Dysregulation of glucocorticoid metabolism in murine obesity: comparable effects of leptin resistance and deficiency

In obese humans, metabolism of glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and A-ring reduction (by 5α- and 5β-reductases) is dysregulated in a tissue specific manner. These changes have been recapitulated in leptin resistant obese Zucker rats but were not observed in high-fat fed Wistar rats. Recent data from mouse models suggest that such discrepancies may reflect differences in leptin signalling. We therefore compared glucocorticoid metabolism in murine models of leptin deficiency and resistance. Male ob/ob and db/db mice and their respective littermate controls (n=10–12/group) were studied at the age of 12 weeks. Enzyme activities and mRNA expression were quantified in snap-frozen tissues. The patterns of altered pathways of steroid metabolism in obesity were similar in ob/ob and db/db mice. In liver, 5β-reductase activity and mRNA were increased and 11β-HSD1 decreased in obese mice, whereas 5α-reductase 1 (5αR1) mRNA was not altered. In visceral adipose depots, 5β-reductase was not expressed, 11β-HSD1 activity was increased and 5αR1 mRNA was not altered in obesity. By contrast, in subcutaneous adipose tissue 11β-HSD1 and 5αR1 mRNA were decreased. Systematic differences were not found between ob/ob and db/db murine models of obesity, suggesting that variations in leptin signalling through the short splice variant of the Ob receptor do not contribute to dysregulation of glucocorticoid metabolism

Systematic reviews and meta-analysis of preclinical studies:why perform them and how to appraise them critically

The use of systematic review and meta-analysis of preclinical studies has become more common, including those of studies describing the modeling of cerebrovascular diseases. Empirical evidence suggests that too many preclinical experiments lack methodological rigor, and this leads to inflated treatment effects. The aim of this review is to describe the concepts of systematic review and meta-analysis and consider how these tools may be used to provide empirical evidence to spur the field to improve the rigor of the conduct and reporting of preclinical research akin to their use in improving the conduct and reporting of randomized controlled trials in clinical research. As with other research domains, systematic reviews are subject to bias. Therefore, we have also suggested guidance for their conduct, reporting, and critical appraisal

Effectiveness of biomaterial-based combination strategies for spinal cord repair – a systematic review and meta-analysis of preclinical literature

Funding This work was supported by the Institute of Medical Sciences of the University of Aberdeen, International Spinal Research Trust, Scottish Rugby Union, RS McDonald Charitable Trust and The European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie grant agreement no. 702213).Peer reviewedPublisher PD

A Chromaticity Analysis and PSF Subtraction Techniques for SCExAO/CHARIS Data

We present an analysis of instrument performance using new observations taken with the Coronagraphic High Angular Resolution Imaging Spectrograph (CHARIS) instrument and the Subaru Coronagraphic Extreme Adaptive Optics (SCExAO) system. In a correlation analysis of our data sets (which use the broadband mode covering the J band through the K band in a single spectrum), we find that chromaticity in the SCExAO/CHARIS system is generally worse than temporal stability. We also develop a point-spread function (PSF) subtraction pipeline optimized for the CHARIS broadband mode, including a forward modeling-based exoplanet algorithmic throughput correction scheme. We then present contrast curves using this newly developed pipeline. An analogous subtraction of the same data sets using only the H-band slices yields the same final contrasts as the full JHK sequences; this result is consistent with our chromaticity analysis, illustrating that PSF subtraction using spectral differential imaging (SDI) in this broadband mode is generally not more effective than SDI in the individual J, H, or K bands. In the future, the data processing framework and analysis developed in this paper will be important to consider for additional SCExAO/CHARIS broadband observations and other ExAO instruments which plan to implement a similar integral field spectrograph broadband mode.Natural Sciences and Engineering Council of Canada through the Postgraduate Scholarships-Doctoral discovery grant; Technologies for Exo-Planetary Science Collaborative Research and Training Experience programs; JSPS [23340051, 26220704, 23103002]; Astrobiology Center of the National Institutes of Natural Sciences, Japan; Mt. Cuba Foundation; directors contingency fund at Subaru Telescope; MEXT of the Japanese government [23103002]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Animal models of chemotherapy-induced peripheral neuropathy:a machine-assisted systematic review and meta-analysis

<div><p>We report a systematic review and meta-analysis of research using animal models of chemotherapy-induced peripheral neuropathy (CIPN). We systematically searched 5 online databases in September 2012 and updated the search in November 2015 using machine learning and text mining to reduce the screening for inclusion workload and improve accuracy. For each comparison, we calculated a standardised mean difference (SMD) effect size, and then combined effects in a random-effects meta-analysis. We assessed the impact of study design factors and reporting of measures to reduce risks of bias. We present power analyses for the most frequently reported behavioural tests; 337 publications were included. Most studies (84%) used male animals only. The most frequently reported outcome measure was evoked limb withdrawal in response to mechanical monofilaments. There was modest reporting of measures to reduce risks of bias. The number of animals required to obtain 80% power with a significance level of 0.05 varied substantially across behavioural tests. In this comprehensive summary of the use of animal models of CIPN, we have identified areas in which the value of preclinical CIPN studies might be increased. Using both sexes of animals in the modelling of CIPN, ensuring that outcome measures align with those most relevant in the clinic, and the animal’s pain contextualised ethology will likely improve external validity. Measures to reduce risk of bias should be employed to increase the internal validity of studies. Different outcome measures have different statistical power, and this can refine our approaches in the modelling of CIPN.</p></div

Subaru/HiCIAO HKsHK_{\rm s} imaging of LkHα\alpha 330 - multi-band detection of the gap and spiral-like structures

We present $H$- and $K_{\rm s}$-bands observations of the LkH$\alpha$ 330 disk with a multi-band detection of the large gap and spiral-like structures. The morphology of the outer disk ($r\sim$0\farcs3) at PA=0--45$^\circ$ and PA=180--290$^\circ$ are likely density wave-induced spirals and comparison between our observational results and simulations suggests a planet formation. We have also investigated the azimuthal profiles at the ring and the outer-disk regions as well as radial profiles in the directions of the spiral-like structures and semi-major axis. Azimuthal analysis shows a large variety in wavelength and implies that the disk has non-axisymmetric dust distributions. The radial profiles in the major-axis direction (PA=$271^\circ$) suggest that the outer region (r\geq0\farcs25) may be influenced by shadows of the inner region of the disk. The spiral-like directions (PA=10$^\circ$ and 230$^\circ$) show different radial profiles, which suggests that the surfaces of the spiral-like structures are highly flared and/or have different dust properties. Finally, a color-map of the disk shows a lack of an outer eastern region in the $H$-band disk, which may hint the presence of an inner object that casts a directional shadow onto the disk.Comment: 12pages, 16 figures, 2 tables, accepted for publication in A

Constraining the Movement of the Spiral Features and the Locations of Planetary Bodies within the AB Aur System

We present new analysis of multi-epoch, H-band, scattered light images of the AB Aur system. We used a Monte Carlo, radiative transfer code to simultaneously model the system's SED and H-band polarized intensity imagery. We find that a disk-dominated model, as opposed to one that is envelope dominated, can plausibly reproduce AB Aur's SED and near-IR imagery. This is consistent with previous modeling attempts presented in the literature and supports the idea that at least a subset of AB Aur's spirals originate within the disk. In light of this, we also analyzed the movement of spiral structures in multi-epoch H-band total light and polarized intensity imagery of the disk. We detect no significant rotation or change in spatial location of the spiral structures in these data, which span a 5.8 year baseline. If such structures are caused by disk-planet interactions, the lack of observed rotation constrains the location of the orbit of planetary perturbers to be >47 AU.Comment: 8 pages, 3 figures, 1 table, Accepted to Ap