A randomized trial of genetic information for personalized nutrition

Personal genetic information has become increasingly accessible to the public as a result of direct-to-consumer (DTC) genetic tests; however, concerns have been raised over their value and potential risks. We compared the effects of providing genotype-based dietary advice with general recommendations on behavioral outcomes using a randomized controlled study. Participants were men and women from the Toronto Nutrigenomics and Health Study between the ages of 20–35 years (n = 149) who completed a survey to assess their awareness of DTC genetic tests and nutrigenomics, as well as potential motivations for undergoing genetic testing. Participants were then randomized into an intervention (I) or control (C) group and were given either genotype-based personalized dietary advice or general dietary advice, respectively. A second survey was administered to assess the participants’ opinions of the dietary reports they received. A greater proportion of participants in the intervention group agreed that they understood the dietary advice they were given (93% (I) vs. 78% (C); p = 0.009). Participants in the intervention group were more likely to agree that the dietary recommendations they received would be useful when considering their diet (88% (I) vs. 72% (C); p = 0.02) and wanted to know more about the recommendations (95% (I) vs. 76% (C); p < 0.0001). Only 9% of participants in the intervention group reported feeling uneasy about learning their genetic information. These findings suggest that individuals find dietary recommendations based on genetics more understandable and more useful than general dietary advice. Very few feel uneasy about receiving their genetic information that relates to personalized nutrition.     

Anthraquinone cytotoxicity and apoptosis in primary cultures of rat hepatocytes

We compared three different anthraquinones, rhein (4,5-dihydroxy-anthraquinone-2-carboxylic acid), danthron (1,8-dihydroxy-anthraquinone) and chrysophanol (1,8-dihydroxy-3-methylanthraquinone), with respect to their toxicity and ability to induce apoptosis in primary cultures of rat hepatocytes. Rhein was the most effective in producing free radicals, and was the only one of the tested anthraquinones that could induce apoptosis. Addition of 50μM rhein to hepatocyte cultures led to depletion of intracellular reduced glutathione (GSH) and ATP and accumulation of lipid peroxidation products. The substances N,N'-diphenyl-p-phenylenediamine (DPPD), dithiothreitol (DTT), nifedipine and desferal all protected the hepatocytes, i.e. prevented viability loss and ATP depletion, and decreased the GSH depletion.

Cultures exposed to rhein for 15min and subsequently rinsed and incubated for 16h under normal culture conditions (complete medium) exhibited apoptosis, as shown by DNA fragmentation, nuclear condensation and positive TUNEL reaction. Pretreatment with the antioxidant DPPD and the iron-chelator desferal gave complete protection against apoptosis.

No signs of oxidative cell damage were detected when the cultures were exposed to danthron or chrysophanol. All three anthraquinones did, however, cause an immediate increase in the intracellular Ca²⁺ concentration.

We conclude that rhein, which contains one carboxyl group, is a suitable substrate for one-electron-reducing enzymes and an effective redox cycler, which leads to the production of oxygen-derived free radicals that eventually induce apoptotic cell death.     

Nitrogen-induced variations in leaf gas exchange of spring triticale under field conditions

Nitrogen (N) is the key factor limiting photosynthetic processes and crop yield. Little is known about the response of leaf gas exchange of spring triticale (Triticosecale Wittm.) to N supply. The effect of N fertilizers on different gas exchange variables, i.e., photosynthetic rate (A), transpiration rate (E), stomatal conductance (g _s), instantaneous water use efficiency (WUE) and maximum quantum yield of photosystem II (PSII) (F _v/F _m), chlorophyll index (SPAD, soil–plant analysis development), and the relationship of these variables with yield were studied in spring triticale grown under field conditions. Six treatments of N—0, 90, 180, 90 + 30, 90 + 30 + 30 kg ha^?1 (applied as ammonium nitrate, AN) and one treatment of N 90 + 30 + 30 kg ha^?1 (applied as urea ammonium nitrate solution, UAN) were compared. The analysis of variance showed that throughout the triticale growing season, N fertilization had significant effects on A, WUE, g _s and SPAD. On average, N fertilizer application increased A values by 14–70%. E and F _v/F _m values were not influenced by N fertilization levels. The effect of growth stage and year on gas exchange variables and F _v/F _m and SPAD was found to be significant. At different growth stages, A values varied and maximum ones were reached at BBCH 31–33 (decimal code system of growth stages) and BBCH 59. With aging, values of A decreased independently of N fertilization level. The gas exchange variables were equally affected by both fertilizer forms. The interplay among grain yield, leaf gas exchange variables, F _v/F _m and SPAD of spring triticale was estimated. The statistical analysis showed that grain yield positively and significantly correlated with A and SPAD values throughout the growing season.     

Adaptive habitat preferences in the Tawny Owl Strix aluco

Capsule: Tawny Owls Strix aluco occupying nest boxes preferred habitats which were positively associated with the probability of nesting success.

Aims: We aimed to determine whether or not: (1) Tawny Owls showed habitat preferences when occupying nest boxes; (2) nesting performance was related to the habitats around occupied nest boxes and (3) habitat availability had changed around available and occupied nest boxes between 1995–2004 and 2005–14.

Methods: Tawny Owls were studied using nest boxes erected in a commercial forest. During nest boxes checks (724 cases), data on occupancy and nesting performance (88 cases) were recorded, and habitat within a 0.4?km radius around nest boxes was analysed.

Results: Tawny Owls had preferences for clearings within forests, mature forests and grasslands but avoided young forests. We found a positive relationship between nesting success and abundance of clearings within the forest, and a negative relationship between nesting success and abundance of young forests. A change in habitat preferences over the two decades was evident, but habitat availabilities remained similar.

Conclusions: Findings indicate adaptive habitat selection in Tawny Owls because preferred habitats were associated with higher fitness and this type of habitat became more frequently selected over time.     

μABC: a systematic microsecond molecular dynamics study of tetranucleotide sequence effects in B-DNA

We present the results of microsecond molecular dynamics simulations carried out by the ABC group of laboratories on a set of B-DNA oligomers containing the 136 distinct tetranucleotide base sequences. We demonstrate that the resulting trajectories have extensively sampled the conformational space accessible to B-DNA at room temperature. We confirm that base sequence effects depend strongly not only on the specific base pair step, but also on the specific base pairs that flank each step. Beyond sequence effects on average helical parameters and conformational fluctuations, we also identify tetranucleotide sequences that oscillate between several distinct conformational substates. By analyzing the conformation of the phosphodiester backbones, it is possible to understand for which sequences these substates will arise, and what impact they will have on specific helical parameters.     

Light Increases Energy Transfer Efficiency in a Boreal Stream

Periphyton communities of a boreal stream were exposed to different light and nutrient levels to estimate energy transfer efficiency from primary to secondary producers using labeling with inorganic ¹³C. In a one-day field experiment, periphyton grown in fast-flow conditions and dominated by opportunistic green algae were exposed to light levels corresponding to sub-saturating (forest shade) and saturating (open stream section) irradiances, and to N and P nutrient additions. In a two-week laboratory experiment, periphyton grown in low-flow conditions and dominated by slowly growing diatoms were incubated under two sub-saturating light and nutrient enrichment levels as well as grazed and non-grazed conditions. Light had significant positive effect on ¹³C uptake by periphyton. In the field experiment, P addition had a positive effect on ¹³C uptake but only at sub-saturating light levels, whereas in the laboratory experiment nutrient additions had no effect on the periphyton biomass, ¹³C uptake, biovolume and community composition. In the laboratory experiment, the grazer (caddisfly) effect on periphyton biomass specific ¹³C uptake and nutrient content was much stronger than the effects of light and nutrients. In particular, grazers significantly reduced periphyton biomass and increased biomass specific ¹³C uptake and C:nutrient ratios. The energy transfer efficiency, estimated as a ratio between ¹³C uptake by caddisfly and periphyton, was positively affected by light conditions, whereas the nutrient effect was not significant. We suggest that the observed effects on energy transfer were related to the increased diet contribution of highly palatable green algae, stimulated by higher light levels. Also, high heterotrophic microbial activity under low light levels would facilitate energy loss through respiration and decrease overall trophic transfer efficiency. These findings suggest that even a small increase in light intensity could result in community-wide effects on periphyton in boreal streams, with a subsequent increase in energy transfer and system productivity.     

Trends in the Attack Rates,Incidence, and Mortality of Stroke during 1986–2012: Data of Kaunas (Lithuania) Stroke Registry

BackgroundThere is a lack of reliable epidemiological data on longitudinal trends in stroke attack rates, incidence, and mortality in the countries of the Baltic region.AimsThe aim of the present study was to explore the longitudinal trends of stroke in middle-aged urban population of Lithuania during the period of 1986 through 2012.MethodsAll stroke events in the studied population were ascertained and validated according to the standardized criteria outlined by the WHO MONICA Project. The study included all patients in Kaunas (Lithuania) city aged 25 to 64 years who experienced a stroke between 1986 and 2012. Estimates of time-trends of the annual percentage change in stroke attack rates, incidence of stroke, and mortality from this condition were made by applying the Joinpoint regression analysis.ResultsDuring the study period, 9,992 stroke events were registered. The overall proportion of recurrent events was 25.7%. Overall, 18.9% of the events (20.0% in men, and 17.4% in women) were fatal within 28 days. During the period of 1986 to 2012, a flat trend in the incidence of stroke was observed among both male and female middle-aged inhabitants of Kaunas city, while attack rates were increasing due to the increase in recurrent strokes. Both mortality and 28-day case fatality of stroke declined significantly over the study period in both sexes.ConclusionsAn increase both in the incidence and recurrence of stroke among middle-aged men residing in Kaunas city and in the recurrence of stroke among women denotes the inefficiency of measures applied both for primary and secondary prevention of stroke in Lithuania. The revision of current prevention strategies and the introduction of new ones are of paramount importance in order to fight the epidemic of stroke.     

Lipophilic 1,4-naphthoquinone derivatives: synthesis and redox properties in solution and entrapped in the aqueous cubic liquid-crystalline phase of monoolein

1,4-Naphthoquinone derivatives (NQD) containing lipophilic alkyl chains, i.e. 2-((Z)-heptadec-8-enyl)-3-methyl 1,4-naphthoquinone (QMe), 2-((Z)-heptadec-8-enyl)-3-hydroxy-1,4-naphthoquinone (QOH) and (Z)-octadec-9-enyl 1,4-naphthoquinone-2-carboxylate (QE) were synthesized. The redox behavior of these NQD was studied in ethanol and entrapped in the reversed bicontinuous cubic phase of space group type Pn3m (Q²²⁴) of aqueous monoolein. In ethanol, cyclic voltammetry curves exhibit two pairs of oxidation-reduction peaks arising from the redox processes controlled by adsorption and molecular diffusion. The NQD molecules are also electrochemically active in the cubic phase, indicating the participation in the 2e⁻, 2H⁺-redox cycle at pH < 9. Therefore, it was concluded that the head group of the entrapped NQD reaches the lipid bilayer interface of cubic phase during the process.     

Stimulation of endothelial IL-8 (eIL-8) production and apoptosis by phenolic metabolites of benzene in HL-60 cells and human bone marrow endothelial cells

Benzene toxicity is considered to be elicited by its metabolites and phenolic metabolites of benzene are known to induce apoptosis in leukemia cells in culture and in human bone marrow progenitor cells. One potential mechanism of apoptosis induced by benzene metabolites that has not been examined is the production of pro-apoptotic cytokines such as endothelial IL-8 from endothelial cells in bone marrow stroma. In this study, we utilized HL-60 cells which are known to produce the endothelial form of IL-8 (eIL-8) and human bone marrow endothelial cells (HBMEC) as model systems. Hydroquinone (HQ), Catechol (Cat) and benzenetriol (BT) all induced eIL-8 production and apoptosis in HL-60 cells. HQ induced a marked 50-70 fold stimulation of eIL-8 levels and HL-60 cells were shown to have the eIL-8 receptor, CXCR1 thus enabling an autocrine pathway of apoptosis. However, treatment with recombinant eIL-8 failed to induce apoptosis in HL-60 cells as previously reported and antibodies to either IL-8 or CXCR1 did not significantly abrogate benzene metabolite-induced apoptosis. HQ and Cat but not BT also induced stimulation of eIL-8 production in HBMEC. These data demonstrate that although metabolites of benzene induce marked stimulation of eIL-8, this is unlikely to be responsible for apoptosis induced in HL-60 cells. Our data also demonstrates that phenolic metabolites of benzene stimulate the production of eIL-8 from HBMEC suggesting that higher levels of endothelial-derived cytokines may occur in bone marrow after benzene exposure.     

Characterization of the B2 receptor and activity of bradykinin analogs in SHP-77 cell line by Cytosensor microphysiometer

The Cytosensor microphysiometer device (Molecular Devices, Sunnyvale, CA) is capable of measuring the rate at which cells acidify their environment in response to ligand–receptor binding. By measuring the extracellular acidification response (ECAR) we characterized some aspects of ligand–B₂ receptor interaction in SHP-77 cell line. SHP-77 cells maximally acidified their environment within 30 s after the exposure to bradykinin (BK) or the BK agonist, B9972, with the maximum effect seen at a ligands concentration of 1 μM. Fetal bovine serum (FBS) modulated the binding of BK or B9972, showing that B9972 is a partial agonist. In addition, the binding of BK agonist or antagonist to the B₂ receptor showed different ECAR and different interaction with other intracellular and plasma membrane proteins. Our microphysiometrical results showed that two parameters, antagonist binding affinity (pD₂) and antagonist potency (pIC₅₀) are required to characterize BK antagonist activity for the B₂ receptor in the SHP-77 cell line. The previously used parameter of B₂ antagonist activity, pA₂, had high variation and poor correlation with the inhibition of SHP-77 cell growth in vitro and suppression of tumor growth when SHP-77 cells were injected to mice. Our results permit us to conclude that BK agonists and antagonists differ in their interactions with the B₂ receptor and consequently elicit different cell responses. Based on our results, we have developed a new microphysiometrical assay for analyzing the activity of BK agonists and antagonist in SHP-77 cells, which may facilitate the discovery of new potent anticancer drugs.