Epigenetic effects of selenium and their implications for health

Alterations of epigenetic marks are linked to normal development and cellular differentiation as well as to the progression of common chronic diseases. The plasticity of these marks provides potential for disease therapies and prevention strategies. Macro- and micro-nutrients have been shown to modulate disease risk in part via effects on the epigenome. The essential micronutrient selenium affects human health outcomes, e.g., cancers, cardiovascular and autoimmune diseases, via selenoproteins and through a range of biologically active dietary selenocompounds and metabolism products thereof. This review provides an assessment of the current literature regarding epigenetic effects of dietary and synthetic selenocompounds, which include the modulation of marks and editors of epigenetic information and interference with one-carbon metabolism, which provides the methyl donor for DNA methylation. The relevance of a selenium-epigenome interaction for human health is discussed, and we also indicate where future studies will be helpful to gain a deeper understanding of epigenetic effects elicited by selenium.     

Phytoferritin and its implications for human health and nutrition

Background

Plant and animal ferritins stem from a common ancestor, but plant ferritins exhibit various features that are different from those of animal ferritins. Phytoferritin is observed in plastids (e.g., chloroplasts in leaves, amyloplasts in tubers and seeds), whereas animal ferritin is largely found in the cytoplasm. The main difference in structure between plant and animal ferritins is the two specific domains (TP and EP) at the N-terminal sequence of phytoferritin, which endow phytoferritin with specific iron chemistry. As a member of the nonheme iron group of dietary iron sources, phytoferritin consists of 24 subunits that assemble into a spherical shell storing up to ∼ 2000 Fe^3 + in the form of an iron oxyhydroxide-phosphate mineral. This feature is distinct from small molecule nonheme iron existing in cereals, which has poor bioavailability.

Scope of review

This review focuses on the relationship between structure and function of phytoferritin and the recent progress in the use of phytoferritin as iron supplement.

Major conclusions

Phytoferritin, especially from legume seeds, represents a novel alternative dietary iron source.

General significance

An understanding of the chemistry and biology of phytoferritin, its interaction with iron, and its stability against gastric digestion is beneficial to design diets that will be used for treatment of global iron deficiency.     

Some new pitch paradoxes and their implications.

This paper explores two new paradoxical sound patterns. The tones used to produce these patterns consist of six octave-related harmonics, whose amplitudes are scaled by a bell-shaped spectral envelope; these tones are clearly defined in terms of pitch class (C, C#, D, and so on) but are poorly defined in terms of height. One pattern consists of two tones that are separated by a half-octave. It is heard as ascending when played in one key, yet as descending when played in a different key. Further, when the pattern is played in any one key it is heard as ascending by some listeners but as descending by others (the tritone paradox). Another pattern that consists of simultaneous pairs of tones displays related properties (the semitone paradox). It is shown that the way the tritone paradox is perceived correlates with the speech characteristics of the listener, including his or her linguistic dialect. The findings suggest that the same, culturally acquired representation of pitch classes influences both speech production and also perception of this musical pattern.     

Glucosinolates in the human diet. Bioavailability and implications for health

The glucosinolates are a large group of sulphur-containing glucosides found in brassica vegetables. After physical damage to the plant tissue, glucosinolates are broken down, by the endogenous enzyme myrosinase, releasing glucose and a complex variety of biologically active products. The most important and extensively studied of these compounds are the isothiocyanates. Glucosinolates can be degraded or leached from vegetable tissue during food processing, but thermal inactivation of myrosinase preserves some intact glucosinolates in cooked vegetables. Once ingested, any remaining intact glucosinolates may be broken down by plant myrosinase in the small intestine, or by bacterial myrosinase in the colon. Isothiocyanates are absorbed from the small bowel and colon, and the metabolites are detectable in human urine 2–3 h after consumption of brassica vegetables. Isothiocyanates are potent inducers of Phase II enzymes in vitro, and they have been shown to increase the metabolism and detoxification of chemical carcinogens in vitro and in animal models. Some of these compounds also inhibit mitosis and stimulate apoptosis in human tumour cells, in vitro and in vivo. This second effect raises the possibility that in addition to blocking DNA damage, isothiocyanates may selectively inhibit the growth of tumour cells even after initiation by chemical carcinogens. Epidemiological evidence supports the possibility that glucosinolate breakdown products derived from brassica vegetables may protect against human cancers, especially those of the gastrointestinal tract and lung. To define and exploit these potentially anticarcinogenic effects it is important to understand and manipulate glucosinolate chemistry and metabolism across the whole food-chain, from production and processing to consumption. This revised version was published online in June 2006 with corrections to the Cover Date.     

The radiation bystander effect and its potential implications for human health

A long-held dogma in radiation biology has been that the biological effects of exposure to ionizing radiation occur as a result of damage in directly irradiated cells and that no effect would occur in neighboring unirradiated cells. This paradigm has been frequently challenged by reports of radiation effects in unirradiated or 'bystander' cells receiving signals from directly irradiated cells, an issue that may have substantial impact on radiation risk assessment and development of radiation-based therapies. Radiation-induced bystander effects have been shown in single-cell systems in vitro for an array of cancer relevant endpoints, and may trigger damage in more complex 3-D tissue systems. They may be mediated by soluble factors released by irradiated cells into the extracellular environment and/or by the passage of mediator molecules through gap-junction intercellular communication. To date, evidence that radiation-associated bystander or abscopal responses are effectual in vivo has been limited, but new data suggest that they may significantly affect tumor development in susceptible mouse models. Further understanding of how the signal/s is transmitted to unirradiated cells and tissues and how it provokes long-range and significant responses is crucial. By summarizing the existing evidence of radiation induced bystander-like effects in various systems with emphasis on in vivo findings, we will discuss the potential mechanisms involved in these observations and how effects in bystander cells contribute to uncertainties in assessing cancer risks associated with radiation exposure.     

Bifidobacteria and their role in human health

Summary There is a growing consensus on the beneficial effects of bifidobacteria in human health. It is now clear that bifidobacteria that exist in the large intestine are helpful for maintenance of human health and are far more important thanLactobacillus acidophilus as beneficial intestinal bacteria throughout human life. In other words, the reduction or disappearance of bifidobacteria in the human intestine would indicate an unhealthy state. Oral administration of bifidobacteria may be effective for the improvement of intestinal flora and intestinal environment, for the therapy of enteric and hepatic disorders, for stimulation of the immune response, and possibly for the prevention of cancer and slowing the aging process. However, for consistent and positive results further well-controlled studies are urgently needed.     

Mental health, attachment and breastfeeding: implications for adopted children and their mothers

ABSTRACT : Breastfeeding an adopted child has previously been discussed as something that is nice to do but without potential for significant benefit. This paper reviews the evidence in physiological and behavioural research, that breastfeeding can play a significant role in developing the attachment relationship between child and mother. As illustrated in the case studies presented, in instances of adoption and particularly where the child has experienced abuse or neglect, the impact of breastfeeding can be considerable. Breastfeeding may assist attachment development via the provision of regular intimate interaction between mother and child; the calming, relaxing and analgesic impact of breastfeeding on children; and the stress relieving and maternal sensitivity promoting influence of breastfeeding on mothers. The impact of breastfeeding as observed in cases of adoption has applicability to all breastfeeding situations, but may be especially relevant to other at risk dyads, such as those families with a history of intergenerational relationship trauma; this deserves further investigation.     

Physical-chemical principles underlying RTK activation, and their implications for human disease

RTKs, the second largest family of membrane receptors, exert control over cell proliferation, differentiation and migration. In recent years, our understanding of RTK structure and activation in health and disease has skyrocketed. Here we describe experimental approaches used to interrogate RTKs, and we review the quantitative biophysical frameworks and structural considerations that shape our understanding of RTK function. We discuss current knowledge about RTK interactions, focusing on the role of different domains in RTK homodimerization, and on the importance and challenges in RTK heterodimerization studies. We also review our understanding of pathogenic RTK mutations, and the underlying physical-chemical causes for the pathologies. This article is part of a Special Issue entitled: Protein Folding in Membranes.     

Trends in the state of nature and their implications for human well-being

Two major international initiatives - the Convention on Biological Diversity's target to reduce the rate of biodiversity loss by 2010, and the Millennium Ecosystem Assessment - raise the profile of ecological data on the changing state of nature and its implications for human well-being. This paper is intended to provide a broad overview of current knowledge of these issues. Information on changes in the status of species, size of populations, and extent and condition of habitats is patchy, with little data available for many of the taxa, regions and habitats of greatest importance to the delivery of ecosystem services. However, what we do know strongly suggests that, while exceptions exist, the changes currently underway are for the most part negative, anthropogenic in origin, ominously large and accelerating. The impacts of these changes on human society are idiosyncratic and patchily understood, but for the most part also appear to be negative and substantial. Forecasting future changes is limited by our poor understanding of the cascading impacts of change within communities, of threshold effects, of interactions between the drivers of change, and of linkages between the state of nature and human well-being. In assessing future science needs, we not only see a strong role for ecological data and theory, but also believe that much closer collaboration with social and earth system scientists is essential if ecology is to have a strong bearing on policy makers.     

Allergenic fungi and actinomycetes in smoking materials and their health implications

Street marijuana, commercial cigarettes and pipe tobaccos were studied for the presence of fungi and actinomycetes associated with hypersensitivity pneumonitis. Aspergillus species and thermophilic actinomycetes were isolated from the smoking materials. In addition, Aspergillus fumigatus spores were isolated from marijuana smoke, indicating the potential hazard involved in developing serious disease. Precipitin antibodies against fungi, particularly Aspergillus, showed a higher prevalence in marijuana smokers, whereas only very few cigarette smokers and nonsmokers demonstrated antibodies to fungi. Cigarette smokers and nonsmokers showed more or less similar prevelance of antibodies against thermophilic actinomycetes.     

Ecological implications of behavioural syndromes

Interspecific trait variation has long served as a conceptual foundation for our understanding of ecological patterns and dynamics. In particular, ecologists recognise the important role that animal behaviour plays in shaping ecological processes. An emerging area of interest in animal behaviour, the study of behavioural syndromes (animal personalities) considers how limited behavioural plasticity, as well as behavioural correlations affects an individual's fitness in diverse ecological contexts. In this article we explore how insights from the concept and study of behavioural syndromes provide fresh understanding of major issues in population ecology. We identify several general mechanisms for how population ecology phenomena can be influenced by a species or population's average behavioural type, by within-species variation in behavioural type, or by behavioural correlations across time or across ecological contexts. We note, in particular, the importance of behavioural type-dependent dispersal in spatial ecology. We then review recent literature and provide new syntheses for how these general mechanisms produce novel insights on five major issues in population ecology: (1) limits to species' distribution and abundance; (2) species interactions; (3) population dynamics; (4) relative responses to human-induced rapid environmental change; and (5) ecological invasions.     

An evolutionary perspective on human physical activity: implications for health

At present, human genes and human lives are incongruent, especially in affluent Western nations. When our current genome was originally selected, daily physical exertion was obligatory; our biochemistry and physiology are designed to function optimally in such circumstances. However, today's mechanized, technologically oriented conditions allow and even promote an unprecedentedly sedentary lifestyle. Many important health problems are affected by this imbalance, including atherosclerosis, obesity, age-related fractures and diabetes, among others. Most physicians recognize that regular exercise is a critical component of effective health promotion regimens, but there is substantial disagreement about details, most importantly volume: how much daily caloric expenditure, as physical activity, is desirable. Because epidemiology-based recommendations vary, often confusing and alienating the health-conscious public, an independent estimate, arising from a separate scientific discipline, is desirable, at least for purposes of triangulation. The retrojected level of ancestral physical activity might meet this need. The best available such reconstruction suggests that the World Health Organization's recommendation, a physical activity level of 1.75 ( approximately 2.1 MJ (490 kcal)/d), most closely approximates the Paleolithic standard, that for which our genetic makeup was originally selected.     

Superoxide dismutases and their impact upon human health

Superoxide dismutases (SOD), a group of metal-containing enzymes, have a vital anti-oxidant role in human health, conferred by their scavenging of one of the reactive oxygen species, superoxide anion. Three types of SODs are known in humans, with the most abundant being cytosolic SOD1, identified by its Cu, Zn-containing prosthetic group. The presence of these metals and the coordination to certain amino acids are essential for function. SODs are among the first line of defense in the detoxification of products resulting from oxidative stress. Here, we describe the importance of SOD function, and the need for coordination with other ROS-scavenging enzymes in this pathway of detoxification. The impact of metal-deficient diets (copper or zinc) or incorrect metal ion incorporation (copper chaperone for SOD) onto nascent SOD, are also examined. Finally, human pathologies associated with either SOD dysfunction or decreased activity are discussed with current progress on the development of novel therapies.     

Inflammation and conjugated linoleic acid: mechanisms of action and implications for human health

Data from a number of studies and trials have shown that different conjugated linoleic acids (CLA's) may produce beneficial effects on cancer, atherosclerosis, hypertension, diabetes and changes in body composition. Despite the increasing knowledge about CLA's implications on health, the mechanism of action of these fatty acids is not completely understood. Moreover, human studies indicate that some of these beneficial effects are considerably less evident than anticipated from mice studies, while the efficacy and safety of dietary supplements containing CLA have been questioned in some intervention trials. Recently, it has been suggested that the anti-carcinogenic and anti-atherosclerosis effects of CLA's stem from its anti-inflammatory properties. Because inflammatory responses are associated with the pathophysiology of many diseases, including obesity and the metabolic syndrome, the investigation in this area is of growing interest in recent years.     

Some legal implications of advances in human genetics.

The law which, to some extent at least, reflects contemporary mores, has not kept pace with the recent scientific advances in genetics. Because of the rate of advance in the science of genetics there is a real risk that we shall know how to change the traditional nature of man before we possess the knowledge necessary to enable us to use the new knowledge for humane purposes. Clonal reproduction may produce a creature who, for the purposes of the law, especially the criminal law, which defines when a child becomes a human being in terms of "old-fashioned" motherhood, may not be a human being, so that putting him to death may not be homicide. Similarly, in vitro fertilization and development in an artificial uterus may result in the "birth" of one who, though having human attributes, may not, in law, be a human being. While cloning and in vitro fertilization may not have immediate legal implications because of the state of the art, genetic manipulation in the form of amniocentesis has very real legal implications now because it is a matter of current practice. The assumption that detection of genetic abnormality in the foetus is a beneficial development because it enables parents to have the option of terminating the pregnancy, though valid in the United Kingdom and the United States, is invalid in Canada. Abortion on demand is not part of the law in Canada and the liberalization of the abortion provisions of the Criminal Code of Canada in 1969 expressly avoided including as a criterion for therapeutic abortion the risk that the child, if born, would be likely to suffer from such physical or mental abnormalities as to be seriously handicapped. Beyond the more technical issues raised by scientific advances, however, lies the fundamental question whether a handicapped life is a life not worth living.