Effects of dendritic morphology on CA3 pyramidal cell electrophysiology: a simulation study

We investigated the effect of morphological differences on neuronal firing behavior within the hippocampal CA3 pyramidal cell family by using three-dimensional reconstructions of dendritic morphology in computational simulations of electrophysiology. In this paper, we report for the first time that differences in dendritic structure within the same morphological class can have a dramatic influence on the firing rate and firing mode (spiking versus bursting and type of bursting). Our method consisted of converting morphological measurements from three-dimensional neuroanatomical data of CA3 pyramidal cells into a computational simulator format. In the simulation, active channels were distributed evenly across the cells so that the electrophysiological differences observed in the neurons would only be due to morphological differences. We found that differences in the size of the dendritic tree of CA3 pyramidal cells had a significant qualitative and quantitative effect on the electrophysiological response. Cells with larger dendritic trees: (1) had a lower burst rate, but a higher spike rate within a burst, (2) had higher thresholds for transitions from quiescent to bursting and from bursting to regular spiking and (3) tended to burst with a plateau. Dendritic tree size alone did not account for all the differences in electrophysiological responses. Differences in apical branching, such as the distribution of branch points and terminations per branch order, appear to effect the duration of a burst. These results highlight the importance of considering the contribution of morphology in electrophysiological and simulation studies.

Investigation of K14/K5 as a stem cell marker in the limbal region of the bovine cornea

Background: Identification of stem cells from a corneal epithelial cell population by specific molecular markers has been investigated previously. Expressions of P63, ABCG2 and K14/K5 have all been linked to mammalian corneal epithelial stem cells. Here we report on the limitations of K14/K5 as a limbal stem cell marker. Methodology/Principal Findings: K14/K5 expression was measured by immunohistochemistry, Western blotting and Real time PCR and compared between bovine epithelial cells in the limbus and central cornea. A functional study was also included to investigate changes in K5/14 expression within cultured limbal epithelial cells undergoing forced differentiation. K14 expression (or its partner K5) was detected in quiescent epithelial cells from both the limbal area and central cornea. K14 was localized predominantly to basal epithelial cells in the limbus and suprabasal epithelial cells in the central cornea. Western blotting revealed K14 expression in both limbus and central cornea (higher levels in the limbus). Similarly, quantitative real time PCR found K5, partner to K14, to be expressed in both the central cornea and limbus. Following forced differentiation in culture the limbal epithelial cells revealed an increase in K5/14 gene/protein expression levels in concert with a predictable rise in a known differentiation marker. Conclusions/Significance: K14 and its partner K5 are limited not only to the limbus but also to the central bovine cornea epithelial cells suggesting K14/K5 is not limbal specific in situ. Furthermore K14/K5 expression levels were not lowered (in fact they increased) within a limbal epithelial cell culture undergoing forced differentiation suggesting K14/K5 is an unreliable maker for undifferentiated cells ex vivo.

Modelling acidosis and the cell cycle in multicellular tumour spheroids

A partial differential equation model is developed to understand the effect that nutrient and acidosis have on the distribution of proliferating and quiescent cells and dead cell material (necrotic and apopotic) within a multicellular tumour spheroid. The rates of cell quiescence and necrosis depend upon the local nutrient and acid concentrations and quiescent cells are assumed to consume less nutrient and produce less acid than proliferating cells. Analysis of the differences in nutrient consumption and acid production by quiescent and proliferating cells shows low nutrient levels do not necessarily lead to increased acid concentration via anaerobic metabolism. Rather, it is the balance between proliferating and quiescent cells within the tumour which is important; decreased nutrient levels lead to more quiescent cells, which produce less acid than proliferating cells. We examine this effect via a sensitivity analysis which also includes a quantification of the effect that nutrient and acid concentrations have on the rates of cell quiescence and necrosis.

Multi-year droughts in Europe: analysis of development and causes

Whilst hydrological systems can show resilience to short-term streamflow deficiencies during within-year droughts, prolonged deficits during multi-year droughts are a significant threat to water resources security in Europe. This study uses a threshold-based objective classification of regional hydrological drought to qualitatively examine the characteristics, spatio-temporal evolution and synoptic climatic drivers of multi-year drought events in 1962–64, 1975–76 and 1995–97, on a European scale but with particular focus on the UK. Whilst all three events are multi-year, pan-European phenomena, their development and causes can be contrasted. The critical factor in explaining the unprecedented severity of the 1975–76 event is the consecutive occurrence of winter and summer drought. In contrast, 1962–64 was a succession of dry winters, mitigated by quiescent summers, whilst 1995–97 lacked spatial coherence and was interrupted by wet interludes. Synoptic climatic conditions vary within and between multi-year droughts, suggesting that regional factors modulate the climate signal in streamflow drought occurrence. Despite being underpinned by qualitatively similar climatic conditions and commonalities in evolution and characteristics, each of the three droughts has a unique spatio-temporal signature. An improved understanding of the spatio-temporal evolution and characteristics of multi-year droughts has much to contribute to monitoring and forecasting capability, and to improved mitigation strategies.

On the approximation of local and linear radiative damping in the middle atmosphere

The validity of approximating radiative heating rates in the middle atmosphere by a local linear relaxation to a reference temperature state (i.e., ‘‘Newtonian cooling’’) is investigated. Using radiative heating rate and temperature output from a chemistry–climate model with realistic spatiotemporal variability and realistic chemical and radiative parameterizations, it is found that a linear regressionmodel can capture more than 80% of the variance in longwave heating rates throughout most of the stratosphere and mesosphere, provided that the damping rate is allowed to vary with height, latitude, and season. The linear model describes departures from the climatological mean, not from radiative equilibrium. Photochemical damping rates in the upper stratosphere are similarly diagnosed. Threeimportant exceptions, however, are found.The approximation of linearity breaks down near the edges of the polar vortices in both hemispheres. This nonlinearity can be well captured by including a quadratic term. The use of a scale-independentdamping rate is not well justified in the lower tropical stratosphere because of the presence of a broad spectrum of vertical scales. The local assumption fails entirely during the breakup of the Antarctic vortex, where large fluctuations in temperature near the top of the vortex influence longwave heating rates within the quiescent region below. These results are relevant for mechanistic modeling studies of the middle atmosphere, particularly those investigating the final Antarctic warming.

Persistence and photochemical decay of springtime total ozone anomalies in the Canadian Middle Atmosphere Model

The persistence and decay of springtime total ozone anomalies over the entire extratropics (midlatitudes plus polar regions) is analysed using results from the Canadian Middle Atmosphere Model (CMAM), a comprehensive chemistry-climate model. As in the observations, interannual anomalies established through winter and spring persist with very high correlation coefficients (above 0.8) through summer until early autumn, while decaying in amplitude as a result of photochemical relaxation in the quiescent summertime stratosphere. The persistence and decay of the ozone anomalies in CMAM agrees extremely well with observations, even in the southern hemisphere when the model is run without heterogeneous chemistry (in which case there is no ozone hole and the seasonal cycle of ozone is quite different from observations). However in a version of CMAM with strong vertical diffusion, the northern hemisphere anomalies decay far too rapidly compared to observations. This shows that ozone anomaly persistence and decay does not depend on how the springtime anomalies are created or on their magnitude, but reflects the transport and photochemical decay in the model. The seasonality of the long-term trends over the entire extratropics is found to be explained by the persistence of the interannual anomalies, as in the observations, demonstrating that summertime ozone trends reflect winter/spring trends rather than any change in summertime ozone chemistry. However this mechanism fails in the northern hemisphere midlatitudes because of the relatively large impact, compared to observations, of the CMAM polar anomalies. As in the southern hemisphere, the influence of polar ozone loss in CMAM increases the midlatitude summertime loss, leading to a relatively weak seasonal dependence of ozone loss in the Northern Hemisphere compared to the observations.

Robust approaches to forecasting

We investigate alternative robust approaches to forecasting, using a new class of robust devices, contrasted with equilibrium-correction models. Their forecasting properties are derived facing a range of likely empirical problems at the forecast origin, including measurement errors, impulses, omitted variables, unanticipated location shifts and incorrectly included variables that experience a shift. We derive the resulting forecast biases and error variances, and indicate when the methods are likely to perform well. The robust methods are applied to forecasting US GDP using autoregressive models, and also to autoregressive models with factors extracted from a large dataset of macroeconomic variables. We consider forecasting performance over the Great Recession, and over an earlier more quiescent period.

Lattice dynamics study of microstructures of electrorheological fluids

The lattice dynamics method is used to study the stability of the chain structures formed in electrorheological (ER) fluids. The appearance of the soft modes in the phonon dispersion of the structures indicates that the chains tend to distort and aggregate into thicker columns due to the electrostatic attractive forces and thermal generated forces between them. The results show that the stability of the chains relies on their width and the separation between them. The complete chain structures are more stable than the chains with defects. The results can be used to elucidate the densification phenomenon of the chains in the structuring process of ER fluids in the quiescent state.

Aerosol microphysics simulations of the Mt.~Pinatubo eruption with the UM-UKCA composition-climate model

We use a stratosphere–troposphere composition–climate model with interactive sulfur chemistry and aerosol microphysics, to investigate the effect of the 1991 Mount Pinatubo eruption on stratospheric aerosol properties. Satellite measurements indicate that shortly after the eruption, between 14 and 23 Tg of SO2 (7 to 11.5 Tg of sulfur) was present in the tropical stratosphere. Best estimates of the peak global stratospheric aerosol burden are in the range 19 to 26 Tg, or 3.7 to 6.7 Tg of sulfur assuming a composition of between 59 and 77 % H2SO4. In light of this large uncertainty range, we performed two main simulations with 10 and 20 Tg of SO2 injected into the tropical lower stratosphere. Simulated stratospheric aerosol properties through the 1991 to 1995 period are compared against a range of available satellite and in situ measurements. Stratospheric aerosol optical depth (sAOD) and effective radius from both simulations show good qualitative agreement with the observations, with the timing of peak sAOD and decay timescale matching well with the observations in the tropics and mid-latitudes. However, injecting 20 Tg gives a factor of 2 too high stratospheric aerosol mass burden compared to the satellite data, with consequent strong high biases in simulated sAOD and surface area density, with the 10 Tg injection in much better agreement. Our model cannot explain the large fraction of the injected sulfur that the satellite-derived SO2 and aerosol burdens indicate was removed within the first few months after the eruption. We suggest that either there is an additional alternative loss pathway for the SO2 not included in our model (e.g. via accommodation into ash or ice in the volcanic cloud) or that a larger proportion of the injected sulfur was removed via cross-tropopause transport than in our simulations. We also critically evaluate the simulated evolution of the particle size distribution, comparing in detail to balloon-borne optical particle counter (OPC) measurements from Laramie, Wyoming, USA (41° N). Overall, the model captures remarkably well the complex variations in particle concentration profiles across the different OPC size channels. However, for the 19 to 27 km injection height-range used here, both runs have a modest high bias in the lowermost stratosphere for the finest particles (radii less than 250 nm), and the decay timescale is longer in the model for these particles, with a much later return to background conditions. Also, whereas the 10 Tg run compared best to the satellite measurements, a significant low bias is apparent in the coarser size channels in the volcanically perturbed lower stratosphere. Overall, our results suggest that, with appropriate calibration, aerosol microphysics models are capable of capturing the observed variation in particle size distribution in the stratosphere across both volcanically perturbed and quiescent conditions. Furthermore, additional sensitivity simulations suggest that predictions with the models are robust to uncertainties in sub-grid particle formation and nucleation rates in the stratosphere.

The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling

The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.

Links between tropical Pacific seasonal, interannual and orbital variability during the Holocene

The El Niño/Southern Oscillation (ENSO) is the leading mode of interannual climate variability. However, it is unclear how ENSO has responded to external forcing, particularly orbitally induced changes in the amplitude of the seasonal cycle during the Holocene. Here we present a reconstruction of seasonal and interannual surface conditions in the tropical Pacific Ocean from a network of high-resolution coral and mollusc records that span discrete intervals of the Holocene. We identify several intervals of reduced variance in the 2 to 7 yr ENSO band that are not in phase with orbital changes in equatorial insolation, with a notable 64% reduction between 5,000 and 3,000 years ago. We compare the reconstructed ENSO variance and seasonal cycle with that simulated by nine climate models that include orbital forcing, and find that the models do not capture the timing or amplitude of ENSO variability, nor the mid-Holocene increase in seasonality seen in the observations; moreover, a simulated inverse relationship between the amplitude of the seasonal cycle and ENSO-related variance in sea surface temperatures is not found in our reconstructions. We conclude that the tropical Pacific climate is highly variable and subject to millennial scale quiescent periods. These periods harbour no simple link to orbital forcing, and are not adequately simulated by the current generation of models.

Selective environmental stress caused by magmatic sulfur emissions from continental flood basalt eruptions

Several biotic crises during the past 300 million years have been linked to episodes of continental flood basalt volcanism, and in particular to the release of massive quantities of magmatic sulphur gas species. Flood basalt provinces were typically formed by numerous individual eruptions, each lasting years to decades. However, the environmental impact of these eruptions may have been limited by the occurrence of quiescent periods that lasted hundreds to thousands of years. Here we use a global aerosol model to quantify the sulphur-induced environmental effects of individual, decade-long flood basalt eruptions representative of the Columbia River Basalt Group, 16.5–14.5 million years ago, and the Deccan Traps, 65 million years ago. For a decade-long eruption of Deccan scale, we calculate a decadal-mean reduction in global surface temperature of 4.5 K, which would recover within 50 years after an eruption ceased unless climate feedbacks were very different in deep-time climates. Acid mists and fogs could have caused immediate damage to vegetation in some regions, but acid-sensitive land and marine ecosystems were well-buffered against volcanic sulphur deposition effects even during century-long eruptions. We conclude that magmatic sulphur from flood basalt eruptions would have caused a biotic crisis only if eruption frequencies and lava discharge rates had been high and sustained for several centuries at a time.

Modelling the line variations from the wind-wind shock emissions of WR 30a

The study of Wolf-Rayet stars plays an important role in evolutionary theories of massive stars. Among these objects, similar to 20 per cent are known to be in binary systems and can therefore be used for the mass determination of these stars. Most of these systems are not spatially resolved and spectral lines can be used to constrain the orbital parameters. However, part of the emission may originate in the interaction zone between the stellar winds, modifying the line profiles and thus challenging us to use different models to interpret them. In this work, we analysed the He II lambda 4686 angstrom + C IV lambda 4658 angstrom blended lines of WR 30a (WO4+O5) assuming that part of the emission originate in the wind-wind interaction zone. In fact, this line presents a quiescent base profile, attributed to the WO wind, and a superposed excess, which varies with the orbital phase along the 4.6-d period. Under these assumptions, we were able to fit the excess spectral line profile and central velocity for all phases, except for the longest wavelengths, where a spectral line with constant velocity seems to be present. The fit parameters provide the eccentricity and inclination of the binary orbit, from which it is possible to constrain the stellar masses.

Particle acceleration and magnetic field structure in PKS 2155-304: optical polarimetric observations

In this paper, we present multiband optical polarimetric observations of the very-high energy blazar PKS 2155-304 made simultaneously with a HESS/Fermi high-energy campaign in 2008, when the source was found to be in a low state. The intense daily coverage of the data set allowed us to study in detail the temporal evolution of the emission, and we found that the particle acceleration time-scales are decoupled from the changes in the polarimetric properties of the source. We present a model in which the optical polarimetric emission originates at the polarized mm-wave core and propose an explanation for the lack of correlation between the photometric and polarimetric fluxes. The optical emission is consistent with an inhomogeneous synchrotron source in which the large-scale field is locally organized by a shock in which particle acceleration takes place. Finally, we use these optical polarimetric observations of PKS 2155-304 at a low state to propose an origin for the quiescent gamma-ray flux of the object, in an attempt to provide clues for the source of its recently established persistent TeV emission.

Axillary bud development in pineapple nodal segments correlates with changes on cell cycle gene expression, hormone level, and sucrose and glutamate contents

During the process of lateral organ development after plant decapitation, cell division and differentiation occur in a balanced manner initiated by specific signaling, which triggers the reentrance into the cell cycle. Here, we investigated short-term variations in the content of some endogenous signals, such as auxin, cytokinins (Cks), and other mitogenic stimuli (sucrose and glutamate), which are likely correlated with the cell cycle reactivation in the axillary bud primordium of pineapple nodal segments. Transcript levels of cell cycle-associated genes, CycD2;1, and histone H2A were analyzed. Nodal segments containing the quiescent axillary meristem cells were cultivated in vitro during 24 h after the apex removal and de-rooting. From the moment of stem apex and root removal, decapitated nodal segment (DNS) explants showed a lower indol-3-acetic acid (IAA) concentration than control explants, and soon after, an increase of endogenous sucrose and iP-type Cks were detected. The decrease of IAA may be the primary signal for cell cycle control early in G1 phase, leading to the upregulation of CycD2;1 gene in the first h. Later, the iP-type Cks and sucrose could have triggered the progression to S-phase since there was an increase in H2A expression at the eighth h. DNS explants revealed substantial increase in Z-type Cks and glutamate from the 12th h, suggesting that these mitogens could also operate in promoting pineapple cell cycle progression. We emphasize that the use of non-synchronized tissue rather than synchronous cell suspension culture makes it more difficult to interpret the results of a dynamic cell division process. However, pineapple nodal segments cultivated in vitro may serve as an interesting model to shed light on apical dominance release and the reentrance of quiescent axillary meristem cells into the cell cycle.