Biomarkers in nutritional epidemiology: applications, needs and new horizons

Modern epidemiology suggests a potential interactive association between diet, lifestyle, genetics and the risk of many chronic diseases. As such, many epidemiologic studies attempt to consider assessment of dietary intake alongside genetic measures and other variables of interest. However, given the multi-factorial complexities of dietary exposures, all dietary intake assessment methods are associated with measurement errors which affect dietary estimates and may obscure disease risk associations. For this reason, dietary biomarkers measured in biological specimens are being increasingly used as additional or substitute estimates of dietary intake and nutrient status. Genetic variation may influence dietary intake and nutrient metabolism and may affect the utility of a dietary biomarker to properly reflect dietary exposures. Although there are many functional dietary biomarkers that, if utilized appropriately, can be very informative, a better understanding of the interactions between diet and genes as potentially determining factors in the validity, application and interpretation of dietary biomarkers is necessary. It is the aim of this review to highlight how some important biomarkers are being applied in nutrition epidemiology and to address some associated questions and limitations. This review also emphasizes the need to identify new dietary biomarkers and highlights the emerging field of nutritional metabonomics as an analytical method to assess metabolic profiles as measures of dietary exposures and indicators of dietary patterns, dietary changes or effectiveness of dietary interventions. The review will also touch upon new statistical methodologies for the combination of dietary questionnaire and biomarker data for disease risk assessment. It is clear that dietary biomarkers require much further research in order to be better applied and interpreted. Future priorities should be to integrate high quality dietary intake information, measurements of dietary biomarkers, metabolic profiles of specific dietary patterns, genetics and novel statistical methodology in order to provide important new insights into gene-diet-lifestyle-disease risk associations.     

Genetic polymorphisms and microRNAs: new direction in molecular epidemiology of solid cancer

MicroRNAs (miRNAs) are small non-coding RNAs, which regulate gene expression. Single nucleotide polymorphisms (SNPs) may occur in miRNA biogenesis pathway genes, primary miRNA, pre-miRNA or a mature miRNA sequence. Such polymorphisms may be functional with respect to biogenesis and actions of mature miRNA. Specific SNPs were identified in predicted miRNA target sites within 3' untranslated regions of mRNAs. These SNPs have a potential to affect the efficiency of miRNA binding to the target sites or can create or disrupt binding sites. Resulting gene dysregulation may involve changes in phenotype and may eventually prove critical for the susceptibility to cancer and its onset as well as for estimates of prognosis and therapy response. In this review, we provide a comprehensive list of potentially functional miRNA-related SNPs and summarize their importance as candidate cancer biomarkers.     

Biological horizons in molecular microscopy.

The purpose envisaged in this report is not to provide a comprehensive monography but rather to give a survey, especially for biologists, of the state of the art and of current research trends in molecular microscopy. Following a brief discussion of the obvious discrepancy between instrumental capabilities and the limits of biologically significant information, a definition of the diversifying field is attempted. Four main topics are discussed. First, recent progress in the field of "low noise" specimen supports is reviewed. It is emphasized that a minimum background structure is an important but not the sole criterion for a satisfactory support. It is the ability to adsorb molecules in a predeterminable and orderly fashion which will attract wider attention in the future; positional and orientational order figure as crucial points in the strategem of low dose microscopy. Second, the problem of achieving adequate contrast without the expense of an unfaithful representation of molecular structures is discussed. Contrast is a problem of optimum imaging modes as well as of preparatory techniques. The third topic of discussion is specimen dehydration. Several avenues to circumvent or at least to alleviate dehydration artifacts are outlined. The last chapter focusses on the most fundamental problem in molecular microscopy:radiation damage. A brief synopsis of the physical and physico-chemical processes involved in damaging interactions is given and an attempt is made to tesselate the true picture of radiation damage to lipids and proteins. This might serve as a guidance in assessing the degree of structural fidelity to be expected for a given electron dose. Possibilities to overcome the radiation damage problem are adumbrated.     

Genetic engineering of trees: progress and new horizons

Genetic engineering of trees to improve productivity, wood quality, and resistance to biotic and abiotic stresses has been the primary goal of the forest biotechnology community for decades. We review the extensive progress in these areas and their current status with respect to commercial applications. Examples include novel methods for lignin modification, solutions for long-standing problems related to pathogen resistance, modifications to flowering onset and fertility, and drought and freeze tolerance. There have been numerous successful greenhouse and field demonstrations of genetically engineered trees, but commercial application has been severely limited by social and technical considerations. Key social factors are costly and uncertain regulatory hurdles and sweeping market barriers in the form of forest certification systems that disallow genetically modified trees. These factors limit and, in many cases, preclude field research and commercial adoption. Another challenge is the high cost and uncertainty in transformation efficiency that is needed to apply genetic engineering and gene editing methods to most species and genotypes of commercial importance. Recent advances in developmental gene-based transformation systems and gene editing, if combined with regulatory and certification system reform, could provide the foundation for genetic engineering to become a significant tool for coping with the increasing environmental and biological stresses on planted and wild forests.     

Superchannel of bacteria: biological significance and new horizons

Sphingomonas species A1 is a newly identified pit-forming bacterium that directly incorporates a macromolecule (alginate) into its cytoplasm through a pit-dependent transport system, which we termed a superchannel. A pit is a novel, high-dimensional organ acquired through the fluidity and reconstitution of cell surface molecules, including flagellin, and through cooperation with the transport machinery in the cells, which confers upon bacterial cells a more efficient way to secure and assimilate macromolecules. The analysis of the superchannel changes general ideas regarding the fluidity and function of the cell surface, evolution and origin of cell-surface organs, including flagella, transport, and assimilation systems of macromolecules, and the divergence and energetics of metabolism.     

Rubella in teenagers: epidemiology and prophylaxis in Siena, Italy

Six hundred and fifty-three teenagers (aged 11-13 year) living in Siena and its surroundings (Tuscany, Italy) were the sample for serological screening intended to ascertain immunity to rubella. It was found that 324 of the teenagers (49.62%) lacked antibodies and, hence, were unprotected against the infection. Out of the 324 girls, 196 (around 3/5) were vaccinated using live vaccine. Post-vaccinal complications, with clinical signs of rubella infection, were recorded in almost one third of the vaccinees. Virus isolation from the blood was, in every case, not possible after either 10 or 30 days from vaccination. The serological findings, expressed in hemagglutination inhibition antibodies, could be summarized in the following way: (i) antibodies at low titre were found in only eight out of 184 girls (4.35%) ten days after vaccination; (ii) serological conversion was recorded in 187 out of 188 girls (99.47%) 30 days after vaccination; (iii) the titres were moderately high but much lower than those recorded for the natural infection. The results are discussed in the context of their implications for the strategies of rubella vaccination as far as the safety and the effectiveness of the vaccine are concerned, with emphasis on the duration of the protective immunity.     

Beyond strain typing and molecular epidemiology: integrated genetic epidemiology of infectious diseases

In the past 20 years, genetic and molecular methods for characterizing pathogen strains have taken a major place in modern approaches to epidemiology of parasitic and other infectious diseases. Here, Michel Tibayrenc explains the main concepts used in this field of research, with special emphasis on the approaches developed in his team, and suggests future avenues to explore.     

Modern features of the epidemiology and prophylaxis of influenza

Modern concepts concerning influenza pandemics and epidemics in different countries of the world are presented. The influenza epidemics of the last decade in different countries of the world and their specific features linked with the "drifting" variability of influenza virus have been analyzed. Information on influenza morbidity during the last 30 years is given; on the basis of this information the role of vaccinal prophylaxis and mainly the mass vaccination of school children and students, is shown. The results of the efficacy of such vaccines as live influenza vaccine, American split vaccine, Russian live recombinant vaccine and Grippovac (1995-1996), as well as new-generation vaccine Grippol (1998), are presented. The prospects of the combined use of specific and unspecific prophylaxis have been determined.     

ST-segment elevation myocardial infarction: Historical perspective and new horizons

After a brief history of the emergence of modern therapy for acute ST-elevation myocardial infarction, we discuss the issues that dominate ongoing studies and are the focus of intense debates. The role of angiography, pharmacotherapy, thrombus aspiration, management of multi-vessel disease, mechanical complications and cardiogenic shock and the quest for myocardial salvage are discussed.