PBRM1 acts as a p53 lysine-acetylation reader to suppress renal tumor growth.

p53 acetylation is indispensable for its transcriptional activity and tumor suppressive function. However, the identity of reader protein(s) for p53 acetylation remains elusive. PBRM1, the second most highly mutated tumor suppressor gene in kidney cancer, encodes PBRM1. Here, we identify PBRM1 as a reader for p53 acetylation on lysine 382 (K382Ac) through its bromodomain 4 (BD4). Notably, mutations on key residues of BD4 disrupt recognition of p53 K382Ac. The mutation in BD4 also reduces p53 binding to promoters of target genes such as CDKN1A (p21). Consequently, the PBRM1 BD4 mutant fails to fully support p53 transcriptional activity and is defective as a tumor suppressor. We also find that expressions of PBRM1 and p21 correlate with each other in human kidney cancer samples. Our findings uncover a tumor suppressive mechanism of PBRM1 in kidney cancer and provide a mechanistic insight into the crosstalk between p53 and SWI/SNF complexes

Sperm Micromotors for Cargo Delivery through Flowing Blood

Micromotors are recognized as promising candidates for untethered micromanipulation and targeted cargo delivery in complex biological environments. However, their feasibility in the circulatory system has been limited due to the low thrust force exhibited by many of the reported synthetic micromotors, which is not sufficient to overcome the high flow and complex composition of blood. Here we present a hybrid sperm micromotor that can actively swim against flowing blood (continuous and pulsatile) and perform the function of heparin cargo delivery. In this biohybrid system, the sperm flagellum provides a high propulsion force while the synthetic microstructure serves for magnetic guidance and cargo transport. Moreover, single sperm micromotors can assemble into a train-like carrier after magnetization, allowing the transport of multiple sperm or medical cargoes to the area of interest, serving as potential anticoagulant agents to treat blood clots or other diseases in the circulatory system

Energy Gap from Tunneling and Metallic Sharvin Contacts onto MgB2: Evidence for a Weakened Surface Layer

Point-contact tunnel junctions using a Au tip on sintered MgB2 pellets reveal a sharp superconducting energy gap that is confirmed by subsequent metallic Sharvin contacts made on the same sample. The peak in the tunneling conductance and the Sharvin contact conductance follow the BCS form, but the gap values of 4.3 meV are less than the weak-coupling BCS value of 5.9 meV for the bulk Tc of 39 K. The low value of Delta compared to the BCS value for the bulk Tc is possibly due to chemical reactions at the surface.Comment: 3 pages, 3 figure

ALMA's Polarized View of 10 Protostars in the Perseus Molecular Cloud

We present 870 $\mu$m ALMA dust polarization observations of 10 young Class 0/I protostars in the Perseus Molecular Cloud. At $\sim$ 0.35$"$ (80 au) resolution, all of our sources show some degree of polarization, with most (9/10) showing significantly extended emission in the polarized continuum. Each source has incredibly intricate polarization signatures. In particular, all three disk-candidates have polarization vectors roughly along the minor axis, which is indicative of polarization produced by dust scattering. On $\sim$ 100 au scales, the polarization is at a relatively low level ($\lesssim 1\%$) and is quite ordered. In sources with significant envelope emission, the envelope is typically polarized at a much higher ($\gtrsim 5\%$) level and has a far more disordered morphology. We compute the cumulative probability distributions for both the small (disk-scale) and large (envelope-scale) polarization percentage. We find that the two are intrinsically different, even after accounting for the different detection thresholds in the high/low surface brightness regions. We perform Kolmogorov-Smirnov and Anderson-Darling tests on the distributions of angle offsets of the polarization from the outflow axis. We find disk-candidate sources are different from the non-disk-candidate sources. We conclude that the polarization on the 100 au scale is consistent with the signature of dust scattering for disk-candidates and that the polarization on the envelope-scale in all sources may come from another mechanism, most likely magnetically aligned grains.Comment: 13 pages, 5 figures. Accepted for publication in Ap