PTX3 Intercepts Vascular Inflammation in Systemic Immune-Mediated Diseases

PTX3 is a prototypic soluble pattern recognition receptor, expressed at sites of inflammation and involved in regulation of the tissue homeostasis. PTX3 systemic levels increase in many (but not all) immune-mediated inflammatory conditions. Research on PTX3 as a biomarker has so far focused on single diseases. Here, we performed a multi-group comparative study with the aim of identifying clinical and pathophysiological phenotypes associated with PTX3 release. PTX3 concentration was measured by ELISA in the plasma of 366 subjects, including 96 patients with giant cell arteritis (GCA), 42 with Takayasu's arteritis (TA), 10 with polymyalgia rheumatica (PMR), 63 with ANCA-associated systemic small vessel vasculitides (AAV), 55 with systemic lupus erythematosus (SLE), 21 with rheumatoid arthritis (RA) and 79 healthy controls (HC). Patients with SLE, AAV, TA and GCA, but not patients with RA and PMR, had higher PTX3 levels than HC. PTX3 concentration correlated with disease activity, acute phase reactants and prednisone dose. It was higher in females, in patients with recent-onset disease and in those with previous or current active vasculitis at univariate analysis. Active small- or large- vessel vasculitis were the main independent variables influencing PTX3 levels at multivariate analysis. High levels of PTX3 in the blood can contribute to identify an increased risk of vascular involvement in patients with systemic immune-mediated diseases

Sensitivity of the Mott Transition to Non-cubic Splitting of the Orbital Degeneracy: Application to NH3 K3C60

Within dynamical mean-field theory, we study the metal-insulator transition of a twofold orbitally degenerate Hubbard model as a function of a splitting \Delta of the degeneracy. The phase diagram in the U-\Delta plane exhibits two-band and one-band metals, as well as the Mott insulator. The correlated two-band metal is easily driven to the insulator state by a strikingly weak splitting \Delta << W of the order of the Kondo-peak width zW, where z << 1 is the metal quasiparticle weight. The possible relevance of this result to the insulator-metal transition in the orthorhombic expanded fulleride NH3 K3C60 is discussed.Comment: revtex, 15 pages including 6 ps figures. Submitted to Phys. Rev.

Associations Between Social Capital and Depressive Symptoms Among College Students in 12 Countries: Results of a Cross-National Study

Backhaus I, Ramirez Varela A, Khoo S, et al. Associations Between Social Capital and Depressive Symptoms Among College Students in 12 Countries: Results of a Cross-National Study. Frontiers in Psychology. 2020;11: 644.Introduction: A mental health crisis has hit university campuses across the world. This study sought to determine the prevalence and social determinants of depressive symptoms among university students in twelve countries. Particular focus was placed on the association between social capital and depressive symptoms. Methods: A cross-sectional study was conducted among students at their first year at university in Europe, Asia, the Western Pacific, and Latin and North America. Data were obtained through a self-administered questionnaire, including questions on sociodemographic characteristics, depressive symptoms, and social capital. The simplified Beck’s Depression Inventory was used to measure the severity of depressive symptoms. Social capital was assessed using items drawn from the World Bank Integrated Questionnaire to Measure Social Capital. Multilevel analyses were conducted to determine the relationship between social capital and depressive symptoms, adjusting for individual covariates (e.g., perceived stress) and country-level characteristics (e.g., economic development). Results: Among 4228 students, 48% presented clinically relevant depressive symptoms. Lower levels of cognitive (OR: 1.82, 95% CI: 1.44–2.29) and behavioral social capital (OR: 1.51, 95% CI: 1.29–1.76) were significantly associated with depressive symptoms. The likelihood of having depressive symptoms was also significantly higher among those living in regions with lower levels of social capital. Conclusion: The study demonstrates that lower levels of individual and macro-level social capital contribute to clinically relevant depressive symptoms among university students. Increasing social capital may mitigate depressive symptoms in college students

ANCA-associated vasculitis in childhood: Recent advances

Abstract Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare systemic diseases that usually occur in adulthood. They comprise granulomatosis with polyangiitis (GPA, Wegener’s), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Their clinical presentation is often heterogeneous, with frequent involvement of the respiratory tract, the kidney, the skin and the joints. ANCA-associated vasculitis is rare in childhood but North-American and European cohort studies performed during the last decade have clarified their phenotype, patterns of renal involvement and their prognostic implications, and outcome. Herein, we review the main clinical and therapeutic aspects of childhood-onset ANCA-associated vasculitis, and provide preliminary data on demographic characteristics and organ manifestations of an Italian multicentre cohort

Technical challenges of working with extracellular vesicles

Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review

Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+\u2009ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+\u2009ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA

Identification of SNP and SSR markers in eggplant using RAD tag sequencing

<p>Abstract</p> <p>Background</p> <p>The eggplant (<it>Solanum melongena </it>L.) genome is relatively unexplored, especially compared to those of the other major <it>Solanaceae </it>crops tomato and potato. In particular, no SNP markers are publicly available; on the other hand, over 1,000 SSR markers were developed and publicly available. We have combined the recently developed Restriction-site Associated DNA (RAD) approach with Illumina DNA sequencing for rapid and mass discovery of both SNP and SSR markers for eggplant.</p> <p>Results</p> <p>RAD tags were generated from the genomic DNA of a pair of eggplant mapping parents, and sequenced to produce ~17.5 Mb of sequences arrangeable into ~78,000 contigs. The resulting non-redundant genomic sequence dataset consisted of ~45,000 sequences, of which ~29% were putative coding sequences and ~70% were in common between the mapping parents. The shared sequences allowed the discovery of ~10,000 SNPs and nearly 1,000 indels, equivalent to a SNP frequency of 0.8 per Kb and an indel frequency of 0.07 per Kb. Over 2,000 of the SNPs are likely to be mappable via the Illumina GoldenGate assay. A subset of 384 SNPs was used to successfully fingerprint a panel of eggplant germplasm, producing a set of informative diversity data. The RAD sequences also included nearly 2,000 putative SSRs, and primer pairs were designed to amplify 1,155 loci.</p> <p>Conclusion</p> <p>The high throughput sequencing of the RAD tags allowed the discovery of a large number of DNA markers, which will prove useful for extending our current knowledge of the genome organization of eggplant, for assisting in marker-aided selection and for carrying out comparative genomic analyses within the <it>Solanaceae </it>family.</p

The World Spider Trait database: a centralized global open repository for curated data on spider traits

Spiders are a highly diversified group of arthropods and play an important role in terrestrial ecosystems as ubiquitous predators, which makes them a suitable group to test a variety of eco-evolutionary hypotheses. For this purpose, knowledge of a diverse range of species traits is required. Until now, data on spider traits have been scattered across thousands of publications produced for over two centuries and written in diverse languages. To facilitate access to such data, we developed an online database for archiving and accessing spider traits at a global scale. The database has been designed to accommodate a great variety of traits (e.g. ecological, behavioural and morphological) measured at individual, species or higher taxonomic levels. Records are accompanied by extensive metadata (e.g. location and method). The database is curated by an expert team, regularly updated and open to any user. A future goal of the growing database is to include all published and unpublished data on spider traits provided by experts worldwide and to facilitate broad cross-taxon assays in functional ecology and comparative biology.Fil: Pekár, Stano. Masaryk University; República ChecaFil: Wolff, Jonas O. University of Greifswald; AlemaniaFil: Cernecká, L'udmila. Slovak Academy of Sciences; ArgentinaFil: Birkhofer, Klaus. Brandenburgische Technische Universität Cottbus; AlemaniaFil: Mammola, Stefano. University of Helsinki; FinlandiaFil: Lowe, Elizabeth C.. Macquarie University; AustraliaFil: Fukushima, Caroline S.. University of Helsinki; FinlandiaFil: Herberstein, Marie E.. Macquarie University; AustraliaFil: Kucera, Adam. Masaryk University; República ChecaFil: Buzatto, Bruno A.. University of Western Australia; AustraliaFil: Djoudi, El Aziz. Brandenburgische Technische Universität Cottbus; AlemaniaFil: Domenech, Marc. Universidad de Barcelona; EspañaFil: Enciso, Alison Vanesa. Fundación Protectora Ambiental Planadas Tolima; ColombiaFil: Piñanez Espejo, Yolanda María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Febles, Sara. No especifíca;Fil: García, Luis F. Universidad de la República; UruguayFil: Gonçalves Souza, Thiago. Universidad Federal Rural Pernambuco; BrasilFil: Isaia, Marco. Università di Torino; ItaliaFil: Lafage, Denis. Universite de Rennes I; FranciaFil: Líznarová, Eva. Masaryk University; República ChecaFil: Macías Hernández, Nuria. Universidad de La Laguna; EspañaFil: Fiorini de Magalhaes, Ivan Luiz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Malumbres Olarte, Jagoba. Universidade Dos Açores; PortugalFil: Michálek, Ondrej. Masaryk University; República ChecaFil: Michalik, Peter. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG);Fil: Michalko, Radek. No especifíca;Fil: Milano, Filippo. Università di Torino; ItaliaFil: Munévar, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú; ArgentinaFil: Nentwig, Wolfgang. University of Bern; SuizaFil: Nicolosi, Giuseppe. Università di Torino; ItaliaFil: Painting, Christina J. No especifíca;Fil: Pétillon, Julien. Universite de Rennes I; FranciaFil: Piano, Elena. Università di Torino; ItaliaFil: Privet, Kaïna. Universite de Rennes I; FranciaFil: Ramirez, Martin Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Ramos, Cândida. No especifíca;Fil: Rezác, Milan. No especifíca;Fil: Ridel, Aurélien. Universite de Rennes I; FranciaFil: Ruzicka, Vlastimil. No especifíca;Fil: Santos, Irene. No especifíca;Fil: Sentenská, Lenka. Masaryk University; República ChecaFil: Walker, Leilani. No especifíca;Fil: Wierucka, Kaja. Universitat Zurich; SuizaFil: Zurita, Gustavo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Cardoso, Pedro. No especifíca

Systems Analysis of MVA-C Induced Immune Response Reveals Its Significance as a Vaccine Candidate against HIV/AIDS of Clade C

Based on the partial efficacy of the HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis the biological and immunological characteristics of the attenuated vaccinia virus Ankara strain expressing the HIV-1 antigens Env/Gag-Pol-Nef of HIV-1 of clade C (referred as MVA-C). MVA-C infection of human monocyte derived dendritic cells (moDCs) induced the expression of HIV-1 antigens at high levels from 2 to 8 hpi and triggered moDCs maturation as revealed by enhanced expression of HLA-DR, CD86, CD40, HLA-A2, and CD80 molecules. Infection ex vivo of purified mDC and pDC with MVA-C induced the expression of immunoregulatory pathways associated with antiviral responses, antigen presentation, T cell and B cell responses. Similarly, human whole blood or primary macrophages infected with MVA-C express high levels of proinflammatory cytokines and chemokines involved with T cell activation. The vector MVA-C has the ability to cross-present antigens to HIV-specific CD8 T cells in vitro and to increase CD8 T cell proliferation in a dose-dependent manner. The immunogenic profiling in mice after DNA-C prime/MVA-C boost combination revealed activation of HIV-1-specific CD4 and CD8 T cell memory responses that are polyfunctional and with effector memory phenotype. Env-specific IgG binding antibodies were also produced in animals receiving DNA-C prime/MVA-C boost. Our systems analysis of profiling immune response to MVA-C infection highlights the potential benefit of MVA-C as vaccine candidate against HIV/AIDS for clade C, the prevalent subtype virus in the most affected areas of the world

Recent Progress and Next Steps for the MATHUSLA LLP Detector

We report on recent progress and next steps in the design of the proposed MATHUSLA Long Lived Particle (LLP) detector for the HL-LHC as part of the Snowmass 2021 process. Our understanding of backgrounds has greatly improved, aided by detailed simulation studies, and significant R&D has been performed on designing the scintillator detectors and understanding their performance. The collaboration is on track to complete a Technical Design Report, and there are many opportunities for interested new members to contribute towards the goal of designing and constructing MATHUSLA in time for HL-LHC collisions, which would increase the sensitivity to a large variety of highly motivated LLP signals by orders of magnitude.Comment: Contribution to Snowmass 2021 (EF09, EF10, IF6, IF9), 18 pages, 12 figures. v2: included additional endorser