bluuebunny/crossref_metadata_2025 huggingface dataset:
Recellularizing of human acellular dermal matrices imaged by high‐definition optical coherence tomography
Authors: Boone Marc A. L. M. , Draye Jean Pierre , Verween Gunther , Aiti Annalisa , Pirnay Jean‐Paul , Verbeken Gilbert , De Vos Daniel , Rose Thomas , Jennes Serge , Jemec Gregor B. E. , del Marmol Veronique
Published: February 2015

High‐definition optical coherence tomography (HD‐OCT) permits real‐time 3D imaging of the impact of selected agents on human skin allografts. The real‐time 3D HD‐OCT assessment of (i) the impact on morphological and cellular characteristics of the processing of human acellular dermal matrices (HADMs) and (ii) repopulation of HADMs in vitro by human fibroblasts and remodelling of the extracellular matrix by these cells. Four different skin decellularization methods, Dispase II/Triton X‐100, Dispase II/SDS (sodium dodecyl sulphate), NaCl/Triton X‐100 and NaCl/SDS, were analysed by HD‐OCT. HD‐OCT features of epidermal removal, dermo‐epidermal junction (DEJ) integrity, cellularity and dermal architecture were correlated with reflectance confocal microscopy (RCM), histopathology and immunohistochemistry. Human adult dermal fibroblasts were in vitro seeded on the NaCl/Triton X‐100 processed HADMs, cultured up to 19 days and evaluated by HD‐OCT in comparison with MTT proliferation test and histology. Epidermis was effectively removed by all treatments. DEJ was best preserved after NaCl/Triton X‐100 treatment. Dispase II/SDS treatment seemed to remove all cellular debris in comparison with NaCl/Triton X‐100 but disturbed the DEJ severely. The dermal micro‐architectural structure and vascular spaces of (sub)papillary dermis were best preserved with the NaCl/Triton X‐100. The impact on the 3D structure and vascular holes was detrimental with Dispase II/SDS. Elastic fibre fragmentation was only observed after Dispase II incubation. HD‐OCT showed that NaCl/Triton X‐100 processed matrices permitted in vitro repopulation by human dermal fibroblasts (confirmed by MTT test and histology) and underwent remodelling upon increasing incubation time. Care must be taken in choosing the appropriate processing steps to maintain selected properties of the extracellular matrix in HADMs. Processing HADMs with NaCl/Triton X‐100 permits in vitro the proliferation and remodelling activity of human dermal fibroblasts. HD‐OCT provides unique real‐time and non‐invasive 3D imaging of tissue‐engineered skin constructs and complementary morphological and cytological information.
An extended CCR5 ECL2 peptide forms a helix that binds HIV‐1 gp120 through non‐specific hydrophobic interactions
Authors: Abayev Meital , Moseri Adi , Tchaicheeyan Oren , Kessler Naama , Arshava Boris , Naider Fred , Scherf Tali , Anglister Jacob
Published: February 2015

C‐C chemokine receptor 5 (CCR5) serves as a co‐receptor for HIV‐1. The CCR5 N‐terminal segment, the second extracellular loop (ECL2) and the transmembrane helices have been implicated in binding the envelope glycoprotein gp120. Peptides corresponding to the sequence of the putative ECL2 as well as peptides containing extracellular loops 1 and 3 (ECL1 and ECL3) were found to inhibit HIV‐1 infection. The aromatic residues in the C‐terminal half of an ECL2 peptide were shown to interact with gp120. In the present study, we found that, in aqueous buffer, the segment Q188–Q194 in an elongated ECL2 peptide (R168–K197) forms an amphiphilic helix, which corresponds to the beginning of the fifth transmembrane helix in the crystal structure of CCR5. Two‐dimensional saturation transfer difference NMR spectroscopy and dynamic filtering studies revealed involvement of Y187, F189, W190 and F193 of the helical segment in the interaction with gp120. The crystal structure of CCR5 shows that the aromatic side chains of F189, W190 and F193 point away from the binding pocket and interact with the membrane or with an adjacent CCR5 molecule, and therefore could not interact with gp120 in the intact CCR5 receptor. We conclude that these three aromatic residues of ECL2 peptides interact with gp120 through hydrophobic interactions that are not representative of the interactions of the intact CCR5 receptor. The HIV‐1 inhibition by ECL2 peptides, as well as by ECL1 and ECL3 peptides and peptides corresponding to ECL2 of CXCR4, which serves as an alternative HIV‐1 co‐receptor, suggests that there is a hydrophobic surface in the envelope spike that could be a target for HIV‐1 entry inhibitors.

Database

The structures and NMR data of ECL2S (Q186–T195) were deposited under Protein Data Bank ID 2mzx and BioMagResBank ID 25505.
Insights into the slow‐onset tight‐binding inhibition of Escherichia coli dihydrofolate reductase: detailed mechanistic characterization of pyrrolo [3,2‐f] quinazoline‐1,3‐diamine and its derivatives as novel tight‐binding inhibitors
Authors: Srinivasan Bharath , Skolnick Jeffrey
Published: February 2015

Dihydrofolate reductase (DHFR) is a pivotal enzyme involved in the de novo pathway of purine synthesis, and hence, represents an attractive target to disrupt systems that require rapid DNA turnover. The enzyme acquires resistance to available drugs by various molecular mechanisms, which necessitates the continuous discovery of novel antifolates. Previously, we identified a set of novel molecules that showed binding to E. coli DHFR by means of a thermal shift without establishing whether they inhibited the enzyme. Here, we show that a fraction of those molecules represent potent and novel inhibitors of DHFR activity. 7‐[(4‐aminophenyl)methyl]‐7H‐pyrrolo [3,2‐f] quinazoline‐1,3‐diamine, a molecule with no reported inhibition of DHFR, potently inhibits the enzyme with a Ki value of 7.42 ± 0.92 nm by competitive displacement of the substrate dihydrofolic acid. It shows uncompetitive inhibition vis‐à‐vis NADPH, indicating that the inhibitor has markedly increased affinity for the NADPH‐bound form of the enzyme. Further, we demonstrate that the mode of binding of the inhibitor to the enzyme–NADPH binary complex conforms to the slow‐onset, tight‐binding model. By contrast, mechanistic characterization of the parent molecule 7H‐pyrrolo [3,2‐f] quinazoline‐1,3‐diamine shows that lack of (4‐aminophenyl)‐methyl group at the seventh position abolishes the slow onset of inhibition. This finding provides novel insights into the role of substitutions on inhibitors of E. coli DHFR and represents the first detailed kinetic investigation of a novel diaminopyrroloquinazoline derivative on a prokaryotic DHFR. Furthermore, marked differences in the potency of inhibition for E. coli and human DHFR makes this molecule a promising candidate for development as an antibiotic.
The fate of Amazonian ecosystems over the coming century arising from changes in climate, atmospheric CO2, and land use
Authors: Zhang Ke , de Almeida Castanho Andrea D. , Galbraith David R. , Moghim Sanaz , Levine Naomi M. , Bras Rafael L. , Coe Michael T. , Costa Marcos H. , Malhi Yadvinder , Longo Marcos , Knox Ryan G. , McKnight Shawna , Wang Jingfeng , Moorcroft Paul R.
Published: February 2015

There is considerable interest in understanding the fate of the Amazon over the coming century in the face of climate change, rising atmospheric CO2 levels, ongoing land transformation, and changing fire regimes within the region. In this analysis, we explore the fate of Amazonian ecosystems under the combined impact of these four environmental forcings using three terrestrial biosphere models (ED2, IBIS, and JULES) forced by three bias‐corrected IPCC AR4 climate projections (PCM1, CCSM3, and HadCM3) under two land‐use change scenarios. We assess the relative roles of climate change, CO2 fertilization, land‐use change, and fire in driving the projected changes in Amazonian biomass and forest extent. Our results indicate that the impacts of climate change are primarily determined by the direction and severity of projected changes in regional precipitation: under the driest climate projection, climate change alone is predicted to reduce Amazonian forest cover by an average of 14%. However, the models predict that CO2 fertilization will enhance vegetation productivity and alleviate climate‐induced increases in plant water stress, and, as a result, sustain high biomass forests, even under the driest climate scenario. Land‐use change and climate‐driven changes in fire frequency are predicted to cause additional aboveground biomass loss and reductions in forest extent. The relative impact of land use and fire dynamics compared to climate and CO2 impacts varies considerably, depending on both the climate and land‐use scenario, and on the terrestrial biosphere model used, highlighting the importance of improved quantitative understanding of all four factors – climate change, CO2 fertilization effects, fire, and land use – to the fate of the Amazon over the coming century.
The Memory of the Cambodian Genocide: the Tuol Sleng Genocide Museum
Authors: Brown Caitlin , Millington Chris
Published: February 2015

This article examines the representation of the memory of the Cambodian genocide in the Tuol Sleng Genocide Museum in Phnom Penh. The museum is housed in the former Tuol Sleng prison, a detention and torture centre through which thousands of people passed before execution at the Choeung Ek killing field. From its opening in 1980, the museum was a stake in the ongoing conflict between the new Vietnamese‐backed government and Pol Pot's Khmer Rouge guerrillas. Its focus on encouraging an emotional response from visitors, rather than on pedagogy, was part of the museum's attempt to engender public sympathy for the regime. Furthermore, in order to absolve former Khmer Rouge members in government of blame, the museum sought to attribute responsibility for the atrocities of the period to a handful of ‘criminals’. The article traces the development of the museum and its exhibitions up to the present, commenting on what this public representation of the past reveals about the memory of the genocide and the changing political situation in Cambodia.
Parish Studies and the Debates on Religious Life in the Low Countries (Late Middle Ages and Early Modern Period)
Authors: Bauwens Michal
Published: February 2015

Only very recently has the parish church gained more serious interest among the public and academics in the Low Countries. Until a few years ago, historians studying religious life in the Low Countries ascribed little agency to the parish or parishioners. If the parish was studied, it was usually from an institutional or an art historical point of view. Furthermore, as this strong top‐down approach has persisted in the historiography of religion throughout the 20th century, the idea of medieval decline has remained central in the study of religious change. Debates on Reformation and Counter‐Reformation have also been influenced by this idea of medieval decay. International parish studies and recent studies on religious life during the Late Middle Ages and Early Modern period have, however, illustrated that ordinary believers and communities had an important role in shaping religion. Parish studies that use a perspective from below might just be the key to understanding how religion and religious life changed in the Low Countries during this turbulent period.
Visuality and Its Affects: Some New Directions for Australian Heritage Tourism
Authors: Waterton Emma
Published: February 2015

This review emerges out of long‐standing debates that seek to define Australia's responses to its colonial heritage. In particular, the review will question how ‘affect’ functions as a foundation for shared public understandings of the past and related identities at iconic Australian heritage sites. From there, it will move to explore how visitor photography can be used as (a) a means of capturing and assessing visitors' frames of reference and sensory experience; (b) recovering memories; and (c) imbuing heritage sites with meaning. None of this is easy to pin down methodologically. Indeed, given the relative ‘newness’ of theoretical talk dealing with the politics of affect in the fields of heritage and tourism, little attention to date has been channelled towards figuring out what this might mean empirically. As such, the core component of this review is an examination of the literature that has emerged around visual/performative ethnographies, particularly those that focuses on the visual as a means of capturing what bodies do. Here, a process of being ‘in place’ will be foregrounded, through which individual heritage visitors are transformed from passive viewer into active director, thereby becoming co‐producers in the creation and legitimisation of both historical memories and conceptualisations of present‐day Australian society.
Marginal Creatures: Australian Women War Reporters During World War II
Authors: Baker Jeannine
Published: February 2015

Histories of war reporting have tended to overlook the role of Australian female journalists in covering World War II. During the war, 21 Australian women journalists worked as war reporters for the Australian press, including from overseas military areas. This article provides an overview of the historiography of Australian women war reporters of World War II within an international context. It discusses the benefits of examining the connection between gender and military policy on the accreditation of women war correspondents within a comparative framework. It argues that consideration of national differences in the ways that women journalists were officially perceived, defined and managed is particularly valuable for understanding the challenges faced by Australian women war reporters.
How much do children's body mass indices change over intervals of 6–12 months? Statistics from before and during the obesity epidemic
Authors: von Hippel P. T. , Nahhas R. W. , Czerwinski S. A.
Published: February 2015

Background

Researchers need to evaluate changes in children's body mass index (BMI) over periods of 6 or 12 months, yet reference statistics are limited for change in BMI.

Objectives

We aim to estimate the distribution of changes in children's BMIs over periods of 6 and 12 months.

Methods

We analyze data on two cohorts of children in the Fels Longitudinal Study: an older cohort born 1946–1970 and a recent cohort born 1971–1995. Between ages 3 and 18 years, we calculate changes in BMI over intervals of 6 and 12 months. For each age, sex and cohort, we estimate the mean, standard deviation, skewness, kurtosis and percentiles of change in BMI.

Results

Median BMI growth peaks around age 12–13 years for girls and 13–15 years for boys. Large BMI gains are common in adolescence, and BMI losses are not uncommon at any age. Percentiles of BMI change are quite dispersed, especially for girls and especially in adolescence. In the recent cohort, the adiposity rebound is earlier and BMI gains are larger, especially at the high percentiles.

Conclusions

Researchers can use these estimates to evaluate data quality, evaluate effect sizes and calculate the sample size needed to detect an effect.
Trans‐species communication in the Mycobacterium tuberculosis‐infected macrophage
Authors: Tan Shumin , Russell David G.
Published: February 2015

Much of the infection cycle of Mycobacterium tuberculosis (Mtb) is spent within its host cell, the macrophage. As a consequence of the chronic, enduring nature of the infection, this cell–cell interaction has become highly intimate, and the bacterium has evolved to detect, react to, and manipulate the evolving, immune‐modulated phenotype of its host. In this review, we discuss the nature of the endosomal/lysosomal continuum, the characterization of the bacterium's transcriptional responses during the infection cycle, and the dominant environmental cues that shape this response. We also discuss how the metabolism of both cells is modulated by the infection and the impact that this has on the progression of the granuloma. Finally, we detail how these transcriptional responses can be exploited to construct reporter bacterial strains to probe the temporal and spatial environmental shifts experienced by Mtb during the course of experimental infections. These reporter strains provide new insights into the fitness of Mtb under immune‐ and drug‐mediated pressure.
Sensing of Mycobacterium tuberculosis and consequences to both host and bacillus
Authors: Stamm Chelsea E. , Collins Angela C. , Shiloh Michael U.
Published: February 2015

Mycobacterium tuberculosis (Mtb), the primary causative agent of human tuberculosis, has killed more people than any other bacterial pathogen in human history and remains one of the most important transmissible diseases worldwide. Because of the long‐standing interaction of Mtb with humans, it is no surprise that human mucosal and innate immune cells have evolved multiple mechanisms to detect Mtb during initial contact. To that end, the cell surface of human cells is decorated with numerous pattern recognition receptors for a variety of mycobacterial ligands. Furthermore, once Mtb is ingested into professional phagocytes, other host molecules are engaged to report on the presence of an intracellular pathogen. In this review, we discuss the role of specific mycobacterial products in modulating the host's ability to detect Mtb. In addition, we describe the specific host receptors that mediate the detection of mycobacterial infection and the role of individual receptors in mycobacterial pathogenesis in humans and model organisms.
New insights into TB physiology suggest untapped therapeutic opportunities
Authors: Baer Christina E. , Rubin Eric J. , Sassetti Christopher M.
Published: February 2015

The current regimens used to treat tuberculosis are largely comprised of serendipitously discovered drugs that are combined based on clinical experience. Despite curing millions, these drug regimens are limited by the long course of therapy, the emergence of resistance, and the persistent tissue damage that remains after treatment. The last two decades have produced only a single new drug but have represented a renaissance in our understanding of the physiology of tuberculosis infection. The advent of mycobacterial genetics, sophisticated immunological methods, and imaging technologies have transformed our understanding of bacterial physiology as well as the contribution of the host response to disease outcome. Specific alterations in bacterial metabolism, heterogeneity in bacterial state, and drug penetration all limit the effectiveness of antimicrobial therapy. This review summarizes these new biological insights and discusses strategies to exploit them for the rational development of more effective therapeutics. Three general strategies are discussed. First, our emerging insight into bacterial physiology suggests new pathways that might be targeted to accelerate therapy. Second, we explore whether the concept of genetic synergy can be used to design effective combination therapies. Finally, we outline possible approaches to modulate the host response to accentuate antibiotic efficacy. These biology‐driven strategies promise to produce more effective therapies.
Tuberculosis vaccines: barriers and prospects on the quest for a transformative tool
Authors: Karp Christopher L. , Wilson Christopher B. , Stuart Lynda M.
Published: February 2015

The road to a more efficacious vaccine that could be a truly transformative tool for decreasing tuberculosis morbidity and mortality, along with Mycobacterium tuberculosis transmission, is quite daunting. Despite this, there are reasons for optimism. Abetted by better conceptual clarity, clear acknowledgment of the degree of our current immunobiological ignorance, the availability of powerful new tools for dissecting the immunopathogenesis of human tuberculosis, the generation of more creative diversity in tuberculosis vaccine concepts, the development of better fit‐for‐purpose animal models, and the potential of more pragmatic approaches to the clinical testing of vaccine candidates, the field has promise for delivering novel tools for dealing with this worldwide scourge of poverty.
T cells and adaptive immunity to Mycobacterium tuberculosis in humans
Authors: Jasenosky Luke D. , Scriba Thomas J. , Hanekom Willem A. , Goldfeld Anne E.
Published: February 2015

The adaptive immune response mediated by T cells is critical for control of Mycobacterium tuberculosis (M. tuberculosis) infection in humans. However, the M. tuberculosis antigens and host T‐cell responses that are required for an effective adaptive immune response to M. tuberculosis infection are yet to be defined. Here, we review recent findings on CD4+ and CD8+ T‐cell responses to M. tuberculosis infection and examine the roles of distinct M. tuberculosis‐specific T‐cell subsets in control of de novo and latent M. tuberculosis infection, and in the evolution of T‐cell immunity to M. tuberculosis in response to tuberculosis treatment. In addition, we discuss recent studies that elucidate aspects of M. tuberculosis‐specific adaptive immunity during human immunodeficiency virus co‐infection and summarize recent findings from vaccine trials that provide insight into effective adaptive immune responses to M. tuberculosis infection.
Using the Fraction of Missing Information to Identify Auxiliary Variables for Imputation Procedures via Proxy Pattern‐mixture Models
Authors: Andridge Rebecca , Thompson Katherine Jenny
Published: February 2015

In many surveys, imputation procedures are used to account for non‐response bias induced by either unit non‐response or item non‐response. Such procedures are optimised (in terms of reducing non‐response bias) when the models include covariates that are highly predictive of both response and outcome variables. To achieve this, we propose a method for selecting sets of covariates used in regression imputation models or to determine imputation cells for one or more outcome variables, using the fraction of missing information (FMI) as obtained via a proxy pattern‐mixture (PMM) model as the key metric. In our variable selection approach, we use the PPM model to obtain a maximum likelihood estimate of the FMI for separate sets of candidate imputation models and look for the point at which changes in the FMI level off and further auxiliary variables do not improve the imputation model. We illustrate our proposed approach using empirical data from the Ohio Medicaid Assessment Survey and from the Service Annual Survey.
Photoluminescence Properties of Heavily Eu3+‐Doped BaCa2In6O12 Phosphor for White‐Light‐Emitting Diodes
Authors: Zhang Jiao , Yang Yanmin , Liu Yanzhou , Mi Chao , Li Gang , Han Boning , Zhang Yi , Seo Hyo Jin
Published: February 2015

Heavily Eu3+‐doped BaCa2In6O12 phosphors were prepared by conventional solid‐state reaction, and its structural properties were investigated by means of Rietveld refinement method using an X‐ray source. XRD patterns confirm the hexagonal phase of BaCa2In6O12: Eu3+ phosphors. The obtained spectrum data indicate that the emission spectra of Ba1−xEuxCa2In6O12 samples excited at 393 nm exhibit a series of shaped peaks assigned to the 5D0,1,2,3 →7FJ (J = 0,1,2,3,4) transitions. Luminescence from the higher excited states, such as 5D1, 5D2, and 5D3, were also observed even though the Eu3+ concentration was up to x = 0.4. More importantly, the Ba1−xEuxCa2In6O12 phosphor still emits white luminescence, when the Eu3+ ion concentration is up to x = 0.07 before concentration quenching is observed, which shows that the phosphor is a promising single‐phase phosphor for near ultraviolet (NUV) light‐emitting diodes (LED). Furthermore, the temperature's impact on white luminescent properties was studied. Finally, a white‐light‐emitting diodes (W‐LEDs) fabricated with the Ba0.95Eu0.05Ca2In6O12 phosphor incorporated with an encapsulant in ultraviolet LEDs (λmax = 395 nm) is discussed.
Nocebo and the potential harm of ‘high risk’ labelling: a scoping review
Authors: Symon Andrew , Williams Brian , Adelasoye Qadir A. , Cheyne Helen
Published: February 2015

Aims

A discussion of the existence, prevalence and characteristics of the nocebo effect in health care.

Background

There is increasing but inconsistent evidence for nocebo effects (the opposite of placebo). Causal mechanisms are believed to be similar to placebo (negative effects result from suggestions of negative clinical outcomes). Risk screening in health care may produce this unintended effect through labelling some patients as high risk. Given health care's almost universal coverage this potentially affects many people.

Design

Discussion paper following a scoping review of the existence and frequency of nocebo.

Data sources

Literature databases (PsycINFO, MEDLINE, CCTR, CINAHL and EMBASE) searched from inception dates to 2013.

Implications for nursing

Significant empirical evidence indicates that negative beliefs may impact on health outcomes (incidence estimates range from 3–27%). The nocebo effect, rooted in the complex interplay between physiological functioning and social factors, appears significantly more common among women and where prior negative knowledge or expectations exist. Pre‐existing psychological characteristics (anxiety, neuroses, panic disorder or pessimism) exacerbate it.

Conclusion

While the placebo effect is well documented, there has been no systematic attempt to synthesize primary empirical research on the role of nocebo. It is possible that nocebo outcomes may be preventable through careful consideration of information provision and the prior identification of potentially high risk individuals. This paper summarizes the scale and importance of the nocebo effect, its distribution according to a range of social and clinical variables and its known relation to psychological precursors. It identifies important gaps in the research literature.
Association Between Low Education and Higher Global Cardiovascular Risk
Authors: Di Chiara Tiziana , Scaglione Alessandra , Corrao Salvatore , Argano Christiano , Pinto Antonio , Scaglione Rosario
Published: February 2015

This study was designed to evaluate the impact of educational status on global cardiovascular risk in a southern Italian urban population. The study population consisted of 488 consecutive outpatients aged 18 years and older. Educational status was categorized according to the number of years of formal education as follows: (1) low education group (<10 years) and (2) medium‐high education group (10–15 years). In both groups, cardiometabolic comorbidities (obesity, visceral obesity, diabetes, dyslipidemia, metabolic syndrome, microalbuminuria, left ventricular hypertrophy) and global cardiovascular risk, according to international guidelines, were analyzed. Left ventricular mass index and ejection fraction by echocardiography and E/A ratio, by pulsed‐wave Doppler, were calculated. The low education group was characterized by a significantly higher prevalence of patients with visceral obesity (P=.021), hypertension (P=.010), metabolic syndrome (P=.000), and microalbuminuria (P=.000) and greater global cardiovascular risk (P=.000). Significantly increased levels of microalbuminuria (P=.000) and significantly decreased values of E/A ratio (P=.000) were also detected in the low education group. Global cardiovascular risk correlated directly with waist‐to‐hip ratio (P=.010), microalbuminuria (P=.015), and the metabolic syndrome (P>.012) and inversely with educational status (P=.000). Education was independently (P=.000) associated with global cardiovascular risk. These data indicate a strong association between low education and cardiometabolic comorbidities suitable to influence the evolution of chronic degenerative diseases. Preventive strategies need to be more efficient and more effective in this patient population.
Sulindac has strong antifibrotic effects by suppressing STAT3‐related miR‐21
Authors: Zhou Xue , Li You‐Jie , Gao Shu‐Yan , Wang Xiao‐Zhi , Wang Ping‐Yu , Yan Yun‐Fei , Xie Shu‐Yang , Lv Chang‐Jun
Published: February 2015

Pulmonary fibrosis (PF) is a disease with an unknown cause and a poor prognosis. In this study, we aimed to explore the pathogenesis of PF and the mechanism of sulindac in attenuating bleomycin (BLM)‐induced PF. The rat PF model was induced by BLM and verified through histological studies and hydroxyproline assay. The severity of BLM‐induced PF in rats and other effects, such as the extent of the wet lung to bw ratios, thickening of alveolar interval or collagen deposition, was obviously ameliorated in sulindac‐treated rat lungs compared with BLM‐induced lungs. Sulindac also reversed the epithelial mesenchymal transition (EMT) and inhibited the PF process by restoring the levels of E‐cadherin and α‐smooth muscle actin (SMA) in A549 cells. Our results further demonstrated that the above effects of sulindac might be related to regulating of interferon gamma (IFN‐γ) expression, which further affects signal transducers and activators of transcription 3 (STAT3) and phosphorylated STAT3 (p‐STAT3) levels. Moreover, higher miR‐21 levels with the decreased E‐cadherin and increased α‐SMA expressions were found in transforming growth factor‐β1‐treated A549 cells, which can be reversed by sulindac. Collectively, our results demonstrate that by decreasing IFN‐γ‐induced STAT3/p‐STAT3 expression to down‐regulate miR‐21, sulindac could significantly reverse EMT in A549 cells and prevent BLM‐induced PF.
High glucose‐induced intestinal epithelial barrier damage is aggravated by syndecan‐1 destruction and heparanase overexpression
Authors: Qing Qing , Zhang Shaoheng , Chen Ye , Li Runhua , Mao Hua , Chen Qikui
Published: February 2015

Syndecan‐1 (Sdc1) and its endo‐beta‐d‐glucuronidase heparanase (HPSE) are implicated in maintenance of intestinal epithelial barrier (IEB), but their alterations and roles in high‐glucose/hyperglycaemia (HG) conditions have not been fully investigated. This study aimed to determine the expression pattern, the possible regulation mechanism of Sdc1 and HPSE in HG conditions, and their potential effects on IEB. Therefore, diabetic mice/cell models were developed, and tissue/serum samples, cell lysate and culture supernatants were harvested. The expression of Sdc1 and HPSE in control, HG and designated interventions groups were detected. Phosphorylations of mitogen‐activated protein kinase signalling pathway (MAPK), the expressions of Occludin and ZO‐1, and the levels of transepithelial electrical resistance (TEER) were measured and monitored. The results showed that in HG conditions, intestinal tissue and cellular Sdc1 were significantly decreased, but the expression of HPSE, and soluble Sdc1 in serum and culture supernatants were remarkably increased. Such alterations of Sdc1 and HPSE were associated with solely p38 MAPK activation, and were correlated with the reductions of Occludin, ZO‐1 and TEER. Heparin (Sdc1 analogue) and SB203580 (a p38 MAPK inhibitor), instead of insulin, alleviated Sdc1 destruction and HPSE overexpression, and effectively prevented against the reductions of tight junctions and the abnormality of intestinal permeability in HG conditions. In conclusion, we confirm the unique alterations of Sdc1 and HPSE in HG conditions, and found their interactions with p38 MAPK activation and IEB. These indicate that Sdc1/HPSE modulation can be viewed as an important complementary treatment for relieving HG‐induced gastrointestinal damage.
Petrology of metapelites in the Bugaboo aureole, British Columbia, Canada
Authors: Pattison D. R. M. , DeBuhr C. L.
Published: February 2015

Contact metamorphism of greenschist facies Neoproterozoic turbidites by the Cretaceous Bugaboo Batholith in southeastern British Columbia has resulted in a well‐developed contact aureole. The aureole is about 1 km wide and can be divided into three main zones: (i) spotted phyllite zone, extending from the first appearance of spots of cordierite or andalusite to the last occurrence of primary chlorite; (ii) cordierite + andalusite + biotite zone, comprising hornfelses or schists with abundant porphyroblasts of cordierite and andalusite and, at higher grades, fibrolitic sillimanite; and (iii) K‐feldspar zone, characterized by hornfelses and schists that, in the inner part of this zone, are variably migmatitic. Four parts of the aureole were examined, three of which are characterized by schists, and one of which (Cobalt Lake area) is characterized by hornfelses and has exceptional exposure and comparatively unaltered rocks. Petrographic, modal, mineral‐compositional and whole rock‐compositional data were collected from the Cobalt Lake transect, allowing the prograde reaction sequence to be inferred. Notable features of the aureole at Cobalt Lake include: initial development of andalusite and plagioclase at the expense of paragonite‐rich white mica; a narrow interval across which cordierite, andalusite and biotite increase markedly at the expense of chlorite; gradual development of andalusite and biotite at the expense of cordierite and muscovite upgrade of chlorite consumption; and near‐simultaneous development of andalusite + K‐feldspar and sillimanite, the latter indicating a pressure of contact metamorphism of ~3 kbar. In other parts of the aureole, the development of sillimanite downgrade of the initial development of K‐feldspar suggests slightly higher pressures of contact metamorphism. Lack of correspondence between the observed sequence of reactions in the aureole and those predicted thermodynamically suggests that modifications to some of the thermodynamic data or activity–composition models may be required. Textural features in the aureole suggest the influence of kinetic factors on metamorphic recrystallization, including: (i) deformation‐catalysed reaction in the schists compared to the hornfelses, as indicated by different mineral‐growth sequences inferred from microstructures, and (ii) heating rate‐controlled recrystallization, as indicated by the decrease in grain size of hornfelses with increasing metamorphic grade.
G protein‐coupled estrogen receptor‐mediated effects on cytosolic calcium and nanomechanics in brain microvascular endothelial cells
Authors: Altmann Joseph B. , Yan Guang , Meeks Jeffrey F. , Abood Mary E. , Brailoiu Eugen , Brailoiu G. Cristina
Published: February 2015

G protein‐coupled estrogen receptor (GPER) is a relatively recently identified non‐nuclear estrogen receptor, expressed in several tissues, including brain and blood vessels. The mechanisms elicited by GPER activation in brain microvascular endothelial cells are incompletely understood. The purpose of this work was to assess the effects of GPER activation on cytosolic Ca2+ concentration, [Ca2+]i, nitric oxide production, membrane potential and cell nanomechanics in rat brain microvascular endothelial cells (RBMVEC). Extracellular but not intracellular administration of G‐1, a selective GPER agonist, or extracellular administration of 17‐β‐estradiol and tamoxifen, increased [Ca2+]i in RBMVEC. The effect of G‐1 on [Ca2+]i was abolished in Ca2+‐free saline or in the presence of a L‐type Ca2+ channel blocker. G‐1 increased nitric oxide production in RBMVEC; the effect was prevented by NG‐nitro‐l‐arginine methyl ester. G‐1 elicited membrane hyperpolarization that was abolished by the antagonists of small and intermediate‐conductance Ca2+‐activated K+ channels, apamin, and charibdotoxin. GPER‐mediated responses were sensitive to G‐36, a GPER antagonist. In addition, atomic force microscopy studies revealed that G‐1 increased the modulus of elasticity, indicative of cytoskeletal changes and increase in RBMVEC stiffness. Our results unravel the mechanisms underlying GPER‐mediated effects in RBMVEC with implications for the effect of estrogen on cerebral microvasculature.

image

Activation of the G protein‐coupled estrogen receptor (GPER) in rat brain microvascular endothelial cells (RBMVEC) increases [Ca2+]i by promoting Ca2+ influx. The increase in [Ca2+]i leads to membrane hyperpolarization, nitric oxide (NO) production, and to cytoskeletal changes and increased cell stiffness. Our results unravel the mechanisms underlying GPER‐mediated effects in RBMVEC with implications for the effect of estrogen on cerebral microvasculature.
Masculinisation of the Zebra Finch Song System: Roles of Oestradiol and the Z‐chromosome Gene Tubulin‐Specific Chaperone Protein A
Authors: Beach L. Q. , Wade J.
Published: February 2015

Robust sex differences in brain and behaviour exist in zebra finches. Only males sing, and forebrain song control regions are more developed in males. The factors driving these differences are not clear, although numerous experiments have shown that oestradiol (E2) administered to female hatchlings partially masculinises brain and behaviour. Recent studies suggest that an increased expression of Z‐chromosome genes in males (ZZ; females: ZW) might also play a role. The Z‐gene tubulin‐specific chaperone A (TBCA) exhibits increased expression in the lateral magnocellular nucleus of the anterior nidopallium (LMAN) of juvenile males compared to females; TBCA+ cells project to the robust nucleus of the arcopallium (RA). In the present study, we investigated the role of TBCA and tested hypotheses with respect to the interactive or additive effects of E2 and TBCA. We first examined whether E2 in hatchling zebra finches modulates TBCA expression in the LMAN. It affected neither the mRNA, nor protein in either sex. We then unilaterally delivered TBCA small interfering (si)RNA to the LMAN of developing females treated with E2 or vehicle and males treated with the aromatase inhibitor, fadrozole, or its control. In both sexes, decreasing TBCA in LMAN reduced RA cell number, cell size and volume. It also decreased LMAN volume in females. Fadrozole in males increased LMAN volume and RA cell size. TBCA siRNA delivered to the LMAN also decreased the projection from this brain region to the RA, as indicated by anterograde tract tracing. The results suggest that TBCA is involved in masculinising the song system. However, because no interactions between the siRNA and hormone manipulations were detected, TBCA does not appear to modulate effects of E2 in the zebra finch song circuit.
The Molecular Mechanisms of Neural Flow Coupling: A New Concept
Authors: Nakada Tsutomu
Published: February 2015

The phenomenon known as neural flow coupling (NFC) occurs at the capillary level where there are no known pressure controlling structures. Recent developments in advanced magnetic resonance imaging technologies have made possible in vivo direct investigations of water physiology that have shed new insight on the water dynamics of the cortical pericapillary space and their complex functionality in relation to NFC. Neural activities initiate a chain of events that ultimately affect NFC. First, neural activities generate extracellular acidification. Extracellular acidosis in turn produces inhibition of aquaporin‐4 (AQP‐4) located at the end feet of pericapillary astrocytes, the water channel which regulates water influx into the pericapillary space and, hence, interstitial flow. Reduction of pericapillary water pressure results in a negative balance between pericapillary and intraluminal capillary pressure, allowing for capillary caliber expansion. Proton permeability through the tight junctions of the blood brain barrier is significantly high owing to the Grotthuss proton “tunneling” mechanism and, therefore, carbonic anhydrase (CA) type IV (CA‐IV) anchored to the luminal surface of brain capillaries functions as scavenger of extracellular protons. CA‐IV inhibition by acetazolamide or carbon dioxide results in the accumulation of extracellular protons, causing AQP‐4 inhibition and a secondary increase in rCBF.
Dural Arteriovenous Fistula Mimicking a Brainstem Glioma
Authors: Le Guennec Loïc , Leclercq Delphine , Szatmary Zoltan , Idbaih Ahmed , Reyes‐Botero German , Delattre Jean‐Yves , Psimaras Dimitri
Published: February 2015

BACKGROUND

Brainstem intracranial dural arteriovenous fistulas are extremely rare and can mimic a glioma at the time of presentation.

CASE

We report a patient with an infiltrating brainstem lesion that finally revealed an intracranial dural arteriovenous fistula, with full neurological improvement after embolization.

CONCLUSION

A careful radiological study looking for dilated vessels around the brainstem is necessary in the workup of an infiltrating brainstem lesion, in order to rule out intracranial dural arteriovenous fistula.
Single‐ or multiple‐session viscosupplementation protocols for temporomandibular joint degenerative disorders: a randomized clinical trial
Authors: Guarda‐Nardini L. , Rossi A. , Arboretti R. , Bonnini S. , Stellini E. , Manfredini D.
Published: February 2015

The aim of the study was to compare the effectiveness of two single‐session protocols, either adopting high‐ (protocol A) or medium‐molecular weight hyaluronic acid (protocol B), with the reference five‐session protocol of temporomandibular joint (TMJ) lavage plus viscosupplementation (protocol C) in the management of chronic TMJ degenerative disorders. A randomized clinical trial (RCT) with ten participants per treatment group was designed, with multiple observation points, ending at 6 months after treatment. Pain levels on a 10‐point VAS scale were selected as the primary outcome variable to rate treatment effectiveness, along with a number of secondary outcome parameters. Findings showed that Group C patients had the highest decrease in pain levels. Nonparametric permutation analyses revealed that the global effect of treatment was significantly different between the three protocols (P = 0·024). Pairwise comparisons showed that the differences of treatment effect between the two single‐session interventions were negligible (global P‐value = 0·93). On the contrary, the five‐session protocol was significantly superior to both single‐session protocols (global P‐values ranging from 0·003 to 0·012). In conclusion, in a population of age‐, sex‐, and psychosocial aspects‐matched study groups, the standard of reference five‐session protocol proved to be superior at 6 months as far as the decrease in pain levels was concerned, whilst there were no differences between the two single‐session interventions. The absence of differences in treatment effect as for some other secondary clinical outcome variables may suggest that there is further space for future investigations attempting to reduce the number of multiple interventions for TMJ viscosupplementation.
Branching Deregulation and Merger Optimality
Authors: Lozano‐Vivas Ana , Meléndez‐Jiménez Miguel A. , Morales Antonio J.
Published: February 2015

The US banking industry has been characterized by intense merger activity. We claim that the loosening of geographic constraints is responsible for this consolidation process, irrespective of value‐maximizing motives. We demonstrate this by putting forward a theoretical model of banking competition and studying banks' strategic responses to deregulation. We show that even in the absence of economies of scale and scope, mergers represent an optimal response. Also, we show that the consolidation process is characterized by merger waves and that some equilibrium mergers are not profitable per se—they yield losses—but become profitable as the waves of mergers unfold.
Homeostasis of the temperature sensitivity of respiration over a range of growth temperatures indicated by a modified Arrhenius model
Authors: Noguchi Ko , Yamori Wataru , Hikosaka Kouki , Terashima Ichiro
Published: February 2015

The temperature dependence of plant respiratory rate (R) changes in response to growth temperature. Here, we used a modified Arrhenius model incorporating the temperature dependence of activation energy (Eo), and compared the temperature dependence of R between cold‐sensitive and cold‐tolerant species.

We analyzed the temperature dependences of leaf CO2 efflux rate of plants cultivated at low (LT) or high temperature (HT).

In plants grown at HT (HT plants), Eo at low measurement temperature varied among species, but Eo at growth temperature in HT plants did not vary and was comparable to that in plants grown at LT (LT plants), suggesting that the limiting process was similar at the respective growth temperatures. In LT plants, the integrated value of loge R, a measure of respiratory capacity, in cold‐sensitive species was lower than that in cold‐tolerant species. When plants were transferred from HT to LT, the respiratory capacity changed promptly after the transfer compared with the other parameters.

These results suggest that a similar process limits R at different growth temperatures, and that the lower capacity of the respiratory system in cold‐sensitive species may explain their low growth rate at LT.
An Analysis of Consumer Response to Corruption: Italy's Calciopoli Scandal
Authors: Buraimo Babatunde , Migali Giuseppe , Simmons Robert
Published: February 2015

The Calciopoli episode affecting Italian football in the 2005–6 season serves as an opportunity for an empirical investigation into consumer (fan) behavior, following league‐imposed punishments on clubs whose officials were found guilty of corrupt practices. Using a difference‐in‐differences estimation method, we find that home attendances for convicted teams fell by around 16%, relative to those clubs not subject to punishment. We show further that the fall in attendances resulted in non‐trivial gate revenue reductions. Our results suggest that a sizeable number of fans of the punished clubs were subsequently deterred from supporting their teams inside the stadium.
Labour Demand Adjustment: Does Foreign Ownership Matter?
Authors: Dhyne Emmanuel , Fuss Catherine , Mathieu Claude
Published: February 2015

This paper examines whether multinationals differ in their employment adjustment from domestic companies, using a panel of 5,544 Belgian firms observed between 1998 and 2005. More precisely, we estimate labour adjustment costs by worker and firm types. We propose a new flexible specification that takes into account the role of firm size in adjustment costs. Our results indicate that adjusting white‐collar employment is around half as costly for multinational firms (MNFs) as for domestic firms of the same size. The remaining differential in adjustment costs between MNFs and domestic firms might result, among other things, from multinationals' stronger bargaining power.
Design and validation of pictograms in a pediatric anaphylaxis action plan
Authors: Mok Garrick , Vaillancourt Régis , Irwin Danica , Wong Alexandre , Zemek Roger , Alqurashi Waleed
Published: February 2015

Background

Current anaphylaxis action plans (AAPs) are based on written instructions without inclusion of pictograms.

Objectives

To develop an AAP with pictorial aids and to prospectively validate the pictogram components of this plan.

Methods

Participants recruited from the emergency department and allergy clinic participated in a questionnaire to validate pictograms depicting key counseling points of an anaphylactic reaction. Children ≥10 years of age and caregivers of children <10 years with acute anaphylaxis or who carried epinephrine auto‐injector for confirmed allergy were eligible. Guessability, translucency, and recall were assessed for 11 pictogram designs. Pictograms identified as correct or partially correct by at least 85% of participants were considered valid. Three independent reviewers assessed these outcome measures.

Results

Of the 115 total participants, 73 (63%) were female, 76 (66%) were parents/guardians, and 39 (34%) were children aged 10–17. Overall, 10 pictograms (91%) reached ≥85% for correct guessability, translucency, and recall. Four pictograms were redesigned to reach the preset validation target. One pictogram depicting symptom management (5‐min wait time after first epinephrine treatment) reached 82% translucency after redesign. However, it reached 98% and 100% of correct guessability and recall, respectively.

Conclusions

We prospectively designed and validated a set of pictograms to be included in an AAP. The incorporation of validated pictograms into an AAP may potentially increase comprehension of the triggers, signs and symptoms, and management of an anaphylactic reaction.