bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear pore density controls heterochromatin reorganization during senescence
Authors: Boumendilrid Charlene , Hari Priya , Olsen Karl C. F. , Acosta Juan Carlos , Bickmore Wendy A. 
Published: July 2018

AbstractOncogene induced senescence (OIS) is a cell cycle arrest program triggered by oncogenic signalling. An important characteristic of OIS is activation of the senescence associated secretory phenotype (SASP)1 which can reinforce cell cycle arrest, lead to paracrine senescence but also promote tumour progression2–4. Concomitant with cell cycle arrest and the SASP activation, OIS cells undergo a striking nuclear chromatin reorganization, with loss of heterochromatin from the nuclear periphery and the appearance of internal senescence-associated heterochromatin foci (SAHF)5. The mechanisms by which SAHF are formed, and their role in cell cycle arrest and expression of the SASP, remain poorly understood. Here we show that nuclear pore density increases during OIS and is responsible for SAHF formation. In particular, we show that the nucleoporin TPR is required for both SAHF formation and maintenance. The TPR-induced loss of SAHF does not affect cell cycle arrest but completely abrogates the SASP. Our results uncover a previously unknown role of nuclear pores in heterochromatin reorganization in mammalian nuclei and in senescence, which uncouples the cell cycle arrest from the SASP.
Landscape pivot points and responses to water balance in national parks of the southwest US
Authors: Thoma David P. , Munson Seth M. , Witwicki Dana L. 
Published: July 2018

Abstract

A recent drying trend that is expected to continue in the southwestern US underscores the need for site‐specific and near real‐time understanding of vegetation vulnerability so that land management actions can be implemented at the right time and place.

We related the annual integrated normalized difference vegetation index (iNDVI), a proxy for vegetation production, to water balance across landscapes of the Colorado Plateau. We determined how changes in production per unit of water (vegetation responses) and the water balance amounts at which production shifted from above to below average values (pivot points), varied across dominant vegetation and soil types.

Precipitation (PRCP), actual evapotranspiration (AET), water deficit (D), and soil moisture (SM) explained 13%–82% of variation in vegetation production. Along an increasing water availability gradient, vegetation responses to PRCP and AET increased, responses to SM decreased, and responses to D became more negative. We found trade‐offs between vegetation responses and pivot points within and across all vegetation types that were mediated by soil properties.

Synthesis and applications. The water needed by native vegetation to maintain production depends on plant traits. The water available to vegetation depends on climate and soil properties that change along environmental gradients. Tracking this biologically relevant water availability in relation to water need provides an indicator of vegetation growth or stress that can help guide the time and place for management actions.
In Vivo Metabolic Tracing Demonstrates the Site‐Specific Contribution of Hepatic Ethanol Metabolism to Histone Acetylation
Authors: Kriss Crystina L. , Gregory‐Lott Emily , Storey Aaron J. , Tackett Alan J. , Wahls Wayne P. , Stevens Stanley M. 
Published: July 2018

BackgroundEpigenetic dysregulation through ethanol (EtOH)‐induced changes in DNA methylation and histone modifications has been implicated in several alcohol‐related disorders such as alcoholic liver disease. EtOH metabolism in the liver results in the formation of acetate, a metabolite that can be converted to acetyl‐CoA, which can then be used by histone acetyltransferases to acetylate lysine residues. EtOH metabolism in the liver can also indirectly influence lysine acetylation through NAD+‐dependent sirtuin activity that is altered due to increases in NADH. As a proof‐of‐concept study to determine the direct influence of hepatic EtOH metabolism on histone acetylation changes, we used heavy‐labeled EtOH (13C2) and mass spectrometry (MS) to site specifically characterize lysine acetylation on histone proteins.MethodsEight‐week‐old male C57BL/6J mice were gavaged using a bolus dose of either 13C2‐labeled EtOH (5 g/kg) or maltose dextrin. Blood and livers were collected at 0, 4, and 24 hours followed by histone protein enrichment and derivatization using acid extraction and propionylation, respectively. Metabolic tracing and relative quantitation of acetylated histone proteins were performed using a hybrid quadrupole‐orbitrap mass spectrometer. Data were analyzed using MaxQuant, Xcalibur Qual Browser, and the Bioconductor package “mzR.” The contribution of EtOH to histone acetylation was quantified using the change in relative abundance of stable isotope incorporation in acetylated peptides detected by MS.ResultsData show significant incorporation of the EtOH‐derived 13C2‐label into N‐terminal lysine acetylation sites on histones H3 and H4 after 4 hours, with rapid turnover of labeled histone acetylation sites and return to endogenous levels at 24 hours postgavage. Moreover, site‐specific selectivity was observed in regard to label incorporation into certain lysine acetylation sites as determined by tandem mass spectrometry and comparison to isotope simulations.ConclusionsThese data provide the first quantitative evidence of how hepatic EtOH metabolism directly influences histone lysine acetylation in a site‐specific manner and may influence EtOH‐induced gene expression through these transcriptionally activating chromatin marks.
A Critical Review and Meta‐Analysis of the Associations Between Acculturation and Alcohol Use Outcomes Among Hispanic Americans
Authors: Lui P. Priscilla , Zamboanga Byron L. 
Published: July 2018

Acculturation has been studied as one key sociocultural determinant that helps explain ethnic disparities in alcohol use outcomes among Hispanic Americans. Primary studies and other systematic reviews have found between‐study inconsistencies regarding the extent to which acculturation is associated with alcohol use outcomes among Hispanic Americans. To better examine whether acculturation is distinctly linked to drinker status, drinking frequency, volume, intensity, binge drinking, and hazardous alcohol use/drinking problems, and to identify individual and methodological factors that moderate these associations, we conducted a comprehensive research synthesis. A systematic review was conducted on research pertaining to the associations between acculturation and alcohol use among Hispanics. We included 88 independent study samples (N = 68,282) coded from 68 manuscripts published in 1987 to 2017. Standard and robust variance estimation (RVE) meta‐analyses were conducted to calculate the correlations between acculturation and overall alcohol use. We also conducted a series of analyses to examine the weighted mean correlations between acculturation and 6 specific drinking outcomes. We found a statistically significant correlation between acculturation and overall alcohol use (r = 0.09, p < 0.001). Acculturation was associated with drinker status (r = 0.10, p < 0.001), drinking intensity (r = 0.09, p = 0.001), binge drinking (r = 0.05, p = 0.006), and hazardous alcohol use/drinking problems (r = 0.06, p = 0.006), but not drinking frequency (r = 0.02, p = 0.56) or volume (r = 0.01, p = 0.73). Gender, acculturation dimension, acculturation domain, age group, and sampling settings were found to explain between‐study variability in some of these associations. Findings show small relations between acculturation and various alcohol use outcomes, but the effects are relatively more robust among Hispanic women, adults, and when studies measured U.S. cultural orientation, linguistic acculturation, and behavioral practices.
The soluble isoform of human FcɛRI is an endogenous inhibitor of IgE‐mediated mast cell responses
Authors: Moñino‐Romero S. , Erkert L. , Schmidthaler K. , Diesner S. C. , Sallis B. F. , Pennington L. , Jardetzky T. , Oettgen H. C. , Bohle B. , Fiebiger E. , Szépfalusi Z. 
Published: July 2018

AbstractBackgroundThe soluble isoform of FcɛRI, the high‐affinity IgE receptor (sFcεRI), is a protein of the IgE network with poorly defined functions.ObjectiveTo define cellular sources and signals that result in the production of human sFcεRI and study its in vivo functions.MethodsFcεRI‐transfected human cell lines (MelJuso), human monocyte‐derived dendritic cells (moDCs), and murine bone marrow‐derived mast cells (MC) were stimulated by FcεRI cross‐linking and release of sFcεRI was analyzed (ELISA, Western Blot). Lysosomal‐associated membrane protein 1 degranulation assays and human basophil activation tests (BATs) were used to study IgE‐dependent activation. Recombinant sFcεRI (rsFcεRI) was used to assess its role in murine models of anaphylaxis with WT (wild‐type) and IgE−/− (IgE‐deficient) mice.ResultsAntigen‐specific cross‐linking of IgE‐loaded FcɛRI on MelJuso cells that express the trimeric or tetrameric receptor isoform induced the production of sFcεRI. Using MCs and moDCs, we confirmed that IgE/FcɛRI activation induces sFcɛRI release. We demonstrated that generation of sFcɛRI requires Src phosphorylation and endo/lysosomal acidification. In experimental mouse models, sFcɛRI diminishes the severity of IgE‐mediated anaphylaxis. BATs confirmed that, comparable to the anti‐IgE monoclonal antibody omalizumab, sFcɛRI is an inhibitor of the human innate IgE effector axis, implying that sFcɛRI and omalizumab potentially inhibit each other in vivo.ConclusionsFcɛRI is produced after antigen‐specific IgE/FcɛRI‐mediated activation signals and functions as an endogenous inhibitor of IgE loading to FcɛRI and IgE‐mediated activation. Our results imply, therefore, that sFcɛRI contributes to a negative regulatory feedback loop that aims at preventing overshooting responses after IgE‐mediated immune activation.
Protruded retinal layers within the optic nerve head neuroretinal rim
Authors: Torres Lucas A. , Vianna Jayme R. , Jarrar Faisal , Sharpe Glen P. , Araie Makoto , Caprioli Joseph , Demirel Shaban , Girkin Christopher A. , Hangai Masanori , Iwase Aiko , Liebmann Jeffrey M. , Mardin Christian Y. , Nakazawa Toru , Quigley Harry A. , Scheuerle Alexander F. , Sugiyama Kazuhisa , Tanihara Hidenobu , Tomita Goji , Yanagi Yasuo , Burgoyne Claude F. , Chauhan Balwantray C. 
Published: July 2018

AbstractPurposeTo determine the frequency with which retinal tissues other than the nerve fibre layer, hereafter referred to as protruded retinal layers (PRL), are a component of optical coherence tomography (OCT) neuroretinal rim measurements.MethodsNinety healthy (30 White, Black and Japanese, respectively) subjects were included in the study. A radial scan pattern (24 B‐scans centred on Bruch's membrane opening [BMO]) was used. For each of the 48 minimum rim width (MRW) measurement points, we determined whether PRL were present, absent or indeterminate. When present, the proportion of PRL within the MRW was quantified.ResultsProtruded retinal layers were present in 503 (11.6%), absent in 3805 (88.1%) and indeterminate in 12 (0.3%) measurement points. Overall, 69 (76.6%) subjects had ≥1 points with PRL, with White subjects having the highest frequency and Japanese the lowest (29 [97%] and 18 [60%], respectively; p < 0.01). PRL were present in one‐third of points in the temporal sector, but ≤5% in other sectors. When present, the median PRL thickness was 53.0 (interquartile range [IQR]: 33.0 to 78.5) μm, representing 20.6 (IQR: 13.0 to 28.5)% of MRW. Globally, the median PRL thickness comprised 1.3 (IQR: 0.2 to 3.5)% of the MRW; however, in the temporal sector, it exceeded 30% of MRW in some subjects.ConclusionsProtruded retinal layers are a component of MRW measurements in most normal subjects, occurring in almost 12% of all measurement points analysed. There were racial variations in the presence of PRL and a significantly higher frequency of PRL in the temporal sector.
One year effectiveness study of intravitreal aflibercept in neovascular age‐related macular degeneration: a meta‐analysis
Authors: Guo Michael Y. , Cheng Jasmine , Etminan Mahyar , Zafari Zafar , Maberley David 
Published: July 2018

AbstractThe current body of evidence on the efficacy and safety of aflibercept for age‐related macular degeneration (AMD) is steadily growing as large clinical trials and observational studies are continually completed. Our aim was to analyse 1‐year visual acuity (VA) outcomes in response to aflibercept therapy and identify factors affecting treatment response using evidence generated from a pooled analysis of current studies. A literature review of multiple electronic databases (EMBASE, MEDLINE, MedMEME) revealed 12 studies meeting inclusion and exclusion criteria for statistical analysis. Treatment posology, baseline patient characteristics, study type, sample size and 12‐month change in VA were pooled in a meta‐analysis with VA change as the main outcome. Data were then stratified by study design and posology in subgroup analyses. A meta‐regression was conducted to regress 12‐month VA change against posology, baseline VA and age. Users of aflibercept experienced an overall increase of 7.37 letters (95% confidence interval: 6.27–8.48, p heterogeneity: <0.001) in VA at 12 months of follow‐up. In subgroup analyses, mean VA change was higher for randomized control trials and cohorts following regular posology (>7 injections/year) compared to observational studies and irregular posology. The meta‐regression showed larger VA gains with regular posology compared to an irregular posology, and decreased effect size as age increased. This meta‐analysis strongly suggests improved VA outcomes at 12 months in patients with wet AMD for 2.0 mg aflibercept, comparable to but slightly lower than landmark trials. Increased injection frequency and younger age demonstrates a trend with improved outcomes.
Comparative morphology of the avian maxillary bone (os maxillare) based on an examination of macerated juvenile skeletons
Authors: Mayr Gerald 
Published: July 2018

AbstractFor the first time, isolated maxillary bones of juvenile neornithine birds are examined and compared. Contrary to the anatomical terminology currently employed, the avian maxillare exhibits five rather than four processes. In addition to the praemaxillary, jugal, nasal, and maxillopalatine processes, all palaeognathous and many neognathous birds also have a palatine process. The occurrence of these processes is, however, variable across different clades and only few taxa exhibit a pentaradiate maxillare with all five processes. Within Neognathae, a great morphological variability exists in the shape of the maxillopalatine process, which is more easily studied in juvenile individuals, in which the bones of the beak and palate are not co‐ossified. In some Neognathae, a caudally facing recess is situated in the junction of the maxillopalatine and jugal processes, which is likely to be homologous to the pneumatic recess of palaeognathous birds. Several derived morphologies of potential phylogenetic significance for the characterization of neognathous clades are identified and major morphological transformations in the lineage leading towards modern birds are highlighted.
Skin resident memory CD8+ T cells are phenotypically and functionally distinct from circulating populations and lack immediate cytotoxic function
Authors: Seidel J A , Vukmanovic-Stejic M , Muller-Durovic B , Patel N , Fuentes-Duculan J , Henson S M , Krueger J G , Rustin M H A , Nestle F O , Lacy K E , Akbar A N 
Published: July 2018

Summary
The in-depth understanding of skin resident memory CD8+ T lymphocytes (TRM) may help to uncover strategies for their manipulation during disease. We investigated isolated TRM from healthy human skin, which expressed the residence marker CD69, and compared them to circulating CD8+ T cell populations from the same donors. There were significantly increased proportions of CD8+CD45RA−CD27− T cells in the skin that expressed low levels of killer cell lectin-like receptor G1 (KLRG1), CD57, perforin and granzyme B. The CD8+ TRM in skin were therefore phenotypically distinct from circulating CD8+CD45RA−CD27− T cells that expressed high levels of all these molecules. Nevertheless, the activation of CD8+ TRM with T cell receptor (TCR)/CD28 or interleukin (IL)-2 or IL-15 in vitro induced the expression of granzyme B. Blocking signalling through the inhibitory receptor programmed cell death 1 (PD)-1 further boosted granzyme B expression. A unique feature of some CD8+ TRM cells was their ability to secrete high levels of tumour necrosis factor (TNF)-α and IL-2, a cytokine combination that was not seen frequently in circulating CD8+ T cells. The cutaneous CD8+ TRM are therefore diverse, and appear to be phenotypically and functionally distinct from circulating cells. Indeed, the surface receptors used to distinguish differentiation stages of blood T cells cannot be applied to T cells in the skin. Furthermore, the function of cutaneous TRM appears to be stringently controlled by environmental signals in situ.
CRISPR-based reagents to study the influence of the epigenome on gene expression
Authors: Lavender P , Kelly A , Hendy E , McErlean P 
Published: July 2018

Summary
The use of epigenome editing is set to expand our knowledge of how epigenetic landscapes facilitate gene expression capacity within a given cell. As epigenetic landscape profiling in health and disease becomes more commonplace, so does the requirement to assess the functional impact that particular regulatory domains and DNA methylation profiles have upon gene expression capacity. That functional assessment is particularly pertinent when analysing epigenomes in disease states where the reversible nature of histone and DNA modification might yield plausible therapeutic targets. In this review we discuss first the nature of the epigenetic landscape, secondly the types of factors that deposit and erase the various modifications, consider how modifications transduce their signals, and lastly address current tools for experimental epigenome editing with particular emphasis on the immune system.
Experiences of self‐management among young adults with Type 1 diabetes in the context of a structured education programme: a qualitative study
Authors: Sanders T. , Elliott J. , Norman P. , Johnson B. , Heller S. 
Published: July 2018

AbstractAimsTo explore the experiences of young adults with regard to self‐management of Type 1 diabetes in the context of a structured education programme.MethodsQualitative interviews and focus groups were conducted with young adults attending a structured education course promoting a flexible and self‐directed format. Participants attending the structured education courses were recruited using purposive sampling to acquire a broad mix of participants based on age and equal numbers of young men and women. Fifteen interviews were conducted 12 weeks after each course, whilst seven focus groups and observations of the course delivery were conducted at two course sites and were led by nurse/dietitian educators representing two different diabetes centres (paediatric and adult). The interview and focus group data were audio recorded and transcribed, coded, and analysed thematically to identify similarities and differences.ResultsThe analysis revealed three themes, ‘we're in it together’, ‘tacit benefits’ and ‘transitions beyond the structured education programme’. The findings show that structured education programmes can facilitate reflective critical thinking and greater engagement with diabetes self‐management if they: a) foster maximal learning from fellow participants to decrease feelings of isolation, b) maximize engagement during the course by delivering the content in a flexible manner, and c) recognize the social and emotional needs of young adults.ConclusionStructured education courses can result in improved critical thinking and engagement with diabetes self‐management by empowering young adults through a flexible and self‐directed learning style that encourages peer group discussion.
The effect of Bruton's tyrosine kinase (BTK) inhibitors on collagen‐induced platelet aggregation, BTK, and tyrosine kinase expressed in hepatocellular carcinoma (TEC)
Authors: Chen Jun , Kinoshita Taisei , Gururaja Tarikere , Sukbuntherng Juthamas , James Danelle , Lu Daniel , Whang Jennifer , Versele Matthias , Chang Betty Y. 
Published: July 2018

AbstractObjectivesBruton's tyrosine kinase (BTK) and tyrosine kinase expressed in hepatocellular carcinoma (TEC) are expressed by human platelets. These kinases participate in platelet activation through the collagen receptor glycoprotein VI and may perform overlapping functions. In clinical studies, BTK inhibitors (ibrutinib, acalabrutinib, tirabrutinib, zanubrutinib) have been associated with increased bleeding risk, which may result from inhibition of BTK alone or of both BTK and TEC, although the role of TEC in bleeding risk remains unclear.MethodsHere, in vitro catalytic and binding activities of ibrutinib and acalabrutinib were determined with four assay systems. Platelet aggregation assays determined inhibitor potency and its relationship to selectivity between BTK and TEC.ResultsNeither inhibitor was substantially more selective for BTK over TEC. The potencies at which BTK inhibitors suppressed platelet aggregation correlated with the potencies in on‐target BTK assays, including those in cells. At clinically relevant plasma concentration, ibrutinib, acalabrutinib, and tirabrutinib inhibited collagen‐induced platelet aggregation to a similar extent, despite differing in vitro IC50s.ConclusionsOur results suggest BTK inhibition is the primary driver for inhibition of platelet aggregation. The subtle differences between these inhibitors suggest only randomized, double‐blind, placebo‐controlled clinical studies can fully address the bleeding risks of different BTK inhibitors.