Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells

Nucleotide excision repair (NER) is the most versatile DNA repair system that deals with the major UV photoproducts in DNA, as well as many other DNA adducts. The early steps of NER are well understood, whereas the later steps of repair synthesis and ligation are not. In particular, which polymerases are definitely involved in repair synthesis and how they are recruited to the damaged sites has not yet been established. We report that, in human fibroblasts, approximately half of the repair synthesis requires both polκ and polδ, and both polymerases can be recovered in the same repair complexes. Polκ is recruited to repair sites by ubiquitinated PCNA and XRCC1 and polδ by the classical replication factor complex RFC1-RFC, together with a polymerase accessory factor, p66, and unmodified PCNA. The remaining repair synthesis is dependent on polɛ, recruitment of which is dependent on the alternative clamp loader CTF18-RFC

MPGN Type 3 Associated with Pemphigus Herpetiformis Mimicking PGNMID and Dermatitis Herpetiformis

A 45-year-old man suffering from dermal blistering disease with proteinuria and hematuria underwent renal biopsy. The renal biopsy specimen suggested proliferative glomerulonephritis with monoclonal IgG deposits under routine light, immunofluorescence and electron microscopy. The staining for IgG subclasses (IgG1 and IgG2) and κ/λ light chain indicated secondary immune complex type MPGN type 3. The patient had been diagnosed as having dermatitis herpetiformis (DH), a phenotype of gluten hypersensitivity prior to the appearance of the renal abnormality. Although common autoantibodies might be related to the pathogenesis of disorders in the skin and kidney, DH is mainly driven by IgA autoantibody, while MPGN is induced by IgG immune complexes. IgA was not observed in the glomeruli by immunofluorescence. Neither the examination for DH specific autoantibodies nor HLA-DQB1 genotype supported the diagnosis of DH. Reassessment of the skin biopsy record revealed that the blister was localized in the epidermis, suggesting pemphigus herpetiformis by IgG class anti-epidermal autoantibody, which also affected the renal disorder

Achieving accurate geo-location detection using joint RSS-DOA factor graph technique

This paper proposes a detection technique based on factor graph (FG) to estimate the position of radio wave emitter. To obtain accurate estimation, we combine received signal strength (RSS) and direction of arrival (DOA) schemes into a single factor graph, called joint RSS-DOA, where soft information as mean and variance of the estimated target position are exchanged between the two schemes. The performance of DOA in this paper is used to modify variance approximation of the target location. We introduce the weighting factors for RSS and for DOA to avoid the soft information of DOA factor graph be ignored. With the proposed technique, the complexity is kept low, because only mean and variance are exchanged between the factor nodes. Ray-tracing data is used in outdoor application to create power delay profile (PDP) for the RSS-based factor graph and evaluate 5, 10, and 20 training points. The results confirmed that proposed joint RSS-DOA has best accuracy in detection compared to RSS-based or DOA-based only factor graph. To the best of our knowledge, we are the first showing successful results of FG based geo-location using Ray-tracing data

Increased expression of α4β7 integrin on food allergen-stimulated CD4+ T cells in active food allergic enterocolitis

We used flow cytometry to investigate the expression of α4β7 integrin on peripheral blood CD4+ T cells stimulated with αs-casein, one of the major allergens in milk allergy, in patients with milk-induced enterocolitis. In the active state of the disease, the levels of α4β7 integrin on αs-casein-stimulated CD4+ T cells, as well as the numbers of positive cells, were higher than in the age-matched control. Upon outgrowing milk allergy, α4β7 integrin levels decreased to the same levels as in the healthy control. The proliferative responses of peripheral blood mononuclear cells to αs-casein in the active state did not differ from those in the outgrown state, suggesting that the expression of α4β7 integrin on milk allergen-activated T cells is a marker of the activation state leading to the pathogenesis of milk-allergic enterocolitis

Identification of a novel mechanism of action of bovine IgG antibodies specific for Staphylococcus aureus

Staphylococcus aureus is a major pathogen that causes subclinical mastitis associated with huge economic losses to the dairy industry. A few vaccines for bovine mastitis are available, and they are expected to induce the production of S. aureus-specific antibodies that prevent bacterial adherence to host cells or promote opsonization by phagocytes. However, the efficacy of such vaccines are still under debate; therefore, further research focusing on improving the current vaccines by seeking additional mechanisms of action is required to reduce economic losses due to mastitis in the dairy industry. Here, we generated S. aureus-specific bovine IgG antibodies (anti-S. aureus) that directly inhibited bacterial growth in vitro. Inhibition depended on specificity for anti-S. aureus, not the interaction between Protein A and the fragment crystallizable region of the IgG antibodies or bacterial agglutination. An in vitro culture study using S. aureus strain JE2 and its deletion mutant JE2ΔSrtA, which lacks the gene encoding sortase A, revealed that the effect of anti-S. aureus was sortase-A-independent. Sortase A is involved in the synthesis of cell-wall-associated proteins. Thus, other surface molecules, such as membrane proteins, cell surface polysaccharides, or both, may trigger the inhibition of bacterial growth by anti-S. aureus. Together, our findings contribute insights into developing new strategies to further improve the available mastitis vaccine by designing a novel antigen on the surface of S. aureus to induce inhibitory signals that prevent bacterial growth

Identification of a novel mechanism of action of bovine IgG antibodies specific for Staphylococcus aureus

International audienceAbstractStaphylococcus aureus is a major pathogen that causes subclinical mastitis associated with huge economic losses to the dairy industry. A few vaccines for bovine mastitis are available, and they are expected to induce the production of S. aureus-specific antibodies that prevent bacterial adherence to host cells or promote opsonization by phagocytes. However, the efficacy of such vaccines are still under debate; therefore, further research focusing on improving the current vaccines by seeking additional mechanisms of action is required to reduce economic losses due to mastitis in the dairy industry. Here, we generated S. aureus-specific bovine IgG antibodies (anti-S. aureus) that directly inhibited bacterial growth in vitro. Inhibition depended on specificity for anti-S. aureus, not the interaction between Protein A and the fragment crystallizable region of the IgG antibodies or bacterial agglutination. An in vitro culture study using S. aureus strain JE2 and its deletion mutant JE2ΔSrtA, which lacks the gene encoding sortase A, revealed that the effect of anti-S. aureus was sortase-A-independent. Sortase A is involved in the synthesis of cell-wall-associated proteins. Thus, other surface molecules, such as membrane proteins, cell surface polysaccharides, or both, may trigger the inhibition of bacterial growth by anti-S. aureus. Together, our findings contribute insights into developing new strategies to further improve the available mastitis vaccine by designing a novel antigen on the surface of S. aureus to induce inhibitory signals that prevent bacterial growth