Ion permeation through a narrow cavity constriction in KCNQ1 channels: Mechanism and implications for pathogenic variants.

KCNQ1 potassium channels play a pivotal role in the physiology and pathophysiology of several human excitable and epithelial tissues. The latest cryo-electron microscopy (cryo-EM) structures provide unique insights into channel function and pharmacology, opening avenues for different therapeutic strategies against human diseases associated with KCNQ1 mutations. However, these structures also raise fundamental questions about the mechanisms of ion permeation.

The rise and transformation of Bronze Age pastoralists in the Caucasus.

The Caucasus and surrounding areas, with their rich metal resources, became a crucible of the Bronze Age and the birthplace of the earliest steppe pastoralist societies. Yet, despite this region having a large influence on the subsequent development of Europe and Asia, questions remain regarding its hunter-gatherer past and its formation of expansionist mobile steppe societies. Here we present new genome-wide data for 131 individuals from 38 archaeological sites spanning 6,000 years.

Combinational regularity analysis (CORA): An introduction for psychologists.

Increasingly, psychologists make use of modern configurational comparative methods (CCMs), such as qualitative comparative analysis (QCA) and coincidence analysis (CNA), to infer regularity-theoretic causal structures from psychological data. At the same time, existing CCMs remain unable to reveal such structures in the presence of complex effects. Given the strong emphasis configurational methodology generally puts on the notion of complex causation, and the ubiquity of multieffect problems in psychological research, such as multimorbidity and polypharmacy, this limitation is severe.

Case-to-factor Ratios and Model Specification in Qualitative Comparative Analysis.

Qualitative comparative analysis (QCA) is an empirical research method that has gained some popularity in the social sciences. At the same time, the literature has long been convinced that QCA is prone to committing causal fallacies when confronted with non-causal data. More specifically, beyond a certain case-to-factor ratio, the method is believed to fail in recognizing real data.