| 1371. |
- Mer, Arvind Singh, et al.
(författare)
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Biological and therapeutic implications of a unique subtype of NPM1 mutated AML
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- In acute myeloid leukemia (AML), molecular heterogeneity across patients constitutes a major challenge for prognosis and therapy. AML with NPM1 mutation is a distinct genetic entity in the revised World Health Organization classification. However, differing patterns of co-mutation and response to therapy within this group necessitate further stratification. Here we report two distinct subtypes within NPM1 mutated AML patients, which we label as primitive and committed based on the respective presence or absence of a stem cell signature. Using gene expression (RNA-seq), epigenomic (ATAC-seq) and immunophenotyping (CyToF) analysis, we associate each subtype with specific molecular characteristics, disease differentiation state and patient survival. Using ex vivo drug sensitivity profiling, we show a differential drug response of the subtypes to specific kinase inhibitors, irrespective of the FLT3-ITD status. Differential drug responses of the primitive and committed subtype are validated in an independent AML cohort. Our results highlight heterogeneity among NPM1 mutated AML patient samples based on stemness and suggest that the addition of kinase inhibitors to the treatment of cases with the primitive signature, lacking FLT3-ITD, could have therapeutic benefit. Molecular heterogeneity of acute myeloid leukaemia (AML) across patients is a major challenge for prognosis and therapy. Here, the authors show that NPM1 mutated AML is a heterogeneous class, consisting of two subtypes which exhibit distinct molecular characteristics, differentiation state, patient survival and drug response.
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| 1372. |
- Mergenthaler, K., et al.
(författare)
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Anti-Stokes photoluminescence probing k-conservation and thermalization of minority carriers in degenerately doped semiconductors
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- It has recently been found that anti-Stokes photoluminescence can be observed in degenerately n-doped indium phosphide nanowires, when exciting directly into the electron gas. This anti-Stokes mechanism has not been observed before and allows the study of carrier relaxation and recombination using standard photoluminescence techniques. It is important to know if this anti-Stokes photoluminescence also occurs in bulk semiconductors as well as its relation to carrier recombination and relaxation. Here we show that similar anti-Stokes photoluminescence can indeed be observed in degenerately doped bulk indium phosphide and gallium arsenide and is caused by minority carriers scattering to high momenta by phonons. We find in addition that the radiative electron-hole recombination is highly momentum-conserving and that photogenerated minority carriers recombine before relaxing to the band edge at low temperatures. These observations challenge the use of models assuming thermalization of minority carriers in the analysis of highly doped devices.
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| 1373. |
- Merkl, Philipp, et al.
(författare)
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Proximity control of interlayer exciton-phonon hybridization in van der Waals heterostructures
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Van der Waals stacking has provided unprecedented flexibility in shaping many-body interactions by controlling electronic quantum confinement and orbital overlap. Theory has predicted that also electron-phonon coupling critically influences the quantum ground state of low-dimensional systems. Here we introduce proximity-controlled strong-coupling between Coulomb correlations and lattice dynamics in neighbouring van der Waals materials, creating new electrically neutral hybrid eigenmodes. Specifically, we explore how the internal orbital 1s-2p transition of Coulomb-bound electron-hole pairs in monolayer tungsten diselenide resonantly hybridizes with lattice vibrations of a polar capping layer of gypsum, giving rise to exciton-phonon mixed eigenmodes, called excitonic Lyman polarons. Tuning orbital exciton resonances across the vibrational resonances, we observe distinct anticrossing and polarons with adjustable exciton and phonon compositions. Such proximity-induced hybridization can be further controlled by quantum designing the spatial wavefunction overlap of excitons and phonons, providing a promising new strategy to engineer novel ground states of two-dimensional systems. Here, the authors demonstrate proximity-controlled strong-coupling between Coulomb correlations and lattice dynamics in neighbouring van der Waals materials (WSe2 and a gypsum layer), creating electrically neutral hybrid exciton-phonon eigenmodes called excitonic Lyman polarons.
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| 1374. |
- Merkl, Philipp, et al.
(författare)
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Twist-tailoring Coulomb correlations in van der Waals homobilayers
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The recent discovery of artificial phase transitions induced by stacking monolayer materials at magic twist angles represents a paradigm shift for solid state physics. Twist-induced changes of the single-particle band structure have been studied extensively, yet a precise understanding of the underlying Coulomb correlations has remained challenging. Here we reveal in experiment and theory, how the twist angle alone affects the Coulomb-induced internal structure and mutual interactions of excitons. In homobilayers of WSe2, we trace the internal 1s–2p resonance of excitons with phase-locked mid-infrared pulses as a function of the twist angle. Remarkably, the exciton binding energy is renormalized by up to a factor of two, their lifetime exhibits an enhancement by more than an order of magnitude, and the exciton-exciton interaction is widely tunable. Our work opens the possibility of tailoring quasiparticles in search of unexplored phases of matter in a broad range of van der Waals heterostructures.
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| 1375. |
- Merte, Lindsay, et al.
(författare)
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Water clustering on nanostructured iron oxide films
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The adhesion of water to solid surfaces is characterized by the tendency to balance competing molecule-molecule and molecule-surface interactions. Hydroxyl groups form strong hydrogen bonds to water molecules and are known to substantially influence the wetting behaviour of oxide surfaces, but it is not well-understood how these hydroxyl groups and their distribution on a surface affect the molecular-scale structure at the interface. Here we report a study of water clustering on a moire-structured iron oxide thin film with a controlled density of hydroxyl groups. While large amorphous monolayer islands form on the bare film, the hydroxylated iron oxide film acts as a hydrophilic nanotemplate, causing the formation of a regular array of ice-like hexameric nanoclusters. The formation of this ordered phase is localized at the nanometre scale; with increasing water coverage, ordered and amorphous water are found to coexist at adjacent hydroxylated and hydroxyl-free domains of the moire structure.
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| 1376. |
- Metelev, Mikhail, et al.
(författare)
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Direct measurements of mRNA translation kinetics in living cells
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Metelev et al. use single-molecule tracking to study kinetics of translation directly in E. coli cells, and how it is affected by translation inhibitors and rRNA mutations. Their results support widespread 70S re-initiation on mRNAs. Ribosome mediated mRNA translation is central to life. The cycle of translation, however, has been characterized mostly using reconstituted systems, with only few techniques applicable for studies in the living cell. Here we describe a live-cell ribosome-labeling method, which allows us to characterize the whole processes of finding and translating an mRNA, using single-molecule tracking techniques. We find that more than 90% of both bacterial ribosomal subunits are engaged in translation at any particular time, and that the 30S and 50S ribosomal subunits spend the same average time bound to an mRNA, revealing that 30S re-initiation on poly-cistronic mRNAs is not prevalent in E. coli. Instead, our results are best explained by substantial 70S re-initiation of translation of poly-cistronic mRNAs, which is further corroborated by experiments with translation initiation inhibitors. Finally, we find that a variety of previously described orthogonal ribosomes, with altered anti-Shine-Dalgarno sequences, show significant binding to endogenous mRNAs.
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| 1377. |
- Metere, Alfredo, et al.
(författare)
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A new kind of soft-matter quasicrystal
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Ingår i: Nature Communications. - 2041-1723.
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Tidskriftsartikel (refereegranskat)abstract
- Quasiperiodic order in mesoscopic soft-matter systems is now a new research frontier of rapidly growing interest \cite{DUB}. Here, we report a novel kind of soft-matter quasicrystal that has so far never been observed, nor theoretically predicted. It represents a structure composed of hexagonally densely packed particle layers axially stacked in a $ABA...$ order, resembling smectic-$B$ crystal \cite{CHANDR}. In contrast to the latter, $A$ and $B$ layers in this structure are rotated by $30^{\circ}$ with respect to each other, in the layer plane, which induces 12-fold global rotational symmetry. So far, the only kind of quasiperiodic order observed in smectic phases \cite{CHANDR} has been twist grain boundaries (TGB) structure induced by commensurate helical rotation of the smectic slabs around the axis parallel to the layer plane \cite{LUB, GOOD}. The quasicrystal we report was produced in a molecular-dynamics simulation of a single-component system of particles interacting via a spherically-symmetric potential, as a result of a first-order phase transition from a liquid phase under constant-density cooling. This finding implies that a similarly structured quasicrystal can possibly be produced by the mesogens of the kind that produce smectic-B crystals. The simple isotropic form of the pair potential used in this simulation makes it possible to expect that this type of quasicrystal can also be produced in a system of spherically-shaped colloidal particles with appropriately tuned force field.
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| 1378. |
- Metskas, Lauren Ann, et al.
(författare)
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Rubisco forms a lattice inside alpha-carboxysomes
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Many autotrophic bacteria rely on Rubisco for carbon dioxide fixation. Here the authors report the position, orientation, and structure of Rubisco within alpha-carboxysomes; showing how it polymerizes and can form a lattice inside this compartment. Despite the importance of microcompartments in prokaryotic biology and bioengineering, structural heterogeneity has prevented a complete understanding of their architecture, ultrastructure, and spatial organization. Here, we employ cryo-electron tomography to image alpha-carboxysomes, a pseudo-icosahedral microcompartment responsible for carbon fixation. We have solved a high-resolution subtomogram average of the Rubisco cargo inside the carboxysome, and determined the arrangement of the enzyme. We find that the H. neapolitanus Rubisco polymerizes in vivo, mediated by the small Rubisco subunit. These fibrils can further pack to form a lattice with six-fold pseudo-symmetry. This arrangement preserves freedom of motion and accessibility around the Rubisco active site and the binding sites for two other carboxysome proteins, CsoSCA (a carbonic anhydrase) and the disordered CsoS2, even at Rubisco concentrations exceeding 800 mu M. This characterization of Rubisco cargo inside the alpha-carboxysome provides insight into the balance between order and disorder in microcompartment organization.
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| 1379. |
- Meyer, Peter A., et al.
(författare)
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Data publication with the structural biology data grid supports live analysis
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data. sbgrid. org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis.
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| 1380. |
- Mezger, A, et al.
(författare)
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High-throughput chromatin accessibility profiling at single-cell resolution
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3647-
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Tidskriftsartikel (refereegranskat)abstract
- Here we develop a high-throughput single-cell ATAC-seq (assay for transposition of accessible chromatin) method to measure physical access to DNA in whole cells. Our approach integrates fluorescence imaging and addressable reagent deposition across a massively parallel (5184) nano-well array, yielding a nearly 20-fold improvement in throughput (up to ~1800 cells/chip, 4–5 h on-chip processing time) and library preparation cost (~81¢ per cell) compared to prior microfluidic implementations. We apply this method to measure regulatory variation in peripheral blood mononuclear cells (PBMCs) and show robust, de novo clustering of single cells by hematopoietic cell type.
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