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COVID-19 disease have become so far the most important sanitary crisis in the XXI century. In light of the events, any clinical resource should be considered to alleviate this crisis. Severe COVID-19 cases present a so-called cytokine storm as the most life-threatening symptom accompanied by lung fibrosis. Galectin-3 has been widely described as regulator of both processes. Hereby, we present compelling evidences on the potential role of galectin-3 in COVID-19 in the regulation of the inflammatory response, fibrosis and infection progression. Moreover, we provide a strong rationale of the utility of measuring plasma galectin-3 as a prognosis biomarker for COVID-19 patients and propose that inhibition of galectin-3 represents a feasible and promising new therapeutical approach., This work was supported by grants from the Swedish Research Council (2019-06333, AB-S), and the Strong Research Environment MultiPark (Multidisciplinary Research in Parkinson’s and Alzheimer’s Disease at Lund University), Bagadilico (Linné consortium sponsored by the Swedish Research Council), the Swedish Alzheimer’s Foundation, Swedish Brain Foundation, A.E. Berger Foundation, Gyllenstiern-ska Krapperup Foundation, the Royal Physiographic Society, Crafoord Foundation, Olle Engkvist Byggmästare Foundation, Wiberg Foundation, G&J Kock Foundation, Stohnes Foundation, and Swedish Dementia Association and the Medical Faculty at Lund University. This perspective was also funded by the Spanish Ministerio de Ciencia, Innovación y Universidades/FEDER/UE RTI2018-098645-B-100, FEDER ICDCi-USE US-1265062, and US-1264806. JG-R has been funded by a grant from the Spanish Ministerio de Economia y Competitividad SAF2015-64171-R (MINECO/FEDER, EU).

Curved crystals are a simple but powerful approach to bridge the gap between single crystal surfaces and nanoparticle catalysts, by allowing a rational assessment of the role of active step sites in gas-surface reactions. Using a curved Rh(111) crystal, here, we investigate the effect of A-type (square geometry) and B-type (triangular geometry) atomic packing of steps on the catalytic CO oxidation on Rh at millibar pressures. Imaging the crystal during reaction ignition with laser-induced CO2 fluorescence demonstrates a two-step process, where B-steps ignite at lower temperature than A-steps. Such fundamental dissimilarity is explained in ambient pressure X-ray photoemission (AP-XPS) experiments, which reveal partial CO desorption and oxygen buildup only at B-steps. AP-XPS also proves that A-B step asymmetries extend to the active stage: at A-steps, low-active O–Rh–O trilayers buildup immediately after ignition, while highly active chemisorbed O is the dominant species on B-type steps. We conclude that B-steps are more efficient than A-steps for the CO oxidation., We acknowledge financial support from Grant Nos. PID2020-116093RB-C44 and PID2019-107338RB-C6-3, funded by the Spanish MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”, the Basque Government (Grant No. IT-1591-22), Knut and Alice Wallenberg (KAW) project “Atomistic design of new catalysts” (Project No. KAW2015.0058), the Swedish Research Council (Project No. 2018-03434), the Swedish Foundation for Strategic Research (Project No. ITM17-0045), the Å Forsk Foundation, and the Crafoord Foundation. This research used resources of the 23-ID-2 (IOS) beamline of the National Synchrotron Light Source II, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Brookhaven National Laboratory, under Contract No. DE-SC0012704. Part of these experiments were performed at Circe beamline at ALBA Synchrotron with the collaboration of ALBA staff., Open Access funding is provided by the University of the Basque Country.

The advent of high-throughput single-cell transcriptomic analysis of microglia has revealed different phenotypes that are inherently associated with disease conditions. A common feature of some of these activated phenotypes is the upregulation of galectin-3. Representative examples of these phenotypes include disease-associated microglia (DAM) and white-associated microglia (WAM), whose role(s) in neuroprotection/neurotoxicity is a matter of high interest in the microglia community. In this review, we summarise the main findings that demonstrate the ability of galectin-3 to interact with key pattern recognition receptors, including, among others, TLR4 and TREM2 and the importance of galectin-3 in the regulation of microglia activation. Finally, we discuss increasing evidence supporting the involvement of this lectin in the main neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, and stroke., We thank the Spanish Ministerio de Ciencia, Innovación y Universidades/FEDER/UE RTI2018-098645-B-100, PID2019-107948RA-I00 and RYC-2017-21804; the Agencia Española de Investigación PID2021-124096OB-I00 and PID2021-126090OA-I00; the Spanish Junta de Andalucia /FEDER/EU P18-RT-1372 and the Spanish FEDER I + D + i-USE US-1264806, US-1264152 and US-1265062 from University of Seville. This work has also been supported by the Strategic Research Area MultiPark (Multidisciplinary Research focused on neurodegenerative diseases) at Lund University, the Swedish Alzheimer foundation, the Swedish Brain Foundation, the Crafoord Foundation, the Swedish Dementia Association, the G&J Kock Foundation, the Olle Engkvist Foundation, the Swedish Research Council (Project 2019-06333), the Royal Physiographic Society (42222 and 40594), the A.E. Berger Foundation, the Swedish Parkinson Foundation and the Medical Faculty at Lund University. Open access funding provided by Lund University.

ApoE is the major lipid and cholesterol carrier in the CNS. There are three major human polymorphisms, apoE2, apoE3, and apoE4, and the genetic expression of APOE4 is one of the most influential risk factors for the development of late-onset Alzheimer's disease (AD). Neuroinflammation has become the third hallmark of AD, together with Amyloid-β plaques and neurofibrillary tangles of hyperphosphorylated aggregated tau protein. This review aims to broadly and extensively describe the differential aspects concerning apoE. Starting from the evolution of apoE to how APOE's single-nucleotide polymorphisms affect its structure, function, and involvement during health and disease. This review reflects on how APOE's polymorphisms impact critical aspects of AD pathology, such as the neuroinflammatory response, particularly the effect of APOE on astrocytic and microglial function and microglial dynamics, synaptic function, amyloid-β load, tau pathology, autophagy, and cell-cell communication. We discuss influential factors affecting AD pathology combined with the APOE genotype, such as sex, age, diet, physical exercise, current therapies and clinical trials in the AD field. The impact of the APOE genotype in other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies and Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, and multiple sclerosis, is also addressed. Therefore, this review gathers the most relevant findings related to the APOE genotype up to date and its implications on AD and CNS pathologies to provide a deeper understanding of the knowledge in the APOE field., Open access funding provided by Lund University. This work was supported by The Strategic Research Area MultiPark (Multidisciplinary Research in neurodegenerative diseases) at Lund University, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, Crafoord Foundation, Swedish Dementia Association, G&J Kock Foundation, Olle Engkvist Foundation, the Swedish Medical Research Council, the Swedish Parkinson Foundation, the A.E. Berger Foundation, the Thurings Foundation, and the Swedish mental health foundation to T.D., M.S, A.B-S. The Royal Physiographic Society of Lund grant to R.F–C. SYNDEGEN, Marie Curie grant n°721802 to G.K.G and S.K. We also thank the Spanish Ministerio de Ciencia e Innovación/FEDER/UE/PID2021-124096OB-I00; the Spanish Junta de Andalucia/FEDER/EU P18-RT-1372 and the Spanish FEDER I + D + i-USE US-1264806 to J.L.V.

[Background] The risk of developing Alzheimer's disease (AD) is modulated by genetic and environmental factors. Early-life stress (ELS) exposure during critical periods of brain development can impact later brain function and health, including increasing the risk of developing AD. Microglial dysfunction and neuroinflammation have been implicated as playing a role in AD pathology and may be modulated by ELS. To complicate matters further, sex-specific effects have been noted in response to ELS and in the incidence and progression of AD., [Methods] Here, we subjected male and female mice with either a wild type or 5xFAD familial AD-model background to maternal separation (MS) from postnatal day 2 to 14 to induce ELS., [Results] We detected hippocampal neuroinflammatory alterations already at postnatal day 15. By 4 months of age, MS mice presented increased immobility time in the forced swim test and a lower discrimination index in the novel object recognition memory test compared to controls. We found altered Bdnf and Arc expression in the hippocampus and increased microglial activation in the prefrontal cortex due to MS in a sex-dependent manner. In 5xFAD mice specifically, MS exacerbated amyloid-beta deposition, particularly in females. In the periphery, the immune cell population was altered by MS exposure., [Conclusion] Overall, our results demonstrate that MS has both short- and long-term effects on brain regions related to memory and on the inflammatory system, both in the brain and periphery. These ELS-related effects that are detectable even in adulthood may exacerbate pathology and increase the risk of developing AD via sex-specific mechanisms., Open access funding provided by Lund University. This study was funded by the Olle Engkvist Foundation, the Swedish Medical Research Council, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, the Crafoord Foundation, the Swedish Dementia Association, the G&J Kock Foundation, the Royal Physiographic Society, the Fredrik O Ingrid Thurings Stiftelse, the A.E. Berger Foundation, the Swedish Parkinson Foundation and the Strategic Research Area MultiPark at Lund University.

Producción Científica, Objectives: Restenosis after vessel angioplasty due to dedifferentiation of the vascular smooth muscle cells (VSMCs) limits the success of surgical treatment of vascular occlusions. Type 2 diabetes (T2DM) has a major impact on restenosis, with patients exhibiting more aggressive forms of vascular disease and poorer outcomes after surgery. Kv1.3 channels are critical players in VSMC proliferation. Kv1.3 blockers inhibit VSMCs MEK/ERK signalling and prevent vessel restenosis. We hypothesize that dysregulation of microRNAs (miR) play critical roles in adverse remodelling, contributing to Kv1.3 blockers efficacy in T2DM VSMCs. Methods and results: We used clinically relevant in vivo models of vascular risk factors (VRF) and vessels and VSMCs from T2DM patients. Results: Human T2DM vessels showed increased remodelling, and changes persisted in culture, with augmented VSMCs migration and proliferation. Moreover, there were downregulation of PI3K/AKT/mTOR and upregulation of MEK/ERK pathways, with increased miR-126 expression. The inhibitory effects of Kv1.3 blockers on remodelling were significantly enhanced in T2DM VSMCs and in VRF model. Finally, miR-126 overexpression confered “diabetic” phenotype to non-T2DM VSMCs by downregulating PI3K/AKT axis. Conclusions: miR-126 plays crucial roles in T2DM VSMC metabolic memory through activation of MEK/ERK pathway, enhancing the efficacy of Kv1.3 blockers in the prevention of restenosis in T2DM patients., Ministerio de Economía, Industria y Competitividad (grant BFU2016-75360-R and SAF2016-77871-C2-1-R), Junta de Castilla y León (grants VA114P17; VA172P20 and CLU-2019-02), Novo Nordisk Foundation (grant 34366), Swedish Research Council (grants 2017–00860 and 2020-01145), Swedish Heart and Lung Foundation (grant 20200322)

Microglia, the immune sentinel of the central nervous system (CNS), are generated from yolk sac erythromyeloid progenitors that populate the developing CNS. Interestingly, a specific type of bone marrow-derived monocyte is able to express a yolk sac microglial signature and populate CNS in disease. Here we have examined human bone marrow (hBM) in an attempt to identify novel cell sources for generating microglia-like cells to use in cell-based therapies and in vitro modeling. We demonstrate that hBM stroma harbors a progenitor cell that we name stromal microglial progenitor (STR-MP). STR-MP single-cell gene analysis revealed the expression of the consensus genetic microglial signature and microglial-specific genes present in development and CNS pathologies. STR-MPs can be expanded and generate microglia-like cells in vitro, which we name stromal microglia (STR-M). STR-M cells show phagocytic ability, classically activate, and survive and phagocyte in human brain tissue. Thus, our results reveal that hBM harbors a source of microglia-like precursors that can be used in patient-centered fast derivative approaches., This work was supported by Craafordska Stiftelsen, the Royal Physiographic Society of Lund, Per Eric and Ulla Shyberg's Foundation, and Viveca Jeppsson.

The extreme 2018 hot drought that affected central and northern Europe led to the worst wildfire season in Sweden in over a century. The Ljusdal fire complex, the largest area burnt that year (8995 ha), offered a rare opportunity to quantify the combined impacts of wildfire and post-fire management on Scandinavian boreal forests. We present chamber measurements of soil CO2 and CH4 fluxes, soil microclimate and nutrient content from five Pinus sylvestris sites for the first growing season after the fire. We analysed the effects of three factors on forest soils: burn severity, salvage-logging and stand age. None of these caused significant differences in soil CH4 uptake. Soil respiration, however, declined significantly after a high-severity fire (complete tree mortality) but not after a low-severity fire (no tree mortality), despite substantial losses of the organic layer. Tree root respiration is thus key in determining post-fire soil CO2 emissions and may benefit, along with heterotrophic respiration, from the nutrient pulse after a low-severity fire. Salvage-logging after a high-severity fire had no significant effects on soil carbon fluxes, microclimate or nutrient content compared with leaving the dead trees standing, although differences are expected to emerge in the long term. In contrast, the impact of stand age was substantial: a young burnt stand experienced more extreme microclimate, lower soil nutrient supply and significantly lower soil respiration than a mature burnt stand, due to a thinner organic layer and the decade-long effects of a previous clear-cut and soil scarification. Disturbance history and burn severity are, therefore, important factors for predicting changes in the boreal forest carbon sink after wildfires. The presented short-term effects and ongoing monitoring will provide essential information for sustainable management strategies in response to the increasing risk of wildfire., This project has been funded by Swedish Research Council Formas grants 2018-02700, 2019-00836, the strategic research program of the Crafoord Foundation grant 20190763, and the Swedish Strategic Research Area BECC (Biodiversity and Ecosystem Services in a Changing Climate). C.S. also received funding from the Spanish ‘Ramon y Cajal’ programme, Ref. N. RYC2018-025797-I.

Publisher's version (útgefin grein), Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies., We acknowledge the contribution from the EchoGen Consortium.

In Brief Melo et al. show that geosmin mediates egg laying in the yellow fever mosquito Aedes aegypti, which associates geosmin with microbes present in the larval aquatic habitat. The authors further show that geosmin can be used as bait in oviposition traps and that geosmin can be substituted by beetroot peel for mosquito trapping in developing countries., Graphical Abstract

The PI3K pathway is a major driver of cancer progression. However, clinical resistance to PI3K inhibition is common. IBL-302 is a novel highly specific triple PIM, PI3K, and mTOR inhibitor. Screening IBL-302 in over 700 cell lines representing 47 tumor types identified neuroblastoma as a strong candidate for PIM/PI3K/mTOR inhibition. IBL-302 was more effective than single PI3K inhibition in vitro, and IBL-302 treatment of neuroblastoma patient-derived xenograft (PDX) cells induced apoptosis, differentiated tumor cells, and decreased N-Myc protein levels. IBL-302 further enhanced the effect of the common cytotoxic chemotherapies cisplatin, doxorubicin, and etoposide. Global genome, proteome, and phospho-proteome analyses identified crucial biological processes, including cell motility and apoptosis, targeted by IBL-302 treatment. While IBL-302 treatment alone reduced tumor growth in vivo, combination therapy with low-dose cisplatin inhibited neuroblastoma PDX growth. Complementing conventional chemotherapy treatment with PIM/PI3K/mTOR inhibition has the potential to improve clinical outcomes and reduce severe late effects in children with high-risk neuroblastoma. This work was supported by funding from the Swedish Cancer Society (to SM, DB), the Swedish Research Council (to DB), the Swedish Childhood Cancer Fund (to SM, KvS, DB), Region Skåne and the research funds of Skåne University Hospital (to DB), the Mary Bevé Foundation (to SM, KvS, DB), Magnus Bergvalls stiftelse (to SM, DB), the Thelma Zoéga Foundation (to SM), Hans von Kantzow Foundation (to SM), Crafoord Foundation (to DB), Åke Wiberg Foundation (to DB), Jeanssons Stiftelser (to DB), Ollie och Elof Ericssons stiftelser (to DB), Berth von Kantzows stiftelse (to DB), the Royal Physiographic Society of Lund (to SM, DB), and the Spanish Ministry of Health and Social Policy (ADE 08 / 90038 ) and the Spanish Ministry of Science and Innovation (CIT- 090000 - 2008 - 14 ) (to JP, SMa, CBA). We would like to thank the Local MS Support at Medical Faculty, Lund University. The authors would like to acknowledge support of the National Genomics Infrastructure (NGI)/Uppsala Genome Center and UPPMAX for providing assistance in massive parallel sequencing and computational infrastructure. Work performed at NGI/Uppsala Genome Center has been funded by RFI/VR and Science for Life Laboratory, Sweden Sí

Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer’s disease) mice and found specifically expressed in microglia associated with Aβ plaques. Single-nucleotide polymorphisms in the LGALS3 gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar Aβ. Gal3 deletion decreased the Aβ burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aβ monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aβ aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 carbohydrate recognition domain. Furthermore, gal3 was shown to stimulate TREM2–DAP12 signaling in a reporter cell line. Overall, our data support the view that gal3 inhibition may be a potential pharmacological approach to counteract AD., This work was supported by Grants from the Swedish Research Council, and the Strong Research Environment MultiPark (Multidisciplinary Research in Parkinson’s and Alzheimer’s Disease at Lund University), Bagadilico (Linné consortium sponsored by the Swedish Research Council), the Swedish Alzheimer’s Foundation, Swedish Brain Foundation, A.E. Berger Foundation, Gyllenstiernska Krapperup Foundation, the Royal Physiographic Society, Crafoord Foundation, Olle Engkvist Byggmästare Foundation, Wiberg Foundation, G&J Kock Foundation, Stohnes Foundation, Swedish Dementia Association and the Medical Faculty at Lund University. This work was supported by Grant SAF2015-64171R (Spanish MINECO/FEDER, UE), by Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union through grants PI15/00796 and PI18/01557 (to AG), PI15/00957 and PI18/01556 (to JV), and CIBERNED (to AG and JV), by Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucia Proyecto de Excelencia (CTS-2035) (to JV and AG), and by Malaga University grant PPIT.UMA.B1.2017/26 (to RSV). AV and GCB received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant agreement no. 115976 (PHAGO). CIBERNED “Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid (Spain)”. HL and AF were supported by the Swedish Research Council, the Swedish Brain Foundation, the Alzheimer Foundation and the Åhlén Foundation. UJN was supported by Grants from the Knut and Alice Wallenberg Foundation (KAW 2013.0022) and the Swedish Research Council (Grant no. 621-2012-2978).

Understanding how specific atom sites on metal surfaces lower the energy barrier for chemical reactions is vital in catalysis. Studies on simplified model systems have shown that atoms arranged as steps on the surface play an important role in catalytic reactions, but a direct comparison of how the light-off temperature is affected by the atom orientation on the step has not yet been possible due to methodological constraints. Here we report in situ spatially resolved measurements of the CO production over a cylindrical-shaped Pd catalyst and show that the light-off temperature at different parts of the crystal depends on the step orientation of the two types of steps (named A and B). Our finding is supported by density functional theory calculations, revealing that the steps, in contrast to what has been previously reported in the literature, are not directly involved in the reaction onset but have the role of releasing stress., The authors thank the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Swedish Foundation for Strategic Research, and the Crafoord Foundation. Support by the MAX IV staff is gratefully acknowledged. The calculations were performed at C3SE through a SNIC grant. J.E.O. acknowledges support from the Spanish Ministry of Economy (MAT2013-46593-C6-4-P) and the Basque Government (IT621-13).

Background : The gut microbiota plays an important role in the development of obesity and obesity-associated impairments such as low-grade inflammation. Lingonberries have been shown to prevent diet-induced obesity and low-grade inflammation. However, it is not known whether the effect of lingonberry supplementation is related to modifications of the gut microbiota. The aim of the present study was to describe whether consumption of different batches of lingonberries alters the composition of the gut microbiota, which could be relevant for the protective effect against high fat (HF)-induced metabolic alterations. Methods : Three groups of C57BL/6J mice were fed HF diet with or without a supplement of 20% lingonberries from two different batches (Lingon1 and Lingon2) during 11 weeks. The composition and functionality of the cecal microbiota were assessed by 16S rRNA sequencing and PICRUSt. In addition, parameters related to obesity, insulin sensitivity, hepatic steatosis, inflammation and gut barrier function were examined. Results : HF-induced obesity was only prevented by the Lingon1 diet, whereas both batches of lingonberries reduced plasma levels of markers of inflammation and endotoxemia (SAA and LBP) as well as modified the composition and functionality of the gut microbiota, compared to the HF control group. The relative abundance of Akkermansia and Faecalibacterium , genera associated with healthy gut mucosa and anti-inflammation, was found to increase in response to lingonberry intake. Conclusions : Our results show that supplementation with lingonberries to an HF diet prevents low-grade inflammation and is associated with significant changes of the microbiota composition. Notably, the anti-inflammatory properties of lingonberries seem to be independent of effects on body weight gain. Keywords: obesity; Akkermansia; hepatic steatosis; berries; metabolic endotoxemia; LBP; high-fat diet (Published: 27 April 2016) Citation: Food & Nutrition Research 2016, 60: 29993 - http://dx.doi.org/10.3402/fnr.v60.29993

The Open Cluster Chemical Abundances and Mapping (OCCAM) survey aims to constrain key Galactic dynamical and chemical evolution parameters by the construction of a large, comprehensive, uniform, infrared-based spectroscopic data set of hundreds of open clusters. This fourth contribution from the OCCAM survey presents analysis using Sloan Digital Sky Survey/APOGEE DR16 of a sample of 128 open clusters, 71 of which we designate to be "high quality" based on the appearance of their color-magnitude diagram. We find the APOGEE DR16 derived [Fe/H] abundances to be in good agreement with previous high-resolution spectroscopic open cluster abundance studies. Using the high-quality sample, we measure Galactic abundance gradients in 16 elements, and find evolution of some of the [X/Fe] gradients as a function of age. We find an overall Galactic [Fe/H] versus R gradient of -0.068 ± 0.001 dex kpc over the range of 6 < R < 13.9 kpc; however, we note that this result is sensitive to the distance catalog used, varying as much as 15%. We formally derive the location of a break in the [Fe/H] abundance gradient as a free parameter in the gradient fit for the first time. We also measure significant Galactic gradients in O, Mg, S, Ca, Mn, Cr, Cu, Na, Al, and K, some of which are measured for the first time. Our large sample allows us to examine four well-populated age bins in order to explore the time evolution of gradients for a large number of elements and comment on possible implications for Galactic chemical evolution and radial migration., comments. J.D. and P.M.F. acknowledge support for this research from the National Science Foundation (AST-1311835 & AST-1715662). K.C. acknowledges support for this research from the National Science Foundation (AST-0907873). D.A.G.H. acknowledges support from the State Research Agency (AEI) of the Spanish Ministry of Science, Innovation, and Universities (MCIU), and the European Regional Development Fund (FEDER) under grant AYA2017-88254-P. D.G. and D.M. gratefully acknowledge support from the Chilean Centro de Excelencia en Astrofísica y Tecnologías Afines (CATA) BASAL grant AFB-170002. D.G. also acknowledges financial support from the Dirección de Investigación y Desarrollo de la Universidad de La Serena through the Programa de Incentivo a la Investigación de Académicos (PIA-DIDULS). D.M. is also supported by the Programa Iniciativa Científica Milenio grant IC120009, awarded to the Millennium Institute of Astrophysics (MAS), and by Proyecto FONDECYT regular No. 1170121. H.J. acknowledges support from the Crafoord Foundation, Stiftelsen Olle Engkvist Byggmästare, and Ruth och Nils-Erik Stenbäcks stiftelse. A.R.-L. acknowledges financial support provided in Chile by Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) through the FONDECYT project 1170476 and by the QUIMAL project 130001 Funding for SDSS-III has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, and the U.S. Department of Energy Office of Science. The SDSS-III website is http://www.sdss3.org/. SDSS-III is managed by the Astrophysical Research Consortium for the Participating Institutions of the SDSS-III Collaboration including the University of Arizona, the Brazilian Participation Group, Brookhaven National Laboratory, Carnegie Mellon University, University of Florida, the French Participation Group, the German Participation Group, Harvard University, the Instituto de Astrofisica de Canarias, the Michigan State/Notre Dame/JINA Participation Group, Johns Hopkins University, Lawrence Berkeley National Laboratory, Max Planck Institute for Astrophysics, Max Planck Institute for Extraterrestrial Physics, New Mexico State University, New York University, Ohio State University, Pennsylvania State University, University of Portsmouth, Princeton University, the Spanish Participation Group, University of Tokyo, University of Utah, Vanderbilt University, University of Virginia, University of Washington, and Yale University. Funding for the Sloan Digital Sky Survey IV has been provided by the Alfred P. Sloan Foundation, the U.S. Department of Energy Office of Science, and the Participating Institutions. SDSS-IV acknowledges support and resources from the Center for High-Performance Computing at the University of Utah. The SDSS website is www.sdss.org.

International audience; AIMS: Exaggerated hepatic glucose production is one of the hallmarks of type 2 diabetes. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound. However, the effects of SFN in hepatocytes are yet unclear. Accumulating evidence points to the close structural contacts between the ER and mitochondria, known as mitochondria-associated ER membranes (MAMs), as important hubs for hepatic metabolism. We wanted to investigate whether SFN could affect hepatic glucose production and MAMs. MATERIALS AND METHODS: We used proximity ligation assays, analysis of ER stress markers and glucose production assays in hepatoma cell lines, primary mouse hepatocytes and diabetic animal models. RESULTS: SFN counteracted the increase of glucose production in palmitate-treated mouse hepatocytes. SFN also counteracted palmitate-induced MAM disruptions. Moreover, SFN decreased the ER stress markers CHOP and Grp78. In ob/ob mice, SFN improved glucose tolerance and reduced exaggerated glucose production. In livers of these mice, SFN increased MAM protein content, restored impaired VDAC1-IP3R1 interactions and reduced ER stress markers. In mice on HFHSD, SFN improved glucose tolerance, MAM protein content and ER-mitochondria interactions to a similar extent to that of metformin. CONCLUSIONS: The present findings show that MAMs are severely reduced in animal models of glucose intolerance, which reinforces the role of MAMs as a hub for insulin signaling in the liver. We also show that SFN restores MAMs and improves glucose tolerance by a similar magnitude to that of metformin. These data highlight SFN as a new potential anti-diabetic compound.

Background Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death and promotes functional recovery after stroke. However, the core actions of endogenous IFN-β signaling in stroke are unclear. Methods To address this question, we used two clinically relevant models of focal cerebral ischemia, transient and permanent middle cerebral artery occlusion, and two genetically modified mouse lines, lacking either IFN-β or its receptor, the IFN-α/β receptor. Subsets of inflammatory and immune cells isolated from the brain, blood, and spleen were studied using flow cytometry. Sensorimotor deficits were assessed by a modified composite neuroscore, the rotating pole and grip strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. Results Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation of circulating cytokines and splenic immune cell populations in wild-type and IFN-βKO mice further supports an important immunoregulatory function of IFN-β in stroke. Moreover, we observed a significant weight loss 2–3 days and a reduction in grip strength 2 days after stroke in the IFN-βKO group, while endogenous IFN-β signaling did not affect the infarct volume. Conclusions We conclude that endogenous IFN-β signaling attenuates local inflammation, regulates peripheral immune cells, and, thereby, may contribute positively to stroke outcome. Electronic supplementary material The online version of this article (doi:10.1186/s12974-015-0427-0) contains supplementary material, which is available to authorized users.

16 pages, 5 figures, 3 tables, 1 appendix, Parasites exert important top-down control of their host populations. The host-parasite system formed by Alexandrium minutum (Dinophyceae) and Parvilucifera sinerae (Perkinsozoa) offers an opportunity to advance our knowledge of parasitism in planktonic communities. In this study, DNA extracted from 73 clonal strains of P. sinerae, from 10 different locations along the Atlantic and Mediterranean coasts, was used to genetically characterize this parasitoid at the species level. All strains showed identical sequences of the small and large subunits and internal transcribed spacer of the ribosomal RNA, as well as of the β-tubulin genes. However, the phenotypical characterization showed variability in terms of host invasion, zoospore success, maturation time, half-maximal infection, and infection rate. This characterization grouped the strains within 3 phenotypic types distinguished by virulence traits. A particular virulence pattern could not be ascribed to host-cell bloom appearance or to the location or year of parasite-strain isolation; rather, some parasitoid strains from the same bloom significantly differed in their virulence traits. Identical markers such as ITS and β-tubulin genes of P. sinerae strains from different geographic areas and from different years precludes their use in assessing intra-specific diversity and could indicate a recent dispersion of this species, This study was supported by the Spanish Ministry of Science and Innovation through the project PARAL (CTM2009-08399). [...] R.I.F. was funded by the Crafoord Foundation (Sweden, contract 2011:0882)

Background : Interstitial lung disease often occurs as an early complication of systemic sclerosis (SSc). The aim was to investigate whether impulse oscillometry (IOS) could be used to evaluate lung impairment in SSc. Methods : Seventy-eight SSc patients, of which 65 had limited cutaneous SSc (lcSSc) and 13 had diffuse cutaneous SSc (dcSSc), were subjected to high-resolution computed tomography (HRCT) and pulmonary function tests (spirometry, IOS, and single breath CO diffusion capacity test). Twenty-six healthy individuals served as controls. Results : Patients with lcSSc had higher levels of peripheral airway resistance, that is, R5–R20 (difference between resistance at 5 Hz and resistance at 20 Hz) showed a median (and interquartile range) of 0.05 (0.02–0.09) in lcSSc, 0.01 (0.00–0.04) in dcSSc and 0.04 (0.01–0.06) in healthy controls. They also had higher levels of reactance: reactance area was 0.26 (0.15–0.56) in lcSSc, 0.20 (0.11–0.29) in dcSSc and 0.18 (0.08–0.30) in healthy controls, and resonant frequency was 10.9 (8.8–14.8) in lcSSc, 9.0 (8.3–11.6) in dcSSc and 9.1 (8.0–13.1) in healthy controls. Airway reactance correlated to fibrotic findings on HRCT, such as ground glass opacities and reticulations. Discussion : This implies that IOS parameters to some extent are related to fibrosis in patients with SSc. Keywords: fibrosis; impulse oscillometry; reactance; resistance; systemic sclerosis (Published: 21 October 2015) Citation: European Clinical Respiratory Journal 2015, 2: 28667 - http://dx.doi.org/10.3402/ecrj.v2.28667

et al., [Objective]: Actin dynamics in vascular smooth muscle is known to regulate contractile differentiation and may play a role in the pathogenesis of vascular disease. However, the list of genes regulated by actin polymerization in smooth muscle remains incomprehensive. Thus, the objective of this study was to identify actin-regulated genes in smooth muscle and to demonstrate the role of these genes in the regulation of vascular smooth muscle phenotype. [Approach and Results]: Mouse aortic smooth muscle cells were treated with an actin-stabilizing agent, jasplakinolide, and analyzed by microarrays. Several transcripts were upregulated including both known and previously unknown actin-regulated genes. Dystrophin and synaptopodin 2 were selected for further analysis in models of phenotypic modulation and vascular disease. These genes were highly expressed in differentiated versus synthetic smooth muscle and their expression was promoted by the transcription factors myocardin and myocardin-related transcription factor A. Furthermore, the expression of both synaptopodin 2 and dystrophin was significantly reduced in balloon-injured human arteries. Finally, using a dystrophin mutant mdx mouse and synaptopodin 2 knockdown, we demonstrate that these genes are involved in the regulation of smooth muscle differentiation and function. [Conclusions]: This study demonstrates novel genes that are promoted by actin polymerization, that regulate smooth muscle function, and that are deregulated in models of vascular disease. Thus, targeting actin polymerization or the genes controlled in this manner can lead to novel therapeutic options against vascular pathologies that involve phenotypic modulation of smooth muscle cells., This work was supported by the Swedish Research Council; the Swedish Heart and Lung Foundation, the Crafoord Foundation; the Royal Physiographic Society; the Per-Eric and Ulla Schyberg Foundation; the Åke Wiberg Foundation; the Jeansson Foundation; the Tore Nilson Foundation; the Greta and Johan Kock Foundation; the Magnus Bergvall Foundation, the Zoegas foundation and the Lars Hierta Memorial Foundation. K.M. Turczyńska was in part supported by the European Union FP7 Marie Curie Initial Training Network Small Artery Remodeling (SmArt). M.T. Pérez-García was supported by grants from the Instituto de Salud Carlos III (ISCIII-FEDER RD12/0042/0006 (Heracles Program) and Spanish MINECO grant BFU2010-15898 (M.T. Pérez-García) and BFU2013-45867-R.