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In the last decade, new non-apoptotic roles have been ascribed to apoptotic caspases. This family of proteins plays an important role in the sculpting of the brain in the early stages of development by eliminating excessive and nonfunctional synapses and extra cells. Consequently, impairments in this process can underlie many neurological and mental illnesses. This view is particularly relevant to dopamine because it plays a pleiotropic role in motor control, motivation, and reward processing. In this study, we analyze the effects of the elimination of caspase-8 (CASP8) on the development of catecholaminergic neurons using neurochemical, ultrastructural, and behavioral tests. To do this, we selectively delete the CASP8 gene in cells that express tyrosine hydroxylase with the help of recombination through the Cre-loxP system. Our results show that the number of dopaminergic neurons increases in the substantia nigra. In the striatum, the basal extracellular level of dopamine and potassium-evoked dopamine release decreased significantly in mice lacking CASP8, clearly showing the low dopamine functioning in tissues innervated by this neurotransmitter. This view is supported by electron microscopy analysis of striatal synapses. Interestingly, behavioral analysis demonstrates that mice lacking CASP8 show changes reminiscent of autism spectrum disorders (ASD). Our research reactivates the possible role of dopamine transmission in the pathogenesis of ASD and provides a mild model of autism., This work was supported by grants from the Spanish Ministerio de Economía y Competitividad (RTI2018-098645-B-I00), and the Junta de Andalucía (Consejería de Economía y Conocimiento; P18-RT-1372 and US-1264806). JA and EP-V were supported by a MINECO (PID2019-109569GB-I00) grant. IS-P, LB, CL-M, and EB were supported by the “Fondo Europeo de Desarrollo Regional” (FEDER)-UE “A way to build Europe” from the “Ministerio de Economía y Competitividad” (RTI2018-099778-B-I00); from the “Plan Nacional sobre Drogas, Ministerio de Sanidad, Consumo y Bienestar Social” (2019I041); from “Ministerio de Salud-Instituto de Salud Carlos III (PI18/01691); from the “Programa Operativo de Andalucía FEDER, Iniciativa Territorial Integrada ITI 2014-2020 Consejería Salud y Familias, Junta de Andalucía” (PI-0080-2017, PI-0009-2017), "Consejería de Salud y Familias, Junta de Andalucía" (PI-0134-2018 and PEMP-0008-2020); from the "Consejería de Transformación Económica, Industria, Conocimiento y Universidad, Junta de Andalucía" (P20_00958 and CTS-510); from the CEIMAR (CEIJ-003); from the “Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz-INiBICA” (LI19/06IN-CO22; IN-C09); from the “CIBERSAM” (CB07/09/0033) and from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 955684. Images were obtained in the Centro de Investigación, Tecnología e Innovación de la Universidad de Sevilla (CITIUS).

Prion diseases are caused by the conversion of physiological PrPC into the pathogenic misfolded protein PrPSc, conferring new properties to PrPSc that vary upon prion strains. In this work, we analyze the thermostability of three prion strains (BSE, RML and 22L) that were heated at 98 °C for 2 hours. PrPSc resistance to proteinase K (PrPres), residual infectivity by mouse bioassay and in vitro templating activity by protein misfolding cyclic amplification (PMCA) were studied. Heated strains showed a huge loss of PrPres and a radically different infectivity loss: RML was the most thermolabile strain (6 to 7 log10 infectivity loss), followed by 22L (5 log10) while BSE was the most thermostable strain with low or null infectivity reduction showing a clear dissociation between PrPres and infectivity. These results indicate that thermostability is a strain-specific feature, measurable by PMCA and mouse bioassay, and a great tool to distinguish prion strains.

International audience; The cytokinin signaling pathway, which is mediated by Arabidopsis response regulator (ARR) proteins, has been involved in the modulation of some disease-resistance responses. Here, we describe novel functions of ARR6 in the control of plant disease-resistance and cell-wall composition. Plants impaired in ARR6 function (arr6) were more resistant and susceptible, respectively, to the necrotrophic fungus Plectosphaerella cucumerina and to the vascular bacterium Ralstonia solanacearum, whereas Arabidopsis plants that overexpress ARR6 showed the opposite phenotypes, which further support a role of ARR6 in the modulation of disease-resistance responses against these pathogens. Transcriptomics and metabolomics analyses revealed that, in arr6 plants, canonical disease-resistance pathways, like those activated by defensive phytohormones, were not altered, whereas immune responses triggered by microbe-associated molecular patterns were slightly enhanced. Cell-wall composition of arr6 plants was found to be severely altered compared with that of wild-type plants. Remarkably, pectin-enriched cell-wall fractions extracted from arr6 walls triggered more intense immune responses than those activated by similar wall fractions from wild-type plants, suggesting that arr6 pectin fraction is enriched in wall-related damage-associated molecular patterns, which trigger immune responses. This work supports a novel function of ARR6 in the control of cell-wall composition and disease resistance and reinforces the role of the plant cell wall in the modulation of specific immune responses.

Atypical/Nor98 scrapie (AS) is a prion disease of small ruminants. Currently there are no efficient measures to control this form of prion disease, and, importantly, the zoonotic potential and the risk that AS might represent for other farmed animal species remains largely unknown. In this study, we investigated the capacity of AS to propagate in bovine PrP transgenic mice. Unexpectedly, the transmission of AS isolates originating from 5 different European countries to bovine PrP mice resulted in the propagation of the classical BSE (c-BSE) agent. Detection of prion seeding activity in vitro by protein misfolding cyclic amplification (PMCA) demonstrated that low levels of the c-BSE agent were present in the original AS isolates. C-BSE prion seeding activity was also detected in brain tissue of ovine PrP mice inoculated with limiting dilutions (endpoint titration) of ovine AS isolates. These results are consistent with the emergence and replication of c-BSE prions during the in vivo propagation of AS isolates in the natural host. These data also indicate that c-BSE prions, a known zonotic agent in humans, can emerge as a dominant prion strain during passage of AS between different species. These findings provide an unprecedented insight into the evolution of mammalian prion strain properties triggered by intra- and interspecies passage. From a public health perspective, the presence of c-BSE in AS isolates suggest that cattle exposure to small ruminant tissues and products could lead to new occurrences of c-BSE. info:eu-repo/semantics/acceptedVersion

Producción Científica, The metallic cyanoacetylides LiC3N, NaC3N, MgC3N, and CaC3N have been investigated by combined spectroscopy measurements and theoretical calculations. The theoretical calculations predict for the four species that the linear isomer with the formula MCCCN (M = Li, Na, Mg, and Ca) is the most stable one. We used laser ablation molecular beam Fourier transform microwave (FTMW) spectroscopy to synthesize these species by the reaction of metal vapors, produced by laser ablation, and 3-bromo-2-propynenitrile (BrCCCN). Pure rotational spectra were observed by FTMW spectroscopy in the 2–18 GHz frequency region only for LiCCCN and NaCCCN, while no spectral signatures for MgCCCN and CaCCCN could be detected. Finally, we have searched for LiCCCN and NaCCCN species toward the carbon-rich evolved star IRC +10 216, but only upper limits to their abundances have been obtained., Consejo Europeo de Investigación a través del VII Programa Marco de Investigación y Desarrollo (grant 610256 NANOCOSMOS), Ministerio de Economía, Industria y Competitividad (grants CTQ 2013-40717-P / CTQ 2013-76393-P / AYA2017-87515-P / Consolider-Ingenio 2010 CSD2009-00038), Junta de Castilla y León (grants VA175U13 / VA010G18 / VA077U13)

Urbanization changes the landscape structure and ecological processes of natural habitats. While urban areas expose animal communities to novel challenges, they may also provide more stable environments in which environmental fluctuations are buffered. Species´ ecology and physiology may determine their capacity to cope with the city life. However, the physiological mechanisms underlying organismal responses to urbanization, and whether different physiological systems are equally affected by urban environments remain poorly understood. This severely limits our capacity to predict the impact of anthropogenic habitats on wild populations. In this study, we measured indicators of physiological stress at the endocrine, immune and cellular level (feather corticosterone levels, heterophil to lymphocyte ratio, and heat-shock proteins) in urban and non-urban European blackbirds (Turdus merula) across 10 European populations. Among the three variables, we found consistent differences in feather corticosterone, which was higher in non-urban habitats. This effect seems to be dependent on sex, being greater in males. In contrast, we found no significant differences between urban and non-urban habitats in the two other physiological indicators. The discrepancy between these different measurements of physiological stress highlights the importance of including multiple physiological variables to understand the impact of urbanization on species' physiology. Overall, our findings suggest that adult European blackbirds living in urban and non-urban habitats do not differ in terms of physiological stress at an organismal level. Furthermore, we found large differences among populations on the strength and direction of the urbanization effect, which illustrates the relevance of spatial replication when investigating urban-induced physiological responses., JDI was funded by a postdoctoral contract (TAHUB-104) from the program “Andalucía Talent Hub” (co-funded by the European's Union Seventh Framework Program Marie Skłodowska-Curie actions -COFUND- and the regional Government of Andalucía). DG was funded by a research grant from the Spanish Ministerio de Ciencia, Innovación y Universidades (CGL2014-55577-R). JF was funded by a research grant from the Spanish Ministerio de Economía y Competitividad (CGL2012-30759). ADF was supported by a Severo-Ochoa grant from the Spanish Ministerio de Economía y Competitividad (SVP-2014-068571).

SummaryDE-ETIOLATED 1 (DET1) is an evolutionarily conserved component of the ubiquitination machinery that mediates the destabilization of key regulators of cell differentiation and proliferation in multicellular organisms. In this study, we provide evidence from Arabidopsis that DET1 is essential for the regulation of histone H2B monoubiquitination (H2Bub) over most genes by controlling the stability of a plant deubiquitination module (DUBm). In contrast with yeast and metazoan DUB modules that are associated with the large SAGA complex, the Arabidopsis DUBm only comprises three proteins (hereafter named SGF11, ENY2 and UBP22) and appears to act independently as a major H2Bub deubiquitinase activity. Our study further unveils that DET1-DDB1-Associated-1 (DDA1) protein interacts with SGF11in vivo, linking the DET1 complex to light-dependent ubiquitin-mediated proteolytic degradation of the DUBm. Collectively, these findings uncover a signaling path controlling DUBm availability, potentially adjusting H2Bub turnover capacity to the cell transcriptional status.

In this study, we present a combined experimental and theoretical study of the geometry, electronic structure, morphology, and photoluminescence properties of CaZrO3:Eu3+ materials. The polymeric precursor method was employed to synthesize CaZrO3:Eu3+ crystals, while density functional theory calculations were performed to determine the geometrical and electronic properties of CaZrO3:Eu3+ in its ground and excited electronic states (singlet and triplet). The results were combined with X-ray diffraction (XRD) measurements to elucidate the local structural changes induced by the introduction of Eu3+ in the crystal lattice. This process results in the formation of intermediate levels in the band-gap (Egap) region, narrowing its width. The PL emissions were rationalized by characterizing the electronic structure of the excited singlet and triplet electronic states, which provided deep insight into the main structural and electronic fingerprints associated with [CaO8], [EuO8], and [ZrO6] clusters. In addition, the Wulff construction, obtained from the first-principles calculations, was used to clarify the experimental morphologies. These results extend our fundamental understanding of the atomic processes that underpin the Eu doping of CaZrO3.

International audience; The liver is the most important link between the circadian system and metabolism. As a food-entrainable oscillator, the hepatic clock needs to be entrained by food-related signals. The objective of the present study was to investigate the possible role of ghrelin (an orexigenic peptide mainly synthesized in the gastrointestinal tract) as an endogenous synchronizer of the liver oscillator in teleosts. To achieve this aim, we first examined the presence of ghrelin receptors in the liver of goldfish. Then, the ghrelin regulation of clock gene expression in the goldfish liver was studied. Finally, the possible involvement of the phospholipase C/ protein kinase C (PLC/ PKC) and adenylate cyclase/protein kinase A (AC/PKA) intracellular signalling pathways was investigated. Ghrelin receptor transcripts, ghs-r1a, are present in the majority of goldfish hepatic cells. Ghrelin induced the mRNA expression of the positive (gbmal1a, gclock1a) and negative (gper genes) elements of the main loop of the molecular clock machinery, as well as grev-erba (auxiliary loop) in cultured liver. These effects were blocked, at least in part, by a ghrelin antagonist. Incubation of liver with a PLC inhibitor (U73122), a PKC activator (phorbol 12-myristate 13-acetate) and a PKC inhibitor (chelerythrine chloride) demonstrated that the PLC/ PKC pathway mediates such ghrelin actions. Experiments with an AC activator (forskolin) and a PKA inhibitor (H89) showed that grev-erba regulation could be due to activation of PKA. Taken together, the present results show for the first time in vertebrates a direct action of ghrelin on hepatic clock genes and support a role for this hormone as a temporal messenger in the entrainment of liver circadian functions.

Paired box 4 (PAX4) is a key factor in the generation of insulin producing beta-cells during embryonic development. In adult islets, PAX4 expression is sequestered to a subset of beta-cells that are prone to proliferation and more resistant to stress-induced apoptosis. The importance of this transcription factor for adequate pancreatic islets functionality has been manifested by the association of mutations in PAX4 with the development of diabetes, independently of its etiology. Overexpression of this factor in adult islets stimulates beta-cell proliferation and increases their resistance to apoptosis. Additionally, in an experimental model of autoimmune diabetes, a novel immunomodulatory function for this factor has been suggested. Altogether these data pinpoint at PAX4 as an important target for novel regenerative therapies for diabetes treatment, aiming at the preservation of the remaining beta-cells in parallel to the stimulation of their proliferation to replenish the beta-cell mass lost during the progression of the disease. However, the adequate development of such therapies requires the knowledge of the molecular mechanisms controlling the expression of PAX4 as well as the downstream effectors that could account for PAX4 action.

Laser-based sources of ionizing radiation have attracted a considerable attention in the last years for their broad potential applications. However the stability and robustness of such sources is still an issue that needs to be addressed. Aiming to solve such problems, we propose a source that uses a liquid jet -rather than a solid- as a target for the production of X-rays. Liquid jets offer always a clean surface for every laser shot which represent a clear advantage over solids. In this work, we present an experimental characterization of the X-ray emission of such targets, and study the efficiency of the process when two temporally delayed pulses are used. According to the obtained results, the X-ray yield is comparable with commonly used targets., 8 pages. 7 Figures

In this study, we investigate the structure, antifungal activity, and optical properties of β-Ag2MoO4 using experimental and theoretical approaches. β-Ag2MoO4 samples were prepared by a co-precipitation method using different solvents (water, ethanol and ammonia), and their antifungal activity against Candida albicans was investigated. The samples were characterized by X-ray diffraction, micro-Raman spectroscopy, field emission scanning electron microscopy, and transmission electron microscopy with energy dispersive spectroscopy. The optical properties were investigated by UV-Vis spectroscopy and photoluminescence measurements at room temperature. The thermodynamic equilibrium shape of the β-Ag2MoO4 crystals was determined based on the surface energies calculated using Wulff construction. The (011) orientation was the predominant surface in the morphology. The experimental morphology was obtained by varying the surface energy ratio for each facet. A large decrease in surface energy for the (111) surface provided the experimental morphology for crystals synthesized using water and ethanol as solvents; when the surface energies for both (011) and (001) surfaces increased, the crystal morphology obtained using ammonia as a solvent was reproduced. A correlation between the exposed surfaces and antifungal activity was revealed, and an explanation to this behavior that arises from different morphologies and structural data was provided. Theoretical calculations confirm the rationality of the experimental scheme and elucidate the underlying reason for the fungistatic and fungicidal activity against Candida albicans. This work was financially supported by the following Brazilian research financing institutions: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq): 237944/2012-0; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP): 2013/07296-2, and Spanish research funding institutions: CTQ2012-36253-C03-02 project (Ministerio de Economia y Competitividad), Prometeo II/2014/022 and ACOMP/ 2014/270 projects (Generalitat Valenciana), and Programa de Cooperación Cientifíca con Iberoamerica (Brasil) of Ministerio de Educación (PHBP14-00020). J. A. acknowledges Ministerio de Economia y Competitividad, “Salvador Madariaga” program, PRX15/00261. L. G. acknowledges Banco Santander (Becas Iberoamérica: Jóvenes profesores e investigadores).

Introduction The evidence on the relationship between breast cancer and different types of antihypertensive drugs taken for at least 5 years is limited and inconsistent. Furthermore, the debate has recently been fueled again with new data reporting an increased risk of breast cancer among women with a long history of use of antihypertensive drugs compared with nonusers. Methods In this case-control study, we report the antihypertensive drugs–breast cancer relationship in 1,736 breast cancer cases and 1,895 healthy controls; results are reported stratifying by the women’s characteristics (i.e., menopausal status or body mass index category) tumor characteristics and length of use of antihypertensive drugs. Results The relationship among breast cancer and use of calcium channel blockers (CCB) for 5 or more years had odds ratio (OR) = 1.77 (95% CI, 0.99 to 3.17). Stratifying by BMI, the OR increased significantly in the group with BMI ≥ 25 (OR 2.54, 95% CI, 1.24 to 5.22). CCBs were even more strongly associated with more aggressive tumors, (OR for invasive tumors = 1.96, 95% CI = 1.09 to 3.53; OR for non ductal cancers = 3.97, 95% CI = 1.73 to 9.05; OR for Erbb2+ cancer = 2.97, 95% CI: 1.20 to 7.32). On the other hand, premenopausal women were the only group in which angiotensin II receptor blockers may be associated with breast cancer (OR = 4.27, 95% CI = 1.32 to 13.84) but this could not be identified with any type or stage. Use of angiotensin-converting-enzyme inhibitors, beta blockers and diuretics were not associated with risk. Conclusions In this large population-based study we found that long term use of calcium channel blockers is associated with some subtypes of breast cancer (and with breast cancer in overweight women)., The study was partially funded by the "Accion Transversal del Cancer" project, approved by the Spanish Council of Ministers on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PI09/00773-Cantabria, PI09/01286-Leon, PI09/01903-Valencia, PI09/02078-Huelva, PI09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219), by the Fundacion Marques de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economia y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Tematica de Investigacion del Cancer (RTICC) del ISCIII (RD12/0036/0036)), by the Junta de Castilla y Leon (LE22A10-2), by the Consejeria de Salud of the Junta de Andalucia (2009-S0143), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation and by the Catalan Government DURSI grant 2009SGR1489.

International audience; Oxidatively generated DNA lesions are numerous and versatile, and have been the subject of intensive research since the discovery of 8-oxoguanine in 1984. Even for this prototypical lesion, the precise mechanism of formation remains elusive due to the inherent difficulties in characterizing high-energy intermediates. We have probed the stability of the guanine endoperoxide in B-DNA as a key intermediate and determined a unique activation free energy of around 6 kcal mol−1 for the formation of the first C−O covalent bond upon the attack of singlet molecular oxygen (1O2) on the central guanine of a solvated 13 base-pair poly(dG-dC), described by means of quantum mechanics/molecular mechanics (QM/MM) simulations. The B-helix remains stable upon oxidation in spite of the bulky character of the guanine endoperoxide. Our modeling study has revealed the nature of the versatile 1O2 attack in terms of free energy and shows a sensitivity to electrostatics and solvation as it involves a charge-separated intermediate.

The rotational spectrum of the pentafluoropyridine-Ne complex, generated in a supersonic jet, has been investigated using chirped-pulse microwave Fourier transform spectroscopy in the 2–8 GHz range. The spectra of the 20Ne and 22Ne species have been observed, and the rotational constants have been used to determine the structure of the complex. This structure, and those of the previously experimentally studied complexes benzene-Ne and pyridine-Ne, are an excellent benchmark for the theoretical calculations on these adducts. These complexes and hexafluorobenzene- Ne have been investigated at the CCSD/6-311++G(2d,p) level. The calculations reproduce the experimental structures well and show how the van der Waals complexes are stronger for the perfluorinated compound., This research was funded by the Ministerio de Economía y Competitividad of Spain, Grant CTQ2016-75253-P, the Ministerio de Ciencia, Innovación y Universidades of Spain, Grant No. PGC2018-094644-B-C22 and Comunidad Autónoma de Madrid, Grant no. P2018/EMT-4329 AIRTEC-CM)

BackgroundNeutrophils are involved in the pathophysiology of allergic asthma, where the Eosinophil Cationic Protein(ECP) is a critical inflammatory mediator. Although ECP production is attributed to eosinophils, we reported that ECP is also present in neutrophils from allergic patients where, in contrast to eosinophils, it is produced in an IgE-dependent manner. Given the key role of ECP in asthma, we investigated the molecular mechanisms involved in ECP production as well as the effects induced by agonists and widely used clinical approaches. We also analyzed the correlation between ECP production and lung function.MethodsNeutrophils from allergic asthmatic patients were challenged with allergens, alone or in combination with cytokines, in the presence of cell-signaling inhibitors and clinical drugs. We analyzed ECP levels by ELISA and confocal microscopy. Lung function was assessed by spirometry.ResultsIgE-mediated ECP release is dependent on phosphoinositide 3-kinase, the extracellular signal-regulated kinase (ERK1/2) and the production of reactive oxygen species by NADPH-oxidase. Calcineurin phosphatase and the transcription factor NFAT are also involved. ECP release is enhanced by the cytokines interleukin (IL)-5 and granulocyte macrophage-colony stimulating factor, and inhibited by interferon-γ, IL-10, clinical drugs (formoterol, tiotropium and budesonide) and allergen-specific IT. We also found an inverse correlation between asthma severity and ECP levels.ConclusionsOur results suggest the molecular pathways involved in ECP production and potential therapeutic targets. We also provide a new method to evaluate disease severity in asthmatic patients based on the quantification ofin vitroECP production by peripheral neutrophils.

Osteosarcoma is one of the most common types of bone cancers among paediatric patients. Despite the advances made in surgery, chemo-, and radiotherapy, the mortality rate of metastatic osteosarcoma remains unchangeably high. The standard drug combination used to treat this bone cancer has remained the same for the last 20 years, and it produces many dangerous side effects. Through history, from ancient to modern times, nature has been a remarkable source of chemical diversity, used to alleviate human disease. The application of modern scientific technology to the study of natural products has identified many specific molecules with anti-cancer properties. This review describes the latest discovered anti-cancer compounds extracted from traditional medicinal plants, with a focus on osteosarcoma research, and on their cellular and molecular mechanisms of action. The presented compounds have proven to kill osteosarcoma cells by interfering with different pathways: apoptosis induction, stimulation of autophagy, generation of reactive oxygen species, etc. This wide variety of cellular targets confer natural products the potential to be used as chemotherapeutic drugs, and also the ability to act as sensitizers in drug combination treatments. The major hindrance for these molecules is low bioavailability. A problem that may be solved by chemical modification or nano-encapsulation.

Desde fines del siglo XVII la producción y exportación de aguardientes constituyó uno de los sectores más dinámicos de la economía catalana. A fines del siglo XVIII este comercio entró en crisis y cedió el protagonismo a las exportaciones de vino común. A lo largo del artículo, defendemos la hipótesis que el relevo fue posible gracias a una nueva vinicultura, producto de los avances de la química, que facilitó, por un lado, los instrumentos necesarios para la conservación de los vinos, y, en segundo lugar, la elaboración de vinos adaptados a los diferentes mercados gracias a los coupages y vinos de imitación. Fue en este marco en el que la producción de aguardiente volvió a jugar un papel fundamental para el encabezamiento de los vinos que se destinaban a la exportación y para todo tipo de coupages e imitaciones, para las que resultaba un ingrediente indispensable., From the end of the 17th century, the production and export of distilled spirits from wine has been one of the most dynamic sectors of the Catalan economy. At the end of the 18th century, this trade got into crisis and gave prominence to table wine exports. Throughout the article, we defend the hypothesis that the replacement was possible thanks to a new winemaking, product of the advances in chemistry, which provided, on the one hand, the necessary instruments for the preservation of wines, and, secondly, making wines adapted to different markets thanks to coupages and imitation wines. It was within this framework that the production of spirits again played a fundamental role for fortifying wines that were destined for exports and for all kinds of coupages and imitations, for which they were an indispensable ingredient.

[Introduction] Extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) infections are difficult to treat. We aimed to compare aminoglycosides or polymyxin monotherapy versus other antibiotic regimens (carbapenems, aztreonam, ceftazidime, cefepime, ceftolozane-tazobactam, or ceftazidime-avibactam) in complicated urinary tract infections (cUTI) caused by XDR-PA., [Methods] Study performed at a tertiary-care hospital from 2010 to 2019. All consecutive adult patients with XDR-PA urine cultures and diagnosed with cUTI were retrospectively reviewed. XDR phenotype was defined according to Magiorakos et al. A propensity score was used as a covariate in multivariate analyses and for matching. Primary outcome was early clinical failure and at end of treatment (EOT). Main secondary outcomes were 30- and 90-day mortality, microbiological clearance, and antibiotic-related side effects., [Results] Of the 465 episodes screened, 101 were included, 48% were treated with aminoglycoside or colistin monotherapy. Most XDR-PA were susceptible to colistin (100%) and amikacin (43%). Patients treated with antibiotic regimens other than aminoglycosides or polymyxin monotherapy were more likely to have hematologic malignancy (p, [Conclusions] Aminoglycosides or polymyxin monotherapy showed good efficacy and safety profile in treating cUTI caused by XDR-PA. These results may be useful for antibiotic stewardship activities., This work was supported by the Ministerio de Economia y competitividad of Spain, Instituto de Salud Carlos III [grant number PI17/00251 to J.P.H.], co-financed by the European Development Regional Fund ‘A way to achieve Europe’ (ERDF), Operative program Intelligent Growth 2014–2020. Silvia Gómez-Zorrilla has received a research grant from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) to support her research. The journal’s Rapid Service Fee was funded by the authors.

Extra virgin olive oil (EVOO) is the typical source of fats in the Mediterranean diet [...]

Magnetite nanorods (MNRs) are synthesized based on the use of hematite nanoparticles of the desired geometry and dimensions as templates. The nanorods are shown to be highly monodisperse, with a 5:1 axial ratio, and with a 275 nm long semiaxis. The MNRs are intended to be employed as magnetic hyperthermia and photothermia agents, and as drug vehicles. To achieve a better control of their photothermia response, the particles are coated with a layer of gold, after applying a branched polyethyleneimine (PEI, 2 kDa molecular weight) shell. Magnetic hyperthermia is performed by application of alternating magnetic fields with frequencies in the range 118-210 kHz and amplitudes up to 22 kA/m. Photothermia is carried out by subjecting the particles to a near-infrared (850 nm) laser, and three monochromatic lasers in the visible spectrum with wavelengths 480 nm, 505 nm, and 638 nm. Best results are obtained with the 505 nm laser, because of the proximity between this wavelength and that of the plasmon resonance. A so-called dual therapy is also tested, and the heating of the samples is found to be faster than with either method separately, so the strengths of the individual fields can be reduced. Due to toxicity concerns with PEI coatings, viability of human hepatoblastoma HepG2 cells was tested after contact with nanorod suspensions up to 500 mu g/mL in concentration. It was found that the cell viability was indistinguishable from control systems, so the particles can be considered non-cytotoxic in vitro. Finally, the release of the antitumor drug doxorubicin is investigated for the first time in the presence of the two external fields, and of their combination, with a clear improvement in the rate of drug release in the latter case., Ministry of Science and Innovation, Spain (MICINN) EQC2019-005930-P, Spanish Government PID2019109294RB-100, Junta de Andalucia, European Commission, Consejeria de Economia y Conocimiento/Proyectos de I + D + I del Plan Andaluz de Investigacion, Desarrollo e Innovacion/Grants P20_00346, P20_00233

Infections by multidrug-resistant Enterobacteriaceae (MRE) are life-threatening to patients. The intestinal microbiome protects against MRE colonization, but antibiotics cause collateral damage to commensals and open the way to colonization and subsequent infection. Despite the significance of this problem, the specific commensals and mechanisms that restrict MRE colonization remain largely unknown. Here, by performing a multi-omic prospective study of hospitalized patients combined with mice experiments, we find that Lactobacillus is key, though not sufficient, to restrict MRE gut colonization. Lactobacillus rhamnosus and murinus increase the levels of Clostridiales bacteria, which induces a hostile environment for MRE growth through increased butyrate levels and reduced nutrient sources. This mechanism of colonization resistance, an interaction between Lactobacillus spp. and Clostridiales involving cooperation between microbiota members, is conserved in mice and patients. These results stress the importance of exploiting microbiome interactions for developing effective probiotics that prevent infections in hospitalized patients.

International audience; The current treatment options for type 2 diabetes mellitus do not adequately control the disease in many patients. Consequently, there is a need for new drugs to prevent and treat type 2 diabetes mellitus. Among the new potential pharmacological strategies, activators of peroxisome proliferator-activated receptor (PPAR)β/δ show promise. Remarkably, most of the antidiabetic effects of PPARβ/δ agonists involve AMP-activated protein kinase (AMPK) activation. This review summarizes the recent mechanistic insights into the antidiabetic effects of the PPARβ/δ-AMPK pathway, including the upregulation of glucose uptake, muscle remodeling, enhanced fatty acid oxidation, and autophagy, as well as the inhibition of endoplasmic reticulum stress and inflammation. A better understanding of the mechanisms underlying the effects resulting from the PPARβ/δ-AMPK pathway may provide the basis for the development of new therapies in the prevention and treatment of insulin resistance and type 2 diabetes mellitus.

The detection of regions with unusually high risk plays an important role in disease mapping and the analysis of public health data. In particular, the detection of groups of areas (i.e., clusters) where the risk is significantly high is often conducted by public health authorities. Many methods have been proposed for the detection of these disease clusters, most of them based on moving windows, such as Kulldorff's spatial scan statistic. Here we describe a model-based approach for the detection of disease clusters implemented in the DClusterm package. Our model-based approach is based on representing a large number of possible clusters by dummy variables and then fitting many generalized linear models to the data where these covariates are included one at a time. Cluster detection is done by performing a variable or model selection among all fitted models using different criteria. Because of our model-based approach, cluster detection can be performed using different types of likelihoods and latent effects. We cover the detection of spatial and spatiotemporal clusters, as well as how to account for covariates, zero-inflated datasets and overdispersion in the data.

The detection of a drug belonging to the Sulfonamide class of compounds, namely Sulfapyridine, is reported in this work using an in-situ and fast potentiometric method. The strategy employed for this detection is based on the novel ion pair complex, [Sulfapyridine-H]+[Co(C2B9H11)2]- acting as the active site for highly selective recognition of Sulfapyridine. This enables the sensor's selectivity to be improved by incorporating the target molecule to the selective membrane. In this work, all solid state Sulfapyridine selective microelectrodes based on PVC-type membranes were prepared using three different plasticizers and the aforementioned ion pair complex. The sensors developed have provided quick and accurate response within the range of 10−6 mol/dm3 to 10−3 mol/dm3 of Sulfapyridine concentration and showed a Nernstian slope between 47 and 61 depending upon the type of plasticizer used. The lowest limit of detection achieved was 4 μmol/dm3. The potentiometric coefficient of selectivity, KA,Bpot, has shown that the Sulfapyridine-selective microsensors were highly selective towards Sulfapyridine even when compared to other members of the Sulfonamides class of compounds. In addition, from the Reilley diagram it can be observed that the sensor signal is stable for a working pH interval between 6.00 and 8.00.

In this work, the authors present their recent progress in the development of a platform for the mid-infrared wavelength range, based on suspended silicon waveguides with subwavelength metamaterial cladding. The platform has some intrinsic advantages, which make it a very promising candidate for sensing applications in the molecular fingerprint region. Specifically, it can cover the full transparency window of silicon (up to a wavelength of 8 μm), only requires one lithographic etch-step and can be designed for strong light-matter interaction. Design rules, practical aspects of the fabrication process and experimental results of a complete set of elemental building blocks operating at two very different wavelengths, 3.8 and 7.7 μm, are discussed. Propagation losses as low as 0.82 dB/cm at λ0 = 3.8 μm and 3.1 dB/cm at λ0 = 7.7 μm are attained for the interconnecting waveguides.

Diagnosis of transmissible spongiform encephalopathies (TSEs), or prion diseases, is based on the detection of proteinase K (PK)-resistant PrPSc in post-mortem tissues as indication of infection and disease. Since PrPSc detection is not considered a reliable method for in vivo diagnosis in most TSEs, it is of crucial importance to identify an alternative source of biomarkers to provide useful alternatives for current diagnostic methodology. Ovine scrapie is the prototype of TSEs and has been known for a long time. Using this natural model of TSE, we investigated the presence of PrPSc in exosomes derived from plasma and cerebrospinal fluid (CSF) by protein misfolding cyclic amplification (PMCA) and the levels of candidate microRNAs (miRNAs) by quantitative PCR (qPCR). Significant scrapie-associated increase was found for miR-21-5p in plasma-derived but not in CSF-derived exosomes. However, miR-342-3p, miR-146a-5p, miR-128-3p and miR-21-5p displayed higher levels in total CSF from scrapie-infected sheep. The analysis of overexpressed miRNAs in this biofluid, together with plasma exosomal miR-21-5p, could help in scrapie diagnosis once the presence of the disease is suspected. In addition, we found the presence of PrPSc in most CSF-derived exosomes from clinically affected sheep, which may facilitate in vivo diagnosis of prion diseases, at least during the clinical stage.

International audience; Sustained exercise promotes growth in different fish species, and in gilthead seabream we have demonstrated that it improves nutrient use efficiency. This study assesses for differences in growth rate, tissue composition and energy metabolism in gilthead seabream juveniles fed two diets: high-protein (HP; 54% protein, 15% lipid) or high energy (HE; 50% protein, 20% lipid), under voluntary swimming (VS) or moderate-to-low-intensity sustained swimming (SS) for 6 weeks. HE fed fish under VS conditions showed lower body weight and higher muscle lipid content than HP fed fish, but no differences between the two groups were observed under SS conditions. Irrespective of the swimming regime, the white muscle stable isotopes profile of the HE group revealed increased nitrogen and carbon turnovers. Nitrogen fractionation increased in the HP fed fish under SS, indicating enhanced dietary protein oxidation. Hepatic gene expression markers of energy metabolism and mitochondrial biogenesis showed clear differences between the two diets under VS: a significant shift in the COX/CS ratio, modifications in UCPs, and downregulation of PGC1a in the HE-fed fish. Swimming induced mitochondrial remodeling through upregulation of fusion and fission markers, and removing almost all the differences observed under VS. In the HE-fed fish, white skeletal muscle benefited from the increased energy demand, amending the oxidative uncoupling produced under the VS condition by an excess of lipids and the pro-fission state observed in mitochondria. Contrarily, red muscle revealed more tolerant to the energy content of the HE diet, even under VS conditions, with higher expression of oxidative enzymes (COX and CS) without any sign of mitochondrial stress or mitochondrial biogenesis induction. Furthermore, this tissue had enough plasticity to shift its metabolism under higher energy demand (SS), again equalizing the differences observed between diets under VS condition. Globally, the balance between dietary nutrients affects mitochondrial regulation due to their use as energy fuels, but exercise corrects imbalances allowing practical diets with lower protein and higher lipid content without detrimental effects.

Integrated metamaterials are redefining the capabilities of silicon photonic chips. In providing lithographic control over dielectric permittivity, dispersion and anisotropy, they are enabling photonic devices with unprecedented performance. However, the implementation of these materials at telecom wavelengths often requires a fabrication resolution of the order of 100 nm and below, pushing current wafer-scale fabrication technology to its limits and hindering the widespread exploitation of on-chip metamaterials. Herein, a subwavelength grating metamaterial with bricked topology is proposed, that provides lithographic control over the metamaterial dispersion and anisotropy using a single etch Manhattan-like geometry with pixel dimensions up to 150 x 150 nm(2), thereby easing the path toward fabrication at wafer-scale. The behavior of these structures as biaxial crystals is analytically shown, validating their use in high performance on-chip beam-splitters. Through engineering of the metamaterial anisotropy tensor, the splitters are shown to exhibit sub-decibel insertion losses and imbalance over a 400 nm design bandwidth, via 3D FDTD simulations. The excellent device performance is demonstrated over a 140 nm bandwidth, limited by the measurement setup.

Galaxies with nuclear bars are believed to efficiently drive gas inward, generating a nuclear starburst and possibly an active galactic nucleus. We confirm this scenario for the isolated, double-barred, luminous infrared galaxy ESO 320-G030 based on an analysis of Herschel and ALMA spectroscopic observations. Herschel/PACS and SPIRE observations of ESO 320-G030 show absorption or emission in 18 lines of H2O, which we combine with the ALMA H2O 4(23)-3(30) 448 GHz line (E-upper similar to 400 K) and continuum images to study the physical properties of the nuclear region. Radiative transfer models indicate that three nuclear components are required to account for the multi-transition H2O and continuum data. An envelope, with radius R similar to 130-150 pc, dust temperature T-dust approximate to 50 K, and N-H2 similar to 2x10(23) cm(-2), surrounds a nuclear disk with R similar to 40 pc that is optically thick in the far-infrared (tau (100 mu m)similar to 1.5-3, N-H2 similar to 2x10(24) cm(-2)). In addition, an extremely compact (R similar to 12 pc), warm (approximate to 100 K), and buried (tau (100 mu m)> 5, N-H2 greater than or similar to 5x10(24) cm(-2)) core component is required to account for the very high-lying H2O absorption lines. The three nuclear components account for 70% of the galaxy luminosity (SFR similar to 16-18 M-circle dot yr(-1)). The nucleus is fed by a molecular inflow observed in CO 2-1 with ALMA, which is associated with the nuclear bar. With decreasing radius (r=450-225 pc), the mass inflow rate increases up to M-inf similar to 20 M yr(-1), which is similar to the nuclear star formation rate (SFR), indicating that the starburst is sustained by the inflow. At lower r, similar to 100-150 pc, the inflow is best probed by the far-infrared OH ground-state doublets, with an estimated M-inf similar to 30 M yr(-1). The inferred short timescale of similar to 20 Myr for nuclear gas replenishment indicates quick secular evolution, and indicates that we are witnessing an intermediate stage (< 100 Myr) proto-pseudobulge fed by a massive inflow that is driven by a strong nuclear bar. We also apply the H2O model to the Herschel far-infrared spectroscopic observations of H218O, OH, 18OH, OH+, H2O+, H3O+, NH, NH2, NH3, CH, CH+, 13CH+, HF, SH, and C3, and we estimate their abundances. © ESO 2021., EG-A is grateful for the warm hospitality of the Harvard-Smithsonian Center for Astrophysics, where part of the present study was carried out, and thanks Javier Goicoechea for useful conversations on the far-IR spectrum of Sgr B2, Alex Crespo Gomez for sharing preliminary results on the stellar kinematics in ESO 320-G030, and Juan Rafael Martinez-Galarza for useful conversations on the Bayesian analysis. We thank the anonymous referee for constructive and helpful comments on the manuscript. PACS was developed by a consortium of institutes led by MPE (Germany) and including UVIE (Austria); KU Leuven, CSL, IMEC (Belgium); CEA, LAM (France); MPIA (Germany); INAFIFSI/OAA/OAP/OAT, LENS, SISSA (Italy); IAC (Spain). This development has been supported by the funding agencies BMVIT (Austria), ESA-PRODEX (Belgium), CEA/CNES (France), DLR (Germany), ASI/INAF (Italy), and CICYT/MCYT (Spain). SPIRE was developed by a consortium of institutes led by Cardiff University (UK) and including Univ. Lethbridge (Canada); NAOC (China); CEA, LAM (France); IFSI, Univ. Padua (Italy); IAC (Spain); Stockholm Observatory (Sweden); Imperial College London, RAL, UCL-MSSL, UKATC, Univ. Sussex (UK); and Caltech, JPL, NHSC, Univ.Colorado (USA). This development has been supported by national funding agencies: CSA (Canada); NAOC (China); CEA, CNES, CNRS (France); ASI (Italy); MCINN (Spain); SNSB (Sweden); STFC, UKSA (UK); and NASA (USA). This paper makes use of the following ALMA data: ADS/JAO.ALMA#2016.1.00263.S and ADS/JAO.ALMA#2013.1.00271.S. ALMA is a partnership of ESO (representing its member states), NSF (USA) and NINS (Japan), together with NRC (Canada) and NSC and ASIAA (Taiwan) and KASI (Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO and NAOJ. Based on observations made with ESO Telescopes at the Paranal Observatory under programme ID 086.B-0901(A). EG-A is a Research Associate at the Harvard-Smithsonian Center for Astrophysics. EG-A, JM-P, and FR-V thank the Spanish Ministerio de Economia y Competitividad for support under projects ESP2017-86582-C4-1-R and PID2019-105552RB-C41. EG-A and HAS thank NASA grant ADAP NNX15AE56G. MP-S acknowledges support from the Comunidad de Madrid, Spain, through Atraccion de Talento Investigador Grant 2018-T1/TIC-11035 and PID2019-105423GA-I00 (MCIU/AEI/FEDER,UE). AA-H and SG-B acknowledge support through grant PGC2018-094671-B-I00 (MCIU/AEI/FEDER,UE). LC, AA-H, MP-S, and JM-P acknowledge support under project No. MDM-2017-0737 Unidad de Excelencia "Maria de Maeztu" - Centro de Astrobiologia (INTA-CSIC). SG-B acknowledges support from the Spanish MINECO and FEDER funding grant AYA2016-76682-C3-2-P. C.Y. acknowledges support from an ESO Fellowship. LC acknowledges support from the Spanish Ministerio de Economia y Competitividad for support under project ESP2017-83197. SC acknowledges financial support from the State Agency for Research of the Spanish MCIU through the 'Center of Excellence Severo Ochoa' award to the Instituto de Astrofisica de Andalucia (SEV-2017-0709). This research has made use of NASA's Astrophysics Data System (ADS) and of GILDAS software.

In order to assess whether previous hepatic IR (Hepatic-IRfasting) and beta-cell functionality could modulate type 2 diabetes remission and the need for starting glucose-lowering treatment, newly-diagnosed type 2 diabetes participants who had never received glucose-lowering treatment (190 out of 1002) from the CORDIOPREV study (a prospective, randomized and controlled clinical trial), were randomized to consume a Mediterranean or a low-fat diet. Type 2 diabetes remission was defined according to the ADA recommendation for levels of HbA1c, fasting plasma glucose and 2h plasma glucose after OGTT, and having maintained them for at least 2 consecutive years. Patients were classified according to the median of Hepatic-IRfasting and beta-cell functionality, measured as the disposition index (DI) at baseline. Cox proportional hazards regression determined the potential for Hepatic-IRfasting and DI indexes as predictors of diabetes remission and the probability of starting pharmacological treatment after a five-year follow-up. Low-Hepatic-IRfasting or high-DI patients had a higher probability of diabetes remission than high-Hepatic-IRfasting or low-DI subjects (HR:1.79;95%CI 1.06-3.05; and HR:2.66;95%CI 1.60-4.43, respectively) after a dietary intervention with no pharmacological treatment and no weight loss. The combination of low-Hepatic-IRfasting and high-DI presented the highest probability of remission (HR:4.63;95%CI 2.00-10.70). Among patients maintaining diabetes, those with high- Hepatic-IRfasting and low-DI showed the highest risk of starting glucose-lowering therapy (HR:3.24;95%CI 1.50-7.02). Newly-diagnosed type 2 diabetes patients with better beta-cell functionality and lower Hepatic-IRfasting had a higher probability of type 2 diabetes remission in a dietary intervention without pharmacological treatment or weight loss, whereas among patients not achieving remission, those with worse beta-cell functionality and higher Hepatic-IRfasting index had the highest risk of starting glucose-lowering treatment after five years of follow-up. BACKGROUND: Our current knowledge regarding the etiology of type 2 diabetes points to hepatic insulin resistance and beta cell functionality as two major abnormalities underlying the disease. Previous studies have associated type 2 diabetes remission with weight loss, together with a decrease in liver fat content and a higher beta cell recovery. TRANSLATIONAL SIGNIFICANCE: Patients with lower hepatic insulin resistance and better beta cell functionality had a higher probability of remission without significant weight loss or pharmacological treatment. These results suggest that clinicians could identify patients with specific phenotypes in early-diagnosed type 2 diabetes that could be the key to achieve higher remission rates without weight loss or pharmacological treatment.

En este trabajo, nos proponemos estudiar los recursos lingüísticos empleados para la intensificación y la expresión afectiva en un corpus epistolar del siglo XVIII. Las cartas que componen este corpus se caracterizan por estar escritas por mujeres a otras mujeres de su familia con las que mantienen una relación simétrica; tienen, por tanto, un carácter privado, lo que las hace un objeto de estudio idóneo para observar los rasgos discursivos hallados en ellas pertenecientes tanto a la distancia como a la inmediatez comunicativa. Además, con este artículo se contribuye al estudio de un periodo menos atendido en la lingüística histórica y que está en auge en la actualidad: el denominado primer español moderno (1650-1825). Del análisis emprendido se deduce que los recursos intensificadores y afectivos se dan de manera abundante y variada en estos textos y se constituyen como una característica pragmática propia de ellos. La abundancia de estas expresiones puede explicarse porque, al ser un rasgo asumido y esperado por los usuarios de las cartas, el valor intensificador y afectivo termina mitigándose, por lo que es necesario utilizar un mayor número de recursos con una gran carga pragmática para conseguir el efecto deseado In this work, we intend to study the linguistic resources used for intensification and affective expression in an epistolary corpus from the 18th Century. The letters composing this corpus are characterized by being written by women and addressed to other female relatives, with whom they maintain a symmetrical relationship. Therefore, they have a private character, which makes them an ideal object of study to observe discursive features related to both communicative distance and immediacy. In addition, this article contributes to the study of a less addressed period in historical linguistics: the so-called first modern Spanish (1650-1825). This analysis suggests that intensifying and affective resources are abundant and varied in these texts, and that they constitute a pragmatic feature characteristic of these letters. The abundance of these expressions could be explained by the fact that, since affection and a close communication is assumed in this type of letters, there would be a need of a greater use of resources with a pragmatic load to emphasize their affective value and achieve the desired effect Ministerio de Economia y Competitividad (MINECO). España

© 2021 by the authors., The physiological and endocrine benefits of sustained exercise in fish were largely demonstrated, and this work examines how the swimming activity can modify the effects of two diets (high-protein, HP: 54% proteins, 15% lipids; high-energy, HE: 50% proteins, 20% lipids) on different growth performance markers in gilthead sea bream juveniles. After 6 weeks of experimentation, fish under voluntary swimming and fed with HP showed significantly higher circulating growth hormone (GH) levels and plasma GH/insulin-like growth-1 (IGF-1) ratio than fish fed with HE, but under exercise, differences disappeared. The transcriptional profile of the GH-IGFs axis molecules and myogenic regulatory factors in liver and muscle was barely affected by diet and swimming conditions. Under voluntary swimming, fish fed with HE showed significantly increased mRNA levels of capn1, capn2, capn3, capns1a, n3, and ub, decreased gene and protein expression of Ctsl and Mafbx and lower muscle texture than fish fed with HP. When fish were exposed to sustained exercise, diet-induced differences in proteases’ expression and muscle texture almost disappeared. Overall, these results suggest that exercise might be a useful tool to minimize nutrient imbalances and that proteolytic genes could be good markers of the culture conditions and dietary treatments in fish., This study was supported by the projects from the “Ministerio de Economía y Competitividad” (MINECO) AGL2015-70679-R and RTI2018-100757-B-I00 to J.G. and J.B., and the “Xarxa de Refèrencia d’R+D+I en Aqüicultura” and the 2017SGR1574 from the “Generalitat de Catalunya”. M.P.- A., I.G.-P. and E.J.V. were supported by predoctoral fellowships from the MINECO, BES-2016-078697, PRE2019-089578 and BES-2013-062949, respectively.

Cirrus (Ci) clouds play an important role in the atmospheric radiative balance, and hence in Climate Change. In this work, a polarized Micro-Pulse Lidar (P-MPL), standard NASA/Micro Pulse NETwork (MPLNET) system, deployed at the INTA/El Arenosillo station in Huelva (SW Iberian Peninsula) is used for Ci detection and characterization for the first time at this site. Three days were selected on the basis of the predominantly detected Ci clouds in dependence on their cloud optical depth (COD). Hence, three Ci cloud categories were examined at day-times for comparison with solar radiation issues: 19 cases of sub-visuals (svCi, COD: 0.01–0.03) on 1 October 2016, 7 cases of semitransparents (stCi, COD: 0.03–0.30) on 8 May 2017, and 17 cases of opaques (opCi, COD: 0.3–3.0) on 28 October 2016. Their radiative-relevant optical, macro- and micro-physical properties were retrieved. The mean COD for the svCi, stCi and opCi groups was 0.02 ± 0.01, 0.22 ± 0.08 and 0.93 ± 0.40, respectively; in overall, their lidar ratio ranged between 25 and 35 sr. Ci clouds were detected at 11–13 km height (top boundaries) with geometrical thicknesses of 1.7–2.0 km. Temperatures reported at those altitudes corresponded to lower values than the thermal threshold for homogenous ice formation. Volume linear depolarization ratios of 0.3–0.4 (and normalized backscattering ratios higher than 0.9) also confirmed Ci clouds purely composed of ice particles. Their effective radius was within the interval of 9–15 μm size, and the ice water path ranged from 0.02 (svCi) to 9.9 (opCi) g m. The Cirrus Cloud Radiative Effect (CCRE) was estimated using a Radiative Transfer (RT) model for Ci-free conditions and Ci-mode (Ci presence) scenarios. RT simulations were performed for deriving the CCRE at the top-of-atmosphere (TOA) and on surface (SRF), and also the atmospheric CCRE, for the overall shortwave (SW) range and their spectral sub-intervals (UV, VIS and NIR). A good agreement was first obtained for the RT simulations as validated against solar radiation measurements under clean conditions for solar zenith angles less than 75° (differences were mainly within ±20 W m and correlation coefficients close to 1). By considering all the Ci clouds, independently on their COD, the mean SW CCRE values at TOA and SRF were, respectively, −30 ± 26 and − 24 ± 19 W m, being the mean atmospheric CCRE of −7 ± 7 W m; these values are in good agreement with global annual estimates found for Ci clouds. By using linear regression analysis, a Ci-induced enhancing cooling radiative effect was observed as COD increased for all the spectral ranges, with high correlations. In particular, the SW CCRE at TOA and SRF, and the atmospheric CCRE, presented COD-dependent rates of −74 ± 4, −55 ± 5, −19 ± 2 W mτ, respectively. Additionally, increasing negative rates are found from UV to NIR for each Ci category, reflecting a higher cooling NIR contribution w.r.t. UV and VIS ranges to the SW CCRE, and being also more pronounced at the TOA w.r.t. on SRF, as expected. The contribution of the SW CCRE to the net (SW + LW) radiative balance can be also potentially relevant. These results are especially significant for space-borne photometric/radiometric instrumentation and can contribute to validation purposes of the next ESA's EarthCARE mission, whose principal scientific goal is focused on radiation-aerosol-cloud interaction research., With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737)

We used high-spatial resolution (70 pc; 0$ {{\overset{\prime\prime}{.}}} $3) CO multi-transition (J = 1-0, 2-1, 4-3, and 6-5) ALMA data to study the physical conditions and kinematics of the cold molecular outflow in the local luminous infrared galaxy (LIRG) ESO 320-G030 (d = 48 Mpc, LIR/L = 1011.3). ESO 320-G030 is a double-barred isolated spiral, but its compact and obscured nuclear starburst (SFR ∼15 M yr-1; AV ∼40 mag) resembles those of ultra-luminous infrared galaxies (LIR/L > 1012). In the outflow, the CO(1-0)/CO(2-1) ratio is enhanced with respect to the rest of the galaxy and the CO(4-3) transition is undetected. This indicates that the outflowing molecular gas is less excited than the molecular gas in the nuclear starburst (i.e., outflow launching site) and in the galaxy disk. Non-local thermodynamic equilibrium radiative transfer modeling reveals that the properties of the molecular clouds in the outflow differ from those of the nuclear and disk clouds: The kinetic temperature is lower (Tkin ∼ 9 K) in the outflow, and the outflowing clouds have lower column densities. Assuming a 10-4 CO abundance, the large internal velocity gradients, 60-45+250 km s-1 pc-1, imply that the outflowing molecular clouds are not bound by self-gravity. All this suggests that the life-cycle (formation, collapse, dissipation) of the galaxy disk molecular clouds might differ from that of the outflowing molecular clouds which might not be able to form stars. The low kinetic temperature of the molecular outflow remains constant at radial distances between 0.3 and 1.7 kpc. This indicates that the heating by the hotter ionized outflow phase is not efficient and may favor the survival of the molecular gas phase in the outflow. The spatially resolved velocity structure of the outflow shows a 0.8 km s-1 pc-1 velocity gradient between 190 pc and 560 pc and then a constant maximum outflow velocity of about 700-800 km s-1 up to 1.7 kpc. This could be compatible with a pure gravitational evolution of the outflow, which would require coupled variations of the mass outflow rate and the outflow launching velocity distribution. Alternatively, a combination of ram pressure acceleration and cloud evaporation could explain the observed kinematics and the total size of the cold molecular phase of the outflow. © ESO 2020., MPS acknowledges support from the Comunidad de Madrid through the Atracción de Talento Investigador Grant 2018-T1/TIC11035, PID2019-105423GA-I00 (MCIU/AEI/FEDER,UE), and STFC through Grants ST/N000919/1 and ST/N002717/1. L. C. acknowledge financial support by the Spanish MICINN under Grant ESP2017-83197. A. A.-H., S. G.-B., and A. U. acknowledge support through Grant PGC2018-094671-B-I00 (MCIU/AEI/FEDER,UE). E. GA is a Research Associate at the HarvardSmithsonian Center for Astrophysics, and thanks the Spanish Ministerio de Economía y Competitividad for support under project ESP2017-86582-C4- 1-R. J. P.-L. acknowledge financial support by the Spanish MICINN under Grant AYA2017-85170-R. M. P. S., A. A.-H., L. C., J. P.-L. and S. A. work was done under project No. MDM-2017-0737 Unidad de Excelencia “María de Maeztu”- Centro de Astrobiología (INTA-CSIC). DR acknowledges support from ST/S000488/1 and the University of Oxford Fell Fund. This paper makes use of the following ALMA data: ADS/JAO.ALMA#2016.1.00263.S, ADS/JAO.ALMA#2013.1.00271.S. ALMA is a partnership of ESO (representing its member states), NSF (USA) and NINS (Japan), together with NRC (Canada) and NSC and ASIAA (Taiwan) and KASI (Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO and NAOJ. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc