Multifunctional Eu-doped NaGd(MoO4)(2) nanoparticles functionalized with poly(L-lysine) for optical and MRI imaging

A method for the synthesis of non-aggregated and highly uniform Eu3+ doped NaGd(MoO4)(2) nanoparticles is reported for the first time. The obtained particles present tetragonal structure, ellipsoidal shape and their size can be varied by adjusting the experimental synthesis parameters. These nanoparticles, which were coated with citrate anions and functionalised with PLL, have also been developed in order to improve their colloidal stability in physiological medium (2-(N-morpholino) ethanesulfonic acid, MES). A study of the luminescent dynamics of the samples as a function of the Eu doping level has been conducted in order to find the optimum nanophosphors, whose magnetic relaxivity and cell viability have also been evaluated for the first time for this system, in order to assess their suitability as multifunctional probes for optical (in vitro) and magnetic bioimaging applications

Divergent genomic trajectories predate the origin of animals and fungi

22 pages, 4 figures, supplementary information https://doi.org/10.1038/s41586-022-05110-4.-- Data availability: The raw sequence data and assembled genomes generated in this study have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB52884 (https://www.ebi.ac.uk/ena/browser/view/PRJEB52884). The genome assemblies are also available in figshare (https://doi.org/10.6084/m9.figshare.19895962.v1). Protein sequences of the species used in this study were downloaded from the GenBank public databases (https://www.ncbi.nlm.nih.gov/protein/), Uniprot (https://www.uniprot.org/), JGI genome database (https://genome.jgi.doe.gov/portal/) and Ensembl genomes (https://www.ensembl.org). The following specific databases were also used in this study: Pfam A v29 (https://pfam.xfam.org/), EggNOG emapperdb-4.5.1 (http://eggnog5.embl.de) and UniProt reference proteomes release 2016_02 (https://www.uniprot.org/). The supporting data files of this study are available in the following repository: https://doi.org/10.6084/m9.figshare.13140191.v1.-- Code availability: The most relevant custom code developed for this study (the MAPBOS pipeline and the machine learning classifiers) is available at https://doi.org/10.5281/zenodo.6586559Animals and fungi have radically distinct morphologies, yet both evolved within the same eukaryotic supergroup: Opisthokonta1,2. Here we reconstructed the trajectory of genetic changes that accompanied the origin of Metazoa and Fungi since the divergence of Opisthokonta with a dataset that includes four novel genomes from crucial positions in the Opisthokonta phylogeny. We show that animals arose only after the accumulation of genes functionally important for their multicellularity, a tendency that began in the pre-metazoan ancestors and later accelerated in the metazoan root. By contrast, the pre-fungal ancestors experienced net losses of most functional categories, including those gained in the path to Metazoa. On a broad-scale functional level, fungal genomes contain a higher proportion of metabolic genes and diverged less from the last common ancestor of Opisthokonta than did the gene repertoires of Metazoa. Metazoa and Fungi also show differences regarding gene gain mechanisms. Gene fusions are more prevalent in Metazoa, whereas a larger fraction of gene gains were detected as horizontal gene transfers in Fungi and protists, in agreement with the long-standing idea that transfers would be less relevant in Metazoa due to germline isolation3,4,5. Together, our results indicate that animals and fungi evolved under two contrasting trajectories of genetic change that predated the origin of both groups. The gradual establishment of two clearly differentiated genomic contexts thus set the stage for the emergence of Metazoa and FungiE.O.-P. was supported by a predoctoral FPI grant from MINECO (BES-2015-072241) and by ESF Investing in your future. E.O.-P., D.L-E., A.S.A. and I.R.-T. received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7-2007-2013) (Grant agreement No. 616960) and also from grants (BFU2014-57779-P and PID2020-120609GB-I00) by MCIN/AEI/10.13039/501100011033 and ‘ERDF A way of making Europe’. E.O.-P. and G.J.Sz. received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 714774). T.A.W. was supported by a Royal Society University Research Fellowship (URF\R\201024) and NERC standard grant NE/P00251X/1. This work was supported by the Gordon and Betty Moore Foundation through grant GBMF9741 to T.A.W. and G.J.Sz. J.S.P. and E.B. received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7-2007-2013) (Grant agreement No. 615274). D.V.T. and cell culturing were supported by the Russian Science Foundation grant no. 18-14-00239, https://rscf.ru/project/18-14-00239/. Culture of P. vietnamica was obtained as the result of field work in Vietnam as part of the project ‘Ecolan 3.2’ of the Russian–Vietnam Tropical Center. P.J.K. is supported by an Investigator Award from the Gordon and Betty Moore Foundation (https://doi.org/10.37807/GBMF9201)With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)Peer reviewe

Hodgkin's lymphoma masquerading as vertebral osteomyelitis in a man with diabetes: a case report

<p>Abstract</p> <p>Introduction</p> <p>Infection and malignancy often have common characteristics which render the differential diagnosis for a prolonged fever difficult. Imaging and tissue biopsy are crucial in making a correct diagnosis, though differentiating between chronic osteomyelitis and malignancy is not always straightforward as they possess many overlapping features.</p> <p>Case Presentation</p> <p>A 52-year-old Caucasian man was treated with antibiotics for his diabetic foot infection after a superficial culture showed <it>Staphylococcus aureus</it>. He had persistent fevers for several weeks and later developed acute onset of back pain which was treated with several courses of antibiotics. Radiographic and pathological findings were atypical, and a diagnosis of Hodgkin's lymphoma was made 12 weeks later.</p> <p>Conclusion</p> <p>Clinicians should maintain a suspicion for Hodgkin's lymphoma or other occult malignancy when features of presumed osteomyelitis are atypical. Chronic vertebral osteomyelitis in particular often lacks features common to acute infectious disease processes, and the chronic lymphocytic infiltrates seen on histopathology have very similar features to Hodgkin's lymphoma, highlighting a similar inflammatory microenvironment sustained by both processes.</p

Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype

Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions

Molecular Analysis of Serum and Bronchoalveolar Lavage in a Mouse Model of Influenza Reveals Markers of Disease Severity That Can Be Clinically Useful in Humans

Background: Management of influenza, a major contributor to the worldwide disease burden, is complicated by lack of reliable methods for early identification of susceptible individuals. Identification of molecular markers that can augment existing diagnostic tools for prediction of severity can be expected to greatly improve disease management capabilities. Methodology/Principal Findings: We have analyzed cytokines, proteome flux and protein adducts in bronchoalveolar lavage (BAL) and sera from mice infected with influenza A virus (PR8 strain) using a previously established non-lethal model of influenza infection. Through detailed cytokine and protein adduct measurements of murine BAL, we first established the temporal profile of innate and adaptive responses as well as macrophage and neutrophil activities in response to influenza infection. A similar analysis was also performed with sera from a longitudinal cohort of influenza patients. We then used an iTRAQ-based, comparative serum proteome analysis to catalog the proteome flux in the murine BAL during the stages correlating with “peak viremia,” “inflammatory damage,” as well as the “recovery phase.” In addition to activation of acute phase responses, a distinct class of lung proteins including surfactant proteins was found to be depleted from the BAL coincident with their “appearance” in the serum, presumably due to leakage of the protein following loss of the integrity of the lung/epithelial barrier. Serum levels of at least two of these proteins were elevated in influenza patients during the febrile phase of infection compared to healthy controls or to the same patients at convalescence. Conclusions/Significance: The findings from this study provide a molecular description of disease progression in a mouse model of influenza and demonstrate its potential for translation into a novel class of markers for measurement of acute lung injury and improved case management.Singapore. National Research FoundationSingapore-MIT Alliance for Research and Technology (ID-IRG research program

Ecological association between a deprivation index and mortality in France over the period 1997 – 2001: variations with spatial scale, degree of urbanicity, age, gender and cause of death

<p>Abstract</p> <p>Background</p> <p>Spatial health inequalities have often been analysed in terms of deprivation. The aim of this study was to create an ecological deprivation index and evaluate its association with mortality over the entire mainland France territory. More specifically, the variations with the degree of urbanicity, spatial scale, age, gender and cause of death, which influence the association between mortality and deprivation, have been described.</p> <p>Methods</p> <p>The deprivation index, 'FDep99', was developed at the '<it>commune</it>'(smallest administrative unit in France) level as the first component of a principal component analysis of four socioeconomic variables.</p> <p>Proxies of the Carstairs and Townsend indices were calculated for comparison.</p> <p>The spatial association between FDep99 and mortality was studied using five different spatial scales, and by degree of urbanicity (five urban unit categories), age, gender and cause of death, over the period 1997–2001.</p> <p>'Avoidable' causes of death were also considered for subjects aged less than 65 years. They were defined as causes related to risk behaviour and primary prevention (alcohol, smoking, accidents).</p> <p>Results</p> <p>The association between the FDep99 index and mortality was positive and quasi-log-linear, for all geographic scales. The standardized mortality ratio (SMR) was 24% higher for the <it>communes </it>of the most deprived quintile than for those of the least deprived quintile. The between-urban unit category and between-<it>région </it>heterogeneities of the log-linear associations were not statistically significant. The association was positive for all the categories studied and was significantly greater for subjects aged less than 65 years, for men, and for 'avoidable' mortality.</p> <p>The amplitude and regularity of the associations between mortality and the Townsend and Carstairs indices were lower.</p> <p>Conclusion</p> <p>The deprivation index proposed reflects a major part of spatial socioeconomic heterogeneity, in a homogeneous manner over the whole country. The index may be routinely used by healthcare authorities to observe, analyse, and manage spatial health inequalities.</p

Ecological factors related to the widespread distribution of sylvatic Rhodnius ecuadoriensis populations in southern Ecuador

<p>Abstract</p> <p>Background</p> <p>Chagas disease transmission risk is a function of the presence of triatomines in domestic habitats. <it>Rhodnius ecuadoriensis </it>is one of the main vectors implicated in transmission of <it>Trypanosoma cruzi </it>in Ecuador. This triatomine species is present in domestic, peridomestic and sylvatic habitats in the country. To determine the distribution of sylvatic populations of <it>R. ecuadoriensis </it>and the factors related to this distribution, triatomine searches were conducted between 2005 and 2009 in southern Ecuador.</p> <p>Methods</p> <p>Manual triatomine searches were conducted by skilled bug collectors in 23 communities. Sylvatic searched sites were selected by a) directed sampling, where microhabitats were selected by the searchers and b) random sampling, where sampling points where randomly generated. Domiciliary triatomine searches were conducted using the one man-hour method. Natural trypanosome infection was determined by microscopic examination and PCR. Generalized linear models were used to test the effect of environmental factors on the presence of sylvatic triatomines.</p> <p>Results</p> <p>In total, 1,923 sylvatic individuals were collected representing a sampling effort of 751 man-hours. Collected sylvatic triatomines were associated with mammal and bird nests. The 1,219 sampled nests presented an infestation index of 11.9%, a crowding of 13 bugs per infested nest, and a colonization of 80% of the nests. Triatomine abundance was significantly higher in squirrel (<it>Sciurus stramineus</it>) nests located above five meters from ground level and close to the houses. In addition, 8.5% of the 820 examined houses in the same localities were infested with triatomines. There was a significant correlation between <it>R. ecuadoriensis </it>infestation rates found in sylvatic and synanthropic environments within communities (<it>p </it>= 0.012). Parasitological analysis revealed that 64.7% and 15.7% of the sylvatic bugs examined (n = 300) were infected with <it>Trypanosoma cruzi </it>and <it>T. rangeli </it>respectively, and 8% of the bugs presented mixed infections.</p> <p>Conclusions</p> <p>The wide distribution of sylvatic <it>R. ecuadoriensis </it>populations may jeopardize the effectiveness of control campaigns conducted to eliminate domestic populations of this species. Also, the high <it>T. cruzi </it>infection rates found in sylvatic <it>R. ecuadoriensis </it>populations in southern Ecuador could constitute a risk for house re-infestation and persistent long-term Chagas disease transmission in the region.</p

Multiorgan Metastasis of Human HER-2+ Breast Cancer in Rag2−/−;Il2rg−/− Mice and Treatment with PI3K Inhibitor

In vivo studies of the metastatic process are severely hampered by the fact that most human tumor cell lines derived from highly metastatic tumors fail to consistently metastasize in immunodeficient mice like nude mice. We describe a model system based on a highly immunodeficient double knockout mouse, Rag2−/−;Il2rg−/−, which lacks T, B and NK cell activity. In this model human metastatic HER-2+ breast cancer cells displayed their full multiorgan metastatic potential, without the need for selections or additional manipulations of the system. Human HER-2+ breast cancer cell lines MDA-MB-453 and BT-474 injected into Rag2−/−;Il2rg−/− mice faithfully reproduced human cancer dissemination, with multiple metastatic sites that included lungs, bones, brain, liver, ovaries, and others. Multiorgan metastatic spread was obtained both from local tumors, growing orthotopically or subcutaneously, and from cells injected intravenously. The problem of brain recurrencies is acutely felt in HER-2+ breast cancer, because monoclonal antibodies against HER-2 penetrate poorly the blood-brain barrier. We studied whether a novel oral small molecule inhibitor of downstream PI3K, selected for its penetration of the blood-brain barrier, could affect multiorgan metastatic spread in Rag2−/−; Il2rg−/− mice. NVP-BKM120 effectively controlled metastatic growth in multiple organs, and resulted in a significant proportion of mice free from brain and bone metastases. Human HER-2+ human breast cancer cells in Rag2−/−;Il2rg−/− mice faithfully reproduced the multiorgan metastatic pattern observed in patients, thus allowing the investigation of metastatic mechanisms and the preclinical study of novel antimetastatic agents