LDL receptor related proteins 5 and 6 (LRP5/6) and their Drosophila homolog Arrow are single-span transmembrane proteins essential for Wnt/beta-catenin signaling, likely via acting as Wnt coreceptors. How Wnt activates LRP5/6/Arrow to initiate signal transduction is not well defined. Here we show that a PPPSP motif, which is reiterated five times in the LRP5/6/Arrow intracellular domain, is necessary and sufficient to trigger Wnt/beta-catenin signaling. A single PPPSP motif, upon transfer to the LDL receptor, fully activates the Wnt pathway, inducing complete axis duplication in Xenopus and TCF/beta-catenin-responsive transcription in human cells. We further show that Wnt signal-ing stimulates, and requires, phosphorylation of the PPPSP motif, which creates an inducible docking site for Axin, a scaffolding protein controlling beta-catenin stability. Our study identifies a critical signaling module and a key phosphorylation-dependent activation step of the Wnt receptor complex and reveals a unifying logic for transmembrane signaling by Wnts, growth factors, and cytokines.

A propagating Majorana mode Although Majorana fermions remain elusive as elementary particles, their solid-state analogs have been observed in hybrid semiconductor-superconductor nanowires. In a nanowire setting, the Majorana states are localized at the ends of the wire. He et al. built a two-dimensional heterostructure in which a one-dimensional Majorana mode is predicted to run along the sample edge (see the Perspective by Pribiag). The heterostructure consisted of a quantum anomalous Hall insulator (QAHI) bar contacted by a superconductor. The authors used an external magnetic field as a “knob” to tune into a regime where a Majorana mode was propagating along the edge of the QAHI bar covered by the superconductor. A signature of this propagation—half-quantized conductance—was then observed in transport experiments. Science , this issue p. 294 ; see also p. 252

Materials capable of the safe and efficient capture or degradation of toxic chemicals, including chemical warfare agents (CWAs) and toxic industrial chemicals (TICs), are critically important in the modern age due to continuous threats of these chemicals to human life, both directly and indirectly. Metal−organic frameworks (MOFs), atomically precise hybrid materials that are synthesized via the self-assembly of metal cations or clusters and organic linkers, offer a unique solid adsorbent design platform due to their great synthetic versatility. This review will focus on recent advancements in MOF-based adsorbent design for protection against chemical warfare agents (organophosphorus nerve agents, blistering agents, and their simulants) and toxic industrial chemicals such as H 2 S, NH 3 , SO 2 , CO, NO 2 , and NO. CONTENTS 1. Introduction 8130 2. Capture of Chemical Warfare Agents and Simulants 8132 2.1. Organophosphorous Agents and Their Simulants 8132 2.2. Mustard Gas (HD) and Its Simulants 8135 3. Capture of Toxic Industrial Chemicals (TICs) 8137 3.1. Hydrogen Sulfide (H 2 S) 8137 3.2. Ammonia (NH 3 ) 8141 3.3. Sulfur Dioxide (SO 2 ) 8144 3.4. Carbon Monoxide (CO) 8147 3.5. Nitrogen Oxides (NO x ) 8150 4. Conclusions and Outlook 8152

Oxidative stress causes mitochondrial dysfunction and metabolic complications through unknown mechanisms. Cardiolipin (CL) is a key mitochondrial phospholipid required for oxidative phosphorylation. Oxidative damage to CL from pathological remodeling is implicated in the etiology of mitochondrial dysfunction commonly associated with diabetes, obesity, and other metabolic diseases. Here we show that ALCAT1, a lyso-CL acyltransferase up-regulated by oxidative stress and diet-induced obesity (DIO), catalyzes the synthesis of CL species which are highly sensitive to oxidative damage, leading to mitochondrial dysfunction, ROS production, and insulin resistance. These metabolic disorders were reminiscent of those observed in type 2 diabetes, and were reversed by rosiglitazone treatment. Consequently, ALCAT1 deficiency prevented the onset of DIO and significantly improved mitochondrial complex I activity, lipid oxidation, and insulin signaling in ALCAT1−/− mice. Collectively, these findings identify a key role of ALCAT1 in regulating CL remodeling, mitochondrial dysfunction, and susceptibility to DIO.

A historical overview of the activation and porosity of MOFs including strategies to design and preserve permanent porosity in MOFs.