Nutrigenomics: integrating genomic approaches into nutrition research

It has been suggested that the supermarket of today will be the pharmacy of tomorrow. Such statements have been derived from recognition of our increasing ability to optimize nutrition, and maintain a state of good health through longer periods of life. The new field of nutrigenomics, which focuses on the interaction between bioactive dietary components and the genome, recognizes that current nutritional guidelines may be ideal for only a relatively small proportion of the population. There is good evidence that nutrition has significant influences on the expression of genes, and, likewise, genetic variation can have a significant effect on food intake, metabolic response to food, individual nutrient requirements, food safety, and the efficacy of disease-protective dietary factors. For example, a significant number of human studies in various areas are increasing the evidence for interactions between single nucleotide polymorphisms (SNPs) in various genes and the metabolic response to diet, including the risk of obesity. Many of the same genetic polymorphisms and dietary patterns that influence obesity or cardiovascular disease also affect cancer, since overweight individuals are at increased risk of cancer development. The control of food intake is profoundly affected by polymorphisms either in genes encoding taste receptors or in genes encoding a number of peripheral signaling peptides such as insulin, leptin, ghrelin, cholecystokinin, and corresponding receptors. Total dietary intake, and the satiety value of various foods, will profoundly influence the effects of these genes. Identifying key SNPs that are likely to influence the health of an individual provides an approach to understanding and, ultimately, to optimizing nutrition at the population or individual level. Traditional methods for identification of SNPs may involve consideration of individual variants, using methodologies such as restriction fragment length polymorphisms or quantitative real-time PCR assays. New developments allow identification of up to 500,000 SNPs in an individual, and with increasingly lowered pricings these developments may explode the population-level potential for dietary optimization based on nutrigenomic approaches.     

New perspectives on cocaine addiction: recent findings from animal research

Research with laboratory animals has provided several insights into the nature of cocaine abuse and addiction. First, the nature of drug addiction has been reevaluated and the emphasis has shifted from physical dependence to compulsive drug-taking behavior. Second, animal studies suggest that cocaine is at least as addictive as heroin and possibly even more addictive. Third, cocaine is potentially more dangerous than heroin as evidenced by the higher fatality rate seen in laboratory animals given unlimited access to these drugs. Fourth, the neural basis of cocaine reinforcement has been identified and involves an enhancement of dopaminergic neurotransmission in the ventral tegmental dopamine system. Other addictive drugs (e.g., opiates) may also derive at least part of their reinforcing impact by pharmacologically activating this reward system. Fifth, although the biological consequences of repeated cocaine self-administration on central nervous system functioning are poorly understood, preliminary findings suggest that intravenous cocaine self-administration may decrease neural functioning in this brain reward system. This has important clinical implications because diminished functioning of an important brain reward system may significantly contribute to relapse into cocaine addiction. These and other findings from experimentation with laboratory animals suggest new considerations for the etiology and treatment of drug addiction.     

Balancing animal research with animal well-being: establishment of goals and harmonization of approaches

A resource is provided for the creation of an institutional program that balances the scientific mission of an institution with the well-being of the animals used in support of the research. The concept of harmonizing scientific goals with animal well-being was first suggested in the early part of the twentieth century and later revitalized in the literature of the 1950s. Harmonization can best be achieved through the promotion of a team initiative. The team should include, at a minimum, the scientist, veterinarian, institutional animal care and use committee, and animal care staff. It is the responsibility of this animal research team to promote and balance the generation of scientifically valid data with animal well-being. The team must strive to minimize or eliminate non-protocol variables that could adversely affect the validity and repeatability of the experimental data. Good experimental design coupled with excellent communication between team members can often minimize or eliminate many variables and result in both better science and animal well-being. To ensure the scientific validity of experimental data, scientists must be aware of the complex nature of the environment in which their animals are maintained. To ensure repeatablity of an experiment, scientists must document and publish both the inanimate and social environments in which their animals are housed. Better documentation of environmental variables and their correlation with experimental results will promote critical knowledge about the relationships between an animal's environment, its well-being, and science.     

Cancer systems epidemiology: Overcoming misconceptions and integrating systems approaches into cancer research

Patricia Mabry and coauthors discuss application of systems approaches in cancer research.

Summary points

• While traditional epidemiological approaches have helped generate important insights about cancer prevention and treatment, they have important limitations and alone cannot bridge the gaps that continue to exist in cancer research and knowledge.
• One shortcoming is the failure to fully account for and characterize the complexity of various systems (e.g., biological, behavioral, social, environmental, and economic) that can lead to cancer and are affected by cancer.
• Systems approaches can help researchers, clinicians, and other decision makers better understand complex systems and address these systems at many levels, ranging from the cellular to the societal scale.
• Systems mapping can shed light on otherwise hidden mental models, and dynamic modeling can enable virtual experimentation—the systematic exploration of counterfactual scenarios not observable in the real world.
• We present and discuss 14 common misconceptions that will need to be overcome in order for systems epidemiology to realize its potential role in cancer prevention and control.
• Examples of systems approaches applied to cancer-related research topics are given to illustrate the utility of systems approaches to transform cancer epidemiology to cancer systems epidemiology.

     

Cooperation: integrating evolutionary and ecological perspectives

Putting a competitive squeeze on a cooperative group has long been considered to encourage cheats. Now we learn that competition, by driving diversification among cooperators, can create groups that are both more productive and more resistant to defection.     

Orientation of the human sacrum: anthropological perspectives and methodological approaches

Discovering the nature of sacral orientation is of considerable anthropological importance. Therefore, this study aims at presenting a new anthropologically based definition for sacral anatomical orientation (SAO) angle, establishing standards of SAO for human population; examining the relationship between pelvic incidence (PI) and SAO; and associating SAO with demographic parameters. The study population consisted of 424 adult and 14 sub-adult (13-18 years, for SAO only) pelvises. Sacral orientation was measured using two different definitions: a) SAO is the angle created between the intersection of a line running parallel to the superior surface of the sacrum and a line running between the anterior superior iliac spine (ASIS) and the anterior-superior edge of the symphysis pubis; b) PI is the angle created between the perpendicular to the sacral plate at its midpoint and the line connecting this point to the middle of the axis of the acetabulum. SAO was measured using a specially designed mechanical measurement tool and a 3D digitizer. PI was measured via the 3D digitizer. The methods developed by us for measuring SAO and PI in skeletal material are valid and reliable. SAO and PI measures were highly correlated (r = -0.824, P < 0.001). The average SAO was 49.01 degrees (SD = 10.16), and the average PI 54.08 degrees (SD = 12.64). SAO was independent of ethnicity and sex, yet age dependent. This study establishes a methodology for estimating SAO and PI in skeletal material and furnishes the anthropological milieu with base line data regarding these parameters. Future studies in human evolution can greatly benefit from this study.     

MHC-based vaccination approaches: progress and perspectives

The major histocompatibility complex (MHC) harbours genes whose primary function in regulating immune responsiveness to infection is to present foreign antigens to cytotoxic T lymphocytes (CTLs) and T helper cells. In the case of infection by human immunodeficiency virus (HIV), defining the optimal HIV epitopes that are recognised by CTLs is important for vaccine design, and this in turn will depend on the characteristics of the predominant infecting virus. Moreover, the particular MHC human leukocyte antigens (HLAs) expressed by a geographical population is important since these are likely to determine which HIV epitopes are immunodominant in the anti-HIV immune response. Consideration of these aspects has lead to the dawn of a new era of MHC-based vaccine design, in which the CTL epitopes are selected on the basis of the frequency of restricting MHC alleles. This article reviews data on the distribution patterns of molecular subtypes of HLA class I and class II extended haplotypes, discussing distribution among Asian Indians but with reference to global distributions. These data provide a genetic basis for the possible predisposition and fast progression of HIV infections in the Indian population. Since there is selective predominance of different HLA alleles and haplotypes in different populations, a dedicated screening effort is required at the global level to develop MHC-based vaccines against infectious diseases. It is hoped that this might lead to the development of multivalent, poly-epitope, subtype-specific HIV vaccines that are specific for the target geographical location.     

Cross-cultural,developmental psychology: integrating approaches and key insights

Like psychology more broadly, developmental psychology has long suffered from a narrow focus on children from WEIRD societies—or those that are Western, Educated, Industrialized, Rich, and Democratic. In this review, we discuss how developmental scientists have sought to correct this bias through two complementary approaches: one centered on detailed, ethnographic investigations of child development within populations (increasing the depth of our understanding) and one focused on larger, multi-site studies that test children on standardized tasks across populations (increasing breadth). We review key papers from each of these approaches, describe how they are currently practiced, and discuss their strengths and weaknesses. Next, we highlight exemplary papers from the adult literature that offer useful insights, namely the importance of formal modeling and a greater focus on studying variation at multiple levels of analysis. We end by outlining best practices for future waves of cross-cultural, developmental science. Overall, we argue that a more integrated perspective, combining the strengths of the breadth & depth approaches, can help better elucidate the developmental origins of human behavioral diversity.     

Introduction: integrating genetic and cultural evolutionary approaches to language

The papers in this special issue of Human Biology address recent research in the field of language evolution, both the genetic evolution of the language faculty and the cultural evolution of specific languages. While both of these areas have received increasing interest in recent years, there is also a need to integrate these somewhat separate efforts and explore the relevant gene-culture coevolutionary interactions. Here we summarize the individual contributions, set them in the context of the wider literature, and identify outstanding future research questions. The first set of papers concerns the comparative study of nonhuman communication in primates and birds from both a behavioral and neurobiological perspective, revealing evidence for several common language-related traits in various nonhuman species and providing clues as to the evolutionary origin and function of the human language faculty. The second set of papers discusses the consequences of viewing language as a culturally evolving system in its own right, including claims that this removes the need for strong genetic biases for language acquisition, and that phylogenetic evolutionary methods can be used to reconstruct language histories. We conclude by highlighting outstanding areas for future research, including identifying the precise selection pressures that gave rise to the language faculty in ancestral hominin species, and determining the strength, domain specificity, and origin of the cultural transmission biases that shape languages as they pass along successive generations of language learners.     

Farm animal embryo technologies: achievements and perspectives

Progress and changes in embryo technology in farm animals are briefly reviewed in terms of how well embryos can be made and used and what the subject has taught us about the maintenance of pregnancy and reproduction in general. Generalizations are made about the need to not accept dogma, how initially complex techniques always become simplified and thereby more applicable, and the need for the support of long-term and basic research. Personal views are offered on how best to prepare and motivate the next generation of scientists in the field, and the need for scientists to engage in the debate of how embryo technologies should be used responsibly in countering global inequalities.     

Endocrine disruptors in marine organisms: approaches and perspectives

Organic pollutants exhibiting endocrine disrupting activity (Endocrine Disruptors--EDs) are prevalent over a wide range in the aquatic ecosystems; most EDs are resistant to environmental degradation and are considered ubiquitous contaminants. The actual potency of EDs is low compared to that of natural hormones, but environmental concentrations may still be sufficiently high to produce detrimental biological effects. Most information on the biological effects and mechanisms of action of EDs has been focused on vertebrates. Here we summarize recent progress in studies on selected aspects of endocrine disruption in marine organisms that are still poorly understood and that certainly deserve further research in the near future. This review, divided in four sections, focuses mainly on invertebrates (effects of EDs and mechanisms of action) and presents data on top predators (large pelagic fish and cetaceans), a group of vertebrates that are particularly at risk due to their position in the food chain. The first section deals with basic pathways of steroid biosynthesis and metabolism as a target for endocrine disruption in invertebrates. In the second section, data on the effects and alternative mechanisms of action of estrogenic compounds in mussel immunocytes are presented, addressing to the importance of investigating full range responses to estrogenic chemicals in ecologically relevant invertebrate species. In the third section we review the potential use of vitellogenin (Vtg)-like proteins as a biomarker of endocrine disruption in marine bivalve molluscs, used worldwide as sentinels in marine biomonitoring programmes. Finally, we summarize the results of a recent survey on ED accumulation and effects on marine fish and mammals, utilizing both classical biomarkers of endocrine disruption in vertebrates and non-lethal techniques, such as non-destructive biomarkers, indicating the toxicological risk for top predator species in the Mediterranean. Overall, the reviewed data underline the potential to identify specific types of responses to specific groups of chemicals such as EDs in order to develop suitable biomarkers that could be useful as diagnostic tools for endocrine disruption in marine invertebrates and vertebrates.     

Ecology and biology of paddlefish in North America: historical perspectives,management approaches,and research priorities

Paddlefish (Polyodon spathula, Polyodontidae)are large, mostly-riverine fish that once wereabundant in medium- to large-sized river systemsthroughout much of the central United States. Concernfor paddlefish populations has grown from a regionalfisheries issue to one of national importance for theUnited States. In 1989, the U.S. Fish and WildlifeService (USFWS) was petitioned to list paddlefish asa federally threatened species under the EndangeredSpecies Act. The petition was not granted, primarilybecause of a lack of empirical data on paddlefishpopulation size, age structure, growth, or harvestrates across the present 22-state range. Nonetheless,concern for paddlefish populations prompted the USFWSto recommend that paddlefish be protected through theConvention on International Trade in EndangeredSpecies of Wild Fauna and Flora (CITES). The additionof paddlefish to Appendix II of CITES, which wasapproved in March 1992, provides a mechanism tocurtail illegal trade in paddlefish and their partsand supports a variety of conservation plans. Paddlefish populations have been negatively affectedby overharvest, river modifications, and pollution,but the paddlefish still occupies much of its historicrange and most extant populations seem to be stable. Although many facets of paddlefish biology andecology are well understood, the lack of informationon larval and juvenile ecology, mechanisms thatdetermine recruitment, population size and vitalrates, interjurisdictional movements, and the effectsof anthropogenic activities present significantobstacles for managing paddlefish populations. Questions about the size and structure of localpopulations, and how such populations are affected bynavigation traffic, dams, and pollution are regardedas medium priority areas for future research. Theavailability of suitable spawning habitat and overallreproductive success in impounded rivers are unknownand represent critical areas for future research. Research on reproductive and recruitment success inimpounded rivers have significant implications formanaging paddlefish, as rivers are modified furtherfor human use.     

AIDS-associated malignancies: research perspectives

The appearance in 1981 of a usually rare malignancy, Kaposi’s sarcoma, in homosexual men [1] was one of the first harbingers of an epidemic caused by a retrovirus, human immunodeficiency virus (HIV), which causes the acquired immunodeficiency syndrome (AIDS). Lymphoid and other malignancies were also increased, most strikingly non-Hodgkin’s lymphoma and primary central nervous system (CNS) lymphoma. Advances in molecular biology, immunology, virology, and anti-viral therapy have combined to create unique research opportunities. One developing theme is the role of viral co-infection and malignancy. Human herpes virus 8 (HHV8), Epstein-Barr virus (EBV) and papilloma virus each may have a causal role in the development of HIV-associated malignancy. New antiretroviral therapies are able to substantially reverse or delay the profound immunosuppression of HIV infection. The changes in the epidemiology of malignancies, and understanding the mechanism of action of these new therapeutics provide research opportunities to understand the pathogenesis of these malignancies. The opportunities to discover the consequences of T-cell based immunodeficiency and the interactions with specific viral pathogens will likely lead to progress in HIV treatment and new strategies for other malignancies.