A yeast cell cycle model integrating stress, signaling, and physiology.

The cell division cycle in eukaryotic cells is a series of highly coordinated molecular interactions that ensure that cell growth, duplication of genetic material, and actual cell division are precisely orchestrated to give rise to two viable progeny cells. Moreover, the cell cycle machinery is responsible for incorporating information about external cues or internal processes that the cell must keep track of to ensure a coordinated, timely progression of all related processes. This is most pronounced in multicellular organisms, but also a cardinal feature in model organisms such as baker's yeast. The complex and integrative behavior is difficult to grasp and requires mathematical modeling to fully understand the quantitative interplay of the single components within the entire system. Here, we present a self-oscillating mathematical model of the yeast cell cycle that comprises all major cyclins and their main regulators. Furthermore, it accounts for the regulation of the cell cycle machinery by a series of external stimuli such as mating pheromones and changes in osmotic pressure or nutrient quality. We demonstrate how the external perturbations modify the dynamics of cell cycle components and how the cell cycle resumes after adaptation to or relief from stress.

Sperm migration in the genital tract-In silico experiments identify key factors for reproductive success.

Sperm migration in the female genital tract controls sperm selection and, therefore, reproductive success as male gametes are conditioned for fertilization while their number is dramatically reduced. Mechanisms underlying sperm migration are mostly unknown, since in vivo investigations are mostly unfeasible for ethical or practical reasons. By presenting a spatio-temporal model of the mammalian female genital tract combined with agent-based description of sperm motion and interaction as well as parameterizing it with bovine data, we offer an alternative possibility for studying sperm migration in silico. The model incorporates genital tract geometry as well as biophysical principles of sperm motion observed in vitro such as positive rheotaxis and thigmotaxis. This model for sperm migration from vagina to oviducts was successfully tested against in vivo data from literature. We found that physical sperm characteristics such as velocity and directional stability as well as sperm-fluid interactions and wall alignment are critical for success, i.e. sperms reaching the oviducts. Therefore, we propose that these identified sperm parameters should be considered in detail for conditioning sperm in artificial selection procedures since the natural processes are normally bypassed in reproductive in vitro technologies. The tremendous impact of mucus flow to support sperm accumulation in the oviduct highlights the importance of a species-specific optimum time window for artificial insemination regarding ovulation. Predictions from our extendable in silico experimental system will improve assisted reproduction in humans, endangered species, and livestock.

Catchment soils as a factor of trace metal accumulation in sediments of the reservoir Klingenberg (eastern Ore Mountains, Germany).

The release and accumulation dynamics of trace metals in soils and aquatic sediments were exemplarily investigated in the catchment area of the Reservoir Klingenberg (Germany). Catchment soils were examined for mobilizable and total concentrations of arsenic (As), cadmium (Cd), chrome (Cr), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) and compared with trace metal quantities accumulated in riverbed and reservoir sediments. The comparison of all samples showed relatively small variations of Cr (7.96-46.0 mg/kg), Fe (7.79-40.4 g/kg), and Ni (6.06-56.5 mg/kg), while stronger differences were found for As (11.2-164 mg/kg), Cd (0.14-30.5 mg/kg), Mn (0.08-1.84 g/kg), Pb (20.7-183 mg/kg), and Zn (69.1-916 mg/kg). The catchment soils were slightly enriched by Cd, Pb, and Zn. Especially Cd and Zn were characterized by large mobilizable proportions. The mean trace metal concentrations in riverbed sediments were higher than in catchment soils, while reservoir sediments accumulated the highest amounts of the analyzed elements. The enrichment of trace metals in reservoir sediments was generally determined by the sedimentation of fine particles, while the distribution of As, Fe, and Mn was additionally impacted by redox conditions. For Cd and Zn, which in comparison were most enriched in riverbed and reservoir sediments, a significant release from soils by leaching processes was observed. The accumulation of As and Pb in reservoir sediments was influenced to a greater extent by soil erosion and by anthropogenic or chalcogen sources in the catchment.

SBtab: a flexible table format for data exchange in systems biology.

UNLABELLED: : SBtab is a table-based data format for Systems Biology, designed to support automated data integration and model building. It uses the structure of spreadsheets and defines conventions for table structure, controlled vocabularies and semantic annotations. The format comes with predefined table types for experimental data and SBML-compliant model structures and can easily be customized to cover new types of data. AVAILABILITY AND IMPLEMENTATION: SBtab documents can be created and edited with any text editor or spreadsheet tool. The website www.sbtab.net provides online tools for syntax validation and conversion to SBML and HTML, as well as software for using SBtab in MS Excel, MATLAB and R. The stand-alone Python code contains functions for file parsing, validation, conversion to SBML and HTML and an interface to SQLite databases, to be integrated into Systems Biology workflows. A detailed specification of SBtab, including examples and descriptions of table types and available tools, can be found at www.sbtab.net CONTACT: : wolfram.liebermeister@gmail.com.

Metabolites of the PAH diol epoxide pathway and other urinary biomarkers of phenanthrene and pyrene in workers with and without exposure to bitumen fumes.

PURPOSE: This study investigates the diol epoxide pathway of phenanthrene (PHE) together with phenolic metabolites of PHE and pyrene (PYR) in workers with and without exposure to bitumen fumes. METHODS: The metabolite concentrations were determined in urine samples collected from 91 mastic asphalt workers and 42 construction workers as reference group before and after shift. During shift, vapours and aerosols of bitumen were measured according to a German protocol in the workers' breathing zone. RESULTS: The median concentration of vapours and aerosols of bitumen in mastic asphalt workers was 6.3 mg/m3. Metabolite concentrations were highest in post-shift urines of smokers with bitumen exposure and showed an increase during shift. The Spearman correlations between the creatinine-adjusted concentrations of metabolites and vapours and aerosols of bitumen in non-smokers were weak (e.g. sum of Di-OH-PYR: 0.28) or negligible (e.g. 1,2-PHE-diol: 0.08; PHE-tetrol: 0.12). Metabolites from the diol epoxide pathway of PHE were excreted in higher concentrations than phenolic metabolites (post-shift, non-smoking asphalt workers: 1,2-PHE-diol 2.59 µg/g crea vs. sum of all OH-PHE 1.87 µg/g crea). 1,2-PHE-diol was weakly correlated with PHE-tetrol (Spearman coefficient 0.30), an endpoint of the diol epoxide pathway. By contrast, we found a close correlation between the sum of 1,6-DiOH-PYR and 1,8-DiOH-PYR with 1-OH-PYR (Spearman coefficient 0.76). CONCLUSIONS: Most urinary PAH metabolites were higher after shift in bitumen-exposed workers, although the association with bitumen was weak or negligible likely due to the small PAH content. The additional metabolites of PHE and PYR complete the picture of the complex metabolic pathways. Nevertheless, none of the PAH metabolites can be considered to be a specific biomarker for bitumen exposure.

Oxidatively damaged guanosine in white blood cells and in urine of welders: associations with exposure to welding fumes and body iron stores.

The International Agency for Research on Cancer considers the carcinogenicity of welding fume of priority for re-evaluation. Genotoxic effects in experimental animals are still inconclusive. Here, we investigated the association of personal exposure to metals in respirable welding fumes during a working shift with oxidatively damaged guanosine in DNA of white blood cells (WBC) and in postshift urine samples from 238 welders. Medians of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were 2.35/10(6) dGuo in DNA of WBC and 4.33 µg/g creatinine in urine. The median of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) was 7.03 µg/g creatinine in urine. The extent of both urinary parameters was higher in welders applying techniques with high particle emission rates to stainless steel than in tungsten inert gas welders (8-oxodGuo: 9.96 vs. 4.49 µg/L, 8-oxoGuo: 15.7 vs. 7.7 µg/L), but this apparent difference diminished after creatinine adjustment. We applied random intercept models to estimate the influence of airborne and systemic exposure to metals on oxidatively damaged guanosine in WBC and urine together with covariates. We observed a highly significant nonlinear association of urinary 8-oxoGuo with serum ferritin (P < 0.0001) and higher 8-oxoGuo concentrations for respirable iron >1,000 µg/m(3) compared to ≤57 µg/m(3). Similar effects were found for manganese. Airborne chromium but not nickel was associated with all oxidatively modified guanosine measures, whereas urinary chromium as well as nickel showed associations with urinary modified guanosines. In summary, oxidatively damaged urinary guanosine was associated with airborne and systemic exposure to metals in welders and showed a strong relation to body iron stores.

Influence of welding fume on systemic iron status.

Iron is the major metal found in welding fumes, and although it is an essential trace element, its overload causes toxicity due to Fenton reactions. To avoid oxidative damage, excess iron is bound to ferritin, and as a result, serum ferritin (SF) is a recognized biomarker for iron stores, with high concentrations linked to inflammation and potentially also cancer. However, little is known about iron overload in welders. Within this study, we assessed the iron status and quantitative associations between airborne iron, body iron stores, and iron homeostasis in 192 welders not wearing dust masks. Welders were equipped with personal samplers in order to determine the levels of respirable iron in the breathing zone during a working shift. SF, prohepcidin and other markers of iron status were determined in blood samples collected after shift. The impact of iron exposure and other factors on SF and prohepcidin were estimated using multiple regression models. Our results indicate that respirable iron is a significant predictor of SF and prohepcidin. Concentrations of SF varied according to the welding technique and respiratory protection used, with a median of 103 µg l(-1) in tungsten inert gas welders, 125 µg l(-1) in those wearing air-purifying respirators, and 161 µg l(-1) in other welders. Compared to welders with low iron stores (SF < 25 µg l(-1)), those with excess body iron (SF ≥ 400 µg l(-1)) worked under a higher median concentration of airborne iron (60 µg m(-3) versus 148 µg m(-3)). Even though air concentrations of respirable iron and manganese were highly correlated, and low iron stores have been reported to increase manganese uptake in the gastrointestinal tract, no correlation was seen between SF and manganese in blood. In conclusion, monitoring SF may be a reasonable method for health surveillance of welders. Respiratory protection with air-purifying respirators can decrease iron exposure and avoid chronically higher SF in welders working with high-emission technologies.

Reduction in welding fume and metal exposure of stainless steel welders: an example from the WELDOX study.

PURPOSE: In a plant where flux-cored arc welding was applied to stainless steel, we investigated changes in airborne and internal metal exposure following improvements of exhaust ventilation and respiratory protection. METHODS: Twelve welders were examined at a time in 2008 and in 2011 after improving health protection. Seven welders were enrolled in both surveys. Exposure measurement was performed by personal sampling of respirable welding fume inside the welding helmets during one work shift. Urine and blood samples were taken after the shift. Chromium (Cr), nickel (Ni), and manganese (Mn) were determined in air and biological samples. RESULTS: The geometric mean of respirable particles could be reduced from 4.1 mg/m(3) in 2008-0.5 mg/m(3) in 2011. Exposure to airborne metal compounds was also strongly reduced (Mn: 399 vs. 6.8 µg/m(3); Cr: 187 vs. 6.3 µg/m(3); Ni: 76 vs. 2.8 µg/m(3)), with the most striking reduction inside helmets with purified air supply. Area sampling revealed several concentrations above established or proposed exposure limits. Urinary metal concentrations were also reduced, but to a lesser extent (Cr: 14.8 vs. 4.5 µg/L; Ni: 7.9 vs. 3.1 µg/L). Although biologically regulated, the mean Mn concentration in blood declined from 12.8 to 8.9 µg/L. CONCLUSION: This intervention study demonstrated a distinct reduction in the exposure of welders using improved exhaust ventilation and welding helmets with purified air supply in the daily routine. Data from area sampling and biomonitoring indicated that the area background level may add considerably to the internal exposure.

Exposure to inhalable, respirable, and ultrafine particles in welding fume.

This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m(-3) for inhalable and 1.29 mg m(-3) for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m(-3)). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements

Levels and determinants of exposure to vapours and aerosols of bitumen.

Bitumen (referred to as asphalt in the United States) is a widely used construction material, and emissions from hot bitumen applications have been a long-standing health concern. One objective of the Human Bitumen Study was to identify potential determinants of the exposure to bitumen. The study population analysed comprised 259 male mastic asphalt workers recruited between 2003 and 2008. Personal air sampling in the workers' breathing zone was carried out during the shift to measure exposure to vapours and aerosols of bitumen. The majority of workers were engaged in building construction, where exposure levels were lower than in tunnels but higher than at road construction sites. At building construction sites, exposure levels were influenced by the room size, the processing temperature of the mastic asphalt and the job task. The results show that protective measures should include a reduction in the processing temperature.

Air sampling and determination of vapours and aerosols of bitumen and polycyclic aromatic hydrocarbons in the Human Bitumen Study.

The chemical complexity of emissions from bitumen applications is a challenge in the assessment of exposure. Personal sampling of vapours and aerosols of bitumen was organized in 320 bitumen-exposed workers and 69 non-exposed construction workers during 2001-2008. Area sampling was conducted at 44 construction sites. Area and personal sampling of vapours and aerosols of bitumen showed similar concentrations between 5 and 10 mg/m(3), while area sampling yielded higher concentrations above the former occupational exposure limit (OEL) of 10 mg/m(3). The median concentration of personal bitumen exposure was 3.46 mg/m(3) (inter-quartile range 1.80-5.90 mg/m(3)). Only few workers were exposed above the former OEL. The specificity of the method measuring C-H stretch vibration is limited. This accounts for a median background level of 0.20 mg/m³ in non-exposed workers which is likely due to ubiquitous aliphatic hydrocarbons. Further, area measurements of polycyclic aromatic hydrocarbons (PAHs) were taken at 25 construction sites. U.S. EPA PAHs were determined with GC/MS, with the result of a median concentration of 2.47 µg/m(3) at 15 mastic asphalt worksites associated with vapours and aerosols of bitumen, with a Spearman correlation coefficient of 0.45 (95% CI -0.13 to 0.78). PAH exposure at mastic-asphalt works was higher than at reference worksites (median 0.21 µg/m(3)), but about one order of magnitude lower compared to coke-oven works. For a comparison of concentrations of vapours and aerosols of bitumen and PAHs in asphalt works, differences in sampling and analytical methods must to be taken into account.

Joint recording of contamination status, multi-element dynamics, and source identification on a sub-catchment scale: The example Lahn River (Germany).

Investigations on the enrichment level, binding dynamics, and source identification of contaminants are important objectives of environmental research into surface waters, but are often carried out independently of each other. To simultaneously address these issues an investigative approach is presented that combines multi-element analyses of water and suspended particulate matter (SPM) and is applied on the scale of a sub-catchment, using the Lahn River (Germany) as an example. Analyses of water and SPM comprised phosphorus (P), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), lead (Pb), and uranium (U). For the dissolved phase, the investigations additionally included nitrogen compounds (NH4, NO3) and dissolved organic carbon (DOC). SPM of the Lahn showed increased average concentrations of Zn (2.13 g kg-1), Cd (4.01 mg kg-1), and Pb (160 mg kg-1). The water phase sampled from points along the length of the Lahn showed significant spatial differences in the dissolved concentrations of Mn (15.7-98.4 µg l-1), Co (0.08-0.66 µg l-1), Ni (0.75-4.69 µg l-1), Zn (19.9-187 µg l-1), and Cd (0.01-0.18 µg l-1), which could be attributed to the inflow of two tributaries draining historic mining areas. The study emphasizes the importance of mine waters during low water periods and proves that such sources can differently affect the SPM quality and the dissolved concentrations of their receiving waters.

Occupational exposure to polycyclic aromatic hydrocarbons and DNA damage by industry: a nationwide study in Germany.

Exposure to polycyclic aromatic hydrocarbons (PAH) and DNA damage were analyzed in coke oven (n = 37), refractory (n = 96), graphite electrode (n = 26), and converter workers (n = 12), whereas construction workers (n = 48) served as referents. PAH exposure was assessed by personal air sampling during shift and biological monitoring in urine post shift (1-hydroxypyrene, 1-OHP and 1-, 2 + 9-, 3-, 4-hydroxyphenanthrenes, SigmaOHPHE). DNA damage was measured by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and DNA strand breaks in blood post shift. Median 1-OHP and SigmaOHPHE were highest in converter workers (13.5 and 37.2 microg/g crea). The industrial setting contributed to the metabolite concentrations rather than the air-borne concentration alone. Other routes of uptake, probably dermal, influenced associations between air-borne concentrations and levels of PAH metabolites in urine making biomonitoring results preferred parameters to assess exposure to PAH. DNA damage in terms of 8-oxo-dGuo and DNA strand breaks was higher in exposed workers compared to referents ranking highest for graphite-electrode production. The type of industry contributed to genotoxic DNA damage and DNA damage was not unequivocally associated to PAH on the individual level most likely due to potential contributions of co-exposures.

Chromated metal products may be hazardous to patients with chromate allergy.

BACKGROUND: Hidden allergen exposure may contribute to persistence and relapse of chromate dermatitis. According to case reports, chromated metal products, such as screws, fittings, etc., may be relevant allergen sources for patients sensitized to chromate. OBJECTIVES: To examine concomitant patch test reactivity to potassium dichromate 0.5% petrolatum (pet.) and three different types of chromated metal rings. PATIENTS/METHODS: Patients with proven or suspected chromate allergy were patch tested with potassium dichromate 0.5% pet. and three different types of chromated metal rings (yellow, olive, and black). Hexavalent chromium Cr(VI) release from the patch tested rings was chemically analysed. RESULTS: Ninety-five patients were tested: 49/95 (52%) reacted to potassium dichromate and 25/95 (26%) reacted to black chromated rings. Reactions to chromated rings exclusively occurred in patients reacting to potassium dichromate. Of 20 patients with a strong reaction to potassium dichromate, 14 reacted to black chromated rings. These were shown to have a high Cr(VI) release. Only two patients reacted to the other chromated rings, which had a very low Cr(VI) release. CONCLUSIONS: Handling chromated metal products must be regarded a hazard to chromate-sensitive patients, in particular those with a strong sensitization.

Biological monitoring as a useful tool for the detection of a coal-tar contamination in bitumen-exposed workers.

In our research project entitled "Chemical irritative and/or genotoxic effect of fumes of bitumen under high processing temperatures on the airways," 73 mastic asphalt workers exposed to fumes of bitumen and 49 construction nonexposed workers were analyzed and compared with respect to polycyclic aromatic hydrocarbons (PAHs) exposure and exposure-related health effects. In order to assess the internal exposure the monohydroxylated metabolites of pyrene, 1- hydroxypyrene (1-OHP), and phenanthrene, 1-, 2- and 9-, and 3- and 4-hydroxyphenanthrene (OHPH) were determined in pre- and post-shift urinary samples. Significantly higher concentrations 1-OHP and OHPH were detected in the post-shift urine samples of 7 mastic asphalt workers working on the same construction site compared to the reference workers and all other 66 mastic asphalt workers. The adjusted mean OHPH in the reference, 66 mastic worker, and 7 worker subgroups was 1022, 1544, and 12919 ng/g creatinine (crn) respectively, indicating a marked rise in the 7 worker subgroup. In addition, there was a more than 12-fold increase of PAH metabolites from pre- to post-shift in these 7 workers, whereas in the other mastic asphalt workers there was only a twofold rise in PAH-metabolite concentration between pre- and post-shift values. The analysis of a drilling core from the construction site of the seven workers led to the detection of the source for this marked PAH exposure during the working shift as being coal tar plates, which were, without knowledge of the workers and coordinators, the underground material of the mastic asphalt layer. The evaluation of the stationary workplace concentration showed enhanced levels of phenanthrene, pyrene, fluorene, anthracene, and acenaphthene during working shifts at the construction site of these seven workers. Our study shows that biological monitoring is also a useful tool for the detection of unrecognized sources with high PAH concentrations.

Impacts of dam draining on the mobility of heavy metals and arsenic in water and basin bottom sediments of three studied dams in Germany.

The draining of a dam is a relatively rare event, however, it can have severe consequences for a watercourse connected to that reservoir. In order to understand the effects of the draining on the mobility of pollutants stored in the bottom sediments, the concentrations of heavy metals and arsenic were measured in pore water, river water, and sediments sampled from three emptied reservoirs in Germany. Two of these sites were analyzed immediately after the draining, while the third reservoir was studied one and a half years after the complete discharge of the stored water. Heavy metal and arsenic concentrations within the sediments varied among the studied dams as a result of different geological characteristics and the degree of anthropogenic impacts. Based on the analysis of pore water samples, the concentrations of heavy metals and arsenic were not significantly altered shortly after the draining. However, increased concentrations of As, Fe, Cd, Ni, and Zn were measured in pore water samples after a longer duration of sediment exposure, which altered the redox conditions and sediment properties. The changes in Cu, Cr, Mn, and Pb concentrations in pore water samples were less pronounced. As a result of the pore water drainage increased dissolved heavy metal concentrations were found in the discharge water immediately after draining. At the third site, which had been emptied for one and a half years, only for Mn, a concentration increase was detected in the reservoir discharge water, which emphasizes the strong temporal dynamic of the mobilization of the analyzed elements.

Assessment of DNA damage in WBCs of workers occupationally exposed to fumes and aerosols of bitumen.

We conducted a cross-shift study with 66 bitumen-exposed mastic asphalt workers and 49 construction workers without exposure to bitumen. Exposure was assessed using personal monitoring of airborne bitumen exposure, urinary 1-hydroxypyrene (1-OHP), and the sum of 1-, 2 + 9-,3-,4-hydroxyphenanthrene (OHPH). Genotoxic effects in WBC were determined with nonspecific DNA adduct levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and the formation of DNA strand breaks and alkali-labile sites. Concentration of fumes and aerosols of bitumen correlated significantly with the concentrations of 1-OHP and OHPH after shift (r(s) = 0.27; P = 0.03 and r(s) = 0.55; P < 0.0001, respectively). Bitumen-exposed workers had more DNA strand breaks than the reference group (P < 0.0001) at both time points and a significant correlation with 1-OHP and OHPH in the postshift urines (r(s) = 0.32; P = 0.001 and r(s) = 0.27; P = 0.004, respectively). Paradoxically, we measured higher levels of DNA strand breaks, although not significant, in both study groups before shift. 8-OxodGuo adduct levels did not correlate with DNA strand breaks. Further, 8-oxodGuo levels were associated neither with personal exposure to bitumen nor with urinary metabolite concentrations. Significantly more DNA adducts were observed after shift not only in bitumen-exposed workers but also in the reference group. Only low-exposed workers had significantly elevated 8-oxodGuo adduct levels before as well as after shift (P = 0.0002 and P = 0.02, respectively). Our results show that exposure to fumes and aerosols of bitumen may contribute to an increased DNA damage assessed with strand breaks.

Computational Modeling of Lipid Metabolism in Yeast.

Lipid metabolism is essential for all major cell functions and has recently gained increasing attention in research and health studies. However, mathematical modeling by means of classical approaches such as stoichiometric networks and ordinary differential equation systems has not yet provided satisfactory insights, due to the complexity of lipid metabolism characterized by many different species with only slight differences and by promiscuous multifunctional enzymes. Here, we present an object-oriented stochastic model approach as a way to cope with the complex lipid metabolic network. While all lipid species are treated objects in the model, they can be modified by the respective converting reactions based on reaction rules, a hybrid method that integrates benefits of agent-based and classical stochastic simulation. This approach allows to follow the dynamics of all lipid species with different fatty acids, different degrees of saturation and different headgroups over time and to analyze the effect of parameter changes, potential mutations in the catalyzing enzymes or provision of different precursors. Applied to yeast metabolism during one cell cycle period, we could analyze the distribution of all lipids to the various membranes in time-dependent manner. The presented approach allows to efficiently treat the complexity of cellular lipid metabolism and to derive conclusions on the time- and location-dependent distributions of lipid species and their properties such as saturation. It is widely applicable, easily extendable and will provide further insights in healthy and diseased states of cell metabolism.

Strategies for structuring interdisciplinary education in Systems Biology: an European perspective.

Systems Biology is an approach to biology and medicine that has the potential to lead to a better understanding of how biological properties emerge from the interaction of genes, proteins, molecules, cells and organisms. The approach aims at elucidating how these interactions govern biological function by employing experimental data, mathematical models and computational simulations. As Systems Biology is inherently multidisciplinary, education within this field meets numerous hurdles including departmental barriers, availability of all required expertise locally, appropriate teaching material and example curricula. As university education at the Bachelor's level is traditionally built upon disciplinary degrees, we believe that the most effective way to implement education in Systems Biology would be at the Master's level, as it offers a more flexible framework. Our team of experts and active performers of Systems Biology education suggest here (i) a definition of the skills that students should acquire within a Master's programme in Systems Biology, (ii) a possible basic educational curriculum with flexibility to adjust to different application areas and local research strengths, (iii) a description of possible career paths for students who undergo such an education, (iv) conditions that should improve the recruitment of students to such programmes and (v) mechanisms for collaboration and excellence spreading among education professionals. With the growing interest of industry in applying Systems Biology approaches in their fields, a concerted action between academia and industry is needed to build this expertise. Here we present a reflection of the European situation and expertise, where most of the challenges we discuss are universal, anticipating that our suggestions will be useful internationally. We believe that one of the overriding goals of any Systems Biology education should be a student's ability to phrase and communicate research questions in such a manner that they can be solved by the integration of experiments and modelling, as well as to communicate and collaborate productively across different experimental and theoretical disciplines in research and development.

Toward Community Standards and Software for Whole-Cell Modeling.

OBJECTIVE: Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate comprehensive models of complex cells. METHODS: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in the Systems Biology Markup Language. RESULTS: Our analysis revealed several challenges to representing WC models using the current standards. CONCLUSION: We, therefore, propose several new WC modeling standards, software, and databases. SIGNIFICANCE: We anticipate that these new standards and software will enable more comprehensive models.