Role of caffeine in DNA recognition of a potential food‐carcinogen benzo[a]pyrene and UVA induced DNA damage

Electron transfer (ET) reactions are important for their implications in both oxidative and reductive DNA damages. The current contribution investigates the efficacy of caffeine, a xanthine alkaloid in preventing UVA radiation induced ET from a carcinogen, benzo[a]pyrene (BP) to DNA by forming stable caffeine–BP complexes. While steady‐state emission and absorption results emphasize the role of caffeine in hosting BP in aqueous medium, the molecular modeling studies propose the energetically favorable structure of caffeine–BP complex. The picosecond‐resolved emission spectroscopic studies precisely explore the caffeine‐mediated inhibition of ET from BP to DNA under UVA radiation. The potential therapeutic activity of caffeine in preventing DNA damage has been ensured by agarose gel electrophoresis. Furthermore, time‐gated fluorescence microscopy has been used to monitor caffeine‐mediated exclusion of BP from various cell lines including squamous epithelial cells, WI‐38 (fibroblast), MCF‐7 (breast cancer) and HeLa (cervical cancer) cells. Our in vitro and ex vivo experimental results provide imperative evidences about the role of caffeine in modified biomolecular recognition of a model carcinogen BP by DNA resulting dissociation of the carcinogen from various cell lines, implicating its potential medicinal applications in the prevention of other toxic organic molecule induced cellular damages. Copyright © 2014 John Wiley & Sons, Ltd.     

Cysteine function governs its conservation and degeneration and restricts its utilization on protein surfaces

Cysteine (Cys) is an enigmatic amino acid residue. Although one of the least abundant, it often occurs in the functional sites of proteins. Whereas free Cys is a polar amino acid, Cys in proteins is often buried, and its classification on the hydrophobicity scale is ambiguous. We hypothesized that the deviation of Cys residues from the properties of a free amino acid is due to their reactivity and addressed this possibility by examining Cys in large protein structure data sets. Compared to other amino acids, Cys was characterized by the most extreme conservation pattern, with the majority of Cys being either highly conserved or poorly conserved. In addition, clustering of Cys with another Cys residue was associated with high conservation, whereas exposure of Cys on protein surfaces was associated with low conservation. Moreover, although clustered Cys behaved as polar residues, isolated Cys was the most buried residue of all, in disagreement with known chemical properties of Cys. Thus, the anomalous hydrophobic behavior and conservation pattern of Cys can be explained by elimination of isolated Cys from protein surfaces during evolution and by clustering of other Cys residues. These findings indicate that Cys abundance is governed by Cys function in proteins rather than by the sheer chemical-physical properties of free amino acids, and suggest that a high tendency of Cys to be functionally active can considerably limit its abundance on protein surfaces.     

急性冷暴露和冷习服对大鼠和雏鸡某些内分泌活动影响的比较生理学研究

目的：探讨冷应激对哺乳类和禽类某些内分泌活动影响的比较生理学机制。方法：Wistar大鼠和罗曼雄性雏鸡进行急性冷暴露和冷习服实验,探讨急性冷暴露和冷习服对大鼠和雏鸡某些内分泌活动的影响。结果：大鼠在急性冷暴露后血清T3水平在4-36 h有不同程度的升高,而雏鸡的T3浓度则在冷暴露后除12 h有所升高外,其他时间均低于冷暴露前的水平;大鼠血清T4在冷暴露后2 h时升高,而后逐渐降低,而雏鸡冷暴露后2~4 h升高,12 h降低,而后又升高;血清胰岛素（Insulin）的变化趋势大鼠和雏鸡基本一致,均在冷暴露2 h升高,而后渐降;皮质醇（Cortisol）的变化,大鼠为冷暴露后2 h明显升高,而后渐降,而雏鸡则一直保持较高水平;冷习服后大鼠和雏鸡血清的几种激素水平变化趋势基本一致,即冷习服后血清T3升高,T4下降,胰岛素降低,而皮质醇则呈升高趋势。结论：冷应激对哺乳动物和禽类的内分泌活动具有差异性。     

Steroid hormone levels associated with passive and active smoking

Context

Cigarette tobacco smoke is a potent environmental contaminant known to adversely affect health including fertility and pregnancy.

Objective

To examine the associations between second-hand cigarette tobacco-smoke exposure, or active smoking and serum concentrations of steroid hormones using tandem mass spectrometry.

Design

Healthy women (18-45 y) from the general community in the Metropolitan Washington, DC were recruited at the follicular stage of their menstrual cycle. Participants were assigned to one of three study groups: active smokers (N = 107), passive smokers (N = 86), or non-smokers (N = 100). Classifications were based on a combination of self-reporting and serum cotinine concentrations.

Methods

Serum androgens, estrogens, progestins, androstenedione, aldosterone, cortisol, corticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 11-deoxycortisol and 25-hydroxy-vitamin D3 (25-OHVitD3) and cotinine were measured by isotope dilution tandem mass spectrometry (LC/MS/MS) (API-5000). Kruskal-Wallis tests were used to assess median differences among the three groups, with Dunn's multiple comparison test for post hoc analysis.

Results

Serum estrone, estradiol, and estriol concentrations were lower in active and passive smokers than in non-smokers. The three study groups differed significantly in serum concentrations of 16-OHE1, aldosterone and 25-OHVitD3, as well as in the ratios of many of the steroids. Pair-wise comparison of the groups demonstrated significant differences in hormone concentrations between (i) smokers and non-smokers for aldosterone: (ii) passive smokers and non-smokers for aldosterone, progesterone and estriol. Moreover, for smokers and passive smokers, there were no significant differences in these hormone concentrations.

Conclusions

Smoke exposure was associated with lower than normal median steroid hormone concentrations. These processes may be instrumental in explaining some adverse effects of tobacco smoke on female health and fertility.     

Critical Role of Lipid Scramblase TMEM16F in Phosphatidylserine Exposure and Repair of Plasma Membrane after Pore Formation

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A neutron activation technique for manganese measurements in humans

Manganese (Mn) is an essential element for humans, animals, and plants and is required for growth, development, and maintenance of health. Studies show that Mn metabolism is similar to that of iron, therefore, increased Mn levels in humans could interfere with the absorption of dietary iron leading to anemia. Also, excess exposure to Mn dust, leads to nervous system disorders similar to Parkinson's disease. Higher exposure to Mn is essentially related to industrial pollution. Thus, there is a benefit in developing a clean non-invasive technique for monitoring such increased levels of Mn in order to understand the risk of disease and development of appropriate treatments.To this end, the feasibility of Mn measurements with their minimum detection limits (MDL) has been reported earlier from the McMaster group. This work presents improvement to Mn assessment using an upgraded system and optimized times of irradiation and counting for induced gamma activity of Mn. The technique utilizes the high proton current Tandetron accelerator producing neutrons via the ⁷Li(p,n)⁷Be reaction at McMaster University and an array of nine NaI (Tl) detectors in a 4π geometry for delayed counting of gamma rays. The neutron irradiation of a set of phantoms was performed with protocols having different proton energy, current and time of irradiation. The improved MDLs estimated using the upgraded set up and constrained timings are reported as 0.67 μgMn/gCa for 2.3 MeV protons and 0.71 μgMn/gCa for 2.0 MeV protons. These are a factor of about 2.3 times better than previous measurements done at McMaster University using the in vivo set-up. Also, because of lower dose-equivalent and a relatively close MDL, the combination of: 2.0 MeV; 300 μA; 3 min protocol is recommended as compared to 2.3 MeV; 400 μA; 45 s protocol for further measurements of Mn in vivo.     

壳聚糖对急性氨氮胁迫下中华鳖稚鳖非特异性免疫反应的影响

本研究旨在探讨壳聚糖对急性氨氮胁迫下中华鳖(Pelodiscus sinensis)稚鳖非特异性免疫功能的影响。实验共设5组,实验组中华鳖分别腹腔注射0mg/ml(C0组)、1mg/ml(C1组)、5mg/ml(C2组)、50mg/ml(C3组)壳聚糖溶液0.1ml,并饲养于总氨氮浓度(TAN)为110mg/L的水环境中;对照组注射等量生理盐水溶液并饲养于新鲜晾晒自来水中。注射7d后观测外周血和脾脏中淋巴细胞ANAE阳性率、血清旁路途径溶血活性、血清溶菌活性。与对照组相比,C0组外周血T淋巴细胞ANAE阳性率和血清旁路途径溶血活性均有显著提高,脾脏T淋巴细胞和血清溶菌活性没有显著变化。与C0组相比,注射壳聚糖各组外周血T淋巴细胞ANAE阳性率和血清溶血活性均有不同程度的显著下降,并且恢复到接近对照组的水平(P>0.05),只有C3组溶血活性显著低于对照组;注射壳聚糖对脾脏中T淋巴细胞ANAE活性没有显著影响。C2组溶菌活性显著高于其他组,其他各组间差异不显著。表明壳聚糖对氨氮胁迫导致的免疫应激反应有一定的拮抗作用,其作用强度因壳聚糖浓度和免疫指标不同而异     

Analysis of exposure-time-response relationships using a spline weight function

To examine the time-dependent effects of exposure histories on disease, we estimate a weight function within a generalized linear model. The shape of the weight function, which is modeled as a cubic B-spline, gives information about the impact of exposure increments at different times on disease risk. The method is evaluated in a simulation study and is applied to data on smoking histories and lung cancer from a recent case-control study in Germany.     

Prediction of herbage yield in grassland: How well do Ellenberg N‐values perform?

Question: How useful are Ellenberg N‐values for predicting the herbage yield of Central European grasslands in comparison to approaches based on ordination scores of plant species composition or on soil parameters? Location: Central Germany (11°00′‐11°37’E, 50°21‐50°34’N, 500–840 m a.s.l.). Methods: Based on data from a field survey in 2001, the following models were constructed for predicting herbage yield in montane Central European grasslands: (1) Linear regression of mean Ellenberg N‐, R‐ and F‐values; (2) Linear regression of ordination scores derived from Non‐metric Multidimensional Scaling (NMDS) of vegetation data; and (3) Multiple linear regression (MLR) of soil variables. Models were evaluated by cross‐validation and validation with additional data collected in 2002. Results: Best predictions were obtained with models based on species composition. Ellenberg N‐values and NMDS scores performed equally well and better than models based on Ellenberg R‐ or F‐values. Predictions based on soil variables were least accurate. When tested with data from 2002, models based on Ellenberg N‐values or on NMDS scores accurately predicted productivity rank order of sites, but not the actual herbage yield of particular sites. Conclusions: Mean Ellenberg N‐values, which are easy to calculate, are as accurate as ordination scores in predicting herbage yield from plant species composition. In contrast, models based on soil variables may be useful for generating hypotheses about the factors limiting herbage yield, but not for prediction. We support the view that Ellenberg N‐values should be called productivity values rather than nitrogen values.     

The association between exposure determined by radiofrequency personal exposimeters and human exposure: A simulation study

The selection of an adequate exposure assessment approach is imperative for the quality of epidemiological studies. The use of personal exposimeters turned out to be a reasonable approach to determine exposure profiles, however, certain limitations regarding the absolute values delivered by the devices have to be considered. Apart from the limited dynamic range, it has to be taken into account that these devices give only an approximation of the exposure due to the influence of the body of the person carrying the exposimeter, the receiver characteristics of the exposimeter, as well as the dependence of the measured value on frequency band, channel, slot configuration, and communication traffic. In this study, the relationship between the field strength measured close to the human body at the location of the exposimeter and the exposure, that is, the field strength at the location of the human body without the human body present, is investigated by numerical means using the Visible Human model as an anatomical phantom. Two different scenarios were chosen: (1) For FM, GSM, and UMTS an urban outdoor scenario was examined that included a transmitting antenna mounted on the roof of one of four buildings at a street crossing, (2) For WLAN an indoor scenario was investigated. For GSM the average degree of underestimation by the exposimeter (relation of the average field levels at the location of the exposimeter to the field level averaged over the volume of the human body without the body present) was 0.76, and for UMTS 0.87; for FM no underestimation was found, the ratio was 1. In the case of WLAN the degree of underestimation was more pronounced, the ratio was 0.64. This study clearly suggests that a careful evaluation of correction factors for different scenarios is needed prior to the definition of the study protocol. It has to be noted that the reference scenario used in this study does not allow for final conclusions on general correction factors. Bioelectromagnetics 31:535–545, 2010. © 2010 Wiley‐Liss, Inc.