Phylloxera and the grapevine: a sense of common purpose?

The purpose of life is its continuation: survival is the reason things live. Here we explore this 'basic' of biology, by reference to the extraordinary life-cycle of the aphid-like pest phylloxera, and the complexity of its relationship with its host the grapevine. The effort and ingenuity that phylloxera employs to continue itself leads to a doubt that survival alone is sufficient reason. It has frequently been suggested that the reduction of life to a catalogue of facts (by science) creates this doubt, because it robs existence of its essence (which is something other than its mechanics). The part that science is said to steal is what Robert Pirsig calls Quality-the harmonious balance of things. Pirsig seems to imply that this is something inherent in things-and independent from us. A more mundane explanation is that the difference between facts and the complete reality is us-the tendency of mind to connect freely between different kinds of information. This possibility is briefly illustrated here by a myth based on the facts of phylloxera.

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit vascular smooth muscle cell proliferation via differential effects on the cell cycle

Abnormal vascular smooth muscle cell (VSMC) proliferation plays an important role in the pathogenesis of both atherosclerosis and restenosis. Recent studies suggest that high-dose salicylates, in addition to inhibiting cyclooxygenase activity, exert an antiproliferative effect on VSMC growth both in-vitro and in-vivo. However, whether all non-steroidal anti-inflammatory drugs (NSAIDs) exert similar anti proliferative effects on VSMCs, and do so via a common mechanism of action, remains to be shown. In this study, we demonstrate that the NSAIDs aspirin, sodium salicylate, diclofenac, ibuprofen, indometacin and sulindac induce a dose-dependent inhibition of proliferation in rat A10 VSMCs in the absence of significant cytotoxicity. Flow cytometric analyses showed that exposure of A10 cells to diclofenac, indometacin, ibuprofen and sulindac, in the presence of the mitotic inhibitor, nocodazole, led to a significant G0/G1 arrest. In contrast, the salicylates failed to induce a significant G1 arrest since flow cytometry profiles were not significantly different from control cells. Cyclin A levels were elevated, and hyperphosphorylated p107 was present at significant levels, in salicylate-treated A10 cells, consistent with a post-G1/S block, whereas cyclin A levels were low, and hypophosphorylated p107 was the dominant form, in cells treated with other NSAIDs consistent with a G1 arrest. The ubiquitously expressed cyclin-dependent kinase (CDK) inhibitors, p21 and p27, were increased in all NSAID-treated cells. Our results suggest that diclofenac, indometacin, ibuprofen and sulindac inhibit VSMC proliferation by arresting the cell cycle in the G1 phase, whereas the growth inhibitory effect of salicylates probably affects the late S and/or G2/M phases. Irrespective of mechanism, our results suggest that NSAIDs might be of benefit in the treatment of certain vasculoproliferative disorders.

Reprogramming the cell cycle machinery to treat cardiovascular disease

Coronary artery disease is one of the most common heart pathologies. Restriction of blood flow to the heart by atherosclerotic lesions, leading to angina pectoris and myocardial infarction, damages the heart, resulting in impaired cardiac function. Damaged myocardium is replaced by scar tissue since surviving cardiomyocytes are unable to proliferate to replace lost heart tissue. Although narrowing of the coronary arteries can be treated successfully using coronary revascularisation procedures, re-occlusion of the treated vessels remains a significant clinical problem. Cell cycle control mechanisms are key in both the impaired cardiac repair by surviving cardiomyocytes and re-narrowing of treated vessels by maladaptive proliferation of vascular smooth muscle cells. Strategies targeting the cell cycle machinery in the heart and vasculature offer promise both for the improvement of cardiac repair following MI and the prevention of restenosis and bypass graft failure following revascularisation procedures.

Localization to the nucleolus is a common feature of coronavirus nucleoproteins and the protein may disrupt host cell division

The subcellular localization of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) (group I and group II coronaviruses, respectively) nucleoproteins (N proteins) were examined by confocal microscopy. The proteins were shown to localize either to the cytoplasm alone or to the cytoplasm and a structure in the nucleus. This feature was confirmed to be the nucleolus by using specific antibodies to nucleolin, a major component of the nucleolus, and by confocal microscopy to image sections through a cell expressing N protein. These findings are consistent with our previous report for infectious bronchitis virus (group III coronavirus) (J. A. Hiscox et al., J. Virol. 75:506-512, 2001), indicating that nucleolar localization of the N protein is a common feature of the coronavirus family and is possibly of functional significance. Nucleolar localization signals were identified in the domain III region of the N protein from all three coronavirus groups, and this suggested that transport of N protein to the nucleus might be an active process. In addition, our results suggest that the N protein might function to disrupt cell division. Thus, we observed that approximately 30% of cells transfected with the N protein appeared to be undergoing cell division. The most likely explanation for this is that the N protein induced a cell cycle delay or arrest, most likely in the G2/M phase. In a fraction of transfected cells expressing coronavirus N proteins, we observed multinucleate cells and dividing cells with nucleoli (which are only present during interphase). These findings are consistent with the possible inhibition of cytokinesis in these cells.

Hydrological cycle in the Danube basin in present-day and XXII century simulations by IPCCAR4 global climate models

We present an intercomparison and verification analysis of 20 GCMs (Global Circulation Models) included in the 4th IPCC assessment report regarding their representation of the hydrological cycle on the Danube river basin for 1961–2000 and for the 2161–2200 SRESA1B scenario runs. The basin-scale properties of the hydrological cycle are computed by spatially integrating the precipitation, evaporation, and runoff fields using the Voronoi-Thiessen tessellation formalism. The span of the model- simulated mean annual water balances is of the same order of magnitude of the observed Danube discharge of the Delta; the true value is within the range simulated by the models. Some land components seem to have deficiencies since there are cases of violation of water conservation when annual means are considered. The overall performance and the degree of agreement of the GCMs are comparable to those of the RCMs (Regional Climate Models) analyzed in a previous work, in spite of the much higher resolution and common nesting of the RCMs. The reanalyses are shown to feature several inconsistencies and cannot be used as a verification benchmark for the hydrological cycle in the Danubian region. In the scenario runs, for basically all models the water balance decreases, whereas its interannual variability increases. Changes in the strength of the hydrological cycle are not consistent among models: it is confirmed that capturing the impact of climate change on the hydrological cycle is not an easy task over land areas. Moreover, in several cases we find that qualitatively different behaviors emerge among the models: the ensemble mean does not represent any sort of average model, and often it falls between the models’ clusters.

The role of horizontal resolution in simulating drivers of the global hydrological cycle

The role of atmospheric general circulation model (AGCM) horizontal resolution in representing the global energy budget and hydrological cycle is assessed, with the aim of improving the understanding of model uncertainties in simulating the hydrological cycle. We use two AGCMs from the UK Met Office Hadley Centre: HadGEM1-A at resolutions ranging from 270 to 60 km, and HadGEM3-A ranging from 135 to 25 km. The models exhibit a stable hydrological cycle, although too intense compared to reanalyses and observations. This over-intensity is explained by excess surface shortwave radiation, a common error in general circulation models (GCMs). This result is insensitive to resolution. However, as resolution is increased, precipitation decreases over the ocean and increases over the land. This is associated with an increase in atmospheric moisture transport from ocean to land, which changes the partitioning of moisture fluxes that contribute to precipitation over land from less local to more non-local moisture sources. The results start to converge at 60-km resolution, which underlines the excessive reliance of the mean hydrological cycle on physical parametrization (local unresolved processes) versus model dynamics (large-scale resolved processes) in coarser HadGEM1 and HadGEM3 GCMs. This finding may be valid for other GCMs, showing the necessity to analyze other chains of GCMs that may become available in the future with such a range of horizontal resolutions. Our finding supports the hypothesis that heterogeneity in model parametrization is one of the underlying causes of model disagreement in the Coupled Model Intercomparison Project (CMIP) exercises.

Propagation of the Madden–Julian Oscillation and scale interaction with the diurnal cycle in a high-resolution GCM

The Madden–Julian Oscillation (MJO) is the chief source of tropical intra-seasonal variability, but is simulated poorly by most state-of-the-art GCMs. Common errors include a lack of eastward propagation at the correct frequency and zonal extent, and too small a ratio of eastward- to westward-propagating variability. Here it is shown that HiGEM, a high-resolution GCM, simulates a very realistic MJO with approximately the correct spatial and temporal scale. Many MJO studies in GCMs are limited to diagnostics which average over a latitude band around the equator, allowing an analysis of the MJO’s structure in time and longitude only. In this study a wider range of diagnostics is applied. It is argued that such an approach is necessary for a comprehensive analysis of a model’s MJO. The standard analysis of Wheeler and Hendon (Mon Wea Rev 132(8):1917–1932, 2004; WH04) is applied to produce composites, which show a realistic spatial structure in the MJO envelopes but for the timing of the peak precipitation in the inter-tropical convergence zone, which bifurcates the MJO signal. Further diagnostics are developed to analyse the MJO’s episodic nature and the “MJO inertia” (the tendency to remain in the same WH04 phase from one day to the next). HiGEM favours phases 2, 3, 6 and 7; has too much MJO inertia; and dies out too frequently in phase 3. Recent research has shown that a key feature of the MJO is its interaction with the diurnal cycle over the Maritime Continent. This interaction is present in HiGEM but is unrealistically weak.

Arthur et ses barons rebelles: la fin remaniée et abrégée de la Suite Vulgate dans le manuscrit du cycle du Graal, Paris, BNF fr. 344

The ms. Paris, BnF, fr. 344 was produced in Lorraine at the end of the thirteenth century and contains the whole Lancelot-Grail cycle. It presents an abridged version of the end of the Vulgate Sequel to Merlin. The rewriting of the end of the sequel glosses over the romantic episodes of the common version and focuses on the figure of Arthur, a legitimate sovereign and skilful war leader confronted by his barons’ dissidence. From the end of f° 182 to f° 184v°, BnF, fr. 344, narrates the departure of Kings Ban and Bohort for the Continent, the embassy of King Loth and his sons, and the fight against the Saxons of the Christian coalition gathered at Logres for the feast of the Holy Cross. This article shows the ideological implications of the abridgement and the illustration used at the end of the Vulgate Sequel in ms. fr. 344, as it exalts Arthur’s kingship and insists on the rallying, penance and submission of his rebelled vassals.

A multi-model evaluation of aerosols over South Asia: common problems and possible causes

Atmospheric pollution over South Asia attracts special attention due to its effects on regional climate, water cycle and human health. These effects are potentially growing owing to rising trends of anthropogenic aerosol emissions. In this study, the spatio-temporal aerosol distributions over South Asia from seven global aerosol models are evaluated against aerosol retrievals from NASA satellite sensors and ground-based measurements for the period of 2000–2007. Overall, substantial underestimations of aerosol loading over South Asia are found systematically in most model simulations. Averaged over the entire South Asia, the annual mean aerosol optical depth (AOD) is underestimated by a range 15 to 44% across models compared to MISR (Multi-angle Imaging SpectroRadiometer), which is the lowest bound among various satellite AOD retrievals (from MISR, SeaWiFS (Sea-Viewing Wide Field-of-View Sensor), MODIS (Moderate Resolution Imaging Spectroradiometer) Aqua and Terra). In particular during the post-monsoon and wintertime periods (i.e., October–January), when agricultural waste burning and anthropogenic emissions dominate, models fail to capture AOD and aerosol absorption optical depth (AAOD) over the Indo–Gangetic Plain (IGP) compared to ground-based Aerosol Robotic Network (AERONET) sunphotometer measurements. The underestimations of aerosol loading in models generally occur in the lower troposphere (below 2 km) based on the comparisons of aerosol extinction profiles calculated by the models with those from Cloud–Aerosol Lidar with Orthogonal Polarization (CALIOP) data. Furthermore, surface concentrations of all aerosol components (sulfate, nitrate, organic aerosol (OA) and black carbon (BC)) from the models are found much lower than in situ measurements in winter. Several possible causes for these common problems of underestimating aerosols in models during the post-monsoon and wintertime periods are identified: the aerosol hygroscopic growth and formation of secondary inorganic aerosol are suppressed in the models because relative humidity (RH) is biased far too low in the boundary layer and thus foggy conditions are poorly represented in current models, the nitrate aerosol is either missing or inadequately accounted for, and emissions from agricultural waste burning and biofuel usage are too low in the emission inventories. These common problems and possible causes found in multiple models point out directions for future model improvements in this important region.

Evaluation of methods of detecting cell reactive oxygen species production for drug screening and cell cycle studies

Intracellular reactive oxygen species (ROS) production is essential to normal cell function. However, excessive ROS production causes oxidative damage and cell death. Many pharmacological compounds exert their effects on cell cycle progression by changing intracellular redox state and in many cases cause oxidative damage leading to drug cytotoxicity. Appropriate measurement of intracellular ROS levels during cell cycle progression is therefore crucial in understanding redox-regulation of cell function and drug toxicity and for the development of new drugs. However, due to the extremely short half-life of ROS, measuring the changes in intracellular ROS levels during a particular phase of cell cycle for drug intervention can be challenging. In this article, we have provided updated information on the rationale, the applications, the advantages and limitations of common methods for screening drug effects on intracellular ROS production linked to cell cycle study. Our aim is to facilitate biomedical scientists and researchers in the pharmaceutical industry in choosing or developing specific experimental regimens to suit their research needs.