Spectroscopic fingerprint of chiral Majorana modes at the edge of a quantum anomalous Hall insulator/superconductor heterostructure.

With the recent discovery of the quantum anomalous Hall insulator (QAHI), which exhibits the conductive quantum Hall edge states without external magnetic field, it becomes possible to create a topological superconductor (SC) by introducing superconductivity into these edge states. In this case, 2 distinct topological superconducting phases with 1 or 2 chiral Majorana edge modes were theoretically predicted, characterized by Chern numbers (N) of 1 and 2, respectively. We present spectroscopic evidence from Andreev reflection experiments for the presence of chiral Majorana modes in an Nb/(Cr0.12Bi0.26Sb0.62)2Te3 heterostructure with distinct signatures attributed to 2 different topological superconducting phases. The results are in qualitatively good agreement with the theoretical predictions.

Histone lysine demethylase KDM4B regulates the alternative splicing of the androgen receptor in response to androgen deprivation.

Alternative splicing is emerging as an oncogenic mechanism. In prostate cancer, generation of constitutively active forms of androgen receptor (AR) variants including AR-V7 plays an important role in progression of castration-resistant prostate cancer (CRPC). AR-V7 is generated by alternative splicing that results in inclusion of cryptic exon CE3 and translation of truncated AR protein that lacks the ligand binding domain. Whether AR-V7 can be a driver for CRPC remains controversial as the oncogenic mechanism of AR-V7 activation remains elusive. Here, we found that KDM4B promotes AR-V7 and identified a novel regulatory mechanism. KDM4B is phosphorylated by protein kinase A under conditions that promote castration-resistance, eliciting its binding to the splicing factor SF3B3. KDM4B binds RNA specifically near the 5'-CE3, upregulates the chromatin accessibility, and couples the spliceosome to the chromatin. Our data suggest that KDM4B can function as a signal responsive trans-acting splicing factor and scaffold that recruits and stabilizes the spliceosome near the alternative exon, thus promoting its inclusion. Genome-wide profiling of KDM4B-regulated genes also identified additional alternative splicing events implicated in tumorigenesis. Our study defines KDM4B-regulated alternative splicing as a pivotal mechanism for generating AR-V7 and a contributing factor for CRPC, providing insight for mechanistic targeting of CRPC.

Detectability of active triangulation range finder: a solar irradiance approach.

Active triangulation range finders are widely used in a variety of applications such as robotics and assistive technologies. The power of the laser source should be carefully selected in order to satisfy detectability and still remain eye-safe. In this paper, we present a systematic approach to assess the detectability of an active triangulation range finder in an outdoor environment. For the first time, we accurately quantify the background noise of a laser system due to solar irradiance by coupling the Perez all-weather sky model and ray tracing techniques. The model is validated with measurements with a modeling error of less than 14.0%. Being highly generic and sufficiently flexible, the proposed model serves as a guide to define a laser system for any geographical location and microclimate.

Recent Advances of WEE1 Inhibitors and Statins in Cancers With p53 Mutations.

p53 is among the most frequently mutated tumor suppressor genes given its prevalence in >50% of all human cancers. One critical tumor suppression function of p53 is to regulate transcription of downstream genes and maintain genomic stability by inducing the G1/S checkpoint in response to DNA damage. Tumor cells lacking functional p53 are defective in the G1/S checkpoint and become highly dependent on the G2/M checkpoint to maintain genomic stability and are consequently vulnerable to Wee1 inhibitors, which override the cell cycle G2/M checkpoint and induce cell death through mitotic catastrophe. In addition to the lost tumor suppression function, many mutated p53 (Mutp53) proteins acquire gain-of-function (GOF) activities as oncogenes to promote cancer progression, which manifest through aberrant expression of p53. In cancer cells with GOF Mutp53, statins can induce CHIP-mediated degradation of Mutp53 within the mevalonate pathway by blocking the interaction between mutp53 and DNAJA1. Therefore, targeting critical downstream pathways of Mutp53 provides an alternative strategy for treating cancers expressing Mutp53. In this review, we summarize recent advances with Wee1 inhibitors, statins, and mevalonate pathway inhibitors in cancers with p53 mutations.

Kramers nodal line metals.

Recently, it was pointed out that all chiral crystals with spin-orbit coupling (SOC) can be Kramers Weyl semimetals (KWSs) which possess Weyl points pinned at time-reversal invariant momenta. In this work, we show that all achiral non-centrosymmetric materials with SOC can be a new class of topological materials, which we term Kramers nodal line metals (KNLMs). In KNLMs, there are doubly degenerate lines, which we call Kramers nodal lines (KNLs), connecting time-reversal invariant momenta. The KNLs create two types of Fermi surfaces, namely, the spindle torus type and the octdong type. Interestingly, all the electrons on octdong Fermi surfaces are described by two-dimensional massless Dirac Hamiltonians. These materials support quantized optical conductance in thin films. We further show that KNLMs can be regarded as parent states of KWSs. Therefore, we conclude that all non-centrosymmetric metals with SOC are topological, as they can be either KWSs or KNLMs.

Histone lysine dimethyl-demethylase KDM3A controls pathological cardiac hypertrophy and fibrosis.

Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular morbidity and mortality. Pathological LVH engages transcriptional programs including reactivation of canonical fetal genes and those inducing fibrosis. Histone lysine demethylases (KDMs) are emerging regulators of transcriptional reprogramming in cancer, though their potential role in abnormal heart growth and fibrosis remains little understood. Here, we investigate gain and loss of function of an H3K9me2 specific demethylase, Kdm3a, and show it promotes LVH and fibrosis in response to pressure-overload. Cardiomyocyte KDM3A activates Timp1 transcription with pro-fibrotic activity. By contrast, a pan-KDM inhibitor, JIB-04, suppresses pressure overload-induced LVH and fibrosis. JIB-04 inhibits KDM3A and suppresses the transcription of fibrotic genes that overlap with genes downregulated in Kdm3a-KO mice versus WT controls. Our study provides genetic and biochemical evidence for a pro-hypertrophic function of KDM3A and proof-of principle for pharmacological targeting of KDMs as an effective strategy to counter LVH and pathological fibrosis.