ALBERT

Description: The predicted effect of effective population size on the distribution of fitness effects and substitution rate is critically dependent on the relationship between sequence and fitness. This highlights the importance of using models that are informed by the molecular biology, biochemistry, and biophysics of the evolving systems. We describe a computational model based on fundamental aspects of biophysics, the requirement for (most) proteins to be thermodynamically stable. Using this model, we find that differences in population size have minimal impact on the distribution of population-scaled fitness effects, as well as on the rate of molecular evolution. This is because larger populations result in selection for more stable proteins that are less affected by mutations. This reduction in the magnitude of the fitness effects almost exactly cancels the greater selective pressure resulting from the larger population size. Conversely, changes in the population size in either direction cause transient increases in the substitution rate. As differences in population size often correspond to changes in population size, this makes comparisons of substitution rates in different lineages difficult to interpret.

Description: Regional and local patterns in depth to water table, hydrochemistry and peat properties of bogs and their laggs in coastal British Columbia Hydrology and Earth System Sciences, 17, 3421-3435, 2013 Author(s): S. A. Howie and H. J. van Meerveld In restoration planning for damaged raised bogs, the lagg at the bog margin is often not given considerable weight and is sometimes disregarded entirely. However, the lagg is critical for the proper functioning of the bog, as it supports the water mound in the bog. In order to include the lagg in a restoration plan for a raised bog, it is necessary to understand the hydrological characteristics and functions of this rarely studied transition zone. We studied 13 coastal British Columbia (BC) bogs and identified two different gradients in depth to water table, hydrochemistry and peat properties: (1) a local bog expanse–bog margin gradient, and (2) a regional gradient related to climate and proximity to the ocean. Depth to water table generally increased across the transition from bog expanse to bog margin. In the bog expanse, pH was above 4.2 in the Pacific Oceanic wetland region (cooler and wetter climate) and below 4.3 in the Pacific Temperate wetland region (warmer and drier climate). Both pH and pH-corrected electrical conductivity increased significantly across the transition from bog expanse to bog margin, though not in all cases. Na + and Mg 2+ concentrations were generally highest in exposed, oceanic bogs and lower in inland bogs. Ash content in peat samples increased across the bog expanse–bog margin transition, and appears to be a useful abiotic indicator of the location of the bog margin. The observed variation in the hydrological and hydrochemical gradients across the bog expanse–bog margin transition highlights both local and regional diversity of bogs and their associated laggs.

Description: Imperfect scaling in distributions of radar-derived rainfall fields Hydrology and Earth System Sciences Discussions, 10, 11385-11422, 2013 Author(s): M. J. van den Berg, L. Delobbe, and N. E. C. Verhoest Fine scale rainfall observations for modeling exercises are often not available, but rather coarser data derived from a variety of sources are used. Effectively using these data sources in models often requires the probability distribution of the data at the applicable scale. Although numerous models for scaling distributions exist, these are often based on theoretical developments, rather than on data. In this study, we develop a model based on the α-stable distribution of rainfall fields, and tested on 5 min radar data from a Belgian weather radar. We use these data to estimate functions that describe parameters of the distribution over various scales. Moreover, we study how the mean of the distribution and the intermittency change with scale, and validate and design functions to describe the shape parameter of the distribution. This information was combined into an effective model of the distribution. Finally, the model was fitted to data from numerous storms, and the resulting parameters were compared to investigate the change in scaling behavior through time.

Description: Spatially resolved information on karst conduit flow from in-cave dye-tracing Hydrology and Earth System Sciences Discussions, 10, 11311-11335, 2013 Author(s): U. Lauber, W. Ufrecht, and N. Goldscheider Artificial tracers are powerful tools to investigate karst systems. Tracers are commonly injected into sinking streams or dolines, while springs serve as monitoring sites. The obtained flow and transport parameters represent mixed information from the vadose, epiphreatic and phreatic zones, i.e., the aquifer remains a black box. Accessible active caves constitute valuable but underexploited natural laboratories to gain detailed insights into the hydrologic functioning of the aquifer. Two multi-tracer tests in the catchment of a major karst spring (Blautopf, Germany) with injections and monitoring in two associated water caves aimed at obtaining spatially and temporally resolved information on groundwater flow in different compartments of the system. Two tracers were injected in the caves to characterize the hydraulic connections between them and with the spring. Two injections at the land surface, far from the spring, aimed at resolving the aquifer's internal drainage structure. Tracer breakthrough curves were monitored by field fluorimeters in caves and at the spring. Results demonstrate the dendritic drainage structure of the aquifer. It was possible to obtain relevant flow and transport parameters for different sections of this system. The highest mean flow velocities (275 m h −1 ) were observed in the near-spring epiphreatic section (open-channel flow), while velocities in the phreatic zone (pressurized flow) were one order of magnitude lower. Determined conduit water volumes confirm results of water balances and hydrograph analyses. In conclusion, experiments and monitoring in caves can deliver spatially resolved information on karst aquifer heterogeneity and dynamics that cannot be obtained by traditional investigative methods.

Description: On the lack of robustness of hydrologic models regarding water balance simulation – a diagnostic approach on 20 mountainous catchments using three models of increasing complexity Hydrology and Earth System Sciences Discussions, 10, 11337-11383, 2013 Author(s): L. Coron, V. Andréassian, C. Perrin, M. Bourqui, and F. Hendrickx This paper investigates the robustness of rainfall–runoff models when their parameters are transferred in time. More specifically, we studied their ability to simulate water balance on periods with different hydroclimatic characteristics. The testing procedure consisted in a series of parameter transfers between 10-yr periods and the systematic analysis of mean-volume errors. This procedure was applied to three conceptual models of different structural complexity over 20 mountainous catchments in southern France. The results showed that robustness problems are common. Errors on 10-yr-mean flows were significant for all three models and calibration periods, even when the entire record was used for calibration. Various graphical and numerical tools were used to show strong similarities between the shapes of mean flow biases calculated on a 10-yr-long sliding window when various parameter sets are used. Unexpected behavioural similarities were observed between the three models tested, considering their large differences in structural complexity. While the actual causes for robustness problems in these models remain unclear, this work stresses the limited transferability in time of the water balance adjustments made through parameter optimization. Although absolute differences between simulations obtained with different calibrated parameter sets were sometimes substantial, relative differences in simulated mean flows between time periods remained similar regardless of the calibrated parameter sets.

Description: Bayesian networks modelling in support to cross-cutting analysis of water supply and sanitation in developing countries Hydrology and Earth System Sciences, 17, 3397-3419, 2013 Author(s): C. Dondeynaz, J. López Puga, and C. Carmona Moreno Despite the efforts made towards the Millennium Development Goals targets during the last decade, improved access to water supply or basic sanitation still remains unavailable for millions of people across the world. This paper proposes a set of models that use 25 key variables and country profiles from the WatSan4Dev data set involving water supply and sanitation (Dondeynaz et al., 2012). This paper suggests the use of Bayesian network modelling methods because they are more easily adapted to deal with non-normal distributions, and integrate a qualitative approach for data analysis. They also offer the advantage of integrating preliminary knowledge into the probabilistic models. The statistical performance of the proposed models ranges between 20 and 5% error rates, which are very satisfactory taking into account the strong heterogeneity of variables. Probabilistic scenarios run from the models allow an assessment of the relationships between human development, external support, governance aspects, economic activities and water supply and sanitation (WSS) access. According to models proposed in this paper, gaining a strong poverty reduction will require the WSS access to reach 75–76% through: (1) the management of ongoing urbanisation processes to avoid slums development; and (2) the improvement of health care, for instance for children. Improving governance, such as institutional efficiency, capacities to make and apply rules, or control of corruption is positively associated with WSS sustainable development. The first condition for an increment of the HDP (human development and poverty) remains of course an improvement of the economic conditions with higher household incomes. Moreover, a significant country commitment to the environment, associated with civil society freedom of expression constitutes a favourable setting for sustainable WSS services delivery. Intensive agriculture using irrigation practises also appears as a mean for sustainable WSS thanks to multi-uses and complementarities. With a WSS sector organised at national level, irrigation practices can support the structuring and efficiency of the agriculture sector. It may then induce rural development in areas where WSS access often is set back compared to urban areas 1 . External financial support, called Official Development Assistance (ODA CI), plays a role in WSS improvement but comes last in the sensitivity analyses of models. An overall 47% of the Official Development Assistance goes first to poor countries, and is associated to governance aspects: (1) political stability and (2) country commitment to the environment and civil society degree of freedom. These governance aspects constitute a good framework for aid implementation in recipient countries. Modelling is run with the five groups of countries as defined in Dondeynaz et al. (2012). Models for profile 4 (essential external support) and profile 5 (primary material consumption) are specifically detailed and analysed in this paper. For countries in profile 4, fighting against water scarcity and progressing desertification should be the priority. However, for countries in profile 5, efforts should first concentrate on consolidation of political stability while supporting diversification of the economic activities. Nevertheless, for both profiles, reduction of poverty should remain the first priority as previously indicated. 1 JMP statistics, 2004 http://www.wssinfo.org/data-estimates/table/ , last access: 22 July 2013.

Description: Technical Note: A comparison of model and empirical measures of catchment-scale effective energy and mass transfer Hydrology and Earth System Sciences, 17, 3389-3395, 2013 Author(s): C. Rasmussen and E. L. Gallo Recent work suggests that a coupled effective energy and mass transfer (EEMT) term, which includes the energy associated with effective precipitation and primary production, may serve as a robust prediction parameter of critical zone structure and function. However, the models used to estimate EEMT have been solely based on long-term climatological data with little validation using direct empirical measures of energy, water, and carbon balances. Here we compare catchment-scale EEMT estimates generated using two distinct approaches: (1) EEMT modeled using the established methodology based on estimates of monthly effective precipitation and net primary production derived from climatological data, and (2) empirical catchment-scale EEMT estimated using data from 86 catchments of the Model Parameter Estimation Experiment (MOPEX) and MOD17A3 annual net primary production (NPP) product derived from Moderate Resolution Imaging Spectroradiometer (MODIS). Results indicated positive and significant linear correspondence ( R 2 = 0.75; P 〈 0.001) between model and empirical measures with an average root mean square error (RMSE) of 4.86 MJ m −2 yr −1 . Modeled EEMT values were consistently greater than empirical measures of EEMT. Empirical catchment estimates of the energy associated with effective precipitation ( E PPT ) were calculated using a mass balance approach that accounts for water losses to quick surface runoff not accounted for in the climatologically modeled E PPT . Similarly, local controls on primary production such as solar radiation and nutrient limitation were not explicitly included in the climatologically based estimates of energy associated with primary production ( E BIO ), whereas these were captured in the remotely sensed MODIS NPP data. These differences likely explain the greater estimate of modeled EEMT relative to the empirical measures. There was significant positive correlation between catchment aridity and the fraction of EEMT partitioned into E BIO ( F BIO ), with an increase in F BIO as a fraction of the total as aridity increases and percentage of catchment woody plant cover decreases. In summary, the data indicated strong correspondence between model and empirical measures of EEMT with limited bias that agree well with other empirical measures of catchment energy and water partitioning and plant cover.

Description: Review Article: On the relation between the seismic activity and the Hurst exponent of the geomagnetic field at the time of the 2000 Izu swarm Natural Hazards and Earth System Science, 13, 2189-2194, 2013 Author(s): F. Masci and J. N. Thomas Many papers document the observation of earthquake-related precursory signatures in geomagnetic field data. However, the significance of these findings is ambiguous because the authors did not adequately take into account that these signals could have been generated by other sources, and the seismogenic origin of these signals have not been validated by comparison with independent datasets. Thus, they are not reliable examples of magnetic disturbances induced by the seismic activity. Hayakawa et al. (2004) claim that at the time of the 2000 Izu swarm the Hurst exponent of the Ultra-Low-Frequency (ULF: 0.001–10 Hz) band of the geomagnetic field varied in accord with the energy released by the seismicity. The present paper demonstrates that the behaviour of the Hurst exponent was insufficiently investigated and also misinterpreted by the authors. We clearly show that during the Izu swarm the changes of the Hurst exponent were strongly related to the level of global geomagnetic activity and not to the increase of the local seismic activity.

Description: Forest fire danger rating in complex topography – results from a case study in the Bavarian Alps in autumn 2011 Natural Hazards and Earth System Science, 13, 2157-2167, 2013 Author(s): C. Schunk, C. Wastl, M. Leuchner, C. Schuster, and A. Menzel Forest fire danger rating based on sparse meteorological stations is known to be potentially misleading when assigned to larger areas of complex topography. This case study examines several fire danger indices based on data from two meteorological stations at different elevations during a major drought period. This drought was caused by a persistent high pressure system, inducing a pronounced temperature inversion and its associated thermal belt with much warmer, dryer conditions in intermediate elevations. Thus, a massive drying of fuels, leading to higher fire danger levels, and multiple fire occurrences at mid-slope positions were contrasted by moderate fire danger especially in the valleys. The ability of fire danger indices to resolve this situation was studied based on a comparison with the actual fire danger as determined from expert observations, fire occurrences and fuel moisture measurements. The results revealed that, during temperature inversion, differences in daily cycles of meteorological parameters influence fire danger and that these are not resolved by standard meteorological stations and fire danger indices (calculated on a once-a-day basis). Additional stations in higher locations or high-resolution meteorological models combined with fire danger indices accepting at least hourly input data may allow reasonable fire danger calculations under these circumstances.

Description: Preface "Landslide hazard and risk assessment at different scales" Natural Hazards and Earth System Science, 13, 2169-2171, 2013 Author(s): P. Reichenbach, A. Günther, and T. Glade

Description: O -GlcNAcylation is an inducible, highly dynamic and reversible post-translational modification, mediated by a unique enzyme named O -linked N -acetyl- d -glucosamine ( O -GlcNAc) transferase (OGT). In response to nutrients, O -GlcNAc levels are differentially regulated on many cellular proteins involved in gene expression, translation, immune reactions, protein degradation, protein–protein interaction, apoptosis and signal transduction. In contrast to eukaryotic cells, little is known about the role of O -GlcNAcylation in the viral life cycle. Here, we show that the overexpression of the OGT reduces the replication efficiency of Kaposi's sarcoma-associated herpesvirus (KSHV) in a dose-dependent manner. In order to investigate the global impact of O -GlcNAcylation in the KSHV life cycle, we systematically analyzed the 85 annotated KSHV-encoded open reading frames for O -GlcNAc modification. For this purpose, an immunoprecipitation (IP) strategy with three different approaches was carried out and the O -GlcNAc signal of the identified proteins was properly controlled for specificity. Out of the 85 KSHV-encoded proteins, 18 proteins were found to be direct targets for O -GlcNAcylation. Selected proteins were further confirmed by mass spectrometry for O -GlcNAc modification. Correlation of the functional annotation and the O -GlcNAc status of KSHV proteins showed that the predominant targets were proteins involved in viral DNA synthesis and replication. These results indicate that O -GlcNAcylation plays a major role in the regulation of KSHV propagation.

Description: Galectins are potent adhesion/growth-regulatory effectors with characteristic expression profiles. Understanding the molecular basis of gene regulation in each case requires detailed information on copy number of genes and sequence(s) of their promoter(s). Our report reveals plasticity in this respect between galectins and species. We here describe occurrence of a two-gene constellation for human galectin (Gal)-7 and define current extent of promoter-sequence divergence. Interestingly, cross-species genome analyses also detected single-copy display. Because the regulatory potential will then be different, extrapolations of expression profiles are precluded between respective species pairs. Gal-4 coding in chromosomal vicinity was found to be confined to one gene, whereas copy-number variation also applied to Gal-9. The example of rat Gal-9 teaches the lesson that the presence of multiple bands in Southern blotting despite a single-copy gene constellation is attributable to two pseudogenes. The documented copy-number variability should thus be taken into consideration when studying regulation of galectin genes, in a species and in comparison between species.

Description: In studying the molecular basis for the potent immune activity of previously described gamma and delta inulin particles and to assist in production of inulin adjuvants under Good Manufacturing Practice, we identified five new inulin isoforms, bringing the total to seven plus the amorphous form. These isoforms comprise the step-wise inulin developmental series amorphous -〉 alpha-1 (AI-1) -〉 alpha-2 (AI-2) -〉 gamma (GI) -〉 delta (DI) -〉 zeta (ZI) -〉 epsilon (EI) -〉 omega (OI) in which each higher isoform can be made either by precipitating dissolved inulin or by direct conversion from its precursor, both cases using regularly increasing temperatures. At higher temperatures, the shorter inulin polymer chains are released from the particle and so the key difference between isoforms is that each higher isoform comprises longer polymer chains than its precursor. An increasing trend of degree of polymerization is confirmed by end-group analysis using 1 H nuclear magnetic resonance spectroscopy. Inulin isoforms were characterized by the critical temperatures of abrupt phase-shifts (solubilizations or precipitations) in water suspensions. Such (aqueous) "melting" or "freezing" points are diagnostic and occur in strikingly periodic steps reflecting quantal increases in noncovalent bonding strength and increments in average polymer lengths. The (dry) melting points as measured by modulated differential scanning calorimetry similarly increase in regular steps. We conclude that the isoforms differ in repeated increments of a precisely repeating structural element. Each isoform has a different spectrum of biological activities and we show the higher inulin isoforms to be more potent alternative complement pathway activators.

Description: The methylotrophic yeast, Pichia pastoris , is an important organism used for the production of therapeutic proteins. Previously, we have reported the glycoengineering of this organism to produce human-like N -linked glycans but up to now no one has addressed engineering the O -linked glycosylation pathway. Typically, O -linked glycans produced by wild-type P. pastoris are linear chains of four to five α-linked mannose residues, which may be capped with β- or phospho-mannose. Previous genetic engineering of the N-linked glycosylation pathway of P. pastoris has eliminated both of these two latter modifications, resulting in O -linked glycans which are linear α-linked mannose structures. Here, we describe a method for the co-expression of an α-1,2-mannosidase, which reduces these glycans to primarily a single O -linked mannose residue. In doing so, we have reduced the potential of these glycans to interact with carbohydrate-binding proteins, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin. Furthermore, the introduction of the enzyme protein- O -linked-mannose β-1,2- N -acetylglucosaminyltransferase 1, resulted in the capping of the single O -linked mannose residues with N -acetylglucosamine. Subsequently, this glycoform was extended into human-like sialylated glycans, similar in structure to α-dystroglycan-type glycoforms. As such, this represents the first example of sialylated O -linked glycans being produced in yeast and extends the utility of the P. pastoris production platform beyond N -linked glycosylated biotherapeutics to include molecules possessing O -linked glycans.

Description: Neurons and other cells require intracellular transport of essential components for viability and function. Previous work has shown that while net amyloid precursor protein (APP) transport is generally anterograde, individual vesicles containing APP move bi-directionally. This discrepancy highlights our poor understanding of the in vivo regulation of APP-vesicle transport. Here, we show that reduction of presenilin (PS) or suppression of gamma-secretase activity substantially increases anterograde and retrograde velocities for APP vesicles. Strikingly, PS deficiency has no effect on an unrelated cargo vesicle class containing synaptotagmin, which is powered by a different kinesin motor. Increased velocities caused by PS or gamma-secretase reduction require functional kinesin-1 and dynein motors. Together, our findings suggest that a normal function of PS is to repress kinesin-1 and dynein motor activity during axonal transport of APP vesicles. Furthermore, our data suggest that axonal transport defects induced by loss of PS-mediated regulatory effects on APP-vesicle motility could be a major cause of neuronal and synaptic defects observed in Alzheimer's Disease (AD) pathogenesis. Thus, perturbations of APP/PS transport could contribute to early neuropathology observed in AD, and highlight a potential novel therapeutic pathway for early intervention, prior to neuronal loss and clinical manifestation of disease.

Description: With age, muscle mass and integrity are progressively lost leaving the elderly frail, weak and unable to independently care for themselves. Defined as sarcopenia, this age-related muscle atrophy appears to be multifactorial but its definite cause is still unknown. Mitochondrial dysfunction has been implicated in this process. Using a novel transgenic mouse model of mitochondrial DNA (mtDNA) double-strand breaks (DSBs) that presents a premature aging-like phenotype, we studied the role of mtDNA damage in muscle wasting. We caused DSBs in mtDNA of adult mice using a ubiquitously expressed mitochondrial-targeted endonuclease, mito- Pst I. We found that a short, transient systemic mtDNA damage led to muscle wasting and a decline in locomotor activity later in life. We found a significant decline in muscle satellite cells, which decreases the muscle's capacity to regenerate and repair during aging. This phenotype was associated with impairment in acetylcholinesterase (AChE) activity and assembly at the neuromuscular junction (NMJ), also associated with muscle aging. Our data suggests that systemic mitochondrial dysfunction plays important roles in age-related muscle wasting by preferentially affecting the myosatellite cell pool.

Description: Populations of widely distributed species encounter and must adapt to local environmental conditions. However, comprehensive characterization of the genetic basis of adaptation is demanding, requiring genome-wide genotype data, multiple sampled populations, and an understanding of population structure and potential selection pressures. Here, we used single-nucleotide polymorphism genotyping and data on numerous environmental variables to describe the genetic basis of local adaptation in 21 populations of teosinte, the wild ancestor of maize. We found complex hierarchical genetic structure created by altitude, dispersal events, and admixture among subspecies, which complicated identification of locally beneficial alleles. Patterns of linkage disequilibrium revealed four large putative inversion polymorphisms showing clinal patterns of frequency. Population differentiation and environmental correlations suggest that both inversions and intergenic polymorphisms are involved in local adaptation.

Description: This work provides a distributed fault-tolerant event region detection algorithm for wireless sensor networks. The proposed algorithm can identify faulty and fault-free sensors and ignore the abnormal readings to avoid false alarm. Moreover, every event region can also be detected and identified. Simulation results show that fault detection accuracy (FDA) is greater than 92%, false alarm rate (FAR) is near 0%, and event detection accuracy (EDA) is greater than 99% under uniform distribution. FDA is greater than 92%, FAR is less than 1.2%, and EDA is greater than 88% under random distribution when sensor fault probability is less than 0.3.

Description: Not all calcite ballast is created equal: differing effects of foraminiferan and coccolith calcite on the formation and sinking of aggregates Biogeosciences Discussions, 10, 14861-14885, 2013 Author(s): K. Schmidt, C. L. De La Rocha, M. Gallinari, and G. Cortese Correlation between particulate organic carbon (POC) and calcium carbonate sinking through the deep ocean has led to the idea that ballast provided by calcium carbonate is important for the export of POC from the surface ocean. While this idea is certainly to some extent true, it is worth considering in more nuance, for example, examining the different effects on the aggregation and sinking of POC of small, non-sinking calcite particles like coccoliths and large, rapidly sinking calcite like planktonic foraminiferan tests. We have done that here in a simple experiment carried out in roller tanks that allow particles to sink continuously without being impeded by container walls. Coccoliths were efficiently incorporated into aggregates that formed during the experiment, increasing their sinking speed compared to similarly sized aggregates lacking added calcite ballast. The foraminiferan tests, which sank as fast as 700 m d −1 , became associated with only very minor amounts of POC. In addition, when they collided with other, larger, foraminferan-less aggregates, they fragmented them into two smaller, more slowly sinking aggregates. While these effects were certainly exaggerated within the confines of the roller tanks, they clearly demonstrate that calcium carbonate ballast is not just calcium carbonate ballast- different forms of calcium carbonate ballast have notably different effects on POC aggregation, sinking, and export.

Description: Antecedent flow conditions and nitrate concentrations in the Mississippi River Basin Hydrology and Earth System Sciences Discussions, 10, 11451-11484, 2013 Author(s): J. C. Murphy, R. M. Hirsch, and L. A. Sprague The influence of antecedent flow conditions on nitrate concentrations was explored at eight sites in the Mississippi River Basin, USA. Antecedent moisture conditions have been shown to influence nutrient export from small, relatively homogenous basins, but this influence has not been observed at a regional or continental scale. Antecedent flow conditions were quantified as the ratio between the mean daily flow of the previous year and the mean daily flow from the period of record ( Q ratio), and the Q ratio was statistically related to nitrate anomalies (the unexplained variability in nitrate concentration after filtering out season, long-term trend, and contemporaneous flow effects) at each site. Nitrate anomaly and Q ratio were negatively related at three of the four major tributary sites and upstream in the Mississippi River, indicating that when the previous year was drier than average, at these sites, nitrate concentrations were higher than expected. The strength of these relationships increased when data were subdivided by contemporaneous flow conditions. Five of the eight sites had significant negative relationships ( p ≤ 0.05) at high or moderately high contemporaneous flows, suggesting nitrate that accumulates in these basins during a drought is flushed during subsequent storm events. At half of the sites, when flow during the previous year was 50% drier than average, nitrate concentration can be from 9 and 27% higher than nitrate concentrations that follow a year with average daily flow. Conversely, nitrate concentration can be from 8 and 21% lower than expected when the previous year was 50% wetter than average. These relationships between nitrate concentration and Q ratio serve as the basis for future studies that can better define specific hydrologic processes occurring during and after a drought, which influence nitrate concentration, such as the duration or magnitude of low flows, and the timing of low and high flows.

Description: We used a one-dimensional simulation program Solar Cell Capacitance Simulator in 1 Dimension (SCAPS-1D) to investigate Copper-Indium-Gallium-Diselenide- (CIGS-) based solar cells properties. Starting with a conventional ZnO-B/i-ZnO/CdS/CIGS structure, we simulated the parameters of current-voltage characteristics and showed how the absorber layer thickness, hole density, and band gap influence the short-circuit current density (), open-circuit voltage (), fill factor (FF), and efficiency of solar cell. Our simulation results showed that all electrical parameters are greatly affected by the absorber thickness (w) below 1000 nm, due to the increase of back-contact recombination and very poor absorption. Increasing hole density (p) or absorber band gap () improves and leads to high efficiency, which equals value of 16.1% when p = 1016 cm−3 and  eV. In order to reduce back-contact recombination, the effect of a very thin layer with high band gap inserted near the back contact and acting as electrons reflector, the so-called back-electron reflector (EBR), has been investigated. The performances of the solar cells are significantly improved, when ultrathin absorbers (w 〈 500 nm) are used; the corresponding gain of due to the EBR is 3 mA/cm2. Our results are in good agreement with those reported in the literature from experiments.

Description: Tidally induced velocity variations of the Beardmore Glacier, Antarctica, and their representation in satellite measurements of ice velocity The Cryosphere, 7, 1375-1384, 2013 Author(s): O. J. Marsh, W. Rack, D. Floricioiu, N. R. Golledge, and W. Lawson Ocean tides close to the grounding line of outlet glaciers around Antarctica have been shown to directly influence ice velocity, both linearly and non-linearly. These fluctuations can be significant and have the potential to affect satellite measurements of ice discharge, which assume displacement between satellite passes to be consistent and representative of annual means. Satellite observations of horizontal velocity variation in the grounding zone are also contaminated by vertical tidal effects, the importance of which is highlighted here in speckle tracking measurements. Eight TerraSAR-X scenes from the grounding zone of the Beardmore Glacier are analysed in conjunction with GPS measurements to determine short-term and decadal trends in ice velocity. Diurnal tides produce horizontal velocity fluctuations of 〉50% on the ice shelf, recorded in the GPS data 4 km downstream of the grounding line. This variability decreases rapidly to 〈5% only 15 km upstream of the grounding line. Daily fluctuations are smoothed to 〈1% in the 11-day repeat pass TerraSAR-X imagery, but fortnightly variations over this period are still visible and show that satellite-velocity measurements can be affected by tides over longer periods. The measured tidal displacement observed in radar look direction over floating ice also allows the grounding line to be identified, using differential speckle tracking where phase information cannot be easily unwrapped.

Description: Contribution of snow and glacier melt to discharge for highly glacierised catchments in Norway Hydrology and Earth System Sciences Discussions, 10, 11485-11517, 2013 Author(s): M. Engelhardt, T. V. Schuler, and L. M. Andreassen Glacierised catchments significantly alter the streamflow regime due to snow and glacier meltwater contribution to discharge. In this study, we modelled the mass balance and discharge rates for three highly glacierised catchments (〉50% glacier cover) in western Norway over the period 1961–2012. The spatial pattern of the catchments follows a gradient in climate continentality from west to east. The model uses gridded temperature and precipitation values from seNorge ( http://senorge.no ) as input which are available at a daily resolution. It accounts for accumulation of snow, transformation of snow to firn and ice, evaporation and melt. The model was calibrated for each catchment based on measurements of seasonal glacier mass-balances and daily discharge rates. For validation, daily melt rates were compared with measurements from sonic rangers located in the ablation zones of two of the glaciers and an uncertainty analysis was performed for the third catchment. The discharge contributions from snowmelt, glacier melt and rain were analysed with respect to spatial variations and temporal evolution. The model simulations reveal an increase of the relative contribution from glacier melt for the three catchments from less than 10% in the early 1990s to 15–30% in the late 2000s. The decline in precipitation by 10–20% in the same period was therefore overcompensated resulting in an increase of the annual discharge by 5–20%. Annual discharge sums and annual glacier melt are strongest correlated with annual and winter precipitation at the most maritime glacier and, with increased climate continentality, variations in both glacier melt contribution and annual discharge are becoming stronger correlated with variations in summer temperatures.

Description: A catalytic adsorptive cathodic stripping voltammetric method on an improved bismuth film electrode (BiFE) for the determination of trace germanium in the presence of pyrogallol has been investigated. A well-defined and sensitive stripping peak of Ge(IV)-pyrogallol complex was observed at −0.79 V (versus SCE) in a 0.1 M acetate buffer solution (pH 4.8) at a deposition potential of −0.34 V. The reduction current is catalytically enhanced by adding KBrO3. The experimental variables and potential interference were studied. Compared with the BiFE plated in the solution prepared based on HAc-NaAc without trisodium citrate, the improved BiFE electrodeposited in the solution of HAc-NaAc containing trisodium citrate displayed a better electroanalytical performance for the determination of germanium(IV). Under the optimized conditions, the detection limit of Ge(IV) was 60 ng L−1, and the relative standard deviation (RSD) was 3.73% at 5 μg L−1 level (). This method was successfully applied to determine the total germanium in several Chinese herbal remedies.

Description: Changes of antioxidant properties of -lipoic acid (LA) after UV irradiation were studied. LA is the typical drug used in diabetic neuropathy. Quenching of free radicals is an important factor of therapy by using this substance. -Lipoic acid is exposed to UV irradiation during the storage. The aim of our studies was to examine the effect of UV irradiation on the interactions of LA with free radicals. The -lipoic acid was irradiated by UVA 315–400 nm light during 10 to 110 minutes by intervals of 10 minutes. The electron paramagnetic resonance spectroscopy was used as the experimental technique. The antioxidant properties of LA were spectroscopically confirmed. The strong effect of UV irradiation on interactions of -lipoic acid with free radicals was observed. It was pointed out that interactions of LA with free radicals decrease after its exposition on UV. The interactions of LA with free radicals were higher after the sample irradiation during 10 minutes than for the samples irradiated longer (20–110 minutes). The results are important for problems connected with photomedicine; they pointed out that -lipoic acid should not be stored on UV exposition. Application of electron paramagnetic resonance spectroscopy to characterize interactions of pharmacological substance with free radicals was confirmed.

Description: Copper antimony sulfide (CAS) is a relatively new class of sustainable absorber material, utilizing cost effective and abundant elements. Band gap engineered, modified CAS thin films were synthesized using electrodeposition and elevated temperature sulfurization approach. A testing analog of copper zinc antimony sulfide (CZAS) film-electrolyte interface was created in order to evaluate photoelectrochemical performance of the thin film of absorber materials. Eu3+/Eu2+ redox couple was selected for this purpose, based on its relative band offset with copper antimony sulfide. It was observed that zinc has a significant effect on CAS film properties. An enhanced photocurrent was observed for CAS film, modified with zinc addition. A detailed investigation has been carried out by changing stoichiometry, and corresponding surface and optical characterization results have been evaluated. A summary of favorable processing parameters of the films showing enhanced photoelectrochemical response is presented.

Description: In CdS/CdTe solar cells, chemical interdiffusion at the interface gives rise to the formation of an interlayer of the ternary compound . In this work, we evaluate the effects of this interlayer in CdS/CdTe photovoltaic cells in order to improve theoretical results describing experimental - (capacitance versus voltage) characteristics. We extended our previous theoretical methodology developed on the basis of three cardinal equations (Castillo-Alvarado et al., 2010). The present results provide a better fit to experimental data obtained from CdS/CdTe solar cells grown in our laboratory by the chemical bath deposition (for CdS film) and the close-spaced vapor transport (for CdTe film) techniques.

Description: In a silicon wafer-based photovoltaic (PV) module, significant power is lost due to current transport through the ribbons interconnecting neighbour cells. Using halved cells in PV modules is an effective method to reduce the resistive power loss which has already been applied by some major PV manufacturers (Mitsubishi, BP Solar) in their commercial available PV modules. As a consequence, quantitative analysis of PV modules using halved cells is needed. In this paper we investigate theoretically and experimentally the difference between modules made with halved and full-size solar cells. Theoretically, we find an improvement in fill factor of 1.8% absolute and output power of 90 mW for the halved cell minimodule. Experimentally, we find an improvement in fill factor of 1.3% absolute and output power of 60 mW for the halved cell module. Also, we investigate theoretically how this effect confers to the case of large-size modules. It is found that the performance increment of halved cell PV modules is even higher for high-efficiency solar cells. After that, the resistive loss of large-size modules with different interconnection schemes is analysed. Finally, factors influencing the performance and cost of industrial halved cell PV modules are discussed.

Description: In three-phase photovoltaic (PV) system, three-phase filter inductors are important part for the output electrical power quality. The comparison analyses of three-phase discrete filter inductors and two kinds of three-phase integrated filter inductors in three-phase PV inverter are proposed. Firstly, the three-phase PV inverter operation with discrete filter inductors is analyzed, and the design of discrete filter inductors is given; then operation of the three-phase PV inverter with three-phase integrated five-limb magnetic core filter inductors is analyzed, the design of integrated filter inductors with five-limb magnetic core is given, then the operation of three-phase PV inverter with three-phase integrated three-limb magnetic core filter inductors is analyzed, and the design of integrated filter inductors with three limbs magnetic core is given. The conclusion of comparison between three-phase discrete filter inductors and two kinds of three-phase integrated filter inductors is done; it means that the three-phase discrete filter inductors can achieve better output electrical power quality with lower power density and three-phase integrated filter inductors can achieve higher power density with lower output electrical power quality. Finally, the experiment results are given to compare the volume and filter effect of three kinds of filter inductors in three-phase PV inverter.

Description: Decadal trends in the Antarctic sea ice extent ultimately controlled by ice-ocean feedback The Cryosphere Discussions, 7, 4585-4632, 2013 Author(s): H. Goosse and V. Zunz The large natural variability of the Antarctic sea ice is a key characteristic of the system that might be responsible for the small positive trend in sea ice extent observed since 1979. In order to gain insight in the processes responsible for this variability, we have analysed in a control simulation performed with a coupled climate model a strong positive ice-ocean feedback that amplifies sea ice variations. When sea ice concentration increases in a region, in particular close to the ice edge, the mixed layer depth tends to decrease. This can be caused by a net inflow of ice and thus of freshwater that stabilizes the water column. Another stabilizing mechanism at interannual time scales that appears more widespread in our simulation is associated with the downward salt transport due to the seasonal cycle of ice formation: brine is released in winter when ice is formed and mixed over a deep layer while the freshwater flux caused by ice melting is included in a shallow layer, resulting in a net vertical transport of salt. Because of this stronger stratification due to the presence of sea ice, more heat is stored at depth in the ocean and the vertical oceanic heat flux is reduced, which contributes to maintain a higher ice extent. This positive feedback is not associated with a particular spatial pattern. Consequently, the spatial distribution of the trend in ice concentration is largely imposed by the wind changes that can provide the initial perturbation. A positive freshwater flux could alternatively be the initial trigger but the amplitude of the final response of the sea ice extent is finally set up by the amplification related to ice-ocean feedback. Initial conditions have also an influence as the chance to have a large increase in ice extent is higher if starting from a state characterized by a low value.

Description: There is much interest in using high-throughput DNA sequencing methodology to monitor microorganisms, complex plant and animal communities. However, there are experimental and analytical issues to consider before applying a sequencing technology, which was originally developed for genome projects, to ecological projects. Many of these issues have been highlighted by recent microbial studies. Understanding how high-throughput sequencing is best implemented is important for the interpretation of recent results and the success of future applications. Addressing complex biological questions with metagenomics requires the interaction of researchers who bring different skill sets to problem solving. Educators can help by nurturing a collaborative interdisciplinary approach to genome science, which is essential for effective problem solving. Educators are in a position to help students, teachers, the public and policy makers interpret the new knowledge that metagenomics brings. To do this, they need to understand, not only the excitement of the science but also the pitfalls and shortcomings of methodology and research designs. We review these issues and some of the research directions that are helping to move the field forward.

Description: We believe that undergraduate biology students must acquire a foundational background in computing including how to formulate a computational problem; develop an algorithmic solution; implement their solution in software and then test, document and use their code to explore biological phenomena. Moreover, by learning these skills in the first year, students acquire a powerful tool set that they can use and build on throughout their studies. To address this need, we have developed a first-year undergraduate course that teaches students the foundations of computational thinking and programming in the context of problems in biology. This article describes the structure and content of the course and summarizes assessment data on both affective and learning outcomes.

Description: Bioinformatics is an integral part of modern life sciences. It has revolutionized and redefined how research is carried out and has had an enormous impact on biotechnology, medicine, agriculture and related areas. Yet, it is only rarely integrated into high school teaching and learning programs, playing almost no role in preparing the next generation of information-oriented citizens. Here, we describe the design principles of bioinformatics learning environments, including our own, that are aimed at introducing bioinformatics into senior high school curricula through engaging learners in scientifically authentic inquiry activities. We discuss the bioinformatics-related benefits and challenges that high school teachers and students face in the course of the implementation process, in light of previous studies and our own experience. Based on these lessons, we present a new approach for characterizing the questions embedded in bioinformatics teaching and learning units, based on three criteria: the type of domain-specific knowledge required to answer each question (declarative knowledge, procedural knowledge, strategic knowledge, situational knowledge), the scientific approach from which each question stems (biological, bioinformatics, a combination of the two) and the associated cognitive process dimension (remember, understand, apply, analyze, evaluate, create). We demonstrate the feasibility of this approach using a learning environment, which we developed for the high school level, and suggest some of its implications. This review sheds light on unique and critical characteristics related to broader integration of bioinformatics in secondary education, which are also relevant to the undergraduate level, and especially on curriculum design, development of suitable learning environments and teaching and learning processes.

Description: Next-generation sequencing (NGS) is increasingly being adopted as the backbone of biomedical research. With the commercialization of various affordable desktop sequencers, NGS will be reached by increasing numbers of cellular and molecular biologists, necessitating community consensus on bioinformatics protocols to tackle the exponential increase in quantity of sequence data. The current resources for NGS informatics are extremely fragmented. Finding a centralized synthesis is difficult. A multitude of tools exist for NGS data analysis; however, none of these satisfies all possible uses and needs. This gap in functionality could be filled by integrating different methods in customized pipelines, an approach helped by the open-source nature of many NGS programmes. Drawing from community spirit and with the use of the Wikipedia framework, we have initiated a collaborative NGS resource: The NGS WikiBook. We have collected a sufficient amount of text to incentivize a broader community to contribute to it. Users can search, browse, edit and create new content, so as to facilitate self-learning and feedback to the community. The overall structure and style for this dynamic material is designed for the bench biologists and non-bioinformaticians. The flexibility of online material allows the readers to ignore details in a first read, yet have immediate access to the information they need. Each chapter comes with practical exercises so readers may familiarize themselves with each step. The NGS WikiBook aims to create a collective laboratory book and protocol that explains the key concepts and describes best practices in this fast-evolving field.

Description: Contribution of directly connected and isolated impervious areas to urban drainage network hydrographs Hydrology and Earth System Sciences, 17, 3473-3483, 2013 Author(s): Y. Seo, N.-J. Choi, and A. R. Schmidt This paper addresses the mass balance error observed in runoff hydrographs in urban watersheds by introducing assumptions regarding the contribution of infiltrated rainfall from pervious areas and isolated impervious area (IIA) to the runoff hydrograph. Rainfall infiltrating into pervious areas has been assumed not to contribute to the runoff hydrograph until Hortonian excess rainfall occurs. However, mass balance analysis in an urban watershed indicates that rainfall infiltrated to pervious areas can contribute directly to the runoff hydrograph, thereby offering an explanation for the long hydrograph tail commonly observed in runoff from urban storm sewers. In this study, a hydrologic analysis based on the width function is introduced, with two types of width functions obtained from both pervious and impervious areas, respectively. The width function can be regarded as the direct interpretation of the network response. These two width functions are derived to obtain distinct response functions for directly connected impervious areas (DCIA), IIA, and pervious areas. The results show significant improvement in the estimation of runoff hydrographs and suggest the need to consider the flow contribution from pervious areas to the runoff hydrograph. It also implies that additional contribution from flow paths through joints and cracks in sewer pipes needs to be taken into account to improve the estimation of runoff hydrographs in urban catchments.

Description: It is widely accepted that tumorigenesis is a multistep process characterized by the sequential accumulation of genetic alterations. However, the molecular basis of genomic instability in cancer is still partially understood. The observation that hereditary cancers are often characterized by mutations in DNA repair and checkpoint genes suggests that accumulation of DNA damage is a major contributor to the oncogenic transformation. It is therefore of great interest to identify all the cellular pathways that contribute to the response to DNA damage. Recently, RNA processing has emerged as a novel pathway that may contribute to the maintenance of genome stability. In this review, we illustrate several different mechanisms through which pre-mRNA splicing and genomic stability can influence each other. We specifically focus on the role of splicing factors in the DNA damage response and describe how, in turn, activation of the DDR can influence the activity of splicing factors.

Description: The components and claddings of low-rise buildings are usually destroyed first during typhoon disasters in coastal areas. Roof accessory structures can change the flow pattern on the roof, thus effectively reducing the wind load on the roof surface and the damage to the low-rise buildings. Three types of aerodynamic mitigation plates, that is, (1) 0.3 m high full-length roof-edge plate, (2) 0.3 m high and 0.5 m + 0.5 m long roof-corner plate, and (3) discrete roof-edge plates with different spaces (which can be used as advertisement boards), are studied on the basis of the field measurement results under roof pitches of 10° and 18.4°. By comparing the results of the roof with and without constructed plates, it is implied that the three types of plates can affect the formation of conical vortexes and can significantly reduce the mean and fluctuating pressure coefficients in the windward corner. Compared with the constructed plate, the roof ridge has a larger influence on the wind loads on leeward roof.

Description: Composite silicon dioxide-titanium dioxide (SiO2-TiO2) films are deposited on a large area of 15.6 × 15.6 cm2 textured multicrystalline silicon solar cells to increase the incident light trapped within the device. For further improvement of the antireflective coatings (ARCs) quality, dimethylformamide (DMF) solution is added to the original SiO2-TiO2 solutions. DMF solution solves the cracking problem, thus effectively decreasing reflectance as well as surface recombination. The ARCs prepared by sol-gel process and plasma-enhanced chemical vapor deposition (PECVD) on multicrystalline silicon substrate are compared. The average efficiency of the devices with improved sol-gel ARCs is 16.3%, only 0.5% lower than that of devices with PECVD ARCs (16.8%). However, from equipment depreciation point of view (the expiration date of equipment is generally considered as 5 years), the running cost (USD/watt) of sol-gel technique is 80% lower than that of PECVD method for the first five years and 66% lower than that of PECVD method from the start of the sixth year. This result proves that sol-gel-deposited ARCs process has potential applications in manufacturing low-cost, large-area solar cells.

Description: Phenology as a strategy for carbon optimality: a global model Biogeosciences Discussions, 10, 15107-15152, 2013 Author(s): S. Caldararu, D. W. Purves, and P. I. Palmer Phenology is essential to our understanding of biogeochemical cycles and the climate system. We develop a global mechanistic model of leaf phenology based on the hypothesis that phenology is a strategy for optimal carbon gain at the canopy level so that trees adjust leaf gains and losses in response to environmental factors such as light, temperature and soil moisture, to achieve maximum carbon assimilation. We fit this model to five years of satellite observations of leaf area index (LAI) using a Bayesian fitting algorithm. We show that our model is able to reproduce phenological patterns for all vegetation types and use it to explore variations in growing season length and the climate factors that limit leaf growth for different biomes. Phenology in wet tropical areas is limited by leaf age physiological constraints while at higher latitude leaf seasonality is limited by low temperature and light availability. Leaf growth in grassland regions is limited by water availability but often in combination with other factors. This model will advance the current understanding of phenology for ecosystem carbon models and our ability to predict future phenological behaviour.

Description: Bias correction can modify climate model-simulated precipitation changes without adverse affect on the ensemble mean Hydrology and Earth System Sciences Discussions, 10, 11585-11611, 2013 Author(s): E. P. Maurer and D. W. Pierce When applied to remove climate model biases in precipitation, quantile mapping can in some settings modify the simulated trends. This has important implications when the precipitation will be used to drive an impacts model that is sensitive to changes in precipitation. We use daily precipitation output from 12 general circulation models (GCMs) over the conterminous United States interpolated to a common 1° grid, and gridded observations aggregated to the same scale, to compare precipitation differences before and after quantile mapping bias correction. The change in seasonal mean (winter, DJF, and summer, JJA) precipitation between different 30-yr historical periods is compared to examine (1) the consensus among GCMs as to whether the bias correction tends to amplify or diminish their simulated precipitation trends, and (2) whether the modification of the change in precipitation tends to improve or degrade the correspondence to observed changes in precipitation for the same periods. In some cases, for a particular GCM, the trend modification can be as large as the original simulated change, though the areas where this occurs varies among GCMs so the ensemble median shows smaller trend modification. In specific locations and seasons the trend modification by quantile mapping improves correspondence with observed trends, and in others it degrades it. In the majority of the domain the ensemble median is for little effect on the correspondence of simulated precipitation trends with observed. This highlights the need to use an ensemble of GCMs rather than relying on a small number of models to estimate impacts.

Description: Linking ICT and society in early warning and adaptation to hydrological extremes in mountains Natural Hazards and Earth System Science, 13, 2253-2270, 2013 Author(s): C. de Jong The assessment of the societal impact of hydrological extremes is particularly important in mountain regions, since mountains can be considered both as the generators and victims of extreme events. ICT can provide a powerful tool for transmitting hydro-meteorological information to predict, prepare and adapt to such events. However, in remote regions, such as mountains, the poles, deserts and islands, preventive and adaptive measures are often restricted by data availability and lack and/or incoherence of data networks. This paper distinguishes between early warning of floods and droughts, emphasising the latter in particular in mountains and explores the possibilities of enhancing the role of society in data collection, the identification, activation and application of stakeholder knowledge and transferral of data from gauged to ungauged catchments.

Description: Cooperative communications that take advantage of the broadcasting nature of wireless environments can help to increase system throughput in wireless ad hoc networks. However, the promised throughput might be lost in presence of the error transmission and the interference caused by relay transmission in cooperative communication. In this paper, we introduced the relay selection schemes that can control the interference at the relay to prevent the relay that may harm other pairs. Then, we proposed the throughput-optimal scheduling that takes into account error probability in decision and maximizes throughput, that is, the amount of packets transmitted without error in network. In addition, we derive a simple and lightweight framework to implement the proposed policy in distributed manner. The simulation results show that the proposed scheduling policy outperforms the noncooperative policy and multihop relay policy.

Description: The genomes of related species contain valuable information on the history of the considered taxa. Great apes in particular exhibit variation of evolutionary patterns along their genomes. However, the great ape data also bring new challenges, such as the presence of incomplete lineage sorting and ancestral shared polymorphisms. Previous methods for genome-scale analysis are restricted to very few individuals or cannot disentangle the contribution of mutation rates and fixation biases. This represents a limitation both for the understanding of these forces as well as for the detection of regions affected by selection. Here, we present a new model designed to estimate mutation rates and fixation biases from genetic variation within and between species. We relax the assumption of instantaneous substitutions, modeling substitutions as mutational events followed by a gradual fixation. Hence, we straightforwardly account for shared ancestral polymorphisms and incomplete lineage sorting. We analyze genome-wide synonymous site alignments of human, chimpanzee, and two orangutan species. From each taxon, we include data from several individuals. We estimate mutation rates and GC-biased gene conversion intensity. We find that both mutation rates and biased gene conversion vary with GC content. We also find lineage-specific differences, with weaker fixation biases in orangutan species, suggesting a reduced historical effective population size. Finally, our results are consistent with directional selection acting on coding sequences in relation to exonic splicing enhancers.

Description: Genetic control of male or female gonad development displays between different groups of organisms a remarkable diversity of "master sex-determining genes" at the top of the genetic hierarchies, whereas downstream components surprisingly appear to be evolutionarily more conserved. Without much further studies, conservation of sequence has been equalized to conservation of function. We have used the medaka fish to investigate the generality of this paradigm. In medaka, the master male sex-determining gene is dmrt1bY , a highly conserved downstream regulator of sex determination in vertebrates. To understand its function in orchestrating the complex gene regulatory network, we have identified targets genes and regulated pathways of Dmrt1bY. Monitoring gene expression and interactions by transgenic fluorescent reporter fish lines, in vivo tissue-chromatin immunoprecipitation and in vitro gene regulation assays revealed concordance but also major discrepancies between mammals and medaka, notably amongst spatial, temporal expression patterns and regulations of the canonical Hedgehog and R-spondin/Wnt/Follistatin signaling pathways. Examination of Foxl2 protein distribution in the medaka ovary defined a new subpopulation of theca cells, where ovarian-type aromatase transcriptional regulation appears to be independent of Foxl2. In summary, these data show that the regulation of the downstream regulatory network of sex determination is less conserved than previously thought.

Description: Timing of sea ice retreat can alter phytoplankton community structure in the western Arctic Ocean Biogeosciences Discussions, 10, 15153-15180, 2013 Author(s): given_name prefix surname suffix, A. Fujiwara, T. Hirawake, K. Suzuki, I. Imai, and S.-I. Saitoh This study assesses the response of phytoplankton assemblages to recent climate change, especially with regard to the shrinking of sea ice in the northern Chukchi Sea of the western Arctic Ocean. Distribution patterns of phytoplankton groups in the late summers of 2008–2010 were analyzed based on HPLC pigment signatures and, the following four major algal groups were inferred via multiple regression and cluster analyses: prasinophytes, diatoms, haptophytes and dinoflagellates. A remarkable interannual difference in the distribution pattern of the groups was found in the northern basin area. Haptophytes dominated and dispersed widely in warm surface waters in 2008, whereas prasinophytes dominated in cold water in 2009 and 2010. A difference in the onset date of sea ice retreat was evident among years – the sea ice retreat in 2008 was 1–2 months earlier than in 2009 and 2010. The spatial distribution of early sea ice retreat matched the areas in which a shift in algal community composition was observed. Steel-Dwass's multiple comparison tests were used to assess the physical, chemical and biological parameters of the four clusters. We found a statistically significant difference in temperature between the haptophyte-dominated cluster and the other clusters, suggesting that the change in the phytoplankton communities was related to the earlier sea ice retreat in 2008 and the corollary increase in sea surface temperatures. Longer periods of open water during the summer, which are expected in the future, may affect food webs and biogeochemical cycles in the western Arctic due to shifts in phytoplankton community structure.

Description: Continuous deployment of antifungals in treating infections caused by dimorphic opportunistic pathogen Candida albicans has led to the emergence of drug resistance resulting in cross-resistance to many unrelated drugs, a phenomenon termed multidrug resistance (MDR). Despite the current understanding of major factors which contribute to MDR mechanisms, there are many lines of evidence suggesting that it is a complex interplay of multiple factors which may be contributed by still unknown mechanisms. Coincidentally with the increased usage of antifungal drugs, the number of reports for antifungal drug resistance has also increased which further highlights the need for understanding novel molecular mechanisms which can be explored to combat MDR, namely, ROS, iron, hypoxia, lipids, morphogenesis, and transcriptional and signaling networks. Considering the worrying evolution of MDR and significance of C. albicans being the most prevalent human fungal pathogen, this review summarizes these new regulatory mechanisms which could be exploited to prevent MDR development in C. albicans as established from recent studies.

Description: Snow on the Ross Ice Shelf: comparison of reanalyses and observations from automatic weather stations The Cryosphere, 7, 1399-1410, 2013 Author(s): L. Cohen and S. Dean Snow accumulation measurements from automatic weather stations (AWS) around the Ross Ice Shelf (RIS), Antarctica, are used to provide a new set of ground-based observations which are compared to precipitation from the ECMWF ERA-Interim and NCEP/NCAR Reanalysis-2 datasets. The high temporal resolution of the AWS snow accumulation measurements allow for an event-based comparison of reanalyses precipitation to the in situ observations. Snow accumulation records from nine AWS provide multiple years of accumulation data between 2008 and 2012 over a relatively large, homogeneous region of Antarctica, and also provide the basis for a statistical evaluation of accumulation and precipitation events. The complex effects of wind on snow accumulation (which can both limit and enhance accumulation) complicate the use of the accumulation measurements, but this analysis shows that they can provide a valuable source of ground-based observations for comparisons to modelled precipitation on synoptic timescales. The analysis shows that ERA-Interim reproduces more precipitation events than NCEP-2, and these events correspond to an average 8.2% more precipitation. Significant correlations between reanalyses and AWS event sizes are seen at several stations and show that ERA-Interim consistently produces larger precipitation events than NCEP-2.

Description: A novel preference ranking organization method by similarity to ideal solution (PROMSIS) vertical handoff algorithm is proposed for heterogeneous wireless networks, and its essential idea includes the preference structure of the PROMETHEE and the concept of Euclid distance of the TOPSIS. Four 3GPP defined traffic classes are considered in performance evaluation. An attribute matrix is constructed considering some major attributes. Handoff decision meeting multiattribute QoS requirement is made according to the traffic features. The weight relation of decision elements is determined with the least square (LS) approach. The final decision is made using the proposed PROMSIS algorithm based on the attribute matrix and weight vector. The simulation results have manifested that the proposed PROMSIS algorithm can provide satisfactory vertical handoff performance, and the LS-PROMSIS algorithm can be fit to the characteristics of the traffic.

Description: Motivation: Pyrosequencing technology provides an important new approach to more extensively characterize diverse sequence populations and detect low frequency variants. However, the promise of this technology has been difficult to realize, as careful correction of sequencing errors is crucial to distinguish rare variants (~1%) in an infected host with high sensitivity and specificity. Results: We developed a new approach, referred to as Indel and Carryforward Correction (ICC), to cluster sequences without substitutions and locally correct only indel and carryforward sequencing errors within clusters to ensure that no rare variants are lost. ICC performs sequence clustering in the order of (i) homopolymer indel patterns only, (ii) indel patterns only and (iii) carryforward errors only, without the requirement of a distance cutoff value. Overall, ICC removed 93–95% of sequencing errors found in control datasets. On pyrosequencing data from a PCR fragment derived from 15 HIV-1 plasmid clones mixed at various frequencies as low as 0.1%, ICC achieved the highest sensitivity and similar specificity compared with other commonly used error correction and variant calling algorithms. Availability and implementation: Source code is freely available for download at http://indra.mullins.microbiol.washington.edu/ICC . It is implemented in Perl and supported on Linux, Mac OS X and MS Windows. Contact: jmullins@uw.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: : Tiki proteins appear to antagonize Wnt signalling pathway by acting as Wnt proteases, thereby affecting Wnt solubility by its amino-terminal cleavage. Tiki1 protease activity was shown to be metal ion-dependent and was inhibited by chelating agents and thus was tentatively proposed to be a metalloprotease. Nevertheless, Tiki proteins exhibit no detectable sequence similarity to previously described metalloproteases, but instead have been reported as being homologues of TraB proteins (Pfam ID: PF01963), a widely distributed family of unknown function and structure. Here, we show that Tiki proteins are members of a new superfamily of domains contained not just in TraB proteins, but also in erythromycin esterase (Pfam ID: PF05139), DUF399 (domain of unknown function 399; Pfam ID: PF04187) and MARTX toxins that contribute to host invasion and pathogenesis by bacteria. We establish the core fold of this enzymatic domain and its catalytic residues. Contact: luis.sanchezpulido@dpag.ox.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: The research area metabolomics achieved tremendous popularity and development in the last couple of years. Owing to its unique interdisciplinarity, it requires to combine knowledge from various scientific disciplines. Advances in the high-throughput technology and the consequently growing quality and quantity of data put new demands on applied analytical and computational methods. Exploration of finally generated and analyzed datasets furthermore relies on powerful tools for data mining and visualization. Results: To cover and keep up with these requirements, we have created MeltDB 2.0, a next-generation web application addressing storage, sharing, standardization, integration and analysis of metabolomics experiments. New features improve both efficiency and effectivity of the entire processing pipeline of chromatographic raw data from pre-processing to the derivation of new biological knowledge. First, the generation of high-quality metabolic datasets has been vastly simplified. Second, the new statistics tool box allows to investigate these datasets according to a wide spectrum of scientific and explorative questions. Availability: The system is publicly available at https://meltdb.cebitec.uni-bielefeld.de . A login is required but freely available. Contact: nkessler@cebitec.uni-bielefeld.de

Description: Motivation: High - throughput next - generation sequencing technologies enable increasingly fast and affordable sequencing of genomes and transcriptomes, with a broad range of applications. The quality of the sequencing data is crucial for all applications. A significant portion of the data produced contains errors, and ever more efficient error correction programs are needed. Results: We propose RACER (Rapid and Accurate Correction of Errors in Reads), a new software program for correcting errors in sequencing data. RACER has better error-correcting performance than existing programs, is faster and requires less memory. To support our claims, we performed extensive comparison with the existing leading programs on a variety of real datasets. Availability: RACER is freely available for non-commercial use at www.csd.uwo.ca/~ilie/RACER/ . Contact: ilie@csd.uwo.ca Supplementary information: Supplementary data are available at Bioinformatics online.

Description: : Interactions between various types of molecules that regulate crucial cellular processes are extensively investigated by high-throughput experiments and require dedicated computational methods for the analysis of the resulting data. In many cases, these data can be represented as a bipartite graph because it describes interactions between elements of two different types such as the influence of different experimental conditions on cellular variables or the direct interaction between receptors and their activators/inhibitors. One of the major challenges in the analysis of such noisy datasets is the statistical evaluation of the relationship between any two elements of the same type. Here, we present SICOP (significant co-interaction patterns), an implementation of a method that provides such an evaluation based on the number of their common interaction partners, their so-called co-interaction. This general network analytic method, proved successful in diverse fields, provides a framework for assessing the significance of this relationship by comparison with the expected co-interaction in a suitable null model of the same bipartite graph. SICOP takes into consideration up to two distinct types of interactions such as up- or downregulation. The tool is written in Java and accepts several common input formats and supports different output formats, facilitating further analysis and visualization. Its key features include a user-friendly interface, easy installation and platform independence. Availability: The software is open source and available at cna.cs.uni-kl.de/SICOP under the terms of the GNU General Public Licence (version 3 or later). Contact: agnes.horvat@iwr.uni-heidelberg.de or zweig@cs.uni-kl.de

Description: : Molecular recognition features (MoRFs) are small, intrinsically disordered regions in proteins that undergo a disorder-to-order transition on binding to their partners. MoRFs are involved in protein–protein interactions and may function as the initial step in molecular recognition. The aim of this work was to collect, organize and store all membrane proteins that contain MoRFs. Membrane proteins constitute ~30% of fully sequenced proteomes and are responsible for a wide variety of cellular functions. MoRFs were classified according to their secondary structure, after interacting with their partners. We identified MoRFs in transmembrane and peripheral membrane proteins. The position of transmembrane protein MoRFs was determined in relation to a protein’s topology. All information was stored in a publicly available mySQL database with a user-friendly web interface. A Jmol applet is integrated for visualization of the structures. mpMoRFsDB provides valuable information related to disorder-based protein–protein interactions in membrane proteins. Availability: http://bioinformatics.biol.uoa.gr/mpMoRFsDB Contact: shamodr@biol.uoa.gr

Description: : The signaling Petri net (SPN) simulator, designed to provide insights into the trends of molecules’ activity levels in response to an external stimulus, contributes to the systems biology necessity of analyzing the dynamics of large-scale cellular networks. Implemented into the freely available software, BioLayout Express 3D , the simulator is publicly available and easy to use, provided the input files are prepared in the GraphML format, typically using the network editing software, yEd, and standards specific to the software. However, analysis of complex networks represented using other systems biology formatting languages (on which popular software, such as CellDesigner and Cytoscape, are based) requires manual manipulation, a step that is prone to error and limits the use of the SPN simulator in BioLayout Express 3D . To overcome this, we present a Cytoscape plug-in that enables users to automatically convert networks for analysis with the SPN simulator from the standard systems biology markup language. The automation of this step opens the SPN simulator to a far larger user group than has previously been possible. Availability and implementation: Distributed under the GNU General Public License Version 3 at http://apps.cytoscape.org/apps/spnconverter . Contact: christine@picb.ac.cn

Description: Motivation: Conformational diversity is a key concept in the understanding of different issues related with protein function such as the study of catalytic processes in enzymes, protein-protein recognition, protein evolution and the origins of new biological functions. Here, we present a database of proteins with different degrees of conformational diversity. Conformational Diversity of Native State (CoDNaS) is a redundant collection of three-dimensional structures for the same protein derived from protein data bank. Structures for the same protein obtained under different crystallographic conditions have been associated with snapshots of protein dynamism and consequently could characterize protein conformers. CoDNaS allows the user to explore global and local structural differences among conformers as a function of different parameters such as presence of ligand, post-translational modifications, changes in oligomeric states and differences in pH and temperature. Additionally, CoDNaS contains information about protein taxonomy and function, disorder level and structural classification offering useful information to explore the underlying mechanism of conformational diversity and its close relationship with protein function. Currently, CoDNaS has 122 122 structures integrating 12 684 entries, with an average of 9.63 conformers per protein. Availability: The database is freely available at http://www.codnas.com.ar/ . Contact: gusparisi@gmail.com

Description: Motivation: Recent experimental advancements allow determining positions of nucleosomes for complete genomes. However, the resulting nucleosome occupancy maps are averages of heterogeneous cell populations. Accordingly, they represent a snapshot of a dynamic ensemble at a single time point with an overlay of many configurations from different cells. To study the organization of nucleosomes along the genome and to understand the mechanisms of nucleosome translocation, it is necessary to retrieve features of specific conformations from the population average. Results: Here, we present a method for identifying non-overlapping nucleosome configurations that combines binary-variable analysis and a Monte Carlo approach with a simulated annealing scheme. In this manner, we obtain specific nucleosome configurations and optimized solutions for the complex positioning patterns from experimental data. We apply the method to compare nucleosome positioning at transcription factor binding sites in different mouse cell types. Our method can model nucleosome translocations at regulatory genomic elements and generate configurations for simulations of the spatial folding of the nucleosome chain. Availability: Source code, precompiled binaries, test data and a web-based test installation are freely available at http://bioinformatics.fh-stralsund.de/nucpos/ Contact: gero.wedemann@fh-stralsund.de Supplementary Information: Supplementary data are available at Bioinformatics online.

Description: Wolbachia , endosymbiotic bacteria of the order Rickettsiales, are widespread in arthropods but also present in nematodes. In arthropods, A and B supergroup Wolbachia are generally associated with distortion of host reproduction. In filarial nematodes, including some human parasites, multiple lines of experimental evidence indicate that C and D supergroup Wolbachia are essential for the survival of the host, and here the symbiotic relationship is considered mutualistic. The origin of this mutualistic endosymbiosis is of interest for both basic and applied reasons: How does a parasite become a mutualist? Could intervention in the mutualism aid in treatment of human disease? Correct rooting and high-quality resolution of Wolbachia relationships are required to resolve this question. However, because of the large genetic distance between Wolbachia and the nearest outgroups, and the limited number of genomes so far available for large-scale analyses, current phylogenies do not provide robust answers. We therefore sequenced the genome of the D supergroup Wolbachia endosymbiont of Litomosoides sigmodontis , revisited the selection of loci for phylogenomic analyses, and performed a phylogenomic analysis including available complete genomes (from isolates in supergroups A, B, C, and D). Using 90 orthologous genes with reliable phylogenetic signals, we obtained a robust phylogenetic reconstruction, including a highly supported root to the Wolbachia phylogeny between a (A + B) clade and a (C + D) clade. Although we currently lack data from several Wolbachia supergroups, notably F, our analysis supports a model wherein the putatively mutualist endosymbiotic relationship between Wolbachia and nematodes originated from a single transition event.

Description: n-type ZnO:Cu photoanodes were fabricated by simple spray pyrolysis deposition technique. Influence of low concentration (range ~10−4–10−1%) of Cu doping in hexagonal ZnO lattice on its photoelectrochemical performance has been investigated. The doped photoanodes displayed 7-time enhanced conversion efficiencies with respect to their undoped counterpart, as estimated from the photocurrents generated under simulated solar radiation. This is the highest enhancement in the solar conversion efficiency reported so far for the Cu-doped ZnO. This performance is attributed to the red shift in the band gap of the Cu-doped films and is in accordance with the incident-photon-current-conversion efficiency (IPCE) measurements. Electrochemical studies reveal an n-type nature of these photoanodes. Thus, the study indicates a high potential of doped ZnO films for solar energy applications, in purview of the development of simple nanostructuring methodologies.

Description: Many insects rely on bacterial symbionts with tiny genomes specialized for provisioning nutrients lacking in host diets. Xylem sap and phloem sap are both deficient as insect diets, but differ dramatically in nutrient content, potentially affecting symbiont genome evolution. For sap-feeding insects, sequenced symbiont genomes are available only for phloem-feeding examples from the suborder Sternorrhyncha and xylem-feeding examples from the suborder Auchenorrhyncha, confounding comparisons. We sequenced genomes of the obligate symbionts, Sulcia muelleri and Nasuia deltocephalinicola , of the phloem-feeding pest insect, Macrosteles quadrilineatus (Auchenorrhyncha: Cicadellidae). Our results reveal that Nasuia- ALF has the smallest bacterial genome yet sequenced (112 kb), and that the Sulcia- ALF genome (190 kb) is smaller than that of Sulcia in other insect lineages. Together, these symbionts retain the capability to synthesize the 10 essential amino acids, as observed for several symbiont pairs from xylem-feeding Auchenorrhyncha. Nasuia retains genes enabling synthesis of two amino acids, DNA replication, transcription, and translation. Both symbionts have lost genes underlying ATP synthesis through oxidative phosphorylation, possibly as a consequence of the enriched sugar content of phloem. Shared genomic features, including reassignment of the UGA codon from Stop to tryptophan, and phylogenetic results suggest that Nasuia -ALF is most closely related to Zinderia , the betaproteobacterial symbiont of spittlebugs. Thus, Nasuia / Zinderia and Sulcia likely represent ancient associates that have co-resided in hosts since the divergence of leafhoppers and spittlebugs 〉200 Ma, and possibly since the origin of the Auchenorrhyncha, 〉260 Ma.

Description: It has been argued that scale is the central problem in ecology ( Levin, 1992 ). Studies on carbon cycles and global climate change, the current major themes in modern ecology, require the interfacing of phenomena that occur on different scales of space, time, and ecological organization. For several decades, tremendous efforts have been made to reveal the general patterns of, and the mechanisms for the global carbon cycles. However, many uncertainties remain, particularly on local to regional scales. To reduce these uncertainties, regional collaborations across the board of nations are required.

Description: Aims Boreal forest is the largest and contains the most soil carbon among global terrestrial biomes. Soil respiration during the prolonged winter period may play an important role in the carbon cycles in boreal forests. This study aims to explore the characteristics of winter soil respiration in the boreal forest and to show how it is regulated by environmental factors, such as soil temperature, soil moisture and snowpack. Methods Soil respiration in an old-growth larch forest ( Larix gmelinii Ruppr.) in Northeast China was intensively measured during the winter soil-freezing process in 2011 using an automated soil CO 2 flux system. The effects of soil temperature, soil moisture and thin snowpack on soil respiration and its temperature sensitivity were investigated. Important Findings Total soil respiration and heterotrophic respiration both showed a declining trend during the observation period, and no significant difference was found between soil respiration and heterotrophic respiration until the snowpack exceeded 20cm. Soil respiration was exponentially correlated with soil temperature and its temperature sensitivity (Q 10 value) for the entire measurement duration was 10.5. Snow depth and soil moisture both showed positive effects on the temperature sensitivity of soil respiration. Based on the change in the Q 10 value, we proposed a ‘freeze–thaw critical point’ hypothesis, which states that the Q 10 value above freeze–thaw critical point is much higher than that below it (16.0 vs . 3.5), and this was probably regulated by the abrupt change in soil water availability during the soil-freezing process. Our findings suggest interactive effects of multiple environmental factors on winter soil respiration and recommend adopting the freeze–thaw critical point to model soil respiration in a changing winter climate.

Description: Aims Clear-cutting is a common forest management practice, especially in subtropical China. However, the potential ecological consequences of clear-cutting remain unclear. In particular, the effect of clear-cutting on soil processes, such as the carbon cycle, has not been quantified in subtropical forests. Here, we investigated the response of soil respiration (Rs) to clear-cutting during a 12-month period in a subtropical forest in eastern China. Methods We randomly selected four clear-cut (CC) plots and four corresponding undisturbed forest (UF) plots. Measurements of Rs were made at monthly time points and were combined with continuous climatic measurements in both CC and UF. Daily Rs was estimated by interpolating data with an exponential model dependent on soil temperature. Daily Rs was cumulated to annual Rs estimates. Important Findings In the first year after clear-cutting, annual estimates of Rs in CC (508±23g C m –2 yr –1 ) showed no significant difference to UF plots (480±12g C m –2 yr –1 ). During the summer, soil temperatures were usually higher, whereas the soil volumetric water content was lower in CC than in UF plots. The long-term effects of clear-cutting on Rs are not significant, although there might be effects during the first several months after clear-cutting. Compared with previous work, this pattern was more pronounced in our subtropical forest than in the temperate and boreal forests that have been studied by others. With aboveground residuals off-site after clear-cutting, our results indicate that the stimulation of increasing root debris, as well as environmental changes, will not lead to a significant increase in Rs. In addition, long-term Rs will not show a significant decrease from the termination of root respiration, and this observation might be because of the influence of fast-growing vegetation after clear-cutting in situ .

Description: Aims Understanding carbon (C) and nitrogen (N) dynamics and their dependence on the stand density of an even-aged, mature forest provides knowledge that is important for forest management. This study investigated the differences in ecosystem total C and N storage and flux between a low-density stand (LD) and a high-density stand (HD) and examined the effects of stand density on aboveground net primary productivity (ANPP), total belowground C allocation (TBCA) and net ecosystem production (NEP) in a naturally regenerated, 65- to 75-year-old Pinus densiflora S. et Z. forest. Methods LD (450 trees ha –1 ) and HD (842 trees ha –1 ) were established in an even-aged, mature P. densiflora forest in September 2006. The forest had been naturally regenerated following harvesting, and the stand density was naturally maintained without any artificial management such as thinning. The diameter at breast height (DBH ≥ 5.0cm) of all live stems within the stands was measured yearly from 2007 to 2011. To compare C and N storage and fluxes in LD and HD, C and N pools in aboveground and belowground biomass, the forest floor, coarse woody debris (CWD) and soil; soil CO 2 efflux ( R S ); autotrophic respiration ( R A ); litter production; and soil N availability were measured. Further, ANPP, TBCA and NEP were estimated from plot-based measurement data. Important Findings Ecosystem C (Mg C ha –1 ) and N (Mg N ha –1 ) storage was, respectively, 173.0±7.3 (mean ± SE) and 4.69±0.30 for LD and 162±11.8 and 4.08±0.18 for HD. There were no significant differences in C and N storage in the ecosystem components, except for soils, between the two stands. In contrast, there were significant differences in aboveground ANPP and TBCA between the two stands ( P 〈 0.05). Litterfall, biomass increment and R S were major C flux components with values of, respectively, 3.89, 3.74 and 9.07 Mg C ha –1 year –1 in LD and 3.15, 2.94 and 7.06 Mg C ha –1 year –1 in HD. Biometric-based NEP (Mg C ha –1 year –1 ) was 4.18 in LD and 5.50 in HD. Although the even-aged, mature P. densiflora forest had similar C and N allocation patterns, it showed different C and N dynamics depending on stand density. The results of the current study will be useful for elucidating the effects of stand density on C and N storage and fluxes, which are important issues in managing natural mature forest ecosystems.

Description: Aims Tropical forest plays a key role in global C cycle; however, there are few studies on the C budget in the tropical rainforests in Asia. This study aims to (i) reveal the seasonal patterns of total soil respiration ( R T ), litter respiration ( R L ) and soil respiration without surface organic litter ( R NL ) in the primary and secondary Asian tropical mountain rainforests and (ii) quantify the effects of soil temperature, soil moisture and substrate availability on soil respiration. Methods The seasonal dynamics of soil CO 2 efflux was measured by an automatic chamber system (Li-8100), within the primary and secondary tropical mountain rainforests located at the Jianfengling National Reserve in Hainan Island, China. The litter removal treatment was used to assess the contribution of litter to belowground CO 2 production. Important Findings The annual R T was higher in the primary forest (16.73±0.87 Mg C ha –1 ) than in the secondary forest (15.10±0.26 Mg C ha –1 ). The rates of R T , R NL and R L were all significantly higher in the hot and wet season (May–October) than those in the cool and dry season (November–April). Soil temperature at 5cm depth could explain 55–61% of the seasonal variation in R T , and the temperature sensitivity index ( Q 10 ) ranked by R L ( Q 10 = 3.39) 〉 R T (2.17) 〉 R NL (1.76) in the primary forest and by R L (4.31) 〉 R T (1.86) 〉 R NL (1.58) in the secondary forest. The contribution of R L to R T was 22–23%, while litter input and R T had 1 month time lag. In addition, the seasonal variation of R T was mainly determined by soil temperature and substrate availability. Our findings suggested that global warming and increased substrate availability are likely to cause considerable losses of soil C in the tropical forests.

Description: Aims Understanding of the ecophysiological dynamics of forest canopy photosynthesis and its spatial and temporal scaling is crucial for revealing ecological response to climate change. Combined observations and analyses of plant ecophysiology and optical remote sensing would enable us to achieve these studies. In order to examine the utility of spectral vegetation indices (VIs) for assessing ecosystem-level photosynthesis, we investigated the relationships between canopy-scale photosynthetic productivity and canopy spectral reflectance over seasons for 5 years in a cool, temperate deciduous broadleaf forest at ‘Takayama’ super site in central Japan. Methods Daily photosynthetic capacity was assessed by in situ canopy leaf area index (LAI), (LAI x V cmax [single-leaf photosynthetic capacity]), and the daily maximum rate of gross primary production (GPP max ) was estimated by an ecosystem carbon cycle model. We examined five VIs: normalized difference vegetation index (NDVI), enhanced vegetation index (EVI), green–red vegetation index (GRVI), chlorophyll index (CI) and canopy chlorophyll index (CCI), which were obtained by the in situ measurements of canopy spectral reflectance. Important Findings Our in situ observation of leaf and canopy characteristics, which were analyzed by an ecosystem carbon cycling model, revealed that their phenological changes are responsible for seasonal and interannual variations in canopy photosynthesis. Significant correlations were found between the five VIs and canopy photosynthetic capacity over the seasons and years; four of the VIs showed hysteresis-type relationships and only CCI showed rather linear relationship. Among the VIs examined, we applied EVI–GPP max relationship to EVI data obtained by Moderate Resolution Imaging Spectroradiometer to estimate the temporal and spatial variation in GPP max over central Japan. Our findings would improve the accuracy of satellite-based estimate of forest photosynthetic productivity in fine spatial and temporal resolutions, which are necessary for detecting any response of terrestrial ecosystem to meteorological fluctuations.

Description: Aims This study aimed to develop radial growth models and to predict the potential spatial distribution of Pinus densiflora (Japanese red pine) and Quercus spp. (Oaks) in South Korea, considering topographic and climatic factors. Methods We used a dataset of diameter at breast height and radial growth estimates of individual trees, topographic and climatic factors in systematic sample plots distributed over the whole of South Korea. On the basis that radial growth is attributed primarily to tree age, we developed a radial growth model employing tree age as an explanatory variable. We estimated standard growth (SG), defined as radial growth of the tree at age 30, to eliminate the influence of tree age on radial growth. In addition, SG estimates including the Topographic Wetness Index, temperature and precipitation were calculated by the Generalized Additive Model. Important Findings As a result of variogram analysis of SG, we found spatial autocorrelation between SG, topographic and climatic factors. Incremental temperature had negative impacts on radial growth of P. densiflora and positive impacts on that of Quercus spp. Precipitation was associated with positive effects on both tree species. Based on the model, we found that radial growth of P. densiflora would be more vulnerable than that of Quercus spp. to climatic factors. Through simulation with the radial growth model, it was predicted that P. densiflora stands would be gradually replaced with Quercus spp. stands in eastern coastal and southern regions of South Korea in the future. The models developed in this study will be helpful for understanding the impact of climatic factors on tree growth and for predicting changes in distribution of P. densiflora and Quercus spp. due to climate change in South Korea.

Description: With the growing interest in ubiquitous technologies recently, many studies have been conducted in order to manage wireless sensor network, which is the central component in ubiquitous environment. To manage a certain wireless sensor network, a variety of techniques can be applied and thereby the network can be managed. However, it is very complicated and time-consuming to incorporate and manage more than a heterogeneous wireless sensor network since each network has different data, meanings, and terms. Instead of conducting verification through examining the detailed technology or simulation in order to manage a variety of wireless sensor networks, we suggest a methodology which manages data coming from the various sensors mentioned above, a technique by which those data from various sensor networks are managed in each different network, and a methodology which manages sensor networks where management languages exist. This paper defined the network-related terminology using Protégé for the tools and definitions necessary for ontology-based methodology, thereby defined OWL and the related rules, and suggested a methodology for incorporated management. In addition, this study showed that the methodology presented in this study has expandability and it can incorporate and manage a variety of wireless sensor networks.

Description: Aims Vast grasslands on the Tibetan Plateau are almost all under livestock grazing. It is unclear, however, what is the role that the grazing will play in carbon cycle of the grassland under future climate warming. We found in our previous study that experimental warming can shift the optimum temperature of saturated photosynthetic rate into higher temperature in alpine plants. In this study, we proposed and tested the hypothesis that livestock grazing would alter the warming effect on photosynthetic and respiration through changing physical environments of grassland plants. Methods Experimental warming was carried by using an infrared heating system to increase the air temperature by 1.2 and 1.7°C during the day and night, respectively. The warming and ambient temperature treatments were crossed over to the two grazing treatments, grazing and un-grazed treatments, respectively. To assess the effects of grazing and warming, we examined photosynthesis, dark respiration, maximum rates of the photosynthetic electron transport ( J max ), RuBP carboxylation ( V cmax ) and temperature sensitivity of respiration Q 10 in Gentiana straminea , an alpine species widely distributed on the Tibetan grassland. Leaf morphological and chemical properties were also examined to understand the physiological responses. Important findings 1) Light-saturated photosynthetic rate ( A max ) of G. straminea showed similar temperature optimum at around 16°C in plants from all experimental conditions. Experimental warming increased A max at all measuring temperatures from 10 to 25°C, but the positive effect of the warming occurred only in plants grown under the un-grazed conditions. Under the same measuring temperature, A max was significantly higher in plants from the grazed than the un-grazed condition. 2) There was significant crossing effect of warming and grazing on the temperature sensitivity ( Q 10 ) of leaf dark respiration. Under the un-grazed condition, plants from the warming treatment showed lower respiration rate but similar Q 10 in comparison with plants from the ambient temperature treatment. However, under the grazed condition Q 10 was significantly lower in plants from the warming than the ambient treatment. 3) The results indicate that livestock grazing can alter the warming effects on leaf photosynthesis and temperature sensitivity of leaf dark respiration through changing physical environment of the grassland plants. The study suggests for the first time that grazing effects should be taken into account in predicting global warming effects on photosynthesis and respiration of plants in those grasslands with livestock grazing.

Description: The environmental impact of the Puyehue–Cordon Caulle 2011 volcanic eruption on Buenos Aires Natural Hazards and Earth System Science, 13, 2319-2330, 2013 Author(s): G. B. Raga, D. Baumgardner, A. G. Ulke, M. Torres Brizuela, and B. Kucienska On 4 June 2011, the volcanic complex Puyehue–Cordon Caulle located in the Chilean Andes erupted, producing a plume of gases and particles that eventually circled the Southern Hemisphere, disrupting air travel and depositing ash in large quantities. On eight occasions, the plume passed over the city of Buenos Aires, Argentina, leading local authorities to close the two international airports. The eruption occurred during an on-going field campaign when measurements of the properties of atmospheric aerosol particles were being made in Buenos Aires as part of a year-long study of the concentration and optical properties of aerosol at one site in the city. The suite of instruments deployed in Buenos Aires were not tailored to measurements of volcanic ash, but were designed to characterize urban conditions. Nevertheless, these measurements were analysed for periods when vertical profiles of aerosol backscatter, made with a ceilometer, clearly showed the presence of the volcano plume over the research site and resulted in airport closure. Aerosol optical thickness derived from AERONET, MODIS and a ceilometer at our research site, all show enhanced values clearly indicating that the three platforms identified the volcanic plume simultaneously. However, a quantitative comparison of the different estimates proves difficult, suggesting large spatial and temporal variability of the plume. Our results indicate that the number concentration of condensation nuclei (CN), the mass concentration of particle-bound polycyclic aromatic hydrocarbons (PPAH) and the light absorption coefficient exceeded the average background values by more than one standard deviation during the events of volcanic plume. The anomalous concentrations of CN suggest new particle formation, presumably from the conversion of SO 2 , while the anomalous concentrations of PPAH may come from the uptake of PAHs on the plume particles or from chemical reactions on the surface of plume particles. The anomalous absorption coefficients indicate that plume particles may contain certain compounds that can absorb radiation at 550 nm. Another possible explanation consistent with the observations is the scavenging of black carbon from urban sources as the plume descends through the boundary layer to the surface. In addition, the volcanic plume influenced the local meteorology resulting in a decrease of the temperature when compared to the average temperature during days with no plume present.

Description: Contribution of land use changes to future flood damage along the river Meuse in the Walloon region Natural Hazards and Earth System Science, 13, 2301-2318, 2013 Author(s): A. Beckers, B. Dewals, S. Erpicum, S. Dujardin, S. Detrembleur, J. Teller, M. Pirotton, and P. Archambeau Managing flood risk in Europe is a critical issue because climate change is expected to increase flood hazard in many european countries. Beside climate change, land use evolution is also a key factor influencing future flood risk. The core contribution of this paper is a new methodology to model residential land use evolution. Based on two climate scenarios ("dry" and "wet"), the method is applied to study the evolution of flood damage by 2100 along the river Meuse. Nine urbanization scenarios were developed: three of them assume a "current trend" land use evolution, leading to a significant urban sprawl, while six others assume a dense urban development, characterized by a higher density and a higher diversity of urban functions in the urbanized areas. Using damage curves, the damage estimation was performed by combining inundation maps for the present and future 100 yr flood with present and future land use maps and specific prices. According to the dry scenario, the flood discharge is expected not to increase. In this case, land use changes increase flood damages by 1–40%, to €334–462 million in 2100. In the wet scenario, the relative increase in flood damage is 540–630%, corresponding to total damages of €2.1–2.4 billion. In this extreme scenario, the influence of climate on the overall damage is 3–8 times higher than the effect of land use change. However, for seven municipalities along the river Meuse, these two factors have a comparable influence. Consequently, in the "wet" scenario and at the level of the whole Meuse valley in the Walloon region, careful spatial planning would reduce the increase in flood damage by no more than 11–23%; but, at the level of several municipalities, more sustainable spatial planning would reduce future flood damage to a much greater degree.

Description: Uptake of phytodetritus by benthic foraminifera under oxygen depletion at the Indian Margin (Arabian Sea) Biogeosciences Discussions, 10, 15305-15335, 2013 Author(s): A. J. Enge, U. Witte, M. Kucera, and P. Heinz Benthic foraminifera in sediments on the Indian margin of the Arabian Sea where the oxygen minimum zone (OMZ) impinges on the continental slope are exposed to particularly severe levels of oxygen depletion. Food supply for the benthic community is high but delivered in distinct pulses during upwelling and water mixing events associated with summer and winter monsoon periods. In order to investigate the response by benthic foraminifera to such pulsed food delivery under oxygen concentrations of less than 0.1 mL L −1 (4.5 μmol L −1 ), an in situ isotope labeling experiment ( 13 C, 15 N) was performed at the western continental slope of India at 540 m water depth (OMZ core region). The assemblage of living foraminifera (〉125 μm) in the uppermost centimeter at this depth is characterized by an unexpectedly high population density of 3982 ind. 10 cm −2 and a strong dominance by few calcareous species. For the experiment, we concentrated on the nine most abundant taxa, which constitute 93% of the entire foraminifera population at 0–1 cm sediment depth. Increased concentrations of 13 C and 15 N in the cytoplasm indicate that all investigated taxa took up the labeled phytodetritus during the 4 day experimental phase. In total, these nine species had assimilated 113.8 mg C m −2 (17.5% of the total added carbon). The uptake of nitrogen by the three most abundant taxa ( Bolivina aff. B. dilatata , Cassidulina sp., Bulimina gibba ) was 2.7 mg N m −2 (2% of the total added nitrogen) and showed the successful application of 15 N as tracer in foraminiferal studies. The short-term response to the offered phytodetritus varied largely among foraminiferal species with Uvigerina schwageri being by far the most important species in short-term processing whereas the most abundant taxa Bolivina aff. B. dilatata and Cassidulina sp. showed comparably low uptake of the offered food. We suggest that the observed species-specific differences are related to individual biomass of species and to specific feeding preferences. The high numbers of living foraminifera and their rapid response to deposited fresh phytodetritus demonstrate the importance of foraminifera in short-term carbon cycling under oxygen-depleted conditions. We propose that foraminifera at the studied site benefit from unique adaptations in their metabolisms to nearly anoxic conditions as well as from the exclusion of macrofauna and the resulting relaxation of competition for food and low predation pressure.

Description: A general treatment of snow microstructure exemplified by an improved relation for thermal conductivity The Cryosphere, 7, 1473-1480, 2013 Author(s): H. Löwe, F. Riche, and M. Schneebeli Finding relevant microstructural parameters beyond density is a longstanding problem which hinders the formulation of accurate parameterizations of physical properties of snow. Towards a remedy, we address the effective thermal conductivity tensor of snow via anisotropic, second-order bounds. The bound provides an explicit expression for the thermal conductivity and predicts the relevance of a microstructural anisotropy parameter Q , which is given by an integral over the two-point correlation function and unambiguously defined for arbitrary snow structures. For validation we compiled a comprehensive data set of 167 snow samples. The set comprises individual samples of various snow types and entire time series of metamorphism experiments under isothermal and temperature gradient conditions. All samples were digitally reconstructed by micro-computed tomography to perform microstructure-based simulations of heat transport. The incorporation of anisotropy via Q considerably reduces the root mean square error over the usual density-based parameterization. The systematic quantification of anisotropy via the two-point correlation function suggests a generalizable route to incorporate microstructure into snowpack models. We indicate the inter-relation of the conductivity to other properties and outline a potential impact of Q on dielectric constant, permeability and adsorption rate of diffusing species in the pore space.

Description: Summertime canopy albedo is sensitive to forest thinning Biogeosciences Discussions, 10, 15373-15414, 2013 Author(s): J. Otto, D. Berveiller, F.-M. Bréon, N. Delpierre, G. Geppert, A. Granier, W. Jans, A. Knohl, A. Kuusk, B. Longdoz, E. Moors, M. Mund, B. Pinty, M.-J. Schelhaas, and S. Luyssaert Despite an emerging body of literature linking canopy albedo to forest management, understanding of the process is still fragmented. We combined a stand-level forest gap model with a canopy radiation transfer model and satellite-derived model parameters to quantify the effects of forest thinning, that is removing trees at a certain time during the forest rotation, on summertime canopy albedo. The effects of different forest species (pine, beech, oak) and four thinning strategies (light to intense thinning regimes) were examined. During stand establishment, summertime canopy albedo is driven by tree species. In the later stages of stand development, the effect of tree species on summertime canopy albedo decreases in favour of an increasing influence of forest thinning on summertime canopy albedo. These trends continue until the end of the rotation where thinning explains up to 50% of the variance in near-infrared canopy albedo and up to 70% of the variance in visible canopy albedo. More intense thinning lowers the summertime shortwave albedo in the canopy by as much as 0.02 compared to unthinned forest. The structural changes associated with forest thinning can be described by the change in LAI in combination with crown volume. However, forests with identical canopy structure can have different summertime albedo values due to their location: the further north a forest is situated, the more the solar zenith angle increases and thus the higher is the summertime canopy albedo, independent of the wavelength. Despite the increase of absolute summertime canopy albedo values with latitude, the difference in canopy albedo between managed and unmanaged forest decreases with increasing latitude. Forest management thus strongly altered summertime forest albedo.

Description: Antenna array synthesis is an important issue in MIMO radars. By judiciously designing antenna positions, one can create a very long virtual array steering vector with a small number of antennas and therefore achieve very high spatial resolution at a small cost. This paper presents a combinatorial methodology based on cyclic difference sets (CDSs) for minimum redundancy (MR) MIMO array synthesis which seeks to maximize the virtual array aperture for a given number of antennas. First, the key features of CDSs and the CDS-based MR-MIMO layouts are described. Then, the analytical expression of the maximum contiguous virtual array aperture is derived. Further, based on this expression, an enumerative shifting procedure is developed for identifying the optimal CDS-based MR-MIMO layout. Selected examples are analyzed to point out the computational effectiveness of the CDS-based MR-MIMO array synthesis.

Description: Wireless sensor networks (WSNs) are becoming bigger, and with this growth comes the need for new automatic mechanisms for initializations done by hand. One of those mechanisms is the assignment of addresses to nodes. Several solutions were already proposed for mobile ad hoc networks but they either (i) do not scale well for WSN; (ii) have no energy constraints; (iii) have no security considerations; (iv) or have no mechanisms to handle fusion of network partitions. We proposed an address self-assignment protocol which uses negative acknowledgements and an improved version of a flood control mechanism to minimize the energy spent; uses a technique named whispering to achieve robustness against malicious nodes; is able to detect dynamic network re-joint and dynamic node addition without exchanging specific messages; and handles both dynamic events without compromising routing tables.

Description: Prions are considered the best example to prove that the biological information can be transferred protein to protein through a conformational change. The term “prion-like” is used to describe molecular mechanisms that share similarities with the mammalian prion protein self-perpetuating aggregation and spreading characteristics. Since prions are presumably composed only of protein and are infectious, the more similar the mechanisms that occur in the different neurodegenerative diseases, the more these processes will resemble an infection. In vitro and in vivo experiments carried out during the last decade in different neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's diseases (PD), and amyotrophic lateral sclerosis (ALS) have shown a convergence toward a unique mechanism of misfolded protein propagation. In spite of the term “infection” that could be used to explain the mechanism governing the diversity of the pathological processes, other concepts as “seeding” or “de novo induction” are being used to describe the in vivo propagation and transmissibility of misfolded proteins. The current studies are demanding an extended definition of “disease-causing agents” to include those already accepted as well as other misfolded proteins. In this new scenario, “seeding” would be a type of mechanism by which an infectious agent can be transmitted but should not be used to define a whole “infection” process.

Description: Plants are unique among eukaryotes in having evolved organelles: the protein storage vacuole, protein body, and chloroplast. Disulfide transfer pathways that function in the endoplasmic reticulum (ER) and chloroplasts of plants play critical roles in the development of protein storage organelles and the biogenesis of chloroplasts, respectively. Disulfide bond formation requires the cooperative function of disulfide-generating enzymes (e.g., ER oxidoreductase 1), which generate disulfide bonds de novo, and disulfide carrier proteins (e.g., protein disulfide isomerase), which transfer disulfides to substrates by means of thiol-disulfide exchange reactions. Selective molecular communication between disulfide-generating enzymes and disulfide carrier proteins, which reflects the molecular and structural diversity of disulfide carrier proteins, is key to the efficient transfer of disulfides to specific sets of substrates. This review focuses on recent advances in our understanding of the mechanisms and functions of the various disulfide transfer pathways involved in oxidative protein folding in the ER, chloroplasts, and mitochondria of plants.

Description: We have developed a new screening methodology for identifying all genes that control the expression of a target gene through genetic or metabolic interactions. The screen combines mutant libraries with luciferase reporter constructs, whose expression can be monitored in vivo and over time in different environmental conditions. We apply the method to identify the genes that control the expression of the gene acs , encoding the acetyl coenzyme A synthetase, in Escherichia coli . We confirm most of the known genetic regulators, including CRP–cAMP, IHF and components of the phosphotransferase system. In addition, we identify new regulatory interactions, many of which involve metabolic intermediates or metabolic sensing, such as the genes pgi, pfkA , sucB and lpdA , encoding enzymes in glycolysis and the TCA cycle. Some of these novel interactions were validated by quantitative reverse transcriptase-polymerase chain reaction. More generally, we observe that a large number of mutants directly or indirectly influence acs expression, an effect confirmed for a second promoter, sdhC . The method is applicable to any promoter fused to a luminescent reporter gene in combination with a deletion mutant library.

Description: Tandem repeats (TRs) are often present in proteins with crucial functions, responsible for resistance, pathogenicity and associated with infectious or neurodegenerative diseases. This motivates numerous studies of TRs and their evolution, requiring accurate multiple sequence alignment. TRs may be lost or inserted at any position of a TR region by replication slippage or recombination, but current methods assume fixed unit boundaries, and yet are of high complexity. We present a new global graph-based alignment method that does not restrict TR unit indels by unit boundaries. TR indels are modeled separately and penalized using the phylogeny-aware alignment algorithm. This ensures enhanced accuracy of reconstructed alignments, disentangling TRs and measuring indel events and rates in a biologically meaningful way. Our method detects not only duplication events but also all changes in TR regions owing to recombination, strand slippage and other events inserting or deleting TR units. We evaluate our method by simulation incorporating TR evolution, by either sampling TRs from a profile hidden Markov model or by mimicking strand slippage with duplications. The new method is illustrated on a family of type III effectors, a pathogenicity determinant in agriculturally important bacteria Ralstonia solanacearum. We show that TR indel rate variation contributes to the diversification of this protein family.

Description: A renewed interest in non-coding RNA (ncRNA) has led to the discovery of novel RNA species and post-transcriptional ribonucleoside modifications, and an emerging appreciation for the role of ncRNA in RNA epigenetics. Although much can be learned by amplification-based analysis of ncRNA sequence and quantity, there is a significant need for direct analysis of RNA, which has led to numerous methods for purification of specific ncRNA molecules. However, no single method allows purification of the full range of cellular ncRNA species. To this end, we developed a multidimensional chromatographic platform to resolve, isolate and quantify all canonical ncRNAs in a single sample of cells or tissue, as well as novel ncRNA species. The applicability of the platform is demonstrated in analyses of ncRNA from bacteria, human cells and plasmodium-infected reticulocytes, as well as a viral RNA genome. Among the many potential applications of this platform are a system-level analysis of the dozens of modified ribonucleosides in ncRNA, characterization of novel long ncRNA species, enhanced detection of rare transcript variants and analysis of viral genomes.

Description: The synthesis of protein from messenger RNA during translation is a highly dynamic process that plays a key role in controlling the efficiency and fidelity of genome-wide protein expression. The availability of aminoacylated transfer RNA (tRNA) is a major factor influencing the speed of ribosomal movement, which depending on codon choices, varies considerably along a transcript. Furthermore, it has been shown experimentally that tRNA availability can vary significantly under different growth and stress conditions, offering the cell a way to adapt translational dynamics across the genome. Existing models of translation have neglected fluctuations of tRNA pools, instead assuming fixed tRNA availabilities over time. This has lead to an incomplete understanding of this process. Here, we show for the entire Escherichia coli genome how and to what extent translational speed profiles, which capture local aspects of translational elongation, respond to measured shifts in tRNA availability. We find that translational profiles across the genome are affected to differing degrees, with genes that are essential or related to fundamental processes such as translation, being more robust than those linked to regulation. Furthermore, we reveal how fluctuating tRNA availability influences profiles of specific sequences known to play a significant role in translational control of gene expression.

Description: Central to Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas systems are repeated RNA sequences that serve as Cas-protein–binding templates. Classification is based on the architectural composition of associated Cas proteins, considering repeat evolution is essential to complete the picture. We compiled the largest data set of CRISPRs to date, performed comprehensive, independent clustering analyses and identified a novel set of 40 conserved sequence families and 33 potential structure motifs for Cas-endoribonucleases with some distinct conservation patterns. Evolutionary relationships are presented as a hierarchical map of sequence and structure similarities for both a quick and detailed insight into the diversity of CRISPR-Cas systems. In a comparison with Cas-subtypes, I-C, I-E, I-F and type II were strongly coupled and the remaining type I and type III subtypes were loosely coupled to repeat and Cas1 evolution, respectively. Subtypes with a strong link to CRISPR evolution were almost exclusive to bacteria; nevertheless, we identified rare examples of potential horizontal transfer of I-C and I-E systems into archaeal organisms. Our easy-to-use web server provides an automated assignment of newly sequenced CRISPRs to our classification system and enables more informed choices on future hypotheses in CRISPR-Cas research: http://rna.informatik.uni-freiburg.de/CRISPRmap .

Description: Escherichia coli Exonuclease IX (ExoIX), encoded by the xni gene, was the first identified member of a novel subfamily of ubiquitous flap endonucleases (FENs), which possess only one of the two catalytic metal-binding sites characteristic of other FENs. We have solved the first structure of one of these enzymes, that of ExoIX itself, at high resolution in DNA-bound and DNA-free forms. In the enzyme–DNA cocrystal, the single catalytic site binds two magnesium ions. The structures also reveal a binding site in the C-terminal domain where a potassium ion is directly coordinated by five main chain carbonyl groups, and we show this site is essential for DNA binding. This site resembles structurally and functionally the potassium sites in the human FEN1 and exonuclease 1 enzymes. Fluorescence anisotropy measurements and the crystal structures of the ExoIX:DNA complexes show that this potassium ion interacts directly with a phosphate diester in the substrate DNA.

Description: One of the obstacles hindering a better understanding of cancer is its heterogeneity. However, computational approaches to model cancer heterogeneity have lagged behind. To bridge this gap, we have developed a new probabilistic approach that models individual cancer cases as mixtures of subtypes. Our approach can be seen as a meta-model that summarizes the results of a large number of alternative models. It does not assume predefined subtypes nor does it assume that such subtypes have to be sharply defined. Instead given a measure of phenotypic similarity between patients and a list of potential explanatory features, such as mutations, copy number variation, microRNA levels, etc., it explains phenotypic similarities with the help of these features. We applied our approach to Glioblastoma Multiforme (GBM). The resulting model Prob_GBM, not only correctly inferred known relationships but also identified new properties underlining phenotypic similarities. The proposed probabilistic framework can be applied to model relations between similarity of gene expression and a broad spectrum of potential genetic causes.

Description: Estrogen regulates over a thousand genes, with an equal number of them being induced or repressed. The distinct mechanisms underlying these dual transcriptional effects remain largely unknown. We derived comprehensive views of the transcription machineries assembled at estrogen-responsive genes through integrating multiple types of genomic data. In the absence of estrogen, the majority of genes formed higher-order chromatin structures, including DNA loops tethered to protein complexes involving RNA polymerase II (Pol II), estrogen receptor alpha (ERα) and ERα-pioneer factors. Genes to be ‘repressed’ by estrogen showed active transcription at promoters and throughout the gene bodies; genes to be ‘induced’ exhibited active transcription initiation at promoters, but with transcription paused in gene bodies. In the presence of estrogen, the majority of estrogen-induced genes retained the original higher-order chromatin structures, whereas most estrogen-repressed genes underwent a chromatin reconfiguration. For estrogen-induced genes, estrogen enhances transcription elongation, potentially through recruitment of co-activators or release of co-repressors with unique roles in elongation. For estrogen-repressed genes, estrogen treatment leads to chromatin structure reconfiguration, thereby disrupting the originally transcription-efficient chromatin structures. Our in silico studies have shown that estrogen regulates gene expression, at least in part, through modifying previously assembled higher-order complexes, rather than by facilitating de novo assembly of machineries.

Description: The mineralocorticoid receptor (MR) is a ligand-induced transcription factor belonging to the steroid receptor family and involved in water-electrolyte homeostasis, blood pressure regulation, inflammation and fibrosis in the renocardiovascular system. The MR shares a common hormone-response-element with the glucocorticoid receptor but nevertheless elicits MR-specific effects including enhanced epidermal growth factor receptor (EGFR) expression via unknown mechanisms. The EGFR is a receptor tyrosine kinase that leads to activation of MAP kinases, but that can also function as a signal transducer for other signaling pathways. In the present study, we mechanistically investigate the interaction between a newly discovered MR- but not glucocorticoid receptor- responsive-element (=MRE1) of the EGFR promoter, specificity protein 1 (SP1) and MR to gain general insights into MR-specificity. Biological relevance of the interaction for EGFR expression and consequently for different signaling pathways in general is demonstrated in human, rat and murine vascular smooth muscle cells and cells of EGFR knockout mice. A genome-wide promoter search for identical binding regions followed by quantitative PCR validation suggests that the identified MR-SP1–MRE1 interaction might be applicable to other genes. Overall, a novel principle of MR-specific gene expression is explored that applies to the pathophysiologically relevant expression of the EGFR and potentially also to other genes.

Description: Selective inhibitory crosstalk has been known to occur within the signaling pathways of the dioxin (AhR) and estrogen (ERα) receptors. More specifically, ERα represses a cytochrome P450-encoding gene ( CYP1A1 ) that converts cellular estradiol into a metabolite that inhibits the cell cycle, while it has no effect on a P450-encoding gene ( CYP1B1 ) that converts estrodiol into a genotoxic product. Here we show that ERα represses CYP1A1 by targeting the Dnmt3B DNA methyltransferase and concomitant DNA methylation of the promoter. We also find that histone H2A.Z can positively contribute to CYP1A1 gene expression, and its presence at that gene is inversely correlated with DNA methylation. Taken together, our results provide a framework for how ERα can repress transcription, and how that impinges on the production of an enzyme that generates genotoxic estradiol metabolites, and potential breast cancer progression. Finally, our results reveal a new mechanism for how H2A.Z can positively influence gene expression, which is by potentially competing with DNA methylation events in breast cancer cells.

Description: TFIIIB and TFIIIC are multi-subunit factors required for transcription by RNA polymerase III. We present a genome-wide high-resolution footprint map of TFIIIB–TFIIIC complexes in Saccharomyces cerevisiae , obtained by paired-end sequencing of micrococcal nuclease-resistant DNA. On tRNA genes, TFIIIB and TFIIIC form stable complexes with the same distinctive occupancy pattern but in mirror image, termed ‘bootprints’. Global analysis reveals that the TFIIIB–TFIIIC transcription complex exhibits remarkable structural elasticity: tRNA genes vary significantly in length but remain protected by TFIIIC. Introns, when present, are markedly less protected. The RNA polymerase III transcription terminator is flexibly accommodated within the transcription complex and, unexpectedly, plays a major structural role by delimiting its 3'-boundary. The ETC sites, where TFIIIC binds without TFIIIB, exhibit different bootprints, suggesting that TFIIIC forms complexes involving other factors. We confirm six ETC sites and report a new site ( ETC10 ). Surprisingly, TFIIIC, but not TFIIIB, interacts with some centromeric nucleosomes, suggesting that interactions between TFIIIC and the centromere may be important in the 3D organization of the nucleus.

Description: The process of DNA mismatch repair is initiated when MutS recognizes mismatched DNA bases and starts the repair cascade. The Escherichia coli MutS protein exists in an equilibrium between dimers and tetramers, which has compromised biophysical analysis. To uncouple these states, we have generated stable dimers and tetramers, respectively. These proteins allowed kinetic analysis of DNA recognition and structural analysis of the full-length protein by X-ray crystallography and small angle X-ray scattering. Our structural data reveal that the tetramerization domains are flexible with respect to the body of the protein, resulting in mostly extended structures. Tetrameric MutS has a slow dissociation from DNA, which can be due to occasional bending over and binding DNA in its two binding sites. In contrast, the dimer dissociation is faster, primarily dependent on a combination of the type of mismatch and the flanking sequence. In the presence of ATP, we could distinguish two kinetic groups: DNA sequences where MutS forms sliding clamps and those where sliding clamps are not formed efficiently. Interestingly, this inability to undergo a conformational change rather than mismatch affinity is correlated with mismatch repair.

Description: Phosphorylation of histone H4 serine 47 (H4S47ph) is catalyzed by Pak2, a member of the p21-activated serine/threonine protein kinase (Pak) family and regulates the deposition of histone variant H3.3. However, the phosphatase(s) involved in the regulation of H4S47ph levels was unknown. Here, we show that three phosphatases (PP1α, PP1β and Wip1) regulate H4S47ph levels and H3.3 deposition. Depletion of each of the three phosphatases results in increased H4S47ph levels. Moreover, PP1α, PP1β and Wip1 bind H3-H4 in vitro and in vivo , whereas only PP1α and PP1β, but not Wip1, interact with Pak2 in vivo . These results suggest that PP1α, PP1β and Wip1 regulate the levels of H4S47ph through directly acting on H4S47ph, with PP1α and PP1β also likely regulating the activity of Pak2. Finally, depletion of PP1α, PP1β and Wip1 leads to increased H3.3 occupancy at candidate genes tested, elevated H3.3 deposition and enhanced association of H3.3 with its chaperones HIRA and Daxx. These results reveal a novel role of three phosphatases in chromatin dynamics in mammalian cells.

Description: Previously we identified Rrp1 and Rrp2 as two proteins required for the Sfr1/Swi5-dependent branch of homologous recombination (HR) in Schizosaccharomyces pombe . Here we use a yeast two-hybrid approach to demonstrate that Rrp1 and Rrp2 can interact with each other and with Swi5, an HR mediator protein. Rrp1 and Rrp2 form co-localizing methyl methanesulphonate–induced foci in nuclei, further suggesting they function as a complex. To place the Rrp1/2 proteins more accurately within HR sub-pathways, we carried out extensive epistasis analysis between mutants defining Rrp1/2, Rad51 (recombinase), Swi5 and Rad57 (HR-mediators) plus the anti-recombinogenic helicases Srs2 and Rqh1. We confirm that Rrp1 and Rrp2 act together with Srs2 and Swi5 and independently of Rad57 and show that Rqh1 also acts independently of Rrp1/2. Mutants devoid of Srs2 are characterized by elevated recombination frequency with a concomitant increase in the percentage of conversion-type recombinants. Strains devoid of Rrp1 or Rrp2 did not show a change in HR frequency, but the number of conversion-type recombinants was increased, suggesting a possible function for Rrp1/2 with Srs2 in counteracting Rad51 activity. Our data allow us to propose a model placing Rrp1 and Rrp2 functioning together with Swi5 and Srs2 in a synthesis-dependent strand annealing HR repair pathway.