资源环境科技发展态势分析平台

Voltage-gated potassium (K-v) channels coordinate electrical signalling and control cell volume by gating in response to membrane depolarization or hyperpolarization. However, although voltage-sensing domains transduce transmembrane electric field changes by a common mechanism involving the outward or inward translocation of gating charges(1-3), the general determinants of channel gating polarity remain poorly understood(4). Here we suggest a molecular mechanism for electromechanical coupling and gating polarity in non-domain-swapped K-v channels on the basis of the cryo-electron microscopy structure of KAT1, the hyperpolarization-activated K-v channel from Arabidopsis thaliana. KAT1 displays a depolarized voltage sensor, which interacts with a closed pore domain directly via two interfaces and indirectly via an intercalated phospholipid. Functional evaluation of KAT1 structure-guided mutants at the sensor-pore interfaces suggests a mechanism in which direct interaction between the sensor and the C-linker hairpin in the adjacent pore subunit is the primary determinant of gating polarity. We suggest that an inward motion of the S4 sensor helix of approximately 5-7 angstrom can underlie a direct-coupling mechanism, driving a conformational reorientation of the C-linker and ultimately opening the activation gate formed by the S6 intracellular bundle. This direct-coupling mechanism contrasts with allosteric mechanisms proposed for hyperpolarization-activated cyclic nucleotide-gated channels(5), and may represent an unexpected link between depolarization- and hyperpolarization-activated channels.

The cryo-electron microscopy structure of the hyperpolarization-activated K+ channel KAT1 points to a direct-coupling mechanism between S4 movement and the reorientation of the C-linker.

Insights into the interactions between pro- and anti-vaccination clusters on Facebook can enable policies and approaches that attempt to interrupt the shift to anti-vaccination views and persuade undecided individuals to adopt a pro-vaccination stance.

Distrust in scientific expertise(1-14) is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks(2-4), as happened for measles in 2019(5,6). Homemade remedies(7,8) and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice(9-11). There is a lack of understanding about how this distrust evolves at the system level(13,14). Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change(11), and highlight the key role of network cluster dynamics in multi-species ecologies(15).