bluuebunny/crossref_metadata_2025_split huggingface dataset:
CO‐CBS‐H2S Axis: From Vascular Mediator to Cancer Regulator
Authors: Suematsu Makoto , Nakamura Takashi , Tokumoto Yasuhito , Yamamoto Takehiro , Kajimura Mayumi , Kabe Yasuaki 
Published: November 2015

AbstractCO is a gaseous mediator generated by HO. Our previous studies revealed that CO generated from inducible HO‐1 or from constitutive HO‐2 modulates function of different heme proteins or enzymes through binding to their prosthetic ferrous heme to alter their structures, regulating biological function of cells and organs. Such CO‐directed target macromolecules include sGC and CBS. In the liver, CO serves as a sinusoidal dilator through its action on sGC in hepatic stellate cells, while the same gas accounts for vasoconstrictor that inhibits H2S generated by CO‐sensitive CBS in astrocytes. Since molecular O2 is a substrate for HO, the latter mechanism contributes to hypoxic vasodilation in neurovascular units. We have recently uncovered that stress‐inducible CO in and around cancer cells suppresses CBS to result in decreased methylation of PFKFB3, the enzyme regulating PFK‐1, leading to a shift of glucose biotransformation from glycolysis toward pentose phosphate pathway; such a metabolic remodeling causes chemoresistance through increasing NADPH and reduced glutathione under stress conditions for cancer cells. This article reviews the intriguing networks of CO‐sensitive metabolic regulatory mechanisms in microcirculation and cancer.
Comparison of health risk behavior, awareness, and health benefit beliefs of health science and non‐health science students: An international study
Authors: Peltzer Karl , Pengpid Supa , Yung Tony K. C. , Aounallah‐Skhiri Hajer , Rehman Rehana 
Published: November 2015

AbstractThis study determines the differences in health risk behavior, knowledge, and health benefit beliefs between health science and non‐health science university students in 17 low and middle income countries. Anonymous questionnaire data were collected in a cross‐sectional survey of 13,042 undergraduate university students (4,981 health science and 8,061 non‐health science students) from 17 universities in 17 countries across Asia, Africa, and the Americas. Results indicate that overall, health science students had the same mean number of health risk behaviors as non‐health science university students. Regarding addictive risk behavior, fewer health science students used tobacco, were binge drinkers, or gambled once a week or more. Health science students also had a greater awareness of health behavior risks (5.5) than non‐health science students (4.6). Linear regression analysis found a strong association with poor or weak health benefit beliefs and the health risk behavior index. There was no association between risk awareness and health risk behavior among health science students and an inverse association among non‐health science students.
Introducing an algal carbon‐concentrating mechanism into higher plants: location and incorporation of key components
Authors: Atkinson Nicky , Feike Doreen , Mackinder Luke C. M. , Meyer Moritz T. , Griffiths Howard , Jonikas Martin C. , Smith Alison M. , McCormick Alistair J. 
Published: November 2015

SummaryMany eukaryotic green algae possess biophysical carbon‐concentrating mechanisms (CCMs) that enhance photosynthetic efficiency and thus permit high growth rates at low CO2 concentrations. They are thus an attractive option for improving productivity in higher plants. In this study, the intracellular locations of ten CCM components in the unicellular green alga Chlamydomonas reinhardtii were confirmed. When expressed in tobacco, all of these components except chloroplastic carbonic anhydrases CAH3 and CAH6 had the same intracellular locations as in Chlamydomonas. CAH6 could be directed to the chloroplast by fusion to an Arabidopsis chloroplast transit peptide. Similarly, the putative inorganic carbon (Ci) transporter LCI1 was directed to the chloroplast from its native location on the plasma membrane. CCP1 and CCP2 proteins, putative Ci transporters previously reported to be in the chloroplast envelope, localized to mitochondria in both Chlamydomonas and tobacco, suggesting that the algal CCM model requires expansion to include a role for mitochondria. For the Ci transporters LCIA and HLA3, membrane location and Ci transport capacity were confirmed by heterologous expression and H14CO3‐ uptake assays in Xenopus oocytes. Both were expressed in Arabidopsis resulting in growth comparable with that of wild‐type plants. We conclude that CCM components from Chlamydomonas can be expressed both transiently (in tobacco) and stably (in Arabidopsis) and retargeted to appropriate locations in higher plant cells. As expression of individual Ci transporters did not enhance Arabidopsis growth, stacking of further CCM components will probably be required to achieve a significant increase in photosynthetic efficiency in this species.
Big Business in a Thin Market: Understanding the Privatization of Residential Care for Children and Youth in Sweden
Authors: Meagher Gabrielle , Lundström Tommy , Sallnäs Marie , Wiklund Stefan 
Published: November 2015

AbstractThis article analyzes the transformation of Swedish residential care for children from a regionally coordinated, public social service system into a thin, but highly profitable, national spot market in which large corporations have a growing presence. Marketization and privatization are theorized as complex processes, through which the institutional structure and logics of this small, but significant, social policy field changed profoundly. Using official documents, register data, media reports and existing research, three consecutive phases in the development of the children's home market are identified since the early 1980s. Change was driven on one hand by policies inspired by New Public Management, which shifted public authority horizontally to the private sector, and vertically to local authorities (funding) and to the state (regulation). On the other hand were the responses of local authorities and private actors to the changing incentives that policy shifts entailed. During the first two phases, both the proportion and size of for‐profit providers increased, and the model of family‐like care was replaced by a professional model. Cutting across the trend of privatization in the third phase was establishment of a parallel system of homes for unaccompanied refugee children – mostly in public ownership. Similarities with privatization in the English system of children's care homes are noted. By showing how the Swedish market for residential care has been created by policy and by actors’ responses to those reforms, the article provides a foundation for thinking through how the predictable, significant and well‐documented problems of such care markets might be addressed.
Public Attitudes towards Income Redistribution: Evidence from Hong Kong
Authors: Wu Alfred M. , Chou Kee‐Lee 
Published: November 2015

AbstractThe drivers of public support for redistributive policy have stimulated academic debate around the world. The majority of studies use cross‐country surveys conducted in the Organisation for Economic Co‐operation and Development countries to contribute to the debate on whether self‐interest or social values have more influence on public attitudes towards redistribution. Drawing on a phone survey conducted in 2013, this study advances the discussion by investigating public attitudes towards redistribution and social policy changes against the backdrop of buoyant government revenues in Hong Kong. The Hong Kong welfare model, best seen as a parallel to the liberal welfare state, is selective and residual. Contrary to the usual assumption, the social values hypothesis, viewing poverty as societal problems instead of individual reasons, has been supported in the Hong Kong context. It lends support to greater redistribution in a residual welfare state. The policy implications of the findings are also discussed.
Mitochondrial dynamics, mitophagy and cardiovascular disease
Authors: Vásquez‐Trincado César , García‐Carvajal Ivonne , Pennanen Christian , Parra Valentina , Hill Joseph A. , Rothermel Beverly A. , Lavandero Sergio 
Published: November 2015

AbstractCardiac hypertrophy is often initiated as an adaptive response to haemodynamic stress or myocardial injury, and allows the heart to meet an increased demand for oxygen. Although initially beneficial, hypertrophy can ultimately contribute to the progression of cardiac disease, leading to an increase in interstitial fibrosis and a decrease in ventricular function. Metabolic changes have emerged as key mechanisms involved in the development and progression of pathological remodelling. As the myocardium is a highly oxidative tissue, mitochondria play a central role in maintaining optimal performance of the heart. ‘Mitochondrial dynamics’, the processes of mitochondrial fusion, fission, biogenesis and mitophagy that determine mitochondrial morphology, quality and abundance have recently been implicated in cardiovascular disease. Studies link mitochondrial dynamics to the balance between energy demand and nutrient supply, suggesting that changes in mitochondrial morphology may act as a mechanism for bioenergetic adaptation during cardiac pathological remodelling. Another critical function of mitochondrial dynamics is the removal of damaged and dysfunctional mitochondria through mitophagy, which is dependent on the fission/fusion cycle. In this article, we discuss the latest findings regarding the impact of mitochondrial dynamics and mitophagy on the development and progression of cardiovascular pathologies, including diabetic cardiomyopathy, atherosclerosis, damage from ischaemia–reperfusion, cardiac hypertrophy and decompensated heart failure. We will address the ability of mitochondrial fusion and fission to impact all cell types within the myocardium, including cardiac myocytes, cardiac fibroblasts and vascular smooth muscle cells. Finally, we will discuss how these findings can be applied to improve the treatment and prevention of cardiovascular diseases.
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Synapse‐specific expression of calcium‐permeable AMPA receptors in neocortical layer 5
Authors: Lalanne Txomin , Oyrer Julia , Mancino Adamo , Gregor Erica , Chung Andrew , Huynh Louis , Burwell Sasha , Maheux Jérôme , Farrant Mark , Sjöström P. Jesper 
Published: November 2015

Key points
In the hippocampus, calcium‐permeable AMPA receptors have been found in a restricted subset of neuronal types that inhibit other neurons, although their localization in the neocortex is less well understood.
In the present study, we looked for calcium‐permeable AMPA receptors in two distinct populations of neocortical inhibitory neurons: basket cells and Martinotti cells. We found them in the former but not in the latter. Furthermore, in basket cells, these receptors were associated with particularly fast responses.
Computer modelling predicted (and experiments verified) that fast calcium‐permeable AMPA receptors enable basket cells to respond rapidly, such that they promptly inhibit neighbouring cells and shut down activity.
The results obtained in the present study help our understanding of pathologies such as stroke and epilepsy that have been associated with disordered regulation of calcium‐permeable AMPA receptors.
AbstractAMPA‐type glutamate receptors (AMPARs) lacking an edited GluA2 subunit are calcium‐permeable (CP) and contribute to synaptic plasticity in several hippocampal interneuron types, although their precise role in the neocortex is not well described. We explored the presence of CP‐AMPARs at pyramidal cell (PC) inputs to Martinotti cells (MCs) and basket cells (BCs) in layer 5 of the developing mouse visual cortex (postnatal days 12–21). GluA2 immunolabelling was stronger in MCs than in BCs. A differential presence of CP‐AMPARs at PC‐BC and PC‐MC synapses was confirmed electrophysiologically, based on measures of spermine‐dependent rectification and CP‐AMPAR blockade by 1‐naphtyl acetyl spermine using recordings from synaptically connected cell pairs, NPEC‐AMPA uncaging and miniature current recordings. In addition, CP‐AMPAR expression in BCs was correlated with rapidly decaying synaptic currents. Computer modelling predicted that this reduces spike latencies and sharpens suprathreshold responses in BCs, which we verified experimentally using the dynamic clamp technique. Thus, the synapse‐specific expression of CP‐AMPARs may critically influence both plasticity and information processing in neocortical microcircuits.
Purinergic signalling mediates bidirectional crosstalk between chemoreceptor type I and glial‐like type II cells of the rat carotid body
Authors: Murali Sindhubarathi , Nurse Colin A. 
Published: November 2015

Key points
Carotid body chemoreceptors are organized in clusters containing receptor type I and contiguous glial‐like type II cells.
While type I cells depolarize and release ATP during chemostimulation, the role of type II cells which express purinergic P2Y2 receptors (P2Y2Rs) and ATP‐permeable pannexin‐1 (Panx‐1) channels, is unclear.
Here, we show that in isolated rat chemoreceptor clusters, type I cell depolarization induced by hypoxia, hypercapnia, or high K+ caused delayed intracellular Ca2+ elevations (Δ[Ca2+]i) in nearby type II cells that were inhibited by the P2Y2R blocker suramin, or by the nucleoside hydrolase apyrase.
Likewise, stimulation of P2Y2Rs on type II cells caused a delayed, secondary Δ[Ca2+]i in nearby type I cells that was inhibited by blockers of Panx‐1 channels, adenosine A2A receptors and 5′‐ectonucleotidase.
We propose that reciprocal crosstalk between type I and type II cells contributes to sensory processing in the carotid body via purinergic signalling pathways.
AbstractThe mammalian carotid body (CB) is excited by blood‐borne stimuli including hypoxia and acid hypercapnia, leading to respiratory and cardiovascular reflex responses. This chemosensory organ consists of innervated clusters of receptor type I cells, ensheathed by processes of adjacent glial‐like type II cells. ATP is a major excitatory neurotransmitter released from type I cells and type II cells express purinergic P2Y2 receptors (P2Y2Rs), the activation of which leads to the opening of ATP‐permeable, pannexin‐1 (Panx‐1) channels. While these properties support crosstalk between type I and type II cells during chemotransduction, direct evidence is lacking. To address this, we first exposed isolated rat chemoreceptor clusters to acute hypoxia, isohydric hypercapnia, or the depolarizing stimulus high K+, and monitored intracellular [Ca2+] using Fura‐2. As expected, these stimuli induced intracellular [Ca2+] elevations (Δ[Ca2+]i) in type I cells. Interestingly, however, there was often a delayed, secondary Δ[Ca2+]i in nearby type II cells that was reversibly inhibited by the P2Y2R antagonist suramin, or by the nucleoside hydrolase apyrase. By contrast, type II cell stimulation with the P2Y2R agonist uridine‐5′‐triphosphate (100 μm) often led to a delayed, secondary Δ[Ca2+]i response in nearby type I cells that was reversibly inhibited by the Panx‐1 blocker carbenoxolone (5 μm). This Δ[Ca2+]i response was also strongly inhibited by blockers of either the adenosine A2A receptor (SCH 58261) or of the 5′‐ectonucleotidase (AOPCP), suggesting it was due to adenosine arising from breakdown of ATP released through Panx‐1 channels. Collectively, these data strongly suggest that purinergic signalling mechanisms mediate crosstalk between CB chemoreceptor and glial cells during chemotransduction.
Implementation of Next-Generation Sequencing for Hepatitis B Virus Resistance Testing and Genotyping in a Clinical Microbiology Laboratory
Authors: Lowe Christopher F. , Merrick Linda , Harrigan P. Richard , Mazzulli Tony , Sherlock Christopher H. , Ritchie Gordon 
Published: November 2015

ABSTRACT

Sanger sequencing or DNA hybridization have been the primary modalities for hepatitis B (HBV) resistance testing and genotyping; however, there are limitations, such as low sensitivity and the inability to detect novel mutations. Next-generation sequencing (NGS) for HBV can overcome these limitations, but there is limited guidance for clinical microbiology laboratories to validate this novel technology. In this study, we describe an approach to implementing deep pyrosequencing for HBV resistance testing and genotyping in a clinical virology laboratory. A nested PCR targeting the
pol
region of HBV (codons 143 to 281) was developed, and the PCR product was sequenced by the 454 Junior (Roche). Interpretation was performed by ABL TherapyEdge based on European Association for the Study of the Liver (EASL) guidelines. Previously characterized HBV samples by INNO-LiPA (LiPA) were compared to NGS with discordant results arbitrated by Sanger sequencing. Genotyping of 105 distinct samples revealed a concordance of 95.2% (100/105), with Sanger sequencing confirming the NGS result. Resistance testing by NGS was concordant with LiPA in 85% (68/80) of previously characterized samples. Additional mutations were found in 8 samples, which related to the identification of low-level mutant subpopulations present at <10% (6/8). To balance the costs of testing for the validation study, reproducibility of the NGS was investigated through an analysis of sequence variants at loci not associated with resistance in a single patient sample. Our validation approach attempts to balance costs with efficient data acquisition.
Evaluation of a Genus- and Group-Specific Rapid PCR Assay Panel on Synovial Fluid for Diagnosis of Prosthetic Knee Infection
Authors: Melendez Dante P. , Greenwood-Quaintance Kerryl E. , Berbari Elie F. , Osmon Douglas R. , Mandrekar Jayawant N. , Hanssen Arlen D. , Patel Robin 
Published: November 2015

ABSTRACT

We evaluated a genus- and group-specific PCR assay panel using 284 prosthetic knee synovial fluid samples collected from patients presenting to our institution with implant failure. Using the Musculoskeletal Infection Society diagnostic criteria, 88 and 196 samples were classified as showing prosthetic joint infection (PJI) and aseptic failure (AF), respectively. Sensitivities of the synovial fluid PCR panel and culture were 55.6% and 76.1% (
P
≤ 0.001), respectively, and specificities were 91.8% and 97.4% (
P
= 0.016), respectively. Among the 70 subjects who had received antibiotics within the month preceding synovial fluid aspiration (48 of whom had PJI), PCR panel and synovial fluid culture sensitivities were 64.5% and 85.4%, respectively (
P
< 0.0001). In this group, the PCR panel detected
Staphylococcus aureus
in two culture-negative PJI cases. Overall, the evaluated molecular diagnostic tool had low sensitivity when applied to synovial fluid.
Genome-Wide Mapping of the Binding Sites and Structural Analysis of Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 2 Reveal that It Is a DNA-Binding Transcription Factor
Authors: Hu Haidai , Dong Jiazhen , Liang Deguang , Gao Zengqiang , Bai Lei , Sun Rui , Hu Hao , Zhang Heng , Dong Yuhui , Lan Ke 
Published: November 2015

ABSTRACT

The oncogenic herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is known to encode four viral interferon regulatory factors (vIRF1 to -4) to subvert the host antiviral immune response, but their detailed DNA-binding profiles as transcription factors in the host remain uncharacterized. Here, we first performed genome-wide vIRF2-binding site mapping in the human genome using chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq). vIRF2 was capable of binding to the promoter regions of 100 putative target genes. Importantly, we confirmed that vIRF2 can specifically interact with the promoters of the genes encoding PIK3C3, HMGCR, and HMGCL, which are associated with autophagosome formation or tumor progression and metastasis, and regulate their transcription
in vivo
. The crystal structure of the vIRF2 DNA-binding domain (DBD) (referred to here as vIRF2
DBD
) showed variable loop conformations and positive-charge distributions different from those of vIRF1 and cellular IRFs that are associated with DNA-binding specificities. Structure-based mutagenesis revealed that Arg82 and Arg85 are required for the
in vitro
DNA-binding activity of vIRF2
DBD
and can abolish the transcription regulation function of vIRF2 on the promoter reporter activity of
PIK3C3
,
HMGCR
, and
HMGCL
. Collectively, our study provided unique insights into the DNA-binding potency of vIRF2 and suggested that vIRF2 could act as a transcription factor of its target genes in the host antiviral immune response.

IMPORTANCE
The oncogenic herpesvirus KSHV is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. KSHV has developed a unique mechanism to subvert the host antiviral immune responses by encoding four homologues of cellular interferon regulatory factors (vIRF1 to -4). However, none of their DNA-binding profiles in the human genome have been characterized until now, and the structural basis for their diverse DNA-binding properties remain poorly understood. In this study, we performed the first genome-wide vIRF2-binding site mapping in the human genome and found vIRF2 can bind to the promoter regions of 100 target cellular genes. X-ray structure analysis and functional studies provided unique insights into its DNA-binding potency and regulation of target gene expression. Our study suggested that vIRF2 could act as a transcription factor of its target genes and contribute to KSHV infection and pathogenesis through versatile functions.