Engineered glyphosate resistance is the most widely adopted genetically modified trait in agriculture, gaining widespread acceptance by providing a simple robust weed control system. However, ...extensive and sustained use of glyphosate as a sole weed control mechanism has led to field selection for glyphosate-resistant weeds and has induced significant population shifts to weeds with inherent tolerance to glyphosate. Additional weed control mechanisms that can complement glyphosate-resistant crops are, therefore, urgently needed. 2,4-dichlorophenoxyacetic acid (2,4-D) is an effective lowcost, broad-spectrum herbicide that controls many of the weeds developing resistance to glyphosate. We investigated the substrate preferences of bacterial aryloxyalkanoate dioxygenase enzymes (AADs) that can effectively degrade 2,4-D and have found that some members of this class can act on other widely used herbicides in addition to their activity on 2,4-D. AAD-1 cleaves the aryloxyphenoxypropionate family of grass-active herbicides, and AAD-12 acts on pyridyloxyacetate auxin herbicides such as triclopyr and fluroxypyr. Maize plants transformed with an AAD-1 gene showed robust crop resistance to aryloxyphenoxypropionate herbicides over four generations and were also not injured by 2,4-D applications at any growth stage. Arabidopsis plants expressing AAD-12 were resistant to 2,4-D as well as triclopyr and fluroxypyr, and transgenic soybean plants expressing AAD-12 maintained field resistance to 2,4-D over five generations. These results show that single AAD transgenes can provide simultaneous resistance to a broad repertoire of agronomically important classes of herbicides, including 2,4-D, with utility in both monocot and dicot crops. These transgenes can help preserve the productivity and environmental benefits of herbicide-resistant crops.
Towards a Phenomenology of Musical Borrowing Hallowell, Sean Russell
Organised sound : an international journal of music technology,
08/2019, Letnik:
24, Številka:
2
Journal Article
Recenzirano
In discourse on the topic, the question of what constitutes a musical ‘borrowing’, if raised at all, is usually restricted in scope and framed as one of terminology – that is, of determining the ...right term to characterise a particular borrowing act. In this way has arisen a welter of terms that, however expressive of nuance, have precluded evaluation of the phenomenon as such. This is in part a consequence of general disregard for the fact that to conceive of musical borrowing entails correlative concepts, all of which precondition it, yet none self-evidently. Further preclusive of clarity, the musico-analytic lens of borrowing is typically invoked only in counterpoint to a quintessentially Western aesthetic category of composition ex nihilo. As a consequence, the fundamental role played by borrowing in musical domains situated at the periphery of the Western art music tradition, specifically pre-modern polyphony and twentieth-century musique concrète, has been overlooked. This article seeks to bridge such lacunae in our understanding of musical borrowing via phenomenological investigation into its conceptual and historical foundations. A more comprehensive evaluation of musical borrowing, one capable of accounting for its diverse instantiations while simultaneously disclosing what makes all of them ‘borrowings’ in the first place, is thereby attainable.
Employees with mental health problems often struggle to remain in employment. During the COVID-19 pandemic, these employees face multiple additional stressors, which are likely to worsen their mental ...health and work productivity. Currently, it is unclear how to best support employees with mental health problems (and their managers) to improve wellbeing and productivity. We aim to develop a new intervention (MENTOR) that will jointly involve employees, managers, and a new professional (mental health employment liaison worker, MHELW), to help employees who are still at work with a mental health condition and currently receiving professional support for their mental health. A feasibility pilot study will then be undertaken to examine the feasibility and acceptability of the intervention from the perspective of employees and line managers. The study involves a feasibility randomised controlled study comparing outcomes of participants randomised to receive the intervention (MENTOR) with wait-list controls. Participants allocated to the waitlist control group will receive the intervention after three months. We aim to randomise 56 employee-manager pairs recruited from multiple organisations in the Midlands region of England. An intervention including 10 sessions for employees and managers (3 individual sessions and 4 joint sessions) will be delivered over 12 weeks by trained MHELWs. Primary outcomes include measures of feasibility and acceptability of the intervention and work productivity. Secondary outcomes include mental health outcomes. Qualitative interviews will be undertaken with a purposively selected sub-sample of employees and line managers at three-month post-intervention assessment. To our knowledge, this will be the first trial with a joint employee-manager intervention delivered by MHELWs. Anticipated challenges are dual-level consent (employees and managers), participants' attrition, and recruitment strategies. If the intervention and trial processes are shown to be feasible and acceptable, the outcomes from this study will inform future randomised controlled trials. Trial registration: This trial is pre-registered with the ISRCTN registry, registration number: ISRCTN79256498. Protocol version: 3.0_March_2023. https://www.isrctn.com/ISRCTN79256498.
Abstract
Background
Persons experiencing homelessness (PEH) face up to twelve times higher mortality rates compared to the general population. There is a need to develop, evaluate and implement novel ...interventions to minimise such inequalities. This paper aims to present outcomes of a national stakeholder engagement event that was conducted to discuss research priorities around healthcare of PEH in the United Kingdom (UK).
Main body
A national stakeholder event was organised in Birmingham, UK. This workshop aimed to engage diverse stakeholders from a variety of background including representations from clinical practice, substance misuse, anti-slavery network, public health practice, local authority, homelessness charities, drugs and alcohol services, Public Health England and academia.
A total of five key priority areas for research were identified which included: a) interventions to improve access to health services and preventative services; b) interventions to prevent drug and alcohol related deaths; c) improving existing services through quality improvement; d) identifying PEH’s preferences of services; and e) interventions to break the link between vulnerabilities, particularly- modern day slavery and homelessness. Effective partnerships across diverse stakeholder groups were deemed to be imperative in developing, testing and implementing novel interventions.
Conclusions
Maximising access to services, prevention of early deaths linked to drugs and alcohol, and identifying effective and ineffective policies and programmes were identified as priority research areas in relation to healthcare of PEH. The outcomes of this discussion will enable design and conduct of interdisciplinary research programmes to address the syndemics of homelessness and linked adverse health outcomes. Priorities identified here are likely to be applicable internationally.
The phosphoinositide 3-kinase (PI3K) pathway is one of the most commonly misregulated signaling pathways in human cancers, but its impact on the tumor microenvironment has not been considered as ...deeply as its autonomous impact on tumor cells. In this study, we show that NF-κB is activated by the two most common PI3K mutations, PIK3CA E545K and H1047R. We found that markers of NF-κB are most strongly upregulated under conditions of growth factor deprivation. Gene expression analysis conducted on cells deprived of growth factors identified the repertoire of genes altered by oncogenic PI3K mutations following growth factor deprivation. This gene set most closely correlated with gene signatures from claudin-low and basal-like breast tumors, subtypes frequently exhibiting constitutive PI3K/Akt activity. An NF-κB-dependent subset of genes driven by oncogenic PI3K mutations was also identified that encoded primarily secreted proteins, suggesting a paracrine role for this gene set. Interestingly, while NF-κB activated by oncogenes such as Ras and EGF receptor leads to cell-autonomous effects, abrogating NF-κB in PI3K-transformed cells did not decrease proliferation or induce apoptosis. However, conditioned media from PI3K mutant-expressing cells led to increased STAT3 activation in recipient THP-1 monocytes or normal epithelial cells in a NF-κB and interleukin-6-dependent manner. Together, our findings describe a PI3K-driven, NF-κB-dependent transcriptional profile that may play a critical role in promoting a microenvironment amenable to tumor progression. These data also indicate that NF-κB plays diverse roles downstream from different oncogenic signaling pathways.
In the Philippines, 180 out of 421 rivers are heavily polluted and may soon be declared biologically dead. In the province of Bataan, industrial activities lead to contamination and water quality ...degradation. This makes the Talisay River in Balanga, Bataan, prone to the effects of establishments activities such as sewage from commercial and residential areas. The researchers aim to utilize the Granulated Filtering Media (GFM) as an adsorbent made up of fly ash, gypsum powder, coco peat, and cement for wastewater treatment of the polluted creek at Balanga City, Bataan. This GFM was subjected to seven-day water quality monitoring and tests to obtain its pollutant-reduction capability on the study site when incorporated into gabion mattresses. Study's water quality assessment tests revealed peak reductions showing that the gabion mattresses with GFM installed significantly reduced pollutant parameters like nutrients such as phosphate (79 %), nitrate (41 %), and ammonia (65 %) as well as water quality parameters such as chemical oxygen demand (42 %), turbidity (18 %), total dissolved solids (64 %), electric conductivity (51 %), and peak increases in DO (56 %), and pH level (3 %). The significant relationships of all the pollutant parameters observed were validated through Principal Component Analysis, extracted from 2D Loadings’ variance explained of 71.2 %, with 57.6 % attributed to the first principal component and 13.6 % to the second, and a 3D Biplot that explained 82.7 % of the variance, with 57.6 % from the first component, 13.6 % from second and 11.5 % from the third component.
A transgene, flanked by zinc finger nuclease (ZFN) cleavage sites, was deleted from a stably transformed plant by crossing it with a second plant expressing a corresponding ZFN gene. A target ...construct, containing a GUS reporter gene flanked by ZFN cleavage sites, a GFP reporter gene and a PAT selectable marker gene, was transformed into tobacco. Basta®-resistant plants were regenerated and screened for GUS and GFP expression. A second construct, containing a ZFN gene driven by the constitutive CsVMV promoter and an HPT selectable marker gene, was also transformed into tobacco. Selected T₀ plants were grown to maturity and allowed to self-pollinate. Homozygous target plants, which expressed GUS and GFP, were crossed with homozygous ZFN plants, which expressed the ZFN gene. Numerous GUS-negative plants were observed among the hybrids with one particular cross displaying ~35% GUS-negative plants. Evidence for complete deletion of a 4.3 kb sequence comprising the GUS gene was obtained and sequence confirmed. Co-segregation in F₂ progenies of ‘truncated' and ‘intact' target sequences with expected reporter gene phenotypes were observed. Since ZFNs can be designed to bind and cleave a wide range of DNA sequences, these results constitute a general strategy for creating targeted gene deletions.
Genome modification by homology‐directed repair (HDR) is an attractive tool for the controlled genetic manipulation of plants. Here, we report the HDR‐mediated gene exchange of expression cassettes ...in tobacco BY‐2 cells using a designed zinc finger nuclease (ZFN). The target contained a 7‐kb fragment flanked by two ZFN cutting sites. That fragment was replaced with a 4‐kb donor cassette, which integrates gene markers for selection (kanamycin resistance) and for scoring targeting (red fluorescent protein, RFP). Candidates resulting from cassette exchange were identified by molecular analysis of calli generated by transformation via direct DNA delivery. The precision of HDR‐mediated donor integration was evaluated by Southern blot analysis, sequencing of the integration locus and analysis of RFP fluorescence by flow cytometry. Screening of 1326 kanamycin‐resistant calli yielded 18 HDR events, 16 of which had a perfect cassette exchange at the insert junction and 13 of which produced functional RFP. Our results demonstrate that ZFN‐based HDR can be used for high frequency, precise, targeted exchange of fragments of sizes that are commercially relevant in plants.
Background
Mental health problems affect 1 in 6 workers annually and are one of the leading causes of sickness absence, with stress, anxiety, and depression being responsible for half of all working ...days lost in the United Kingdom. Primary interventions with a preventative focus are widely acknowledged as the priority for workplace mental health interventions. Line managers hold a primary role in preventing poor mental health within the workplace and, therefore, need to be equipped with the skills and knowledge to effectively carry out this role. However, most previous intervention studies have directly focused on increasing line managers’ understanding and awareness of mental health rather than giving them the skills and competencies to take a proactive preventative approach in how they manage and design work. The Managing Minds at Work (MMW) digital training intervention was collaboratively designed to address this gap. The intervention aims to increase line managers’ knowledge and confidence in preventing work-related stress and promoting mental health at work. It consists of 5 modules providing evidence-based interactive content on looking after your mental health, designing and managing work to promote mental well-being, management competencies that prevent work-related stress, developing a psychologically safe workplace, and having conversations about mental health at work.
Objective
The primary aim of this study is to pilot and feasibility test MMW, a digital training intervention for line managers.
Methods
We use a cluster randomized controlled trial design consisting of 2 arms, the intervention arm and a 3-month waitlist control, in this multicenter feasibility pilot study. Line managers in the intervention arm will complete a baseline questionnaire at screening, immediately post intervention (approximately 6 weeks after baseline), and at 3- and 6-month follow-ups. Line managers in the control arm will complete an initial baseline questionnaire, repeated after 3 months on the waitlist. They will then be granted access to the MMW intervention, following which they will complete the questionnaire post intervention. The direct reports of the line managers in both arms of the trial will also be invited to take part by completing questionnaires at baseline and follow-up. As a feasibility pilot study, a formal sample size is not required. A minimum of 8 clusters (randomized into 2 groups of 4) will be sought to inform a future trial from work organizations of different types and sectors.
Results
Recruitment for the study closed in January 2022. Overall, 24 organizations and 224 line managers have been recruited. Data analysis was finished in August 2023.
Conclusions
The results from this feasibility study will provide insight into the usability and acceptability of the MMW intervention and its potential for improving line manager outcomes and those of their direct reports. These results will inform the development of subsequent trials.
Trial Registration
ClinicalTrials.gov NCT05154019; https://clinicaltrials.gov/study/NCT05154019
International Registered Report Identifier (IRRID)
DERR1-10.2196/48758
Background The cost of sickness absence has major social, psychological and financial implications for individuals and organisations. Return-to-work (RTW) interventions that support good quality ...communication and contact with the workplace can reduce the length of sickness absence by between 15 and 30 days. However, initiatives promoting a sustainable return to work for workers with poor mental health on long-term sickness absence across small, medium and large enterprises (SMEs and LEs) are limited. This paper describes the protocol of a pilot randomised controlled trial (RCT) to test the feasibility of implementing a RTW intervention across SMEs and LEs across all sectors. Methods and design A two-arm feasibility RCT with a 4-month intervention will be conducted in SMEs and LE enterprises from the Midlands region, UK. At least 8 organisations (4 controls and interventions), and at least 60 workers and/or managers, will be recruited and randomised into the intervention and control group (30 interventions, 30 controls). Workers on long-term sickness absence (LTSA) (between 8 and 50 days) and managers with a worker on LTSA will be eligible to participate. The intervention is a behavioural change programme, including a managers and workers RTW toolkit, focused on supporting sickness absence and RTW through the provision of knowledge, problem-solving, action planning, goal setting and positive communication that leads to a sustainable RTW. Organisations assigned to the control group will continue with their usual practice. Measurements of mental health, RTW, work outcomes, quality-of-life, workplace support and communication and other demographic data will be taken at baseline, 2 months and 4 months. Feasibility will be assessed based on recruitment, retention, attrition, completion of measures and intervention compliance for which specific process and research outcomes have been established. A process evaluation will explore the experiences and acceptability of the intervention components and evaluation measures. Exploratory economic evaluation will be conducted to further inform a definitive trial. Discussion This is a novel intervention using a worker-manager approach to promote a sustainable return to work of workers on long-term sick leave due to poor mental wellbeing. If this intervention is shown to be feasible, the outcomes will inform a larger scale randomised control trial. Trial registration ISRCTN90032009 (retrospectively registered, date registered 15th December 2020) Keywords: Return to work, Long-term sickness absence, Mental health, Small and medium enterprises, Large enterprises, Positive communication, Worker, Manager, Intervention
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