The interaction of Trypanosoma congolense with endothelial cells

Factors which affect adhesion of cultured Trypanosoma congolense bloodstream forms to mammalian feeder cells have been examined. Using an in vitro binding assay, the initial events following interaction of trypanosomes with bovine aorta endothelial (BAE) cells were monitored by both light- and electron microscopy. Metabolic inhibitors and other biochemicals were incubated with either cells or parasites, to test whether any inhibited the process. Our findings suggest that adhesion of the parasites is an active process requiring metabolic energy from the trypanosomes, but not from endothelial cells. We also provide data suggesting that T. congolense bloodstream forms possess a lectin-like domain, localized at distinct sites on their flagellar surface, which interacts with specific carbohydrate receptors, most likely sialic acid residues, on the endothelial cell plasma membrane. We also suggest that the cytoskeletal protein actin is probably involved in this interactio

Src/FAK-mediated regulation of E-cadherin as a mechanism for controlling collective cell movement Insights from in vivo imaging

Recent advances in confocal and multi-photon microscopy, together with fluorescent probe development, have enabled cancer biology studies to go beyond the culture dish and interrogate cancer-associated processes in the complex in vivo environment. Regulation of the tumor suppressor protein E-cadherin plays an important role in cancer development and progression, and may contribute to the decision between ‘single cell’ and ‘collective invasion’ in vivo. Mounting evidence from in vitro and in vivo experiments places the two nonreceptor protein tyrosine kinases Src and Focal Adhesion Kinase at the heart of E-cadherin regulation and the crosstalk between integrins and cadherins. Here we discuss recent insights, attained using high-resolution fluorescent in vivo imaging, into the regulation of E-cadherin and collective invasion. We focus on the regulatory crosstalk between the Src/FAK signaling axis and E-cadherin in vivo

Satellite data relay and platform locating in oceanography. Report of the In Situ Ocean Science Working Group

The present and future use of satellites to locate offshore platforms and relay data from in situ sensors to shore was examined. A system of the ARGOS type will satisfy the increasing demand for oceanographic information through data relay and platform location. The improved ship navigation provided by the Global Positioning System (GPS) will allow direct observation of currents from underway ships. Ocean systems are described and demand estimates on satellite systems are determined. The capabilities of the ARGOS system is assessed, including anticipated demand in the next decade

FAK and talin: Who is taking whom to the integrin engagement party?

In this issue, Lawson et al. provide new insight into the relationship between FAK and talin during assembly of integrin adhesions on fibronectin. They show that FAK is upstream of talin, and that talin is not required for FAK recruitment or for integrin activation at nascent adhesions. However, FAK-talin binding is required for adhesion turnover and cell motility. The findings question the view that talin is always upstream of focal adhesion protein recruitment to clustered integrin sites

Evaluating Process-Based Integrated Assessment Models of Climate Change Mitigation

Process-based integrated assessment models (IAMs) analyse transformation pathways to mitigate climate change. Confidence in models is established by testing their structural assumptions and comparing their behaviour against observations as well as other models. Climate model evaluation is concerted, and prominently reported in a dedicated chapter in the IPCC WG1 assessments. By comparison, evaluation of process-based IAMs tends to be less visible and more dispersed among modelling teams, with the exception of model inter-comparison projects. We contribute the first comprehensive analysis of process-based IAM evaluation, drawing on a wide range of examples across eight different evaluation methods testing both structural and behavioural validity. For each evaluation method, we compare its application to process-based IAMs with its application to climate models, noting similarities and differences, and seeking useful insights for strengthening the evaluation of process-based IAMs. We find that each evaluation method has distinctive strengths and limitations, as well as constraints on their application. We develop a systematic evaluation framework combining multiple methods that should be embedded within the development and use of process-based IAMs

Preventive medical care in remote Aboriginal communities in the Northern Territory: a follow-up study of the impact of clinical guidelines, computerised recall and reminder systems, and audit and feedback

Background Interventions to improve delivery of preventive medical services have been shown to be effective in North America and the UK. However, there are few studies of the extent to which the impact of such interventions has been sustained, or of the impact of such interventions in disadvantaged populations or remote settings. This paper describes the trends in delivery of preventive medical services following a multifaceted intervention in remote community health centres in the Northern Territory of Australia. Methods The intervention comprised the development and dissemination of best practice guidelines supported by an electronic client register, recall and reminder systems and associated staff training, and audit and feedback. Clinical records in seven community health centres were audited at regular intervals against best practice guidelines over a period of three years, with feedback of audit findings to health centre staff and management. Results Levels of service delivery varied between services and between communities. There was an initial improvement in service levels for most services following the intervention, but improvements were in general not fully sustained over the three year period. Conclusions Improvements in service delivery are consistent with the international experience, although baseline and follow-up levels are in many cases higher than reported for comparable studies in North America and the UK. Sustainability of improvements may be achieved by institutionalisation of relevant work practices and enhanced health centre capacity

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Measurement of the Total Active 8B Solar Neutrino Flux at the Sudbury Neutrino Observatory with Enhanced Neutral Current Sensitivity

The Sudbury Neutrino Observatory (SNO) has precisely determined the total active (nu_x) 8B solar neutrino flux without assumptions about the energy dependence of the nu_e survival probability. The measurements were made with dissolved NaCl in the heavy water to enhance the sensitivity and signature for neutral-current interactions. The flux is found to be 5.21 +/- 0.27 (stat) +/- 0.38 (syst) x10^6 cm^{-2}s^{-1}, in agreement with previous measurements and standard solar models. A global analysis of these and other solar and reactor neutrino results yields Delta m^{2} = 7.1^{+1.2}_{-0.6}x10^{-5} ev^2 and theta = 32.5^{+2.4}_{-2.3} degrees. Maximal mixing is rejected at the equivalent of 5.4 standard deviations.Comment: Submitted to Phys. Rev. Let

Energy cost and return for hunting in African wild dogs and Cheetahs

African wild dogs (Lycaon pictus) are reported to hunt with energetically costly long chase distances. We used high-resolution GPS and inertial technology to record 1,119 high-speed chases of all members of a pack of six adult African wild dogs in northern Botswana. Dogs performed multiple short, high-speed, mostly unsuccessful chases to capture prey, while cheetahs (Acinonyx jubatus) undertook even shorter, higher-speed hunts. We used an energy balance model to show that the energy return from group hunting and feeding substantially outweighs the cost of multiple short chases, which indicates that African wild dogs are more energetically robust than previously believed. Comparison with cheetah illustrates the trade-off between sheer athleticism and high individual kill rate characteristic of cheetahs, and the energetic robustness of frequent opportunistic group hunting and feeding by African wild dogs

Instability and Spatiotemporal Dynamics of Alternans in Paced Cardiac Tissue

We derive an equation that governs the spatiotemporal dynamics of small amplitude alternans in paced cardiac tissue. We show that a pattern-forming linear instability leads to the spontaneous formation of stationary or traveling waves whose nodes divide the tissue into regions with opposite phase of oscillation of action potential duration. This instability is important because it creates dynamically an heterogeneous electrical substrate for inducing fibrillation if the tissue size exceeds a fraction of the pattern wavelength. We compute this wavelength analytically as a function of three basic length scales characterizing dispersion and inter-cellular electrical coupling.Comment: 4 pages, 3 figures, submitted to PR