Knockout of the Glucocorticoid Receptor Impairs Reproduction in Female Zebrafish

none8The pleiotropic effects of glucocorticoids in metabolic, developmental, immune and stress response processes have been extensively investigated; conversely, their roles in reproduction are still less documented. It is well known that stress or long-lasting therapies can cause a strong increase in these hormones, negatively affecting reproduction. Moreover, the need of glucocorticoid (GC) homeostatic levels is highlighted by the reduced fertility reported in the zebrafish glucocorticoid receptor mutant (nr3c1ia30/ia30) line (hereafter named gr-/-). Starting from such evidence, in this study, we have investigated the role of glucocorticoid receptor (Gr) in the reproduction of female zebrafish. Key signals orchestrating the reproductive process at the brain, liver, and ovarian levels were analyzed using a multidisciplinary approach. An impairment of the kiss-GnRH system was observed at the central level in (gr-/-) mutants as compared to wild-type (wt) females while, in the liver, vitellogenin (vtg) mRNA transcription was not affected. Changes were instead observed in the ovary, particularly in maturing and fully grown follicles (classes III and IV), as documented by the mRNA levels of signals involved in oocyte maturation and ovulation. Follicles isolated from gr-/- females displayed a decreased level of signals involved in the acquisition of competence and maturation, causing a reduction in ovulation with respect to wt females. Fourier transform infrared imaging (FTIRI) analysis of gr-/- follicle cytoplasm showed major changes in macromolecule abundance and distribution with a clear alteration of oocyte composition. Finally, differences in the molecular structure of the zona radiata layer of gr-/- follicles are likely to contribute to the reduced fertilization rate observed in mutants.openMaradonna, Francesca; Gioacchini, Giorgia; Notarstefano, Valentina; Fontana, Camilla Maria; Citton, Filippo; Dalla Valle, Luisa; Giorgini, Elisabetta; Carnevali, OlianaMaradonna, Francesca; Gioacchini, Giorgia; Notarstefano, Valentina; Fontana, Camilla Maria; Citton, Filippo; Dalla Valle, Luisa; Giorgini, Elisabetta; Carnevali, Olian

Sex dimorphism in the myocardial response to aortic stenosis

Objectives: The goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers. Background: AS is a disease of both valve and left ventricle (LV). Sex differences in LV remodeling are reported in AS and may play a role in disease phenotyping. Methods: This study was a prospective assessment of patients awaiting surgical valve replacement for severe AS using echocardiography, the 6-min walking test, biomarkers (high-sensitivity troponin T and N-terminal pro-brain natriuretic peptide), and CMR with late gadolinium enhancement and extracellular volume fraction, which dichotomizes the myocardium into matrix and cell volumes. LV remodeling was categorized into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy

DOPAL initiates αSynuclein-dependent impaired proteostasis and degeneration of neuronal projections in Parkinson’s disease

Dopamine dyshomeostasis has been acknowledged among the determinants of nigrostriatal neuron degeneration in Parkinson’s disease (PD). Several studies in experimental models and postmortem PD patients underlined increasing levels of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL has been shown to covalently modify the presynaptic protein αSynuclein (αSyn), whose misfolding and aggregation represent a major trait of PD pathology, triggering αSyn oligomerization in dopaminergic neurons. Here, we demonstrated that DOPAL elicits αSyn accumulation and hampers αSyn clearance in primary neurons. DOPAL-induced αSyn buildup lessens neuronal resilience, compromises synaptic integrity, and overwhelms protein quality control pathways in neurites. The progressive decline of neuronal homeostasis further leads to dopaminergic neuron loss and motor impairment, as showed in in vivo models. Finally, we developed a specific antibody which detected increased DOPAL-modified αSyn in human striatal tissues from idiopathic PD patients, corroborating the translational relevance of αSyn-DOPAL interplay in PD neurodegeneration

Investigation of the molecular mechanisms which contribute to the survival of the polychaete Platynereis spp. under ocean acidification conditions in the CO2 vent system of Ischia Island (Italy)

The continuous increase of CO2 emissions in the atmosphere due to anthropogenic activities is one of the most important factors that contribute to Climate Change and generates the phenomenon known as Ocean Acidification (OA). Research conducted at the CO2 vents of Castello Aragonese (Ischia, Italy), which represents a natural laboratory for the study of OA, demonstrated that some organisms, such as polychaetes, thrive under acidified conditions through different adaptation mechanisms. Some functional and ecological traits promoting tolerance to acidification in these organisms have been identified, while the molecular and physiological mechanisms underlying acclimatisation or genetic adaptation are still largely unknown. Therefore, in this study we investigated epigenetic traits, as histone acetylation and methylation, in Platynereis spp. individuals coming from the Castello vent, and from a nearby control site, in two different periods of the year (November-June). Untargeted metabolomics analysis was also carried out in specimens from the two sites. We found a different profile of acetylation of H2B histone in the control site compared to the vent as a function of the sampling period. Metabolomic analysis showed clear separation in the pattern of metabolites in polychaetes from the control site with respect to those from the Castello vent. Specifically, a significant reduction of lipid/sterols and nucleosides was measured in polychaetes from the vent. Overall results contribute to better understand the potential metabolic pathways involved in the tolerance to OA

Optimized Photometric Redshifts for the Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey (CANDELS)

We present the first comprehensive release of photometric redshifts (photo-z's) from the Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey (CANDELS) team. We use statistics based upon the Quantile-Quantile (Q--Q) plot to identify biases and signatures of underestimated or overestimated errors in photo-z probability density functions (PDFs) produced by six groups in the collaboration; correcting for these effects makes the resulting PDFs better match the statistical definition of a PDF. After correcting each group's PDF, we explore three methods of combining the different groups' PDFs for a given object into a consensus curve. Two of these methods are based on identifying the minimum f-divergence curve, i.e., the PDF that is closest in aggregate to the other PDFs in a set (analogous to the median of an array of numbers). We demonstrate that these techniques yield improved results using sets of spectroscopic redshifts independent of those used to optimize PDF modifications. The best photo-z PDFs and point estimates are achieved with the minimum f-divergence using the best 4 PDFs for each object (mFDa4) and the Hierarchical Bayesian (HB4) methods, respectively. The HB4 photo-z point estimates produced $\sigma_{\rm NMAD} = 0.0227/0.0189$ and $|\Delta z/(1+z)| > 0.15$ outlier fraction = 0.067/0.019 for spectroscopic and 3D-HST redshifts, respectively. Finally, we describe the structure and provide guidance for the use of the CANDELS photo-z catalogs, which are available at https://archive.stsci.edu/hlsp/candels.Comment: 35 pages, 19 figures, submitted to ApJ, data available at https://archive.stsci.edu/hlsp/candel

Optimized Photometric Redshifts for the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS)

We present the first comprehensive release of photometric redshifts (photo- z's) from the Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey (CANDELS) team. We use statistics based upon the Quantile-Quantile (Q-Q) plot to identify biases and signatures of underestimated or overestimated errors in photo- z probability density functions (PDFs) produced by six groups in the collaboration; correcting for these effects makes the resulting PDFs better match the statistical definition of a PDF. After correcting each group’s PDF, we explore three methods of combining the different groups’ PDFs for a given object into a consensus curve. Two of these methods are based on identifying the minimum f-divergence curve, i.e., the PDF that is closest in aggregate to the other PDFs in a set (analogous to the median of an array of numbers). We demonstrate that these techniques yield improved results using sets of spectroscopic redshifts independent of those used to optimize PDF modifications. The best photo- z PDFs and point estimates are achieved with the minimum f-divergence using the best four PDFs for each object (mFDa4) and the hierarchical Bayesian (HB4) methods, respectively. The HB4 photo- z point estimates produced σ NMAD = 0.0227/0.0189 and ∣Δz/(1 + z)∣ &gt; 0.15 outlier fraction = 0.067/0.019 for spectroscopic and 3D Hubble Space Telescope redshifts, respectively. Finally, we describe the structure and provide guidance for the use of the CANDELS photo- z catalogs, which are available at https://archive.stsci.edu/prepds/candels/.</p

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London