bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular mechanisms used by chaperones to reduce the toxicity of aberrant protein oligomers
Authors: Mannini Benedetta , Cascella Roberta , Zampagni Mariagioia , van Waarde-Verhagen Maria , Meehan Sarah , Roodveldt Cintia , Campioni Silvia , Boninsegna Matilde , Penco Amanda , Relini Annalisa , Kampinga Harm H. , Dobson Christopher M. , Wilson Mark R. , Cecchi Cristina , Chiti Fabrizio
Published: July 2012

Chaperones are the primary regulators of the proteostasis network and are known to facilitate protein folding, inhibit protein aggregation, and promote disaggregation and clearance of misfolded aggregates inside cells. We have tested the effects of five chaperones on the toxicity of misfolded oligomers preformed from three different proteins added extracellularly to cultured cells. All the chaperones were found to decrease oligomer toxicity significantly, even at very low chaperone/protein molar ratios, provided that they were added extracellularly rather than being overexpressed in the cytosol. Infrared spectroscopy and site-directed labeling experiments using pyrene ruled out structural reorganizations within the discrete oligomers. Rather, confocal microscopy, SDS-PAGE, and intrinsic fluorescence measurements indicated tight binding between oligomers and chaperones. Moreover, atomic force microscopy imaging indicated that larger assemblies of oligomers are formed in the presence of the chaperones. This suggests that the chaperones bind to the oligomers and promote their assembly into larger species, with consequent shielding of the reactive surfaces and a decrease in their diffusional mobility. Overall, the data indicate a generic ability of chaperones to neutralize extracellular misfolded oligomers efficiently and reveal that further assembly of protein oligomers into larger species can be an effective strategy to neutralize such extracellular species.
Diversification of complex butterfly wing patterns by repeated regulatory evolution of aWntligand
Authors: Martin Arnaud , Papa Riccardo , Nadeau Nicola J. , Hill Ryan I. , Counterman Brian A. , Halder Georg , Jiggins Chris D. , Kronforst Marcus R. , Long Anthony D. , McMillan W. Owen , Reed Robert D.
Published: July 2012

Although animals display a rich variety of shapes and patterns, the genetic changes that explain how complex forms arise are still unclear. Here we take advantage of the extensive diversity ofHeliconiusbutterflies to identify a gene that causes adaptive variation of black wing patterns within and between species. Linkage mapping in two species groups, gene-expression analysis in seven species, and pharmacological treatments all indicate thatcis-regulatory evolution of theWntAligand underpins discrete changes in color pattern features across theHeliconiusgenus. These results illustrate how the direct modulation of morphogen sources can generate a wide array of unique morphologies, thus providing a link between natural genetic variation, pattern formation, and adaptation.
Crystal structure of IgE bound to its B-cell receptor CD23 reveals a mechanism of reciprocal allosteric inhibition with high affinity receptor FcεRI
Authors: Dhaliwal Balvinder , Yuan Daopeng , Pang Marie O. Y. , Henry Alistair J. , Cain Katharine , Oxbrow Amanda , Fabiane Stella M. , Beavil Andrew J. , McDonnell James M. , Gould Hannah J. , Sutton Brian J.
Published: July 2012

The role of IgE in allergic disease mechanisms is performed principally through its interactions with two receptors, FcεRI on mast cells and basophils, and CD23 (FcεRII) on B cells. The former mediates allergic hypersensitivity, the latter regulates IgE levels, and both receptors, also expressed on antigen-presenting cells, contribute to allergen uptake and presentation to the immune system. We have solved the crystal structure of the soluble lectin-like “head” domain of CD23 (derCD23) bound to a subfragment of IgE-Fc consisting of the dimer of Cε3 and Cε4 domains (Fcε3-4). One CD23 head binds to each heavy chain at the interface between the two domains, explaining the known 2:1 stoichiometry and suggesting mechanisms for cross-linking membrane-bound trimeric CD23 by IgE, or membrane IgE by soluble trimeric forms of CD23, both of which may contribute to the regulation of IgE synthesis by B cells. The two symmetrically located binding sites are distant from the single FcεRI binding site, which lies at the opposite ends of the Cε3 domains. Structural comparisons with both free IgE-Fc and its FcεRI complex reveal not only that the conformational changes in IgE-Fc required for CD23 binding are incompatible with FcεRI binding, but also that the converse is true. The two binding sites are allosterically linked. We demonstrate experimentally the reciprocal inhibition of CD23 and FcεRI binding in solution and suggest that the mutual exclusion of receptor binding allows IgE to function independently through its two receptors.
Historical genomics of North American maize
Authors: van Heerwaarden Joost , Hufford Matthew B. , Ross-Ibarra Jeffrey
Published: July 2012

Since the advent of modern plant breeding in the 1930s, North American maize has undergone a dramatic adaptation to high-input agriculture. Despite the importance of genetic contributions to historical yield increases, little is known about the underlying genomic changes. Here we use high-density SNP genotyping to characterize a set of North American maize lines spanning the history of modern breeding. We provide a unique analysis of genome-wide developments in genetic diversity, ancestry, and selection. The genomic history of maize is marked by a steady increase in genetic differentiation and linkage disequilibrium, whereas allele frequencies in the total population have remained relatively constant. These changes are associated with increasing genetic separation of breeding pools and decreased diversity in the ancestry of individual lines. We confirm that modern heterotic groups are the product of ongoing divergence from a relatively homogeneous landrace population, but show that differential landrace ancestry remains evident. Using a recent association approach, we characterize signals of directional selection throughout the genome, identifying a number of candidate genes of potential agronomic relevance. However, overall we find that selection has had limited impact on genome-wide patterns of diversity and ancestry, with little evidence for individual lines contributing disproportionately to the accumulation of favorable alleles in today's elite germplasm. Our data suggest breeding progress has mainly involved selection and recombination of relatively common alleles, contributed by a representative but limited set of ancestral lines.
Yip1 domain family, member 6 (Yipf6) mutation induces spontaneous intestinal inflammation in mice
Authors: Brandl Katharina , Tomisato Wataru , Li Xiaohong , Neppl Christina , Pirie Elaine , Falk Werner , Xia Yu , Moresco Eva Marie Y. , Baccala Roberto , Theofilopoulos Argyrios N. , Schnabl Bernd , Beutler Bruce
Published: July 2012

Using an environmentally sensitized genetic screen we identified mutations that cause inflammatory colitis in mice. The X-linked
Klein-Zschocher
(
KLZ
) mutation created a null allele of
Yipf6
, a member of a gene family believed to regulate vesicular transport in yeast, but without known functions in mammals. Yipf6 is a five transmembrane-spanning protein associated with Golgi compartments.
Klein-Zschocher
mutants were extremely sensitive to colitis induced by dextran sodium sulfate (DSS) and developed spontaneous ileitis and colitis after 16 mo of age in specific pathogen-free housing conditions. Electron microscopy, gene expression, and immunocytochemistry analyses provided evidence that impaired intestinal homeostasis stemmed from defective formation and secretion of large secretory granules from Paneth and goblet cells. These studies support a tissue- and organ-specific function for Yipf6 in the maintenance of intestinal homeostasis and implicate the orthologous human gene as a disease susceptibility locus.
Comparison of Gill Nets and Fixed‐Frame Trawls for Sampling Threadfin Shad in Tropical Reservoirs
Authors: Prchalová Marie , Neal J. Wesley , Muñoz‐Hincapié Milton , Jůza Tomáš , Říha Milan , Peterka Jiří , Kubečka Jan
Published: July 2012

Threadfin shad Dorosoma petenense populations were sampled quarterly from 2010 to 2011 to determine appropriate sampling techniques for this species in tropical reservoirs of Puerto Rico. Offshore gill netting and night trawling were compared in terms of catch per unit of effort, size distribution, sampling precision, and bycatch. In total, 90 gill net–trawl pairs of catches were compared, which collected more than 80,000 threadfin shad. Gill‐net and trawl catches were not correlated in either number or biomass. Coefficients of variation were greater in gill‐net sampling (0.761 for numbers, 0.747 for biomass) than in trawl sampling (0.433 and 0.465, respectively) and were not dependent on reservoir, sampling season, reservoir section, or any combination of these factors for any gear. There was no correspondence in size distributions between gill‐net and trawl catches. Gill nets collected threadfin shad in the range of 23–169 mm total length (TL) and displayed strong mesh size selectivity, causing distinct unrealistic peaks in size distribution. Gill nets underestimated threadfin shad smaller than 35 mm TL and overestimated shad bigger than 90 mm TL. The size range of threadfin shad collected via trawl was 10–108 mm TL, and trawls did not appear to be as size selective for fish up to 80 mm TL. Trawling was found to be the superior sampling technique for shad populations in pelagic habitats of Puerto Rican reservoirs, which consisted mainly of fish up to 80 mm TL. Trawling provided a more realistic picture of size distributions, collected far less bycatch, was less affected by the schooling of shad, and was less laborious and more cost‐effective than gill nets.
Biomechanics of Cervical “Skip” Corpectomy Versus Standard Multilevel Corpectomy
Authors: Yilmaz Murat , Yüksel Kasim Zafer , Baek Seungwon , Newcomb Anna G.U.S. , Dalbayrak Sedat , Sonntag Volker K.H. , Crawford Neil R.
Published: July 2012

Study Design:

In vitro biomechanical study of flexibility with finite-element simulation to estimate screw stresses.

Objective:

To compare cervical spinal stability after a standard plated 3-level corpectomy with stability after a plated 3-level “skip” corpectomy where the middle vertebra is left intact (ie, two 1-level corpectomies), and to quantify pullout forces acting on the screws during various loading modes.

Summary of Background Data:

Clinically, 3-level cervical plated corpectomy has a high rate of failure, partially because only 4 contact points affix the plate to the upper and lower intact vertebrae. Leaving the intermediate vertebral body intact for additional fixation points may overcome this problem while still allowing dural sac decompression.

Methods:

Quasistatic nonconstraining torque (maximum 1 N m) induced flexion, extension, lateral bending, and axial rotation while angular motion was recorded stereophotogrammetrically. Specimens were tested intact and after corpectomy with standard plated and strut-grafted 3-level corpectomy (7 specimens) or “skip” corpectomy (7 specimens). Screw stresses were quantified using a validated finite-element model of C3–C7 mimicking experimentally tested groups. Skip corpectomy with C5 screws omitted was also simulated.

Results:

Plated skip corpectomy tended to be more stable than plated standard corpectomy, but the difference was not significant. Compared with standard plated corpectomy, plated skip corpectomy reduced peak screw pullout force during axial rotation (mode of loading of highest peak force) by 15% (4-screw attachment) and 19% (6-screw attachment).

Conclusions:

Skip corpectomy is a good alternative to standard 3-level corpectomy to improve stability, especially during lateral bending. Under pure moment loading, the screws of a cervical multilevel plate experience the highest pullout forces during axial rotation. Thus, limiting this movement in patients undergoing plated multilevel corpectomy may be reasonable, especially until solid fusion is achieved.
THE USE OF VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITOR FOR CHOROIDAL NEOVASCULARIZATION COMPLICATING POSTERIOR UVEITIS IN EYES WITH FLUOCINOLONE ACETONIDE IMPLANTS
Authors: Lee Shelly T. , Gupta Seema R. , Richards Amanda B. , Suhler Eric B. , Smith Justine R. , Flaxel Christina J.
Published: July 2012

Purpose:

To present a series of eyes with multifocal choroiditis and panuveitis (MFC) treated with fluocinolone acetonide intravitreal implants. All eyes developed recurrent choroidal neovascularization (CNV) and were treated with intravitreal bevacizumab or ranibizumab.

Methods:

Retrospective chart review. Data collected included demographics, details of previous immunosuppressive therapy, preinjection Snellen visual acuity, and central macular thickness measured by optical coherence tomography, total injections administered, and postinjection central macular thickness and visual acuity. Patients were followed up for a minimum of 25 months from the first fluocinolone acetonide implant. Duration from implantation to first injection and complications, including development of cataracts, glaucoma, and recurrent inflammation, were followed.

Patients:

Three patients treated for MFC at the Casey Eye Institute, a tertiary care referral center at Oregon Health & Science University, from 2005–2008 were studied. All three received fluocinolone acetonide implants and later underwent intravitreal anti–vascular endothelial growth factor (VEGF) therapy for CNV.

Results:

Preinjection visual acuity in 3 patients was 1.2, 0.54, and 0.48 logarithm of minimal angle of resolution (mean 0.74). Postinjection visual acuity in 3 patients was 1.0, 0.40, and 0.0 logarithm of minimal angle of resolution (mean 0.47). Preinjection central macular thicknesses were 855 μm, 215 μm, and 276 μm (mean 449 μm). Postinjection central macular thicknesses were 220 μm, 190 μm, and 223 μm (mean 211 μm). Anti-VEGF injections did not reactivate inflammation. Advancing cataracts contributed to worsening visual acuity postinjection. The total number of anti-VEGF injections until resolution of intraretinal and subretinal fluid associated with CNV was 6 injections for case 1, 1 for case 2, and 8 for case 3 (mean 5, range 1–8).

Conclusion:

Intravitreal anti-VEGF therapy was successful in treating recurrent CNV in MFC patients with well-controlled inflammation after insertion of fluocinolone acetonide implants. Anti-VEGF therapy should be considered in treating active CNV in eyes with MFC and quiescent inflammatory disease.
Profiles of neutralizing antibody response in chronically human immunodeficiency virus type 1 clade B′-infected former plasma donors from China naïve to antiretroviral therapy
Authors: Hu Xintao , Hong Kunxue , Zhao Chunhong , Zheng Yang , Ma Liying , Ruan Yuhua , Gao Hongmei , Greene Kelli , Sarzotti-Kelsoe Marcella , Montefiori David C. , Shao Yiming
Published: July 2012

Broadly neutralizing antibodies (NAbs) such as those generated in chronic human immunodeficiency virus type 1 (HIV-1) infection are considered a key component for an effective HIV-1 vaccine. Here, we measured NAb responses using a panel of 25 Env-pseudotyped viruses, including clade B, C, A, CRF07_BC and CRF01_AE strains, against plasma samples from 103 subjects in a former plasma donor cohort in central China, who were infected with HIV-1 clade B′ for at least 10 years and naïve to antiretroviral therapy at the time of sampling. We found that 64 % of samples (n = 66) neutralized at least half of the viruses tested and 2 % (n = 2) neutralized all of the viruses, while 5 % (n = 5) neutralized none of the viruses tested. Strikingly, 29 % of plasma samples (n = 30) neutralized >80 % of the viral strains tested, indicating the presence of broadly reactive NAbs in these patients. When the magnitude (geometric mean ID50 titres, GMTs) or breadth of neutralization was assessed for correlation with CD4 count or plasma viral load, the only significant positive correlations were observed between viral load and neutralization magnitude (r = 0.2189, P = 0.0263) and between viral load and neutralization breadth (r = 0.1970, P = 0.0461). A moderate difference between progressors and long-term non-progressors was observed in both the breadth (P = 0.0316) and the potency (P = 0.0300). A significant difference was found in the GMTs between intra-clade and inter-clade strains (P<0.001). Heat-map analysis based on k-means clustering of plasma determined a statistically stable cluster of plasma with cross-reactive and potent neutralizing reactivity. These samples could provide physical biomaterials for further virological and serological studies from which useful insights into rational HIV-1 vaccine development and therapeutic design might be derived.
Antigenic analysis of highly pathogenic avian influenza virus H5N1 sublineages co-circulating in Egypt
Authors: Watanabe Yohei , Ibrahim Madiha S. , Ellakany Hany F. , Kawashita Norihito , Daidoji Tomo , Takagi Tatsuya , Yasunaga Teruo , Nakaya Takaaki , Ikuta Kazuyoshi
Published: July 2012

Highly pathogenic avian influenza virus H5N1 has spread across Eurasia and Africa, and outbreaks are now endemic in several countries, including Indonesia, Vietnam and Egypt. Continuous circulation of H5N1 virus in Egypt, from a single infected source, has led to significant genetic diversification with phylogenetically separable sublineages, providing an opportunity to study the impact of genetic evolution on viral phenotypic variation. In this study, we analysed the phylogeny of H5 haemagglutinin (HA) genes in influenza viruses isolated in Egypt from 2006 to 2011 and investigated the effect of conserved amino acid mutations in the HA genes in each of the sublineages on their antigenicity. The analysis showed that viruses in at least four sublineages still persisted in poultry in Egypt as of 2011. Using reverse genetics to generate HA-reassortment viruses with specific HA mutations, we found antigenic drift in the HA in two influenza virus sublineages, compared with the other currently co-circulating influenza virus sublineages in Egypt. Moreover, the two sublineages with significant antigenic drift were antigenically distinguishable. Our findings suggested that phylogenetically divergent H5N1 viruses, which were not antigenically cross-reactive, were co-circulating in Egypt, indicating that there was a problem in using a single influenza virus strain as seed virus to produce influenza virus vaccine in Egypt and providing data for designing more efficacious control strategies in H5N1-endemic areas.
Inhibition of Tiller Bud Outgrowth in thetinMutant of Wheat Is Associated with Precocious Internode Development
Authors: Kebrom Tesfamichael H. , Chandler Peter M. , Swain Steve M. , King Rod W. , Richards Richard A. , Spielmeyer Wolfgang
Published: July 2012

Tillering (branching) is a major yield component and, therefore, a target for improving the yield of crops. However, tillering is regulated by complex interactions of endogenous and environmental signals, and the knowledge required to achieve optimal tiller number through genetic and agronomic means is still lacking. Regulatory mechanisms may be revealed through physiological and molecular characterization of naturally occurring and induced tillering mutants in the major crops. Here we characterize a reduced tillering (tin, for tiller inhibition) mutant of wheat (Triticum aestivum). The reduced tillering in tin is due to early cessation of tiller bud outgrowth during the transition of the shoot apex from the vegetative to the reproductive stage. There was no observed difference in the development of the main stem shoot apex between tin and the wild type. However, tin initiated internode development earlier and, unlike the wild type, the basal internodes in tin were solid rather than hollow. We hypothesize that tin represents a novel type of reduced tillering mutant associated with precocious internode elongation that diverts sucrose (Suc) away from developing tillers. Consistent with this hypothesis, we have observed upregulation of a gene induced by Suc starvation, downregulation of a Suc-inducible gene, and a reduced Suc content in dormant tin buds. The increased expression of the wheat Dormancy-associated (DRM1-like) and Teosinte Branched1 (TB1-like) genes and the reduced expression of cell cycle genes also indicate bud dormancy in tin. These results highlight the significance of Suc in shoot branching and the possibility of optimizing tillering by manipulating the timing of internode elongation.
Strains in light-ion-implanted polycrystals: influence of grain orientation
Authors: Richard Axel , Palancher Hervé , Castelier É. , Micha J.-S. , Gamaleri M. , Carlot G. , Rouquette H. , Goudeau P. , Martin G. , Rieutord F. , Piron J. P. , Garcia P.
Published: July 2012

The implantation of He ions in UO2polycrystals induces a strain in the implanted layer which can be characterized using Laue micro X-ray diffraction (µ-XRD). The strain tensor resulting from the ion implantation may not be reduced to a single out-of-plane strain component: it also has nonzero shear components. Their strong dependence upon crystal orientation is modeled using elasticity theory. This work demonstrates the potential of Laue µ-XRD for characterizing radiation effects in materials.
(1-{[2-(6-Methoxynaphthalen-1-yl)ethyl]amino}ethylidene)oxidanium bromide monohydrate
Authors: Huang Yu , Zhong Jia-Liang , Hanbin Shan , Li Min , Yuan Zhe-Dong
Published: July 2012

The title salt, C15H18NO2+·Br−·H2O, is an analogue of the antidepressant drug agomelatine. The cation is protonated at the carbonyl O atom of its amide group. The side chain at the 1-position adopts an extended conformation, with all non-H atoms lying in the same plane as the naphthalene ring. This is in contrast with the crystal structures known for three agomelatine polymorphs, and also with two known cocrystals containing agomelatine. The structure displays three types of hydrogen bond, namely C=O—H...O, N—H...Br and O—H...Br, which define a two-dimensional network parallel to the (100) plane. The naphthalene rings interdigitate in a `zipper-like' fashion between these hydrogen-bonded networks, forming an offset arrangement. Direct face-to-face π–π contacts between naphthalene rings are not present in the structure.
Crystallographic input data for (001)-, (110)- and (111)-oriented superlattices
Authors: Touaa Z , Sekkal Nadir
Published: July 2012

General aspects concerned with (001)-, (110)- and (111)-oriented superlattices (SLs) have been investigated. In particular, the symmetry of these systems have been derived and given in detail. As a test, the obtained data have been utilized to calculate electronic structures and gaps of a standard GaAs/AlAs system using an accurate version of the first principle full potential linear muffin-tin orbital (FPLMTO) method based on a local-density functional approximation (LDA).
(2RS)-2-(2,4-Difluorophenyl)-1-[(4-iodobenzyl)(methyl)amino]-3-(1H-1,2,4-triazol-1-yl)propan-2-ol
Authors: Xiong Hui-Ping , Gao Shou-Hong , Li Chun-Tong , Wu Zhi-Jun
Published: July 2012

In the title compound (common name: iodiconazole), C19H19F2IN4O, there is an intramolecular O—H...N hydrogen bond and molecules are linked by weak interactions only, namely C—H...N, C—H...O and C—H...F hydrogen bonds, and π-electron ring–π-electron ring interactions between the triazole rings with centroid–centroid distances of 3.725 (3) Å.
The cost‐effectiveness of UK parenting programmes for preventing children's behaviour problems – a review of the evidence
Authors: Stevens Madeleine
Published: July 2012

Parenting programmes are widely used in the UK, promoted in policy documents as a cost‐effective way for children's services to address behaviour problems and thereby the longer‐term costs associated with conduct disorders, particularly antisocial behaviour and criminality. To explore whether these programmes are a cost‐effective component of family intervention, this paper examines evidence from cost‐effectiveness studies based on randomized controlled trials, modelling studies estimating longer‐term costs and outcomes, and studies estimating costs of UK parenting programmes, including evidence from routine practice. Findings indicate that parenting programmes have the potential to be cost‐saving in the long term; however, gaps in the evidence include: lack of follow‐up of families who drop out of programmes, absence of control groups in longer‐term follow‐ups, and little information about costs and effects of programmes in routine practice. The size of savings resulting from implementation of effective parenting programmes will depend on the extent to which families likely to be most costly to society attend and experience lasting benefit.
Three models of collaborative child protection: what is their influence on short stays in foster care?
Authors: Garcia Antonio , Puckett Alan , Ezell Mark , Pecora Peter J. , Tanoury Theresa , Rodriguez Wenceslao
Published: July 2012

The paper articulates three models of collaboration between child protection services and law enforcement agencies on investigations of child maltreatment, and examines the relative impact of each model on child removals and short‐term foster care placements. An extensive review of the research literature is used to derive lessons for jurisdictions using the different models. Promising strategies from several jurisdictions are described as they relate to collaborative investigations, child removal and short‐term placements. Finally, we provide recommendations to improve child protection investigations and reduce the use of short‐term foster care placements.
Is measurement of maternal serum TSH sufficient screening in early pregnancy? A case for more randomized trials
Authors: Ghassabian Akhgar , Tiemeier Henning
Published: July 2012

During the past decades, observational studies have demonstrated a relationship between thyroid dysfunction in pregnancy and a range of adverse outcomes in both mother and offspring. However, results from the few randomized trials of screening for thyroid dysfunction in pregnant women have not shown any benefit for women or their children. Before implementing screening in pregnant women at population level, randomized trials are needed to show that screening with subsequent intervention is effective for mothers or children. Here, we review the literature and argue that the findings from existing trials are not conclusive. Until such conclusive evidence from randomized trials is available, the best advice to the clinician is to screen only high‐risk pregnant women. Such women, for example those with symptoms or a history of thyroid problems, should be screened using trimester‐specific reference ranges for thyroid stimulating hormone (TSH) levels. We recommend new prospective randomized trials that combine different thyroid parameters as the screening tool, apply trimester‐specific ranges for thyroid hormones and examine whether screening and intervention during the first trimester of pregnancy will improve neuropsychological outcomes in the offspring.
Independent association of elevated serum hepatocyte growth factor levels with development of insulin resistance in a 10‐year prospective study
Authors: Tsukagawa Eri , Adachi Hisashi , Hirai Yuji , Enomoto Mika , Fukami Ako , Ogata Kinuka , Kasahara Akiko , Yokoi Kanako , Imaizumi Tsutomu
Published: July 2012

Objective

Hepatocyte growth factor (HGF) receptors form a hybrid complex with insulin receptors in the liver of mice, which lead to robust signalling to regulate glucose metabolism. Serum HGF levels are high in subjects with metabolic syndrome and/or obesity. Accordingly, we prospectively investigated the relationship between HGF and the development of insulin resistance (IR) in a general population without IR at baseline.

Methods

A total of 1492 subjects received health examinations. After excluding subjects with diabetes and/or IR (n = 402) at baseline, the remaining subjects (n = 1090) were followed‐up 10 years later. Complete data sets were available from 716 subjects for prospective analysis. Logistic regression was performed to determine factors associated with the development of IR after 10 years.

Results

In subjects without diabetes at baseline, serum HGF levels were higher (0·26 ± 0·10 ng/ml, n = 259) in subjects with IR than without it (0·22 ± 0·09 ng/ml, n = 1090). After deleting subjects who developed liver disease during follow‐up, 188 were found to have developed IR at 10 years after the original screening. HGF (P < 0·05), age (P < 0·001), homoeostasis model assessment index (P < 0·001), HDL‐c (P < 0·05; inversely) and hypertensive medication (P < 0·05) were significantly associated with the development of IR by multivariate stepwise logistic regression analysis. A significant (P < 0·05) relative risk [1·75 (95%CI: 1·01–3·12)] for the development of IR was observed in the highest (≥0·30 ng/ml) vs the lowest categories (<0·15 ng/ml) of HGF after adjustments for confounders.

Conclusions

Our 10‐year prospective study suggests that elevated serum HGF levels were significantly associated with the development of IR.
Comparing the potential for dispersal via waterbirds of a native and an invasive brine shrimp
Authors: SÁNCHEZ MARTA I. , HORTAS FRANCISCO , FIGUEROLA JORDI , GREEN ANDY J.
Published: July 2012

1. Migratory waterbirds are likely to have a major role in the spread of many exotic aquatic invertebrates by passive dispersal. However, in the field, this has so far only been confirmed in the case of the American brine shrimp Artemia franciscana, which is spreading quickly around the Mediterranean region.

2. We compared experimentally the capacity of A. franciscana and the native brine shrimp Artemia parthenogenetica to disperse via migratory shorebirds. After Artemia resting eggs (cysts) were fed to Redshank Tringa totanus and Dunlin Calidris alpina, we compared the proportion that survived gut passage, their hatchability and their retention time within the gut. We also tested the ability of cysts to stick to the feathers of Black‐tailed Godwit Limosa limosa.

3. The proportion of ingested cysts retrieved from faeces was the same for each Artemia species (8%), and there were no significant differences in retention time (mean 1.2 h and maximum 10 h for A. parthenogenetica, 1.4 and 12 h for A. franciscana) or hatchability (11% versus 14%). The two shorebird species showed similar retention times and retrieval rates, but cysts recovered from Dunlin had a significantly higher hatchability. Only one of the 1000 A. parthenogenetica cysts and three of the 1000 A. franciscana cysts stuck to feathers.

4. These results indicate that both non‐native and native brine shrimps have a similar high capacity for endozoochory via birds, and that the invasiveness of A. franciscana is probably explained by its competitive superiority owing to high fecundity and release from cestode parasitism. Owing to their different migratory behaviour, Redshank and Dunlin are likely to have different roles as brine shrimp vectors. Brine shrimps provide a suitable model for understanding the role of birds in the dispersal of exotic aquatic invertebrates.
Conflict and containment events in inpatient psychiatric units
Authors: Ross Jamie , Bowers Len , Stewart Duncan
Published: July 2012

Aims and objectives.  To describe the types and frequency of conflict behaviours exhibited by patients during the first 2 weeks of admission to acute psychiatric units, the methods staff use to manage them and bring to the surface underlying common patterns.

Background.  Many studies have investigated the prevalence and impact of psychiatric inpatient aggression. Much of the research to date has studied conflict and containment behaviours separately; however, some studies have reported relationships between certain behaviours suggesting that there are complex causal links between conflict and containment behaviours.

Design.  A cross‐sectional survey of conflict and containment events.

Methods.  Nursing notes were accessed for 522 patients during the first 2 weeks of admission, in 84 wards in 31 hospitals in the South East of England. Conflict and containment events occurring during this period were recorded retrospectively.

Results.  Factor analysis revealed six patterns of conflict behaviour, which were related to containment methods and patient demographic factors. These factors confirm some previously reported patterns of conflict.

Conclusions.  This study brings to light underlying common patterns of disruptive behaviour by psychiatric inpatients. The reasons for these remain obscure, but may relate to (1) national variations in policy and practice shaping static structural differences of interest between patients and staff and (2) normal developmental age and gender‐specific behaviours.

Relevance to clinical practice.  Conflict behaviour patterns may be differently motivated and therefore require different management strategies by staff. There is a need for awareness by clinical staff to the fact that different types of conflict behaviours may be co‐occurring or indicative of each other. Clinical staff should consider that implementation of and changes to hospital policies have the potential to change the nature and frequencies of certain conflict behaviours by patients.
Impact of lingual plates on the interocclusal free way space: a pilot study
Authors: BARBEZAT C. , SRINIVASAN M. , SCHIMMEL M. , HORI K. , TAMINE K. , ONO T. , MÜLLER F.
Published: July 2012

Summary  Palatal augmentation prostheses are commonly used in the treatment for dysphagia. By lowering the palatal contours, the tongue contact is increased and thus the bolus propulsion facilitated. However, the unfavourable weight of such appliances may be avoided when using lingual plates. Hence, the aim of this study is to investigate the effect of two different types of lingual plates on the vertical dimension in rest position. Eleven healthy dentate subjects with an average age of 35·5 years (26–60 years) volunteered in this pilot study. The vertical overbites were measured on plaster models. Two different designs of the experimental lingual plates were tested in this pilot study (P‐type & D‐type). The inter‐occlusal freeway space was measured using the electromagnetic K7 jaw‐tracking system (Myotronics, USA), while the subjects were seated in an upright position. They were asked to close from rest position into maximum intercuspation for about 2 s. Recordings were performed without the plates and subsequently with each of the two plate designs in situ. All recordings were performed three times and the second closing movement of each recording was used for the analysis. After averaging the repetitions without experimental lingual plates, with P‐type and D‐type plates, the differences were analysed using a Kruskall–Wallis test. The results showed no significantly increased freeway space while using both types of lingual plates. Hence, it can be concluded that any altered tongue pressure during swallowing with lingual plates is not related to an increase in vertical dimension.
Virological response and safety of 24‐week telaprevir alone in Japanese patients infected with hepatitis C virus subtype 1b
Authors: Toyota J. , Ozeki I. , Karino Y. , Asahina Y. , Izumi N. , Takahashi S. , Kawakami Y. , Chayama K. , Kamiya N. , Aoki K. , Yamada I. , Suzuki Y. , Suzuki F. , Kumada H.
Published: July 2012

Summary.  Hepatitis C virus (HCV) subtype 1b, which infects approximately 70% of Japanese carriers, is likely to be more eradicable by a telaprevir regimen than subtype 1a because of the higher genetic barrier of Val36 and Arg155 substitutions. The aims of this exploratory study were to evaluate the virological response and safety of 24‐week oral administration of telaprevir alone in chronic HCV subtype 1b infection. Fifteen treatment‐naïve patients were treated with telaprevir 750 mg every 8 h for 24 weeks. All patients were Japanese whose median age was 58.0 years (range: 45–68), and six patients (40%) were men. Median baseline HCV RNA level was 6.80 log10 IU/mL (range: 3.55–7.10). The HCV RNA levels decreased to undetectable in five patients (33%) within 8 weeks. Three patients (20%) with negative HCV RNA by Week 4 achieved end of treatment response. One patient (7%) who achieved sustained virological response had a low baseline viraemia of 3.55 log10 IU/mL. Most of the adverse events including anaemia and skin disorders were mild to moderate. Developed variants were T54A and A156V/T/F/Y with or without secondary substitutions rather than V36M ± R155K. Telaprevir alone for 24 weeks in Japanese patients with HCV subtype 1b resulted in an sustained viral response rate of 7% (1/15) and was well tolerated for 24 weeks. These results will support the implementation of further studies on oral combination of telaprevir with other direct‐acting antiviral agents in patients infected with HCV subtype 1b.
Arabidopsis thaliana ASN2 encoding asparagine synthetase is involved in the control of nitrogen assimilation and export during vegetative growth
Authors: GAUFICHON LAURE , MASCLAUX‐DAUBRESSE CÉLINE , TCHERKEZ GUILLAUME , REISDORF‐CREN MICHÈLE , SAKAKIBARA YUKIKO , HASE TOSHIHARU , CLÉMENT GILLES , AVICE JEAN‐CHRISTOPHE , GRANDJEAN OLIVIER , MARMAGNE ANNE , BOUTET‐MERCEY STÉPHANIE , AZZOPARDI MARIANNE , SOULAY FABIENNE , SUZUKI AKIRA
Published: July 2012

We investigated the function of ASN2, one of the three genes encoding asparagine synthetase (EC 6.3.5.4), which is the most highly expressed in vegetative leaves of Arabidopsis thaliana. Expression of ASN2 and parallel higher asparagine content in darkness suggest that leaf metabolism involves ASN2 for asparagine synthesis. In asn2‐1 knockout and asn2‐2 knockdown lines, ASN2 disruption caused a defective growth phenotype and ammonium accumulation. The asn2 mutant leaves displayed a depleted asparagine and an accumulation of alanine, GABA, pyruvate and fumarate, indicating an alanine formation from pyruvate through the GABA shunt to consume excess ammonium in the absence of asparagine synthesis. By contrast, asparagine did not contribute to photorespiratory nitrogen recycle as photosynthetic net CO2 assimilation was not significantly different between lines under both 21 and 2% O2. ASN2 was found in phloem companion cells by in situ hybridization and immunolocalization. Moreover, lack of asparagine in asn2 phloem sap and lowered 15N flux to sinks, accompanied by the delayed yellowing (senescence) of asn2 leaves, in the absence of asparagine support a specific role of asparagine in phloem loading and nitrogen reallocation. We conclude that ASN2 is essential for nitrogen assimilation, distribution and remobilization (via the phloem) within the plant.
Distribution and characterization of Streptomyces species causing potato common scab in Germany
Authors: Leiminger J. , Frank M. , Wenk C. , Poschenrieder G. , Kellermann A. , Schwarzfischer A.
Published: July 2012

Field‐grown potatoes showing scab infections were sampled in two successive years and analysed for prevailing Streptomyces strains. In 2008 and 2009, 293 Streptomyces isolates were collected in Germany and analysed for morphology, pathogenicity and strain type. Isolates varied in mycelium colour, sporulation and pigmentation. Based on their morphology, no clear differentiation of species was possible. At the genetic level, sampled isolates, as well as a number of type strains from culture collections, were characterized by PCR using 16S rRNA‐specific primers and PCR‐RFLP of the 16S–23S internal transcribed spacer (ITS) region with Hpy99I. Using this fingerprinting approach, Streptomyces species could be differentiated genotypically. The data from this study show that diversity among scab‐causing species in Germany is much higher than previously thought. Isolates belonged to various Streptomyces spp. previously associated with common scab. This is apparently the first report of pathogenic strains of S. europaeiscabiei, S. stelliscabiei, S. acidiscabiei, S. turgidiscabiei and S. bottropensis within Germany. Streptomyces europaeiscabiei was the predominant species found. Other scab‐causing species were identified, but their local distribution was uneven. For most of the isolates, the presence of the txtAB gene was demonstrated, indicating pathogenicity. This analysis is one of the first reports to examine the distribution of common scab‐causing species in Germany.
A comparison of neuropeptide expression in skin with allergic contact dermatitis in human and mouse
Authors: Lim Yun Young , Kim Hyeong Mi , Lee Hye In , Mun Seog‐Kyun , Kim Chan Woong , Kim Myeung Nam , Kim Beom Joon
Published: July 2012

Background  Allergic contact dermatitis (ACD) is a manifestation of a cell‐mediated immune response, but its mechanism remains unknown. Recently, we investigated whether ACD involves various neuropeptides. Substance P (SP) is a neuropeptide that is known to act as a neurokinin receptor when the immune response is initiated. Calcitonin gene‐related peptide (CGRP) is a distinct typical neuropeptide and, with SP, induces the immune response. Neuropeptides in neurogenic inflammation are regulated by the inactivation of receptors and enzymes that can cause neuropeptide degradation (e.g. angiotensin‐converting enzyme [ACE]), but no enzyme that can degrade SP and CGRP has yet been reported.

Methods  We investigated changes in the expression of SP and CGRP, as representative of typical neuropeptides, in ACD skin in mouse and human and the effect of ACE expression on the degradation of these neuropeptides using reverse transcription polymerase chain reaction and immunoblot assay. We also examined the relationship between ACD and neuropeptides in skin tissue from human ACD subjects and mice with induced ACD by analyzing cytokine expression and the results of hematoxylin and eosin staining and immunofluorescence assay.

Results  Expression of SP, CGRP, and ACE was higher in skin tissues from animals with acute ACD than in normal animal skin. However, CGRP expression in human skin with acute ACD was lower than in normal skin, unlike expression of SP and ACE, both of which were higher in ACD human skin than in normal human skin.

Conclusions  We found different patterns of neuropeptide expression in human versus mouse skin. These neuropeptide activities were influenced by an increase in neuropeptide degrading enzymes. Our findings show that when SP is produced, expression of CGRP is suppressed in human skin with ACD. The reduction of CGRP expression in patients with acute ACD is caused by mast cells activated by SP.
A comparison of the contrast stains, Chicago blue, chlorazole black, and Parker ink, for the rapid diagnosis of skin and nail infections
Authors: Tambosis Evanthia , Lim Christopher
Published: July 2012

Background  The cheapest, most rapid method for the diagnosis of mycotic skin and nail infections is direct examination of samples using a KOH preparation. The standard KOH wet mount lacks a color contrast. Various contrast dyes are available. Parker ink is one which has been extensively used, however in recent times the stain no longer provides a suitable color contrast. Two other dyes that are available are Chicago blue and chlorazole black.

Methods  100 samples of skin or nails were prospectively examined using Chicago blue, chlorazole black, and Parker ink‐KOH stains. The samples were also cultured, with culture being the diagnostic gold standard.

Results  The sensitivities and specificities of the Chicago blue, chlorazole black and Parker ink stains were 78% & 96%; 63% & 97%; and 48% and 96%, respectively.

Conclusion  The Chicago blue‐KOH stain provides a good color contrast and is a suitable replacement for the Parker ink‐KOH stain. It is suitable for use in the dermatologist’s office or in the laboratory.
Comparison of lateral thermal injury and healing of porcine skin incisions performed by CO2‐laser, monopolar electrosurgery and radiosurgery: a preliminary study based on histological and immunohistochemical results
Authors: Schoinohoriti Ourania K. , Chrysomali Evanthia , Tzerbos Fotis , Ιatrou Ioannis
Published: July 2012

Background  Despite the wide application of lasers and electrosurgery in dermatology, the pertinent literature provides conflicting data regarding the lateral thermal injury (LTI) associated with these instruments and its effects on wound healing. This study aims to quantitate the LTI produced by CO2‐laser, monopolar electrosurgery (MES), and radiosurgery (MRS) and determine its effects on the healing process (re‐epithelialization and inflammatory response) of incisional wounds.

Methods  Five adult swine of similar weight (22.8–25 kg) were submitted to standardized full‐thickness incisions on the lateral abdominal skin by the above instruments (at settings similar to those used in clinical practice) and scalpel (control group). Full‐thickness specimens from the surgical site were harvested immediately afterwards and 48 hours later (days 1 and 3). The animals were euthanized by intravenous administration of propofol and pentobarbital. All specimens were formalin fixed, paraffin embedded, cut, and stained with hematoxylin‐eosin to quantitate the extent of LTI and inflammatory infiltration. Sections of day 3 were stained with the MIB‐1 monoclonal antibody to detect Ki‐67 as a marker of epithelial cell proliferation adjacently to the incisions.

Results  LTI was most extensive in the CO2‐laser‐group but did not differ significantly between MES‐ and MRS‐groups. Immunohistochemistry ascertained significantly greater epithelial cell proliferation in the CO2‐laser‐group. Inflammatory infiltration was significantly greater in the CO2‐laser‐group, when compared with the controls but did not differ significantly between the MES/MRS and control groups.

Conclusion  CO2 laser incisions exhibit more extensive LTI, epithelial cell proliferation, and inflammatory response. Confirmation of these findings requires a greater sample.
The leprosy agents Mycobacterium lepromatosis and Mycobacterium leprae in Mexico
Authors: Han Xiang Y. , Sizer Kurt Clement , Velarde‐Félix Jesús S. , Frias‐Castro Luis O. , Vargas‐Ocampo Francisco
Published: July 2012

Background  Mycobacterium leprae was the only known cause of leprosy until 2008, when a new species, named Mycobacterium lepromatosis, was found to cause diffuse lepromatous leprosy (DLL), a unique form of leprosy endemic in Mexico.

Methods  We sought to differentiate the leprosy agents among 120 Mexican patients with various clinical forms of leprosy and to compare their relative prevalences and disease features. Archived skin biopsy specimens from these patients were tested for both M. leprae and M. lepromatosis using polymerase chain reaction‐based species‐specific assays.

Results  Etiologic species were confirmed in 87 (72.5%) patients, of whom 55 were infected with M. lepromatosis, 18 with M. leprae, and 14 with both organisms. The endemic regions of each agent differed but overlapped. Patients with M. lepromatosis were younger and were distributed across more states; their clinical diagnoses included DLL (n = 13), lepromatous leprosy (LL) (n = 34), and eight other forms of leprosy. By contrast, the diagnoses of patients with M. leprae did not include DLL but did include LL (n = 15) and three other forms of leprosy. Thus, M. lepromatosis caused DLL specifically (P = 0.023). Patients with M. lepromatosis also showed more variable skin lesions; the extremities were the most common sites of biopsy in these patients. Finally, patients with dual infections manifested all clinical forms and accounted for 16.1% of all species‐confirmed cases.

Conclusions  Mycobacterium lepromatosis is another cause of leprosy and is probably more prevalent than M. leprae in Mexico. It mainly causes LL and also specifically DLL. Dual infections caused by both species may occur in endemic areas.