Delayed bolting in rocket for improved quality and greater sustainability

Wild rocket (Diplotaxis tenuifolia) has recently become a popular salad leaf in the UK due to its peppery taste. It is grown widely in Italy but is now being produced in Spring and Summer in England. It is part of the Brassicaceae family and thus has a high level of homology at the DNA level to other Brassica species and Arabidopsis. This project aims to produce late bolting genotypes of rocket to incorporate into commercial breeding programmes. Delayed bolting is important as current varieties flower at unpredictable times and often earlier than desired. This is a problem because when rocket flowers it becomes unsaleable. Ethyl methanesulphonate (EMS) was used to generate a mutant population of rocket. Late bolting lines were selected and whole genome sequencing was used to identify single nucleotide polymorphisms (SNPs) induced by the EMS which may be a cause of the late bolting phenotype. Six flowering pathway genes have been isolated from rocket and have been tested to see if they can functionally complement A. thaliana knockout lines in these genes. Further work was carried out to investigate how these genes were expressed over diurnal and developmental time courses to understand their function in the flowering time pathway in rocket. Together, these results show that most of the flowering pathway genes isolated from rocket are functional orthologues of those in Arabidopsis. The photoperiodic and vernalization requirements of rocket were investigated and it was found that rocket does not have a vernalization requirement and is a facultative long day plant. Targeted mutagenesis using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated system (cas9) was employed for the introduction of mutations into the FLOWERING LOCUS T (FT) gene in rocket and Arabidopsis. Many late flowering Arabidopsis lines were identified and sequencing revealed the successful manipulation of the FT gene. Two late bolting rocket lines were also identified. Overall, the project aims were achieved as late bolting rocket lines have been produced and will be incorporated into a rocket breeding programme

FLC expression is down-regulated by cold treatment in Diplotaxis tenuifolia (wild rocket), but flowering time is unaffected

Wild rocket (Diplotaxis tenuifolia) has become a very popular salad leaf due to its peppery taste. It is part of the Brassicaceae family and thus has a high level of homology at the DNA level to other Brassica species including Arabidopsis thaliana. The vernalization and photoperiodic requirements of wild rocket have not been reported to date. Photoperiodic experiments described here demonstrate that rocket is a facultative long day plant. To investigate the vernalization requirement, both seed and young plants were given vernalization treatments at 4 °C for different lengths of time. A rocket homologue of FLOWERING LOCUS C (DtFLC) was isolated and shown to functionally complement the Arabidopsis FRI+flc3 null mutant. Whilst the expression of DtFLC was significantly reduced after just one week of cold treatment, cold treatments of two to eight weeks had no significant effect on bolting time of wild rocket indicating that rocket does not have a vernalization requirement. These findings illustrate that important fundamental differences can exist between model and crop plant species, such as in this case where down-regulation of DtFLC expression does not enable earlier flowering in wild rocket as it does in Arabidopsis and many other Brassica species

Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation

The gastrointestinal mucus layer is colonized by a dense community of microbes catabolizing dietary and host carbohydrates during their expansion in the gut. Alterations in mucosal carbohydrate availability impact on the composition of microbial species. Ruminococcus gnavus is a commensal anaerobe present in the gastrointestinal tract of > 90% of humans and overrepresented in inflammatory bowel diseases (IBD). Using a combination of genomics, enzymology and crystallography, we show that the mucin-degrader R. gnavus ATCC 29149 strain produces an intramolecular trans-sialidase (IT-sialidase) that cleaves off terminal alpha 2-3-linked sialic acid from glycoproteins, releasing 2,7-anhydro-Neu5Ac instead of sialic acid. Evidence of IT-sialidases in human metagenomes indicates that this enzyme occurs in healthy subjects but is more prevalent in IBD metagenomes. Our results uncover a previously unrecognized enzymatic activity in the gut microbiota, which may contribute to the adaptation of intestinal bacteria to the mucosal environment in health and disease.Peer reviewe

Risk factor studies of age-at-onset in a sample ascertained for Parkinson disease affected sibling pairs: a cautionary tale

An association between exposure to a risk factor and age-at-onset of disease may reflect an effect on the rate of disease occurrence or an acceleration of the disease process. The difference in age-at-onset arising from case-only studies, however, may also reflect secular trends in the prevalence of exposure to the risk factor. Comparisons of age-at-onset associated with risk factors are commonly performed in case series enrolled for genetic linkage analysis of late onset diseases. We describe how the results of age-at-onset studies of environmental risk factors reflect the underlying structure of the source population, rather than an association with age-at-onset, by contrasting the effects of coffee drinking and cigarette smoking on Parkinson disease age-at-onset with the effects on age-at-enrollment in a population based study sample. Despite earlier evidence to suggest a protective association of coffee drinking and cigarette smoking with Parkinson disease risk, the age-at-onset results are comparable to the patterns observed in the population sample, and thus a causal inference from the age-at-onset effect may not be justified. Protective effects of multivitamin use on PD age-at-onset are also shown to be subject to a bias from the relationship between age and multivitamin initiation. Case-only studies of age-at-onset must be performed with an appreciation for the association between risk factors and age and ageing in the source population

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Impact of glacial activity on the weathering of Hf isotopes – Observations from Southwest Greenland

Data for the modern oceans and their authigenic precipitates suggest incongruent release of hafnium (Hf) isotopes by chemical weathering of the continents. The fact that weathering during recent glacial periods is associated with more congruent release of Hf isotopes has led to the hypothesis that the incongruency may be controlled by retention of unradiogenic Hf by zircons, and that glacial grinding enhances release of Hf from zircons. Here we study the relationship between glacial weathering processes and Hf isotope compositions released to rivers fed by land-terminating glaciers of the Greenland Ice Sheet, as well as neighbouring non-glacial streams. The weathered source rocks in the studied area mostly consist of gneisses, but also include amphibolites of the same age (1.9 Ga). Hafnium and neodymium isotope compositions in catchment sediments and in the riverine suspended load are consistent with a predominantly gneissic source containing variable trace amounts of zircon and different abundances of hornblende, garnet and titanite. Glacially sourced rivers and non-glacial streams fed by precipitation and lakes show very unradiogenic Nd isotopic compositions, in a narrow range (ɛNd = −42.8 to −37.9). Hafnium isotopes, on the other hand, are much more radiogenic and variable, with ɛHf between −18.3 and −0.9 in glacial rivers, and even more radiogenic values of +15.8 to +46.3 in non-glacial streams. Although relatively unradiogenic Hf is released by glacial weathering, glacial rivers actually fall close to the seawater array in Hf-Nd isotope space and are not distinctly unradiogenic. Based on their abundance in rocks and sediments and their isotope compositions, different minerals contribute to the radiogenic Hf in solution with a decreasing relevance from garnet to titanite, hornblende and apatite. Neodymium isotopes preclude a much stronger representation of titanite, hornblende and apatite in solution, such as might result from differences in dissolution rates, than estimated from mineral abundance. The strong contrast in Hf isotope compositions between glacial rivers and non-glacial streams results mostly from different contributions from garnet and zircon, where zircon weathering is more efficient in the subglacial environment. A key difference between glacial and non-glacial waters is the water-rock interaction time. While glacial rivers receive continuous contributions from long residence time waters of distributed subglacial drainage systems, non-glacial streams are characterized by fast superficial drainage above the permafrost horizon. Therefore, the increased congruency in Hf isotope weathering in glacial systems could simply reflect the hydrological conditions at the base of the ice-sheet and glaciers, with zircon weathering contributions increasing with water-rock interaction time

Understanding the influences on successful quality improvement in emergency general surgery: learning from the RCS Chole-QuIC project

Abstract: Background: Acute gallstone disease is the highest volume Emergency General Surgical presentation in the UK. Recent data indicate wide variations in the quality of care provided across the country, with national guidance for care delivery not implemented in most UK hospitals. Against this backdrop, the Royal College of Surgeons of England set up a 13-hospital quality improvement collaborative (Chole-QuIC) to support clinical teams to reduce time to surgery for patients with acute gallstone disease requiring emergency cholecystectomy. Methods: Prospective, mixed-methods process evaluation to answer the following: (1) how was the collaborative delivered by the faculty and received, understood and enacted by the participants; (2) what influenced teams’ ability to improve care for patients requiring emergency cholecystectomy? We collected and analysed a range of data including field notes, ethnographic observations of meetings, and project documentation. Analysis was based on the framework approach, informed by Normalisation Process Theory, and involved the creation of comparative case studies based on hospital performance during the project. Results: Chole-QuIC was delivered as planned and was well received and understood by participants. Four hospitals were identified as highly successful, based upon a substantial increase in the number of patients having surgery in line with national guidance. Conversely, four hospitals were identified as challenged, achieving no significant improvement. The comparative analysis indicate that six inter-related influences appeared most associated with improvement: (1) achieving clarity of purpose amongst site leads and key stakeholders; (2) capacity to lead and effective project support; (3) ideas to action; (4) learning from own and others’ experience; (5) creating additional capacity to do emergency cholecystectomies; and (6) coordinating/managing the patient pathway. Conclusion: Collaborative-based quality improvement is a viable strategy for emergency surgery but success requires the deployment of effective clinical strategies in conjunction with improvement strategies. In particular, achieving clarity of purpose about proposed changes amongst key stakeholders was a vital precursor to improvement, enabling the creation of additional surgical capacity and new pathways to be implemented effectively. Protected time, testing ideas, and the ability to learn quickly from data and experience were associated with greater impact within this cohort

Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure

Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinant

APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies