Cancer cells restrict immunogenicity of retrotransposon expression via distinct mechanisms.

To thrive, cancer cells must navigate acute inflammatory signaling accompanying oncogenic transformation, such as via overexpression of repeat elements. We examined the relationship between immunostimulatory repeat expression, tumor evolution, and the tumor-immune microenvironment. Integration of multimodal data from a cohort of pancreatic ductal adenocarcinoma (PDAC) patients revealed expression of specific Alu repeats predicted to form double-stranded RNAs (dsRNAs) and trigger retinoic-acid-inducible gene I (RIG-I)-like-receptor (RLR)-associated type-I interferon (IFN) signaling.

Retroelement decay by the exonuclease XRN1 is a viral mimicry dependency in cancer.

Viral mimicry describes the immune response induced by endogenous stimuli such as double-stranded RNA (dsRNA) from endogenous retroelements. Activation of viral mimicry has the potential to kill cancer cells or augment anti-tumor immune responses. Here, we systematically identify mechanisms of viral mimicry adaptation associated with cancer cell dependencies.

Recontact to return new or updated genetic results in the clinical laboratory setting.

Objective: The purpose of this study was to recontact individuals with clinically actionable test results identified through a retrospective research study and to provide a framework for laboratories to recontact patients.

Methods: Genetic testing was conducted on 2977 individuals originally referred for and hereditary breast and ovarian cancer testing that had a negative genetic test result. A gene panel was used to identify pathogenic variants in known or newly discovered genes that could explain the underlying cause of disease; however, analysis was restricted to for the purposes of this study.

A transfer-learning approach to predict antigen immunogenicity and T-cell receptor specificity.

Antigen immunogenicity and the specificity of binding of T-cell receptors to antigens are key properties underlying effective immune responses. Here we propose diffRBM, an approach based on transfer learning and Restricted Boltzmann Machines, to build sequence-based predictive models of these properties. DiffRBM is designed to learn the distinctive patterns in amino-acid composition that, on the one hand, underlie the antigen's probability of triggering a response, and on the other hand the T-cell receptor's ability to bind to a given antigen.

Generative and interpretable machine learning for aptamer design and analysis of in vitro sequence selection.

Selection protocols such as SELEX, where molecules are selected over multiple rounds for their ability to bind to a target of interest, are popular methods for obtaining binders for diagnostic and therapeutic purposes. We show that Restricted Boltzmann Machines (RBMs), an unsupervised two-layer neural network architecture, can successfully be trained on sequence ensembles from single rounds of SELEX experiments for thrombin aptamers. RBMs assign scores to sequences that can be directly related to their fitnesses estimated through experimental enrichment ratios.

Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: a multicentric prospective study in real life.

Background: Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies.

Fast and non-destructive neutron activation analysis for simultaneous determination of TiO and SiO in sunscreens with attention to regulatory and research issues.

A new instrumental neutron activation analysis (INAA) for the simultaneous determination of titanium (TiO) and silica (SiO) dioxide as UV-filters in sunscreens is described. Samples are encapsulated, neutron irradiated (30 s) and after a suitable decay (3 min), the induced Ti (T = 5.76 min) and Al (T = 6.

sgDI-tector: defective interfering viral genome bioinformatics for detection of coronavirus subgenomic RNAs.

Coronavirus RNA-dependent RNA polymerases produce subgenomic RNAs (sgRNAs) that encode viral structural and accessory proteins. User-friendly bioinformatic tools to detect and quantify sgRNA production are urgently needed to study the growing number of next-generation sequencing (NGS) data of SARS-CoV-2. We introduced sgDI-tector to identify and quantify sgRNA in SARS-CoV-2 NGS data.

The Heterogeneous Landscape and Early Evolution of Pathogen-Associated CpG Dinucleotides in SARS-CoV-2.

COVID-19 can lead to acute respiratory syndrome, which can be due to dysregulated immune signaling. We analyze the distribution of CpG dinucleotides, a pathogen-associated molecular pattern, in the SARS-CoV-2 genome. We characterize CpG content by a CpG force that accounts for statistical constraints acting on the genome at the nucleotidic and amino acid levels.

Genotoxicity and Immunotoxicity of Titanium Dioxide-Embedded Mesoporous Silica Nanoparticles (TiO@MSN) in Primary Peripheral Human Blood Mononuclear Cells (PBMC).

TiO nanoparticles (TiO NPs) are the nanomaterial most produced as an ultraviolet (UV) filter. However, TiO is a semiconductor and, in nanoparticle size, is a strong photocatalyst, raising concerns about photomutagenesis. Mesoporous silica nanoparticles (MSN) were synthetized incorporating TiO NPs (TiO@MSN) to develop a cosmetic UV filter.

The Heterogeneous Landscape and Early Evolution of Pathogen-Associated CpG Dinucleotides in SARS-CoV-2.

SARS-CoV-2 infection can lead to acute respiratory syndrome in patients, which can be due in part to dysregulated immune signalling. We analyze here the occurrences of CpG dinucleotides, which are putative pathogen-associated molecular patterns, along the viral sequence. Carrying out a comparative analysis with other ssRNA viruses and within the  family, we find the CpG content of SARS-CoV-2, while low compared to other betacoronaviruses, widely fluctuates along its primary sequence.

Axion Search with a Quantum-Limited Ferromagnetic Haloscope.

A ferromagnetic axion haloscope searches for dark matter in the form of axions by exploiting their interaction with electronic spins. It is composed of an axion-to-electromagnetic field transducer coupled to a sensitive rf detector. The former is a photon-magnon hybrid system, and the latter is based on a quantum-limited Josephson parametric amplifier.

Urticaria: recommendations from the Italian Society of Allergology, Asthma and Clinical Immunology and the Italian Society of Allergological, Occupational and Environmental Dermatology.

Background: Urticaria is a disorder affecting skin and mucosal tissues characterized by the occurrence of wheals, angioedema or both, the latter defining the urticaria-angioedema syndrome. It is estimated that 12-22% of the general population has suffered at least one subtype of urticaria during life, but only a small percentage (estimated at 7.6-16%) has acute urticaria, because it is usually self-limited and resolves spontaneously without requiring medical attention.

Mineralogy and textures of riebeckitic asbestos (crocidolite): The role of single versus agglomerated fibres in toxicological experiments.

Asbestos may cause adverse effects, but relationship between mineralogy and texture of fibres versus toxicity is still lacking. Toxicological studies can be interpreted and compared only if quantitative features of fibres are determined. Here, riebeckitic ("crocidolite") amphibole fibres were analysed by XRPD, FTIR, SEM-EDS and EMP-WDS; only crystals with stochiometry Na(FeMg)FeSiO(OH) are present in the starting material used for the experiments.

In vivo inflammatory effects of ceria nanoparticles on CD-1 mouse: evaluation by hematological, histological, and TEM analysis.

The attention on CeO2-NPs environmental and in vivo effects is due to their presence in diesel exhaust and in diesel filters that release a more water-soluble form of ceria NPs, as well as to their use for medical applications. In this work, acute and subacute in vivo toxicity assays demonstrate no lethal effect of these NPs. Anyhow, performing in vivo evaluations on CD-1 mouse systems, we demonstrate that it is even not correct to assert that ceria NPs are harmless for living systems as they can induce status of inflammation, revealed by hematological-chemical-clinical assays as well as histological and TEM microscope observations.

Cytotoxicity and genotoxicity of ceria nanoparticles on different cell lines in vitro.

Owing to their radical scavenging and UV-filtering properties, ceria nanoparticles (CeO(2)-NPs) are currently used for various applications, including as catalysts in diesel particulate filters. Because of their ability to filter UV light, CeO(2)-NPs have garnered significant interest in the medical field and, consequently, are poised for use in various applications. The aim of this work was to investigate the effects of short-term (24 h) and long-term (10 days) CeO(2)-NP exposure to A549, CaCo2 and HepG2 cell lines.

Local structural disorder in REFeAsO oxypnictides by RE L(3) edge XANES.

The REFeAsO (RE = La, Pr, Nd and Sm) system has been studied by RE L(3) x-ray absorption near edge structure (XANES) spectroscopy to explore the contribution of the REO spacers between the electronically active FeAs slabs in these materials. The XANES spectra have been simulated by full multiple scattering calculations to describe the different experimental features and their evolution with the RE size. The near edge feature just above the L(3) white line is found to be sensitive to the ordering/disordering of oxygen atoms in the REO layers.

Clastogenic but not apoptotic effects on human artery endothelial cells by concentrations of inorganic lead inhibiting their nitric oxide production.

Human coronary artery endothelial cells (HCAEC 5156) were cultured as monolayers and exposed to concentrations of lead (as acetate, Pb) in the culture medium similar or lower than those commonly found in the blood of human beings occupationally or environmentally exposed to this element. Only at the concentration of 200 ng/mL, Pb reduced growth rate of HCAEC 5156 cells starting from the 3rd day and up too the 5th day of incubation. On the other hand, Pb (0.

[Serum tryptase: marker of occupational anaphylaxis].

Tryptase is a protein released by mast cells, which is involved in the enhancement of inflammatory sequences in immune-mediated reactions. According with our experience, some patients having a reaction clinically classified as anaphylaxis, showed high levels of tryptase (> 20 ng/l) but also of serum specific IgE, showing the immune-mediated nature of the reactions. On the other hand workers without specific IgE and with low levels of tryptase probably had developed pseudoallergic (anaphylactoid) reactions.

Effect of the compound L-mimosine in an in vivo model of chronic granuloma formation induced by potassium permanganate (KMNO4).

The plant amino acid L-mimosine has recently been suggested to inhibit cells at a regulatory step in late G1 phase before establishment of active DNA replication forks. In addition, L-mimosine is an extremely effective inhibitor of DNA replication in chromosomes of mammalian nuclei. In this work, the effect of L-mimosine on chronic inflammation induced by dorsal injections of 0.

Leishmania antibodies in children’s serum samples in correlation with the disease in dogs.

Sera of 489 children from Northern Greece aged between 6 months and 15 years of age and aflicted with different clinical entities, were tested for anti – Leishmania infantum specific IgG and IgM antibodies, using an ELISA (enzyme linked immunosorbent assay) technique. In this survey, a remarkably high percentage (8.5%) of hospitalized children reacted positively to this method.

A spectrum of antibody (IgG. IgG1, IgM) response in mice infected with trichinella spiralis treated with L-mimosine.

The purpose of this study was to demonstrate the anti-inflammatory effects of L-mimosine on chronic inflammation, by investigating its effect on the immunological response of BALB/c mice infected with the nematode parasite Trichinella spiralis. Specific anti-parasite immunoglobulins (IgG, IgG1 and IgM) were detected by the ELISA method in the serum of both the treated and the untreated animals at different periods of time for 60 days post infection. Two groups consisting of 18 mice each were used.

Catcholamine and nitric oxide systems as targets of chronic lead exposure in inducing selective functional impairment.

Rats were exposed for ten months to 60 ppm of lead (Pb, as acetate) in drinking water to further assess cardiovascular effects of chronic Pb exposure. At the end of the treatment, mean blood Pb was 3.1+/-0.