Consequences of Artificial Light at Night: The Linkage between Chasing Darkness Away and Epigenetic Modifications

Epigenetics is an important tool for understanding the relation between environmental exposures and cellular functions, including metabolic and proliferative responses. At our research center, we have devolved a mouse model for characterizing the relation between exposure to artificial light at night (ALAN) and both global DNA methylation (GDM) and breast cancer. Generally, the model describes a close association between ALAN and cancer responses. Cancer responses are eminent at all light spectra, with the prevalent manifestation at the shorter end of the visible spectrum. ALAN-induced pineal melatonin suppression is the principal candidate mechanism mediating the environmental exposure at the molecular level by eliciting aberrant GDM modifications. The carcinogenic potential of ALAN can be ameliorated in mice by exogenous melatonin treatment. In contrast to BALB/c mice, humans are diurnal species, and thus, it is of great interest to evaluate the ALAN-melatonin-GDM nexus also in a diurnal mouse model. The fat sand rat (Psammomys obesus) provides an appropriate model as its responses to photoperiod are comparable to humans. Interestingly, melatonin and thyroxin have opposite effects on GDM levels in P. obesus. Melatonin, GDM levels, and even thyroxin may be utilized as novel biomarkers for detection, staging, therapy, and prevention of breast cancer progression

Heterogeneity of Target Antigens in Sarcoidosis-Associated Membranous Nephropathy

Introduction: Membranous nephropathy (MN) is the most common glomerular disease associated with sarcoidosis. The target antigen M-type phospholipase A2 receptor 1 (PLA2R) has been identified in a subset of sarcoidosis-associated MN. The target antigen is not known in the remaining sarcoidosis-associated MN. Methods: Data of patients with history of sarcoidosis and biopsy-proven MN were retrieved and analyzed. Mass spectrometry (MS/MS) was performed on all kidney biopsies of sarcoidosis-associated MN to detect the target antigens. Immunohistochemistry (IHC) studies were performed to confirm and localize the target antigens along the glomerular basement membrane (GBM). Results: Eighteen patients with history of sarcoidosis and biopsy-proven MN were identified, of whom 3 were known to be PLA2R-negative, and in the remaining patients the target antigen was unknown. Thirteen (72%) patients were males; the median age at MN diagnosis was 54.5 years. The median proteinuria at presentation was proteinuria 9.8 g/24 h. Eight patients (44.4%) had concurrent sarcoidosis. Using MS/MS, we detected PLA2R and neural epidermal growth factor-like-1 protein (NELL1) in 7 (46.6%) and 4 (22.2%) patients, respectively. In addition, 1 case each (5.5%) was positive for thrombospondin type 1 domain-containing 7A (THSD7A), protocadherin-7 (PCDH7), and putative antigen Serpin B12. No known target antigen was detected in the remaining 4 patients (22.2%). Conclusion: Patients with sarcoidosis and MN exhibit heterogeneous target antigens. We identified, along with PLA2R, the presence of previously unreported antigens, including NELL1, PCDH7, and THSD7A. The incidence of the target antigens in sarcoidosis appears to mirror the overall incidence of target antigens in MN. MN in sarcoidosis may be the result of a heightened immune response and is not associated with a single target antige

Maintenance of Remission and Risk of Relapse in Myeloperoxidase-Positive ANCA-Associated Vasculitis with Kidney Involvement

Background The optimal strategy for remission-maintenance therapy in patients with myeloperoxidase-ANCA (MPO-ANCA)-associated vasculitis is not established. Defining parameters to guide maintenance therapy is required.Methods This was a retrospective cohort study of all patients with MPO-ANCA-associated vasculitis (microscopic with polyangiitis and granulomatosis with polyangiitis) and GN followed at the Mayo Clinic between 1996 and 2015. Relapse rate, MPO-ANCA status, and remission-maintenance therapies were reviewed. Logistic regression models, Kaplan-Meier method, and Cox proportional hazards regression models were applied.Results We analyzed 159 patients with active MPO-ANCA-associated vasculitis with GN. Sixty-six (42%) patients had at least one relapse, and 52 (33%) relapsed before 60 months. Patients with MPO-ANCA who became persistently negative did not relapse (hazard ratio [HR], 0.03; 95% confidence interval [95% CI], 0.002 to 0.431; P=0.01). The reappearance of MPO-ANCA was associated with a higher risk of relapse (HR, 1.91; 95% CI, 1.109 to 3.293; P=0.02). Immunosuppression was withdrawn in 80 (50%) patients, and this was less likely in those who received cyclophosphamide for remission induction or in patients with persistently positive MPO-ANCA (odds ratio [OR], 0.44; 95% CI, 0.228 to 0.861; P=0.02 and OR, 0.42; 95% CI, 0.213 to 0.820; P=0.01, respectively). Relapse frequency was not different between patients with persistently positive MPO-ANCA and patients with MPO-ANCA reappearance (44% versus 39%, P=0.49), irrespective of remission-maintenance treatment. Ear, nose, and throat involvement (OR, 6.10; 95% CI, 1.280 to 29.010; P=0.02) and MPO-ANCA reappearance (OR, 9.25; 95% CI, 3.126 to 27.361; P < 0.001) were independently associated with relapse after treatment withdrawal.Conclusions Patients persistently MPO-ANCA negative are at low risk for relapse even without remission maintenance therapy. Persistence or subsequent reappearance of MPO-ANCA is associated with a higher risk of relapse

Nature, extent and ecological implications of night-time light from road vehicles

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record1.The erosion of night‐time by the introduction of artificial lighting constitutes a profound pressure on the natural environment. It has altered what had for millennia been reliable signals from natural light cycles used for regulating a host of biological processes, with impacts ranging from changes in gene expression to ecosystem processes. 2.Studies of these impacts have focused almost exclusively on those resulting from stationary sources of light emissions, and particularly streetlights. However, mobile sources, especially road vehicle headlights, contribute substantial additional emissions. 3.The ecological impacts of light emissions from vehicle headlights are likely to be especially high because these are (i) focused so as to light roadsides at higher intensities than commonly experienced from other sources, and well above activation thresholds for many biological processes; (ii) projected largely in a horizontal plane and thus can carry over long distances; (iii) introduced into much larger areas of the landscape than experience street lighting; (iv) typically broad ‘white’ spectrum, which substantially overlaps the action spectra of many biological processes; and (v) often experienced at roadsides as series of pulses of light (produced by passage of vehicles), a dynamic known to have major biological impacts. 4.The ecological impacts of road vehicle headlights will markedly increase with projected global growth in numbers of vehicles and the road network, increasing the local severity of emissions (because vehicle numbers are increasing faster than growth in the road network) and introducing emissions into areas from which they were previously absent. The effects will be further exacerbated by technological developments that are increasing the intensity of headlight emissions and the amounts of blue light in emission spectra. 5.Synthesis and applications. Emissions from vehicle headlights need to be considered as a major, and growing, source of ecological impacts of artificial night‐time lighting. It will be a significant challenge to minimize these impacts whilst balancing drivers’ needs at night and avoiding risk and discomfort for other road users. Nonetheless, there is potential to identify solutions to these conflicts, both through the design of headlights and that of roads.The research leading to this article has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 268504 and Natural Environment Research Council grants NE/N001672/1 and NE/P01156X/1

Hormonally mediated effects of artificial light at night on behavior and fitness: linking endocrine mechanisms with function.

Alternation between day and night is a predictable environmental fluctuation that organisms use to time their activities. Since the invention of artificial lighting, this predictability has been disrupted and continues to change in a unidirectional fashion with increasing urbanization. As hormones mediate individual responses to changing environments, endocrine systems might be one of the first systems affected, as well as being the first line of defense to ameliorate any negative health impacts. In this Review, we first highlight how light can influence endocrine function in vertebrates. We then focus on four endocrine axes that might be affected by artificial light at night (ALAN): pineal, reproductive, adrenal and thyroid. Throughout, we highlight key findings, rather than performing an exhaustive review, in order to emphasize knowledge gaps that are hindering progress on proposing impactful and concrete plans to ameliorate the negative effects of ALAN. We discuss these findings with respect to impacts on human and animal health, with a focus on the consequences of anthropogenic modification of the night-time environment for non-human organisms. Lastly, we stress the need for the integration of field and lab experiments as well as the need for long-term integrative eco-physiological studies in the rapidly expanding field of light pollution

Environmental Challenges and Physiological Solutions: Comparative Energetic Daily Rhythms of Field Mice Populations from Different Ecosystems

Daily and seasonal variations in physiological characteristics of mammals can be considered adaptations to temporal habitat variables. Across different ecosystems, physiological adjustments are expected to be sensitive to different environmental signals such as changes in photoperiod, temperature or water and food availability; the relative importance of a particular signal being dependent on the ecosystem in question. Energy intake, oxygen consumption (VO(2)) and body temperature (T(b)) daily rhythms were compared between two populations of the broad-toothed field mouse Apodemus mystacinus, one from a Mediterranean and another from a sub-Alpine ecosystem. Mice were acclimated to short-day (SD) 'winter' and long-day (LD) 'summer' photoperiods under different levels of salinity simulating osmotic challenges. Mediterranean mice had higher VO(2) values than sub-Alpine mice. In addition, mice exposed to short days had higher VO(2) values when given water with a high salinity compared with mice exposed to long days. By comparison, across both populations, increasing salinity resulted in a decreased T(b) in SD- but not in LD-mice. Thus, SD-mice may conserve energy by decreasing T(b) during ('winter') conditions which are expected to be cool, whereas LD-mice might do the opposite and maintain a higher T(b) during ('summer') conditions which are expected to be warm. LD-mice behaved to reduce energy expenditure, which might be considered a useful trait during 'summer' conditions. Overall, increasing salinity was a clear signal for Mediterranean-mice with resultant effects on VO(2) and T(b) daily rhythms but had less of an effect on sub-Alpine mice, which were more responsive to changes in photoperiod. Results provide an insight into how different populations respond physiologically to various environmental challenges