Myristic acid potentiates palmitic acid-induced lipotoxicity and steatohepatitis associated with lipodystrophy by sustaning de novo ceramide synthesis.

Palmitic acid (PA) induces hepatocyte apoptosis and fuels de novo ceramide synthesis in the endoplasmic reticulum (ER). Myristic acid (MA), a free fatty acid highly abundant in copra/palmist oils, is a predictor of nonalcoholic steatohepatitis (NASH) and stimulates ceramide synthesis. Here we investigated the synergism between MA and PA in ceramide synthesis, ER stress, lipotoxicity and NASH. Unlike PA, MA is not lipotoxic but potentiated PA-mediated lipoapoptosis, ER stress, caspase-3 activation and cytochrome c release in primary mouse hepatocytes (PMH). Moreover, MA kinetically sustained PA-induced total ceramide content by stimulating dehydroceramide desaturase and switched the ceramide profile from decreased to increased ceramide 14:0/ceramide16:0, without changing medium and long-chain ceramide species. PMH were more sensitive to equimolar ceramide14:0/ceramide16:0 exposure, which mimics the outcome of PA plus MA treatment on ceramide homeostasis, than to either ceramide alone. Treatment with myriocin to inhibit ceramide synthesis and tauroursodeoxycholic acid to prevent ER stress ameliorated PA plus MA induced apoptosis, similar to the protection afforded by the antioxidant BHA, the pan-caspase inhibitor z-VAD-Fmk and JNK inhibition. Moreover, ruthenium red protected PMH against PA and MA-induced cell death. Recapitulating in vitro findings, mice fed a diet enriched in PA plus MA exhibited lipodystrophy, hepatosplenomegaly, increased liver ceramide content and cholesterol levels, ER stress, liver damage, inflammation and fibrosis compared to mice fed diets enriched in PA or MA alone. The deleterious effects of PA plus MA-enriched diet were largely prevented by in vivo myriocin treatment. These findings indicate a causal link between ceramide synthesis and ER stress in lipotoxicity, and imply that the consumption of diets enriched in MA and PA can cause NASH associated with lipodystrophy

Biodegradation kinetics of dissolved organic matter chromatographic fractions

Controls on the degradation of dissolved organic matter (DOM) are complex but key to understand the role of freshwaters in the carbon cycle. Both the origin and previous degradation history have been suggested to determine DOM reactivity, but it is still a major challenge to understand the links between DOM composition and biodegradation kinetics. An appropriate context to study these links are intermittent rivers, as summer drought naturally diversifies DOM sources and sinks. Here we investigated the biodegradation kinetics of DOM in the main aquatic environments present in a temporary river. During dark incubations we traced the dynamics of bulk DOM and its main chromatographic fractions defined using LC-OCD: high molecular weight substances (HMWS), low molecular weight substances (LMWS), and humic substances and building blocks. Bulk DOM decay patterns were successfully fitted to the reactivity continuum (RC) biodegradation model. The RC parameters depicted running waters as the sites presenting a more reactive DOM, and temporary pools, enriched in leaf litter, as the ones with slowest DOM decay. The decay patterns of each DOM fraction were consistent throughout sites. LMWS and HMWS decayed in all cases and could be modeled using the RC model. Notably, the dynamics of LMWS controlled the bulk DOM kinetics. We discuss the mechanistic basis for the chromatographic fractions' kinetics during biodegradation and the implications that preconditioning and summer drought can have for DOM biodegradation in intermittent rivers

Fair scans of the seesaw. Consequences for predictions on LFV processes

Usual analyses based on scans of the seesaw parameter-space can be biassed since they do not cover in a fair way the complete parameter-space. More precisely, we show that in the common "R-parametrization", many acceptable R-matrices, compatible with the perturbativity of Yukawa couplings, are normally disregarded from the beginning, which produces biasses in the results. We give a straightforward procedure to scan the space of complex R-matrices in a complete way, giving a very simple rule to incorporate the perturbativity requirement as a condition for the entries of the R-matrix, something not considered before. As a relevant application of this, we show that the extended believe that BR(mu --> e, gamma) in supersymmetric seesaw models depends strongly on the value of theta_13 is an "optical effect" produced by such biassed scans, and does not hold after a careful analytical and numerical study. When the complete scan is done, BR(mu --> e, gamma) gets very insensitive to theta_13. Moreover, the values of the branching ratio are typically larger than those quoted in the literature, due to the large number of acceptable points in the parameter-space which were not considered before. Including (unflavoured) leptogenesis does not introduce any further dependence on theta_13, although decreases the typical value of BR(mu --> e, gamma).Comment: 22 pages, 5 figure

Human Metapneumovirus Infections during COVID-19 Pandemic, Spain

We describe an unusual outbreak of respiratory infections caused by human metapneumovirus in children during the sixth wave of COVID-19 in Spain, associated with the Omicron variant. Patients in this outbreak were older than usual and showed more hypoxia and pneumonia, longer length of stay, and greater need for intensive care.This study was partially funded by FIS (Fondo de Investigaciones Sanitarias-Spanish Health Research Fund), grant nos. PI06/0532, PI09/0246, PI12/0129, PI18CIII/00009, PI21CIII/00019, and PI21/00377.S

Flat Tree-level Inflationary Potentials in Light of CMB and LSS Data

We use cosmic microwave background and large scale structure data to test a broad and physically well-motivated class of inflationary models: those with flat tree-level potentials (typical in supersymmetry). The non-trivial features of the potential arise from radiative corrections which give a simple logarithmic dependence on the inflaton field, making the models very predictive. We also consider a modified scenario with new physics beyond a certain high-energy cut-off showing up as non-renormalizable operators (NRO) in the inflaton field. We find that both kinds of models fit remarkably well CMB and LSS data, with very few free parameters. Besides, a large part of these models naturally predict a reasonable number of e-folds. A robust feature of these scenarios is the smallness of tensor perturbations (r < 10^{-3}). The NRO case can give a sizeable running of the spectral index while achieving a sufficient number of e-folds. We use Bayesian model comparison tools to assess the relative performance of the models. We believe that these scenarios can be considered as a standard physical class of inflationary models, on a similar footing with monomial potentials.Comment: 42 LaTeX pages, 8 figure

Work and heat fluctuations in two-state systems: a trajectory thermodynamics formalism

Two-state models provide phenomenological descriptions of many different systems, ranging from physics to chemistry and biology. We investigate work fluctuations in an ensemble of two-state systems driven out of equilibrium under the action of an external perturbation. We calculate the probability density P(W) that a work equal to W is exerted upon the system along a given non-equilibrium trajectory and introduce a trajectory thermodynamics formalism to quantify work fluctuations in the large-size limit. We then define a trajectory entropy S(W) that counts the number of non-equilibrium trajectories P(W)=exp(S(W)/kT) with work equal to W. A trajectory free-energy F(W) can also be defined, which has a minimum at a value of the work that has to be efficiently sampled to quantitatively test the Jarzynski equality. Within this formalism a Lagrange multiplier is also introduced, the inverse of which plays the role of a trajectory temperature. Our solution for P(W) exactly satisfies the fluctuation theorem by Crooks and allows us to investigate heat-fluctuations for a protocol that is invariant under time reversal. The heat distribution is then characterized by a Gaussian component (describing small and frequent heat exchange events) and exponential tails (describing the statistics of large deviations and rare events). For the latter, the width of the exponential tails is related to the aforementioned trajectory temperature. Finite-size effects to the large-N theory and the recovery of work distributions for finite N are also discussed. Finally, we pay particular attention to the case of magnetic nanoparticle systems under the action of a magnetic field H where work and heat fluctuations are predicted to be observable in ramping experiments in micro-SQUIDs.Comment: 28 pages, 14 figures (Latex

Maternal occupational exposures and fetal growth in a Spanish birth cohort

While the epidemiologic literature suggests certain maternal occupational exposures may be associated with reduced measures of size at birth, the occupational literature employing fetal biometry data to assess fetal growth is sparse. The present study examines associations between maternal occupational exposures and ultrasound-measured fetal growth. We included 1,739 singleton pregnancies from the INfancia y Medio Ambiente (INMA) project (2003-2008). At 32 weeks of pregnancy, interviewers ascertained mothers' employment status and assessed job-related physical loads, work schedules, and job strain during pregnancy. Job titles were linked to a job-exposure matrix to estimate exposure to 10 endocrine disrupting chemical (EDC) groups. We calculated z-scores from longitudinal growth curves representing trajectories from 0-12, 12-20 and 20-34 gestational weeks for abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), and estimated fetal weight (EFW). Linear mixed models clustered by IMNA region (i.e., Gipuzkoa, Sabadell, Valencia) were used to examine associations between occupational exposures and fetal growth. Effect estimates are presented as percentage change in fetal growth. There was limited evidence of associations between work-related non-chemical stressors and fetal growth. We observed associations of similar magnitude between multiple EDC groups and decreased EFW trajectories during 20-34 gestational weeks (phthalates: -1.4% [-3.5, 0.6%]; alkylphenolic compounds (APCs): -1.1% [-2.3, 0.1%]; miscellaneous chemicals: -1.5% [-3.7, 0.8%]), while miscellaneous chemicals were associated with increased BPD from 12-20 weeks (2.1% [0.8, 3.5%]). Notably, 67% of women exposed to phthalates were hairdressers; 68% of women exposed to APCs worked as domestic cleaners. In conclusion, we found limited evidence that maternal occupational exposures impact fetal growth. Further research should consider the combined impact of multiple workplace exposures.This work was supported by grants from the National Institutes of Health/National Institute of Environmental Health Sciences (R01ES028842, PI: KWW), Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663, FIS-PI18/01142 incl. FEDER funds; Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051, CPII18/00018, and CP16/00128), Generalitat de Catalunya-CIRIT 1999SGR 00241, EU Commission (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249) and Conselleria d’Educació AICO/2020/285, and Alicia Koplowitz Foundation 2017, Department of Health of the Basque Government (2005111093), Provincial Government of Gipuzkoa (DFG06/002), and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). We also acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. JI, DGRdP, and GLD were partly supported by the Southwest Center for Occupational and Environmental Health (SWCOEH), the Centers for Disease Control and Prevention (CDC) National Institute for Occupational Safety and Health (NIOSH) Education and Research Center (T42OH008421) at The University of Texas Health Science Center at Houston (UTHealth) School of Public Health. KWW and ES were supported in part by the by the Gulf Coast Center for Precision Environmental Health (GC-CPEH) at Baylor College of Medicine (P30ES030285). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Collaborative peer validation of a harmonized SPME-GC-MS method for analysis of selected volatile compounds in virgin olive oils [intervalidazione di un metodo armonizzato SPME-GC-MS per l¿analisi di composti volatili selezionati in oli di oliva vergini]

Final version is available in open access in publisher’s site.-- This abstract is based on the published article: Ramón Aparicio-Ruiz, Clemente Ortiz Romero, Enrico Casadei, Diego L. García-González, Maurizio Servili, Roberto Selvaggini, Florence Lacoste, Julien Escobessa, Stefania Vichi, Beatriz Quintanilla-Casas, Pierre-Alain Golay, Paolo Lucci, Erica Moret, Enrico Valli, Alessandra Bendini, Tullia Gallina Toschi. Collaborative peer validation of a harmonized SPME-GC-MS method for analysis of selected volatile compounds in virgin olive oils, Food Control, Volume 135, 2022, 108756, https://doi.org/10.1016/j.foodcont.2021.108756.-- http://hdl.handle.net/10261/258960The evaluation of the sensory attributes in virgin olive oil (VOO) is carried out according to the standard method of panel test [1, 2]. Recently, it has been proposed as SPME-GC-FID method as the most ade- quate instrumental method to determine volatiles compounds in VOO to support the sensory panels test [3]. This method developed in the European funded project OLEUM, in which all the variables have been defined and harmonized, has been tested in three laboratories to perform an inter-laboratory validation of the quantification of the most relevant VOCs that are responsible for VOO sensory attributes. The valida- tion study was carried out for each one of the selected molecules in order to have an individual infor- mation for each analyte. With the same objective, in the present work, five laboratories, all being active partners in the OLEUM project, carried out an inter-lab evaluation of the SPME-GC-MS joint protocol. The validation was carried out by each laboratory following the same analytical conditions and on the same samples, in order to make the results obtained by each laboratory comparable in a harmonized procedure and methodology, as previously done with FID [3]

A multiproxy study distinguishes environmental change from diagenetic alteration in the recent sedimentary record of the inner Cadiz Bay (SW Spain)

In this study, we reconstruct the recent environmental evolution of the inner Cadiz Bay using sedimentary records reaching back as far as AD 1700. We report lithological descriptions of the sediments and extensive mineralogical and geochemical analyses. An extraction technique that identifies different Fe phases provides an assessment of diagenetic alteration, which allows an estimation of the original organic matter inputs to the inner Cadiz Bay. Downcore variations in Corg/N ratios, δ13Corg and δ15N are related to changes in organic matter sources and the trophic state of the water column. The downcore records of selected trace metals (e.g. Pb, Zn and Cu) are interpreted to reflect changes in heavy metal pollution in the bay, while records of other elements (e.g. Mn and P) are likely overprinted by diagenetic alteration. Major environmental shifts took place during the 20th century, when the population around Cadiz Bay increased exponentially. Increases in sediment accumulation rates, organic matter inputs and heavy metal contents, in parallel with increases in δ13Corg and δ15N over this period, are interpreted as direct effects of the increasing anthropogenic influence in the area. The results of this study suggest that multiproxy approaches and detailed consideration of diagenetic overprinting are required to reconstruct past environmental conditions from coastal sediments