Age-Associated Loss of Lamin-B Leads to Systemic Inflammation and Gut Hyperplasia

SummaryAging of immune organs, termed as immunosenescence, is suspected to promote systemic inflammation and age-associated disease. The cause of immunosenescence and how it promotes disease, however, has remained unclear. We report that the Drosophila fat body, a major immune organ, undergoes immunosenescence and mounts strong systemic inflammation that leads to deregulation of immune deficiency (IMD) signaling in the midgut of old animals. Inflamed old fat bodies secrete circulating peptidoglycan recognition proteins that repress IMD activity in the midgut, thereby promoting gut hyperplasia. Further, fat body immunosenecence is caused by age-associated lamin-B reduction specifically in fat body cells, which then contributes to heterochromatin loss and derepression of genes involved in immune responses. As lamin-associated heterochromatin domains are enriched for genes involved in immune response in both Drosophila and mammalian cells, our findings may provide insights into the cause and consequence of immunosenescence during mammalian aging.PaperFlic

γ-Tubulin complexes in microtubule nucleation and beyond

Tremendous progress has been made in understanding the functions of γ-tubulin and, in particular, its role in microtubule nucleation since the publication of its discovery in 1989. The structure of γ-tubulin has been determined, and the components of γ-tubulin complexes have been identified. Significant progress in understanding the structure of the γ-tubulin ring complex and its components has led to a persuasive model for how these complexes nucleate microtubule assembly. At the same time, data have accumulated that γ-tubulin has important but less well understood functions that are not simply a consequence of its function in microtubule nucleation. These include roles in the regulation of plus-end microtubule dynamics, gene regulation, and mitotic and cell cycle regulation. Finally, evidence is emerging that γ-tubulin mutations or alterations of γ-tubulin expression play an important role in certain types of cancer and in other diseases

A mechanism of coupling RCC1 mobility to RanGTP production on the chromatin in vivo

The RanGTP gradient across the interphase nuclear envelope and on the condensed mitotic chromosomes is essential for many cellular processes, including nucleocytoplasmic transport and spindle assembly. Although the chromosome-associated enzyme RCC1 is responsible for RanGTP production, the mechanism of generating and maintaining the RanGTP gradient in vivo remains unknown. Here, we report that regulator of chromosome condensation (RCC1) rapidly associates and dissociates with both interphase and mitotic chromosomes in living cells, and that this mobility is regulated during the cell cycle. Our kinetic modeling suggests that RCC1 couples its catalytic activity to chromosome binding to generate a RanGTP gradient. Indeed, we have demonstrated experimentally that the interaction of RCC1 with the chromatin is coupled to the nucleotide exchange on Ran in vivo. The coupling is due to the stable binding of the binary complex of RCC1–Ran to chromatin. Successful nucleotide exchange dissociates the binary complex, permitting the release of RCC1 and RanGTP from the chromatin and the production of RanGTP on the chromatin surface

One Transformer Can Understand Both 2D & 3D Molecular Data

Unlike vision and language data which usually has a unique format, molecules can naturally be characterized using different chemical formulations. One can view a molecule as a 2D graph or define it as a collection of atoms located in a 3D space. For molecular representation learning, most previous works designed neural networks only for a particular data format, making the learned models likely to fail for other data formats. We believe a general-purpose neural network model for chemistry should be able to handle molecular tasks across data modalities. To achieve this goal, in this work, we develop a novel Transformer-based Molecular model called Transformer-M, which can take molecular data of 2D or 3D formats as input and generate meaningful semantic representations. Using the standard Transformer as the backbone architecture, Transformer-M develops two separated channels to encode 2D and 3D structural information and incorporate them with the atom features in the network modules. When the input data is in a particular format, the corresponding channel will be activated, and the other will be disabled. By training on 2D and 3D molecular data with properly designed supervised signals, Transformer-M automatically learns to leverage knowledge from different data modalities and correctly capture the representations. We conducted extensive experiments for Transformer-M. All empirical results show that Transformer-M can simultaneously achieve strong performance on 2D and 3D tasks, suggesting its broad applicability. The code and models will be made publicly available at https://github.com/lsj2408/Transformer-M.Comment: 20 pages; ICLR 2023, Camera Ready Version; Code: https://github.com/lsj2408/Transformer-

HI content of massive red spiral galaxies observed by FAST

A sample of 279 massive red spirals was selected optically by Guo et al. (2020), among which 166 galaxies have been observed by the ALFALFA survey. In this work, we observe HI content of the rest 113 massive red spiral galaxies using the Five-hundred-meter Aperture Spherical radio Telescope (FAST). 75 of the 113 galaxies have HI detection with a signal-to-noise ratio (S/N) greater than 4.7. Compared with the red spirals in the same sample that have been observed by the ALFALFA survey, galaxies observed by FAST have on average a higher S/N, and reach to a lower HI mass. To investigate why many red spirals contain a significant amount of HI mass, we check color profiles of the massive red spirals using images observed by the DESI Legacy Imaging Surveys. We find that galaxies with HI detection have bluer outer disks than the galaxies without HI detection, for both ALFALFA and FAST samples. For galaxies with HI detection, there exists a clear correlation between galaxy HI mass and g-r color at outer radius: galaxies with higher HI masses have bluer outer disks. The results indicate that optically selected massive red spirals are not fully quenched, and the HI gas observed in many of the galaxies may exist in their outer blue disks.Comment: 11 pages, 9 figures, accepted by MNRAS; Table 1 is available in the source file