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Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).

The study of secondary organic aerosol (SOA) in laboratory settings has greatly increased our knowledge of the diverse chemical processes and environmental conditions responsible for the formation of particulate matter starting from biogenic and anthropogenic volatile compounds. However, characteristics of the different experimental setups and the way they impact the composition and the timescale of formation of SOA are still subject to debate. In this study, SOA samples were generated using a potential aerosol mass (PAM) oxidation flow reactor using α-pinene, naphthalene and isoprene as precursors. The PAM reactor facilitated exploration of SOA composition over atmospherically relevant photochemical ageing timescales that are unattainable in environmental chambers. The SOA samples were analyzed using two state-of-the-art analytical techniques for SOA characterization – proton nuclear magnetic resonance (1H-NMR) spectroscopy and HPLC determination of humic-like substances (HULIS). Results were compared with previous Aerodyne aerosol mass spectrometer (AMS) measurements. The combined 1H-NMR, HPLC, and AMS datasets show that the composition of the studied SOA systems tend to converge to highly oxidized organic compounds upon prolonged OH exposures. Further, our 1H-NMR findings show that only α-pinene SOA acquires spectroscopic features comparable to those of ambient OA when exposed to at least 1 × 1012 molec OH cm−3 × s OH exposure, or multiple days of equivalent atmospheric OH oxidation. Over multiple days of equivalent OH exposure, the formation of HULIS is observed in both α-pinene SOA and in naphthalene SOA (maximum yields: 16 and 30 %, respectively, of total analyzed water-soluble organic carbon, WSOC), providing evidence of the formation of humic-like polycarboxylic acids in unseeded SOA.

Atmospheric organic aerosols are generally classified as primary and secondary (POA and SOA) according to their formation processes. An actual separation, however, is challenging when the timescales of emission and gas-to-particle formation overlap. The presence of SOA formation in biomass burning plumes leads to scientific questions about whether the oxidized fraction of biomass burning aerosol is rather of secondary or primary origin, as some studies would suggest, and about the chemical compositions of oxidized biomass burning POA and SOA. In this study, we apply nuclear magnetic resonance (NMR) spectroscopy to investigate the functional group composition of fresh and aged biomass burning aerosols during an intensive field campaign in the Po Valley, Italy. The campaign was part of the EUCAARI project and was held at the rural station of San Pietro Capofiume in spring 2008. Factor analysis applied to the set of NMR spectra was used to apportion the wood burning contribution and other organic carbon (OC) source contributions, including aliphatic amines. Our NMR results, referred to the polar, water-soluble fraction of OC, show that fresh wood burning particles are composed of polyols and aromatic compounds, with a sharp resemblance to wood burning POA produced in wood stoves, while aged samples are clearly depleted of alcohols and are enriched in aliphatic acids with a smaller contribution of aromatic compounds. The comparison with biomass burning organic aerosols (BBOA) determined by high-resolution aerosol mass spectrometry (HR-TOF-AMS) at the site shows only a partial overlap between NMR BB-POA and AMS BBOA, which can be explained by either the inability of BBOA to capture all BB-POA composition, especially the alcohol fraction, or the fact that BBOA account for insoluble organic compounds unmeasured by the NMR. Therefore, an unambiguous composition for biomass burning POA could not be derived from this study, with NMR analysis indicating a higher O / C ratio compared to that measured for AMS BBOA. The comparison between the two techniques substantially improves when adding factors tracing possible contributions from biomass burning SOA, showing that the operational definitions of biomass burning organic aerosols are more consistent between techniques when including more factors tracing chemical classes over a range of oxidation levels. Overall, the non-fossil total carbon fraction was 50–57%, depending on the assumptions about the 14C content of non-fossil carbon, and the fraction of organic carbon estimated to be oxidized organic aerosol (OOA) from HR-TOF-AMS measurements was 73–100% modern.

Nuclear magnetic resonance (NMR) spectroscopy is used to investigate the chemical composition of organic aerosol in terms of functional group distribution with a special focus on secondary organic aerosol (SOA) formation. The knowledge of the functional group composition is a benchmark for understanding how SOA components partition into the particulate phase and undergo chemical transformation. The paper presents a new chemical derivatization procedure coupled to proton NMR (H-1 NMR) analysis for the specific determination of total carbonylic groups in atmospheric aerosol samples, which couples with the procedure for determination of total carboxylic acid groups described in a previous work. A first deployment of the combined techniques for the analysis of PM10 samples collected in the Po Valley in the warm season shows that the concentration in the particulate phase of total carbonyls varies and covaries with respect to those of carboxylic acids and of less-oxidized functional groups. The proposed methodology provides the breakdown of the oxygenated fraction of the organic aerosol into major functional groups through well-established chemical methods and can be used to benchmark the more sensitive and widely used aerosol mass spectrometric techniques.

The chemical composition of carbonaceous aerosols collected during the LBA-SMOCC field experiment, conducted in Rondônia, Brazil, in 2002 during the transition from the dry to the wet season, was investigated by a suite of state-of-the-art analytical techniques. The period of most intense biomass burning was characterized by high concentrations of submicron particles rich in carbonaceous material and water-soluble organic compounds (WSOC). At the onset of the rainy period, submicron total carbon (TC) concentrations decreased by about 20 times. In contrast, the concentration of supermicron TC was fairly constant throughout the experiment, pointing to a constant emission of coarse particles from the natural background. About 6–8% of TC (9–11% of WSOC) was speciated at the molecular level by GC-MS and liquid chromatography. Polyhydroxylated compounds, aliphatic and aromatic acids were the main classes of compounds accounted for by individual compound analysis. Functional group analysis by proton NMR and chromatographic separation on ion-exchange columns allowed characterization of ca.50–90% of WSOC into broad chemical classes (neutral species/light acids/humic-like substances). In spite of the significant change in the chemical composition of tracer compounds from the dry to the wet period, the functional groups and the general chemical classes of WSOC changed only to a small extent. Model compounds representing size-resolved WSOC chemical composition for the different periods of the campaign are then proposed in this paper, based on the chemical characterization by both individual compound analysis and functional group analysis deployed during the LBA-SMOCC experiment. Model compounds reproduce quantitatively the average chemical structure of WSOC and can be used as best-guess surrogates in microphysical models involving organic aerosol particles over tropical areas affected by biomass burning.

Relevant concentrations of dimethyl- and diethylammonium salts(DMA(+) and DEA(+))were measured in submicrometer marine aerosol collected over the North Atlantic during periods of high biological activity (HBA) in clean air masses (median concentration (minimum-maximum) = 26 (6-56) ng m(-3)). Much lower concentrations were measured during periods of low biological activity (LBA): 1 (

Lymphomatoid granulomatosis (LYG) is a rare B-cell lymphoproliferative disorder predominantly involving the lungs, but poorly-recognized among clinicians and pathologists. It is an Epstein-Barr virus (EBV)-driven disease mimicking several other diseases on clinical and radiological grounds, generally showing multiple, bilateral nodular, ill-defined infiltrates of the lungs tending to coalescence and/or cavitation. LYG often affects middle-aged males with an underlying immunodeficiency and commonly involves skin and central nervous system during disease progression. Diagnosis requires a generous biopsy and careful histologic examination with immunohistochemical staining and molecular demonstration of EBV genome in large atypical B-cells. LYG is graded as I to III based on the number of large EBV-positive B-cells; grades II/III are now considered as a peculiar variant of T-cell rich diffuse large B-cell lymphoma. In this brief review, clinical, radiologic and pathologic features of LYG will be analyzed with focus on differential diagnosis, the most appropriate treatment and prognosis.

Atmospheric organic aerosols are generally classified into primary and secondary (POA and SOA) according to their formation processes. An actual separation, however, is challenging when the timescales of emission and of gas-to-particle formation overlap. The presence of SOA formation in biomass burning plumes leads to scientific questions about whether the oxidized fraction of biomass burning aerosol is rather of secondary or primary origin, as some studies would suggest, and about the chemical compositions of oxidized biomass burning POA and SOA. In this study, we apply nuclear magnetic resonance (NMR) spectroscopy to investigate the functional group composition of fresh and aged biomass burning aerosols during an intensive field campaign in the Po Valley, Italy. The campaign was part of the EUCAARI project and was held at the rural station of San Pietro Capofiume in spring 2008. Factor analysis applied to the set of NMR spectra was used to apportion the wood burning contribution and other organic carbon (OC) source contributions, including aliphatic amines. Our NMR results, referred to the polar, water-soluble fraction of OC, show that fresh wood burning particles are composed of polyols and aromatic compounds, with a sharp resemblance with wood burning POA produced in wood stoves, while aged samples are clearly depleted of alcohols and are enriched in aliphatic acids with a smaller contribution of aromatic compounds. The comparison with biomass burning organic aerosols (BBOA) determined by high resolution aerosol mass spectrometry (HR-TOF-AMS) at the site shows only a partial overlap between NMR BB-POA and AMS BBOA, which can be explained by either the inability of BBOA to capture all BB-POA composition, especially the alcohol fraction, or the fact that BBOA account for insoluble organic compounds unmeasured by the NMR. Therefore, an unambiguous composition for biomass burning POA could not be derived from this study, with NMR analysis indicating a higher O / C ratio compared to that measured for AMS BBOA. The comparison between the two techniques substantially improves when adding factors tracing possible contributions from biomass burning SOA, showing that the operational definitions of biomass burning organic aerosols are more consistent between techniques when including more factors tracing chemical classes over a range of oxidation levels. Overall, the non-fossil total carbon fraction was 50–57%, depending on the assumptions on the 14C content of non-fossil carbon, and the fraction of organic carbon estimated to be oxidized organic aerosol (OOA) from HR-TOF-AMS measurements was 73–100% modern.

Water soluble organic compounds (WSOC) in aerosol samples collected in the Amazon Basin in a period encompassing the middle/late dry season and the beginning of the wet season, were investigated by H NMR spectroscopy. HiVol filter samples (PM2.5 and PM>2.5) and size-segregated samples from multistage impactor were subjected to H NMR characterization. The H NMR methodology, recently developed for the analysis of organic aerosol samples, has been improved by exploiting chemical methylation of carboxylic groups with diazomethane, which allows the direct determination of the carboxylic acid content of WSOC. The content of carboxylic carbons for the different periods and sizes ranged from 12% to 20% of total measured carbon depending on the season and aerosol size, with higher contents for the fine particles in the transition and wet periods with respect to the dry period. A comprehensive picture is presented of WSOC functional groups in aerosol samples representative of the biomass burning period, as well as of transition and semi-clean atmospheric conditions. A difference in composition between fine (PM2.5) and coarse (PM>2.5) size fractions emerged from the NMR data, the former showing higher alkylic content, the latter being largely dominated by R-O-H (or R-O-R') functional groups. Very small particles (

The properties of atmospheric aerosol organic compounds are often simulated in models by arbitrarily choosing model compounds which have, in most cases, little contact with the physical reality. We propose here a procedure with which to derive a simplied model of the water soluble organic fraction of the atmospheric aerosol. Quantitative measurements of organic carbon concentration and proton concentration of the main functional groups contained in the aerosol water soluble organic compounds (WSOC) mixture are used to formulate a set of a few model compounds,representative of the whole WSOC mass, which can simulate in models the chemical and physical properties of aerosol WSOC.

A new procedure based on switchable polarity solvents (SPS) was proposed for lipid extraction of wet algal samples or cultures, thereby circumventing the need for an energy intensive drying step and facilitating easy recovery of the lipids from the extraction liquid. Lipids were extracted by using N,N-dimethylcyclohexylamine (DMCHA) and recovered by adding CO2, thereby switching DMCHA into a hydrogen carbonate ammonium salt and resulting in the formation of a separate liquid lipid phase.

Lipid extraction is a critical step in the development of biofuels from microalgae. Here a new procedure was proposed to extract hydrocarbons from dried and water-suspended samples of the microalga Botryococcus braunii by using switchable-polarity solvents (SPS) based on 1,8-diazabicyclo-[5.4.0]-undec-7-ene (DBU) and an alcohol. The high affinity of the non-ionic form of DBU/alcohol SPS towards non-polar compounds was exploited to extract hydrocarbons from algae, while the ionic character of the DBU-alkyl carbonate form, obtained by the addition of CO(2), was used to recover hydrocarbons from the SPS. DBU/octanol and DBU/ethanol SPS were tested for the extraction efficiency of lipids from freeze-dried B. braunii samples and compared with n-hexane and chloroform/methanol. The DBU/octanol system was further evaluated for the extraction of hydrocarbons directly from algal culture samples. DBU/octanol exhibited the highest yields of extracted hydrocarbons from both freeze-dried and liquid algal samples (16% and 8.2% respectively against 7.8% and 5.6% with n-hexane).

The atmospheric organic aerosol composition is characterized by a great diversity of functional groups and chemical species, challenging simple classification schemes. Traditional offline chemical methods identify chemical classes based on the retention behaviour on chromatographic columns and absorbing beds. Such an approach led to the isolation of complex mixtures of compounds such as the humic-like substances (HULIS). More recently, online aerosol mass spectrometry (AMS) was employed to identify chemical classes by extracting fragmentation patterns from experimental data series using statistical methods (factor analysis), providing simplified schemes for the classification of oxygenated organic aerosols (OOAs) on the basis of the distribution of oxygen-containing functionalities. The analysis of numerous AMS data sets suggested the occurrence of very oxidized OOAs which were postulated to correspond to HULIS. However, only a few efforts were made to test the correspondence of the AMS classes of OOAs with the traditional classifications from the offline methods. In this paper, we consider a case study representative of polluted continental regional background environments. We examine the AMS factors for OOAs identified by positive matrix factorization (PMF) and compare them to chemical classes of water-soluble organic carbon (WSOC) analysed offline on a set of filters collected in parallel. WSOC fractionation was performed by means of factor analysis applied to proton nuclear magnetic resonance (NMR) spectroscopic data, and by applying an ion-exchange chromatographic method for direct quantification of HULIS. Results show that the very oxidized low-volatility OOAs from AMS correlate with the NMR factor showing HULIS features and also with true "chromatographic" HULIS. On the other hand, UV/VIS-absorbing polyacids (or HULIS {sensu stricto}) isolated on ion-exchange beds were only a fraction of the AMS and NMR organic carbon fractions showing functional groups attributable to highly substituted carboxylic acids, suggesting that unspeciated low-molecular weight organic acids contribute to HULIS in the broad sense.