Revisiting the helium isotope-shift puzzle with improved uncertainties from nuclear structure corrections

Measurements of the difference between the squared charge radii of the helion ($^3$He nucleus) and the $\alpha$-particle ($^4$He nucleus) have been characterized by longstanding tensions, recently spotlighted in the 3.6 $\sigma$ discrepancy of the extractions from ordinary atoms versus those from muonic atoms. Here, we present a novel analysis of uncertainties in nuclear structure corrections that must be supplied by theory to enable the extraction of the difference in radii from spectroscopic experiments. We use modern Bayesian inference techniques to quantify uncertainties stemming from the truncation of the chiral effective field theory expansion of the nuclear force for both muonic and ordinary atoms. With the new nuclear structure input, the helium isotope-shift puzzle cannot be explained, rather it is reinforced to a 4 $\sigma$ discrepancy.Comment: 5 pages, 3 figures, 2 table

Characterization and quantifi cation of endogenous fatty acid nitroalkene metabolites in human urine

The oxidation and nitration of unsaturated fatty acids transforms cell membrane and lipoprotein constituents into mediators that regulate signal transduction. The formation of 9-NO2-octadeca-9,11-dienoic acid and 12-NO2-octadeca- 9,11-dienoic acid stems from peroxynitrite- and myeloperoxidase-derived nitrogen dioxide reactions as well as secondary to nitrite disproportionation under the acidic conditions of digestion. Broad anti-inflammatory and tissue-protective responses are mediated by nitro-fatty acids. It is now shown that electrophilic fatty acid nitroalkenes are present in the urine of healthy human volunteers (9.9 + 4.0 pmol/mg creatinine); along with electrophilic 16- and 14-carbon nitroalkenyl β-oxidation metabolites. High resolution mass determinations and co-elution with isotopically-labeled metabolites support renal excretion of cysteine-nitroalkene conjugates. These products of Michael addition are in equilibrium with the free nitroalkene pool in urine and are displaced by thiol reaction with HgCl2. This reaction increases the level of free nitroalkene fraction >10-fold and displays a KD of 7.5x10-6 M. In aggregate, the data indicates that formation of Michael adducts by electrophilic fatty acids is favored under biological conditions and that reversal of these addition reactions is critical for detecting both parent nitroalkenes and their metabolites. The measurement of this class of mediators can constitute a sensitive non-invasive index of metabolic and inflammatory status.Fil: Salvatore, Sonia Rosana. University of Pittsburgh; Estados UnidosFil: Vitturi, Dario A.. University of Pittsburgh; Estados UnidosFil: Baker, Paul R. S.. University of Pittsburgh; Estados UnidosFil: Bonacci, Gustavo Roberto. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Koenitzer, Jeffrey R.. University of Pittsburgh; Estados UnidosFil: Woodcock, Steven R.. University of Pittsburgh; Estados UnidosFil: Freeman, Bruce A.. University of Pittsburgh; Estados UnidosFil: Schopfer, Francisco J.. University of Pittsburgh; Estados Unido

Modulation of Nitro-fatty acid signaling: prostaglandin reductase-1 is a Nitroalkene reductase

Background: Nitroalkenes are electrophilic anti-inflammatory mediators that signal via Michael addition and are metabolized in vivo. Results: Prostaglandin reductase-1 is identified as a nitroalkene reductase. Conclusion: Prostaglandin reductase-1 reduces fatty acid nitroalkenes to nitroalkanes, inactivating electrophilic reactivity. Significance: A mammalian enzyme is identified that metabolizes fatty acid nitroalkenes in vivo to silence their signaling reactions.Fil: Vitturi, Dario A.. University of Pittsburgh; Estados UnidosFil: Chen, Chen Shan. University of Pittsburgh; Estados UnidosFil: Woodcock, Steven R.. University of Pittsburgh; Estados UnidosFil: Salvatore, Sonia R.. University of Pittsburgh; Estados UnidosFil: Bonacci, Gustavo Roberto. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Koenitzer, Jeffrey R.. University of Pittsburgh; Estados UnidosFil: Stewart, Nicolas A.. University of Pittsburgh; Estados UnidosFil: Wakabayashi, Nobunao. University of Pittsburgh; Estados UnidosFil: Kensler, Thomas W.. University of Pittsburgh; Estados UnidosFil: Freeman, Bruce A.. University of Pittsburgh; Estados UnidosFil: Schopfer, Francisco J.. University of Pittsburgh; Estados Unido

Vagal afferents contribute to sympathoexcitation-driven metabolic dysfunctions

Multiple crosstalk between peripheral organs and the nervous system are required to maintain physiological and metabolic homeostasis. Using Vav3-deficient mice as a model for chronic sympathoexcitation-associated disorders, we report here that afferent fibers of the hepatic branch of the vagus nerve are needed for the development of the peripheral sympathoexcitation, tachycardia, tachypnea, insulin resistance, liver steatosis and adipose tissue thermogenesis present in those mice. This neuronal pathway contributes to proper activity of the rostral ventrolateral medulla, a sympathoregulatory brainstem center hyperactive in Vav3−/− mice. Vagal afferent inputs are also required for the development of additional pathophysiological conditions associated with deregulated rostral ventrolateral medulla activity. By contrast, they are dispensable for other peripheral sympathoexcitation-associated disorders sparing metabolic alterations in liver.X R B is supported by grants from the Castilla-León Government (CSI252P18, CLC-2017-01), the Spanish Ministry of Science, Innovation and Universities (MSIU) (SAF2015-64556-R), Worldwide Cancer Research (14-1248), the Ramón Areces Foundation, and the Spanish Association against Cancer (GC16173472GARC). X R B’s institution is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia of the Ministry of Education of the Castilla-León Government (CLC-2017-01). S R-F and L F L-M contracts have been supported by funding from the MISIU (BES-2013-063573) and the Spanish Ministry of Education, Culture and Sports (L F L-M, FPU13/02923), respectively. Both Spanish and Castilla-León government-associated funding is partially supported by the European Regional Development Fund

Vagal afferents contribute to sympathoexcitation-driven metabolic dysfunctions

[EN] Multiple crosstalk between peripheral organs and the nervous system are required to maintain physiological and metabolic homeostasis. Using Vav3–deficient mice as a model for chronic sympathoexcitation–associated disorders, we report here that afferent fibers of the hepatic branch of the vagus nerve are needed for the development of the peripheral sympathoexcitation, tachycardia, tachypnea, insulin resistance, liver steatosis, and adipose tissue thermogenesis present in those mice. This neuronal pathway contributes to proper activity of the rostral ventrolateral medulla, a sympathoregulatory brainstem center hyperactive in Vav3 –/– mice. Vagal afferent inputs are also required for the development of additional pathophysiological conditions associated with deregulated rostral ventrolateral medulla activity. By contrast, they are dispensable for other peripheral sympathoexcitation–associated disorders sparing metabolic alterations in liver

Prevalence of metabolic syndrome: a comparative analysis in an unselected sample of mediterranean subjects.

Abstract AIM: The metabolic syndrome (MS) is associated with increased cardiovascular and cerebrovascular risk. This study aimed to compare the difference of the three established diagnostic criteria of MS, developed by Adult Treatment Panel III (ATP III), American Heart Association (AHA) and National Heart Lung and Blood Institute (NHLBI), and International Diabetes Federation (IDF), with regard to the prevalence of the syndrome and the ability to correctly identify individuals with cardiovascular or cerebrovascular disease or subclinical atherosclerosis. METHODS: We studied 947 consecutive patients underwent clinical evaluation between the 1997-2002. The project design included a medical assessment, biochemical analyses and the ecocolordoppler examination of carotid arteries. RESULTS: The MS prevalence was 37% in ATPIII subjects, 36% in AHA/NHLBI subjects and 43% in IDF subjects. Excluding patients with diabetes (N.=259), the MS prevalence ranged from 32% (ATPIII and AHA/NHLBI subjects) and 40% (IDF subjects). By most criteria, MS-positive subjects had significant incidence of carotid atherosclerosis (P<0.05) and cardiovascular events (P<0.05) than MS-negative subjects, but not cerebrovascular events. Finally, patients with MS had higher serum levels of fibrinogen (P<0.04). CONCLUSION: Subclinical atherosclerosis and cardiovascular events were increased in presence of the MS, irrespective of the several definitions

VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma

Regenerative proliferation capacity and poor differentiation are histological features usually linked to poor prognosis in head and neck squamous cell carcinoma (hnSCC). However, the pathways that regulate them remain ill-characterized. Here, we show that those traits can be triggered by the RHO GTPase activator VAV2 in keratinocytes present in the skin and oral mucosa. VAV2 is also required to maintain those traits in hnSCC patient-derived cells. This function, which is both catalysis- and RHO GTPase-dependent, is mediated by c-Myc- and YAP/TAZ-dependent transcriptomal programs associated with regenerative proliferation and cell undifferentiation, respectively. High levels of VAV2 transcripts and VAV2-regulated gene signatures are both associated with poor hnSCC patient prognosis. These results unveil a druggable pathway linked to the malignancy of specific SCC subtypes. The Rho signalling pathway is frequently activated in squamous carcinomas. Here, the authors find that the Rho GEF VAV2 is over expressed in both cutaneous and head and neck squamous cell carcinomas and that at the molecular level VAV2 promotes a pro-tumorigenic stem cell-like signalling programme

Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives

Dietary ω-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic α,β-unsaturated ketone derivatives of the ω-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2- dependent phase 2 gene expression and suppression of pro-inflammatory NF-κB-driven gene expression. Herein, the endogenous generation of ω-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial. Methods: Endogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30-55 years of age with a reported EPA+DHA consumption of ≤ 300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or identical appearing soybean oil (control condition, n = 21). Participants and laboratory technicians remained blinded to treatment assignments. Results: 5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels. Conclusions: The endogenous detection of these electro.©2014 Cipollina et al

Spectrophotometric Modeling and Mapping of (101955) Bennu

Using hyperspectral data collected by OVIRS, the visible and infrared spectrometer on board the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) spacecraft, we modeled the global average spectrophotometric properties of the carbonaceous asteroid (101955) Bennu and mapped their variations. We restricted our analysis to 0.4–2.5 μm to avoid the wavelengths where thermal emission from the asteroid dominates (>2.5 μm). Bennu has global photometric properties typical of dark asteroids; we found a geometric albedo of 0.046 ± 0.007 and a linear phase slope of 0.024 ± 0.007 mag deg−1 at 0.55 μm. The average spectral slope of Bennu’s normal albedo is −0.0030 μm−1, and the phase-reddening parameter is 4.3 × 10−4 μm−1 deg−1, both over the spectral range of 0.5–2.0 μm. We produced normal albedo maps and phase slope maps at all spectral channels, from which we derived spectral slope and phase-reddening maps. Correlation analysis suggests that phase slope variations on Bennu are likely due to photometric roughness variation. A correlation between photometric and thermal roughness is evident, implying that the roughness of Bennu is self-similar on scales from tens of microns to meters. Our analysis reveals latitudinal trends in the spectral color slope and phase reddening on Bennu. The equatorial region appears to be redder than the global average, and the spectral slope decreases toward higher latitudes. Phase reddening on Bennu is relatively weak in the equatorial region and shows an asymmetry between the northern and southern hemispheres. We attributed the latitudinal trend to the geophysical conditions on Bennu that result in a global pattern of mass flow toward the equator