Changes in Dry State Hemoglobin over Time Do Not Increase the Potential for Oxidative DNA Damage in Dried Blood

BACKGROUND: Hemoglobin (Hb) is the iron-containing oxygen transport protein present in the red blood cells of vertebrates. Ancient DNA and forensic scientists are particularly interested in Hb reactions in the dry state because both regularly encounter aged, dried bloodstains. The DNA in such stains may be oxidatively damaged and, in theory, may be deteriorated by the presence of Hb. To understand the nature of the oxidative systems potentially available to degrade DNA in the presence of dried Hb, we need to determine what molecular species Hb forms over time. These species will determine what type of iron (i.e. Fe(2+)/Fe(3+)/Fe(4+)) is available to participate in further chemical reactions. The availability of "free" iron will affect the ability of the system to undergo Fenton-type reactions which generate the highly reactive hydroxyl radical (OH*). The OH* can directly damage DNA. METHODOLOGY/PRINCIPAL FINDINGS: Oxygenated Hb (oxyHb) converts over time to oxidized Hb (metHb), but this happens more quickly in the dry state than in the hydrated state, as shown by monitoring stabilized oxyHb. In addition, dry state oxyHb converts into at least one other unknown species other than metHb. Although "free" iron was detectable as both Fe(2+) and Fe(3+) in dry and hydrated oxyHb and metHb, the amount of ions detected did not increase over time. There was no evidence that Hb becomes more prone to generating OH* as it ages in either the hydrated or dry states. CONCLUSIONS: The Hb molecule in the dried state undergoes oxidative changes and releases reactive Fe(II) cations. These changes, however, do not appear to increase the ability of Hb to act as a more aggressive Fenton reagent over time. Nevertheless, the presence of Hb in the vicinity of DNA in dried bloodstains creates the opportunity for OH*-induced oxidative damage to the deoxyribose sugar and the DNA nucleobases

eBank UK: linking research data, scholarly communication and learning

This paper includes an overview of the changing landscape of scholarly communication and describes outcomes from the innovative eBank UK project, which seeks to build links from e-research through to e-learning. As introduction, the scholarly knowledge cycle is described and the role of digital repositories and aggregator services in linking data-sets from Grid-enabled projects to e-prints through to peer-reviewed articles as resources in portals and Learning Management Systems, are assessed. The development outcomes from the eBank UK project are presented including the distributed information architecture, requirements for common ontologies, data models, metadata schema, open linking technologies, provenance and workflows. Some emerging challenges for the future are presented in conclusion

Peroxynitrite releases copper from caeruloplasmin: implications for atherosclerosis

AbstractPeroxynitrite may be formed in the vasculature by the reaction of puperoxide with nitric oxide. When the blue copper-containing protein, caeruloplasmin, is incubated with peroxynitrite, copper is released, and ferroxidase activity and the blue colouration are lost. When plasma from normal subjects is incubated with peroxynitrite, the oxidant reacts with numerous plasma constituents but is still able to release copper from caeruloplasmin. As the ferroxidase activity of caeruloplasmin is lost in plasma in the presence of peroxynitrite, a second ferroxidase activity associated with peroxidised lipids, and not inhibited by azide, is formed

Risks in circular business models innovation: A cross-industrial case study for composite materials

Circular business models (CBMs) are key enablers to implement circular economy (CE), yet they entail risks, which often discourage organisations. This work aims to explore the main risk factors perceived by the manufacturing industry in transitioning to CBMs to enable the development of appropriate risk management strategies. A cross- industrial multiple-case study research design was used to explore risk factors across seven organisations planning the transition to CBMs for composite-based products and involving three different CBM types—‘Circular Supplies’, ‘Product Life Extension’ and ‘Hybrid’. Results evidenced that risks are multi-disciplinary but are not equally per- ceived across different CBM types. Customers' perceptions of CE products, economic cycle and take-back systems were prevalent across all CBMs. Supply and technological risks were prioritised for ‘Circular Supplies’ CBM, whereas political and regulatory risks for ‘Product Life Extension’ CBM. This research contributes to the CE field by evaluating and prioritising the perceived risk factors in transitioning to CBMs and first disaggregating such risk factors according to CBM types. Critical risk patterns identified across different industries and CBM types enable mitigating actions to be prioritised

Manipulating mentors' assessment decisions: Do underperforming student nurses use coercive strategies to influence mentors' practical assessment decisions?

There is growing evidence of a culture of expectation among nursing students in Universities which leads to narcissistic behaviour. Evidence is growing that some student nurses are disrespectful and rude towards their university lecturers. There has been little investigation into whether they exhibit similar behaviour towards their mentors during practical placements, particularly when they, the students, are not meeting the required standards for practice. This paper focuses on adding to the evidence around a unique finding ��� that student nurses can use coercive and manipulative behaviour to elicit a successful outcome to their practice learning assessment (as noted in Hunt et al. (2016, p 82)). Four types of coercive student behaviour were identified and classified as: ingratiators, diverters, disparagers and aggressors, each of which engendered varying degrees of fear and guilt in mentors. The effects of each type of behaviour are discussed and considered in the light of psychological contracts. Mechanisms to maintain effective working relationships between student nurses and mentors and bolster the robustness of the practical assessment process under such circumstances are discussed

Redesigning metal interference screws can improve ease of insertion while maintaining fixation of soft-tissue anterior cruciate ligament reconstruction grafts

Purpose: To compare the fixation strength and loads on insertion of a titanium alloy interference screw with a modified tip against a conventional titanium interference screw. Methods: Slippage of bovine digital extensor tendons (as substitutes for human tendon grafts) under cyclic loading and interference fixation strength under a pullout test were recorded in 10 cadaveric knees, with 2 tunnels drilled in each femur and tibia to provide pair-wise comparisons between the modified-tip screw (MS) and conventional screw (CS). To analyze screw insertion, 10 surgeons blindly inserted pairs of the MS and CS into bone-substitute blocks (with polyester shoelaces as graft substitutes), with insertion loads measured using a force/torque sensor. Results: No differences were found between the MS and CS either in graft slippage from the femur (P = .661) or tibia (P = .950) or in ultimate load to failure from the femur (P = .952) or tibia (P = .126). On insertion, the MS required less axial force application (78 ± 38 N, P = .001) and fewer attempted turns (2 ± 1, P < .001) to engage with the bone tunnel than the CS (99 ± 43 N and 4 ± 4, respectively). In 90% of the paired insertion tests, the screw identified by the surgeon as being easier to initially insert was the MS. Conclusions: The MS was found to be easier to engage with the bone tunnel and initially insert than the CS while still achieving similar immediate postsurgical fixation strength. Clinical Relevance: The study shows that screw designs can be improved to ease insertion into a bone tunnel, which should reduce any likelihood of ligament reconstruction graft damage

Tests of amounts and times of application of nitrogen and of sequential sprays of aphicide and fungicides on winter wheat, following either beans or wheat, and the effects of take-all (Gaeumannomyces graminis var. tritici ), on two varieties at Saxmundham, Suffolk 1980-3

RESP-9258 and RESP-924

Directing Differentiation of Pluripotent Stem Cells Toward Retinal Pigment Epithelium Lineage

Development of efficient and reproducible conditions for directed differentiation of pluripotent stem cells into specific cell types is important not only to understand early human development but also to enable more practical applications, such as in vitro disease modeling, drug discovery, and cell therapies. The differentiation of stem cells to retinal pigment epithelium (RPE) in particular holds promise as a source of cells for therapeutic replacement in age-related macular degeneration. Here we show development of an efficient method for deriving homogeneous RPE populations in a period of 45 days using an adherent, monolayer system and defined xeno-free media and matrices. The method utilizes sequential inhibition and activation of the Activin and bone morphogenetic protein signaling pathways and can be applied to both human embryonic stem cells and induced pluripotent stem cells as the starting population. In addition, we use whole genome transcript analysis to characterize cells at different stages of differentiation that provides further understanding of the developmental dynamics and fate specification of RPE. We show that with the described method, RPE develop through stages consistent with their formation during embryonic development. This characterization- together with the absence of steps involving embryoid bodies, three-dimensional culture, or manual dissections, which are common features of other protocols-makes this process very attractive for use in research as well as for clinical applications. SIGNIFICANCE: This report describes a novel method of directed differentiation to generate retinal pigment epithelium (RPE) cells from pluripotent stem cells. The employed method is based on adherent monolayer culture using xeno-free conditions and manipulation of the Activin and bone morphogenetic protein signaling pathway using small molecules and recombinant proteins. Whole genome microarray analysis was performed to characterize the differentiation process and understand the developmental path of RPE generation in vitro. This method can be applied for generation of RPE for research as well as for clinical applications