Conceptual Model of Resolution

In this document, we look at three aspects of the resolution of identifiers to a URI representing the resource: dynamic data citation, content negotiation, and machine-enabled licence information

NF-κB regulates neuronal ankyrin-G via a negative feedback loop.

The axon initial segment (AIS) is a neuronal compartment defined by ankyrin-G expression. We here demonstrate that the IKK-complex co-localizes and interacts with the cytoskeletal anchor protein ankyrin-G in immunoprecipitation and proximity-ligation experiments in cortical neurons. Overexpression of the 270 kDa variant of ankyrin-G suppressed, while gene-silencing of ankyrin-G expression increased nuclear factor-κB (NF-κB) activity in primary neurons, suggesting that ankyrin-G sequesters the transcription factor in the AIS. We also found that p65 bound to the ank3 (ankyrin-G) promoter sequence in chromatin immunoprecipitation analyses thereby increasing ank3 expression and ankyrin-G levels at the AIS. Gene-silencing of p65 or ankyrin-G overexpression suppressed ank3 reporter activity. Collectively these data demonstrate that p65/NF-κB controls ankyrin-G levels via a negative feedback loop, thereby linking NF-κB signaling with neuronal polarity and axonal plasticity

The use of bioreactors as in vitro models in pharmaceutical research

Bringing a new drug to market is costly in terms of capital and time investments, and any development issues encountered during late-stage clinical trials can often be the result of in vitro-in vivo extrapolations (IVIVE) not accurately reflecting clinical outcome. In the discipline of drug metabolism and pharmacokinetics (DMPK), current in vitro cellular methods do not provide the 3D structure and function of organs found in vivo; therefore, new dynamic methods need to be established to aid improvement of IVIVE. In this review, we highlight the importance of model progression into dynamic systems for use within drug development, focusing on devices developed currently in the areas of the liver and blood-brain barrier (BBB), and the potential to develop models for other organ systems, such as the kidney. We discuss the development of dynamic 3D bioreactor-based systems as in vitro models for use in DMPK studies

Fibroblast growth factor homologous factor 1 interacts with NEMO to regulate NF-κB signaling in neurons.

Neuronal survival and plasticity critically depend on constitutive activity of the transcription factor nuclear factor-κB (NF-κB). We here describe a role for a small intracellular fibroblast growth factor homologue, the fibroblast growth factor homologous factor 1 (FHF1/FGF12), in the regulation of NF-κB activity in mature neurons. FHFs have previously been described to control neuronal excitability, and mutations in FHF isoforms give rise to a form of progressive spinocerebellar ataxia. Using a protein-array approach, we identified FHF1b as a novel interactor of the canonical NF-κB modulator IKKγ/NEMO. Co-immunoprecipitation, pull-down and GAL4-reporter experiments, as well as proximity ligation assays, confirmed the interaction of FHF1 and NEMO and demonstrated that a major site of interaction occurred within the axon initial segment. Fhf1 gene silencing strongly activated neuronal NF-κB activity and increased neurite lengths, branching patterns and spine counts in mature cortical neurons. The effects of FHF1 on neuronal NF-κB activity and morphology required the presence of NEMO. Our results imply that FHF1 negatively regulates the constitutive NF-κB activity in neurons

Connecting Researchers to Data Repositories in the Earth, Space, and Environmental Sciences

The Repository Finder tool was developed to help researchers in the domain of Earth, space, and environmental sciences to identify appropriate repositories where they can deposit their research data and to promote practices that implement the FAIR Principles, encouraging progress toward sharing data that are findable, accessible, interoperable, and reusable. Requirements for the design of the tool were gathered through a series of workshops and working groups as a part of the Enabling FAIR Data initiative led by the American Geophysical Union that included the development of a decision tree that researchers may follow in selecting a data repository, interviews with domain repository managers, and usability testing. The tool is hosted on the web by DataCite and enables a researcher to query all data repositories by keyword or to view a list of domain repositories that accept data for deposit, support open access, and provide persistent identifiers. Metadata records from the re3data.org registry of research data repositories and the returned results highlight repositories that have achieved trustworthy digital repository certification through a formal procedure such as the CoreTrust Seal

Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus

Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections – an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions

Imported Infectious Disease and Purpose of Travel, Switzerland

Travelers who visited friends or relatives were more likely to receive a diagnosis of malaria or viral hepatitis than those who traveled for other reasons

Software Citation Implementation Challenges

The main output of the FORCE11 Software Citation working group (https://www.force11.org/group/software-citation-working-group) was a paper on software citation principles (https://doi.org/10.7717/peerj-cs.86) published in September 2016. This paper laid out a set of six high-level principles for software citation (importance, credit and attribution, unique identification, persistence, accessibility, and specificity) and discussed how they could be used to implement software citation in the scholarly community. In a series of talks and other activities, we have promoted software citation using these increasingly accepted principles. At the time the initial paper was published, we also provided guidance and examples on how to make software citable, though we now realize there are unresolved problems with that guidance. The purpose of this document is to provide an explanation of current issues impacting scholarly attribution of research software, organize updated implementation guidance, and identify where best practices and solutions are still needed

CoScience : gemeinsam forschen und publizieren mit dem Netz

Der Arbeitsalltag von Wissenschaftlerinnen und Wissenschaftlern hat sich in den letzten Jahren dramatisch verändert. Forschen, Schreiben und Publizieren sind mittlerweile stark durch netzbasierte Anwendungen geprägt. Das digitale Zeitalter aber hat nicht nur neue technische Werkzeuge hervorgebracht, sondern auch neue Wege eröffnet, um Wissen zu generieren und zu verbreiten. Dies gilt sowohl innerhalb der akademischen Welt als auch über diese hinaus. Das Arbeiten mit dem Netz stellt unsere bisherigen etablierten wissenschaftlichen Praktiken in Frage. Forschung wird zunehmend vernetzt, kollaborativ, multimedial, trans- bzw. interdisziplinär durchgeführt. Das vorliegende Handbuch beschreibt diese sich herausbildenden wissenschaftlichen Praktiken. Ziel der Autoren war es dabei, ein praxisnahes und leicht verständliches Handbuch zu schreiben

Spatial variation in the fine-structure constant -- new results from VLT/UVES

(abridged) We present a new analysis of a large sample of quasar absorption-line spectra obtained using UVES (the Ultraviolet and Visual Echelle Spectrograph) on the VLT (Very Large Telescope) in Chile. In the VLT sample (154 absorbers), we find evidence that alpha increases with increasing cosmological distance from Earth. However, as previously shown, the Keck sample (141 absorbers) provided evidence for a smaller alpha in the distant absorption clouds. Upon combining the samples an apparent variation of alpha across the sky emerges which is well represented by an angular dipole model pointing in the direction RA=(17.3 +/- 1.0) hr, dec. = (-61 +/- 10) deg, with amplitude (0.97 +0.22/-0.20) x 10^(-5). The dipole model is required at the 4.1 sigma statistical significance level over a simple monopole model where alpha is the same across the sky (but possibly different to the current laboratory value). The data sets reveal a number of remarkable consistencies: various data cuts are consistent and there is consistency in the overlap region of the Keck and VLT samples. Assuming a dipole-only (i.e. no-monopole) model whose amplitude grows proportionally with `lookback-time distance' (r=ct, where t is the lookback time), the amplitude is (1.1 +/- 0.2) x 10^(-6) GLyr^(-1) and the model is significant at the 4.2 sigma confidence level over the null model [Delta alpha]/alpha = 0). We apply robustness checks and demonstrate that the dipole effect does not originate from a small subset of the absorbers or spectra. We present an analysis of systematic effects, and are unable to identify any single systematic effect which can emulate the observed variation in alpha.Comment: 47 pages, 35 figures. Accepted for publication by Monthly Notices of the Royal Astronomical Society. Please see http://astronomy.swin.edu.au/~mmurphy/pub.html for an ASCII version of table A1 and the full set of Voigt profile fits for appendix