MS

thesisThe relationship of fibrinolytic activity produced by baby hamster kidney (BHK-21) cells to surface properties and growth of the cells has been studied. Hydrolysis of fibrin clots and casein was used to detect cellular protease activity. Cloned, high passage sublines of the BHK-21/C13 cell line were found to produce increased fibrinolysis when compared to low passage BHK-21/C13 cells (C13). Low passage C13 cells were also found to produce an inhibitor of the cellular fibrinolysin. This inhibitory activity was detected when low and high protease-producing cell lines were co-cultivated and could be removed from the C13 cells by trypsin treatment. Inhibitor could again be detected in C13 cell cultures after 6-8.5 hours incubation at 37°C following typsinization. This substance was not detected in supernatant fluids from growing C13 cells and its production was inhibited by incubation of cells at 4°C. All high protease-producing cultures formed colonies in agar suspension, exhibited quantitative increases in agglutinability by concanavalin A (Con A) when compared to low passage cell cultures and grew faster as judged by transfer behavior of cells and increased rates of accumulation of cells in metaphase when grown in the presence of mitotic inhibitor. Low protease-producing C13 cells and sublines low in protease activity isolated from high passage cultures did not grow in agar suspension, exhibited slower growth rates and decreased agglutinability by Con A. Low protease-producing C13 cells could be stimulated to produce increase amounts of fibrinolytic activity with accompanying changes in surface properties characteristic of transformed cells by addition of purines such as hypoxanthine or adenosine to culture media. The effect was reversed by deletion of the purines. Growth of C13 cell in agar suspension did not occur with purine supplementation alone. With the addition of hypoxanthine and thymidine or adenosine and thymidine or adenosine and thymidine, C13 cells formed colonies in agar suspension which were similar to those formed by high protease-producing cell lines. Fibrinolytic activity could be detected from the colonies formed by C13 cells in agar suspension. Treatment of C13 cells suspended in agar with trypsin or fibrinolytically active culture fluids from high protease-producing cells did not result in the multiplication of the cells in agar. Temperature sensitive BHK-21 cells were isolated which were defective for cytokinesis but not karyokinesis. At 39-40°C these cells became enlarged and multinucleated. The defect did not appear to be associated with the cellular fibrinolysin because protease activity could be detected at the permissive and non-permissive temperatures. Growth of temperature sensitive cells in agar suspension did not occur at 39-40°C but cell enlargement, vacillation and lysis were observed in a large portion of the cell population. The data demonstrate that growth in agar suspension, increased Con A agglutinability and increased growth rates are positively associated in some way with the detection of increased fibrinolysis. An increase in the amount of fibrinolysin.produced by high passage BHK-21 cultures was always associated with increase Con A agglutinability of cells. Although increased fibrinolytic activity could always be detected from cells which grew in agar suspension, and increase in protease synthesis was not always followed by growth in agar suspension. This suggests that factors in addition to the fibrinolysin produced by cell are involved in growth regulation

Childfree: Why does someone not want to have children?

Denne artikkelen handler om hva som gjør at noen mennesker ønsker å være barnfri. Betegnelsen «barnfri» er ment å beskrive personer som lever uten barn fordi de ønsker eller har valgt det selv. Datamaterialet er åtte kvalitative intervjuer med tre menn og fem kvinner mellom 38 og 54 år som alle identifiserer seg som barnfrie. Artikkelen utforsker innvirkningen av individuelle og sosiale faktorer for informantenes ønsker og valg om å være barnfri og diskuterer skillet mellom barnfrihet og ufrivillig barnløshet. Resultatene viser at informantenes forståelse av å være barnfri er noe som har utviklet seg gjennom ulike livsløpsprosesser, der ulike forhold i livssituasjonen har hatt betydning for ønsket eller valget om å leve uten barn. De fleste informantene kunne vært åpen for å få barn dersom livssituasjonen hadde utviklet seg til å bli annerledes.publishedVersio

Celebrating diversity: focus on inclusion

As teachers, we are privileged to have the opportunity to work in diverse contexts and with diverse groups and individuals. The richness and opportunities within today’s classrooms provide a wealth of opportunities to learn from, and with our students, parents, community and colleagues. By sharing perspectives and histories that may be unfamiliar to us and to others, opportunities are created that must be embraced in order to break down the many social injustices that still exist, and which limit the opportunities of students to fulfil their full potential

Post-transcriptional regulation of satellite cell quiescence by TTP-mediated mRNA decay.

Skeletal muscle satellite cells in their niche are quiescent and upon muscle injury, exit quiescence, proliferate to repair muscle tissue, and self-renew to replenish the satellite cell population. To understand the mechanisms involved in maintaining satellite cell quiescence, we identified gene transcripts that were differentially expressed during satellite cell activation following muscle injury. Transcripts encoding RNA binding proteins were among the most significantly changed and included the mRNA decay factor Tristetraprolin. Tristetraprolin promotes the decay of MyoD mRNA, which encodes a transcriptional regulator of myogenic commitment, via binding to the MyoD mRNA 3' untranslated region. Upon satellite cell activation, p38α/β MAPK phosphorylates MAPKAP2 and inactivates Tristetraprolin, stabilizing MyoD mRNA. Satellite cell specific knockdown of Tristetraprolin precociously activates satellite cells in vivo, enabling MyoD accumulation, differentiation and cell fusion into myofibers. Regulation of mRNAs by Tristetraprolin appears to function as one of several critical post-transcriptional regulatory mechanisms controlling satellite cell homeostasis

IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. Discussion: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. Conclusions: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public’s health

A qualitative analysis of self-harm and suicide in Sri Lankan printed newspapers

Background: Media reporting may influence suicidal behavior. In-depth exploration of how self-harm and suicide are portrayed in newspaper articles in a middle-income country such as Sri Lanka is lacking. Aims: We aimed to explore how self-harm and suicide are portrayed in Sri Lankan printed newspapers. Method: Seven English- and Sinhala-language Sri Lankan newspapers were screened for articles reporting on self-harm and suicide (December 1, 2014 to January 31, 2015). A thematic analysis was conducted. Results: In the 78 articles identified for analysis, certain aspects were overemphasized (inappropriate behavior) and others underemphasized (alcohol and complexities of self-harm). Explanations of self-harm were one-sided and a suicide prevention narrative was lacking. Limitations: Another time-frame and inclusion of Tamil newspapers as well as social media and online publications would provide additional understanding. Conclusion: The study found an indication of simplistic reporting. Greater focus on prevention and a nuanced portrayal of self-harm could reduce stigma and imitative behavior

Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain

The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30–50% (4–6 mM versus 7–9 mM in controls). The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced

Examining barriers to healthcare providers’ adoption of a hospital-wide electronic patient journey board

Background: The dynamic environment that characterizes patient care in hospitals requires extensive communication between staff. Electronic status board applications are used to improve the flow of communication in hospitals. To date there has been limited work exploring the adoption of these applications in general acute ward settings. Aim: This study aimed to identify barriers to the adoption of an electronic patient journey board (EPJB)1 application in acute wards of a hospital. Method: Data were collected at a large public teaching hospital in Sydney, Australia. The EPJB was implemented across all hospital wards with the aim of improving multidisciplinary communication in wards. Observations (29.5 h) and contextual interviews (n = 33) with hospital staff were conducted in two acute wards of the hospital. Results: Two manual whiteboards were used on wards, in addition to the EPJB, to compensate for information not being available or accessible on the EPJB. Despite the stated purpose of the EPJB, the tool did not appear to support team communication on wards. Barriers to adoption and optimal use of the EPJB included inappropriate location and configuration of the system, limitations in information timeliness, quality and lack of customisation (for different user groups), inconsistent information updates and the absence of a shared understanding of the purpose of the EPJB among the various user groups. Conclusion: Multiple socio-technical barriers influenced uptake and optimal use of the EPJB by healthcare providers. Engaging users early in the design and implementation of electronic status board applications is required to ensure effective use of these complex interventions on general wards

Integrated single- and two-photon light sheet microscopy using accelerating beams

The authors thank the UK Engineering and Physical Sciences Research Council (grant EP/J01771/X) and the European Union project FAMOS (FP7 ICT, contract no. 317744) for funding. P.P. acknowledges funding by the Estonian Research Council (grants PUTJD8 and PUT369).We demonstrate the first light sheet microscope using propagation invariant, accelerating Airy beams that operates both in single- and two-photon modes. The use of the Airy beam permits us to develop an ultra compact, high resolution light sheet system without beam scanning. In two-photon mode, an increase in the field of view over the use of a standard Gaussian beam by a factor of six is demonstrated. This implementation for light sheet microscopy opens up new possibilities across a wide range of biomedical applications, especially for the study of neuronal processes.Publisher PDFPeer reviewe