The acute ecotoxicity of different diameters of silica and polyethyleneimine polystyrene (PS-PEI) nanoparticles (NPs) was assessed on a test battery of aquatic organisms representing different ...trophic levels. Daphnia magna, Thamnocephalus platyurus, Pseudokirchneriella subcapitata and Vibrio fischeri, were employed in a series of standard acute ecotoxicity tests and work was complemented with two cytotoxicological end points on a rainbow trout gonadal cell line (RTG-2). Physico-chemical characterization of the NPs was performed in the different test media employed, using dynamic light scattering (DLS) and zeta potentiometry. In contrast to silica NPs exposure, for which no effect was observed for concentrations up to 1000μgml−1 for all in vivo aquatic organisms tested, significant toxicity was detected after exposure to PS-PEI NPs at concentrations from 0.40μgml−1 to 416.5μgml−1. Differing sensitivities for each NP diameter for the different organisms were observed as: P. subcapitata≥D. magna>T. platyurus>V. fischeri. The effects observed were dependent in some cases on the NP size, a higher effect being observed for the larger NPs. Finally, cytotoxicity studies showed an effect at the highest concentrations for both sets of NPs which was greater in the case of the PS-PEI NPs. However, as agglomeration and sedimentation of the nanoparticles was observed at these concentrations, the cytotoxicity studies were found not to be a reliable ecotoxicity test model.
► The acute ecotoxicity of model nanoparticles on aquatic organisms is studied. ► Established methods for ecotoxicological chemical risk assessment are employed. ► Cytotoxic models are deemed unsuitable due to nanoparticle agglomeration. ► Other standardized methods are deemed suitable for nanoparticle testing. ► The polystyrene or silica nanoparticles are suitable positive or negative controls.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Surface-enhanced Raman scattering (SERS) is a powerful and sensitive technique for the detection of fingerprint signals of molecules and for the investigation of a series of surface chemical ...reactions. Many studies introduced quantitative applications of SERS in various fields, and several SERS methods have been implemented for each specific application, ranging in performance characteristics, analytes used, instruments, and analytical matrices. In general, very few methods have been validated according to international guidelines. As a consequence, the application of SERS in highly regulated environments is still considered risky, and the perception of a poorly reproducible and insufficiently robust analytical technique has persistently retarded its routine implementation. Collaborative trials are a type of interlaboratory study (ILS) frequently performed to ascertain the quality of a single analytical method. The idea of an ILS of quantification with SERS arose within the framework of Working Group 1 (WG1) of the EU COST Action BM1401 Raman4Clinics in an effort to overcome the problematic perception of quantitative SERS methods. Here, we report the first interlaboratory SERS study ever conducted, involving 15 laboratories and 44 researchers. In this study, we tried to define a methodology to assess the reproducibility and trueness of a quantitative SERS method and to compare different methods. In our opinion, this is a first important step toward a “standardization” process of SERS protocols, not proposed by a single laboratory but by a larger community.
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IJS, KILJ, NUK, PNG, UL, UM
Currently, nitrogen fertilizers are utilized to meet 48% of the total global food demand. The demand for nitrogen fertilizers is expected to grow as global populations continue to rise. The use of ...nitrogen fertilizers is associated with many negative environmental impacts and is a key source of greenhouse and harmful gas emissions. In recent years, urease and nitrification inhibitors have emerged as mitigation tools that are presently utilized in agriculture to prevent nitrogen losses and reduce greenhouse and harmful gas emissions that are associated with the use of nitrogen-based fertilizers. Both classes of inhibitor work by different mechanisms and have different physiochemical properties. Consequently, each class must be evaluated on its own merits. Although there are many benefits associated with the use of these inhibitors, little is known about their potential to enter the food chain, an event that may pose challenges to food safety. This phenomenon was highlighted when the nitrification inhibitor dicyandiamide was found as a residual contaminant in milk products in 2013. This comprehensive review aims to discuss the uses of inhibitor technologies in agriculture and their possible impacts on dairy product safety and quality, highlighting areas of concern with regards to the introduction of these inhibitor technologies into the dairy supply chain. Furthermore, this review discusses the benefits and challenges of inhibitor usage with a focus on EU regulations, as well as associated health concerns, chemical behavior, and analytical detection methods for these compounds within milk and environmental matrices.
Abstract
We use both chirped-pulse Fourier transform and frequency-modulated absorption spectroscopy to study the rotational spectrum of 2-methoxyethanol (CH
3
OCH
2
CH
2
OH) in several frequency ...regions ranging from 8.7 to 500 GHz. The resulting rotational parameters permitted a search for this molecule in Atacama Large Millimeter/submillimeter Array (ALMA) observations toward the massive protocluster NGC 6334I, as well as source B of the low-mass protostellar system IRAS 16293−2422. A total of 25 rotational transitions are observed in the ALMA Band 4 data toward NGC 6334I, resulting in the first interstellar detection of 2-methoxyethanol. A column density of
1.3
−
0.9
+
1.4
×
10
17
cm
−2
is derived at an excitation temperature of
143
−
39
+
31
K. However, molecular signal is not observed in the Band 7 data toward IRAS 16293−2422B, and an upper-limit column density of 2.5 × 10
15
cm
−2
is determined. Various possible formation pathways—including radical recombination and insertion reactions—are discussed. We also investigate physical differences between the two interstellar sources that could result in the observed abundance variations.
Improvements in immunosuppression have modified short‐term survival of deceased‐donor allografts, but not their rate of long‐term failure. Mismatches between donor and recipient HLA play an important ...role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short‐ and long‐term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large‐scale genome‐wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant‐pairs with replication in 5866 complete pairs. We studied deceased‐donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long‐ or short‐term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.
The largest multicenter genome‐wide association study to date on short‐ and long‐term renal transplantation outcomes finds no loci outside the HLA region, highlighting challenges in phenotypic heterogeneity and sample size while also providing a reference dataset for future meta‐analyses.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Grass uptake and phytoaccumulation factors of N-(n-butyl) thiophosphoric triamide (NBPT) and dicyandiamide (DCD) were quantified. Following the application of urea fertilizer treated with the ...inhibitors in Irish grassland, grass samples were collected at 5, 10, 15, 20, and 30 day time intervals following five application cycles. Uptake of NBPT by grass was below the limit of quantitation of the analytical method (0.010 mg NBPT kg
-1
). Dicyandiamide concentrations in grass ranged from 0.004 to 28 mg kg
-1
with the highest concentrations measured on days 5 and 10. A reducing trend in concentration was found after day 15. The DCD phytoaccumulation factor was ranged from 0.004% to 1.1% showing that DCD can be taken up by grass at low levels when co-applied with granular urea. In contrast, NBPT was not detected indicating that grass uptake is unlikely when co-applied with granular urea fertilizer. The contrasting results are likely due to very different longevity of DCD and NBPT along with the much lower rate of NBPT, which is used compared with DCD.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The selective inhibitor of nuclear export (SINE) compounds selinexor (KPT-330) and eltanexor (KPT-8602) are from a novel class of small molecules that target exportin-1 (XPO1 CRM1), an essential ...nucleo-cytoplasmic transport protein responsible for the nuclear export of major tumor suppressor proteins and growth regulators such as p53, p21, and p27. XPO1 also affects the translation of messenger RNAs for critical oncogenes, including MYC, BCL2, MCL1, and BCL6, by blocking the export of the translation initiation factor eIF4E. Early trials with venetoclax (ABT-199), a potent, selective inhibitor of BCL2, have revealed responses across a variety of hematologic malignancies. However, many tumors are not responsive to venetoclax. We used models of acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL) to determine in vitro and in vivo responses to treatment with venetoclax and SINE compounds combined. Cotreatment with venetoclax and SINE compounds demonstrated loss of viability in multiple cell lines. Further in vitro analyses showed that this enhanced cell death was the result of an increase in apoptosis that led to a loss of clonogenicity in methylcellulose assays, coinciding with activation of p53 and loss of MCL1. Treatment with SINE compounds and venetoclax combined led to a reduction in tumor growth in both AML and DLBCL xenografts. Immunohistochemical analysis of tissue sections revealed that the reduction in tumor cells was partly the result of an induction of apoptosis. The enhanced effects of this combination were validated in primary AML and DLBCL patient cells. Our studies reveal synergy with SINE compounds and venetoclax in aggressive hematologic malignancies and provide a rationale for pursuing this approach in a clinical trial.
•Co-inhibition of XPO1 and BCL2 induces apoptosis in AML cells and decreases leukemia burden in cell line and patient-derived xenografts.•Combining SINE compounds with venetoclax shrinks tumors and extends survival in DLBCL xenografts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We generated a murine monoclonal antibody (B28p) detecting an antigenic determinant shared by the immunoglobulin superfamily receptor translocation-associated 1 (IRTA1) receptor (the immunogen used ...to raise B28p) and an unrelated 28-kDa protein that was subsequently subjected to extensive characterization. The expression of the 28-kDa protein in normal lymphohematopoietic tissues was restricted to B cells and plasma cells and clearly differed from that expected for IRTA1 (selectively expressed by mucosa-associated lymphoid tissue MALT marginal zone B cells). Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)/mass-spectrometry analysis identified the 28-kDa protein as human tumor protein D52 (TPD52), whose expression had been previously described only in normal and neoplastic epithelia. Specific B28p reactivity with TPD52 was confirmed by immunostaining/immunoblotting of TPD52-transfected cells. TPD52 expression pattern in normal and neoplastic B cells was unique. In fact, unlike other B-cell molecules (paired box 5 PAX5, CD19, CD79a, CD20, CD22), which are down-regulated during differentiation from B cells to plasma cells, TPD52 expression reached its maximum levels at the plasma cell stage. In the Thiel myeloma cell line, TPD52 bound to annexin VI in a Ca(2+)-dependent manner, suggesting that these molecules may act in concert to regulate secretory processes in plasma cells, similarly to what was observed in pancreatic acinar cells. Finally, the anti-TPD52 monoclonal antibody served as a valuable tool for the diagnosis of B-cell malignancies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We generated a murine monoclonal antibody (B28p) detecting an antigenic determinant shared by the immunoglobulin superfamily receptor translocation-associated 1 (IRTA1) receptor (the immunogen used ...to raise B28p) and an unrelated 28-kDa protein that was subsequently subjected to extensive characterization. The expression of the 28-kDa protein in normal lymphohematopoietic tissues was restricted to B cells and plasma cells and clearly differed from that expected for IRTA1 (selectively expressed by mucosa-associated lymphoid tissue MALT marginal zone B cells). Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)/mass-spectrometry analysis identified the 28-kDa protein as human tumor protein D52 (TPD52), whose expression had been previously described only in normal and neoplastic epithelia. Specific B28p reactivity with TPD52 was confirmed by immunostaining/immunoblotting of TPD52-transfected cells. TPD52 expression pattern in normal and neoplastic B cells was unique. In fact, unlike other B-cell molecules (paired box 5 PAX5, CD19, CD79a, CD20, CD22), which are down-regulated during differentiation from B cells to plasma cells, TPD52 expression reached its maximum levels at the plasma cell stage. In the Thiel myeloma cell line, TPD52 bound to annexin VI in a Ca2+-dependent manner, suggesting that these molecules may act in concert to regulate secretory processes in plasma cells, similarly to what was observed in pancreatic acinar cells. Finally, the anti-TPD52 monoclonal antibody served as a valuable tool for the diagnosis of B-cell malignancies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Wheat streak mosaic virus (WSMV) can cause significant yield loss in wheat (Triticum aestivum L.) in the Great Plains of North America. A recently identified WSMV resistance gene, Wsm2, was mapped to ...chromosome 3BS in germplasm line ‘CO960293–2’. Effective genetic markers tightly linked to the gene will enhance the selection of WSMV‐resistant lines through marker‐assisted selection. We have mapped Wsm2 using a high‐density map developed from the wheat 90K Infinium iSelect single‐nucleotide polymorphism (SNP) array with recombinant inbred lines from the cross between CO960293–2 and susceptible cultivar ‘TAM 111’. Array‐based SNPs that mapped within 4 cM of Wsm2 on chromosome 3BS were converted to Kompetitive Allele Specific Polymerase Chain Reaction (KASP) assays in this study. Six KASP SNPs were validated in two doubled haploid populations developed from crosses of ‘RonL’ × ‘Ripper’ and ‘Snowmass’ × ‘Antero’. RonL and Snowmass possess the Wsm2 gene from CO960293–2. Three closely linked KASP SNPs, converted from IAAV6442, BS00018764_51, and wsnp_Ra_c16264_24873670, showed high sensitivity and specificity (0.83 ≤ sensitivity ≤ 0.97, 0.89 ≤ specificity ≤ 0.99). The latter two were also validated in six F2 breeding populations. These three KASP SNPs were effective in differentiating resistant and susceptible genotypes. Comparative mapping was performed using sequences of SNPs flanking Wsm2 and identified candidate genes and regions in Brachypodium and rice (Oryza sativa L. ssp. japonica). The KASP SNPs developed in this study should be useful for marker‐assisted selection of Wsm2 in wheat breeding programs, and the newly constructed map will also facilitate map based cloning of Wsm2.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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