Skin homeostasis is maintained by stem cells, which must communicate to balance their regenerative behaviors. Yet, how adult stem cells signal across regenerative tissue remains unknown due to ...challenges in studying signaling dynamics in live mice. We combined live imaging in the mouse basal stem cell layer with machine learning tools to analyze patterns of Ca2+ signaling. We show that basal cells display dynamic intercellular Ca2+ signaling among local neighborhoods. We find that these Ca2+ signals are coordinated across thousands of cells and that this coordination is an emergent property of the stem cell layer. We demonstrate that G2 cells are required to initiate normal levels of Ca2+ signaling, while connexin43 connects basal cells to orchestrate tissue-wide coordination of Ca2+ signaling. Lastly, we find that Ca2+ signaling drives cell cycle progression, revealing a communication feedback loop. This work provides resolution into how stem cells at different cell cycle stages coordinate tissue-wide signaling during epidermal regeneration.
The inability of the ß-cell to meet the demand for insulin brought about by insulin resistance leads to type 2 diabetes. In adults, ß-cell replication is one of the mechanisms thought to cause the ...expansion of ß-cell mass. Efforts to treat diabetes require knowledge of the pathways that drive facultative ß-cell proliferation in vivo. A robust physiological stimulus of ß-cell expansion is pregnancy and identifying the mechanisms underlying this stimulus may provide therapeutic leads for the treatment of type 2 diabetes. The peak in ß-cell proliferation during pregnancy occurs on d 14.5 of gestation in mice. Using advanced genomic approaches, we globally characterize the gene expression signature of pancreatic islets on d 14.5 of gestation during pregnancy. We identify a total of 1907 genes as differentially expressed in the islet during pregnancy. The islet’s ability to compensate for relative insulin deficiency during metabolic stress is associated with the induction of both proliferative and survival pathways. A comparison of the genes induced in three different models of islet expansion suggests that diverse mechanisms can be recruited to expand islet mass. The identification of many novel genes involved in islet expansion during pregnancy provides an important resource for diabetes researchers to further investigate how these factors contribute to the maintenance of not only islet mass, but ultimately ß-cell mass.
Gene expression analysis in islets during pregnancy highlights potential novel factors associated with both proliferative and survival signals required for islet expansion.
► We provide the first standardized chemical durability test on tellurite glasses. ► The glasses we studied showed a wide variety of chemical durability. ► The best-performing glass showed good ...halide retention following melting and durability testing. ► These glasses have very high densities resulting in high volumetric waste loading ability.
Tellurite glasses have historically been shown to host large concentrations of halides. They are here considered for the first time as a waste form for immobilizing chloride wastes, such as may be generated in the proposed molten alkali salt electrochemical separations step in nuclear fuel reprocessing. Key properties of several tellurite glasses are determined to assess acceptability as a chloride waste form. TeO2 glasses with other oxides (PbO, Al2O3+B2O3, WO3, P2O5, or ZnO) were fabricated with and without 10mass% of a simulated (non-radioactive) mixed alkali, alkaline-earth, and rare earth chloride waste. Measured chemical durability is compared for the glasses, as determined by the product consistency test (PCT), a common standardized chemical durability test often used to validate borosilicate glass waste forms. The glass with the most promise as a waste form is the TeO2–PbO system, as it offers good halide retention, a low sodium release (by PCT) comparable with high-level waste silicate glass waste forms, and a high storage density.
Extracellular-regulated kinases (ERK1, ERK2) play important roles in the malignant behaviour of breast cancer cells in vitro. In our present study, 148 clinical breast cancer samples (120 cases with ...follow-up data) were studied for the expression of ERK1, ERK2 and their phosphorylated forms p-ERK1 and p-ERK2 by immunoblotting, and p-ERK1/2 expression in corresponding paraffin sections was analysed by immunohistochemistry. The results were correlated with established clinical and histological prognostic parameters, follow-up data and expression of seven cell-cycle regulatory proteins as well as MMP1, MMP9, PAI-1 and AP-1 transcription factors, which had been analysed before. High p-ERK1 expression as determined by immunoblots correlated significantly with a low frequency of recurrences and infrequent fatal outcome (P = 0.007 and 0.008) and was an independent indicator of long relapse-free and overall survival in multivariate analysis. By immunohistochemistry, strong p-ERK staining in tumour cells was associated with early stages (P = 0.020), negative nodal status (P = 0.003) and long recurrence-free survival (P = 0.017). In contrast, expression of the unphosphorylated kinases ERK1 and ERK2 was not associated with clinical and histological prognostic parameters, except a positive correlation with oestrogen receptor status. Comparison with the expression of formerly analysed cell-cycle- and invasion-associated proteins corroborates our conclusion that activation of ERK1 and ERK2 is not associated with enhanced proliferation and invasion of mammary carcinomas.
Information technology in health care has a clear potential to improve the quality and efficiency of health care, especially in the area of medication processes. On the other hand, existing studies ...show possible adverse effects on patient safety when IT for medication-related processes is developed, introduced or used inappropriately.
To summarize definitions and observations on IT usage in pharmacotherapy and to derive recommendations and future research priorities for decision makers and domain experts.
This memorandum was developed in a consensus-based iterative process that included workshops and e-mail discussions among 21 experts coordinated by the Drug Information Systems Working Group of the German Society for Medical Informatics, Biometry and Epidemiology (GMDS).
The recommendations address, among other things, a stepwise and comprehensive strategy for IT usage in medication processes, the integration of contextual information for alert generation, the involvement of patients, the semantic integration of information resources, usability and adaptability of IT solutions, and the need for their continuous evaluation.
Information technology can help to improve medication safety. However, challenges remain regarding access to information, quality of information, and measurable benefits.
A pilot-plant scale desymmetrization of the cyclic meso-epoxide 4b, using a chiral lithium amide prepared from symmetrical diamine 17, was designed and implemented to provide allylic alcohol 3b in ...high yield and greater than 99% ee. This chiral alcohol was converted to ketone 2b, a key intermediate in a new asymmetric synthesis of LY459477. Chiral diamine 17 was prepared from a readily available chiral precursor, (R)-α-methylbenzylamine, and could be recovered from the reaction mixture and reused. Studies performed to probe the mechanism of the rearrangement reaction of epoxide 4b showed that diamine 17 provided an optimal combination of selectivity and scaleability for this process.
This paper proposes a Green Light Optimized Speed Advisory (GLOSA) application implementation in a typical reference area, and presents the results of its performance analysis using an integrated ...cooperative ITS simulation platform. Our interest was to monitor the impacts of GLOSA on fuel and traffic efficiency by introducing metrics for average fuel consumption and average stop time behind a traffic light, respectively. For gathering the results we implemented a traffic scenario defining a single route through an urban area including two traffic lights. The simulations are varied for different penetration rates of GLOSA-equipped vehicles and traffic density. Our results indicate that GLOSA systems could improve fuel consumption and reduce traffic congestion in junctions.
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