| 1. |
- Liberles, David A., et al.
(author)
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The interface of protein structure, protein biophysics, and molecular evolution
- 2012
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In: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 21:6, s. 769-785
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Research review (peer-reviewed)abstract
- The interface of protein structural biology, protein biophysics, molecular evolution, and molecular population genetics forms the foundations for a mechanistic understanding of many aspects of protein biochemistry. Current efforts in interdisciplinary protein modeling are in their infancy and the state-of-the art of such models is described. Beyond the relationship between amino acid substitution and static protein structure, protein function, and corresponding organismal fitness, other considerations are also discussed. More complex mutational processes such as insertion and deletion and domain rearrangements and even circular permutations should be evaluated. The role of intrinsically disordered proteins is still controversial, but may be increasingly important to consider. Protein geometry and protein dynamics as a deviation from static considerations of protein structure are also important. Protein expression level is known to be a major determinant of evolutionary rate and several considerations including selection at the mRNA level and the role of interaction specificity are discussed. Lastly, the relationship between modeling and needed high-throughput experimental data as well as experimental examination of protein evolution using ancestral sequence resurrection and in vitro biochemistry are presented, towards an aim of ultimately generating better models for biological inference and prediction.
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| 2. |
- Ignatenko, O. V., et al.
(author)
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Electrochemistry of chemically trapped dimeric and monomeric recombinant horseradish peroxidase
- 2013
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In: Advances in Biosensors and Bioelectronics. - : Science and Engineering Publishing Company. - 2326-473X. ; 2:3, s. 25-34
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Journal article (peer-reviewed)abstract
- Native horseradish peroxidase (nHRP) exists in the aggregated form in concentrated water solutions as shown by dynamic light scattering (DLS). This is in contrast to recombinant horseradish peroxidase (recHRP) which mainly exists as a dimer. The native enzyme aggregates could be broken into the particles of nm-size only under the conditions of high ionic strength (0.5-1 M NaCl). Chemical cross-linking of recHRP with glutaraldehyde in water solutions yields 40% of the dimer. The chemically trapped dimeric and monomeric forms of recHRP were separated by gel-filtration, their substrate specificity towards a number of organic substrates compared. Parameters of direct and mediated electron transfer on graphite electrodes catalyzed by both preparations were analyzed. The difference in behavior of the monomeric and dimeric enzyme forms observed in electrochemical experiments was interpreted as a result of a “double” coverage of the electrode surface with the molecules of cross-linked dimeric enzyme, in contrast to both modified monomeric and original, unmodified recHRP providing “monolayer” coverage. In addition to the stabilization effects achieved due to enzyme surface modification with glutaraldehyde, the “double” coverage doubles the enzyme activity per surface unit.
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| 4. |
- Sujan, Ayesha C., et al.
(author)
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A Genetically Informed Study of the Associations Between Maternal Age at Childbearing and Adverse Perinatal Outcomes
- 2016
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In: Behavior Genetics. - New York, USA : Springer. - 0001-8244 .- 1573-3297. ; 46:3, s. 431-456
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Journal article (peer-reviewed)abstract
- We examined associations of maternal age at childbearing (MAC) with gestational age and fetal growth (i.e., birth weight adjusting for gestational age), using two genetically informed designs (cousin and sibling comparisons) and data from two cohorts, a population-based Swedish sample and a nationally representative United States sample. We also conducted sensitivity analyses to test limitations of the designs. The findings were consistent across samples and suggested that, associations observed in the population between younger MAC and shorter gestational age were confounded by shared familial factors; however, associations of advanced MAC with shorter gestational age remained robust after accounting for shared familial factors. In contrast to the gestational age findings, neither early nor advanced MAC was associated with lower fetal growth after accounting for shared familial factors. Given certain assumptions, these findings provide support for a causal association between advanced MAC and shorter gestational age. The results also suggest that there are not causal associations between early MAC and shorter gestational age, between early MAC and lower fetal growth, and between advanced MAC and lower fetal growth.
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| 7. |
- Bälter, Katarina, et al.
(author)
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Is a diet low in greenhouse gas emissions a nutritious diet? : - Analyses of self-selected diets in the LifeGene study
- 2017
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In: Archives of Public Health. - : BioMed Central Ltd.. - 0778-7367 .- 2049-3258. ; 75:1
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Journal article (peer-reviewed)abstract
- Background: Climate change is an urgent global issue and the food sector is a major contributor to greenhouse gas emissions (GHGE). Here we study if a diet low in GHGE could be a nutritious diet compared to the Nordic Nutrition Recommendations (NNR). Methods: The environmental impact of foods from Life Cycle Assessment (LCA) data was linked to a food frequency questionnaire (FFQ) filled out by 5,364 participants in the Swedish LifeGene study. Thereafter, we calculated the daily emission of CO2 equivalents (CO2e) as well as the intake of selected nutrients associated with vegetables, fruits, meat and dairy products. The CO2e was divided into quartiles were quartile 1 corresponds to a diet generating the lowest CO2e, and quartile 4 corresponds to a diet with the highest CO2e. Results: The overall diet-related emission was 4.7kg CO2e/day and person, corresponding to 1.7 ton CO2e/year. In general, there were only small differences in nutrient intake between groups of varying levels of CO2e, regardless if the intake was analyzed as absolute intake, energy percent or as nutrient density. Moreover, adherence to NNR was high for the group with the lowest CO2e, except for saturated fat where the intake was higher than recommended for all CO2e groups. On the other hand, only the group with the lowest CO2e fulfilled recommended intake of fiber. However, none of the CO2e groups reached the recommended intake of folate and vitamin D. Conclusions: Here we show that a self-selected diet low in CO2e provides comparable intake of nutrients as a diet high in in CO2e.
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| 8. |
- Christensen, S. E., et al.
(author)
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Two New Meal- and Web-Based Interactive Food Frequency Questionnaires: Validation of Energy and Macronutrient Intake
- 2013
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In: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 15:6
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Journal article (peer-reviewed)abstract
- Background: Meal-Q and its shorter version, MiniMeal-Q, are 2 new Web-based food frequency questionnaires. Their meal-based and interactive format was designed to promote ease of use and to minimize answering time, desirable improvements in large epidemiological studies. Objective: We evaluated the validity of energy and macronutrient intake assessed with Meal-Q and MiniMeal-Q as well as the reproducibility of Meal-Q. Methods: Healthy volunteers aged 20-63 years recruited from Stockholm County filled out the 174-item Meal-Q. The questionnaire was compared to 7-day weighed food records (WFR; n=163), for energy and macronutrient intake, and to doubly labeled water (DLW; n=39), for total energy expenditure. In addition, the 126-item MiniMeal-Q was evaluated in a simulated validation using truncated Meal-Q data. We also assessed the answering time and ease of use of both questionnaires. Results: Bland-Altman plots showed a varying bias within the intake range for all validity comparisons. Cross-classification of quartiles placed 70%-86% in the same/adjacent quartile with WFR and 77% with DLW. Deattenuated and energy-adjusted Pearson correlation coefficients with the WFR ranged from r=0.33-0.74 for macronutrients and was r=0.18 for energy. Correlations with DLW were r=0.42 for Meal-Q and r=0.38 for MiniMeal-Q. Intraclass correlations for Meal-Q ranged from r=0.57-0.90. Median answering time was 17 minutes for Meal-Q and 7 minutes for MiniMeal-Q, and participants rated both questionnaires as easy to use. Conclusions: Meal-Q and MiniMeal-Q are easy to use and have short answering times. The ranking agreement is good for most of the nutrients for both questionnaires and Meal-Q shows fair reproducibility.
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| 9. |
- D'Onofrio, Brian M., et al.
(author)
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Translational Epidemiologic Approaches to Understanding the Consequences of Early-Life Exposures
- 2016
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In: Behavior Genetics. - New York, USA : Springer. - 0001-8244 .- 1573-3297. ; 46:3, s. 315-328
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Research review (peer-reviewed)abstract
- Prominent developmental theories posit a causal link between early-life exposures and later functioning. Yet, observed associations with early exposures may not reflect causal effects because of genetic and environmental confounding. The current manuscript describes how a systematic series of epidemiologic analyses that combine several genetically-informative designs and statistical approaches can help distinguish between competing theories. In particular, the manuscript details how combining the use of measured covariates with sibling-comparisons, cousin-comparisons, and additional designs can help elucidate the sources of covariation between early-life exposures and later outcomes, including the roles of (a) factors that are not shared in families, including a potential causal effect of the exposure; (b) carryover effects from the exposure of one child to the next; and (c) familial confounding. We also describe key assumptions and how they can be critically evaluated. Furthermore, we outline how subsequent analyses, including effect decomposition with respect to measured, plausible mediators, and quantitative genetic models can help further specify the underlying processes that account for the associations between early-life exposures and offspring outcomes.
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