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The control of light-matter interaction at the quantum level usually requires coherent laser fields. But already an exchange of virtual photons with the electromagnetic vacuum field alone can lead to quantum coherences, which subsequently suppress spontaneous emission. We demonstrate such spontaneously generated coherences (SGC) in a large ensemble of nuclei operating in the x-ray regime, resonantly coupled to a common cavity environment. The observed SGC originates from two fundamentally different mechanisms related to cooperative emission and magnetically controlled anisotropy of the cavity vacuum. This approach opens new perspectives for quantum control, quantum state engineering and simulation of quantum many-body physics in an essentially decoherence-free setting.

Nanobodies can be seen as next‐generation tools for the recognition and modulation of antigens that are inaccessible to conventional antibodies. Due to their compact structure and high stability, nanobodies see frequent usage in basic research, and their chemical functionalization opens the way towards promising diagnostic and therapeutic applications. In this Review, central aspects of nanobody functionalization are presented, together with selected applications. While early conjugation strategies relied on the random modification of natural amino acids, more recent studies have focused on the site‐specific attachment of functional moieties. Such techniques include chemoenzymatic approaches, expressed protein ligation, and amber suppression in combination with bioorthogonal modification strategies. Recent applications range from sophisticated imaging and mass spectrometry to the delivery of nanobodies into living cells for the visualization and manipulation of intracellular antigens.

We describe anew technique in protein synthesis that extends the existing repertoire of methods for protein modification:Achemoselective reaction that induces reactivity for as ubsequent bioconjugation. An azide-modified building blockr eacts first with an ethynylphosphonite through aS taudinger-phosphonite reaction (SPhR) to give an ethynylphosphonamidate.T he resulting electron-deficient triple bond subsequently undergoes ac ysteine-selective reaction with proteins or antibodies.W ed emonstrate that ethynylphosphonamidates display excellent cysteine-selective reactivity combined with superior stability of the thiol adducts,w hen compared to classical maleimide linkages.T his turns our technique into av ersatile and powerfult ool for the facile construction of stable functional protein conjugates.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.Figure 4. a) Synthetic scheme for phosphonamidate attachmentofthe Cy5f luorophore to trastuzumab(anti-Her2 antibody) to generate an AFC. b) Immunostaining of fixed cells either over-expressing the cell-surface receptor Her2 (BT474) or exhibiting low Her2 expression levels (MDAMB468). The merged images show the signal from the DNA stain DAPI in blue and the Cy5signal in red. Scale bar:10mm. c) Synthetic scheme for the attachmento fphosphonamidite-modified cCPPs 8 and 9 to aeGFP mutant with asingle addressable cysteine. d) Fluorescence imaging of HeLa cells after incubation with eGFP alone and eGFP-cTat at 50 mm.I mages show the GFP channel in green and the Hoechst 33342 nuclear stain in blue. Scale bar:2 0mm. Forfurther information see the SupportingInformation. Angewandte Chemie Communications

Cells closely coordinate cell division with chromosome replication and segregation; however, the mechanisms responsible for this coordination still remain largely unknown. Here, we analyzed the spatial arrangement and temporal dynamics of the 9.1 Mb circular chromosome in the rod-shaped cells of Myxococcus xanthus. For chromosome segregation, M. xanthus uses a parABS system, which is essential, and lack of ParB results in chromosome segregation defects as well as cell divisions over nucleoids and the formation of anucleate cells. From the determination of the dynamic subcellular location of six genetic loci, we conclude that in newborn cells ori, as monitored following the ParB/parS complex, and ter regions are localized in the subpolar regions of the old and new cell pole, respectively and each separated from the nearest pole by approximately 1 µm. The bulk of the chromosome is arranged between the two subpolar regions, thus leaving the two large subpolar regions devoid of DNA. Upon replication, one ori region remains in the original subpolar region while the second copy segregates unidirectionally to the opposite subpolar region followed by the rest of the chromosome. In parallel, the ter region of the mother chromosome relocates, most likely passively, to midcell, where it is replicated. Consequently, after completion of replication and segregation, the two chromosomes show an ori-ter-ter-ori arrangement with mirror symmetry about a transverse axis at midcell. Upon completion of segregation of the ParB/parS complex, ParA localizes in large patches in the DNA-free subpolar regions. Using an Ssb-YFP fusion as a proxy for replisome localization, we observed that the two replisomes track independently of each other from a subpolar region towards ter. We conclude that M. xanthus chromosome arrangement and dynamics combine features from previously described systems with new features leading to a novel spatiotemporal arrangement pattern.

SummaryCell division site positioning is precisely regulated to generate correctly sized and shaped daughters. We uncover a novel strategy to position the FtsZ cytokinetic ring at midcell in the social bacterium Myxococcus xanthus. PomX, PomY and the nucleoid-binding ParA/MinD ATPase PomZ self-assemble forming a large nucleoid-associated complex that localizes at the division site before FtsZ to directly guide and stimulate division. PomXYZ localization is generated through self-organized biased random motion on the nucleoid towards midcell and constrained motion at midcell. Experiments and theory show that PomXYZ motion is produced by diffusive PomZ fluxes on the nucleoid into the complex. Flux differences scale with the intracellular asymmetry of the complex and are converted into a local PomZ concentration gradient across the complex with translocation towards the higher PomZ concentration. At midcell, fluxes equalize resulting in constrained motion. Flux-based mechanisms may represent a general paradigm for positioning of macromolecular structures in bacteria.

Modern x-ray light sources promise access to structure and dynamics of matter in largely unexplored spectral regions. However, the desired information is encoded in the light intensity and phase, whereas detectors register only the intensity. This phase problem is ubiquitous in crystallography and imaging and impedes the exploration of quantum effects at x-ray energies. Here, we demonstrate phase-sensitive measurements characterizing the quantum state of a nuclear two-level system at hard x-ray energies. The nuclei are initially prepared in a superposition state. Subsequently, the relative phase of this superposition is interferometrically reconstructed from the emitted x rays. Our results form a first step towards x-ray quantum state tomography and provide new avenues for structure determination and precision metrology via x-ray Fano interference.

Purpose: To study mechanisms of therapy resistance and disease progression, we analyzed the evolution of cytogenetically normal acute myeloid leukemia (CN-AML) based on somatic alterations. Experimental Design: We performed exome sequencing of matched diagnosis, remission, and relapse samples from 50 CN-AML patients treated with intensive chemotherapy. Mutation patterns were correlated with clinical parameters. Results: Evolutionary patterns correlated with clinical outcome. Gain of mutations was associated with late relapse. Alterations of epigenetic regulators were frequently gained at relapse with recurring alterations of KDM6A constituting a mechanism of cytarabine resistance. Low KDM6A expression correlated with adverse clinical outcome, particularly in male patients. At complete remission, persistent mutations representing preleukemic lesions were observed in 48% of patients. The persistence of DNMT3A mutations correlated with shorter time to relapse. Conclusions: Chemotherapy resistance might be acquired through gain of mutations. Insights into the evolution during therapy and disease progression lay the foundation for tailored approaches to treat or prevent relapse of CN-AML. Clin Cancer Res; 24(7); 1716–26. ©2018 AACR.