were more frequently CD4-positive and CD62L-positive, but less frequently CD8-positive, CD103-positive and CD69-positive than lamina propria T cells. LFMC from ileum compared with colon showed no differences in mononuclear cell composition. Anti-CD3/CD28 stimulation induced similar proliferation of LFMC and LPMC from ileum and colon, as well as secretion of high levels of interferon-γ, tumour necrosis factor-α and interleukin (IL)-2, but lower levels of IL-4, IL-6 and IL-10. LFMC from colon secreted more IL-2 than those from ileum. Our study shows that mucosal lymphoid follicles can be identified clearly in adult human colon and yield viable immune cells sufficient for phenotypical and functional analysis. The cellular composition of LFMC from ileum and colon is similar, and both secrete predominantly T helper type 1 cytokines.
Polycomb complexes regulate cellular senescence by repression of ARF in cooperation with E2F3
Authors: Miki Jun , Fujimura Yu‐ichi , Koseki Haruhiko , Kamijo Takehiko
Published: January 2009

Cellular senescence is a program in normal cells triggered in response to various types of stress that cells experience when they are explanted into culture. In this study, functional analyses on the role of the class II polycomb complex in cellular senescence were performed using mouse embryo fibroblasts (MEFs) with a genetically deleted member of the complex, Mel18. Mel18‐null MEFs undergo typical premature senescence accompanied by the up‐regulation of ARF/p53/p16INK4a and decrease of Ring1b/Bmi1. Our results demonstrated that ARF or p53 deletion cancels the senescence in Mel18‐null MEFs, and the fact that p16INK4a is up‐regulated in double‐null MEFs suggests that the ARF/p53 pathway plays a central role in stress‐induced senescence. The in vivo binding of Ring1b and E2F3b to the ARF promoter decreased progressively in senescence, and Mel18 inactivation accelerated the exfoliation of Ring1b/E2F3b from the promoter sequence, indicating the cooperation of polycombs/E2F3b on ARF expression and cellular senescence. Taken together, it seems that class II polycomb proteins and E2F3b dually control cellular senescence via the ARF/p53 pathway.
Structural basis of PSGL‐1 binding to ERM proteins
Authors: Takai Yumiko , Kitano Ken , Terawaki Shin‐ichi , Maesaki Ryoko , Hakoshima Toshio
Published: January 2009

P‐selectin glycoprotein ligand‐1 (PSGL‐1), an adhesion molecule with O‐glycosylated extracellular sialomucins, is involved in leukocyte inflammatory responses. On activation, ezrin–radixin–moesin (ERM) proteins mediate the redistribution of PSGL‐1 on polarized cell surfaces to facilitate binding to target molecules. ERM proteins recognize a short binding motif, Motif‐1, conserved in cytoplasmic tails of adhesion molecules, whereas PSGL‐1 lacks Motif‐1 residues important for binding to ERM proteins. The crystal structure of the complex between the radixin FERM domain and a PSGL‐1 juxtamembrane peptide reveals that the peptide binds the groove of FERM subdomain C by forming a β‐strand associated with strand β5C, followed by a loop flipped out towards the solvent. The Motif‐1 310 helix present in the FERM–ICAM‐2 complex is absent in PSGL‐1 given the absence of a critical Motif‐1 alanine residue, and PSGL‐1 reduces its contact area with subdomain C. Non‐conserved positions are occupied by large residues Met9 and His8, which stabilize peptide conformation and enhance groove binding. Non‐conserved residues play an important role in compensating for loss of binding energy resulting from the absence of conserved residues important for binding.
DNA supercoiling factor positively regulates expression of the homeotic gene Abdominal‐B in Drosophila melanogaster
Authors: Ogasawara Youhei , Furuhashi Hirofumi , Hirose Susumu
Published: January 2009

DNA supercoiling factor (SCF) generates unconstrained negative supercoils of DNA in conjunction with eukaryotic topoisomerase II. In Drosophila melanogaster, SCF localizes to puffs on polytene chromosomes and is required for dosage compensation via hypertranscripton of genes on the male X chromosome. The present study investigated the role of SCF on autosomes. Although RNAi knockdown of scf results in male lethality, some escapers showed anterior homeotic transformation of the male sixth abdominal segment, similar to that arising from reduced expression of Abdominal‐B (Abd‐B). Heterozygotes for an scf mutant allele (scf1) displayed suppression of Pc mutation‐dependent posterior transformation and enhancement of anterior transformation caused by trxG mutations. The level of Abd‐B mRNA decreased in scf1 embryos compared with wild‐type. Tiling array experiments showed the presence of significant SCF signals in an Abd‐B promoter region. Expression from the basal Abd‐B promoter on a transgene was reduced in scf1 embryos compared with wild‐type. Collectively, these results demonstrate that SCF occupies the promoter region of Abd‐B and activates expression for the proper formation of abdominal segments. Furthermore, preferential occupancy of SCF around transcription start sites of many active genes suggests a role for the factor in positive regulation of promoters.
The Lys313 residue of the human Rad51 protein negatively regulates the strand‐exchange activity
Authors: Ishida Takako , Takizawa Yoshimasa , Sakane Isao , Kurumizaka Hitoshi
Published: January 2009

The Rad51 protein, which catalyzes homologous‐pairing and strand‐exchange reactions, is an essential enzyme for homologous recombinational repair (HRR) and meiotic homologous recombination in eukaryotes. In humans, the conventional Rad51 (HsRad51) protein has a Lys residue at position 313; however, the HsRad51‐Q313 protein, in which the Lys313 residue is replaced by Gln, was reported as an isoform, probably corresponding to a polymorphic variant. In this study, we purified the HsRad51‐K313 and HsRad51‐Q313 isoforms and analyzed their biochemical activities in vitro. Compared to the conventional HsRad51‐K313 protein, the HsRad51‐Q313 protein exhibited significantly enhanced strand‐exchange activity under conditions with Ca2+, although the difference was not observed without Ca2+. A double‐stranded DNA (dsDNA) unwinding assay revealed that the HsRad51‐Q313 protein clearly showed enhanced DNA unwinding activity, probably due to its enhanced filament‐formation ability. Mutational analyses of the HsRad51‐Lys313 residue revealed that positively charged residues (Lys and Arg), but not negatively charged, polar and hydrophobic residues (Glu, Gln and Met, respectively), at position 313 reduced the strand‐exchange and DNA unwinding abilities of the HsRad51 protein. These results suggest that the electrostatic environment around position 313 is important for the regulation of the HsRad51 recombinase activity.
Some ignimbrite localities of the English Lake District
Authors: Horsley David
Published: January 2009

The English Lake District, comprising much of the county of Cumbria, is rightly celebrated for the glories of its scenery, its association with poets and artists, and its geology. One of the founding National Parks in the United Kingdom, it receives thousands of visitors world‐wide every year. Geologically, the Borrowdale Volcanic Group, and its ignimbrites in particular, is worthy of greater study; its localities are available to all.
Depth and shape estimates from simultaneous inversion of magnetic fields and their gradient components using differential similarity transforms
Authors: Stavrev Petar , Gerovska Daniela , Araúzo‐Bravo Marcos J.
Published: January 2009

The differential similarity transform of a magnetic anomaly is a linear combination of its intensity and gradient components. This transform is sensitive to the distance between a chosen central point of similarity and the source and depends on the degree of homogeneity of the field. Taking advantage of this property, a new field inversion method resulting in the evaluation of source position and shape type is proposed and implemented. The field gradient components are measured directly in magnetic gradiometry, or they can be calculated from the measured field data. Regional and local linear backgrounds are accounted for by the method. The method can be applied on either regularly or irregularly‐spaced data sets, on even or uneven surfaces of observation. The solving of the systems of equations is not necessary. A semi‐automated inversion for both location and shape of the sources is implemented. Model and field tests illustrate the effectiveness of the proposed inversion technique for depth and shape estimates.
Use of stored carbon reserves in growth of temperate tree roots and leaf buds: analyses using radiocarbon measurements and modeling
Authors: GAUDINSKI J. B. , TORN M. S. , RILEY W. J. , SWANSTON C. , TRUMBORE S. E. , JOSLIN J. D. , MAJDI H. , DAWSON T. E. , HANSON P. J.
Published: January 2009

Characterizing the use of carbon (C) reserves in trees is important for understanding regional and global C cycles, stress responses, asynchrony between photosynthetic activity and growth demand, and isotopic exchanges in studies of tree physiology and ecosystem C cycling. Using an inadvertent, whole‐ecosystem radiocarbon (14C) release in a temperate deciduous oak forest and numerical modeling, we estimated that the mean age of stored C used to grow both leaf buds and new roots is 0.7 years and about 55% of new‐root growth annually comes from stored C. Therefore, the calculated mean age of C used to grow new‐root tissue is ∼0.4 years. In short, new roots contain a lot of stored C but it is young in age. Additionally, the type of structure used to model stored C input is important. Model structures that did not include storage, or that assumed stored and new C mixed well (within root or shoot tissues) before being used for root growth, did not fit the data nearly as well as when a distinct storage pool was used. Consistent with these whole‐ecosystem labeling results, the mean age of C in new‐root tissues determined using ‘bomb‐14C’ in three additional forest sites in North America and Europe (one deciduous, two coniferous) was less than 1–2 years. The effect of stored reserves on estimated ages of fine roots is unlikely to be large in most natural abundance isotope studies. However, models of root C dynamics should take stored reserves into account, particularly for pulse‐labeling studies and fast‐cycling roots (<1 years).
Physiological responses of two contrasting desert plant species to precipitation variability are differentially regulated by soil moisture and nitrogen dynamics
Authors: PATRICK LISA D. , OGLE KIONA , BELL COLIN W. , ZAK JOHN , TISSUE DAVID
Published: January 2009

Alterations in global and regional precipitation patterns are expected to affect plant and ecosystem productivity, especially in water‐limited ecosystems. This study examined the effects of natural and supplemental (25% increase) seasonal precipitation on a sotol grassland ecosystem in Big Bend National Park in the Chihuahuan Desert. Physiological responses – leaf photosynthesis at saturating light (Asat), stomatal conductance (gs), and leaf nitrogen [N] – of two species differing in their life form and physiological strategies (Dasylirion leiophyllum, a C3shrub;Bouteloua curtipendula, a C4grass) were measured over 3 years (2004–2006) that differed greatly in their annual and seasonal precipitation patterns (2004: wet, 2005: average, 2006: dry). Precipitation inputs are likely to affect leaf‐level physiology through the direct effects of altered soil water and soil nitrogen. Thus, the effects of precipitation, watering treatment, soil moisture, and nitrogen were quantified via multivariate hierarchical Bayesian models that explicitly linked the leaf and soil responses. The two species differed in their physiological responses to precipitation and were differentially controlled by soil water vs. soil nitrogen. In the relatively deeply rooted C3shrub,D. leiophyllum, Asatwas highest in moist periods and was primarily regulated by deep (16–30 cm) soil water. In the shallow‐rooted C4grass,B. curtipendula, Asatwas only coupled to leaf [N], both of which increased in dry periods when soil [N] was highest. Supplemental watering during the wet year generally decreasedAsatand leaf [N] inD. leiophyllum, perhaps due to nutrient limitation, and physiological responses in this species were influenced by the cumulative effects of 5 years of supplemental watering. Both species are common in this ecosystem and responded strongly, yet differently, to soil moisture and nitrogen, suggesting that changes in the timing and magnitude of precipitation may have consequences for plant carbon gain, with the potential to alter community composition.
Estimating colonization potential of migrant tree species
Authors: IBÁÑEZ INÉS , CLARK JAMES S. , DIETZE MICHAEL C.
Published: January 2009

Plant populations migrating in response to climate change will have to colonize established communities. Even if a population disperses to a new region with a favorable climate, interactions with other species may prevent its establishment and further spread. The potential of these species to grow along with residents will be a critical factor controlling their response to climate change. To determine the capacity of migrating species to colonize established communities we conducted extensive long‐term transplant experiments where potential tree migrant species, i.e. species within ‘migration range,’ were planted side by side with resident ones. Potential immigrants were selected to be representative species of their native communities. For both groups, residents and potential migrants (17 species), we compared their growth response along gradients in soil moisture and light availability. Rather than manipulate climate directly, we exploited natural microclimatic gradients and the fluctuations in climate that occurred during the 5‐year experiment. Experimental results were used to estimate growth in the context of novel climate and relevant establishment factors. Results suggest that potential immigrant species had similar growth rates in the new environment than those from resident species ensuring their ability to establish in the area. However, contrary to our expectations, the soil moisture requirements for the immigrant group were similar to those of the resident species. These results could have major implications for vegetation changes under the predicted drier climate for the region. If it is the case that neither resident species nor potential migrants are able to maintain stable populations, the region may experience a decline in local biodiversity.
Spontaneous complement activation on human B cells results in localized membrane depolarization and the clustering of complement receptor type 2 and C3 fragments
Authors: Løbner Morten , Leslie Robert G. Q. , Prodinger Wolfgang M. , Nielsen Claus H.
Published: January 2009

While our previous studies have demonstrated that complement activation induced by complement receptors type 2 (CR2/CD21) and 1 (CR1/CD35) results in C3‐fragment deposition and membrane attack complex (MAC) formation in human B cells, the consequences of these events for B‐cell functions remain unknown. In the present study, we show that CR2‐induced complement activation results in membrane depolarization, as indicated by annexin V binding, with kinetics similar to those of C3‐fragment deposition and different from those of MAC formation. On the other hand, like MAC formation, depolarization requires activation of complement via the alternative pathway, as indicated by total inhibition upon neutralization of factor D, and is abrogated by combined blockade of CR1 and CR2, but not of either receptor alone. The membrane depolarization is not associated with the apoptosis of B cells, as examined by co‐staining with APO‐2.7 or by the TdT‐mediated biotin–dUTP nick‐end labelling (TUNEL) assay. Confocal microscopy revealed that depolarization and C3 deposition, unlike MAC deposition, are limited to restricted areas on the B‐cell surface. Double staining revealed a close association between the C3‐fragment patches and membrane depolarization, as well as redistribution of lipid rafts to these areas. We propose that these events may play a role in the regulation of B‐cell signalling and cross‐talk with T cells.
Genetic and epigenetic networks controlling T helper 1 cell differentiation
Authors: Placek Katarzyna , Coffre Maryaline , Maiella Sylvie , Bianchi Elisabetta , Rogge Lars
Published: January 2009

Significant progress has been made during the past years in our understanding of the mechanisms that control the differentiation of naïve CD4+ T cells into effector T‐cell subsets with distinct functional properties. Previous work allowed the identification of key molecules involved in regulating this highly complex process, such as cytokines and their receptors, signal transducers and transcription factors. More recently, the emphasis of research in this field has been to elucidate how the multiplicity of signals is integrated to shape a T helper subset‐specific gene‐expression program controlling differentiation and effector functions. In this review we will highlight advances that have been made in unravelling the genetic and epigenetic networks controlling differentiation of naïve CD4+ T cells into interferon‐γ(IFN‐γ)‐secreting T helper type 1 (Th1) cells.
Clinical efficiency of a natural resin fluoride varnish (Shellac F) in reducing dentin hypersensitivity
Authors: HOANG‐DAO B.‐T. , HOANG‐TU H. , TRAN‐THI N.‐N. , KOUBI G. , CAMPS J. , ABOUT I.
Published: January 2009

Summary  Previous in vitro permeability and scanning electron microscopic studies have demonstrated the effectiveness of a new natural based‐resin varnish (Shellac F) in dentin permeability reduction and effective tubule occlusion. The aim of this randomized double‐blind, controlled, split mouth 8‐week clinical study was to evaluate the efficiency of Shellac F in reducing dentin hypersensitivity. Ten patients (eight women: two men) completed the study. A quadrant including at least one hypersensitive tooth (Visual Analog Scale – VAS = 15 mm to air blast) was considered as a unit and randomly assigned to different groups for Shellac F, Duraphat®, Isodan®. Three applications of each material were completed at days 0, 1 and 7. The subjective response was assessed by tactile and thermal/evaporative methods. Data were collected at baseline and after the first application, at 15 min, 1, 7, 14, 28 and 56 days. Analysis was based on Kruskall–Wallis test, Wilcoxon signed rank test and the method of the least square means. No statistically significant difference was noted between Shellac F and the two control materials. Regardless of the type of stimulus, Shellac F showed significant immediate and progressive continuous efficiency in reducing dentin hypersensitivity until 56 days (VAS of 14 ± 12 mm and provoking pain force of 89 ± 12 cN, respectively, compared with 38 ± 23 mm and 41 ± 10 cN at baseline), corresponding to a highly effective relief dentin hypersensitivity. Shellac F reduced dentin hypersensitivity and did not differ from the two desensitizing agents used as controls.
Marginal fit of 14‐unit zirconia fixed dental prosthesis retainers
Authors: BEUER F. , NEUMEIER P. , NAUMANN M.
Published: January 2009

Summary  The marginal fit of 14‐unit fixed dental prosthesis retainers and single‐crown copings fabricated by the same computer‐aided design (CAD)/computer‐aided manufacturing (CAM) system were evaluated in vitro hypothesizing that the marginal opening might be independent of the type of restoration. Eight ivorine maxillary teeth (FDI locations 27, 25, 23, 21, 11, 13, 15 and 17) were prepared to accommodate a 14‐unit prosthesis. Ten fixed dental prosthesis retainers and 40 single‐crown‐copings were fabricated using Zeno CAD/CAM on 20 master dies. Four cross‐sections were made from each tooth and the marginal gap dimensions were measured. One‐way anova was used to test the difference between the experimental groups and two‐way anova and a post hoc test (Student–Newman–Keuls) were carried out to determine the influence of the location of the abutment tooth and the measurement location within the abutment tooth in the experimental groups (P < 0·05). Mean marginal gap dimensions and standard deviations for fixed dental prosthesis retainers and single‐crown copings were 25 ± 29 and 13 ± 12 μm, respectively. The type of restoration showed a significant influence (P < 0·001) on the marginal gap. The location of the abutment tooth (P < 0·001) and the measurement location (P < 0·001) exhibited significant influence on marginal gaps of fixed dental prosthesis retainers while no influence on single‐crown copings could be detected. The highest marginal gaps were found at the palatal surface of the incisor and canine of the 14‐unit fixed dental prosthesis retainers. Fourteen‐unit fixed dental prosthesis showed significantly higher marginal openings than single crowns fabricated under the same conditions. However, both restorations showed clinically acceptable marginal openings.
Acid stress activation of the σE stress response in Salmonella enterica serovar Typhimurium
Authors: Muller Cécile , Bang Iel‐Soo , Velayudhan Jyoti , Karlinsey Joyce , Papenfort Kai , Vogel Jörg , Fang Ferric C.
Published: January 2009

The alternative sigma factor σE is activated by unfolded outer membrane proteins (OMPs) and plays an essential role in Salmonella pathogenesis. The canonical pathway of σE activation in response to envelope stress involves sequential proteolysis of the anti‐sigma factor RseA by the PDZ proteases DegS and RseP. Here we show that σE in Salmonella enterica sv. Typhimurium can also be activated by acid stress. A σE‐deficient mutant exhibits increased susceptibility to acid pH and reduced survival in an acidified phagosomal vacuole. Acid activation of σE‐dependent gene expression is independent of the unfolded OMP signal or the DegS protease but requires processing of RseA by RseP. The RseP PDZ domain is indispensable for acid induction, suggesting that acid stress may disrupt an inhibitory interaction between RseA and the RseP PDZ domain to allow RseA proteolysis in the absence of antecedent action of DegS. These observations demonstrate a novel environmental stimulus and activation pathway for the σE regulon that appear to be critically important during Salmonella–host cell interactions.
Effect of spinal cord stimulation in a rodent model of post‐operative ileus
Authors: Maher J. , Johnson A. C. , Newman R. , Mendez S. , Hoffmann T. J. , Foreman R. , Greenwood‐van Meerveld B.
Published: January 2009

Abstract  Post‐operative ileus (POI) is a transient impairment of gastrointestinal (GI) transit that develops after abdominal surgery. The goal of this study was to investigate the effect of spinal cord stimulation (SCS) on gastric emptying and upper GI transit in a rat model of POI. All rats had an electrode placed on the dorsal surface of the spinal cord between the T5 and T8 segments. After recovery, gastric emptying and upper GI transit (geometric centre and head of meal) were assessed using a radiolabelled meal fed to each rat via oral gavage. In unanaesthetized rats, SCS (15, 25, 50, 100, 200 Hz, 0.2 ms at 90% motor threshold for 15 min) was performed immediately after the meal. The sham control group had no current applied. The naïve group was without POI or SCS. Gastric emptying was significantly delayed in sham‐stimulated rats with POI compared with naïve controls (39.8 ± 6.2%vs 76.5 ± 4.9%, P < 0.001). In rats with POI that underwent SCS, there was a significant acceleration of gastric emptying to levels that resembled those of naïve controls (65.1 ± 7.4%, P < 0.05). However, while SCS did not normalize the geometric centre and head of the meal when compared with the naïve group, it did significantly improve both parameters compared with the sham stimulation group. In summary, SCS normalizes gastric emptying and improves upper GI transit in a rodent model of POI. Further experiments are required to address the mechanism(s) by which SCS exhibits prokinetic activity.
Development of the enteric nervous system: bringing together cells, signals and genes
Authors: Burns A. J. , Pachnis V.
Published: January 2009

Abstract  The enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract that controls essential functions such as motility, secretion and blood flow, comprises a vast number of neurons and glial cells that are organized into complex networks of interconnected ganglia distributed throughout the entire length of the gut wall. Enteric neurons and glia are derived from neural crest cells that undergo extensive migration, proliferation, differentiation and survival in order to form a functional ENS. Investigations of the developmental processes that underlie ENS formation in animal models, and of the common human congenital ENS abnormality Hirschsprung’s disease, have been intimately related and recently led to major advances in the field. This review touches on some of these advances and introduces two topics that are elaborated upon in this journal issue: (i) genome wide approaches for profiling gene expression in wild type and mutant ENS that have been used to identify novel molecules with important roles in enteric neurogenesis, and (ii) the use of multilineage ENS progenitors isolated from embryonic or postnatal gut as novel cell replacement therapies for Hirschsprung’s disease. Such studies will not only unravel the mechanisms underlying ENS development, but will also shed light on the pathogenesis of ENS developmental disorders and help to establish novel therapeutic strategies for restoring or repairing malfunctioning enteric neural circuits prevalent in numerous gastrointestinal diseases.
The costing and funding of longitudinal birth cohort studies
Authors: Doyle Alan , Golding Jean
Published: January 2009

Key to the success of any longitudinal birth cohort study is the availability of appropriate and long‐term levels of funding. The ease or difficulty of obtaining necessary funds to carry out data collection, preparation and documentation efficiently will determine the quality of data and the ease with which it is made available for collaborators. Various strategies for acquiring funding are outlined.
A case of lethal hypophosphatasia providing new insights into the perinatal benign form of hypophosphatasia and expression of the ALPL gene
Authors: Brun‐Heath I , Chabrol E , Fox M , Drexler K , Petit C , Taillandier A , De Mazancourt P , Serre J‐L , Mornet E
Published: January 2009

Hypophosphatasia is a rare inherited bone disease caused by mutations in the alkaline phosphatase liver‐type gene (ALPL) gene, with extensive allelic heterogeneity leading to a range of clinical phenotypes. We report here a patient who died from severe lethal hypophosphatasia, who was compound heterozygous for the mutation c.1133A>T (D361V) and the newly detected missense mutation c791A>G, and whose parents were both healthy. Because the c.1133A>T (D361V) mutation was previously reported to have a dominant‐negative effect and to be responsible for the uncommon perinatal benign form of the disease, we studied the expression of the ALPL gene in this family. Analysis at the messenger RNA (mRNA) level, both quantitative and qualitative, showed that the paternal c.1133A>T (D361V) mutation was associated with over‐expression of the ALPL gene and that the maternal c.791A>G mutation lead to complete skipping of exon 7. The results provide an explanation of the lethal phenotype in the patient where the two ALPL alleles are non‐functional and in the asymptomatic father where over‐expression of the normal allele could counteract the effect of the c.1133A>T (D361V) mutation by providing an increased level of normal mRNA. This may also explain the variable expression of hypophosphatasia observed in parents of patients with the perinatal benign form.
Genetic heterogeneity of autosomal dominant hypercholesterolemia
Authors: Varret M , Abifadel M , Rabès J‐P , Boileau C
Published: January 2009

Autosomal dominant hypercholesterolemia (ADH) is characterized by isolated elevation of plasmatic low‐density lipoprotein cholesterol associated with high risk of premature cardiovascular complications. More than 1000 mutations in the LDLR gene and 9 in the APOB gene have been implicated. We have shown further heterogeneity with the discovery of missense mutations in the PCSK9 gene resulting in ADH. Different studies have tried to evaluate the respective contribution of mutations in each gene to the disease, but results were not always in agreement. After a brief overview of mutations reported for each gene, strategies and results of these different studies are reviewed and analyzed. Altogether, numerous reports give evidence for the existence of a greater level of genetic heterogeneity in ADH and the involvement of still unknown genes.
Polymorphisms spanning the 0N exon and promoter of the estrogen receptor‐beta (ERβ) gene ESR2 are associated with venous ulceration
Authors: Ashworth JJ , Smyth JV , Pendleton N , Horan M , Payton A , Worthington J , Ollier WE , Ashcroft GS
Published: January 2009

Venous ulcers are characterized by excessive inflammation and raised levels of proinflammatory cytokines. Estrogen has been shown to accelerate the rate of wound healing in elderly subjects by dampening the inflammatory response. The estrogen receptor (ER) proteins, ER‐alpha (ERα) and ER‐beta (ERβ) mediate the actions of estrogen during wound repair through the activation or repression of target gene transcription. Recent evidence implicates the chromosomal region harboring the ERβ gene with venous ulceration in a British Caucasian population, highlighting the need to conduct further genetic interrogation. To address this, we conducted a case‐control study to investigate whether single nucleotide polymorphisms in the ERβ gene are associated with venous ulceration in elderly (age >50 years) subjects. We recruited a case group (n = 124, 56 males and 68 females) consisting of patients with an active venous ulcer and a control group consisting of individuals from the general population with no evidence of venous disease or history of venous ulceration (n = 380, 189 males and 191 females). Polymorphisms in close proximity to upstream regulatory regions of the ERβ gene, including the 0N exon and promoter transcribed in inflammatory cells, were significantly (p < 0.05) associated with venous ulceration. A major susceptibility haplotype carried by 23% (26/112) of cases compared with only 10% (27/276) of controls (odds ratio = 2.8, 95% confidence interval = 1.6−5.0) was significantly (p < 0.01) associated with elevated serum levels of tumor necrosis factor‐alpha. In conclusion, common variation in the regulatory regions of the ERβ gene may pre‐dispose to venous ulceration in a British Caucasian population.
Myocardin gene regulatory variants as surrogate markers of cardiac hypertrophy – study in a genetically homogeneous population
Authors: Kontaraki JE , Parthenakis FI , Patrianakos AP , Karalis IK , Vardas PE
Published: January 2009

Myocardin is thought to contribute to heart hypertrophy as assessed in animal models. The aim of this study was to identify polymorphisms on the myocardin gene and investigate possible relationships with left ventricular structure in human hypertrophic cardiomyopathy (HCM). Eighty‐four native Cretan individuals (36 patients with HCM and 48 healthy controls) were examined by direct sequencing and subsequent restriction fragment length polymorphism analysis and six polymorphisms were identified in the promoter region at positions −435T>C (rs758187), −629A>T (rs8071072), −1030C>G (rs1233851), −1069A>G, −1166A>G and −1406G>A (rs976906). Allele and haplotype frequencies were not significantly different between patients and controls. However, patients carrying the [−435C;−629T] allelic variant had decreased left ventricular wall thickness (LVWT, p = 0.020) and left ventricular mass (p = 0.006) as compared with the wild‐type genotype. Carrier status of this myocardin promoter allelic variant was also associated with significant lower myocardin mRNA levels in peripheral blood (p = 0.039). Thus, a myocardin promoter allelic variant existing in the normal Cretan population was associated with decreased left ventricular mass in HCM patients and decreased myocardin mRNA levels in peripheral blood. Our results may be limited by the limited sample size, but are strengthened by the genetic homogeneity of the Cretan population. Our data suggest that functional natural myocardin promoter variation might be a genetic factor contributing to inter‐individual differences in the development of cardiac hypertrophy.
Skeletal dysplasias and the growth plate
Authors: Alman BA
Published: January 2009

Skeletal dysplasias are disorders in which there is derangement in the growth or shape of the skeleton. Long bone grows from cartilage that persists near the ends until skeletal maturity as the growth plate. Developmental biology work has identified the major regulatory proteins in growth plate chondroyte function. There are hundreds of skeletal dysplasias, and the molecular genetic etiology of many was defined in the past decade and a half. Now that the causative genes for these disorders have been identified, they can be broadly classified by the function of the protein that these genes encode for into disorders caused by extracellular structural proteins, proteins that regulate normal growth plate chondrocyte differentiation and patterning, and enzymes that process these proteins. There are clinical similarities within each group, and the phenotype can be predicted based on the role of the mutated protein in normal growth plate function. As such, this framework to classify the skeletal dysplasias has practical clinical implications.
Cultural enhancement of a clinical service to meet the needs of indigenous people; genetic service development in response to issues for New Zealand Maori
Authors: Port RV , Arnold J , Kerr D , Gravish N , Winship I
Published: January 2009

The delivery of good health care services within clinical settings is predicated by an understanding of the needs of the stakeholders*. Most of the information generated to date on the transfer of mutational analysis to clinical service has been within a Eurocentric model favouring individual autonomy. It is predictable that this model does not easily translate for other cultures.

Current genetic technology has elucidated the molecular basis of many diseases. In familial cancer and other late‐onset disorders, there is now the possibility of ‘prediction’ where a high risk conferred by family history can be confirmed or negated by genetic testing. In paediatric disorders, prediction is offered in the form of prenatal or pre‐implantation genetic diagnosis. We report on the processes undertaken in an attempt to provide a culturally sensitive service for the Maori people of Aotearoa, New Zealand.
MMP2 promoter polymorphism (C‐1306T) and risk of recurrence in patients with hepatocellular carcinoma after transplantation
Authors: Wu LM , Zhang F , Xie HY , Xu X , Chen QX , Yin SY , Liu XC , Zhou L , Xu XB , Sun YL , Zheng SS
Published: January 2009

Genetic variants in matrix metalloproteinase (MMP) gene may influence the biological function of these enzymes and change their role in carcinogenesis and progression. The effect of MMP2 C‐1306T and MMP9 C‐1562T polymorphisms on genetic susceptibility has been investigated in various kinds of cancer. However, the relationship between these polymorphisms and risk of recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has not been reported. The present study was designed to investigate the association of these two loci with the risk of HCC recurrence in 93 HCC patients treated with LT. Genotyping was performed using direct DNA sequencing. For MMP2 C‐1306T variant, patients with CT heterozygous conferred a 58% reduction in recurrence risk (risk ratio: 0.419; 95% confidence interval: 0.177–0.994). The mean recurrence‐free survival for CT genotype was significantly longer than that for homozygous CC patients (30.4 vs 19.3 months, p = 0.019). However, no association was found between MMP9 C‐1562T polymorphisms and recurrence of HCC (p = 0.259). These findings suggest that MMP2 promoter polymorphisms may provide some predictive value for HCC recurrence after LT.