The impact of high-salt diet on asthma in humans and mice: Effect on specific T-cell signatures and microbiome.

BACKGROUND: The rise in asthma has been linked to different environmental and lifestyle factors including dietary habits. Whether dietary salt contributes to asthma incidence, remains controversial. We aimed to investigate the impact of higher salt intake on asthma incidence in humans and to evaluate underlying mechanisms using mouse models. METHODS: Epidemiological research was conducted using the UK Biobank Resource. Data were obtained from 42,976 participants with a history of allergies. 24-h sodium excretion was estimated from spot urine, and its association with asthma incidence was assessed by Cox regression, adjusting for relevant covariates. For mechanistic studies, a mouse model of mite-induced allergic airway inflammation (AAI) fed with high-salt diet (HSD) or normal-salt chow was used to characterize disease development. The microbiome of lung and feces (as proxy for gut) was analyzed via 16S rRNA gene based metabarcoding approach. RESULTS: In humans, urinary sodium excretion was directly associated with asthma incidence among females but not among males. HSD-fed female mice displayed an aggravated AAI characterized by increased levels of total IgE, a TH2-TH17-biased inflammatory cell infiltration accompanied by upregulation of osmosensitive stress genes. HSD induced distinct changes in serum short chain fatty acids and in both gut and lung microbiome, with a lower Bacteroidetes to Firmicutes ratio and decreased Lactobacillus relative abundance in the gut, and enriched members of Gammaproteobacteria in the lung. CONCLUSIONS: High dietary salt consumption correlates with asthma incidence in female adults with a history of allergies. Female mice revealed HSD-induced T-cell lung profiles accompanied by alterations of gut and lung microbiome.

Penning trap mass measurements of the deuteron and the HD+ molecular ion.

The masses of the lightest atomic nuclei and the electron mass1 are interlinked, and their values affect observables in atomic2, molecular3-5 and neutrino physics6, as well as metrology. The most precise values for these fundamental parameters come from Penning trap mass spectrometry, which achieves relative mass uncertainties of the order of 10-11. However, redundancy checks using data from different experiments reveal considerable inconsistencies in the masses of the proton, the deuteron and the helion (the nucleus of helium-3), suggesting that the uncertainty of these values may have been underestimated. Here we present results from absolute mass measurements of the deuteron and the HD+ molecular ion using 12C as a mass reference. Our value for the deuteron mass, 2.013553212535(17) atomic mass units, has better precision than the CODATA value7 by a factor of 2.4 and differs from it by 4.8 standard deviations. With a relative uncertainty of eight parts per trillion, this is the most precise mass value measured directly in atomic mass units. Furthermore, our measurement of the mass of the HD+ molecular ion, 3.021378241561(61) atomic mass units, not only allows a rigorous consistency check of our results for the masses of the deuteron (this work) and the proton8, but also establishes an additional link for the masses of tritium9 and helium-3 (ref. 10) to the atomic mass unit. Combined with a recent measurement of the deuteron-to-proton mass ratio11, the uncertainty of the reference value of the proton mass7 can be reduced by a factor of three.

Sodium chloride is an ionic checkpoint for human TH2 cells and shapes the atopic skin microenvironment.

The incidence of allergic diseases has increased over the past 50 years, likely due to environmental factors. However, the nature of these factors and the mode of action by which they induce the type 2 immune deviation characteristic of atopic diseases remain unclear. It has previously been reported that dietary sodium chloride promotes the polarization of T helper 17 (TH17) cells with implications for autoimmune diseases such as multiple sclerosis. Here, we demonstrate that sodium chloride also potently promotes TH2 cell responses on multiple regulatory levels. Sodium chloride enhanced interleukin-4 (IL-4) and IL-13 production while suppressing interferon-γ (IFN-γ) production in memory T cells. It diverted alternative T cell fates into the TH2 cell phenotype and also induced de novo TH2 cell polarization from naïve T cell precursors. Mechanistically, sodium chloride exerted its effects via the osmosensitive transcription factor NFAT5 and the kinase SGK-1, which regulated TH2 signature cytokines and master transcription factors in hyperosmolar salt conditions. The skin of patients suffering from atopic dermatitis contained elevated sodium compared to nonlesional atopic and healthy skin. These results suggest that sodium chloride represents a so far overlooked cutaneous microenvironmental checkpoint in atopic dermatitis that can induce TH2 cell responses, the orchestrators of atopic diseases.

First Ionization Potentials of Fm, Md, No, and Lr: Verification of Filling-Up of 5f Electrons and Confirmation of the Actinide Series.

We report the first ionization potentials (IP1) of the heavy actinides, fermium (Fm, atomic number Z = 100), mendelevium (Md, Z = 101), nobelium (No, Z = 102), and lawrencium (Lr, Z = 103), determined using a method based on a surface ionization process coupled to an online mass separation technique in an atom-at-a-time regime. The measured IP1 values agree well with those predicted by state-of-the-art relativistic calculations performed alongside the present measurements. Similar to the well-established behavior for the lanthanides, the IP1 values of the heavy actinides up to No increase with filling up the 5f orbital, while that of Lr is the lowest among the actinides. These results clearly demonstrate that the 5f orbital is fully filled at No with the [Rn]5f147s2 configuration and that Lr has a weakly bound electron outside the No core. In analogy to the lanthanide series, the present results unequivocally verify that the actinide series ends with Lr.