Mango "Ataulfo" peel is a rich source of polyphenols (PP), with antioxidant and anti-cancer properties; however, it is unknown whether such antiproliferative activity is related to PP's antioxidant ...activity. The content (HPLC-DAD), antioxidant (DPPH, FRAP, ORAC), and antiproliferative activities (MTT) of free (FP) and chemically-released PP from mango 'Ataulfo' peel after alkaline (AKP) and acid (AP) hydrolysis, were evaluated. AKP fraction was higher (µg/g DW) in gallic acid (GA; 23,816 ± 284) than AP (5610 ± 8) of FR (not detected) fractions. AKP fraction and GA showed the highest antioxidant activity (DPPH/FRAP/ORAC) and GA's antioxidant activity follows a single electron transfer (SET) mechanism. AKP and GA also showed the best antiproliferative activity against human colon adenocarcinoma cells (LS180; IC
(µg/mL) 138.2 ± 2.5 and 45.7 ± 5.2) and mouse connective cells (L929; 93.5 ± 7.7 and 65.3 ± 1.2); Cheminformatics confirmed the hydrophilic nature (LogP, 0.6) and a good absorption capacity (75%) for GA. Data suggests that GA's antiproliferative activity appears to be related to its antioxidant mechanism, although other mechanisms after its absorption could also be involved.
The Bayesian isochrone fitting using the Markov chain Monte Carlo algorithm is applied, to derive the probability distribution of the parameters age, metallicity, reddening, and absolute distance ...modulus. We introduce the SIRIUS code by means of simulated color-magnitude diagrams (CMDs), including the analysis of multiple stellar populations (MPs). The population tagging is applied from the red giant branch to the bottom of the main sequence. Through sanity checks using synthetic Hubble Space Telescope CMDs of globular clusters we verify the code reliability in the context of simple and MPs. In such tests, the formal uncertainties in age or age difference, metallicity, reddening, and absolute distance modulus can reach 400 Myr, 0.03 dex, 0.01 mag, and 0.03 mag, respectively. We apply the method to analyze NGC 6752, using Dartmouth stellar evolutionary models. Assuming a single stellar population, we derive an age of 13.7 0.5 Gyr and a distance of , with the latter in agreement within 3 with the inverse Gaia parallax. In the analysis of the MPs, three populations are clearly identified. From the Chromosome Map and UV/Optical two-color diagrams inspection, we found a fraction of stars of 25 5, 46 7, and 29 5 %, for the first, second, and third generations, respectively. These fractions are in good agreement with the literature. An age difference of 500 410 Myr between the first and the third generation is found, with the uncertainty decreasing to 400 Myr when the helium enhancement is taken into account.
The fractional quantum Hall effect stands as a quintessential manifestation of an interacting two-dimensional electron system. One of the fractional quantum Hall effect's most fundamental ...characteristics is the energy gap separating the incompressible ground state from its excitations. Yet, despite nearly four decades of investigations, a quantitative agreement between the theoretically calculated and experimentally measured energy gaps is lacking. Here we report a systematic experimental study that incorporates very high-quality two-dimensional electron systems confined to GaAs quantum wells with fixed density and varying well widths. The results demonstrate a clear decrease of the energy gap as the electron layer is made thicker and the short-range component of the Coulomb interaction is weakened. We also provide a quantitative comparison between the measured energy gaps and the available theoretical calculations that takes into account the role of finite layer thickness and Landau level mixing. All the measured energy gaps fall below the calculations, but as the electron layer thickness increases, the results of experiments and calculations come closer. Accounting for the role of disorder in a phenomenological manner, we find better overall agreement between the measured and calculated energy gaps, although some puzzling discrepancies remain.
Background & Aims p53 and its transcriptional target miRNA34a have been implicated in the pathogenesis of fatty liver. We tested the efficacy of a p53 inhibitor, pifithrin-α p -nitro (PFT) in ...attenuating steatosis, associated oxidative stress and apoptosis in a murine model of non-alcoholic fatty liver disease (NAFLD). Methods C57BL/6 mice were fed a high-fat (HFD) or control diet for 8 weeks; PFT or DMSO (vehicle) was administered three times per week. Markers of oxidative stress and apoptosis as well as mediators of hepatic fatty acid metabolism were assessed by immunohistochemistry, Western blot, real-time PCR, and biochemical assays. Results PFT administration suppressed HFD-induced weight gain, ALT elevation, steatosis, oxidative stress, and apoptosis. PFT treatment blunted the HFD-induced upregulation of miRNA34a and increased SIRT1 expression. In the livers of HFD-fed, PFT-treated mice, activation of the SIRT1/PGC1α/PPARα axis increased the expression of malonyl-CoA decarboxylase (MLYCD), an enzyme responsible for malonyl-CoA (mCoA) degradation. Additionally, the SIRT1/LKB1/AMPK pathway (upstream activator of MLYCD) was promoted by PFT. Thus, induction of these two pathways by PFT diminished the hepatic mCoA content by enhancing MLYCD expression and function. Since mCoA inhibits carnitine palmitoyltransferase 1 (CPT1), the decrease of hepatic mCoA in the PFT-treated, HFD-fed mice increased CPT1 activity, favored fatty acid oxidation, and decreased steatosis. Additionally, we demonstrated that PFT abrogated steatosis and promoted MLYCD expression in palmitoleic acid-treated human HepaRG cells. Conclusions The p53 inhibitor PFT diminished hepatic triglyceride accumulation and lipotoxicity in mice fed a HFD, by depleting mCoA and favoring the β-oxidation of fatty acids.
Soliton formation in on-chip micro-comb generation balances cavity dispersion and nonlinearity and allows coherent, low-noise comb operation. We study the intracavity waveform of an on-chip ...microcavity soliton in a silicon nitride microresonator configured with a drop port. Whereas combs measured at the through port are accompanied by a very strong pump line which accounts for >99% of the output power, our experiments reveal that inside the microcavity, most of the power is in the soliton. Time-domain measurements performed at the drop port provide information that directly reflects the intracavity field. Data confirm a train of bright, close to bandwidth-limited pulses, accompanied by a weak continuous wave (CW) background with a small phase shift relative to the comb.
Antigen-presenting cells (APCs) integrate signals emanating from local pathology and program appropriate T cell responses. In allogeneic hematopoietic stem cell transplantation (alloHCT), recipient ...conditioning releases damage-associated molecular patterns (DAMPs) that generate proinflammatory APCs that secrete IL-12, which is a driver of donor Th1 responses, causing graft-versus-host disease (GVHD). Nevertheless, other mechanisms exist to initiate alloreactive T cell responses, as recipients with disrupted DAMP signaling or lacking IL-12 develop GVHD. We established that tissue damage signals are perceived directly by donor CD4+ T cells and promoted T cell expansion and differentiation. Specifically, the fibroblastic reticular cell-derived DAMP IL-33 is increased by recipient conditioning and is critical for the initial activation, proliferation, and differentiation of alloreactive Th1 cells. IL-33 stimulation of CD4+ T cells was not required for lymphopenia-induced expansion, however. IL-33 promoted IL-12-independent expression of Tbet and generation of Th1 cells that infiltrated GVHD target tissues. Mechanistically, IL-33 augmented CD4+ T cell TCR-associated signaling pathways in response to alloantigen. This enhanced T cell expansion and Th1 polarization, but inhibited the expression of regulatory molecules such as IL-10 and Foxp3. These data establish an unappreciated role for IL-33 as a costimulatory signal for donor Th1 generation after alloHCT.
Dermal exposure to metals has previously received less attention than oral/inhalation exposure. Nonetheless, human health risk is significant for certain contaminants and exposure scenarios. The ...present study aims to (1) characterize two certified reference soils (SQC001, BGS 102); and (2) assess Cr, Ni, Pb, and Zn dermal bioaccessibility via in vitro assays using three synthetic sweat formulations (EN 1811, pH 6.5 (Sweat A), NIHS 96-10, pH 4.7 (Sweat B), and a more complex pH 5.5 formulation containing amino acids (Sweat C)) and two sebum formulations. Metals bioaccessibility in sweat followed Sweat B > Sweat C > Sweat A, attributed to sweat B lower pH. Dermal bioaccessibility in both sebum formulations was lower than 1% for Ni and Pb and below 9% for Cr and Zn, possibly due to low affinity of metals for non-polar lipids. It must be noted that bioaccessible Zn in BGS 102 was higher when extracted with synthetic sebum compared to any of the synthetic sweat formulations. Metal bioaccessibility in sweat was considerably higher for SQC001 (up to 76.6% for Zn using Sweat B) than for BGS 102 (ranging between 0.02 and 1.3% for all elements and all sweat formulations), attributed to higher pH, higher organic carbon, and higher cation exchange capacity of reference soil BGS 102. Sebum formulations spiked with metals generally entailed low metal recovery (except for Zn), which may explain overall low bioaccessibility values for sebum. Sebum and sweat formulation, and soil properties seem to control in vitro dermal bioaccessibility of metals.
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•Metal bioaccessibility is higher (up to 77%) in sweat formulations having lower pH.•Metal bioaccessibility in synthetic sebum is generally low (up to 9%).•Bioaccessibility is related to soil properties (pH, OM, CEC).•Some sebum formulations can extract more metals (Cr and Zn) from soils than sweat formulations.
The Chagas disease is caused by the parasite Trypanosoma cruzi, which infect blood-feeding triatomine bugs to finally reach mammal hosts. Chagas disease is endemic in Latin America, and is ranked ...among the 13 neglected tropical diseases worldwide. Currently, an estimate of 7 million people is infected by T. cruzi, leading to about 22 000 deaths per year throughout the Americas. As occurs with other vectors, a major question towards control programs is what makes a susceptible bug. In this review, we focus on findings linked to insect gut structure and microbiota, immunity, genetics, blood sources, abiotic factors (with special reference to ambient temperature and altitude) to understand the interactions occurring between T. cruzi and triatomine bugs, under a co-evolutionary scenario. These factors lead to varying fitness benefits and costs for bugs, explaining why infection in the insect takes place and how it varies in time and space. Our analysis highlights that major factors are gut components and microbiota, blood sources and temperature. Although their close interaction has never been clarified, knowledge reviewed here may help to boost the success of triatomine control programs, reducing the use of insecticides.
Hypothalamic circuits compute systemic information to control metabolism. Astrocytes residing within the hypothalamus directly sense nutrients and hormones, integrating metabolic information, and ...modulating neuronal responses. Nevertheless, the role of the astrocytic circadian clock on the control of energy balance remains unclear. We used mice with a targeted ablation of the core‐clock gene Bmal1 within Gfap‐expressing astrocytes to gain insight on the role played by this transcription factor in astrocytes. While this mutation does not substantially affect the phenotype in mice fed normo‐caloric diet, under high‐fat diet we unmasked a thermogenic phenotype consisting of increased energy expenditure, and catabolism in brown adipose and overall metabolic improvement consisting of better glycemia control, and body composition. Transcriptomic analysis in the ventromedial hypothalamus revealed an enhanced response to moderate cellular stress, including ER‐stress response, unfolded protein response and autophagy. We identified Xbp1 and Atf1 as two key transcription factors enhancing cellular stress responses. Therefore, we unveiled a previously unknown role of the astrocytic circadian clock modulating energy balance through the regulation of cellular stress responses within the VMH.
Main Points
The molecular clock in Gfap+ astrocytes modulate energy expenditure.
BMAL1 in Gfap+ astrocytes regulate BAT activity under DIO.
BMAL1 in Gfap+ astrocytes control transcriptional stress response in the VMH under DIO.
A fundamental concept in physics is the Fermi surface, the constant-energy surface in momentum space encompassing all the occupied quantum states at absolute zero temperature. In 1960, Luttinger ...postulated that the area enclosed by the Fermi surface should remain unaffected even when electron-electron interaction is turned on, so long as the interaction does not cause a phase transition. Understanding what determines the Fermi surface size is a crucial and yet unsolved problem in strongly interacting systems such as high Tc superconductors. Here we present a precise test of the Luttinger theorem for a two-dimensional Fermi liquid system where the exotic quasiparticles themselves emerge from the strong interaction, namely, for the Fermi sea of composite fermions (CFs). Via direct, geometric resonance measurements of the CFs' Fermi wave vector down to very low electron densities, we show that the Luttinger theorem is obeyed over a significant range of interaction strengths, in the sense that the Fermi sea area is determined by the density of the minority carriers in the lowest Landau level. Our data also address the ongoing debates on whether or not CFs obey particle-hole symmetry, and if they are Dirac particles. We find that particle-hole symmetry is obeyed, but the measured Fermi sea area differs quantitatively from that predicted by the Dirac model for CFs.
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