H7N9 influenza A virus transmission in a multispecies barnyard model

Influenza A viruses are a diverse group of pathogens that have been responsible for millions of human and avian deaths throughout history. Here, we illustrate the transmission potential of H7N9 influenza A virus between Coturnix quail (Coturnix sp.), domestic ducks (Anas platyrhynchos domesticus), chickens (Gallus gallus domesticus), and house sparrows (Passer domesticus) co-housed in an artificial barnyard setting. In each of four replicates, individuals from a single species were infected with the virus. Quail shed virus orally and were a source of infection for both chickens and ducks. Infected chickens transmitted the virus to quail but not to ducks or house sparrows. Infected ducks transmitted to chickens, resulting in seroconversion without viral shedding. House sparrows did not shed virus sufficiently to transmit to other species. These results demonstrate that onward transmission varies by index species, and that gallinaceous birds are more likely to maintain H7N9 than ducks or passerines

Susceptibility of Wild Canids to SARS-CoV-2

We assessed 2 wild canid species, red foxes (Vulpes vulpes) and coyotes (Canis latrans), for susceptibility to SARS-CoV-2. After experimental inoculation, red foxes became infected and shed infectious virus. Conversely, experimentally challenged coyotes did not become infected; therefore, coyotes are unlikely to be competent hosts for SARS-CoV-2. Throughout the COVID-19 pandemic, multiple instances of natural infections with SARS-CoV-2 have been reported in pet dogs, likely after exposure to an infected human (1–3). Domestic dogs appear to be minimally susceptible to SARS-CoV-2, as indicated by experimental inoculations resulting in reverse transcription PCR–positive samples and low titer antibody responses but no clinical disease nor shedding of infectious virus (4,5). The ability of SARS-CoV-2 to infect domestic dogs, in addition to several other species of carnivores, suggests that additional members of the canid family might be susceptible to infection. Wild canids, such as red foxes (Vulpes vulpes) and coyotes (Canis latrans), are of particular interest given how widely distributed these animals are, their frequent proximity to humans, and that they prey, scavenge upon, or otherwise interact with species demonstrated to be susceptible to SARS-CoV-2, including felids, skunks, rodents, and white-tailed deer (6,7). Foxes (species not specified) have been included in modeling efforts and serosurveillance studies aiming to predict animal hosts of SARS-CoV-2, but their ability to serve as hosts for SARS-CoV-2 remains unclear

Experimental Infection of Brazilian Free-Tailed Bats (\u3ci\u3eTadarida brasiliensis\u3c/i\u3e) with Two Strains of SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is presumed to have originated from wildlife and shares homology with other bat coronaviruses. Determining the susceptibility of North American bat species to SARS-CoV-2 is of utmost importance for making decisions regarding wildlife management, public health, and conservation. In this study, Brazilian free-tailed bats (Tadarida brasiliensis) were experimentally infected with two strains of SARS-CoV-2 (parental WA01 and Delta variant), evaluated for clinical disease, sampled for viral shedding and antibody production, and analyzed for pathology. None of the bats (n = 18) developed clinical disease associated with infection, shed infectious virus, or developed histopathological lesions associated with SARS-CoV-2 infection. All bats had low levels of viral RNA in oral swabs, six bats had low levels of viral RNA present in the lungs during acute infection, and one of the four bats that were maintained until 28 days post-infection developed a neutralizing antibody response. These findings suggest that Brazilian free-tailed bats are permissive to infection by SARS-CoV-2, but they are unlikely to contribute to environmental maintenance or transmission

A potential role for sirtuin-1 in Alzheimer\u27s disease: Reviewing the biological and environmental evidence

Sirtuin-1 (Sirt1), encoded by the SIRT1 gene, is a conserved Nicotinamide adenine dinucleotide (NAD+) dependent deacetylase enzyme, considered as the master regulator of metabolism in humans. Sirt1 contributes to a wide range of biological pathways via several mechanisms influenced by lifestyle, such as diet and exercise. The importance of a healthy lifestyle is of relevance to highly prevalent modern chronic diseases, such as Alzheimer\u27s disease (AD). There is growing evidence at multiple levels for a role of Sirt1/SIRT1 in AD pathological mechanisms. As such, this review will explore the relevance of Sirt1 to AD pathological mechanisms, by describing the involvement of Sirt1/SIRT1 in the development of AD pathological hallmarks, through its impact on the metabolism of amyloid- and degradation of phosphorylated tau. We then explore the involvement of Sirt1/SIRT1 across different AD-relevant biological processes, including cholesterol metabolism, inflammation, circadian rhythm, and gut microbiome, before discussing the interplay between Sirt1 and AD-related lifestyle factors, such as diet, physical activity, and smoking, as well as depression, a common comorbidity. Genome-wide association studies have explored potential associations between SIRT1 and AD, as well as AD risk factors and co-morbidities. We summarize this evidence at the genetic level to highlight links between SIRT1 and AD, particularly associations with AD-related risk factors, such as heart disease. Finally, we review the current literature of potential interactions between SIRT1 genetic variants and lifestyle factors and how this evidence supports the need for further research to determine the relevance of these interactions with respect to AD and dementia

Helical cationic antimicrobial peptide length and its impact on membrane disruption

AbstractCationic antimicrobial peptides (CAMPs) are important elements of innate immunity in higher organisms, representing an ancient defense mechanism against pathogenic bacteria. These peptides exhibit broad-spectrum antimicrobial activities, utilizing mechanisms that involve targeting bacterial membranes. Recently, a 34-residue CAMP (NA-CATH) was identified in cDNA from the venom gland of the Chinese cobra (Naja atra). A semi-conserved 11-residue pattern observed in the NA-CATH sequence provided the basis for generating an 11-residue truncated peptide, ATRA-1A, and its corresponding D-peptide isomer. While the antimicrobial and biophysical properties of the ATRA-1A stereoisomers have been investigated, their modes of action remain unclear. More broadly, mechanistic differences that can arise when investigating minimal antimicrobial units within larger naturally occurring CAMPs have not been rigorously explored. Therefore, the studies reported here are focused on this question and the interactions of full-length NA-CATH and the truncated ATRA-1A isomers with bacterial membranes. The results of these studies indicate that in engineering the ATRA-1A isomers, the associated change in peptide length and charge dramatically impacts not only their antimicrobial effectiveness, but also the mechanism of action they employ relative to that of the full-length parent peptide NA-CATH. These insights are relevant to future efforts to develop shorter versions of larger naturally occurring CAMPs for potential therapeutic applications

A novel vaccine candidate against rabbit hemorrhagic disease virus 2 (RHDV2) confers protection in domestic rabbits

OBJECTIVE To evaluate efficacy of a novel vaccine against rabbit hemorrhagic disease virus 2 (RHDV2) in domestic rabbits. ANIMALS 40 New Zealand White rabbits obtained from a commercial breeder. PROCEDURES Rabbits were vaccinated and held at the production facility for the duration of the vaccination phase and transferred to Colorado State University for challenge with RHDV2. Rabbits were challenged with oral suspensions containing infectious virus and monitored for clinical disease for up to 10 days. Rabbits that died or were euthanized following infection were necropsied, and livers were evaluated for viral RNA via RT-PCR. RESULTS None of the vaccinated animals (0/9) exhibited clinical disease or mortality following infection with RHDV2 while 9/13 (69%) of the control animals succumbed to lethal disease following infection. CLINICAL RELEVANCE The novel vaccine described herein provided complete protection against lethal infection following RHDV2 challenge. Outside of emergency use, there are currently no licensed vaccines against RHDV2 on the market in the United States; as such, this vaccine candidate would provide an option for control of this disease now that RHDV2 has become established in North America

In-Flight Water Quality Monitoring on the International Space Station (ISS): Measuring Biocide Concentrations with Colorimetric Solid Phase Extraction (CSPE)

The colorimetric water quality monitoring kit (CWQMK) was delivered to the International Space Station (ISS) on STS-128/17A and was initially deployed in September 2009. The kit was flown as a station development test objective (SDTO) experiment to evaluate the acceptability of colorimetric solid phase extraction (CSPE) technology for routine water quality monitoring on the ISS. During the SDTO experiment, water samples from the U.S. water processor assembly (WPA), the U.S. potable water dispenser (PWD), and the Russian system for dispensing ground-supplied water (SVO-ZV) were collected and analyzed with the CWQMK. Samples from the U.S. segment of the ISS were analyzed for molecular iodine, which is the biocide added to water in the WPA. Samples from the SVOZV system were analyzed for ionic silver, the biocide used on the Russian segment of the ISS. In all, thirteen in-flight analysis sessions were completed as part of the SDTO experiment. This paper provides an overview of the experiment and reports the results obtained with the CWQMK. The forward plan for certifying the CWQMK as operational hardware and expanding the capabilities of the kit are also discussed

The use of proactive risk management to reduce emergency service vehicle crashes among firefighters

Introduction: Emergency service vehicle crashes (ESVCs), including rollovers and collisions with other vehicles and fixed objects, are a leading cause of death among U.S. firefighters. Risk management (RM) is a proactive intervention to identifying and mitigating occupational risks and hazards. The goal of this study was to assess the effect of RM in reducing ESVCs. Methods: Three fire departments (A, B and C), representing urban and suburban geographies, and serving medium to large populations, participated in facilitated RM programs to reduce their ESVCs. Interventions were chosen by each department to address their department-specific circumstances and highest risks. Monthly crash rates per 10,000 calls were calculated for each department an average of 28 months before and 23 months after the start of the RM programs. Interrupted time series analysis was used to assess the effect of the RM programs on monthly crash rates. Poisson regression was used to estimate the number of crashes avoided. Economic data from Department A were analyzed to estimate cost savings. Results: Department A had a 15.4% (P = 0.30) reduction in the overall monthly crash rate immediately post-RM and a 1% (P = 0.18) decline per month thereafter. The estimated two-year average cost savings due to 167 crashes avoided was $253,100 (95$192,355 - $313,885). Department B had a 9.7% (P = 0.70) increase in the overall monthly crash rate immediately post-RM and showed no significant changes in their monthly crash rate. Department C had a 28.4% (P = 0.001) reduction in overall monthly crash rate immediately post-RM and a 1.2% (P = 0.09) increase per month thereafter, with an estimated 122 crashes avoided. Conclusions: RM programs have the potential to reduce ESVCs in the fire service and their associated costs; results may vary based on the interventions chosen and how they are implemented. Practical applications: Risk management may be an effective and broadly implemented intervention to reduce ESVCs in the US fire service. (C) 2019 The Author(s). National Safety Council and Elsevier Ltd.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Grb7 SH2 domain structure and interactions with a cyclic peptide inhibitor of cancer cell migration and proliferation

<p>Abstract</p> <p>Background</p> <p>Human growth factor receptor bound protein 7 (Grb7) is an adapter protein that mediates the coupling of tyrosine kinases with their downstream signaling pathways. Grb7 is frequently overexpressed in invasive and metastatic human cancers and is implicated in cancer progression via its interaction with the ErbB2 receptor and focal adhesion kinase (FAK) that play critical roles in cell proliferation and migration. It is thus a prime target for the development of novel anti-cancer therapies. Recently, an inhibitory peptide (G7-18NATE) has been developed which binds specifically to the Grb7 SH2 domain and is able to attenuate cancer cell proliferation and migration in various cancer cell lines.</p> <p>Results</p> <p>As a first step towards understanding how Grb7 may be inhibited by G7-18NATE, we solved the crystal structure of the Grb7 SH2 domain to 2.1 Å resolution. We describe the details of the peptide binding site underlying target specificity, as well as the dimer interface of Grb 7 SH2. Dimer formation of Grb7 was determined to be in the μM range using analytical ultracentrifugation for both full-length Grb7 and the SH2 domain alone, suggesting the SH2 domain forms the basis of a physiological dimer. ITC measurements of the interaction of the G7-18NATE peptide with the Grb7 SH2 domain revealed that it binds with a binding affinity of K_d= ~35.7 μM and NMR spectroscopy titration experiments revealed that peptide binding causes perturbations to both the ligand binding surface of the Grb7 SH2 domain as well as to the dimer interface, suggesting that dimerisation of Grb7 is impacted on by peptide binding.</p> <p>Conclusion</p> <p>Together the data allow us to propose a model of the Grb7 SH2 domain/G7-18NATE interaction and to rationalize the basis for the observed binding specificity and affinity. We propose that the current study will assist with the development of second generation Grb7 SH2 domain inhibitors, potentially leading to novel inhibitors of cancer cell migration and invasion.</p