bluuebunny/crossref_metadata_2025 huggingface dataset:
Tph2 gene deletion enhances amphetamine‐induced hypermotility: effect of 5‐HT restoration and role of striatal noradrenaline release
Authors: Carli Mirjana , Kostoula Chrysaugi , Sacchetti Giuseppina , Mainolfi Pierangela , Anastasia Alessia , Villani Claudia , Invernizzi Roberto William
Published: August 2015

Variants of tryptophan hydroxylase‐2 (Tph2), the gene encoding enzyme responsible for the synthesis of brain serotonin (5‐HT), have been associated with neuropsychiatric disorders, substance abuse and addiction. This study assessed the effect of Tph2 gene deletion on motor behavior and found that motor activity induced by 2.5 and 5 mg/kg amphetamine was enhanced in Tph2−/− mice. Using the in vivo microdialysis technique we found that the ability of amphetamine to stimulate noradrenaline (NA) release in the striatum was reduced by about 50% in Tph2−/− mice while the release of dopamine (DA) was not affected. Tph2 deletion did not affect the release of NA and DA in the prefrontal cortex. The role of endogenous 5‐HT in enhancing the effect of amphetamine was confirmed showing that treatment with the 5‐HT precursor 5‐hydroxytryptophan (10 mg/kg) restored tissue and extracellular levels of brain 5‐HT and the effects of amphetamine on striatal NA release and motor activity in Tph2−/− mice. Treatment with the NA precursor dihydroxyphenylserine (400 mg/kg) was sufficient to restore the effect of amphetamine on striatal NA release and motor activity in Tph2−/− mice. These findings indicate that amphetamine‐induced hyperactivity is attenuated by endogenous 5‐HT through the inhibition of striatal NA release. Tph2−/− mice may be a useful preclinical model to assess the role of 5‐HT‐dependent mechanisms in the action of psychostimulants.

image

Acute sensitivity to the motor effects of amphetamine has been associated to increased risk of psychostimulant abuse. Here, we show that deletion of Tph2, the gene responsible for brain 5‐HT synthesis, enhances the motor effect of amphetamine in mice through the inhibition of striatal NA release. This suggests that Tph2−/− mice is a useful preclinical model to assess the role of 5‐HT‐dependent mechanisms in psychostimulants action. Tph2, tryptophan hydroxylase‐2.
Functional and homeostatic defects of regulatory T cells in patients with coronary artery disease
Authors: Hasib L. , Lundberg A. K. , Zachrisson H. , Ernerudh J. , Jonasson L.
Published: August 2015

Objective

Regulatory T cells (Tregs) are considered atheroprotective, and low levels have been associated with the acute coronary syndrome (ACS), particularly non‐ST elevation (NSTE)‐ACS. However, the functional properties as well as homeostasis of Tregs are mainly unknown in coronary artery disease (CAD). Here, we investigated the composition and functional properties of naïve (n) and memory (m)Tregs in patients with NSTE‐ACS and in patients 6–12 months post‐ACS.

Methods

Based on the expression of CD25, FOXP3, CD127, CD45RA, CD39 and CTLA‐4, Treg subsets were defined by flow cytometry in whole blood or isolated CD4+ T cells. The functional properties of nTregs and mTregs were examined in terms of proliferative capacity and modulation of cytokine secretion. To understand the potential consequences of Treg defects, we also investigated correlations with lipopolysaccharide (LPS)‐induced cytokine secretion and ultrasound‐defined carotid atherosclerosis.

Results

Both NSTE‐ACS and post‐ACS patients exhibited reduced levels of nTregs (P < 0.001) compared with healthy control subjects, but without compensatory increases in mTregs. Both nTregs and mTregs from patients showed significantly lower replicative rates and impaired capacity to modulate T‐cell proliferation and secretion of interferon‐gamma and IL‐10. The Treg defect was also associated with LPS‐induced cytokine secretion and increased burden of carotid atherosclerosis.

Conclusion

Our results demonstrate a functional and homeostatic Treg defect in patients with NSTE‐ACS and also in stabilized patients 6–12 months after ACS. Moreover, this defect was associated with a subclinical proinflammatory and atherogenic state. We believe that the failure to preserve Treg function and homeostasis reflects a need for immune‐restoring strategies in CAD.
Alligator osteoderms as a source of labile calcium for eggshell formation
Authors: Dacke C. G. , Elsey R. M. , Trosclair P. L. , Sugiyama T. , Nevarez J. G. , Schweitzer M. H.
Published: August 2015

The calcium (Ca) demand on alligators in active reproduction is significant, yet the source of this additional Ca is unclear. Three possible sources for Ca mobilization are endolymphatic deposits, as in anurans and some lizards; short‐lived skeletal medullary bone or analogous deposits, as in birds; or some other source such as the osteoderm layer of the integument or simply mobilization of structural bone. Here, we investigate possible extra‐skeletal sources for labile Ca in the reproducing alligator, including endolymphatic Ca deposits, by analogy with anuran amphibian and some reptiles and integumentary osteodermal (scale) Ca deposits. We conducted X‐ray image analyses of skulls for the presence of significant endolymphatic Ca deposits. We also examined dermal bone of scutes (osteoderm, scales) from the dorsal integument using both X‐ray and histological analyses. Tissues from reproducing females containing mature but unovulated follicles were compared with those from specimens that had nested (laid eggs) or contained eggs within the oviduct at advanced stages of calcification. A small number of immature specimens and an adult male were also compared. No clear differences were observed in endolymphatic deposits between pre‐ and post‐ovulatory specimens. Scute (osteoderm) X‐ray density was significantly greater in females with ripe ovarian follicles compared with those that had recently laid (nested) or contained heavily calcified eggs within their oviducts. The latter groups also showed histological evidence of scute resorption compared with the former, suggesting that the scutes play a role in Ca storage during egglay.
Changes in temporomandibular joint morphology in class II patients treated with fixed mandibular repositioning and evaluated through 3D imaging: a systematic review
Authors: Al‐Saleh M. A. Q. , Alsufyani N. , Flores‐Mir C. , Nebbe B. , Major P. W.
Published: August 2015

To estimate the effects of skeletal class II malocclusion treatment using fixed mandibular repositioning appliances on the position and morphology of the temporomandibular joint (TMJ). Two independent reviewers performed comprehensive electronic searches of MEDLINE, EMBASE, EBM reviews and Scopus (until May 5, 2015). The references of the identified articles were also manually searched. All studies investigating morphological changes of the TMJ articular disc, condyle and glenoid fossa with 3D imaging following non‐surgical fixed mandibular repositioning appliances in growing individuals with class II malocclusions were included in the analysis. Of the 269 articles initially reviewed, only 12 articles used magnetic resonance imaging and two articles used computed tomography (CT) or cone‐beam CT images. Treatment effect on condyle and glenoid fossa was discussed in eight articles. Treatment effect on TMJ articular disc position and morphology was discussed in seven articles. All articles showed a high risk of bias due to deficient methodology: inadequate consideration of confounding variables, blinding of image assessment, selection or absence of control group and outcome measurement. Reported changes in osseous remodelling, condylar and disc position were contradictory. The selected articles failed to establish conclusive evidence of the exact nature of TMJ tissue response to fixed mandibular repositioning appliances.
Interpersonal Process of Emotional Labor: The Role of Negative and Positive Customer Treatment
Authors: Zhan Yujie , Wang Mo , Shi Junqi
Published: August 2015

Emotional labor refers to the process of regulating both feelings and expressions in response to the display rules for promoting organizational goals. Existing literature has provided strong evidence for the impact of emotional labor (i.e., surface acting and deep acting) on service employees’ emotional exhaustion. However, the empirical examination of the mechanisms underlying this association is largely missing from prior research. Drawing on the social interaction model of emotion regulation, this article reported 2 daily diary studies examining the role of customer treatment toward employees in channeling emotional labor's impact on employee emotional well‐being. Specifically, Study 1 measured emotional labor at the between‐person level as habitual emotional regulation strategies used by service employees, and Study 2 measured emotional labor at the within‐person level to capture its fluctuations. Results showed that employees engaging in more surface acting were more likely to receive negative treatment from customers, which in turn increased their negative affect and emotional exhaustion. Further, employees engaging in more deep acting were more likely to receive positive treatment from customers, which in turn increased their positive affect. Implications and limitations of these findings were discussed.
Therapy‐related B‐lymphoblastic leukemia associated with Philadelphia chromosome and MLL rearrangement: Single institution experience and the review of the literature
Authors: Matnani Rahul , Parekh Vishwas , Borate Uma , Brazelton Jason , Reddy Vishnu , Peker Deniz
Published: August 2015

Therapy related acute lymphoblastic leukemia (t‐ALL) of B cell origin is rare and constitutes approximately 2% of all ALL. Previously compiled data on the complete cytogenetic analysis of 48 t‐B‐ALL cases suggested that MLL rearrangement at 11q23 gene locus is the most common abnormality. Philadelphia chromosome (Ph) and a normal karyotype were reported as the second and third most common karyotypes, respectively. We investigated cytogenetic karyotypes of six t‐B‐ALL cases with a pre‐B cell immunophenotype. Ph + t‐B‐ALL was noted in four of six patients previously treated with radiation and/or chemotherapy. In addition, one case demonstrated MLL rearrangement at 11q23 locus while one case demonstrated normal cytogenetic karyotype. Five of the six t‐B‐ALL patients had persistent leukemia following initiation of chemotherapy for secondary leukemia with survival ranging from 10 to 21 months. To our knowledge, only fourteen patients with Ph + t‐B‐ALL have been described in the literature. In the current study, three of four cases with Ph + t‐B‐ALL were associated with treated breast carcinoma while one patient was treated for Hodgkin lymphoma. All four patients had undergone radiation therapy. The results may indicate a plausible association between Ph+t‐B‐ALL and prior radiation exposure.
On the Path to Trade Liberalisation: Political Regimes in Trade Negotiations
Authors: Mölders Florian
Published: August 2015

The number of free trade agreements (FTA) has increased substantially since 1990 despite efforts to promote multilateral trade liberalisation. While there is evidence on the determinants of FTA formation, still little is known on the processing of trade agreements, particularly regarding the pre‐implementation duration. This paper fills the research gap by using event data on the negotiation, the signing and the implementation of trade agreements. Duration analysis is employed to examine the connection between regime types and the lengths of the negotiation and the ratification stages. The results support the claim that higher levels of democratisation are associated with shorter negotiations, while political constraints lead to delays. Moreover, the depth of an agreement matters: a higher number of WTO‐X and WTO+ provisions do not only prolong the negotiation stage, but also the subsequent ratification. Against the background of potential anticipation effects of trade agreements, these results are of interest for exporting firms that assess the timing of implementation.
International Transmission Mechanisms and Contagion in Housing Markets
Authors: Nanda Anupam , Yeh Jia‐Huey
Published: August 2015

This paper explores international transmission mechanism and its role in contagion effect in the housing markets across six major Asian cities. The analysis is based on the identification of house price diffusion effects through a global vector autoregressive (GVAR) model estimated using quarterly data for six major Asian cities (Hong Kong, Tokyo, Seoul, Singapore, Taipei and Bangkok) from 1991Q1 to 2011Q2. The empirical results indicate that the open economies heavily relying on international trade such as Singapore, Japan (Tokyo), Taiwan (Taipei) and Thailand (Bangkok) show positive correlations between the economy's openness and house prices, which is consistent with the Balassa–Samuelson hypothesis. Interestingly, some region‐specific conditions also appear to play important roles as determinants of house price movements, which may be driven by restrictive housing policies and demand–supply imbalances such as Singapore and Bangkok. These results are reasonably robust across several model specifications. The findings bear significant implications for formulation of investment strategy and public policies.
Evaluation of an immunochromatographic test for feline AB system blood typing
Authors: Spada Eva , Proverbio Daniela , Baggiani Luciana , Bagnagatti De Giorgi Giada , Perego Roberta , Ferro Elisabetta
Published: August 2015

Objective

To determine the accuracy of an immunochromatographic cartridge (IC) test for blood typing feline type A, B, and AB blood samples.

Design

Prospective observational study.

Setting

University teaching hospital.

Samples

Fifty‐one nonanemic and 19 anemic feline blood samples.

Interventions

Samples were blood typed by both card agglutination (CA) and IC techniques. Discordant results were analyzed using a back‐typing technique for the presence of alloantibodies. Repeatability and reproducibility of the IC method were evaluated. Accuracy of the IC method was determined for feline whole blood anticoagulated with EDTA and citrate phosphate dextrose adenine (CPDA1), for feline‐packed RBCs with CPDA1 and saline adenine glucose‐mannitol, and for autoagglutinated and hemolytic samples. Accuracy of IC testing was determined for feline blood after room temperature, 4 ± 2, −20, and −80°C storage following 24, 48, 72, and 96 hours, and after 1, 2, 3, and 4 weeks of storage.

Measurements and Main Results

In anemic and nonanemic samples the IC technique had a specificity, sensitivity, positive predictive value, and negative predictive value of 100% in detecting feline blood types A, B, and AB, outperforming a CA test. Results were repeatable and reproducible. Using IC it was possible to blood type samples anticoagulated with EDTA and CPDA1, packed RBC samples with CPDA1 and saline adenine glucose‐mannitol, autoagglutinated and hemolytic samples, and samples stored at 4 ± 2°C and at room temperature for up to 1 month.

Conclusions

The IC technique is an accurate assay for the identification of A, B, and AB blood types in anemic and nonanemic feline blood. It has a higher sensitivity and specificity than the CA test, and can be used in samples stored with common anticoagulants or preservative solutions used in feline transfusion medicine.
The Self-Presentation Motives for Physical Activity Questionnaire: Instrument Development and Preliminary Construct Validity Evidence
Authors: Howle Timothy C. , Dimmock James A. , Whipp Peter R. , Jackson Ben
Published: August 2015

With the aim of advancing the literature on impression management in physical activity settings, we developed a theoretically derived 2 by 2 instrument that was designed to measure different types of context-specific selfpresentation motives. Following item generation and expert review (Study 1), the instrument was completed by 206 group exercise class attendees (Study 2) and 463 high school physical education students (Study 3). Our analyses supported the intended factor structure (i.e., reflecting acquisitive-agentic, acquisitive-communal, protective-agentic, and protective-communal motives). We found some support for construct validity, and the self-presentation motives were associated with variables of theoretical and applied interest (e.g., impression motivation and construction, social anxiety, social and achievement goals, efficacy beliefs, engagement). Taken together, the results indicate that the Self-presentation Motives for Physical Activity Questionnaire (SMPAQ) may be useful for measuring various types of self-presentation motives in physical activity settings.
Perfectionism and Burnout in Junior Athletes: A Three-Month Longitudinal Study
Authors: Madigan Daniel J. , Stoeber Joachim , Passfield Louis
Published: August 2015

Perfectionism in sports has been shown to be associated with burnout in athletes. Whether perfectionism predicts longitudinal changes in athlete burnout, however, is still unclear. Using a two-wave cross-lagged panel design, the current study examined perfectionistic strivings, perfectionistic concerns, and athlete burnout in 101 junior athletes (mean age 17.7 years) over 3 months of active training. When structural equation modeling was employed to test a series of competing models, the best-fitting model showed opposite patterns for perfectionistic strivings and perfectionistic concerns. Whereas perfectionistic concerns predicted increases in athlete burnout over the 3 mon ths, perfectionistic strivings predicted decreases. The present findings suggest that perfectionistic concerns are a risk factor for junior athletes contributing to the development of athlete burnout whereas perfectionistic strivings appear to be a protective factor.
Systematic Review and Meta-analysis of Randomized Controlled Trials of Antibiotics and Antiseptics for Preventing Infection in People Receiving Primary Total Hip and Knee Prostheses
Authors: Voigt Jeffrey , Mosier Michael , Darouiche Rabih
Published: August 2015

Infection rates in primary (first-time) major joint arthroplasty continue to be a significant issue. The effect of antibiotic and antiseptic prophylaxis on outcomes for this type of surgery has not been adequately reviewed. A systematic search of the main databases for randomized controlled trials (RCTs) evaluating antibiotics and antiseptics was conducted to evaluate the predetermined endpoints of infection, adverse events, costs, quality of life, and concentration levels of antibiotics. A meta-analysis using pooled effect estimates and fixed-effect and random-effect models of risk ratios (RR), calculated with 95% confidence intervals (CI), was utilized. Thirty (30) RCTs examined the effects of antibiotic and antiseptic prophylaxis on infections after primary total hip arthroplasty (THA) (total of 11,597 participants) and total knee arthroplasty (TKA) (total of 6,141 participants). For THA, preoperative systemic intravenous (i.v.) antibiotic prophylaxis may be effective in reducing the incidence of infection after THA from 6 months to ≥5 years. For TKA, there is no RCT evidence that antibiotics and/or antiseptics have any effect on infection rate. Preoperative systemic antibiotic prophylaxis in primary THA may be effective at reducing infection rate. There is no evidence that timing, route of administration, or concentration levels have an effect on reducing infections, adverse events, or costs in THA or TKA. Many of the trials included in this study were published in the 1980s and 1990s. Thus, it would be important to replicate a number of them based on current patient demographics and incidence of bacterial resistance.
Evaluation of Sulfobutylether-β-Cyclodextrin Exposure in a Critically Ill Patient Receiving Intravenous Posaconazole While Undergoing Continuous Venovenous Hemofiltration
Authors: Morris Amanda A. , Mueller Scott W. , Rower Joseph E. , Washburn Taylor , Kiser Tyree H.
Published: August 2015

We present a 31-year-old female who had undergone an allogeneic bone marrow transplantation and who was started on intravenous posaconazole for pulmonary mycosis while undergoing continuous venovenous hemofiltration (CVVH). We performed steady-state pharmacokinetic evaluations for both posaconazole and sulfobutylether-β-cyclodextrin (SBECD). SBECD was effectively removed by CVVH, with observed exposure similar to that for patients with moderate renal impairment. Intravenous posaconazole at standard doses may be utilized in critically ill patients undergoing CVVH without significant risk of SBECD accumulation.
Primary Structural Variation in Anaplasma marginale Msp2 Efficiently Generates Immune Escape Variants
Authors: Graça Telmo , Paradiso Lydia , Broschat Shira L. , Noh Susan M. , Palmer Guy H.
Published: August 2015

Antigenic variation allows microbial pathogens to evade immune clearance and establish persistent infection.
Anaplasma marginale
utilizes gene conversion of a repertoire of silent
msp2
alleles into a single active expression site to encode unique Msp2 variants. As the genomic complement of
msp2
alleles alone is insufficient to generate the number of variants required for persistence,
A. marginale
uses segmental gene conversion, in which oligonucleotide segments from multiple alleles are recombined into the expression site to generate a novel
msp2
mosaic not represented elsewhere in the genome. Whether these segmental changes are sufficient to evade a broad antibody response is unknown. We addressed this question by identifying Msp2 variants that differed in primary structure within the immunogenic hypervariable region microdomains and tested whether they represented true antigenic variants. The minimal primary structural difference between variants was a single amino acid resulting from a codon insertion, and overall, the amino acid identity among paired microdomains ranged from 18 to 92%. Collectively, 89% of the expressed structural variants were also antigenic variants across all biological replicates, independent of a specific host major histocompatibility complex haplotype. Biological relevance is supported by the following: (i) all structural variants were expressed during infection of a natural host, (ii) the structural variation observed in the microdomains corresponded to the mean length of variants generated by segmental gene conversion, and (iii) antigenic variants were identified using a broad antibody response that developed during infection of a natural host. The findings demonstrate that segmental gene conversion efficiently generates Msp2 antigenic variants.
Positive Effect of Carbon Sources on Natural Transformation in Escherichia coli: Role of Low-Level Cyclic AMP (cAMP)-cAMP Receptor Protein in the Derepression of
rpoS
Authors: Guo Mengyue , Wang Huanyu , Xie Nengbin , Xie Zhixiong
Published: August 2015

Natural plasmid transformation of
Escherichia coli
is a complex process that occurs strictly on agar plates and requires the global stress response factor σ
S
. Here, we showed that additional carbon sources could significantly enhance the transformability of
E. coli
. Inactivation of phosphotransferase system genes (
ptsH
,
ptsG
, and
crr
) caused an increase in the transformation frequency, and the addition of cyclic AMP (cAMP) neutralized the promotional effect of carbon sources. This implies a negative role of cAMP in natural transformation. Further study showed that
crp
and
cyaA
mutations conferred a higher transformation frequency, suggesting that the cAMP-cAMP receptor protein (CRP) complex has an inhibitory effect on transformation. Moreover, we observed that
rpoS
is negatively regulated by cAMP-CRP in early log phase and that both
crp
and
cyaA
mutants show no transformation superiority when
rpoS
is knocked out. Therefore, it can be concluded that both the
crp
and
cyaA
mutations derepress
rpoS
expression in early log phase, whereby they aid in the promotion of natural transformation ability. We also showed that the accumulation of RpoS during early log phase can account for the enhanced transformation aroused by additional carbon sources. Our results thus demonstrated that the presence of additional carbon sources promotes competence development and natural transformation by reducing cAMP-CRP and, thus, derepressing
rpoS
expression during log phase. This finding could contribute to a better understanding of the relationship between nutrition state and competence, as well as the mechanism of natural plasmid transformation in
E. coli
.

IMPORTANCE
Escherichia coli
, which is not usually considered to be naturally transformable, was found to spontaneously take up plasmid DNA on agar plates. Researching the mechanism of natural transformation is important for understanding the role of transformation in evolution, as well as in the transfer of pathogenicity and antibiotic resistance genes. In this work, we found that carbon sources significantly improve transformation by decreasing cAMP. Then, the low level of cAMP-CRP derepresses the general stress response regulator RpoS via a biphasic regulatory pattern, thereby contributing to transformation. Thus, we demonstrate the mechanism by which carbon sources affect natural transformation, which is important for revealing information about the interplay between nutrition state and competence development in
E. coli
.
Loss of Antibiotic Tolerance in Sod-Deficient Mutants Is Dependent on the Energy Source and Arginine Catabolism in Enterococci
Authors: Ladjouzi Rabia , Bizzini Alain , van Schaik Willem , Zhang Xinglin , Rincé Alain , Benachour Abdellah , Hartke Axel
Published: August 2015

Enterococci are naturally tolerant to typically bactericidal cell wall-active antibiotics, meaning that their growth is inhibited but they are not killed even when exposed to a high concentration of the drug. The molecular reasons for this extraordinary tolerance are still incompletely understood. Previous work showed that resistance to killing collapsed specifically in mutants affected in superoxide dismutase (Sod) activity, arguing that bactericidal antibiotic treatment led to induction of a superoxide burst. In the present work, we show that loss of antibiotic tolerance in Δ
sodA
mutants of pathogenic enterococci is dependent on the energy source present during antibiotic treatment. Hexoses induce greater killing than the pentose ribose, and no killing was observed with glycerol as the energy source. These results point to glycolytic reactions as crucial for antibiotic-mediated killing of Δ
sodA
mutants. A transposon mutant library was constructed in
Enterococcus faecalis ΔsodA
mutants and screened for restored tolerance of vancomycin. Partially restored tolerance was observed in mutants with transposon integrations into intergenic regions upstream of regulators implicated in arginine catabolism. In these mutants, the arginine deiminase operon was highly upregulated. A model for the action of cell wall-active antibiotics in tolerant and nontolerant bacteria is proposed.

IMPORTANCE
Antibiotic tolerance is a serious clinical concern, since tolerant bacteria have considerably increased abilities to resist killing by bactericidal drugs. Using enterococci as models for highly antibiotic-tolerant pathogens, we showed that tolerance of these bacteria is linked to their superoxide dismutase (Sod), arguing that bactericidal antibiotics induce generation of reactive oxygen species inside cells. Wild-type strains are tolerant because they detoxify these deleterious molecules by the activity of Sod, whereas Sod-deficient strains are killed. This study showed that killing depends on the energy source present during treatment and that an increase in arginine catabolism partially restored tolerance of the Sod mutants. These results are used to propose a mode-of-action model of cell wall-active antibiotics in tolerant and nontolerant bacteria.
Cross Talk Inhibition Nullified by a Receiver Domain Missense Substitution
Authors: Huynh TuAnh Ngoc , Lin Hsia-Yin , Noriega Chris E. , Lin Alice V. , Stewart Valley
Published: August 2015

In two-component signal transduction, a sensor protein transmitter module controls cognate receiver domain phosphorylation. Most receiver domain sequences contain a small residue (Gly or Ala) at position T + 1 just distal to the essential Thr or Ser residue that forms part of the active site. However, some members of the NarL receiver subfamily have a large hydrophobic residue at position T + 1. Our laboratory previously isolated a NarL mutant in which the T + 1 residue Val-88 was replaced with an orthodox small Ala. This NarL V88A mutant confers a striking phenotype in which high-level target operon expression is both signal (nitrate) and sensor (NarX and NarQ) independent. This suggests that the NarL V88A protein is phosphorylated by cross talk from noncognate sources. Although cross talk was enhanced in
ackA
null strains that accumulate acetyl phosphate, it persisted in
pta ackA
double null strains that cannot synthesize this compound and was observed also in
narL
+
strains. This indicates that acetate metabolism has complex roles in mediating NarL cross talk. Contrariwise, cross talk was sharply diminished in an
arcB barA
double null strain, suggesting that the encoded sensors contribute substantially to NarL V88A cross talk. Separately, the V88A substitution altered the
in vitro
rates of NarL autodephosphorylation and transmitter-stimulated dephosphorylation and decreased affinity for the cognate sensor, NarX. Together, these experiments show that the residue at position T + 1 can strongly influence two distinct aspects of receiver domain function, the autodephosphorylation rate and cross talk inhibition.

IMPORTANCE
Many bacterial species contain a dozen or more discrete sensor-response regulator two-component systems that convert a specific input into a distinct output pattern. Cross talk, the unwanted transfer of signals between circuits, occurs when a response regulator is phosphorylated inappropriately from a noncognate source. Cross talk is inhibited in part by the high interaction specificity between cognate sensor-response regulator pairs. This study shows that a relatively subtle missense change from Val to Ala nullifies cross talk inhibition, enabling at least two noncognate sensors to enforce an inappropriate output independently of the relevant input.
Toxic shock syndrome post open reduction and Kirschner wire fixation of a humeral lateral condyle fracture
Authors: Chan Yuen , Selvaratnam Veenesh , Garg Neeraj
Published: August 2015

Use of Kirschner wires (K-wires) is the most common method of fracture stabilisation in lateral condyle fracture fixation in children. We report a case of toxic shock syndrome (TSS) following an open reduction and internal fixation using K-wires for a humeral lateral condyle fracture in a 5-year-old girl. TSS is a toxin-mediated multisystem illness. It typically presents with shock and it is most often attributed to toxin-producing strains ofStaphylococcus aureusandStreptococcus pyogenes. It can lead to multiorgan failure and, ultimately, death. It is important to be aware of TSS, as it can present within any setting. Patients often have non-specific symptoms and their condition can worsen rapidly. TSS postorthopaedic surgery is rare; however, due to the serious nature of this disease, it is important to promptly recognise and diagnose TSS, and to ensure appropriate treatment is started without delay.
Treatment for tuberculosis in a patient with Dubin-Johnson syndrome
Authors: Alpana Meena , Daga Mradul Kumar , Aggarwal Sunita , Nidhi Anand
Published: August 2015

Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder characterised by conjugated hyperbilirubinemia resulting from mutations of ABCC2/MRP2 gene. The beneficial effects of ursodeoxycholic acid (UDCA) and rifampicin were found to be complementary in the treatment of cholestatic liver disease secondary to DJS. We present a case of a young woman with tubercular meningitis. She was started on modified antitubercular therapy in view of conjugated hyperbilirubinemia. However, reinitiation of rifampicin resulted in redevelopment of jaundice. Liver biopsy was suggestive of DJS. The patient was started on rifampicin along with UDCA. There was improvement in hyperbilirubinemia and a full course of antituberculous therapy without further worsening of the disorder was possible. This is a rare case of DJS with tuberculosis, showing beneficial effects of rifampicin and UDCA combination therapy, which so far has been considered doubtful. It is uncertain what the level of efficacy of therapy is in various MRP2 gene mutations.
Behavioural physical activity interventions in participants with lower-limb osteoarthritis: a systematic review with meta-analysis
Authors: Williamson Wilby , Kluzek Stefan , Roberts Nia , Richards Justin , Arden Nigel , Leeson Paul , Newton Julia , Foster Charlie
Published: August 2015

Objective

To assess effectiveness of osteoarthritis interventions to promote long-term physical activity behaviour change.

Design

A systematic review and meta-analysis. Protocol registration PROSPERO CRD4201300444 5 (http://www.crd.york.ac.uk/prospero/).

Study selection

Randomised controlled trials (RCTs) comparing physical activity interventions with placebo, no/or minimal intervention in community-dwelling adults with symptomatic knee or hip osteoarthritis. Primary outcomes were change in physical activity or cardiopulmonary fitness after a minimum follow-up of 6 months.

Data extraction

Outcomes were measures of physical activity (self-reported and objectively measured) and cardiovascular fitness. Standard mean differences between postintervention values were used to describe the effect sizes.

Results

27 984 titles were screened and 180 papers reviewed in full. Eleven RCTs satisfied inclusion criteria, total study population of 2741 participants, mean age 62.2. The commonest reasons for study exclusion were follow-up less than 6 months and no physical activity measures. The majority of included interventions implement an arthritis self-management programme targeting coping skills and self-efficacy. Seven studies used self-report measures, the pooled effect of these studies was small with significant heterogeneity between studies (SMD 0.22 with 95% CI −0.11 to 0.56, z=1.30 (p=0.19) I2statistic of 85%). Subgroup analysis of 6–12 month outcome reduced heterogeneity and increased intervention effect compared to control (SMD 0.53, 95% CI 0.41 to 0.65, z=8.84 (p<0.00001) I2of 66%).

Conclusions

Arthritis self-management programmes achieve a small but significant improvement in physical activity in the short term. Effectiveness of intervention declines with extended follow-up beyond 12 months with no significant benefit compared to control. The small number of studies (11 RCTs) limited ability to define effective delivery methods. Investigation of behavioural lifestyle interventions for lower limb osteoarthritis populations would benefit from consensus on methodology and outcome reporting. This includes use of validated physical activity reporting tools and planning for long-term follow-up.
A police education programme to integrate occupational safety and HIV prevention: protocol for a modified stepped-wedge study design with parallel prospective cohorts to assess behavioural outcomes
Authors: Strathdee Steffanie A , Arredondo Jaime , Rocha Teresita , Abramovitz Daniela , Rolon Maria Luisa , Patiño Mandujano Efrain , Rangel Maria Gudelia , Olivarria Horcasitas Omar , Gaines Tommi , Patterson Thomas L , Beletsky Leo
Published: August 2015

Introduction

Policing practices are key drivers of HIV among people who inject drugs (PWID). This paper describes the protocol for the first study to prospectively examine the impact of a police education programme (PEP) to align law enforcement and HIV prevention. PEPs incorporating HIV prevention (including harm reduction programmes like syringe exchange) have been successfully piloted in several countries but were limited to brief pre–post assessments; the impact of PEPs on policingbehavioursand occupational safety is unknown.

Objectives

Proyecto ESCUDO (SHIELD) aims to evaluate the efficacy of the PEP on uptake of occupational safety procedures, as assessed through the incidence of needle stick injuries (NSIs) (primary outcome) and changes in knowledge of transmission, prevention and treatment of HIV and viral hepatitis; attitudes towards PWID, adverse behaviours that interfere with HIV prevention and protective behaviours (secondary outcomes).

Methods/analysis

ESCUDO is a hybrid type I design that simultaneously tests an intervention and an implementation strategy. Using a modified stepped-wedge design involving all active duty street-level police officers in Tijuana (N=∼1200), we will administer one 3 h PEP course to groups of 20–50 officers until the entire force is trained. NSI incidence and geocoded arrest data will be assessed from department-wide de-identified data. Of the consenting police officers, a subcohort (N=500) will be randomly sampled from each class to undergo pre-PEP and post-PEP surveys with a semiannual follow-up for 2 years to assess self-reported NSIs, attitudes and behaviour changes. The impact on PWIDs will be externally validated through a parallel cohort of Tijuana PWIDs.

Ethics/dissemination

Research ethics approval was obtained from the USA and Mexico. Findings will be disseminated through open access to protocol materials through the Law Enforcement and HIV Network.

Trial registration number

NCT02444403.
Critical reaction forces of glulam members with tension-side notches at end supports
Authors: Weckendorf Jan , Meleki Kiwelu Henry , Smith Ian
Published: August 2015

Tests were carried out on softwood structural glued-laminated-timber (glulam) members to calibrate a linear elastic fracture mechanics design method for bending members having tension-side end notches. Fifty-eight specimens with depths up to 646 mm represented 11 combinations of member size, notch depth, member geometry, loading arrangement, and glulam type. Specimens were loaded until they sustained significant damage at or near notch locations, but none of them failed as bending members. Notch damage started with creation of short stable cracks parallel to the laminations and ended with episodically crack growth. Typically, crack initiation is at about half the load level associated with episodic crack growth. Contrary to current design practice loads positioned close to notched end supports were found to influence strengths of members significantly, and their effects should be taken into account. The findings have been implemented in the 2014 edition of CAN/CSA Standard 086 “Engineering Design in Wood”.
Evaluation of the pathogenic potential, antimicrobial susceptibility, and genomic relations of Yersinia enterocolitica strains from food and human origin
Authors: Lucero-Estrada Cecilia S.M. , Soria José Miguel , Favier Gabriela Isabel , Escudero María Esther
Published: August 2015

Yersinia enterocolitica is a food-borne pathogen that causes gastroenteritis with occasional postinfection sequels. This study was aimed to determinate the pathogenic potential, antimicrobial susceptibility, and genomic relationships of Y. enterocolitica strains of different bioserotypes (B/O) isolated from foods and human samples in San Luis, Argentina. Strains obtained by culture were bioserotyped and characterized by phenotypic and genotypic virulence markers, antimicrobial susceptibility, and pulsed-field gel electrophoresis (PFGE). Yersinia enterocolitica was detected in 9.2% of 380 samples, with a distribution of 10.6% (30/284) for food products and 5.2% (5/96) for human samples. Regarding the pathogenic potential, B1A strains of different serotypes were virF– ail–, of which 72.0% (13/18) were ystB+ with virulence-related phenotypic characteristics. Among B2/O:9 isolates, 75.0% (9/12) exhibited the genotype virF+ ail+ ystB– along with phenotypic traits associated with virulence; the same genotype was observed in 80.0% (4/5) of B3/O:3 and B3/O:5 strains. By PFGE, it was possible to separate Y. enterocolitica biotypes into 4 clonal groups (A to D) with 23 genomic types, generating a discriminatory index of 0.96. All isolates were susceptible to antimicrobials used for clinical treatment. This study highlights the presence of pathogenic bioserotypes and the high genomic diversity of the Y. enterocolitica strains isolated in our region.
Stock market network’s topological stability: Evidence from planar maximally filtered graph and minimal spanning tree
Authors: Yan Xin-Guo , Xie Chi , Wang Gang-Jin
Published: August 2015

We study the topological stability of stock market network by investigating the topological robustness, namely the ability of the network to resist structural or topological changes. The stock market network is extracted by minimal spanning tree (MST) and planar maximally filtered graph (PMFG). We find that the specific delisting thresholds of the listed companies exist in both MST and PMFG networks. In comparison with MST, PMFG provides more information and is better for the aim of exploring stock market network’s robustness. The PMFG before the US sub-prime crisis (i.e., from June 2005 to May 2007) has a stronger robustness against the intentional topological damage than the other two sub-periods (i.e., from June 2007 to May 2009 and from June 2009 to May 2011). We also find that the nonfractal property exists in MSTs of S&P 500, i.e., the highly connected nodes link with each other directly, which indicates that the MSTs are vulnerable to the removal of such important nodes. Moreover, the financial institutions and high technology companies are important in maintaining the stability of S&P 500 network.
Structures and stabilities of (OsnN)0,±(n = 7 − 11) clusters
Authors: Guo W. L. , Zhang L. L. , Luo M. , Zhang X. R.
Published: August 2015

Structures and stabilities of [Formula: see text] clusters have been systematically studied via using density functional theory (DFT) with generalized gradient approximation (GGA). The calculations show that the stable configurations of [Formula: see text] are such structures with one N atom bonded to the external of the basic constructions consisting of Os atoms. Meanwhile, [Formula: see text] clusters [Formula: see text] represent “magic number” effect, and 8 is the magic number. Additionally, the ground-state structures of [Formula: see text] clusters have the best stability, while that of [Formula: see text] cluster possesses the worst stability. The result of the study on the ionization potential (IP) and the electron affinity (EA) shows that there are not topological differences among the configurations of [Formula: see text][Formula: see text] clusters.
Quantum gravity: A brief history of ideas and some prospects
Authors: Carlip Steven , Chiou Dah-Wei , Ni Wei-Tou , Woodard Richard
Published: August 2015

We present a bird's-eye survey on the development of fundamental ideas of quantum gravity, placing emphasis on perturbative approaches, string theory, loop quantum gravity (LQG) and black hole thermodynamics. The early ideas at the dawn of quantum gravity as well as the possible observations of quantum gravitational effects in the foreseeable future are also briefly discussed.
Are superheavy stable quark clusters viable candidates for the dark matter?
Authors: Borštnik Norma Mankoč , Rosina Mitja
Published: August 2015

The explanation for the origin of families of quarks and leptons and their properties is one of the most promising ways to understand the assumptions of the Standard Model. The Spin-Charge-Family theory [N. S. M. Borštnik, Phys. Lett. B 292 (1992) 25; J. Math. Phys. 34 (1993) 3731; Int. J. Theor. Phys. 40 (2001) 315; Mod. Phys. Lett. A 10 (1995) 587; J. Modern Phys. 4 (2013) 823; arXiv:1312.15; Phys. Rev. D 91 (2015) 065004; [arXiv:1409.7791; arXiv:1312.1542; arXiv:1502.06786v1, http://arXiv.org/abs/1409.4981 ; A. Borštnik and N. S. M. Borštnik, Phys. Rev. D 74 (2006) 073013, arXiv:hep-ph/0512062, arXiv:hep-ph/0401043, arXiv:hep-ph/0401055, arXiv:hep-ph/0301029; G. Bregar and N. S. M. Borštnik, arXiv:1412.5866; G. Bregar et al., New J. Phys. 10 (2008) 093002; G. Bregar and N. S. M. Borštnik, arXiv:1502.06786v1, arXiv:1412.5866; N. S. M. Borštnik, Proc. 13th Workshop “What Comes Beyond the Standard Models”, Bled, 12–22 July 2010, eds. N. S. M. Borštnik et al., DMFA Založništvo, Ljubljana, December 2010, pp. 105–129], which does propose the mechanism for the appearance of families and offers an explanation for all the assumptions of the Standard Model, predicts two decoupled groups of four families. The lightest of the upper four families has stable members, which are correspondingly candidates to constitute the dark matter [G. Bregar and N. S. M. Borštnik, Phys. Rev. D 80 (2009) 083534, arXiv:1412.5866]. In this paper, we study the weak and the “nuclear” (determined by the color interaction among the heavy fifth family quarks) scattering of such a very heavy baryon by ordinary nucleons in order to show that the cross-section is very small and consistent with the observation in most experiments so far, provided that the quark mass of this baryon is about 100[Formula: see text]TeV or above.
Phase Difference in Lateral Synchronization of Pedestrian Floors Using a Modified Hybrid Van der pol/Rayleigh Oscillator
Authors: Kumar Anil , Erlicher Silvano , Argoul Pierre
Published: August 2015

The modified hybrid Van der Pol/Rayleigh (MHVR) oscillator was originally proposed by the authors to model the lateral oscillations of a pedestrian walking on a rigid floor and it was shown that for the autonomous case, the MHVR oscillator can correctly fit the experimental data. The case of a pedestrian walking on a laterally moving floor is modeled by a nonautonomous oscillator. The case of a floor subjected to a harmonic lateral motion has been then studied by the authors, with focus on the amplitude and stability of the entrained response, i.e. the response having the same frequency as that of the given periodic excitation. For the nonautonomous (moving floor) case, the main focus of this paper is on the analysis of the phase difference between the oscillator entrained response and the external excitation. Both analytical and numerical calculations have been performed. The approximate analytical method is the harmonic balance method. Then, the model is used to represent the experimental results for the pedestrian lateral oscillations during walking. Comparison is made for the examples along with discussions.
N-Valid trees in wavelet theory on Vilenkin groups
Authors: Lukomskii S. F. , Berdnikov G. S.
Published: August 2015

We consider a class of (N, M)-elementary step functions on the p-adic Vilenkin group. We prove that (N, M)-elementary step function generates a MRA on p-adic Vilenkin group if and only if it is generated by a special N-valid rooted tree on the set of vertices {0,1,…p - 1} with the vector (0,…,0) ∈ ℤN as a root.
Developing a Traffic Management Framework for Coastal Expressway Bridges under Adverse Weather Conditions: Case Study of Rain Day in Shenzhen, China
Authors: Jiang Chenming , John Lu Jian , Jiang Yuming , Cai Xiaonan , Ni Anning
Published: August 2015

Adverse weather can reduce visibility and road surface friction, lower vehicle maneuverability, and increase crash frequency and injury severity. The impacts of adverse weather and its interactions with drivers and roadway on the operation and management of expressway or expressway bridges have drawn the researchers’ and managers’ attention to develop traffic management frameworks to mitigate the negative influence. Considering the peculiar geographical location and meteorological conditions, the Guangshen Coast Expressway-Shenzhen Segment (GSCE-SS) was selected as a case in this study to illustrate the proposed traffic management framework on rain days. Conditions categorized by rainfall intensity and traffic flow were the main precondition to make the management decisions. CORSIM simulator was used to develop the alternate routes choice schemes, providing reference for other systems in the proposed traffic management framework. Maps of (a) entrance ramp control (ERC) strategies; (b) mainline control strategies; (c) alternate routes choice; (d) information release schemes, under scenarios of different volume and rainstorm warning grades (BLUE to RED), were drawn to present a reference or demonstration for managers of long-span expressway bridges not only in China, but even in the world.