bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoplasmic reticulum‐associated N‐glycan degradation of cold‐upregulated glycoproteins in response to chilling stress in Arabidopsis
Authors: Ma Jun , Wang Dinghe , She Jessica , Li Jianming , Zhu Jian‐Kang , She Yi‐Min
Published: May 2016

N‐glycosylation has a great impact on glycoprotein structure, conformation, stability, solubility, immunogenicity and enzyme activity. Structural characterization of N‐glycoproteome has been challenging but can provide insights into the extent of protein folding and surface topology. We describe a highly sensitive proteomics method for large‐scale identification and quantification of glycoproteins in Arabidopsis through 15N‐metabolic labeling, selective enrichment of glycopeptides, data‐dependent MS/MS analysis and automated database searching.

In‐house databases of Arabidopsis glycoproteins and glycopeptides containing Asn‐X‐Ser/Thr/Cys motifs were constructed by reducing 20% and 90% of the public database size, respectively, to enable a rapid analysis of large datasets for comprehensive identification and quantification of glycoproteins and heterogeneous N‐glycans in a complex mixture.

Proteome‐wide analysis identified c. 100 stress‐related N‐glycoproteins, of which the endoplasmic reticulum (ER) resident proteins were examined to be up‐regulated. Quantitative measurements provided a molecular signature specific to glycoproteins for determining the degree of plant stress at low temperature.

Structural N‐glycoproteomics following time‐course cold treatments revealed the stress‐responsive degradation of high‐mannose type N‐glycans in ER in response to chilling stress, which may aid in elucidating the cellular mechanisms of protein relocation, transport, trafficking, misfolding and degradation under stress conditions.
High glucose‐induced oxidative stress increases IL‐8 production in human gingival epithelial cells
Authors: Kashiwagi Y , Takedachi M , Mori K , Kubota M , Yamada S , Kitamura M , Murakami S
Published: May 2016

Objective

Diabetes is often associated with increased prevalence and severity of periodontal disease. We hypothesized that gingival epithelial cells modify periodontal disease progression and predicted that hyperglycemia would activate an inflammatory response in human gingival epithelial cells (HGECs).

Materials and Methods

We tested our hypothesis in immortalized HGECs (epi 4 cells) isolated from periodontal tissue and transfected with the simian virus 40 T antigen. The epi 4 cells were cultured in high (25 mM, HG) and normal (6 mM, NG) glucose conditions.

Results

The epi 4 cells showed increased interleukin‐8 (IL‐8) protein secretion and mRNA expression when cultured in HG, compared with in NG. These effects were not associated with increased cell proliferation and were not observed in a hyperosmolar control group (normal glucose with 19 mM mannitol). Increased IL‐8 secretion in HG was inhibited by pretreatment with an antioxidant, N‐acetylcysteine, or a protein kinase C inhibitor, Ro31‐8220. Hyperglycemia did not affect IL‐8 secretion by gingival fibroblasts or periodontal ligament cells. In epi 4 cells, hyperglycemia also induced expression of toll‐like receptor 2 (TLR2) but not TLR4.

Conclusion

These findings suggest a potential participation of epithelial cells in periodontal disease during diabetes by evoking an excessive host inflammatory response.
Phenotypical characterization of children with hypersensitivity reactions to NSAIDs
Authors: Cousin Mathias , Chiriac Anca , Molinari Nicolas , Demoly Pascal , Caimmi Davide
Published: May 2016

Background

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are the main cause of drug‐induced hypersensitivity in children. Many classifications have been proposed, focusing on adults. So far, no large study has deeply investigated a pediatric cohort. The aim of the present study was to describe a population of NSAID hypersensitive patients reporting a reaction during their childhood and to verify whether it is possible to classify pediatric patients, following the EAACI/ENDA classification.

Methods

We conducted a historical prospective study including patients evaluated from 1996 to 2015 in the allergy unit of the Montpellier University Hospital. We included 635 patients. For each patient, we recorded clinical manifestations and possible comorbidities and tried to identify possible risk factors.

Results

NSAID hypersensitivity was diagnosed in 107 of 635 patients (16.9%). In this group, 43 patients (40.2%) could not be classified following the ENDA recommendations. The main discrepancies were on the patients’ clinical manifestations and on their possible underlying diseases. We identified, on a multivariate analysis, some risk factors for NSAID hypersensitivity: chronic urticaria (OR 7.737, 3.375–18.296 95%CI), atopic status (OR 2.514, 1.504–4.364 95%CI), and allergic rhinoconjunctivitis (OR 1.799, 1.138–2.837 95%CI). On the basis of our results, we are proposing an adapted classification for NSAID hypersensitivity in children.

Conclusions

The current ENDA classification does not seem to be adapted for pediatric patients; a modified version does. Our study could help allergists better understand the differences between adults and children in developing hypersensitivity reactions to NSAIDs, but further large‐scale prospective longitudinal analyses are required to validate this new classification.
Vaccines: could asthma in young children be a preventable disease? ‬‬‬‬‬‬‬
Authors: Elenius Varpu , Jartti Tuomas
Published: May 2016

‬The long battle with asthma is far from over in developed countries. Its incidence, prevalence, and severity have been increasing for decades. By reducing the risk for asthma, significant healthcare costs can be saved. The desire to create a vaccine that might prevent asthma in young children is attractive and widely considered one of the main goals in translational asthma research. Several vaccination strategies have been tested. These include allergen‐specific immunotherapy, vaccination against infectious pathogens, and modification of cell and cytokine responses. The lack of success in the prevention of asthma in young children lies on the complexity of the disease, which involves many genetic, epigenetic, and environmental interactions. This review provides a summary of current literature and aims to address key questions how to develop vaccines to prevent asthma in young children. ‬‬‬‬‬‬‬‬‬‬‬‬‬‬
Impact of Buserelin Acetate or hCG Administration on the Day of First Artificial Insemination on Subsequent Luteal Profile and Conception Rate in Murrah Buffalo (Bubalus bubalis)
Authors: Pandey AK , Ghuman SPS , Dhaliwal GS , Agarwal SK , Phogat JB
Published: May 2016

Contents

This study was designed to investigate the impact of buserelin acetate (BA) or human chorionic gonadotropin (hCG) administration on the day of first artificial insemination (AI) on subsequent luteal profile (diameter of corpus luteum (CL) and plasma progesterone) and conception rate in Murrah buffalo. The present experiment was carried out at two locations in 117 buffalo that were oestrus‐synchronized using cloprostenol (500 μg) administered (i.m.) 11 days apart followed by AI during standing oestrus. Based on treatment (i.m.) at the time of AI, buffalo were randomly categorized (n = 39 in each group) into control (isotonic saline solution, 5 ml), dAI‐BA (buserelin acetate, 20 μg) and dAI‐hCG (hCG, 3000 IU) group. Out of these, 14 buffalo of each group were subjected to ovarian ultrasonography on the day of oestrus to monitor the preovulatory follicle and on days 5, 12, 16 and 21 post‐ovulation to monitor CL diameter. On the day of each sonography, jugular vein blood samples were collected for the estimation of progesterone concentrations. All the buffalo (n = 117) were confirmed for pregnancy on day 40 post‐ovulation. The conception rate was better (p < 0.05) in dAI‐BA (51.3%) and dAI‐hCG (66.7%) groups as compared to their control counterparts (30.8%). Furthermore, the buffalo of dAI‐hCG group had improved (p < 0.05) luteal profile, whereas the buffalo of dAI‐BA group failed (p > 0.05) to exhibit stimulatory impact of treatment on luteal profile when compared to control group. In brief, buserelin acetate or hCG treatment on the day of first AI leads to an increase in conception rate; however, an appreciable impact on post‐ovulation luteal profile was observed only in hCG‐treated Murrah buffalo.
Statistical inference on restricted partial linear regression models with partial distortion measurement errors
Authors: Zhang Jun , Zhou Nanguang , Sun Zipeng , Li Gaorong , Wei Zhenghong
Published: May 2016

We consider the estimation and hypothesis testing problems for the partial linear regression models when some variables are distorted with errors by some unknown functions of commonly observable confounding variable. The proposed estimation procedure is designed to accommodate undistorted as well as distorted variables. To test a hypothesis on the parametric components, a restricted least squares estimator is proposed under the null hypothesis. Asymptotic properties for the estimators are established. A test statistic based on the difference between the residual sums of squares under the null and alternative hypotheses is proposed, and we also obtain the asymptotic properties of the test statistic. A wild bootstrap procedure is proposed to calculate critical values. Simulation studies are conducted to demonstrate the performance of the proposed procedure, and a real example is analyzed for an illustration.
I am the 9%: Making the case for whole‐blood platelets
Authors: Seheult J. N. , Triulzi D.J. , Yazer M. H.
Published: May 2016

SYNOPSIS

Over the last 15 years, there has been a trend in the United States towards the increasing use of apheresis platelet (AP) concentrates over whole‐blood‐derived platelets (WBP). Although 1‐h‐ and 24‐h‐corrected count increments tend to be higher with AP, this does not translate into improved haemostatic efficiency when used to prevent bleeding in haematology/oncology patients. WBP expose the recipient to more donors than apheresis products. However, recent studies have shown no significant differences in the rates of bacterial contamination, human leukocyte antigen alloimmunisation, RhD alloimmunisation, transfusion‐related acute lung injury or febrile non‐haemolytic transfusion reactions between these two products. Given the overall low rates of virally contaminated units in the era of nucleic acid testing and rigorous donor screening, the difference in donor exposures of 4–6 vs 1 has minimal clinical relevance. Although studies point to a marginally increased risk of donor adverse events associated with WBP, the absolute risk is too miniscule to act as a deterrent to making whole‐blood donations. Both types of platelet concentrates should therefore be considered clinically equivalent; in this light, the most responsible use of the community donor resource pool, which both optimises the utility of a whole‐blood donation and meets the clinical needs of thrombocytopenic recipients, is to have a mix of both types of platelet products so as to mitigate the risk of shortages.
Implementation Strategies for Same Day Discharge Post Percutaneous Coronary Intervention: An Integrative Review
Authors: Chen Yingyan , Marshall Andrea , Lin Frances
Published: May 2016

Background

Same day discharge following percutaneous coronary intervention has emerged worldwide to enhance discharge efficiency and decrease length of stay. However, uptake of this practice is variable and strategies to support its implementation have not been examined.

Research Question

Among patients who undergo nonurgent percutaneous coronary intervention, what components are included in and which strategies are used to facilitate the implementation of same day discharge in clinical practice?

Methods

An integrative review was conducted. Keywords including same day discharge, outpatient, percutaneous coronary intervention, outpatient coronary stenting were used to search databases including Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica dataBase, Cochrane, and Medline between 1990 and 2014. Data were extracted and summarized specific to: (a) components of same day discharge, (b) patient selection, and (c) strategies used to implement same day discharge.

Results

Nineteen articles were included that provided information about implementation strategies for same day discharge. Variability was identified in how same day discharge was operationalized, how patients were selected, and the strategies that were used to implement same day discharge. Culture, patient preference, and acceptance of same day discharge were important for its implementation. Guideline or protocol, physical environment, champion, education, audit or feedback, and team building were all found to be important strategies in implementing same day discharge.

Linking Evidence to Action

The results of this integrative review inform our understanding of how same day discharge is operationalized and what strategies can be used to implement same day discharge. The findings of the review highlight that there is a need for more research examining implementation strategies in a detailed manner that can assist others to introduce and sustain same day discharge in routine practice.
Ventilatory responses to muscle metaboreflex activation in chronic obstructive pulmonary disease
Authors: Bruce Richard M. , Turner Alice , White Michael J.
Published: May 2016

Key points

Recent evidence indicates a role for group III/IV muscle afferents in reflex control of the human ventilatory response to exercise.

Dyspnoea in chronic obstructive pulmonary disease (COPD) may be linked to this reflex response.

This study shows that activation of the muscle metaboreflex causes a ventilatory response in COPD patients but not in healthy controls.

This indicates abnormal involvement of muscle afferents in the control of ventilation in COPD which may be a contributing factor to exercise dyspnoea.

Blockade of thin fibre muscle afferent feedback during dynamic exercise reduces exercise hyperpnoea in health and chronic obstructive pulmonary disease (COPD). Therefore, we hypothesised that activation of the muscle metaboreflex at rest would cause hyperpnoea. We evaluated the effect of muscle metaboreflex activation on ventilation, in resting COPD patients and healthy participants. Following a bout of rhythmic hand grip exercise, post exercise circulatory occlusion (PECO) was applied to the resting forearm to sustain activation of the muscle metaboreflex, in 18 COPD patients (FEV1/FVC ratio < 70%), 9 also classified as chronically hypercapnic, and 9 age‐ and gender‐matched controls. The cardiovascular response to exercise and the sustained blood pressure elevation during PECO was similar in patients and controls. During exercise ventilation increased by 6.64 ± 0.84 in controls and significantly (P < 0.05) more, 8.38 ± 0.81 l min−1, in patients. During PECO it fell to baseline levels in controls but remained significantly (P < 0.05) elevated by 2.78 ± 0.51 l min−1 in patients until release of circulatory occlusion, with no significant difference in responses between patient groups. Muscle metaboreflex activation causes increased ventilation in COPD patients but not in healthy participants. Chronic hypercapnia in COPD patients does not exaggerate this response. The muscle metaboreflex appears to be abnormally involved in the control of ventilation in COPD and may be a contributing factor to exercise dyspnoea.
Simultaneous Determination of Disassembly Sequence and Disassembly-to-Order Decisions Using Simulation Optimization
Authors: Ilgin Mehmet Ali , Taşoğlu Gökçeçiçek Tuna
Published: May 2016

Strict environmental regulations and increasing public awareness toward environmental issues force many companies to establish dedicated facilities for product recovery. All product recovery options require some level of disassembly. That is why, the cost-effective management of product recovery operations highly depends on the effective planning of disassembly operations. There are two crucial issues common to most disassembly systems. The first issue is disassembly sequencing which involves the determination of an optimal or near optimal disassembly sequence. The second issue is disassembly-to-order (DTO) problem which involves the determination of the number of end of life (EOL) products to process to fulfill the demand for specified numbers of components and materials. Although disassembly sequencing decisions directly affects the various costs associated with a disassembly-to-order problem, these two issues are treated separately in the literature. In this study, a genetic algorithm (GA) based simulation optimization approach was proposed for the simultaneous determination of disassembly sequence and disassembly-to-order decisions. The applicability of the proposed approach was illustrated by providing a numerical example and the best values of GA parameters were identified by carrying out a Taguchi experimental design.
Chaotic and Hyperchaotic Dynamics of Smart Valves System Subject to a Sudden Contraction
Authors: Naseradinmousavi Peiman , Segala David B. , Nataraj C.
Published: May 2016

In this paper, we focus on determining the safe operational domain of a coupled actuator–valve configuration. The so-called “smart valves” system has increasingly been used in critical applications and missions including municipal piping networks, oil and gas fields, petrochemical plants, and more importantly, the U.S. Navy ships. A comprehensive dynamic analysis is hence needed to be carried out for capturing dangerous behaviors observed repeatedly in practice. Using some powerful tools of nonlinear dynamic analysis including Lyapunov exponents and Poincaré map, a comprehensive stability map is provided in order to determine the safe operational domain of the network in addition to characterizing the responses obtained. Coupled chaotic and hyperchaotic dynamics of two coupled solenoid-actuated butterfly valves are captured by running the network for some critical values through interconnected flow loads affected by the coupled actuators' variables. The significant effect of an unstable configuration of the valve–actuator on another set is thoroughly investigated to discuss the expected stability issues of a remote set due to others and vice versa.
Necessity and Freedom in Ostrovsky's Thunder
Authors: Zohrab Irene
Published: May 2016

Necessity and Freedom in Ostrovsky's Thunder
Euripides' Iphigenia in Tauris and Homer
Authors: Davidson John
Published: May 2016

Euripides' Iphigenia in Tauris and Homer
Animals show how Zika harms fetuses
Authors: Cohen Jon
Published: May 2016

Mouse and monkey models detail viral attack on the placenta and the brain.
How the Venus flytrap acquired its taste for meat
Authors: Stokstad Erik
Published: May 2016

Plant turned preexisting defenses against insect pests into tools for catching and eating prey.
Superresolution microscopy
Authors: Perkel Jeffrey M.
Published: May 2016

From van Leeuwenhoek to the new millennium, microscopy was governed by one seemingly unbreakable principle: The ability to resolve two objects is constrained by the wavelength of the light used to view them. But in 2000, researchers showed this so-called diffraction limit could be broken, unveiling over the next decade an alphabet soup of superresolution techniques from GSDIM and PALM to SIM, STED, and STORM. The
resulting images are both beautiful and revealing, documenting biological phenomena and structures that researchers never even knew they were missing.
A high-yielding, strictly regioselective prebiotic purine nucleoside formation pathway
Authors: Becker Sidney , Thoma Ines , Deutsch Amrei , Gehrke Tim , Mayer Peter , Zipse Hendrik , Carell Thomas
Published: May 2016

Making RNA in the prebiotic world

The RNA World hypothesis posits that RNA was one of the first self-replicating molecules leading to the origin of life. The nucleotide bases of RNA—A, U, C, and G—are chemically complex, and it has been unclear how the large purine bases A and G might have arisen on prebiotic Earth. Becker
et al.
show that the A and G bases can be synthesized easily and in high yield from prebiotically reasonable precursors, lending further support to the RNA World hypothesis.

Science
, this issue p.
833
Reconciling after civil conflict increases social capital but decreases individual well-being
Authors: Cilliers Jacobus , Dube Oeindrila , Siddiqi Bilal
Published: May 2016

The psychological cost of reconciliation

During civil wars, individuals and communities who were previously good neighbors can end up fighting each other. One approach to reknit these sundered social ties is to bring perpetrators and victims together in truth and reconciliation forums. Cillierset al.found that these forums have helped to reestablish social bonds in Sierra Leone, but that they have also imposed a cost on the victims' mental health (see the Perspective by Casey and Glennerster).

Science, this issue p.787; see also p.766
Photochemical route for synthesizing atomically dispersed palladium catalysts
Authors: Liu Pengxin , Zhao Yun , Qin Ruixuan , Mo Shiguang , Chen Guangxu , Gu Lin , Chevrier Daniel M. , Zhang Peng , Guo Qing , Zang Dandan , Wu Binghui , Fu Gang , Zheng Nanfeng
Published: May 2016

Lightly dispersed palladium

Catalysts made from atomically dispersed metal atoms on oxide supports can exhibit very high per atom activity. However, the low loadings needed to prevent metal particle formation can limit overall performance. Liu
et al.
stably decorated titanium oxide nanosheets with relatively high loadings of single palladium atoms by reducing the ions with ultraviolet light and ethylene glycol. These catalysts cleaved H
2
into atoms and were highly effective for hydrogenating alkenes and aldehydes.

Science
, this issue p.
797
Reconciliation in Sierra Leone
Authors: Casey Katherine , Glennerster Rachel
Published: May 2016

Short, low-cost interventions can help communities to recover from civil war
Dientamoeba fragilis, the Neglected Trichomonad of the Human Bowel
Authors: Stark Damien , Barratt Joel , Chan Douglas , Ellis John T.
Published: May 2016

Dientamoeba fragilis
is a protozoan parasite of the human bowel, commonly reported throughout the world in association with gastrointestinal symptoms. Despite its initial discovery over 100 years ago, arguably, we know less about this peculiar organism than any other pathogenic or potentially pathogenic protozoan that infects humans. The details of its life cycle and mode of transmission are not completely known, and its potential as a human pathogen is debated within the scientific community. Recently, several major advances have been made with respect to this organism's life cycle and molecular biology. While many questions remain unanswered, these and other recent advances have given rise to some intriguing new leads, which will pave the way for future research. This review encompasses a large body of knowledge generated on various aspects of
D. fragilis
over the last century, together with an update on the most recent developments. This includes an update on the latest diagnostic techniques and treatments, the clinical aspects of dientamoebiasis, the development of an animal model, the description of a
D. fragilis
cyst stage, and the sequencing of the first
D. fragilis
transcriptome.
Evaluation of the Novel HISCL Chemiluminescence Enzyme Immunoassay for Laboratory Screening of Hepatitis C Virus
Authors: Feng Shu , Wei Bin , Liu Qianqian , Wang Tingting , Li Dongdong , Rao Chenli , Tao Chuanmin , Wang Lanlan
Published: May 2016

The hepatitis C virus (HCV) antibody assay remains the first-line screening test to identify HCV infection. The newly arrived HISCL Anti-HCV assay had a satisfactory seroconversion sensitivity. Its sensitivity and specificity were 98.97 and 100% for clinical samples. In general, the HISCL Anti-HCV assay may be a novel choice for clinical HCV screening.
Development of a TaqMan Array Card for Pneumococcal Serotyping on Isolates and Nasopharyngeal Samples
Authors: Pholwat Suporn , Sakai Fuminori , Turner Paul , Vidal Jorge E. , Houpt Eric R.
Published: May 2016

Streptococcus pneumoniae
is both a commensal and a major pathogen that causes invasive disease in people of all ages. The introduction of serotype-specific pneumococcal vaccines has reduced the burden of disease but has also led to replacement with new strains; thus, serotyping remains important for vaccine-related disease surveillance. Conventional serotyping methods are laborious and expensive. We developed an easy-to-perform genotypic TaqMan array card (TAC) to identify
S. pneumoniae
strains, including
lytA
-based sequences, and 53 sequence-specific PCRs to identify 74 serotypes/serogroups covering all current vaccine types as well as prevalent nonvaccine types. The TAC method was evaluated on 146 clinical
S. pneumoniae
isolates and 13 nonpneumococcal species that naturally inhabit the upper respiratory tract and yielded 97% (142/146) sensitivity and 100% (13/13) specificity versus results of standard Quellung serotyping. The calculated limit of detection was 20 to 200 fg (∼8 to 84 genome equivalents) per reaction. On 23 blinded nasopharyngeal specimens that were pneumococcus culture positive, the TAC pan-pneumococcus
lytA
assay was positive in 21 (91% sensitivity versus culture). On TAC
lytA
-positive specimens, a serotype result was obtained on 86%, and the result was 95% accurate versus the subsequent culture's Quellung result. TAC also detected mixed serotypes in two specimens where Quellung detected only the predominant serotype. This TAC method yields fast and comprehensive serotyping compared to the standard method and may be useful on direct specimens.
Structural and Biochemical Analyses of Swine Major Histocompatibility Complex Class I Complexes and Prediction of the Epitope Map of Important Influenza A Virus Strains
Authors: Fan Shuhua , Wu Yanan , Wang Song , Wang Zhenbao , Jiang Bo , Liu Yanjie , Liang Ruiying , Zhou Wenzhong , Zhang Nianzhi , Xia Chun
Published: May 2016

The lack of a peptide-swine leukocyte antigen class I (pSLA I) complex structure presents difficulties for the study of swine cytotoxic T lymphocyte (CTL) immunity and molecule vaccine development to eliminate important swine viral diseases, such as influenza A virus (IAV). Here, after cloning and comparing 28 SLA I allelic genes from Chinese Heishan pigs, pSLA-3*hs0202 was crystalized and solved. SLA-3*hs0202 binding with sβ2m and a KMNTQFTAV (hemagglutinin [HA]-KMN9) peptide from the 2009 pandemic swine H1N1 strain clearly displayed two distinct conformations with HA-KMN9 peptides in the structures, which are believed to be beneficial to stimulate a broad spectrum of CTL immune responses. Notably, we found that different HA-KMN9 conformations are caused, not only by the flexibility of the side chains of residues in the peptide-binding groove (PBG), but also by the skewing of α1 and α2 helixes forming the PBG. In addition, alanine scanning and circular-dichroism (CD) spectra confirmed that the B, D, and F pockets play critical biochemical roles in determining the peptide-binding motif of SLA-3*hs0202. Based on biochemical parameters and comparisons to similar pockets in other known major histocompatibility complex class I (MHC-I) structures, the fundamental motif for SLA-3*hs0202 was determined to be X-(M/A/R)-(N/Q/R/F)-X-X-X-X-X-(V/I) by refolding
in vitro
and multiple mutant peptides. Finally, 28 SLA-3*hs0202-restricted epitope candidates were identified from important IAV strains, and two of them have been found in humans as HLA-A*0201-specific IAV epitopes. Structural and biochemical illumination of pSLA-3*hs0202 can benefit vaccine development to control IAV in swine.

IMPORTANCE
We crystalized and solved the first SLA-3 structure, SLA-3*hs0202, and found that it could present the same IAV peptide with two distinct conformations. Unlike previous findings showing that variable peptide conformations are caused only by the flexibility of the side chains in the groove, the skewing of the α1 and α2 helixes is important in the different peptide conformations in SLA-3*hs0202. We also determined the fundamental motif for SLA-3*hs0202 to be X-(M/A/R)-(N/Q/R/F)-X-X-X-X-X-(V/I) based on a series of structural and biochemical analyses, and 28 SLA-3*hs0202-restricted epitope candidates were identified from important IAV strains. We believe our structure and analyses of pSLA-3*hs0202 can benefit vaccine development to control IAV in swine.
Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1 Encodes an Extra Accessory Protein, ORFX, Involved in Modulation of the Host Immune Response
Authors: Zeng Lei-Ping , Gao Yu-Tao , Ge Xing-Yi , Zhang Qian , Peng Cheng , Yang Xing-Lou , Tan Bing , Chen Jing , Chmura Aleksei A. , Daszak Peter , Shi Zheng-Li
Published: May 2016

Bats harbor severe acute respiratory syndrome (SARS)-like coronaviruses (SL-CoVs) from which the causative agent of the 2002-2003 SARS pandemic is thought to have originated. However, despite the fact that a large number of genetically diverse SL-CoV sequences have been detected in bats, only two strains (named WIV1 and WIV16) have been successfully cultured
in vitro
. These two strains differ from SARS-CoV only in containing an extra open reading frame (ORF) (named ORFX), between ORF6 and ORF7, which has no homology to any known protein sequences. In this study, we constructed a full-length cDNA clone of SL-CoV WIV1 (rWIV1), an ORFX deletion mutant (rWIV1-ΔX), and a green fluorescent protein (GFP)-expressing mutant (rWIV1-GFP-ΔX). Northern blotting and fluorescence microscopy indicate that ORFX was expressed during WIV1 infection. A virus infection assay showed that rWIV1-ΔX replicated as efficiently as rWIV1 in Vero E6, Calu-3, and HeLa-hACE2 cells. Further study showed that ORFX could inhibit interferon production and activate NF-κB. Our results demonstrate for the first time that the unique ORFX in the WIV1 strain is a functional gene involving modulation of the host immune response but is not essential for
in vitro
viral replication.

IMPORTANCE
Bats harbor genetically diverse SARS-like coronaviruses (SL-CoVs), and some of them have the potential for interspecies transmission. A unique open reading frame (ORFX) was identified in the genomes of two recently isolated bat SL-CoV strains (WIV1 and -16). It will therefore be critical to clarify whether and how this protein contributes to virulence during viral infection. Here we revealed that the unique ORFX is a functional gene that is involved in the modulation of the host immune response but is not essential for
in vitro
viral replication. Our results provide important information for further exploration of the ORFX function in the future. Moreover, the reverse genetics system we constructed will be helpful for study of the pathogenesis of this group of viruses and to develop therapeutics for future control of emerging SARS-like infections.
The Interactome of the Glucocorticoid Receptor and Its Influence on the Actions of Glucocorticoids in Combatting Inflammatory and Infectious Diseases
Authors: Petta Ioanna , Dejager Lien , Ballegeer Marlies , Lievens Sam , Tavernier Jan , De Bosscher Karolien , Libert Claude
Published: May 2016

Glucocorticoids (GCs) have been widely used for decades as a first-line treatment for inflammatory and autoimmune diseases. However, their use is often hampered by the onset of adverse effects or resistance. GCs mediate their effects via binding to glucocorticoid receptor (GR), a transcription factor belonging to the family of nuclear receptors. An important aspect of GR's actions, including its anti-inflammatory capacity, involves its interactions with various proteins, such as transcription factors, cofactors, and modifying enzymes, which codetermine receptor functionality. In this review, we provide a state-of-the-art overview of the protein-protein interactions (PPIs) of GR that positively or negatively affect its anti-inflammatory properties, along with mechanistic insights, if known. Emphasis is placed on the interactions that affect its anti-inflammatory effects in the presence of inflammatory and microbial diseases.
Metabolic and Community Synergy of Oral Bacteria in Colorectal Cancer
Authors: Flynn Kaitlin J. , Baxter Nielson T. , Schloss Patrick D.
Published: May 2016

The oral periodontopathic bacterium
Fusobacterium nucleatum
has been repeatedly associated with colorectal tumors. Molecular analysis has identified specific virulence factors that promote tumorigenesis in the colon. However, other oral community members, such as members of the
Porphyromonas
spp., are also found with
F. nucleatum
on colonic tumors, and thus, narrow studies of individual pathogens do not take community-wide virulence properties into account. A broader view of oral bacterial physiology and pathogenesis identifies two factors that could promote colonization and persistence of oral bacterial communities in the colon. The polymicrobial nature of oral biofilms and the asaccharolytic metabolism of many of these species make them well suited to life in the microenvironment of colonic lesions. Consideration of these two factors offers a novel perspective on the role of oral microbiota in the initiation, development, and treatment of colorectal cancer.
Thrombocytopenia and fever: not just another infection…
Authors: Sriskandarajah Priya , Davies Rhys
Published: May 2016

Diffuse large B-cell lymphoma (DLBCL) is a high-grade, aggressive disease that typically presents with widespread lymphadenopathy and active ‘B’ symptoms, making it easy to recognise and manage. However, a small proportion of patients can present with no evidence of lymphadenopathy or organomegaly, with the disease confined to the bone marrow; this presentation is also known as ‘Primary Bone Marrow DLBCL’. Subsequently, diagnosis can be a challenge, resulting in delayed treatment and an overall poorer prognosis. Given the rarity of this disease, we wished to describe a patient who presented initially with fevers associated with isolated thrombocytopenia and was later diagnosed with this condition. Unfortunately, due to the aggressive nature of this disease, subsequent treatment was unsuccessful. Overall, we felt that in future cases of fevers with thrombocytopenia, clinicians should include this rare lymphoma subtype as part of the differential diagnosis, as early identification and treatment can be associated with a favourable outcome.
Socioeconomic status and glycemic control in adult patients with type 2 diabetes: a mediation analysis
Authors: Houle Janie , Lauzier-Jobin François , Beaulieu Marie-Dominique , Meunier Sophie , Coulombe Simon , Côté José , Lespérance François , Chiasson Jean-Louis , Bherer Louis , Lambert Jean
Published: May 2016

Objective

The purpose of this study is to examine the contribution of health behaviors (self-management and coping), quality of care, and individual characteristics (depressive symptoms, self-efficacy, illness representations) as mediators in the relationship between socioeconomic status (SES) and glycemic control.

Methods

A sample of 295 adult patients with type 2 diabetes was recruited at the end of a diabetes education course. Glycemic control was evaluated through glycosylated hemoglobin (HbA1c). Living in poverty and education level were used as indicators of SES.

Results

Bootstrapping analysis showed that the significant effects of poverty and education level on HbA1cwere mediated by avoidance coping and depressive symptoms. The representation that diabetes is unpredictable significantly mediated the relationship between living in poverty and HbA1c, while healthy diet mediated the relationship between education level and HbA1c.

Conclusions

To improve glycemic control among patients with low SES, professionals should regularly screen for depression, offering treatment when needed, and pay attention to patients' illness representations and coping strategies for handling stress related to their chronic disease. They should also support patients in improving their self-management skills for a healthy diet.
Simulated presence therapy for dementia: a systematic review protocol
Authors: Abraha Iosief , Rimland Joseph M , Lozano-Montoya Isabel , Dell'Aquila Giuseppina , Vélez-Díaz-Pallarés Manuel , Trotta Fabiana M , Cherubini Antonio
Published: May 2016

Introduction

The majority of patients with dementia develop behavioural and psychological symptoms of dementia (BPSD). Non-pharmacological interventions are an appealing alternative for the treatment of BPSD in patients with dementia. Simulated presence therapy (SPT) is a simple and inexpensive non-pharmacological intervention that can be used to treat BPSD. We propose a Cochrane protocol for the collection and assessment of evidence concerning the efficacy of SPT to treat relevant outcomes in people with dementia.

Methods and analysis

We will search the following electronic databases: the Cochrane Dementia and Cognitive Improvement Group's Specialised Register MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, CENTRAL and a number of trial registers as well as grey literature sources. We will include randomised and quasi-randomised controlled trials (including cross-over studies) that evaluated SPT in people with dementia. Comparators such as usual care with no additional activity, or any activity that differs in content and approach from SPT, but is additional to usual care, will be considered. The primary outcomes of interest will comprise behavioural and psychological symptoms, as measured by relevant scales, and quality of life. Two review authors working independently and in tandem will be involved in title and abstract screening, full-text screening and data abstraction. Where possible, quantitative data will be pooled, and relative risk and mean difference with 95% CI will be employed for dichotomous and continuous data, respectively. Assessment of risk of bias will be performed using the Cochrane risk-of-bias tool and the Grades of Recommendation, Assessment, Development and Evaluation approach.

Ethics and dissemination

Ethics approval is not required. The final results of this systematic review will be presented to the Cochrane Library and will also be disseminated at relevant conference presentations.

Trial registration number

CRD42015029778.
Hyaluronan synthase 2 is an adverse prognostic marker in androgen receptor-negative breast cancer
Authors: Zhang Hong , Tsang Julia Y S , Ni Yun-Bi , Chan Siu-Ki , Chan Kui-Fat , Cheung Sai-Yin , Tse Gary M
Published: May 2016

Aims

The important role of hyaluronan synthase 2 (HAS2), an isozyme responsible for hyaluronan synthesis, in cancer has been increasingly recognised. However, only a few studies with inconsistent results have been reported in breast cancers. With a large cohort, we aim to determine the clinical significance of HAS2 in breast cancers.

Methods

We examined HAS2 expression in 1142 breast cancers using immunohistochemistry.

Results

HAS2 was associated with both prognostically favourable (androgen receptor (AR), p<0.001) and unfavourable (basal and epithelial mesenchymal transition markers, p≤0.039) biomarkers. In addition, HAS2 showed differential associations with various features and outcome between AR+ and AR− subgroups. HAS2+AR− breast cancers showed significantly worse outcome than other subgroups, and HAS2+AR− subgroup was an independent adverse prognostic factor for disease-free survival (HR 1.309, p=0.046). Interestingly, HAS2 was associated with many poor prognostic features (including higher grade, lymphovascular invasion, basal-like breast cancer subtype, high Ki67 and basal marker expression) only in AR−, but not AR+ breast cancers.

Conclusions

HAS2 has been proposed to be a target for therapeutic intervention in cancer. Our findings suggested a possible antagonistic role of AR pathway on HAS2 function. It will be interesting to further investigate their precise interaction, which may have important implication in HAS2 targeting.
Surface plasmon on graphene at finite T
Authors: Bordag M. , Pirozhenko I. G.
Published: May 2016

Using the recently developed polarization tensor in [Formula: see text] dimensions for the electronic excitations of graphene, we investigate the influence of temperature on the surface plasmons on graphene. We consider nonzero mass gap, but zero chemical potential. Plasmons may exist for both polarizations, transverse electric (TE) and transverse magnetic (TM), of the electromagnetic field. For TE, the momentum region, where the dispersion function is real, appears bounded from below, whereas for TM it is bounded from above. We discuss the similarities of these features with those found previously in the case with nonzero chemical potential, but zero temperature.
ENTREPRENEURIAL BRICOLAGE — DEVELOPING RECIPES TO SUPPORT INNOVATION
Authors: BECKETT RONALD C
Published: May 2016

In some large enterprises introducing radical innovation may prove difficult, but introducing a combination of incremental changes may be more practical, particularly in the services sector where existing resources are utilized, and this may be seen as a process of entrepreneurial bricolage. For small resource-limited firms there may be no alternative but to draw on novel combinations of existing resources. The term bricolage comes from a French expression for “tinkering” and this is what it is suggested many innovative SMEs do — learn-by-doing. The notion of entrepreneurial bricolage has been used to describe a process for assembling readily available physical and knowledge assets in novel combinations for a business purpose, creating product and process “recipes”. In this paper, we explore the research question: How can entrepreneurial bricolage be represented as a coherent process?
ANALYSING UBER IN SOCIAL MEDIA — DISRUPTIVE TECHNOLOGY OR INSTITUTIONAL DISRUPTION?
Authors: LAURELL CHRISTOFER , SANDSTRÖM CHRISTIAN
Published: May 2016

Extant literature suggests that market disruptions take place because of two main reasons: technological disruption or institutional change. In view of these two alternative explanations, this paper aims to explore how the recent rise of the collaborative consumption platform Uber is perceived by consumers and whether this platform is primarily regarded as a technological innovation or as an institutional disruption. Drawing from a dataset of more than 6500 user-generated contents in social media, our findings suggest that Uber is not primarily perceived as a technological innovation, but rather as an institutional disruption.
Inflammasomes in the urinary tract: a disease-based review
Authors: Purves J. Todd , Hughes F. Monty
Published: May 2016

Inflammasomes are supramolecular structures that sense molecular patterns from pathogenic organisms or damaged cells and trigger an innate immune response, most commonly through production of the proinflammatory cytokines IL-1β and IL-18, but also through less understood mechanisms independent of these cytokines. Great strides have been made in understanding these structures and their dysfunction in various inflammatory diseases, lending new insights into urological and renal problems. From a clinical perspective, benign urinary pathology almost universally involves the inflammatory process, and understanding how inflammasomes translate etiological conditions (diabetes, obstruction, stones, urinary tract infections, etc.) into acute and chronic inflammatory responses is critical to understanding these diseases at a molecular level. To date, inflammasome components have been found in the bladder, prostate, and kidney and have been shown to be activated in response to several infectious and noninfectious insults. In this review, we summarize what is known regarding inflammasomes in both the upper and lower urinary tract and describe several common disease states where they potentially play critical roles.
Temporal dynamics of visual category representation in the macaque inferior temporal cortex
Authors: Dehaqani Mohammad-Reza A. , Vahabie Abdol-Hossein , Kiani Roozbeh , Ahmadabadi Majid Nili , Araabi Babak Nadjar , Esteky Hossein
Published: May 2016

Object categories are recognized at multiple levels of hierarchical abstractions. Psychophysical studies have shown a more rapid perceptual access to the mid-level category information (e.g., human faces) than the higher (superordinate; e.g., animal) or the lower (subordinate; e.g., face identity) level. Mid-level category members share many features, whereas few features are shared among members of different mid-level categories. To understand better the neural basis of expedited access to mid-level category information, we examined neural responses of the inferior temporal (IT) cortex of macaque monkeys viewing a large number of object images. We found an earlier representation of mid-level categories in the IT population and single-unit responses compared with superordinate- and subordinate-level categories. The short-latency representation of mid-level category information shows that visual cortex first divides the category shape space at its sharpest boundaries, defined by high/low within/between-group similarity. This short-latency, mid-level category boundary map may be a prerequisite for representation of other categories at more global and finer scales.
Motor learning and cross-limb transfer rely upon distinct neural adaptation processes
Authors: Stöckel Tino , Carroll Timothy J. , Summers Jeffery J. , Hinder Mark R.
Published: May 2016

Performance benefits conferred in the untrained limb after unilateral motor practice are termed cross-limb transfer. Although the effect is robust, the neural mechanisms remain incompletely understood. In this study we used noninvasive brain stimulation to reveal that the neural adaptations that mediate motor learning in the trained limb are distinct from those that underlie cross-limb transfer to the opposite limb. Thirty-six participants practiced a ballistic motor task with their right index finger (150 trials), followed by intermittent theta-burst stimulation (iTBS) applied to the trained (contralateral) primary motor cortex (cM1 group), the untrained (ipsilateral) M1 (iM1 group), or the vertex (sham group). After stimulation, another 150 training trials were undertaken. Motor performance and corticospinal excitability were assessed before motor training, pre- and post-iTBS, and after the second training bout. For all groups, training significantly increased performance and excitability of the trained hand, and performance, but not excitability, of the untrained hand, indicating transfer at the level of task performance. The typical facilitatory effect of iTBS on MEPs was reversed for cM1, suggesting homeostatic metaplasticity, and prior performance gains in the trained hand were degraded, suggesting that iTBS interfered with learning. In stark contrast, iM1 iTBS facilitated both performance and excitability for the untrained hand. Importantly, the effects of cM1 and iM1 iTBS on behavior were exclusive to the hand contralateral to stimulation, suggesting that adaptations within the untrained M1 contribute to cross-limb transfer. However, the neural processes that mediate learning in the trained hemisphere vs. transfer in the untrained hemisphere appear distinct.