Liver-fatty acid binding protein (L-FABP) is an abundant intracellular lipid-carrier protein. The hypothesis that perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and certain related ...perfluorooctanesulfonamide-based fluorochemicals (PFOSAs) can interfere with the binding affinity of L-FABP for fatty acids was tested. The relative effectiveness of PFOA, PFOS, N-ethylperfluorooctanesulfonamide (N-EtFOSA), N-ethylperfluorooctanesulfonamido ethanol (N-EtFOSE), and of the strong peroxisome proliferator Wyeth-14 643 (WY) to inhibit 11-(5-dimethylaminonapthalenesulphonyl)-undecanoic acid (DAUDA) binding to-L-FABP was determined. The dissociation constant (Kd) of the DAUDA-L-FABP complex was 0.47 nM. PFOS exhibited the highest level of inhibition of DAUDA-L-FABP binding in the competitive binding assays, followed by N-EtFOSA, WY, and, with equal IC
50s, N-EtFOSE and PFOA. The in vitro data presented in this study support the hypothesis that these fluorochemicals may interfere with the binding of fatty acids or other endogenous ligands to L-FABP. Furthermore, this work provides evidence to support the hypothesis that displacement of endogenous ligands from L-FABP may contribute to toxicity in rodents fed these fluorochemicals.
Clusters of imprinted genes are often controlled by an imprinting center that is necessary for allele-specific gene expression and to reprogram parent-of-origin information between generations. An ...imprinted domain at 15q11–q13 is responsible for both Angelman syndrome (AS) and Prader–Willi syndrome (PWS), two clinically distinct neurodevelopmental disorders. Angelman syndrome arises from the lack of maternal contribution from the locus, whereas Prader–Willi syndrome results from the absence of paternally expressed genes. In some rare cases of PWS and AS, small deletions may lead to incorrect parent-of-origin allele identity. DNA sequences common to these deletions define a bipartite imprinting center for the AS–PWS locus. The PWS–smallest region of deletion overlap (SRO) element of the imprinting center activates expression of genes from the paternal allele. The AS–SRO element generates maternal allele identity by epigenetically inactivating the PWS–SRO in oocytes so that paternal genes are silenced on the future maternal allele. Here we have investigated functional activities of the AS–SRO, the element necessary for maternal allele identity. We find that, in humans, the AS–SRO is an oocyte-specific promoter that generates transcripts that transit the PWS–SRO. Similar upstream promoters were detected in bovine oocytes. This result is consistent with a model in which imprinting centers become DNA methylated and acquire maternal allele identity in oocytes in response to transiting transcription.
In 2007, the International Agency for Research on Cancer classified shift work involving circadian disruption as probably carcinogenic to humans (group 2A), primarily based on experimental and ...epidemiologic evidence for breast cancer. In order to examine options for evidence-based preventive actions, 16 researchers in basic, epidemiological and applied sciences convened at a workshop in Copenhagen 26-27 October 2011. This paper summarizes the evidence from epidemiological and experimental studies and presents possible recommendations for prevention of the effects of night work on breast cancer. Among those studies that quantified duration of shift work, there were statistically significant elevations in risk only after about 20 years working night shift. It is unclear from these studies whether or not there is a modest but real elevated risk for shorter durations. Hence, restriction of the total number of years working night shift could be one future preventive recommendation for shift workers. The diurnal secretion of melatonin by the pineal gland with peak in secretory activity during the night is a good biochemical marker of the circadian rhythm. Disruption of the diurnal melatonin secretion pattern can be diminished by restricting the number of consecutive night shifts. Reddish light and reduced light intensity during work at night could potentially help diminish the inhibitory activity of light with strong intensity on the melatonin secretion, but further mechanistic insight is needed before definite recommendations can be made. Earlier or more intensive mammography screening among female night shift worker is not recommended because the harm-benefit ratio in this age group may not be beneficial. Preventive effects of melatonin supplementation on breast cancer risk have not been clearly documented, but may be a promising avenue if a lack of side effects can be shown even after long-term ingestion.women with previous or current breast cancer should be advised not to work night shifts because of strong experimental evidence demonstrating accelerated tumor growth by suppression of melatonin secretion. Work during the night is widespread worldwide. To provide additional evidence-based recommendations on prevention of diseases related to night shift work, large studies on the impact of various shift schedules and type of light on circadian rhythms need to be conducted in real work environments.
Background: Previous studies have reported conflicting results on the relation between serum osteoprotegerin (OPG) concentration and carotid intima media thickness (CIMT). Patients/methods: The ...present study was conducted to investigate the relations between OPG, risk factors for cardiovascular diseases (CVD) and carotid intima media thickness (CIMT) in a large cross‐sectional study including 6516 subjects aged 25–85 years who participated in a population‐based health survey. Results: CIMT increased significantly across tertiles of OPG after adjustment for traditional cardiovascular risk factors such as age, gender, smoking, total cholesterol, high‐density lipoprotein (HDL) cholesterol, C‐reactive protein (CRP), body mass index (BMI), systolic blood pressure, CVD and diabetes mellitus (P < 0.0001). There was a significant interaction between age and OPG (P = 0.026). The risk of being in the uppermost quartile of CIMT was reduced (OR 0.52, 95% CI 0.30–0.88) with each standard deviation (SD) higher level of OPG in subjects < 45 years (n = 444), whereas subjects ≥ 55 years of age (n = 4884) had an increased risk of being in the uppermost quartile of CIMT (OR 1.19, 95% CI 1.10–1.29) after adjustment for traditional CVD risk factors. Conclusions: Age has a differential impact on the association between OPG and CIMT in a general population. The present findings may suggest that increased serum OPG does not promote early atherosclerosis in younger subjects.
Measurements of organic carbon (OC) and black carbon (BC) concentrations over a variety of locations worldwide have been analyzed to infer the spatial distributions of the ratios of OC to BC. Since ...these ratios determine the relative amounts of scattering and absorption, they are often used to estimate the radiative forcing due to aerosols. An artifact in the protocol for filter measurements of OC has led to widespread overestimates of the ratio of OC to BC in atmospheric aerosols. We developed a criterion to correct for this artifact and analyze corrected OC to BC ratios. The OC to BC ratios, ranging from 1.3 to 2.4, appear relatively constant and are generally unaffected by seasonality, sources, or technology changes, at the locations considered here. The ratios compare well with emission inventories over Europe and China but are a factor of 2 lower in other regions. The reduced estimate for OC/BC in aerosols strengthens the argument that reduction of soot emissions maybe a useful approach to slow global warming.
Background: Recent studies indicate that arterial cardiovascular diseases and venous thromboembolism (VTE) share common risk factors. A family history of myocardial infarction (MI) is a strong and ...independent risk factor for future MI. Objectives: The purpose of the present study was to determine the impact of cardiovascular risk factors, including family history of MI, on the incidence of VTE in a prospective, population‐based study. Patients and methods: Traditional cardiovascular risk factors and family history of MI were registered in 21 330 subjects, aged 25–96 years, enrolled in the Tromsø study in 1994–95. First‐lifetime VTE events during follow‐up were registered up to 1 September 2007. Results: There were 327 VTE events (1.40 per 1000 person‐years), 138 (42%) unprovoked, during a mean of 10.9 years of follow‐up. In age‐ and gender‐adjusted analysis, age hazard ratio (HR) per decade, 1.97; 95% confidence interval (CI), 1.82–2.12, gender (men vs. women; HR, 1.25; 95% CI, 1.01–1.55), body mass index (BMI; HR per 3 kg m−2, 1.21; 95% CI, 1.13–1.31), and family history of MI (HR, 1.31; 95% CI, 1.04–1.65) were significantly associated with VTE. Family history of MI remained a significant risk factor for total VTE (HR, 1.27; 95% CI, 1.01–1.60) and unprovoked VTE (HR, 1.46; 95% CI, 1.03–2.07) in multivariable analysis. Blood pressure, total cholesterol, HDL‐cholesterol, triglycerides, and smoking were not independently associated with total VTE. Conclusions: Family history of MI is a risk factor for both MI and VTE, and provides further evidence of a link between venous and arterial thrombosis.
An occultation of ε Orionis by Enceladus' plume was observed with Enceladus at an orbital longitude near apoapsis in order to investigate whether water vapor flow is modulated diurnally, similar to ...ice particles. The occultation showed that the bulk water vapor emanating from Enceladus changes little with orbital position. The amount of gas in at least one supersonic jet increased significantly, implying that the increase in the number of particles lofted at apoapsis could be due to more gas coming from the supersonic jets and not the overall gas flux from the tiger stripe fissures that cross Enceladus' south polar region.
Key Points
Supersonic gas jets in Enceladus' water vapor plume loft more particles when Enceladus is at apoapsis
The bulk quantity of gas from fissures across Enceladus' south pole is relatively unaffected by the position of Enceladus in its orbit
Solid-state zinc-ion batteries (SSZIBs) are receiving much attention as low-cost and safe energy storage technology for emerging applications in flexible and wearable devices, and grid storage. ...However, the development of SSZIBs faces many challenges from key battery materials development to structure design. Herein, we review the most recent progress in the development of polymer electrolytes, cell chemistry and configuration, and demonstration of SSZIBs. In conclusion, perspectives for future research in materials, interface, and assessment of SSZIBs are discussed.
It has been suggested that for fluids in which the rate of strain varies appreciably over length scales of the order of the intermolecular interaction range, the viscosity must be treated as a ...nonlocal property of the fluid. The shear stress can then be postulated to be a convolution of this nonlocal viscosity kernel with the strain rate over all space. In this Letter, we confirm that this postulate is correct by a combination of analytical and numerical methods for an atomic fluid out of equilibrium. Furthermore, we show that a gradient expansion of the nonlocal constitutive equation gives a reasonable approximation to the shear stress in the small wave vector limit.
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