43 research outputs found

    Post-pollination sepal longevity of female flower co-regulated by energy-associated multiple pathways in dioecious spinach

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    Reproductive growth is a bioenergetic process with high energy consumption. Pollination induces female flower longevity in spinach by accelerating sepal retention and development. Cellular bioenergetics involved in cellular growth is at the foundation of all developmental activities. By contrast, how pollination alter the sepal cells bioenergetics to support energy requirement and anabolic biomass accumulation for development is less well understood. To investigate pollination-induced energy-associated pathway changes in sepal tissues after pollination, we utilized RNA-sequencing to identify transcripts that were differentially expressed between unpollinated (UNP) and pollinated flower sepals at 12, 48, and 96HAP. In total, over 6756 non-redundant DEGs were identified followed by pairwise comparisons (i.e. UNP vs 12HAP, UNP vs 48HAP, and UNP vs 96HAP). KEGG enrichment showed that the central carbon metabolic pathway was significantly activated after pollination and governed by pivotal energy-associated regulation pathways such as glycolysis, the citric acid cycle, oxidative phosphorylation, photosynthesis, and pentose phosphate pathways. Co-expression networks confirmed the synergistically regulation interactions among these pathways. Gene expression changes in these pathways were not observed after fertilization at 12HAP, but started after fertilization at 48HAP, and significant changes in gene expression occurred at 96HAP when there is considerable sepal development. These results were also supported by qPCR validation. Our results suggest that multiple energy-associated pathways may play a pivotal regulatory role in post-pollination sepal longevity for developing the seed coat, and proposed an energy pathway model regulating sepal retention in spinach

    Altered expression of inflammation-associated molecules in striatum: an implication for sensitivity to heavy ion radiations

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    Background and objectiveHeavy ion radiation is one of the major hazards astronauts face during space expeditions, adversely affecting the central nervous system. Radiation causes severe damage to sensitive brain regions, especially the striatum, resulting in cognitive impairment and other physiological issues in astronauts. However, the intensity of brain damage and associated underlying molecular pathological mechanisms mediated by heavy ion radiation are still unknown. The present study is aimed to identify the damaging effect of heavy ion radiation on the striatum and associated underlying pathological mechanisms.Materials and methodsTwo parallel cohorts of rats were exposed to radiation in multiple doses and times. Cohort I was exposed to 15 Gy of 12C6+ ions radiation, whereas cohort II was exposed to 3.4 Gy and 8 Gy with 56Fe26+ ions irradiation. Physiological and behavioural tests were performed, followed by 18F-FDG-PET scans, transcriptomics analysis of the striatum, and in-vitro studies to verify the interconnection between immune cells and neurons.ResultsBoth cohorts revealed more persistent striatum dysfunction than other brain regions under heavy ion radiation at multiple doses and time, exposed by physiological, behavioural, and 18F-FDG-PET scans. Transcriptomic analysis revealed that striatum dysfunction is linked with an abnormal immune system. In vitro studies demonstrated that radiation mediated diversified effects on different immune cells and sustained monocyte viability but inhibited its differentiation and migration, leading to chronic neuroinflammation in the striatum and might affect other associated brain regions.ConclusionOur findings suggest that striatum dysfunction under heavy ion radiation activates abnormal immune systems, leading to chronic neuroinflammation and neuronal injury

    Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity

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    A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia. We identified individuals carrying homozygous predicted loss-of-function (pLoF) mutations, and performed phenotypic analysis involving more than 200 biochemical and disease traits. We enumerated 49,138 rare (<1% minor allele frequency) pLoF mutations. These pLoF mutations are estimated to knock out 1,317 genes, each in at least one participant. Homozygosity for pLoF mutations at PLA2G7 was associated with absent enzymatic activity of soluble lipoprotein-associated phospholipase A2; at CYP2F1, with higher plasma interleukin-8 concentrations; at TREH, with lower concentrations of apoB-containing lipoprotein subfractions; at either A3GALT2 or NRG4, with markedly reduced plasma insulin C-peptide concentrations; and at SLC9A3R1, with mediators of calcium and phosphate signalling. Heterozygous deficiency of APOC3 has been shown to protect against coronary heart disease; we identified APOC3 homozygous pLoF carriers in our cohort. We recruited these human knockouts and challenged them with an oral fat load. Compared with family members lacking the mutation, individuals with APOC3 knocked out displayed marked blunting of the usual post-prandial rise in plasma triglycerides. Overall, these observations provide a roadmap for a 'human knockout project', a systematic effort to understand the phenotypic consequences of complete disruption of genes in humans.D.S. is supported by grants from the National Institutes of Health, the Fogarty International, the Wellcome Trust, the British Heart Foundation, and Pfizer. P.N. is supported by the John S. LaDue Memorial Fellowship in Cardiology from Harvard Medical School. H.-H.W. is supported by a grant from the Samsung Medical Center, Korea (SMO116163). S.K. is supported by the Ofer and Shelly Nemirovsky MGH Research Scholar Award and by grants from the National Institutes of Health (R01HL107816), the Donovan Family Foundation, and Fondation Leducq. Exome sequencing was supported by a grant from the NHGRI (5U54HG003067-11) to S.G. and E.S.L. D.G.M. is supported by a grant from the National Institutes of Health (R01GM104371). J.D. holds a British Heart Foundation Chair, European Research Council Senior Investigator Award, and NIHR Senior Investigator Award. The Cardiovascular Epidemiology Unit at the University of Cambridge, which supported the field work and genotyping of PROMIS, is funded by the UK Medical Research Council, British Heart Foundation, and NIHR Cambridge Biomedical Research Centre ... Fieldwork in the PROMIS study has been supported through funds available to investigators at the Center for Non-Communicable Diseases, Pakistan and the University of Cambridge, UK

    Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

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    Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

    DataSheet_1_Post-pollination sepal longevity of female flower co-regulated by energy-associated multiple pathways in dioecious spinach.pdf

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    Reproductive growth is a bioenergetic process with high energy consumption. Pollination induces female flower longevity in spinach by accelerating sepal retention and development. Cellular bioenergetics involved in cellular growth is at the foundation of all developmental activities. By contrast, how pollination alter the sepal cells bioenergetics to support energy requirement and anabolic biomass accumulation for development is less well understood. To investigate pollination-induced energy-associated pathway changes in sepal tissues after pollination, we utilized RNA-sequencing to identify transcripts that were differentially expressed between unpollinated (UNP) and pollinated flower sepals at 12, 48, and 96HAP. In total, over 6756 non-redundant DEGs were identified followed by pairwise comparisons (i.e. UNP vs 12HAP, UNP vs 48HAP, and UNP vs 96HAP). KEGG enrichment showed that the central carbon metabolic pathway was significantly activated after pollination and governed by pivotal energy-associated regulation pathways such as glycolysis, the citric acid cycle, oxidative phosphorylation, photosynthesis, and pentose phosphate pathways. Co-expression networks confirmed the synergistically regulation interactions among these pathways. Gene expression changes in these pathways were not observed after fertilization at 12HAP, but started after fertilization at 48HAP, and significant changes in gene expression occurred at 96HAP when there is considerable sepal development. These results were also supported by qPCR validation. Our results suggest that multiple energy-associated pathways may play a pivotal regulatory role in post-pollination sepal longevity for developing the seed coat, and proposed an energy pathway model regulating sepal retention in spinach.</p
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