Report of the Committee on Resolutions- Declaration

Pamphlet concerning a declaration made by the National Educational Association at the forty-fourth annual convention

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Modeling focal epileptic activity in the Wilson-Cowan model with depolarization block

Measurements of neuronal signals during human seizure activity and evoked epileptic activity in experimental models suggest that, in these pathological states, the individual nerve cells experience an activity driven depolarization block, i.e. they saturate. We examined the effect of such a saturation in the Wilson–Cowan formalism by adapting the nonlinear activation function; we substituted the commonly applied sigmoid for a Gaussian function. We discuss experimental recordings during a seizure that support this substitution. Next we perform a bifurcation analysis on the Wilson–Cowan model with a Gaussian activation function. The main effect is an additional stable equilibrium with high excitatory and low inhibitory activity. Analysis of coupled local networks then shows that such high activity can stay localized or spread. Specifically, in a spatial continuum we show a wavefront with inhibition leading followed by excitatory activity. We relate our model simulations to observations of spreading activity during seizures

Governing multisectoral action for health in low- and middle-income countries

Kumanan Rasanathan and colleagues argue that the potential of multisectoral collaboration for improving health remains untapped in many low- and middle-income countries

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Progress report no. 1

Statement of responsibility on title-page reads: Editors: I.A. Forbes, M.J. Driscoll, D.D. Lanning, I. Kaplan, N.C. Rasmussen; Contributors: S.A. Ali, S.T. Brewer, D.K. Choi, F.M. Clikeman, W.R. Corcoran, M.J. Driscoll, I.A. Forbes, C.W. Forsberg, S.L. Ho, C.S. Kang, I. Kaplan, J.L. Klucar, D.D. Lanning, T.C. Leung, E.L. McFarland P.G. Mertens, N.R. Ortiz, A. Pant, N.A. Passman, N.C. Rasmussen, M.K. Sheaffer, D.A. Shupe, G.E. Sullivan, A.T. Supple, J.W. Synan, C.P. Tzanos, W.J. Westlake"MIT-4105-3."Includes bibliographical referencesProgress report; June 30, 1970U.S. Atomic Energy Commission contracts: AT(30-1)410

CRISPR/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion

CRISPR is widely used to disrupt gene function by inducing small insertions and deletions. Here, we show that some single-guide RNAs (sgRNAs) can induce exon skipping or large genomic deletions that delete exons. For example, CRISPR-mediated editing of β-catenin exon 3, which encodes an autoinhibitory domain, induces partial skipping of the in-frame exon and nuclear accumulation of β-catenin. A single sgRNA can induce small insertions or deletions that partially alter splicing or unexpected larger deletions that remove exons. Exon skipping adds to the unexpected outcomes that must be accounted for, and perhaps taken advantage of, in CRISPR experiments. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1237-8) contains supplementary material, which is available to authorized users

Population genomics of sub-Saharan Drosophila melanogaster: African diversity and non-African admixture

(ABRIDGED) We report the genome sequencing of 139 wild-derived strains of D. melanogaster, representing 22 population samples from the sub-Saharan ancestral range of this species, along with one European population. Most genomes were sequenced above 25X depth from haploid embryos. Results indicated a pervasive influence of non-African admixture in many African populations, motivating the development and application of a novel admixture detection method. Admixture proportions varied among populations, with greater admixture in urban locations. Admixture levels also varied across the genome, with localized peaks and valleys suggestive of a non-neutral introgression process. Genomes from the same location differed starkly in ancestry, suggesting that isolation mechanisms may exist within African populations. After removing putatively admixed genomic segments, the greatest genetic diversity was observed in southern Africa (e.g. Zambia), while diversity in other populations was largely consistent with a geographic expansion from this potentially ancestral region. The European population showed different levels of diversity reduction on each chromosome arm, and some African populations displayed chromosome arm-specific diversity reductions. Inversions in the European sample were associated with strong elevations in diversity across chromosome arms. Genomic scans were conducted to identify loci that may represent targets of positive selection. A disproportionate number of candidate selective sweep regions were located near genes with varied roles in gene regulation. Outliers for Europe-Africa FST were found to be enriched in genomic regions of locally elevated cosmopolitan admixture, possibly reflecting a role for some of these loci in driving the introgression of non-African alleles into African populations

Copy Number Variation and Transposable Elements Feature in Recent, Ongoing Adaptation at the Cyp6g1 Locus

The increased transcription of the Cyp6g1 gene of Drosophila melanogaster, and consequent resistance to insecticides such as DDT, is a widely cited example of adaptation mediated by cis-regulatory change. A fragment of an Accord transposable element inserted upstream of the Cyp6g1 gene is causally associated with resistance and has spread to high frequencies in populations around the world since the 1940s. Here we report the existence of a natural allelic series at this locus of D. melanogaster, involving copy number variation of Cyp6g1, and two additional transposable element insertions (a P and an HMS-Beagle). We provide evidence that this genetic variation underpins phenotypic variation, as the more derived the allele, the greater the level of DDT resistance. Tracking the spatial and temporal patterns of allele frequency changes indicates that the multiple steps of the allelic series are adaptive. Further, a DDT association study shows that the most resistant allele, Cyp6g1-[BP], is greatly enriched in the top 5% of the phenotypic distribution and accounts for ∼16% of the underlying phenotypic variation in resistance to DDT. In contrast, copy number variation for another candidate resistance gene, Cyp12d1, is not associated with resistance. Thus the Cyp6g1 locus is a major contributor to DDT resistance in field populations, and evolution at this locus features multiple adaptive steps occurring in rapid succession