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Transcriptome analysis of circulating tumor cells (CTCs) provides insights into monitoring target therapeutics and underlying tumor metastasis. Here the authors present Hydro-Seq, a contamination-free high-throughput hydrodynamic scRNA-seq barcoding technique for rare CTCs.

Abstract Since current experimental models of Atrial Fibrillation (AF) have significant limitations, we used human embryonic stem cells (hESCs) to generate an atrial-specific tissue model of AF for pharmacologic testing. We generated atrial-like cardiomyocytes (CMs) from hESCs which preferentially expressed atrial-specific genes, and had shorter action potential (AP) durations compared to ventricular-like CMs. We then generated confluent atrial-like CM sheets and interrogated them using optical mapping techniques. Atrial-like CM sheets (~1 cm in diameter) showed uniform AP propagation, and rapid re-entrant rotor patterns, as seen in AF could be induced. Anti-arrhythmic drugs were tested on single atrial-like CMs and cell sheets. Flecainide profoundly slowed upstroke velocity without affecting AP duration, leading to reduced conduction velocities (CVs), curvatures and cycle lengths of rotors, consistent with increased rotor organization and expansion. By contrast, consistent with block of rapid delayed rectifier K+ currents (Ikr) and AP prolongation in isolated atrial-like CMs, dofetilide prolonged APs and reduced cycle lengths of rotors in cell sheets without affecting CV. In conclusion, using our hESC-derived atrial CM preparations, we demonstrate that flecainide and dofetilide modulate reentrant arrhythmogenic rotor activation patterns in a manner that helps explain their efficacy in treating and preventing AF.

Abstract Machine-learned potentials (MLPs) have exhibited remarkable accuracy, yet the lack of general-purpose MLPs for a broad spectrum of elements and their alloys limits their applicability. Here, we present a promising approach for constructing a unified general-purpose MLP for numerous elements, demonstrated through a model (UNEP-v1) for 16 elemental metals and their alloys. To achieve a complete representation of the chemical space, we show, via principal component analysis and diverse test datasets, that employing one-component and two-component systems suffices. Our unified UNEP-v1 model exhibits superior performance across various physical properties compared to a widely used embedded-atom method potential, while maintaining remarkable efficiency. We demonstrate our approach’s effectiveness through reproducing experimentally observed chemical order and stable phases, and large-scale simulations of plasticity and primary radiation damage in MoTaVW alloys.

N-terminal protein acetylation is required for plant viability. Here the authors show that reducing N-terminal acetylation by NatA leads to an increase in global protein turnover that is facilitated by absent masking of a novel N-degron

Monitoring the activity of the processive motor protein kinesin-1 in live cells is currently difficult. Here the authors report the fluorogenic small molecule QPD-OTf, a kinesin-1 substrate that causes activity-dependent dye precipitation.

Skeletal muscle cells have long been considered to be made primarily of many individual, parallel myofibrils. Here, the authors show that the striated muscle contractile machinery forms a highly branched, mesh-like myofibrillar matrix connected across the entire length and width of the muscle cell.

Bioluminescence resonance energy transfer (BRET) has been mostly employed in imaging applications. Here the authors use BRET to activate a ruthenium-based photocatalyst and perform a bioorthogonal chemical reaction, which can be used to uncage small molecule drugs in a cellular context.

Abstract Growth of eukaryotic cells is regulated by the target of rapamycin (TOR). The strongest activator of TOR in metazoa is amino acid availability. The established transducers of amino acid sensing to TOR in metazoa are absent in plants. Hence, a fundamental question is how amino acid sensing is achieved in photo-autotrophic organisms. Here we demonstrate that the plant Arabidopsis does not sense the sulfur-containing amino acid cysteine itself, but its biosynthetic precursors. We identify the kinase GCN2 as a sensor of the carbon/nitrogen precursor availability, whereas limitation of the sulfur precursor is transduced to TOR by downregulation of glucose metabolism. The downregulated TOR activity caused decreased translation, lowered meristematic activity, and elevated autophagy. Our results uncover a plant-specific adaptation of TOR function. In concert with GCN2, TOR allows photo-autotrophic eukaryotes to coordinate the fluxes of carbon, nitrogen, and sulfur for efficient cysteine biosynthesis under varying external nutrient supply.