Negative effects of nitrogen deposition on Swiss butterflies.

Nitrogen (N) deposition from agriculture and combustion of fossil fuels is a major threat to plant diversity, but its effects on organisms at higher trophic levels are unclear. We investigated how N deposition may affect species richness and abundance (number of individuals per species) in butterflies. We reviewed the peer-reviewed literature on variables used to explain spatial variation in butterfly species richness and found that vegetation variables appeared to be as important as climate and habitat variables in explaining butterfly species richness. It thus seemed likely that increased N deposition could indirectly affect butterfly communities via its influence on plant communities. To test this prediction, we analyzed data from the Swiss biodiversity monitoring program for vascular plants and butterflies in 383 study sites of 1 km2 that are evenly distributed throughout Switzerland. The area has a modeled N deposition gradient of 2-44 kg N ha-1 year-1 . We used traditional linear models and structural equation models to infer the drivers of the spatial variation in butterfly species richness across Switzerland. High N deposition was consistently linked to low butterfly diversity, suggesting a net loss of butterfly diversity through increased N deposition. We hypothesize that at low elevations, N deposition may contribute to a reduction in butterfly species richness via microclimatic cooling due to increased plant biomass. At higher elevations, negative effects of N deposition on butterfly species richness may also be mediated by reduced plant species richness. In most butterfly species, abundance was negatively related to N deposition, but the strongest negative effects were found for species of conservation concern. We conclude that in addition to factors such as intensified agriculture, habitat fragmentation, and climate change, N deposition is likely to play a key role in negatively affecting butterfly diversity and abundance.

Efectos Negativos del Depósito de Nitrógeno sobre las Mariposas Suizas Resumen El depósito de nitrógeno (N) proveniente de la agricultura y la quema de combustibles fósiles es una gran amenaza para la diversidad botánica, pero sus efectos sobre organismos que se encuentran en niveles tróficos más altos no están claros. Investigamos cómo el depósito de N puede afectar a la riqueza y abundancia (número de individuos por especie) de especies de mariposas. Analizamos la literatura revisada por pares sobre las variables usadas para explicar la variación espacial en la riqueza de especies de mariposas y descubrimos que las variables de vegetación resultaron ser tan importantes como las variables climáticas y de hábitat para explicar la riqueza de especies de mariposas. Por lo tanto, parece probable que el incremento en el depósito de N podría afectar indirectamente a las comunidades de mariposas por medio de su influencia sobre las comunidades botánicas. Para probar esta predicción analizamos datos del programa de monitoreo de biodiversidad suiza de plantas vasculares y mariposas en 383 sitios de estudio de 1 km2 que están distribuidos uniformemente por toda Suiza. El área tiene un gradiente modelado de depósito de N de 2-44 kg N ha−1 año−1 . Usamos modelos lineales tradicionales y modelos de ecuación estructural para inferir los determinantes de la variación espacial en la riqueza de especies de mariposas en Suiza. El nivel elevado de depósito de N estuvo vinculado consistentemente con la diversidad baja de mariposas, lo que sugiere una pérdida neta de diversidad de mariposas causada por el incremento en el depósito de N. Nuestra hipótesis establece que, a elevaciones bajas, el depósito de N puede contribuir a la reducción en la riqueza de especies de mariposas por medio del enfriamiento microclimático debido al incremento en la biomasa de las plantas. A elevaciones más altas, los efectos negativos del depósito de N sobre la riqueza de especies de mariposas también podrían ser mediados por la riqueza reducida de especies de plantas. En la mayoría de las especies de mariposas, la abundancia tuvo una relación negativa con el depósito de N, pero el efecto negativo más fuerte se halló para las especies de importancia para la conservación. Concluimos que además de los factores como la agricultura intensificada, la fragmentación del hábitat y el cambio climático, el depósito de N probablemente tenga un papel importante en los efectos negativos sobre la diversidad y abundancia de mariposas.

Species turnover reveals hidden effects of decreasing nitrogen deposition in mountain hay meadows.

Nitrogen (N) deposition is a major threat to biodiversity in many habitats. The recent introduction of cleaner technologies in Switzerland has led to a reduction in the emissions of nitrogen oxides, with a consequent decrease in N deposition. We examined different drivers of plant community change, that is, N deposition, climate warming, and land-use change, in Swiss mountain hay meadows, using data from the Swiss biodiversity monitoring program. We compared indicator values of species that disappeared from or colonized a site (species turnover) with the indicator values of randomly chosen species from the same site. While oligotrophic plant species were more likely to colonize, compared to random expectation, we found only weak shifts in plant community composition. In particular, the average nutrient value of plant communities remained stable over time (2003-2017). We found the largest deviations from random expectation in the nutrient values of colonizing species, suggesting that N deposition or other factors that change the nutrient content of soils were important drivers of the species composition change over the last 15 years in Swiss mountain hay meadows. In addition, we observed an overall replacement of species with lower indicator values for temperature with species with higher values. Apparently, the community effects of the replacement of eutrophic species with oligotrophic species was outweighed by climate warming. Our results add to the increasing evidence that plant communities in changing environments may be relatively stable regarding average species richness or average indicator values, but that this apparent stability is often accompanied by a marked turnover of species.

Temporal change of the accumulation of persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons (PAHs) in lichens in Switzerland between 1995 and 2014.

The aim of this study was to assess the temporal change of atmospheric deposition patterns of persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons (PAHs) in Switzerland between 1995 and 2014 by a passive biomonitoring with lichens. Lichen tissues sampled at 16 representative sites in the same season of 1995 and 2014 were analyzed for a total of 94 individual and 27 sum parameters of POPs and PAHs by means of gas chromatography-mass spectrometry (GC/MS). The comparative analyses showed a decrease of 40 to 80% (medians) for most of the POPs and PAHs concentration in lichens at all site categories. Reduction in tissue concentration of the polychlorinated dibenzo-p-dioxins/furans (PCDD/PCDFs), such as the highly toxic 2,3,7,8-TetraCDD and the TEQ according to WHO (2005) were 66% and 73%, respectively. For the dioxin- and non-dioxin-like PCBs, a decrease of 67% and 58% was found. The average decrease of 30 organochlorine pesticides and insecticides (OCPs) was 65%, with a 94% decrease for lindane. For the 27 PAHs and for benzo(a)pyrene, an average decrease of 58% and 59% was found. Polybrominated diphenyl ethers (PBDE) showed reduced concentrations in lichens at rural and agglomeration sites, but an increase of contamination was observed at industrial and road traffic sites. The direct comparison of changes of POPs and PAHs concentrations in lichens and of emissions between 1995 and 2014 revealed consistent results. The results of this study highlight for the first time in biota the positive effect of emission regulation of POPs in Switzerland.

Using change-point models to estimate empirical critical loads for nitrogen in mountain ecosystems.

To protect ecosystems and their services, the critical load concept has been implemented under the framework of the Convention on Long-range Transboundary Air Pollution (UNECE) to develop effects-oriented air pollution abatement strategies. Critical loads are thresholds below which damaging effects on sensitive habitats do not occur according to current knowledge. Here we use change-point models applied in a Bayesian context to overcome some of the difficulties when estimating empirical critical loads for nitrogen (N) from empirical data. We tested the method using simulated data with varying sample sizes, varying effects of confounding variables, and with varying negative effects of N deposition on species richness. The method was applied to the national-scale plant species richness data from mountain hay meadows and (sub)alpine scrubs sites in Switzerland. Seven confounding factors (elevation, inclination, precipitation, calcareous content, aspect as well as indicator values for humidity and light) were selected based on earlier studies examining numerous environmental factors to explain Swiss vascular plant diversity. The estimated critical load confirmed the existing empirical critical load of 5-15 kg N ha-1 yr-1 for (sub)alpine scrubs, while for mountain hay meadows the estimated critical load was at the lower end of the current empirical critical load range. Based on these results, we suggest to narrow down the critical load range for mountain hay meadows to 10-15 kg N ha-1 yr-1.

Particulate Matter and Subclinical Atherosclerosis: Associations between Different Particle Sizes and Sources with Carotid Intima-Media Thickness in the SAPALDIA Study.

BACKGROUND: Subclinical atherosclerosis has been associated with long-term exposure to particulate matter (PM), but the relevance of particle size and sources of exposure remains unclear. OBJECTIVES: We investigated the association of long-term exposure to PM10 (≤ 10 µm), PM2.5 (≤ 2.5 µm: total mass, vehicular, and crustal sources), and ultrafine particles [UFP < 0.1 µm: particle number concentration (PNC) and lung-deposited surface area (LDSA)] with carotid intima-media thickness (CIMT). METHODS: We used data from 1,503 participants ≥ 50 years old who participated in the third examination of the Swiss SAPALDIA cohort. Exposures were obtained from dispersion models and land-use regression models. Covariate information, including previous cardiovascular risk factors, was obtained from the second and third SAPALDIA examinations. RESULTS: The adjusted percent difference in CIMT associated with an exposure contrast between the 10th and 90th percentile was 1.58% (95% CI: -0.30, 3.47%) for PM10, 2.10% (95% CI: 0.04, 4.16%) for PM2.5, 1.67% (95% CI: -0.13, 3.48%) for the vehicular source of PM2.5, -0.58% (95% CI: -3.95, 2.79%) for the crustal source of PM2.5, 2.06% (95% CI: 0.03, 4.10%) for PNC, and 2.32% (95% CI: 0.23, 4.40%) for LDSA. Stronger associations were observed among diabetics, subjects with low-educational level, and those at higher cardiovascular risk. CONCLUSIONS: CIMT was associated with exposure to PM10, PM2.5, and UFP. The PM2.5 source-specific analysis showed a positive association for the vehicular source but not for the crustal source. Although the effects of PNC and LDSA were similar in magnitude, two-pollutant and residual-based models suggested that LDSA may be a better marker for the health relevance of UFP. Citation: Aguilera I, Dratva J, Caviezel S, Burdet L, de Groot E, Ducret-Stich RE, Eeftens M, Keidel D, Meier R, Perez L, Rothe T, Schaffner E, Schmit-Trucksäss A, Tsai MY, Schindler C, Künzli N, Probst-Hensch N. 2016. Particulate matter and subclinical atherosclerosis: associations between different particle sizes and sources with carotid intima-media thickness in the SAPALDIA study. Environ Health Perspect 124:1700-1706; http://dx.doi.org/10.1289/EHP161.

Development of land use regression models for nitrogen dioxide, ultrafine particles, lung deposited surface area, and four other markers of particulate matter pollution in the Swiss SAPALDIA regions.

BACKGROUND: Land Use Regression (LUR) is a popular method to explain and predict spatial contrasts in air pollution concentrations, but LUR models for ultrafine particles, such as particle number concentration (PNC) are especially scarce. Moreover, no models have been previously presented for the lung deposited surface area (LDSA) of ultrafine particles. The additional value of ultrafine particle metrics has not been well investigated due to lack of exposure measurements and models. METHODS: Air pollution measurements were performed in 2011 and 2012 in the eight areas of the Swiss SAPALDIA study at up to 40 sites per area for NO2 and at 20 sites in four areas for markers of particulate air pollution. We developed multi-area LUR models for biannual average concentrations of PM2.5, PM2.5 absorbance, PM10, PMcoarse, PNC and LDSA, as well as alpine, non-alpine and study area specific models for NO2, using predictor variables which were available at a national level. Models were validated using leave-one-out cross-validation, as well as independent external validation with routine monitoring data. RESULTS: Model explained variance (R(2)) was moderate for the various PM mass fractions PM2.5 (0.57), PM10 (0.63) and PMcoarse (0.45), and was high for PM2.5 absorbance (0.81), PNC (0.87) and LDSA (0.91). Study-area specific LUR models for NO2 (R(2) range 0.52-0.89) outperformed combined-area alpine (R (2) = 0.53) and non-alpine (R (2) = 0.65) models in terms of both cross-validation and independent external validation, and were better able to account for between-area variability. Predictor variables related to traffic and national dispersion model estimates were important predictors. CONCLUSIONS: LUR models for all pollutants captured spatial variability of long-term average concentrations, performed adequately in validation, and could be successfully applied to the SAPALDIA cohort. Dispersion model predictions or area indicators served well to capture the between area variance. For NO2, applying study-area specific models was preferable over applying combined-area alpine/non-alpine models. Correlations between pollutants were higher in the model predictions than in the measurements, so it will remain challenging to disentangle their health effects.

Modeling indoor air pollution of outdoor origin in homes of SAPALDIA subjects in Switzerland.

Given the shrinking spatial contrasts in outdoor air pollution in Switzerland and the trends toward tightly insulated buildings, the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) needs to understand to what extent outdoor air pollution remains a determinant for residential indoor exposure. The objectives of this paper are to identify determining factors for indoor air pollution concentrations of particulate matter (PM), ultrafine particles in the size range from 15 to 300nm, black smoke measured as light absorbance of PM (PMabsorbance) and nitrogen dioxide (NO2) and to develop predictive indoor models for SAPALDIA. Multivariable regression models were developed based on indoor and outdoor measurements among homes of selected SAPALDIA participants in three urban (Basel, Geneva, Lugano) and one rural region (Wald ZH) in Switzerland, various home characteristics and reported indoor sources such as cooking. Outdoor levels of air pollutants were important predictors for indoor air pollutants, except for the coarse particle fraction. The fractions of outdoor concentrations infiltrating indoors were between 30% and 66%, the highest one was observed for PMabsorbance. A modifying effect of open windows was found for NO2 and the ultrafine particle number concentration. Cooking was associated with increased particle and NO2 levels. This study shows that outdoor air pollution remains an important determinant of residential indoor air pollution in Switzerland.

Land use regression models for crustal and traffic-related PM2.5 constituents in four areas of the SAPALDIA study.

Many studies have documented adverse health effects of long-term exposure to fine particulate matter (PM2.5), but there is still limited knowledge regarding the causal relationship between specific sources of PM2.5 and such health effects. The spatial variability of PM2.5 constituents and sources, as a exposure assessment strategy for investigating source contributions to health effects, has been little explored so far. Between 2011 and 2012, three measurement campaigns of PM and nitrogen dioxide (NO2) were performed in 80 sites across four areas of the Swiss Study on Air Pollution and Lung and heart Diseases in Adults (SAPALDIA). Reflectance analysis and energy dispersive X-ray fluorescence (XRF) were performed on PM2.5 filter samples to estimate light absorbance and trace element concentrations, respectively. Three air pollution source factors were identified using principal-component factor analysis: vehicular, crustal, and long-range transport. Land use regression (LUR) models were developed for temporally-adjusted scores of each factor, combining the four study areas. Model performance was assessed using two cross-validation methods. Model explained variance was high for the vehicular factor (R(2)=0.76), moderate for the crustal factor (R(2)=0.46), and low for the long-range transport factor (R(2)=0.19). The cross-validation methods suggested that models for the vehicular and crustal factors moderately accounted for both the between and within-area variability, and therefore can be applied to the four study areas to estimate long-term exposures within the SAPALDIA study population. The combination of source apportionment techniques and LUR modelling may help in identifying air pollution sources and disentangling their contribution to observed health effects in epidemiologic studies.

Ambient ultrafine particle levels at residential and reference sites in urban and rural Switzerland.

Although there is evidence that ultrafine particles (UFP) do affect human health there are currently no legal ambient standards. The main reasons are the absence of spatially resolved exposure data to investigate long-term health effects and the challenge of defining representative reference sites for monitoring given the high dependence of UFP on proximity to sources. The objectives of this study were to evaluate the spatial distribution of UFP in four areas of the Swiss Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) and to investigate the representativeness of routine air monitoring stations for residential sites in these areas. Repeated UFP measurements during three seasons have been conducted at a total of 80 residential sites and four area specific reference sites over a median duration of 7 days. Arithmetic mean residential PNC scattered around the median of 10,800 particles/cm(3) (interquartile range [IQR] = 7800 particles/cm(3)). Spatial within area contrasts (90th/10th percentile ratios) were around two; increased contrasts were observed during weekday rush-hours. Temporal UFP patterns were comparable at reference and residential sites in all areas. Our data show that central monitoring sites can represent residential conditions when locations are well chosen with respect to the local sources--namely traffic. For epidemiological research, locally resolved spatial models are needed to estimate individuals' long-term exposures to UFP of outdoor origin at home, during commute and at work.

Differences in indoor versus outdoor concentrations of ultrafine particles, PM2.5, PMabsorbance and NO2 in Swiss homes.

Indoor air quality is a growing concern as we spend the majority of time indoors and as new buildings are increasingly airtight for energy saving purposes. For a better understanding of residential indoor air pollution in Switzerland we conducted repeated 1-2-week-long indoor and outdoor measurements of particle number concentrations (PNC), particulate matter (PM), light absorbance of PM2.5 (PMabsorbance) and nitrogen dioxide (NO2). Residents of all homes were enrolled in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). Indoor levels were comparable in urban areas and generally low in rural homes. Average indoor levels were 7800 particles/cm(3) (interquartile range=7200); 8.7 µg/m(3) (6.5) PM2.5 and 10.2 µg/m(3) (11.2) NO2. All pollutants showed large variability of indoor/outdoor ratios between sites. We observed similar diurnal patterns for indoor and outdoor PNC. Nevertheless, the correlation of average indoor and outdoor PNC between sites as well as longitudinal indoor/outdoor correlations within sites were low. Our results show that a careful evaluation of home characteristics is needed when estimating indoor exposure to pollutants with outdoor origin.

Associations of short-term particle and noise exposures with markers of cardiovascular and respiratory health among highway maintenance workers.

BACKGROUND: Highway maintenance workers are constantly and simultaneously exposed to traffic-related particle and noise emissions, both of which have been linked to increased cardiovascular morbidity and mortality in population-based epidemiology studies. OBJECTIVES: We aimed to investigate short-term health effects related to particle and noise exposure. METHODS: We monitored 18 maintenance workers, during as many as five 24-hr periods from a total of 50 observation days. We measured their exposure to fine particulate matter (diameter ≤ 2.5 µm; PM2.5), ultrafine particles, and noise, and the cardiopulmonary health end points: blood pressure, proinflammatory and prothrombotic markers in the blood, lung function, and fractional exhaled nitric oxide (FeNO) measured approximately 15 hr after work. Heart rate variability was assessed during a sleep period approximately 10 hr after work. RESULTS: PM2.5 exposure was significantly associated with C-reactive protein and serum amyloid A, and was negatively associated with tumor necrosis factor α. None of the particle metrics were significantly associated with von Willebrand factor or tissue factor expression. PM2.5 and work noise were associated with markers of increased heart rate variability, and with increased high-frequency and low-frequency power. Systolic and diastolic blood pressure on the following morning were significantly associated with noise exposure after work, and nonsignificantly associated with PM2.5. We observed no significant associations between any of the exposures and lung function or FeNO. CONCLUSIONS: Our findings suggest that exposure to particles and noise during highway maintenance work might pose a cardiovascular health risk. Actions to reduce these exposures could lead to better health for this population of workers.

Exposure of highway maintenance workers to fine particulate matter and noise.

In this study, we assessed the mixed exposure of highway maintenance workers to airborne particles, noise, and gaseous co-pollutants. The aim was to provide a better understanding of the workers' exposure to facilitate the evaluation of short-term effects on cardiovascular health endpoints. To quantify the workers' exposure, we monitored 18 subjects during 50 non-consecutive work shifts. Exposure assessment was based on personal and work site measurements and included fine particulate matter (PM2.5), particle number concentration (PNC), noise (Leq), and the gaseous co-pollutants: carbon monoxide, nitrogen dioxide, and ozone. Mean work shift PM2.5 concentrations (gravimetric measurements) ranged from 20.3 to 321 µg m(-3) (mean 62 µg m(-3)) and PNC were between 1.6×10(4) and 4.1×10(5) particles cm(-3) (8.9×10(4) particles cm(-3)). Noise levels were generally high with Leq over work shifts from 73.3 to 96.0 dB(A); the averaged Leq over all work shifts was 87.2 dB(A). The highest exposure to fine and ultrafine particles was measured during grass mowing and lumbering when motorized brush cutters and chain saws were used. Highest noise levels, caused by pneumatic hammers, were measured during paving and guardrail repair. We found moderate Spearman correlations between PNC and PM2.5 (r = 0.56); PNC, PM2.5, and CO (r = 0.60 and r = 0.50) as well as PNC and noise (r = 0.50). Variability and correlation of parameters were influenced by work activities that included equipment causing combined air pollutant and noise emissions (e.g. brush cutters and chain saws). We conclude that highway maintenance workers are frequently exposed to elevated airborne particle and noise levels compared with the average population. This elevated exposure is a consequence of the permanent proximity to highway traffic with additional peak exposures caused by emissions of the work-related equipment.

Helminth products bypass the need for TSLP in Th2 immune responses by directly modulating dendritic cell function.

Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine, mainly expressed by epithelial cells, and key to the development of allergic responses. The well-documented involvement of TSLP in allergy has led to the conviction that TSLP promotes the development of inflammatory Th2 cell responses. However, we now report that the interaction of TSLP with its receptor (TSLPR) has no functional impact on the development of protective Th2 immune responses after infection with 2 helminth pathogens, Heligmosomoides polygyrus and Nippostrongylus brasiliensis. Mice deficient in the TSLP binding chain of the TSLPR (TSLPR(-/-)) exhibited normal Th2 cell differentiation, protective immunity and memory responses against these two distinct rodent helminths. In contrast TSLP was found to be necessary for the development of protective Th2 responses upon infection with the helminth Trichuris muris (T. muris). TSLP inhibited IL-12p40 production in response to T. muris infection, and treatment of TSLPR(-/-) animals with neutralizing anti-IL-12p40 monoclonal antibody (mAb) was able to reverse susceptibility and attenuate IFN-gamma production. We additionally demonstrated that excretory-secretory (ES) products from H. polygyrus and N. brasiliensis, but not T. muris, were capable of directly suppressing dendritic cell (DC) production of IL-12p40, thus bypassing the need for TSLP. Taken together, our data show that the primary function of TSLP is to directly suppress IL-12 secretion, thus supporting Th2 immune responses.

IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo.

Th17 cells have been recognized as the central effectors in organ-related autoimmune diseases. IL-6 is a key factor that reciprocally regulates Th17 and Foxp3(+) Treg differentiation by inhibition of TGF-beta induced Foxp3 and induction of RORgammat, a Th17 lineage-specific transcription factor. Recently IL-21 has been suggested to induce RORgammat and Th17 development in the absence of IL-6. However, the relevance of IL-21 for Th17-dependent inflammatory responses in vivo remains unclear. In this study, we demonstrate that differentiation of IL-17-producing CD4 T cells, their recruitment to inflamed organs, and the development of autoimmune disease was not affected in il21R(-/-) and il21(-/-) mice in models of myelin oligodendrocyte glycoprotein-induced autoimmune encephalitis and autoimmune myocarditis. IL-6 induced Th17 differentiation independent of and much more potently than IL-21 in vitro. These data suggest that IL-6 is sufficient to drive Th17 development and associated autoimmunity in vivo in the absence of IL-21 or IL-21R.

A calcium-gated lid and a large beta-roll sandwich are revealed by the crystal structure of extracellular lipase from Serratia marcescens.

Lipase LipA from Serratia marcescens is a 613-amino acid enzyme belonging to family I.3 of lipolytic enzymes that has an important biotechnological application in the production of a chiral precursor for the coronary vasodilator diltiazem. Like other family I.3 lipases, LipA is secreted by Gram-negative bacteria via a type I secretion system and possesses 13 copies of a calcium binding tandem repeat motif, GGXGXDXUX (U, hydrophobic amino acids), in the C-terminal part of the polypeptide chain. The 1.8-A crystal structure of LipA reveals a close relation to eukaryotic lipases, whereas family I.1 and I.2 enzymes appear to be more distantly related. Interestingly, the structure shows for the N-terminal lipase domain a variation on the canonical alpha/beta hydrolase fold in an open conformation, where the putative lid helix is anchored by a Ca(2+) ion essential for activity. Another novel feature observed in this lipase structure is the presence of a helical hairpin additional to the putative lid helix that exposes a hydrophobic surface to the aqueous medium and might function as an additional lid. The tandem repeats form two separated parallel beta-roll domains that pack tightly against each other. Variations of the consensus sequence of the tandem repeats within the second beta-roll result in an asymmetric Ca(2+) binding on only one side of the roll. The analysis of the properties of the beta-roll domains suggests an intramolecular chaperone function.

The molecular architecture of the metalloprotease FtsH.

The ATP-dependent integral membrane protease FtsH is universally conserved in bacteria. Orthologs exist in chloroplasts and mitochondria, where in humans the loss of a close FtsH-homolog causes a form of spastic paraplegia. FtsH plays a crucial role in quality control by degrading unneeded or damaged membrane proteins, but it also targets soluble signaling factors like sigma(32) and lambda-CII. We report here the crystal structure of a soluble FtsH construct that is functional in caseinolytic and ATPase assays. The molecular architecture of this hexameric molecule consists of two rings where the protease domains possess an all-helical fold and form a flat hexagon that is covered by a toroid built by the AAA domains. The active site of the protease classifies FtsH as an Asp-zincin, contrary to a previous report. The different symmetries of protease and AAA rings suggest a possible translocation mechanism of the target polypeptide chain into the interior of the molecule where the proteolytic sites are located.

The molecular basis of vitamin E retention: structure of human alpha-tocopherol transfer protein.

Alpha-tocopherol transfer protein (alpha-TTP) is a liver protein responsible for the selective retention of alpha-tocopherol from dietary vitamin E, which is a mixture of alpha, beta, gamma, and delta-tocopherols and the corresponding tocotrienols. The alpha-TTP-mediated transfer of alpha-tocopherol into nascent VLDL is the major determinant of plasma alpha-tocopherol levels in humans. Mutations in the alpha-TTP gene have been detected in patients suffering from low plasma alpha-tocopherol and ataxia with isolated vitamin E deficiency (AVED). The crystal structure of alpha-TTP reveals two conformations. In its closed tocopherol-charged form, a mobile helical surface segment seals the hydrophobic binding pocket. In the presence of detergents, an open conformation is observed, which probably represents the membrane-bound form. The selectivity of alpha-TTP for RRR-alpha-tocopherol is explained from the van der Waals contacts occurring in the lipid-binding pocket. Mapping the known mutations leading to AVED onto the crystal structure shows that no mutations occur directly in the binding pocket.