The Cre/lox system is a fundamental tool for functional genomic studies, and a number of Cre lines have been generated to target genes of interest spatially and temporally in defined cells or tissues; this approach has greatly expanded our knowledge of gene functions. However, the limitations of this system have recently been recognized, and we must address the challenge of so‐called nonspecific/off‐target effects when a Cre line is utilized to investigate a gene of interest. For example, cathepsin K (Ctsk) has been used as a specific osteoclast marker, and Cre driven by its promoter is widely utilized for osteoclast investigations. However, Ctsk‐Cre expression has recently been identified in other cell types, such as osteocytes, periosteal stem cells, and tenocytes. To better understand Ctsk‐Cre expression and ensure appropriate use of this Cre line, we performed a comprehensive analysis of Ctsk‐Cre expression at the single‐cell level in major organs and tissues using two green fluorescent protein (GFP) reporters (ROSA nT‐nG and ROSA tdT) and a tissue clearing technique in young and aging mice. The expression profile was further verified by immunofluorescence staining and droplet digital RT‐PCR. The results demonstrate that Ctsk‐Cre is expressed not only in osteoclasts but also at various levels in osteoblast lineage cells and other major organs/tissues, particularly in the brain, kidney, pancreas, and blood vessels. Furthermore, Ctsk‐Cre expression increases markedly in the bone marrow, skeletal muscle, and intervertebral discs in aging mice. These data will be valuable for accurately interpreting data obtained from in vivo studies using Ctsk‐Cre mice to avoid potentially misleading conclusions. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
This paper examines the pricing efficiency of 8‐K filings for events other than earnings announcements. Since these filings provide timely information that is material to investors and explain variations in quarterly returns to a degree similar to other disclosures, understanding how the stock price absorbs their information is important for investors, regulators, and academics. By testing the statistical correlation between the immediate stock returns in response to these filings and subsequent stock returns before, during, and after the forthcoming earnings announcement, we find evidence of investor overreaction to good news but underreaction to bad news in the immediate window. Essentially, the price increases too much for good news but fails to decrease enough for bad news, resulting in overpricing for both. Most of the correction for this overpricing occurs in the period leading up to the forthcoming earnings announcement, while the rest happens during the announcement. Drawing on Miller (1977), we further illustrate that, in the presence of short‐sale constraints, increase in investor disagreement spurred by interpretation difficulty is the most likely mechanism for the observed overpricing. We fail to find sufficient evidence in support of alternative mechanisms, including managerial disclosure strategies, analyst optimistic bias, and retail investor participation. This asymmetric mispricing for non‐earnings 8‐Ks contrasts with the symmetric mispricing commonly found for other types of disclosures, where investors either systematically underreact or overreact to public information. Our results could broadly speak to the pricing of other public information that is inherently difficult to interpret.
Of note, buttonhole cannulation with blunt needles was used in all AVF. 2 In conclusion, we report for the first time from a European unit an incidence of AVF-related hemorrhage, almost exclusively observed as a consequence of AVF infection. We emphasize the importance of early surgical referral in case of signs of imminent AVF rupture, such as necrotic scabs or suppurated puncture sites, particularly when using the buttonhole cannulation method. 1. Ellingson KD, Palekar RS, Lucero CA et al. Vascular access hemorrhages contribute to deaths among hemodialysis patients.
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