bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colonic Epithelial Surfactant Protein D Expression Correlates with Inflammation in Clinical Colonic Inflammatory Bowel Disease
Authors: Nexoe Anders B , Pilecki Bartosz , Von Huth Sebastian , Husby Steffen , Pedersen Andreas A , Detlefsen Sönke , Marcussen Niels , Moeller Jesper B , Holmskov Uffe , Sorensen Grith L 
Published: February 2019

AbstractBackgroundInflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract. Surfactant protein D (SP-D) is expressed in the intestinal epithelium and is essential for innate host defense and regulation of inflammatory responses. Genetic variations of SP-D are associated with IBD, but the effects of SP-D in clinical disease development have not been clarified. We hypothesized that colonic epithelial SP-D expression is increased in parallel with intestinal inflammation with the capacity to dampen deleterious effects.MethodsSurgical specimens from IBD patients including Crohn’s disease (n = 9) and ulcerative colitis (n = 18) were scored for expression of SP-D and inflammatory activity. Cohoused Sftpd+/+ and Sftpd-/- mouse littermates were subjected to dextran sodium sulfate (DSS) for 7 days to induce colitis. Colonic tissue was scored for histologic damage and analyzed for inflammatory markers and expression of SP-D.ResultsSurgical specimens from IBD patients showed a strong positive correlation between immunoscore for SP-D and inflammatory activity (R2 = 0.78, P < 0.0001). In mice, colonic epithelial SP-D expression was very low, and DSS-induced colitis was unaffected by SP-D deficiency, although DSS induced transcription of colonic SP-D to a mild degree.ConclusionsA strong positive correlation between inflammatory activity and epithelial expression of SP-D was observed in surgical specimens from IBD patients supporting a role for SP-D in clinical disease. The in vivo study was inconclusive due to very low intestinal SP-D expression in the mouse. Further studies are warranted to support that increased SP-D expression in the human colonic epithelium is protective against intestinal inflammation.
Advocating for Patients With Inflammatory Bowel Disease: How to Navigate the Prior Authorization Process
Authors: Bhat Shubha , Zahorian Toni , Robert Regine , Farraye Francis A 
Published: February 2019

Abstract
In an effort to manage health care costs and avoid improper medication use, prior authorizations (PAs) have become a standard stipulation required by payers in the determination of medication coverage. For gastroenterologists managing patients, especially those with inflammatory bowel disease (IBD), the PA process is time-consuming and further complicated by 2 additional factors: step therapy requirements and failure of payers to recognize updated IBD treatment pathways. These factors often lead to PA denials and cause treatment delays, which in turn can lead to disease progression, ongoing patient suffering, and ultimately an increase in both direct and indirect total costs. In this manuscript, the PA process, PA models, tips and available resources to navigate the PA process, and future advocacy efforts are discussed with the intent to help gastroenterology practices optimize PA outcomes and improve the care provided to patients with IBD and other gastrointestinal disorders.
Elucidating the role of maternal environmental exposures on offspring health and disease using two-sample Mendelian randomization
Authors: Evans David M , Moen Gunn-Helen , Hwang Liang-Dar , Lawlor Debbie A , Warrington Nicole M 
Published: February 2019

Abstract

Background
There is considerable interest in estimating the causal effect of a range of maternal environmental exposures on offspring health-related outcomes. Previous attempts to do this using Mendelian randomization methodologies have been hampered by the paucity of epidemiological cohorts with large numbers of genotyped mother–offspring pairs.

Methods
We describe a new statistical model that we have created which can be used to estimate the effect of maternal genotypes on offspring outcomes conditional on offspring genotype, using both individual-level and summary-results data, even when the extent of sample overlap is unknown.

Results
We describe how the estimates obtained from our method can subsequently be used in large-scale two-sample Mendelian randomization studies to investigate the causal effect of maternal environmental exposures on offspring outcomes. This includes studies that aim to assess the causal effect of in utero exposures related to fetal growth restriction on future risk of disease in offspring. We illustrate our framework using examples related to offspring birthweight and cardiometabolic disease, although the general principles we espouse are relevant for many other offspring phenotypes.

Conclusions
We advocate for the establishment of large-scale international genetics consortia that are focused on the identification of maternal genetic effects and committed to the public sharing of genome-wide summary-results data from such efforts. This information will facilitate the application of powerful two-sample Mendelian randomization studies of maternal exposures and offspring outcomes.
How Norman Angell Reveals the Significance of Marxism and Socialism in Early IR and a Debate before the “First Great Debate”1
Authors: Villanueva Ricardo 
Published: February 2019

AbstractA widespread belief in the field of international relations (IR) is that the first years of the discipline were characterized by a liberal “idealist” theoretical dominance followed by the so-called “first great debate,” in which the “idealist” school was intellectually surpassed by a realist tradition. The purpose of this article is to join previous revisionist studies and challenge this conventional narrative. Building primarily on the international thought and work of Norman Angell on imperialism, this article reveals that there was an important intellectual contest preceding the denominated “first great debate.” It also shows that even though Angell was not a Marxist, his figure discloses Marxism as an important theoretical force in the genesis of the discipline.
Causal Change Detection in Possibly Integrated Systems: Revisiting the Money–Income Relationship*
Authors: Shi Shuping , Hurn Stan , Phillips Peter C B 
Published: February 2019

AbstractThis paper re-examines changes in the causal link between money and income in the United States over the past half century (1959–2014). Three methods for the data-driven discovery of change points in causal relationships are proposed, all of which can be implemented without prior detrending of the data. These methods are a forward recursive algorithm, a rolling window algorithm, and a recursive evolving algorithm all of which utilize subsample tests of Granger causality within a lag-augmented vector autoregressive framework. The limit distributions for these subsample Wald tests are provided. Bootstrap methods are developed to control family-wise size in the implementation of the recursive testing algorithms. The results from a suite of simulation experiments suggest that the recursive evolving window algorithm provides the most reliable results, followed by the rolling window method. The forward expanding window procedure is shown to have the worst performance. Both the rolling window and recursive evolving approaches find evidence of Granger causality running from money to income during the Volcker period in the 1980s. The forward algorithm does not find any evidence of causality over the entire sample period.
Discovery of a putative supernova remnant around the long-period X-ray pulsar SXP 1323 in the Small Magellanic Cloud
Authors: Gvaramadze V V , Kniazev A Y , Oskinova L M 
Published: February 2019

ABSTRACT
We report the discovery of a circular shell centred on the Be X-ray binary (BeXB) SXP 1323 in the Small Magellanic Cloud. The shell was detected in an H α image obtained with the Very Large Telescope. Follow-up spectroscopy with the Southern African Large Telescope showed that the shell expands with a velocity of ${\approx }100{\rm \, km\, s^{-1}}$ and that its emission is due to shock excitation. We suggest that this shell is a remnant of the supernova explosion that led to the formation of SXP 1323’s neutron star ${\approx }40\, 000$ yr ago. SXP 1323 represents the second known case of a BeXB associated with a supernova remnant (the first one is SXP 1062). Interestingly, both of these BeXBs harbour long-period pulsars and are located in a low-metallicity galaxy.
Defining the Therapeutic Singing Voice: An Analysis of Four Music Therapists’ Clinical Work
Authors: Bingham Martina C 
Published: February 2019

AbstractThe purpose of this study was to examine the ways music therapists use their singing voices in music therapy sessions and, in doing so, to provide a working definition of the therapeutic singing voice. Four music therapists were observed leading at least 10 music therapy sessions each in order to examine the ways they used their singing voices in clinical practice. Interviews with each of these therapists, at the completion of session observations, enriched these observational data. Data were analyzed in two stages. First, individual singing voice profiles were developed for each music therapist, and second, these profiles were integrated to define essential singing voice characteristics. These characteristics included flexible postures and physicality, diverse breathing methods and strategies of phonation, flexible resonance strategies, improvisational skills, and knowledge of diverse music genres. Implications for vocal education and training in music therapy programs are discussed.
The divergent logics of industrial change: a comparison of export-cheese processors in Nicaragua
Authors: Fuentes Alberto 
Published: February 2019

AbstractAccording to the industrial policy literature, market failures hamper industrialization processes among private sector firms. Its proposed state-centered solution builds on a conception of these firms as solely profit-maximizing and largely unable to independently solve collection action dilemmas. This article offers a more nuanced portrayal of the private sector’s behavior. It draws upon a broad comparative institutional literature on embedded capitalism and an empirical study of the unexpected industrial transformation of cheese processors in rural Nicaragua to claim that nonmarket logics, such as the familial or community logics, may similarly impinge upon firm action. These logics endow firms with contrasting understandings of group boundaries, on the one hand, and organizational priorities and associated governance mechanisms, on the other—two factors that, together, produce divergent, and often effective, responses to collective action dilemmas. The article concludes with a review of the argument’s implications for industrial policy.
Arenaviridae exoribonuclease presents genomic RNA edition capacity
Authors: Yekwa Elsie , Aphibanthammakit Chutima , Carnec Xavier , Coutard Bruno , Picard Caroline , Canard Bruno , Baize Sylvain , Ferron François 
Published: February 2019

AbstractThe Arenaviridae is a large family of viruses causing both acute and persistent infections and causing significant public health concerns in afflicted regions. A “trademark” of infection is the quick and efficient immuno-suppression mediated in part by a 3’-5’ RNA exonuclease domain (ExoN) of the Nucleoprotein (NP). Mopeia virus, the eastern African counterpart of Lassa virus, carries such ExoN domain, but does not suppress the host innate immunity. We have recently reported the crystal structure of the Mopeia virus ExoN domain, which presents a conserved fold and active site. In the present study, we show that the ExoN activity rules out a direct link between ExoN activity and alteration of the host innate immunity. We found that the Arenavirus ExoN, however, is able to excise mis-incorporated bases present at the 3’-end of double stranded RNA. ExoN(-) arenaviruses cultured in cells dampened in innate immunity still replicated in spite of a significant reduction in the viral charge over several passages. The remaining ExoN(-) virus population showed an increased base substitution rate on a narrow nucleotide spectrum, linking the ExoN activity to genome editing. Since, the Arenavirus ExoN belongs to the same nuclease family as that of the nsp14 coronavirus ExoN ; which has been recently shown to promote viral RNA synthesis proofreading; we propose that Arenavirus ExoN is involved in a “limited RNA editing” mechanism mainly controlled by structural constraints and a low mutational/fitness ratio.Author summaryOnly Arenaviridae and Coronaviridae encode a 3’-5’ RNA exonuclease domain (ExoN) in their genome. This activity is either used to counteract the innate immunity response during viral infection or to ensure genome stability during replication. Mopeia virus (MOPV), the eastern African counterpart of Lassa virus, carries such ExoN domain, but does not suppress the host innate immunity. We studied MOPV ExoN activity both in vitro and in cellula to assess the role of ExoN MOPV and found that the Arenaviral ExoN is fully active on dsRNA, and is able like the one of Coronaviridae to excise a mismatched base. We measured genetic stability and found evidence of a limited spectrum of RNA synthesis proofreading mechanism, together with a strongly impacted viral replication. We propose that the Arenaviral ExoN is involved in a functional check of the conserved RNA structures of the viral genome.
Socioeconomic inequality in recent adverse mortality trends in Scotland
Authors: Fenton Lynda , Wyper Grant , McCartney Gerry , Minton Jon 
Published: February 2019

Structured AbstractBackgroundGains in life expectancies have stalled in Scotland, as in several other countries, since around 2012. The relationship between stalling mortality improvements and socioeconomic inequalities in health is unclear.MethodsWe calculate the percentage improvement in age-standardised mortality rates (ASMR) in Scotland overall, by sex, and by Scottish Index of Multiple Deprivation (SIMD) quintile and gender, for two periods: 2006-2011 and 2012-2017. We then calculate the socioeconomic gradient in improvements for both periods.ResultsBetween 2006 and 2011, ASMRs fell by 10.6% (10.1% in females; 11.8% in males), but between 2012 and 2017 ASMRs only fell by 2.6% (3.5% in females; 2.0% in males). The socioeconomic gradient in ASMR improvement more than quadrupled, from 0.4% per quintile in 2006-2011 (0.7% in females; 0.6% in males) to 1.7% (2.0% in females; 1.4% in males). Within the most deprived quintile, ASMRs fell in the 2006-2011 period (8.6% overall; 7.2% in females; 9.8% in males), but rose in the 2012-2017 period (by 1.5% overall; 0.7% in females; 2.1% in males).ConclusionAs mortality improvements in Scotland stalled in 2012-2017, socioeconomic gradients in mortality became steeper, with increased mortality rates over this period in the most socioeconomically deprived fifth of the population.What we already knowImprovements in mortality rates slowed markedly around 2012 in Scotland and a number of other high-income countries.Scotland has large socioeconomic health inequalities, and the absolute gap in premature mortality between most and least deprived has increased since 2013.The relationship between stalling mortality improvements and socioeconomic inequalities in health is unclear.What this study addsStalling in mortality improvement has occurred across the whole population of Scotland, but is most acute in the most socioeconomically deprived areas.Mortality improvements went into reverse (i.e. deteriorated) in the most deprived fifth of areas between 2012 and 2017.Research to further characterise and explain recent aggregate trends should incorporate consideration of the importance of socioeconomic inequalities within proposed explanations.
Environmental morphing enables informed dispersal of the dandelion diaspore
Authors: Seale Madeleine , Zhdanov Oleksandr , Soons Merel B. , Cummins Cathal , Kroll Erika , Blatt Michael R. , Zare-Behtash Hossein , Busse Angela , Mastropaolo Enrico , Bullock James M. , Viola Ignazio Maria , Nakayama Naomi 
Published: February 2019

SummaryAnimal migration is highly sensitised to environmental cues, but plant dispersal is considered largely passive. The common dandelion, Taraxacum officinale, bears an intricate haired pappus facilitating flight. The pappus enables the formation of a separated vortex ring during flight; however, the pappus structure is not static but reversibly changes shape by closing in response to moisture. We hypothesised that this leads to changed dispersal properties in response to environmental conditions. Using wind tunnel experiments for flow visualisation, particle image velocimetry, and flight tests we characterised the fluid mechanics effects of the pappus morphing. We also modelled dispersal to understand the impact of pappus morphing on diaspore distribution. Pappus morphing dramatically alters the fluid mechanics of diaspore flight. We found that when the pappus closes in moist conditions, the drag coefficient decreases and thus the falling velocity is greatly increased. Detachment of diaspores from the parent plant also substantially decreases. The change in detachment when the pappus closes increases dispersal distances by reducing diaspore release when wind speeds are low. We propose that moisture-dependent pappus-morphing is a form of informed dispersal allowing rapid responses to changing conditions.
Predictability in the evolution of Orthopteran cardenolide insensitivity
Authors: Yang Lu , Ravikanthachari Nitin , Mariño-Pérez Ricardo , Deshmukh Riddhi , Wu Mariana , Rosenstein Adam , Kunte Krushnamegh , Song Hojun , Andolfatto Peter 
Published: February 2019

AbstractThe repeated evolutionary specialisation of distantly related insects to cardenolide-containing host plants provides a stunning example of parallel adaptation. Hundreds of herbivorous insect species have independently evolved insensitivity to cardenolides, which are potent inhibitors of the alpha-subunit of Na+, K+-ATPase (ATPα). Previous studies investigating ATPα-mediated cardenolide insensitivity in five insect orders have revealed remarkably high levels of parallelism in the evolution of this trait, including the frequent occurrence of parallel amino acid substitutions at two sites and recurrent episodes of duplication followed by neo-functionalisation. Here we add data for a sixth insect order, Orthoptera, which includes an ancient group of highly aposematic cardenolide-sequestering grasshoppers in the family Pyrgomorphidae. We find that Orthopterans exhibit largely predictable patterns of evolution of insensitivity established by sampling other insect orders. Taken together the data lend further support to the proposal that negative pleiotropic constraints are a key determinant in the evolution of cardenolide insensitivity in insects. Furthermore, analysis of our expanded taxonomic survey implicates positive selection acting on site 111 of cardenolide-sequestering species with a single-copy of ATPα, and sites 115, 118 and 122 in lineages with neo-functionalised duplicate copies, all of which are sites of frequent parallel amino acid substitution.
Cell wall integrity signaling regulates cell wall regeneration via transcriptional activation inChlamydomonas reinhardtii
Authors: Cronmiller Evan , Toor Deepak , Shao Nai Chun , Kariyawasam Thamali , Wang Ming Hsiu , Lee Jae-Hyeok 
Published: February 2019

AbstractAn intact cell wall is critical for protecting the cell from osmotic challenges and harmful environments. Signaling mechanisms are necessary to monitor cell wall integrity and to regulate cell wall production and remodeling during growth and division cycles. The green alga,Chlamydomonas, has a proteinaceous cell wall of defined structure that is readily removed by gametolysin (g-lysin), a metalloprotease released during sexual mating. Naked cells treated with g-lysin induce the mRNA accumulation of > 100 cell wall-related genes within an hour, offering a system to study signaling and regulatory mechanisms forde novocell wall assembly. Combining quantitative RT-PCR and luciferase reporter assays to probe transcript accumulation and promoter activity, we revealed that up to 500-fold upregulation of cell wall-related genes was driven at least partly by transcriptional activation upon g-lysin treatment. To investigate how naked cells trigger this rapid transcriptional activation, we tested whether osmotic stress and cell wall integrity are involved in this process. Under a constant hypotonic condition, comparable levels of cell wall-gene activation were observed by g-lysin treatment. In contrast, cells in an iso- or hypertonic condition showed up to 80% reduction in the g-lysin-induced gene activation, suggesting that hypotonic conditions are required for full-scale responses to g-lysin treatment. To test whether mechanical perturbation is involved, we isolated and examined a new set of cell wall mutants with defective or little cell walls. All cell wall mutants examined showed a constitutive upregulation of cell wall-related genes at the level, which would only be achieved by the g-lysin treatment in wild-type cells. Our study suggests a signaling that monitors mechanical defects of cell walls and regulates cell wall-gene expression inChlamydomonas, which may relate to cell wall integrity signaling mechanisms in plants.
Insulin-stimulated glucose uptake partly relies on p21-activated kinase (PAK)-2, but not PAK1, in mouse skeletal muscle
Authors: Møller Lisbeth L. V. , Jaurji Merna , Kjøbsted Rasmus , Joseph Giselle A. , Madsen Agnete B. , Knudsen Jonas R. , Lundsgaard Annemarie , Andersen Nicoline R. , Schjerling Peter , Jensen Thomas E. , Krauss Robert S. , Richter Erik A. , Sylow Lykke 
Published: February 2019

AbstractObjectiveSkeletal muscle glucose uptake is essential for maintaining whole-body glucose homeostasis and accounts for the majority of glucose disposal in response to insulin. The group I p21-activated kinase (PAK) isoforms PAK1 and PAK2 are activated in response to insulin in skeletal muscle. Interestingly, PAK1/2 signalling is impaired in insulin-resistant mouse and human skeletal muscle and PAK1 has been suggested to be required for insulin-stimulated GLUT4 translocation. However, the relative contribution of PAK1 and PAK2 to insulin-stimulated glucose uptake in mature skeletal muscle is unresolved. The aim of the present investigation was to determine the requirement for PAK1 and PAK2 in whole-body glucose homeostasis and insulin-stimulated glucose uptake in skeletal muscle.MethodsGlucose uptake was measured in isolated skeletal muscle incubated with a pharmacological inhibitor (IPA-3) of group I PAKs and in muscle from whole-body PAK1 knockout (KO), muscle-specific PAK2 (m)KO and double whole-body PAK1 and muscle-specific PAK2 knockout mice.ResultsThe whole-body respiratory exchange ratio was largely unaffected by lack of PAK1 and/or PAK2. Whole-body glucose tolerance was mildly impaired in PAK2 mKO, but not PAK1 KO mice. IPA-3 partially reduced (−20%) insulin-stimulated glucose uptake in mouse soleus muscle. In contrast to a previous study of GLUT4 translocation in PAK1 KO mice, PAK1 KO muscles displayed normal insulin-stimulated glucose uptake in vivo and in isolated muscle. On the contrary, glucose uptake was slightly reduced in response to insulin in glycolytic extensor digitorum longus muscle lacking PAK2, alone (−18%) or in combination with PAK1 KO (−12%).ConclusionsInsulin-stimulated glucose uptake partly relies on PAK2, but not PAK1, in mouse skeletal muscle. Thus, the present study challenges that group I PAKs, and especially PAK1, are major regulators of whole-body glucose homeostasis and insulin-stimulated glucose uptake in skeletal muscle.