Metatranscriptomics reveals metabolic adaptation and induction of virulence factors by Haemophilus parasuis during lung infection

Haemophilus parasuis is a common inhabitant of the upper respiratory tract of pigs, and the causative agent of Glässer's disease. This disease is characterized by polyserositis and arthritis, produced by the severe inflammation caused by the systemic spread of the bacterium. After an initial colonization of the upper respiratory tract, H. parasuis enters the lung during the early stages of pig infection. In order to study gene expression at this location, we sequenced the ex vivo and in vivo H. parasuis Nagasaki transcriptome in the lung using a metatranscriptomic approach. Comparison of gene expression under these conditions with that found in conventional plate culture showed generally reduced expression of genes associated with anabolic and catabolic pathways, coupled with up-regulation of membrane-related genes involved in carbon acquisition, iron binding and pathogenesis. Some of the up-regulated membrane genes, including ABC transporters, virulence-associated autotransporters (vtaAs) and several hypothetical proteins, were only present in virulent H. parasuis strains, highlighting their significance as markers of disease potential. Finally, the analysis also revealed the presence of numerous antisense transcripts with possible roles in gene regulation. In summary, this data sheds some light on the scarcely studied in vivo transcriptome of H. parasuis, revealing nutritional virulence as an adaptive strategy for host survival, besides induction of classical virulence factors

Report of the Link Resolver Investigation Team

This report was commissioned to explore whether the University Library should improve and update its ProQuest­provided link resolver interface, 360 Link Legacy. To develop a recommendation and propose an implementation plan, an investigation team: evaluated the existing interface; researched how users encounter and interact with the existing interface; identified essential and desired requirements for interface improvements; and reviewed three link resolver tools (360 Link Legacy [current solution], 360 Link 2.0 [the updated version of current solution], and Umlaut [open­ source software]). After considering the above research, as well as the feedback of many library stakeholders, the investigation team recommends that the library should update its link resolver interface, using the Umlaut open­source software.http://deepblue.lib.umich.edu/bitstream/2027.42/117361/1/Link Resolver Investigation Team Report.pdfDescription of Link Resolver Investigation Team Report.pdf : Final Repor

Frequency and risk factors for prevalent, incident, and persistent genital carcinogenic human papillomavirus infection in sexually active women: community based cohort study

Objective To investigate frequency and risk factors for prevalent, incident, and persistent carcinogenic human papillomavirus (HPV) in young women before the introduction of immunisation against HPV types 16 and 18 for schoolgirls

Report of the Link Resolver Implementation Team

The Link Resolver Implementation Team was charged in March 2016 with carrying out the recommendations of the Link Resolver Investigation Team (http://hdl.handle.net/2027.42/117361), which were to re-launch the MGet It link resolver service as a locally-hosted application using the existing 360 Link knowledge base and the Umlaut open-source software. Specifically, the Implementation Team was asked to: 1) Design a user interface using Umlaut and the 360 Link API; 2) Select and prioritize added services in the link resolver menu interface; 3) Determine what, if anything, should be part of a report-a-problem link and implement corresponding workflows; and 4) Determine in which circumstances the link resolver menu page should appear for which kinds of users. This report outlines our decisions on these three points, details user studies to design the interface, and describes the roll-out process. The new MGet It service was released as a limited beta for library staff on September 14, 2016. After a period of review and feedback from library staff, and subsequent adjustments to the interface, the new interface replaced the native 360 Link interface on Monday, October 17, 2016.http://deepblue.lib.umich.edu/bitstream/2027.42/135723/1/link resolver implementation team final report.pdfDescription of link resolver implementation team final report.pdf : Final Repor

Early Radio and X-Ray Observations of the Youngest Nearby Type Ia Supernova PTF 11kly (SN 2011fe)

On 2011 August 24 (UT) the Palomar Transient Factory (PTF) discovered PTF11kly (SN 2011fe), the youngest and most nearby Type Ia supernova (SN Ia) in decades. We followed this event up in the radio (centimeter and millimeter bands) and X-ray bands, starting about a day after the estimated explosion time.We present our analysis of the radio and X-ray observations, yielding the tightest constraints yet placed on the pre-explosion mass-loss rate from the progenitor system of this supernova. We find a robust limit of Ṁ ≾ 10^(−8)(w/100 km s^(−1))M_☉ yr^(−1) from sensitive X-ray non-detections, as well as a similar limit from radio data, which depends, however, on assumptions about microphysical parameters. We discuss our results in the context of single-degenerate models for SNe Ia and find that our observations modestly disfavor symbiotic progenitor models involving a red giant donor, but cannot constrain systems accreting from main-sequence or sub-giant stars, including the popular supersoft channel. In view of the proximity of PTF11kly and the sensitivity of our prompt observations, we would have to wait for a long time (a decade or longer) in order to more meaningfully probe the circumstellar matter of SNe Ia

Guided Internet-delivered cognitive behaviour therapy for perfectionism in a non-clinical sample of adolescents: A study protocol for a randomised controlled trial

Background: Perfectionism is elevated across a range of psychopathologies and has been shown to impede treatment outcomes. There is also evidence suggesting elevated perfectionism may contribute to the onset and maintenance of non-suicidal self-injury. There is a growing body of evidence suggesting that Internet-delivered cognitive-behavioural therapy for perfectionism reduces perfectionism and symptoms of psychological disorders and that reductions are maintained at 3-month and 6-month follow-up. There may also be reductions in non-suicidal self-injury, although no study has investigated this potential benefit. Given that associations between perfectionism and psychopathology are observed across both adults and adolescents, the need for the development of interventions targeting adolescents is essential for early intervention and prevention. Methods: The present study will employ a randomised controlled trial to examine the efficacy of 8-week guided Internet-delivered cognitive-behavioural therapy for perfectionism in adolescents compared to a waitlist control group. The primary outcome is perfectionism, and secondary outcomes include symptoms of psychological disorders, well-being, and non-suicidal self-injury. Outcomes will be assessed at pre-intervention, post-intervention, 1-month follow-up, 3-month follow-up, and 6-month follow-up. A minimum of 240 participants will be recruited online through social media, Australian universities, and schools across Australia. Generalised linear mixed models will be used to test for changes in outcomes between the intervention group and the waitlist control. Discussion: The outcomes of this trial will contribute to the literature on perfectionism and psychopathology in adolescents, as well as the efficacy of guided Internet-delivered interventions for adolescents. Trial registration: The trial was registered on the 20th of June 2019 at the Australia New Zealand Clinical Trials Registry (ACTRN12619000881134). Trial status: This is protocol version 1.0. Participant recruitment began on 31 July 2019 and is still actively running with an anticipated completion date in the fourth quarter of 2020

Meox2 Haploinsufficiency Accelerates Axonal Degeneration in DBA/2J Glaucoma.

Purpose: Glaucoma is a complex disease with major risk factors including advancing age and increased intraocular pressure (IOP). Dissecting these earliest events will likely identify new avenues for therapeutics. Previously, we performed transcriptional profiling in DBA/2J (D2) mice, a widely used mouse model relevant to glaucoma. Here, we use these data to identify and test regulators of early gene expression changes in DBA/2J glaucoma. Methods: Upstream regulator analysis (URA) in Ingenuity Pathway Analysis was performed to identify potential master regulators of differentially expressed genes. The function of one putative regulator, mesenchyme homeobox 2 (Meox2), was tested using a combination of genetic, biochemical, and immunofluorescence approaches. Results: URA identified Meox2 as a potential regulator of early gene expression changes in the optic nerve head (ONH) of DBA/2J mice. Meox2 haploinsufficiency did not affect the characteristic diseases of the iris or IOP elevation seen in DBA/2J mice but did cause a significant increase in the numbers of eyes with axon damage compared to controls. While young mice appeared normal, aged Meox2 haploinsufficient DBA/2J mice showed a 44% reduction in MEOX2 protein levels. This correlated with modulation of age- and disease-specific vascular and myeloid alterations. Conclusions: Our data support a model whereby Meox2 controls IOP-dependent vascular remodeling and neuroinflammation to promote axon survival. Promoting these earliest responses prior to IOP elevation may be a viable neuroprotective strategy to delay or prevent human glaucoma

LSQ13ddu: a rapidly evolving stripped-envelope supernova with early circumstellar interaction signatures

This paper describes the rapidly evolving and unusual supernova LSQ13ddu, discovered by the La Silla-QUEST survey. LSQ13ddu displayed a rapid rise of just 4.8 ± 0.9 d to reach a peak brightness of −19.70 ± 0.02 mag in the LSQgr band. Early spectra of LSQ13ddu showed the presence of weak and narrow HeI features arising from interaction with circumstellar material (CSM). These interaction signatures weakened quickly, with broad features consistent with those seen in stripped-envelope SNe becoming dominant around two weeks after maximum. The narrow HeI velocities are consistent with the wind velocities of luminous blue variables but its spectra lack the typically seen hydrogen features. The fast and bright early light curve is inconsistent with radioactive ⁵⁶Ni powering but can be explained through a combination of CSM interaction and an underlying ⁵⁶Ni decay component that dominates the later time behaviour of LSQ13ddu. Based on the strength of the underlying broad features, LSQ13ddu appears deficient in He compared to standard SNe Ib

A robust system for RNA interference in the chicken using a modified microRNA operon

AbstractRNA interference (RNAi) provides an effective method to silence gene expression and investigate gene function. However, RNAi tools for the chicken embryo have largely been adapted from vectors designed for mammalian cells. Here we present plasmid and retroviral RNAi vectors specifically designed for optimal gene silencing in chicken cells. The vectors use a chicken U6 promoter to express RNAs modelled on microRNA30, which are embedded within chicken microRNA operon sequences to ensure optimal Drosha and Dicer processing of transcripts. The chicken U6 promoter works significantly better than promoters of mammalian origin and in combination with a microRNA operon expression cassette (MOEC), achieves up to 90% silencing of target genes. By using a MOEC, we show that it is also possible to simultaneously silence two genes with a single vector. The vectors express either RFP or GFP markers, allowing simple in vivo tracking of vector delivery. Using these plasmids, we demonstrate effective silencing of Pax3, Pax6, Nkx2.1, Nkx2.2, Notch1 and Shh in discrete regions of the chicken embryonic nervous system. The efficiency and ease of use of this RNAi system paves the way for large-scale genetic screens in the chicken embryo

Measuring nickel masses in Type Ia supernovae using cobalt emission in nebular phase spectra

The light curves of Type Ia supernovae (SNe Ia) are powered by the radioactive decay of $^{56}$Ni to $^{56}$Co at early times, and the decay of $^{56}$Co to $^{56}$Fe from ~60 days after explosion. We examine the evolution of the [Co III] 5892 A emission complex during the nebular phase for SNe Ia with multiple nebular spectra and show that the line flux follows the square of the mass of $^{56}$Co as a function of time. This result indicates both efficient local energy deposition from positrons produced in $^{56}$Co decay, and long-term stability of the ionization state of the nebula. We compile 77 nebular spectra of 25 SN Ia from the literature and present 17 new nebular spectra of 7 SNe Ia, including SN2014J. From these we measure the flux in the [Co III] 5892 A line and remove its well-behaved time dependence to infer the initial mass of $^{56}$Ni ($M_{Ni}$) produced in the explosion. We then examine $^{56}$Ni yields for different SN Ia ejected masses ($M_{ej}$ - calculated using the relation between light curve width and ejected mass) and find the $^{56}$Ni masses of SNe Ia fall into two regimes: for narrow light curves (low stretch s~0.7-0.9), $M_{Ni}$ is clustered near $M_{Ni}$ ~ 0.4$M_\odot$ and shows a shallow increase as $M_{ej}$ increases from ~1-1.4$M_\odot$; at high stretch, $M_{ej}$ clusters at the Chandrasekhar mass (1.4$M_\odot$) while $M_{Ni}$ spans a broad range from 0.6-1.2$M_\odot$. This could constitute evidence for two distinct SN Ia explosion mechanisms.Comment: 16 pages, 12 figures (main text), plus data tables in appendix. Spectra released on WISeREP. Submitted to MNRAS, comments welcom