bluuebunny/crossref_metadata_2025 huggingface dataset:
Contextualizing the Education Effect on Women's Employment: A Cross‐National Comparative Analysis
Authors: Steiber Nadia , Berghammer Caroline , Haas Barbara
Published: October 2015

The authors examine how and why the effect of education on women's employment varies cross‐nationally. First, they present a theoretical model that (a) outlines the micro‐level mechanisms underlying education effects on women's employment in the couple context and (b) proposes contextual moderators at the country level. Second, they test the theoretical model against survey data from the United Nations' Generations and Gender Programme for 5 European countries (Austria, France, Germany, Hungary, and Norway). The data comprise 10,048 educationally homogamous heterosexual couples involving a woman age 20–45. The results indicate that more highly educated couples are more likely to have dual‐earner arrangements in each country, yet the strength of education effects varied substantially between countries and across the family life cycle. In contrast to prior work, the authors find that education effects are not generally smaller in countries that are supportive of women's employment. This relation holds only for later child‐rearing phases.
Cloning and functional characterization of the Arabidopsis N‐acetylserotonin O‐methyltransferase responsible for melatonin synthesis
Authors: Byeon Yeong , Lee Hye‐Jung , Lee Hyoung Yool , Back Kyoungwhan
Published: October 2015

The N‐acetylserotonin O‐methyltransferase (ASMT) gene encodes the enzyme that catalyzes the conversion of N‐acetylserotonin to melatonin as the last step in melatonin biosynthesis. The first plant ASMT gene to be cloned was from rice. An orthologous gene encoding a protein with ASMT activity and only 39.7% amino acid sequence identity to the rice ASMT protein was recently isolated from apple (Malus zumi). The low homology of the apple ASMT sequence prompted us to screen the Arabidopsis genome for a homologous ASMT gene. The At4g35160 gene exhibited the highest sequence identity (31%) to the rice ASMT gene, followed by the At1g76790 gene with 29% sequence identity. We purified recombinant proteins expressed from the two Arabidopsis genes. The At4g35160 recombinant protein exhibited ASMT enzyme activity, but the At1g76790 recombinant protein did not; thus, we designated At4g35160 as an Arabidopsis thaliana ASMT (AtASMT) gene. The AtASMT protein catalyzed the conversion of N‐acetylserotonin to melatonin and serotonin to 5‐methoxytryptamine with Vmax values of 0.11 and 0.29 pkat/mg protein, respectively. However, AtASMT exhibited no caffeic acid O‐methyltransferase activity, suggesting that its function was highly specific to melatonin synthesis. AtASMT transcripts were induced by cadmium treatment in Arabidopsis followed by increased melatonin synthesis. Similar to other ASMT proteins, AtASMT was localized in the cytoplasm and its ectopic overexpression in rice resulted in increased ASMT enzyme activity and melatonin production, indicating the involvement of AtASMT in melatonin synthesis.
Why we need more algal metagenomes1
Authors: Graham Linda E. , Wilcox Lee W. , Knack Jennifer J.
Published: October 2015

A recent perspective article ably argued that fully sequencing more algal genomes would enable progress in diverse areas of fundamental and applied studies. More algal genomes would add resources needed to build well‐supported phylogenies, improve our understanding of how horizontal gene transfer has influenced the evolution of algal genomes, provide useful ecological insights, and generate information essential to manipulating the genomes of industrially useful algae (J. Phycol. 51:1). We agree that more algal genomes would be quite beneficial, and also propose that more algal metagenomes would enable progress in both predictable and unforeseen directions.
Impact of eradicating hepatitis C virus on the work productivity of chronic hepatitis C (CH‐C) patients: an economic model from five European countries
Authors: Younossi Z. , Brown A. , Buti M. , Fagiuoli S. , Mauss S. , Rosenberg W. , Serfaty L. , Srivastava A. , Smith N. , Stepanova M. , Beckerman R.
Published: October 2015

CH‐C negatively affects work productivity (WP), creating a large economic burden. The aim of this study was to model the impact of sustained virologic response (SVR) on WP in CHC genotype 1 (GT1) patients in five European countries (EU5). Work Productivity and Activity Index‐Specific Health Problem questionnaire was administered to patients across the ION clinical trials (n = 629 European patients). The analysis modelled a population of GT1 CHC patients over one year, who had been either not treated or treated with LDV/SOF. Sensitivity analyses assessed the possibility that CHC patients’ labour costs were lower than the general population's and presented results by fibrosis stage. Before initiation of treatment, EU patients with CHC GT1 exhibited absenteeism and presenteeism impairments of 3.54% and 9.12%, respectively. About 91.8% of EU patients in the ION trials achieved SVR and improved absenteeism and presenteeism impairments by 16.3% and 19.5%, respectively. Monetizing these data, treatment with LDV/SOF resulted in an annual productivity gain of €435 million and a weighted average per‐employed patient (PEP) gain of €900 in the EU5. PEP gains from treatment are projected to be higher in cirrhotic than in noncirrhotic patients. If CHC patients are assumed to earn 20% less than the general population, gains of €348 million (€720 PEP) annually are projected. CHC results in a significant economic burden to European society. Due to improvements in WP, SVR with treatment could provide substantial economic gains, partly offsetting the direct costs related to its widespread use.
Mechanisms of adaptation and progression in idiosyncratic drug induced liver injury, clinical implications
Authors: Dara Lily , Liu Zhang‐Xu , Kaplowitz Neil
Published: October 2015

In the past decade our understanding of idiosyncratic drug induced liver injury (IDILI) and the contribution of genetic susceptibility and the adaptive immune system to the pathogenesis of this disease process has grown tremendously. One of the characteristics of IDILI is that it occurs rarely and only in a subset of individuals with a presumed susceptibility to the drug. Despite a clear association between single nucleotide polymorphisms in human leukocyte antigen (HLA) genes and certain drugs that cause IDILI, not all individuals with susceptible HLA genotypes develop clinically significant liver injury when exposed to drugs. The adaptation hypothesis has been put forth as an explanation for why only a small percentage of susceptible individuals develop overt IDILI and severe injury, while the majority with susceptible genotypes develop only mild abnormalities that resolve spontaneously upon continuation of the drug. This spontaneous resolution is referred to as clinical adaptation. Failure to adapt or defective adaptation leads to clinically significant liver injury. In this review we explore the immuno‐tolerant microenvironment of the liver and the mechanisms of clinical adaptation in IDILI with a focus on the role of immune‐tolerance and cellular adaptive responses.
Clinical Guideline for Female Lower Urinary Tract Symptoms
Authors: TAKAHASHI Satoru , TAKEI Mineo , NISHIZAWA Osamu , YAMAGUCHI Osamu , KATO Kumiko , GOTOH Momokazu , YOSHIMURA Yasukuni , TAKEYAMA Masami , OZAWA Hideo , SHIMADA Makoto , YAMANISHI Tomonori , YOSHIDA Masaki , TOMOE Hikaru , YOKOYAMA Osamu , KOYAMA Masayasu
Published: October 2015

The “Japanese Clinical Guideline for Female Lower Urinary Tract Symptoms,” published in Japan in November 2013, contains two algorithms (a primary and a specialized treatment algorithm) that are novel worldwide as they cover female lower urinary tract symptoms other than urinary incontinence. For primary treatment, necessary types of evaluation include querying the patient regarding symptoms and medical history, examining physical findings, and performing urinalysis. The types of evaluations that should be performed for select cases include evaluation with symptom/quality of life (QOL) questionnaires, urination records, residual urine measurement, urine cytology, urine culture, serum creatinine measurement, and ultrasonography. If the main symptoms are voiding/post‐voiding, specialized treatment should be considered because multiple conditions may be involved. When storage difficulties are the main symptoms, the patient should be assessed using the primary algorithm. When conditions such as overactive bladder or stress incontinence are diagnosed and treatment is administered, but sufficient improvement is not achieved, the specialized algorithm should be considered. In case of specialized treatment, physiological re‐evaluation, urinary tract/pelvic imaging evaluation, and urodynamic testing are conducted for conditions such as refractory overactive bladder and stress incontinence. There are two causes of voiding/post‐voiding symptoms: lower urinary tract obstruction and detrusor underactivity. Lower urinary tract obstruction caused by pelvic organ prolapse may be improved by surgery.
Effects of amino acid starvation on RelA diffusive behavior in live Escherichia coli
Authors: Li Wenting , Bouveret Emmanuelle , Zhang Yan , Liu Kuanqing , Wang Jue D. , Weisshaar James C.
Published: October 2015

During amino acid starvation, bacterial cells rapidly synthesize the nucleotides (p)ppGpp, causing a massive re‐programming of the transcriptional profile known as the stringent response. The (p)ppGpp synthase RelA is activated by ribosomes harboring an uncharged tRNA at the A site. It is unclear whether synthesis occurs while RelA is bound to the ribosome or free in the cytoplasm. We present a study of three Escherichia coli strains, each expressing a different RelA‐fluorescent protein (RelA‐FP) construct: RelA‐YFP, RelA‐mEos2 and RelA‐Dendra2. Single‐molecule localization and tracking studies were carried out under normal growth conditions and during amino acid starvation. Study of three labeling schemes enabled us to assess potential problems with FP labeling of RelA. The diffusive trajectories and axial spatial distributions indicate that amino acid starvation induces net binding of all three RelA‐FP constructs to 70S ribosomes. The data are most consistent with a model in which RelA synthesizes (p)ppGpp while bound to the 70S ribosome. We suggest a ‘short hopping time’ model of RelA activity during starvation. Our results contradict an earlier study of RelA‐Dendra2 diffusion that inferred off‐ribosome synthesis of (p)ppGpp. The reasons for the discrepancy remain unclear.
Does Conflict Content Affect Learning from Simulations? A Cross‐National Inquiry into the Israeli‐Palestinian and Guatemalan Conflict Scenarios
Authors: Cuhadar C. Esra , Kampf Ronit
Published: October 2015

It is important to find out whether the content of a simulation has any effect on learning, whether students learn better when the simulation is about a conflict they directly experience as opposed to a conflict they have hardly heard about, and whether learning about a specific conflict changes from one identity group to another. In this article, we address these questions in a five‐group experimental study, with direct parties to the conflict (Israeli‐Jewish, Palestinian, and Guatemalan), third/secondary parties to the conflict (Turkish, American, and Brazilian), and distant parties to the conflict. Our results indicate that learning varies not only from one group to the other, but also with the salience of the conflict. While the simulations increase the level of knowledge about that particular conflict in almost all situations, when attitude change is concerned, the effects diversify from one group to the other.
Done But Not Published: The Dissertation Journeys of Roy J. Lewicki and J. Keith Murnighan
Authors: Kopelman Shirli , Lytle Anne L. , Wang Cynthia S. , Lewicki Roy J. , Murnighan J. Keith , Bazerman Max H.
Published: October 2015

This article explores the tumultuous path to publication that begins for many of us with trying to publish our dissertation. We invited Roy J. Lewicki and J. Keith Murnighan—the 2013 and 2015 recipients of the International Association for Conflict Management (IACM) Lifetime Achievement Award—to reflect on this process, as neither of them were successful in getting their dissertation articles published. We also asked them to reflect on the twists and turns of academic publishing, and we asked Max Bazerman to integrate these reflections. Together, we hope to spark generative conversations that will enable scholars to successfully navigate their academic careers.
Recurrent lupus nephritis after transplantation: Clinicopathological evaluation with protocol biopsies
Authors: Çeltİk Aygül , Şen Saİt , Tamer Abdülkerİm Furkan , Yılmaz Mümtaz , Sarsık Banu , Özkahya Mehmet , Başçı Alı , Töz Hüseyİn
Published: October 2015

Aim

Lupus nephritis (LN) is an important complication of systemic lupus erythematosus (SLE). The aim is to use indication and protocol biopsies to determine clinicopathological findings and outcomes of patients with LN undergoing kidney transplantation (KTx).

Methods

Patients who underwent KTx due to LN were retrospectively analyzed. Recurrent LN (RLN) was diagnosed by transplant kidney biopsy.

Results

Among 955 KTx patients, 12 patients with LN as the cause of end‐stage renal disease were enrolled. Five patients were male. Mean follow‐up time was 63 ± 34 months. At the last follow‐up visit, mean levels of serum creatinine and proteinuria were 137.0 ± 69.0 µmol/L and 0.26 ± 0.26 g/day, respectively. Eighteen indication and 22 protocol biopsies were performed; 27 biopsies were additionally evaluated by immunofluorescence. In two recipients, subclinical RLN was confirmed by protocol biopsies. Clinical recurrence occurred in four patients. Among patients with RLN, time from diagnosis of LN to KTx was significantly shorter and use of ATG as induction treatment was significantly lower. Graft loss occurred in two recipients who had clinical RLN. Five‐year overall graft survival was 85.7%.

Conclusion

Kidney transplantation is a reasonable option for patients with ESRD secondary to SLE. However, recurrence of LN is common if protocol biopsies are included in post‐transplantation surveillance.
TaGS5‐3A, a grain size gene selected during wheat improvement for larger kernel and yield
Authors: Ma Lin , Li Tian , Hao Chenyang , Wang Yuquan , Chen Xinhong , Zhang Xueyong
Published: October 2015

Grain size is a dominant component of grain weight in cereals. Earlier studies have shown that OsGS5 plays a major role in regulating both grain size and weight in rice via promotion of cell division. In this study, we isolated TaGS5 homoeologues in wheat and mapped them on chromosomes 3A, 3B and 3D. Temporal and spatial expression analysis showed that TaGS5 homoeologues were preferentially expressed in young spikes and developing grains. Two alleles of TaGS5‐3A, TaGS5‐3A‐T and TaGS5‐3A‐G were identified in wheat accessions, and a functional marker was developed to discriminate them. Association analysis revealed that TaGS5‐3A‐T was significantly correlated with larger grain size and higher thousand kernel weight. Biochemical assays showed that TaGS5‐3A‐T possesses a higher enzymatic activity than TaGS5‐3A‐G. Transgenic rice lines overexpressing TaGS5‐3A‐T also exhibited larger grain size and higher thousand kernel weight than TaGS5‐3A‐G lines, and the transcript levels of cell cycle‐related genes in TaGS5‐3A‐T lines were higher than those in TaGS5‐3A‐G lines. Furthermore, systematic evolution analysis in diploid, tetraploid and hexaploid wheat showed that TaGS5‐3A underwent strong artificial selection during wheat polyploidization events and the frequency changes of two alleles demonstrated that TaGS5‐3A‐T was favoured in global modern wheat cultivars. These results suggest that TaGS5‐3A is a positive regulator of grain size and its favoured allele TaGS5‐3A‐T exhibits a larger potential application in wheat high‐yield breeding.
Electrophysiological correlates of emotional meaning in context in relation to facets of schizotypal personality traits: A dimensional study
Authors: Terrien Sarah , Gobin Pamela , Iakimova Galina , Coutté Alexandre , Thuaire Flavien , Baltazart Véronique , Mazzola‐Pomietto Pascale , Besche‐Richard Chrystel
Published: October 2015

Aims

The aim of this study was to investigate the neurocognitive processes mediating the processing of emotional information during the integration of contextual and social information in a schizotypal population.

Methods

One hundred and thirty‐one healthy participants were evaluated using the Schizotypal Personality Questionnaire and event‐related potentials were recorded during a linguistic task in which participants read sentence pairs describing short social situations to themselves. The first sentence implicitly conveyed the positive or negative emotional state of a character. The second sentence was emotionally congruent or incongruent with the first sentence.

Results

Across our overall sample, our results revealed a greater N400 effect at right sites than left sites, whereas the late positive component effect was only observed at left sites. Concerning the correlation results, we observed a negative link between positive and global schizotypy and N400 modulation in response to congruent targets for positive context sentences. Results also showed a positive correlation between negative schizotypy and late positive component modulation in response to congruent targets for negative context sentences.

Conclusions

These results suggest that the different facets of the schizotypal personality traits influenced the integration of emotional context at the level of both early and later‐mobilized neurocognitive processes.
Novel In Vitro Antioxidant and Photoprotection Capacity of Plants from High Altitude Ecosystems of Colombia
Authors: Mejía‐Giraldo Juan C. , Henao‐Zuluaga Kelly , Gallardo Cecilia , Atehortúa Lucia , Puertas‐Mejía Miguel A.
Published: October 2015

Currently, plants have gained widespread interest as a source of natural sunscreen. Specifically, plants from high altitude ecosystems are exposed to high UVR levels; therefore, they must produce an adaptive chemical response. The aim of this study was to evaluate the photo‐protection and antioxidant capacity in vitro of nine plants from high altitude ecosystems in Antioquia, Colombia (Sphagnum meridense, Calamagrostis effusa, Lycopodiella alopecuroides, Morella parvifolia, Baccharis antioquensis, Pentacalia pulchella, Castilleja fissifolia, Hesperomeles ferruginea and Hypericum juniperinum). B. antioquensis and P. pulchella extracts showed the best results over a broad spectrum UVA‐UVB with antioxidant capacity in vitro. However, B. antioquensis extracts presented the highest absorption coefficient in UVB‐UVA range among plants under study. Furthermore, the gel formulation containing the crude extract of B. antioquensis showed significant values of UVAPF, UVA/UVB ratio, critical wavelength (λc) and SPF (3, 0.78 380 nm and 4.73 ± 0.26; respectively), indicating interesting photostability and antiradical capacities. All of these properties could be improve in order to satisfy the requirements for broad‐spectrum UVB/UVA protection. Finally, P. pulchella and B. antioquensis extracts could be a potential source of a new natural sunscreen compounds with photostable and antiradical properties.
The host immune response to gastrointestinal nematode infection in sheep
Authors: McRae K. M. , Stear M. J. , Good B. , Keane O. M.
Published: October 2015

Gastrointestinal nematode infection represents a major threat to the health, welfare and productivity of sheep populations worldwide. Infected lambs have a reduced ability to absorb nutrients from the gastrointestinal tract, resulting in morbidity and occasional mortality. The current chemo‐dominant approach to nematode control is considered unsustainable due to the increasing incidence of anthelmintic resistance. In addition, there is growing consumer demand for food products from animals not subjected to chemical treatment. Future mechanisms of nematode control must rely on alternative, sustainable strategies such as vaccination or selective breeding of resistant animals. Such strategies take advantage of the host's natural immune response to nematodes. The ability to resist gastrointestinal nematode infection is considered to be dependent on the development of a protective acquired immune response, although the precise immune mechanisms involved in initiating this process remain to be fully elucidated. In this study, current knowledge on the innate and acquired host immune response to gastrointestinal nematode infection in sheep and the development of immunity is reviewed.
Preparing for (valenced) action: The role of differential effort in the orthogonalized go/no‐go task
Authors: Schevernels Hanne , Bombeke Klaas , Krebs Ruth M. , Boehler C. Nico
Published: October 2015

Associating reward to task performance has been shown to benefit scores of cognitive functions. Importantly, this typically entails associating reward to the execution of a response, hence intertwining action‐related processes with motivational ones. However, recently, preparatory action requirements (go/no‐go) and outcome valence (reward/punishment) were elegantly separated using a cued orthogonalized go/no‐go task. Functional magnetic resonance imaging results from this task showed that typical areas of the “reward network,” like the dopaminergic midbrain and the striatum, predominantly encode action rather than valence, displaying enhanced activity when preparing for action (go) compared to inaction (no‐go). In the current study, we used ERPs to probe for differences in preparatory state related to cognitive effort in this task, which has similarly been linked to reward‐network activity. Importantly, the contingent negative variation, which is linked to effortful cognitive preparation processes during cue‐target intervals, was clearly observed in go trials but not in no‐go trials. Moreover, target‐locked ERP results (N1 and P3) suggested that attention to the target was enhanced when an action had to be performed (go trials), and typical inhibition‐related ERP components were not observed in no‐go trials, suggesting a lack of active response inhibition. Finally, feedback‐related P3 results could suggest that correct feedback was valued more in motivated go trials, again implying that more effort was required to correctly perform the task. Together, these results indicate that the anticipation of action compared to inaction simultaneously entails differences in mental effort, highlighting the need for further dissociation of these concepts.
Proteomic Characterization of Zinc‐Binding Proteins of Canine Seminal Plasma
Authors: Mogielnicka‐Brzozowska M , Kowalska N , Fraser L , Kordan W
Published: October 2015

Contents

The zinc‐binding proteins (ZnBPs) of the seminal plasma are implicated in different processes related to sperm–egg fusion. The aim of this study was to characterize the ZnBPs of canine seminal plasma using two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE) and mass spectrometry. The ZnBPs were isolated from the ejaculates of five dogs by affinity chromatography and subjected to 2D‐PAGE analysis. The acquired spots, detected across the gels, were analysed by mass spectrometry. Using 2D‐PAGE analysis, it was shown that canine seminal plasma comprised about 46–57 zinc‐binding polypeptides, with molecular mass ranging from 9.3 to 138.7 kDa and pI at pH 5.2–10.0. It was found that zinc‐binding polypeptides of low molecular masses (9.3–19.0 kDa and pI at pH 6.1–10.0) were predominant in the seminal plasma, and seven polypeptides, with molecular masses ranging from 11.7 to 15.4 kDa and pI at pH 6.8–8.7, were characterized by high optical density values. In addition, analysis with mass spectrometry (LC‐MS‐MS/MS) revealed that the identified seven polypeptides are canine prostate‐specific esterase (CPSE), which is the main proteolytic enzyme of the seminal plasma. The findings of this study indicate an important regulatory role of seminal plasma zinc ions in the functional activity of CPSE, which is of great significance for maintaining the normal function of canine prostate and the spermatozoa functions.
Patterns of International Capital Flows and Productivity Growth: New Evidence
Authors: MacDonald Margaux
Published: October 2015

Recent evidence from developing and emerging economies shows a negative correlation between growth and net capital inflows, a contradiction to neoclassical growth theory. I provide updated and disaggregated evidence on the origins of this puzzle. An analysis of the components of capital flows and of gross portfolio positions shows that foreign direct investment is directed towards countries with the highest growth rates, but that portfolio investment outflows exceed these inflows. Liberalized capital accounts further exacerbate this pattern. My results suggest a desire for international portfolio diversification in liquid assets by fast‐growing countries lies at the heart of the puzzle.
From Registers to Repertoires of Identification in National Identity Discourses: A Comparative Study of Nationally Mixed People in France, Germany, and the United Kingdom
Authors: Unterreiner Anne
Published: October 2015

As nationally mixed people have parents born in different countries, they can potentially identify with multiple national reference groups, allowing the researcher to study national identification processes. The analysis of approximately one hundred people of nationally mixed background living in France, Germany, and the United Kingdom highlights different registers of identification. There are important differences in how nationally mixed people articulate them, which leads to the identification of different national repertoires of identification. In France, a strong French national identity was emphasized, whereas German national identity seems more fragile because it depends mainly on cultural socialization. In the United Kingdom, non‐national identities are developed in a context where the national community is not clearly defined, while ethnicity is publicly recognized. The register and repertoire of identification concepts thus allow the researcher to analyse identity discourses and then explain national differences through international comparison.
Migrant Responses to Popular Uses of the Australian Flag
Authors: Austin Catherine , Fozdar Farida
Published: October 2015

Australian nationalism, once seen as laconic and understated, has become increasingly shrill over the last fifteen years. One evidence is the growing popular use of Australian flags, particularly their display on cars to celebrate the national day. Popular use of the flag has been encouraged by relevant government bodies, such as the National Australia Day Council. This article explores migrants' responses to the flag display. Qualitative interviews and focus group discussions identified a continuum of reactions ranging from inclusion to exclusion. Contrary to expectations, many migrants see it as simply a demonstration of festivity and pride, in which they feel included. While recognizing that the flag display could represent exclusionary nationalism, migrants carefully attribute this usage to a limited number of individuals, rather than seeing it as emblematic of a more generally held sentiment. Additionally, migrants tend to read the flag through civic, transnational, and multicultural lenses, in order to see themselves as included in the identity that it is seen to portray.
Boundaries in Shaping the Rohingya Identity and the Shifting Context of Borderland Politics
Authors: Farzana Kazi Fahmida
Published: October 2015

In recent years, new waves of ethnic violence in the Arakan (Rakhine) state of Burma (Myanmar) have resulted in increased internal displacement and the continued exodus of the Rohingya people to neighbouring countries. At the heart of this problem is the fact that Burma (which the Rohingyas claim as their ancestral land) and Bangladesh (where many Rohingyas are unwelcome and/or undocumented refugees) continue to deny the Rohingyas their political identity, each insisting that the displaced Rohingyas are the responsibility of the other. This study examines the history of the region to explore how political identities are shaped (generally) and how Rohingya refugees in Bangladesh, living along the borders, identify themselves in the midst of political sovereignty claims and a social space that exists across artificially drawn borders (specifically). This article argues that the true political identity of the displaced Rohingya refugees can be located in their social memory and their life‐politics in the borderlands. In this social memory, the Rohingyas' beliefs in ethnicity, identity, and belongingness play an important role in shaping their current identity. Their production of cultural artefacts while in exile suggests a non‐conventional resistance, and the close proximity of the refugees to their homeland creates a completely different psychology of attachment and alienation, which needs further attention in refugee studies. Such an understanding of life‐politics along the border may challenge our current understanding of borderland conflicts within the framework of state‐imposed boundaries. The boundaries of identity may go beyond traditional notions of national borders and the identity of the state.
Interleukin‐21 Induces Proliferation and Proinflammatory Cytokine Profile of Fibroblast‐like Synoviocytes of Patients with Rheumatoid Arthritis
Authors: Xing R. , Yang L. , Jin Y. , Sun L. , Li C. , Li Z. , Zhao J. , Liu X.
Published: October 2015

Fibroblast‐like synoviocytes (FLS) play a pivotal role in the pathogenesis of rheumatoid arthritis (RA) through aggressive proliferation and invasion, and certain proinflammatory cytokines may affect synoviocyte proliferation. To evaluate whether interleukin‐21 (IL‐21) could promote proliferation and proinflammatory cytokine production by RA‐FLS, immunohistochemistry and immunoblotting were performed to observe the expression of IL‐21 receptor (IL‐21R) in synovial tissues and FLS from RA and osteoarthritis (OA) patients. The MTS assay was used to analyse RA‐FLS proliferation. The concentrations of IL‐6 and tumour necrosis factor‐α (TNF‐α) in culture supernatants were determined by enzyme‐linked immunosorbent assay (ELISA). The signalling pathways triggered by IL‐21 were characterized by immunoblotting. IL‐21R was upregulated in the synovial tissues and FLS of RA patients as compared with OA patients. IL‐21 stimulated RA‐FLS proliferation and promoted the production of TNF‐α and IL‐6 and blockade of IL‐21/IL‐21R pathway with IL‐21R.Fc attenuated IL‐21‐induced proliferation and secretion of TNF‐α and IL‐6. Moreover, IL‐21 induced activation of the ERK1/2, PI3K/AKT and STAT3 pathways, and blockade of these pathways attenuated IL‐21‐induced proliferation and secretion of TNF‐α and IL‐6. These results suggest that IL‐21 could promote RA‐FLS proliferation and production of proinflammatory cytokines. Therefore, therapeutic strategies targeting IL‐21 might be effective for the treatment of RA.
Variation in attrition at subnational level: review of the Botswana National HIV/AIDS Treatment (Masa) programme data (2002–2013)
Authors: Farahani Mansour , Price Natalie , El‐Halabi Shenaaz , Mlaudzi Naledi , Keapoletswe Koona , Lebelonyane Refeletswe , Fetogang Ernest Benny , Chebani Tony , Kebaabetswe Poloko , Masupe Tiny , Gabaake Keba , Auld Andrew , Nkomazana Oathokwa , Marlink Richard
Published: October 2015

Objective

To evaluate the variation in all‐cause attrition [mortality and loss to follow‐up (LTFU)] among HIV‐infected individuals in Botswana by health district during the rapid and massive scale‐up of the National Treatment Program.

Methods

Analysis of routinely collected longitudinal data from 226 030 patients who received ART through the Botswana National HIV/AIDS Treatment Program across all 24 health districts from 2002 to 2013. A time‐to‐event analysis was used to measure crude mortality and loss to follow‐up rates (LTFU). A marginal structural model was used to evaluate mortality and LTFU rates by district over time, adjusted for individual‐level risk factors (e.g. age, gender, baseline CD4, year of treatment initiation and antiretroviral regimen).

Results

Mortality rates in the districts ranged from the lowest 1.0 (95% CI 0.9–1.1) in Selibe‐Phikwe, to the highest 5.0 (95% CI 4.0–6.1), in Mabutsane. There was a wide range of overall LTFU across districts, including rates as low as 4.6 (95% CI 4.4–4.9) losses per 100 person‐years in Ngamiland, and 5.9 (95% CI 5.6–6.2) losses per 100 person‐years in South East district, to rates as high as 25.4 (95% CI 23.08–27.89) losses per 100 person‐years in Mabutsane and 46.3 (95% CI 43.48–49.23) losses per 100 person‐years in Okavango. Even when known risk factors for mortality and LTFU were adjusted for, district was a significant predictor of both mortality and LTFU rates.

Conclusion

We found statistically significant variation in attrition (mortality and LTFU) and data quality among districts. These findings suggest that district‐level contextual factors affect retention in treatment. Further research needs to investigate factors that can potentially cause this variation.
A refined genome‐scale reconstruction of Chlamydomonas metabolism provides a platform for systems‐level analyses
Authors: Imam Saheed , Schäuble Sascha , Valenzuela Jacob , López García de Lomana Adrián , Carter Warren , Price Nathan D. , Baliga Nitin S.
Published: October 2015

Microalgae have reemerged as organisms of prime biotechnological interest due to their ability to synthesize a suite of valuable chemicals. To harness the capabilities of these organisms, we need a comprehensive systems‐level understanding of their metabolism, which can be fundamentally achieved through large‐scale mechanistic models of metabolism. In this study, we present a revised and significantly improved genome‐scale metabolic model for the widely‐studied microalga, Chlamydomonas reinhardtii. The model, iCre1355, represents a major advance over previous models, both in content and predictive power. iCre1355 encompasses a broad range of metabolic functions encoded across the nuclear, chloroplast and mitochondrial genomes accounting for 1355 genes (1460 transcripts), 2394 and 1133 metabolites. We found improved performance over the previous metabolic model based on comparisons of predictive accuracy across 306 phenotypes (from 81 mutants), lipid yield analysis and growth rates derived from chemostat‐grown cells (under three conditions). Measurement of macronutrient uptake revealed carbon and phosphate to be good predictors of growth rate, while nitrogen consumption appeared to be in excess. We analyzed high‐resolution time series transcriptomics data using iCre1355 to uncover dynamic pathway‐level changes that occur in response to nitrogen starvation and changes in light intensity. This approach enabled accurate prediction of growth rates, the cessation of growth and accumulation of triacylglycerols during nitrogen starvation, and the temporal response of different growth‐associated pathways to increased light intensity. Thus, iCre1355 represents an experimentally validated genome‐scale reconstruction of C. reinhardtii metabolism that should serve as a useful resource for studying the metabolic processes of this and related microalgae.
Technical Note: MR‐visualization of interventional devices using transient field alterations and balanced steady‐state free precession imaging
Authors: Eibofner Frank , Martirosian Petros , Würslin Christian , Graf Hansjörg , Syha Roland , Clasen Stephan
Published: October 2015

Purpose:

In interventional magnetic resonance imaging, instruments can be equipped with conducting wires for visualization by current application. The potential of sequence triggered application of transient direct currents in balanced steady‐state free precession (bSSFP) imaging is demonstrated.

Methods:

A conductor and a modified catheter were examined in water phantoms and in an ex vivo porcine liver. The current was switched by a trigger pulse in the bSSFP sequence in an interval between radiofrequency pulse and signal acquisition. Magnitude and phase images were recorded. Regions with transient field alterations were evaluated by a postprocessing algorithm. A phase mask was computed and overlaid with the magnitude image.

Results:

Transient field alterations caused continuous phase shifts, which were separated by the postprocessing algorithm from phase jumps due to persistent field alterations. The overlaid images revealed the position of the conductor. The modified catheter generated visible phase offset in all orientations toward the static magnetic field and could be unambiguously localized in the ex vivo porcine liver.

Conclusions:

The application of a sequence triggered, direct current in combination with phase imaging allows conspicuous localization of interventional devices with a bSSFP sequence.
Room acoustical parameters of two electronically connected rooms
Authors: Zidan Hassan EL-Banna , Svensson U. Peter , Nielsen Johan L.
Published: October 2015

The acoustical properties of two rooms that are one-way connected electroacoustically, e.g., in a telephone/video conference, can be analyzed through the total impulse response from a source in one room to the receiver in the other room. The total impulse response is a convolution of the two involved room impulse responses, and such a model is analyzed in this paper. The room impulse response model used here facilitates convolution analysis as the model is quite simple and composed of two terms only, a direct sound term and an exponentially decaying random Gaussian noise term. Analytical expressions have been derived for the energy decay function, leading to estimates of room acoustical parameters like clarity and the modulation transfer functions for such convolved impulse responses. Background noise expressions are also introduced to allow signal-to-noise ratio studies. Estimates of acoustic parameter values have been compared with measurements to evaluate the model used and verify the results achieved.
Reflectance measurement validation using acoustic horns
Authors: Rasetshwane Daniel M. , Neely Stephen T.
Published: October 2015

Variability in wideband acoustic reflectance (and absorbance) measurements adversely affects the clinical utility of reflectance for diagnosis of middle-ear disorders. A reflectance standard would encourage consistency across different measurement systems and help identify calibration related issues. Theoretical equations exist for the reflectance of finite-length exponential, conical, and parabolic acoustic horns. Reflectance measurements were repeatedly made in each of these three horn shapes and the results were compared to the corresponding theoretical reflectance. A method is described of adjusting acoustic impedance measurements to compensate for spreading of the wave front that propagates from the small diameter sound port of the probe to the larger diameter of the acoustic cavity. Agreement between measured and theoretical reflectance was less than 1 dB at most frequencies in the range from 0.2 to 10 kHz. Pearson correlation coefficients were greater than 0.95 between measured and theoretical time-domain reflectance within the flare region of the horns. The agreement suggests that the distributed reflectance of acoustic horns may be useful for validating reflectance measurements made in human ear canals; however, refinements to reflectance measurement methods may still be needed.
Case Study: Nutritional and Lifestyle Support to Reduce Infection Incidence in an International-Standard Premier League Soccer Player
Authors: Ranchordas Mayur K. , Bannock Laurent , Robinson Scott L.
Published: October 2015

Professional soccer players are exposed to large amounts of physiological and psychological stress, which can increase infection risk and threaten availability for training and competition. Accordingly, it is important for practitioners to implement strategies that support player well-being and prevent illness. This case study demonstrates how a scientifically supported and practically applicable nutrition and lifestyle strategy can reduce infection incidence in an illness-prone professional soccer player. In the 3 months before the intervention, the player had 3 upper-respiratory tract infections (URTIs) and subsequently missed 3 competitive matches and 2 weeks’ training. He routinely commenced morning training sessions in the fasted state and was estimated to be in a large daily energy deficit. Throughout the 12-week intervention, the amount, composition, and timing of energy intake was altered, quercetin and vitamin D were supplemented, and the player was provided with a daily sleep and hygiene protocol. There was a positive increase in serum vitamin D 25(OH) concentration from baseline to Week 12 (53 n·mol-1 to 120 n·mol-1) and salivary immunoglobulin-A (98 mg·dl-1 to 135 mg·dl-1), as well as a decline in the number of URTI symptoms (1.8 ± 2.0 vs. 0.25 ± 0.5 for Weeks 0–4 and Weeks 8–12, respectively). More important, he maintained availability for all training and matches over the 12-week period. We offer this case study as a real-world applied example for other players and practitioners seeking to deploy nutrition and lifestyle strategies to reduce risk of illness and maximize player availability.
GPR3, a therapeutic target for AD?
Authors: Smith Orla
Published: October 2015

In mouse models of Alzheimer’s disease, loss of GPR3 reduces symptoms.
Hedgehog stimulates polyamine biosynthesis
Authors: VanHook Annalisa M.
Published: October 2015

Hedgehog signaling promotes neural proliferation by stimulating the biosynthesis of polyamines through a noncanonical mechanism.
Keeping a leash on cancer-killing cells
Authors: Ray L. Bryan
Published: October 2015

Cancer-targeted T cells get a fail-safe control mechanism.
A tripartite gene silencing complex
Authors: Riddihough Guy
Published: October 2015

The structure of a gene silencing complex reveals how it self-activates and is inhibited by a cancer-associated chromatin mutation.
Finding the good in malaria
Authors: Ferrarelli Leslie K.
Published: October 2015

A protein isolated from malaria enables drugs to home in on tumor cells.
Effect of
SLCO1B1
Polymorphisms on Rifabutin Pharmacokinetics in African HIV-Infected Patients with Tuberculosis
Authors: Hennig Stefanie , Naiker Suhashni , Reddy Tarylee , Egan Deirdre , Kellerman Tracy , Wiesner Lubbe , Owen Andrew , McIlleron Helen , Pym Alexander
Published: October 2015

Rifabutin, used to treat HIV-infected tuberculosis, shows highly variable drug exposure, complicating dosing. Effects of
SLCO1B1
polymorphisms on rifabutin pharmacokinetics were investigated in 35 African HIV-infected tuberculosis patients after multiple doses. Nonlinear mixed-effects modeling found that influential covariates for the pharmacokinetics were weight, sex, and a 30% increased bioavailability among heterozygous carriers of
SLCO1B1
rs1104581 (previously associated with low rifampin concentrations). Larger studies are needed to understand the complex interactions of host genetics in HIV-infected tuberculosis patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00640887.)
Multidrug-Resistant Neisseria gonorrhoeae Isolates from Nanjing, China, Are Sensitive to Killing by a Novel DNA Gyrase Inhibitor, ETX0914 (AZD0914)
Authors: Su Xiao-Hong , Wang Bao-Xi , Le Wen-Jing , Liu Yu-Rong , Wan Chuan , Li Sai , Alm Richard A. , Mueller John P. , Rice Peter A.
Published: October 2015

We tested the activity of ETX0914 against 187
Neisseria gonorrhoeae
isolates from men with urethritis in Nanjing, China, in 2013. The MIC
50
, MIC
90
, and MIC range for ETX0914 were 0.03 μg/ml, 0.06 μg/ml, and ≤0.002 to 0.125 μg/ml, respectively. All isolates were resistant to ciprofloxacin, and 36.9% (69/187) were resistant to azithromycin. Of the isolates, 46.5% were penicillinase-producing
N. gonorrhoeae
(PPNG), 36% were tetracycline-resistant
N. gonorrhoeae
(TRNG), and 13% (24 isolates) had an MIC of 0.125 μg/ml for ceftriaxone. ETX0914 may be an effective treatment option for gonorrhea.
Pharmacokinetics/Pharmacodynamics of Peptide Deformylase Inhibitor GSK1322322 against Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in Rodent Models of Infection
Authors: Hoover Jennifer , Lewandowski Thomas , Straub Robert J. , Novick Steven J. , DeMarsh Peter , Aubart Kelly , Rittenhouse Stephen , Zalacain Magdalena
Published: October 2015

GSK1322322 is a novel inhibitor of peptide deformylase (PDF) with goodin vitroactivity against bacteria associated with community-acquired pneumonia and skin infections. We have characterized thein vivopharmacodynamics (PD) of GSK1322322 in immunocompetent animal models of infection withStreptococcus pneumoniaeandHaemophilus influenzae(mouse lung model) and withStaphylococcus aureus(rat abscess model) and determined the pharmacokinetic (PK)/PD index that best correlates with efficacy and its magnitude. Oral PK studies with both models showed slightly higher-than-dose-proportional exposure, with 3-fold increases in area under the concentration-time curve (AUC) with doubling doses. GSK1322322 exhibited dose-dependentin vivoefficacy against multiple isolates ofS. pneumoniae,H. influenzae, andS. aureus. Dose fractionation studies with twoS. pneumoniaeandS. aureusisolates showed that therapeutic outcome correlated best with the free AUC/MIC (fAUC/MIC) index inS. pneumoniae(R2, 0.83), whereasfAUC/MIC and free maximum drug concentration (fCmax)/MIC were the best efficacy predictors forS. aureus(R2, 0.9 and 0.91, respectively). Median dailyfAUC/MIC values required for stasis and for a 1-log10reduction in bacterial burden were 8.1 and 14.4 for 11S. pneumoniaeisolates (R2, 0.62) and 7.2 and 13.0 for fiveH. influenzaeisolates (R2, 0.93). The data showed that for eightS. aureusisolates,fAUC correlated better with efficacy thanfAUC/MIC (R2, 0.91 and 0.76, respectively), as efficacious AUCs were similar for all isolates, independent of their GSK1322322 MIC (range, 0.5 to 4 μg/ml). MedianfAUCs of 2.1 and 6.3 μg · h/ml were associated with stasis and 1-log10reductions, respectively, forS. aureus.
In Vitro
Pharmacodynamics of Human Simulated Exposures of Telavancin against Methicillin-Susceptible and -Resistant Staphylococcus aureus with and without Prior Vancomycin Exposure
Authors: Thabit Abrar K. , Nicolau David P. , Kuti Joseph L.
Published: October 2015

Telavancin is a lipoglycopeptide with potent activity against methicillin-resistant
Staphylococcus aureus
(MRSA) and methicillin-susceptible
S. aureus
(MSSA). The activity of telavancin against MRSA and MSSA after prior vancomycin exposure was studied in an
in vitro
pharmacodynamic model. Two clinical MRSA and two MSSA isolates, all with vancomycin MICs of 2 μg/ml, were subjected to humanized free drug exposures of vancomycin at 1 g every 12 h (q12h) for 96 h, telavancin at 750 mg q24h for 96 h, and vancomycin at 1 g q12h for 72 h followed by telavancin at 750 mg q24h for 48 h (120 h total). The microbiological responses were measured by changes from 0 h in log
10
CFU/ml at the end of experiments and area under the bacterial killing and regrowth curves over 96 h (AUBC
0−96
). The control isolates grew to 8.8 ± 0.3 log
10
CFU/ml. Initially, all regimens caused −4.5 ± 0.9 reductions in log
10
CFU/ml by 48 h followed by slight regrowth over the following 48 to 72 h. After 96 h, vancomycin and telavancin achieved −3.7 ± 0.9 and −3.8 ± 0.8 log
10
CFU/ml changes from baseline, respectively (
P
= 0.74). Sequential exposure to telavancin after vancomycin did not result in additional CFU reductions or increases, with ultimate log
10
CFU/ml reductions of −4.3 ± 1.1 at 96 h and −4.2 ± 1.3 at 120 h (
P
> 0.05 for all comparisons at 96 h). The AUBC
0–96
was significantly smaller for the regimen of telavancin for 96 h than for the regimens of vancomycin for 96 h and vancomycin followed by telavancin (
P
≤ 0.04). No resistance was observed throughout the experiment. Against these MRSA and MSSA isolates with vancomycin MICs of 2 μg/ml, telavancin was comparable with vancomycin and its activity was unaffected by prior vancomycin exposure.