By using synchrotron X-ray powder diffraction, the temperature dependent phase diagram of the hybrid perovskite tri-halide compounds, methyl ammonium lead iodide (MAPbI
, MA
= CH
NH
) and methyl ...ammonium lead bromide (MAPbBr
), as well as of their solid solutions, has been established. The existence of a large miscibility gap between 0.29 ≤
≤ 0.92 (±0.02) for the MAPb(I
Br
)
solid solution has been proven. A systematic study of the lattice parameters for the solid solution series at room temperature revealed distinct deviations from Vegard's law. Furthermore, temperature dependent measurements showed that a strong temperature dependency of lattice parameters from the composition is present for iodine rich compositions. In contrast, the bromine rich compositions show an unusually low dependency of the phase transition temperature from the degree of substitution.
The hallmark of canonical Wnt signaling is the transcriptional induction of Wnt target genes by the beta-catenin/TCF complex. Several studies have proposed alternative interaction partners for ...beta-catenin or TCF, but the relevance of potential bifurcations in the distal Wnt pathway remains unclear. Here we study on a genome-wide scale the requirement for Armadillo (Arm, Drosophila beta-catenin) and Pangolin (Pan, Drosophila TCF) in the Wnt/Wingless(Wg)-induced transcriptional response of Drosophila Kc cells. Using somatic genetics, we demonstrate that both Arm and Pan are absolutely required for mediating activation and repression of target genes. Furthermore, by means of STARR-sequencing we identified Wnt/Wg-responsive enhancer elements and found that all responsive enhancers depend on Pan. Together, our results confirm the dogma of canonical Wnt/Wg signaling and argue against the existence of distal pathway branches in this system.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An isotope-selective responsive system based on molecular recognition in porous materials has potential for the storage and purification of isotopic mixtures but is considered unachievable because of ...the almost identical physicochemical properties of the isotopes. Herein, a unique isotope-responsive breathing transition of the flexible metal–organic framework (MOF), MIL-53(Al), which can selectively recognize and respond to only D2 molecules through a secondary breathing transition, is reported. This novel phenomenon is examined using in situ neutron diffraction experiments under the same conditions for H2 and D2 sorption experiments. This work can guide the development of a novel isotope-selective recognition system and provide opportunities to fabricate flexible MOF systems for energy-efficient purification of the isotopic mixture.
The solid solution series NaMgH3−xFx (x = 0, 0.5, 1, 1.5, 2, 2.5, 3) was synthesized by solid-state reactions under hydrogen gas pressure from binary ionic hydrides, fluorides and magnesium. Rietveld ...refinement based on X-ray powder diffraction data revealed the GdFeO3-structure type for all compounds and a trend of lattice parameters according to Vegard's law. The anion distribution in NaMgD2F and NaMgD1.5F1.5 was found to be statistical by Rietveld refinement based on neutron powder diffraction data. Photoluminescence measurements on europium(II) substituted NaMgH3−xFx revealed a strong red shift of the emission wavelength (λem = 665nm for NaMgH2F:Eu) in comparison to violet emitting NaMgF3:Eu.
Solid solutions NaMgH3−xFx crystallize with the GdFeO3 type structure and statistical distribution of anions (right). Samples doped with europium emit orange to violet light (left) upon excitation with UV radiation depending on the substitutional degree x. Display omitted
•Solid solutions NaMgH3−xFx crystallize with the GdFeO3 type structure.•Hydride and fluoride anions are statistically distributed as proven by X-ray and neutron diffraction.•Under UV excitation, samples doped with europium emit orange to violet light depending on x.
Switchable metal-organic frameworks (MOFs) have been proposed for various energy-related storage and separation applications, but the mechanistic understanding of adsorption-induced switching ...transitions is still at an early stage. Here we report critical design criteria for negative gas adsorption (NGA), a counterintuitive feature of pressure amplifying materials, hitherto uniquely observed in a highly porous framework compound (DUT-49). These criteria are derived by analysing the physical effects of micromechanics, pore size, interpenetration, adsorption enthalpies, and the pore filling mechanism using advanced in situ X-ray and neutron diffraction, NMR spectroscopy, and calorimetric techniques parallelised to adsorption for a series of six isoreticular networks. Aided by computational modelling, we identify DUT-50 as a new pressure amplifying material featuring distinct NGA transitions upon methane and argon adsorption. In situ neutron diffraction analysis of the methane (CD
) adsorption sites at 111 K supported by grand canonical Monte Carlo simulations reveals a sudden population of the largest mesopore to be the critical filling step initiating structural contraction and NGA. In contrast, interpenetration leads to framework stiffening and specific pore volume reduction, both factors effectively suppressing NGA transitions.
Siglec-15 is a conserved sialic acid-binding Ig-like lectin expressed on osteoclast progenitors, which plays an important role in osteoclast development and function. It is also expressed by ...tumor-associated macrophages and by some tumors, where it is thought to contribute to the immunosuppressive microenvironment. It was shown previously that engagement of macrophage-expressed Siglec-15 with tumor cells expressing its ligand, sialyl Tn (sTn), triggered production of TGF-β. In the present study, we have further investigated the interaction between Siglec-15 and sTn on tumor cells and its functional consequences. Based on binding assays with lung and breast cancer cell lines and glycan-modified cells, we failed to see evidence for recognition of sTn by Siglec-15. However, using a microarray of diverse, structurally defined glycans, we show that Siglec-15 binds with higher avidity to sialylated glycans other than sTn or related antigen sequences. In addition, we were unable to demonstrate enhanced TGF-β secretion following co-culture of Siglec-15-expressing monocytic cell lines with tumor cells expressing sTn or following Siglec-15 cross-linking with monoclonal antibodies. However, we did observe activation of the SYK/MAPK signaling pathway following antibody cross-linking of Siglec-15 that may modulate the functional activity of macrophages.
Ramsdellite-like Li2Ti3O7 is an excellent, strongly anisotropic lithium-ion conductor with various proposed applications in energy storage and lithium processing. Diffusion pathways have not yet been ...thoroughly studied, in spite of their importance for these purposes; even the precise crystal structure of this material is a subject of ongoing discussion. Herein, we use variable-temperature neutron diffraction in the metastability range of ramsdellite-like Li2Ti3O7 to probe the nontrivial lithium-ion distribution. Refinement with anisotropic displacement parameters including anharmonic terms identifies the room-temperature structure as statically disordered snapshot of the dynamic behavior at synthesis temperature. Mapping of scattering-length density, reconstructed using maximum-entropy methods (MEM), shows the signature of partial relaxation and activation of lithium movement with increasing temperature. Scrutinous topological analyses of procrystal voids and Voronoi–Dirichlet partitioning (VDP) reveal lithium diffusion along ribbons in the interstitial channels as the major and diffusion through framework vacancies as the most probable minor mechanism. By rationalizing former empirical results, we provide deeper insight into this paradigmatic example of strongly anisotropic lithium-ion conductors.
Display omitted
•In ramsdellite-like Li2Ti3O7, interstitial lithium ions are complexly distributed.•Framework cation positions are not significantly occupied by lithium ions.•Heating successively leads to relaxation, increased mobility, and decomposition.•Spacious interstitial channels contain the major pathway of lithium diffusion.•Framework vacancies are the most probable minor pathway of lithium diffusion.
The cellular response to heat stress is an ancient and evolutionarily highly conserved defence mechanism characterised by the transcriptional up-regulation of cyto-protective genes and a partial ...inhibition of splicing. These features closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative stress as well as of the inflammatory response, mainly due to its role in the transcriptional regulation process. In addition, there are also several lines of evidence implicating BRD4 in the splicing process. Using RNA-sequencing we found a significant increase in splicing inhibition, in particular intron retentions (IR), following heat treatment in BRD4-depleted cells. This leads to a decrease of mRNA abundancy of the affected transcripts, most likely due to premature termination codons. Subsequent experiments revealed that BRD4 interacts with the heat shock factor 1 (HSF1) such that under heat stress BRD4 is recruited to nuclear stress bodies and non-coding SatIII RNA transcripts are up-regulated. These findings implicate BRD4 as an important regulator of splicing during heat stress. Our data which links BRD4 to the stress induced splicing process may provide novel mechanisms of BRD4 inhibitors in regard to anti-cancer therapies.
Poly (ADP)-ribose polymerase (PARP) inhibitors have entered routine clinical practice for the treatment of high-grade serous ovarian cancer (HGSOC), yet the molecular mechanisms underlying treatment ...response to PARP1 inhibition (PARP1i) are not fully understood.
Here, we used unbiased mass spectrometry based proteomics with data-driven protein network analysis to systematically characterize how HGSOC cells respond to PARP1i treatment.
We found that PARP1i leads to pronounced proteomic changes in a diverse set of cellular processes in HGSOC cancer cells, consistent with transcript changes in an independent perturbation dataset. We interpret decreases in the levels of the pro-proliferative transcription factors SP1 and β-catenin and in growth factor signaling as reflecting the anti-proliferative effect of PARP1i; and the strong activation of pro-survival processes NF-κB signaling and lipid metabolism as PARPi-induced adaptive resistance mechanisms. Based on these observations, we nominate several protein targets for therapeutic inhibition in combination with PARP1i. When tested experimentally, the combination of PARPi with an inhibitor of fatty acid synthase (TVB-2640) has a 3-fold synergistic effect and is therefore of particular pre-clinical interest.
Our study improves the current understanding of PARP1 function, highlights the potential that the anti-tumor efficacy of PARP1i may not only rely on DNA damage repair mechanisms and informs on the rational design of PARP1i combination therapies in ovarian cancer.
Using gas sorption measurements at ambient temperatures and in situ neutron powder diffraction methods, we have studied the interaction strengths and coordination geometries of O
and N
near the ...non-occupied coordination site (open metal site) in the isostructural MOF structures of the CPO-27-M/M-MOF-74 series (with M = Co, Ni, Mn and Cu). Our experimental observations are compared to periodic quantum chemical model calculations. Contrary to recent computational studies, our results, both experimental and theoretical, unequivocally suggest rather weak interactions between the M(ii) coordinatively unsaturated centers and the adsorbate molecules, being mainly dispersive and electrostatic in nature. As a consequence, they exclude significant orbital charge transfer effects that could lead to superoxide/peroxide formation. Calculated binding energies appear in good agreement with the measured isosteric heats of adsorption in the range of 10-20 kJ mol
. These, relatively weak host-guest interactions, lead to a tilted end-on geometry in all of the investigated M(ii)-guest molecule adducts.
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