Gestational diabetes mellitus follow-up in Norwegian primary health care: a qualitative study

Background Women with gestational diabetes mellitus (GDM) have a tenfold increased risk of developing diabetes, and a high risk of recurrent GDM. Endorsing the life-course approach aiming to prevent disease and promote health across generations, the Norwegian GDM guideline recommends follow-up in primary care after delivery, with information on the increased risks, lifestyle counselling, and annual diabetes screening. Few reports exist on Norwegian women’s experiences of GDM follow-up. Aim To elucidate women’s experiences with follow-up of GDM in pregnancy and after delivery, and to explore their attitudes to diabetes risk and motivation for lifestyle changes. Design & setting Qualitative study in primary care in the region of Stavanger, Norway. Method Semi-structured in-depth interviews were conducted 24–30 months after delivery with 14 women aged 28–44 years, with a history of GDM. Data were analysed thematically. Results Most women were satisfied with the follow-up during pregnancy; however, only two women were followed-up according to the guideline after delivery. In most encounters with GPs after delivery, GDM was not mentioned. To continue the healthy lifestyle adopted in pregnancy, awareness of future risk was a motivational factor, and the women asked for tailored information on individual risk and improved support. The main themes emerging from the analysis were as follows: stigma and shame; uncertainty; gaining control and finding balance; and a need for support to sustain change. Conclusion Women experienced a lack of support for GDM in Norwegian primary care after delivery. To maintain a healthy lifestyle, women suggested being given tailored information and improved support.publishedVersio

Measuring Extinction Curves of Lensing Galaxies

We critique the method of constructing extinction curves of lensing galaxies using multiply imaged QSOs. If one of the two QSO images is lightly reddened or if the dust along both sightlines has the same properties then the method works well and produces an extinction curve for the lensing galaxy. These cases are likely rare and hard to confirm. However, if the dust along each sightline has different properties then the resulting curve is no longer a measurement of extinction. Instead, it is a measurement of the difference between two extinction curves. This "lens difference curve'' does contain information about the dust properties, but extracting a meaningful extinction curve is not possible without additional, currently unknown information. As a quantitative example, we show that the combination of two Cardelli, Clayton, & Mathis (CCM) type extinction curves having different values of R(V) will produce a CCM extinction curve with a value of R(V) which is dependent on the individual R(V) values and the ratio of V band extinctions. The resulting lens difference curve is not an average of the dust along the two sightlines. We find that lens difference curves with any value of R(V), even negative values, can be produced by a combination of two reddened sightlines with different CCM extinction curves with R(V) values consistent with Milky Way dust (2.1 < R(V) < 5.6). This may explain extreme values of R(V) inferred by this method in previous studies. But lens difference curves with more normal values of R(V) are just as likely to be composed of two dust extinction curves with R(V) values different than that of the lens difference curve. While it is not possible to determine the individual extinction curves making up a lens difference curve, there is information about a galaxy's dust contained in the lens difference curves.Comment: 15 pages, 4 figues, ApJ in pres

The Role of Ancestral Duplicated Genes in Adaptation to Growth on Lactate, a Non-Fermentable Carbon Source for the Yeast Saccharomyces cerevisiae

[EN] The cell central metabolism has been shaped throughout evolutionary times when facing challenges from the availability of resources. In the budding yeast, Saccharomyces cerevisiae, a set of duplicated genes originating from an ancestral whole-genome and several coetaneous small-scale duplication events drive energy transfer through glucose metabolism as the main carbon source either by fermentation or respiration. These duplicates (~a third of the genome) have been dated back to approximately 100 MY, allowing for enough evolutionary time to diverge in both sequence and function. Gene duplication has been proposed as a molecular mechanism of biological innovation, maintaining balance between mutational robustness and evolvability of the system. However, some questions concerning the molecular mechanisms behind duplicated genes transcriptional plasticity and functional divergence remain unresolved. In this work we challenged S. cerevisiae to the use of lactic acid/lactate as the sole carbon source and performed a small adaptive laboratory evolution to this non-fermentative carbon source, determining phenotypic and transcriptomic changes. We observed growth adaptation to acidic stress, by reduction of growth rate and increase in biomass production, while the transcriptomic response was mainly driven by repression of the whole-genome duplicates, those implied in glycolysis and overexpression of ROS response. The contribution of several duplicated pairs to this carbon source switch and acidic stress is also discussed.This research was funded by Spanish National Plan for Scientific and Technical Research and Innovation from the Spanish Ministry of Economy and Competitiveness (MINECOFEDER), actually the Ministry of Science and Innovation (MCIN), Spanish Research Agency (AEI), MCIN/AEI/10.13039/501100011033 and ERDF A way of making Europe (FEDER "Una forma de hacer Europa") with grant number BFU2015-66073-P (to M.A.F.) and Generalitat Valenciana, Conselleria de Innovacion, Universidades y Sociedad Digital with grant number SEJI/2018/046 (to C.T.). F.M. was supported by a Spanish PhD Fellowship number FPI BES-2016-076677, from MCIN/AEI/10.13039/501100011033 and ESF "Investing in your future".Mattenberger, F.; Fares Riaño, MA.; Toft, C.; Sabater-Muñoz, B. (2021). The Role of Ancestral Duplicated Genes in Adaptation to Growth on Lactate, a Non-Fermentable Carbon Source for the Yeast Saccharomyces cerevisiae. International Journal of Molecular Sciences. 22(22):1-17. https://doi.org/10.3390/ijms222212293S117222

Expression properties exhibit correlated patterns with the fate of duplicated genes, their divergence, and transcriptional plasticity in Saccharomycotina

[EN] Gene duplication is an important source of novelties and genome complexity. What genes are preserved as duplicated through long evolutionary times can shape the evolution of innovations. Identifying factors that influence gene duplicability is therefore an important aim in evolutionary biology. Here, we show that in the yeast Saccharomyces cerevisiae the levels of gene expression correlate with gene duplicability, its divergence, and transcriptional plasticity. Genes that were highly expressed before duplication are more likely to be preserved as duplicates for longer evolutionary times and wider phylogenetic ranges than genes that were lowly expressed. Duplicates with higher expression levels exhibit greater divergence between their gene copies. Duplicates that exhibit higher expression divergence are those enriched for TATA-containing promoters. These duplicates also show transcriptional plasticity, which seems to be involved in the origin of adaptations to environmental stresses in yeast. While the expression properties of genes strongly affect their duplicability, divergence and transcriptional plasticity are enhanced after gene duplication. We conclude that highly expressed genes are more likely to be preserved as duplicates due to their promoter architectures, their greater tolerance to expression noise, and their ability to reduce the noise-plasticity conflict.We would like to thank members of Fares' Lab for a careful reading and discussion of the results in the manuscript. We are also grateful to colleagues at Trinity College for helpful discussions. This work was supported by a grant from the Spanish Ministerio de Economia y Competitividad (MINECO-FEDER; BFU2015-66073-P) to M.A.F. F.M. is supported by a PhD grant from the Spanish Ministerio de Economia y Competitividad (reference: BES-2016-076677). C.T. was supported by a grant Juan de la Cierva from the Spanish Ministerio de Economia y Competitividad (reference: JCA-2012-14056).Mattenberger, F.; Sabater-Muñoz, B.; Toft, C.; Sablok, G.; Fares Riaño, MA. (2017). Expression properties exhibit correlated patterns with the fate of duplicated genes, their divergence, and transcriptional plasticity in Saccharomycotina. DNA Research. 24(6):559-570. https://doi.org/10.1093/dnares/dsx025S559570246Ohno, S. (1999). Gene duplication and the uniqueness of vertebrate genomes circa 1970–1999. Seminars in Cell & Developmental Biology, 10(5), 517-522. doi:10.1006/scdb.1999.0332Lynch, M. (2000). The Evolutionary Fate and Consequences of Duplicate Genes. Science, 290(5494), 1151-1155. doi:10.1126/science.290.5494.1151Otto, S. P., & Whitton, J. (2000). Polyploid Incidence and Evolution. Annual Review of Genetics, 34(1), 401-437. doi:10.1146/annurev.genet.34.1.401Carretero-Paulet, L., & Fares, M. A. (2012). Evolutionary Dynamics and Functional Specialization of Plant Paralogs Formed by Whole and Small-Scale Genome Duplications. Molecular Biology and Evolution, 29(11), 3541-3551. doi:10.1093/molbev/mss162Cui, L. (2006). Widespread genome duplications throughout the history of flowering plants. Genome Research, 16(6), 738-749. doi:10.1101/gr.4825606Holub, E. B. (2001). The arms race is ancient history in Arabidopsis, the wildflower. Nature Reviews Genetics, 2(7), 516-527. doi:10.1038/35080508Lespinet, O. (2002). The Role of Lineage-Specific Gene Family Expansion in the Evolution of Eukaryotes. Genome Research, 12(7), 1048-1059. doi:10.1101/gr.174302Wendel, J. F. (2000). Plant Molecular Biology, 42(1), 225-249. doi:10.1023/a:1006392424384Soltis, D. E., Albert, V. A., Leebens-Mack, J., Bell, C. D., Paterson, A. H., Zheng, C., … Soltis, P. S. (2009). Polyploidy and angiosperm diversification. American Journal of Botany, 96(1), 336-348. doi:10.3732/ajb.0800079De Peer, Y. V. (2004). 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Rate Asymmetry After Genome Duplication Causes Substantial Long-Branch Attraction Artifacts in the Phylogeny of Saccharomyces Species. Molecular Biology and Evolution, 23(2), 245-253. doi:10.1093/molbev/msj027Freeling, M. (2009). Bias in Plant Gene Content Following Different Sorts of Duplication: Tandem, Whole-Genome, Segmental, or by Transposition. Annual Review of Plant Biology, 60(1), 433-453. doi:10.1146/annurev.arplant.043008.092122Conant, G. C., Birchler, J. A., & Pires, J. C. (2014). Dosage, duplication, and diploidization: clarifying the interplay of multiple models for duplicate gene evolution over time. Current Opinion in Plant Biology, 19, 91-98. doi:10.1016/j.pbi.2014.05.008Keane, O. M., Toft, C., Carretero-Paulet, L., Jones, G. W., & Fares, M. A. (2014). Preservation of genetic and regulatory robustness in ancient gene duplicates ofSaccharomyces cerevisiae. Genome Research, 24(11), 1830-1841. doi:10.1101/gr.176792.114Fares, M. A. (2015). 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Comparative Genomics Between Saccharomyces kudriavzevii and S. cerevisiae Applied to Identify Mechanisms Involved in Adaptation

Yeasts belonging to the Saccharomyces genus play an important role in human-driven fermentations. The species S. cerevisiae has been widely studied because it is the dominant yeast in most fermentations and it has been widely used as a model eukaryotic organism. Recently, other species of the Saccharomyces genus are gaining interest to solve the new challenges that the fermentation industry are facing. One of these species is S. kudriavzevii, which exhibits interesting physiological properties compared to S. cerevisiae, such as a better adaptation to grow at low temperatures, a higher glycerol synthesis and lower ethanol production. The aim of this study is to understand the molecular basis behind these phenotypic differences of biotechnological interest by using a species-based comparative genomics approach. In this work, we sequenced, assembled and annotated two new genomes of S. kudriavzevii. We used a combination of different statistical methods to identify functional divergence, signatures of positive selection and acceleration of substitution rates at specific amino acid sites of proteins in S. kudriavzevii when compared to S. cerevisiae, and vice versa. We provide a list of candidate genes in which positive selection could be acting during the evolution of both S. cerevisiae and S. kudriavzevii clades. Some of them could be related to certain important differences in metabolism previously reported by other authors such us DAL3 and ARO4, involved in nitrogen assimilation and amino acid biosynthesis. In addition, three of those genes (FBA1, ZIP1, and RQC2) showed accelerated evolutionary rates in Sk branch. Finally, genes of the riboflavin biosynthesis were also among those genes with a significant higher rate of nucleotide substitution and those proteins have amino acid positions contributing to functional divergence

Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry

Calmodulin; Cardiomyopathies; Neurological disordersCalmodulina; Miocardiopatías; Trastornos neurológicosCalmodulina; Miocardiopaties; Trastorns neurològicsAims: Calmodulinopathy due to mutations in any of the three CALM genes (CALM1-3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. Methods and results: The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5-19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. Conclusion: Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter-defibrillator.The ICalmR is one of the registries supported by ERN GUARD-Heart. This research was supported by the Italian Ministry of Health Ricerca Corrente ‘Registro internazionale delle calmodulinopatie’ to L.C., F.D., P.J.S., M.C.K., and C.S.; by the 2019-ATESP-0045 Fondo di Ateneo Quota Competitiva to L.C.; and partially by the Fondation Leducq grant 18CVD05 ‘Towards Precision Medicine with Human iPSCs for Cardiac Channelopathies’ to L.C., M.-C.K., L.S., and P.J.S. J.B., L.C., and P.J.S. were partially supported by the European Joint Programme on Rare Diseases: LQTS-NEXT grant. R.H. was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, The Labatt Family Heart Centre, the Cartwright Family Fellowship, the Carter Heart Arrhythmia Trainee Fund and the Caitlin Elizabeth Morris fund. J.P.K. was supported by the Medical Research Council (MRC) Clinical Academic Research Partnership (CARP) Award (MR/T024062/1). G.R.W. was supported by an NIH K23HL130554 grant. A.A.M.W. was supported by the Netherlands Cardiovascular Research Initiative (CVON PREDICT-2). M.J.A. was supported in part by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program. M.T.O. was supported in part by the Danish Independent Research Council (Grant no. 2032–00333B) and the Lundbeck Foundation (Grant no. R324-2019-1933). H.K.J. was supported by the Novo Nordisk Foundation (Grant NNF 18OC0031258)

A binary interaction map between turnip mosaic virus and Arabidopsis thaliana proteomes

[EN] Viruses are obligate intracellular parasites that have co-evolved with their hosts to establish an intricate network of protein-protein interactions. Here, we followed a high-throughput yeast two-hybrid screening to identify 378 novel protein-protein interactions between turnip mosaic virus (TuMV) and its natural host Arabidopsis thaliana. We identified the RNA-dependent RNA polymerase NIb as the viral protein with the largest number of contacts, including key salicylic acid-dependent transcription regulators. We verified a subset of 25 interactions in planta by bimolecular fluorescence complementation assays. We then constructed and analyzed a network comprising 399 TuMV-A. thaliana interactions together with intravirus and intrahost connections. In particular, we found that the host proteins targeted by TuMV are enriched in different aspects of plant responses to infections, are more connected and have an increased capacity to spread information throughout the cell proteome, display higher expression levels, and have been subject to stronger purifying selection than expected by chance. The proviral or antiviral role of ten host proteins was validated by characterizing the infection dynamics in the corresponding mutant plants, supporting a proviral role for the transcriptional regulator TGA1. Comparison with similar studies with animal viruses, highlights shared fundamental features in their mode of action.We thank Francisca de la Iglesia and Paula Agudo for excellent technical assistance and the rest of the EvolSysVir lab for fruitful discussions. This work was supported by grants PID2019-103998GB-I00 and PGC2018-101410-B-I00 (Agencia Estatal de Investigacion - FEDER) to S.F.E. and G.R., respectively, and PROMETEO/2019/012 (Generalitat Valenciana) to S.F.E.Martínez, F.; Carrasco, JL.; Toft, C.; Hillung, J.; Giménez-Santamarina, S.; Yenush, L.; Rodrigo Tarrega, G.... (2023). A binary interaction map between turnip mosaic virus and Arabidopsis thaliana proteomes. Communications Biology. 6(1):1-18. https://doi.org/10.1038/s42003-023-04427-81186