13 research outputs found

    Sulfur assimilation using gaseous carbonyl sulfideby the soil fungus Trichoderma harzianum

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    Fungi have the capacity to assimilate a diverse range of both inorganic and organic sulfur compounds. It has been recognized that all sulfur sources taken up by fungi are in soluble forms. In this study, we present evidence that fungi can utilize gaseous carbonyl sulfide(COS) for the assimilation of a sulfur compound. We found that the filamentousfungus Trichoderma harzianum strain THIF08, which has constitutively high COS-degrading activity, was able to grow with COS as the sole sulfur source. Cultivation with 34S-labeled COS revealed that sulfur atom from COS was incorporated into intracellular metabolites such as glutathione and ergothioneine. COS degradation by strain THIF08, in which as much of the moisture derived from the agar medium as possible was removed, indicated that gaseous COS was taken up directly into the cell. Escherichia coli transformed with a COS hydrolase (COSase) gene, which is clade D of the β-class carbonic anhydrase subfamily enzyme with high specificity for COS but low activity for CO2 hydration, showed that the COSase is involved in COS assimilation. Comparison of sulfur metabolites of strain THIF08 revealed a higher relative abundance of reduced sulfur compounds under the COS-supplemented condition than the sulfate-supplemented condition, suggesting that sulfur assimilation is more energetically efficient with COS than with sulfate because there is no redox change of sulfur. Phylogenetic analysis of the genes encoding COSase, which are distributed in a wide range of fungal taxa, suggests that the common ancestor of Ascomycota, Basidiomycota, and Mucoromycota acquired COSase at about 790-670 Ma. © 2024 Iizuka et al

    Microstructure and mechanical properties of high-manganese-containing high-speed twin-roll cast Al-Mn-Si alloy strips and their cold-rolled sheets

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    Al-Mn based alloys with high-manganese content are expected to have improved mechanical properties due to solid solution hardening and/or dispersion hardening. However, the increase of Mn solubility of the alloy is difficult by using the conventional DC casting. In order to solve this problem, in the present study, we focused on the twin-roll casting method which is characterized by high cooling rates. Several kinds of high Mn-containing Al-Mn-Si alloy strips were fabricated by using a vertical-type high-speed twin-roll caster equipped with a pair of water-cooled copper rolls. Direct temperature measurement of the liquid melt during the casting was also performed. The alloy strips of various compositions containing up to 4 Mn and 2 Si (wt%) were successfully obtained. By observing the microstructure of the cross section of the strip, we found the characteristic solidified structure. The solidified structure consisted of three layers. Two solidified shells with a columnar dendrite structure grew from the roll surfaces toward the strip center. In the mid-thickness region, the band structure consisting of equiaxed dendrites and globular grains was observed between the solidified shells. Very fine primary particles were observed in the matrix near the strip surface, while, relatively coarse particles with blocky and needle-like shape were observed in the central band of the as-cast strip. The electric conductivity measurement was performed for the as-cast strips. Mn solubility in Al matrix was estimated from the obtained values. The estimated Mn solubility in the Al-2Mn-xSi strips was between 1.5 ~ 1.8wt% Mn. It was over 1.43wt%Mn for the Al-4Mn-xSi strips. We found that the Mn solubility of the as-cast strips was considerably high. The strips were cold-rolled to the sheets and then annealed at various conditions. They were subjected to the tensile tests, and the effects of solid solution hardening and dispersion hardening are discussed

    Microstructure and mechanical properties of high-manganese-containing high-speed twin-roll cast Al-Mn-Si alloy strips and their cold-rolled sheets

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    Al-Mn based alloys with high-manganese content are expected to have improved mechanical properties due to solid solution hardening and/or dispersion hardening. However, the increase of Mn solubility of the alloy is difficult by using the conventional DC casting. In order to solve this problem, in the present study, we focused on the twin-roll casting method which is characterized by high cooling rates. Several kinds of high Mn-containing Al-Mn-Si alloy strips were fabricated by using a vertical-type high-speed twin-roll caster equipped with a pair of water-cooled copper rolls. Direct temperature measurement of the liquid melt during the casting was also performed. The alloy strips of various compositions containing up to 4 Mn and 2 Si (wt%) were successfully obtained. By observing the microstructure of the cross section of the strip, we found the characteristic solidified structure. The solidified structure consisted of three layers. Two solidified shells with a columnar dendrite structure grew from the roll surfaces toward the strip center. In the mid-thickness region, the band structure consisting of equiaxed dendrites and globular grains was observed between the solidified shells. Very fine primary particles were observed in the matrix near the strip surface, while, relatively coarse particles with blocky and needle-like shape were observed in the central band of the as-cast strip. The electric conductivity measurement was performed for the as-cast strips. Mn solubility in Al matrix was estimated from the obtained values. The estimated Mn solubility in the Al-2Mn-xSi strips was between 1.5 ~ 1.8wt% Mn. It was over 1.43wt%Mn for the Al-4Mn-xSi strips. We found that the Mn solubility of the as-cast strips was considerably high. The strips were cold-rolled to the sheets and then annealed at various conditions. They were subjected to the tensile tests, and the effects of solid solution hardening and dispersion hardening are discussed

    Development of a Novel CD26-Targeted Chimeric Antigen Receptor T-Cell Therapy for CD26-Expressing T-Cell Malignancies

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    Chimeric-antigen-receptor (CAR) T-cell therapy for CD19-expressing B-cell malignancies is already widely adopted in clinical practice. On the other hand, the development of CAR-T-cell therapy for T-cell malignancies is in its nascent stage. One of the potential targets is CD26, to which we have developed and evaluated the efficacy and safety of the humanized monoclonal antibody YS110. We generated second (CD28) and third (CD28/4-1BB) generation CD26-targeted CAR-T-cells (CD26-2G/3G) using YS110 as the single-chain variable fragment. When co-cultured with CD26-overexpressing target cells, CD26-2G/3G strongly expressed the activation marker CD69 and secreted IFNgamma. In vitro studies targeting the T-cell leukemia cell line HSB2 showed that CD26-2G/3G exhibited significant anti-leukemia effects with the secretion of granzymeB, TNFα, and IL-8, with 3G being superior to 2G. CD26-2G/3G was also highly effective against T-cell lymphoma cells derived from patients. In an in vivo mouse model in which a T-cell lymphoma cell line, KARPAS299, was transplanted subcutaneously, CD26-3G inhibited tumor growth, whereas 2G had no effect. Furthermore, in a systemic dissemination model in which HSB2 was administered intravenously, CD26-3G inhibited tumor growth more potently than 2G, resulting in greater survival benefit. The third-generation CD26-targeted CAR-T-cell therapy may be a promising treatment modality for T-cell malignancies
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