Mitochondrial decline precedes phenotype development in the complement factor H mouse model of retinal degeneration but can be corrected by near infrared light

AbstractMitochondria produce adenosine triphosphate (ATP), critical for cellular metabolism. ATP declines with age, which is associated with inflammation. Here, we measure retinal and brain ATP in normal C57BL/6 and complement factor H knockout mice (Cfh−/−), which are proposed as a model of age-related macular degeneration. We show a significant premature 30% decline in retinal ATP in Cfh−/− mice and a subsequent shift in expression of a heat shock protein that is predominantly mitochondrial (Hsp60). Changes in Hsp60 are associated with stress and neuroprotection. We find no differences in brain ATP between C57BL/6 and Cfh−/− mice. Near infrared (NIR) increases ATP and reduces inflammation. ATP decline in Cfh−/− mice was corrected with NIR which also shifted Hsp60 labeling patterns. ATP decline in Cfh−/− mice occurs before inflammation becomes established and photoreceptor loss occurs and may relate to disease etiology. However, ATP levels were corrected with NIR. In summary, we provide evidence for a mitochondrial basis for this disease in mice and correct this with simple light exposure known to improve mitochondrial function

Ecohydrological separation in wet, low energy northern environments? A preliminary assessment using different soil water extraction techniques

Funded by European Research Council ERC. Grant Number: project GA 335910 VEWA ACKNOWLEDGEMENTS The constructive comments and suggestions from two anonymous reviewers greatly improved an earlier version of this manuscript. Jon Dick, Jason Lesselsand Jane Bang Poulsen are thanked for assistance with data collection; Audrey Innes for sample preparation and assistance with the cryogenic extraction of water samples; Paula Craib for glassware design; Colleagues in Prof. J. Anderson’s lab for day-to-day assistance incryogenic extraction; Todd Dawson and Nathalie Schultz for providing information on extraction techniques and the analysis of vegetation water; Hedda Weitz for help with the centrifugation of soil samples;and Iain Malcolm and colleagues at the Marine Scotland Freshwater Lab for providing meteorological data. We thank Jason Newton and the Scottish Universities Environmental Research Centre (SUERC) Mass Spectrometry Facility Laboratory in East Kilbride for theisotopic analyses of the xylem water samples. The European Research Council ERC (project GA 335910VEWA) is thanked for funding.Peer reviewedPostprin

Medicare-Paid Naloxone: Trends in Non-Metropolitan and Metropolitan Areas

Overview of Key Findings Medicare pays for the largest share (\u3e 30%) of naloxone dispensed from retail pharmacies in non-metropolitan areas. Medicare-paid dispensing has grown since 2013, but from 2017-2018 dispensing growth in non-metropolitan areas slowed considerably compared to metropolitan areas (42% v 121%, respectively). As of 2018, the rate of naloxone dispensing to Medicare enrollees in metropolitan areas was approximately double that in non-metropolitan areas (4.9 v 2.9 per 1,000 enrollees, respectively)

An Integrated Assessment Framework for Uncertainty Studies in Global and Regional Climate Change: The IGSM-CAM

http://globalchange.mit.edu/research/publicationsThis paper describes an integrated assessment framework for uncertainty studies in global and regional climate change. In this framework, the Massachusetts Institute of Technology (MIT) Integrated Global System Model (IGSM), an integrated assessment model that couples an earth system model of intermediate complexity to a human activity model, is linked to the National Center for Atmospheric Research (NCAR) Community Atmosphere Model (CAM). Since the IGSM-CAM incorporates a human activity model, it is possible to analyze uncertainties in emissions resulting from uncertainties intrinsic to the economic model, from parametric uncertainty to uncertainty in future climate policies. Another major feature is the flexibility to vary key climate parameters controlling the climate response: climate sensitivity, net aerosol forcing and ocean heat uptake rate. Thus, the IGSM-CAM is a computationally efficient framework to explore the uncertainty in future global and regional climate change due to uncertainty in the climate response and projected emissions. This study further presents 21st century simulations based on two emissions scenarios (unconstrained scenario and stabilization scenario at 660 ppm CO2-equivalent by 2100) and three sets of climate parameters. The chosen climate parameters provide a good approximation for the median, and the 5th and 95th percentiles of the probability distribution of 21st century climate change. As such, this study presents new estimates of the 90% probability interval of regional climate change for different emissions scenarios. These results underscore the large uncertainty in regional climate change resulting from uncertainty in climate parameters and emissions, and the statistical uncertainty due to natural variability.The Joint Program on the Science and Policy of Global Change is funded by a number of federal agencies and a consortium of 40 industrial and foundation sponsors. (For the complete list see http://globalchange.mit.edu/sponsors/current.html)

Platelet-activating factor receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is an ether phospholipid mediator associated with platelet coagulation, but also subserves inflammatory roles. The PAF receptor (provisional nomenclature recommended by NC-IUPHAR [37]) is activated by PAF and other suggested endogenous ligands are oxidized phosphatidylcholine [73] and lysophosphatidylcholine [96]. It may also be activated by bacterial lipopolysaccharide [89]