The JAX Synteny Browser for mouse-human comparative genomics.

Visualizing regions of conserved synteny between two genomes is supported by numerous software applications. However, none of the current applications allow researchers to select genome features to display or highlight in blocks of synteny based on the annotated biological properties of the features (e.g., type, function, and/or phenotype association). To address this usability gap, we developed an interactive web-based conserved synteny browser, The Jackson Laboratory (JAX) Synteny Browser. The browser allows researchers to highlight or selectively display genome features in the reference and/or the comparison genome according to the biological attributes of the features. Although the current implementation for the browser is limited to the reference genomes for the laboratory mouse and human, the software platform is intentionally genome agnostic. The JAX Synteny Browser software can be deployed for any two genomes where genome coordinates for syntenic blocks are defined and for which biological attributes of the features in one or both genomes are available in widely used standard bioinformatics file formats. The JAX Synteny Browser is available at: http://syntenybrowser.jax.org/. The code base is available from GitHub: https://github.com/TheJacksonLaboratory/syntenybrowser and is distributed under the Creative Commons Attribution license (CC BY)

Towards an effective potential for the monomer, dimer, hexamer, solid and liquid forms of hydrogen fluoride

We present an attempt to build up a new two-body effective potential for hydrogen fluoride, fitted to theoretical and experimental data relevant not only to the gas and liquid phases, but also to the crystal. The model is simple enough to be used in Molecular Dynamics and Monte Carlo simulations. The potential consists of: a) an intra-molecular contribution, allowing for variations of the molecular length, plus b) an inter-molecular part, with three charged sites on each monomer and a Buckingham "exp-6" interaction between fluorines. The model is able to reproduce a significant number of observables on the monomer, dimer, hexamer, solid and liquid forms of HF. The shortcomings of the model are pointed out and possible improvements are finally discussed.Comment: LaTeX, 24 pages, 2 figures. For related papers see also http://www.chim.unifi.it:8080/~valle

Aseismic slip and seismogenic coupling along the central San Andreas Fault

International audienceWe use high-resolution Synthetic Aperture Radar- and GPS-derived observations of surfacedisplacements to derive the first probabilistic estimates of fault coupling along the creeping section of theSan Andreas Fault, in between the terminations of the 1857 and 1906 magnitude 7.9 earthquakes. Usinga fully Bayesian approach enables unequaled resolution and allows us to infer a high probability ofsignificant fault locking along the creeping section. The inferred discreet locked asperities are consistentwith evidence for magnitude 6+ earthquakes over the past century in this area and may be associated withthe initiation phase of the 1857 earthquake. As creeping segments may be related to the initiation andtermination of seismic ruptures, such distribution of locked and creeping asperities highlights the centralrole of the creeping section on the occurrence of major earthquakes along the San Andreas Fault

Genomic data analysis workflows for tumors from patient-derived xenografts (PDXs): challenges and guidelines.

BACKGROUND: Patient-derived xenograft (PDX) models are in vivo models of human cancer that have been used for translational cancer research and therapy selection for individual patients. The Jackson Laboratory (JAX) PDX resource comprises 455 models originating from 34 different primary sites (as of 05/08/2019). The models undergo rigorous quality control and are genomically characterized to identify somatic mutations, copy number alterations, and transcriptional profiles. Bioinformatics workflows for analyzing genomic data obtained from human tumors engrafted in a mouse host (i.e., Patient-Derived Xenografts; PDXs) must address challenges such as discriminating between mouse and human sequence reads and accurately identifying somatic mutations and copy number alterations when paired non-tumor DNA from the patient is not available for comparison. RESULTS: We report here data analysis workflows and guidelines that address these challenges and achieve reliable identification of somatic mutations, copy number alterations, and transcriptomic profiles of tumors from PDX models that lack genomic data from paired non-tumor tissue for comparison. Our workflows incorporate commonly used software and public databases but are tailored to address the specific challenges of PDX genomics data analysis through parameter tuning and customized data filters and result in improved accuracy for the detection of somatic alterations in PDX models. We also report a gene expression-based classifier that can identify EBV-transformed tumors. We validated our analytical approaches using data simulations and demonstrated the overall concordance of the genomic properties of xenograft tumors with data from primary human tumors in The Cancer Genome Atlas (TCGA). CONCLUSIONS: The analysis workflows that we have developed to accurately predict somatic profiles of tumors from PDX models that lack normal tissue for comparison enable the identification of the key oncogenic genomic and expression signatures to support model selection and/or biomarker development in therapeutic studies. A reference implementation of our analysis recommendations is available at https://github.com/TheJacksonLaboratory/PDX-Analysis-Workflows

Canonical A-to-I and C-to-U RNA Editing Is Enriched at 3′UTRs and microRNA Target Sites in Multiple Mouse Tissues

RNA editing is a process that modifies RNA nucleotides and changes the efficiency and fidelity of the central dogma. Enzymes that catalyze RNA editing are required for life, and defects in RNA editing are associated with many diseases. Recent advances in sequencing have enabled the genome-wide identification of RNA editing sites in mammalian transcriptomes. Here, we demonstrate that canonical RNA editing (A-to-I and C-to-U) occurs in liver, white adipose, and bone tissues of the laboratory mouse, and we show that apparent non-canonical editing (all other possible base substitutions) is an artifact of current high-throughput sequencing technology. Further, we report that high-confidence canonical RNA editing sites can cause non-synonymous amino acid changes and are significantly enriched in 3′ UTRs, specifically at microRNA target sites, suggesting both regulatory and functional consequences for RNA editing

Healthcare professionals' perceptions of pain in infants at risk for neurological impairment

BACKGROUND: To determine whether healthcare professionals perceive the pain of infants differently due to their understanding of that infant's level of risk for neurological impairment. METHOD: Neonatal Intensive Care Units (NICU's) at two tertiary pediatric centers. Ninety-five healthcare professionals who practice in the NICU (50 nurses, 19 physicians, 17 respiratory therapists, 9 other) participated. They rated the pain (0–10 scale and 0–6 Faces Pain Scale), distress (0–10), effectiveness of cuddling to relieve pain (0–10) and time to calm without intervention (seconds) for nine video clips of neonates receiving a heel stick. Prior to each rating, they were provided with descriptions that suggested the infant had mild, moderate or severe risk for neurological impairment. Ratings were examined as a function of the level of risk described. RESULTS: Professionals' ratings of pain, distress, and time to calm did not vary significantly with level of risk, but ratings of the effectiveness of cuddling were significantly lower as risk increased [F (2,93) = 4.4, p = .02]. No differences in ratings were found due to participants' age, gender or site of study. Physicians' ratings were significantly lower than nurses' across ratings. CONCLUSION: Professionals provided with visual information regarding an infants' pain during a procedure did not display the belief that infants' level of risk for neurological impairment affected their pain experience. Professionals' estimates of the effectiveness of a nonpharmacological intervention did differ due to level of risk

Exploring ethical issues associated with using online surveys in educational research

Online surveys are increasingly used in educational research, yet little attention has focused on ethical issues associated with their use in educational settings. Here, we draw on the broader literature to discuss 5 key ethical issues in the context of educational survey research: dual teacher/researcher roles; informed consent; use of incentives; privacy, anonymity, and confidentiality; and data quality. We illustrate methods of addressing these issues with our experiences conducing online surveys in educational contexts. Moving beyond the procedural ethics approach commonly adopted in quantitative educational research, we recommend adopting a situated/process ethics approach to identify and respond to ethical issues that may arise during the conduct, analysis, and reporting of online survey research. The benefits of online surveying in comparison to traditional survey methods are highlighted, including the potential for online surveys to provide ethically defensible methods of conducting research that would not be feasible in offline education research settings

Leishmania-Induced Inactivation of the Macrophage Transcription Factor AP-1 Is Mediated by the Parasite Metalloprotease GP63

Leishmania parasites have evolved sophisticated mechanisms to subvert macrophage immune responses by altering the host cell signal transduction machinery, including inhibition of JAK/STAT signalling and other transcription factors such as AP-1, CREB and NF-κB. AP-1 regulates pro-inflammatory cytokines, chemokines and nitric oxide production. Herein we show that upon Leishmania infection, AP-1 activity within host cells is abolished and correlates with lower expression of 5 of the 7 AP-1 subunits. Of interest, c-Jun, the central component of AP-1, is cleaved by Leishmania. Furthermore, the cleavage of c-Jun is dependent on the expression and activity of the major Leishmania surface protease GP63. Immunoprecipitation of c-Jun from nuclear extracts showed that GP63 interacts, and cleaves c-Jun at the perinuclear area shortly after infection. Phagocytosis inhibition by cytochalasin D did not block c-Jun down-regulation, suggesting that internalization of the parasite might not be necessary to deliver GP63 molecules inside the host cell. This observation was corroborated by the maintenance of c-Jun cleavage upon incubation with L. mexicana culture supernatant, suggesting that secreted, soluble GP63 could use a phagocytosis-independent mechanism to enter the host cell. In support of this, disruption of macrophage lipid raft microdomains by Methyl β-Cyclodextrin (MβCD) partially inhibits the degradation of full length c-Jun. Together our results indicate a novel role of the surface protease GP63 in the Leishmania-mediated subversion of host AP-1 activity