bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single molecule-level detection and long read-based phasing of epigenetic variations in bacterial methylomes
Authors: Beaulaurier John , Zhu Shijia , Sebra Robert , Zhang Xue-Song , Rosenbluh Chaggai , Deikus Gintaras , Shen Nan , Munera Diana , Waldor Matthew K. , Blaser Martin , Chess Andrew , Schadt Eric E. , Fang Gang 
Published: September 2014

AbstractComprehensive genome-wide analyses of bacterial DNA methylation have not been possible until the recent advent of single molecule, real-time (SMRT) sequencing. This technology enables the direct detection of N6-methyladenine (6mA) and 4-methylcytosine (4mC) at single nucleotide resolution on a genome-wide scale. The distributions of these two major types of DNA methylation, along with 5-methylcytosine (5mC), comprise the bacterial methylome, some rare exceptions notwithstanding. SMRT sequencing has already revealed marked diversity in bacterial methylomes as well as the existence of heterogeneity of methylation in cells in single bacterial colonies, where such ‘epigenetic’ variation can enable bacterial populations to rapidly adapt to changing conditions. However, current methods for studying bacterial methylomes using SMRT sequencing mainly rely on population-level summaries that do not provide the single-cell resolution necessary for dissecting the epigenetic heterogeneity in bacterial populations. Here, we present a novel SMRT sequencing-based framework, consisting of two complementary methods, for single molecule-level detection of DNA methylation and assessment of methyltransferase activity through single molecule-level long read-based epigenetic phasing. Using seven bacterial strains and integrating data from SMRT and Illumina sequencing, we show that our method yields significantly improved resolution compared to existing population-level methods, and reveals several distinct types of epigenetic heterogeneity. Our approach enables new investigations of the complex architecture and dynamics of bacterial methylomes and provides a powerful new tool for the study of bacterial epigenetic control.
The development of whole-system integrated care in England
Authors: Kennedy Claire , Morioka Simon 
Published: September 2014

Purpose
– The purpose of this paper is to detail the research and findings from a piece of work commissioned by the Local Government Association in England, in May 2013 into the current implementation of integrated care.

Design/methodology/approach
– The field research was carried out by Integrating Care, a collaborative drawn from leading academics, health and social care executives, analysts and clinicians working in the field of integrated care; along with consultancy support from public sector consultancies PPL and GE Healthcare Finnamore. It comprised a series of local interviews, workshops, modelling and analysis and ongoing engagement.

Findings
– The paper describes the outputs that were delivered to support the development of “whole-system” integrated health and social care drawing on national and international best-practice, and knowledge gained from experiences of implementation.

Social implications
– The paper concludes by drawing together the key lessons from the overarching analysis of whole-system integration. This includes the opportunities and the complexities of redesigning and re-implementing better co-ordinated health and social care provision at scale, as experienced in England currently.

Originality/value
– The paper describes the specific challenges posed through the fieldwork and ongoing development process of integration in England, and the paper reflects upon some of the deeper questions that this has led to. The paper then draws together the research and analysis with emerging, strategic questions around the concept of value in health provision; and begins to question whether this has yet been demonstrated; and, if not, what a demonstration and evidencing of “value” in this context might look like.
“Sliding Doors”: innovative approaches to supporting culture change
Authors: Walker Gill , Gillies Laura 
Published: September 2014

Purpose
– Reshaping Care for Older People (RCOP) and Integration of Health and Social Care are central to providing a care system in Scotland that meets older people's current and future needs. Their implementation requires a workforce with the appropriate knowledge, skills and values to engage with older people across health and social care sectors, which requires a change in professionals’ thinking about services. The paper aims to discuss these issues.

Design/methodology/approach
– NHS Education for Scotland, the Scottish Social Services Council and a learning and development consultancy designed and delivered innovative education resources to support health and social care staff across Scotland to understand the new agenda and recognise its meaning for practice.

Findings
– Two related resources were developed: workshop using actors to depict scenarios from older people's lives to support participants to reflect on the new policy direction and outcomes-focused approaches; and an online resource using the same characters that can be delivered locally for groups and individuals. Participants were enabled to identify what they need to do differently and how they can support one another to make necessary changes. A formal evaluation has been commissioned.

Originality/value
– The resource characters represent the people the new policy is designed to affect. By following their lives through an educational drama approach, health and social care staff can understand the difference RCOP and the integration agenda can make and recognise their part in effecting change.
How exotic plants integrate into pollination networks
Authors: Stouffer Daniel B. , Cirtwill Alyssa R. , Bascompte Jordi 
Published: September 2014

Summary

There is increasing world‐wide concern about the impact of the introduction of exotic species on ecological communities. Since many exotic plants depend on native pollinators to successfully establish, it is of paramount importance that we understand precisely how exotic species integrate into existing plant–pollinator communities.

In this manuscript, we have studied a global data base of empirical pollination networks to determine whether community, network, species or interaction characteristics can help identify invaded communities.

We found that a limited number of community and network properties showed significant differences across the empirical data sets – namely networks with exotic plants present are characterized by greater total, plant and pollinator richness, as well as higher values of relative nestedness.

We also observed significant differences in terms of the pollinators that interact with the exotic plants. In particular, we found that specialist pollinators that are also weak contributors to community nestedness are far more likely to interact with exotic plants than would be expected by chance alone.

Synthesis. By virtue of their interactions, it appears that exotic plants may provide a key service to a community's specialist pollinators as well as fill otherwise vacant ‘coevolutionary niches’.
Multilead Template‐Derived Residua of Surface ECGS for Quantitative Assessment of Arrhythmia Risk
Authors: Nearing Bruce D. , Verrier Richard L. 
Published: September 2014

BackgroundContemporary electrocardiographic (ECG) markers including ventricular ectopy and arrhythmias have not proved reliable in risk assessment for life‐threatening arrhythmias.MethodsWe developed the “Multilead ECG Template‐Derived Residua” approach to remove intrinsic morphologic differences and allow calculation of pathologic ECG heterogeneities among spatially separated leads. Prediction by R‐wave and T‐wave heterogeneity (RWH, TWH) analysis was tested in simulated and clinical ECGs.ResultsAn enabling description of the Residua algorithm is provided. Simulated ECGs with but not without Residua produced a linear relationship (correlation coefficient r2 = 0.999) between input and output RWH and TWH values. In heart failure patients, Residua disclosed a marked crescendo in RWH from 164.1 ± 33.1 at baseline to 299.8 ± 54.5 μV and TWH from 134.5 ± 20.6 at baseline to 239.2 ± 37.0 μV at 30–45 minutes before the arrhythmia (both, P < 0.05), which remained elevated until arrhythmia onset. Without Residua, mean RWH and TWH were elevated at 1061.0 ± 222.9 and 882.5 ± 375.2 μV, respectively, throughout the recording and were not different prior to ventricular tachycardia onset.ConclusionsCalculation of ECG‐template derived Residua provides a highly accurate means for assessing arrhythmia risk from standard ECGs. Potential widespread applications include resting diagnostic 12‐lead, ambulatory, and exercise ECGs, electrophysiologic study laboratory recordings, and implantable devices.
Significance of Fragmented QRS Complexes for Identifying Left Ventricular Hypertrophy in Patients with Hypertension
Authors: Zhang Baowei , Zhen Ya , Shen Dongli , Zhang Guohui 
Published: September 2014

BackgroundFragmented QRS complexes (fQRS) were associated with left ventricular mass (LVM) in hypertensive patients. Our study aimed to investigate the association between fQRS and left ventricular hypertrophy (LVH) in hypertensive patients.MethodsTwo hundred thirty‐six hypertensive patients were divided into fQRS group and non‐fQRS group. fQRS were defined as the presence of an additional R wave, notching in the R or S wave, or the presence of >1 R' in two contiguous leads. Echocardiography was used to detect LVH.ResultsPatients with fQRS had higher levels of LVM than patients without fQRS (181.55 ± 65.64 g vs. 149.21 ± 35.08 g, P < 0.001). Receiver operating characteristic curves showed areas under the curve was 0.62 for fQRS (95% CI 0.54–0.69, P = 0.003). In univariate analyses, the presence of fQRS on ECG was positively associated with LVM. Multiple regression analyses found fQRS was associated with LVM, independently.ConclusionfQRS is a common electrocardiographic phenomenon in patients with hypertension. Although the diagnostic value for LVH is limited, the presence of fQRS on ECG is associated with a higher risk for worse LVH.
Rare platelet GPCR variants: what can we learn?
Authors: Nisar S P , Jones M L , Cunningham M R , Mumford A D , Mundell S J ,   UK GAPP Study Group
Published: September 2014

Platelet‐expressed GPCRs are critical regulators of platelet function. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis associated with coronary atherosclerosis and ischaemic stroke. However, anti‐thrombotic drug therapy is associated with high inter‐patient variability in therapeutic response and adverse bleeding side effects. In order to optimize the use of existing anti‐platelet drugs and to develop new therapies, more detailed knowledge is required relating to the molecular mechanisms that regulate GPCR and therefore platelet function. One approach has been to identify rare, function‐disrupting mutations within key platelet proteins in patients with bleeding disorders. In this review, we describe how an integrated functional genomics strategy has contributed important structure‐function information about platelet GPCRs with specific emphasis upon purinergic and thromboxane A2 receptors. We also discuss the potential implications these findings have for pharmacotherapy and for understanding the molecular basis of mild bleeding disorders.Linked ArticlesThis article is part of a themed section on 5th BPS Focused Meeting on Cell Signalling. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐13
Real Time Three‐Dimensional Transthoracic Echocardiography in Assessment of Stented Coarctation of Aorta: A Case‐Based Presentation
Authors: Almomani Ahmed , Modi Shreyas , Ahmad Masood 
Published: September 2014

Mini‐AbstractThe treatment for aortic coarctation has evolved from surgical repair to percutaneous endovascular balloon angioplasty and stenting. Imaging techniques are playing an important role in assessment of these patients. We present a case in whom an accurate assessment of the patency of the stent and the adequacy of flow were obtained by real time three‐dimensional echocardiography. Compared to other imaging modalities, echocardiography is inexpensive. It also avoids the risks of radiation and contrast associated with computed tomographic (CT) angiography, and the potential artifacts that may occur with cardiac magnetic resonance (MR). Real time three‐dimensional echocardiography from a transthoracic approach appears promising in evaluating morphology and functionality of the stented coarctation of the descending aorta.
Real Time Three‐Dimensional Transesophageal Echocardiography Demonstration of Membranous Septal Aneurysm Causing Severe Right Ventricular Outflow Tract Obstruction
Authors: Mahesh Saktheeswaran K. , Kumar Senthil , Satheesh Santhosh , Jayaraman Balachander 
Published: September 2014

Mini‐AbstractIn addition to infundibular muscular hypertrophy and anomalous muscle bundles in the right ventricular body, large membranous septal aneurysms (MSA), sinus of Valsalva aneurysms, and aneurysms derived from the embryonic venous valve protruding through the tricuspid valve can cause right ventricular outflow obstruction in a patient with ventricular septal defect. Here we describe an adult with a small perimembranous ventricular septal defect complicated by a large MSA causing severe right ventricular outflow obstruction evaluated with real time three‐dimensional transesophageal echocardiography.
Role of pleiotropy during adaptation of TEM‐1 β‐lactamase to two novel antibiotics
Authors: Schenk Martijn F. , Witte Sariette , Salverda Merijn L. M. , Koopmanschap Bertha , Krug Joachim , de Visser J. Arjan G. M. 
Published: September 2014

AbstractPleiotropy is a key feature of the genotype–phenotype map, and its form and extent have many evolutionary implications, including for the dynamics of adaptation and the evolution of specialization. Similarly, pleiotropic effects of antibiotic resistance mutations may affect the evolution of antibiotic resistance in the simultaneous or fluctuating presence of different antibiotics. Here, we study the role of pleiotropy during the in vitro adaptation of the enzyme TEM‐1 β‐lactamase to two novel antibiotics, cefotaxime (CTX) and ceftazidime (CAZ). We subject replicate lines for four rounds of evolution to selection with CTX and CAZ alone, and in their combined and fluctuating presence. Evolved alleles show positive correlated responses when selecting with single antibiotics. Nevertheless, pleiotropic constraints are apparent from the effects of single mutations and from selected alleles showing smaller correlated than direct responses and smaller responses after simultaneous and fluctuating selection with both than with single antibiotics. We speculate that these constraints result from structural changes in the oxyanion pocket surrounding the active site, where accommodation of CTX and the larger CAZ is balanced against their positioning with respect to the active site. Our findings suggest limited benefits from the combined or fluctuating application of these related cephalosporins for containing antibiotic resistance.
Knockdown of lecithin retinol acyltransferase increases all‐trans retinoic acid levels and restores retinoid sensitivity in malignant melanoma cells
Authors: Amann Philipp M. , Czaja Katharina , Bazhin Alexandr V. , Rühl Ralph , Skazik Claudia , Heise Ruth , Marquardt Yvonne , Eichmüller Stefan B. , Merk Hans F. , Baron Jens M. 
Published: September 2014

AbstractRetinoids such as all‐trans retinoic acid (ATRA) influence cell growth, differentiation and apoptosis and may play decisive roles in tumor development and progression. An essential retinoid‐metabolizing enzyme known as lecithin retinol acyltransferase (LRAT) is expressed in melanoma cells but not in melanocytes catalysing the esterification of all‐trans retinol (ATRol). In this study, we show that a stable LRAT knockdown (KD) in the human melanoma cell line SkMel23 leads to significantly increased levels of the substrate ATRol and biologically active ATRA. LRAT KD restored cellular sensitivity to retinoids analysed in cell culture assays and melanoma 3D skin models. Furthermore, ATRA‐induced gene regulatory mechanisms drive depletion of added ATRol in LRAT KD cells. PCR analysis revealed a significant upregulation of retinoid‐regulated genes such as CYP26A1 and STRA6 in LRAT KD cells, suggesting their possible involvement in mediating retinoid resistance in melanoma cells. In conclusion, LRAT seems to be important for melanoma progression. We propose that reduction in ATRol levels in melanoma cells by LRAT leads to a disturbance in cellular retinoid level. Balanced LRAT expression and activity may provide protection against melanoma development and progression. Pharmacological inhibition of LRAT activity could be a promising strategy for overcoming retinoid insensitivity in human melanoma cells.
Reforestation with native mixed‐species plantings in a temperate continental climate effectively sequesters and stabilizes carbon within decades
Authors: Cunningham Shaun C. , Cavagnaro Timothy R. , Mac Nally Ralph , Paul Keryn I. , Baker Patrick J. , Beringer Jason , Thomson James R. , Thompson Ross M. 
Published: September 2014

AbstractReforestation has large potential for mitigating climate change through carbon sequestration. Native mixed‐species plantings have a higher potential to reverse biodiversity loss than do plantations of production species, but there are few data on their capacity to store carbon. A chronosequence (5–45 years) of 36 native mixed‐species plantings, paired with adjacent pastures, was measured to investigate changes to stocks among C pools following reforestation of agricultural land in the medium rainfall zone (400–800 mm yr−1) of temperate Australia. These mixed‐species plantings accumulated 3.09 ± 0.85 t C ha−1 yr−1 in aboveground biomass and 0.18 ± 0.05 t C ha−1 yr−1 in plant litter, reaching amounts comparable to those measured in remnant woodlands by 20 years and 36 years after reforestation respectively. Soil C was slower to increase, with increases seen only after 45 years, at which time stocks had not reached the amounts found in remnant woodlands. The amount of trees (tree density and basal area) was positively associated with the accumulation of carbon in aboveground biomass and litter. In contrast, changes to soil C were most strongly related to the productivity of the location (a forest productivity index and soil N content in the adjacent pasture). At 30 years, native mixed‐species plantings had increased the stability of soil C stocks, with higher amounts of recalcitrant C and higher C : N ratios than their adjacent pastures. Reforestation with native mixed‐species plantings did not significantly change the availability of macronutrients (N, K, Ca, Mg, P, and S) or micronutrients (Fe, B, Mn, Zn, and Cu), content of plant toxins (Al, Si), acidity, or salinity (Na, electrical conductivity) in the soil. In this medium rainfall area, native mixed‐species plantings provided comparable rates of C sequestration to local production species, with the probable additional benefit of providing better quality habitat for native biota. These results demonstrate that reforestation using native mixed‐species plantings is an effective alternative for carbon sequestration to standard monocultures of production species in medium rainfall areas of temperate continental climates, where they can effectively store C, convert C into stable pools and provide greater benefits for biodiversity.
Association Between Tension‐Type Headache and Migraine With Sleep Bruxism: A Systematic Review
Authors: De Luca Canto Graziela , Singh Vandana , Bigal Marcelo E. , Major Paul W. , Flores‐Mir Carlos 
Published: September 2014

AimTo evaluate the association between tension‐type headache and migraine with sleep bruxism (SB).BackgroundThe association between SB and headaches has been discussed in both children and adults. Although several studies suggested a possible association, no systematic analysis of the available published studies exists to evaluate the quantity, quality, and risk of bias among those studies.MethodsA systematic review was undertaken, including articles that classified the headaches according to the International Classification of Headache Disorders and SB according to the criteria of the American Association of Sleep Medicine. Only articles in which the objective was to investigate the association between primary headaches (tension‐type and migraine) and SB were selected. Detailed individual search strategies for The Cochrane Library, MEDLINE, EMBASE, PubMed, and LILACS were developed. The reference lists from selected articles were also checked. A partial grey literature search was taken by using Google Scholar. The methodology of selected studies was evaluated using the quality in prognosis studies tool.ResultsOf 449 identified citations, only 2 studies, both studying adults, fulfilled the inclusion criteria. The presence of SB significantly increased the odds (study 1: odds ratio [OR] 3.12 [1.25‐7.7] and study 2: OR 3.8; 1.83‐7.84) for headaches, although studies reported different headache type.ConclusionThere is not enough scientific evidence to either support or refute the association between tension‐type headache and migraine with SB in children. Adults with SB appear to be more likely to have headache.
Characterisation of Apatites as Potential Uranium Reference Materials for Fission‐track Dating by LA‐ICP‐MS
Authors: Soares Cleber J. , Mertz‐Kraus Regina , Guedes Sandro , Stockli Daniel F. , Zack Thomas 
Published: September 2014

We report homogeneity tests on large natural apatite crystals to evaluate their potential as U reference materials for apatite fission‐track (AFT) thermochronology by laser ablation‐inductively coupled plasma‐mass spectrometry (LA‐ICP‐MS). The homogeneity tests include the measurements of major element concentrations by electron probe microanalysis (EPMA), whereas for U concentration, isotope dilution (ID) ICP‐MS and laser ablation (LA) ICP‐MS were employed. Two apatite crystals are potential reference materials for LA‐ICP‐MS analysis: a 1 cm3 fraction of a Durango crystal (7.5 μg g−1 U) and a 1 cm3 Mud Tank crystal (6.9 μg g−1 U). The relative standard deviation (1 RSD) of the U concentration determined by ID‐ICP‐MS of both apatite crystals was ≤ 1.5%, whereas 1 RSD for the LA‐ICP‐MS results was better than 4%, providing sufficient homogeneity for fission‐track dating. The results on the U homogeneity for two different apatite samples are an important step towards establishing in situ dating routines for AFT analysis by LA‐ICP‐MS.