Dopexamine can attenuate the inflammatory response and protect against organ injury in the absence of significant effects on hemodynamics or regional microvascular flow

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Virtual Structure Constants as Intersection Numbers of Moduli Space of Polynomial Maps with Two Marked Points

In this paper, we derive the virtual structure constants used in mirror computation of degree k hypersurface in CP^{N-1}, by using localization computation applied to moduli space of polynomial maps from CP^{1} to CP^{N-1} with two marked points. We also apply this technique to non-nef local geometry O(1)+O(-3)->CP^{1} and realize mirror computation without using Birkhoff factorization.Comment: 10 pages, latex, a minor change in Section 4, English is refined, Some typing errors in Section 3 are correcte

Elevation of serum sphingosine-1-phosphate attenuates impaired cardiac function in experimental sepsis

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.This study was supported by the Federal Ministry of Education and Research (BMBF, Germany, FKZ 01EO1502). This work was supported, in part, by the William Harvey Research Foundation and forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit that is supported and funded by the National Institute of Health Research. This work also contributes to the Organ Protection research theme of the Barts Centre for Trauma Sciences supported by the Barts and The London Charity (Award 753/1722). JP was supported by the German Research Foundation SFB 1039. AH was supported by the Swiss National Science Foundation

Circadian and Feeding Rhythms Orchestrate the Diurnal Liver Acetylome.

Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is therefore highly relevant in the context of circadian biology, but its characterization on the proteome-wide scale and its circadian clock dependence are still poorly described. Here, we provide a comprehensive and rhythmic acetylome map of the mouse liver. Rhythmic acetylated proteins showed subcellular localization-specific phases that correlated with the related metabolites in the regulated pathways. Mitochondrial proteins were over-represented among the rhythmically acetylated proteins and were highly correlated with SIRT3-dependent deacetylation. SIRT3 activity being nicotinamide adenine dinucleotide (NAD) <sup>+</sup> level-dependent, we show that NAD <sup>+</sup> is orchestrated by both feeding rhythms and the circadian clock through the NAD <sup>+</sup> salvage pathway but also via the nicotinamide riboside pathway. Hence, the diurnal acetylome relies on a functional circadian clock and affects important diurnal metabolic pathways in the mouse liver

Impact of changing oxygenation policies on retinopathy of prematurity in a neonatal unit in Argentina.

AIMS: To assess the impact of different oxygenation policies on the rate and severity of retinopathy of prematurity (ROP). METHODS: Between January 2003 and December 2006, infants of 1500 g birthweight (BW) or less and/or 32 weeks gestational age (GA) or less, and larger, more mature infants with risk factors for ROP were examined through three different time periods: period 1: high target oxygen saturation levels (88-96%) and treatment at threshold ROP; period 2: low target oxygen saturation levels (83-93%) and treatment at threshold ROP; period 3: low target oxygen saturation and treatment at type 1 ROP. RESULTS: Type 1 ROP was detected more frequently in babies of 32 weeks GA or less (50/365, 13.7%) than in more mature babies (15/1167, 1.3%; p<0.001). The rate of type 1 ROP in period 1 was 6.9%; period 2, 3.6% and period 3, 1.8%. Rates of stage 3 ROP declined over time in both BW/GA groups (from 9.0% to 4.1% to 2.0%) as did rates of plus disease (from 7.5% to 3.6% to 1.8%). Mean BW and GA declined from period 1 to period 3, and death rates remained unchanged. 74.4% of babies received all the examinations required; 48.1% of treatments were undertaken after discharge from the neonatal unit. CONCLUSIONS: Lower target oxygen saturation was associated with a lower rate of severe ROP without increasing mortality, and changed the characteristics of affected babies. Screening criteria need to remain wide enough to identify all babies at risk of ROP needing treatment

One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond.

Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1-42 peptide chain [Aβ1-42] &gt;0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, Aβ1-42, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers

Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1)H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P&lt;5×10(-8)) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44)) and lysine (rs8101881, P = 1.2×10(-33)), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers