bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects ofP16DNA Methylation on Proliferation, Senescence, and Lifespan of Human Fibroblasts
Authors: Gan Ying , Cui Chenghua , Xiang Shengyan , Zhang Baozhen , Deng Dajun 
Published: August 2018

ABSTRACTThe aim is to study the effects ofP16DNA methylation on lifespan of normal cells. An expression-controllable pTRIPZ vector expressing P26-specific zinc finger binding protein-based methyltransferase (P16-Dnmt) was used to induceP16methylation in primary CCD-I8C0 fibroblasts via stable transfection. Long-term dynamic IncuCyte analysis showed that CCD-I8C0 fibroblasts expressing baseline P16-Dnmt continued proliferating until passage-26 in the 53thpost-transfection week, while vector control cells stopped proliferating at passage-6 and completely died 2 weeks later. The proliferation rate of baseline P16-Dnmt cells was significantly higher than that of vector control cells. The proportion of P-galactosidase-positive staining cells was significantly decreased in baseline P16-Dnmt cells compared to vector control cells. The P16 expression was lost in baseline P16-Dnmt cells at and after passage-6. The average telomere length in baseline P16-Dnmt cells also gradually decreased. In conclusion,P16methylation could prevent senescence, promote proliferation, and expand lifespan of human fibroblasts, which may play a role in cancer development.SummaryA zinc finger protein-based DNA methyltransferase (P16-Dnmt) expressed at the baseline level could specifically methylateP16promoter CpG islands.P16methylation induced by baseline P16-Dnmt could significantly prevent senescence, promote proliferation, and expand lifespan of primary human fibroblasts.
Assessing genomic admixture between cryptic Plutella moth species following secondary contact
Authors: Ward Christopher M. , Baxter Simon W. 
Published: August 2018

AbstractCryptic species are genetically distinct taxa without obvious variation in morphology and are occasionally discovered using molecular or sequence datasets of populations previously thought to be a single species. The world-wide Brassica pest, Plutella xylostella (diamondback moth), has been a problematic insect in Australia since 1882, yet a morphologically cryptic species with apparent endemism (P. australiana) was only recognized in 2013. Plutella xylostella and P. australiana are able to hybridize under laboratory conditions, and it was unknown whether introgression of adaptive traits could occur in the field to improve fitness and potentially increase pressure on agriculture. Phylogenetic reconstruction of 29 nuclear genomes confirmed P. xylostella and P. australiana are divergent, and molecular dating with 13 mitochondrial genes estimated a common Plutella ancestor 1.96±0.175 MYA. Sympatric Australian populations and allopatric Hawaiian P. xylostella populations were used to test whether neutral or adaptive introgression had occurred between the two Australian species. We used three approaches to test for genomic admixture in empirical and simulated datasets including i) the f3 statistic at the level of the population, ii) pairwise comparisons of Nei’s absolute genetic divergence (dXY) between populations and iii) changes in phylogenetic branch lengths between individuals across 50 kb genomic windows. These complementary approaches all supported reproductive isolation of the Plutella species in Australia, despite their ability to hybridize. Finally, we highlight the most divergent genomic regions between the two cryptic Plutella species and find they contain genes involved with processes including digestion, detoxification and DNA binding.
Ontology of RNA Sequencing (ORNASEQ) and its application
Authors: Fisher Stephen A , Kim Junhyong 
Published: August 2018

AbstractBackground:Next-generation RNA sequencing is a rapidly developing technology with complex procedures encompassing different experimental modalities. As the technology evolves and its use expand, so does the need to capture the data provenance from these sequencing studies and the need to create new tools to manage and manipulate these provenance stores.Results:Here we used the Ontology for Biomedical Investigations (OBI) and many other ontologies from the Open Biological and Biomedical Ontology (OBO) Foundry as a framework from which to create an application ontology (ORNASEQ: Ontology of RNA sequencing) to capture data provenance for next-generation RNA sequencing studies. Additionally, we provide an extensive real-life sample provenance data set for use in developing new provenance tools and additional sequencing data models.Conclusions:The Ontology of RNA Sequencing (ORNASEQ) provides core terms for use in building data models to capture the provenance from next-generation RNA sequencing studies. The supplied sample provenance data also exemplifies many of the complexities of RNA sequencing studies and underscores the need for potent workflow management systems.
Genetic control of the HDL proteome
Authors: Pamir Nathalie , Pan Calvin , Plubell Deanna L. , Hutchins Patrick M. , Tang Chongren , Wimberger Jake , Irwin Angela , Vallim Thomas Q. de Aguiar , Heinecke Jay W. , Lusis Aldons J. 
Published: August 2018

AbstractHigh-density lipoproteins (HDL) are nanoparticles with >80 associated proteins, phospholipids, cholesterol and cholesteryl esters. A comprehensive genetic analysis of the regulation of proteome of HDL isolated from a panel of 100 diverse inbred strains of mice, Hybrid Mouse Diversity Panel (HMDP), revealed widely varied HDL protein levels across the strains. Some of this variation was explained by local, cis-acting regulation, termed cis-protein quantitative trait loci. Variations in apolipoprotein A-II and apolipoprotein C-3 affected the abundance of multiple HDL proteins indicating a coordinated regulation. We identified modules of co-varying proteins and define a protein-protein interaction network describing the protein composition of the naturally occurring subspecies of HDL in mice. Sterol efflux capacity varied up to 3-fold across the strains and HDL proteins displayed distinct correlation patterns with macrophage and ABCA1 specific cholesterol efflux capacity and cholesterol exchange, suggesting that subspecies of HDL participate in discrete functions. The baseline and stimulated sterol efflux capacity phenotypes associated with distinct QTLs with smaller effect size suggesting a multi genetic regulation. Our results highlight the complexity of HDL particles by revealing high degree of heterogeneity and intercorrelation, some of which is associated with functional variation, supporting the concept that HDL-cholesterol alone is not an accurate measure of HDL’s properties such as protection against CAD.
Acute Psychological Stress Triggers Circulating Cell-Free Mitochondrial DNA
Authors: Trumpff Caroline , Marsland Anna L. , Basualto-Alarcón Carla , Martin James L. , Carroll Judith E. , Sturm Gabriel , Vincent Amy E. , Mosharov Eugene V. , Gu Zhenglong , Kaufman Brett A. , Picard Martin 
Published: August 2018

AbstractIntrinsic biological mechanisms transduce psychological stress into physiological adaptation, but the role of mitochondria and mitochondrial DNA (mtDNA) in this process has not been defined in humans. Here, we show that similar to physical injury, psychological stress triggers elevation in circulating cell- free mtDNA (ccf-mtDNA). Healthy midlife adults exposed on two separate occasions to a brief psychological challenge exhibit a 2-3-fold increase in ccf-mtDNA, with no change in nuclear DNA levels, establishing the magnitude and specificity to ccf-mtDNA. In cell-based studies, we show that glucocorticoid signaling – a consequence of psychological stress in humans – is sufficient to induce mtDNA extrusion in a time frame consistent with human psychophysiology. Collectively, these findings provide the first evidence that psychological stress induces ccf-mtDNA and implicate glucocorticoid signaling as a trigger for ccf-mtDNA release. Further work is needed to examine the functional significance of psychological stress-induced ccf-mtDNA as a mitokine in humans.
TF-TWAS: Transcription-factor polymorphism associated with tissue-specific gene expression
Authors: Tang Yi-Ching , Gottlieb Assaf 
Published: August 2018

AbstractTranscriptional regulation is associated with a broad range of diseases. Methods associating genetic polymorphism with gene transcription levels offer key insights for understanding the transcriptional regulation plan. The majority of gene imputation methods focus on modeling polymorphism in the cis regions of the gene, partially owing to the large genetic search space. We hypothesize that polymorphism within transcription factors (TFs) may help explain transcription levels of their transcribed genes.Here, we test this hypothesis by developing TF-TWAS: imputation models that integrate transcription factor information with transcription-wide association study methodology. By comparing TF-TWAS models to base models that use only gene cis information, we are able to estimate possible mechanisms of the TF polymorphism effect – TF expression or binding affinity within four tissues – whole blood, liver, brain hippocampus and coronary artery.We identified 48 genes where the TF-TWAS models explain significantly better their expression than cis models alone in at least one of the four tissues. Sixteen of these genes are associated with various diseases, including cancer, neurological, psychiatric and rare genetic diseases. Our method is a new expansion to transcriptome-wide association studies and enables the identification of new associations between polymorphism in transcription factor and gene transcription levels.
Spatial organization of Clostridium difficile S-layer biogenesis
Authors: Oatley Peter , Kirk Joseph A. , Ma Shuwen , Jones Simon , Fagan Robert P. 
Published: August 2018

AbstractSurface layers (S-layers) are protective protein coats which form around all archaea and most bacterial cells. Clostridium difficile is a Gram-positive bacterium with an S-layer covering its peptidoglycan cell wall. The S-layer in C. difficile is constructed mainly of S-layer protein A (SlpA), which is a key virulence factor and an absolute requirement for disease. S-layer biogenesis is a complex multi-step process, disruption of which has severe consequences for the bacterium. We examined the subcellular localization of SlpA secretion and S-layer growth; observing formation of S-layer at specific sites that coincide with cell wall synthesis, while the secretion of SlpA from the cell is relatively delocalized. We conclude that this delocalized secretion of SlpA leads to a pool of precursor in the cell wall which is available to repair openings in the S-layer formed during cell growth or following damage.
Bipolar Switching by HCN Voltage Sensor Underlies Hyperpolarization Activation
Authors: Cowgill John , Klenchin Vadim A. , Alvarez-Baron Claudia , Tewari Debanjan , Blair Alexander , Chanda Baron 
Published: August 2018

SUMMARYDespite sharing a common architecture with archetypal voltage-gated ion channels (VGIC), the hyperpolarization- and cyclic AMP-activated ion (HCN) channels open upon hyperpolarization rather than depolarization. The basic motions of voltage sensor and pore gates are conserved implying that these domains are inversely coupled in HCN channels. Using structure-guided protein engineering, we systematically assembled an array of mosaic channels that display the full complement of voltage-activation phenotypes observed in the VGIC superfamily. Our studies reveal that the voltage-sensing S3b-S4 transmembrane segment of the HCN channel has an intrinsic ability to drive pore opening in either direction. Specific contacts at the pore-voltage sensor interface and unique interactions near the pore gate forces the HCN channel into a hERG-like inactivated state, thereby obscuring their opening upon depolarization. Our findings reveal an unexpected common principle underpinning voltage gating in the VGIC superfamily and identify the essential determinants of gating polarity.
A screen for targets of the Drosophila pseudokinase Tribbles identifies Neuralized and Mindbomb, ubiquitin ligases that mediate Notch signaling
Authors: Shipman Anna , Nauman Christopher , Haymans Britney , Silverstein Rachel , Dobens Leonard L. 
Published: August 2018

ABSTRACTDrosophila Tribbles (Trbl) is the founding member of a family of pseudokinases with conserved roles in antagonizing cell division, tissue growth and cell differentiation. In humans, three Tribbles isoforms serve as adaptor proteins, binding targets such as Cdc25 phosphatase, Akt kinase or the transcription factor C/EBP to block their activity or direct their proteosomal degradation. Mutations in Tribbles family members are associated with susceptibility to diabetes and cancer, notably Notch-induced tumor growth. Trbl misexpression in the fly wing disk leads to a block in mitosis associated with decreased levels of String/Cdc25 and increased levels of Cyclin B leading to reduced overall wing size and reduced trichome density. We show these Trbl growth-restricting phenotypes can be suppressed by manipulating levels of known Trbl targets, and use this sensitized wing system to screen a collection of growth regulating open reading frames (ORFs) to search for enhancers and suppressors affecting cell and tissue size. By precisely measuring morphometric changes in wing phenotypes using a computer-based tool, we detected synthetic interactions with several E3 ubiquitin ligases, and focused our analysis on the Notch pathway components Neuralized (Neur) and Mindbomb1 (Mib1). In the wing, notum and egg chamber epithelia, Trbl misexpression suppressed Neur and Mib1 activities and stabilized the accumulation of both proteins. To understand these interactions, we used yeast two-hybrid assays to show Trbl physically bound to both Neur and Mib1. Our data are consistent with published reports that mammalian Tribbles3 modulates Notch responses by binding and stabilizing Mindbomb and indicate that a wing misexpression approach is useful to identify novel components in a conserved Tribbles signaling pathway.AUTHOR SUMMARYTribbles pseudokinases are adaptor molecules, binding diverse targets regulating cell differentiation, growth and proliferation and directing their proteasomal degradation. To search for novel targets of Drosophila Tribbles, we adopted a wing co-misexpression scheme and measured changes in cell/tissue size to identify enhancers and suppressors of the Tribbles phenotype. We show the Notch pathway components Neuralized and Mindbomb1 E3 ligases act as Tribbles suppressors and demonstrate that Tribbles modulates their levels and activites. Recent demonstration that mammalian Tribbles 3 binds the E3 ligase Mindbomb to promote ligand-mediated Notch activation implies a conserved role for Tribbles family members in Notch activation.
“Stickiness”: gauging students’ attention to online learning activities
Authors: Robinson Ainslie , Cook David 
Published: August 2018

Purpose
Online content developers use the term “stickiness” to refer to the ability of their online service or game to attract and hold the attention of users and create a compelling and magnetic reason for them to return repeatedly (examples include virtual pets and social media). In business circles, the same term connotes the level of consumer loyalty to a particular brand. This paper aims to extend the concept of “stickiness” not only to describe repeat return and commitment to the learning “product”, but also as a measure of the extent to which students are engaged in online learning opportunities.

Design/methodology/approach
This paper explores the efficacy of several approaches to the monitoring and measuring of online learning environments, and proposes a framework for assessing the extent to which these environments are compelling, engaging and “sticky”.

Findings
In particular, the exploration so far has highlighted the difference between how lecturers have monitored the engagement of students in a face-to-face setting versus the online teaching environment.

Practical implications
In the higher education environment where increasingly students are being asked to access learning in the online space, it is vital for teachers to be in a position to monitor and guide students in their engagement with online materials.

Originality/value
The mere presence of learning materials online is not sufficient evidence of engagement. This paper offers options for testing specific attention to online materials allowing greater assurance around engagement with relevant and effective online learning activities.
Populism and Fiscal Illusion
Authors: Davidson Sinclair 
Published: August 2018

AbstractThere is a widespread concern that anti‐elitist or populist opinion is on the rise. The policy concern is that political opportunists would exploit voter rational ignorance for their own cynical purposes. In this article I demonstrate that, in the field of taxation, this sort of behaviour already occurs. Fiscal illusion can be described as deceiving taxpayer‐voters into paying more tax than they would otherwise agree to. Taxpayers are already victims of political opportunism unrelated to the rise of populism.
Top‐Down Constitutional Conventions
Authors: Perry Adam , Tucker Adam 
Published: August 2018

AbstractMany scholars think that all conventions of the constitution emerge from the bottom up, out of the practices of constitutional actors. Here we develop the first systematic account of conventions that are imposed from the top down, through prescriptions by constitutional actors. We show that ‘top‐down conventions’ (as we term them) can be created through the use of normative rule‐making powers; that powers of the right kind are sometimes conferred by ‘bottom‐up conventions’; that these powers are often exercised; and, as a result, that top‐down conventions are increasingly common. We show, too, that as the formal, systematic, and intentional products of a small number of constitutional actors, top‐down conventions are a potentially illegitimate form of constitutional regulation.
Childhood growth of singletons conceived following in vitro fertilisation or intracytoplasmic sperm injection: a systematic review and meta‐analysis
Authors: Bay B , Lyngsø J , Hohwü L , Kesmodel US 
Published: August 2018

BackgroundAssisted reproductive techniques are associated with an increased risk of adverse pregnancy outcomes, including low birthweight and intrauterine growth restriction. Yet, the long‐term follow‐up on the growth of these children is limited.ObjectiveTo systematically review the literature on post‐neonatal height and weight among children conceived following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment, compared with that of children born after spontaneous conception.Search strategyA systematic computerised literature search using the online databases PubMed, Embase, and Scopus.Selection criteriaCohort or case–control studies with an exposed group of singletons conceived following IVF or ICSI along with a control group of spontaneously conceived singletons.Data collection and analysisStudies were reviewed by at least two authors. Meta‐analyses were conducted using Cochrane Review Manager. The quality of the studies was assessed with the Newcastle–Ottawa Scale.Main resultsTwenty studies were included, with 13 of these eligible for meta‐analyses. The meta‐analyses compared 3972 children born after IVF/ICSI with 11 012 spontaneously conceived children and revealed no statistically significant difference in child weight [mean difference (MD) in weight of −160 g; 95% confidence interval (95% CI) −360, 3]. When stratifying by age of child at follow‐up, we found a significant lower weight in children aged 0–4 years conceived following IVF/ICSI treatment (MD −180 g; 95% CI −320, −4), but this was no longer significant in children from 5 years of age (MD −160 g; 95% CI −580, 260). The pooled analysis revealed no statistically significant difference in childhood height.ConclusionsIn vitro fertilisation/ICSI was not associated with long‐term weight and height.Tweetable abstractChildren born following IVF/ICSI do not have impaired long‐term weight or height compared with spontaneously conceived children.
Application of 2012 EULAR/ACR criteria for polymyalgia rheumatica to Korean patients previously classified by Chuang and Hunder criteria or Healey criteria
Authors: Park Eun Seong , Ahn Sung Soo , Jung Seung Min , Song Jungsik , Park Yong‐Beom , Lee Sang‐Won 
Published: August 2018

AbstractAimTo apply 2012 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria to Korean patients previously classified as polymyalgia rheumatica (PMR) by Chuang and Hunder criteria or Healey criteria and investigated whether they might be still reclassified as PMR or not.MethodsWe retrospectively reviewed the medical records of 113 previously classified PMR patients. We applied 2012 EULAR/ACR criteria without ultrasonography to PMR patients, and fulfilment required at least 4 points. We evaluated odds ratios (OR) using logistic regression analyses.ResultsThe mean age was 61.7 years. Seventy‐one patients (62.8%) fulfilled Chuang and Hunder criteria, and 113 patients (100%) met Healey criteria. When we applied 2012 EULAR/ACR criteria, 98 patients fulfilled essential items (≥50 years, bilateral shoulder aching and abnormal C‐reactive protein or erythrocyte sedimentation rate), and only 80 patients achieved points ≥4. Eight patients fulfilling the criteria exhibited higher frequencies of all the detailed items than those who did not. In multivariate logistic regression analysis, absence of rheumatoid factor or anti‐citrullinated peptide antibodies was the only independent contributing item to the fulfilment of 2012 EULAR/ACR criteria (OR 23.571, 95% CI 6.357‐87.407, P < .001). When we reclassified 33 excluded patients, the most common newly classified disease was generalized osteoarthritis (24.2%), followed by osteoporosis with compression fracture (15.2%).ConclusionEighty of 113 patients (81.6%) previously classified by Chuang and Hunder criteria or Healey criteria fulfilled 2012 EULAR/ACR criteria for PMR.
Vasculitis research: Current trends and future perspectives
Authors: Misra Durga P. , Naidu Godasi S. R. S. N. K. , Agarwal Vikas , Sharma Aman 
Published: August 2018

AbstractWe discuss recent and prospective research in small and large vessel vasculitis. Large cohorts of Takayasu arteritis (TA) have been recently published from across the world, clarifying our understanding of this uncommon disease. Novel open‐ended approaches like large‐scale genotyping, proteomics and metabolomics have helped gain novel insights into TA, giant cell arteritis (GCA) and anti‐neutrophil cytoplasmic antibody‐associated vasculitis (AAV). Recent advances in the imaging of TA and GCA offer promise for earlier diagnosis and better monitoring of response to therapy. Although two randomized controlled trials of abatacept and tocilizumab failed to meet their primary end‐points, successful large‐scale studies of abatacept and tocilizumab in GCA hold promise for better disease control. While cyclophosphamide has revolutionized the management of AAV, increasing use of rituximab as an alternative induction regimen, as well as use of novel approaches involving reduced or no corticosteroid use for AAV and alternative agents such as avacopan (a complement 5a receptor antagonist) hold promise for lesser toxic induction regimens in the future. Increasingly, the risk of cardiovascular events and comorbidities such as osteoporosis are being recognized as factors affecting long‐term prospects of patients with vasculitis. There is a shift in emphasis to utilize patient‐reported outcomes to more accurately gauge the impact of vasculitides and their treatment.