The response of early neural genes to FGF signaling or inhibition of BMP indicate the absence of a conserved neural induction module

<p>Abstract</p> <p>Background</p> <p>The molecular mechanism that initiates the formation of the vertebrate central nervous system has long been debated. Studies in <it>Xenopus </it>and mouse demonstrate that inhibition of BMP signaling is sufficient to induce neural tissue in explants or ES cells respectively, whereas studies in chick argue that instructive FGF signaling is also required for the expression of neural genes. Although additional signals may be involved in neural induction and patterning, here we focus on the roles of BMP inhibition and FGF8a.</p> <p>Results</p> <p>To address the question of necessity and sufficiency of BMP inhibition and FGF signaling, we compared the temporal expression of the five earliest genes expressed in the neuroectoderm and determined their requirements for induction at the onset of neural plate formation in <it>Xenopus</it>. Our results demonstrate that the onset and peak of expression of the genes vary and that they have different regulatory requirements and are therefore unlikely to share a conserved neural induction regulatory module. Even though all require inhibition of BMP for expression, some also require FGF signaling; expression of the early-onset pan-neural genes <it>sox2 </it>and <it>foxd5α </it>requires FGF signaling while other early genes, <it>sox3</it>, <it>geminin </it>and <it>zicr1 </it>are induced by BMP inhibition alone.</p> <p>Conclusions</p> <p>We demonstrate that BMP inhibition and FGF signaling induce neural genes independently of each other. Together our data indicate that although the spatiotemporal expression patterns of early neural genes are similar, the mechanisms involved in their expression are distinct and there are different signaling requirements for the expression of each gene.</p

Cancer prevention and therapy through the modulation of the tumor microenvironment

Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adaptive immunity. Here we highlight specific biological processes that could be exploited as targets for the prevention and therapy of cancer. Specifically, we describe how inhibition of targets such as cholesterol synthesis and metabolites, reactive oxygen species and hypoxia, macrophage activation and conversion, indoleamine 2,3-dioxygenase regulation of dendritic cells, vascular endothelial growth factor regulation of angiogenesis, fibrosis inhibition, endoglin, and Janus kinase signaling emerge as examples of important potential nexuses in the regulation of tumorigenesis and the tumor microenvironment that can be targeted. We have also identified therapeutic agents as approaches, in particular natural products such as berberine, resveratrol, onionin A, epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin, piperine, and zerumbone, that may warrant further investigation to target the tumor microenvironment for the treatment and/or prevention of cancer

Development and Implementation of a Peer Mentoring Program for Early Career Gerontological Faculty: Mentoring Early Career Gerontological Faculty

In conjunction with the National Hartford Centers of Gerontological Nursing Excellence (NHCGNE), formerly known as the Building Academic Geriatric Nursing Capacity Initiative (BAGNC), the Hartford Gerontological Nursing Leaders (HGNL) developed and executed a program beginning in 2011 to enhance both (a) the experience of newly selected scholars and fellows to the NHCGNE and (b) the ongoing professional development of the HGNL. The purpose of this article is to describe key strategies used to develop and execute the mentoring program and to present the formative and summative program evaluation

Recommendations for a national agenda to substantially reduce cervical cancer

PURPOSE: Prophylactic human papillomavirus (HPV) vaccines and new HPV screening tests, combined with traditional Pap test screening, provide an unprecedented opportunity to greatly reduce cervical cancer in the USA. Despite these advances, thousands of women continue to be diagnosed with and die of this highly preventable disease each year. This paper describes the initiatives and recommendations of national cervical cancer experts toward preventing and possibly eliminating this disease. METHODS: In May 2011, Cervical Cancer-Free America, a national initiative, convened a cervical cancer summit in Washington, DC. Over 120 experts from the public and private sector met to develop a national agenda for reducing cervical cancer morbidity and mortality in the USA. RESULTS: Summit participants evaluated four broad challenges to reducing cervical cancer: (1) low use of HPV vaccines, (2) low use of cervical cancer screening, (3) screening errors, and (4) lack of continuity of care for women diagnosed with cervical cancer. The summit offered 12 concrete recommendations to guide future national and local efforts toward this goal. CONCLUSIONS: Cervical cancer incidence and mortality can be greatly reduced by better deploying existing methods and systems. The challenge lies in ensuring that the array of available prevention options are accessible and utilized by all age-appropriate women-particularly minority and underserved women who are disproportionately affected by this disease. The consensus was that cervical cancer can be greatly reduced and that prevention efforts can lead the way towards a dramatic reduction in this preventable disease in our country

Gaia-ESO Survey: INTRIGOSS - A New Library of High-resolution Synthetic Spectra

We present a high resolution synthetic spectral library, INTRIGOSS, designed for studying FGK stars. The library is based on atmosphere models computed with specified individual element abundances via ATLAS12 code. Normalized SPectra (NSP) and surface Flux SPectra (FSP), in the 4830-5400 A, wavelength range, were computed with the SPECTRUM code. INTRIGOSS uses the solar composition by Grevesse et al. 2007 and four [alpha/Fe] abundance ratios and consists of 15,232 spectra. The synthetic spectra are computed with astrophysical gf-values derived by comparing synthetic predictions with a very high SNR solar spectrum and the UVES-U580 spectra of five cool giants. The validity of the NSPs is assessed by using the UVES-U580 spectra of 2212 stars observed in the framework of the Gaia-ESO Survey and characterized by homogeneous and accurate atmospheric parameter values and by detailed chemical compositions. The greater accuracy of NSPs with respect to spectra from the AMBRE, GES_Grid, PHOENIX, C14, and B17 synthetic spectral libraries is demonstrated by evaluating the consistency of the predictions of the different libraries for the UVES-U580 sample stars. The validity of the FSPs is checked by comparing their prediction with both observed spectral energy distribution and spectral indices. The comparison of FSPs with SEDs derived from ELODIE, INDO--U.S., and MILES libraries indicates that the former reproduce the observed flux distributions within a few percent and without any systematic trend. The good agreement between observational and synthetic Lick/SDSS indices shows that the predicted blanketing of FSPs well reproduces the observed one, thus confirming the reliability of INTRIGOSS FSPs

The Gaia-ESO Survey: dynamical models of flattened, rotating globular clusters

We present a family of self-consistent axisymmetric rotating globular cluster models which are fitted to spectroscopic data for NGC 362, NGC 1851, NGC 2808, NGC 4372, NGC 5927 and NGC 6752 to provide constraints on their physical and kinematic properties, including their rotation signals. They are constructed by flattening Modified Plummer profiles, which have the same asymptotic behaviour as classical Plummer models, but can provide better fits to young clusters due to a slower turnover in the density profile. The models are in dynamical equilibrium as they depend solely on the action variables. We employ a fully Bayesian scheme to investigate the uncertainty in our model parameters (including mass-to-light ratios and inclination angles) and evaluate the Bayesian evidence ratio for rotating to non-rotating models. We find convincing levels of rotation only in NGC 2808. In the other clusters, there is just a hint of rotation (in particular, NGC 4372 and NGC 5927), as the data quality does not allow us to draw strong conclusions. Where rotation is present, we find that it is confined to the central regions, within radii of R ≤ 2rh. As part of this work, we have developed a novel q-Gaussian basis expansion of the line-of-sight velocity distributions, from which general models can be constructed via interpolation on the basis coefficients