Subventricular zone stem cells are heterogeneous with respect to their embryonic origins and neurogenic fates in the adult olfactory bulb

Wedetermined the embryonic origins of adult forebrain subventricular zone (SVZ) stem cells by Cre-lox fate mapping in transgenic mice. We found that all parts of the telencephalic neuroepithelium, including the medial ganglionic eminence and lateral ganglionic eminence (LGE) and the cerebral cortex, contribute multipotent, self-renewing stem cells to the adult SVZ. Descendants of the embryonic LGE and cortex settle in ventral and dorsal aspects of the dorsolateral SVZ, respectively. Both populations contribute new (5-bromo-2(')-deoxyuridine- labeled) tyrosine hydroxylase- and calretinin-positive interneurons to the adult olfactory bulb. However, calbindin-positive interneurons in the olfactory glomeruli were generated exclusively by LGE- derived stem cells. Thus, different SVZ stem cells have different embryonic origins, colonize different parts of the SVZ, and generate different neuronal progeny, suggesting that some aspects of embryonic patterning are preserved in the adult SVZ. This could have important implications for the design of endogenous stem cell-based therapies in the future

Issues in science education A bibliographic survey

SIGLEAvailable from British Library Lending Division - LD:85/08551(Issues) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Succinct Greedy Graph Drawing in the Hyperbolic Plane

We describe an efficient method for drawing any n-vertex simple graph G in the hyperbolic plane. Our algorithm produces greedy drawings, which support greedy geometric routing, so that a message M between any pair of vertices may be routed geometrically, simply by having each vertex that receives M pass it along to any neighbor that is closer in the hyperbolic metric to the message's eventual destination. More importantly, for networking applications, our algorithm produces succinct drawings, in that each of the vertex positions in one of our embeddings can be represented using O(log n) bits and the calculation of which neighbor to send a message to may be performed efficiently using these representations. These properties are useful, for example, for routing in sensor networks, where storage and bandwidth are limited.Comment: 12 pages, 8 figure

Heterogeneity of neural tube defects in Europe: The significance of site of defect and presence of other major anomalies in relation to geographic differences in prevalence

In the period 1980-1987, neural tube defects were two to three times more prevalent in populations covered by EUROCAT registries in the United Kingdom and Ireland (UKI) than in Continental Europe and Malta (CEM). 1864 NTD cases in a total population of 580,000 births in UKI and 455 cases in a population of 380,000 births in CEM were analysed to find if there were differences in the ratio of prevalence rates between UKI and CEM according to site of the defect and association with non-central nervous system (CNS) anomalies. The prevalence rate ratio was high for anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida, and low for encephalocele, lower spina bifida, and anencephaly without other neural tube defects. There was a greater female excess for anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida than for other defects in both geographic areas. There was a female excess for encephalocele in UKI but a male excess in CEM. Certain sites (anencephaly with accompanying spina bifida, iniencephaly, and encephalocele) were more likely to have accompanying non-CNS anomalies. The prevalence rate ratio of multiply malformed NTD was in general lower than for isolated NTD but showed the same pattern by site. The prevalence rate ratio was high for multiply malformed anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida. The sex ratio was similar between isolated and multiply malformed cases when site of the defect is taken into account. It is concluded that the geographic prevalence pattern and sex ratio differ according to site of NTD but do not differ substantially according to whether NTD is isolated or associated with non-CNS anomalies

Connections between theta-graphs, Delaunay triangulations, and orthogonal surfaces

Abstract. Θk-graphs are geometric graphs that appear in the context of graph navigation. The shortest-path metric of these graphs is known to approximate the Euclidean complete graph up to a factor depending on the cone number k and the dimension of the space. TD-Delaunay graphs, a.k.a. triangular-distance Delaunay triangulations, introduced by Chew, have been shown to be plane 2-spanners of the 2D Euclidean complete graph, i.e., the distance in the TD-Delaunay graph between any two points is no more than twice the distance in the plane. Orthogonal surfaces are geometric objects defined from independent sets of points of the Euclidean space. Orthogonal surfaces are well studied in combinatorics (orders, integer programming) and in algebra. From orthogonal surfaces, geometric graphs, called geodesic embeddings can be built. In this paper, we introduce a specific subgraph of the Θ6-graph defined in the 2D Euclidean space, namely the half-Θ6-graph, composed of the evencone edges of the Θ6-graph. Our main contribution is to show that these graphs are exactly the TD-Delaunay graphs, and are strongly connected to the geodesic embeddings of orthogonal surfaces of coplanar points in the 3D Euclidean space. Using these new bridges between these three fields, we establish: – Every Θ6-graph is the union of two spanning TD-Delaunay graphs. In particular, Θ6-graphs are 2-spanners of the Euclidean graph, and the bound of 2 on the stretch factor is the best possible. It was not known that Θ6-graphs are t-spanners for some constant t, and Θ7-graphs were only known to be t-spanners for t ≈ 7.562. – Every plane triangulation is TD-Delaunay realizable, i.e., every combinatorial plane graph for which all its interior faces are triangles is the TD-Delaunay graph of some point set in the plane. Such realizability property does not hold for classical Delaunay triangulations

Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19

COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment. © 2021, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]