Genome Sequencing Technologies and Nursing

Background Advances in DNA sequencing technology have resulted in an abundance of personalized data with challenging clinical utility and meaning for clinicians. This wealth of data has potential to dramatically impact the quality of healthcare. Nurses are at the focal point in educating patients regarding relevant healthcare needs; therefore, an understanding of sequencing technology and utilizing these data are critical. Aim The objective of this study was to explicate the role of nurses and nurse scientists as integral members of healthcare teams in improving understanding of DNA sequencing data and translational genomics for patients. Approach A history of the nurse role in newborn screening is used as an exemplar. Discussion This study serves as an exemplar on how genome sequencing has been utilized in nursing science and incorporates linkages of other omics approaches used by nurses that are included in this special issue. This special issue showcased nurse scientists conducting multi-omic research from various methods, including targeted candidate genes, pharmacogenomics, proteomics, epigenomics, and the microbiome. From this vantage point, we provide an overview of the roles of nurse scientists in genome sequencing research and provide recommendations for the best utilization of nurses and nurse scientists related to genome sequencing

Can a speed breeding approach accelerate genetic gain in pigeonpea?

Pure line breeding is a resource-intensive activity that takes 10 years or more to develop a new cultivar. In some crops, conducting off-season nurseries has significantly reduced the length of the breeding cycle. This approach could not be exploited in pigeonpea [Cajanus cajan (L.) Millsp.], because traditionally it has been a photoperiod-sensitive crop that requires long periods of darkness to induce flowering. However, the recent success of breeding early maturing photoperiod-insensitive genotypes has opened up the possibility of adopting ‘speed breeding’ techniques to enable rapid generation turnover. This paper outlines a speed breeding approach that integrates the use of immature seed germination for rapid generation advancement and a "single pod descent" method of breeding. To accelerate line development, while conserving genetic variability, the approach permits four generations per year and can fast-track field evaluation of resulting homozygous lines. Therefore, the breeding strategy conserves resources and has potential to deliver new early maturing cultivars within a substantially reduced timeframe of 4–5 years

Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation

Copyright © 2006 Company of BiologistsOocytes regulate follicle growth by secreting paracrine growth factors that act on neighbouring granulosa cells (GCs). Those factors identified to date are mainly members of the transforming growth factor-ß (TGFß) superfamily, but little is known about which specific receptor/signalling system(s) they employ. This study was conducted to determine the requisite pathways utilised by oocytes to promote GC proliferation. We used an established oocyte-secreted mitogen bioassay, where denuded mouse oocytes are co-cultured with mural GCs. Oocytes, growth differentiation factor-9 (GDF9), TGFß1 and activin-A all promoted GC DNA synthesis, but bone-morphogenetic protein 6 (BMP6) did not. Subsequently, we tested the capacity of various TGFß superfamily receptor ectodomains (ECD) to neutralise oocyte- or specific growth factor-stimulated GC proliferation. The BMP type-II receptor (BMPR-II) ECD antagonised oocyte and GDF9 bioactivity dose-dependently, but had no or minimal effect on TGFß1 and activin-A bioactivity, demonstrating its specificity. The TGFßR-II, activinR-IIA and activinR-IIB ECDs all failed to neutralise oocyte- or GDF9-stimulated GC DNA synthesis, whereas they did antagonise the activity of their respective native ligands. An activin receptor-like kinase (ALK) 4/5/7 inhibitor, SB431542, also antagonised both oocyte and GDF9 bioactivity in a dose-dependent manner. Consistent with these findings, oocytes, GDF9 and TGFß1 all activated SMAD2/3 reporter constructs in transfected GC, and led to phosphorylation of SMAD2 proteins in treated cells. Surprisingly, oocytes did not activate the SMAD1/5/8 pathway in transfected GCs although exogenous BMP6 did. This study indicates that oocyte paracrine factors primarily utilise a similar signalling pathway first identified for GDF9 that employs an unusual combination of TGFß superfamily receptors, the BMPR-II and a SMAD2/3 stimulatory ALK (4, 5 or 7), for transmitting their mitogenic actions in GC. This cell-signalling pathway may also have relevance in the hypothalamic-pituitary axis and in germ-somatic cell interactions in the testis.Robert B. Gilchrist, Lesley J. Ritter, Samu Myllymaa, Noora Kaivo-Oja, Rebecca A. Dragovic, Theresa E. Hickey, Olli Ritvos and David G. Mottershea

MitoQ supplementation augments acute exercise-induced increases in muscle PGC1α mRNA and improves training-induced increases in peak power independent of mitochondrial content and function in untrained middle-aged men

The role of mitochondrial ROS in signalling muscle adaptations to exercise training has not been explored in detail. We investigated the effect of supplementation with the mitochondria-targeted antioxidant MitoQ on a) the skeletal muscle mitochondrial and antioxidant gene transcriptional response to acute high-intensity exercise and b) skeletal muscle mitochondrial content and function following exercise training. In a randomised, double-blind, placebo-controlled, parallel design study, 23 untrained men (age: 44 ± 7 years, VO2peak: 39.6 ± 7.9 ml/kg/min) were randomised to receive either MitoQ (20 mg/d) or a placebo for 10 days before completing a bout of high-intensity interval exercise (cycle ergometer, 10 × 60 s at VO2peak workload with 75 s rest). Blood samples and vastus lateralis muscle biopsies were collected before exercise and immediately and 3 h after exercise. Participants then completed high-intensity interval training (HIIT; 3 sessions per week for 3 weeks) and another blood sample and muscle biopsy were collected. There was no effect of acute exercise or MitoQ on systemic (plasma protein carbonyls and reduced glutathione) or skeletal muscle (mtDNA damage and 4-HNE) oxidative stress biomarkers. Acute exercise-induced increases in skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) mRNA expression were augmented in the MitoQ group. Despite this, training-induced increases in skeletal muscle mitochondrial content were similar between groups. HIIT-induced increases in VO2peak and 20 km time trial performance were also similar between groups while training-induced increases in peak power achieved during the VO2peak test were augmented in the MitoQ group. These data suggest that training-induced increases in peak power are enhanced following MitoQ supplementation, which may be related to the augmentation of skeletal muscle PGC1α expression following acute exercise. However, these effects do not appear to be related to an effect of MitoQ supplementation on exercise-induced oxidative stress or training-induced mitochondrial biogenesis in skeletal muscle

Cardiometabolic Plasticity in Response to a Short-Term Diet and Exercise Intervention in Young Hispanic and NonHispanic White Adults

BACKGROUND: Young adult Mexican Americans (MA) exhibit lower insulin sensitivity (Si) than nonHispanic whites (NHW), even when controlling for fitness and adiposity. It is unclear if MA are as responsive to the same lifestyle intervention as NHW. OBJECTIVE: We developed a model to examine cardiometabolic plasticity (i.e., changes in Si and plasma lipids) in MA compared to NHW adults in response to a diet-exercise intervention. DESIGN: Sedentary subjects (20 NHW: 11F, 9M, 23.0 y, 25.5 kg/m(2); 17 MA: 13F, 4M, 22.7 y, 25.4 kg/m(2)) consumed their habitual diets and remained sedentary for 7 days, after which fasting blood samples were obtained, and a 3-h intravenous glucose tolerance test (IVGTT) was performed with the insulin area under the curve (IAUC) used to estimate Si. Subjects then completed a 7-day diet/exercise intervention (diet: low saturated fat, low added sugar, high fiber; exercise: cycling, six total sessions lasting 40-45 min/session at 65% VO(2) max). Pre-intervention tests were repeated. RESULTS: Pre intervention IAUC was 28% higher (p<0.05) in MA (IAUC pre  =  2298 µU*180 min/mL) than in NHW (IAUC = 1795 µU*180 min/mL). Following the intervention, there was a significant reduction in IAUC in MA (29%) and NHW (32%), however, the IAUC remained higher (p<0.05) for MA (post  = 1635 µU*180 min/mL) than for NHW (post = 1211 µU*180 min/mL). Pre test plasma lipids were not different in MA compared to NHW. Plasma cholesterol and TG concentrations significantly improved in both groups, but concentrations of low density lipoprotein-cholesterol and small dense LDL particles significantly improved only in the NHW. CONCLUSION: With a short-term diet-exercise intervention, the magnitude of improvements in Si and serum cholesterol and TG in Hispanics are similar to those in NHW. However, because at the outset MA were less insulin sensitive compared to NHW, within the short timeframe studied the ethnic gap in insulin sensitivity remained

Multi-omic profiling reveals the ataxia protein sacsin is required for integrin trafficking and synaptic organization

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset cerebellar ataxia caused by mutations in SACS, which encodes the protein sacsin. Cellular ARSACS phenotypes include mitochondrial dysfunction, intermediate filament disorganization, and progressive death of cerebellar Purkinje neurons. It is unclear why the loss of sacsin causes these deficits or why they manifest as cerebellar ataxia. Here, we perform multi-omic profiling in sacsin knockout (KO) cells and identify alterations in microtubule dynamics and mislocalization of focal adhesion (FA) proteins, including multiple integrins. Deficits in FA structure, signaling, and function can be rescued by targeting PTEN, a negative regulator of FA signaling. ARSACS mice possess mislocalization of ITGA1 in Purkinje neurons and synaptic disorganization in the deep cerebellar nucleus (DCN). The sacsin interactome reveals that sacsin regulates interactions between cytoskeletal and synaptic adhesion proteins. Our findings suggest that disrupted trafficking of synaptic adhesion proteins is a causal molecular deficit in ARSACS

Technological perspectives for plant breeding

New Breeding Technologies? For some, both inside and outside the scientific community, this phrase is synonymous with gene editing—or used exclusively to describe the application of CRISPR/Cas9 to plant improvement. Much as, historically, the term ‘biotech crops’ has been hijacked to only mean crop plants produced using genetic engineering. However, ‘breeding technologies’ refers not only to genetic modification using techniques of molecular biology, but also to a vast number of other techniques developed for breeding via the application of scientific advancements emanating from disciplines such as computer science, plant biology, statistics, automation, robotics and artificial intelligence. This concept is not new: in reality, technology has been a feature of crop improvement since early in the last century..

In Defence of Public Higher Education: Knowledge for a Successful Society (The Alternative White Paper for HE)

The present Conservative Government, like the Coalition Government that preceded it, has an ideological predisposition towards the market and its supposed benefits to consumers, but appears to have no vision of Higher Education and its benefits to students and to the whole of society. These wider societal benefits can be summarised under three aspects: * educating the next generation of the population * carrying out research to address social and scientific challenges * maintaining an independent platform for research into society and science to facilitate democratic debate. The last of these, sometimes drawn under the umbrella of ‘academic freedom’, is the basis of the historic contract between Universities and the State. We contend, following the UNESCO Recommendation (1997), that academic freedom must be sufficient to guarantee the independence of scientific inquiry, commentary and teaching. Pressures from funding agencies and the state are usually cited as the principal threats to academic independence. The last decade has seen the rise of a third threat, namely an increasing managerial interference in academic life deriving from the introduction of market imperatives. These three societal benefits are interconnected. Without independent research there can be no scientific independence and no cutting-edge teaching. Without a focus on critique and challenge, students may see ‘education’ as a mere process of accumulating ‘facts’ to meet test criteria. A narrow focus on the acquisition of qualifications undermines the education process itself. Employers have criticised graduate recruits for insufficient creativity, of being rote-taught and thus un-adaptable to a modern business subject to rapid technological change. Importantly, critical skills are necessary to meet the challenge of business and for inclusive democratic engagement. The idea of a University that unites these three aspects is undermined by a new model of Higher Education Institution that sees the investment in human capital only as a private benefit. The Government’s White Paper, Success as a Knowledge Economy, and associated legislative programme, consolidate a fee-loan (or debt-finance) model of funding which puts the costs of higher education onto new graduates and future taxpayers, while reducing taxes for current taxpayers – many of whom directly benefit from publicly-supported higher education, or from its wider public benefits. The Government suggests that it is merely replacing direct public funding with one that places the ‘student at the heart of the system’. But it proposes that public funding should be directed towards the realisation of the private benefits of higher education, and it fails to acknowledge the wider public benefits that higher education affords. In truth, the proposals place the market at the heart of the system and subordinate the student as a consumer of higher education, with loans functioning as a voucher to present at a university of choice (providing that the student has the grades required). It is our view that this new funding model is wrong in principle and deficient in practice. The regulatory framework that is being introduced in its wake will undermine the declared aims to improve teaching quality, to enhance social mobility, and to improve access and achievement. The extension of university title to for-profit providers will also threaten the wider public benefits of higher education, by allowing them to compete as single-function institutions, and giving them access to publicly-supported loans for their students without a guarantee of their longer term stability. This will intensify existing competition and encourage a ‘race to the bottom’. Our defence of an alternative vision of Higher Education takes place in the context of a dismal lack of leadership by the various mission groups representing universities in the sector – for example, Universities UK and the Russell Group – and other bodies responsible for the sector. Their willing advocacy of a fee-loan model of funding (to avoid possible cuts) has abdicated their leadership role in a proper debate on the values of public higher education. This failure to defend the values of the very public higher education they are chartered to provide is in marked contrast to representations made by another group. Lobbyists on behalf of for-profit providers are seeking a supposed ‘level-playing field’ in undergraduate degree provision, despite having no track record of success in the UK, a disastrous record in the USA, and no desire to provide any wider public benefit of their existence. The Government’s position is also in marked contrast to public attitudes. The British Social Attitudes Survey (NatCen) has, before and since the introduction of tuition fee changes, regularly asked questions about public attitudes to higher education and inequality. The majority of the population has consistently opposed high levels of student debt, believed that education has a value beyond simply providing the means to a better job, and maintained that inequality in Britain is an obstacle to the fulfillment of opportunities. Perhaps surprisingly, this commitment to the values of publicly-funded higher education is especially marked among those without graduate-level qualifications. Politicians who argue that the latter resent paying taxes to finance education for ‘middle-class people’ should seek evidence for this assertion. But the ‘debate’ among politicians, members of the BIS secretariat and corporate lobbyists over the issue has been remarkable for its superficial, un-evidenced character. It has also been remarkable for the absence of full public debate (Leach 2016). This Alternative White Paper aims to correct this imbalance. We need a proper debate about the future of UK Higher Education