Concise visualization is critical to present large amounts of information in a minimal space that can be interpreted quickly. Clinical applications in precision medicine present an important use case ...due to the time dependent nature of the interpretations, although visualization is increasingly necessary across the life sciences. In this paper we describe the Lollipops software for the presentation of panel or exome sequencing results. Source code and binaries are freely available at https://github.com/pbnjay/lollipops. Although other software and web resources exist to produce lollipop diagrams, these packages are less suited to clinical applications. The demands of precision medicine require the ability to easily fit into a workflow and incorporate external information without manual intervention.
The Lollipops software provides a simple command line interface that only requires an official gene symbol and mutation list making it easily scriptable. External information is integrated using the publicly available Uniprot and Pfam resources. Heuristics are used to select the most informative components and condense them for a concise plot. The output is a flexible Scalable Vector Graphic (SVG) diagram that can be displayed in a web page or graphic illustration tool.
The Lollipops software creates information-dense, publication-quality mutation plots for automated pipelines and high-throughput workflows in precision medicine. The automatic data integration enables clinical data security, and visualization heuristics concisely present knowledge with minimal user configuration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Hand, foot, and mouth disease is a common childhood illness caused by enteroviruses. Increasingly, the disease has a substantial burden throughout east and southeast Asia. To ...better inform vaccine and other interventions, we characterised the epidemiology of hand, foot, and mouth disease in China on the basis of enhanced surveillance. Methods We extracted epidemiological, clinical, and laboratory data from cases of hand, foot, and mouth disease reported to the Chinese Center for Disease Control and Prevention between Jan 1, 2008, and Dec 31, 2012. We then compiled climatic, geographical, and demographic information. All analyses were stratified by age, disease severity, laboratory confirmation status, and enterovirus serotype. Findings The surveillance registry included 7 200 092 probable cases of hand, foot, and mouth disease (annual incidence, 1·2 per 1000 person-years from 2010–12), of which 267 942 (3·7%) were laboratory confirmed and 2457 (0·03%) were fatal. Incidence and mortality were highest in children aged 12–23 months (38·2 cases per 1000 person-years and 1·5 deaths per 100 000 person-years in 2012). Median duration from onset to diagnosis was 1·5 days (IQR 0·5–2·5) and median duration from onset to death was 3·5 days (2·5–4·5). The absolute number of patients with cardiopulmonary or neurological complications was 82 486 (case-severity rate 1·1%), and 2457 of 82486 patients with severe disease died (fatality rate 3·0%); 1617 of 1737 laboratory confirmed deaths (93%) were associated with enterovirus 71. Every year in June, hand, foot, and mouth disease peaked in north China, whereas southern China had semiannual outbreaks in May and September–October. Geographical differences in seasonal patterns were weakly associated with climate and demographic factors (variance explained 8–23% and 3–19%, respectively). Interpretation This is the largest population-based study up to now of the epidemiology of hand, foot, and mouth disease. Future mitigation policies should take into account the heterogeneities of disease burden identified. Additional epidemiological and serological studies are warranted to elucidate the dynamics and immunity patterns of local hand, foot, and mouth disease and to optimise interventions. Funding China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases, WHO, The Li Ka Shing Oxford Global Health Programme and Wellcome Trust, Harvard Center for Communicable Disease Dynamics, and Health and Medical Research Fund, Government of Hong Kong Special Administrative Region.
Roughly half the individuals who experience childhood maltreatment also experience depressive symptoms in adulthood; however, many current treatments are ineffective. Allostatic load (AL) offers a ...method of exploring this relationship through the lens of biometric dysregulation that may explain these increased odds for depressive symptoms in adulthood. We attempted to expand the limited research base on AL, depressive symptoms, and childhood maltreatment by examining how these variables are associated in a U.S. community sample.
Data were acquired through secondary analysis of the Midlife in the United States Refresher biomarker survey (n = 691). Depression severity, measured by the Center for Epidemiologic Studies Depression Scale, served as the dependent variable, while summed scores for the Childhood Trauma Questionnaire, and a 16 measure AL index served as independent variables. All analyses were stratified by sex (n male = 347, n female = 344). The Perceived Stress Scale was included to control for recent stress. An OLS regression was used to understand the relationship between depression and predictor variables before then being tested for the possible mediating role of AL.
Comparison of OLS models yielded notable differences in predicting depressive symptoms between males and females, namely that while maltreatment was significant for both groups, AL was only significant for females. Mediation by allostatic load was not significant for males or females.
We explored the possible mediation of childhood maltreatment and adulthood depressive symptoms by AL. While our study did not confirm mediation, this was the first known study to explore these relationships in a U.S., community sample. Sex stratification reveals a clear need for accounting for sex differences in predictor variables for future studies.
•Prior research has identified allostatic load as a mediator between childhood trauma and adulthood depression.•We attempted to expand these findings to a U.S. community sample.•Mediation analysis was not significant; however, multivariate models revealed notable sex differences in predictor variables.•Allostatic load was a significant predictor of depression for only female participants.
Susceptibility to tuberculosis is historically ascribed to an inadequate immune response that fails to control infecting mycobacteria. In zebrafish, we find that susceptibility to Mycobacterium ...marinum can result from either inadequate or excessive acute inflammation. Modulation of the leukotriene A4 hydrolase (LTA4H) locus, which controls the balance of pro- and anti-inflammatory eicosanoids, reveals two distinct molecular routes to mycobacterial susceptibility converging on dysregulated TNF levels: inadequate inflammation caused by excess lipoxins and hyperinflammation driven by excess leukotriene B4. We identify therapies that specifically target each of these extremes. In humans, we identify a single nucleotide polymorphism in the LTA4H promoter that regulates its transcriptional activity. In tuberculous meningitis, the polymorphism is associated with inflammatory cell recruitment, patient survival and response to adjunctive anti-inflammatory therapy. Together, our findings suggest that host-directed therapies tailored to patient LTA4H genotypes may counter detrimental effects of either extreme of inflammation.
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► Conserved eicosanoids are regulated by LTA4H activity and impact inflammatory state ► Genotype-directed modulation of TNF improves outcomes in a zebrafish tuberculosis model ► Drug therapies tailored to lta4h genotype improve infection outcome in zebrafish ► In humans, LTA4H genotype associates with responsiveness to therapy for TB meningitis
A polymorphism in a locus that controls the balance between pro- and anti-inflammatory mediators is predictive of response to anti-inflammatory therapy in tuberculous meningitis.
We conduct a techno-economic analysis of Li-ion NMC-G prismatic pouch battery and pack designs for electric vehicle applications. We develop models of power capability and manufacturing operations to ...identify the minimum cost cell and pack designs for a variety of plug-in hybrid electric vehicle (PHEV) and battery electric vehicle (BEV) requirements. We find that economies of scale in battery manufacturing are reached quickly at a production volume of ~200-300 MWh annually. Increased volume does little to reduce unit costs, except potentially indirectly through factors such as experience, learning, and innovation. We also find that vehicle applications with larger energy requirements are able to utilize cheaper cells due in part to the use of thicker electrodes. The effect on cost can be substantial. In our base case, we estimate pack-level battery production costs of ~$545 kWh super(-1) for a PHEV with a 10 mile (16 km) all-electric range (PHEV sub(10)) and ~$230 kWh super(-1) for a BEV with a 200 mile (320 km) all-electric range (BEV sub(200)). This 58% reduction, from $545 kWh super(-1) to $230 kWh super(-1), is a larger effect than the uncertainty represented by our optimistic and pessimistic scenarios. Electrodes thicker than about 100 or 125 microns are not currently used in practice due to manufacturing and durability concerns, but relaxing this constraint could further lower the cost of larger capacity BEV200 packs by up to an additional 8%.
Abstract
The Bowfin (
Amia calva
), as currently recognized, represents the sole living member of the family Amiidae, which dates back to approximately 150 Ma. Prior to 1896, 13 species of extant ...Bowfins had been described, but these were all placed into a single species with no rationale or analysis given. This situation has persisted until the present day, with little attention given to re-evaluation of those previously described nominal forms. Here, we present a phylogenomic analysis based on over 21,000 single nucleotide polymorphisms (SNPs) from 94 individuals that unambiguously demonstrates the presence of at least two independent evolutionary lineages within extant
Amia
populations that merit species-level standing, as well as the possibility of two more. These findings not only expand the recognizable species diversity in an iconic, ancient lineage, but also demonstrate the utility of such methods in addressing previously intractable questions of molecular systematics and phylogeography in slowly evolving groups of ancient fishes.
Cultivated hexaploid oat (Common oat; Avena sativa) has held a significant place within the global crop community for centuries; although its cultivation has decreased over the past century, its ...nutritional benefits have garnered increased interest for human consumption. We report the development of fully annotated, chromosome-scale assemblies for the extant progenitor species of the A
- and C
-subgenomes, Avena atlantica and Avena eriantha respectively. The diploid Avena species serve as important genetic resources for improving common oat's adaptive and food quality characteristics.
The A. atlantica and A. eriantha genome assemblies span 3.69 and 3.78 Gb with an N50 of 513 and 535 Mb, respectively. Annotation of the genomes, using sequenced transcriptomes, identified ~ 50,000 gene models in each species-including 2965 resistance gene analogs across both species. Analysis of these assemblies classified much of each genome as repetitive sequence (~ 83%), including species-specific, centromeric-specific, and telomeric-specific repeats. LTR retrotransposons make up most of the classified elements. Genome-wide syntenic comparisons with other members of the Pooideae revealed orthologous relationships, while comparisons with genetic maps from common oat clarified subgenome origins for each of the 21 hexaploid linkage groups. The utility of the diploid genomes was demonstrated by identifying putative candidate genes for flowering time (HD3A) and crown rust resistance (Pc91). We also investigate the phylogenetic relationships among other A- and C-genome Avena species.
The genomes we report here are the first chromosome-scale assemblies for the tribe Poeae, subtribe Aveninae. Our analyses provide important insight into the evolution and complexity of common hexaploid oat, including subgenome origin, homoeologous relationships, and major intra- and intergenomic rearrangements. They also provide the annotation framework needed to accelerate gene discovery and plant breeding.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Little is known about the religious factors that contribute to religious identity dissonance (ID) for sexual minority men. Our aim was to model the path of religious factors to depression symptoms ...through ID and internalized stigma (IS). US sexual minority men (N = 168) participated in a survey about religious factors and mental health. Serial mediation of religious factors through ID and IS to depression symptoms was assessed using Hayes PROCESS macro. Results indicate that two religious factors significantly increase depression through ID and IS. Negative parental religious messages about LGBTQ people play a meaningful role in ID and increasing depression.
Overconsumption of processed foods has led to an increase in chronic diet-related diseases such obesity and type 2 diabetes. Although diets high in fresh fruits and vegetables are linked with ...healthier outcomes, the specific mechanisms for these relationships are poorly understood. Experiments examining plant phytochemical production and breeding programs, or separately on the health effects of nutritional supplements have yielded results that are sparse, siloed, and difficult to integrate between the domains of human health and agriculture. To connect plant products to health outcomes through their molecular mechanism an integrated computational resource is necessary. We created the Aliment to Bodily Condition Knowledgebase (ABCkb) to connect plants to human health by creating a stepwise path from plant formula omitted plant product formula omitted human gene formula omitted pathways formula omitted indication. ABCkb integrates 11 curated sources as well as relationships mined from Medline abstracts by loading into a graph database which is deployed via a Docker container. This new resource, provided in a queryable container with a user-friendly interface connects plant products with human health outcomes for generating nutritive hypotheses. All scripts used are available on github (https://github.com/atrautm1/ABCkb) along with basic directions for building the knowledgebase and a browsable interface is available (https://abckb.charlotte.edu).
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