Interferon α kinoid induces neutralizing anti-interferon α antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon α kinoid phase I/II study.

IFN α Kinoid (IFN-K) is a therapeutic vaccine composed of IFNα2b coupled to a carrier protein. In a phase I/II placebo-controlled trial, we observed that IFN-K significantly decreases the IFN gene signature in whole blood RNA samples from SLE patients. Here, we analysed extended follow-up data from IFN-K-treated patients, in order to evaluate persistence of neutralizing anti-IFNα Abs antibodies (Abs), and gene expression profiling. Serum and whole blood RNA samples were obtained in IFN-K-treated patients included in the follow-up study, in order to determine binding and neutralizing anti-IFNα Ab titres, and perform high-throughput transcriptomic studies. Neutralization studies of 13 IFNα subtypes demonstrated the polyclonal nature of the Ab response induced by IFN-K. Follow-up analyses in six patients confirmed a significant correlation between neutralizing anti-IFNα Ab titres and decrease in IFN scores compared to baseline. These analyses also revealed an inhibitory effect of IFNα blockade on the expression of B cell associated transcripts. IFN-K induces a polyclonal anti-IFNα response that decreases IFN- and B cell-associated transcripts. ClinicalTrials.gov, clinicaltrials.gov, NCT01058343

Antibody and T cell responses induced in chickens immunized with avian influenza virus N1 and NP DNA vaccine with chicken IL-15 and IL-18.

e had examined the immunogenicity of a series of plasmid DNAs which include neuraminidase (NA) and nucleoprotein (NP) genes from avian influenza virus (AIV). The interleukin-15 (IL-15) and interleukin-18 (IL-18) as genetic adjuvants were used for immunization in combination with the N1 and NP AIV genes. In the first trial, 8 groups of chickens were established with 10 specific-pathogen-free (SPF) chickens per group while, in the second trial 7 SPF chickens per group were used. The overall N1 enzyme-linked immunosorbent assay (ELISA) titer in chickens immunized with the pDis/N1+pDis/IL-15 was higher compared to the chickens immunized with the pDis/N1 and this suggesting that chicken IL-15 could play a role in enhancing the humoral immune response. Besides that, the chickens that were immunized at 14-day-old (Trial 2) showed a higher N1 antibody titer compared to the chickens that were immunized at 1-day-old (Trial 1). Despite the delayed in NP antibody responses, the chickens co-administrated with IL-15 were able to induce earlier and higher antibody response compared to the pDis/NP and pDis/NP+pDis/IL-18 inoculated groups. The pDis/N1+pDis/IL-15 inoculated chickens also induced higher CD8+ T cells increase than the pDis/N1 group in both trials (P0.05) in inducing CD4+ and CD8+ T cells when co-administered with the pDis/IL-18 in both trials in comparison to the pDis/NP. Our data suggest that the pDis/N1+pDis/IL-15 combination has the potential to be used as a DNA vaccine against AIV in chickens

Characterization of cadmium proteinuria in man and rat.

In workers chronically exposed to cadmium and without signs of renal insufficiency, plasma proteins with molecular weight ranging from 11,800 to 450,000 are excreted in greater amount in urine. Increased urinary excretion of low and high molecular weight proteins can occur independently. Because of its greater stability in urine and provided a sensitive immunological technique is used, the determination of retinol-binding protein is a more practical and reliable test of proximal tubular function than beta 2-microglobulin. The evaluation of renal function of workers removed from cadmium exposure indicates that cadmium-induced renal lesions, albeit of slow progression, are not reversible when exposures ceases. In workers chronically exposed to cadmium or removed from cadmium exposure, metallothionein in urine is directly correlated with cadmium in urine but not with cadmium in blood or years of cadmium exposure. The association between cadmium in urine and metallothionein in urine is independent of the status of renal function and the intensity of current exposure to cadmium. Whereas the repeated IP injection of high doses of cadmium to rat gives rise to a mixed or tubular type proteinuria, the prolonged oral administration of cadmium results mainly in the development of a glomerular type proteinuria. The former is usually reversible after cessation of treatment whereas the latter is not. Circulating antiglomerular basement membrane antibodies have been found in man and in rat chronically exposed to cadmium. The pathogenic significance of this finding deserves further investigation

Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model

Plasmacytoid dendritic cells (pDCs) have long been implicated in the pathogenesis of lupus. However, this conclusion has been largely based on a correlative link between the copious production of IFN-α/β by pDCs and the IFN-α/β “signature” often seen in human lupus patients. The specific contribution of pDCs to disease in vivo has not been investigated in detail. For this reason, we generated a strain of BXSB lupus-prone mice in which pDCs can be selectively depleted in vivo. Early, transient ablation of pDCs before disease initiation resulted in reduced splenomegaly and lymphadenopathy, impaired expansion and activation of T and B cells, reduced antibodies against nuclear autoantigens and improved kidney pathology. Amelioration of pathology coincided with decreased transcription of IFN-α/β–induced genes in tissues. PDC depletion had an immediate impact on the activation of immune cells, and importantly, the beneficial effects on pathology were sustained even though pDCs later recovered, indicating an early pDC contribution to disease. Together, our findings demonstrate a critical function for pDCs during the IFN-α/β–dependent initiation of autoimmune lupus and point to pDCs as an attractive therapeutic target for the treatment of SLE

Synthesis and characterization of hypoxia-mimicking bioactive glasses for skeletal regeneration

The cellular response to hypoxia (low oxygen pressure) is vital for skeletal tissue development and regeneration. Numerous processes, including progenitor cell recruitment, differentiation and angiogenesis, are activated via the hypoxia pathway. Novel materials-based strategies designed to activate the hypoxia pathway are therefore of great interest for orthopaedic tissue engineering. Resorbable bioactive glasses (BGs) were developed to activate the hypoxia pathway by the controlled release of cobalt ions (at physiological relevant concentrations) whilst controlling BG apatite-forming ability. Two series of soda-lime-phosphosilicate glasses were synthesised with increasing concentrations of cobalt. Compositions were calculated to maintain constant network connectivity (2.13) by considering that cobalt is taking part in the network in the first series, and is acting as a network modifier in the second series. Mg2+ and Zn2+ were added to one of the Co2+-containing glasses to inhibit HCA formation. The presence of HCA formation is undesirable for the use of BG in soft tissues e. g. cartilage. Cobalt was present in both the silicate and phosphate phases of the BG. In addition, evidence was found that it plays a dual role in the silicate phase, entering the network as well as disrupting it as a network modifying oxide. Consistent with this dual role, the presence of cobalt in the BG was shown to decrease ion release. HCA formation was delayed with cobalt addition as well as incorporation of Mg2+ and Zn2+ into the BGs. Importantly, cobalt release was found to be proportional to cobalt content of the BGs enabling the controlled delivery of cobalt in therapeutically active doses

Synovial Tissue: Turning the Page to Precision Medicine in Arthritis

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease targeting the joints. Current treatment strategies are based on clinical, biological and radiological features, yet still fail to reach the goal of early low disease activity in a significant number of cases. Hence, there is a need for refining current treatment algorithms, using accurate markers of response to therapy. Because RA induces histological and molecular alterations in the synovium even before apparition of clinical symptoms, synovial biopsies are a promising tool in the search of such new biomarkers. Histological and molecular characteristics of RA synovitis are heterogeneous. Variations in synovial lining layer hyperplasia, in cellular infiltration of the sublining by immune cells of myeloid and lymphoid lineages, and in molecular triggers of these features are currently categorized using well-defined pathotypes: myeloid, lymphoid, fibroid and pauci-immune. Here, we first bring the plasticity of RA synovitis under scrutiny, i.e., how variations in synovial characteristics are associated with relevant clinical features (disease duration, disease activity, effects of therapies, disease severity). Primary response to a specific drug could be, at least theoretically, related to the representation of the molecular pathway targeted by the drug in the synovium. Alternatively, absence of primary response to a specific agent could be due to disease severity, i.e., overrepresentation of all synovial molecular pathways driving disease activity overwhelming the capacity of any drug to block them. Using this theoretical frame, we will highlight how the findings of previous studies trying to link response to therapy with synovial changes provide promising perspectives on bridging the gap to personalized medicine in RA

Operational energy use versus LCA : case study The Mobble for Solar Decathlon Europe 2019 competition

Studies have shown that the building sector is the biggest contributor to global warming, generating 40 to 50 % of the global output of greenhouse gas emissions. Furthermore, this industry consumes up to 40 % of the materials entering the global economy and produces one third of the total waste. In Belgium alone, estimations put the building sector’s waste output at fifteen million ton of construction waste on a yearly basis. Therefore, a more environmental-friendly thinking is required, that also considers the impact of construction materials on the environment. For highly insulated buildings the environmental impact of additional construction materials might supersede the reduction in energy use that can be obtained throughout its service life. A trade-off should be made between the embedded and operational energy. For the Solar Decathlon competition 2019 in Szentendre an energy efficient house The Mobble was designed and built, for which detailed dynamic energy simulations were performed in Modelica/Dymola, and as well, a life cycle assessment was done using the simulation software Simapro. Even so, the potential of Personal Comfort Systems (PCS) is investigated through the energy simulations. The result of the trade-off for this case-study shows on the one hand a clear potential of advanced demand control HVAC systems and on the other hand clear limits to the increase of insulation thickness. However, for this specific case it was shown that the optimal insulation thickness from environmental point of view is still well above the minimum requirement in the Belgian building code, even for very efficient HVAC systems

The first great inventions

36 pages color illustrations 23 cm. Chanticleer wonder-story books. Designed by the Isotype Institute and printed in six-color offset lithography by Waldheim-Eberle, Vienna, Austria Color illustrated, double title page. Case binding with original color paper dust jacket.https://digitalcommons.risd.edu/specialcollections_books_illustration/1007/thumbnail.jp