Dendritic cells treated with chloroquine modulate experimental autoimmune encephalomyelitis

Chloroquine (CQ), an antimalarial drug, has been shown to modulate the immune system and reduce the severity of experimental autoimmune encephalomyelitis (EAE). The mechanisms of disease suppression are dependent on regulatory T cell induction, although Tregs-independent mechanisms exist. We aimed to evaluate whether CQ is capable to modulate bone marrow-derived dendritic cells (DCs) both phenotypically and functionally as well as whether transfer of CQ-modulated DCs reduces EAE course. Our results show that CQ-treated DCs presented altered ultrastructure morphology and lower expression of molecules involved in antigen presentation. Consequently, T cell proliferation was diminished in coculture experiments. When transferred into EAE mice, DC-CQ was able to reduce the clinical manifestation of the disease through the modulation of the immune response against neuroantigens. The data presented herein indicate that chloroquine-mediated modulation of the immune system is achieved by a direct effect on DCs and that DC-CQ adoptive transfer may be a promising approach for avoiding drug toxicity922124132FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2011/17965-3; 2011/13191-3; 2012/08303-

The RIBES strategy for ex situ conservation: conventional and modern techniques for seed conservation

The Italian seed bank network (RIBES) aims to improve the quality and safety of the germplasm reserves of native plant species in Italy to ensure the long-term conservation of endangered and/or endemic flora. The strategy includes traditional methods to secure seed conservation. A comprehensive priority list for seed collection is being defined, it was prepared by crossing data of various checklists (red lists, endemics) and will soon be cross-referenced with an updated list of accessions of the whole network. A safety-backup program of duplicates will quickly be implemented to secure the conservation of the most threatened species in at least two seed banks of the network. On the other hand, the RIBES strategy also includes research by applying modern techniques. In collaboration with the Millennium Seed Bank, research on the storage behaviour of seeds and spores through thermal analysis is ongoing to inform conservation. Using the Differential Scanning Calorimetry (DSC), we could evaluate seed lipid properties such as glass transition temperature, melting, crystallization, oxidation behaviour, and thermal stability. Finally, RIBES participates as a co-funder in the LIFE Nature project SEEDFORCE, coordinating 11 seed banks of the network for collecting seeds/spores of 29 threatened species of EU interest

The RIBES strategy for ex situ conservation: conventional and modern techniques for seed conservation

The Italian seed bank network (RIBES) aims to improve the quality and safety of the germplasm reserves of native plant species in Italy to ensure the long-term conservation of endangered and/or endemic flora. The strategy includes traditional methods to secure seed conservation. A comprehensive priority list for seed collection is being defined, it was prepared by crossing data of various checklists (red lists, endemics) and will soon be cross-referenced with an updated list of accessions of the whole network. A safety-backup program of duplicates will quickly be implemented to secure the conservation of the most threatened species in at least two seed banks of the network. On the other hand, the RIBES strategy also includes research by applying modern techniques. In collaboration with the Millennium Seed Bank, research on the storage behaviour of seeds and spores through thermal analysis is ongoing to inform conservation. Using the Differential Scanning Calorimetry (DSC), we could evaluate seed lipid properties such as glass transition temperature, melting, crystallization, oxidation behaviour, and thermal stability. Finally, RIBES participates as a co-funder in the LIFE Nature project SEEDFORCE, coordinating 11 seed banks of the network for collecting seeds/spores of 29 threatened species of EU interest

Comparison of different real time VOC measurement techniques in a ponderosa pine forest

Volatile organic compound (VOC) mixing ratios measured by five independent instruments are compared at a forested site dominated by ponderosa pine (Pinus Ponderosa) during the BEACHON-ROCS field study in summer 2010. The instruments included a Proton Transfer Reaction Time of Flight Mass Spectrometer (PTR-TOF-MS), a Proton Transfer Reaction Quadrupole Mass Spectrometer (PTR-MS), a Fast Online Gas-Chromatograph coupled to a Mass Spectrometer (GC/MS; TOGA), a Thermal Dissociation Chemical Ionization Mass Spectrometer (PAN-CIMS) and a Fiber Laser-Induced Fluorescence Instrument (FILIF). The species discussed in this comparison include the most important biogenic VOCs and a selected suite of oxygenated VOCs that are thought to dominate the VOC reactivity at this particular site as well as typical anthropogenic VOCs that showed low mixing ratios at this site. Good agreement was observed for methanol, the sum of the oxygenated hemiterpene 2-methyl-3-buten-2-ol (MBO) and the hemiterpene isoprene, acetaldehyde, the sum of acetone and propanal, benzene and the sum of methyl ethyl ketone (MEK) and butanal. Measurements of the above VOCs conducted by different instruments agree within 20%. The ability to differentiate the presence of toluene and cymene by PTR-TOF-MS is tested based on a comparison with GC-MS measurements, suggesting a study-average relative contribution of 74% for toluene and 26% for cymene. Similarly, 2-hydroxy-2-methylpropanal (HMPR) is found to interfere with the sum of methyl vinyl ketone and methacrolein (MVK + MAC) using PTR-(TOF)-MS at this site. A study-average relative contribution of 85% for MVK + MAC and 15% for HMPR was determined. The sum of monoterpenes measured by PTR-MS and PTR-TOF-MS was generally 20–25% higher than the sum of speciated monoterpenes measured by TOGA, which included α-pinene, β-pinene, camphene, carene, myrcene, limonene, cineole as well as other terpenes. However, this difference is consistent throughout the study, and likely points to an offset in calibration, rather than a difference in the ability to measure the sum of terpenes. The contribution of isoprene relative to MBO inferred from PTR-MS and PTR-TOF-MS was smaller than 12% while GC-MS data suggested an average of 21% of isoprene relative to MBO. This comparison demonstrates that the current capability of VOC measurements to account for OH reactivity associated with the measured VOCs is within 20%

Comparison of different real time VOC measurement techniques in a ponderosa pine forest

Volatile organic compound (VOC) mixing ratios measured by five independent instruments are compared at a forested site dominated by ponderosa pine (Pinus Ponderosa) during the BEACHON-ROCS field study in summer 2010. The instruments included a Proton Transfer Reaction Time of Flight Mass Spectrometer (PTR-TOF-MS), a Proton Transfer Reaction Quadrupole Mass Spectrometer (PTR-MS), a Fast Online Gas-Chromatograph coupled to a Mass Spectrometer (GC/MS; TOGA), a Thermal Dissociation Chemical Ionization Mass Spectrometer (PAN-CIMS) and a Fiber Laser-Induced Fluorescence Instrument (FILIF). The species discussed in this comparison include the most important biogenic VOCs and a selected suite of oxygenated VOCs that are thought to dominate the VOC reactivity at this particular site as well as typical anthropogenic VOCs that showed low mixing ratios at this site. Good agreement was observed for methanol, the sum of the oxygenated hemiterpene 2-methyl-3-buten-2-ol (MBO) and the hemiterpene isoprene, acetaldehyde, the sum of acetone and propanal, benzene and the sum of methyl ethyl ketone (MEK) and butanal. Measurements of the above VOCs conducted by different instruments agree within 20%. The ability to differentiate the presence of toluene and cymene by PTR-TOF-MS is tested based on a comparison with GC-MS measurements, suggesting a study-average relative contribution of 74% for toluene and 26% for cymene. Similarly, 2-hydroxy-2-methylpropanal (HMPR) is found to interfere with the sum of methyl vinyl ketone and methacrolein (MVK + MAC) using PTR-(TOF)-MS at this site. A study-average relative contribution of 85% for MVK + MAC and 15% for HMPR was determined. The sum of monoterpenes measured by PTR-MS and PTR-TOF-MS was generally 20–25% higher than the sum of speciated monoterpenes measured by TOGA, which included α-pinene, β-pinene, camphene, carene, myrcene, limonene, cineole as well as other terpenes. However, this difference is consistent throughout the study, and likely points to an offset in calibration, rather than a difference in the ability to measure the sum of terpenes. The contribution of isoprene relative to MBO inferred from PTR-MS and PTR-TOF-MS was smaller than 12% while GC-MS data suggested an average of 21% of isoprene relative to MBO. This comparison demonstrates that the current capability of VOC measurements to account for OH reactivity associated with the measured VOCs is within 20%

The associations of earlier trauma exposures and history of mental disorders with PTSD after subsequent traumas

Although earlier trauma exposure is known to predict posttraumatic stress disorder (PTSD) after subsequent traumas, it is unclear whether this association is limited to cases where the earlier trauma led to PTSD. Resolution of this uncertainty has important implications for research on pretrauma vulnerability to PTSD. We examined this issue in the World Health Organization (WHO) World Mental Health (WMH) Surveys with 34 676 respondents who reported lifetime trauma exposure. One lifetime trauma was selected randomly for each respondent. DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) PTSD due to that trauma was assessed. We reported in a previous paper that four earlier traumas involving interpersonal violence significantly predicted PTSD after subsequent random traumas (odds ratio (OR)=1.3-2.5). We also assessed 14 lifetime DSM-IV mood, anxiety, disruptive behavior and substance disorders before random traumas. We show in the current report that only prior anxiety disorders significantly predicted PTSD in a multivariate model (OR=1.5-4.3) and that these disorders interacted significantly with three of the earlier traumas (witnessing atrocities, physical violence victimization and rape). History of witnessing atrocities significantly predicted PTSD after subsequent random traumas only among respondents with prior PTSD (OR=5.6). Histories of physical violence victimization (OR=1.5) and rape after age 17 years (OR=17.6) significantly predicted only among respondents with no history of prior anxiety disorders. Although only preliminary due to reliance on retrospective reports, these results suggest that history of anxiety disorders and history of a limited number of earlier traumas might usefully be targeted in future prospective studies as distinct foci of research on individual differences in vulnerability to PTSD after subsequent traumas.The ESEMeD project is funded by the European Commission (Contracts QLG5-1999-01042; SANCO 2004123, and EAHC 20081308), (the Piedmont Region (Italy)), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnología, Spain (SAF 2000-158-CE), Departament de Salut, Generalitat de Catalunya, Spain, Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP), and other local agencies and by an unrestricted educational grant from GlaxoSmithKline

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

The Total Carbon Column Observing Network's GGG2020 data version

The Total Carbon Column Observing Network (TCCON) measures column-average mole fractions of several greenhouse gases (GHGs), beginning in 2004, from over 30 current or past measurement sites around the world using solar absorption spectroscopy in the near-infrared (near-IR) region. TCCON GHG data have been used extensively for multiple purposes, including in studies of the carbon cycle and anthropogenic emissions, as well as to validate and improve observations from space-based sensors. Here, we describe an update to the retrieval algorithm used to process the TCCON near-IR solar spectra and to generate the associated data products. This version, called GGG2020, was initially released in April 2022. It includes updates and improvements to all steps of the retrieval, including but not limited to the conversion of the original interferograms into spectra, the spectroscopic information used in the column retrieval, post hoc air mass dependence correction, and scaling to align with the calibration scales of in situ GHG measurements. All TCCON data are available through https://tccondata.org/ (last access: 22 April 2024) and are hosted on CaltechDATA (https://data.caltech.edu/, last access: 22 April 2024). Each TCCON site has a unique DOI for its data record. An archive of all the sites' data is also available with the DOI https://doi.org/10.14291/TCCON.GGG2020 (Total Carbon Column Observing Network (TCCON) Team, 2022). The hosted files are updated approximately monthly, and TCCON sites are required to deliver data to the archive no later than 1 year after acquisition. Full details of data locations are provided in the “Code and data availability” section.</p

Preserving biodiversity in marginal rural areas: Assessment of morphological and genetic variability of a sicilian common bean germplasm collection

The historical cultivation of common bean (Phaseolus vulgaris L.) has resulted in the development of local populations/cultivars in restricted Italian rural areas. Many common bean landraces, still cultivated in small mountain areas from Sicily, have become outdated and endangered due to the commercial varieties spreading. These accessions are poorly known but often represent a genetic heritage to be preserved and enhanced. The ex situ conservation of fifty-seven Sicilian common bean landraces was carried out at the “Living Plants Germplasm Bank” at Ucria (Messina, Italy), founded by the Nebrodi Regional Park, together with the “Sicilian Plant Germplasm Repository” of University of Palermo (SPGR/PA). To assess the germplasm genetic diversity, nineteen morphological traits and eight Simple Sequence Repeats (SSRs) were used. Genetic distances among landraces were calculated to construct a clustering tree by using unweighted pair group method arithmetic (UPGMA). Seed germplasm diversity of Sicilian common bean varied from 80.7% to 93.3%, based on six seed descriptors and six leaf, flower, and pod descriptors, respectively, while cluster genetic analysis depicted a clear separation among all the 57 landraces. Principal coordinates (PCoA) and STRUCTURE analyses showed a prevalent rate of admixture between Mesoamerican and Andean gene pools in Sicilian common bean collection, confirming its heterogeneity. The observed high level of diversity evidenced the needs to adopt accurate criterion to plan a definitive ex situ germplasm collection to share agrobiodiversity with local farmers and to avoid any further loss of genetic resources in rural and protected areas