Mechanisms by which circadian rhythm disruption may lead to cancer

Humans have evolved in a rhythmic environment and display daily (circadian) rhythms in physiology, metabolism and behaviour that are in synchrony with the solar day. Modern lifestyles have compromised the exposure to bright light during the day and dark nights, resulting in the desynchronisation of endogenously generated circadian rhythms from the external environment and loss of coordination between rhythms within the body. This has detrimental effects on physical and mental health, due to the misregulation and uncoupling of important cellular and physiological processes. Long-term shift workers who are exposed to bright light at night experience the greatest disruption of their circadian rhythms. Studies have shown an association between exposure to light at night, circadian rhythm disruption and an increased risk of cancer. Previous reviews have explored the relevance of light and melatonin in cancer, but here we explore the correlation of circadian rhythm disruption and cancer in terms of molecular mechanisms affecting circadian gene expression and melatonin secretion

Suppression of quantum oscillations and the dependence on site energies in electronic excitation transfer in the Fenna-Matthews-Olson trimer

Energy transfer in the photosynthetic complex of the Green Sulfur Bacteria known as the Fenna-Matthews-Olson (FMO) complex is studied theoretically taking all three subunits (monomers) of the FMO trimer and the recently found eighth bacteriochlorophyll (BChl) molecule into account. We find that in all considered cases there is very little transfer between the monomers. Since it is believed that the eighth BChl is located near the main light harvesting antenna we look at the differences in transfer between the situation when BChl 8 is initially excited and the usually considered case when BChl 1 or 6 is initially excited. We find strong differences in the transfer dynamics, both qualitatively and quantitatively. When the excited state dynamics is initialized at site eight of the FMO complex, we see a slow exponential-like decay of the excitation. This is in contrast to the oscillations and a relatively fast transfer that occurs when only seven sites or initialization at sites 1 and 6 is considered. Additionally we show that differences in the values of the electronic transition energies found in the literature lead to a large difference in the transfer dynamics

Fish of Lake Mead and Lake Mohave

This publication offers an in-depth study of the fish and other organisms that live in Lakes Mead and Mohave. The history and background of the two lakes is offered, as well as information about diseases, parasites, and unusual fish occurrences. Food sources, predation and competition are also discussed

Reliability of histopathologic diagnosis of fibrotic interstitial lung disease: an international collaborative standardization project

Malaltia pulmonar intersticial; Fibrosi pulmonar; Pneumònia intersticial habitualEnfermedad pulmonar intersticial; Fibrosis pulmonar; Neumonía intersticial habitualInterstitial lung disease; Pulmonary fibrosis; Usual interstitial pneumoniaBackground Current interstitial lung disease (ILD) diagnostic guidelines assess criteria across clinical, radiologic and pathologic domains. Significant interobserver variation in histopathologic evaluation has previously been shown but the specific source of these discrepancies is poorly documented. We sought to document specific areas of difficulty and develop improved criteria that would reduce overall interobserver variation. Methods Using an internet-based approach, we reviewed selected images of specific diagnostic features of ILD histopathology and whole slide images of fibrotic ILD. After an initial round of review, we confirmed the presence of interobserver variation among our group. We then developed refined criteria and reviewed a second set of cases. Results The initial round reproduced the existing literature on interobserver variation in diagnosis of ILD. Cases which were pre-selected as inconsistent with usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) were confirmed as such by multi-observer review. Cases which were thought to be in the spectrum of chronic fibrotic ILD for which UIP/IPF were in the differential showed marked variation in nearly all aspects of ILD evaluation including extent of inflammation and extent and pattern of fibrosis. A proposed set of more explicit criteria had only modest effects on this outcome. While we were only modestly successful in reducing interobserver variation, we did identify specific reasons that current histopathologic criteria of fibrotic ILD are not well defined in practice. Conclusions Any additional classification scheme must address interobserver variation in histopathologic diagnosis of fibrotic ILD order to remain clinically relevant. Improvements to tissue-based diagnostics may require substantial resources such as larger datasets or novel technologies to improve reproducibility. Benchmarks should be established for expected outcomes among clinically defined subgroups as a quality metric.This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors

Genetic fingerprinting reveals natal origins of male leatherback turtles encountered in the Atlantic Ocean and Mediterranean Sea

This paper is not subject to U.S. copyright. The definitive version was published in Marine Biology 164 (2017): 181, doi:10.1007/s00227-017-3211-0.Understanding population dynamics in broadly distributed marine species with cryptic life history stages is challenging. Information on the population dynamics of sea turtles tends to be biased toward females, due to their accessibility for study on nesting beaches. Males are encountered only at sea; there is little information about their migratory routes, residence areas, foraging zones, and population boundaries. In particular, male leatherbacks (Dermochelys coriacea) are quite elusive; little is known about adult and juvenile male distribution or behavior. The at-sea distribution of male turtles from different breeding populations is not known. Here, 122 captured or stranded male leatherback turtles from the USA, Turkey, France, and Canada (collected 1997–2012) were assigned to one of nine Atlantic basin populations using genetic analysis with microsatellite DNA markers. We found that all turtles originated from western Atlantic nesting beaches (Trinidad 55%, French Guiana 31%, and Costa Rica 14%). Although genetic data for other Atlantic nesting populations were represented in the assignment analysis (St. Croix, Brazil, Florida, and Africa (west and south), none of the male leatherbacks included in this study were shown to originate from these populations. This was an unexpected result based on estimated source population sizes. One stranded turtle from Turkey was assigned to French Guiana, while others that were stranded in France were from Trinidad or French Guiana breeding populations. For 12 male leatherbacks in our dataset, natal origins determined from the genetic assignment tests were compared to published satellite and flipper tag information to provide evidence of natal homing for male leatherbacks, which corroborated our genetic findings. Our focused study on male leatherback natal origins provides information not previously known for this cryptic, but essential component of the breeding population. This method should provide a guideline for future studies, with the ultimate goal of improving management and conservation strategies for threatened and endangered species by taking the male component of the breeding population into account.Sample collection in Nova Scotia, Canada, was supported by funding from Canadian Wildlife Federation, Environment Canada, Fisheries and Oceans Canada, George Cedric Metcalf Foundation, Habitat Stewardship Program for Species at Risk, National Fish and Wildlife Foundation (USA), National Marine Fisheries Service (USA), Natural Sciences and Engineering Research Council of Canada, and World Wildlife Fund Canada. Funding for US samples was provided by National Oceanic and Atmospheric Administration, Massachusetts Division of Marine Fisheries, National Fish and Wildlife Foundation, and Cape Cod Commercial Fisherman’s Alliance. Funding support for this analysis and for Kelly R. Stewart was provided by a Lenfest Ocean Program Grant

Impaired Mitochondrial Function and Insulin Resistance of Skeletal Muscle in Mitochondrial Diabetes

OBJECTIVE - Impaired muscular mitochondrial function is related to common insulin resistance in type 2 diabetes. Mitochondrial diseases frequently lead to diabetes, which is mostly attributed to defective beta-cell mitochondria and secretion. RESEARCH DESIGN AND METHODS - We assessed muscular mitochondrial function and lipid deposition in liver (hepatocellular lipids [HCLs]) and muscle (intramyocellular lipids [IMCLs]) using P-31/H-1 magnetic resonance spectroscopy and insulin sensitivity and endogenous glucose production (EGP) using hyperinsulinemic-euglycemic clamps combined with isotopic tracer dilution in one female patient suffering from MELAS(myopathy,encephalopathy, lactic acidosis, and stroke-like episodes) syndrome and in six control subjects. RESULTS - The MELAS patient showed impaired insulin sensitivity (4.3 vs. 8.6 +/- 0.5 mg . kg(-1) . min(-1)) and suppression of EGP (69 vs. 94 +/- 1%), and her baseline and insulin-stimulated ATP synthesis were reduced (7.3 and 8.9 vs. 10.6 +/- 1.0 and 12.8 +/- 1.3 mu mol . l(-1) . min(-1)) compared with those of the control subjects. HCLs and IMCLs were comparable between the MELAS patient and control subjects. CONCLUSIONS - Impairment of muscle mitochondrial fitness promotes insulin resistance and could thereby contribute to the development of diabetes in some patients with the MELAS syndrome

Assessing the validity and reliability and determining cut-points of the Actiwatch 2 in measuring physical activity

Objective: The Actiwatch 2 (AW2) is a wrist-worn accelerometer typically used to measure sleep. Although it can measure physical activity, there is limited evidence supporting its validity. We assessed the validity and reliability of the AW2 to measure sedentary behavior and physical activity (light, moderate, vigorous intensities), and reported their respective count cut-points. Approach: Twenty-eight males and 22 females completed a task battery comprising three sedentary tasks and six randomized physical activity tasks at varying intensities, whilst wearing the AW2, a reference accelerometry device (Actigraph GT3X) and a cardiopulmonary gas analyzer on two separate occasions. Validity was assessed using correlations (AW2 counts versus GT3X counts and metabolic equivalent (MET) values), reliability using Bland–Altman analyses, and cut-points were determined using receiver operating characteristic (ROC) area under the curve (AUC) analyses. Main results: AW2 counts were positively correlated with GT3X counts (rho = 0.902, p < 0.001) and METs (rho = 0.900, p < 0.001). AW2-derived counts were comparable across independent assessment periods. Sedentary (AUC = 0.99, cut-point: 256 cpm) and vigorous activity (AUC = 0.95, cut-point: 720 cpm) were strongly characterized, and moderate activity (AUC = 0.66, cut-point: 418 cpm) was weakly characterized. Significance: The use of the AW2 in physical activity monitoring looks promising for sedentary behavior, moderate and vigorous activity, however, further validation is needed

Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

Background: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti- inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 mM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl 2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 mg/kg) significantly lengthened the QT c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT c . Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 mM) decreased the amplitude of rapid (I Kr ) and slow (I Ks ) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I Ca ) was slightly diminished, but the transient outward (I to ) and inward rectifier (I K1 ) potassium currents were not influenced. Conclusions: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve

Multilayer metamaterial absorbers inspired by perfectly matched layers

We derive periodic multilayer absorbers with effective uniaxial properties similar to perfectly matched layers (PML). This approximate representation of PML is based on the effective medium theory and we call it an effective medium PML (EM-PML). We compare the spatial reflection spectrum of the layered absorbers to that of a PML material and demonstrate that after neglecting gain and magnetic properties, the absorber remains functional. This opens a route to create electromagnetic absorbers for real and not only numerical applications and as an example we introduce a layered absorber for the wavelength of $8$~$\mu$m made of SiO$_2$ and NaCl. We also show that similar cylindrical core-shell nanostructures derived from flat multilayers also exhibit very good absorptive and reflective properties despite the different geometry