Optogenetic ß cell interrogation in vivo reveals a functional hierarchy directing the Ca2+ response to glucose supported by vitamin B6.

Coordination of cellular activity through Ca2+ enables ß cells to secrete precise quantities of insulin. To explore how the Ca2+ response is orchestrated in space and time, we implement optogenetic systems to probe the role of individual ß cells in the glucose response. By targeted ß cell activation/inactivation in zebrafish, we reveal a hierarchy of cells, each with a different level of influence over islet-wide Ca2+ dynamics. First-responder ß cells lie at the top of the hierarchy, essential for initiating the first-phase Ca2+ response. Silencing first responders impairs the Ca2+ response to glucose. Conversely, selective activation of first responders demonstrates their increased capability to raise pan-islet Ca2+ levels compared to followers. By photolabeling and transcriptionally profiling ß cells that differ in their thresholds to a glucose-stimulated Ca2+ response, we highlight vitamin B6 production as a signature pathway of first responders. We further define an evolutionarily conserved requirement for vitamin B6 in enabling the Ca2+ response to glucose in mammalian systems.

Multi-qubit quantum computing using discrete-time quantum walks on closed graphs.

Universal quantum computation can be realised using both continuous-time and discrete-time quantum walks. We present a version based on single particle discrete-time quantum walk to realize multi-qubit computation tasks. The scalability of the scheme is demonstrated by using a set of walk operations on a closed lattice form to implement the universal set of quantum gates on multi-qubit system. We also present a set of experimentally realizable walk operations that can implement Grover's algorithm, quantum Fourier transformation and quantum phase estimation algorithms. An elementary implementation of error detection and correction is also presented. Analysis of space and time complexity of the scheme highlights the advantages of quantum walk based model for quantum computation on systems where implementation of quantum walk evolution operations is an inherent feature of the system.

RUFY3 links Arl8b and JIP4-Dynein complex to regulate lysosome size and positioning.

The bidirectional movement of lysosomes on microtubule tracks regulates their whole-cell spatial arrangement. Arl8b, a small GTP-binding (G) protein, promotes lysosome anterograde trafficking mediated by kinesin-1. Herein, we report an Arl8b effector, RUFY3, which regulates the retrograde transport of lysosomes. We show that RUFY3 interacts with the JIP4-dynein-dynactin complex and facilitates Arl8b association with the retrograde motor complex. Accordingly, RUFY3 knockdown disrupts the positioning of Arl8b-positive endosomes and reduces Arl8b colocalization with Rab7-marked late endosomal compartments. Moreover, we find that RUFY3 regulates nutrient-dependent lysosome distribution, although autophagosome-lysosome fusion and autophagic cargo degradation are not impaired upon RUFY3 depletion. Interestingly, lysosome size is significantly reduced in RUFY3 depleted cells, which could be rescued by inhibition of the lysosome reformation regulatory factor PIKFYVE. These findings suggest a model in which the perinuclear cloud arrangement of lysosomes regulates both the positioning and size of these proteolytic compartments.

A single-cell atlas of de novo ß-cell regeneration reveals the contribution of hybrid ß/δ-cells to diabetes recovery in zebrafish.

Regeneration-competent species possess the ability to reverse the progression of severe diseases by restoring the function of the damaged tissue. However, the cellular dynamics underlying this capability remain unexplored. Here, we have used single-cell transcriptomics to map de novo ß-cell regeneration during induction and recovery from diabetes in zebrafish. We show that the zebrafish has evolved two distinct types of somatostatin-producing δ-cells, which we term δ1- and δ2-cells. Moreover, we characterize a small population of glucose-responsive islet cells, which share the hormones and fate-determinants of both ß- and δ1-cells. The transcriptomic analysis of ß-cell regeneration reveals that ß/δ hybrid cells provide a prominent source of insulin expression during diabetes recovery. Using in vivo calcium imaging and cell tracking, we further show that the hybrid cells form de novo and acquire glucose-responsiveness in the course of regeneration. The overexpression of dkk3, a gene enriched in hybrid cells, increases their formation in the absence of ß-cell injury. Finally, interspecies comparison shows that plastic δ1-cells are partially related to PP cells in the human pancreas. Our work provides an atlas of ß-cell regeneration and indicates that the rapid formation of glucose-responsive hybrid cells contributes to the resolution of diabetes in zebrafish.

Universal quantum computing using single-particle discrete-time quantum walk.

Quantum walk has been regarded as a primitive to universal quantum computation. In this paper, we demonstrate the realization of the universal set of quantum gates on two- and three-qubit systems by using the operations required to describe the single particle discrete-time quantum walk on a position space. The idea is to utilize the effective Hilbert space of the single qubit and the position space on which it evolves in order to realize multi-qubit states and universal set of quantum gates on them. Realization of many non-trivial gates and engineering arbitrary states is simpler in the proposed quantum walk model when compared to the circuit based model of computation. We will also discuss the scalability of the model and some propositions for using lesser number of qubits in realizing larger qubit systems.

AIE-active mechanoluminescent discotic liquid crystals for applications in OLEDs and bio-imaging.

A multifunctional molecular design of fluorescent discotic liquid crystal (DLC) consisting of a tetraphenylethylene core is reported, which is found to serve as an excellent solid-state emitter in OLED devices with EQE of 4.4% and tunable mechanochromism. X-ray diffraction studies unveiled that change in supramolecular self-assembly is the physical origin of mechanochromism. The luminescent DLC molecule has been shown to act as a highly selective probe for labelling acidic cellular compartments (such as lysosomes) in bio-imaging using HeLa cells.

Incorporating Motility in the Motor: Role of the Hook Protein Family in Regulating Dynein Motility.

Cytoplasmic dynein is a retrograde microtubule-based motor transporting cellular cargo, including organelles, vesicular intermediates, RNA granules, and proteins, thus regulating their subcellular distribution and function. Mammalian dynein associates with dynactin, a multisubunit protein complex that is necessary for the processive motility of dynein along the microtubule tracks. Recent studies have shown that the interaction between dynein and dynactin is enhanced in the presence of a coiled-coil activating adaptor protein, which performs dual functions of recruiting dynein and dynactin to their cargoes and inducing the superprocessive motility of the motor complex. One such family of coiled-coil activating adaptor proteins is the Hook family of proteins that are conserved across evolution with three paralogs in the case of mammals, namely, HOOK1-HOOK3. This Perspective aims to provide an overview of the Hook protein structure and the cellular functions of Hook proteins, with an emphasis on the recent developments in understanding their role as activating dynein adaptors.