Polymer nanodiscs support the functional extraction of an artificial transmembrane cytochrome.

Polymer nanodiscs are an attractive alternative to surfactants for studying integral membrane proteins within their native lipid environment. Here, we investigate the use of such polymers to isolate a computationally-designed de novo membrane cytochrome named CytbX. We show that the block copolymers known as CyclAPols can efficiently extract CytbX directly from biomembranes and are compatible with the downstream purification and biophysical characterisation of this artificial protein.

Delineating redox cooperativity in water-soluble and membrane multiheme cytochromes through protein design.

Nature has evolved diverse electron transport proteins and multiprotein assemblies essential to the generation and transduction of biological energy. However, substantially modifying or adapting these proteins for user-defined applications or to gain fundamental mechanistic insight can be hindered by their inherent complexity. De novo protein design offers an attractive route to stripping away this confounding complexity, enabling us to probe the fundamental workings of these bioenergetic proteins and systems, while providing robust, modular platforms for constructing completely artificial electron-conducting circuitry.

Neuromodulation of striatal D1 cells shapes BOLD fluctuations in anatomically connected thalamic and cortical regions.

Understanding how the brain's macroscale dynamics are shaped by underlying microscale mechanisms is a key problem in neuroscience. In animal models, we can now investigate this relationship in unprecedented detail by directly manipulating cellular-level properties while measuring the whole-brain response using resting-state fMRI. Here, we focused on understanding how blood-oxygen-level-dependent (BOLD) dynamics, measured within a structurally well-defined striato-thalamo-cortical circuit in mice, are shaped by chemogenetically exciting or inhibiting D1 medium spiny neurons (MSNs) of the right dorsomedial caudate putamen (CPdm).

Efficacy of Single Wound Infiltration With Bupivacaine and Adrenaline During Cesarean Delivery for Reduction of Postoperative Pain: A Randomized Clinical Trial.

Importance: Most women report moderate to severe pain after cesarean delivery. The extent of the ability of surgical wound infiltration with local anesthetic agents during cesarean delivery for the reduction of postoperative pain is uncertain.

Objective: To examine the efficacy of single wound infiltration with bupivacaine and adrenaline during cesarean delivery for the reduction of postoperative pain.