Increased platelet reactivity and platelet–leukocyte aggregation after elective coronary bypass surgery

Inflammatory mechanisms are activated, and thrombotic complications occur during the initial months after coronary artery bypass grafting (CABG). Therefore, changes over time of platelet activation and platelet–leukocyte interactions after CABG are of interest. Whole-blood flow cytometry was performed before, and 4–6 days, one month, and three months after elective CABG in 54 men with stable coronary artery disease treated with acetylsalicylic acid (ASA). Single platelets and platelet–leukocyte aggregates (PLAs) among monocytes (P-Mon), neutrophils (P-Neu), and lymphocytes (P-Lym) were studied without and with stimulation by submaximal concentrations of ADP, thrombin, and the thromboxane analog U46619. White blood cell counts were increased during the initial postoperative course, and platelet counts were increased after one month. Platelet P-selectin expression was significantly enhanced at one month when stimulated by thrombin and U46619 and at three months with ADP and thrombin. All PLAs subtypes were increased at one month without stimulation in vitro. P-Mon and P-Neu stimulated by ADP, thrombin, or U46619 were significantly increased one month after the operation but decreased compared to baseline at three months. Agonist stimulated P-Lyms were increased at one month and remained increased at three months after ADP stimulation. There was significant platelet activation and formation of PLAs unstimulated and after agonist stimulation by ADP, thrombin, and a thromboxane analog after CABG in patients with stable coronary artery disease irrespective of ASA treatment. Changes observed up to three months after CABG support further studies of the clinical implications of protracted increases in platelet activation and platelet–leukocyte interactions

Prestressed Gridshell Structures

This paper describes a method for the form finding of shell structures composed of both compression and tension members which may lie in one layer or two layers. The length of some of the members can be constrained to a fixed length yielding some control of the resulting form found shape. The form finding is accomplished by adjusting the nodal positions until an equilibrium state is reached using dynamic relaxation. If part of a structure is unstable due to compression forces, then a negative mass must be used in the dynamic relaxation. The length constraint is met by adjusting the force density during form finding, again using dynamic relaxation. Finally, case studies are presented where the applied load and the prestress is used to govern the form found shape

‘Candidatus Aquirickettsiella gammari’ (Gammaproteobacteria: Legionellales: Coxiellaceae): A bacterial pathogen of the freshwater crustacean Gammarus fossarum (Malacostraca: Amphipoda)

Invasive and non-native species can pose risks to vulnerable ecosystems by co-introducing bacterial pathogens. Alternatively, co-introduced bacterial pathogens may regulate invasive population size and invasive traits. We describe a novel candidate genus and species of bacteria (‘Candidatus Aquirickettsiella gammari’) found to infect Gammarus fossarum, from its native range in Poland. The bacterium develops intracellularly within the haemocytes and cells of the musculature, hepatopancreas, connective tissues, nervous system and gonad of the host. The developmental cycle of ‘Candidatus Aquirickettsiella gammari’ includes an elementary body (496.73 nm ± 37.56 nm in length, and 176.89 nm ± 36.29 nm in width), an elliptical, condensed spherical stage (737.61 nm ± 44.51 nm in length and 300.07 nm ± 44.02 nm in width), a divisional stage, and a spherical initial body (1397.59 nm ± 21.26 nm in diameter). We provide a partial genome for ‘Candidatus Aquirickettsiella gammari’, which clades phylogenetically alongside environmental 16S rRNA sequences from aquatic habitats, and bacterial symbionts from aquatic isopods (Asellus aquaticus), grouping separately from the Rickettsiella, a genus that includes bacterial pathogens of terrestrial insects and isopods. Increased understanding of the diversity of symbionts carried by G. fossarum identifies those that might regulate host population size, or those that could pose a risk to native species in the invasive range. Identification of ‘Candidatus Aquirickettsiella gammari’ and its potential for adaptation as a biological control agent is explored

Mapping the water chemistry of the Clyde Basin drainage network

Mapping the chemistry of stream and river water across the Clyde Basin serves both to characterise the water quality and assess the dominant controls. Surveys of the Clyde drainage network, undertaken between 2003 and 2010, have generated data encompassing rural and urban streams, rivers, and estuarine water. Mapping displays the large spatial variability in chemical composition across the Basin and the varying influences of controls such as rainfall, land cover and geology. They also display the chemistry of the urban area within the context of the wider drainage network. This presentation highlights the upcoming production of an online atlas and database of surface-water chemistry which characterises the Clyde drainage network and provides a new resource for stakeholder organisation

Therapeutic Targeting of Replicative Immortality

One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells’ heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy

CRUW Mechanical Pulping sub-project 1: Effect of different refining pressures and energy using spruce TMP pulps from Braviken

The mechanical pulping industry faces continued rising energy costs and increasing competition for raw material. In order to produce improved products based on mechanical pulp at lower energy consumption it is necessary to have a better understanding of the development of fundamental fibre properties during the processes. In particular, changes in fibre collapsibility, fibre fibrillation and fibre and surface development are of great interest. The overall goal of the CRUW Mechanical Pulping project is “Support development of more energy efficient mechanical pulping processes by increasing the knowledge on ultrastructural phenomena in mechanical pulping”. This project is working closely together with the Industrial Research College for Mechanical Pulping Technology bringing in the ultrastructural competence to more clearly understand and explain phenomena observed in these projects thus making it easier to develop new and improved processes to reduce energy consumption. This report presents results from CRUW Mechanical Pulping sub-project 1: ”Effect of different refining pressures and energy using spruce TMP pulps from Braviken”. The influence of temperature on the softening of lignin and hence improved (easier) fibre separation and treatment was noted earlier (Becker et al. 1977; Salmén 1984). Based on this knowledge, different process alternatives have been suggested to reduce energy demand for the refining process. One of the earliest publications on a technical system utilizing higher temperature and pressure was by Höglund et al. 1997 (Thermopulp). These results have been reproduced in many studies and are today considered general knowledge. There are however many practical problems with such a system. For example, the resulting very small refining gaps are difficult to control and it has therefore taken time to establish this technology in the industry. In the new TMP line at Braviken, the refiners are equipped to run at higher temperature/pressure than normal and it has therefore been interesting to study these pulps in order to explain the effects on pulp/fibres at an ultrastructural level. It should be noted that in a fibre-water-steam system, temperature and pressure are not independent variables and higher pressure means higher temperature and vice versa

Genome response to tissue plasminogen activator in experimental ischemic stroke

Background: Tissue plasminogen activator (tPA) is known to have functions beyond fibrinolysis in acute ischemic stroke, such as blood brain barrier disruption. To further delineate tPA functions in the blood, we examined the gene expression profiles induced by tPA in a rat model of ischemic stroke. Results: tPA differentially expressed 929 genes in the blood of rats (p ≤ 0.05, fold change ≥ |1.2|). Genes identified had functions related to modulation of immune cells. tPA gene expression was found to be dependent on the reperfusion status of cerebral vasculature. The majority of genes regulated by tPA were different from genes regulated by ischemic stroke. Conclusions: tPA modulates gene expression in the blood of rats involving immune cells in a manner that is dependent on the status of vascular reperfusion. These non-fibrinolytic activities of tPA in the blood serve to better understand tPA-related complications.Glen C Jickling, Xinhua Zhan, Bradley P Ander, Renee J Turner, Boryana Stamova, Huichun Xu, Yingfang Tian, Dazhi Liu, Ryan R Davis, Paul A Lapchak and Frank R Shar

Therapeutic targeting of replicative immortality

One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells’ heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy

Museum object handling: a health promoting community-based activity for dementia care

In a quasi-experimental design (N = 80), this study examined the wellbeing impact of handling museum artefacts, by testing for differences across domain, time, gender and stages of dementia. Results indicated people with early and moderate impairment showed positive increases in wellbeing, regardless of the type of dementia but those with early stage dementia showed larger positive increases in wellbeing. We can feel confident that for most people with early to middle stage dementia, handling museum objects in a supportive group environment, increases subjective wellbeing and should be considered part of a health promotion strategy in dementia care