Socioeconomic and ethnical disparity in coronary heart disease outcomes in Denmark and the effect of cardiac rehabilitation-A nationwide registry study

AIMS: Cardiovascular patients with low socioeconomic status and non-western ethnic background have worse prognostic outcomes. The aim of this nationwide study was first to address whether short-term effects of hospital-based outpatient cardiac rehabilitation (CR) are similar across educational level and ethnic background, and secondly to study whether known disparity in long-term prognosis in patients with cardiovascular disese is diminished by CR participation. METHODS: All patients with myocardial infarction and/or coronary revascularization from August 2015 until March 2018 in the Danish national patient registry or the Danish cardiac rehabilitation database (DHRD) were included. We used descriptive statistics to address disparity in achievement of quality indicators in CR, and Cox proportional hazard regression to examine the association between the disparity measures and MACE (cardiovascular hospitalization and all-cause mortality) with adjustment for age, gender, index-diagnose and co-morbidity. RESULTS: We identified 34,511 patients of whom 19,383 had participated in CR and 9,882 provided information on CR outcomes from the DHRD. We demonstrated a socioeconomic gradient in improvements in VO(2peak), and non-western patients were less often screened for depression or receive dietary consulting. We found a strong socioeconomic gradient in MACE irrespective of CR participation, medication, and risk factor control (adjusted HR 0.65 (95% CI 0.56–0.77) for high versus low education). Non-western origin was associated with higher risk of MACE (adjusted HR 1.2 (1.1–1.4)). CONCLUSION: We found only minor socioeconomic and ethnic differences in achievement of CR quality indicators but strong differences in CHD prognosis indication that conventional risk factor control and medical treatment following CR do not diminish the socioeconomic and ethnical disparity in CHD prognosis

The molecular basis of ATM-dependent dimerization of the Mdc1 DNA damage checkpoint mediator

Mdc1 is a large modular phosphoprotein scaffold that maintains signaling and repair complexes at double-stranded DNA break sites. Mdc1 is anchored to damaged chromatin through interaction of its C-terminal BRCT-repeat domain with the tail of γH2AX following DNA damage, but the role of the N-terminal forkhead-associated (FHA) domain remains unclear. We show that a major binding target of the Mdc1 FHA domain is a previously unidentified DNA damage and ATM-dependent phosphorylation site near the N-terminus of Mdc1 itself. Binding to this motif stabilizes a weak self-association of the FHA domain to form a tight dimer. X-ray structures of free and complexed Mdc1 FHA domain reveal a ‘head-to-tail' dimerization mechanism that is closely related to that seen in pre-activated forms of the Chk2 DNA damage kinase, and which both positively and negatively influences Mdc1 FHA domain-mediated interactions in human cells prior to and following DNA damag

Use of Cis-[18F]Fluoro-Proline for Assessment of Exercise-Related Collagen Synthesis in Musculoskeletal Connective Tissue

Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[18F]fluoro-proline (cis-Fpro), for non-invasive assessment of collagen synthesis in rat musculoskeletal tissues at rest and following short-term (3 days) treadmill running. Musculoskeletal collagen synthesis was studied in rats at rest and 24 h post-exercise. At each session, rats were PET scanned at two time points following injection of cis-FPro: (60 and 240 min p.i). SUV were calculated for Achilles tendon, calf muscle and tibial bone. The PET-derived results were compared to mRNA expression of collagen type I and III. Tibial bone had the highest SUV that increased significantly (p<0.001) from the early (60 min) to the late (240 min) PET scan, while SUV in tendon and muscle decreased (p<0.001). Exercise had no influence on SUV, which was contradicted by an increased gene expression of collagen type I and III in muscle and tendon. The clearly, visible uptake of cis-Fpro in the collagen-rich musculoskeletal tissues is promising for multi-tissue studies in vivo. The tissue-specific differences with the highest basal uptake in bone are in accordance with earlier studies relying on tissue incorporation of isotopic-labelled proline. A possible explanation of the failure to demonstrate enhanced collagen synthesis following exercise, despite augmented collagen type I and III transcription, is that SUV calculations are not sensitive enough to detect minor changes in collagen synthesis. Further studies including kinetic compartment modeling must be performed to establish whether cis-Fpro can be used for non-invasive in-vivo assessment of exercise-induced changes in musculoskeletal collagen synthesis

The molecular basis of ATM-dependent dimerization of the Mdc1 DNA damage checkpoint mediator

Mdc1 is a large modular phosphoprotein scaffold that maintains signaling and repair complexes at double-stranded DNA break sites. Mdc1 is anchored to damaged chromatin through interaction of its C-terminal BRCT-repeat domain with the tail of γH2AX following DNA damage, but the role of the N-terminal forkhead-associated (FHA) domain remains unclear. We show that a major binding target of the Mdc1 FHA domain is a previously unidentified DNA damage and ATM-dependent phosphorylation site near the N-terminus of Mdc1 itself. Binding to this motif stabilizes a weak self-association of the FHA domain to form a tight dimer. X-ray structures of free and complexed Mdc1 FHA domain reveal a ‘head-to-tail’ dimerization mechanism that is closely related to that seen in pre-activated forms of the Chk2 DNA damage kinase, and which both positively and negatively influences Mdc1 FHA domain-mediated interactions in human cells prior to and following DNA damage

Chromosome-scale genome assembly provides insights into rye biology, evolution and agronomic potential

Rye (Secale cereale L.) is an exceptionally climate-resilient cereal crop, used extensively to produce improved wheat varieties via introgressive hybridization and possessing the entire repertoire of genes necessary to enable hybrid breeding. Rye is allogamous and only recently domesticated, thus giving cultivated ryes access to a diverse and exploitable wild gene pool. To further enhance the agronomic potential of rye, we produced a chromosome-scale annotated assembly of the 7.9-gigabase rye genome and extensively validated its quality by using a suite of molecular genetic resources. We demonstrate applications of this resource with a broad range of investigations. We present findings on cultivated rye's incomplete genetic isolation from wild relatives, mechanisms of genome structural evolution, pathogen resistance, low-temperature tolerance, fertility control systems for hybrid breeding and the yield benefits of rye-wheat introgressions.Peer reviewe

The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage

Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in trans signalling mechanism that triggers pan-nuclear silencing of rRNA transcription in response to DNA damage. This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle dependent. Finally, we provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli regulates rRNA silencing in trans in the presence of distant chromosome breaks

Light regulation of quality and growth of basil

Quality of fresh products is determined by genotype and environmental practices. Light intensity and spectrum are environmental factors which have significant effects on quality. Light can increase the content of metabolites, such as carbohydrates and antioxidants. To maintain shelf life of fresh products low temperature storage is often used during the postharvest phase as the water loss and metabolic rates slows down which will delay senescence. However, crops of tropical origin are sensitive to temperatures below 10-12 °C. One of such crops is basil (Ocimum&nbsp;basilicum&nbsp;L.). Basil suffers from chilling injury (CI) when stored at low temperature. CI is visible within a few days as dark spots on the leaves. Thus, there is a large potential to improve the chilling tolerance of basil. Chilling tolerance may be improved by an increase in carbohydrates and antioxidants such as phenolic compounds. They may scavenge the reactive oxygen species produced during chilling. In this thesis it was investigated if an increase in light intensity and modification of the light spectrum (i.e. an increase in percentage of blue light) could increase the content of carbohydrates and antioxidants resulting in improved chilling tolerance. Furthermore, it was investigated if the addition of far-red (FR) during cultivation would increase the levels of hormones related to chilling tolerance and in turn improve the postharvest chilling tolerance. Light also affects the morphology which is an important quality parameter. Thus, response of growth and morphology to light intensity and spectra was also studied. In a number of experiments basil was grown in a climate chamber in a vertical farming set-up and the effect of light intensity and spectra on at-harvest and postharvest quality were studied

Response of Basil Growth and Morphology to Light Intensity and Spectrum in a Vertical Farm

Vertical farming is becoming increasingly popular for production of leafy vegetables and herbs, with basil (Ocimum basilicum L.) as one of the most popular herbs. In basil most research has focused on increasing secondary metabolites with light spectra. However, knowledge about the effect of light intensity (photosynthetic photon flux density, PPFD) and spectra on growth and morphology is key for optimizing quality at harvest. The impact of PPFD and spectrum on plant growth and development is species dependent and currently few studies in basil are available. Understanding the response to End-Of-Production (EOP) light of growth and morphology is important for successful vertical farming. We performed a comprehensive series of experiments, where the effects of EOP PPFD, fraction of blue and their interaction on the growth and morphology were analyzed in two green and one purple basil cultivar. In addition, the impact of different EOP intensities and duration of far-red were investigated. We found that increasing the PPFD increased fresh mass, dry matter content and plant height in all three cultivars. The responses were linear or quadratic depending on the cultivar. A high fraction of blue (>90%) increased plant height and decreased the dry mass partitioning to the leaves. The only interaction found between the fraction of blue and overall PPFD was on plant height in the green cultivar whereas other growth parameters and morphology responded stronger to PPFD than to the fraction of blue light. Plant dry matter production was increased with the addition of far-red. Far-red EOP intensity treatments enhanced the fraction of dry mass partitioned to the leaves, whereas a prolonged far-red treatment enhanced partitioning to the stem. Both plant fresh mass and dry matter content were improved by applying high PPFD shortly before harvest. Light spectra were found to be of less importance than PPFD with respect to plant dry matter content. Light use efficiency (LUE) based on fresh mass decreased with increasing PPFD whereas LUE based on dry mass increased with increasing PPFD, when given as EOP treatments. The overall physiological mechanisms of the light intensity and spectral effects are discussed

Gradually increasing light intensity during the growth period increases dry weight production compared to constant or gradually decreasing light intensity in lettuce

The objective of this research was to investigate the effects of gradually increasing or decreasing photosynthetic photon flux density (PPFD) during cultivation compared to a constant PPFD on biomass production. Lettuce plants (Lactuca sativa L. ‘Expertise’) were grown in climate rooms in which every three days the PPFD was increased by 16 µmol m−2 s−1 (from 140 to 300 µmol m−2 s−1 from day 0 to 30), decreased (from 300 to 140 µmol m−2 s−1), or kept constant (221 µmol m−2 s−1), while the total light integral at the end of the cultivation period (30 d) was the same for all three treatments. Gradually increasing PPFD resulted in a 16 or 13% increase in total plant dry weight compared to treatments with decreasing or constant PPFD, respectively. This increase was explained by a higher light interception mainly because, in this treatment, most of the light was provided at the end of the cultivation period when the leaf area index was high. Consequently, the light use efficiency based on incident PPFD was highest when PPFD gradually increased, even though the light use efficiency based on intercepted PPFD was highest when PPFD gradually decreased during cultivation. Despite the higher shoot dry weight when PPFD gradually increased, shoot fresh weight was not significantly affected by the light treatments. This difference in response between fresh and dry weight resulted from a higher shoot dry matter content when PPFD gradually increased. Our results show that gradually increasing PPFD had a positive effect on dry weight accumulation and increased dry matter content, but did not affect the shelf life. So, although vertical farms enable growers to keep all conditions constant, some dynamic variation of conditions might be needed for optimizing the light use efficiency

Lack of Blue Light Regulation of Antioxidants and Chilling Tolerance in Basil

Blue light, measuring from 400 to 500 nm, is generally assumed to increase the content of antioxidants in plants independent of the species. Blue light stimulates the biosynthesis of phenolic compounds such as flavonoids and their subclass anthocyanins from the phenylpropanoid pathway. Flavonoids, anthocyanins, and phenolic acids are strong reactive oxygen species (ROS) scavengers and may lessen the symptoms of abiotic stresses such as chilling. We tested the hypothesis that a high percentage of blue light induces the accumulation of antioxidants and that this effect depends on the photosynthetic photon flux density (PPFD, 400–700 nm). The effect may be more pronounced at a lower PPFD. We investigated the changes in primary and secondary metabolites of basil in response to the percentage of blue light (9, 33, 65, and 100%) applied either as a 5-day End-Of-Production (EOP) treatment or continuous throughout the growth cycle in the green cv. Dolly. We also studied if the response to the percentage of blue light (9 or 90%) was dependent on the total PPFD (100 or 300 μmol m–2 s–1 PPFD) when applied as a 5-day EOP treatment in the green cv. Dolly and the purple cv. Rosie. For both green and purple basil, it was found that the percentage of blue light had little effect on the levels of antioxidants (rosmarinic acid, total ascorbic acid, total flavonoids, and total anthocyanins) at harvest and no interactive effect with PPFD was found. Antioxidants generally decreased during postharvest storage, wherein the decrease was more pronounced at 4 than at 12°C. Chilling injury, as judged from a decrease in Fv/Fm values and from the occurrence of black necrotic areas, was not affected by the percentage of blue light. Particularly, chilling tolerance in the purple cultivar was increased in plants grown under higher PPFD. This may be related to the increased levels of soluble sugar and starch in leaves from high PPFD treated plants