The cells lining skin capillaries are constantly sending each other messages—tiny pulses of calcium that help regulate blood flow, sense physical forces and keep vessel walls intact. Scientists have known about this signaling for decades. What they didn’t know, until now, is that it follows a remarkably organized pattern, one that persists across days and weeks, governed by a network of cells that have, in a sense, assigned themselves permanent roles.

A new study from Yale School of Medicine (YSM) and University of California, Los Angeles (UCLA), published in Proceedings of the National Academy of Sciences, reveals not only that this network exists, but also what happens when it breaks down—and how it might be restored.

The study was done in the lab of Valentina Greco, Ph.D., Carolyn Walch Slayman Professor of Genetics at YSM and a Howard Hughes Medical Institute investigator, in close collaboration with the labs of Julia Mack, Ph.D., and Chen Yuan Kam, Ph.D., both at UCLA.

An interesting review on adenoviral cell entry and trafficking. Its discussion of how species B adenoviruses tolerate lower endosomal pH and accumulate in later-endosomal compartments before escaping were particularly intriguing. Link.

Adenoviruses represent exceptional candidates for wide-ranging therapeutic applications, from vectors for gene therapy to oncolytics for cancer treatments. The first ever commercial gene therapy medicine was based on a recombinant adenovirus vector, while most recently, adenoviral vectors have proven critical as vaccine platforms in effectively controlling the global coronavirus pandemic. Here, we discuss factors involved in adenovirus cell binding, entry, and trafficking; how they influence efficiency of adenovirus-based vectors; and how they can be manipulated to enhance efficacy of genetically modified adenoviral variants. We focus particularly on endocytosis and how different adenovirus serotypes employ different endocytic pathways to gain cell entry, and thus, have different intracellular trafficking pathways that subsequently trigger different host antiviral responses.

Two proteins with opposing functions orchestrate the development and maintenance of healthy skin, Stanford Medicine researchers have found. Modulating their activity with topical drugs could reduce inflammation, aid wound healing and slow or halt the growth of skin cancer, the researchers believe. The findings are published in the journal Science.

The proteins are part of a family called ubiquitin-like proteins. Ubiquitination controls the targeted destruction and disposal of unneeded proteins in a cell. But in the skin, certain ubiquitin-like proteins instead switch on or off wide swaths of genes involved in cellular growth and development, the study found. In particular, they trigger progenitor (stem) cells in the lower layer of the skin to either mature and migrate to the skin surface or to self-renew.

“These two ubiquitin-like protein systems are remarkably dedicated and opposite in their functions,” said Paul Khavari, MD, Ph.D., chair of dermatology at the Stanford School of Medicine and senior author of the study. “One promotes the stem-cell state while the other drives differentiation. It’s like having two opposing forces that determine a cell’s fate.”