Long non-coding RNA-mediated transcriptional interference of a permease gene confers drug tolerance in fission yeast

Most long non-coding RNAs (lncRNAs) encoded by eukaryotic genomes remain uncharacterized. Here we focus on a set of intergenic lncRNAs in fission yeast. Deleting one of these lncRNAs exhibited a clear phenotype: drug sensitivity. Detailed analyses of the affected locus revealed that transcription of the nc-tgp1 lncRNA regulates drug tolerance by repressing the adjacent phosphate-responsive permease gene transporter for glycerophosphodiester 1 (tgp1(+)). We demonstrate that the act of transcribing nc-tgp1 over the tgp1(+) promoter increases nucleosome density, prevents transcription factor access and thus represses tgp1(+) without the need for RNA interference or heterochromatin components. We therefore conclude that tgp1(+) is regulated by transcriptional interference. Accordingly, decreased nc-tgp1 transcription permits tgp1(+) expression upon phosphate starvation. Furthermore, nc-tgp1 loss induces tgp1(+) even in repressive conditions. Notably, drug sensitivity results directly from tgp1(+) expression in the absence of the nc-tgp1 RNA. Thus, transcription of an lncRNA governs drug tolerance in fission yeast

High-entropy alloy CoCrFeMnNi produced by powder metallurgy

Lately high-entropy alloys (HEAs) have been the topic of extensive research, as these materials are promising candidates for many challenging applications, as for example tools, moulds and functional coatings. In contrast to conventional alloys, HEAs consist of five or more principal elements, each having a concentration between 5 and 35 at.-%. Against expectations, HEAs show a rather simple microstructure consisting preferentially of cubic phases. Due to this microstructure, HEAs show promising properties, e.g. in terms of high-temperature stability, high strength and ductility. Within this research, a single-phase CoCrFeMnNi HEA was produced by powder metallurgy (PM). In contrast to conventional metallurgy, PM offers a lot of advantages, e.g. good material efficiency and high shape complexity. Gas atomised powder was used and selected PM methods are presented (e.g. pressureless sintering, spark plasma sintering, additive manufacturing (EBM)). The process methods were evaluated by characterising the material properties (density, microstructure, mechanical properties) of the compacted and sintered samples

Defect Study in CoCrFeMnNi High Entropy Alloy by Positron Annihilation Lifetime Spectroscopy

Positron annihilation lifetime spectroscopy is applied to study the crystal defects in CoCrFeMnNi high entropy alloy. The material is measured in the as‐received (electro eroded; non‐etched) state; it shows a defect‐related positron lifetime of 220 ps, corresponding most likely to divacancies, with a relatively high concentration. Furthermore, this sample is annealed in the temperature range up to 1000 K and positron lifetime is measured after each annealing step. The average positron lifetime is found to decrease with annealing and reaches 121 ps after annealing at 1000 K, indicating the existence of some remaining defects in the material. To show whether the observed defects are present in the bulk sample or only in the surface area, another sample is deeply etched and shows only one lifetime component of 112 ps, which is assigned to the defect‐free bulk lifetime in this alloy. This study indicated that the investigates high entropy alloy (in etched state) does not contain open‐volume defects within the sensitivity range of positron annihilation. Here, the defects observed in the non‐etched sample are present in the subsurface region, which are assumed to be generated most probably during wire‐erosion of the samples. In addition, X‐ray diffraction results indicate that the crystal structure is FCC with a lattice constant of (3.597 ± 0.002) Å, which is not affected by annealing

Phase analysis of CoVCRWFExMnyniZ high-entropy alloy and the influence of titanium addition

High-entropy alloys (HEAs) are one of the most promising topics over the past decade. Their unique properties, as for example high-temperature stability and high strength, make them a potential candidate material for many challenging applications, as for example tools, moulds and functional coatings. Within this research a single-phase CoCrFeMnNi HEA was produced by gas atomization and melting processes. The process methods were evaluated by characterizing the material properties (density, microstructure, mechanical properties) of the compacted samples. Furthermore, the stability of the known fcc solid solution phase by progressive variation of the composition as well as the addition of titanium are evaluated after melting

Overexpression of the anti-apoptotic protein AVEN contributes to increased malignancy in hematopoietic neoplasms.

AVEN has been identified as an inhibitor of apoptosis, which binds to the adaptor protein, APAF-1, and thereby prevents apoptosome formation and mitochondrial apoptosis. Recent data have demonstrated high expression levels of AVEN messenger RNA in acute leukemias as well as a positive correlation between AVEN mRNA overexpression and poor prognosis in childhood acute lymphoblastic leukemia. On the basis of these data, we investigated the potential involvement of AVEN in tumorigenesis. First, we confirmed the overexpression of AVEN in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) patient samples. We then established a transgenic mouse model with T-cell-specific overexpression of AVEN, with which we demonstrated the oncogenic cooperation of AVEN with heterozygous loss of p53. Finally, we used a subcutaneous xenograft mouse model to show that AVEN knockdown in the T-ALL cell lines, MOLT-4 and CCRF-CEM, and in the acute myeloblastic leukemia cell line, Kasumi-1, leads to a halt in tumor growth owing to the increased apoptosis and decreased proliferation of tumor cells. Collectively, our data demonstrate that the anti-apoptotic molecule, AVEN, functions as an oncoprotein in hematopoietic neoplasms