bluuebunny/crossref_metadata_2025 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

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

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

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.
Describing the Roles and Responsibilities of Nutrition Staff and Nutrition Care Policies in Acute Care Facilities
Authors: Hand Rosa K. , Abram Jenica K.
Published: July 2017

Using the results from a survey of 101 acute care facilities, this article describes the roles of nutrition professionals and nutrition care policies. The most common roles for clinical nutrition managers were policy development and monitoring for quality care (>98%); nutrition and dietetic technicians, registered were most commonly involved in patient education (93%). Responsibility for nutrition screening varies, with nurses and registered dietitian nutritionists most frequently involved. The plurality of facilities (48%) requires a nutrition assessment within 2 days of positive screening. These data illuminate standard nutrition practices in acute care facilities and can be used for comparisons between facilities and over time.
Use of Computer-Assisted Instruction for Teaching Nutrition-Focused Physical Examination to Dietetics Students
Authors: Redgate Jillian , Brody Rebecca , Marcus Andrea Fleisch , Tomesko Jennifer , Gomes Allison , Touger-Decker Riva
Published: July 2017

The purpose of this study was to assess changes in knowledge scores of dietetic students enrolled in a computer-assisted instruction (CAI) module about nutrition focused physical examination (NFPE). The module included live virtual classroom sessions, multi-media presentations, online discussion forums, and case studies. Students completed multiple-choice pre/postassessments and course evaluations. All 21 participants had significant increases in knowledge scores from a mean of 29.2 (SD = 4.47) at pretest to a mean of 39.4 (SD = 2.91) at posttest (p < .001). Student evaluations were positive. These findings support future larger controlled trials to assess use of CAI for NFPE training with dietetic students.
Assessing the Efficacy of Nutritional Rating Systems in Altering Unhealthy Dietary Patterns
Authors: Faltus Colleen M.
Published: July 2017

On the basis of the rates of obesity and other chronic diseases in the United States, the appropriate tools for adopting healthier lifestyles are needed. The objective of this project was to compile information from registered dietitians regarding the efficacy of 5 nutritional rating systems for altering unhealthy dietary patterns. A validated electronic survey was administered through an electronic survey system to all US-based registered dietitians (n = 90 224). Findings indicate that nutrient-specific rating systems were more likely to be effective in altering unhealthy dietary patterns than summary indicator nutritional ratings systems (P < .001) when analyzing data by region and experience.
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.

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

Anthozoaclass 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

Environmentally 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

Background

Connective 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.

Results

To 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.

Conclusions

The 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

Animal 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.

ABBREVIATIONS

2AFC

2-Alternative Forced Choice

F0

Fundamental Frequency

HIGHLIGHTS

Pitch discrimination thresholds of ferrets were 10 times larger than those of humans on a go/no-go task

Ferrets’ pitch thresholds are similar to those reported for a range of other mammals

Pitch 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

Background

Dispersed 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.

Results

To 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.

Conclusions

Through 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

Developing 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.
Evolutionary origins and diversification of testis-specific short histone H2A variants in mammals
Authors: Molaro Antoine , Young Janet M. , Malik Harmit S.
Published: July 2017

Eukaryotic genomes must accomplish the tradeoff between compact packaging for genome stability and inheritance, and accessibility for gene expression. They do so using post-translational modifications of four ancient canonical histone proteins (H2A, H2B, H3 and H4), and by deploying histone variants with specialized chromatin functions. While some histone variants are highly conserved across eukaryotes, others carry out lineage-specific functions. Here, we characterize the evolution of male germline-specific “short H2A variants”, which wrap shorter DNA fragments than canonical H2A. In addition to three previously described H2A.B, H2A.L and H2A.P variants, we describe a novel, extremely short H2A histone variant: H2A.Q. We show thatH2A.B, H2A.L, H2A.PandH2A.Qare most closely related to a novel, more canonical mmH2A variant found only in monotremes and marsupials. Using phylogenomics, we trace the origins and early diversification of short histone variants into four distinct clades to the ancestral X chromosome of placental mammals. We show that short H2A variants further diversified by repeated lineage-specific amplifications and losses, including pseudogenization ofH2A.Lin many primates. We also uncover evidence for concerted evolution ofH2A.BandH2A.Lgenes by gene conversion in many species, involving loci separated by large distances. Finally, we find that short H2As evolve more rapidly than any other histone variant, with evidence that positive selection has acted uponH2A.Pin primates. Based on their X chromosomal location and pattern of genetic innovation, we speculate that short H2A histone variants are engaged in a form of genetic conflict involving the mammalian sex chromosomes.
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

Single 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

Phosphatidylinositol-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.

Highlights

In vitroblockade of PI3K p110δ with CAL-101 endows antitumor T cells with a stronger memory phenotype than those treated with AKTi

The strong memory phenotype of CAL-101 treated cells translates into improved survival of mice bearing aggressive tumors after adoptive transfer of these T cells

Human CAR engineered T cells treated with CAL-101 possess an enhanced memory phenotype and robust antitumor efficacy

The 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 phenotype

eTOC Blurb

Bowers 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.
An Automated Approach to the Quantitation of Vocalizations and Vocal Learning in the Songbird
Authors: Mets David G. , Brainard Michael S.
Published: July 2017

Studies of learning mechanisms critically depend on the ability to accurately assess learning outcomes. This assessment can be impeded by the often complex, multidimensional nature of behavior. We present a novel, automated approach to evaluating imitative learning that is founded in information theory. Conceptually, our approach estimates the amount of information present in a reference behavior that is absent from the learned behavior. We validate our approach through examination of songbird vocalizations, complex learned behaviors the study of which has provided many insights into sensory-motor learning in general and vocal learning in particular. Historically, learning has been holistically assessed by human inspection or through comparison of specific song features selected by experimenters (e.g. fundamental frequency, spectral entropy). In contrast, our approach relies on statistical models that broadly capture the structure of each song, and then uses these models to estimate the amount of information in the reference song but absent from the learned song. We show that our information theoretic measure of song learning (contrast entropy) is well correlated with human evaluation of song learning. We then expand the analysis beyond song learning and show that contrast entropy also detects the typical song deterioration that occurs following deafening. More broadly, this approach potentially provides a framework for assessing learning across a broad range of similarly structured behaviors.

Author Summary

Measuring learning outcomes is a critical objective of research into the neural, molecular, and behavioral mechanisms that support learning. Demonstration that a given manipulation results in better or worse learning outcomes requires an accurate and consistent measurement of learning quality. However, many behaviors (e.g. speech, walking, and reading) are complex and multidimensional, confounding the assessment of learning. One behavior subject to such confounds, vocal learning in Estrildid finches, has emerged as a vital model for sensory motor learning broadly and human speech learning in particular. Here, we demonstrate a new approach, founded in information theory, to the assessment of learning for complex high dimensional behaviors. Conceptually, we determine the amount of information (across many dimensions) present in a reference behavior and then assess how much of that information is present in the resultant learned behavior. We show that this measure provides an accurate, holistic, and automated assessment of vocal learning in Estrildid finches. Potentially, this same approach could be deployed to assess shared content in any multidimensional data, behavioral or otherwise.
Two Chinese medicine species constants and the accurate identification of Chinese medicines
Authors: zou Huabin
Published: July 2017

Since the ancient times, all over the world, the identification of herbal medicines have to be based on empirical knowledge. In this article two species constants of traditional Chinese medicines(TCM) were discovered relying on the maximum information states of Dual index information theory equation, or common heredity and variation information theory. The two species constants, common peak ratiosPg= 61% andPg= 70%, which corresponding to symmetry and asymmetry variation states, respectively, were used as two absolute quantitative criteria to identify complex biology systems-TCM. Considered the influences of many other factors on components and experiment processes, the practical theoretical identification standards should be establishedPg≧58~64% andPg≧67~73%, within the relativeerror within −3% and + 3% of information value around the maximum information states. Combining the maximum number of effective sample optimum method with this two theoretical standards, the optimized classification of a TCM sample set can be carried out correctly. 42 samples belonging to four species of combination Chinese medicines were tested. The infrared (IR) fingerprint spectra (FPS) of their powder were measured and analyzed by means of the approach provided above. Among the six pairs of four Chinese medicine species, five of them follow the species constantPg=61%, one of them obeys thePg= 70%. The correct recognition ratio of samples was 95.2%, and that of species was 100%.
SOD1A4Vaggregation alters ubiquitin homeostasis in a cell model of ALS
Authors: Farrawell Natalie E. , Lambert-Smith Isabella , Mitchell Kristen , McKenna Jessie , McAlary Luke , Ciryam Prajwal , Vine Kara L. , Saunders Darren N. , Yerbury Justin J.
Published: July 2017

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving the selective death of upper and lower motor neurons in the primary motor cortex and spinal cord. A hallmark of ALS pathology is the accumulation of ubiquitinated protein inclusions within motor neurons. Previous studies suggest the sequestration of ubiquitin (Ub) into inclusions reduces the availability of free Ub, which is essential for cellular function and survival. However, the dynamics of the Ub landscape in ALS have not yet been described. Here we show that Ub homeostasis is altered in a SOD1 cell model of ALS. Utilising fluorescently tagged Ub, we followed the distribution of Ub in living cells expressing SOD1 and show that Ub is present at the earliest stages of SOD1 aggregation. We also report that cells containing aggregates of mutant SOD1 have greater ubiquitin-proteasome system (UPS) dysfunction as measured by the accumulation of the fluorescent proteasome reporter tdTomatoCL1. Furthermore, SOD1 aggregation is associated with the redistribution of Ub and depletion of the free Ub pool. Ubiquitomics analysis indicates that mutant SOD1 is associated with a shift of Ub to a pool of supersaturated proteins including those associated with oxidative phosphorylation and metabolism, corresponding with altered mitochondrial morphology and function. Taken together, these results suggest misfolded SOD1 contributes to UPS dysfunction and that Ub homeostasis is an important target for monitoring pathological changes in ALS.
A geography aware reconciliation method to investigate diversification patterns in host/parasite interactions
Authors: Berry V. , Chevenet F. , Doyon J-P. , Jousselin E.
Published: July 2017

Cospeciation studies aim at investigating whether hosts and symbionts speciate simultaneously or whether the associations diversify through host shifts. This problem is often tackled through reconciliation analyses that map the symbiont phylogeny onto the host phylogeny by mixing different types of diversification events. These reconciliations can be difficult to interpret and not always biologically realistic. Researchers have underlined that the biogeographic histories of both hosts and symbionts influence the probability of cospeciation and host switches, but up to now no reconciliation software integrates geographic data. We present a new functionality in theMowglisoftware that bridges this gap. The user can provide geographic information on both the host and symbiont extant and ancestral taxa. Constraints in the reconciliation algorithm have been implemented to generate biologically realistic codiversification scenarios. We apply our method to the fig/fig wasp association and infer diversification scenarios that differ from reconciliations ignoring geographic information. In addition, we updated the reconciliation viewerSylvXin order to visualize ancestral character states on the phylogenetic trees and highlight zones that are geographically inconsistent in reconciliations computed without geographic constraints. We suggest that the comparison of reconciliations obtained with and without constraints can help solving ambiguities in the biogeographic histories of the partners. With the development of robust methods in historical biogeography and the advent of next-generation sequencing that leads to better-resolved trees, a geography aware reconciliation method represents a substantial advance that is likely to be useful to researchers studying the evolution of biotic interactions and biogeography.
GDSCTools for Mining Pharmacogenomic Interactions in Cancer
Authors: Cokelaer Thomas , Chen Elisabeth , Iorio Francesco , Menden Michael P. , Lightfoot Howard , Saez-Rodriguez Julio , Garnett Mathew J.
Published: July 2017

Motivation

Large pharmacogenomic screenings integrate heterogeneous cancer genomic data sets as well as anti-cancer drug responses on thousand human cancer cell lines. Mining this data to identify new therapies for cancer sub-populations would benefit from common data structures, modular computational biology tools and user-friendly interfaces.

Results

We have developed GDSCTools: a software aimed at the identification of clinically relevant genomic markers of drug response. The Genomics of Drug Sensitivity in Cancer (GDSC) database (www.cancerRxgene.org) integrates heterogeneous cancer genomic data sets as well as anti-cancer drug responses on a thousand cancer cell lines. Including statistical tools (ANOVA) and predictive methods (Elastic Net), as well as common data structures, GDSCTools allows users to reproduce published results from GDSC, to analyse their own drug responses or genomic datasets, and to implement new analytical methods.

Contact

thomas.cokelaer@pasteur.fr
Distinct roles of cohesin-SA1 and cohesin-SA2 in 3D chromosome organization
Authors: Kojic Aleksandar , Cuadrado Ana , Koninck Magali De , Rodríguez-Corsino Miriam , Gómez-López Gonzalo , Le Dily François , Marti-Renom Marc A. , Losada Ana
Published: July 2017

In addition to mediating sister chromatid cohesion, cohesin plays a central role in DNA looping and segmentation of the genome into contact domains (TADs). Two variant cohesin complexes that contain either STAG/SA1 or SA2 are present in all cell types. Here we addressed their specific contribution to genome architecture in non-transformed human cells. We found that cohesin-SA1 drives stacking of cohesin rings at CTCF-bound sites and thereby contributes to the stabilization and preservation of TAD boundaries. In contrast, a more dynamic cohesin-SA2 promotes cell type-specific contacts between enhancers and promoters within TADs independently of CTCF. SA2 loss, a condition frequently observed in cancer cells, results in increased intra-TAD interactions, likely altering the expression of key cell identity genes.
Genome-wide genetic data on ~500,000 UK Biobank participants
Authors: Bycroft Clare , Freeman Colin , Petkova Desislava , Band Gavin , Elliott Lloyd T. , Sharp Kevin , Motyer Allan , Vukcevic Damjan , Delaneau Olivier , O’Connell Jared , Cortes Adrian , Welsh Samantha , McVean Gil , Leslie Stephen , Donnelly Peter , Marchini Jonathan
Published: July 2017

The UK Biobank project is a large prospective cohort study of ~500,000 individuals from across the United Kingdom, aged between 40-69 at recruitment. A rich variety of phenotypic and health-related information is available on each participant, making the resource unprecedented in its size and scope. Here we describe the genome-wide genotype data (~805,000 markers) collected on all individuals in the cohort and its quality control procedures. Genotype data on this scale offers novel opportunities for assessing quality issues, although the wide range of ancestries of the individuals in the cohort also creates particular challenges. We also conducted a set of analyses that reveal properties of the genetic data – such as population structure and relatedness – that can be important for downstream analyses. In addition, we phased and imputed genotypes into the dataset, using computationally efficient methods combined with the Haplotype Reference Consortium (HRC) and UK10K haplotype resource. This increases the number of testable variants by over 100-fold to ~96 million variants. We also imputed classical allelic variation at 11 human leukocyte antigen (HLA) genes, and as a quality control check of this imputation, we replicate signals of known associations between HLA alleles and many common diseases. We describe tools that allow efficient genome-wide association studies (GWAS) of multiple traits and fast phenome-wide association studies (PheWAS), which work together with a new compressed file format that has been used to distribute the dataset. As a further check of the genotyped and imputed datasets, we performed a test-case genome-wide association scan on a well-studied human trait, standing height.
Fusion detection and quantification by pseudoalignment
Authors: Melsted Páll , Hateley Shannon , Joseph Isaac Charles , Pimentel Harold , Bray Nicolas , Pachter Lior
Published: July 2017

RNA sequencing in cancer cells is a powerful technique to detect chromosomal rearrangements, allowing forde novodiscovery of actively expressed fusion genes. Here we focus on the problem of detecting gene fusions from raw sequencing data, assembling the reads to define fusion transcripts and their associated breakpoints, and quantifying their abundances. Building on the pseudoalignment idea that simplifies and accelerates transcript quantification, we introduce a novel approach to fusion detection based on inspecting paired reads that cannot be pseudoaligned due to conflicting matches. The method and software, called pizzly, filters false positives, assembles new transcripts from the fusion reads, and reports candidate fusions. With pizzly, fusion detection from raw RNA-Seq reads can be performed in a matter of minutes, making the program suitable for the analysis of large cancer gene expression databases and for clinical use. pizzly is available athttps://github.com/pmelsted/pizzly
Vermont: a multi-perspective visual interactive platform for mutational analysis
Authors: Fassio Alexandre V , Martins Pedro M , Guimarães Samuel da S , Junior Sócrates S A , Ribeiro Vagner S , de Melo-Minardi Raquel C , de A Silveira Sabrina
Published: July 2017

Background

A huge amount of data about genomes and sequence variation is available and continues to grow on a large scale, which makes experimentally characterizing these mutations infeasible regarding disease association and effects on protein structure and function. Therefore, reliable computational approaches are needed to support the understanding of mutations and their impacts. Here, we present VERMONT 2.0, a visual interactive platform that combines sequence and structural parameters with interactive visualizations to make the impact of protein point mutations more understandable.

Results

We aimed to contribute a novel visual analytics oriented method to analyze and gain insight on the impact of protein point mutations. To assess the ability of VERMONT to do this, we visually examined a set of mutations that were experimentally characterized to determine if VERMONT could identify damaging mutations and why they can be considered so.

Conclusions

VERMONT allowed us to understand mutations by interpreting position-specific structural and physicochemical properties. Additionally, we note some specific positions we believe have an impact on protein function/structure in the case of mutation.
Use of a Sibling Subtraction Method (SSM) for Identifying Causal Mutations inC. elegansby Whole-Genome Sequencing
Authors: Joseph Braveen B. , Blouin Nicolas A. , Fay David S.
Published: July 2017

Whole-genome sequencing (WGS) has become an indispensible tool for identifying causal mutations obtained from genetic screens. To reduce the number of causal mutation candidates typically uncovered by WGS,C. elegansresearchers have developed several strategies. One involves crossing N2-background mutants to the polymorphic strain CB4856, which can be used to simultaneously identify mutant-strain variants and obtain high-density mapping information. This approach, however, is not well suited for uncovering mutations in complex genetic backgrounds, and CB4856 polymorphisms can alter phenotypes. Several other approaches make use of DNA variants introduced by mutagenesis. This information is used to implicate genomic regions with high densities of DNA lesions that persist after mutant backcrossing, but these methods provide lower mapping resolution than use of CB4856. To identify suppressor mutations using WGS, we developed a new approach termed the Sibling Subtraction Method (SSM). This method works by eliminating variants present in both mutants and their non-mutant siblings, thus greatly reducing the number of candidates. We used this method here with two members of theC. elegansNimA-related kinase family,nekl-2andnekl-3. Combining weak aphenotypic alleles ofnekl-2andnekl-3leads to penetrant molting defects and larval arrest. We isolated ~50 suppressors ofnekl-2; nekl-3synthetic lethality using F1-clonal screening methods and a toxin-based counter-selection strategy. When applied to five of the identified suppressors, SSM led to only one to four suppressor candidates per strain. Thus SSM is a powerful approach for identifying causal mutations in any genetic background and provides an alternative to current methods.
Common neural responses to narrative speech in disorders of consciousness
Authors: Iotzov Ivan , Fidali Brian C , Petroni Agustin , Conte Mary M , Schiff Nicholas D , Parra Lucas C
Published: July 2017

Objective

Clinical assessment of auditory attention in patients with disorders of consciousness is often limited by motor impairment. Here, we employ inter-subject correlations among electroencephalography responses to naturalistic speech in order to assay auditory attention among patients and healthy controls.

Methods

Electroencephalographic data were recorded from 20 subjects with disorders of consciousness and 14 healthy controls during of two narrative audio stimuli, presented both forwards and time-reversed. Inter-subject correlation of evoked electroencephalography signals were calculated, comparing responses of both groups to those of the healthy control subjects. This analysis was performed blinded and subsequently compared to the diagnostic status of each patient based on the Coma Recovery Scale-Revised.

Results

Subjects with disorders of consciousness exhibit significantly lower inter-subject correlation than healthy controls during narrative speech. Additionally, while healthy subjects had higher inter-subject correlation values in forward vs. backwards presentation, neural responses did not vary significantly with the direction of playback in subjects with disorders of consciousness. Increased inter-subject correlation values in the backward speech condition were noted with improving disorder of consciousness diagnosis, both in cross-sectional analysis and in a subset of patients with longitudinal data.

Interpretation

Inter-subject correlation of neural responses to narrative speech audition differentiates healthy controls from patients and appears to index clinical diagnoses in disorders of consciousness.