Structural basis for ion selectivity in potassium-selective channelrhodopsins.

KCR channelrhodopsins (K+-selective light-gated ion channels) have received attention as potential inhibitory optogenetic tools but more broadly pose a fundamental mystery regarding how their K+ selectivity is achieved. Here, we present 2.5-2.7 Å cryo-electron microscopy structures of HcKCR1 and HcKCR2 and of a structure-guided mutant with enhanced K+ selectivity. Structural, electrophysiological, computational, spectroscopic, and biochemical analyses reveal a distinctive mechanism for K+ selectivity; rather than forming the symmetrical filter of canonical K+ channels achieving both selectivity and dehydration, instead, three extracellular-vestibule residues within each monomer form a flexible asymmetric selectivity gate, while a distinct dehydration pathway extends intracellularly. Structural comparisons reveal a retinal-binding pocket that induces retinal rotation (accounting for HcKCR1/HcKCR2 spectral differences), and design of corresponding KCR variants with increased K+ selectivity (KALI-1/KALI-2) provides key advantages for optogenetic inhibition in vitro and in vivo. Thus, discovery of a mechanism for ion-channel K+ selectivity also provides a framework for next-generation optogenetics.

Social object play between captive bottlenose and Risso's dolphins.

Many animal species engage in social object play with movable objects. Two bottlenose dolphins (Tursiops truncatus) and one Risso's dolphin (Grampus griseus) owned by the Kujukushima Aquarium, Japan, occasionally shared and played with an object. Herein, we report social object play between two dolphins exchanging a ball in water. Just before delivery of the ball, one dolphin made an action to request the ball from the dolphin that possessed the ball. This request behavior is also discussed in this report. This study is the first to report two different cetacean species engaging in social object play with one object.

Spontaneous prosocial choice by captive bottlenose dolphins, Tursiops truncatus.

Dolphins exhibit prosocial behavior across several different contexts. However, only a few experimental studies have investigated the psychological mechanisms underlying this behavior. In this study, we investigated the mechanisms underlying prosociality in bottlenose dolphins (Tursiops truncatus). In the experiments, water shower devices, developed as environmental enrichment items, were used. Two paradigms were used to measure prosociality. The first was the prosocial choice task, involving the subject typically being offered one choice between two options. The first option provided a reward (take a shower) to both the subject and partner (prosocial choice). The second option provided a reward only to the subject (selfish choice). The second paradigm was the giving assistance task, involving the subject being provided a choice between providing instrumental help to the partner (prosocial choice) or doing nothing. It was observed that the subjects chose the prosocial choices in both paradigms. In these experiments, prosocial choices were spontaneously taken without requests from the partners. These results indicated that the dolphins show preference for other-regarding behavior.

Structural basis for specific inhibition of Autotaxin by a DNA aptamer.

ATX is a plasma lysophospholipase D that hydrolyzes lysophosphatidylcholine (LPC) and produces lysophosphatidic acid. To date, no ATX-inhibition-mediated treatment strategies for human diseases have been established. Here, we report anti-ATX DNA aptamers that inhibit ATX with high specificity and efficacy. We solved the crystal structure of ATX in complex with the anti-ATX aptamer RB011, at 2.0-Å resolution. RB011 binds in the vicinity of the active site through base-specific interactions, thus preventing the access of the choline moiety of LPC substrates. Using the structural information, we developed the modified anti-ATX DNA aptamer RB014, which exhibited in vivo efficacy in a bleomycin-induced pulmonary fibrosis mouse model. Our findings reveal the structural basis for the specific inhibition of ATX by the anti-ATX aptamer and highlight the therapeutic potential of anti-ATX aptamers for the treatment of human diseases, such as pulmonary fibrosis.