Regulation of retinol-binding protein secretion and expression in the ovine conceptus and uterus by retinoids and steroids

During early pregnancy in sheep, implantation occurs relatively late and fetal-maternal interactions are critical to maintenance of pregnancy, embryonic survival and development. Reproductive processes are mediated in part by conceptus secretory proteins and uterine proteins. Vitamin A (retinol) plays a role in reproductive processes and must be present in precise amounts for normal embryonic development. Most retinol is stored in the liver and transported bound to retinol-binding protein (RBP). Within the liver, the levels of RBP are regulated by retinoid status. Previous studies have suggested that placental RBP may be secreted in an apo- form by the conceptus in order to buffer the teratogenic effects of retinoids. The purpose of this study was to determine if retinoids influence RBP secretion by the conceptus and to determine if conceptus RBP is secreted in an apo- or holo- form. Day 14 ovine conceptuses were obtained from uterine flushes and cultured in Dulbecco\u27s minimal essential medium (DMEM) for 24 and 48 hours with addition of retinoids (10 µM all-trans retinol, 1 or 10 µM all-trans retinoic acid) in order to evaluate the effects of retinoid treatment on secretion and synthesis of RBP by the conceptus. Concentration of RBP was determined by an enzyme linked immunosorbant assay (ELISA) in culture medium and solubilized conceptus tissues. Retinol concentration of control conceptus cultures (no addition of retinoids) was analysed by extracting culture medium and quantifying retinol-associated fluorescence of the extracts. There were no differences in RBP concentration due to treatments in either the culture medium or conceptus tissues. Retinol was undetectable in the medium of control conceptus cultures. The results of this study demonstrate regulation of RBP in the conceptus may be different than that of the liver since physiological doses of retinoids did not have an effect on RBP secretion or synthesis in the day 14 ovine conceptus. The failure to detect retinol in medium of control conceptus cultures indicates that either RBP is secreted in an apo- form or retinol concentrations were below the sensitivity of the assay

Proposed Indicators to Measure the Environmental Responsibiity of Oil and Gas Companies and Regulatory Reforms to Improve Access to Information about Offshore Drilling

This paper suggests a set of indicators to evaluate and predict the environmental performance of companies proposing to drill for oil or gas in the U.S. Arctic and recommends mechanisms for improving public access to, and intra- and inter-agency sharing of, information from companies engaged in offshore drilling. We use the term “performance indicator” to refer to an observable metric that correlates with an aspect of an operator’s performance that is either too difficult to measure directly, or too broad to be reduced to a single, precisely quantifiable metric. Performance indicators can be used to compare an operator’s performance in a particular year against its performance in previous years or against average industry performance

Proposed Indicators to Measure the Environmental Responsibiity of Oil and Gas Companies and Regulatory Reforms to Improve Access to Information about Offshore Drilling

This paper suggests a set of indicators to evaluate and predict the environmental performance of companies proposing to drill for oil or gas in the U.S. Arctic and recommends mechanisms for improving public access to, and intra- and inter-agency sharing of, information from companies engaged in offshore drilling. We use the term “performance indicator” to refer to an observable metric that correlates with an aspect of an operator’s performance that is either too difficult to measure directly, or too broad to be reduced to a single, precisely quantifiable metric. Performance indicators can be used to compare an operator’s performance in a particular year against its performance in previous years or against average industry performance

The Effects of a Feedback Package on the Facial Orientation of a Young Girl with Autism During Restricted and Free Operant Conditions

A multiple baseline design across activities and people was used to assess the effectiveness of a feedback package on the facial orientation of a young girl with autism. During baseline, observations indicated low rates of facial orientation and high rates of gaze avoidance during conversation (restricted operant) and play (free operant) conditions. After treatment, facial orientation rates increased and gaze avoidance rates decreased to levels similar to typically-developing peers and maintained at one month follow up. These results suggest that the feedback package was effective in producing durable facial orientation across different environments and people. Possible interpretations, strengths, and limitations are discussed

The 14q32 maternally imprinted locus is a major source of longitudinally stable circulating microRNAs as measured by small RNA sequencing.

Understanding the normal temporal variation of serum molecules is a critical factor for identifying useful candidate biomarkers for the diagnosis and prognosis of chronic disease. Using small RNA sequencing in a longitudinal study of 66 women with no history of cancer, we determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2-5 years in the course of the screening trial, UKCTOCS. We were able to define a subset of longitudinally stable miRNAs (ICC >0.75) that were individually discriminating of women who had no cancer over the study period. These miRNAs were dominated by those originating from the C14MC cluster that is subject to maternal imprinting. This assessment was not significantly affected by common confounders such as age, BMI or time to centrifugation nor alternative methods to data normalisation. Our analysis provides important benchmark data supporting the development of miRNA biomarkers for the impact of life-course exposure as well as diagnosis and prognostication of chronic disease

Dietary Supplementation with Omega-3 Polyunsaturated Fatty Acids Reduces Opioid-Seeking Behaviors and Alters the Gut Microbiome.

Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses observed in human opioid addiction. The mechanisms associated with opioid dependence, the accompanying withdrawal symptoms, and the relapses that are often observed months or years after opioid dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure whereby the level of administration is self-directed with periods of behavior acquisition, maintenance, and then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that dietary interventions that reduce inflammation, including omega-3 polyunsaturated fatty acids (n-3 PUFAs), may reduce substance misuse liability. Using the self-directed intake model, we characterize the observed profile of opioid use and demonstrate that an n-3-PUFA-enriched diet ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile the microbiome composition and the effects of chronic opioid exposure and n-3 PUFA supplementation. We demonstrate that the withdrawal of opioids led to a significant depletion in specific microbiota genera, whereas n-3 PUFA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we examined the activation state of microglia in the striatum and found that n-3 PUFA supplementation reduced the basal activation state of microglia. These preclinical data suggest that a diet enriched in n-3 PUFAs could be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid addiction

Engineering <i>Mycoplasma pneumoniae</i> to bypass the association with Guillain-Barré syndrome

A non-pathogenic Mycoplasma pneumoniae-based chassis is leading the development of live biotherapeutic products (LBPs) for respiratory diseases. However, reports connecting Guillain-Barré syndrome (GBS) cases to prior M. pneumoniae infections represent a concern for exploiting such a chassis. Galactolipids, especially galactocerebroside (GalCer), are considered the most likely M. pneumoniae antigens triggering autoimmune responses associated with GBS development. In this work, we generated different strains lacking genes involved in galactolipids biosynthesis. Glycolipid profiling of the strains demonstrated that some mutants show a complete lack of galactolipids. Cross-reactivity assays with sera from GBS patients with prior M. pneumoniae infection showed that certain engineered strains exhibit reduced antibody recognition. However, correlation analyses of these results with the glycolipid profile of the engineered strains suggest that other factors different from GalCer contribute to sera recognition, including total ceramide levels, dihexosylceramide (DHCer), and diglycosyldiacylglycerol (DGDAG). Finally, we discuss the best candidate strains as potential GBS-free Mycoplasma chassis.</p

Australia’s COVID-19 pandemic housing policy responses

This research reviewed Australia’s COVID-19 housing policy responses to better understand their intervention approach, underlying logic, short and long term goals, target groups and level of success. It considered literature and policy from Australia and a small number of international comparator policies; conducted online surveys of landlords and of economists; and consulted key stake holders. Given Australia’s federated system of government, considerable differences quickly emerged between intervention approaches across states and territories. This was also driven by the extent to which different jurisdictions were impacted by the spread of the virus, the extent and frequency of lockdowns, and damage to state/local economies. The national and state policy measures implemented to support home ownership achieved the desired goal of providing short-term stimulus to the residential building sector and support to the broader economy. However, a range of anticipated and unforeseen consequences have precipitated as a result of concentrated demand-side subsidies, low interest rates and flexible lending conditions. The establishment of an agile infrastructure to support information sharing will support more effective and innovative housing policy development in the future. The state-to-state infrastructure and approaches that were developed rapidly and which supported jurisdictional responses to COVID-19 provide a template for a shelf-ready policy-sharing practice that warrants supported development across governments. This could usefully include local government as well as state and territory and national tiers of governance

Public Health and the Built Environment: Historical, Empirical, and Theoretical Foundations for an Expanded Role

In 2000, the Center for Disease Control and Prevention\u27s National Center for Environmental Health issued a report that explored some of the ways in which sprawl impacts public health. The report has generated great interest, and state health officials are beginning to discuss the relationship between land use and public health. The CDC report has also produced a backlash. For example, the Southern California Building Industry Association labeled the report a ludicrous sham and argued that the CDC should stick to fighting physical diseases, not defending political ones. In this environment, it is understandable if the CDC looks to such critiques as simply the latest partisan recruit to a political debate. But critics of the CDC\u27s efforts in this area may substantially overstate their case in the other direction. There is now and has long been a demonstrated connection between health, including physical disease, and the built environment. Moreover, government has intervened in the past in response to this connection and it continues to do so. While neither past practice nor current evidence make government intervention inevitable, this paper argues that such intervention is appropriate and supported by theory as well as history and empirical evidence