The challenges for molecular nutrition research 3: comparative nutrigenomics research as a basis for entering the systems level

Human nutrition and metabolism may serve as the paradigm for the complex interplay of the genome with its environment. The concept of nutrigenomics now enables science with new tools and comprehensive analytical techniques to investigate this interaction at all levels of the complexity of the organism. Moreover, nutrigenomics seeks to better define the homeostatic control mechanisms, identify the de-regulation in the early phases of diet-related diseases, and attempts to assess to what extent an individual's sensitizing genotype contributes to the overall health or disease state. In a comparative approach nutrigenomics uses biological systems of increasing complexity from yeast to mammalian models to define the general rules of metabolic and genetic mechanisms in adaptations to the nutritional environment. Powerful information technology, bioinformatics and knowledge management tools as well as new mathematical and computational approaches now make it possible to study these molecular mechanisms at the cellular, organ and whole organism level and take it on to modeling the processes in a "systems biology" approach. This review summarizes some of the concepts of a comparative approach to nutrigenomics research, identifies current lacks and proposes a concerted scientific effort to create the basis for nutritional systems biology.     

Natural variation reveals contrasting abilities to cope with alkaline and saline soil among different <Emphasis Type="Italic">Medicago truncatula</Emphasis> genotypes

Aims

Urban soils are the basis of many ecosystem services in cities. Here, we examine formerly residential vacant lot soils in Cleveland, Ohio and Detroit, Michigan, USA for their potential to provide multiple ecosystem services. We examine two key contrasts: 1) differences between cities and 2) differences within vacant lots created during demolition, specifically pre-existing (i.e., prior to demolition) soils outside of the building footprint and fill soils added within the former building’s footprint.

Methods

Deep soil cores were collected from vacant lots in Cleveland and Detroit. Soil properties that are proxies for three ecosystem services were measured: hydraulic conductivity for stormwater retention, topsoil depth and soil nitrogen (N) level for support for plant growth, and soil carbon (C) content for C storage.

Results

Both city and soil group contrasts created distinct ecosystem service provisioning based on proxy measures. Cleveland soils had greater hydraulic conductivity and greater soil C and N levels but thinner topsoil layers than Detroit. Within vacant lots of both cities, pre-existing soils had greater soil C and N levels, but lower hydraulic conductivity values than fill soils.

Conclusions

Soil properties of vacant lots were generally suitable for providing multiple ecosystem services. City-level differences in soil properties created differences in ecosystem service potential between cities and these differences were evident in pre-existing and fill soils. When comparing between cities, though, fill soils were more similar than pre-existing soils indicating some homogenization of ecosystem service potential with greater redistribution of soil.

     

Hypertension Is a Conditional Factor for the Development of Cardiac Hypertrophy in Type 2 Diabetic Mice

Background

Type 2 diabetes is frequently associated with co-morbidities, including hypertension. Here we investigated if hypertension is a critical factor in myocardial remodeling and the development of cardiac dysfunction in type 2 diabetic db/db mice.

Methods

Thereto, 14-wks-old male db/db mice and non-diabetic db/+ mice received vehicle or angiotensin II (AngII) for 4 wks to induce mild hypertension (n = 9–10 per group). Left ventricular (LV) function was assessed by serial echocardiography and during a dobutamine stress test. LV tissue was subjected to molecular and (immuno)histochemical analysis to assess effects on hypertrophy, fibrosis and inflammation.

Results

Vehicle-treated diabetic mice neither displayed marked myocardial structural remodeling nor cardiac dysfunction. AngII-treatment did not affect body weight and fasting glucose levels, and induced a comparable increase in blood pressure in diabetic and control mice. Nonetheless, AngII-induced LV hypertrophy was significantly more pronounced in diabetic than in control mice as assessed by LV mass (increase +51% and +34%, respectively, p<0.01) and cardiomyocyte size (+53% and +31%, p<0.001). This was associated with enhanced LV mRNA expression of markers of hypertrophy and fibrosis and reduced activation of AMP-activated protein kinase (AMPK), while accumulation of Advanced Glycation End products (AGEs) and the expression levels of markers of inflammation were not altered. Moreover, AngII-treatment reduced LV fractional shortening and contractility in diabetic mice, but not in control mice.

Conclusions

Collectively, the present findings indicate that type 2 diabetes in its early stage is not yet associated with adverse cardiac structural changes, but already renders the heart more susceptible to hypertension-induced hypertrophic remodeling.     

Spontaneous curvature of phosphatidic acid and lysophosphatidic acid

The formation of phosphatidic acid (PA) from lysophosphatidic acid (LPA), diacylglycerol, or phosphatidylcholine plays a key role in the regulation of intracellular membrane fission events, but the underlying molecular mechanism has not been resolved. A likely possibility is that PA affects local membrane curvature facilitating membrane bending and fission. To examine this possibility, we determined the spontaneous radius of curvature (R(0p)) of PA and LPA, carrying oleoyl fatty acids, using well-established X-ray diffraction methods. We found that, under physiological conditions of pH and salt concentration (pH 7.0, 150 mM NaCl), the R(0p) values of PA and LPA were -46 A and +20 A, respectively. Thus PA has considerable negative spontaneous curvature while LPA has the most positive spontaneous curvature of any membrane lipid measured to date. The further addition of Ca(2+) did not significantly affect lipid spontaneous curvature; however, omitting NaCl from the hydration buffer greatly reduced the spontaneous curvature of PA, turning it into a cylindrically shaped lipid molecule (R(0p) of -1.3 x 10(2) A). Our quantitative data on the spontaneous radius of curvature of PA and LPA at a physiological pH and salt concentration will be instrumental in developing future models of biomembrane fission.     

Large-scale identification of polymorphic microsatellites using an <Emphasis Type="Italic">in silico</Emphasis> approach

Background  

Simple Sequence Repeat (SSR) or microsatellite markers are valuable for genetic research. Experimental methods to develop SSR markers are laborious, time consuming and expensive. In silico approaches have become a practicable and relatively inexpensive alternative during the last decade, although testing putative SSR markers still is time consuming and expensive. In many species only a relatively small percentage of SSR markers turn out to be polymorphic. This is particularly true for markers derived from expressed sequence tags (ESTs). In EST databases a large redundancy of sequences is present, which may contain information on length-polymorphisms in the SSR they contain, and whether they have been derived from heterozygotes or from different genotypes. Up to now, although a number of programs have been developed to identify SSRs in EST sequences, no software can detect putatively polymorphic SSRs.