Impact of Selection and Demography on the Diffusion of Lactase Persistence

BACKGROUND: The lactase enzyme allows lactose digestion in fresh milk. Its activity strongly decreases after the weaning phase in most humans, but persists at a high frequency in Europe and some nomadic populations. Two hypotheses are usually proposed to explain the particular distribution of the lactase persistence phenotype. The gene-culture coevolution hypothesis supposes a nutritional advantage of lactose digestion in pastoral populations. The calcium assimilation hypothesis suggests that carriers of the lactase persistence allele(s) (LCT*P) are favoured in high-latitude regions, where sunshine is insufficient to allow accurate vitamin-D synthesis. In this work, we test the validity of these two hypotheses on a large worldwide dataset of lactase persistence frequencies by using several complementary approaches. METHODOLOGY: We first analyse the distribution of lactase persistence in various continents in relation to geographic variation, pastoralism levels, and the genetic patterns observed for other independent polymorphisms. Then we use computer simulations and a large database of archaeological dates for the introduction of domestication to explore the evolution of these frequencies in Europe according to different demographic scenarios and selection intensities. CONCLUSIONS: Our results show that gene-culture coevolution is a likely hypothesis in Africa as high LCT*P frequencies are preferentially found in pastoral populations. In Europe, we show that population history played an important role in the diffusion of lactase persistence over the continent. Moreover, selection pressure on lactase persistence has been very high in the North-western part of the continent, by contrast to the South-eastern part where genetic drift alone can explain the observed frequencies. This selection pressure increasing with latitude is highly compatible with the calcium assimilation hypothesis while the gene-culture coevolution hypothesis cannot be ruled out if a positively selected lactase gene was carried at the front of the expansion wave during the Neolithic transition in Europe

Identification of emulsifier potato peptides by bioinformatics: application to omega-3 delivery emulsions and release from potato industry side streams

We are grateful for the financial support from Innovation Fund Denmark (Grant nr: 7045-00021B, PROVIDE project). We also acknowledge K.M.C. amba (Brande, Denmark) and A.K.V. amba (Langholt, Denmark) for providing the potato samples used in this study.In this work, we developed a novel approach combining bioinformatics, testing of functionality and bottom-up proteomics to obtain peptide emulsifiers from potato side-streams. This is a significant advancement in the process to obtain emulsifier peptides and it is applicable to any type of protein. Our results indicated that structure at the interface is the major determining factor of the emulsifying activity of peptide emulsifiers. Fish oil-in-water emulsions with high physical stability were stabilized with peptides to be predicted to have facial amphiphilicity: (i) peptides with predominantly α-helix conformation at the interface and having 18–29 amino acids, and (ii) peptides with predominantly β-strand conformation at the interface and having 13–15 amino acids. In addition, high physically stable emulsions were obtained with peptides that were predicted to have axial hydrophobic/hydrophilic regions. Peptides containing the sequence FCLKVGV showed high in vitro antioxidant activity and led to emulsions with high oxidative stability. Peptide-level proteomics data and sequence analysis revealed the feasibility to obtain the potent emulsifier peptides found in this study (e.g. γ-1) by trypsin-based hydrolysis of different side streams in the potato industry.Innovation Fund Denmark 7045-00021

IGF-1, IGFBP-1, and IGFBP-3 Polymorphisms Predict Circulating IGF Levels but Not Breast Cancer Risk: Findings from the Breast and Prostate Cancer Cohort Consortium (BPC3)

IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-I and IGFBP-3 levels and breast cancer risk within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-I and 6,275 for circulating IGFBP-3 analyses) comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the genes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP) were selected to provide high coverage of common haplotypes; the haplotype structure was defined across four haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-I levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF levels does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women

Approaches to Enhance the Functional Properties of Pea Protein through Processing

Pea protein is a trending food ingredient because it has commercial availability, low cost, low allergenicity, non-GMO status, and good sustainability. However, the utilization of pea protein is limited by the relatively poor functional properties of commercial proteins. The functional properties of commercial proteins are reduced because of the effects of denaturation that occurs during the isolation process. By better understanding and controlling the damage that occurs during the commercial isolation process, the functional properties can be increased, promoting wider use in the food industry. To better understand the reduced functionality of commercial pea proteins, five commercial proteins were evaluated for their physicochemical and emulsification properties. Four of the five commercial proteins exhibited low solubility, high surface hydrophobicity, and an abundance of large insoluble aggregates. Commercial isolates are typically spray dried, while laboratory isolates are freeze dried, which suggested that the spray drying process is related to the reduced functional properties of pea protein. To evaluate the impact of spray drying on the physicochemical and emulsification properties of pea proteins, the spray drying temperature and pH were varied. Spray drying temperature had a minimal effect, while spray drying at pH 9.0 improved the solubility and emulsifying properties. The utilization of molecular interaction inhibitors indicated that hydrophobic interactions played a key role in the reduction of pea protein functional properties. Spray drying alone was not the only cause for the poor functional properties exhibited by commercial proteins. Heating the protein during isolation to encourage denaturation reduced the functional properties to the level of commercial proteins. High-pressure homogenization and optimized isolation conditions were investigated to determine their effect on the functionality of heated pea protein. The combination of homogenization during heating and drying at elevated pH (9.0) was able to effectively protect the protein during the isolation process and resulted in similar solubility and emulsification properties to an unheated sample. This information can be used to design better production methods for the isolation of pea protein

Implementing guidelines on the prevention of opportunistic infections in inflammatory bowel disease

Introduction: Opportunistic infections are a key safety concern in the management of patients with inflammatory bowel disease (IBD). Despite the existence of international guidelines, many gastroenterologists have not adopted routine screening and vaccination. The aim of this study was to modify clinical behaviour by use of a simple screening tool. Methods: A screening and vaccination proforma for hepatitis B, varicella, Influenza, Pneumococcus, human papillomavirus, tuberculosis, hepatitis C and HIV was provided to each participating gastroenterologist. Gastroenterologists were surveyed for awareness of vaccine recommendations and current practice prior to and following the introduction of the proforma. Rates of immunity and the proportion of patients receiving the recommended screening and vaccinations were documented. Results: 30 gastroenterologists at 8 different IBD centres took part in the assessment. A total of 919 patients were included (55% female, 65% Crohn's, 33% ulcerative colitis, 2% indeterminate IBD). Introduction of the proforma increased self-reported gastroenterologist screening from 47% to 97% pre- and post-intervention respectively, p

Why aqueous alteration in asteroids was isochemical: high porosity≠high permeability

Carbonaceous chondrite meteorites are the most compositionally primitive rocks in the solar system, but the most chemically pristine (CI1 and CM2 chondrites) have experienced pervasive aqueous alteration, apparently within asteroid parent bodies. Unfractionated soluble elements suggest very limited flow of liquid water, indicting a closed-system at scales large than 100's μm, consistent with data from oxygen isotopes, and meteorite petrography. However, numerical studies persistently predict large-scale (10's km) water transport in model asteroids, either in convecting cells, or via ‘exhalation’ flow — an open-system at scales up to 10's km. These models have tended to use permeabilites in the range 10− 13 to 10− 11 m2. We show that the permeability of plausible chondritic starting materials lies in the range 10− 19 to 10− 17 m2 (0.1–10 μD): around six orders-of-magnitude lower than previously assumed. This low permeability is largely a result of the extreme fine grain-size of primitive chondritic materials. Applying these permeability estimates in numerical models, we predict very limited liquid water flow (distances of 100's µm at most), even in a high porosity, water-saturated asteroid, with a high thermal gradient, over millions of years. Isochemical alteration, with flow over minimal lengthscales, is not a special circumstance. It is inevitable, once we consider the fundamental material properties of these rocks. To achieve large-scale flow it would require average matrix grain sizes in primitive materials of 10's–100's μm — orders of magnitude larger than observed. Finally, in addition to reconciling numerical modelling with meteorite data, our work explains several other features of these enigmatic rocks, most particularly, why the most chemically primitive meteorites are also the most altered