Overview of the Role for Calreticulin in the Enhancement of Wound Healing through Multiple Biological Effects

Calreticulin (CRT), an intracellular chaperone protein crucial for the proper folding and transport of proteins through the endoplasmic reticulum, has more recent acclaim as a critical regulator of extracellular functions, particularly in mediating cellular migration and as a requirement for phagocytosis of apoptotic cells. Consistent with these functions, we show that the topical application of CRT has profound effects on the process of wound healing by causing a dose-dependent increase in epithelial migration and granulation tissue formation in both murine and porcine normal and impaired animal models of skin injury. These effects of CRT are substantiated, in vitro, as we show that CRT strongly induces cell migration/wound closure of human keratinocytes and fibroblasts, using a wound/scratch plate assay, and stimulates cellular proliferation of human keratinocytes, fibroblasts, and vascular endothelial cells, providing mechanistic insight into how CRT functions in repair. Similarly, in both animal models, the histology of the wounds show marked proliferation of basal keratinocytes and dermal fibroblasts, dense cellularity of the dermis with notably increased numbers of macrophages and well-organized collagen fibril deposition. Thus, CRT profoundly affects the wound healing process by recruiting cells essential for repair into the wound, stimulating cell growth, and increasing extracellular matrix production

Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome

The acetylase inhibitor spermidine and the sirtuin-1 activator resveratrol disrupt the antagonistic network of acetylases and deacetylases that regulate autophagy

Induction of autophagy by spermidine promotes longevity.

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The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Possibly no baseline severity effect for antidepressants versus placebo but for antipsychotics. Why?

Ten years ago, a meta-regression analysis (Kirsch et al., 2008) of 35 clinical trials submitted to the FDA found that the efficacy of antidepressants compared to placebo increases with baseline severity, and that a clinically significant effect defined as an effect size of at least 0.50 can only be expected in patients with a Hamilton Depression Rating Score of approximately 28. This was interpreted by Kirsch et al. to mean that antidepressants are efficacious for depression only for patients who are severely ill at baseline. This paper had a major impact on treatment guidelines and fueled a heated discussion about the usefulness of these agents (Cipriani and Geddes, 2014)

Possibly no baseline severity effect for antidepressants versus placebo but for antipsychotics. Why?

Ten years ago, a meta-regression analysis (Kirsch et al., 2008) of 35 clinical trials submitted to the FDA found that the efficacy of antidepressants compared to placebo increases with baseline severity, and that a clinically significant effect defined as an effect size of at least 0.50 can only be expected in patients with a Hamilton Depression Rating Score of approximately 28. This was interpreted by Kirsch et al. to mean that antidepressants are efficacious for depression only for patients who are severely ill at baseline. This paper had a major impact on treatment guidelines and fueled a heated discussion about the usefulness of these agents (Cipriani and Geddes, 2014)

Data on Cu- and Ni-Si-Mn-rich solute clustering in a neutron irradiated austenitic stainless steel

International audienc

Data on Cu- and Ni-Si-Mn-rich solute clustering in a neutron irradiated austenitic stainless steel

International audienc