Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy

MTHFR is an important enzyme in the metabolism of folic acid and is crucial for reproductive function. Variation in the sequence of MTHFR has been implicated in subfertility, but definitive data are lacking. In the present study, a detailed analysis of two common MTHFR polymorphisms (c.677C>T and c.1298A>C) was performed. Additionally, for the first time, the frequencies of different MTHFR alleles were assessed in preimplantation embryos. Several striking discoveries were made. Firstly, results demonstrated that maternal MTHFR c.1298A>C genotype strongly influences the likelihood of a pregnancy occurring, with the 1298C allele being significantly overrepresented amongst women who have undergone several unsuccessful assisted reproductive treatments. Secondly, parental MTHFR genotypes were shown to affect the production of aneuploid embryos, indicating that MTHFR is one of the few known human genes with the capacity to modulate rates of chromosome abnormality. Thirdly, an unusual deviation from Hardy-Weinberg equilibrium was noted for the c.677C>T polymorphism in subfertile patients, especially those who had experienced recurrent failure of embryo implantation or miscarriage, potentially explained by a rare case of heterozygote disadvantage. Finally, a dramatic impact of the MTHFR 677T allele on the capacity of chromosomally normal embryos to implant is described. Not only do these findings raise a series of interesting biological questions, but they also argue that testing of MTHFR could be of great clinical value, identifying patients at high risk of implantation failure and revealing the most viable embryos during in vitro fertilisation (IVF) cycles

Burnout in health-care professionals during reorganizations and downsizing. A cohort study in nurses

Background: Burnout is a psychological reaction triggered by interaction between personal characteristics and stress factors. Reorganizations and downsizing with increased workload imply stress for health-care professionals. This is a study of burnout in nurses during a period with two comprehensive reorganizations. Methods: In this quasi-experimental retrospective cohort study, burnout was assessed in nurses with long work experience in three surveys during a 30 months' period with two comprehensive reorganizations and downsizing of a hospital unit with mostly seriously ill patients with cancer. Burnout was measured with Bergen Burnout Indicator (BBI) at each survey, and "Sense of Coherence" (SOC) with Antonovsky's questionnaire at the last survey. Results: One man and 45 women aged 30 to 65 years were invited to the surveys. There was a significant increase in burnout during the study period, the mean increase in BBI-score was 12.5 pr year (p<0.001). The proportion of satisfied nurses at the first and last survey were 84% and 35% respectively, and the proportions with burnout were 0% and 29% respectively (p<0.001). Except for auxiliary nurses with experience from the medical department, all subgroups experienced a significant increase in BBI. Burnout was associated with low SOC (p<0.001, r square 0.33). Conclusions: There was a significant development of burnout in a group of nurses during a period with two reorganizations and downsizing. Burnout was associated with low SOC. Working with seriously ill patients with cancer has probably made the nurses exceptionally vulnerable to the stress and workload related to the reorganizations

Mindful "Vitality in Practice": an intervention to improve the work engagement and energy balance among workers; the development and design of the randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Modern working life has become more mental and less physical in nature, contributing to impaired mental health and a disturbed energy balance. This may result in mental health problems and overweight. Both are significant threats to the health of workers and thus also a financial burden for society, including employers. Targeting work engagement and energy balance could prevent impaired mental health and overweight, respectively.</p> <p>Methods/Design</p> <p>The study population consists of highly educated workers in two Dutch research institutes. The intervention was systematically developed, based on the Intervention Mapping (IM) protocol, involving workers and management in the process. The workers' needs were assessed by combining the results of interviews, focus group discussions and a questionnaire with available literature. Suitable methods and strategies were selected resulting in an intervention including: eight weeks of customized mindfulness training, followed by eight sessions of e-coaching and supporting elements, such as providing fruit and snack vegetables at the workplace, lunch walking routes, and a buddy system. The effects of the intervention will be evaluated in a RCT, with measurements at baseline, six months (T1) and 12 months (T2). In addition, cost-effectiveness and process of the intervention will also be evaluated.</p> <p>Discussion</p> <p>At baseline the level of work engagement of the sample was "average". Of the study population, 60.1% did not engage in vigorous physical activity at all. An average working day consists of eight sedentary hours. For the Phase II RCT, there were no significant differences between the intervention and the control group at baseline, except for vigorous physical activity. The baseline characteristics of the study population were congruent with the results of the needs assessment. The IM protocol used for the systematic development of the intervention produced an appropriate intervention to test in the planned RCT.</p> <p>Trial registration number</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2199">NTR2199</a></p

Whole-genome resequencing of Cucurbita pepo morphotypes to discover genomic variants associated with morphology and horticulturally valuable traits

[EN] Cucurbita pepo contains two cultivated subspecies, each of which encompasses four fruit-shape morphotypes (cultivar groups). The Pumpkin, Vegetable Marrow, Cocozelle, and Zucchini Groups are of subsp. pepo and the Acorn, Crookneck, Scallop, and Straightneck Groups are of subsp. ovifera. Recently, a de novo assembly of the C. pepo subsp. pepo Zucchini genome was published, providing insights into its evolution. To expand our knowledge of evolutionary processes within C. pepo and to identify variants associated with particular morphotypes, we performed whole-genome resequencing of seven of these eight C. pepo morphotypes. We report for the first time whole-genome resequencing of the four subsp. pepo (Pumpkin, Vegetable Marrow, Cocozelle, green Zucchini, and yellow Zucchini) morphotypes and three of the subsp. ovifera (Acorn, Crookneck, and Scallop) morphotypes. A high-depth resequencing approach was followed, using the BGISEQ-500 platform that enables the identification of rare variants, with an average of 33.5X. Approximately 94.5% of the clean reads were mapped against the reference Zucchini genome. In total, 3,823,977 high confidence single-nucleotide polymorphisms (SNPs) were identified. Within each accession, SNPs varied from 636,918 in green Zucchini to 2,656,513 in Crookneck, and were distributed homogeneously along the chromosomes. Clear differences between subspecies pepo and ovifera in genetic variation and linkage disequilibrium are highlighted. In fact, comparison between subspecies pepo and ovifera indicated 5710 genes (22.5%) with Fst > 0.80 and 1059 genes (4.1%) with Fst = 1.00 as potential candidate genes that were fixed during the independent evolution and domestication of the two subspecies. Linkage disequilibrium was greater in subsp. ovifera than in subsp. pepo, perhaps reflective of the earlier differentiation of morphotypes within subsp. ovifera. Some morphotype-specific genes have been localized. Our results offer new clues that may provide an improved understanding of the underlying genomic regions involved in the independent evolution and domestication of the two subspecies. Comparisons among SNPs unique to particular subspecies or morphotypes may provide candidate genes responsible for traits of high economic importance.This work has been supported by Hellenic Agricultural Organization (ELGO) Demeter. Furthermore, we thank the Conselleria de Educacio, Investigacio, Cultura i Esport (Generalitat Valenciana) for funding Project Prometeo 2017/078 "Seleccion de Variedades Tradicionales y Desarrollo de Nuevas Variedades de Cucurbitaceas Adaptadas a la Produccion Ecologica". Also, this work was supported by Chiang Mai University.Xanthopoulou, A.; Montero-Pau, J.; Mellidou, I.; Kissoudis, C.; Blanca Postigo, JM.; Picó Sirvent, MB.; Tsaballa, A.... (2019). Whole-genome resequencing of Cucurbita pepo morphotypes to discover genomic variants associated with morphology and horticulturally valuable traits. Horticulture Research. 6:1-17. https://doi.org/10.1038/s41438-019-0176-9S1176Maynard, D. & Paris, H. in The Encyclopedia of Fruits & Nuts (eds Paull, R. E. & Janick, J.) 276–313 (CABI, New Jersey, U.S.A., 2018).Paris, H. S. in Genetics and Genomics of Cucurbitaceae, Grumet, Rebecca, Katzir, Nurit, Garcia-Mas, Jordi (Eds.) 111–154 (Springer, New York, U.S.A., 2016).Whitaker, T. W. & Davis, G. N. Cucurbits (Leonard Hill (Books) Ltd., London, and Interscience Publishers Inc., New York, 1962).Paris, H. S. History of the cultivar-groups of Cucurbita pepo. Hortic. Rev. 25, 71–170 (2001).Paris, H. S. A proposed subspecific classifiaction for Cucurbita pepo. Phytologia (USA) 61, 133–138 (1986).Lira, R., Andres, T. C. & Nee, M. in Systematic and Ecogeographic Studies on Crop Genepools, Vol. 9, 1–115 (International Plant Genetic Resources Institute, Roma, Italia, 1995).Castellanos-Morales, G. Historical biogeography and phylogeny of Cucurbita: insights from ancestral area reconstruction and niche evolution. Mol. Phylogenet. Evol. 128, 38–54 (2018).Paris, H. S., Lebeda, A., Křistkova, E., Andres, T. C. & Nee, M. H. Parallel evolution under domestication and phenotypic differentiation of the cultivated subspecies of Cucurbita pepo (Cucurbitaceae). Econ. Bot. 66, 71–90 (2012).Dong, W., Wu, D., Li, G., Wu, D. & Wang, Z. Next-generation sequencing from bulked segregant analysis identifies a dwarfism gene in watermelon. Sci. Rep. 8, 2908 (2018).Galpaz, N. et al. Deciphering genetic factors that determine melon fruit‐quality traits using RNA‐Seq‐based high‐resolution QTL and eQTL mapping. Plant J. 94, 169–191 (2018).Gur, A. et al. Genome-wide linkage-disequilibrium mapping to the candidate gene level in melon (Cucumis melo). Sci. Rep. 7, 9770 (2017).Blanca, J. et al. Transcriptome characterization and high throughput SSRs and SNPs discovery in Cucurbita pepo (Cucurbitaceae). BMC Genom. 12, 104 (2011).Esteras, C. et al. High-throughput SNP genotyping in Cucurbita pepo for map construction and quantitative trait loci mapping. BMC Genom. 13, 80 (2012).Montero-Pau, J. et al. An SNP-based saturated genetic map and QTL analysis of fruit-related traits in Zucchini using genotyping-by-sequencing. BMC Genom. 18, 94 (2017).Vicente-Dólera, N. et al. First TILLING platform in Cucurbita pepo: a new mutant resource for gene function and crop improvement. PLoS ONE 9, e112743 (2014).Wyatt, L. E., Strickler, S. R., Mueller, L. A. & Mazourek, M. An acorn squash (Cucurbita pepo ssp. ovifera) fruit and seed transcriptome as a resource for the study of fruit traits in Cucurbita. Hortic. Res. 2, 14070 (2015).Xanthopoulou, A. et al. De novo comparative transcriptome analysis of genes involved in fruit morphology of pumpkin cultivars with extreme size difference and development of EST-SSR markers. Gene 622, 50–66 (2017).Montero‐Pau, J. et al. De novo assembly of the zucchini genome reveals a whole‐genome duplication associated with the origin of the Cucurbita genus. Plant Biotechnol. J. 16, 1161–1171 (2018).Garcia-Mas, J. et al. Cloning and mapping of resistance gene homologues in melon. Plant Sci. 161, 165–172 (2001).Xanthopoulou, A. et al. Comparative analysis of genetic diversity in Greek Genebank collection of summer squash (‘Cucurbita pepo’) landraces using start codon targeted (SCoT) polymorphism and ISSR markers. Aust. J. Crop Sci. 9, 14 (2015).Huang, J. et al. A reference human genome dataset of the BGISEQ-500 sequencer. Gigascience 6, gix024 (2017).Natarajan, K. N. et al. Comparative analysis of sequencing technologies for single-cell transcriptomics. Genome Biol. 20, 70 (2019).Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009).Tian, L. et al. Transcript and proteomic analysis of developing white lupin (Lupinus albus L.) roots. BMC Plant Biol. 9, 1 (2009).Li, H. et al. The sequence alignment/map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010).Bradbury, P. J. et al. TASSEL: software for association mapping of complex traits in diverse samples. Bioinformatics 23, 2633–2635 (2007).Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015).Team, R. C. (2015). http://www.r-project.org/ .Krzywinski, M. I. et al. Circos: an information aesthetic for comparative genomics. Genome Res. 19, 1639–1645 (2009).Kosman, E. & Leonard, K. J. Similarity coefficients for molecular markers in studies of genetic relationships between individuals for haploid, diploid, and polyploid species. Mol. Ecol. 14, 415–424 (2005).Huson, D. H. & Bryant, D. Estimating Phylogenetic Trees and Networks Using SplitsTree 4. www.splitstree.org (2005).Danecek, P. et al. The variant call format and VCFtools. Bioinformatics 27, 2156–2158 (2011).Cingolani, P. et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strainw1118; iso-2; iso-3. Fly 6, 80–92 (2012).Wu, S. et al. A common genetic mechanism underlies morphological diversity in fruits and other plant organs. Nat. Commun. 9, 4734 (2018).Drevensek, S. et al. The Arabidopsis TRM1–TON1 interaction reveals a recruitment network common to plant cortical microtubule arrays and eukaryotic centrosomes. Plant Cell 24, 178–191 (2012).Sievers, F. et al. Fast, scalable generation of high‐quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011).Nguyen, L.-T., Schmidt, H. A., von Haeseler, A. & Minh, B. Q. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol. Biol. Evol. 32, 268–274 (2014).Kalyaanamoorthy, S., Minh, B. Q., Wong, T. K. F., von Haeseler, A. & Jermiin, L. S. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat. Methods 14, 587 (2017).Hoang, D. T., Chernomor, O., von Haeseler, A., Minh, B. Q. & Vinh, L. S. UFBoot2: improving the ultrafast bootstrap approximation. Mol. Biol. Evol. 35, 518–522 (2017).Bailey, T. L. et al. MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res. 37, W202–W208 (2009).Leida, C. et al. Variability of candidate genes, genetic structure and association with sugar accumulation and climacteric behavior in a broad germplasm collection of melon (Cucumis melo L.). BMC Genet. 16, 28 (2015).Esteras, C. et al. SNP genotyping in melons: genetic variation, population structure, and linkage disequilibrium. Theor. Appl. Genet. 126, 1285–1303 (2013).Maria José Gonzalo et al. Re-evaluation of the role of Indian germplasm as center of melon diversification based on genotyping-by-sequencing analysis. BMC Genom. 20, p. 448 (2019).Nimmakayala, P. et al. Single nucleotide polymorphisms generated by genotyping by sequencing to characterize genome-wide diversity, linkage disequilibrium, and selective sweeps in cultivated watermelon. BMC Genom. 15, 767 (2014).Gonzalo, M. J. & Monforte, A. J. in Genetics and Genomics of Cucurbitaceae, Grumet, Rebecca, Katzir, Nurit, Garcia-Mas, Jordi (Eds.) 269–290 (Springer, New York, U.S.A., 2016).Pomares-Viciana, T. et al. First RNA-seq approach to study fruit set and parthenocarpy in zucchini (Cucurbita pepo L.). BMC Plant Biol. 19, 61 (2019).Lu, S. et al. The cauliflower Or gene encodes a DnaJ cysteine-rich domain-containing protein that mediates high levels of β-carotene accumulation. Plant Cell 18, 3594–3605 (2006).Jin, B., Kim, J., Jung, J., Kim, D. & Park, Y. Characterization of IQ domain gene homologs as common candidate genes for elongated fruit shape in cucurbits. Hortic. Sci. Technol. 36, 85–97 (2018).van der Knaap, E. et al. What lies beyond the eye: the molecular mechanisms regulating tomato fruit weight and shape. Front. Plant Sci. 5, 227 (2014).Xiao, H., Jiang, N., Schaffner, E., Stockinger, E. J. & Van Der Knaap, E. A retrotransposon-mediated gene duplication underlies morphological variation of tomato fruit. Science 319, 1527–1530 (2008).Dou, J. et al. Genetic mapping reveals a candidate gene (ClFS1) for fruit shape in watermelon (Citrullus lanatus L.). Theor. Appl. Genet. 131, 947–958 (2018).Pan, Y. et al. Round fruit shape in WI7239 cucumber is controlled by two interacting quantitative trait loci with one putatively encoding a tomato SUN homolog. Theor. Appl. Genet. 130, 573–586 (2017).Liu, J. et al. Banana Ovate family protein MaOFP1 and MADS-box protein MuMADS1 antagonistically regulated banana fruit ripening. PLoS ONE 10, e0123870 (2015).Liu, J. et al. Mu MADS 1 and Ma OFP 1 regulate fruit quality in a tomato ovate mutant. Plant Biotechnol. J. 16, 989–1001 (2018).Cong, B., Barrero, L. S. & Tanksley, S. D. Regulatory change in YABBY-like transcription factor led to evolution of extreme fruit size during tomato domestication. Nat. Genet. 40, 800 (2008).Huang, Z., Van Houten, J., Gonzalez, G., Xiao, H. & van der Knaap, E. Genome-wide identification, phylogeny and expression analysis of SUN, OFP and YABBY gene family in tomato. Mol. Genet. Genom. 288, 111–129 (2013).Bowman, J. L. The YABBY gene family and abaxial cell fate. Curr. Opin. Plant Biol. 3, 17–22 (2000).Liu, J., Van Eck, J., Cong, B. & Tanksley, S. D. A new class of regulatory genes underlying the cause of pear-shaped tomato fruit. Proc. Natl Acad. Sci. USA 99, 13302–13306 (2002).Tsaballa, A., Pasentsis, K., Darzentas, N. & Tsaftaris, A. S. Multiple evidence for the role of an Ovate-like gene in determining fruit shape in pepper. BMC Plant Biol. 11, 46 (2011).Wang, S., Chang, Y., Guo, J. & Chen, J. G. Arabidopsis Ovate family protein 1 is a transcriptional repressor that suppresses cell elongation. Plant J. 50, 858–872 (2007).Lazzaro, M. D., Wu, S., Snouffer, A., Wang, Y. & Van Der Knaap, E. Plant organ shapes are regulated by protein interactions and associations with microtubules. Front. Plant Sci. 9, 1766 (2018)

Enhancing volunteer engagement to achieve desirable outcomes: what can non-profit employers do?

Abstract Engagement is a positive psychological state that is linked with a range of beneficial individual and organizational outcomes. However, the factors associated with volunteer engagement have rarely been examined. Data from 1064 volunteers of a wildlife charity in the United Kingdom revealed that both task- and emotion-oriented organizational support were positively related to volunteer engagement, and volunteer engagement was positively related to volunteer happiness and perceived social worth and negatively related to intent to leave the voluntary organization. Consistent with theory, engagement acted as a mediator between these factors. The implications for future research and the relevance of the findings for voluntary organizations are discussed

Home care in Europe: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Health and social services provided at home are becoming increasingly important. Hence, there is a need for information on home care in Europe. The objective of this literature review was to respond to this need by systematically describing what has been reported on home care in Europe in the scientific literature over the past decade.</p> <p>Methods</p> <p>A systematic literature search was performed for papers on home care published in English, using the following data bases: Cinahl, the Cochrane Library, Embase, Medline, PsycINFO, Sociological Abstracts, Social Services Abstracts, and Social Care Online. Studies were only included if they complied with the definition of home care, were published between January 1998 and October 2009, and dealt with at least one of the 31 specified countries. Clinical interventions, instrument developments, local projects and reviews were excluded. The data extracted included: the characteristics of the study and aspects of home care 'policy & regulation', 'financing', 'organisation & service delivery', and 'clients & informal carers'.</p> <p>Results</p> <p>Seventy-four out of 5,133 potentially relevant studies met the inclusion criteria, providing information on 18 countries. Many focused on the characteristics of home care recipients and on the organisation of home care. Geographical inequalities, market forces, quality and integration of services were also among the issues frequently discussed.</p> <p>Conclusions</p> <p>Home care systems appeared to differ both between and within countries. The papers included, however, provided only a limited picture of home care. Many studies only focused on one aspect of the home care system and international comparative studies were rare. Furthermore, little information emerged on home care financing and on home care in general in Eastern Europe. This review clearly shows the need for more scientific publications on home care, especially studies comparing countries. A comprehensive and more complete insight into the state of home care in Europe requires the gathering of information using a uniform framework and methodology.</p