Synthesis, Regulation and Degradation of Carotenoids Under Low Level UV-B Radiation in the Filamentous Cyanobacterium Chlorogloeopsis fritschii PCC 6912

Carotenoids in cyanobacteria play an important role in protecting against and in repairing damage against low level UV-B radiation. Here we use transcriptomics and metabolomic HPLC pigment analysis to compare carotenoid pathway regulation in the filamentous cyanobacterium Chlorogloeopsis fritschii PCC 6912 exposed to white light and to white light supplemented with low level UV-B. Under UV-B changes in carotenoid transcription regulation were found associated with carotenogenesis (carotenoid synthesis), photoprotection and carotenoid cleavage. Transcriptional regulation was reflected in corresponding pigment signatures. All carotenogenesis pathway genes from geranylgeranyl-diphosphate to lycopene were upregulated. There were significant increases in expression of gene homologs (crtW, crtR, cruF, and cruG) associated with routes to ketolation to produce significant increases in echinenone and canthaxanthin concentrations. There were gene homologs for four β-carotene-ketolases (crtO and crtW) present but only one crtW was upregulated. Putative genes encoding enzymes (CruF, CrtR, and CruG) for the conversion of γ-carotene to myxol 2′-methylpentoside were upregulated. The hydroxylation pathway to nostaxanthin via zeaxanthin and caloxanthin (gene homologs for CrtR and CrtG) were not upregulated, reflected in the unchanged corresponding pigment concentrations in zeaxanthin, caloxanthin and nostaxanthin, Transcripts for the non-photochemical quenching related Orange-Carotenoid-Protein (OCP) and associated Fluoresence-Recovery-Protein (FRP) associated with photoprotection were upregulated, and one carotenoid binding Helical-Carotenoid-Protein (HCP) gene homolog was downregulated. Multiple copies of genes encoding putative apocarotenoid related carotenoid oxygenases responsible for carotenoid cleavage were identified, including an upregulated apo-β-carotenal-oxygenase gene homologous to a retinal producing enzyme. Our study provides holistic insight into the photoregulatory processes that modulate the synthesis, photoprotection and cleavage of carotenoids in cyanobacterial cells exposed to low level UV-B. This is important to understanding how regulation of metabolism responds to a changing environment and how metabolism can be modulated for biotechnological purposes

IFN-γ-producing CD4+ T cells promote experimental cerebral malaria by modulating CD8+ T cell accumulation within the brain.

It is well established that IFN-γ is required for the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the temporal and tissue-specific cellular sources of IFN-γ during P. berghei ANKA infection have not been investigated, and it is not known whether IFN-γ production by a single cell type in isolation can induce cerebral pathology. In this study, using IFN-γ reporter mice, we show that NK cells dominate the IFN-γ response during the early stages of infection in the brain, but not in the spleen, before being replaced by CD4(+) and CD8(+) T cells. Importantly, we demonstrate that IFN-γ-producing CD4(+) T cells, but not innate or CD8(+) T cells, can promote the development of ECM in normally resistant IFN-γ(-/-) mice infected with P. berghei ANKA. Adoptively transferred wild-type CD4(+) T cells accumulate within the spleen, lung, and brain of IFN-γ(-/-) mice and induce ECM through active IFN-γ secretion, which increases the accumulation of endogenous IFN-γ(-/-) CD8(+) T cells within the brain. Depletion of endogenous IFN-γ(-/-) CD8(+) T cells abrogates the ability of wild-type CD4(+) T cells to promote ECM. Finally, we show that IFN-γ production, specifically by CD4(+) T cells, is sufficient to induce expression of CXCL9 and CXCL10 within the brain, providing a mechanistic basis for the enhanced CD8(+) T cell accumulation. To our knowledge, these observations demonstrate, for the first time, the importance of and pathways by which IFN-γ-producing CD4(+) T cells promote the development of ECM during P. berghei ANKA infection

‘It is not a quick fix’ structural and contextual issues that affect implementation of integrated health and well-being services: a qualitative study from North East England

Objective The objective of this article is to examine the factors affecting the design, commissioning and delivery of integrated health and well-being services (IHWSs), which seek to address multiple health-related behaviours, improve well-being and tackle health inequalities using holistic approaches. Study design Qualitative studies embedded within iterative process evaluations. Methods Semi-structured interviews conducted with 16 key informants as part of two separate evaluations of IHWSs in North East England, supplemented by informal observations of service delivery. Transcripts and fieldnotes were analysed thematically. Results The study findings identify a challenging organisational context in which to implement innovative service redesign, as a result of budget cuts and changes in NHS and local authority capacity. Pressures to demonstrate outcomes affected the ability to negotiate the practicalities of joint working. Progress is at risk of being undermined by pressures to disinvest before the long-term benefits to population health and well-being are realised. The findings raise important questions about contract management and relationships between commissioners and providers involved in implementing these new ways of working. Conclusions These findings provide useful learning in terms of the delivery and commissioning of similar IHWSs, contributing to understanding of the benefits and challenges of this model of working

Towards a 'Scandinavian model' for Scotland

The fiscal powers of the Scottish Government have recently been significantly enhanced as a consequence of the implementation of the Scotland Act 2012, which required the Parliament to set a Scottish Rate of Income Tax (SRIT) from April 2016. The SRIT can vary from that in the rest of the UK by up to 10p in the pound. More extensive powers over income tax will come into effect in April 2017 as a consequence of the Scotland Act 2016, which sought to implement the proposals of the Smith Commission (2014). The Scottish Government will then gain the power to set income tax rates and thresholds (but not personal allowances). All income tax receipts on wage income collected in Scotland will be received by the Scottish Government, with a corresponding adjustment in the block grant, as detailed in the new Fiscal Framework (2016). These changes will make Scotland one of the most powerful devolved governments in the world in terms of the proportion of public spending and tax revenues under its control, although there of course remains a debate about how effective these new powers are and whether or not they go far enough

Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death

The purinergic signalling system, which uses purines and pyrimidines as chemical transmitters, and purinoceptors as effectors, is deeply rooted in evolution and development and is a pivotal factor in cell communication. The ATP and its derivatives function as a 'danger signal' in the most primitive forms of life. Purinoceptors are extraordinarily widely distributed in all cell types and tissues and they are involved in the regulation of an even more extraordinary number of biological processes. In addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion, there is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body. In this article, we focus on the latter in the immune/defence system, in stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption, as well as in cancer. Cell Death and Disease (2010) 1, e9; doi:10.1038/cddis.2009.11; published online 14 January 201

Next generation of consumer aerosol valve design using inert gases

The current global consumer aerosol products such as deodorants, hairsprays, air-fresheners, polish, insecticide, disinfectant are primarily utilised unfriendly environmental propellant of liquefied petroleum gas (LPG) for over three decades. The advantages of the new innovative technology described in this paper are: (i) no butane or other liquefied hydrocarbon gas; (ii) compressed air, nitrogen or other safe gas propellant; (iii) customer acceptable spray quality and consistency during can lifetime; (iv) conventional cans and filling technology. Volatile organic compounds and greenhouse gases must be avoided but there are no flashing propellants replacements that would provide the good atomisation and spray reach. On the basis of the energy source for atomising, the only feasible source is inert gas (i.e. compressed air), which improves atomisation by gas bubbles and turbulence inside the atomiser insert of the actuator. This research concentrates on using ‘bubbly flow’ in the valve stem, with injection of compressed gas into the passing flow, thus also generating turbulence. Using a vapour phase tap in conventional aerosol valves allows the propellant gas into the liquid flow upstream of the valve. However, forcing bubbly flow through a valve is not ideal. The novel valves designed here, using compressed gas, thus achieved the following objectives when the correct combination of gas and liquid inlets to the valve, and the type and size of atomiser ‘insert’ were derived: 1. Produced a consistent flow rate and drop size of spray throughout the life of the can, compatible with the current conventional aerosols that use LPG: a new ‘constancy’ parameter is defined and used to this end. 2. Obtained a discharge flow rate suited to the product to be sprayed; typically between 0.4 g/s and 2.5 g/s. 3. Attained the spray droplets size suited to the product to be sprayed; typically between 40 mm and 120 mm

Interval cancers in a national colorectal cancer screening programme

BACKGROUND: Little is known about interval cancers (ICs) in colorectal cancer (CRC) screening. OBJECTIVE: The purpose of this study was to identify IC characteristics and compare these with screen-detected cancers (SCs) and cancers in non-participants (NPCs) over the same time period. DESIGN: This was an observational study done in the first round of the Scottish Bowel Screening Programme. All individuals (772,790), aged 50–74 years, invited to participate between 1 January 2007 and 31 May 2009 were studied by linking their screening records with confirmed CRC records in the Scottish Cancer Registry (SCR). Characteristics of SC, IC and NPC were determined. RESULTS: There were 555 SCs, 502 ICs and 922 NPCs. SCs were at an earlier stage than ICs and NPCs (33.9% Dukes’ A as against 18.7% in IC and 11.3% in NPC), screening preferentially detected cancers in males (64.7% as against 52.8% in IC and 59.7% in NPC): this was independent of a different cancer site distribution in males and females. SC in the colon were less advanced than IC, but not in the rectum. CONCLUSION: ICs account for 47.5% of the CRCs in the screened population, indicating approximately 50% screening test sensitivity: guaiac faecal occult blood testing (gFOBT) sensitivity is less for women than for men and gFOBT screening may not be effective for rectal cancer