The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh

Before birth, B cells develop in the fetal liver (FL). In this study, we show that Gli3 activity in the FL stroma is required for B cell development. In the Gli3-deficient FL, B cell development was reduced at multiple stages, whereas the Sonic hedgehog (Hh [Shh])–deficient FL showed increased B cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hh-reporter mouse showed that Shh signals directly to developing B cells and that Hh pathway activation was increased in developing B cells from Gli3-deficient FLs. RNA sequencing confirmed that Hh-mediated transcription is increased in B-lineage cells from Gli3-deficient FL and showed that these cells expressed reduced levels of B-lineage transcription factors and B cell receptor (BCR)/pre-BCR–signaling genes. Expression of the master regulators of B cell development Ebf1 and Pax5 was reduced in developing B cells from Gli3-deficient FL but increased in Shh-deficient FL, and in vitro Shh treatment or neutralization reduced or increased their expression, respectively

Suppression of planar cell polarity signaling and migration in glioblastoma by Nrdp1-mediated Dvl polyubiquitination.

The lethality of the aggressive brain tumor glioblastoma multiforme (GBM) results in part from its strong propensity to invade surrounding normal brain tissue. Although oncogenic drivers such as epidermal growth factor receptor activation and Phosphatase and Tensin homolog inactivation are thought to promote the motility and invasiveness of GBM cells via phosphatidylinostitol 3-kinase activation, other unexplored mechanisms may also contribute to malignancy. Here we demonstrate that several components of the planar cell polarity (PCP) arm of non-canonical Wnt signaling including VANGL1, VANGL2 and FZD7 are transcriptionally upregulated in glioma and correlate with poorer patient outcome. Knockdown of the core PCP pathway component VANGL1 suppresses the motility of GBM cell lines, pointing to an important mechanistic role for this pathway in glioblastoma malignancy. We further observe that restoration of Nrdp1, a RING finger type E3 ubiquitin ligase whose suppression in GBM also correlates with poor prognosis, reduces GBM cell migration and invasiveness by suppressing PCP signaling. Our observations indicate that Nrdp1 physically interacts with the Vangl1 and Vangl2 proteins to mediate the K63-linked polyubiquitination of the Dishevelled, Egl-10 and Pleckstrin (DEP) domain of the Wnt pathway protein Dishevelled (Dvl). Ubiquitination hinders Dvl binding to phosphatidic acid, an interaction necessary for efficient Dvl recruitment to the plasma membrane upon Wnt stimulation of Fzd receptor and for the propagation of downstream signals. We conclude that the PCP pathway contributes significantly to the motility and hence the invasiveness of GBM cells, and that Nrdp1 acts as a negative regulator of PCP signaling by inhibiting Dvl through a novel polyubiquitination mechanism. We propose that the upregulation of core PCP components, together with the loss of the key negative regulator Nrdp1, act coordinately to promote GBM invasiveness and malignancy

Alternative networks: toward global access to the Internet for all

It is often said that the Internet is ubiquitous in our daily lives, but this holds true only for those who can easily access it. In fact, billions of people are still digitally disconnected, as bringing connectivity to certain zones does not make a good business case. The only solution for these unsatisfied potential users is to directly undertake the building of the infrastructure required to obtaining access to the Internet, typically forming groups in order to share the corresponding cost. This article presents a global classification and a summary of the main characteristics of different Alternative Network deployments that have arisen in recent years with an aim to provide Internet services in places where mainstream network deployments do not exist or are not adequate solutions. The Global Access to the Internet for All Research Group of the Internet Research Task Force, where all authors actively participate, is interested in documenting these emerging deployments. As an outcome of this work, a classification has converged by consensus, where five criteria have been identified and, based on them, four different types of Alternative Networks have been identified and described with real-world examples. Such a classification is useful for a deeper understanding of the common characteristics behind existing and emerging Alternative Networks

Patient safety in dentistry: development of a candidate 'never event' list for primary care

Introduction The 'never event' concept is often used in secondary care and refers to an agreed list of patient safety incidents that 'should not happen if the necessary preventative measures are in place'. Such an intervention may raise awareness of patient safety issues and inform team learning and system improvements in primary care dentistry. Objective To identify and develop a candidate never event list for primary care dentistry. Methods A literature review, eight workshops with dental practitioners and a modified Delphi with 'expert' groups were used to identify and agree candidate never events. Results Two-hundred and fifty dental practitioners suggested 507 never events, reduced to 27 distinct possibilities grouped across seven themes. Most frequently occurring themes were: 'checking medical history and prescribing' (119, 23.5%) and 'infection control and decontamination' (71, 14%). 'Experts' endorsed nine candidate never event statements with one graded as 'extreme risk' (failure to check past medical history) and four as 'high risk' (for example, extracting wrong tooth). Conclusion Consensus on a preliminary list of never events was developed. This is the first known attempt to develop this approach and an important step in determining its value to patient safety. Further work is necessary to develop the utility of this method

Critical statistics in a power-law random banded matrix ensemble

We investigate the statistical properties of the eigenvalues and eigenvectors in a random matrix ensemble with $H_{ij}\sim |i-j|^{-\mu}$. It is known that this model shows a localization-delocalization transition (LDT) as a function of the parameter $\mu$. The model is critical at $\mu=1$ and the eigenstates are multifractals. Based on numerical simulations we demonstrate that the spectral statistics at criticality differs from semi-Poisson statistics which is expected to be a general feature of systems exhibiting a LDT or `weak chaos'.Comment: 4 pages in PS including 5 figure

Search for muon-neutrino emission from GeV and TeV gamma-ray flaring blazars using five years of data of the ANTARES telescope

The ANTARES telescope is well-suited for detecting astrophysical transient neutrino sources as it can observe a full hemisphere of the sky at all times with a high duty cycle. The background due to atmospheric particles can be drastically reduced, and the point-source sensitivity improved, by selecting a narrow time window around possible neutrino production periods. Blazars, being radio-loud active galactic nuclei with their jets pointing almost directly towards the observer, are particularly attractive potential neutrino point sources, since they are among the most likely sources of the very high-energy cosmic rays. Neutrinos and gamma rays may be produced in hadronic interactions with the surrounding medium. Moreover, blazars generally show high time variability in their light curves at different wavelengths and on various time scales. This paper presents a time-dependent analysis applied to a selection of flaring gamma-ray blazars observed by the FERMI/LAT experiment and by TeV Cherenkov telescopes using five years of ANTARES data taken from 2008 to 2012. The results are compatible with fluctuations of the background. Upper limits on the neutrino fluence have been produced and compared to the measured gamma-ray spectral energy distribution.Comment: 27 pages, 16 figure

Development and testing of the Measure of Innovation-Specific Implementation Intentions (MISII) using Rasch measurement theory

© 2018 The Author(s). Background: Implementation is proposed to be a multiphase, multilevel process. After a period of exploration, an adoption decision is made, typically at the upper management or policy level. Nevertheless, movement through each of the subsequent phases of the implementation process involves clinicians or providers at the individual level to adopt the innovation and then change their behavior to use/deliver the innovation. Multiple behavioral change theories propose that intentions are a critical determinant of implementation behavior. However, there is a need for the development and testing of pragmatic measures of providers' intentions to use a specific innovation or evidence-based practice (EBP). Methods: Nine items were developed to assess providers' intentions to use a specific innovation or EBP. Motivational interviewing was the EBP in the study. Items were administered, as part of larger survey, to 179 providers across 38 substance use disorder treatment (SUDT) programs within five agencies in California, USA. Rasch analysis was conducted using RUMM2030 software to assess the items, their overall fit to the Rasch model, the response scale used, individual item fit, differential item functioning (DIF), and person separation. Results: Following a stepwise process, the scale was reduced from nine items to three items to increase the feasibility and acceptability of the scale while maintaining suitable psychometric properties. The three-item unidimensional scale showed good person separation (PSI =.872), no disordering of thresholds, and no evidence of uniform or non-uniform DIF. Rasch analysis supported the viability of the scale as a measure of implementation intentions. Conclusions: The Measure of Innovation-Specific Implementation Intentions (MISII) is a sound measure of providers' intentions to use a specific innovation or EBP. Future evaluation of convergent, divergent, and predictive validity are needed. The study also demonstrates the value of Rasch analysis for testing the psychometric properties of pragmatic implementation measures

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Collection Development Policies in Public Libraries in Australia: A Qualitative Content Analysis

The role that public library collection development polices play inguiding selectors and informing users has been promoted as a pillar of good professional practice. While these policies purport to open up the methods and the criteria used in selection so as to promote transparency and a sense of professional objectivity, how they actually are developed and put into practice has remained largely implicit in the research literature. This analysis revealedthat policies tended to focus on local issues and remained heavily materials focused. How collections are developed to support user’s information needs and substantive issues associated with topicality are largely unarticulated

Murchison Widefield Array limits on radio emission from Antares neutrino events

We present a search, using the Murchison Widefield Array (MWA), for electromagnetic (EM) counterparts to two candidate high-energy neutrino events detected by the ANTARES neutrino telescope in 2013 November and 2014 March. These events were selected by ANTARES because they are consistent, within 0°.4, with the locations of galaxies within 20 Mpc of Earth. Using MWA archival data at frequencies between 118 and 182 MHz, taken ~20 days prior to, at the same time as, and up to a year after the neutrino triggers, we look for transient or strongly variable radio sources that are consistent with the neutrino positions. No such counterparts are detected, and we set a 5s upper limit for low-frequency radio emission of ~1037 erg s-1 for progenitors at 20 Mpc. If the neutrino sources are instead not in nearby galaxies, but originate in binary neutron star coalescences, our limits place the progenitors at z 0.2. While it is possible, due to the high background from atmospheric neutrinos, that neither event is astrophysical, the MWA observations are nevertheless among the first to follow up neutrino candidates in the radio, and illustrate the promise of wide-field instruments like MWA for detecting EM counterparts to such events