bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review and Meta-analysis of the Effort-Reward Imbalance Model of Workplace Stress and Hypothalamic-Pituitary-Adrenal Axis Measures of Stress
Authors: Eddy Pennie , Wertheim Eleanor H. , Hale Matthew W. , Wright Bradley J. 
Published: July 2017

ABSTRACT

Objective
The association between effort-reward imbalance (ERI) and various health outcomes has been well documented over the past 20 years, but the mechanisms responsible for this association remain unclear. The present meta-analysis assessed the associations of ERI and overcommitment (OC) in the workplace with hypothalamic-pituitary-adrenal (HPA) axis measures.

Methods
Electronic databases were searched with the phrase “effort*reward*imbalance,” which yielded 319 studies leading to 56 full-text studies being screened. Thirty-two studies within 14 articles met inclusion criteria and were meta-analyzed using mixed and random effects models.

Results
Greater ERI was associated with increased HPA axis activity (r = .09, p < .001, k = 14, N = 2541). The cortisol awakening response (r = .14, p < .001, k = 9, N = 584) and cortisol waking concentrations (r = .12, p = .01, k = 6, N = 493) were the only HPA measures associated with ERI. OC was also associated with greater HPA axis activity (r = .06, p < .01, k = 10, N = 1918). Cortisol (PM) (r = .13, p = .02, k = 3, N = 295) was the only HPA measure associated with OC.

Conclusions
ERI and OC were similarly related with HPA responsivity. However, because OC moderated the relationship between ERI and HPA axis markers, the importance of OC should not be overlooked. Because OC is likely more malleable than ERI to intervention, this may be a promising avenue for future research.
Accelerated DNA Methylation Age: Associations With Posttraumatic Stress Disorder and Mortality
Authors: Wolf Erika J. , Logue Mark W. , Stoop Tawni B. , Schichman Steven A. , Stone Annjanette , Sadeh Naomi , Hayes Jasmeet P. , Miller Mark W. 
Published: July 2017

ABSTRACT

Objective
Recently developed indices of cellular age based on DNA methylation (DNAm) data, referred to as DNAm age, are being used to study factors that influence the rate of aging and the health correlates of these metrics of the epigenetic clock. This study evaluated associations between trauma exposure, posttraumatic stress disorder (PTSD) symptoms, and accelerated versus decelerated DNAm age among military veterans. We also examined whether accelerated DNAm age predicted mortality over the course of a 6.5-year medical record review period.

Methods
Three hundred thirty-nine genotype-confirmed white, non-Hispanic, middle-aged, trauma-exposed veterans underwent psychiatric assessment and genome-wide DNAm analysis. DNAm age was calculated using a previously validated algorithm. Medical records were available for a subset of 241 veterans and were reviewed approximately 6.5 years after DNA collection and PTSD assessment.

Results
PTSD hyperarousal symptoms were associated with accelerated DNAm age (β = 0.20, p = .009) but trauma exposure and total PTSD severity were not. Accelerated DNAm age was also associated with 13% increased risk for all-cause mortality (hazard ratio = 1.13, 95% confidence interval = 1.01–1.26) during the medical record review period.

Conclusions
Findings of this study replicate the association between PTSD and accelerated DNAm age and suggest that this effect may be specific to the hyperarousal symptom cluster. Results point to the potential utility of DNAm age algorithms for identifying individuals who are aging at an accelerated rate and for determining the factors that influence this process.
The Association of Cigarette Smoking With High-Frequency Heart Rate Variability: An Ecological Momentary Assessment Study
Authors: Bodin Fernando , McIntyre Kathleen M. , Schwartz Joseph E. , McKinley Paula S. , Cardetti Caitlyn , Shapiro Peter A. , Gorenstein Ethan , Sloan Richard P. 
Published: July 2017

ABSTRACT

Objective
Evidence from both laboratory and observational studies suggests that acute and chronic smoking leads to reduced high-frequency heart rate variability (HF-HRV), a measure of cardiac vagal regulation. We used ecological momentary assessment (EMA) to study the effect of smoking on concurrent HF-HRV in a trial measuring the effects of hostility reduction and compared 24-hour HF-HRV in smokers and nonsmokers.

Method
Ambulatory electrocardiogram data were collected before randomization from 149 healthy individuals with high hostility levels (20–45 years, body mass index ≤ 32 kg/m2) and paired with concurrent EMA ratings of smoking and physical position during waking hours. A multilevel mixed model was estimated associating ln(HF-HRV) from smoking status (between-person factor) and person-centered momentary smoking (within-person factor, treated as a random effect), adjusting for momentary physical position, medication use, and consumption of alcohol and caffeine.

Results
Thirty-five smokers and 114 nonsmokers provided both EMA and HF-HRV data. Within smokers, ln HF-HRV was reduced by 0.31 millisecond2 (p = .04) when participants reported having recently smoked cigarettes, compared with when they had not. The 24-hour HF-HRV was significantly lower in smokers (M [SD] = 5.24 [0.14] milliseconds2) than nonsmokers (5.63 ± 0.07 milliseconds2, p = .01).

Conclusions
In healthy smokers with high hostility levels used as their own controls during daily living, smoking acutely reduced HF-HRV. HF-HRV was also reduced in smokers as compared with nonsmokers. Although limited by a small sample of individuals with high hostility levels, these findings nonetheless provide additional evidence that cardiac vagal regulation is lowered by cigarette smoking, which may be one of the numerous pathophysiological effects of smoking.
Update on new muscle glycogenosis
Authors: Laforêt Pascal , Malfatti Edoardo , Vissing John 
Published: July 2017

Purpose of review
The field of muscle glycogenoses has progressed in recent years by the identification of new disorders, and by reaching a better understanding of pathophysiology of the disorders and the physiology of glycogen metabolism.

Recent findings
In this review, we describe the clinical and pathological features of the three most recently described muscle glycogenoses caused by recessive mutations in GYG1, RBCK1 and PGM1. The three involved enzymes play different roles in glycogen metabolism. Glycogenin-1 (GYG1) is involved in the initial steps of glycogen synthesis, whereas phosphoglucomutase catalyzes two metabolic pathways; the connection between galactose and glycogen on one side, and glucose metabolism on the other side. The metabolic consequences of mutations in the ubiquitin ligase gene RBCK1 are still poorly understood. GYG1 deficiency has been associated with cardiomyopathies with abnormal storage material in the heart, but most cases present with a polyglucosan body myopathy without cardiac involvement.

Summary
The recent identification of new glycogenosis not only allows to improve the knowledge of glycogen metabolism, but also builds bridges with protein glycosylation and immune system.
Monomerization of Far-Red Fluorescent Proteins
Authors: Wannier Timothy M. , Gillespie Sarah , Hutchins Nicholas , McIsaac R. Scott , Brown Kevin S. , Mayo Stephen L. 
Published: July 2017

AbstractAnthozoaclass red fluorescent proteins (RFPs) are frequently used as biological markers, with far-red emitting variants (λem~ 600 – 900 nm) sought for whole animal imaging because biological tissues are permeable to light in this range. A barrier to the use of naturally occurring RFP variants as molecular markers is that all are tetrameric, which is not ideal for cell biological applications. Efforts to engineer monomeric RFPs have usually produced dimmer and blue-shifted variants, as the chromophore is sensitive to small structural perturbations. In fact, despite much effort, only four native RFPs have been successfully monomerized, leaving the vast majority of RFP biodiversity untapped in biomarker development. Here we report the generation of monomeric variants of HcRed and mCardinal, both far-red dimers, and describe a comprehensive methodology for the rapid monomerization of novel red-shifted oligomeric RFPs. Among the resultant variants, is mKelly1 (emission maximum: λem= 656 nm), which along with the recently reported mGarnet2 (1), forms a new class of bright, monomeric, far-red FPs.
Spores and soil from six sides: interdisciplinarity and the environmental biology of anthrax (Bacillus anthracis)
Authors: Carlson Colin J. , Getz Wayne M. , Kausrud Kyrre L. , Cizauskas Carrie A. , Blackburn Jason K. , Bustos Carrillo Fausto A. , Colwell Rita , Easterday W. Ryan , Ganz Holly H. , Kamath Pauline L. , Økstad Ole Andreas , Turner Wendy C. , Kolstø Anne-Brit , Stenseth Nils C. 
Published: July 2017

AbstractEnvironmentally Transmitted Diseases Are Comparatively Poorly Understood And Managed, And Their Ecology Is Particularly Understudied. Here We Identify Challenges Of Studying Environmental Transmission And Persistence With A Six-Sided Interdisciplinary Review Of The Biology Of Anthrax (Bacillus Anthracis). Anthrax Is A Zoonotic Disease Capable Of Maintaining Infectious Spore Banks In Soil For Decades (Or Even Potentially Centuries), And The Mechanisms Of Its Environmental Persistence Have Been The Topic Of Significant Research And Controversy. Where Anthrax Is Endemic, It Plays An Important Ecological Role, Shaping The Dynamics Of Entire Herbivore Communities. The Complex Eco-Epidemiology Of Anthrax, And The Mysterious Biology OfBacillus AnthracisDuring Its Environmental Stage, Have Necessitated An Interdisciplinary Approach To Pathogen Research. Here, We Illustrate Different Disciplinary Perspectives Through Key Advances Made By Researchers Working In Etosha National Park, A Long-Term Ecological Research Site In Namibia That Has Exemplified The Complexities Of Anthrax’S Enzootic Process Over Decades Of Surveillance. In Etosha, The Role Of Scavengers And Alternate Routes (Waterborne Transmission And Flies) Has Proved Unimportant, Relative To The Long-Term Persistence Of Anthrax Spores In Soil And Their Infection Of Herbivore Hosts. Carcass Deposition Facilitates Green-Ups Of Vegetation To Attract Herbivores, Potentially Facilitated By Anthrax Spores’ Role In The Rhizosphere. The Underlying Seasonal Pattern Of Vegetation, And Herbivores’ Immune And Behavioral Responses To Anthrax Risk, Interact To Produce Regular “Anthrax Seasons” That Appear To Be A Stable Feature Of The Etosha Ecosystem. Through The Lens Of Microbiologists, Geneticists, Immunologists, Ecologists, Epidemiologists, And Clinicians, We Discuss How Anthrax Dynamics Are Shaped At The Smallest Scale By Population Genetics And Interactions Within The Bacterial Communities Up To The Broadest Scales Of Ecosystem Structure. We Illustrate The Benefits And Challenges Of This Interdisciplinary Approach To Disease Ecology, And Suggest Ways Anthrax Might Offer Insights Into The Biology Of Other Important Pathogens.Bacillus Anthracis,And The More Recently EmergedBacillus CereusBiovarAnthracis, Share Key Features With Other Environmentally-Transmitted Pathogens, Including Several Zoonoses And Panzootics Of Special Interest For Global Health And Conservation Efforts. Understanding The Dynamics Of Anthrax, And Developing Interdisciplinary Research Programs That Explore Environmental Persistence, Is A Critical Step Forward For Understanding These Emerging Threats.
Genome-wide strategies identify molecular niches regulated by connective tissue-associated transcription factors
Authors: Orgeur Mickael , Martens Marvin , Leonte Georgeta , Nassari Sonya , Bonnin Marie-Ange , Börno Stefan T. , Timmermann Bernd , Hecht Jochen , Duprez Delphine , Stricker Sigmar 
Published: July 2017

AbstractBackgroundConnective tissues support, connect and separate tissues and organs, playing crucial roles in development, homeostasis and fibrosis. Cell specification and differentiation is triggered by the activity of specific transcription factors. While key transcription factors have been identified for differentiation processes of most tissues, connective tissue differentiation remains largely unstudied.ResultsTo gain insight into the regulatory cascades involved in connective tissue differentiation, we selected five zinc finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in the differentiation of mesenchymal cells into connective tissue subtypes. We combined RNA-seq with ChIP-seq profiling in chick limb cells following overexpression of individual transcription factors. We identified a set of common genes regulated by all five transcription factors, which constitutes a connective tissue core expression set. This common core was enriched in genes associated with axon guidance and myofibroblast signature. In addition, each of the transcription factors regulated a different set of extracellular matrix components and signalling molecules, which define local molecular niches important for connective tissue development and function.ConclusionsThe established regulatory network identifies common and distinct molecular signatures downstream of five connective tissue-associated transcription factors and provides insight into the signalling pathways governing limb connective tissue differentiation. It also suggests a concept whereby local molecular niches can be created via the expression of specific transcription factors impinging on the specification of microenvironments.
Pitch discrimination performance of ferrets and humans on a go/no-go task
Authors: Walker Kerry MM , Davies Amelia , Bizley Jennifer K , Schnupp Jan WH , King Andrew J 
Published: July 2017

ABSTRACTAnimal models are widely used to examine the neurophysiological basis of human pitch perception, and it is therefore important to understand the similarities and differences in pitch processing across species. Pitch discrimination performance is usually measured using two-alternative forced choice (2AFC) procedures in humans and go/no-go tasks in animals, potentially confounding human-to-animal comparisons. We have previously shown that pitch discrimination thresholds of ferrets on a 2AFC task are markedly poorer than those reported for go/no-go tasks in other non-human species (Walkeret al., 2009). To better compare the pitch discrimination performance of ferret with other species, here we measure pitch change detection thresholds of ferrets and humans on a common, appetitive go/no-go task design. We found that ferrets’ pitch thresholds were ~10 times larger than that of humans on the go/no-go task, and were within the range of thresholds reported in other non-human species. Interestingly, ferrets’ thresholds were 100 times larger than human thresholds on a 2AFC pitch discrimination task using the same stimuli. These results emphasize that sensory discrimination thresholds can differ across tasks, particularly for non-human animals. Performance on our go/no-go task is likely to reflect different neurobiological processes than that on our 2AFC task, as the former required the subjects only to detect a pitch change while the latter required them to label the direction of the pitch change.ABBREVIATIONS2AFC2-Alternative Forced ChoiceF0Fundamental FrequencyHIGHLIGHTSPitch discrimination thresholds of ferrets were 10 times larger than those of humans on a go/no-go taskFerrets’ pitch thresholds are similar to those reported for a range of other mammalsPitch thresholds of ferrets, but not humans, were drastically better on the go/no-go task than a 2AFC task using the same stimuli
MediSyn: uncertainty-aware visualization of multiple biomedical datasets to support drug treatment selection
Authors: He Chen , Micallef Luana , Tanoli Zia-ur-Rehman , Kaski Samuel , Aittokallio Tero , Jacucci Giulio 
Published: July 2017

AbstractBackgroundDispersed biomedical databases limit user exploration to generate structured knowledge.Linked Dataunifies data structures and makes the dispersed data easy to search across resources, but it lacks supporting human cognition to achieve insights. In addition, potential errors in the data are difficult to detect in their free formats. Devising a visualization that synthesizes multiple sources in such a way that links between data sources are transparent, and uncertainties, such as data conflicts, are salient is challenging.ResultsTo investigate the requirements and challenges of uncertainty-aware visualizations of linked data, we developed MediSyn, a system that synthesizes medical datasets to support drug treatment selection. It uses a matrix-based layout to visually link drugs, targets (e.g., mutations), and tumor types. Data uncertainties are salient in MediSyn; for example, (i) missing data are exposed in the matrix view of drug-target relations; (ii) inconsistencies between datasets are shown via overlaid layers; and (iii) data credibility is conveyed through links to data provenance.ConclusionsThrough the synthesis of two manually curated datasets, cancer treatment biomarkers and drug-target bioactivities, a use case shows how MediSyn effectively supports the discovery of drug-repurposing opportunities. A study with six domain experts indicated that MediSyn benefited the drug selection and data inconsistency discovery. Though linked publication sources supported user exploration for further information, the causes of inconsistencies were not easy to find. Additionally, MediSyn could embrace more patient data to increase its informativeness. We derive design implications from the findings.
SANe: The Seed Active Network for Discovering Transcriptional Regulatory Programs of Seed Development
Authors: Gupta Chirag , Krishnan Arjun , Schneider Andrew , Denbow Cynthia , Collakova Eva , Wolinski Pawel , Pereira Andy 
Published: July 2017

AbstractDeveloping seeds undergo coordinated physiological and morphological changes crucial for development of the embryo, dormancy and germination. The metabolic changes that occur during seed development are regulated by interconnected network of Transcription Factors (TFs) that regulate gene expression in a spatiotemporal manner. The complexity of these networks is such that the TFs that play key regulatory roles during seed development are largely unknown. In this study, we created a genome-scale regulatory network dedicated to describing regulation of biological processes within various compartments and developmental stages of Arabidopsis seeds. Differential network analysis revealed key TFs that rewire their targeting patterns specifically during seed development, many of which were already known, and a few novel ones that we verified experimentally. Our method shows that a high-resolution tissue-specific transcriptome dataset can be accurately modeled as a functional regulatory network predictive of related TFs. We provide an easy to use webtool using which researchers can upload a newly generated transcriptome and identify key TFs important to their dataset as well as gauge their regulatory effect on phenotypes observed in the experiment. We refer to this network as Seed Active Network (SANe) and made it accessible athttps://plantstress-pereira.uark.edu/SANe/. We anticipate SANe will facilitate the discovery of TFs yet unknown for their involvement in seed related metabolic pathways and provide an interface to generate new hypothesis for experimentation.
Thecis-regulatory dynamics of embryonic development at single cell resolution
Authors: Cusanovich Darren A. , Reddington James P. , Garfield David A. , Daza Riza , Marco-Ferreres Raquel , Christiansen Lena , Qiu Xiaojie , Steemers Frank , Trapnell Cole , Shendure Jay , Furlong Eileen E.M. 
Published: July 2017

ABSTRACTSingle cell measurements of gene expression are providing new insights into lineage commitment, yet the regulatory changes underlying individual cell trajectories remain elusive. Here, we profiled chromatin accessibility in over 20,000 single nuclei across multiple stages ofDrosophilaembryogenesis. Our data reveal heterogeneity in the regulatory landscape prior to gastrulation that reflects anatomical position, a feature that aligns with future cell fate. During mid embryogenesis, tissue granularity emerges such that cell types can be inferred by their chromatin accessibility, while maintaining a signature of their germ layer of origin. We identify over 30,000 distal elements with tissue-specific accessibility. Using transgenic embryos, we tested the germ layer specificity of a subset of predicted enhancers, achieving near-perfect accuracy. Overall, these data demonstrate the power of shotgun single cell profiling of embryos to resolve dynamic changes in open chromatin during development, and to uncover thecis-regulatory programs of germ layers and cell types.
PI3Kδ inhibition supports memory T cells with enhanced antitumor fitness
Authors: Bowers Jacob S. , Majchrzak Kinga , Nelson Michelle H. , Aksoy Bulent Arman , Wyatt Megan M. , Smith Aubrey S. , Bailey Stefanie R. , Neal Lillian , Hammerbacher Jeff , Paulos Chrystal M. 
Published: July 2017

SUMMARYPhosphatidylinositol-3-kinase p110δ (PI3Kδ) inhibition by Idelalisib (CAL-101) in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells (Tregs). Yet, little is known about the direct impact of PI3Kδ blockade on effector T cells from CAL-101 therapy. Herein, we demonstrate a direct effect of p110δ inactivation via CAL-101 on murine and human CD8+T cells that promotes a strong undifferentiated memory phenotype (elevated CD62L/CCR7, CD127 and Tcf7). These CAL-101 T cells also persisted longer after transfer and exerted stronger antitumor immunity compared to traditionally expanded CD8+T cells in two solid tumor models. Thus, this report describes a novel direct enhancement of CD8+T cell memory by a p110δ inhibitor that leads to markedly improved tumor regression. This finding has significant implications to improve outcomes from next generation cancer immunotherapies.HighlightsIn vitroblockade of PI3K p110δ with CAL-101 endows antitumor T cells with a stronger memory phenotype than those treated with AKTiThe strong memory phenotype of CAL-101 treated cells translates into improved survival of mice bearing aggressive tumors after adoptive transfer of these T cellsHuman CAR engineered T cells treated with CAL-101 possess an enhanced memory phenotype and robust antitumor efficacyThe antitumor efficacy of CAL-101 primed T cells is not mediated by high CD62L or CD127 expression, but is likely driven by their stem memory phenotypeeTOC BlurbBowers et al report a novel function of PI3K blockade using the p110δ subunit inhibitor CAL-101 to induce memory and antitumor potency in CD8+T cells.Ex vivotreatment of T cells with CAL-101 leads to improved antitumor control and subject survival in both murine transgenic T cell and human CAR T cell models.