Purification of neural precursor cells reveals the presence of distinct, stimulus-specific subpopulations of quiescent precursors in the adult mouse hippocampus

The activity of neural precursor cells in the adult hippocampus is regulated by various stimuli; however, whether these stimuli regulate the same or different precursor populations remains unknown. Here, we developed a novel cell-sorting protocol that allows the purification to homogeneity of neurosphere-forming neural precursors from the adult mouse hippocampus and examined the responsiveness of individual precursors to various stimuli using a clonal assay. We show that within the Hes5-GFP(+) /Nestin-GFP(+) /EGFR(+) cell population, which comprises the majority of neurosphere-forming precursors, there are two distinct subpopulations of quiescent precursor cells, one directly activated by high-KCl depolarization, and the other activated by norepinephrine (NE). We then demonstrate that these two populations are differentially distributed along the septotemporal axis of the hippocampus, and show that the NE-responsive precursors are selectively regulated by GABA, whereas the KCl-responsive precursors are selectively modulated by corticosterone. Finally, based on RNAseq analysis by deep sequencing, we show that the progeny generated by activating NE-responsive versus KCl-responsive quiescent precursors are molecularly different. These results demonstrate that the adult hippocampus contains phenotypically similar but stimulus-specific populations of quiescent precursors, which may give rise to neural progeny with different functional capacity

Gauges and functional measures in quantum gravity I: Einstein theory

We perform a general computation of the off-shell one-loop divergences in Einstein gravity, in a two-parameter family of path integral measures, corresponding to different ways of parametrizing the graviton field, and a two-parameter family of gauges. Trying to reduce the gauge- and measure-dependence selects certain classes of measures and gauges respectively. There is a choice of two parameters (corresponding to the exponential parametrization and the partial gauge condition that the quantum field be traceless) that automatically eliminates the dependence on the remaining two parameters and on the cosmological constant. We observe that the divergences are invariant under a Z2 \u201cduality\u201d transformation that (in a particularly important special case) involves the replacement of the densitized metric by a densitized inverse metric as the fundamental quantum variable. This singles out a formulation of unimodular gravity as the unique \u201cself-dual\u201d theory in this class. \ua9 2016, The Author(s)

How to Test Mandatory Text Templates: The European Patient Information Leaflet

The structure of patient information leaflets (PILs) supplied with medicines in the European Union is largely determined by a regulatory template, requiring a fixed sequence of pre-formulated headings and sub-headings. The template has been criticized on various occasions, but it has never been tested with users. This paper proposes an alternative template, informed by templates used in the USA and Australia, and by previous user testing.The main research question is whether the revision better enables users to find relevant information. Besides, the paper proposes a methodology for testing templates. Testing document templates is complex, as they are “empty”. For both the current and the alternative template, we produced a document with bogus text and real headings (reflecting the empty template) and a real-life document with readable text (reflecting the “filled” template). The documents were tested both in Dutch and in English, with 64 British and 64 Dutch users. The test used a set of scenario questions that covers the full range of template (sub)topics; users needed to indicate the text locations where they expected each question to be answered. The revised template improved findability of information; this effect was strongest for the “filled” template with readable text. When participants were shown both filled templates, there was a clear preference for the revised template. A closer analysis of the findability data revealed question-specific effects of topic grouping, topic ordering, subtopic granularity and wording of headings. Most of these favoured the revised template, but our revision led to adverse effects as well, for instance in the new heading Check with your doctor. Language-specific effects showed that the wording of the headings is a delicate task. Generally, we conclude that document template designs can be analyzed in terms of the four parameters grouping, ordering, granularity and wording. Furthermore, they need to be tested on their effects on information findability, with template translations requiring separate testing. The methodology used in this study seems an appropriate one for such tests. More specifically, we find that the new patient information leaflet template proposed here provides better information findability

On the physical mechanism underlying Asymptotic Safety

We identify a simple physical mechanism which is at the heart of Asymptotic Safety in Quantum Einstein Gravity (QEG) according to all available effective average action-based investigations. Upon linearization the gravitational field equations give rise to an inverse propagator for metric fluctuations comprising two pieces: a covariant Laplacian and a curvature dependent potential term. By analogy with elementary magnetic systems they lead to, respectively, dia- and paramagnetic-type interactions of the metric fluctuations with the background gravitational field. We show that above 3 spacetime dimensions the gravitational antiscreening occurring in QEG is entirely due to a strong dominance of the ultralocal paramagnetic interactions over the diamagnetic ones that favor screening. (Below 3 dimensions both the dia- and paramagnetic effects support antiscreening.) The spacetimes of QEG are interpreted as a polarizable medium with a "paramagnetic" response to external perturbations, and similarities with the vacuum state of Yang-Mills theory are pointed out. As a by-product, we resolve a longstanding puzzle concerning the beta function of Newton's constant in 2+{\epsilon} dimensional gravity.Comment: 43 pages, 8 figures; clarifying remarks added; to appear in JHE