Nano‐ and Microscale Confinements in DNA‐Scaffolded Enzyme Cascade Reactions

Artificial reconstruction of naturally evolved principles, such as compartmentalization and cascading of multienzyme complexes, offers enormous potential for the development of biocatalytic materials and processes. Due to their unique addressability at the nanoscale, DNA origami nanostructures (DON) have proven to be an exceptionally powerful tool for studying the fundamental processes in biocatalytic cascades. To systematically investigate the diffusion-reaction network of (co)substrate transfer in enzyme cascades, a model system of stereoselective ketoreductase (KRED) with cofactor regenerating enzyme is assembled in different spatial arrangements on DNA nanostructures and is located in the sphere of microbeads (MB) as a spatially confining nano- and microenvironment, respectively. The results, obtained through the use of highly sensitive analytical methods, Western blot-based quantification of the enzymes, and mass spectrometric (MS) product detection, along with theoretical modeling, provide strong evidence for the presence of two interacting compartments, the diffusion layers around the microbead and the DNA scaffold, which influence the catalytic efficiency of the cascade. It is shown that the microscale compartment exerts a strong influence on the productivity of the cascade, whereas the nanoscale arrangement of enzymes has no influence but can be modulated by the insertion of a diffusion barrier

Amp(1q) and tetraploidy are commonly acquired chromosomal abnormalities in relapsed multiple myeloma.

Long-term disease control in multiple myeloma (MM) is typically an unmet medical need, and most patients experience multiple relapses. Fluorescence in situ hybridization (FISH) is the standard technique to detect chromosomal abnormalities (CAs), which are important to estimate the prognosis of MM and the allocation of risk adapted therapies. In advanced stages, the importance of CAs needs further investigation. From 148 MM patients, two or more paired samples, at least one of which was collected at relapse, were analyzed by FISH. Using targeted next-generation sequencing, we molecularly investigated samples harboring relapse-associated CAs. Sixty-one percent of the patients showed a change in the cytogenetic profile during the disease course, including 10% who acquired high-risk cytogenetics. Amp(1q) (≥4 copies of 1q21), driven by an additional increase in copy number in patients who already had 3 copies of 1q21, was the most common acquired CA with 16% affected patients. Tetraploidy, found in 10% of the samples collected at the last time-point, was unstable over the course of the disease and was associated with TP53 lesions. Our results indicate that cytogenetic progression is common in relapsed patients. The relatively high frequency of amp(1q) suggests an active role for this CA in disease progression

First lifetime investigations of N>82N>82 iodine isotopes: The quest for collectivity

We report on spectroscopic information and lifetime measurements in the neutron-rich I135,137,139 isotopes. This is the first lifetime data on iodine isotopes beyond N=82. Excited states were populated in fast neutron-induced fission of U238 at the ALTO facility of IJCLab with the LICORNE neutron source and detected using the hybrid ν-ball spectrometer. The level schemes of the I135,137,139 isotopes are revised in terms of excited states with up to maximum spin-parity of (33/2+), populated for the first time in fast neutron-induced fission. We provide first results on the lifetimes of the (9/21+) and (13/21+) states in I137 and I139, and the (17/21+) state in I137. In addition, we give upper lifetime limits for the (11/21+) states in I135−139, the (15/21+) state in I137, the (17/21+) state in I139, and reexamine the (29/21+) state in I137. The isomeric data in I135 are reinvestigated, such as the previously known (15/21+) and (23/21−) isomers with T1/2 of 1.64(14) and 4.6(7) ns, respectively, as obtained in this work. The new spectroscopic information is compared to that from spontaneous or thermal-neutron induced fission and discussed in the context of large scale shell-model (LSSM) calculations for the region beyond Sn132, indicating the behavior of collectivity for the three valence-proton iodine chain with N=82,84,86

γ\gamma-ray Spectroscopy of 85^{85}Se Produced in 232^{232}Th Fission

Excited states in the neutron-rich 85Se nucleus have been studied using for the first time a fast neutron-induced fission of 232Th. The experiment was performed at the ALTO facility of the IPN Orsay. Coupling of the LICORNE directional neutron source with the ν-ball high-resolution γ-ray spectrometer provided unique access to high-spin states in neutron-rich fission fragments from the 232Th(n, f) reaction. A preliminary level scheme of 85Se was established by the analysis of prompt γ–γ–γ coincidences. Identification of the all known yrast states in 85Se is the first step towards studies of more neutron-rich Se isotopes