Mechanisms of ATP release and signalling in the blood vessel wall

The nucleotide adenosine 5′-triphosphate (ATP) has classically been considered the cell's primary energy currency. Importantly, a novel role for ATP as an extracellular autocrine and/or paracrine signalling molecule has evolved over the past century and extensive work has been conducted to characterize the ATP-sensitive purinergic receptors expressed on almost all cell types in the body. Extracellular ATP elicits potent effects on vascular cells to regulate blood vessel tone but can also be involved in vascular pathologies such as atherosclerosis. While the effects of purinergic signalling in the vasculature have been well documented, the mechanism(s) mediating the regulated release of ATP from cells in the blood vessel wall and circulation are now a key target of investigation. The aim of this review is to examine the current proposed mechanisms of ATP release from vascular cells, with a special emphasis on the transporters and channels involved in ATP release from vascular smooth muscle cells, endothelial cells, circulating red blood cells, and perivascular sympathetic nerves, including vesicular exocytosis, plasma membrane F1/F0-ATP synthase, ATP-binding cassette (ABC) transporters, connexin hemichannels, and pannexin channel

Sharing a Top Manager’s Experience with the Next Generation: The Use of Electronic Discussions and Short Video Fragments in Teaching

In: A.J. Kallenberg and M.J.J.M. van de Ven (Eds), 2002, The New Educational Benefits of ICT in Higher Education: Proceedings. Rotterdam: Erasmus Plus BV, OECR ISBN 90-9016127-9This paper presents an effective educational method to transfer managerial knowledge to students. This method consists among other of online discussions between small groups of students and video clips of lectures. The set-up of the course and the ICT-tool used in the course were evaluated for two years through a questionnaire among the students. The results show that the applied e-learning concept is highly appreciated and serves as an effective tool to exchange knowledge

Monomeric PcrA helicase processively unwinds plasmid lengths of DNA in the presence of the initiator protein RepD

The helicase PcrA unwinds DNA during asymmetric replication of plasmids, acting with an initiator protein, in our case RepD. Detailed kinetics of PcrA activity were measured using bulk solution and a single-molecule imaging technique to investigate the oligomeric state of the active helicase complex, its processivity and the mechanism of unwinding. By tethering either DNA or PcrA to a microscope coverslip surface, unwinding of both linear and natural circular plasmid DNA by PcrA/RepD was followed in real-time using total internal reflection fluorescence microscopy. Visualization was achieved using a fluorescent single-stranded DNA-binding protein. The single-molecule data show that PcrA, in combination with RepD, can unwind plasmid lengths of DNA in a single run, and that PcrA is active as a monomer. Although the average rate of unwinding was similar in single-molecule and bulk solution assays, the single-molecule experiments revealed a wide distribution of unwinding speeds by different molecules. The average rate of unwinding was several-fold slower than the PcrA translocation rate on single-stranded DNA, suggesting that DNA unwinding may proceed via a partially passive mechanism. However, the fastest dsDNA unwinding rates measured in the single-molecule unwinding assays approached the PcrA translocation speed measured on ssDNA

Velocity and processivity of helicase unwinding of double-stranded nucleic acids

Helicases are molecular motors which unwind double-stranded nucleic acids (dsNA) in cells. Many helicases move with directional bias on single-stranded (ss) nucleic acids, and couple their directional translocation to strand separation. A model of the coupling between translocation and unwinding uses an interaction potential to represent passive and active helicase mechanisms. A passive helicase must wait for thermal fluctuations to open dsNA base pairs before it can advance and inhibit NA closing. An active helicase directly destabilizes dsNA base pairs, accelerating the opening rate. Here we extend this model to include helicase unbinding from the nucleic-acid strand. The helicase processivity depends on the form of the interaction potential. A passive helicase has a mean attachment time which does not change between ss translocation and ds unwinding, while an active helicase in general shows a decrease in attachment time during unwinding relative to ss translocation. In addition, we describe how helicase unwinding velocity and processivity vary if the base-pair binding free energy is changed.Comment: To appear in special issue on molecular motors, Journal of Physics - Condensed Matte

Four problems with global carbon markets: a critical review

This article offers a critique of global carbon markets and trading, with a special focus on the Clean Development Mechanism of the Kyoto Protocol. It explores problems with the use of tradable permits to address climate change revolving around four areas: homogeneity, justice, gaming, and information. Homogeneity problems arise from the non-linear nature of climate change and sensitivity of emissions, which complicate attempts to calculate carbon offsets. Justice problems involve issues of dependency and the concentration of wealth among the rich, meaning carbon trading often counteracts attempts to reduce poverty. Gaming problems include pressures to promote high-volume, least-cost projects and the consequences of emissions leakage. Information problems encompass transaction costs related to carbon trading and market participation and the comparatively weak institutional capacity of project evaluators

Assessing the importance of a self-generated detachment process in river biofilm models

1. Epilithic biofilm biomass was measured for 14 months in two sites, located up- and downstream of the city of Toulouse in the Garonne River (south-west France). Periodical sampling provided a biomass data set to compare with simulations from the model of Uehlinger, Bürher and Reichert (1996: Freshwater Biology, 36, 249–263.), in order to evaluate the impact of hydraulic disturbance. 2. Despite differences in application conditions (e.g. river size, discharge, frequency of disturbance), the base equation satisfactorily predicted biomass between low and high water periods of the year, suggesting that the flood disturbance regime may be considered a universal mechanism controlling periphyton biomass. 3. However modelling gave no agreement with biomass dynamics during the 7-month long low water period that the river experienced. The influence of other biomass-regulating factors (temperature, light and soluble reactive phosphorus) on temporal biomass dynamics was weak. 4. Implementing a supplementary mechanism corresponding to a temperature-dependent self-generated loss because of heterotrophic processes allowed us to accurately reproduce the observed pattern: a succession of two peaks. This case study suggests that during typical summer low water periods (flow stability and favourable temperature) river biofilm modelling requires self-generated detachment to be considered

Upgrade of the Glasgow photon tagging spectrometer for Mainz MAMI-C

The Glasgow photon tagging spectrometer at Mainz has been upgraded so that it can be used with the 1500 MeV electron beam now available from the Mainz microtron MAMI-C. The changes made and the resulting properties of the spectrometer are discussed.Comment: 20 pages, 12 figure

Comparison of rainforest butterfly assemblages across three biogeographical regions using standardized protocols

Insects, like most other organisms, are more diverse in tropical than in temperate regions, but standardized comparisons of diversity among tropical regions are rare. Disentangling the effects of ecological, evolutionary, and biogeographic factors on community diversity requires standardized protocols and long-term studies. We compared the abundance and diversity of butterflies using standardised ‘Pollard walk’ transect counts in the understory of closed-canopy lowland rainforests in Panama (Barro Colorado Island, BCI), Thailand (Khao Chong, KHC) and Papua New Guinea (Wanang, WAN). We observed 1792, 1797 and 3331 butterflies representing 128, 131 and 134 species during 230, 231 and 120 transects at BCI, KHC and WAN, respectively. When corrected for length and duration of transects, butterfly abundance and species richness were highest at WAN and KHC, respectively. Although high butterfly abundance at WAN did not appear to result from methodological artefacts, the biological meaning of this observation remains obscure. The WAN site appeared as floristically diverse as KHC, but supported lower butterfly diversity. This emphasizes that factors other than plant diversity, such as biogeographic history, may be crucial for explaining butterfly diversity. The KHC butterfly fauna may be unusually species rich because the site is at a biogeographic crossroads between the Indochinese and Sundaland regions. In contrast, WAN is firmly within the Australian biogeographic region and relatively low species numbers may result from island biogeographic processes. The common species at each of the three sites shared several traits: fruit and nectar feeders were equally represented, more than half of common species fed on either epiphytes or lianas as larvae, and their range in wing sizes was similar. These observations suggest that Pollard walks in different tropical rainforests target similar assemblages of common species, and, hence, represent a useful tool for long-term monitoring of rainforest butterfly assemblages.Organismic and Evolutionary Biolog

Antagonism of the proinflammatory and pronociceptive actions of canonical and biased agonists of protease-activated receptor-2

Diverse proteases cleave protease-activated receptor-2 (PAR2) on primary sensory neurons and epithelial cells to evoke pain and inflammation. Trypsin and tryptase activate PAR2 by a canonical mechanism that entails cleavage within the extracellular N-terminus revealing a tethered ligand that activates the cleaved receptor. Cathepsin-S and elastase are biased agonists that cleave PAR2 at different sites to activate distinct signalling pathways. Although PAR2 is a therapeutic target for inflammatory and painful diseases, the divergent mechanisms of proteolytic activation complicate the development of therapeutically useful antagonists

Geodetic model of the 2016 Central Italy earthquake sequence inferred from InSAR and GPS data

We investigate a large geodetic data set of interferometric synthetic aperture radar (InSAR)and GPS measurements to determine the source parameters for the three main shocks of the 2016Central Italy earthquake sequence on 24 August and 26 and 30 October (Mw6.1, 5.9, and 6.5,respectively). Our preferred model is consistent with the activation of four main coseismic asperitiesbelonging to the SW dipping normal fault system associated with the Mount Gorzano-Mount Vettore-Mount Bove alignment. Additional slip, equivalent to aMw~ 6.1–6.2 earthquake, on a secondary (1) NEdipping antithetic fault and/or (2) on a WNW dipping low-angle fault in the hanging wall of the mainsystem is required to better reproduce the complex deformation pattern associated with the greatestseismic event (theMw6.5 earthquake). The recognition of ancillary faults involved in the sequencesuggests a complex interaction in the activated crustal volume between the main normal faults and thesecondary structures and a partitioning of strain releas