The TGR5 receptor mediates bile acid-induced itch and analgesia

Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown. We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5. TGR5 was detected in peptidergic neurons of mouse dorsal root ganglia and spinal cord that transmit itch and pain, and in dermal macrophages that contain opioids. Bile acids and a TGR5-selective agonist induced hyperexcitability of dorsal root ganglia neurons and stimulated the release of the itch and analgesia transmitters gastrin-releasing peptide and leucine-enkephalin. Intradermal injection of bile acids and a TGR5-selective agonist stimulated scratching behavior by gastrin-releasing peptide- and opioid-dependent mechanisms in mice. Scratching was attenuated in Tgr5-KO mice but exacerbated in Tgr5-Tg mice (overexpressing mouse TGR5), which exhibited spontaneous pruritus. Intraplantar and intrathecal injection of bile acids caused analgesia to mechanical stimulation of the paw by an opioid-dependent mechanism. Both peripheral and central mechanisms of analgesia were absent from Tgr5-KO mice. Thus, bile acids activate TGR5 on sensory nerves, stimulating the release of neuropeptides in the spinal cord that transmit itch and analgesia. These mechanisms could contribute to pruritus and painless jaundice that occur during cholestatic liver diseases.

A mixture of trans-galactooligosaccharides reduces markers of metabolic syndrome and modulates the fecal microbiota and immune function of overweight adults

Metabolic syndrome is a set of disorders that increases the risk of developing cardiovascular disease. The gut microbiota is altered toward a less beneficial composition in overweight adults and this change can be accompanied by inflammation. Prebiotics such as galactooligosaccharides can positively modify the gut microbiota and immune system; some may also reduce blood lipids. We assessed the effect of a galactooligosaccharide mixture [Bi2 muno (B-GOS)] on markers of metabolic syndrome, gut microbiota, and immune function in 45 overweight adults with $3 risk factors associated with metabolic syndrome in a double-blind, randomized, placebo (maltodextrin)-controlled, crossover study (with a 4-wk wash-out period between interventions). Whole blood, saliva, feces, and anthropometric measurements were taken at the beginning, wk 6, and end of each 12-wk intervention period. Predominant groups of fecal bacteria were quantified and full blood count, markers of inflammation and lipid metabolism, insulin, and glucose were measured. B-GOS increased the number of fecal bifidobacteria at the expense of less desirable groups of bacteria. Increases in fecal secretory IgA and decreases in fecal calprotectin, plasma C-reactive protein, insulin, total cholesterol (TC), TG, and the TC:HDL cholesterol ratio were also observed. Administration of B-GOS to overweight adults resulted in positive effects on the composition of the gut microbiota, the immune response, and insulin, TC, and TG concentrations. B-GOSmay be a useful candidate for the enhancement of gastrointestinal health, immune function, and the reduction of metabolic syndrome risk factors in overweight adults.

The impact of diurnal variability in sea surface temperature on the atlantic air-sea CO2 flux

The effect of diurnal variations in sea surface temperature (SST) on the air-sea flux of CO2 over the central Atlantic ocean and Mediterranean Sea (60 S–60 N, 60 W–45 E) is evaluated for 2005–2006. We use high spatial resolution hourly satellite ocean skin temperature data to determine the diurnal warming (ΔSST). The CO2 flux is then computed using three different temperature fields – a foundation temperature (Tf, measured at a depth where there is no diurnal variation), Tf, plus the hourly ΔSST and Tf, plus the monthly average of the ΔSSTs. This is done in conjunction with a physically-based parameterisation for the gas transfer velocity (NOAA-COARE). The differences between the fluxes evaluated for these three different temperature fields quantify the effects of both diurnal warming and diurnal covariations. We find that including diurnal warming increases the CO2 flux out of this region of the Atlantic for 2005–2006 from 9.6 Tg C a−1 to 30.4 Tg C a−1 (hourly ΔSST) and 31.2 Tg C a−1 (monthly average of ΔSST measurements). Diurnal warming in this region, therefore, has a large impact on the annual net CO2 flux but diurnal covariations are negligible. However, in this region of the Atlantic the uptake and outgassing of CO2 is approximately balanced over the annual cycle, so although we find diurnal warming has a very large effect here, the Atlantic as a whole is a very strong carbon sink (e.g. −920 Tg C a−1 Takahashi et al., 2002) making this is a small contribution to the Atlantic carbon budget.

X‑ray crystal structure of rac-[Ru(phen)2dppz]2+ with d(ATGCAT)2 shows enantiomer orientations and water ordering

We report an atomic resolution X-ray crystal structure containing both enantiomers of rac-[Ru(phen)2dppz]2+ with the d-(ATGCAT)2 DNA duplex (phen = phenanthroline; dppz = dipyridophenazine). The first example of any enantiomeric pair crystallized with a DNA duplex shows different orientations of the Λ and Δ binding sites, separated by a clearly defined structured water monolayer. Job plots show that the same species is present in solution. Each enantiomer is bound at a TG/CA step and shows intercalation from the minor groove. One water molecule is directly located on one phenazine N atom in the Δ-enantiomer only.

Present state of global wetland extent and wetland methane modelling: conclusions from a model inter-comparison project (WETCHIMP)

Global wetlands are believed to be climate sensitive, and are the largest natural emitters of methane (CH4). Increased wetland CH4 emissions could act as a positive feedback to future warming. The Wetland and Wetland CH4 Inter-comparison of Models Project (WETCHIMP) investigated our present ability to simulate large-scale wetland characteristics and corresponding CH4 emissions. To ensure inter-comparability, we used a common experimental protocol driving all models with the same climate and carbon dioxide (CO2) forcing datasets. The WETCHIMP experiments were conducted for model equilibrium states as well as transient simulations covering the last century. Sensitivity experiments investigated model response to changes in selected forcing inputs (precipitation, temperature, and atmospheric CO2 concentration). Ten models participated, covering the spectrum from simple to relatively complex, including models tailored either for regional or global simulations. The models also varied in methods to calculate wetland size and location, with some models simulating wetland area prognostically, while other models relied on remotely sensed inundation datasets, or an approach intermediate between the two. Four major conclusions emerged from the project. First, the suite of models demonstrate extensive disagreement in their simulations of wetland areal extent and CH4 emissions, in both space and time. Simple metrics of wetland area, such as the latitudinal gradient, show large variability, principally between models that use inundation dataset information and those that independently determine wetland area. Agreement between the models improves for zonally summed CH4 emissions, but large variation between the models remains. For annual global CH4 emissions, the models vary by ±40% of the all-model mean (190 Tg CH4 yr−1). Second, all models show a strong positive response to increased atmospheric CO2 concentrations (857 ppm) in both CH4 emissions and wetland area. In response to increasing global temperatures (+3.4 °C globally spatially uniform), on average, the models decreased wetland area and CH4 fluxes, primarily in the tropics, but the magnitude and sign of the response varied greatly. Models were least sensitive to increased global precipitation (+3.9 % globally spatially uniform) with a consistent small positive response in CH4 fluxes and wetland area. Results from the 20th century transient simulation show that interactions between climate forcings could have strong non-linear effects. Third, we presently do not have sufficient wetland methane observation datasets adequate to evaluate model fluxes at a spatial scale comparable to model grid cells (commonly 0.5°). This limitation severely restricts our ability to model global wetland CH4 emissions with confidence. Our simulated wetland extents are also difficult to evaluate due to extensive disagreements between wetland mapping and remotely sensed inundation datasets. Fourth, the large range in predicted CH4 emission rates leads to the conclusion that there is both substantial parameter and structural uncertainty in large-scale CH4 emission models, even after uncertainties in wetland areas are accounted for.

Observations of the eruption of the Sarychev volcano and simulations using the HadGEM2 climate model

In June 2009 the Sarychev volcano located in the Kuril Islands to the northeast of Japan erupted explosively, injecting ash and an estimated 1.2 ± 0.2 Tg of sulfur dioxide into the upper troposphere and lower stratosphere, making it arguably one of the 10 largest stratospheric injections in the last 50 years. During the period immediately after the eruption, we show that the sulfur dioxide (SO2) cloud was clearly detected by retrievals developed for the Infrared Atmospheric Sounding Interferometer (IASI) satellite instrument and that the resultant stratospheric sulfate aerosol was detected by the Optical Spectrograph and Infrared Imaging System (OSIRIS) limb sounder and CALIPSO lidar. Additional surface‐based instrumentation allows assessment of the impact of the eruption on the stratospheric aerosol optical depth. We use a nudged version of the HadGEM2 climate model to investigate how well this state‐of‐the‐science climate model can replicate the distributions of SO2 and sulfate aerosol. The model simulations and OSIRIS measurements suggest that in the Northern Hemisphere the stratospheric aerosol optical depth was enhanced by around a factor of 3 (0.01 at 550 nm), with resultant impacts upon the radiation budget. The simulations indicate that, in the Northern Hemisphere for July 2009, the magnitude of the mean radiative impact from the volcanic aerosols is more than 60% of the direct radiative forcing of all anthropogenic aerosols put together. While the cooling induced by the eruption will likely not be detectable in the observational record, the combination of modeling and measurements would provide an ideal framework for simulating future larger volcanic eruptions.

A multimodel assessment of the influence of regional anthropogenic emission reductions on aerosol direct radiative forcing and the role of intercontinental transport

In this study, we assess changes of aerosol optical depth (AOD) and direct radiative forcing (DRF) in response to the reduction of anthropogenic emissions in four major pollution regions in the Northern Hemisphere by using results from nine global models in the framework of the Hemispheric Transport of Air Pollution (HTAP). DRF at top of atmosphere (TOA) and surface is estimated based on AOD results from the HTAP models and AOD-normalized DRF (NDRF) from a chemical transport model. The multimodel results show that, on average, a 20% reduction of anthropogenic emissions in North America, Europe, East Asia, and South Asia lowers the global mean AOD (all-sky TOA DRF) by 9.2% (9.0%), 3.5% (3.0%), and 9.4% (10.0%) for sulfate, particulate organic matter (POM), and black carbon (BC), respectively. Global annual average TOA all-sky forcing efficiency relative to particle or gaseous precursor emissions from the four regions (expressed as multimodel mean ± one standard deviation) is  ±3.5 ±0.8,  ±4.0 ±1.7, and 29.5 ±18.1mWm ±2 per Tg for sulfate (relative to SO2), POM, and BC, respectively. The impacts of the regional emission reductions on AOD and DRF extend well beyond the source regions because of intercontinental transport (ICT). On an annual basis, ICT accounts for 11 ±5% to 31 ±9% of AOD and DRF in a receptor region at continental or subcontinental scale, with domestic emissions accounting for the remainder, depending on regions and species. For sulfate AOD, the largest ICT contribution of 31 ±9% occurs in South Asia, which is dominated by the emissions from Europe. For BC AOD, the largest ICT contribution of 28 ±18% occurs in North America, which is dominated by the emissions from East Asia. The large spreads among models highlight the need to improve aerosol processes in models, and evaluate and constrain models with observations.

A novel association of a polymorphism in the first intron of adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia in Asian Indians

Adiponectin is an adipose tissue specific protein that is decreased in subjects with obesity and type 2 diabetes. The objective of the present study was to examine whether variants in the regulatory regions of the adiponectin gene contribute to type 2 diabetes in Asian Indians. The study comprised of 2,000 normal glucose tolerant (NGT) and 2,000 type 2 diabetic, unrelated subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Fasting serum adiponectin levels were measured by radioimmunoassay. We identified two proximal promoter SNPs (-11377C-->G and -11282T-->C), one intronic SNP (+10211T-->G) and one exonic SNP (+45T-->G) by SSCP and direct sequencing in a pilot study (n = 500). The +10211T-->G SNP alone was genotyped using PCR-RFLP in 4,000 study subjects. Logistic regression analysis revealed that subjects with TG genotype of +10211T-->G had significantly higher risk for diabetes compared to TT genotype [Odds ratio 1.28; 95% Confidence Interval (CI) 1.07-1.54; P = 0.008]. However, no association with diabetes was observed with GG genotype (P = 0.22). Stratification of the study subjects based on BMI showed that the odds ratio for obesity for the TG genotype was 1.53 (95%CI 1.3-1.8; P < 10(-7)) and that for GG genotype, 2.10 (95% CI 1.3-3.3; P = 0.002). Among NGT subjects, the mean serum adiponectin levels were significantly lower among the GG (P = 0.007) and TG (P = 0.001) genotypes compared to TT genotype. Among Asian Indians there is an association of +10211T-->G polymorphism in the first intron of the adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia.

Association of lipoprotein lipase gene polymorphisms with obesity and type 2 diabetes in an Asian Indian population

AIMS: Lipoprotein lipase (LPL), a pivotal enzyme in lipoprotein metabolism, catalyzes the hydrolysis of triglycerides of very low-density lipoproteins and chylomicrons. Assuming that the variants in the promoter of the LPL gene may be associated with changes in lipid metabolism leading to obesity and type 2 diabetes, we examined the role of promoter variants (-T93G and -G53C) in the LPL gene in an urban South Indian population. METHODS: The study subjects (619 type 2 diabetic and 731 normal glucose-tolerant (NGT) subjects) were chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The polymorphisms were genotyped using polymerase chain reaction-restriction-fragment length polymorphism (PCR-RFLP). Linkage disequilibrium (LD) was estimated from the estimates of haplotypic frequencies. RESULTS: The two polymorphisms studied were not in LD. The -T93G was not associated with type 2 diabetes but was associated with obesity. 11.5% of the obese subjects (62/541) had the XG(TG+GG) genotype compared with 6.4% of the nonobese subjects (52/809; P=0.001). The odds ratio for obesity for the XG genotype was 1.766 (95% CI: 1.19-2.63, P=0.005). Subjects with XG genotype also had higher body mass index and waist circumference compared with those with TT genotype. With respect to G53C, subjects with the XC(GC+CC) genotype had 0.527 and 0.531 times lower risk for developing type 2 diabetes and obesity, respectively. CONCLUSIONS: Among Asian Indians, the -T93G SNP of the LPL gene is associated with obesity but not type 2 diabetes, whereas the -G53C SNP appears to be protective against both obesity and type 2 diabetes.

Efficacy of increased resistant starch consumption in human type 2 diabetes

Resistant starch (RS) has been shown to beneficially affect insulin sensitivity in healthy individuals and those with metabolic syndrome, but its effects on human type 2 diabetes (T2DM) are unknown. This study aimed to determine the effects of increased RS consumption on insulin sensitivity and glucose control and changes in postprandial metabolites and body fat in T2DM. Seventeen individuals with well-controlled T2DM (HbA1c 46.6±2 mmol/mol) consumed, in a random order, either 40 g of type 2 RS (HAM-RS2) or a placebo, daily for 12 weeks with a 12-week washout period in between. At the end of each intervention period, participants attended for three metabolic investigations: a two-step euglycemic–hyperinsulinemic clamp combined with an infusion of [6,6-2H2] glucose, a meal tolerance test (MTT) with arterio-venous sampling across the forearm, and whole-body imaging. HAM-RS2 resulted in significantly lower postprandial glucose concentrations (P=0.045) and a trend for greater glucose uptake across the forearm muscle (P=0.077); however, there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity, or on HbA1c. Fasting non-esterified fatty acid (NEFA) concentrations were significantly lower (P=0.004) and NEFA suppression was greater during the clamp with HAM-RS2 (P=0.001). Fasting triglyceride (TG) concentrations and soleus intramuscular TG concentrations were significantly higher following the consumption of HAM-RS2 (P=0.039 and P=0.027 respectively). Although fasting GLP1 concentrations were significantly lower following HAM-RS2 consumption (P=0.049), postprandial GLP1 excursions during the MTT were significantly greater (P=0.009). HAM-RS2 did not improve tissue insulin sensitivity in well-controlled T2DM, but demonstrated beneficial effects on meal handling, possibly due to higher postprandial GLP1.

Fish oil supplementation alters numbers of circulating endothelial progenitor cells and micro particles independent of eNOS genotype

Background Emerging cellular markers of endothelial damage and repair include endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) respectively. Effects of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) and influence of genetic background on these markers are not known. Objective This study investigated the effects of fish oil supplementation on both classical and novel markers of endothelial function in subjects prospectively genotyped for the Asp298 eNOS polymorphism and at moderate risk of CVD. Design 84 subjects with moderate risk of CVD (n=40 GG and n=44 GT/TT) completed a randomized, double-blind, placebo-controlled, 8-week cross-over trial of fish oil supplementation providing 1.5 g/d LC n-3 PUFA. Effects of genotype and fish oil supplementation on the blood lipid profile, inflammatory markers, vascular function (EndoPAT) and numbers of circulating EPCs and EMP (flow cytometry) were assessed. Results There was no significant effect of fish oil supplementation on blood pressure, plasma lipids or plasma glucose, although there was a trend (P = 0.069) towards a decrease in plasma TG concentration after FO supplementation compared to placebo. GT/TT subjects tended to have higher levels of total cholesterol and LDL-cholesterol, but vascular function was not affected by either treatment or eNOS genotype. Biochemical markers of endothelial function were also unaffected by treatment and eNOS genotype. In contrast, there was a significant effect of fish oil supplementation on cellular markers of endothelial function. Fish oil supplementation increased numbers of EPCs and reduced numbers of EMPs relative to the placebo, potentially favouring maintenance of endothelial integrity. There was no influence of genotype for any of the cellular markers of endothelial function, indicating that the effects of fish oil supplementation were independent of eNOS genotype. Conclusions Emerging cellular markers of endothelial damage, integrity and repair appear to be sensitive to potentially beneficial modification by dietary n-3 PUFA.

Land use and climate change impacts on soil organic carbon stocks in semi-arid Spain

Purpose The sensitivity of soil organic carbon to global change drivers, according to the depth profile, is receiving increasing attention because of its importance in the global carbon cycle and its potential feedback to climate change. A better knowledge of the vertical distribution of SOC and its controlling factors—the aim of this study—will help scientists predict the consequences of global change. Materials and methods The study area was the Murcia Province (S.E. Spain) under semiarid Mediterranean conditions. The database used consists of 312 soil profiles collected in a systematic grid, each 12 km2 covering a total area of 11,004 km2. Statistical analysis to study the relationships between SOC concentration and control factors in different soil use scenarios was conducted at fixed depths of 0–20, 20–40, 40–60, and 60–100 cm. Results and discussion SOC concentration in the top 40 cm ranged between 6.1 and 31.5 g kg−1, with significant differences according to land use, soil type and lithology, while below this depth, no differences were observed (SOC concentration 2.1–6.8 g kg−1). The ANOVA showed that land use was the most important factor controlling SOC concentration in the 0–40 cm depth. Significant differences were found in the relative importance of environmental and textural factors according to land use and soil depth. In forestland, mean annual precipitation and texture were the main predictors of SOC, while in cropland and shrubland, the main predictors were mean annual temperature and lithology. Total SOC stored in the top 1 m in the region was about 79 Tg with a low mean density of 7.18 kg Cm−3. The vertical distribution of SOC was shallower in forestland and deeper in cropland. A reduction in rainfall would lead to SOC decrease in forestland and shrubland, and an increase of mean annual temperature would adversely affect SOC in croplands and shrubland. With increasing depth, the relative importance of climatic factors decreases and texture becomes more important in controlling SOC in all land uses. Conclusions Due to climate change, impacts will be much greater in surface SOC, the strategies for C sequestration should be focused on subsoil sequestration, which was hindered in forestland due to bedrock limitations to soil depth. In these conditions, sequestration in cropland through appropriate management practices is recommended.

Apolipoprotein e genotype has a modest impact on the postprandial plasma response to meals of varying fat composition in healthy men in a randomized controlled trial

BACKGROUND:Apolioprotein E (APOE) genotype is reported to influence a person's fasting lipid profile and potentially the response to dietary fat manipulation. The impact of APOE genotype on the responsiveness to meals of varying fat composition is unknown. OBJECTIVE:We examined the effect of meals containing 50 g of fat rich in saturated fatty acids (SFAs), unsaturated fatty acids (UNSATs), or SFAs with fish oil (SFA-FO) on postprandial lipemia. METHOD:A randomized, controlled, test meal study was performed in men recruited according to the APOE genotype (n = 10 APOE3/3, n = 11 APOE3/E4). RESULTS:For the serum apoE response (meal × genotype interaction P = 0.038), concentrations were on average 8% lower after the UNSAT than the SFA-FO meal in APOE4 carriers (P = 0.015) only. In the genotype groups combined, there was a delay in the time to reach maximum triacylglycerol (TG) concentration (mean ± SEM: 313 ± 25 vs. 266 ± 27 min) and higher maximum nonesterified fatty acid (0.73 ± 0.05 vs. 0.60 ± 0.03 mmol/L) and glucose (7.92 ± 0.22 vs. 7.25 ± 0.22 mmol/L) concentrations after the SFA than the UNSAT meal, respectively (P ≤ 0.05). In the Svedberg flotation rate 60-400 TG-rich lipoprotein fraction, meal × genotype interactions were observed for incremental area under the curve (IAUC) for the TG (P = 0.038) and apoE (P = 0.016) responses with a 58% lower apoE IAUC after the UNSAT than the SFA meal (P = 0.017) in the E4 carriers. CONCLUSIONS:Our data indicate that APOE genotype had a modest impact on the postprandial response to meals of varying fat composition in normolipidemic men. The physiologic importance of greater apoE concentrations after the SFA-rich meals in APOE4 carriers may reflect an impact on TG-rich lipoprotein clearance from the circulation. This trial was registered at clinicaltrials.gov as NCT01522482.

Enhancing the crystallization and orientation of electrospinning poly (lactic acid) (PLLA) by combining with additives

PLLA is a thermoplastic biopolymer and can be used in industrial applications for medical and filtration applications. The brittleness of PLLA is attributed to slow crystallization rates and its glass transition temperature (Tg) is high (60 °C); for this reason, its applications are limited. The orientation, morphology, and crystal structure of the electrospun fibers was investigated by SEM, POM, DSC, FTIR, XRD, and SAXS. Combining with additives leads to a large decrease of fiber diameter, viscosity, and changes of fiber morphology and crystal structure compared to pure PLLA. DSC showed that the Tg of PLLA decreased about 15 °C and there was no change in relaxation enthalpy by the addition of plasticizer. FT-IR indicate a strong interaction between PLLA and additives; a new band appears in the PLLA blend at 1,756 cm−1 at room temperature as a crystalline band without any annealing. In addition, WAXD indicated that the intensities of the two peaks at (200/110) and (203) increased for the blend at room temperature without any annealing in comparison with PLLA; this means that PHB crystallizes in the amorphous region of PLLA. The POM experiments agree with the results from DSC, FTIR, and WAXS measurements, confirming that adding PHB results in an increase in the number of nuclei with much smaller spherulites and enhances the crystallization behavior of this material, thereby improving its potential for applications.

The AeroCom evaluation and intercomparison of organic aerosol in global models

This paper evaluates the current status of global modeling of the organic aerosol (OA) in the troposphere and analyzes the differences between models as well as between models and observations. Thirty-one global chemistry transport models (CTMs) and general circulation models (GCMs) have participated in this intercomparison, in the framework of AeroCom phase II. The simulation of OA varies greatly between models in terms of the magnitude of primary emissions, secondary OA (SOA) formation, the number of OA species used (2 to 62), the complexity of OA parameterizations (gas-particle partitioning, chemical aging, multiphase chemistry, aerosol microphysics), and the OA physical, chemical and optical properties. The diversity of the global OA simulation results has increased since earlier AeroCom experiments, mainly due to the increasing complexity of the SOA parameterization in models, and the implementation of new, highly uncertain, OA sources. Diversity of over one order of magnitude exists in the modeled vertical distribution of OA concentrations that deserves a dedicated future study. Furthermore, although the OA / OC ratio depends on OA sources and atmospheric processing, and is important for model evaluation against OA and OC observations, it is resolved only by a few global models. The median global primary OA (POA) source strength is 56 Tg a−1 (range 34–144 Tg a−1) and the median SOA source strength (natural and anthropogenic) is 19 Tg a−1 (range 13–121 Tg a−1). Among the models that take into account the semi-volatile SOA nature, the median source is calculated to be 51 Tg a−1 (range 16–121 Tg a−1), much larger than the median value of the models that calculate SOA in a more simplistic way (19 Tg a−1; range 13–20 Tg a−1, with one model at 37 Tg a−1). The median atmospheric burden of OA is 1.4 Tg (24 models in the range of 0.6–2.0 Tg and 4 between 2.0 and 3.8 Tg), with a median OA lifetime of 5.4 days (range 3.8–9.6 days). In models that reported both OA and sulfate burdens, the median value of the OA/sulfate burden ratio is calculated to be 0.77; 13 models calculate a ratio lower than 1, and 9 models higher than 1. For 26 models that reported OA deposition fluxes, the median wet removal is 70 Tg a−1 (range 28–209 Tg a−1), which is on average 85% of the total OA deposition. Fine aerosol organic carbon (OC) and OA observations from continuous monitoring networks and individual field campaigns have been used for model evaluation. At urban locations, the model–observation comparison indicates missing knowledge on anthropogenic OA sources, both strength and seasonality. The combined model–measurements analysis suggests the existence of increased OA levels during summer due to biogenic SOA formation over large areas of the USA that can be of the same order of magnitude as the POA, even at urban locations, and contribute to the measured urban seasonal pattern. Global models are able to simulate the high secondary character of OA observed in the atmosphere as a result of SOA formation and POA aging, although the amount of OA present in the atmosphere remains largely underestimated, with a mean normalized bias (MNB) equal to −0.62 (−0.51) based on the comparison against OC (OA) urban data of all models at the surface, −0.15 (+0.51) when compared with remote measurements, and −0.30 for marine locations with OC data. The mean temporal correlations across all stations are low when compared with OC (OA) measurements: 0.47 (0.52) for urban stations, 0.39 (0.37) for remote stations, and 0.25 for marine stations with OC data. The combination of high (negative) MNB and higher correlation at urban stations when compared with the low MNB and lower correlation at remote sites suggests that knowledge about the processes that govern aerosol processing, transport and removal, on top of their sources, is important at the remote stations. There is no clear change in model skill with increasing model complexity with regard to OC or OA mass concentration. However, the complexity is needed in models in order to distinguish between anthropogenic and natural OA as needed for climate mitigation, and to calculate the impact of OA on climate accurately.