ALBERT

Description: Inflammatory immune cells, when activated, display much the same metabolic profile as a glycolytic tumor cell. This involves a shift in metabolism away from oxidative phosphorylation towards aerobic glycolysis, a phenomenon known as the Warburg effect. The result of this change in macrophages is to rapidly provide ATP and metabolic intermediates for the biosynthesis of immune and inflammatory proteins. In addition, a rise in certain tricarboxylic acid cycle intermediates occurs notably in citrate for lipid biosynthesis, and succinate, which activates the transcription factor Hypoxia-inducible factor. In this review we take a look at the emerging evidence for a role for the Warburg effect in the immune and inflammatory responses. The reprogramming of metabolic pathways in macrophages, dendritic cells, and T cells could have relevance in the pathogenesis of inflammatory and metabolic diseases and might provide novel therapeutic strategies. Recent studies reveal that inflammatory cells, when activated, display similar metabolic traits as cancer cells. During an inflammatory response or infection pro-inflammatory immune cells can shift their metabolism away from oxidative phosphorylation towards a high rate of glycolysis, a phenomenon known as the Warburg effect.

Description: Genome-scale metabolic models are mathematically-structured knowledge bases that can be used to predict metabolic pathway usage and growth phenotypes. Furthermore, they can generate and test hypotheses when integrated with experimental data. To maximize the value of these models, centralized repositories of high-quality models must be established, models must adhere to established standards and model components must be linked to relevant databases. Tools for model visualization further enhance their utility. To meet these needs, we present BiGG Models ( http://bigg.ucsd.edu ), a completely redesigned Bi ochemical, G enetic and G enomic knowledge base. BiGG Models contains more than 75 high-quality, manually-curated genome-scale metabolic models. On the website, users can browse, search and visualize models. BiGG Models connects genome-scale models to genome annotations and external databases. Reaction and metabolite identifiers have been standardized across models to conform to community standards and enable rapid comparison across models. Furthermore, BiGG Models provides a comprehensive application programming interface for accessing BiGG Models with modeling and analysis tools. As a resource for highly curated, standardized and accessible models of metabolism, BiGG Models will facilitate diverse systems biology studies and support knowledge-based analysis of diverse experimental data.

Description: The near-surface air temperature lapse rate is an important tool for spatially distributing temperatures in snow- and ice-melt models, but is difficult to parameterize, as it is not simply correlated with boundary-layer meteorological variables, such as temperature itself. This contribution quantifies spring-autumn lapse rate variability over 5 years at Vestari-Hagafellsjökull, a southerly outlet of Langjökull in Iceland. It is observed that summer lapse rates (0.57 °C 100 m −1 ) are significantly lower than non-summer rates, and are also lower than the Saturated Adiabatic Lapse Rate (SALR), which is often adopted in melt models. This is consistent with reduced near-surface temperature sensitivity to free-atmosphere temperature change during the occurrence of melting. A Variable Lapse Rate (VLR) regression model is calibrated with standardized, 750 hPa temperature anomalies derived from ERA-Interim climatology, which is shown to be highly significantly correlated with near-surface temperatures. The modelled VLR overestimates cumulative June–September Positive Degree Days (PDDs) by 3% when used to extrapolate temperatures from 1100 to 500 m a.s.l. on the glacier, whereas the SALR overestimates cumulative PDDs by 14%. ERA-Interim data therefore appear to offer a good representation of free-atmosphere temperature variability over Vestari-Hagafellsjökull, and the modelling approach offers a simple means of improving lapse rate parameterizations in melt models. Copyright © 2012 Royal Meteorological Society

Description: The near-surface air temperature lapse rate is an important tool for spatially distributing temperatures in snow- and ice-melt models, but is difficult to parameterize, as it is not simply correlated with boundary-layer meteorological variables, such as temperature itself. This contribution quantifies spring-autumn lapse rate variability over 5 years at Vestari-Hagafellsjökull, a southerly outlet of Langjökull in Iceland. It is observed that summer lapse rates (0.57 °C 100 m −1 ) are significantly lower than non-summer rates, and are also lower than the Saturated Adiabatic Lapse Rate (SALR), which is often adopted in melt models. This is consistent with reduced near-surface temperature sensitivity to free-atmosphere temperature change during the occurrence of melting. A Variable Lapse Rate (VLR) regression model is calibrated with standardized, 750 hPa temperature anomalies derived from ERA-Interim climatology, which is shown to be highly significantly correlated with near-surface temperatures. The modelled VLR overestimates cumulative June–September Positive Degree Days (PDDs) by 3% when used to extrapolate temperatures from 1100 to 500 m a.s.l. on the glacier, whereas the SALR overestimates cumulative PDDs by 14%. ERA-Interim data therefore appear to offer a good representation of free-atmosphere temperature variability over Vestari-Hagafellsjökull, and the modelling approach offers a simple means of improving lapse rate parameterizations in melt models. Copyright © 2012 Royal Meteorological Society

Description: : JSBML, the official pure Java programming library for the Systems Biology Markup Language (SBML) format, has evolved with the advent of different modeling formalisms in systems biology and their ability to be exchanged and represented via extensions of SBML. JSBML has matured into a major, active open-source project with contributions from a growing, international team of developers who not only maintain compatibility with SBML, but also drive steady improvements to the Java interface and promote ease-of-use with end users. Availability and implementation : Source code, binaries and documentation for JSBML can be freely obtained under the terms of the LGPL 2.1 from the website http://sbml.org/Software/JSBML . More information about JSBML can be found in the user guide at http://sbml.org/Software/JSBML/docs/ . Contact: jsbml-development@googlegroups.com or andraeger@eng.ucsd.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: This study presents the first microsatellite DNA study of population structure of Pacific hake, Merluccius productus (also known as Pacific whiting) within the Salish Sea, which has been identified as a distinct population segment under the US Endangered Species Act and is currently listed as a federal Species of Concern. In contrast, a separate coastal stock component of Pacific hake represents the most abundant commercial groundfish species on the US West Coast. We surveyed variation at 10 microsatellite DNA loci in a total of 655 individuals from three Salish Sea locations (Port Susan (PTS) and Dabob Bay in Washington and south-central Strait of Georgia (SOG) in British Columbia), three coastal locations (two off southern California and one in the Gulf of Alaska), and the Northern Gulf of California (GOC), México. No significant differences were detected among temporal samples from both PTS and SOG locations. Multilocus measures of population subdivision between coastal and Salish Sea populations (all pairwise F ST ≥ 0.03) and between PTS and SOG populations ( F ST ≥ 0.01) suggest a moderate degree of demographic isolation among these spawning populations. No significant genetic differences were found among the three coastal Pacific hake samples; however, Pacific hake from the GOC were significantly differentiated from both coastal ( F ST 〉 0.05) and Salish Sea ( F ST ≥ 0.03) Pacific hake. Correlations between genetic and geographic distance showed that Pacific hake display a very strong isolation by distance signal, both over the whole study area (~4500 km; r 2 = 0.94) and within the Salish Sea (~280 km; r 2 = 0.72). This study suggests that PTS and SOG populations are to some extent demographically isolated from each other.

Description: Accounting for ontogenetic shifts and subregional differences in groundfish distributional responses to warm temperatures, we examined large, quality‐controlled datasets of depth‐stratified, random bottom trawl surveys conducted during summer in three large regions—the Gulf of Alaska and the west coasts of Canada and the US—over the period 1996–2015. Abundant commercial groundfish demonstrated poleward responses to warming temperatures only in a few subregions and moved shallower or deeper to seek colder waters depending on the subregion. They may form geographically distinct thermal ecoregions, instead of continuously moving northward along the northeast Pacific shelf under global warming. Abstract Although climate‐induced shifts in fish distribution have been widely reported at the population level, studies that account for ontogenetic shifts and subregional differences when assessing responses are rare.In this study, groundfish distributional changes in depth, latitude, and longitude were assessed at different size classes by species within nine subregions. We examined large, quality‐controlled datasets of depth‐stratified‐random bottom trawl surveys conducted during summer in three large regions—the Gulf of Alaska and the west coasts of Canada and the United States—over the period 1996–2015, a time period punctuated by a marine “heat wave.” Temporal biases in bottom temperature were minimized by subdividing each region into three subregions, each with short‐duration surveys. Near‐bottom temperatures, weighted by stratum area, were unsynchronized across subregions and exhibited varying subregional interannual variability. The weighted mean bottom depths in the subregions also vary largely among subregions. The centroids (centers of gravity) of groundfish distribution were weighted with catch per unit effort and stratum area for 10 commercially important groundfish species by size class and subregion. Our multivariate analyses showed that there were significant differences in aggregate fish movement responses to warm temperatures across subregions but not among species or sizes. Groundfish demonstrated poleward responses to warming temperatures only in a few subregions and moved shallower or deeper to seek colder waters. The temperature responses of groundfish depended on where they were. Under global warming, groundfish may form geographically distinct thermal ecoregions along the northeast Pacific shelf. Shallow‐depth species exhibited greatly different distributional responses to temperature changes across subregions while deep‐depth species of different subregions tend to have relatively similar temperature responses. Future climate studies would benefit by considering fish distributions on small subregional scales.

Description: The performance of temperature-index melt models is particularly affected by the choice of near-surface lapse rate used to determine the sum of positive daily temperatures at different elevations, and by the choice of factor used to relate this sum to the rate of melting. Data from the Langjökull ice cap are here used to quantify the influence of lapse-rate and degree-day factor variation on temperature-index melt simulations. The lapse rate was significantly lower during summer than in spring or autumn, as a result of diabatic cooling, reducing boundary-layer sensitivity to free-air temperature change. The summer lapse rate was also significantly lower than the Saturated Adiabatic Lapse Rate (SALR). A sensitivity of around 600 mm w.e. cumulative June–August melt per 0.1 °C 100 m –1 change in lapse rate was found across a 500 m altitude range. The sensitivity to a 1 mm w.e. °C –1  d –1 change in DDF varied more: from about 500 mm w.e. cumulative summer melt at low elevation, to about 200 mm w.e. at high elevation, reflecting the decline in melt rates associated with the greater persistence of snow with increasing altitude. The determination of a DDF for snow is complicated by the densification of the ageing snowpack, but the application of a parameterization for near-surface density based on albedo helped account for the development of snow water-equivalence. Lapse rate was parameterized as a function of standardized anomalies in 750 hPa re-analysis temperature, and significantly improved simulation of cumulative summer melt compared to models applying the SALR. Copyright © 2011 John Wiley & Sons, Ltd.

Description: Adaptive laboratory evolution (ALE) has emerged as a valuable method by which to investigate microbial adaptation to a desired environment. Here, we performed ALE to 42 °C of ten parallel populations of Escherichia coli K-12 MG1655 grown in glucose minimal media. Tightly controlled experimental conditions allowed selection based on exponential-phase growth rate, yielding strains that uniformly converged toward a similar phenotype along distinct genetic paths. Adapted strains possessed as few as 6 and as many as 55 mutations, and of the 144 genes that mutated in total, 14 arose independently across two or more strains. This mutational recurrence pointed to the key genetic targets underlying the evolved fitness increase. Genome engineering was used to introduce the novel ALE-acquired alleles in random combinations into the ancestral strain, and competition between these engineered strains reaffirmed the impact of the key mutations on the growth rate at 42 °C. Interestingly, most of the identified key gene targets differed significantly from those found in similar temperature adaptation studies, highlighting the sensitivity of genetic evolution to experimental conditions and ancestral genotype. Additionally, transcriptomic analysis of the ancestral and evolved strains revealed a general trend for restoration of the global expression state back toward preheat stressed levels. This restorative effect was previously documented following evolution to metabolic perturbations, and thus may represent a general feature of ALE experiments. The widespread evolved expression shifts were enabled by a comparatively scant number of regulatory mutations, providing a net fitness benefit but causing suboptimal expression levels for certain genes, such as those governing flagellar formation, which then became targets for additional ameliorating mutations. Overall, the results of this study provide insight into the adaptation process and yield lessons important for the future implementation of ALE as a tool for scientific research and engineering.