| 1. |
- Gross, Sean M., et al.
(author)
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A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses
- 2022
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In: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
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Journal article (peer-reviewed)abstract
- The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
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| 2. |
- Keable, Stephen M., et al.
(author)
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Room temperature XFEL crystallography reveals asymmetry in the vicinity of the two phylloquinones in photosystem I
- 2021
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- Photosystem I (PS I) has a symmetric structure with two highly similar branches of pigments at the center that are involved in electron transfer, but shows very different efficiency along the two branches. We have determined the structure of cyanobacterial PS I at room temperature (RT) using femtosecond X-ray pulses from an X-ray free electron laser (XFEL) that shows a clear expansion of the entire protein complex in the direction of the membrane plane, when compared to previous cryogenic structures. This trend was observed by complementary datasets taken at multiple XFEL beamlines. In the RT structure of PS I, we also observe conformational differences between the two branches in the reaction center around the secondary electron acceptors A1A and A1B. The π-stacked Phe residues are rotated with a more parallel orientation in the A-branch and an almost perpendicular confirmation in the B-branch, and the symmetry breaking PsaB-Trp673 is tilted and further away from A1A. These changes increase the asymmetry between the branches and may provide insights into the preferential directionality of electron transfer.
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| 3. |
- Kobayashi, Lindsay C., et al.
(author)
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Education modifies the relationship between height and cognitive function in a cross-sectional population-based study of older adults in Rural South Africa
- 2019
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In: European Journal of Epidemiology. - : Springer. - 0393-2990 .- 1573-7284. ; 34:2, s. 131-139
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Journal article (peer-reviewed)abstract
- We aimed to estimate the relationship between height (a measure of early-life cumulative net nutrition) and later-life cognitive function among older rural South African adults, and whether education modified this relationship. Data were from baseline in-person interviews with 5059 adults40years in the population-based Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) study in Agincourt sub-district, South Africa, in 2015. Linear regression was used to estimate the relationship between height quintile and latent cognitive function z-score (representing episodic memory, time orientation, and numeracy), with adjustment for life course covariates and a height-by-education interaction. Mean (SD) height was 162.7 (8.9) cm. Nearly half the sample had no formal education (46%; 2307/5059). Mean age- and sex-adjusted cognitive z-scores increased from -0.68 (95% CI: -0.76 to -0.61) in those with no education in the shortest height quintile to 0.62 (95% CI: 0.52-0.71) in those with at least 8years of education in the tallest height quintile. There was a linear height disparity in cognitive z-scores for those with no formal education (adjusted =0.10; 95% CI: 0.08-0.13 per height quintile), but no height disparity in cognitive z-scores in those with any level of education. Short stature is associated with poor cognitive function and may be a risk factor for cognitive impairment among older adults living in rural South Africa. The height disparity in cognitive function was negated for older adults who had any level of education.
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| 4. |
- Vaezghasemi, Masoud, et al.
(author)
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Households, the omitted level in contextual analysis : disentangling the relative influence of households and districts on the variation of BMI about two decades in Indonesia
- 2016
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In: International Journal for Equity in Health. - : Springer Science and Business Media LLC. - 1475-9276. ; 15
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Journal article (peer-reviewed)abstract
- Background: Most of the research investigating the effect of social context on individual health outcomes has interpreted context in terms of the residential environment. In these studies, individuals are nested within their neighbourhoods or communities, disregarding the intermediate household level that lies between individuals and their residential environment. Households are an important determinant of health yet they are rarely included at the contextual level in research examining association between body mass index (BMI) and the social determinants of health. In this study, our main aim was to provide a methodological demonstration of multilevel analysis, which disentangles the simultaneous effects of households and districts as well as their associated predictors on BMI over time.Methods: Using both two- and three-level multilevel analysis, we utilized data from all four cross-sections of the Indonesian Family life Survey (IFLS) 1993 to 2007-8.Results: We found that: (i) the variation in BMI attributable to districts decreased from 4.3 % in 1993 to 1.5 % in 1997-98, and remained constant until 2007-08, while there was an alarming increase in the variation of BMI attributable to households, from 10 % in 2000 to 15 % in 2007-08; (ii) ignoring the household level did not change the relative variance contribution of districts on BMI, but ignoring the district level resulted in overestimation of household effects, and (iii) households' characteristics (socioeconomic status, size, and place of residence) did not attenuate the variation of BMI at the household-level.Conclusions: Estimating the relative importance of multiple social settings allows us to better understand and unpack the variation in clustered or hieratical data in order to make valid and robust inferences. Our findings will help direct investment of limited public health resources to the appropriate context in order to reduce health risk (variation in BMI) and promote population health.
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| 5. |
- Vaezghasemi, Masoud, et al.
(author)
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Inter-individual inequality in BMI : an analysis of Indonesian Family LifeSurveys (1993–2007)
- 2016
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In: SSM - Population Health. - : Elsevier. - 2352-8273. ; 2, s. 876-888
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Journal article (peer-reviewed)abstract
- Widening inequalities in mean Body Mass Index (BMI) between social and economic groups are well documented. However, whether changes in mean BMI are followed by changes in dispersion (or variance) and whether these inequalities are also occurring within social groups or across individuals remain understudied. In addition, a substantial body of literature exists on the global increase in mean BMI and prevalence of overweight and obesity. However, whether this weight gain is shared proportionately across the whole spectrum of BMI distribution, also remains understudied. We examined changes in the distribution of BMI at the population level over time to understand how changes in the dispersion reflect between-group compared to within-group inequalities in weight gain. Moreover, we investigated the entire distribution of BMI to determine in which percentiles the most weight gain is occurring over time. Utilizing four waves (from 1993 to 2007) of Indonesian Family Life Surveys (IFLS), we estimated changes in the mean and the variance of BMI over time and across various socioeconomic groups based on education and households’ expenditure per capita in 53,648 men and women aged 20–50 years. An increase in mean and standard deviation was observed among men (by 4.3% and 25%, respectively) and women (by 7.3% and 20%, respectively) over time. Quantile-Quantile plots showed that higher percentiles had greater increases in BMI compared to the segment of the population at lower percentiles. While between socioeconomic group differences decreased over time, within-group differences increased and were more prominent among individuals with poor education and lower per capita expenditures. Population changes in BMI cannot be fully described by average trends or single parameters such as the mean BMI. Moreover, greater increases in within-group dispersion compared with between-group differences imply that growing inequalities are not merely driven by these socioeconomic factors at the population level.
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