208 research outputs found
The chicken lysozyme locus as a paradigm for the complex developmental regulation of eukaryotic gene loci
Comparison of far field characterisation of DOEs with a goniometric DUV-scatterometer and a CCD-based system
We have measured far field diffraction patterns of different diffractive optical elements at an illumination wavelength of 193 nm using a new type of goniometric DUV (deep ultraviolet) scatterometer, which has been developed and set up recently at the PTB, the national metrology institute of Germany. This system offers both a high dynamic range and angular resolution. The scatterometer is especially suitable to analyse weak background light like stray light and local variations of the diffraction patterns over the DOEs (diffractive optical element). The measurement results are compared with measurements using a CCD (charge-coupled device)-based imaging DOE measurement system from Carl Zeiss SMT. An excellent agreement is demonstrated
Towards the pressure and material gap in heterogeneous catalysis: hydrogenation of acrolein over silver catalysts
Introduction In recent time, increasing effort has been undertaken in order to answer the question, whether it is justified to transfer results from surface science studies, mostly obtained with idealised surfaces under UHV conditions, to "real" catalysis, i.e. high pressures and complex materials (the so-called pressure and material gaps). The DFG (German research foundation) has initialised a priority program (SPP 1091) in order to bring together experts from surface science, materials science, catalysis and theory with the aim of bridging the two gaps in catalysis. Within this priority program, we are currently studying the hydrogenation of acrolein over silver. Acrolein, an ,-unsaturated aldehyde, can be hydrogenated either to propanal (product of C=C-bond hydrogenation) or to allyl alcohol (product of C=O-bond hydrogenation. Whereas typical hydrogenation catalysts like Pt, Ru or Ni mainly produce the saturated aldehyde, selectivities to allyl alcohol of up to 53 % can be obtained when using monometallic silver (or gold) catalysts [ , ]. The aim of our studies is to clarify the influence of reaction pressure and material on the selectivity distribution in the acrolein hydrogenation. Catalytic experiments have been carried out with differently structured samples from single crystals to disperse Ag/support catalysts in a broad pressure range (few mbar up to 20 bar). Various methods like in situ-XAS and XPS, flow-adsorption calorimetry, infrared spectroscopy, and transient analysis of products (TAP) are performed in order to gain insight into the modes of interaction of acrolein and hydrogen with differently structured silver samples. Effects of particle size and shape are also considered as well as the influence of the support material. Experimental and Results would add a few words about the composition (Ag loading, different supports) / preparation of the catalysts and/or a reference Gas phase hydrogenation of acrolein has been carried out in a flow reaction system allowing a pressure in the range from 150 mbar up to 20 bar. When using silica supported silver catalysts, clear relations can be drawn concerning the pressure and material dependence of the selectivity to allyl alcohol: increasing partial pressure of either reactant (hydrogen or acrolein) leads to increased selectivity to allyl alcohol, also, smaller particles favour its formation. However, when using ZnO-supported catalysts, the situation becomes more complex. Catalysts prepared with the same catalyst loading and the same catalyst preparation technique but with different ZnO support materials yielded different selectivities to allyl alcohol at the same conversion. On the other hand, catalysts prepared from different precursors, but with the same support, lead to different activities but similar selectivities to allyl alcohol. TEM investigations of the Ag/ZnO and Ag/SiO2 catalysts reveal, that the particle sizes of the silica-supported catalysts are much smaller (2 nm and 15 nm in average for the two most intensively studied catalysts) whereas the silver particles in the Ag/ZnO catalysts are surprisingly large (50 nm up to several hundreds of nm). This is even more surprising since the activities of the catalysts are in the same order of magnitude, with the SiO2 catalysts however, being a bit more active. All these results indicate, that the product distribution at supported silver catalysts is governed by a complex interplay between particle size (and/or shape), pressure, and, as the obviously most important factor, the support and the interactions between silver and support. To gain more insight into the reasons for the catalytic behaviour of the Ag/support catalysts, the interaction of hydrogen alone with various silver samples has been studied. TAP (temporal analysis of products) indicates, that hydrogen interacts with nanodisperse Ag/SiO2 samples, but not with larger unsupported silver particles (several mm in size) like those from electrolyte silver. However, as monitored by transmission infrared spectroscopy, not only the Ag nanoparticles but also the SiO2 support interacts with hydrogen. SiO2 and Ag/SiO2 samples, after reduction and exposure to 100 mbar D2, show a reversible H-D-exchange, as monitored by the Si-O-H(D) bands. Time resolved IR spectra indicate, that this H-D-exchange is faster at silver-containing samples. From temperature-dependent measurements, activation energies for the H-D-exchange of ca. 28 kJ/mol for Ag/SiO2 and ca. 38 kJ/mol for SiO2 have been calculated. The interaction of acrolein with silver single crystals as well as with supported catalysts has been studied with in-situ-XAS and in-situ XPS. For both techniques the samples were contacted with mixtures of H2/acrolein in the mbar pressure range. Angular dependent XAS measurements on a Ag(111) single crystal indicated that acrolein is in the lying-down orientation. For all the samples measured the 1π* “C=O” transition is clearly increased compared to the 1π* “C=C”. Consequently, the surface concentration of C=O bonds relative to C=C bonds is higher, which is in line with concomitantly measured mass spectrometric data showing high selectivity towards C=C hydrogenation. In-situ XPS revealed that while silver foil is partly oxidic (~5%) the supported silver particles are completely reduced, as Ag is in the zero valence state. Data indicate also small amount of oxygen removal from the ZnO supported samples during the contact with hydrogen. The combination of different results suggests that metal-support interaction plays an important role in the reaction. The major difference in hydrogen activation between supported catalysts and pure silver/support provides us a hint that the so-called “adlineation sites” (the perimeter interface between silver and support) are the key sites in the mechanism
Bacillus pumilus B12 Degrades Polylactic Acid and Degradation Is Affected by Changing Nutrient Conditions
Poly-lactic acid (PLA) is increasingly used as a biodegradable alternative to traditional petroleum-based plastics. In this study, we identify a novel agricultural soil isolate of Bacillus pumilus (B12) that is capable of degrading high molecular weight PLA films. This degradation can be detected on a short timescale, with significant degradation detected within 48-h by the release of L-lactate monomers, allowing for a rapid identification ideal for experimental variation. The validity of using L-lactate as a proxy for degradation of PLA films is corroborated by loss of rigidity and appearance of fractures in PLA films, as measured by atomic force microscopy and scanning electron microscopy (SEM), respectively. Furthermore, we have observed a dose-dependent decrease in PLA degradation in response to an amino acid/nucleotide supplement mix that is driven mainly by the nucleotide base adenine. In addition, amendments of the media with specific carbon sources increase the rate of PLA degradation, while phosphate and potassium additions decrease the rate of PLA degradation by B. pumilus B12. These results suggest B. pumilus B12 is adapting its enzymatic expression based on environmental conditions and that these conditions can be used to study the regulation of this process. Together, this work lays a foundation for studying the bacterial degradation of biodegradable plastics
RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML
Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors. RUNX1-EVI1 directs a stem cell-like transcriptional network reliant on GATA2, whereas that of RUNX1-ETO-expressing cells is more mature and depends on RUNX1. However, both types of AML are dependent on the continuous expression of the fusion proteins. Our data provide a molecular explanation for the differences in clinical prognosis for these types of AML
Silber als Hydrierkatalysator: Rolle des Wasserstoffs und Einfluss der Herstellung und Vorbehandlung auf die katalytischen Eigenschaften
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Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding
The t(8;21) translocation fuses the DNA-binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape, we measured genome-wide RUNX1- and RUNX1/ETO-bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end, we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide redistribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal, and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML
RUNX1 Reshapes the Epigenetic Landscape at the Onset of Haematopoiesis
Cell fate decisions during haematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. To gain insight into how these transcription factors regulate the activation of haematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from haemogenic endothelium (HE) to haematopoietic progenitors. Using a embryonic stem cell differentiation model expressing an inducible Runx1 gene, we show that in the absence of RUNX1, haematopoietic genes bind SCL/TAL1, FLI1 and C/EBPβ and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous de novo sites, initiating a local increase in histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of haematopoietic fate controlled by Runx1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing HE program but instead entails global reorganization of lineage-specific transcription factor assemblies
RUNX1/RUNX1T1 mediates alternative splicing and reorganises the transcriptional landscape in leukemia
Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1
\ua9 2024 The Author(s). AML is characterized by mutations in genes associated with growth regulation such as internal tandem duplications (ITD) in the receptor kinase FLT3. Inhibitors targeting FLT3 (FLT3i) are being used to treat patients with FLT3-ITD+ but most relapse and become resistant. To elucidate the resistance mechanism, we compared the gene regulatory networks (GRNs) of leukemic cells from patients before and after relapse, which revealed that the GRNs of drug-responsive patients were altered by rewiring their AP-1-RUNX1 axis. Moreover, FLT3i induces the upregulation of signaling genes, and we show that multiple cytokines, including interleukin-3 (IL-3), can overcome FLT3 inhibition and send cells back into cycle. FLT3i leads to loss of AP-1 and RUNX1 chromatin binding, which is counteracted by IL-3. However, cytokine-mediated drug resistance can be overcome by a pan-RAS inhibitor. We show that cytokines instruct AML growth via the transcriptional regulators AP-1 and RUNX1 and that pan-RAS drugs bypass this barrier
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