Circuit Topology Analysis of Single-Cell HiC Data.

The 3D fold structure of the genome is intricately linked to its function. As a result, descriptors of 3D genome conformation are becoming increasingly important as markers for disease and therapeutic responses. Circuit topology, a theory of folds, formalizes the arrangement of contacts in an entangled chain.

Ebola virus-like particles reprogram cellular metabolism.

Ebola virus can trigger a release of pro-inflammatory cytokines with subsequent vascular leakage and impairment of clotting finally leading to multiorgan failure and shock after entering and infecting patients. Ebola virus is known to directly target endothelial cells and macrophages, even without infecting them, through direct interactions with viral proteins. These interactions affect cellular mechanics and immune processes, which are tightly linked to other key cellular functions such as metabolism.

Single cell force spectroscopy of erythrocytes at physiological and febrile temperatures reveals mechano-modulatory effects of atorvastatin.

RBCs are mechanically active cells and constantly deform as they circulate through vasculature. Their mechanical properties can be significantly altered by various pathophysiological conditions, and the alterations in RBC mechanics can, in turn, have functional consequences. Although numerous mechanical studies have been conducted on RBCs, surprisingly, strain-rate and temperature dependent mechanics of RBCs have not been systematically examined, and current data is primarily based on measurements at room temperature.

Topological principles of protein folding.

What is the topology of a protein and what governs protein folding to a specific topology? This is a fundamental question in biology. The protein folding reaction is a critically important cellular process, which is failing in many prevalent diseases. Understanding protein folding is also key to the design of new proteins for applications.

Reciprocal regulation of cellular mechanics and metabolism.

Metabolism and mechanics are intrinsically intertwined. External forces, sensed through the cytoskeleton or distortion of the cell and organelles, induce metabolic changes in the cell. The resulting changes in metabolism, in turn, feed back to regulate every level of cell biology, including the mechanical properties of cells and tissues.

Correction to: Signaling lipids as diagnostic biomarkers for ocular surface cicatrizing conjunctivitis.

The correct name of the 11th Author and the missing Acknowledgment is presented in this paper.

Signaling lipids as diagnostic biomarkers for ocular surface cicatrizing conjunctivitis.

Metabolomics has been applied to diagnose diseases, predict disease progression, and design therapeutic strategies in various areas of medicine. However, it remains to be applied to the ocular surface diseases, where biological samples are often of limited quantities. We successfully performed proof-of-concept metabolomics assessment of volume-limited cytology samples from a clinical form of chronic inflammatory cicatrizing conjunctivitis, i.

Dry Eye Disease: Emerging Approaches to Disease Analysis and Therapy.

Dry eye disease (DED) is among the most common ocular disorders affecting tens of millions of individuals worldwide; however, the condition remains incompletely understood and treated. Valuable insights have emerged from multidisciplinary approaches, including immunometabolic analyses, microbiome analyses, and bioengineering. Furthermore, we have seen new developments in clinical assessment approaches and treatment strategies in the recent past.

Mapping a single-molecule folding process onto a topological space.

Physics of protein folding has been dominated by conceptual frameworks including the nucleation-propagation mechanism and the diffusion-collision model, and none address the topological properties of a chain during a folding process. Single-molecule interrogation of folded biomolecules has enabled real-time monitoring of folding processes at an unprecedented resolution. Despite these advances, the topology landscape has not been fully mapped for any chain.

Uncovering hidden disease patterns by simulating clinical diagnostic processes.

Choosing a sequence of observations (often with stochastic outcomes) which maximizes the information gain from a system of interacting variables is essential for a wide range of problems in science and technology, such as clinical diagnostic problems. Here, we use a probabilistic model of diseases and signs/symptoms to simulate the effects of medical decisions on the quality of diagnosis by maximizing an appropriate objective function of the medical observations. The study provides a systematic way of proposing new medical tests, considering the significance of diseases and cost of the suggested observations.

Immunophysical analysis of corneal neovascularization: mechanistic insights and implications for pharmacotherapy.

The cornea lacks adaptive immune cells and vasculature under healthy conditions, but is populated by both cell types under pathologic conditions and after transplantation. Here we propose an immunophysical approach to describe postoperative neovascularization in corneal grafts. We develop a simple dynamic model that captures not only the well-established interactions between innate immunity and vascular dynamics but also incorporates the contributions of adaptive immunity to vascular growth.

On the role of topology in regulating transcriptional cascades.

We study the impact of topology on the response of a transcriptional cascade with certain circuit topologies to a constant and time-varying input signal. We systematically analyze the response of the output to activating and repressing cascades. We identify two types of responses for a linear cascade, namely the "Decaying mode", where the input signal becomes exceedingly weaker as it propagates, and the "Bistable mode", where the input signal can either be amplified or die out in the pathway.

Topology of polymer chains under nanoscale confinement.

Spatial confinement limits the conformational space accessible to biomolecules but the implications for bimolecular topology are not yet known. Folded linear biopolymers can be seen as molecular circuits formed by intramolecular contacts. The pairwise arrangement of intra-chain contacts can be categorized as parallel, series or cross, and has been identified as a topological property.