Studies on the release of neutrophil extracellular traps and IFN-γ as part of the innate immune response to Aspergillus fumigatus and on the fungal stress response via the hybrid sensor kinase TcsC

Aspergillus fumigatus is a saprophytic mold that naturally inhabits the soil. Asexual reproduction yields hardy conidia that circulate in the air and are inhaled daily by humans. The fungus seems not to have evolved distinct mechanisms of pathogenicity, but is capable of responding to many stressful environmental cues present in its naturally harsh niche. The robust conidia present no problem to a fully functioning immune system, but if the innate immune system is compromised, the conidia can become activated and differentiate within the lung tissue to form invasive and disseminating hyphae. The resulting disease is called aspergillosis and is difficult to detect and to treat. To date, scientists have yet to find the factor(s) missing during immunosuppression that allow a healthy patient to easily dispose of A. fumigatus. We explored two possibilities: the production of neutrophil extracellular traps (NETs) and the release of IFN-γ by natural killer (NK) cells. We report here that NETs alone cannot kill the fungus, but do inhibit polar growth. Elongation of hyphal tips is abrogated due to zinc starvation, likely a consequence of the zinc-chelating, NETs-associated protein calprotectin. NK cells alone are also incapable of fungicidal activity, but their release of IFN-γ upon contact with A. fumigatus abrogates hyphal growth by a yet unknown mechanism. In vitro studies of the innate immune response, though helpful, are far from representative of the in vivo response. Neither NETs nor IFN-γ alone can manage Aspergillus infection, but in combination, these and other immune assaults certainly can. The difficulty lies in identifying the precise combination of immune cells and cytokine milieu that in a healthy individual prevent infection. Additionally, we explored mechanisms by which the fungus responds to stress, namely the HOG MAPK pathway, historically involved in osmotic stress response. In filamentous fungi, certain stress signals are sensed by a cytoplasmic hybrid histidine kinase sensor and then passed through the HOG system via phosphorylation. We identified the putative hybrid sensor kinase in A. fumigatus, and generated a corresponding knockout mutant. The ΔtcsC mutant was indeed sensitive to osmotic stress, and resistant to the phenolpyrrole fungicide fludioxonil. In the wild type the addition of either osmotic stress or fludioxonil resulted in SakA phosphorylation and translocation to the nucleus. SakA, the Hog1 homolog in A. fumigatus, is located at the end of the HOG pathway, confirming the role of TcsC as the cytoplasmic sensor upstream of SakA. In hypoxia, on farnesol, and in high concentrations of divalent cations the ΔtcsC mutant exhibited a striking “fluffy” phenotype characterized by the production of tremendous aerial hyphae and little or no differentiation, i.e., no conidiation. Though the ΔtcsC mutant showed no change in virulence compared to wild type, components of the TcsC signalling pathway remain promising targets for antifungal agents

Grief After Death

Child grief and bereavement are widely misunderstood and under addressed, frequently disenfranchising children and teens. Child and family bereavement centers are a crucial resource. I wanted to know how these non-profit organizations benefit young grievers from their own perspective. To strengthen my understanding, I volunteered at FRIENDS WAY in Warwick, Rhode Island for six months to learn more about bereaved children and families and to assess how it serves this client group. A program evaluation was then conducted. Survey questions asked the participants about the value of their experiences, and which specific activities they find most helpful and most enjoyable. Activities covered by the survey included reading books about death, creating artwork, playing board games, and talking in a group setting. The survey also asked general questions about their overall experience at FRIENDS WAY. Sixteen (N=16) children aged 9 to 13 from two peer-based support groups at FRIENDS WAY completed the survey. Participants were selected based on age and ability to answer the survey questions. The results provide a deeper understanding of how bereaved children ages 9 to 13 can receive the most valuable and beneficial support from bereavement centers like FRIENDS WAY

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

Nitrous Oxide for the Management of Labor

The physiologic process of pain in a parturient is multifaceted and can be altered by multiple factors such as prior labor experience, anxiety level, and fear of loss of autonomy. As healthcare providers it is critical to ensure that the access to various approaches of labor analgesia are available to parturients. Many facilities that employ multiple options for parturients have demonstrated improved postpartum maternal satisfaction, self-esteem, and outlook on the newborn. At present, nitrous oxide is becoming increasingly popular in facilities throughout the United States. This literature review describes the knowledge deficit which exists within healthcare facilities which may discourage healthcare staff from offering nitrous oxide. Many facilities lack standardized protocols or references which can promote confidence in healthcare providers offering analgesic techniques such as nitrous oxide. Therefore, this clinical reference has been created in hopes to assist and provide a brief introduction to the topic of nitrous oxide for labor pain management.https://doi.org/10.5281/zenodo.502145

Immunity and Protective Efficacy of a Plant-Based Tobacco Mosaic Virus-like Nanoparticle Vaccine against Influenza a Virus in Mice

Background: The rapid production of influenza vaccines is crucial to meet increasing pandemic response demands. Here, we developed plant-made vaccines comprising centralized consensus influenza hemagglutinin (HA-con) proteins (H1 and H3 subtypes) conjugated to a modified plant virus, tobacco mosaic virus (TMV) nanoparticle (TMV-HA-con). Methods: We compared immune responses and protective efficacy against historical H1 or H3 influenza A virus infections among TMV-HA-con, HA-con protein combined with AddaVax™ adjuvant, and whole-inactivated virus vaccine (Fluzone®). Results: Immunogenicity studies demonstrated robust IgG, IgM, and IgA responses in the TMV-HA-con and HA-con protein vaccinated groups, with relatively low induction of interferon (IFN)-γ+ T-cell responses across all vaccinated groups. The TMV-HA-con and HA-con protein groups displayed partial protection (100% and 80% survival) with minimal weight loss following challenge with two H1N1 strains. The HA-con protein group exhibited 80% and 100% survival against two H3 strains, whereas the TMV-HA-con groups showed reduced protection (20% survival). The Fluzone® group conferred 20–100% survival against two H1N1 strains and one H3N1 strain, but did not protect against H3N2 infection. Conclusions: Our findings indicate that TMV-HA and HA-con protein vaccines with adjuvant induce protective immune responses against influenza A virus infections. Furthermore, our results underscore the potential of plant-based production using TMV-like nanoparticles for developing influenza A virus candidate vaccines

Student engagement and institutional assessment: Current trends and future possibilities

With the National Survey of Student Engagement marking its 20th year, we invite participants to explore the trends and possibilities of engagement as a lens for examining institutional quality. This session, conducted as a research town hall, will focus on three broad areas: 1. Changing demographics—What are the emerging demographics on your campus? How will new kinds of students challenge and shape what we know about engagement? 2. Developments in teaching and learning—Do current measures of engagement adequately cover what is essential to the improvement of student learning? What new forms of engagement should we assess? 3. Approaches to assessment—What trends should a large-scale survey assessment project consider over the next decade to facilitate evidence-informed improvement? After briefly introducing each topic, the presenters will facilitate an active discussion with participants about the trends and possibilities at their institutions and in higher education overall

Movements of marine fish and decapod crustaceans: Process, theory and application

Many marine species have a multi-phase ontogeny, with each phase usually associated with a spatially and temporally discrete set of movements. For many fish and decapod crustaceans that live inshore, a tri-phasic life cycle is widespread, involving: (1) the movement of planktonic eggs and larvae to nursery areas; (2) a range of routine shelter and foraging movements that maintain a home range; and (3) spawning migrations away from the home range to close the life cycle. Additional complexity is found in migrations that are not for the purpose of spawning and movements that result in a relocation of the home range of an individual that cannot be defined as an ontogenetic shift. Tracking and tagging studies confirm that life cycle movements occur across a wide range of spatial and temporal scales. This dynamic multi-scale complexity presents a significant problem in selecting appropriate scales for studying highly mobile marine animals. We address this problem by first comprehensively reviewing the movement patterns of fish and decapod crustaceans that use inshore areas and present a synthesis of life cycle strategies, together with five categories of movement. We then examine the scale-related limitations of traditional approaches to studies of animal-environment relationships. We demonstrate that studies of marine animals have rarely been undertaken at scales appropriate to the way animals use their environment and argue that future studies must incorporate animal movement into the design of sampling strategies. A major limitation of many studies is that they have focused on: (1) a single scale for animals that respond to their environment at multiple scales or (2) a single habitat type for animals that use multiple habitat types. We develop a hierarchical conceptual framework that deals with the problem of scale and environmental heterogeneity and we offer a new definition of 'habitat' from an organism-based perspective. To demonstrate that the conceptual framework can be applied, we explore the range of tools that are currently available for both measuring animal movement patterns and for mapping and quantifying marine environments at multiple scales. The application of a hierarchical approach, together with the coordinated integration of spatial technologies offers an unprecedented opportunity for researchers to tackle a range of animal-environment questions for highly mobile marine animals. Without scale-explicit information on animal movements many marine conservation and resource management strategies are less likely to achieve their primary objectives

NSSE & FSSE 2020: Guidance on COVID-19 Disruptions

COVID-19 is causing unprecedented disruptions to campuses and communities everywhere. To provide guidance to institutions participating in NSSE 2020 and FSSE 2020, we invite you to attend a free webinar on Thursday, March 26 at 2:00 pm (Eastern). We will discuss questions and concerns about the 2020 administration, suggested modifications to reminders and delivery dates, guidance for communicating with students and faculty about survey plans and delivery of incentives, the potential impact on response rates and student engagement results, plans for identifying and analyzing respondents by completion date, and other timely topics. NSSE webinars are live and interactive, providing participants the opportunity to ask questions via a text chat. When you register you will be invited to submit questions and suggestions in advance

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Localization and Broadband Follow-Up of the Gravitational-Wave Transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser InterferometerGravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimatesof the time, significance, and sky location of the event were shared with 63 teams of observers covering radio,optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter wedescribe the low-latency analysis of the GW data and present the sky localization of the first observed compactbinary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-rayCoordinates Network circulars, giving an overview of the participating facilities, the GW sky localizationcoverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger,there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadbandcampaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broadcapabilities of the transient astronomy community and the observing strategies that have been developed to pursueneutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-upcampaign are being disseminated in papers by the individual teams