Pathogenesis and transmission of swine origin A(H3N2)v influenza viruses in ferrets

Recent isolation of a novel swine-origin influenza A H3N2 variant virus [A(H3N2)v] from humans in the United States has raised concern over the pandemic potential of these viruses. Here, we analyzed the virulence, transmissibility, and receptor-binding preference of four A(H3N2)v influenza viruses isolated from humans in 2009, 2010, and 2011. High titers of infectious virus were detected in nasal turbinates and nasal wash samples of A(H3N2)v-inoculated ferrets. All four A(H3N2)v viruses possessed the capacity to spread efficiently between cohoused ferrets, and the 2010 and 2011 A(H3N2)v isolates transmitted efficiently to naïve ferrets by respiratory droplets. A dose-dependent glycan array analysis of A(H3N2)v showed a predominant binding to α2-6–sialylated glycans, similar to human-adapted influenza A viruses. We further tested the viral replication efficiency of A(H3N2)v viruses in a relevant cell line, Calu-3, derived from human bronchial epithelium. The A(H3N2)v viruses replicated in Calu-3 cells to significantly higher titers compared with five common seasonal H3N2 influenza viruses. These findings suggest that A(H3N2)v viruses have the capacity for efficient replication and transmission in mammals and underscore the need for continued public health surveillance.National Institutes of Health (U.S.) (GM 57073)Singapore-MIT Alliance for Research and Technolog

Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events

Peer reviewedPublisher PD

Effect of D222G Mutation in the Hemagglutinin Protein on Receptor Binding, Pathogenesis and Transmissibility of the 2009 Pandemic H1N1 Influenza Virus

Influenza viruses isolated during the 2009 H1N1 pandemic generally lack known molecular determinants of virulence associated with previous pandemic and highly pathogenic avian influenza viruses. The frequency of the amino acid substitution D222G in the hemagglutinin (HA) of 2009 H1N1 viruses isolated from severe but not mild human cases represents the first molecular marker associated with enhanced disease. To assess the relative contribution of this substitution in virus pathogenesis, transmission, and tropism, we introduced D222G by reverse genetics in the wild-type HA of the 2009 H1N1 virus, A/California/04/09 (CA/04). A dose-dependent glycan array analysis with the D222G virus showed a modest reduction in the binding avidity to human-like (α2-6 sialylated glycan) receptors and an increase in the binding to avian-like (α2-3 sialylated glycan) receptors in comparison with wild-type virus. In the ferret pathogenesis model, the D222G mutant virus was found to be similar to wild-type CA/04 virus with respect to lethargy, weight loss and replication efficiency in the upper and lower respiratory tract. Moreover, based on viral detection, the respiratory droplet transmission properties of these two viruses were found to be similar. The D222G virus failed to productively infect mice inoculated by the ocular route, but exhibited greater viral replication and weight loss than wild-type CA/04 virus in mice inoculated by the intranasal route. In a more relevant human cell model, D222G virus replicated with delayed kinetics compared with wild-type virus but to higher titer in human bronchial epithelial cells. These findings suggest that although the D222G mutation does not influence virus transmission, it may be considered a molecular marker for enhanced replication in certain cell types.Centers for Disease Control and Prevention (U.S.)United States. National Institutes of Health (merit award R37 GM057073-13)Singapore-MIT Alliance for Research and Technolog

Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice

available in PMC 2010 October 12Recent reports of mild to severe influenza-like illness in humans caused by a novel swine-origin 2009 A(H1N1) influenza virus underscore the need to better understand the pathogenesis and transmission of these viruses in mammals. In this study, selected 2009 A(H1N1) influenza isolates were assessed for their ability to cause disease in mice and ferrets and compared with a contemporary seasonal H1N1 virus for their ability to transmit to naïve ferrets through respiratory droplets. In contrast to seasonal influenza H1N1 virus, 2009 A(H1N1) influenza viruses caused increased morbidity, replicated to higher titers in lung tissue, and were recovered from the intestinal tract of intranasally inoculated ferrets. The 2009 A(H1N1) influenza viruses exhibited less efficient respiratory droplet transmission in ferrets in comparison with the highly transmissible phenotype of a seasonal H1N1 virus. Transmission of the 2009 A(H1N1) influenza viruses was further corroborated by characterizing the binding specificity of the viral hemagglutinin to the sialylated glycan receptors (in the human host) by use of dose-dependent direct receptor-binding and human lung tissue–binding assays

Особенности развития малого предпринимательства в Украине

В этой работе рассмотрена эволюция предпринимательства Украины на всех этапах ее общественной жизни, в том числе в период экономического кризиса в годы становления независимости. Отражены основные параметры отнесения предприятий к субъектам малого предпринимательства и их роль в развитии экономики государств.У цій роботі розглянута еволюція підприємництва України на всіх етапах її суспільного життя, зокрема в період економічної кризи в роки становлення незалежності. Відображені основні параметри віднесення підприємств до суб'єктів малого підприємництва і їх роль в розвитку економіки держав

The case of the singing vortex’.

A relatively high amplitude, discrete tone is radiated from fully developed tip vortex cavitation under certain conditions. The phenomenon of the "singing vortex" was first reported b

Exploring Parental and Professional Perceptions of Weight Management Services among Under-fives in England:A Qualitative Study

BackgroundChildhood obesity is a significant public health challenge, particularly among children under five. In England, weight management programs aim to address this issue; however, engagement and uptake of these services remain low. Understanding the perceptions of parents and professionals involved in these programs is crucial to enhancing participation and improving health outcomes. This study explores these perceptions to identify barriers and facilitators to effective engagement with weight management services.MethodThis qualitative study used purposive sampling to recruit parents and professionals involved in weight management programs across England. Semi-structured interviews were conducted with 15 participants (8 parents and 7 professionals). Data were transcribed, coded, and thematically analyzed using Braun and Clarke's six-phase framework to identify key themes related to engagement, cultural influences, and program effectiveness.ResultsThe study identified several key themes: parental engagement, the impact of virtual versus face-to-face sessions, motivations for participation, barriers to involvement, and the role of cultural beliefs. Parental involvement was critical for the success of weight management programs, but barriers such as time constraints, cultural beliefs, and socioeconomic factors hindered participation. Professionals highlighted the need for more training and resources to effectively address these challenges. Cultural sensitivities and systemic support were found to be crucial for improving engagement and outcomes.ConclusionsThe findings emphasize the need for culturally tailored, accessible, and sustainable weight management interventions. Enhanced professional training, increased community outreach, and policy-level support are essential to improve engagement and ensure long-term success in addressing childhood obesity

A 3-D security modeling platform for social IoT environments

Social Internet-of-Things (SIoT) environment comprises not only smart devices but also the humans who interact with these IoT devices. The benefits of such system are overshadowed due to the cyber security issues. A novel approach is required to understand the security implication under such a dynamic environment while taking both the social and technical aspects into consideration. This paper addressed such challenges and proposed a 3-D security modeling platform that can capture and model the security requirements in the SIoT environment. The modeling process is graphical notation based and works as a security extension to the Business Process Model and Notation. Still, it utilizes the latest 3-D game technology; thus, the security extensions are generated through the third dimension. Consequently, the introduction of security extensions will not increase the complexity of the original SIoT scenario, while keeping all the key information on the same platform. Together with the proposed security ontology, these comprehensive security notations created a unique platform that aims at addressing the ever complicated security issues in the SIoT environment

The interactions of disability and impairment

Theoretical work on disability is going through an expansive period, built on the growing recognition of disability studies as a discipline and out of the political and analytical push to bring disability into a prominent position within accounts of the intersecting social categories that shape people's lives. A current debate within critical disability studies is whether that study should include impairment and embodiment within its focus. This article argues it should and does so by drawing from symbolic interactionism and embodiment literatures in order to explore how differences in what bodies can do-defined as impairments-come to play a role in how people make sense of themselves through social interaction. We argue that these everyday interactions and the stories we tell within them and about them are important spaces and narratives through which impairment and disability are produced. Interactions and stories are significant both in how they are shaped by wider social norms, collective stories and institutional processes, and also how they at times can provide points of resistance and challenges to such norms, stories and institutions. Therefore, the significance of impairment and interaction is the role they play in both informing self-identity and also broader dynamics of power and inequality

Towards a Framework for the Extension and Visualisation of Cyber Security Requirements in Modelling Language

Every so often papers are published presenting a new extension for modelling cyber security requirements in Business Process Model and Notation (BPMN). The frequent production of new extensions by experts belies the need for a richer and more usable representation of security requirements in BPMN processes. In this paper, we present our work considering an analysis of existing extensions and identify the notational issues present within each of them. We discuss how there is yet no single extension which represents a comprehensive range of cyber security concepts. Consequently, there is no adequate solution for accurately specifying cyber security requirements within BPMN. In order to address this, we propose a new framework that can be used to extend, visualise and verify cyber security requirements in not only BPMN, but any other existing modelling language. The framework comprises of the three core roles necessary for the successful development of a security extension. With each of these being further subdivided into the respective components each role must complete