bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic vitamin A‐enriched diet feeding induces body weight gain and adiposity in lean and glucose‐intolerant obese rats of WNIN/GR‐Ob strain
Authors: Jeyakumar Shanmugam M. , Sheril Alex , Vajreswari Ayyalasomayajula
Published: April 2015

New Findings

What is the central question of this study?

Previously, we reported that chronic feeding of a vitamin A‐enriched diet to euglycaemic obese rats (WNIN/Ob) ameliorated obesity. Does this diet exert similar effects even with a different genetic background, i.e. obese rats of the WNIN/GR‐Ob strain with impaired glucose tolerance?

What is the main finding and its importance?

Vitamin A‐enriched diet aggravated weight gain and adiposity/obesity in both lean and glucose‐intolerant obese rats of the WNIN/GR‐Ob strain. Therefore, the role of genetic factors and their regulation by nutrients in determining health and disease conditions assumes greater significance in experimental and clinical research.

Vitamin A and its metabolites are key regulators of the development of adipose tissue and its associated metabolic complications. Here, we tested, in a glucose‐intolerant obese rat model (the WNIN/GR‐Ob stain), whether feeding a vitamin A‐enriched diet alters adiposity and its associated changes. For this purpose, 30‐week‐old male lean and obese rats were divided into two groups and received either stock diet or vitamin A‐enriched diet [2.6 or 129 mg vitamin A (kg diet)−1, respectively] for 14 weeks. At the end, feeding of the vitamin A‐enriched diet resulted in increased body weight gain/obesity and retroperitoneal white adipose tissue (RPWAT) in both lean and obese rats of the WNIN/GR‐Ob strain, when compared with their respective control animals receiving stock diet, without affecting food intake. An improvement in hypertriglyceridaemia and circulatory non‐esterified fatty acid levels and unaltered hepatic fatty acid oxidative and triglyceride secretory pathway proteins with vitamin A‐enriched diet feeding are suggestive of enhanced hepatic clearance of circulatory lipids, resulting in increased hepatic triglyceride accumulation. Transcriptional analysis of RPWAT showed that feeding the vitamin A‐enriched diet augmented the expression of adipogenic/adipose tissue‐specific genes; peroxisome proliferator‐activated receptor‐γ, stearoyl CoA desaturase 1, retinol saturase, leptin and lipoprotein lipase and vitamin A metabolic pathway genes; retinoic acid receptors, retinoid X receptors and cytochrome P450 26B1. Besides, RPWAT–lipoprotein lipase‐mediated clearance of triglyceride could also have contributed to increased adiposity and improved hypertriglyceridaemia. In conclusion, chronic feeding of vitamin A‐enriched diet induces weight gain and adiposity in both lean and obese rats of the WNIN/GR‐Ob strain, possibly through transcriptional regulation of key adipogenic pathway genes of RPWAT, but improves dyslipidaemia.
Student ability and learning experience in assessing peers alongside supervisors in the long case
Authors: Burgess Annette , Roberts Chris , Black Kirsten , Mellis Craig
Published: April 2015

Background: Peer assessment can provide a valuable method of enriching students’ learning experience, particularly when students act as the assessors, which provides a highly effective enquiry-based learning experience and is increasingly being utilised in medical schools internationally. In preparation for their summative examinations, senior medical students at the Sydney Medical School are required to assess their peers, alongside an academic co-examiner, in the formative long case examinations. This study sought to assess the level of agreement in marking and decision making between student peer and academic assessors, to evaluate the impact of peer assessment on examination performance and to investigate students’ perception of their experience as assessors. Methods: Medical students examined their peers, alongside an academic co-examiner. We randomly allocated half of the student participants to examine a peer, alongside an academic assessor, prior to being examined themselves. The level of agreement in marking was determined by comparing the independent marking sheets of student and academic co-examiners. Data on whether the student was examined before or after assessing a peer (order of examination) were collected and compared to measure whether prior participation as a peer assessor improved student examination performance. Questionnaires and focus group discussions were used to evaluate student peer assessor perceptions. Results: Over a 3-year period (2010 to 2012), 197 students participated as co- examiners and were also examined by their peers, with students marking significantly more leniently than their academic co-examiners. Order of examination had no significant bearing on student examination performance. Students identified several benefits of acting as an examiner, including better insight into examination technique, opportunities for self-reflection and knowledge acquisition, and development of some of the attributes of professionalism. However, students identified difficulty in providing critical feedback to peers.Conclusion: Engagement as an assessor alongside an academic supervisor provides a rich learning experience for students. Additional training in both peer assessment and feedback may increase students’ professional and educational outcomes for future iterations of the activity.
Comprehensive characterization of well-defined silk fibroin surfaces: Toward multitechnique studies of surface modification effects
Authors: Amornsudthiwat Phakdee , Nitschke Mirko , Zimmermann Ralf , Friedrichs Jens , Grundke Karina , Pöschel Kathrin , Damrongsakkul Siriporn , Werner Carsten
Published: April 2015

The study aims at a comprehensive surface characterization of untreated and oxygen plasma-treated silk fibroin with a particular focus on phenomena relevant to biointeraction and cell adhesion. For that purpose, a range of advanced surface diagnostic techniques is employed to thoroughly investigate well-defined and especially clean silk fibroin samples in a comparable setting. This includes surface chemistry and surface charges as factors, which control protein adsorption, but also hydration and swelling of the material as important parameters, which govern the mechanical stiffness at the interface with aqueous media. Oxygen plasma exposure of silk fibroin surfaces reveals that material ablation strongly predominates over the introduction of functional groups even for mild plasma conditions. A substantial increase in mechanical stiffness is identified as the most prominent effect upon this kind of plasma treatment. Regarding the experimental approach and the choice of techniques, the work goes beyond previous studies in this field and paves the way for well-founded investigations of other surface-selective modification procedures that enhance the applicability of silk fibroin in biomedical applications.
MBE growth of sharp interfaces in dilute-nitride quantum wells with improved nitrogen-plasma design
Authors: Vijaya Gopi Krishna , Freundlich Alex , Tang Dinghao , Smith David J.
Published: April 2015

Analysis of structural and luminescence properties of GaAsN epilayers grown by molecular beam epitaxy (MBE) and chemical beam epitaxy on GaAs (001) substrates indicates the possibility of fabricating high nitrogen content (x > 0.03) alloys. The conventional plasma source design where nitrogen flux is controlled using a manual shutter was first implemented. Investigation of structural and optical properties by photoluminescence, high-resolution x-ray diffraction, secondary-ion mass spectrometry, and electron microscopy indicated the presence of thin parasitic layers formed during nitrogen plasma ignition, as well as significant N contamination of GaAs barrier layers, which could severely affect carrier extraction and transport properties in targeted devices. In order to overcome these limitations, a gate-valve-activated run-vent design was implemented that allowed the plasma to operate continuously during MBE growth, while N plasma flux changes during growth were monitored. The potential of this design for achieving very sharp switching schemes compatible with the fabrication of complex dilute-nitride quantum well structures, while preventing N contamination of GaAs barriers, was demonstrated.
Sociodemographic Factors, Population Density, and Bicycling for Transportation in the United States
Authors: Nehme Eileen K. , Pérez Adriana , Ranjit Nalini , Amick Benjamin C. , Kohl Harold W.
Published: April 2015

Background:

Transportation bicycling is a behavior with demonstrated health benefits. Population-representative studies of transportation bicycling in United States are lacking. This study examined associations between sociodemographic factors, population density, and transportation bicycling and described transportation bicyclists by trip purposes, using a US-representative sample.

Methods:

This cross-sectional study used 2009 National Household Travel Survey datasets. Associations among study variables were assessed using weighted multivariable logistic regression.

Results:

On a typical day in 2009, 1% of Americans older than 5 years of age reported a transportation bicycling trip. Transportation cycling was inversely associated with age and directly with being male, with being white, and with population density (≥ 10,000 vs < 500 people/square mile: odd ratio, 2.78, 95% confidence interval, 1.54–5.05). Those whose highest level of education was a high school diploma or some college were least likely to bicycle for transportation. Twenty-one percent of transportation bicyclists reported trips to work, whereas 67% reported trips to social or other activities.

Conclusions:

Transportation bicycling in the United States is associated with sociodemographic characteristics and population density. Bicycles are used for a variety of trip purposes, which has implications for transportation bicycling research based on commuter data and for developing interventions to promote this behavior.
Athletes’ Transgressions and Sponsor Evaluations: A Focus on Consumers’ Moral Reasoning Strategies
Authors: Lee Joon Sung , Kwak Dae Hee , Moore David
Published: April 2015

Marketing managers often face dilemmas when their athlete endorsers are accused of immoral behavior. However, research findings have been equivocal as to whether athletes’ transgressions damage endorsed brand evaluations. Using two experiments, we empirically demonstrate that consumers’ moral reasoning (i.e., moral rationalization, moral coupling, and moral decoupling) has differential effects on evaluations of a transgressor (Study 1). In Study 2, we examine the causal effect of moral reasoning choice on evaluations of the transgressor and the associated brand. Findings show that moral coupling has negative effects on the athlete and brand evaluations, whereas moral decoupling and moral rationalization positively affect brand attitude and purchase intent through positive evaluation of the athlete. Findings from this study provide empirical evidence to explain how and why some consumers continue or discontinue their support for a troubled athlete and associated brand.
Young School Children’s Recess Physical Activity: Movement Patterns and Preferences
Authors: Woods Amelia Mays , Graber Kim C. , Daum David Newman , Gentry Chris
Published: April 2015

This study examined physical activity (PA) variables related to recess PA patterns of kindergarten, first and second grade children, and the social preferences and individuals influencing their PA. Data collected (N = 147) used the System of Observing Children’s Activity and Relationships during Play (SOCARP) instrument. Children were interviewed. Kindergarten boys spent a significantly higher percentage of time in MVPA (t = 3.137, d = .96, p < .008). Kindergarten girls spent significantly more time standing (t = 3.548, d = 1.07, p < .008). Second grade boys spent a significantly (t = 4.44, d = 1.98, p < .0125) more time in sport activities. Second grade girls spent significantly more time in sedentary (t = 4.399, d = 1.11, p < .0125) and locomotor (t = 3.533, d = .899, p < .0125) activities. Participants articulated the prominence of friends, engaging in games/activities, and playing on the playground equipment.
Optimized unconventional superconductivity in a molecular Jahn-Teller metal
Authors: Zadik Ruth H. , Takabayashi Yasuhiro , Klupp Gyöngyi , Colman Ross H. , Ganin Alexey Y. , Potočnik Anton , Jeglič Peter , Arčon Denis , Matus Péter , Kamarás Katalin , Kasahara Yuichi , Iwasa Yoshihiro , Fitch Andrew N. , Ohishi Yasuo , Garbarino Gaston , Kato Kenichi , Rosseinsky Matthew J. , Prassides Kosmas
Published: April 2015

A superconductivity dome is created by the electronic structure of the molecular building block of an unconventional superconductor.
BRAF-induced tumorigenesis is IKKα-dependent but NF-κB–independent
Authors: Margalef Pol , Colomer Carlota , Villanueva Alberto , Montagut Clara , Iglesias Mar , Bellosillo Beatriz , Salazar Ramón , Martínez-Iniesta María , Bigas Anna , Espinosa Lluís
Published: April 2015

Disrupting endosome function may inhibit mutant BRAF–mediated colon cancer growth.
Combined cardiomyocyte PKCδ and PKCε gene deletion uncovers their central role in restraining developmental and reactive heart growth
Authors: Song Moshi , Matkovich Scot J. , Zhang Yan , Hammer Daniel J. , Dorn Gerald W.
Published: April 2015

Two related isoforms of PKC cooperate to limit cardiac hypertrophy during heart development and in response to hemodynamic stress.
Rounding up the usual suspects in O
2
sensing: CO, NO, and H
2
S!
Authors: Fandrey Joachim
Published: April 2015

Hypoxia triggers a signaling pathway that stimulates the carotid body and breathing.
Antifungal Activities of SCY-078 (MK-3118) and Standard Antifungal Agents against Clinical Non-Aspergillus Mold Isolates
Authors: Lamoth Frédéric , Alexander Barbara D.
Published: April 2015

The limited armamentarium of active and oral antifungal drugs against emerging non-
Aspergillus
molds is of particular concern. Current antifungal agents and the new orally available beta-1,3-
d
-glucan synthase inhibitor SCY-078 were tested
in vitro
against 135 clinical non-
Aspergillus
mold isolates. Akin to echinocandins, SCY-078 showed no or poor activity against
Mucoromycotina
and
Fusarium
spp. However, SCY-078 was highly active against
Paecilomyces variotii
and was the only compound displaying some activity against notoriously panresistant
Scedosporium prolificans
.
Comparison of the
In Vitro
Activities of Newer Triazoles and Established Antifungal Agents against Trichophyton rubrum
Authors: Deng Shuwen , Zhang Chao , Seyedmousavi Seyedmojtaba , Zhu Shuang , Tan Xin , Wen Yiyang , Huang Xin , Lei Wenzhi , Zhou Zhaojing , Fang Wenjie , Shen Shuaishuai , Deng Danqi , Pan Weihua , Liao Wanqing
Published: April 2015

One hundred eleven clinical
Trichophyton rubrum
isolates were tested against 7 antifungal agents. The geometric mean MICs of all isolates were, in increasing order: terbinafine, 0.03 mg/liter; voriconazole, 0.05 mg/liter; posaconazole, 0.11 mg/liter; isavuconazole, 0.13 mg/liter; itraconazole, 0.26 mg/liter; griseofulvin, 1.65 mg/liter; and fluconazole, 2.12 mg/liter.
Epidemiology of Vancomycin-Resistant Enterococci in Canadian Hospitals (CANWARD Study, 2007 to 2013)
Authors: Simner P. J. , Adam H. , Baxter M. , McCracken M. , Golding G. , Karlowsky J. A. , Nichol K. , Lagacé-Wiens P. , Gilmour M. W. ,   Canadian Antimicrobial Resistance Alliance (CARA), Hoban D. J. , Zhanel G. G.
Published: April 2015

Of 1,927
Enterococcus
species isolates collected across Canada from 2007 to 2013, 80 (4.2%) were identified as vancomycin-resistant enterococci (VRE). VRE infections during this time tripled in Canadian hospitals, from 1.8% to 6.0% (
P
= 0.03). All VRE were
Enterococcus faecium
, with 90% possessing
vanA
. The prevalence of
vanB
decreased from 37.5% in 2007 to 0% in 2013 (
P
< 0.05). The VRE were multidrug resistant, but 70.6%, 86.3%, and 100% were susceptible to doxycycline, linezolid, and daptomycin, respectively.
Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis
Authors: Gunawardana Manjula , Remedios-Chan Mariana , Miller Christine S. , Fanter Rob , Yang Flora , Marzinke Mark A. , Hendrix Craig W. , Beliveau Martin , Moss John A. , Smith Thomas J. , Baum Marc M.
Published: April 2015

Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day
−1
in vitro
was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml
−1
; interquartile range [IQR], 0.60 to 1.50 ng ml
−1
) and tenofovir (TFV; median, 15.0 ng ml
−1
; IQR, 8.8 to 23.3 ng ml
−1
), the product of
in vivo
TAF hydrolysis. High concentrations (median, 512 fmol/10
6
cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations.
The Serine Protease Autotransporter Pic Modulates Citrobacter rodentium Pathogenesis and Its Innate Recognition by the Host
Authors: Bhullar Kirandeep , Zarepour Maryam , Yu Hongbing , Yang Hong , Croxen Matthew , Stahl Martin , Finlay B. Brett , Turvey Stuart E. , Vallance Bruce A.
Published: April 2015

Bacterial pathogens produce a number of autotransporters that possess diverse functions. These include the family of serine protease autotransporters of
Enterobacteriaceae
(SPATEs) produced by enteric pathogens such as
Shigella flexneri
and enteroaggregative
Escherichia coli
. Of these SPATEs, one termed “protein involved in colonization,” or Pic, has been shown to possess mucinase activity
in vitro
, but to date, its role in
in vivo
enteric pathogenesis is unknown. Testing a
pic
null (Δ
picC
) mutant in
Citrobacter rodentium
, a natural mouse pathogen, found that the
C. rodentium
Δ
picC
strain was impaired in its ability to degrade mucin
in vitro
compared to the wild type. Upon infection of mice, the Δ
picC
mutant exhibited a hypervirulent phenotype with dramatically heavier pathogen burdens found in intestinal crypts. Δ
picC
mutant-infected mice suffered greater barrier disruption and more severe colitis and weight loss, necessitating their euthanization between 10 and 14 days postinfection. Notably, the virulence of the Δ
picC
mutant was normalized when the
picC
gene was restored; however, a PicC point mutant causing loss of mucinase activity did not replicate the Δ
picC
phenotype. Exploring other aspects of PicC function, the Δ
picC
mutant was found to aggregate to higher levels
in vivo
than wild-type
C. rodentium
. Moreover, unlike the wild type, the
C. rodentium
Δ
picC
mutant had a red, dry, and rough (RDAR) morphology
in vitro
and showed increased activation of the innate receptor Toll-like receptor 2 (TLR2). Interestingly, the
C. rodentium
Δ
picC
mutant caused a degree of pathology similar to that of wild-type
C. rodentium
when infecting TLR2-deficient mice, showing that despite its mucinase activity, PicC's major role
in vivo
may be to limit
C. rodentium
's stimulation of the host's innate immune system.
Serratia marcescens Cyclic AMP Receptor Protein Controls Transcription of EepR, a Novel Regulator of Antimicrobial Secondary Metabolites
Authors: Stella Nicholas A. , Lahr Roni M. , Brothers Kimberly M. , Kalivoda Eric J. , Hunt Kristin M. , Kwak Daniel H. , Liu Xinyu , Shanks Robert M. Q.
Published: April 2015

Serratia marcescensgenerates secondary metabolites and secreted enzymes, and it causes hospital infections and community-acquired ocular infections. Previous studies identified cyclic AMP (cAMP) receptor protein (CRP) as an indirect inhibitor of antimicrobial secondary metabolites. Here, we identified a putative two-component regulator that suppressedcrpmutant phenotypes. Evidence supports that the putative response regulatoreepRwas directly transcriptionally inhibited by cAMP-CRP. EepR and the putative sensor kinase EepS were necessary for the biosynthesis of secondary metabolites, including prodigiosin- and serratamolide-dependent phenotypes, swarming motility, and hemolysis. Recombinant EepR bound to the prodigiosin and serratamolide promotersin vitro. Together, these data introduce a novel regulator of secondary metabolites that directly connects the broadly conserved metabolism regulator CRP with biosynthetic genes that may contribute to competition with other microbes.

IMPORTANCEThis study identifies a new transcription factor that is directly controlled by a broadly conserved transcription factor, CRP. CRP is well studied in its role to help bacteria respond to the amount of nutrients in their environment. The new transcription factor EepR is essential for the bacteriumSerratia marcescensto produce two biologically active compounds, prodigiosin and serratamolide. These two compounds are antimicrobial and may allowS. marcescensto compete for limited nutrients with other microorganisms. Results from this study tie together the CRP environmental nutrient sensor with a new regulator of antimicrobial compounds. Beyond microbial ecology, prodigiosin and serratamolide have therapeutic potential; therefore, understanding their regulation is important for both applied and basic science.
Unraveling the Mechanism for the Viability Deficiency of Shewanella oneidensis oxyR Null Mutant
Authors: Shi Miaomiao , Wan Fen , Mao Yinting , Gao Haichun
Published: April 2015

Oxidative stresses triggered by reactive oxygen species (ROS) that damage various cellular components are unavoidable for virtually all living organisms. In defense, microorganisms have evolved sophisticated mechanisms to sense, respond to, and battle against ROS.Shewanella oneidensis, an important research model for applied and environmental microbes, employs OxyR to mediate the response to H2O2by derepressing the production of the major H2O2scavenger KatB as a major means toward these goals. Surprisingly, despite enhanced H2O2degradation, theoxyRmutant carries a viability deficiency phenotype (plating defect), which can be suppressed by the addition of exogenous iron species. Experiments showed that the defect was not due to iron starvation. Rather, multiple lines of evidence suggested that H2O2generated abiotically in lysogeny broth (LB) is responsible for the defect by quickly killing mutant cells. We then showed that the iron species suppressed the plating defect by two distinct mechanisms, either as an H2O2scavenger without involving living cells or as an environmental cue to stimulate an OxyR-independent response to help cells cope with oxidative stress. Based on the suppression of the plating defect by overproduction of H2O2scavengersin vivo, we propose that cellular components that are vulnerable to H2O2and responsible for the defect may reside outside the cytoplasm.

IMPORTANCEIn bacteria, OxyR is the major regulator controlling the cellular response to H2O2. The loss of OxyR results in reduced viability in many species, but the underlying mechanism is unknown. We showed inS. oneidensisthat this defect was due to H2O2generated abiotically in LB. We then showed that this defect could be corrected by the addition of Fe2+or catalase to the LB or increased intracellular production of catalase. Further analyses revealed that Fe2+was able not only to decompose H2O2directly but also to stimulate the activity of OxyR-independent H2O2-scavenging enzymes. Our data indicate that iron species play a previously underappreciated role in protecting cells from H2O2in environments.
The Cyclic AMP-Vfr Signaling Pathway in Pseudomonas aeruginosa Is Inhibited by Cyclic Di-GMP
Authors: Almblad Henrik , Harrison Joe J. , Rybtke Morten , Groizeleau Julie , Givskov Michael , Parsek Matthew R. , Tolker-Nielsen Tim
Published: April 2015

The opportunistic human pathogenPseudomonas aeruginosaexpresses numerous acute virulence factors in the initial phase of infection, and during long-term colonization it undergoes adaptations that optimize survival in the human host. Adaptive changes that often occur during chronic infection give rise to rugose small colony variants (RSCVs), which are hyper-biofilm-forming mutants that commonly possess mutations that increase production of the biofilm-promoting secondary messenger cyclic di-GMP (c-di-GMP). We show that RSCVs display a decreased production of acute virulence factors as a direct result of elevated c-di-GMP content. Overproduction of c-di-GMP causes a decrease in the transcription of virulence factor genes that are regulated by the global virulence regulator Vfr. The low level of Vfr-dependent transcription is caused by a low level of its coactivator, cyclic AMP (cAMP), which is decreased in response to a high level of c-di-GMP. Mutations that cause reversion of the RSCV phenotype concomitantly reactivate Vfr-cAMP signaling. Attempts to uncover the mechanism underlying the observed c-di-GMP-mediated lowering of cAMP content provided evidence that it is not caused by inhibition of adenylate cyclase production or activity and that it is not caused by activation of cAMP phosphodiesterase activity. In addition to the studies of the RSCVs, we present evidence that the deeper layers of wild-typeP. aeruginosabiofilms have high c-di-GMP levels and low cAMP levels.

IMPORTANCEOur work suggests that cross talk between c-di-GMP and cAMP signaling pathways results in downregulation of acute virulence factors inP. aeruginosabiofilm infections. Knowledge about this cross-regulation adds to our understanding of virulence traits and immune evasion byP. aeruginosain chronic infections and may provide new approaches to eradicate biofilm infections.
Diversity of Class 1 Integron Gene Cassette Rearrangements Selected under Antibiotic Pressure
Authors: Barraud Olivier , Ploy Marie-Cécile
Published: April 2015

Integrons are bacterial genetic elements able to capture and express genes contained within mobile gene cassettes. Gene cassettes are expressed via a Pc promoter and can be excised from or integrated into the integron by integrase IntI. Although the mechanisms of gene cassette integration and excision are well known, the kinetics and modes of gene cassette shuffling leading to new gene cassette arrays remain puzzling. It has been proposed that under antibiotic selective pressure, IntI-mediated rearrangements can generate integron variants in which a weakly expressed gene cassette moves closer to Pc, thus leading to higher-level resistance. To test this hypothesis, we used an integron with four gene cassettes,intI1-aac(6′)-Ib-dfrA15-aadA1-catB9, and applied selective pressure with chloramphenicol, resistance to which is encoded bycatB9. Experiments were performed with three different Pc variants corresponding to three IntI1 variants. All three integrases, even when not overexpressed, were able to bringcatB9closer to Pc via excision of thedfrA15andaadA1gene cassettes, allowing their host bacteria to adapt to antibiotic pressure and to grow at high chloramphenicol concentrations. Integrase IntI1R32_H39, reported to have the highest recombination activity, was able, when overexpressed, to trigger multiple gene cassette rearrangements. Although we observed a wide variety of rearrangements withcatB9moving closer to Pc and leading to higher chloramphenicol resistance, “cut-and-paste” relocalization ofcatB9to the first position was not detected. Our results suggest that gene cassette rearrangements via excision are probably less cost-effective than excision and integration of a distal gene cassette closer to Pc.

IMPORTANCEIntegrons are bacterial genetic elements able to capture and express gene cassettes. Gene cassettes are expressed via a Pc promoter; the closer they are to Pc, the more strongly they are expressed. Gene cassettes can be excised from or integrated into the integron by integrase IntI. The kinetics and modes of gene cassette shuffling, leading to new gene cassette arrays remain puzzling. We used an integron with 4 antibiotic resistance gene cassettes and applied selective pressure with the antibiotic for which resistance was encoded by cassette 4. All IntI variants were able to bring cassette 4 closer to Pc. Rearrangements occur via excision of the previous gene cassettes instead of cut-and-paste relocalization of the fourth gene cassette.
Recurrence of aqueous misdirection following pars plana vitrectomy in pseudophakic eyes
Authors: Dave Paaraj , Rao Aparna , Senthil Sirisha , Choudhari Nikhil Shreeram
Published: April 2015

We present a retrospective interventional case series of four patients with pseudophakic eye who developed recurrent aqueous misdirection following pars plana vitrectomy (PPV) for malignant glaucoma (MG). The patients were treated with neodymium: YAG (Yttrium Aluminum Garnet) laser hyaloidotomy/membranotomy through the patent peripheral iridectomy. The main outcome measure was resolution of MG. The intervention resulted in resolution of MG in all four cases. The cause for recurrence was an inflammatory membrane covering the hyaloidotomy opening in three eyes and the haptic of intraocular lens blocking the hyaloidotomy opening in one eye. Recurrence of aqueous misdirection even after vitrectomy may be related to obstruction of aqueous flow through the communication created, either by intraocular lens or fibrin. Treatment of this condition involves restoring aqueous flow to the anterior chamber from the anterior vitreous by treating the cause, and most often the YAG laser hyaloidotomy/membranotomy is successful in relieving the condition.
Orbital cellulitis with periorbital abscess secondary to methicillin-resistantStaphylococcus aureus(MRSA) sepsis in an immunocompetent neonate
Authors: Rao Lavanya G , Rao Krishna , Bhandary Sulatha , Shetty Priyanka Ranjan
Published: April 2015

This article advocates the need for early incision and drainage of periorbital abscesses. We report a case of a 1.5-month-old neonate with orbital cellulitis and periorbital abscess, which had rapidly developed over a period of 3 days. Treatment history revealed methicillin-resistantStaphylococcus aureussepsis treated with intravenous vancomycin, and incision and drainage of abscesses at multiple sites (left parotid region, upper and lower limbs). A small swelling noted on the left temporal region on discharge from the hospital was treated with oral cotrimoxazole. However, it spread rapidly to involve the periorbital tissue and the bones of the orbital walls to form a periorbital abscess and orbital cellulitis.
The effect of teamwork training on team performance and clinical outcome in elective orthopaedic surgery: a controlled interrupted time series study
Authors: Morgan Lauren , Hadi Mohammed , Pickering Sharon , Robertson Eleanor , Griffin Damian , Collins Gary , Rivero-Arias Oliver , Catchpole Ken , McCulloch Peter , New Steve
Published: April 2015

Objectives

To evaluate the effectiveness of aviation-style teamwork training in improving operating theatre team performance and clinical outcomes.

Setting

3 operating theatres in a UK district general hospital, 1 acting as a control group and the other 2 as the intervention group.

Participants

72 operations (37 intervention, 35 control) were observed in full by 2 trained observers during two 3-month observation periods, before and after the intervention period.

Interventions

A 1-day teamwork training course for all staff, followed by 6 weeks of weekly in-service coaching to embed learning.

Primary and secondary outcome measures

We measured team non-technical skills using Oxford NOTECHS II, (evaluating the whole team and the surgical, anaesthetic and nursing subteams, and evaluated technical performance using the Glitch count. We evaluated compliance with the WHO checklist by recording whether time-out (T/O) and sign-out (S/O) were attempted, and whether T/O was fully complied with. We recorded complications, re-admissions and duration of hospital stay using hospital administrative data. We compared the before–after change in the intervention and control groups using 2-way analysis of variance (ANOVA) and regression modelling.

Results

Mean NOTECHS II score increased significantly from 71.6 to 75.4 in the active group but remained static in the control group (p=0.047). Among staff subgroups, the nursing score increased significantly (p=0.006), but the anaesthetic and surgical scores did not. The attempt rate for WHO T/O procedures increased significantly in both active and control groups, but full compliance with T/O improved only in the active group (p=0.003). Mean glitch rate was unchanged in the control group but increased significantly (7.2–10.2/h, p=0.002) in the active group.

Conclusions

Teamwork training was associated with improved non-technical skills in theatre teams but also with a rise in operative glitches.
DEVELOPING A MODEL TO INVOLVE SERVICE USERS IN A MULTI-CENTRED TRIAL OF A COMPLEX INTERVENTION IN PRE-HOSPITAL EMERGENCY CARE
Authors: Koniotou M , Halter M , Evans B A , Porter A , Gaze S ,   on behalf of the Safer 2 Team
Published: April 2015

Background

Research collaborations with patient and professional groups can ensure health research funders are aware of what matters to patients, carers and clinicians. Increasing service user involvement in research improves research quality, accountability and provision of patient-centred services. There is little evidence about involving service users in trials or pre-hospital emergency care research. Most research involving service users concerns a condition or treatment rather than service delivery or point of entry to the healthcare system.

The SAFER 2 trial evaluates a complex intervention enabling paramedics to assess older people who fall and call 999 and, where appropriate, refer them to a community care pathway.

Objective

To describe a model for involving service users in a multi-centred trial in emergency care.

Method

A Standard Operating Procedure (SOP) for including service users was developed by the clinical trials unit West Wales Organisation for Rigorous Trials in Health (WWORTH). This recommends involvement processes and supportive working practices, based on evidence and good practice.

We adapted this SOP to develop a model to involve service users in our trial of a complex intervention in pre-hospital care.

Results

We included service users at three different decision levels of involvement:

Strategic level: Data Monitoring and Ethics Committee, Trial Steering Committee, Trial Management Group and Trial Development Group. These are the standard bodies that manage and oversee the trial.

Local level: management committees. These take decisions about running the trial in each study site.

Service user reference groups: these groups of patients and carers meet with the site researcher to discuss issues affecting patients likely to be recruited into the study.

Conclusion

The principles and processes of the SOP provided a model that could be replicated across each trial site. We found it necessary to tailor and adapt.
Interleukin-33 promotes inflammatory cytokine production in chronic airway inflammation
Authors: Shang Jin , Zhao Junling , Wu Xiaojie , Xu Yongjian , Xie Jungang , Zhao Jianping
Published: April 2015

Interleukin (IL)-33, belonging to the IL-1 family, is a novel cytokine that plays an important role in several chronic inflammatory diseases. Its role in chronic airway inflammation that develops into COPD is widely unknown. To determine this, we identified the expression of IL-33 in human bronchial epithelial layer and detected the inflammatory effects of IL-33 stimulation and the relative signaling pathways in human bronchial epithelial (HBE) cells and peripheral blood mononuclear cells (PBMCs), respectively. In this study, the expression of IL-33 in human bronchial epithelial layer was upregulated in COPD patients compared with normal controls. The expressions of IL-6 and IL-8 were also increased in both HBE cells and PBMCs, stimulated by IL-33 alone or combining the cigarette smoke extract (CSE). And the increased expressions could be partially blocked by ST2-Fc and IL-1RacP-Fc in both HBE cells and PBMCs. The p42/p44 ERK inhibitor in HBE cells and the p38 MAPK inhibitor in PBMCs exerted similar effects. Our data showed that IL-33 could induce and enhance the expression of IL-6 and IL-8 in HBE cells and PBMCs of COPD patients via ST2/IL-1RacP pathway and MAPKs pathway. Thus, the IL-33 is a promoter of chronic airway inflammation that contributes to COPD development.
Time effects on shaft capacity of jacked piles in sand
Authors: Lim Jit Kheng , Lehane Barry
Published: April 2015

This paper examines the effects of time on the shaft capacity of jacked piles in sand through an experimental program performed at three separate test sites in Western Australia. A total of 18 instrumented pile tests were conducted to track the changes of radial stress on the pile shafts, as well as shaft friction, up to a maximum of 72 days after installation. The results confirm that the gains in shaft capacity of jacked piles are small after a period of about 1 day. This observation is in keeping with limited available case history data, but is in stark contrast to the significant capacity gains reported for driven piles. Further examination reveals that set-up effects for jacked piles in sand are relatively significant within one day of installation, and that the increased friction is associated primarily with larger increases in radial effective stress during shearing.
Floer type cohomology on cosymplectic manifolds
Authors: Cho Yong Seung , Chai Young Do
Published: April 2015

We investigate a Floer type cohomology on cosymplectic manifolds M. To do this, we study a symplectic type action functional on the universal covering space of the loop space of contractible loops in M and the moduli space of gradient flow lines of the functional. The cochain complex induced by the critical points of the functional produces Floer type cohomology of M which is naturally isomorphic to a quantum type cohomology of M. We have an Arnold type theorem for Hamiltonian cosymplectomorphisms on compact semipositive cosymplectic manifolds. As an example, we consider the product of a Calabi–Yau 3-fold and the unit circle.
An online identity authentication method for blood smear
Authors: Feng Xiaozhen , Cao Yiping , Peng Kuang , Chen Cheng
Published: April 2015

Blood smear test is the basic method of blood cytology and is also a standard medical test that can help diagnose various conditions and diseases. Morphological examination is the gold standard to determine pathological changes in blood cell morphology. In the biology and medicine automation trend, blood smears' automated management and analysis is very necessary. An online blood smear automatic microscopic image detection system has been constructed. It includes an online blood smear automatic producing part and a blood smear automatic microscopic image detection part. Online identity authentication is at the core of the system. The identifiers printed online always present dot matrix digit code (DMDC) whose stroke is not continuous. Considering the particularities of DMDC and the complexities of online application environment, an online identity authentication method for blood smear with heterological theory is proposed. By synthesizing the certain regional features according to the heterological theory, high identification accuracy and high speed have been guaranteed with few features required. In the experiment, the sufficient correct matches between the tube barcode and the identification result verified its feasibility and validity.
Smart Manufacturing
Authors: Davis Jim , Edgar Thomas , Graybill Robert , Korambath Prakashan , Schott Brian , Swink Denise , Wang Jianwu , Wetzel Jim
Published: April 2015

Historic manufacturing enterprises based on vertically optimized companies, practices, market share, and competitiveness are giving way to enterprises that are responsive across an entire value chain to demand dynamic markets and customized product value adds; increased expectations for environmental sustainability, reduced energy usage, and zero incidents; and faster technology and product adoption. Agile innovation and manufacturing combined with radically increased productivity become engines for competitiveness and reinvestment, not simply for decreased cost. A focus on agility, productivity, energy, and environmental sustainability produces opportunities that are far beyond reducing market volatility. Agility directly impacts innovation, time-to-market, and faster, broader exploration of the trade space. These changes, the forces driving them, and new network-based information technologies offering unprecedented insights and analysis are motivating the advent of smart manufacturing and new information technology infrastructure for manufacturing.
Materials for Flexible, Stretchable Electronics: Graphene and 2D Materials
Authors: Kim Sang Jin , Choi Kyoungjun , Lee Bora , Kim Yuna , Hong Byung Hee
Published: April 2015

Recently, 2D materials have been intensively studied as emerging materials for future electronics, including flexible electronics, photonics, and electrochemical energy storage devices. Among representative 2D materials (such as graphene, boron nitride, and transition metal dichalcogenides) that exhibit extraordinary properties, graphene stands out in the flexible electronics field due to its combination of high electron mobility, high thermal conductivity, high specific surface area, high optical transparency, excellent mechanical flexibility, and environmental stability. This review covers the synthesis, transfer, and characterization methods of graphene and 2D materials and graphene's application to flexible devices as well as comparison with other competing materials.
Long-Range Neural Synchrony in Behavior
Authors: Harris Alexander Z. , Gordon Joshua A.
Published: April 2015

Long-range synchrony between distant brain regions accompanies multiple forms of behavior. This review compares and contrasts the methods by which long-range synchrony is evaluated in both humans and model animals. Three examples of behaviorally relevant long-range synchrony are discussed in detail: gamma-frequency synchrony during visual perception, hippocampal-prefrontal synchrony during working memory, and prefrontal-amygdala synchrony during anxiety. Implications for circuit mechanism, translation, and clinical relevance are discussed.
Optimal Taxation in the Macroeconomics of Climate Change
Authors: Engström Gustav , Gars Johan
Published: April 2015

Climate change has in recent years moved to the forefront of the policy scene. At the same time, the research literature on macroeconomic aspects of climate change has grown and broadened significantly. In this review, we survey and discuss this literature, with special attention given to results that help shed light on important qualitative questions regarding how an optimal carbon tax should be set. The review covers topics such as spatial aspects of optimal taxes, interactions with other taxes, uncertainty, technological change, and the qualitative time profile of the optimal tax.
Integrating Economic Land-Use and Biophysical Models
Authors: Plantinga Andrew J.
Published: April 2015

Land-use change is a leading cause of environmental degradation in terrestrial systems and has important implications for natural resource use. Economists have a long tradition of studying land use and in recent decades have developed empirical land-use models using econometric and optimization approaches. Integration of these land-use and biophysical models allows for a more comprehensive analysis of the consequences of future land-use change and the use of land-use policies to avoid undesirable outcomes. I provide a conceptual framework for the modeling approach, describing the individual components of an analysis as well as how they are linked together. My review describes how the literature has evolved to take advantage of spatial data and greater computing capabilities. Although most researchers have used either an econometric or an optimization approach, there is potential to combine these methods to identify more efficient land-use policies that still meet criteria of tractability and political acceptance.
The Local Economic Impacts of Natural Resource Extraction
Authors: Cust James , Poelhekke Steven
Published: April 2015

Whether it is fair to characterize natural resource wealth as a curse is still debated. Most of the evidence derives from cross-country analyses, providing cases both for and against a potential resource curse. Scholars are increasingly turning to within-country evidence to deepen our understanding of the potential drivers, and outcomes, of resource wealth effects. Moving away from cross-country studies offers new perspectives on the resource curse debate and can help overcome concerns regarding endogeneity. Therefore, scholars are leveraging datasets that provide greater disaggregation of economic responses and exogenous identification of impacts. This article surveys the literature on these studies of local and regional effects of natural resource extraction. We discuss data availability and quality, recent advances in methodological tools, and the main findings of several research areas. These areas include the direct impact of natural resource production on local labor markets and welfare, the effects of government spending channels resulting from mining revenue, and regional spillovers. Finally, we take stock of the state of the literature and provide suggestions for future research.
Chronic stress impacts the cardiovascular system: animal models and clinical outcomes
Authors: Golbidi Saeid , Frisbee Jefferson C. , Laher Ismail
Published: April 2015

Psychological stresses are associated with cardiovascular diseases to the extent that cardiovascular diseases are among the most important group of psychosomatic diseases. The longstanding association between stress and cardiovascular disease exists despite a large ambiguity about the underlying mechanisms. An array of possibilities have been proposed including overactivity of the autonomic nervous system and humoral changes, which then converge on endothelial dysfunction that initiates unwanted cardiovascular consequences. We review some of the features of the two most important stress-activated systems, i.e., the humoral and nervous systems, and focus on alterations in endothelial function that could ensue as a result of these changes. Cardiac and hematologic consequences of stress are also addressed briefly. It is likely that activation of the inflammatory cascade in association with oxidative imbalance represents key pathophysiological components of stress-induced cardiovascular changes. We also review some of the commonly used animal models of stress and discuss the cardiovascular outcomes reported in these models of stress. The unique ability of animals for adaptation under stressful conditions lessens the extrapolation of laboratory findings to conditions of human stress. An animal model of unpredictable chronic stress, which applies various stress modules in a random fashion, might be a useful solution to this predicament. The use of stress markers as indicators of stress intensity is also discussed in various models of animal stress and in clinical studies.