Homogentisate 1-2-Dioxygenase Downregulation in the Chronic Persistence of Pseudomonas aeruginosa Australian Epidemic Strain-1 in the CF Lung

Some Pseudomonas aeruginosa strains including Australian Epidemic Strain-1 (AES-1 or AUS-01) cause persistent chronic infection in cystic fibrosis (CF) patients, with greater morbidity and mortality. Factors conferring persistence are largely unknown. Previously we analysed the transcriptomes of AES-1 grown in Luria broth, nematode growth medium for Caenorhabditis elegans assay (both aerobic) and artificial sputum medium (mainly hyp- oxic). Transcriptional comparisons included chronic AES-1 strains against PAO1 and acute AES-1 (AES-1R) against its chronic isogen (AES-1M), isolated 10.5 years apart from a CF patient and not eradicated in the meantime. Prominent amongst genes downregulated in AES-1M in all comparisons was homogentisate-1-2-dioxygenase (hmgA); an oxygen-dependent gene known to be mutationally deactivated in many chronic infection strains of P. aeruginosa. To investigate if hmgA downregulation and deactivation gave similar viru- lence persistence profiles, a hmgA mutant made in UCBPP-PA14 utilising RedS-recombinase and AES-1M were assessed in the C. elegans virulence assay, and the C57BL/6 mouse for pulmonary colonisation and TNF-α response. In C. elegans, hmgA deactivation resulted in significantly increased PA14 virulence while hmgA downregulation reduced AES-1M virulence. AES-1M was significantly more persistent in mouse lung and showed a significant increase in TNF-α (p<0.0001), sustained even with no detectable bacteria. PA14ΔhmgA did not show increased TNF-α. This study suggests that hmgA may have a role in P. aeruginosa persistence in chronic infection and the results provide a starting point for clarifying the role of hmgA in chronic AES-1

Does repeatedly viewing overweight versus underweight images change perception of and satisfaction with own body size?

Body dissatisfaction is associated with subsequent eating disorders and weight gain. One-off exposure to bodies of different sizes changes perception of others' bodies, and perception of and satisfaction with own body size. The effect of repeated exposure to bodies of different sizes has not been assessed. We randomized women into three groups, and they spent 5 min twice a day for a week completing a one-back task using images of women modified to appear either under, over, or neither over- nor underweight. We tested the effects on their perception of their own and others' body size, and satisfaction with own size. Measures at follow-up were compared between groups, adjusted for baseline measurements. In 93 women aged 18–30 years, images of other women were perceived as larger following exposure to underweight women (and vice versa) (p < 0.001). There was no evidence for a difference in our primary outcome measure (visual analogue scale own size) or in satisfaction with own size. Avatar-constructed ideal (p = 0.03) and avatar-constructed perceived own body size (p = 0.007) both decreased following exposure to underweight women, possibly due to adaptation affecting how the avatar was perceived. Repeated exposure to different sized bodies changes perception of the size of others' bodies, but we did not find evidence that it changes perceived own size

Evolved Eclipsing Binaries and the Age of the Open Cluster NGC 752

We present analyses of improved photometric and spectroscopic observations for two detached eclipsing binaries at the turnoff of the open cluster NGC 752: the 1.01 day binary DS And and the 15.53 d BD $+$37 410. For DS And, we find $M_1 = 1.692\pm0.004\pm0.010 M_\odot$, $R_1 = 2.185\pm0.004\pm0.008 R_\odot$, $M_2 = 1.184\pm0.001\pm0.003 M_\odot$, and $R_2 = 1.200\pm0.003\pm0.005 R_\odot$. We either confirm or newly identify unusual characteristics of both stars in the binary: the primary star is found to be slightly hotter than the main sequence turn off and there is a more substantial discrepancy in its luminosity compared to models (model luminosities are too large by about 40%), while the secondary star is oversized and cooler compared to other main sequence stars in the same cluster. The evidence points to non-standard evolution for both stars, but most plausible paths cannot explain the low luminosity of the primary star. BD $+$37 410 only has one eclipse per cycle, but extensive spectroscopic observations and the TESS light curve constrain the stellar masses well: $M_1 = 1.717\pm0.011 M_\odot$ and $M_2 = 1.175\pm0.005 M_\odot$. The radius of the main sequence primary star near $2.9R_\odot$ definitively requires large convective core overshooting ($> 0.2$ pressure scale heights) in models for its mass, and multiple lines of evidence point toward an age of $1.61\pm0.03\pm0.05$ Gyr (statistical and systematic uncertainties). Because NGC 752 is currently undergoing the transition from non-degenerate to degenerate He ignition of its red clump stars, BD $+$37 410 A directly constrains the star mass where this transition occurs.Comment: 34 pages, 23 figures, accepted for Astronomical Journa

Evolved Eclipsing Binaries and the Age of the Open Cluster NGC 752

We present analyses of improved photometric and spectroscopic observations for two detached eclipsing binaries at the turnoff of the open cluster NGC 752: the 1.01 days binary DS And and the 15.53 days BD +37 410. For DS And, we find M1 = 1.692 ± 0.004 ± 0.010M⊙, R1 = 2.185 ± 0.004 ± 0.008R⊙, M2 = 1.184 ± 0.001 ± 0.003M⊙, and R2 = 1.200 ± 0.003 ± 0.005R⊙. We either confirm or newly identify unusual characteristics of both stars in the binary: the primary star is found to be slightly hotter than the main-sequence turnoff and there is a more substantial discrepancy in its luminosity compared to models (model luminosities are too large by about 40%), while the secondary star is oversized and cooler compared to other main-sequence stars in the same cluster. The evidence points to nonstandard evolution for both stars, but most plausible paths cannot explain the low luminosity of the primary star. BD +37 410 only has one eclipse per cycle, but extensive spectroscopic observations and the Transiting Exoplanet Survey Satellite light curve constrain the stellar masses well: M1 = 1.717 ± 0.011M⊙ and M2 = 1.175 ± 0.005M⊙. The radius of the main-sequence primary star near 2.9R⊙ definitively requires large convective core overshooting (>0.2 pressure scale heights) in models for its mass, and multiple lines of evidence point toward an age of 1.61 ± 0.03 ± 0.05 Gyr (statistical and systematic uncertainties). Because NGC 752 is currently undergoing the transition from nondegenerate to degenerate He ignition of its red clump stars, BD +37 410 A directly constrains the star mass where this transition occurs

Effects of growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values and small sample sizes.

The data set supporting the results of this article is available in the Dryad repository, http://dx.doi.org/10.5061/dryad.6f4qs. Moustakas, A. and Evans, M. R. (2015) Effects of growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values.Plant survival is a key factor in forest dynamics and survival probabilities often vary across life stages. Studies specifically aimed at assessing tree survival are unusual and so data initially designed for other purposes often need to be used; such data are more likely to contain errors than data collected for this specific purpose

Human-based approaches to pharmacology and cardiology: an interdisciplinary and intersectorial workshop.

Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analysis, integration and prediction. This paper describes a Workshop on Computational Cardiovascular Science that created an international, interdisciplinary and inter-sectorial forum to define the next steps for a human-based approach to disease supported by computational methodologies. The main ideas highlighted were (i) a shift towards human-based methodologies, spurred by advances in new in silico, in vivo, in vitro, and ex vivo techniques and the increasing acknowledgement of the limitations of animal models. (ii) Computational approaches complement, expand, bridge, and integrate in vitro, in vivo, and ex vivo experimental and clinical data and methods, and as such they are an integral part of human-based methodologies in pharmacology and medicine. (iii) The effective implementation of multi- and interdisciplinary approaches, teams, and training combining and integrating computational methods with experimental and clinical approaches across academia, industry, and healthcare settings is a priority. (iv) The human-based cross-disciplinary approach requires experts in specific methodologies and domains, who also have the capacity to communicate and collaborate across disciplines and cross-sector environments. (v) This new translational domain for human-based cardiology and pharmacology requires new partnerships supported financially and institutionally across sectors. Institutional, organizational, and social barriers must be identified, understood and overcome in each specific setting

AI-based dimensional neuroimaging system for characterizing heterogeneity in brain structure and function in major depressive disorder:COORDINATE-MDD consortium design and rationale

BACKGROUND: Efforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status and heterogeneous symptom states. METHODS: We describe a consortium to quantify neuroanatomical and neurofunctional heterogeneity via the dimensions of novel multivariate coordinate system (COORDINATE-MDD). Utilizing imaging harmonization and machine learning methods in a large cohort of medication-free, deeply phenotyped MDD participants, patterns of brain alteration are defined in replicable and neurobiologically-based dimensions and offer the potential to predict treatment response at the individual level. International datasets are being shared from multi-ethnic community populations, first episode and recurrent MDD, which are medication-free, in a current depressive episode with prospective longitudinal treatment outcomes and in remission. Neuroimaging data consist of de-identified, individual, structural MRI and resting-state functional MRI with additional positron emission tomography (PET) data at specific sites. State-of-the-art analytic methods include automated image processing for extraction of anatomical and functional imaging variables, statistical harmonization of imaging variables to account for site and scanner variations, and semi-supervised machine learning methods that identify dominant patterns associated with MDD from neural structure and function in healthy participants. RESULTS: We are applying an iterative process by defining the neural dimensions that characterise deeply phenotyped samples and then testing the dimensions in novel samples to assess specificity and reliability. Crucially, we aim to use machine learning methods to identify novel predictors of treatment response based on prospective longitudinal treatment outcome data, and we can externally validate the dimensions in fully independent sites. CONCLUSION: We describe the consortium, imaging protocols and analytics using preliminary results. Our findings thus far demonstrate how datasets across many sites can be harmonized and constructively pooled to enable execution of this large-scale project