CHARACTERIZATION OF THE TWO VACCINIA VIRUS MATURE VIRION-SPECIFIC PROTEINS, A26P AND A25P

Poxviruses produce two morphologically distinct infectious particles, mature virions (MVs) and extracellular virions (EVs). During replication, some MVs differentiate and become wrapped with cellular membranes, transported to the periphery, and exported as EVs. Some orthopoxviruses, e.g., cowpox virus (CPXV), form large, discrete cytoplasmic inclusions called A-type inclusion bodies (ATIs) within which MVs are embedded by a process called occlusion. ATIs are composed of aggregates of the A-type inclusion protein (ATIp), which is truncated in orthopoxviruses such as vaccinia virus (VACV) that fail to form ATIs. VACV does encode a functional A26p, which along with the ATIp is required for occlusion. A26 lacks a transmembrane domain, and nothing is known regarding how it associates with the MV and regulates occlusion. Additionally, little is known about the formation of ATIs and how MVs become embedded within them. Here, experiments show that A26p is incorporated into MVs by the A27p-A17p complex and interacts with A25p, a truncated form of the CPXV ATIp. Restoration of the full-length ATI gene is sufficient for VACV ATI formation and the occlusion of MVs. A26p directly interacts with ATIp, and this interaction, as well as the A26p-A27p interaction, are required for occlusion. The data demonstrates that ATI mRNAs are transported out of viral factories (VFs) and translated in the cytoplasm. ATIs enlarge both by new protein synthesis and by coalescence, which requires microtubules. ATIs do not nucleate around MVs but rather MVs move along microtubules to embed within ATIs. Taken together, the data suggest a model for occlusion in which MVs move along microtubules to ATIs that are translated from mRNAs in the cytoplasm. At the ATIs, A26p has a bridging role between ATIp and A27p, and A27p provides a link to the MV membrane. Although the specificity of A26p for MVs suggested A26p might regulate wrapping, I did not detect an effect of either the deletion of A26 or occlusion on the production of EVs

Domesticating the novel: moral-domestic fiction, 1820-1834.

Since the late 1960s, the marginalised status of women within literary studies has been addressed. Critics such as Kate Millett set the standard for studies of male-authored fiction that read them for signs of their oppressive, patriarchal assumptions. Somewhat differently, Elaine Showaiter's 1977 text A Literature of Their Own proved seminal for its shift in focus towards women's writing, and the aim of detecting female experiences of society. The effort to retrieve lost or neglected fiction by women mobilised many critics, such Sandra Gilbert and Susan Gubar, yet of most significance for the subject matter of this thesis is Ellen Moers. Moers's Literary Women (1976) essentially suggests an expansion of the types of female-authored fiction that should be recovered. For Moers, women's writing does not have to be about isolated, feminist rejections of male-oriented society in order to be worth retrieving. Female novelists of the eighteenth and nineteenth centuries were taking advantage of one of the few outlets available to them to make money, and their works were defined by intertextuality. Moers writes about a 'sounding board' of mutual awareness and resonance that exists between women writers across periods and genres a female tradition of writing is formed by the 'many voices, of different rhythms, pitches, and timbres' by which women writers are encircled. Collectively, existing works such as those by Showalter and Moers offer justification for retrieving a range of lesser-known, seemingly mundane female-authored works from the past, as these contain connections with surrounding works as well as a narrative on women's experiences of society. Currently, however, there is a critical hiatus in which this opportunity is not being satisfied, and many women writers remain neglected. The gap in our knowledge of the female literary tradition can be filled in part by increased familiarisation with the Moral-Domestic genre of the 1820s and 1830s. This genre relates to fictional forbears such as Jane Austen and Maria Edgeworth, as well as later Victorian authors. It also offers a female perspective on a publishing scene whose significance is arguably yet to be fully realised. In this way, the female-authored, Moral-Domestic novels that proliferated in the late-Romantic period represent one, as yet unrecognised voice in Moers's 'sounding board'

Shallow ponds are heterogeneous habitats within a temperate salt marsh ecosystem

Author Posting. © American Geophysical Union, 2017. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Biogeosciences 122 (2017): 1371–1384, doi:10.1002/2017JG003780.Integrating spatial heterogeneity into assessments of salt marsh biogeochemistry is becoming increasingly important because disturbances that reduce plant productivity and soil drainage may contribute to an expansion of shallow ponds. These permanently inundated and sometimes prominent landscape features can exist for decades, yet little is known about pond biogeochemistry or their role in marsh ecosystem functioning. We characterized three ponds in a temperate salt marsh (MA, USA) over alternating periods of tidal isolation and flushing, during summer and fall, by evaluating the composition of plant communities and organic matter pools and measuring surface water oxygen, temperature, and conductivity. The ponds were located in the high marsh and had similar depths, temperatures, and salinities. Despite this, they had different levels of suspended particulate, dissolved, and sediment organic matter and abundances of phytoplankton, macroalgae, and Ruppia maritima. Differences in plant communities were reflected in pond metabolism rates, which ranged from autotrophic to heterotrophic. Integrating ponds into landcover-based estimates of marsh metabolism resulted in slower rates of net production (−8.1 ± 0.3 to −15.7 ± 0.9%) and respiration (−2.9 ± 0.5 to −10.0 ± 0.4%), compared to rates based on emergent grasses alone. Seasonality had a greater effect on pond water chemistry, organic matter pools, and algal abundances than tidal connectivity. Alternating stretches of tidal isolation and flushing did not affect pond salinities or algal communities, suggesting that exchange between ponds and nearby creeks was limited. Overall, we found that ponds are heterogeneous habitats and future expansion could reduce landscape connectivity and the ability of marshes to capture and store carbon.National Science Foundation Grant Number: OCE1233678; PIE-LTER Grant Number: OCE1238212; TIDE Grant Number: OCE13544942017-12-1

Validation of the Persistent Complex Bereavement Disorder (PCBD) Checklist: A Developmentally Informed Assessment Tool for Bereaved Youth

The inclusion of Persistent Complex Bereavement Disorder (PCBD) in the DSMâ 5 appendix signifies a call for research regarding the distinguishing features and clinical utility of proposed PCBD criteria. Rigorously constructed tools for assessing PCBD are lacking, especially for youth. This study evaluated the validity and clinical utility of the PCBD Checklist, a 39â item measure designed to assess PCBD criteria in youth aged 8 to18 years. Test construction procedures involved: (a) reviewing the literature regarding developmental manifestations of proposed criteria, (b) creating a developmentally informed item pool, (c) surveying an expert panel to evaluate the clarity and developmental appropriateness of candidate items, (d) conducting focus groups to evaluate the comprehensibility and acceptability of items, and (e) evaluating psychometric properties in 367 bereaved youth (Mage = 13.49, 55.0% female). The panel, clinicians, and youth provided favorable content validity and comprehensibility ratings for candidate items. As hypothesized, youth who met full PCBD criteria, Criterion B (e.g., preoccupation with the deceased and/or circumstances of the death), or Criterion C (e.g., reactive distress and/or social/identity disruption) reported higher posttraumatic stress and depressive symptoms than youth who did not meet these criteria, ηp2 = .07â .16. Youth who met Criterion C reported greater functional impairment than youth who did not, ηp2 = .08â .12. Youth who qualified for the â traumatic bereavement specifierâ reported more frequent posttraumatic stress symptoms than youth who did not, ηp2 = .04. Findings support the convergent, discriminant, and discriminantâ groups validity, developmental appropriateness, and clinical utility of the PCBD Checklist.ResumenValidación de Lista de verificación del Trastorno por Duelo Complejo Persistente (TDCP): Un informe del desarrollo de herramientas de medición para duelo en jóvenesLISTA DE CHEQUEO DE TRASTORNO DE DUELO COMPLEJO PERSISTENTELa inclusión del trastorno de duelo complejo persistente (TDCP en su sigla en español; PCBD en sus siglas en inglés) en el apéndice del DSMâ 5 significa un llamado para investigar en relación a las características distintivas y la utilidad clínica de los criterios propuestos para el TDCP. Se carece de herramientas rigurosamente construidas para evaluar TDCP, especialmente para jóvenes. Este estudio evalúa la validez y utilidad clínica de la lista de verificación de TPCP, una medida con 39 ítems diseñada para medir el criterio de TDCP en jóvenes de edades entre 8 a 18 años. El procedimiento de construcción del test involucró: (a) revisión de la literatura relacionada con manifestaciones desarrolladas del criterio propuesto; (b) creación de un pool de ítems informados para el desarrollo; (c) encuesta a un panel experto para evaluar la claridad y desarrollo apropiado de los ítems; (d) conducir grupos focales para evaluar la compresibilidad y aceptabilidad de los ítems; y (e) evaluación de propiedades psicométricas en 367 jóvenes en proceso de duelo (M edad = 13.49, 55.0% femenino). El panel, los clínicos y los jóvenes en proceso de duelo proveyeron una validez de contenido favorable y rangos de comprensibilidad para los ítems candidatos. Como se hipotetizó, los jóvenes que cumplieron el criterio completo de TDCP, criterio B (ej., preocupación por el fallecido y/o las circunstancias de la muerte) o el criterio C (ej., estrés reactivo y/o perturbación social/identidad) reportaron alto estrés postraumático y síntomas depresivos que los jóvenes que no cumplen este criterio, ηp2 = .07 a .16. Los jóvenes que no cumplieron el criterio C reportaron mayor deterioro funcional que los jóvenes que no lo cumplieron ηp2 = .08 a .12. Los jóvenes que calificaron para el â duelo traumático especificoâ reportaron mayor frecuencia de síntomas de estrés postraumático que jóvenes que no calificaron ηp2 = .04. 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Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

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

Transcriptional Landscape of the Prenatal Human Brain

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development