Discovery of common marburgvirus protective epitopes in a BALB/c mouse model

<p>Abstract</p> <p>Background</p> <p>Marburg virus (MARV) causes acute hemorrhagic fever that is often lethal, and no licensed vaccines are available for preventing this deadly viral infection. The immune mechanisms for protection against MARV are poorly understood, but previous studies suggest that both antibodies and T cells are required. In our study, we infected BALB/c mice with plaque-purified, nonlethal MARV and used overlapping peptides to map H2^<it>d</it>-restricted CD8+ T-cell epitopes.</p> <p>Methods</p> <p>Splenocytes from mice infected with nonlethal MARV were harvested and stimulated with multiple overlapping 15-mer peptide pools, and reactive CD8+ T cells were evaluated for antigen specificity by measuring upregulation of CD44 and interferon-γ expression. After confirming positive reactivity to specific 15-mer peptides, we used extrapolated 9-mer epitopes to evaluate the induction of cytotoxic T-cell responses and protection from lethal MARV challenge in BALB/c mice.</p> <p>Results</p> <p>We discovered a CD8+ T-cell epitope within both the MARV glycoprotein (GP) and nucleoprotein (NP) that triggered cytotoxic T-cell responses. These responses were also protective when epitope-specific splenocytes were transferred into naïve animals.</p> <p>Conclusion</p> <p>Epitope mapping of MARV GP, NP, and VP40 provides the first evidence that specific MARV-epitope induction of cellular immune responses is sufficient to combat infection. Establishment of CD8+ T-cell epitopes that are reactive to MARV proteins provides an important research tool for dissecting the significance of cellular immune responses in BALB/c mice infected with MARV.</p

The spectrum of gastric cancer as seen in a large quaternary hospital in KwaZulu-Natal, South Africa

Background. Gastric cancer (GC) is the fifth most commonly diagnosed cancer in the world, with the third-highest associated mortality. It has a varying geographical, ethnic and socioeconomic distribution.Objective. To assess the presentation and management of GC in the Durban metropolitan area, South Africa.Methods. A retrospective review of 131 patients treated at the quaternary Inkosi Albert Luthuli Central Hospital in Durban from 2009 to 2014 was performed.Results. The 131 patients were predominantly black African (n=59, 45.0%) and Indian (n=63, 48.1%). Gender was evenly distributed, with 72 males (55.0%) and 59 females (45.0%). The average age of the patients was 60 years (standard deviation 13.3). More than 70% were in advanced stages of cancer and were treated conservatively. There was no significant relationship between body mass index (BMI) and the position of the tumour (p=0.175). Creatinine and albumin levels differed significantly between the genders (p&lt;0.001 and p=0.01, respectively).Conclusions. GC appears to have a disproportionately high prevalence among Indians in Durban, and the prevalence of GC appears to be slightly higher among males. Both these observations may simply reflect referral patterns and warrant further investigation. More than 70% of patients presented with advanced-stage disease, and anaemia was common. No relationship was found between BMI and the location of the tumour, although most of the cancers were in the body and distal part of the stomach

Introduction: On Connection, Diversity, and Resilience in Writing Across the Curriculum

Developed from presentations at the 2018 International Writing Across the Curriculum conference, this collection documents a key moment in the history of WAC, foregrounding connection and diversity as keys to the sustainability of the WAC movement in the face of new and long-standing challenges. Contributors reflect on the history and ongoing evolution of WAC, honoring grassroots efforts while establishing a more unified structure of collaborative leadership and mentorship. The chapters in this collection offer a rich variety of practices, pedagogies, mindsets, and methodologies for readers who are invested in using writing in a wide range of institutional and disciplinary contexts. Boldly engaging such pressing topics as translingualism, anti-racism, emotional labor, and learning analytics, the 18 chapters collected here testify to WAC\u27s durability, persistence, and resilience in an ever-changing educational landscape

TEM Characterization of Solar Wind Effects on Genesis Mission Silicon Collectors

The Genesis Discovery Mission passively allowed solar wind (SW) to implant into substrates during exposure times up to ~853 days from 2001 to 2004. The spacecraft then returned the SW to Earth for analysis. Substrates included semiconductor wafers (silicon, sapphire, and germanium), as well as a number of thin films supported by either silicon or sapphire wafers. During flight, subsets of the SW collectors were exposed to one of 4 SW regimes: bulk solar wind, coronal hole solar wind (CH, high speed), interstream solar wind (IS, low speed) or coronal mass ejections (CMEs). Each SW regime had a different composition and range of ion speeds and, during their collection, uniquely changed their host SW collector. This study focuses on bulk vs IS SW effects on CZ silicon

Changes to TSR control set due to changes in mission and lessons learned

Previous Technical Safety Requirements (TSRs) established to support plutonium production activities at the Rocky Flats Environmental Technology Site (RFETS) were heavily focused on engineered safety features that would mitigate potential accidents. With the change in mission in 1992 to Site closure, and considering antiquated equipment nearing the end of their useful life, a change in philosophy was adopted to emphasize preventive controls that are mostly administrative. The new Administrative Controls (ACs) developed in the last few years include discrete attributes of safety management programs (SMPs) that are specifically credited to prevent or mitigate an accident, and include requirements on handling individual deviations, programmatic deficiencies, and TSR AC violations. The primary benefit of these changes is fewer requirements on equipment that allow the contractor more flexibility to maintain the defense-in-depth safety systems in a more cost-effective manner. A disadvantage of these new ACs is that implementation has become cumbersome and difficult to manage, e.g., resulted in an increased burden of demonstrating compliance and required an additional infrastructure to track deviations and deficiencies. In order to improve the efficiency of the authorization basis (AB) process to support accelerated Site closure according to the 2006 Plan, the Site has recently modified the ABs to better focus on the programmatic elements that were credited in the accident analyses, and to rely on the Integrated Safety Management System to implement SMPs via one general TSR AC requirement. At the request of DOE/RFFO, a self-assessment of the Rocky Flats AB program was performed in November 1998 by Victor Stello, DOE Headquarters, along with representatives from other DOE sites and Defense Programs. Results of this self-assessment confirmed that the proposed AC changes would be beneficial and provided specific recommendations

Leveraging Geospatial Information to address Space Epidemiology through Multi\unicode{x2013}omics \unicode{x2013} Report of an Interdisciplinary Workshop

This article will summarize the workshop proceedings of a workshop conducted at the University of Missouri that addressed the use of multi-omics fused with geospatial information to assess and improve the precision and environmental analysis of indicators of crew space health. The workshop addressed the state of the art of multi-omics research and practice and the potential future use of multi-omics platforms in extreme environments. The workshop also focused on potential new strategies for data collection, analysis, and fusion with crosstalk with the field of environmental health, biosecurity, and radiation safety, addressing gaps and shortfalls and potential new approaches to enhancing astronaut health safety and security. Ultimately, the panel proceedings resulted in a synthesis of new research and translational opportunities to improve space and terrestrial epidemiology. In the future, early disease prevention that employs new and expanded data sources enhanced by the analytic precision of geospatial information and artificial intelligence algorithms.Comment: 9 pages, 1 figur

The spectrum of gastric cancer as seen in a large quaternary hospital in KwaZulu-Natal, South Africa

Background. Gastric cancer (GC) is the fifth most commonly diagnosed cancer in the world, with the third-highest associated mortality. It has a varying geographical, ethnic and socioeconomic distribution.Objective. To assess the presentation and management of GC in the Durban metropolitan area, South Africa.Methods. A retrospective review of 131 patients treated at the quaternary Inkosi Albert Luthuli Central Hospital in Durban from 2009 to 2014 was performed.Results. The 131 patients were predominantly black African (n=59, 45.0%) and Indian (n=63, 48.1%). Gender was evenly distributed, with 72 males (55.0%) and 59 females (45.0%). The average age of the patients was 60 years (standard deviation 13.3). More than 70% were in advanced stages of cancer and were treated conservatively. There was no significant relationship between body mass index (BMI) and the position of the tumour (p=0.175). Creatinine and albumin levels differed significantly between the genders (p&lt;0.001 and p=0.01, respectively).Conclusions. GC appears to have a disproportionately high prevalence among Indians in Durban, and the prevalence of GC appears to be slightly higher among males. Both these observations may simply reflect referral patterns and warrant further investigation. More than 70% of patients presented with advanced-stage disease, and anaemia was common. No relationship was found between BMI and the location of the tumour, although most of the cancers were in the body and distal part of the stomach

Development of a model for marburgvirus based on severe-combined immunodeficiency mice

The filoviruses, Ebola (EBOV) and Marburg (MARV), cause a lethal hemorrhagic fever. Human isolates of MARV are not lethal to immmunocompetent adult mice and, to date, there are no reports of a mouse-adapted MARV model. Previously, a uniformly lethal EBOV-Zaire mouse-adapted virus was developed by performing 9 sequential passages in progressively older mice (suckling to adult). Evaluation of this model identified many similarities between infection in mice and nonhuman primates, including viral tropism for antigen-presenting cells, high viral titers in the spleen and liver, and an equivalent mean time to death. Existence of the EBOV mouse model has increased our understanding of host responses to filovirus infections and likely has accelerated the development of countermeasures, as it is one of the only hemorrhagic fever viruses that has multiple candidate vaccines and therapeutics. Here, we demonstrate that serially passaging liver homogenates from MARV-infected severe combined immunodeficient (scid) mice was highly successful in reducing the time to death in scid mice from 50–70 days to 7–10 days after MARV-Ci67, -Musoke, or -Ravn challenge. We performed serial sampling studies to characterize the pathology of these scid mouse-adapted MARV strains. These scid mouse-adapted MARV models appear to have many similar properties as the MARV models previously developed in guinea pigs and nonhuman primates. Also, as shown here, the scid-adapted MARV mouse models can be used to evaluate the efficacy of candidate antiviral therapeutic molecules, such as phosphorodiamidate morpholino oligomers or antibodies