246 research outputs found
Sample preparation for an optimized extraction of localized metabolites in lichens: Application to Pseudevernia furfuracea
International audienceLichens are symbiotic organisms known for producing unique secondary metabolites with attractive cosmetic and pharmacological properties. In this paper, we investigated three standard methods of preparation of Pseudevernia furfuracea (blender grinding, ball milling, pestle and mortar). The materials obtained were characterized by electronic microscopy, nitrogen adsorption and compared from the point of view of extraction. Their microscopic structure is related to extraction efficiency. In addition, it is shown using thalline reactions and mass spectrometry mapping (TOF-SIMS) that these metabolites are not evenly distributed throughout the organism. Particularly, atranorin (a secondary metabolite of interest) is mainly present in the cortex of Pseudevernia furfuracea. Finally, using microwave assisted extraction (MAE) we obtained evidence that an appropriate preparation can increase the extraction efficiency of atranorin by a factor of fiv
Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency.
PURPOSE: To investigate the clinical and functional aspects of MST1 (STK4) deficiency in a profoundly CD4-lymphopenic kindred with a novel homozygous nonsense mutation in STK4. Although recent studies have described the cellular effects of murine Mst1 deficiency, the phenotype of MST1-deficient human lymphocytes has yet to be fully explored. Patient lymphocytes were therefore investigated in the context of current knowledge of murine Mst1 deficiency. METHODS: Genetic etiology was identified by whole exome sequencing of genomic DNA from two siblings, combined with linkage analysis in the wider family. MST1 protein expression was assessed by immunoblotting. The ability of patient lymphocytes to adhere to ICAM-1 under flow conditions was measured, and transwell assays were used to assess chemotaxis. Chemokine receptor expression was examined by flow cytometry and receptor signalling by immunoblotting. RESULTS: A homozygous nonsense mutation in STK4 (c.442C > T, p.Arg148Stop) was found in the patients, leading to a lack of MST1 protein expression. Patient leukocytes exhibited deficient chemotaxis after stimulation with CXCL11, despite preserved expression of CXCR3. Patient lymphocytes were also unable to bind effectively to immobilised ICAM-1 under flow conditions, in keeping with a failure to develop high affinity binding. CONCLUSION: The observed abnormalities of adhesion and migration imply a profound trafficking defect among human MST1-deficient lymphocytes. By analogy with murine Mst1 deficiency and other defects of leucocyte trafficking, this is likely to contribute to immunodeficiency by impairing key aspects of T-cell development and function such as positive selection in the thymus, thymic egress and immune synapse formation in the periphery.This is thepublished version. It first appeared at http://link.springer.com/article/10.1007%2Fs10875-016-0232-2
Interlaboratory comparison study of the Colony Forming Efficiency assay for assessing cytotoxicity of nanomaterials
Nanotechnology has gained importance in the past years as it provides opportunities for industrial growth and innovation. However, the increasing use of manufactured nanomaterials (NMs) in a number of commercial applications and consumer products raises also safety concerns and questions regarding potential unintended risks to humans and the environment. Since several years the European Commission’s Joint Research Centre (JRC) is putting effort in the development, optimisation and harmonisation of in vitro test methods suitable for screening and hazard assessment of NMs. Work is done in collaboration with international partners, in particular the Organisation for Economic Co-operation and Development (OECD). This report presents the results from an interlaboratory comparison study of the in vitro Colony Forming Efficiency (CFE) cytotoxicity assay performed in the frame of OECD's Working Party of Manufactured Nanomaterials (WPMN). Twelve laboratories from European Commission, France, Italy, Japan, Poland, Republic of Korea, South Africa and Switzerland participated in the study coordinated by JRC. The results show that the CFE assay is a suitable and robust in vitro method to assess cytotoxicity of NMs. The assay protocol is well defined and is easily and reliably transferable to other laboratories. The results obtained show good intra and interlaboratory reproducibility of the assay for both the positive control and the tested nanomaterials.
In conclusion the CFE assay can be recommended as a building block of an in vitro testing battery for NMs toxicity assessment. It could be used as a first choice method to define dose-effect relationships for other in vitro assays.JRC.I.4-Nanobioscience
Retinal Vascular Occlusion after COVID-19 Vaccination : More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study
Background: To investigate whether vaccination against SARS-CoV-2 is associated with
the onset of retinal vascular occlusive disease (RVOD). Methods: In this multicentre study, data
from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch
retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were
retrospectively collected during a 2-month index period (1 June–31 July 2021) according to a defined
protocol. The relation to any previous vaccination was documented for the consecutive case series.
Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case–
control study using age- and sex-matched controls from the general population (study participants
from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was
conducted. Results: Four hundred and twenty-one subjects presenting during the index period
(61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO,
fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred
and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given
were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our
case–control analysis integrating population-based data from the GHS yielded no evidence of an
increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60–1.45, p = 0.75) in connection with
a vaccination within a 4-week window. Conclusions: To date, there has been no evidence of any
association between SARS-CoV-2 vaccination and a higher RVOD risk
New Mass and Radius Constraints on the LHS 1140 Planets -- LHS 1140 b is Either a Temperate Mini-Neptune or a Water World
The two-planet transiting system LHS 1140 has been extensively observed since
its discovery in 2017, notably with , HST, TESS, and ESPRESSO, placing
strong constraints on the parameters of the M4.5 host star and its small
temperate exoplanets, LHS 1140 b and c. Here, we reanalyse the ESPRESSO
observations of LHS 1140 with the novel line-by-line framework designed to
fully exploit the radial velocity content of a stellar spectrum while being
resilient to outlier measurements. The improved radial velocities, combined
with updated stellar parameters, consolidate our knowledge on the mass of LHS
1140 b (5.600.19 M) and LHS 1140 c (1.910.06 M)
with unprecedented precision of 3%. Transits from , HST, and TESS are
jointly analysed for the first time, allowing us to refine the planetary radii
of b (1.7300.025 R) and c (1.2720.026 R).
Stellar abundance measurements of refractory elements (Fe, Mg and Si) obtained
with NIRPS are used to constrain the internal structure of LHS 1140 b. This
planet is unlikely to be a rocky super-Earth as previously reported, but rather
a mini-Neptune with a 0.1% H/He envelope by mass or a water world with a
water-mass fraction between 9 and 19% depending on the atmospheric composition
and relative abundance of Fe and Mg. While the mini-Neptune case would not be
habitable, a water-abundant LHS 1140 b potentially has habitable surface
conditions according to 3D global climate models, suggesting liquid water at
the substellar point for atmospheres with relatively low CO concentration,
from Earth-like to a few bars.Comment: 31 pages, 18 figures, accepted for publication in ApJ
Conversion of t11t13 CLA into c9t11 CLA in Caco-2 Cells and Inhibition by Sterculic Oil
Background : Conjugated linoleic acids (CLA), and principally c9t11 CLA, are suspected to have numerous preventive properties regarding non-infectious pathologies such as inflammatory diseases, atherosclerosis and several types of cancer. C9t11 CLA is produced in the rumen during biohydrogenation of linoleic acid, but can also be synthesized in mammalian tissues from trans-vaccenic acid (C18:1 t11) through the action of delta-9 desaturase (D9D). For several years, it is also known that c9t11 CLA can be synthesized from conjugated linolenic acids (CLnA), i.e. c9t11c13 CLnA and c9t11t13 CLnA. This study aimed at investigating to which extent and by which route c9t11 CLA can be produced from another isomer of CLA, the t11t13 CLA that is structurally very similar to c9t11t13 CLnA, in Caco-2 cells
Early Priming Minimizes the Age-Related Immune Compromise of CD8+ T Cell Diversity and Function
The elderly are particularly susceptible to influenza A virus infections, with increased occurrence, disease severity and reduced vaccine efficacy attributed to declining immunity. Experimentally, the age-dependent decline in influenza-specific CD8+ T cell responsiveness reflects both functional compromise and the emergence of ‘repertoire holes’ arising from the loss of low frequency clonotypes. In this study, we asked whether early priming limits the time-related attrition of immune competence. Though primary responses in aged mice were compromised, animals vaccinated at 6 weeks then challenged >20 months later had T-cell responses that were normal in magnitude. Both functional quality and the persistence of ‘preferred’ TCR clonotypes that expand in a characteristic immunodominance hierarchy were maintained following early priming. Similar to the early priming, vaccination at 22 months followed by challenge retained a response magnitude equivalent to young mice. However, late priming resulted in reduced TCRβ diversity in comparison with vaccination earlier in life. Thus, early priming was critical to maintaining individual and population-wide TCRβ diversity. In summary, early exposure leads to the long-term maintenance of memory T cells and thus preserves optimal, influenza-specific CD8+ T-cell responsiveness and protects against the age-related attrition of naïve T-cell precursors. Our study supports development of vaccines that prime CD8+ T-cells early in life to elicit the broadest possible spectrum of CD8+ T-cell memory and preserve the magnitude, functionality and TCR usage of responding populations. In addition, our study provides the most comprehensive analysis of the aged (primary, secondary primed-early and secondary primed-late) TCR repertoires published to date
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