Epithelial cell-directed efferocytosis in the post-partum mammary gland is necessary for tissue homeostasis and future lactation

<p>Abstract</p> <p>Background</p> <p>Mammary glands harbor a profound burden of apoptotic cells (ACs) during post-lactational involution, but little is known regarding mechanisms by which ACs are cleared from the mammary gland, or consequences if this process is interrupted. We investigated AC clearance, also termed efferocytosis, during post-lactational remodeling, using mice deficient for MerTK, Axl, and Tyro3, three related receptor tyrosine kinases (RTKs) regulating macrophage-mediated efferocytosis in monocytes. MerTK expression, apoptosis and the accumulation of apoptotic debris were examined in histological sections of MerTK-deficient, Axl/Tyro3-deficient, and wild-type mammary glands harvested at specific time points during lactation and synchronized involution. The ability of primary mammary epithelial cells (MECs) to engulf ACs was assessed in culture. Transplant of MerTK-deficient mammary epithelium into cleared WT mammary fat pads was used to assess the contribution of WT mammary macrophages to post-lactational efferocytosis.</p> <p>Results</p> <p>ACs induced MerTK expression in MECs, resulting in elevated MerTK levels at the earliest stages of involution. Loss of MerTK resulted in AC accumulation in post-lactational MerTK-deficient mammary glands, but not in Axl and Tyro3-deficient mammary glands. Increased vascularization, fibrosis, and epithelial hyperproliferation were observed in MerTK-deficient mammary glands through at least 60 days post-weaning, due to failed efferocytosis after lactation, but did not manifest in nulliparous mice. WT host-derived macrophages failed to rescue efferocytosis in transplanted MerTK-deficient mammary epithelium.</p> <p>Conclusion</p> <p>Efferocytosis by MECs through MerTK is crucial for mammary gland homeostasis and function during the post-lactational period. Efferocytosis by MECs thus limits pathologic consequences associated with the apoptotic load following lactation.</p

Effect of acute copper sulfate exposure on olfactory responses to amino acids and pheromones in goldfish (Carassius auratus)

Exposure of olfactory epithelium to environmentally relevant concentrations of copper disrupts olfaction in fish. To examine the dynamics of recovery at both functional and morphological levels after acute copper exposure, unilateral exposure of goldfish olfactory epithelia to 100 μM CuSO4 (10 min) was followed by electro-olfactogram (EOG) recording and scanning electron microscopy. Sensitivity to amino acids (L-arginine and L-serine), generally considered food-related odorants, recovered most rapidly (three days), followed by that to catecholamines(3-O-methoxytyramine),bileacids(taurolithocholic acid) and the steroid pheromone, 17,20 -dihydroxy-4-pregnen- 3-one 20-sulfate, which took 28 days to reach full recovery. Sensitivity to the postovulatory pheromone prostaglandin F2R had not fully recovered even at 28 days. These changes in sensitivity were correlated with changes in the recovery of ciliated and microvillous receptor cell types. Microvillous cells appeared largely unaffected by CuSO4 treatment. Cilia in ciliated receptor neurones, however, appeared damaged one day post-treatment and were virtually absent after three days but had begun to recover after 14 days. Together, these results support the hypothesis that microvillous receptor neurones detect amino acids whereas ciliated receptor neurones were not functional and are responsible for detection of social stimuli (bile acidsandpheromones).Furthermore, differences in sensitivity to copper may be due to different transduction pathways in the different cell types

The SCottish Alcoholic Liver disease Evaluation: a population-level matched cohort study of hospital-based costs, 1991-2011

Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission. 5 matched controls for every incident case were identified from the Scottish population level primary care database. Hospital costs were calculated for both cases and controls using length of stay from morbidity records and hospital-specific daily rates by specialty. Remaining lifetime costs were estimated using parametric survival models and predicted annual costs. 35,208 incident alcoholic liver disease hospitalisations were identified. Mean annual hospital costs for cases were 2.3 times that of controls pre diagnosis (£804 higher) and 10.2 times (£12,774 higher) post diagnosis. Mean incident admission cost was £6,663. Remaining lifetime cost for a male, 50-59 years old, living in the most deprived area diagnosed with acoholic liver disease was estimated to be £65,999 higher than the matched controls (£12,474 for 7.43 years remaining life compared to £1,224 for 21.8 years). In Scotland, alcoholic liver disease diagnosis is associated with significant increases in admissions to hospital both before and after diagnosis. Our results provide robust population level estimates of costs of alcoholic liver disease for the purposes of health-care delivery, planning and future cost-effectiveness analyses

Time Trends in Deaths Before Age 50 Years in People with Type 1 Diabetes:a nationwide analysis from Scotland 2004–2017

Acknowledgements We thank the SDRN Epidemiology Group: J. Chalmers (Diabetes Centre, Victoria Hospital, Kirkcaldy, UK), C. Fischbacher (Information Services Division, NHS National Services Scotland, Edinburgh, UK), B. Kennon (Queen Elizabeth University Hospital, Glasgow, UK), G. Leese (Ninewells Hospital, Dundee, UK), R. Lindsay (British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK), J. McKnight (Western General Hospital, NHS, UK), J. Petrie (Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK), R. McCrimmon (Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK), S. Philip (Grampian Diabetes Research Unit, Diabetes Centre, Aberdeen Royal Infirmary, Aberdeen, UK), D. McAllister (Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK), E. Pearson (Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK) and S. Wild (Usher Institute, University of Edinburgh, Edinburgh, UK). The SDRN Epidemiology Group resource was originally set up under Ethics ref. 11/AL/0225, PAC 33/11 now running under PBPP ref. 1617-0147. Funding This study was supported by funding from Diabetes UK (17/0005627).Peer reviewedPublisher PD

Industrial demand side management status report: Synopsis

Industrial demand side management (DSM) programs, though not as developed or widely implemented as residential and commercial programs, hold the promise of significant energy savings-savings that will benefit industrial firms, utilities and the environment. This paper is a synopsis of a larger research report, Industrial Demand Side Management. A Status Report, prepared for the US Department of Energy. The report provides an overview of and rationale for DSM programs. Benefits and barriers are described, and data from the Manufacturing Energy Consumption Survey are used to estimate potential electricity savings from industrial energy efficiency measures. Overcoming difficulties to effective program implementation is worthwhile, since rough estimates indicate a substantial potential for electricity savings. The report categorizes types of DSM programs, presents several examples of each type, and explores elements of successful programs. Two in-depth case studies (of Boise Cascade and of Eli Lilly and Company) illustrate two types of effective DSM programs. Interviews with staff from state public utility commissions indicate the current thinking about the status and future of industrial DSM programs. Finally, the research report also includes a comprehensive bibliography, a description of technical assistance programs, and an example of a methodology for evaluating potential or actual savings from projects