18 research outputs found

    Ferromagnetic Domain Distribution in Thin Films During Magnetization Reversal

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    We have shown that polarized neutron reflectometry can determine in a model-free way not only the mean magnetization of a ferromagnetic thin film at any point of a hysteresis cycle, but also the mean square dispersion of the magnetization vectors of its lateral domains. This technique is applied to elucidate the mechanism of the magnetization reversal of an exchange-biased Co/CoO bilayer. The reversal process above the blocking temperature is governed by uniaxial domain switching, while below the blocking temperature the reversal of magnetization for the trained sample takes place with substantial domain rotation

    NK-like homeodomain proteins activate NOTCH3-signaling in leukemic T-cells

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    <p>Abstract</p> <p>Background</p> <p>Homeodomain proteins control fundamental cellular processes in development and in cancer if deregulated. Three members of the NK-like subfamily of homeobox genes (NKLs), TLX1, TLX3 and NKX2-5, are implicated in T-cell acute lymphoblastic leukemia (T-ALL). They are activated by particular chromosomal aberrations. However, their precise function in leukemogenesis is still unclear. Here we screened further NKLs in 24 T-ALL cell lines and identified the common expression of MSX2. The subsequent aim of this study was to analyze the role of MSX2 in T-cell differentiation which may be disturbed by oncogenic NKLs.</p> <p>Methods</p> <p>Specific gene activity was examined by quantitative real-time PCR, and globally by expression profiling. Proteins were analyzed by western blot, immuno-cytology and immuno-precipitation. For overexpression studies cell lines were transduced by lentiviruses.</p> <p>Results</p> <p>Quantification of MSX2 mRNA in primary hematopoietic cells demonstrated higher levels in CD34+ stem cells as compared to peripheral blood cells and mature CD3+ T-cells. Furthermore, analysis of MSX2 expression levels in T-cell lines after treatment with core thymic factors confirmed their involvement in regulation. These results indicated that MSX2 represents an hematopoietic NKL family member which is downregulated during T-cell development and may functionally substituted by oncogenic NKLs. For functional analysis JURKAT cells were lentivirally transduced, overexpressing either MSX2 or oncogenic TLX1 and NKX2-5, respectively. These cells displayed transcriptional activation of NOTCH3-signaling, including NOTCH3 and HEY1 as analyzed by gene expression profiling and quantitative RT-PCR, and consistently attenuated sensitivity to gamma-secretase inhibitor as analyzed by MTT-assays. Furthermore, in addition to MSX2, both TLX1 and NKX2-5 proteins interacted with NOTCH-pathway repressors, SPEN/MINT/SHARP and TLE1/GRG1, representing a potential mechanism for (de)regulation. Finally, elevated expression of NOTCH3 and HEY1 was detected in primary TLX1/3 positive T-ALL cells corresponding to the cell line data.</p> <p>Conclusion</p> <p>Identification and analysis of MSX2 in hematopoietic cells implicates a modulatory role via NOTCH3-signaling in early T-cell differentiation. Our data suggest that reduction of NOTCH3-signaling by physiological downregulation of MSX2 expression during T-cell development is abrogated by ectopic expression of oncogenic NKLs, substituting MSX2 function.</p

    Interallelic complementation provides functional evidence for cohesin–cohesin interactions on DNA

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    The cohesin complex (Mcd1p, Smc1p, Smc3p, and Scc3p) has multiple roles in chromosome architecture, such as promoting sister chromatid cohesion, chromosome condensation, DNA repair, and transcriptional regulation. The prevailing embrace model for sister chromatid cohesion posits that a single cohesin complex entraps both sister chromatids. We report interallelic complementation between pairs of nonfunctional mcd1 alleles (mcd1-1 and mcd1-Q266) or smc3 alleles (smc3-42 and smc3-K113R). Cells bearing individual mcd1 or smc3 mutant alleles are inviable and defective for both sister chromatid cohesion and condensation. However, cells coexpressing two defective mcd1 or two defective smc3 alleles are viable and have cohesion and condensation. Because cohesin contains only a single copy of Smc3p or Mcd1p, these examples of interallelic complementation must result from interplay or communication between the two defective cohesin complexes, each harboring one of the mutant allele products. Neither mcd1-1p nor smc3-42p is bound to chromosomes when expressed individually at its restrictive temperature. However, their chromosome binding is restored when they are coexpressed with their chromosome-bound interallelic complementing partner. Our results support a mechanism by which multiple cohesin complexes interact on DNA to mediate cohesion and condensation

    Connectivity to the surface determines diversity patterns in subsurface aquifers of the Fennoscandian shield

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    Little research has been conducted on microbial diversity deep under the Earth/'s surface. In this study, the microbial communities of three deep terrestrial subsurface aquifers were investigated. Temporal community data over 6 years revealed that the phylogenetic structure and community dynamics were highly dependent on the degree of isolation from the earth surface biomes. The microbial community at the shallow site was the most dynamic and was dominated by the sulfur-oxidizing genera Sulfurovum or Sulfurimonas at all-time points. The microbial community in the meteoric water filled intermediate aquifer (water turnover approximately every 5 years) was less variable and was dominated by candidate phylum OD1. Metagenomic analysis of this water demonstrated the occurrence of key genes for nitrogen and carbon fixation, sulfate reduction, sulfide oxidation and fermentation. The deepest water mass (5000 year old waters) had the lowest taxon richness and surprisingly contained Cyanobacteria. The high relative abundance of phylogenetic groups associated with nitrogen and sulfur cycling, as well as fermentation implied that these processes were important in these systems. We conclude that the microbial community patterns appear to be shaped by the availability of energy and nutrient sources via connectivity to the surface or from deep geological processes.Supplementary information available for this article at http://www.nature.com/ismej/journal/vaop/ncurrent/suppinfo/ismej201636s1.html</p
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