Mouse genetics identifies unique and overlapping functions of fibroblast growth factor receptors in keratinocytes

Fibroblast growth factors (FGFs) are key regulators of tissue development, homeostasis and repair, and abnormal FGF signalling is associated with various human diseases. In human and murine epidermis, FGF receptor 3 (FGFR3) activation causes benign skin tumours, but the consequences of FGFR3 deficiency in this tissue have not been determined. Here, we show that FGFR3 in keratinocytes is dispensable for mouse skin development, homeostasis and wound repair. However, the defect in the epidermal barrier and the resulting inflammatory skin disease that develops in mice lacking FGFR1 and FGFR2 in keratinocytes were further aggravated upon additional loss of FGFR3. This caused fibroblast activation and fibrosis in the FGFR1/FGFR2 double-knockout mice and even more in mice lacking all three FGFRs, revealing functional redundancy of FGFR3 with FGFR1 and FGFR2 for maintaining the epidermal barrier. Taken together, our study demonstrates that FGFR1, FGFR2 and FGFR3 act together to maintain epidermal integrity and cutaneous homeostasis, with FGFR2 being the dominant receptor

A kinetic and theoretical study of the borate catalysed reactions of hydrogen peroxide: the role of dioxaborirane as the catalytic intermediate for a wide range of substrates

Our recent work has provided new insights into the equilibria and species that exist in aqueous solution at different pHs for the boric acid – hydrogen peroxide system, and the role of these species in oxidation reactions. Most recently, (M. C. Durrant, D. M. Davies and M. E. Deary, Org. Biomol. Chem., 2011, 9,7249–7254), we have produced strong theoretical and experimental evidence for the existence of a previously unreported monocyclic three membered peroxide species, dioxaborirane, that is the likely catalytic species in borate mediated electrophilic reactions of hydrogen peroxide in alkaline solution. In the present paper, we extend our study of the borate–peroxide system to look at a wide range of substrates that include substituted dimethyl anilines, methyl-p-tolyl sulfoxide, halides, hydrogen sulfide anion, thiosulfate ,thiocyanate, and hydrazine. The unusual selectivity–reactivity pattern of borate catalysed reactions compared with hydrogen peroxide and inorganic or organic peracids previously observed for theorganic sulfides (D. M. Davies, M. E. Deary, K. Quill and R. A. Smith, Chem.–Eur. J., 2005, 11, 3552–3558) is also seen with substituted dimethyl aniline nucleophiles. This provides evidence that the pattern is not due to any latent electrophilic tendency of the organic sulfides and further supports dioxaborirane being the likely reactive intermediate, thus broadening the applicability of this catalytic system. Moreover, density functional theory calculations on our proposed mechanism involving dioxaborirane are consistent with the experimental results for these substrates. Results obtained at high concentrations of both borate and hydrogen peroxide require the inclusion the diperoxodiborate dianion in the kinetic analysis .A scheme detailing our current understanding of the borate–peroxide system is presented

A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait.

In humans, the connection between sleep and mood has long been recognized, although direct molecular evidence is lacking. We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and seasonality scores. hPER3-P415A/H417R transgenic mice showed an altered circadian period under constant light and exhibited phase shifts of the sleep-wake cycle in a short light period (photoperiod) paradigm. Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize PERIOD1/2 proteins, which play critical roles in circadian timing. Although hPER3-P415A/H417R-Tg mice showed a mild depression-like phenotype, Per3 knockout mice demonstrated consistent depression-like behavior, particularly when studied under a short photoperiod, supporting a possible role for PER3 in mood regulation. These findings suggest that PER3 may be a nexus for sleep and mood regulation while fine-tuning these processes to adapt to seasonal changes

Vietnam Veterans Memorial

It is black granite from Bangalore, India, one of only three places in the world (the other countries are Sweden and South Africa) that you could get this amount of black granite in large sizes.https://openscholarship.wustl.edu/bcs/1216/thumbnail.jp

NGO Translation and Translator Practices Explored Through an Ideological Lens

This thesis project looks at translation and translator practices in the world of Canadian development-NGOs. Given this context, both translation and development studies are drawn upon within this project. Focusing on the ideological aspects of these practices, theories of functionalism and critical discourse analysis (CDA), as they relate specifically to translation studies, are employed. After presenting this framework, two types of analyses follow, which allow us to interrogate the ideology of such NGO translation and translator practices. First, the specific translations found in the promotional videos drawn from one organization, Plan Canada, are presented and analyzed. Later, translators and their practices are investigated though empirical research and more general investigations of several different NGOs’ website content. Finally, how ideology is manifested in these practices is related to greater ideological tendencies within our global society

Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia

Avalanche Dynamics in Evolution, Growth, and Depinning Models

The dynamics of complex systems in nature often occurs in terms of punctuations, or avalanches, rather than following a smooth, gradual path. A comprehensive theory of avalanche dynamics in models of growth, interface depinning, and evolution is presented. Specifically, we include the Bak-Sneppen evolution model, the Sneppen interface depinning model, the Zaitsev flux creep model, invasion percolation, and several other depinning models into a unified treatment encompassing a large class of far from equilibrium processes. The formation of fractal structures, the appearance of $1/f$ noise, diffusion with anomalous Hurst exponents, Levy flights, and punctuated equilibria can all be related to the same underlying avalanche dynamics. This dynamics can be represented as a fractal in $d$ spatial plus one temporal dimension. We develop a scaling theory that relates many of the critical exponents in this broad category of extremal models, representing different universality classes, to two basic exponents characterizing the fractal attractor. The exact equations and the derived set of scaling relations are consistent with numerical simulations of the above mentioned models.Comment: 27 pages in revtex, no figures included. Figures or hard copy of the manuscript supplied on reques

Maya Lin in Conversation

Record of a conversation held in Umrath Hall at Washington University in St. Louis on November 17, 2016 between Maya Lin and Sam Fox School faculty and students. The event was co-hosted by Women in Architecture + Design. Contents Introduction / Natasha Tabachnikoff -- Submissions / Sam Fox Students & Faculty -- In conversation / Maya Lin ; transcribed by Jenny Li. Question 1 / Francisco Coch ; Question 2 / Mingxi Li ; Question 3 / Jenna Schnitzler ; Question 4 / Jared Crane ; Question 5 / Natasha Tabachnikoff ; Question 6 / Rita Wang ; Question 7 / Kahlil Irving ; Question 8 / Allie Henner ; Question 9 / Kaitlyn Schwalber -- Maya Lin + urban design / Linda Samuels -- Between art + architecture / Mingxi Li -- Acknowledgements / Yulin Peng.https://openscholarship.wustl.edu/books/1040/thumbnail.jp

Longitudinal Associations of Leisure-Time Physical Activity and Cancer Mortality in the Third National Health and Nutrition Examination Survey (1986–2006)

Longitudinal associations between leisure-time physical activity (LTPA) and overall cancer mortality were evaluated within the Third National Health and Nutrition Examination Survey (NHANES III; 1988–2006; n = 15,535). Mortality status was ascertained using the National Death Index. Self-reported LTPA was divided into inactive, regular low-to-moderate and vigorous activity. A frequency-weighted metabolic equivalents (METS/week) variable was also computed. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated for overall cancer mortality in the whole sample, by body mass index categories and insulin resistance (IR) status. Nonsignificant protective associations were observed for regular low-to-moderate and vigorous activity, and for the highest quartile of METS/week (HRs range: 0.66–0.95). Individuals without IR engaging in regular vigorous activity had a 48% decreased risk of cancer mortality (HR: 0.52; 95% CI: 0.28–0.98) in multivariate analyses. Conversely, nonsignificant positive associations were observed in people with IR. In conclusion, regular vigorous activity may reduce risk of cancer mortality among persons with normal insulin-glucose metabolism in this national sample