The role of nutrition on epigenetic modifications and their implications on health

Nutrition plays a key role in many aspects of health and dietary imbalances are major determinants of chronic diseases including cardiovascular disease, obesity, diabetes and cancer. Adequate nutrition is particularly essential during critical periods in early life (both pre- and postnatal). In this regard, there is extensive epidemiologic and experimental data showing that early sub-optimal nutrition can have health consequences several decades later.     

Long-term effects of dietary isoflavones on uterine gene expression profiles

Isoflavones (ISOs) are bioactive food ingredients of the traditional East Asian diet and currently discussed as alternatives to classical hormone replacement therapies and for reducing the prevalence of hormone-dependent cancers. Although there are many studies on ISOs, not much is known about their long-term effects.Therefore, we performed an animal experiment analyzing the effects of three different diets: a phytoestrogen-free diet, a diet supplemented with genistein (700 μg/g diet) and an ISO-high diet (232 μg daidzein and 240 μg genistein/g) at two distinct time points, juvenile (21 days) and adult (97 days). Exposure started prior to mating of the parents and throughout the life of the offspring.We observed a stronger increase of uterine wet weights in juvenile offspring with genistein exposure (1018 ± 350 mg/kg BW) than with ISO-high diet (497 ± 133 mg/kg BW). Whereas the expression of proliferation related genes (PCNA; Ki67; IGF-1; IGF-1R), analyzed by real-time-qPCR and Western blot, were significantly down-regulated in juvenile animals exposed to genistein. Additionally, genistein exposure led to estrogenic responses, observed upon increase of complement C3 and decrease of estrogen receptors gene expressions, while the exposure to ISO-high diet did not show these effects.In conclusion, both the time point on which phytoestrogen exposure starts together with the composition of the ingested phytoestrogen containing diet are of great importance for the biological response of the offspring.     

Assessment of Optimal Selected Prognostic Factors

The identification and assessment of prognostic factors is one of the major tasks in clinical research. The assessment of one single prognostic factor can be done by recently established methods for using optimal cutpoints. Here, we suggest a method to consider an optimal selected prognostic factor from a set of prognostic factors of interest. This can be viewed as a variable selection method and is the underlying decision problem at each node of various tree building algorithms. We propose to use maximally selected statistics where the selection is defined over the set of prognostic factors and over all cutpoints in each prognostic factor. We demonstrate that it is feasible to compute the approximate null distribution. We illustrate the new variable selection test with data of the German Breast Cancer Study Group and of a small study on patients with diffuse large B‐cell lymphoma. Using the null distribution for a p‐value adjusted regression trees algorithm, we adjust for the number of variables analysed at each node as well. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Paternal inheritance of chloroplast DNA in Larix

Restriction enzyme analysis was used to determine the inheritance of chloroplast DNA in conifers. The plant material studied included five individual trees of European larch (Larix decidua Mill.) and Japanese larch (Larix leptolepis Sieb. & Zucc.) and six hybrids from controlled crosses between these species. The chloroplast DNA fragment patterns generated by Bam-HI and Bcl-I were species-specific. Paternal inheritance of chloroplast DNA patterns was found in most Larix crosses. One hybrid showed maternal chloroplast DNA patterns. In addition, two other hybrids had mixed Bam-HI patterns suggesting recombination between maternal and paternal chloroplast DNA. The mechanisms favoring paternal inheritance in conifers are not known. Paternal inheritance of chloroplast DNA is suggested it to be a general phenomenon in conifers.     

FSH-induced aromatase activity in hamster granulosa cells: effect of estradiol-17β in vitro

Summary We have shown previously that estradiol-17 (E₂) reduces number of ovulations in cyclic rats, induces atresia of the dominant preovulatory follicle in monkeys, and that the initial effects of this treatment include reduced viability and estrogen accumulation in vitro by aspirated granulosa cells (GC) from monkeys and hamsters. The present experiment was designed to determine whether the reduction in estrogen accumulation can be ascribed to a direct action of E₂ on the aromatization of androgen to estrogen in vitro. Female hamsters were injected with 30 I.U. pregnant-mare serum gonadotropin i.p. and sacrificed 3 days later. GC were aspirated from the largest follicles and incubated for 48 h (initial incubation period) in the presence of human pituitary follicle-stimulating hormone (hFSH, 100 ng/ml). Following initial incubation, GC were further incubated for up to 24 h (secondary incubation period). During this subsequent incubation, medium was supplemented with 100nM ³H-1-androstenedione (³H-A₄). Initial incubation with E₂ at doses of 10 ng/ml, 100 ng/ml and 1 m E₂/ml induced variability in GC response, and a maximal depression of 70%. The inhibition by E₂ of hamster GC function in vitro parallels that shown in vivo for both hamsters and monkeys, but contrasts with that shown for rats. Thus, hamsters may represent an appropriate model in which to study the atretogenic effects of E₂ directly on antral follicle development.     

Volume estimation of biological objects by systematic sections

The absolute volume of biological objects is often estimated stereologically from an exhaustive set of systematic sections. The usual volume estimator is the sum of the section contents times the distance between sections. For systematic sectioning with a random start, it has been recently shown that is unbiased when m, the ratio between projected object length and section distance, is an integer number (Cruz-Orive 1985). As this quantity is no integer in the real world, we have explored the properties of in the general and realistic situation m . The unbiasedness of under appropriate sampling conditions is demonstrated for the arbitrary compact set in 3 dimensions by a rigorous proof. Exploration of further properties of for the general triaxial ellipsoid leads to a new class of non-elementary real functions with common formal structure which we denote as np-functions. The relative mean square error (CE ²) of in ellipsoids is an oscillating differentiable np-function, which reduces to the known result CE ²= 1/(5m ⁴) for integer m. As a biological example the absolute volumes of 10 left cardiac ventricles and their internal cavities were estimated from systematic sections. Monte Carlo simulation of replicated systematic sectioning is shown to be improved by using m instead of m . In agreement with the geometric model of ellipsoids with some added shape irregularities, mean empirical CE was proportional to m ^–1.36 and m^–1.73 in the cardiac ventricle and its cavity. The considerable variance reduction by systematic sectioning is shown to be a geometric realization of the principle of antithetic variates.     

Some pharmacological activities of novel adenine-related compounds isolated from a marine sponge Agelas mauritiana

Agelasimine A and agelasimine B, two novel compounds related to adenine, have been isolated from the orange sponge, Agelas mauritiana, and have been tested for a variety of biological activities. Both compounds inhibited proliferation of cultured L1210 leukemia cells at nanomolar concentrations with accumulation in the G1 stage of the cell cycle. However, no prolongation of life was observed in mice bearing P388 leukemia treated with these compounds. In the rat isolated aorta, micromolar concentrations of agelasimines were very effective in inhibiting contractions elicited by potassium chloride but had little or no effect on responses for prostaglandin F2 alpha and had modest effects on the responses to noradrenaline and significant effects on 5-hydroxytryptamine. Agelsamines A and B appeared to be equipotent in causing relaxation in rabbit jejunum and bovine coronary artery, and they also inhibited nucleoside transport into rabbit erythrocytes in micromolar concentrations.     

N-iodoacetyltyramine: preparation and use in 125I labeling by alkylation of sulfhydryl groups

Preparation and use of N-iodoacetyltyramine in generation of 125I-labeled compounds is described. The kinetics of alkylation of N-acetylcysteine by N-iodoacetyltyramine (k2 = 3.0 M-1 s-1) and N-chloroacetyltyramine (k2 = 0.12 M-1 s-1) indicate that N-iodoacetyltyramine is more useful for labeling sulfhydryl-containing compounds to high specific activity with 125I. Conditions for preparation of carrier-free 125I-labeled N-iodoacetyl-3-monoiodotyramine in 50% yield based on starting iodide are described. The high degree of group specificity of N-iodoacetyl-3-monoiodotyramine reaction with sulfhydryl groups is demonstrated by the high reactivity toward sulfhydryl-containing bovine serum albumin and low reactivity toward N-ethylmaleimide-blocked bovine serum albumin and IgG. 125I-labeled N-iodoacetyl-3-monoiodotyramine was also used to prepare an 125I-labeled ACTH derivative that retains full biological activity, further demonstrating the selectivity toward reactions with sulfhydryl groups.