Time to start taking time seriously: how to investigate unexpected biological rhythms within infectious disease research.

The discovery of rhythmicity in host and pathogen activities dates back to the Hippocratic era, but the causes and consequences of these biological rhythms have remained poorly understood. Rhythms in infection phenotypes or traits are observed across taxonomically diverse hosts and pathogens, suggesting general evolutionary principles. Understanding these principles may enable rhythms to be leveraged in manners that improve drug and vaccine efficacy or disrupt pathogen timekeeping to reduce virulence and transmission.

Development of compounds for targeted degradation of mammalian cryptochrome proteins.

The mammalian cryptochrome proteins (CRY1 and CRY2) are transcriptional repressors most notable for their role in circadian transcriptional feedback. Not all circadian rhythms depend on CRY proteins, however, and the CRY proteins are promiscuous interactors that also regulate many other processes. In cells with chronic CRY deficiency, protein homeostasis is highly perturbed, with a basal increase in cellular stress and activation of key inflammatory signalling pathways.

Chronic CRYPTOCHROME deficiency enhances cell-intrinsic antiviral defences.

The within-host environment changes over circadian time and influences the replication and severity of viruses. Genetic knockout of the circadian transcription factors CRYPTOCHROME 1 and CRYPTOCHROME 2 (/; CKO) leads to altered protein homeostasis and chronic activation of the integrated stress response (ISR). The adaptive ISR signalling pathways help restore cellular homeostasis by downregulating protein synthesis in response to endoplasmic reticulum overloading or viral infections.

Negative Pressure Ventilation Ex-Situ Lung Perfusion Preserves Porcine and Human Lungs for 36-Hours.

Introduction: Preclinically, 24-hour continuous Ex-Situ Lung Perfusion (ESLP) is the longest duration achieved in large animal models and rejected human lungs. Here, we present our 36-hour Negative Pressure Ventilation (NPV)-ESLP protocol applied to porcine and rejected human lungs.

Methods: Five sets of donor domestic pig lungs (45-55 kg) underwent 36-hour NPV-ESLP.