Crystallization of the MS2 translational repressor alone and complexed to bromouridine

Journal ArticleThe coat protein from the MS2 bacteriophage plays a dual role by encapsidating viral RNA and also by binding RNA as a translational repressor. In order to study the isolated dimer in a conformation not influenced by capsid interactions, a mutant molecule was crystallized that is defective in capsid assembly but is an active repressor. The unassembled dimer crystallized in the space group P21212 with a = 76.2, b = 55.7, and c = 28.4 A. In these crystals, monomers were related by twofold symmetry. When this dimer was co-crystallized with 5-bromouridine, crystals formed in space group R3 with a = b = 155.9 A, c = 29.9 A, gamma = 120 degrees; the dimer was the asymmetric unit

Multiomics technologies for comprehensive tumor microenvironment analysis in triple-negative breast cancer under neoadjuvant chemotherapy

Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes and is characterized by abundant infiltrating immune cells within the microenvironment. As standard care, chemotherapy remains the fundamental neoadjuvant treatment in TNBC, and there is increasing evidence that supplementation with immune checkpoint inhibitors may potentiate the therapeutic efficiency of neoadjuvant chemotherapy (NAC). However, 20-60% of TNBC patients still have residual tumor burden after NAC and require additional chemotherapy; therefore, it is critical to understand the dynamic change in the tumor microenvironment (TME) during treatment to help improve the rate of complete pathological response and long-term prognosis. Traditional methods, including immunohistochemistry, bulk tumor sequencing, and flow cytometry, have been applied to elucidate the TME of breast cancer, but the low resolution and throughput may overlook key information. With the development of diverse high-throughput technologies, recent reports have provided new insights into TME alterations during NAC in four fields, including tissue imaging, cytometry, next-generation sequencing, and spatial omics. In this review, we discuss the traditional methods and the latest advances in high-throughput techniques to decipher the TME of TNBC and the prospect of translating these techniques to clinical practice

Flow reversals in thermally driven turbulence

We analyze the reversals of the large scale flow in Rayleigh-B\'enard convection both through particle image velocimetry flow visualization and direct numerical simulations (DNS) of the underlying Boussinesq equations in a (quasi) two-dimensional, rectangular geometry of aspect ratio 1. For medium Prandtl number there is a diagonal large scale convection roll and two smaller secondary rolls in the two remaining corners diagonally opposing each other. These corner flow rolls play a crucial role for the large scale wind reversal: They grow in kinetic energy and thus also in size thanks to plume detachments from the boundary layers up to the time that they take over the main, large scale diagonal flow, thus leading to reversal. Based on this mechanism we identify a typical time scale for the reversals. We map out the Rayleigh number vs Prandtl number phase space and find that the occurrence of reversals very sensitively depends on these parameters.Comment: 4 pages, 4 figure

Sex Differences in the White Matter and Myelinated Fibers of APP/PS1 Mice and the Effects of Running Exercise on the Sex Differences of AD Mice

Previous studies have suggested that changes in the white matter might play an important role in the pathogenic processes of Alzheimer's disease (AD). However, no study has investigated sex differences in these changes. Previous studies found that running exercise could delay both the decline in spatial learning and memory abilities as well as the changes in the white matter during early AD in male mice. However, whether exercise also has an effect on the changes in the white matter in female AD mice remains unknown. To address these questions, 6- and 10-month-old male and female APP/PS1 double transgenic AD mice were used. The 6-month-old male and female APP/PS1 double transgenic AD mice underwent a 4-month running exercise regime. The white matter volume and parameters of the myelinated fibers in the white matter of the 10-month-old exercised and non-exercised male and female AD mice were investigated using electron microscopy and stereological methods. There were no significant differences in the mean escape latencies between the male and female AD mice in the non-exercised groups, but after 4 months of treadmill exercise, the mean escape latencies of the female exercised AD mice had significantly shortened compared with those of the male exercised AD mice. The total white matter volume and most of the parameters of the myelinated fibers of the white matter in the female AD mice were significantly lower than those of the male AD mice. The total length of the myelinated fibers with diameters ranging from 0.6 to 0.7 μm, the axonal diameter of the myelinated fibers and the g-ratio of the myelinated fibers in the white matter of the exercised female AD mice were significantly increased compared with those of the non-exercised female AD mice. There were sex-specific differences in the white matter and myelinated fibers of white matter in the AD mice. Running exercise more effectively delayed the decline in spatial learning and memory abilities and delayed the changes in the myelinated fibers of the white matter in female transgenic mice with early AD than in male transgenic mice